1
|
Kumar M, Muthurayar T, Karthika S, Gayathri S, Varalakshmi P, Ashokkumar B. Anti-Diabetic Potentials of Lactobacillus Strains by Modulating Gut Microbiota Structure and β-Cells Regeneration in the Pancreatic Islets of Alloxan-Induced Diabetic Rats. Probiotics Antimicrob Proteins 2025; 17:1096-1116. [PMID: 38329697 DOI: 10.1007/s12602-024-10221-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 01/17/2024] [Indexed: 02/09/2024]
Abstract
Diabetes mellitus, a most common endocrine disorder of glucose metabolism, has become a global epidemic and poses a serious public health threat with an increased socio-economic burden. Escalating incidence of diabetes is correlated with changes in lifestyle and food habits that cause gut microbiome dysbiosis and β-cells damage, which can be addressed with dietary interventions containing probiotics. Hence, the search for probiotics of human origin with anti-diabetic, anti-AGE, and anti-ACE potentials has gained renewed interest for the effective management of diabetes and its associated complications. The present study used an alloxan (AXN)-induced diabetic rat model to investigate the effects of potential probiotic Lacticaseibacillus casei MKU1, Lactiplantibacillus pentosus MKU3, and Lactiplantibacillus plantarum MKU7 administration individually on physiochemical parameters related to diabetic pathogenesis. Experimental animals were randomly allotted into six groups viz. NCG (control), DCG (AXN), DGM (metformin), DGP1 (MKU1), DGP2 (MKU3), and DGP3 (MKU7), and biochemical data like serum glucose, insulin, AngII, ACE, HbA1c, and TNF-α levels were measured until 90 days. Our results suggest that oral administration with MKU1, MKU3, or MKU7 significantly improved serum insulin levels, glycemic control, glucose tolerance, and body weight. Additionally, β-cell mass was increased by preserving islet integrity in Lactobacillus-treated diabetic rats, whereas TNF-α (~40%), AngII (~30%), and ACE levels (~50%) were strongly inhibited and enhanced sIgA production (5.8 folds) abundantly. Furthermore, Lactobacillus administration positively influenced the gut microbiome with a significant increase in the abundance of Lactobacillus species and the beneficial Bacteroides uniformis and Bacteroides fragilis, while decreased the pathogenic Proteus vulgaris and Parabacteroides distasonis. Among the probiotic treatment groups, L. pentosus MKU3 performed greatly in almost all parameters, indicating its potential use for alleviating diabetes-associated complications.
Collapse
Affiliation(s)
- Manoj Kumar
- Department of Genetic Engineering, School of Biotechnology, Madurai Kamaraj University, Madurai, 625 021, India
| | - Tharmar Muthurayar
- Department of Genetic Engineering, School of Biotechnology, Madurai Kamaraj University, Madurai, 625 021, India
| | - Sukumaran Karthika
- Department of Genetic Engineering, School of Biotechnology, Madurai Kamaraj University, Madurai, 625 021, India
| | - Santhalingam Gayathri
- Department of Genetic Engineering, School of Biotechnology, Madurai Kamaraj University, Madurai, 625 021, India
| | - Perumal Varalakshmi
- Department of Molecular Microbiology, School of Biotechnology, Madurai Kamaraj University, Madurai, India
| | - Balasubramaniem Ashokkumar
- Department of Genetic Engineering, School of Biotechnology, Madurai Kamaraj University, Madurai, 625 021, India.
| |
Collapse
|
2
|
Chen Y, Lei Z, Gu D, Zhao H, Yu R, He Q, Xu M, Du H. Gut microbiota: A potential enhancing factor for the therapeutic efficacy of bioactive compounds in herbal medicines. Fitoterapia 2025; 183:106570. [PMID: 40288589 DOI: 10.1016/j.fitote.2025.106570] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/13/2025] [Revised: 04/14/2025] [Accepted: 04/24/2025] [Indexed: 04/29/2025]
Abstract
The therapeutic efficacy of herbal medicines (HMs) is often compromised by the low bioavailability of their bioactive compounds. However, emerging evidence highlights the crucial role of gut microbiota in enhancing their effectiveness. This review summarizes gut microbiota-mediated metabolism of key herbal components, including terpenoids, flavonoids, alkaloids, and quinones. Particular emphasis is placed on the diverse gut microbiota, enzymes, and metabolites that participate in the biotransformation pathways of these active components of HMs. Exploring the metabolism between the gut microbiota and bioactive compounds gives a better understanding of HMs with multiple components against multiple targets, complex mechanisms of action, and diverse physiological activities. This review underscores the critical importance of gut microbiota in modulating and potentially enhancing the pharmacological effects of HMs, which offers new insights into gut microbiota-mediated transformation pathways and molecular mechanisms of bioactive compounds and deepens the understanding of the therapeutic effects of HMs. Moreover, it suggests new research directions for studying HMs based on gut microbiota-mediated biotransformation.
Collapse
Affiliation(s)
- Yu Chen
- Department of Otolaryngology Head and Neck Surgery, West China Hospital, Sichuan University, Chengdu 610041, Sichuan, China
| | - Ziqin Lei
- Department of Pharmacy, Affiliated Hospital of Southwest Jiaotong University, College of Medicine, Southwest Jiaotong University, The Third People's Hospital of Chengdu, Chengdu 610014, Sichuan, China
| | - Deying Gu
- Department of Otolaryngology Head and Neck Surgery, West China Hospital, Sichuan University, Chengdu 610041, Sichuan, China
| | - Huiling Zhao
- Department of Otolaryngology Head and Neck Surgery, West China Hospital, Sichuan University, Chengdu 610041, Sichuan, China
| | - Rong Yu
- Department of Otolaryngology Head and Neck Surgery, West China Hospital, Sichuan University, Chengdu 610041, Sichuan, China
| | - Qin He
- Department of Pharmacy, Affiliated Hospital of Southwest Jiaotong University, College of Medicine, Southwest Jiaotong University, The Third People's Hospital of Chengdu, Chengdu 610014, Sichuan, China
| | - Min Xu
- Department of Pharmacy, Affiliated Hospital of Southwest Jiaotong University, College of Medicine, Southwest Jiaotong University, The Third People's Hospital of Chengdu, Chengdu 610014, Sichuan, China
| | - Huan Du
- Department of Pharmacy, Affiliated Hospital of Southwest Jiaotong University, College of Medicine, Southwest Jiaotong University, The Third People's Hospital of Chengdu, Chengdu 610014, Sichuan, China.
| |
Collapse
|
3
|
Xu JY, Rong XJ, Shen Z, Guo YD, Zhang YX, Ding CC, Wang Y, Han YX, Gao TL, Tie C. Isochlorogenic Acid C Alleviates Allergic Asthma via Interactions Between Its Bioactive Form and the Gut Microbiome. Int J Mol Sci 2025; 26:4864. [PMID: 40430003 DOI: 10.3390/ijms26104864] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/19/2025] [Revised: 05/03/2025] [Accepted: 05/09/2025] [Indexed: 05/29/2025] Open
Abstract
The global prevalence of asthma is approximately 4.3%, and current asthma treatments focus on reducing symptoms, maintaining normal activity levels, and preventing the deterioration of lung function, rather than achieving a cure or complete prevention. We identified isochlorogenic acid C (ICGAC) as a potential natural medicine for the treatment of asthma. However, the bioavailability of ICGAC was low, ranging from 14.4% to 16.9%, suggesting the involvement of the gut microbiota. The full spectrum of ICGAC's anti-asthmatic mechanism remains to be elucidated. This study investigated the mechanism by which ICGAC alleviates allergic asthma through the gut-lung axis. We discovered anti-asthma pathways and targets based on the selective regulation of lipid peroxidation and employed pharmacological tools to preliminarily validate their mechanisms and efficacy. To study the role of ICGAC in regulating the gut microbiota, we performed 16S rRNA gene sequencing and metabolite analysis. Furthermore, by combining molecular biology and lipid metabolomics, we elucidated the underlying anti-asthma mechanisms of ICGAC. The effective form of ICGAC varies between single and long-term administration. The oral administration of ICGAC enhances the gut-microbiota-derived production of short-chain fatty acids (SCFAs) as the active substances, modulates immune cell activity, influences the differentiation of T- and B-cells, and reduces airway inflammation. ICGAC also regulates the metabolic network of lipid mediators (LMs) and polyunsaturated fatty acids (PUFAs), thus exerting anti-inflammatory effects by modulating arachidonate lipoxygenase (ALOX) activity and LM levels. In addition, ICGAC enhanced the antioxidant response by upregulating the expression of glutathione peroxidase 4 (GPX4), solute carrier family 7 member 11 (SLC7A11), and nuclear factor erythroid 2-related factor 2 (Nrf2), while inhibiting the release of interleukin-4 (IL-4), thereby suppressing asthma inflammation and IgE production. The anti-asthmatic mechanism of oral ICGAC involves the inhibition of lipid peroxidation by chlorogenic acid (CGA) and SCFAs produced by the gut microbiota. ICGAC suppresses asthma-associated inflammatory and oxidative stress responses through the upregulation of GPX4, SLC7A11, and Nrf2 in lung tissue. This study not only provides a solid foundation for the potential clinical use of ICGAC in asthma treatment but also offers novel insights for future research and therapeutic strategies targeting asthma.
Collapse
Affiliation(s)
- Jing-Yi Xu
- State Key Laboratory for Fine Exploration and Intelligent Development of Coal Resources & School of Chemical and Environmental Engineering, China University of Mining and Technology-Beijing, Ding 11 Xueyuan Road, Beijing 100083, China
| | - Xiao-Juan Rong
- Xinjiang Institute of Material Medica, Urumqi 830004, China
| | - Zhen Shen
- State Key Laboratory of Bioactive Substances and Function of Natural Medicine, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China
| | - Yun-Dan Guo
- State Key Laboratory of Bioactive Substances and Function of Natural Medicine, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China
| | - Yi-Xuan Zhang
- State Key Laboratory for Fine Exploration and Intelligent Development of Coal Resources & School of Chemical and Environmental Engineering, China University of Mining and Technology-Beijing, Ding 11 Xueyuan Road, Beijing 100083, China
| | - Chen-Chen Ding
- State Key Laboratory for Fine Exploration and Intelligent Development of Coal Resources & School of Chemical and Environmental Engineering, China University of Mining and Technology-Beijing, Ding 11 Xueyuan Road, Beijing 100083, China
| | - Yi Wang
- State Key Laboratory for Fine Exploration and Intelligent Development of Coal Resources & School of Chemical and Environmental Engineering, China University of Mining and Technology-Beijing, Ding 11 Xueyuan Road, Beijing 100083, China
| | - Yan-Xing Han
- State Key Laboratory of Bioactive Substances and Function of Natural Medicine, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China
| | - Tian-Le Gao
- State Key Laboratory of Bioactive Substances and Function of Natural Medicine, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China
| | - Cai Tie
- State Key Laboratory for Fine Exploration and Intelligent Development of Coal Resources & School of Chemical and Environmental Engineering, China University of Mining and Technology-Beijing, Ding 11 Xueyuan Road, Beijing 100083, China
| |
Collapse
|
4
|
Dey P. Comparable hepatocellular metabolomic signatures under glucose and palmitic acid treatment relative to butyrate in relation to metabolic dysfunction-associated fatty liver disease. Arch Physiol Biochem 2025:1-11. [PMID: 40372011 DOI: 10.1080/13813455.2025.2500651] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/19/2025] [Accepted: 04/11/2025] [Indexed: 05/16/2025]
Abstract
INTRODUCTION Among the dietary factors, glucose, and fatty acids are known to trigger fatty liver disease, while butyrate attenuates steatosis. OBJECTIVE To decipher the hepatocellular altered metabolome under nutrient perturbation relevant to fatty liver disease. METHODS HepG2 cells were cultured under the influence of sub-lethal doses of glucose, palmitic acid (PA), and butyrate. Following the treatment, intracellular metabolites were extracted and derivatized for GCMS analysis. Chemical class enrichment, metabolic pathway analysis, and metabolomic interactome analysis were undertaken. RESULTS Glucose, PA and butyrate caused loss of cell viability at 160 mM, 1600 µM, and 40 mM concentration, respectively. A total of 39, 47, 52, and 51 metabolites were identified in control, glucose, PA, and butyrate, respectively, among which 2-ethylhexanoic acid in control and 2-ethylhexan-1-ol in glucose, PA and butyrate were the most abundant metabolites. Pathways related to the mitochondrial electron transport chain were highly enriched in glucose and PA treatments, leading to increased free radicals. The metabolites identified under glucose and PA treatment were linked to the metabolomic markers of metabolic liver diseases. CONCLUSION Our data showed that the hepatocellular metabolome of HepG2 cells under glucose and PA treatment is closely related, while the metabolome and pathways associated with butyrate treatment are associated with energy metabolism and alleviation of fatty liver.
Collapse
Affiliation(s)
- Priyankar Dey
- Department of Biotechnology, Thapar Institute of Engineering and Technology, Patiala, India
| |
Collapse
|
5
|
Watkins BA, Mitchell AE, Shin AC, Dehghani F, Shen CL. Dietary flavonoid actions on senescence, aging, and applications for health. J Nutr Biochem 2025; 139:109862. [PMID: 39929283 DOI: 10.1016/j.jnutbio.2025.109862] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/08/2024] [Revised: 01/04/2025] [Accepted: 02/06/2025] [Indexed: 03/18/2025]
Abstract
Fruits and vegetables contain biologically active phenolic compounds that show mitigating effects against free radical damage and inflammation. The unique properties of phenolic compounds are protection against oxidative stress, and inception and potentiating of inflammation in the body. Aging is manifest with changes in epigenetic modifications and as with living systems undergo entropy. The gradual decline of body functions and in many cases with aging the cellular processes of senescence are contributors to age-related diseases. Herein the focus is on phenolic compounds as a diet approach to delay the negative consequences of aging. The actions of phenolic compounds on the biology of aging and senescence are presented. The phenolic compounds called flavonoids which are found in many fruits are potential antisenescence factors that benefit health by reducing damage to DNA and the senescence-associated phenotypic cell changes in healthy cells during aging. Flavonoids are proposed to delay and palliate aging where senescence is involved. The dietary sources of natural phenolic compounds afford protection in the aging process and include as some examples naringenin, hesperidin, quercetin, kaempferol, luteolin, genistein, epigallocatechin gallate, and resveratrol. Many of these compounds possess antisenescence effects. The purpose of the review is to discuss where food flavonoids interact with the targets of senescence and how these compounds can attenuate aging-related events. The goal is to provide greater insight into dietary flavonoids and how they improve health and lower the consequences of aging. A novel aspect of this review is the application of flavonoids to neuroprotective effects in brain to reduce pain and improve health with aging.
Collapse
Affiliation(s)
- Bruce A Watkins
- Department of Nutrition, University of California, Davis, Davis CA.
| | - Alyson E Mitchell
- Department of Food Science and Technology, University of California, Davis, Davis CA
| | - Andrew C Shin
- Department of Nutritional Sciences, Neurobiology of Nutrition Laboratory, College of Health & Human Sciences, Texas Tech University, Lubbock, TX
| | - Fereshteh Dehghani
- Department of Nutritional Sciences, Neurobiology of Nutrition Laboratory, College of Health & Human Sciences, Texas Tech University, Lubbock, TX
| | - Chwan-Li Shen
- Department of Pathology, Texas Tech University Health Sciences Center, Lubbock, TX 79430; Center of Excellence for Integrative Health, Texas Tech University Health Sciences Center, Lubbock, TX 79430; Center of Excellence for Translational Neuroscience and Therapeutics, Texas Tech University Health Sciences Center, Lubbock, TX 79430
| |
Collapse
|
6
|
Annaházi A, Bauer R, Efferth T, Khayyal MT, Schemann M, Ulrich-Merzenich G, Feinle-Bisset C. A Review of the Mechanisms of Action of the Herbal Medicine, STW 5-II, Underlying Its Efficacy in Disorders of Gut-Brain Interaction. Neurogastroenterol Motil 2025:e70047. [PMID: 40275491 DOI: 10.1111/nmo.70047] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/07/2024] [Revised: 03/28/2025] [Accepted: 04/02/2025] [Indexed: 04/26/2025]
Abstract
BACKGROUND Functional dyspepsia (FD) and irritable bowel syndrome (IBS) are disorders of gut-brain interaction (DGBIs). Patients with these disorders experience abdominal symptoms, frequently in relation to meal intake, and often are treated using pharmacological approaches that offer limited symptom relief. In addition to various pharmacotherapies, established treatment options include lifestyle modifications (such as diet) and, in certain patients, psychological interventions. Because of the limitations of the currently available treatments, many patients look for alternative options, including herbal preparations. PURPOSE In this review, we summarize the preclinical and clinical evidence informing the use of the herbal preparation, STW 5-II, for the treatment of patients with FD and IBS. Data from clinical trials provide evidence that STW 5-II is superior to placebo in offering symptom relief. Moreover, a substantial body of preclinical data on the mechanisms of action of STW 5-II suggests that its ingredients target multiple mechanisms relevant to pathophysiology and symptom generation that may underlie its beneficial clinical effects in patients with DGBIs.
Collapse
Affiliation(s)
- Anita Annaházi
- Chair of Zoology, Technical University of Munich, Freising, Germany
| | - Rudolf Bauer
- Institute of Pharmaceutical Sciences, University of Graz, Graz, Austria
| | - Thomas Efferth
- Department of Pharmaceutical Biology, Johannes Gutenberg University, Mainz, Germany
| | - Mohamed T Khayyal
- Department of Pharmacology and Toxicology, Faculty of Pharmacy, Cairo University, Cairo, Egypt
| | - Michael Schemann
- Chair of Human Biology, Technical University of Munich, Freising, Germany
| | - Gudrun Ulrich-Merzenich
- Synergy Research and Experimental Medicine Research Group, Medical Clinic III, University Hospital Bonn, Bonn, Germany
| | - Christine Feinle-Bisset
- Adelaide Medical School, Faculty of Health and Medical Sciences, University of Adelaide, Adelaide, South Australia, Australia
| |
Collapse
|
7
|
Zhang Y, Yu Q, Tan P, Tian S, Lin J, Li M, Han L, Huang H, Zhang D. Investigation of the hypoglycemic bioactive components of Phyllanthi Fructus through biological assessment combined with ultrafiltration affinity mass spectrometry. Food Funct 2025; 16:422-436. [PMID: 39564797 DOI: 10.1039/d4fo04198d] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2024]
Abstract
Phyllanthi Fructus (PF) is a tropical fruit with the potential to effectively reduce postprandial blood glucose. However, the lack of quantitative evaluation methods and comprehensive understanding of hypoglycemic active compounds has hindered the development and application of functional foods and dietary supplements derived from PF. In this study, based on the "mass reaction parallel line method", with acarbose as the control and PF extract as the test material, a biological evaluation method for PF hypoglycemic activity based on α-glucosidase inhibition was established for the first time. The in vitro and in vivo validation experiments showed that the coefficient (r) of correlation between the biological evaluation results and the AUC of rat postprandial blood glucose concentration was as high as 0.866, which confirmed the reliability of the evaluation method. The analysis of 20 batches of PF samples showed that the hypoglycemia potency of PF ranged from 2.66 to 8.39 U mg-1, with an average value of 4.00 U mg-1, and the standard deviation was 1.5. UF-LC-MS was used to identify 36 components of PF capable of binding to α-glucosidase. Molecular docking results showed that the binding energy was between -3.5 and -14.3 kJ mol-1. The hypoglycemic activity of 17 available control products was tested, and 8 inhibitors were found, including hyperoside, gallic acid, and corilagin. Dose-effect analysis suggested that flavonoids and polyphenols with a phenolic hydroxyl structure could inhibit α-glucosidase. In short, this study provides a basis for the development of PF hypoglycemic functional foods.
Collapse
Affiliation(s)
- Yifan Zhang
- State Key Laboratory of Characteristic Chinese Medicine Resources in Southwest China, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China.
| | - Qiang Yu
- State Key Laboratory of Characteristic Chinese Medicine Resources in Southwest China, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China.
| | - Peng Tan
- State Key Laboratory of Biological Evaluation of Traditional Chinese Medicine Quality, National Administration of TCM, Sichuan Academy of Chinese Medicine Sciences, Chengdu 610041, China
| | - Shimin Tian
- State Key Laboratory of Characteristic Chinese Medicine Resources in Southwest China, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China.
| | - Junzhi Lin
- TCM Regulating Metabolic Diseases Key Laboratory of Sichuan Province, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu 610072, PR China
| | - Mengqi Li
- Sichuan Nursing Vocational College, Chengdu 610100, China
| | - Li Han
- State Key Laboratory of Characteristic Chinese Medicine Resources in Southwest China, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China.
| | - Haozhou Huang
- State Key Laboratory of Southwestern Chinese Medicine Resources, Innovative Institute of Chinese Medicine and Pharmacy, Meishan Hospital, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China.
| | - Dingkun Zhang
- State Key Laboratory of Characteristic Chinese Medicine Resources in Southwest China, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China.
- Tianfu TCM Innovation Harbour, Chengdu University of Traditional Chinese Medicine, Pengzhou 611900, PR China
| |
Collapse
|
8
|
Yang Y, Liu Y, Cheng Y, He H, Liang A, Pan Z, Liu Y, Chen Z. Multi-omics and experimental analysis unveil the key components in Scutellaria baicalensis Georgi to alleviate hepatic fibrosis via regulating cPLA2-mediated arachidonic acid metabolism. J Transl Med 2024; 22:1138. [PMID: 39716274 DOI: 10.1186/s12967-024-05955-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/20/2024] [Accepted: 12/07/2024] [Indexed: 12/25/2024] Open
Abstract
BACKGROUND Scutellaria baicalensis Georgi, a traditional Chinese herb, is known for its various biological effects, including antibacterial, anti-inflammatory, antioxidative, and antitumor properties. However, the function and mechanisms of methanol extract of Scutellaria baicalensis Georgi (MESB) in treating hepatic fibrosis remain unclear. METHODS This study utilized a CCl4-induced mouse model of hepatic fibrosis to assess the effects of MESB through histopathological analysis and serum tests. The anti-fibrosis mechanism of MESB was investigated using qPCR, Western blotting, RNA interference, proteomics, and metabolomics. Spatial metabolomics identified key components of MESB in liver tissue, while molecular docking determined their targets. RESULTS Treatment with MESB alleviated hepatic pathological changes and reversed hepatic fibrosis in the CCl4-induced models, as evidenced by decreased collagen fibers deposition, reduced expression of hepatic fibrosis markers COL1A1, FN, and PAI-1, and lowered serum levels of AST and ALT. In vitro, MESB inhibited the proliferation of LX-2 cells and the expression of hepatic fibrosis markers. Furthermore, MESB intervention modulated various pathways, particularly those involved in metabolic pathways. Subsequent metabolomics analysis demonstrated that MESB disrupted glycerophospholipid metabolism and suppressed arachidonic acid metabolism. MESB downregulated the expression of cPLA2 in LX-2 cells, leading to decreased production of arachidonic acid and its downstream inflammatory mediators. Meanwhile, MESB inhibited the expression of cPLA2 and its downstream NF-κB pathway in the liver tissues of models induced by CCl4. Additionally, silencing cPLA2 markedly reduced the expressions of COL1A1, FN, and PAI-1. Spatial metabolomics analysis confirmed the penetration of baicalein, wogonin and wogonoside into liver tissue. Further results indicated that baicalein and wogonin inhibited the expression of cPLA2, while baicalin and wogonoside do not exhibit this effect. Moreover, molecular docking suggested that baicalein and wogonin possess the potential to directly interact with cPLA2. CONCLUSION This study reveals that MESB is crucial in preventing hepatic fibrosis via the cPLA2-mediated arachidonic acid metabolic pathway, highlighting its key active components as potential drugs for fibrosis treatment.
Collapse
Affiliation(s)
- Yunheng Yang
- Chongqing Key Laboratory of Traditional Chinese Medicine for Prevention and Cure of Metabolic Diseases, College of Traditional Chinese Medicine, Chongqing Medical University, Chongqing, 400016, China
| | - Yi Liu
- Chongqing Key Laboratory of Traditional Chinese Medicine for Prevention and Cure of Metabolic Diseases, College of Traditional Chinese Medicine, Chongqing Medical University, Chongqing, 400016, China
| | - Yujie Cheng
- Chongqing Key Laboratory of Traditional Chinese Medicine for Prevention and Cure of Metabolic Diseases, College of Traditional Chinese Medicine, Chongqing Medical University, Chongqing, 400016, China
| | - Honglin He
- Chongqing Key Laboratory of Traditional Chinese Medicine for Prevention and Cure of Metabolic Diseases, College of Traditional Chinese Medicine, Chongqing Medical University, Chongqing, 400016, China
| | - Ailing Liang
- Chongqing Key Laboratory of Traditional Chinese Medicine for Prevention and Cure of Metabolic Diseases, College of Traditional Chinese Medicine, Chongqing Medical University, Chongqing, 400016, China
| | - Zheng Pan
- Chongqing Key Laboratory of Traditional Chinese Medicine for Prevention and Cure of Metabolic Diseases, College of Traditional Chinese Medicine, Chongqing Medical University, Chongqing, 400016, China
| | - Yuanyuan Liu
- Department of Radiological Medicine, School of Basic Medical Sciences, Chongqing Medical University, Chongqing, 400016, China.
| | - Zhiwei Chen
- Chongqing Key Laboratory of Traditional Chinese Medicine for Prevention and Cure of Metabolic Diseases, College of Traditional Chinese Medicine, Chongqing Medical University, Chongqing, 400016, China.
- College of Traditional Chinese Medicine, Chongqing University of Chinese Medicine, Chongqing, 402760, China.
| |
Collapse
|
9
|
Fan W, Fan L, Wang Z, Mei Y, Liu L, Li L, Yang L, Wang Z. Rare ginsenosides: A unique perspective of ginseng research. J Adv Res 2024; 66:303-328. [PMID: 38195040 PMCID: PMC11674801 DOI: 10.1016/j.jare.2024.01.003] [Citation(s) in RCA: 14] [Impact Index Per Article: 14.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/12/2023] [Revised: 12/29/2023] [Accepted: 01/04/2024] [Indexed: 01/11/2024] Open
Abstract
BACKGROUND Rare ginsenosides (Rg3, Rh2, C-K, etc.) refer to a group of dammarane triterpenoids that exist in low natural abundance, mostly produced by deglycosylation or side chain modification via physicochemical processing or metabolic transformation in gut, and last but not least, exhibited potent biological activity comparing to the primary ginsenosides, which lead to a high concern in both the research and development of ginseng and ginsenoside-related nutraceutical and natural products. Nevertheless, a comprehensive review on these promising compounds is not available yet. AIM OF REVIEW In this review, recent advances of Rare ginsenosides (RGs) were summarized dealing with the structurally diverse characteristics, traditional usage, drug discovery situation, clinical application, pharmacological effects and the underlying mechanisms, structure-activity relationship, toxicity, the stereochemistry properties, and production strategies. KEY SCIENTIFIC CONCEPTS OF REVIEW A total of 144 RGs with diverse skeletons and bioactivities were isolated from Panax species. RGs acted as natural ligands on some specific receptors, such as bile acid receptors, steroid hormone receptors, and adenosine diphosphate (ADP) receptors. The RGs showed promising bioactivities including immunoregulatory and adaptogen-like effect, anti-aging effect, anti-tumor effect, as well as their effects on cardiovascular and cerebrovascular system, central nervous system, obesity and diabetes, and interaction with gut microbiota. Clinical trials indicated the potential of RGs, while high quality data remains inadequate, and no obvious side effects was found. The stereochemistry properties induced by deglycosylation at C (20) were also addressed including pharmacodynamics behaviors, together with the state-of-art analytical strategies for the identification of saponin stereoisomers. Finally, the batch preparation of targeted RGs by designated strategies including heating or acid/ alkaline-assisted processes, and enzymatic biotransformation and biosynthesis were discussed. Hopefully, the present review can provide more clues for the extensive understanding and future in-depth research and development of RGs, originated from the worldwide well recognized ginseng plants.
Collapse
Affiliation(s)
- Wenxiang Fan
- The MOE Key Laboratory of Standardization of Chinese Medicines, Shanghai Key Laboratory of Compound Chinese Medicines, and SATCM Key Laboratory of New Resources and Quality Evaluation of Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China
| | - Linhong Fan
- The MOE Key Laboratory of Standardization of Chinese Medicines, Shanghai Key Laboratory of Compound Chinese Medicines, and SATCM Key Laboratory of New Resources and Quality Evaluation of Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China
| | - Ziying Wang
- The MOE Key Laboratory of Standardization of Chinese Medicines, Shanghai Key Laboratory of Compound Chinese Medicines, and SATCM Key Laboratory of New Resources and Quality Evaluation of Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China
| | - Yuqi Mei
- The MOE Key Laboratory of Standardization of Chinese Medicines, Shanghai Key Laboratory of Compound Chinese Medicines, and SATCM Key Laboratory of New Resources and Quality Evaluation of Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China
| | - Longchan Liu
- The MOE Key Laboratory of Standardization of Chinese Medicines, Shanghai Key Laboratory of Compound Chinese Medicines, and SATCM Key Laboratory of New Resources and Quality Evaluation of Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China
| | - Linnan Li
- The MOE Key Laboratory of Standardization of Chinese Medicines, Shanghai Key Laboratory of Compound Chinese Medicines, and SATCM Key Laboratory of New Resources and Quality Evaluation of Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China
| | - Li Yang
- The MOE Key Laboratory of Standardization of Chinese Medicines, Shanghai Key Laboratory of Compound Chinese Medicines, and SATCM Key Laboratory of New Resources and Quality Evaluation of Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
| | - Zhengtao Wang
- The MOE Key Laboratory of Standardization of Chinese Medicines, Shanghai Key Laboratory of Compound Chinese Medicines, and SATCM Key Laboratory of New Resources and Quality Evaluation of Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
| |
Collapse
|
10
|
Gupta U, Dey P. The oral microbial odyssey influencing chronic metabolic disease. Arch Physiol Biochem 2024; 130:831-847. [PMID: 38145405 DOI: 10.1080/13813455.2023.2296346] [Citation(s) in RCA: 3] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/11/2023] [Revised: 11/30/2023] [Accepted: 12/03/2023] [Indexed: 12/26/2023]
Abstract
INTRODUCTION Since the oral cavity is the gateway to the gut, oral microbes likely hold the potential to influence metabolic disease by affecting the gut microbiota. METHOD A thorough review of literature has been performed to link the alterations in oral microbiota with chronic metabolic disease by influencing the gut microbiota. RESULT A strong correlation exists between abnormalities in oral microbiota and several systemic disorders, such as cardiovascular disease, diabetes, and obesity, which likely initially manifest as oral diseases. Ensuring adequate oral hygiene practices and cultivating diverse oral microflora are crucial for the preservation of general well-being. Oral bacteria have the ability to establish and endure in the gastrointestinal tract, leading to the development of prolonged inflammation and activation of the immune system. Oral microbe-associated prophylactic strategies could be beneficial in mitigating metabolic diseases. CONCLUSION Oral microbiota can have a profound impact on the gut microbiota and influence the pathogenesis of metabolic diseases.
Collapse
Affiliation(s)
- Upasana Gupta
- Department of Biotechnology, Thapar Institute of Engineering & Technology, Patiala, Punjab, India
| | - Priyankar Dey
- Department of Biotechnology, Thapar Institute of Engineering & Technology, Patiala, Punjab, India
| |
Collapse
|
11
|
Idrees M, Javaid S, Nadeem S, Khurshid F, Parveen A, Malik A, Ali Khan A, Akhtar S, Fatima S. Antimicrobial and Hepatoprotective Properties of Pods of Acacia nilotica (L.) Willd. ex Delile: In Vivo and In Silico Approaches. Dose Response 2024; 22:15593258241308998. [PMID: 39679261 PMCID: PMC11639031 DOI: 10.1177/15593258241308998] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2024] [Revised: 11/15/2024] [Accepted: 11/29/2024] [Indexed: 12/17/2024] Open
Abstract
Background Acacia nilotica is a multipurpose plant known for its remedial properties but the antimicrobial and hepatoprotective activity of its pods remained unexplored. Objective This study aimed to evaluate the antimicrobial and hepatoprotective activity of n-hexane (ANPH) and methanol (ANPM) extracts of pods to scientifically validate their medicinal claims. Methods After the pharmacognostic evaluation of pods, in vitro tests were carried out to estimate phenolic and flavonoid content and antimicrobial potential. In vivo experiments involved testing of both extracts (250 and 500 mg/kg) paracetamol (PCM)-induced hepatotoxicity model in rats. The molecular docking studies explored insights into the potential binding capabilities of the ligands with the specific target proteins. Results ANPH and ANPM were enriched with phenols and flavonoids and showed antimicrobial effects. In the hepatoprotective test, the rats chronically treated with extracts had a dose-dependent hepatoprotection as markers of liver functionality were notably reduced (P < 0.05). The in silico studies revealed strong binding interactions of ergost-5-en-3-ol and oxiranyl methyl ester 9-octadecenoic acid with target proteins for antibacterial activity and hepatoprotective activity, respectively. Conclusion The antimicrobial and hepatoprotective potential of pods might be due to their phenols and flavonoids. The Pyrogallol, Ergost-5-en-3-and 9-octadecenoic acid might be bringing these remedial benefits through antioxidant and anti-inflammatory effects.
Collapse
Affiliation(s)
- Mehak Idrees
- Department of Pharmacognosy, Faculty of Pharmacy, Bahauddin Zakariya University, Multan, Pakistan
| | - Sana Javaid
- Department of Pharmacy, The Women University, Multan, Pakistan
| | - Sumaira Nadeem
- Department of Pharmacy, The Women University, Multan, Pakistan
| | - Faria Khurshid
- Department of Pharmacology, Faculty of Pharmacy, University of Balochistan, Quetta, Pakistan
| | - Abida Parveen
- Department of Pharmacology, Faculty of Pharmacy, Bahauddin Zakariya University, Multan, Pakistan
| | - Abdul Malik
- Department of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia
| | - Azmat Ali Khan
- Pharmaceutical Biotechnology Laboratory, Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia
| | - Suhail Akhtar
- Department of Biochemistry, A.T. Still University of Health Sciences, Kirksville, MO, USA
| | - Sabiha Fatima
- Department of Clinical Laboratory Science, College of Applied Medical Sciences, King Saud University, Riyadh, Saudi Arabia
| |
Collapse
|
12
|
Saeed A, Batra N, Rezgui R, Alshaghdali K, Alkhalaf I, Yadav DK, Dey P. Gut microbiota-centered risk factors and altered immunometabolism in the pathogenesis and prophylaxis of Clostridium difficile infection. JOURNAL OF KING SAUD UNIVERSITY - SCIENCE 2024; 36:103374. [DOI: 10.1016/j.jksus.2024.103374] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 03/31/2025]
|
13
|
Zhang H, Liang S, Yin K, Mo Y, Li Y, Lv Y, Zhan H, Zhang Z, Shan Z, Guo Z, Yin S, Yang W. Urinary Equol and Equol-Predicting Microbial Genera Are Favorably Associated with Body Fat Measures among Chinese Adults. J Nutr 2024; 154:2843-2851. [PMID: 39033820 DOI: 10.1016/j.tjnut.2024.07.024] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/03/2024] [Revised: 06/04/2024] [Accepted: 07/16/2024] [Indexed: 07/23/2024] Open
Abstract
BACKGROUND Many studies have investigated the intake of dietary isoflavones in relation to obesity risk, whereas the association using objective biomarkers of isoflavones, particularly equol (a gut-derived metabolite of daidzein with greater bioavailability than other isoflavones) has been less studied. In addition, the associations between equol and gut microbiota profile at the population level remain to be fully characterized. OBJECTIVES We aimed to identify equol-predicting microbial species and to investigate the associations of equol-predicting microbial species and urinary excretion of isoflavones including glycitein, genistein, daidzein, and equol with diverse obesity markers in free living-individuals. METHODS In this 1-y longitudinal study of 754 community-dwelling adults, urinary isoflavones, fecal microbiota, height, weight, and circumferences of waist and hip were measured at baseline and again after 1 y. Liver fat [indicated by the controlled attenuation parameter (CAP)] and other body composition were also measured after 1 y. Linear models and linear mixed-effects models were used to analyze the associations for single measure and repeated measures, respectively. RESULTS Among 305 participants (median age: 50 y, IQR, 37-59 y) including 138 males and 167 females, higher urinary excretion of equol was associated with lower CAP (β = -0.013, P < 0.001) and body fat mass (β= -0.014, P = 0.046). No association was found between any other urinary isoflavones and obesity markers (all P > 0.05). We identified 21 bacterial genera whose relative abundance were positively associated with urinary equol concentrations (all Pfalsediscovery rate < 0.05), and constructed an equol-predicting microbial score to reflect the overall equol-producing potential of host gut microbiota. This score was inversely associated with CAP (β = -0.040, P = 0.011). CONCLUSIONS High urinary equol concentrations and equol-predicting microbial species could be favorably associated with liver fat and other obesity markers.
Collapse
Affiliation(s)
- Honghua Zhang
- Department of Nutrition, Center for Big Data and Population Health of IHM, School of Public Health, Anhui Medical University, Hefei, Anhui, China; Key Laboratory of Population Health Across Life Cycle (Anhui Medical University), Ministry of Education of the People's Republic of China, Anhui, China; NHC Key Laboratory of study on abnormal gametes and reproductive tract, Anhui, China; Anhui Provincial Key Laboratory of Population Health and Aristogenics/Key Laboratory of Environmental Toxicology of Anhui Higher Education Institutes, Anhui Medical University, Hefei, Anhui, China
| | - Shaoxian Liang
- Department of Nutrition, Center for Big Data and Population Health of IHM, School of Public Health, Anhui Medical University, Hefei, Anhui, China
| | - Kewan Yin
- Department of Nutrition, Center for Big Data and Population Health of IHM, School of Public Health, Anhui Medical University, Hefei, Anhui, China
| | - Yufeng Mo
- Department of Nutrition, Center for Big Data and Population Health of IHM, School of Public Health, Anhui Medical University, Hefei, Anhui, China
| | - Yamin Li
- Department of Nutrition, Center for Big Data and Population Health of IHM, School of Public Health, Anhui Medical University, Hefei, Anhui, China
| | - Yaning Lv
- Technology Center of Hefei Customs and Anhui Province Key Laboratory of Analysis and Detection for Food Safety, Hefei, Anhui, China
| | - Hao Zhan
- Technology Center of Hefei Customs and Anhui Province Key Laboratory of Analysis and Detection for Food Safety, Hefei, Anhui, China
| | - Zhuang Zhang
- Department of Nutrition, Center for Big Data and Population Health of IHM, School of Public Health, Anhui Medical University, Hefei, Anhui, China
| | - Zhilei Shan
- Department of Nutrition and Food Hygiene, Hubei Key Laboratory of Food Nutrition and Safety, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Zhiguo Guo
- Department of Gastroenterology, Suzhou Hospital of Anhui Medical University, Anhui, China
| | - Shi Yin
- Department of Geriatrics, Affiliated Provincial Hospital of Anhui Medical University, Anhui Medical University, Hefei, Anhui, China.
| | - Wanshui Yang
- Department of Nutrition, Center for Big Data and Population Health of IHM, School of Public Health, Anhui Medical University, Hefei, Anhui, China; Key Laboratory of Population Health Across Life Cycle (Anhui Medical University), Ministry of Education of the People's Republic of China, Anhui, China; NHC Key Laboratory of study on abnormal gametes and reproductive tract, Anhui, China; Anhui Provincial Key Laboratory of Population Health and Aristogenics/Key Laboratory of Environmental Toxicology of Anhui Higher Education Institutes, Anhui Medical University, Hefei, Anhui, China.
| |
Collapse
|
14
|
Kim Y, Lim J, Oh J. Taming neuroinflammation in Alzheimer's disease: The protective role of phytochemicals through the gut-brain axis. Biomed Pharmacother 2024; 178:117277. [PMID: 39126772 DOI: 10.1016/j.biopha.2024.117277] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2024] [Revised: 08/05/2024] [Accepted: 08/05/2024] [Indexed: 08/12/2024] Open
Abstract
Alzheimer's disease (AD) is a progressive degenerative neurological condition characterized by cognitive decline, primarily affecting memory and logical thinking, attributed to amyloid-β plaques and tau protein tangles in the brain, leading to neuronal loss and brain atrophy. Neuroinflammation, a hallmark of AD, involves the activation of microglia and astrocytes in response to pathological changes, potentially exacerbating neuronal damage. The gut-brain axis is a bidirectional communication pathway between the gastrointestinal and central nervous systems, crucial for maintaining brain health. Phytochemicals, natural compounds found in plants with antioxidant and anti-inflammatory properties, such as flavonoids, curcumin, resveratrol, and quercetin, have emerged as potential modulators of this axis, suggesting implications for AD prevention. Intake of phytochemicals influences the gut microbial composition and its metabolites, thereby impacting neuroinflammation and oxidative stress in the brain. Consumption of phytochemical-rich foods may promote a healthy gut microbiota, fostering the production of anti-inflammatory and neuroprotective substances. Early dietary incorporation of phytochemicals offers a non-invasive strategy for modulating the gut-brain axis and potentially reducing AD risk or delaying its onset. The exploration of interventions targeting the gut-brain axis through phytochemical intake represents a promising avenue for the development of preventive or therapeutic strategies against AD initiation and progression.
Collapse
Affiliation(s)
- Yoonsu Kim
- Department of Integrative Biology, Kyungpook National University, Daegu 41566, Republic of Korea
| | - Jinkyu Lim
- School of Food Science and Biotechnology, Kyungpook National University, Daegu 41566, Republic of Korea.
| | - Jisun Oh
- New Drug Development Center, Daegu-Gyeongbuk Medical Innovation Foundation, Daegu 41061, Republic of Korea.
| |
Collapse
|
15
|
Tewari N, Dey P. Navigating commensal dysbiosis: Gastrointestinal host-pathogen interplay orchestrating opportunistic infections. Microbiol Res 2024; 286:127832. [PMID: 39013300 DOI: 10.1016/j.micres.2024.127832] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/22/2024] [Revised: 06/23/2024] [Accepted: 07/01/2024] [Indexed: 07/18/2024]
Abstract
The gut commensals, which are usually symbiotic or non-harmful bacteria that live in the gastrointestinal tract, have a positive impact on the health of the host. This review, however, specifically discuss distinct conditions where commensals aid in the development of pathogenic opportunistic infections. We discuss that the categorization of gut bacteria as either pathogens or non-pathogens depends on certain circumstances, which are significantly affected by the tissue microenvironment and the dynamic host-microbe interaction. Under favorable circumstances, commensals have the ability to transform into opportunistic pathobionts by undergoing overgrowth. These conditions include changes in the host's physiology, simultaneous infection with other pathogens, effective utilization of nutrients, interactions between different species of bacteria, the formation of protective biofilms, genetic mutations that enhance pathogenicity, acquisition of genes associated with virulence, and the ability to avoid the host's immune response. These processes allow commensals to both initiate infections themselves and aid other pathogens in populating the host. This review highlights the need of having a detailed and sophisticated knowledge of the two-sided nature of gut commensals. Although commensals mostly promote health, they may also become harmful in certain changes in the environment or the body's functioning. This highlights the need of acknowledging the intricate equilibrium in interactions between hosts and microbes, which is crucial for preserving intestinal homeostasis and averting diseases. Finally, we also emphasize the further need of research to better understand and anticipate the behavior of gut commensals in different situations, since they play a crucial and varied role in human health and disease.
Collapse
Affiliation(s)
- Nisha Tewari
- Department of Biotechnology, Thapar Institute of Engineering and Technology, Patiala, Punjab 147004, India
| | - Priyankar Dey
- Department of Biotechnology, Thapar Institute of Engineering and Technology, Patiala, Punjab 147004, India.
| |
Collapse
|
16
|
Perz M, Szymanowska D, Kostrzewa-Susłow E. The Influence of Flavonoids with -Br, -Cl Atoms and -NO 2, -CH 3 Groups on the Growth Kinetics and the Number of Pathogenic and Probiotic Microorganisms. Int J Mol Sci 2024; 25:9269. [PMID: 39273218 PMCID: PMC11395712 DOI: 10.3390/ijms25179269] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/06/2024] [Revised: 08/14/2024] [Accepted: 08/24/2024] [Indexed: 09/15/2024] Open
Abstract
The pursuit of novel or modified substances based on a natural origin, like flavonoids, is essential in addressing the increasing number of diseases and bacterial resistance to antibiotics, as well as in maintaining intestinal balance and enhancing overall gut health. The primary goal of this research was to evaluate the impact of specific flavonoid compounds-chalcones, flavanones, and flavones-substituted with -Br, -Cl, -CH3, and -NO2 on both pathogenic and probiotic microorganisms. Additionally, this study aimed to understand these compounds' influence on standardized normal and pathologically altered intestinal microbiomes. 8-Bromo-6-chloroflavone 4'-O-β-D-(4″-O-methyl)-glucopyranoside and 8-bromo-6-chloroflavanone showed the most promising results as bactericidal agents. They significantly limited or inhibited the growth of pathogenic bacteria without adversely affecting the probiotic's growth. Digestion in vitro studies indicated that 6-methyl-8-nitroflavone and 8-bromo-6-chloroflavone positively modulated the gut microbiome by increasing beneficial bacteria and reducing potentially pathogenic microbes. This effect was most notable in microbiomes characteristic of older individuals and those recovering from chemotherapy or antibiotic treatments. This study underscores the therapeutic potential of flavonoid compounds, particularly those with specific halogen and nitro substitutions, in enhancing gut health.
Collapse
Affiliation(s)
- Martyna Perz
- Department of Food Chemistry and Biocatalysis, Faculty of Biotechnology and Food Science, Wrocław University of Environmental and Life Sciences, 50-375 Wrocław, Poland
| | - Daria Szymanowska
- Department of Biotechnology and Food Microbiology, Faculty of Food Science and Nutrition, Poznań University of Life Sciences, 60-627 Poznań, Poland
- Department of Pharmacognosy and Biomaterials, Faculty of Pharmacy, Poznań University of Medical Sciences, 60-806 Poznań, Poland
| | - Edyta Kostrzewa-Susłow
- Department of Food Chemistry and Biocatalysis, Faculty of Biotechnology and Food Science, Wrocław University of Environmental and Life Sciences, 50-375 Wrocław, Poland
| |
Collapse
|
17
|
Bolat E, Sarıtaş S, Duman H, Eker F, Akdaşçi E, Karav S, Witkowska AM. Polyphenols: Secondary Metabolites with a Biological Impression. Nutrients 2024; 16:2550. [PMID: 39125431 PMCID: PMC11314462 DOI: 10.3390/nu16152550] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/05/2024] [Revised: 07/29/2024] [Accepted: 08/01/2024] [Indexed: 08/12/2024] Open
Abstract
Polyphenols are natural compounds which are plant-based bioactive molecules, and have been the subject of growing interest in recent years. Characterized by multiple varieties, polyphenols are mostly found in fruits and vegetables. Currently, many diseases are waiting for a cure or a solution to reduce their symptoms. However, drug or other chemical strategies have limitations for using a treatment agent or still detection tool of many diseases, and thus researchers still need to investigate preventive or improving treatment. Therefore, it is of interest to elucidate polyphenols, their bioactivity effects, supplementation, and consumption. The disadvantage of polyphenols is that they have a limited bioavailability, although they have multiple beneficial outcomes with their bioactive roles. In this context, several different strategies have been developed to improve bioavailability, particularly liposomal and nanoparticles. As nutrition is one of the most important factors in improving health, the inclusion of plant-based molecules in the daily diet is significant and continues to be enthusiastically researched. Nutrition, which is important for individuals of all ages, is the key to the bioactivity of polyphenols.
Collapse
Affiliation(s)
- Ecem Bolat
- Department of Molecular Biology and Genetics, Çanakkale Onsekiz Mart University, Canakkale 17000, Türkiye; (E.B.); (S.S.); (H.D.); (F.E.); (E.A.)
| | - Sümeyye Sarıtaş
- Department of Molecular Biology and Genetics, Çanakkale Onsekiz Mart University, Canakkale 17000, Türkiye; (E.B.); (S.S.); (H.D.); (F.E.); (E.A.)
| | - Hatice Duman
- Department of Molecular Biology and Genetics, Çanakkale Onsekiz Mart University, Canakkale 17000, Türkiye; (E.B.); (S.S.); (H.D.); (F.E.); (E.A.)
| | - Furkan Eker
- Department of Molecular Biology and Genetics, Çanakkale Onsekiz Mart University, Canakkale 17000, Türkiye; (E.B.); (S.S.); (H.D.); (F.E.); (E.A.)
| | - Emir Akdaşçi
- Department of Molecular Biology and Genetics, Çanakkale Onsekiz Mart University, Canakkale 17000, Türkiye; (E.B.); (S.S.); (H.D.); (F.E.); (E.A.)
| | - Sercan Karav
- Department of Molecular Biology and Genetics, Çanakkale Onsekiz Mart University, Canakkale 17000, Türkiye; (E.B.); (S.S.); (H.D.); (F.E.); (E.A.)
| | - Anna Maria Witkowska
- Department of Food Biotechnology, Bialystok Medical University, 15-089 Bialystok, Poland
| |
Collapse
|
18
|
Servida S, Piontini A, Gori F, Tomaino L, Moroncini G, De Gennaro Colonna V, La Vecchia C, Vigna L. Curcumin and Gut Microbiota: A Narrative Overview with Focus on Glycemic Control. Int J Mol Sci 2024; 25:7710. [PMID: 39062953 PMCID: PMC11277527 DOI: 10.3390/ijms25147710] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/16/2024] [Revised: 07/01/2024] [Accepted: 07/11/2024] [Indexed: 07/28/2024] Open
Abstract
Turmeric is a spice widely used in China, Southeast Asia, and in traditional Ayurvedic medicine. Its safety profile and efficacy as an antioxidant, anti-inflammatory, antimicrobial, antitumor, antidiabetic, and anti-obesity agent have led to extensive research into its potential role in preventing and treating metabolic diseases. The active compound in turmeric is curcumin, which exhibits low systemic bioavailability after oral administration. However, it is detectable in the gut, where it bidirectionally interacts with the gut microbiota (GM), which plays a crucial role in maintaining host health. The favorable effects of curcumin, particularly its hypoglycemic properties, are linked to alteration in intestinal dysbiosis observed in type 2 diabetes mellitus and metabolic syndrome patients. Restoration of the eubiotic GM may contribute to glycemic homeostasis. Preclinical and clinical studies have demonstrated the involvement of the GM in the regulation of glucose and lipid metabolism. Although the underlying mechanism remains incompletely understood, intestinal dysbiosis is associated with insulin resistance, hyperglycemia, and low-grade inflammation. In the present overview, we summarize the biological properties of curcumin, focusing on its link with GM and, therefore, on its potential role in metabolic diseases.
Collapse
Affiliation(s)
- Simona Servida
- Obesity and Work Centre, Occupational Medicine Unit, Clinica del Lavoro L. Devoto, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy; (S.S.); (A.P.); (V.D.G.C.)
| | - Alessandra Piontini
- Obesity and Work Centre, Occupational Medicine Unit, Clinica del Lavoro L. Devoto, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy; (S.S.); (A.P.); (V.D.G.C.)
| | - Francesca Gori
- Department of Anesthesia, Critical Care and Emergency, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy;
| | - Laura Tomaino
- Postgraduate School of Emergency Medicine, Università Politecnica delle Marche, 60121 Ancona, Italy;
- Department of Clinical and Molecular Sciences, Università Politecnica delle Marche, 60121 Ancona, Italy;
| | - Gianluca Moroncini
- Department of Clinical and Molecular Sciences, Università Politecnica delle Marche, 60121 Ancona, Italy;
| | - Vito De Gennaro Colonna
- Obesity and Work Centre, Occupational Medicine Unit, Clinica del Lavoro L. Devoto, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy; (S.S.); (A.P.); (V.D.G.C.)
- Department of Clinical Science and Community Health, DISSCO, Università degli Studi, 20122 Milan, Italy;
| | - Carlo La Vecchia
- Department of Clinical Science and Community Health, DISSCO, Università degli Studi, 20122 Milan, Italy;
| | - Luisella Vigna
- Obesity and Work Centre, Occupational Medicine Unit, Clinica del Lavoro L. Devoto, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy; (S.S.); (A.P.); (V.D.G.C.)
| |
Collapse
|
19
|
Zhang S, Tang S, Liu Z, Lv H, Cai X, Zhong R, Chen L, Zhang H. Baicalin restore intestinal damage after early-life antibiotic therapy: the role of the MAPK signaling pathway. Pharmacol Res 2024; 204:107194. [PMID: 38663526 DOI: 10.1016/j.phrs.2024.107194] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/25/2024] [Revised: 04/09/2024] [Accepted: 04/22/2024] [Indexed: 04/30/2024]
Abstract
Antibiotic related intestinal injury in early life affects subsequent health and susceptibility. Here, we employed weaned piglets as a model to investigate the protective effects of baicalin against early-life antibiotic exposure-induced microbial dysbiosis. Piglets exposed to lincomycin showed a marked reduction in body weight (p < 0.05) and deterioration of jejunum intestinal morphology, alongside an increase in antibiotic-resistant bacteria such as Staphylococcus, Dolosicoccus, Escherichia-Shigella, and Raoultella. In contrast, baicalin treatment resulted in body weights, intestinal morphology, and microbial profiles that closely resembled those of the control group (p > 0.05), with a significant increase in norank_f_Muribaculaceae and Prevotellaceae_NK3B31_group colonization compared with lincomycin group (p < 0.05). Further analysis through fecal microbial transplantation into mice revealed that lincomycin exposure led to significant alterations in intestinal morphology and microbial composition, notably increasing harmful microbes and decreasing beneficial ones such as norank_Muribaculaceae and Akkermansia (p < 0.05). This shift was associated with an increase in harmful metabolites and disruption of the calcium signaling pathway gene expression. Conversely, baicalin supplementation not only counteracted these effects but also enhanced beneficial metabolites and regulated genes within the MAPK signaling pathway (MAP3K11, MAP4K2, MAPK7, MAPK13) and calcium channel proteins (ORA13, CACNA1S, CACNA1F and CACNG8), suggesting a mechanism through which baicalin mitigates antibiotic-induced intestinal and microbial disturbances. These findings highlight baicalin's potential as a plant extract-based intervention for preventing antibiotic-related intestinal injury and offer new targets for therapeutic strategies.
Collapse
Affiliation(s)
- Shunfen Zhang
- State Key Laboratory of Animal Nutrition and Feeding, Institute of Animal Science, Chinese Academy of Agricultural Sciences, Beijing 100193, China; College of Animal Science and Technology, China Agricultural University, Beijing 100193, China
| | - Shanlong Tang
- State Key Laboratory of Animal Nutrition and Feeding, Institute of Animal Science, Chinese Academy of Agricultural Sciences, Beijing 100193, China
| | - Zhengqun Liu
- State Key Laboratory of Animal Nutrition and Feeding, Institute of Animal Science, Chinese Academy of Agricultural Sciences, Beijing 100193, China; Tianjin Key Laboratory of Animal Molecular Breeding and Biotechnology, Tianjin Engineering Research Center of Animal Healthy Farming, Institute of Animal Science and Veterinary, Tianjin Academy of Agricultural Sciences, Tianjin 300381, China
| | - Huiyuan Lv
- College of Animal Science and Technology, China Agricultural University, Beijing 100193, China; Beijing Centre Biology Co., Ltd., Daxing District, Beijing 102218, China
| | - Xueying Cai
- Department of Critical Care, Hangzhou First People's Hospital, Hangzhou 310003, China
| | - Ruqing Zhong
- State Key Laboratory of Animal Nutrition and Feeding, Institute of Animal Science, Chinese Academy of Agricultural Sciences, Beijing 100193, China.
| | - Liang Chen
- State Key Laboratory of Animal Nutrition and Feeding, Institute of Animal Science, Chinese Academy of Agricultural Sciences, Beijing 100193, China.
| | - Hongfu Zhang
- State Key Laboratory of Animal Nutrition and Feeding, Institute of Animal Science, Chinese Academy of Agricultural Sciences, Beijing 100193, China
| |
Collapse
|
20
|
Jaberi KR, Alamdari-palangi V, Savardashtaki A, Vatankhah P, Jamialahmadi T, Tajbakhsh A, Sahebkar A. Modulatory Effects of Phytochemicals on Gut-Brain Axis: Therapeutic Implication. Curr Dev Nutr 2024; 8:103785. [PMID: 38939650 PMCID: PMC11208951 DOI: 10.1016/j.cdnut.2024.103785] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/04/2024] [Revised: 04/23/2024] [Accepted: 05/17/2024] [Indexed: 06/29/2024] Open
Abstract
This article explores the potential therapeutic implications of phytochemicals on the gut-brain axis (GBA), which serves as a communication network between the central nervous system and the enteric nervous system. Phytochemicals, which are compounds derived from plants, have been shown to interact with the gut microbiota, immune system, and neurotransmitter systems, thereby influencing brain function. Phytochemicals such as polyphenols, carotenoids, flavonoids, and terpenoids have been identified as having potential therapeutic implications for various neurological disorders. The GBA plays a critical role in the development and progression of various neurological disorders, including Parkinson's disease, multiple sclerosis, depression, anxiety, and autism spectrum disorders. Dysbiosis, or an imbalance in gut microbiota composition, has been associated with a range of neurological disorders, suggesting that modulating the gut microbiota may have potential therapeutic implications for these conditions. Although these findings are promising, further research is needed to elucidate the optimal use of phytochemicals in neurological disorder treatment, as well as their potential interactions with other medications. The literature review search was conducted using predefined search terms such as phytochemicals, gut-brain axis, neurodegenerative, and Parkinson in PubMed, Embase, and the Cochrane library.
Collapse
Affiliation(s)
- Khojasteh Rahimi Jaberi
- Department of Neuroscience, School of Advanced Medical Sciences and Technologies, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Vahab Alamdari-palangi
- Department of Molecular Medicine, School of Advanced Medical Sciences and Technologies, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Amir Savardashtaki
- Department of Medical Biotechnology, School of Advanced Medical Sciences and Technologies, Shiraz University of Medical Sciences, Shiraz, Iran
- Infertility Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Pooya Vatankhah
- Anesthesiology and Critical Care Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Tannaz Jamialahmadi
- Pharmaceutical Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran
- Medical Toxicology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Amir Tajbakhsh
- Pharmaceutical Sciences Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Amirhossein Sahebkar
- Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran
- Applied Biomedical Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
| |
Collapse
|
21
|
Deng Y, Hou X, Wang H, Du H, Liu Y. Influence of Gut Microbiota-Mediated Immune Regulation on Response to Chemotherapy. Pharmaceuticals (Basel) 2024; 17:604. [PMID: 38794174 PMCID: PMC11123941 DOI: 10.3390/ph17050604] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/12/2024] [Revised: 04/26/2024] [Accepted: 05/06/2024] [Indexed: 05/26/2024] Open
Abstract
The involvement of the gut microbiota in anti-cancer treatment has gained increasing attention. Alterations to the structure and function of the gut bacteria are important factors in the development of cancer as well as the efficacy of chemotherapy. Recent studies have confirmed that the gut microbiota and related metabolites influence the pharmacological activity of chemotherapeutic agents through interactions with the immune system. This review aims to summarize the current knowledge of how malignant tumor and chemotherapy affect the gut microbiota, how the gut microbiota regulates host immune response, and how interactions between the gut microbiota and host immune response influence the efficacy of chemotherapy. Recent advances in strategies for increasing the efficiency of chemotherapy based on the gut microbiota are also described. Deciphering the complex homeostasis maintained by the gut microbiota and host immunity provides a solid scientific basis for bacterial intervention in chemotherapy.
Collapse
Affiliation(s)
- Yufei Deng
- Wuhan Institute of Biomedical Sciences, School of Medicine, Jianghan University, Wuhan 430056, China; (Y.D.); (X.H.); (H.W.)
- Cancer Institute, School of Medicine, Jianghan University, Wuhan 430056, China
| | - Xiaoying Hou
- Wuhan Institute of Biomedical Sciences, School of Medicine, Jianghan University, Wuhan 430056, China; (Y.D.); (X.H.); (H.W.)
- Cancer Institute, School of Medicine, Jianghan University, Wuhan 430056, China
- Hubei Key Laboratory of Cognitive and Affective Disorders, Jianghan University, Wuhan 430056, China
| | - Haiping Wang
- Wuhan Institute of Biomedical Sciences, School of Medicine, Jianghan University, Wuhan 430056, China; (Y.D.); (X.H.); (H.W.)
- Cancer Institute, School of Medicine, Jianghan University, Wuhan 430056, China
- Hubei Key Laboratory of Cognitive and Affective Disorders, Jianghan University, Wuhan 430056, China
| | - Hongzhi Du
- Cancer Institute, School of Medicine, Jianghan University, Wuhan 430056, China
- School of Pharmacy, Hubei University of Chinese Medicine, Wuhan 430065, China
| | - Yuchen Liu
- Wuhan Institute of Biomedical Sciences, School of Medicine, Jianghan University, Wuhan 430056, China; (Y.D.); (X.H.); (H.W.)
- Cancer Institute, School of Medicine, Jianghan University, Wuhan 430056, China
- Hubei Key Laboratory of Cognitive and Affective Disorders, Jianghan University, Wuhan 430056, China
| |
Collapse
|
22
|
Dey P. Good girl goes bad: Understanding how gut commensals cause disease. Microb Pathog 2024; 190:106617. [PMID: 38492827 DOI: 10.1016/j.micpath.2024.106617] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/23/2023] [Revised: 03/09/2024] [Accepted: 03/10/2024] [Indexed: 03/18/2024]
Abstract
This review examines the complex connection between commensal microbiota and the development of opportunistic infections. Several underlying conditions, such as metabolic diseases and weakened immune systems, increase the vulnerability of patients to opportunistic infections. The increasing antibiotic resistance adds significant complexity to the management of infectious diseases. Although commensals have long been considered beneficial, recent research contradicts this notion by uncovering chronic illnesses linked to atypical pathogens or commensal bacteria. This review examines conditions in which commensal bacteria, which are usually beneficial, contribute to developing diseases. Commensals' support for opportunistic infections can be categorized based on factors such as colonization fitness, pathoadaptive mutation, and evasion of host immune response. Individuals with weakened immune systems are especially susceptible, highlighting the importance of mucosal host-microbiota interaction in promoting infection when conditions are inappropriate. Dysregulation of gut microbial homeostasis, immunological modulation, and microbial interactions are caused by several factors that contribute to the development of chronic illnesses. Knowledge about these mechanisms is essential for developing preventive measures, particularly for susceptible populations, and emphasizes the importance of maintaining a balanced gut microbiota in reducing the impact of opportunistic infections.
Collapse
Affiliation(s)
- Priyankar Dey
- Department of Biotechnology, Thapar Institute of Engineering and Technology, Patiala 147004, Punjab, India.
| |
Collapse
|
23
|
Liu Y, Bai X, Wu H, Duan Z, Zhu C, Fu R, Fan D. Ginsenoside CK Alleviates DSS-Induced IBD in Mice by Regulating Tryptophan Metabolism and Activating Aryl Hydrocarbon Receptor via Gut Microbiota Modulation. JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY 2024; 72:9867-9879. [PMID: 38602268 DOI: 10.1021/acs.jafc.4c00245] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 04/12/2024]
Abstract
Dysbiosis of gut microbiota is believed to be associated with inflammatory bowel disease (IBD). Ginsenoside compound K (CK), the main metabolite of Panax ginseng ginsenoside, has proven effective as an anti-inflammatory agent in IBD. However, the mechanisms by which CK modulates gut microbiota to ameliorate IBD remain poorly understood. Herein, CK demonstrated the potential to suppress the release of proinflammatory cytokines by gut microbiota modulation. Notably, supplementation with CK promoted the restoration of a harmonious balance in gut microbiota, primarily by enhancing the populations of Lactobacillus and Akkermansia. Furthermore, CK considerably elevated the concentrations of tryptophan metabolites derived from Lactobacillus that could activate the aryl hydrocarbon receptor. Overall, the promising alleviative efficacy of CK primarily stemmed from the promotion of Lactobacillus growth and production of tryptophan metabolites, suggesting that CK should be regarded as a prospective prebiotic agent for IBD in the future.
Collapse
Affiliation(s)
- Yuan Liu
- Engineering Research Center of Western Resource Innovation Medicine Green Manufacturing, Ministry of Education, School of Chemical Engineering, Northwest University, Xi'an 710069, China
- Biotech. & Biomed. Research Institute, Northwest University, Xi'an 710069, China
| | - Xue Bai
- Engineering Research Center of Western Resource Innovation Medicine Green Manufacturing, Ministry of Education, School of Chemical Engineering, Northwest University, Xi'an 710069, China
- Biotech. & Biomed. Research Institute, Northwest University, Xi'an 710069, China
| | - Huanyan Wu
- Engineering Research Center of Western Resource Innovation Medicine Green Manufacturing, Ministry of Education, School of Chemical Engineering, Northwest University, Xi'an 710069, China
- Biotech. & Biomed. Research Institute, Northwest University, Xi'an 710069, China
| | - Zhiguang Duan
- Engineering Research Center of Western Resource Innovation Medicine Green Manufacturing, Ministry of Education, School of Chemical Engineering, Northwest University, Xi'an 710069, China
- Biotech. & Biomed. Research Institute, Northwest University, Xi'an 710069, China
| | - Chenhui Zhu
- Engineering Research Center of Western Resource Innovation Medicine Green Manufacturing, Ministry of Education, School of Chemical Engineering, Northwest University, Xi'an 710069, China
- Biotech. & Biomed. Research Institute, Northwest University, Xi'an 710069, China
| | - Rongzhan Fu
- Engineering Research Center of Western Resource Innovation Medicine Green Manufacturing, Ministry of Education, School of Chemical Engineering, Northwest University, Xi'an 710069, China
- Biotech. & Biomed. Research Institute, Northwest University, Xi'an 710069, China
| | - Daidi Fan
- Engineering Research Center of Western Resource Innovation Medicine Green Manufacturing, Ministry of Education, School of Chemical Engineering, Northwest University, Xi'an 710069, China
- Biotech. & Biomed. Research Institute, Northwest University, Xi'an 710069, China
| |
Collapse
|
24
|
Dey P, Tewari N, Dutta S, Newman RA, Chaudhuri TK. Oleander attenuates hepatic inflammation in a TLR4-independent manner and by favorable modulation of hepatocellular global metabolome that supports cytoprotection. JOURNAL OF ETHNOPHARMACOLOGY 2024; 323:117717. [PMID: 38181937 DOI: 10.1016/j.jep.2024.117717] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/16/2023] [Revised: 11/21/2023] [Accepted: 01/02/2024] [Indexed: 01/07/2024]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Nerium oleander is used to treat liver-associated chronic metabolic diseases in traditional medicinal systems across the globe. The hepatoprotective effects of oleander are mentioned in Indian and Chinese traditional medicinal literature. AIM OF THE STUDY The present study aimed to investigate the cellular mechanisms behind the hepatoprotective effects of a non-toxic dose of oleander (NO). MATERIALS AND METHODS The hepatoprotective effects of NO were tested against lipopolysaccharide (LPS)-treated HepG2 cells. Oxidative stress response was studied using cellular enzymatic assays, and gene expression was analyzed using qRT-PCR. HepG2 cells were pretreated with TAK-242 (pharmacological inhibitor of TLR4) to decipher the anti-inflammatory mechanisms of NO. Cell-free metabolites were analyzed using GCMS and were subjected to pathway enrichment analysis. RESULTS NO reduced systemic inflammation, serum lipid peroxidation byproducts, and glucose without affecting serum transaminase levels and hepatic histopathological features. NO attenuated the inflammation-induced loss of antioxidant enzyme activities and mRNA expressions of toll-like receptor-4 (TLR4)/nuclear factor κβ (NFκβ)-dependent inflammatory genes. In TAK-242 pretreated cells, LPS was unable to induce inflammatory and oxidative responses. However, NO treatment in TAK-242 pretreated cells with LPS stimulation further reduced the signs of inflammation and improved hepatoprotective activities. A comparative analysis of the intracellular global metabolome from HepG2 cells with and without NO treatment indicated NO-mediated favorable modulation of intracellular metabolic pathways that support cytoprotective activities. CONCLUSION NO protects HepG2 cells from LPS-induced oxidative and inflammatory injury. The hepatoprotective effects of NO are mediated by a TLR4-independent process and through a favorable modulation of the intracellular global metabolome that supports cytoprotection.
Collapse
Affiliation(s)
- Priyankar Dey
- Department of Biotechnology, Thapar Institute of Engineering and Technology, Patiala, 147004, Punjab, India.
| | - Nisha Tewari
- Department of Biotechnology, Thapar Institute of Engineering and Technology, Patiala, 147004, Punjab, India.
| | - Somit Dutta
- Department of Development Biology and Genetics, Indian Institute of Science, Bangalore, 560012, India.
| | - Robert A Newman
- University of Texas MD Anderson Cancer Center, Houston, TX, USA; Phoenix Biotechnology, Inc, San Antonio, TX, USA.
| | - Tapas Kumar Chaudhuri
- Cellular Immunology Laboratory, Department of Zoology, University of North Bengal, Siliguri, India.
| |
Collapse
|
25
|
Zeb F, Naqeeb H, Osaili T, Faris ME, Ismail LC, Obaid RS, Naja F, Radwan H, Hasan H, Hashim M, AlBlooshi S, Alam I. Molecular crosstalk between polyphenols and gut microbiota in cancer prevention. Nutr Res 2024; 124:21-42. [PMID: 38364552 DOI: 10.1016/j.nutres.2024.01.012] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/18/2023] [Revised: 01/24/2024] [Accepted: 01/24/2024] [Indexed: 02/18/2024]
Abstract
A growing body of evidence suggests that cancer remains a significant global health challenge, necessitating the development of novel therapeutic approaches. In recent years, the molecular crosstalk between polyphenols and gut microbiota has emerged as a promising pathway for cancer prevention. Polyphenols, abundant in many plant-based foods, possess diverse bioactive properties, including antioxidant, anti-inflammatory, and anticancer activities. The gut microbiota, a complex microbial community residing in the gastrointestinal tract, plays a crucial role in a host's health and disease risks. This review highlights cancer suppressive and oncogenic mechanisms of gut microbiota, the intricate interplay between gut microbiota modulation and polyphenol biotransformation, and the potential therapeutic implications of this interplay in cancer prevention. Furthermore, this review explores the molecular mechanisms underpinning the synergistic effects of polyphenols and the gut microbiota, such as modulation of signaling pathways and immune response and epigenetic modifications in animal and human studies. The current review also summarizes the challenges and future directions in this field, including the development of personalized approaches that consider interindividual variations in gut microbiota composition and function. Understanding the molecular crosstalk could offer new perspectives for the development of personalized cancer therapies targeting the polyphenol-gut axis. Future clinical trials are needed to validate the potential role of polyphenols and gut microbiota as innovative therapeutic strategies for cancer treatment.
Collapse
Affiliation(s)
- Falak Zeb
- Research Institute for Medical and Health Sciences, University of Sharjah, United Arab Emirates.
| | - Huma Naqeeb
- Department of Clinical Nutrition, Shaukat Khanam Cancer Hospital and Research Center Peshawar, Pakistan; Department of Human Nutrition and Dietetics, Women University Mardan, Pakistan
| | - Tareq Osaili
- Research Institute for Medical and Health Sciences, University of Sharjah, United Arab Emirates; Department of Clinical Nutrition and Dietetics, College of Health Sciences, University of Sharjah, United Arab Emirates; Department of Nutrition and Food Technology, Faculty of Agriculture, Jordan University of Science and Technology, Irbid, Jordan
| | - MoezAllslam Ezzat Faris
- Research Institute for Medical and Health Sciences, University of Sharjah, United Arab Emirates; Department of Clinical Nutrition and Dietetics, College of Health Sciences, University of Sharjah, United Arab Emirates
| | - Leila Cheikh Ismail
- Research Institute for Medical and Health Sciences, University of Sharjah, United Arab Emirates; Department of Clinical Nutrition and Dietetics, College of Health Sciences, University of Sharjah, United Arab Emirates; Department of Women's and Reproductive Health, University of Oxford, Nuffield, Oxford, United Kingdom
| | - Reyad Shakir Obaid
- Research Institute for Medical and Health Sciences, University of Sharjah, United Arab Emirates; Department of Clinical Nutrition and Dietetics, College of Health Sciences, University of Sharjah, United Arab Emirates
| | - Farah Naja
- Research Institute for Medical and Health Sciences, University of Sharjah, United Arab Emirates; Department of Clinical Nutrition and Dietetics, College of Health Sciences, University of Sharjah, United Arab Emirates; Nutrition and Food Sciences Department, American University of Beirut, Beirut, Lebanon
| | - Hadia Radwan
- Research Institute for Medical and Health Sciences, University of Sharjah, United Arab Emirates; Department of Clinical Nutrition and Dietetics, College of Health Sciences, University of Sharjah, United Arab Emirates
| | - Hayder Hasan
- Research Institute for Medical and Health Sciences, University of Sharjah, United Arab Emirates; Department of Clinical Nutrition and Dietetics, College of Health Sciences, University of Sharjah, United Arab Emirates
| | - Mona Hashim
- Research Institute for Medical and Health Sciences, University of Sharjah, United Arab Emirates; Department of Clinical Nutrition and Dietetics, College of Health Sciences, University of Sharjah, United Arab Emirates
| | - Sharifa AlBlooshi
- College of Natural and Health Sciences, Zayed University, United Arab Emirates
| | - Iftikhar Alam
- Department of Human Nutrition and Dietetics, Bacha Khan University Charsadda, Pakistan
| |
Collapse
|
26
|
Xu Q, Wang J, Zhang Y, Li Y, Qin X, Xin Y, Li Y, Xu K, Yang X, Wang X. Atypical Plant miRNA cal-miR2911: Robust Stability against Food Digestion and Specific Promoting Effect on Bifidobacterium in Mice. JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY 2024; 72:4801-4813. [PMID: 38393993 DOI: 10.1021/acs.jafc.3c09511] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/25/2024]
Abstract
Previous studies showed that cal-miR2911, featuring an atypical biogenesis, could target genes of virus and in turn inhibit virus replication. Given its especial sequence motif and cross-kingdom potential, the stability of miR2911 under digestive environment and its impact on intestinal microbes in mice were examined. The results showed that miR2911 was of considerable stability during oral, gastric, and intestinal digestion. The coingested food matrix enhanced its stability in the gastric phase, contributing to the existence of miR2911 in mouse intestines. The survival miR2911 promoted the growth of Bifidobacterium in mice and maintained the overall composition and diversity of the gut microbiota. miR2911 specifically entered the cells of Bifidobacterium adolescentis and potentially modulated the gene expression as evidenced by the dual-luciferase assay. The current study provided evidence on the cross-kingdom communication between dietary miRNAs and gut microbes, suggesting that modulating target bacteria using miRNAs for nutritional and therapeutic ends is promising.
Collapse
Affiliation(s)
- Qin Xu
- College of Food Engineering and Nutritional Science, Shaanxi Normal University, Xi'an, Shaanxi 710062, China
| | - Jianing Wang
- College of Food Engineering and Nutritional Science, Shaanxi Normal University, Xi'an, Shaanxi 710062, China
| | - Yi Zhang
- Department of Food Science, The Pennsylvania State University, University Park, Pennsylvania 16802, United States
| | - Ying Li
- College of Food Engineering and Nutritional Science, Shaanxi Normal University, Xi'an, Shaanxi 710062, China
| | - Xinshu Qin
- College of Food Engineering and Nutritional Science, Shaanxi Normal University, Xi'an, Shaanxi 710062, China
| | - Yirao Xin
- College of Food Engineering and Nutritional Science, Shaanxi Normal University, Xi'an, Shaanxi 710062, China
| | - Yinglei Li
- College of Food Engineering and Nutritional Science, Shaanxi Normal University, Xi'an, Shaanxi 710062, China
| | - Ke Xu
- Department of Joint Surgery, Hong Hui Hospital, Xi'an Jiaotong University, Xi'an, Shaanxi 710054, China
| | - Xingbin Yang
- College of Food Engineering and Nutritional Science, Shaanxi Normal University, Xi'an, Shaanxi 710062, China
| | - Xingyu Wang
- College of Food Engineering and Nutritional Science, Shaanxi Normal University, Xi'an, Shaanxi 710062, China
| |
Collapse
|
27
|
Saha MR, Dey P. Pharmacological benefits of Acacia against metabolic diseases: intestinal-level bioactivities and favorable modulation of gut microbiota. Arch Physiol Biochem 2024; 130:70-86. [PMID: 34411504 DOI: 10.1080/13813455.2021.1966475] [Citation(s) in RCA: 4] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/22/2021] [Accepted: 08/05/2021] [Indexed: 10/20/2022]
Abstract
CONTEXT Obesity-associated chronic metabolic disease is a leading contributor to mortality globally. Plants belonging to the genera Acacia are routinely used for the treatment of diverse metabolic diseases under different ethnomedicinal practices around the globe. OBJECTIVE The current review centres around the pharmacological evidence of intestinal-level mechanisms for metabolic health benefits by Acacia spp. RESULTS Acacia spp. increase the proportions of gut commensals (Bifidobacterium and Lactobacillus) and reduces the population of opportunistic pathobionts (Escherichia coli and Clostridium). Acacia gum that is rich in fibre, can also be a source of prebiotics to improve gut health. The intestinal-level anti-inflammatory activities of Acacia are likely to contribute to improvements in gut barrier function that would prevent gut-to-systemic endotoxin translocation and limit "low-grade" inflammation associated with metabolic diseases. CONCLUSION This comprehensive review for the first time has emphasised the intestinal-level benefits of Acacia spp. which could be instrumental in limiting the burden of metabolic disease.
Collapse
Affiliation(s)
- Manas Ranjan Saha
- Department of Life Science, Vidyasagar Primary Teachers Training Institute (B.Ed.), Malda, India
| | - Priyankar Dey
- Department of Biotechnology, Thapar Institute of Engineering and Technology, Patiala, India
| |
Collapse
|
28
|
Zhang L, Ma XG. A Comprehensive Review on Biotransformation, Interaction, and Health of Gut Microbiota and Bioactive Components. Comb Chem High Throughput Screen 2024; 27:1551-1565. [PMID: 37916626 DOI: 10.2174/0113862073257733231011072004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/02/2023] [Revised: 08/25/2023] [Accepted: 09/06/2023] [Indexed: 11/03/2023]
Abstract
BACKGROUND The relationship between gut microbiota and bioactive components has become the research focus in the world. We attempted to clarify the relationship between biotransformation and metabolites of gut microbiota and bioactive components, and explore the metabolic pathway and mechanism of bioactive ingredients in vivo, which will provide an important theoretical basis for the clinical research of bioactive ingredients and rationality of drugs, and also provide an important reference for the development of new drugs with high bioavailability. METHODS The related references of this review on microbiota and bioactive components were collected from both online and offline databases, such as ScienceDirect, PubMed, Elsevier, Willy, SciFinder, Google Scholar, Web of Science, Baidu Scholar, SciHub, Scopus, and CNKI. RESULTS This review summarized the biotransformation of bioactive components under the action of gut microbiota, including flavonoids, terpenoids, phenylpropanoids, alkaloids, steroids, and other compounds. The interaction of bioactive components and gut microbiota is a key link for drug efficacy. Relevant research is crucial to clarify bioactive components and their mechanisms, which involve the complex interaction among bioactive components, gut microbiota, and intestinal epithelial cells. This review also summarized the individualized, precise, and targeted intervention of gut microbiota in the field of intestinal microorganisms from the aspects of dietary fiber, microecological agents, fecal microbiota transplantation, and postbiotics. It will provide an important reference for intestinal microecology in the field of nutrition and health for people. CONCLUSION To sum up, the importance of human gut microbiota in the research of bioactive components metabolism and transformation has attracted the attention of scholars all over the world. It is believed that with the deepening of research, human gut microbiota will be more widely used in the pharmacodynamic basis, drug toxicity relationship, new drug discovery, drug absorption mechanism, and drug transport mechanism in the future.
Collapse
Affiliation(s)
- Lin Zhang
- Department of Medical Nursing, Jiyuan Vocational and Technical College, 459000 Jiyuan, Henan, P.R. China
| | - Xiao-Gen Ma
- Department of Medical Nursing, Jiyuan Vocational and Technical College, 459000 Jiyuan, Henan, P.R. China
| |
Collapse
|
29
|
Sidhu D, Vasundhara M, Dey P. The intestinal-level metabolic benefits of green tea catechins: Mechanistic insights from pre-clinical and clinical studies. PHYTOMEDICINE : INTERNATIONAL JOURNAL OF PHYTOTHERAPY AND PHYTOPHARMACOLOGY 2024; 123:155207. [PMID: 38000106 DOI: 10.1016/j.phymed.2023.155207] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/25/2023] [Revised: 10/11/2023] [Accepted: 11/08/2023] [Indexed: 11/26/2023]
Abstract
BACKGROUND The intestinal-level host-microbiota interaction has been implicated in the pathogenesis of chronic diseases. The current review is intended to provide a comprehensive insight into deciphering whether intestinal-level bioactivities mediate the overall metabolic health benefits of green tea catechins. PURPOSE We have comprehensively discussed pre-clinical and clinical evidences of intestinal-level changes in metabolism, microbiota, and metabolome due to catechin-rich green tea treatments, ultimately limiting metabolic diseases. Exclusive emphasis has been given to purified catechins and green tea, and discussions on extraintestinal mechanisms of metabolic health benefits were avoided. METHODS A literature search for relevant pre-clinical and clinical studies was performed in various online databases (e.g., PubMed) using specific keywords (e.g., catechin, intestine, microbiota). Out of all the referred literature, ∼15% belonged to 2021-2023, ∼51% were from 2011-2020, and ∼32% from 2000-2010. RESULT The metabolic health benefits of green tea catechins are indeed influenced by the intestinal-level bioactivities, including reduction of mucosal inflammation and oxidative stress, attenuation of gut barrier dysfunction, decrease in intestinal lipid absorption and metabolism, favorable modulation of mucosal nuclear receptor signaling, alterations of the luminal global metabolome, and mitigation of the gut dysbiosis. The results from the recent clinical studies support the pre-clinical evidences. The challenges and pitfalls of the currently available knowledge on catechin bioactivities have been discussed, and constructive directions to harness the translational benefits of green tea through future interventions have been provided. CONCLUSION The metabolism, metabolome, and microbiota at the intestinal epithelia play critical roles in catechin metabolism, pharmacokinetics, bioavailability, and bioactivities. Especially the reciprocal interaction between the catechins and the gut microbiota dictates the metabolic benefits of catechins.
Collapse
Affiliation(s)
- Dwinder Sidhu
- Department of Biotechnology, Thapar Institute of Engineering & Technology, Patiala 147004, India
| | - M Vasundhara
- Department of Biotechnology, Thapar Institute of Engineering & Technology, Patiala 147004, India.
| | - Priyankar Dey
- Department of Biotechnology, Thapar Institute of Engineering & Technology, Patiala 147004, India.
| |
Collapse
|
30
|
Li J, Zhang Q, Li X, Liu J, Wang F, Zhang W, Liu X, Li T, Wang S, Wang Y, Zhang X, Meng Y, Ma Y, Wang H. QingXiaoWuWei decoction alleviates methicillin-resistant Staphylococcus aureus-induced pneumonia in mice by regulating metabolic remodeling and macrophage gene expression network via the microbiota-short-chain fatty acids axis. Microbiol Spectr 2023; 11:e0034423. [PMID: 37823635 PMCID: PMC10714818 DOI: 10.1128/spectrum.00344-23] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/20/2023] [Accepted: 09/06/2023] [Indexed: 10/13/2023] Open
Abstract
IMPORTANCE Methicillin-resistant Staphylococcus aureus (MRSA) colonizes the upper respiratory airways and is resistant to antibiotics. MRSA is a frequently acquired infection in hospital and community settings, including cases of MRSA-induced pneumonia. Multidrug-resistant Staphylococcus aureus and the limited efficacy of antibiotics necessitate alternative strategies for preventing or treating the infection. QingXiaoWuWei decoction (QXWWD) protects against both gut microbiota dysbiosis and MRSA-induced pneumonia. Furthermore, the QXWWD-regulated metabolic remodeling and macrophage gene expression network contribute to its protective effects through the microbiota-short-chain fatty acid axis. The results of this study suggest that QXWWD and its pharmacodynamic compounds might have the potential to prevent and treat pulmonary infections, especially those caused by multidrug-resistant organisms. Our study provides a theoretical basis for the future treatment of pulmonary infectious diseases by manipulating gut microbiota and their metabolites via traditional Chinese medicine.
Collapse
Affiliation(s)
- Jun Li
- College of Pharmacy, Inner Mongolia Medical University, Hohhot, China
| | - Qian Zhang
- College of Pharmacy, Inner Mongolia Medical University, Hohhot, China
| | - Xue Li
- College of Pharmacy, Inner Mongolia Medical University, Hohhot, China
| | - Jing Liu
- College of Pharmacy, Inner Mongolia Medical University, Hohhot, China
| | - Fang Wang
- College of Pharmacy, Inner Mongolia Medical University, Hohhot, China
| | - Wei Zhang
- College of Pharmacy, Inner Mongolia Medical University, Hohhot, China
| | - Xingyue Liu
- First Clinical Medical College, Inner Mongolia Medical University, Hohhot, China
| | - Tiewei Li
- Zhengzhou Key Laboratory of Children’s Infection and Immunity, Children’s Hospital Affiliated to Zhengzhou University, Henan Children’s Hospital, Zhengzhou, China
| | - Shiqi Wang
- First Clinical Medical College, Inner Mongolia Medical University, Hohhot, China
| | - Yuqi Wang
- First Clinical Medical College, Inner Mongolia Medical University, Hohhot, China
| | - Xinyu Zhang
- College of Pharmacy, Inner Mongolia Medical University, Hohhot, China
| | - Yukun Meng
- First Clinical Medical College, Inner Mongolia Medical University, Hohhot, China
| | - Yuheng Ma
- College of Pharmacy, Inner Mongolia Medical University, Hohhot, China
| | - Huanyun Wang
- College of Pharmacy, Inner Mongolia Medical University, Hohhot, China
| |
Collapse
|
31
|
Tahiri M, Johnsrud C, Steffensen IL. Evidence and hypotheses on adverse effects of the food additives carrageenan (E 407)/processed Eucheuma seaweed (E 407a) and carboxymethylcellulose (E 466) on the intestines: a scoping review. Crit Rev Toxicol 2023; 53:521-571. [PMID: 38032203 DOI: 10.1080/10408444.2023.2270574] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/13/2023] [Revised: 10/02/2023] [Accepted: 10/02/2023] [Indexed: 12/01/2023]
Abstract
This scoping review provides an overview of publications reporting adverse effects on the intestines of the food additives carrageenan (CGN) (E 407)/processed Eucheuma seaweed (PES) (E 407a) and carboxymethylcellulose (CMC) (E 466). It includes evidence from human, experimental mammal and in vitro research publications, and other evidence. The databases Medline, Embase, Scopus, Web of Science Core Collection, Cochrane Database of Systematic Reviews and Epistemonikos were searched without time limits, in addition to grey literature. The publications retrieved were screened against predefined criteria. From two literature searches, 2572 records were screened, of which 224 records were included, as well as 38 records from grey literature, making a total of 262 included publications, 196 on CGN and 101 on CMC. These publications were coded and analyzed in Eppi-Reviewer and data gaps presented in interactive maps. For CGN, five, 69 and 33 research publications on humans, experimental mammals and in vitro experiments were found, further separated as degraded or native (non-degraded) CGN. For CMC, three human, 20 animal and 14 in vitro research publications were obtained. The most studied adverse effects on the intestines were for both additives inflammation, the gut microbiome, including fermentation, intestinal permeability, and cancer and metabolic effects, and immune effects for CGN. Further studies should focus on native CGN, in the form and molecular weight used as food additive. For both additives, randomized controlled trials of sufficient power and with realistic dietary exposure levels of single additives, performed in persons of all ages, including potentially vulnerable groups, are needed.
Collapse
Affiliation(s)
- Mirlinda Tahiri
- Department of Food Safety, Division of Climate and Environmental Health, Norwegian Institute of Public Health, Oslo, Norway
| | - Celine Johnsrud
- Department of Food Safety, Division of Climate and Environmental Health, Norwegian Institute of Public Health, Oslo, Norway
| | - Inger-Lise Steffensen
- Department of Food Safety, Division of Climate and Environmental Health, Norwegian Institute of Public Health, Oslo, Norway
| |
Collapse
|
32
|
Dey P, Ray Chaudhuri S. The opportunistic nature of gut commensal microbiota. Crit Rev Microbiol 2023; 49:739-763. [PMID: 36256871 DOI: 10.1080/1040841x.2022.2133987] [Citation(s) in RCA: 18] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/16/2022] [Revised: 07/30/2022] [Accepted: 10/05/2022] [Indexed: 11/03/2022]
Abstract
The abundance of gut commensals has historically been associated with health-promoting effects despite the fact that the definition of good or bad microbiota remains condition-specific. The beneficial or pathogenic nature of microbiota is generally dictated by the dimensions of host-microbiota and microbe-microbe interactions. With the increasing popularity of gut microbiota in human health and disease, emerging evidence suggests opportunistic infections promoted by those gut bacteria that are generally considered beneficial. Therefore, the current review deals with the opportunistic nature of the gut commensals and aims to summarise the concepts behind the occasional commensal-to-pathogenic transformation of the gut microbes. Specifically, relevant clinical and experimental studies have been discussed on the overgrowth and bacteraemia caused by commensals. Three key processes and their underlying mechanisms have been summarised to be responsible for the opportunistic nature of commensals, viz. improved colonisation fitness that is dictated by commensal-pathogen interactions and availability of preferred nutrients; pathoadaptive mutations that can trigger the commensal-to-pathogen transformation; and evasion of host immune response as a survival and proliferation strategy of the microbes. Collectively, this review provides an updated concept summary on the underlying mechanisms of disease causative events driven by gut commensal bacteria.
Collapse
Affiliation(s)
- Priyankar Dey
- Department of Biotechnology, Thapar Institute of Engineering and Technology, Patiala, India
| | - Saumya Ray Chaudhuri
- Council of Scientific and Industrial Research (CSIR), Institute of Microbial Technology, Chandigarh, India
| |
Collapse
|
33
|
Xu Q, Qin X, Zhang Y, Xu K, Li Y, Li Y, Qi B, Li Y, Yang X, Wang X. Plant miRNA bol-miR159 Regulates Gut Microbiota Composition in Mice: In Vivo Evidence of the Crosstalk between Plant miRNAs and Intestinal Microbes. JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY 2023; 71:16160-16173. [PMID: 37862127 DOI: 10.1021/acs.jafc.3c06104] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 10/22/2023]
Abstract
New evidence reveals that bol-miR159, an miRNA rich in fruits and vegetables, cross-kingdomly functions in mammalian bodies. However, whether the miRNA could regulate gut microbiota remains unclear. Here, the effect of miR159 on mouse intestinal microbes was comprehensively examined. The results showed that supplementation of miR159 to the chow diet significantly enhanced the diversity of mouse gut microbiota without causing pathological lesions or inflammatory responses on the intestines. At the phylum level, miR159 increased the abundance of Proteobacteria and decreased the Firmicute-to-Bacteroidetes (F/B) ratio. miR159 had prebiotic-like effects on mouse gut microbiota, as it promoted the growth of the bacteria that is beneficial for maintaining gut health. The miRNA can target bacteria genes and get into the bacteria cells. The data provide direct in vivo evidence on the crosstalk between plant miRNAs and intestinal microbes, highlighting the potential for miRNA-based strategies that modulate gut microbes to improve host health.
Collapse
Affiliation(s)
- Qin Xu
- Shaanxi Engineering Laboratory for Food Green Processing and Safety Control, and Shaanxi Key Laboratory for Hazard Factors Assessment in Processing and Storage of Agricultural Products, College of Food Engineering and Nutritional Science, Shaanxi Normal University, Xi'an, Shaanxi 710062, China
| | - Xinshu Qin
- Shaanxi Engineering Laboratory for Food Green Processing and Safety Control, and Shaanxi Key Laboratory for Hazard Factors Assessment in Processing and Storage of Agricultural Products, College of Food Engineering and Nutritional Science, Shaanxi Normal University, Xi'an, Shaanxi 710062, China
| | - Yi Zhang
- Department of Food Science, The Pennsylvania State University, University Park, Pennsylvania 16802, United States
| | - Ke Xu
- Department of Joint Surgery, Hong Hui Hospital, Xi'an Jiaotong University, Xi'an, Shaanxi 710054, China
| | - Ying Li
- Shaanxi Engineering Laboratory for Food Green Processing and Safety Control, and Shaanxi Key Laboratory for Hazard Factors Assessment in Processing and Storage of Agricultural Products, College of Food Engineering and Nutritional Science, Shaanxi Normal University, Xi'an, Shaanxi 710062, China
| | - Yinglei Li
- Shaanxi Engineering Laboratory for Food Green Processing and Safety Control, and Shaanxi Key Laboratory for Hazard Factors Assessment in Processing and Storage of Agricultural Products, College of Food Engineering and Nutritional Science, Shaanxi Normal University, Xi'an, Shaanxi 710062, China
| | - Bangran Qi
- Shaanxi Engineering Laboratory for Food Green Processing and Safety Control, and Shaanxi Key Laboratory for Hazard Factors Assessment in Processing and Storage of Agricultural Products, College of Food Engineering and Nutritional Science, Shaanxi Normal University, Xi'an, Shaanxi 710062, China
| | - Yan Li
- Shaanxi Engineering Laboratory for Food Green Processing and Safety Control, and Shaanxi Key Laboratory for Hazard Factors Assessment in Processing and Storage of Agricultural Products, College of Food Engineering and Nutritional Science, Shaanxi Normal University, Xi'an, Shaanxi 710062, China
| | - Xingbin Yang
- Shaanxi Engineering Laboratory for Food Green Processing and Safety Control, and Shaanxi Key Laboratory for Hazard Factors Assessment in Processing and Storage of Agricultural Products, College of Food Engineering and Nutritional Science, Shaanxi Normal University, Xi'an, Shaanxi 710062, China
| | - Xingyu Wang
- Shaanxi Engineering Laboratory for Food Green Processing and Safety Control, and Shaanxi Key Laboratory for Hazard Factors Assessment in Processing and Storage of Agricultural Products, College of Food Engineering and Nutritional Science, Shaanxi Normal University, Xi'an, Shaanxi 710062, China
| |
Collapse
|
34
|
Pferschy-Wenzig EM, Kunert O, Thumann T, Moissl-Eichinger C, Bauer R. Characterization of metabolites from milk thistle flavonolignans generated by human fecal microbiota. PHYTOCHEMISTRY 2023; 215:113834. [PMID: 37648045 DOI: 10.1016/j.phytochem.2023.113834] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/20/2023] [Revised: 08/18/2023] [Accepted: 08/20/2023] [Indexed: 09/01/2023]
Abstract
Silymarin, a mixture of diastereomeric and regioisomeric flavonolignans from milk thistle (Silybum marianum (L.) Gaertn.) fruits, is known to possess a panel of pharmacological activities. However, due to low water solubility and extensive phase II metabolism, the oral bioavailability of the flavonolignans is limited. Since their interaction with gut microbiome is likely due to their predominantly fecal excretion route, the biotransformation of milk thistle flavonolignans by gut microorganisms was studied. A 1:1 mixture of the two main silymarin flavonolignans silybins A and B was incubated in human fecal suspension from one donor for 24 h under anoxic conditions. Purification of the incubate allowed to isolate and structurally elucidate the two main metabolites as (2R, 3R)-2-{4-[2-(3,4-dihydroxy-phenyl)-(1R)-1-hydroxymethyl-ethoxy]-3-hydroxy-phenyl}-3,5,7-trihydroxy-chroman-4-one (a product of demethylation and dioxane ring cleavage) and demethylsilybin B. Furthermore, silymarin was incubated with human fecal suspension, and its biotransformation was monitored by means of LC-HRMS metabolite profiling. Apart from the two isolated and structurally elucidated metabolites, several types of biotransformation products could be annotated, including demethylation products, reduction/ring cleavage products, products of demethylation plus reduction/ring cleavage, as well as several low molecular weight aromatic metabolites. The potential pharmacological activities of these gut microbial metabolites deserve closer examination in the future.
Collapse
Affiliation(s)
- Eva-Maria Pferschy-Wenzig
- University of Graz, Institute of Pharmaceutical Sciences, Beethovenstraße 8, 8010, Graz, Austria; BioTechMed- Graz, Mozartgasse 12/II, 8010, Graz, Austria.
| | - Olaf Kunert
- University of Graz, Institute of Pharmaceutical Sciences, Beethovenstraße 8, 8010, Graz, Austria.
| | - Timo Thumann
- University of Graz, Institute of Pharmaceutical Sciences, Beethovenstraße 8, 8010, Graz, Austria.
| | - Christine Moissl-Eichinger
- Medical University Graz, Diagnostic & Research Institute of Hygiene, Microbiology and Environmental Medicine, Neue Stiftingtalstraße 6 (MC1.B.)/III, 8010, Graz, Austria; BioTechMed- Graz, Mozartgasse 12/II, 8010, Graz, Austria.
| | - Rudolf Bauer
- University of Graz, Institute of Pharmaceutical Sciences, Beethovenstraße 8, 8010, Graz, Austria; BioTechMed- Graz, Mozartgasse 12/II, 8010, Graz, Austria.
| |
Collapse
|
35
|
Wang R, Sun Y, Wang M, Li H, Liu S, Liu Z. Therapeutic effect of Eleutherococcus senticosus (Rupr. & Maxim.) Maxim. leaves on ischemic stroke via the microbiota-gut-brain axis. Phytother Res 2023; 37:4801-4818. [PMID: 37518502 DOI: 10.1002/ptr.7947] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/27/2022] [Revised: 06/26/2023] [Accepted: 06/27/2023] [Indexed: 08/01/2023]
Abstract
Eleutherococcus senticosus (Rupr. & Maxim.) Maxim. leaves (ESL) are widely used to treat ischemic stroke (IS); however, the specific mechanism remains unclear. The microbiota-gut-brain axis plays a critical role in IS and has become a potential therapeutic target. This study aimed to reveal and verify the therapeutic effect of ESL on IS through the microbiota-gut-brain axis. Ultra-high-performance liquid chromatography coupled with mass spectrometry-based untargeted/targeted metabolomics combined with 16S rRNA microbiota sequencing strategy were used to investigate the regulatory effect of ESL on the metabolism and intestinal microenvironment after IS. Lactobacillus reuteri and Clostridium butyricum were used to treat rats with IS to verify that elevated levels of probiotics are key factors in the therapeutic effect of ESL. The results showed that IS significantly altered the accumulation of 41 biomarkers, while ESL restored their concentrations back to normal. Moreover, ESL alleviated the dysbiosis of gut microbiota brought on by IS, by reducing the abundance of pathogens and increasing the abundance of probiotics (e.g., Lactobacillus reuteri and Clostridium butyricum); this could reduce post-stroke injury, thereby having a certain protective effect on IS. This study reveals that ESL plays an important role in treating IS through the microbiota-gut-brain axis, maintaining metabolic homeostasis in vivo.
Collapse
Affiliation(s)
- Rongjin Wang
- School of Pharmaceutical Sciences, Jilin University, Changchun, China
| | - Yuzhen Sun
- School of Pharmaceutical Sciences, Jilin University, Changchun, China
| | - Meiyuan Wang
- School of Pharmaceutical Sciences, Jilin University, Changchun, China
| | - Hanlin Li
- School of Pharmaceutical Sciences, Jilin University, Changchun, China
| | - Shu Liu
- National Center of Mass Spectrometry in Changchun & Jilin Provincial Key Laboratory of Chinese Medicine Chemistry and Mass Spectrometry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, China
| | - Zhongying Liu
- School of Pharmaceutical Sciences, Jilin University, Changchun, China
| |
Collapse
|
36
|
Gupta U, Dey P. Rise of the guardians: Gut microbial maneuvers in bacterial infections. Life Sci 2023; 330:121993. [PMID: 37536616 DOI: 10.1016/j.lfs.2023.121993] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/27/2023] [Revised: 07/23/2023] [Accepted: 07/29/2023] [Indexed: 08/05/2023]
Abstract
AIMS Bacterial infections are one of the major causes of mortality globally. The gut microbiota, primarily comprised of the commensals, performs an important role in maintaining intestinal immunometabolic homeostasis. The current review aims to provide a comprehensive understanding of how modulation of the gut microbiota influences opportunistic bacterial infections. MATERIALS AND METHODS Primarily centered around mechanisms related to colonization resistance, nutrient, and metabolite-associated factors, mucosal immune response, and commensal-pathogen reciprocal interactions, we discuss how gut microbiota can promote or prevent bacterial infections. KEY FINDINGS Opportunistic infections can occur directly due to obligate pathogens or indirectly due to the overgrowth of opportunistic pathobionts. Gut microbiota-centered mechanisms of altered intestinal immunometabolic and metabolomic homeostasis play a significant role in infection promotion and prevention. Depletion in the population of commensals, increased abundance of pathobionts, and overall decrease in gut microbial diversity and richness caused due to prolonged antibiotic use are risk factors of opportunistic bacterial infections, including infections from multidrug-resistant spp. Gut commensals can limit opportunistic infections by mechanisms including the production of antimicrobials, short-chain fatty acids, bile acid metabolism, promoting mucin formation, and maintaining immunological balance at the mucosa. Gut microbiota-centered strategies, including the administration of probiotics and fecal microbiota transplantation, could help attenuate opportunistic bacterial infections. SIGNIFICANCE The current review discussed the gut microbial population and function-specific aspects contributing to bacterial infection susceptibility and prophylaxis. Collectively, this review provides a comprehensive understanding of the mechanisms related to the dual role of gut microbiota in bacterial infections.
Collapse
Affiliation(s)
- Upasana Gupta
- Department of Biotechnology, Thapar Institute of Engineering and Technology, Patiala 147004, Punjab, India
| | - Priyankar Dey
- Department of Biotechnology, Thapar Institute of Engineering and Technology, Patiala 147004, Punjab, India.
| |
Collapse
|
37
|
Xu Y, Zhu M, Feng Y, Xu H. Panax notoginseng-microbiota interactions: From plant cultivation to medicinal application. PHYTOMEDICINE : INTERNATIONAL JOURNAL OF PHYTOTHERAPY AND PHYTOPHARMACOLOGY 2023; 119:154978. [PMID: 37549538 DOI: 10.1016/j.phymed.2023.154978] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/03/2023] [Revised: 06/25/2023] [Accepted: 07/15/2023] [Indexed: 08/09/2023]
Abstract
BACKGROUND Microbiomes and their host plants are closely linked with each other; for example, the microbiome affects plant growth, fitness, nutrient uptake, stress tolerance and pathogen resistance, whereas the host plant supports the photosynthetically carbon-rich nutrition of the microbiome. The importance of the microbiome in plant‒soil ecosystems is unquestioned and has expanded to influence the medicinal application of some herbal plants via the gut microbiota. PURPOSE Herbal plant-microbiome interactions may provide novel knowledge to enhance the robustness of herbal plant crop performance and medicinal applications, which requires a systematic review and preceding discussion. STUDY DESIGN AND METHODS The interactions between Panax notoginseng and microorganisms (from soil to host) were reviewed from the literature. The terms "Panax notoginseng" and "microbiota" were used in combination with the keywords "microbiota/microbes", "bacteria/bacterium" or "fungi/fungus" or "endophyte", as well as our targeted bioactive phytochemicals, including saponins and ginsenosides. RESULT Our study focuses on the famous medicinal herb Panax notoginseng F. H. Chen and proposes that the microbiota is a crucial participant not only in the cultivation of this herbal plant but also in its medicinal application. We also summarize and discuss how these plant‒microbe co-associations shape the assembly of plant-related microbiomes and produce bioactive phytochemicals, as well as influence beneficial herbal traits, such as herbal plant health and pharmacology. In addition, we also highlight future directions. CONCLUSION The rhizosphere and endophytic microbiome of Panax notoginseng are indirectly or directly involved in plant health, biomass production, and the synthesis/biotransformation of plant secondary metabolites. Harnessing the microbiome to improve the quality of traditional Chinese medicine and improve the value of medicinal plants for human health is highly promising.
Collapse
Affiliation(s)
- Yu Xu
- School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China
| | - Mengjie Zhu
- School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China
| | - Yibin Feng
- School of Chinese Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong.
| | - Hongxi Xu
- Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, PR China.
| |
Collapse
|
38
|
Dey P. Gut microbial considerations and feasibility of phytochemicals as anti-COVID prophylaxis: Critical role of bioavailability. Phytother Res 2023; 37:4301-4303. [PMID: 36597204 DOI: 10.1002/ptr.7722] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/15/2022] [Revised: 12/19/2022] [Accepted: 12/27/2022] [Indexed: 01/05/2023]
Affiliation(s)
- Priyankar Dey
- Department of Biotechnology, Thapar Institute of Engineering and Technology, Patiala, India
| |
Collapse
|
39
|
Siddiqui SA, Azmy Harahap I, Suthar P, Wu YS, Ghosh N, Castro-Muñoz R. A Comprehensive Review of Phytonutrients as a Dietary Therapy for Obesity. Foods 2023; 12:3610. [PMID: 37835263 PMCID: PMC10572887 DOI: 10.3390/foods12193610] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/25/2023] [Revised: 09/22/2023] [Accepted: 09/25/2023] [Indexed: 10/15/2023] Open
Abstract
Obesity is a complex medical condition mainly caused by eating habits, genetics, lifestyle, and medicine. The present study deals with traditional diets like the Mediterranean diet, Nordic diet, African Heritage diet, Asian diet, and DASH, as these are considered to be sustainable diets for curing obesity. However, the bioavailability of phytonutrients consumed in the diet may vary, depending on several factors such as digestion and absorption of phytonutrients, interaction with other substances, cooking processes, and individual differences. Hence, several phytochemicals, like polyphenols, alkaloids, saponins, terpenoids, etc., have been investigated to assess their efficiencies and safety in the prevention and treatment of obesity. These phytochemicals have anti-obesity effects, mediated via modulation of many pathways, such as decreased lipogenesis, lipid absorption, accelerated lipolysis, energy intake, expenditure, and preadipocyte differentiation and proliferation. Owing to these anti-obesity effects, new food formulations incorporating these phytonutrients were introduced that can be beneficial in reducing the prevalence of obesity and promoting public health.
Collapse
Affiliation(s)
- Shahida Anusha Siddiqui
- Department of Biotechnology and Sustainability, Technical University of Munich, Essigberg 3, 94315 Straubing, Germany
- German Institute of Food Technologies (DIL e.V.), Prof.-von-Klitzing Str. 7, 49610 Quakenbrück, Germany
| | | | - Priyanka Suthar
- Department of Food Science and Technology, Dr. Y. S. Parmar University of Horticulture and Forestry, Solan 173230, Himachal Pradesh, India;
| | - Yuan Seng Wu
- School of Medical and Life Sciences, Sunway University, Subang Jaya 47500, Malaysia;
| | - Nibedita Ghosh
- Department of Pharmacology, Girijananda Chowdhury University, Guwahati 781017, Assam, India;
| | - Roberto Castro-Muñoz
- Tecnologico de Monterrey, Campus Toluca, Av. Eduardo Monroy Cárdenas 2000, San Antonio Buenavista, Toluca de Lerdo 50110, Mexico
- Department of Sanitary Engineering, Faculty of Civil and Environmental Engineering, Gdansk University of Technology, G. Narutowicza St. 11/12, 80-233 Gdansk, Poland
| |
Collapse
|
40
|
Cao Y, Fang X, Sun M, Zhang Y, Shan M, Lan X, Zhu D, Luo H. Preventive and therapeutic effects of natural products and herbal extracts on nonalcoholic fatty liver disease/nonalcoholic steatohepatitis. Phytother Res 2023; 37:3867-3897. [PMID: 37449926 DOI: 10.1002/ptr.7932] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/10/2023] [Revised: 06/21/2023] [Accepted: 06/21/2023] [Indexed: 07/18/2023]
Abstract
Nonalcoholic fatty liver disease (NAFLD) is a common condition that is prevalent in patients who consume little or no alcohol, and is characterized by excessive fat accumulation in the liver. The disease is becoming increasingly common with the rapid economic development of countries. Long-term accumulation of excess fat can lead to NAFLD, which represents a global health problem with no effective therapeutic approach. NAFLD is a complex, multifaceted pathological process that has been the subject of extensive research over the past few decades. Herbal medicines have gained attention as potential therapeutic agents to prevent and treat NAFLD due to their high efficacy and low risk of side effects. Our overview is based on a PubMed and Web of Science database search as of Dec 22 with the keywords: NAFLD/NASH Natural products and NAFLD/NASH Herbal extract. In this review, we evaluate the use of herbal medicines in the treatment of NAFLD. These natural resources have the potential to inform innovative drug research and the development of treatments for NAFLD in the future.
Collapse
Affiliation(s)
- Yiming Cao
- College of Pharmacy, Changchun University of Chinese Medicine, Changchun, China
- Key Laboratory of Effective Components of Traditional Chinese Medicine, Changchun, China
| | - Xiaoxue Fang
- College of Pharmacy, Changchun University of Chinese Medicine, Changchun, China
- Key Laboratory of Effective Components of Traditional Chinese Medicine, Changchun, China
| | - Mingyang Sun
- College of Pharmacy, Changchun University of Chinese Medicine, Changchun, China
- Key Laboratory of Effective Components of Traditional Chinese Medicine, Changchun, China
| | - Yegang Zhang
- College of Pharmacy, Changchun University of Chinese Medicine, Changchun, China
- Key Laboratory of Effective Components of Traditional Chinese Medicine, Changchun, China
| | - Mengyao Shan
- College of Pharmacy, Changchun University of Chinese Medicine, Changchun, China
- Key Laboratory of Effective Components of Traditional Chinese Medicine, Changchun, China
| | - Xintian Lan
- College of Pharmacy, Changchun University of Chinese Medicine, Changchun, China
- Key Laboratory of Effective Components of Traditional Chinese Medicine, Changchun, China
| | - Difu Zhu
- College of Pharmacy, Changchun University of Chinese Medicine, Changchun, China
- Key Laboratory of Effective Components of Traditional Chinese Medicine, Changchun, China
| | - Haoming Luo
- College of Pharmacy, Changchun University of Chinese Medicine, Changchun, China
- Key Laboratory of Effective Components of Traditional Chinese Medicine, Changchun, China
| |
Collapse
|
41
|
Wang H, Zhao T, Liu Z, Danzengquzhen, Cisangzhuoma, Ma J, Li X, Huang X, Li B. The neuromodulatory effects of flavonoids and gut Microbiota through the gut-brain axis. Front Cell Infect Microbiol 2023; 13:1197646. [PMID: 37424784 PMCID: PMC10327292 DOI: 10.3389/fcimb.2023.1197646] [Citation(s) in RCA: 12] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/03/2023] [Accepted: 06/09/2023] [Indexed: 09/10/2023] Open
Abstract
Recent investigations show that dietary consumption of flavonoids could potentially confer neuroprotective effects through a variety of direct and indirect mechanisms. Numerous flavonoids have been shown to cross the BBB and accumulate within the central nervous system (CNS). Some of these compounds purportedly counteract the accumulation and deleterious effects of reactive oxygen species, fostering neuronal survival and proliferation by inhibiting neuroinflammatory and oxidative stress responses. Moreover, several studies suggest that gut microbiota may participate in regulating brain function and host behavior through the production and modulation of bioactive metabolites. Flavonoids may shape gut microbiota composition by acting as carbon substrates to promote the growth of beneficial bacteria that produce these neuroprotective metabolites, consequently antagonizing or suppressing potential pathogens. By influencing the microbiota-gut-brain axis through this selection process, flavonoids may indirectly improve brain health. This review examines the current state of research into the relationship between bioactive flavonoids, gut microbiota, and the gut-brain axis.
Collapse
Affiliation(s)
- Haoran Wang
- Institute of Animal Husbandry and Veterinary, Tibet Academy of Agricultural and Animal Husbandry Sciences, Key Laboratory of Animal Genetics and Breeding on Tibetan Plateau, Ministry of Agriculture and Rural Affairs, Lhasa, China
- School of Public Health, Lanzhou University, Lanzhou, Gansu, China
| | - Tingting Zhao
- Institute of Animal Husbandry and Veterinary, Tibet Academy of Agricultural and Animal Husbandry Sciences, Key Laboratory of Animal Genetics and Breeding on Tibetan Plateau, Ministry of Agriculture and Rural Affairs, Lhasa, China
- School of Public Health, Lanzhou University, Lanzhou, Gansu, China
| | - Zhenjiang Liu
- National Engineering Laboratory for AIDS Vaccine, School of Life Sciences, Jilin University, Changchun, China
| | - Danzengquzhen
- Institute of Animal Husbandry and Veterinary, Tibet Academy of Agricultural and Animal Husbandry Sciences, Key Laboratory of Animal Genetics and Breeding on Tibetan Plateau, Ministry of Agriculture and Rural Affairs, Lhasa, China
| | - Cisangzhuoma
- Institute of Animal Husbandry and Veterinary, Tibet Academy of Agricultural and Animal Husbandry Sciences, Key Laboratory of Animal Genetics and Breeding on Tibetan Plateau, Ministry of Agriculture and Rural Affairs, Lhasa, China
| | - Jinying Ma
- Institute of Animal Husbandry and Veterinary, Tibet Academy of Agricultural and Animal Husbandry Sciences, Key Laboratory of Animal Genetics and Breeding on Tibetan Plateau, Ministry of Agriculture and Rural Affairs, Lhasa, China
| | - Xin Li
- School of Public Health, Lanzhou University, Lanzhou, Gansu, China
| | - Xiaodan Huang
- School of Public Health, Lanzhou University, Lanzhou, Gansu, China
| | - Bin Li
- Institute of Animal Husbandry and Veterinary, Tibet Academy of Agricultural and Animal Husbandry Sciences, Key Laboratory of Animal Genetics and Breeding on Tibetan Plateau, Ministry of Agriculture and Rural Affairs, Lhasa, China
| |
Collapse
|
42
|
Zhang Y, Chen T, Hao X, Hu Y, Chen M, Zhang D, Cai H, Luo J, Kong L, Huang S, Huang Y, Yang N, Liu R, Li Q, Yuan C, Wang C, Zhou H, Huang W, Zhang W. Mapping the regulatory effects of herbal organic compounds on gut bacteria. Pharmacol Res 2023; 193:106804. [PMID: 37244386 DOI: 10.1016/j.phrs.2023.106804] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/15/2023] [Revised: 05/11/2023] [Accepted: 05/23/2023] [Indexed: 05/29/2023]
Affiliation(s)
- Yulong Zhang
- Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha 410078, P. R. China; Institute of Clinical Pharmacology, Central South University, Hunan Key Laboratory of Pharmacogenetics, Changsha 410078, P. R. China
| | - Ting Chen
- Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha 410078, P. R. China; Institute of Clinical Pharmacology, Central South University, Hunan Key Laboratory of Pharmacogenetics, Changsha 410078, P. R. China
| | - Xiaoqing Hao
- Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha 410078, P. R. China; Key Specialty of Clinical Pharmacy, The First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou 510080, P. R. China; The First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou 510080, P. R. China
| | - Yuanjia Hu
- State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao SAR 999078, P. R. China; DPM, Faculty of Health Sciences, University of Macau, Macao SAR 999078, P. R. China
| | - Manyun Chen
- Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha 410078, P. R. China; Institute of Clinical Pharmacology, Central South University, Hunan Key Laboratory of Pharmacogenetics, Changsha 410078, P. R. China
| | - Daiyan Zhang
- State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao SAR 999078, P. R. China
| | - Hong Cai
- State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao SAR 999078, P. R. China
| | - Jun Luo
- Jiangsu Key Laboratory of Bioactive Natural Product Research and State Key Laboratory of Natural Medicines, School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing 210009, P. R. China
| | - Lingyi Kong
- Jiangsu Key Laboratory of Bioactive Natural Product Research and State Key Laboratory of Natural Medicines, School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing 210009, P. R. China
| | - Sutianzi Huang
- Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha 410078, P. R. China; The First Affiliated Hospital of Shantou University Medical College, Shantou 515041, P. R. China
| | - Yuanfei Huang
- Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha 410078, P. R. China; Institute of Clinical Pharmacology, Central South University, Hunan Key Laboratory of Pharmacogenetics, Changsha 410078, P. R. China; Engineering Research Center of Applied Technology of Pharmacogenomics, Ministry of Education, Changsha 410078, P. R. China; National Clinical Research Center for Geriatric Disorders, Changsha 410008, P. R. China
| | - Nian Yang
- Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha 410078, P. R. China; The First Affiliated Hospital of Shantou University Medical College, Shantou 515041, P. R. China
| | - Rong Liu
- Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha 410078, P. R. China; Institute of Clinical Pharmacology, Central South University, Hunan Key Laboratory of Pharmacogenetics, Changsha 410078, P. R. China; Engineering Research Center of Applied Technology of Pharmacogenomics, Ministry of Education, Changsha 410078, P. R. China; National Clinical Research Center for Geriatric Disorders, Changsha 410008, P. R. China
| | - Qing Li
- Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha 410078, P. R. China; Key Specialty of Clinical Pharmacy, The First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou 510080, P. R. China; The First Affiliated Hospital of Shantou University Medical College, Shantou 515041, P. R. China
| | - Chunsu Yuan
- Tang Center of Herbal Medicine Research and Department of Anesthesia & Critical Care, University of Chicago, Chicago, IL 60637, USA
| | - Chongzhi Wang
- Tang Center of Herbal Medicine Research and Department of Anesthesia & Critical Care, University of Chicago, Chicago, IL 60637, USA
| | - Honghao Zhou
- Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha 410078, P. R. China; Institute of Clinical Pharmacology, Central South University, Hunan Key Laboratory of Pharmacogenetics, Changsha 410078, P. R. China; Engineering Research Center of Applied Technology of Pharmacogenomics, Ministry of Education, Changsha 410078, P. R. China; National Clinical Research Center for Geriatric Disorders, Changsha 410008, P. R. China
| | - Weihua Huang
- Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha 410078, P. R. China; Institute of Clinical Pharmacology, Central South University, Hunan Key Laboratory of Pharmacogenetics, Changsha 410078, P. R. China; Engineering Research Center of Applied Technology of Pharmacogenomics, Ministry of Education, Changsha 410078, P. R. China; National Clinical Research Center for Geriatric Disorders, Changsha 410008, P. R. China.
| | - Wei Zhang
- Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha 410078, P. R. China; Key Specialty of Clinical Pharmacy, The First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou 510080, P. R. China; The First Affiliated Hospital of Shantou University Medical College, Shantou 515041, P. R. China; Hunan Provincial Tumor Hospital and the Affiliated Tumor Hospital of Xiangya Medical School, Central South University, Changsha 410006, P. R. China.
| |
Collapse
|
43
|
Nsairat H, Lafi Z, Al-Sulaibi M, Gharaibeh L, Alshaer W. Impact of nanotechnology on the oral delivery of phyto-bioactive compounds. Food Chem 2023; 424:136438. [PMID: 37244187 DOI: 10.1016/j.foodchem.2023.136438] [Citation(s) in RCA: 16] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/06/2023] [Revised: 05/17/2023] [Accepted: 05/18/2023] [Indexed: 05/29/2023]
Abstract
Nanotechnology is an advanced field that has remarkable nutraceutical and food applications. Phyto-bioactive compounds (PBCs) play critical roles in promoting health and disease treatment. However, PBCs generally encounter several limitations that delay their widespread application. For example, most PBCs have low aqueous solubility, poor biostability, poor bioavailability, and a lack of target specificity. Moreover, the high concentrations of effective PBC doses also limit their application. As a result, encapsulating PBCs into an appropriate nanocarrier may increase their solubility and biostability and protect them from premature degradation. Moreover, nanoencapsulation could improve absorption and prolong circulation with a high opportunity for targeted delivery that may decrease unwanted toxicity. This review addresses the main parameters, variables, and barriers that control and affect oral PBC delivery. Moreover, this review discusses the potential role of biocompatible and biodegradable nanocarriers in improving the water solubility, chemical stability, bioavailability, and specificity/selectivity of PBCs.
Collapse
Affiliation(s)
- Hamdi Nsairat
- Pharmacological and Diagnostic Research Center, Faculty of Pharmacy, Al-Ahliyya Amman University, Amman 19328, Jordan.
| | - Zainab Lafi
- Pharmacological and Diagnostic Research Center, Faculty of Pharmacy, Al-Ahliyya Amman University, Amman 19328, Jordan
| | - Mazen Al-Sulaibi
- Pharmacological and Diagnostic Research Center, Faculty of Pharmacy, Al-Ahliyya Amman University, Amman 19328, Jordan
| | - Lobna Gharaibeh
- Pharmacological and Diagnostic Research Center, Faculty of Pharmacy, Al-Ahliyya Amman University, Amman 19328, Jordan
| | - Walhan Alshaer
- Cell Therapy Center, The University of Jordan, Amman 11942, Jordan.
| |
Collapse
|
44
|
Baslam A, Aitbaba A, Lamrani Hanchi A, Tazart Z, Aboufatima R, Soraa N, Ait-El-Mokhtar M, Boussaa S, Baslam M, Chait A. Modulation of Gut Microbiome in Ecstasy/MDMA-Induced Behavioral and Biochemical Impairment in Rats and Potential of Post-Treatment with Anacyclus pyrethrum L. Aqueous Extract to Mitigate Adverse Effects. Int J Mol Sci 2023; 24:ijms24109086. [PMID: 37240429 DOI: 10.3390/ijms24109086] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/25/2023] [Revised: 05/16/2023] [Accepted: 05/20/2023] [Indexed: 05/28/2023] Open
Abstract
The use of illicit substances continues to pose a substantial threat to global health, affecting millions of individuals annually. Evidence suggests the existence of a 'brain-gut axis' as the involving connection between the central nervous system and gut microbiome (GM). Dysbiosis of the GM has been associated with the pathogenesis of various chronic diseases, including metabolic, malignant, and inflammatory conditions. However, little is currently known about the involvement of this axis in modulating the GM in response to psychoactive substances. In this study, we investigated the effect of MDMA (3,4-methylenedioxymethamphetamine, "Ecstasy")-dependence on the behavioral and biochemical responses, and the diversity and abundance of the gut microbiome in rats post-treated (or not) with aqueous extract of Anacyclus pyrethrum (AEAP), which has been reported to exhibit anticonvulsant activity. The dependency was validated using the conditioned place preference (CPP) paradigm, behavioral, and biochemical tests, while the gut microbiota was identified using matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS). The CPP and behavioral tests confirmed the presence of MDMA withdrawal syndrome. Interestingly, treatment with AEAP led to a compositional shift in the GM compared to the MDMA-treated rats. Specifically, the AEAP group yielded a higher relative abundance of Lactobacillus and Bifidobacter, while animals receiving MDMA had higher levels of E. coli. These findings suggest that A. pyrethrum therapy may directly modulate the gut microbiome, highlighting a potential target for regulating and treating substance use disorders.
Collapse
Affiliation(s)
- Abdelmounaim Baslam
- Laboratory of Pharmacology, Neurobiology, Anthropobiology and Environment, Faculty of Sciences Semlalia, Cadi Ayyad University, Marrakesh 40000, Morocco
| | - Abdelfatah Aitbaba
- Laboratory of Pharmacology, Neurobiology, Anthropobiology and Environment, Faculty of Sciences Semlalia, Cadi Ayyad University, Marrakesh 40000, Morocco
| | - Asmae Lamrani Hanchi
- Laboratory of Microbiology, University Hospital Mohamed VI, Faculty of Medicine and Pharmacy, Cadi Ayyad University, Marrakesh 40000, Morocco
| | - Zakaria Tazart
- Department of Food Sciences and Nutrition, Faculty of Health Sciences, University of Malta, Msida 2080, Malta
| | - Rachida Aboufatima
- Laboratory of Biological Engineering, Faculty of Sciences and Technology, Sultan Moulay Slimane University, Beni Mellal 23000, Morocco
| | - Nabila Soraa
- Laboratory of Microbiology, University Hospital Mohamed VI, Faculty of Medicine and Pharmacy, Cadi Ayyad University, Marrakesh 40000, Morocco
| | - Mohamed Ait-El-Mokhtar
- Laboratory of Biochemistry, Environment & Agri-Food URAC 36, Department of Biology, Faculty of Science and Techniques-Mohammedia, Hassan II University of Casablanca, Mohammedia 20000, Morocco
| | - Samia Boussaa
- ISPITS-Higher Institute of Nursing and Health Techniques, Ministry of Health and Social Protection, Rabat 10000, Morocco
| | - Marouane Baslam
- Laboratory of Biochemistry, Department of Applied Biological Chemistry, Faculty of Agriculture, University of Niigata, Niigata 950-2181, Japan
- Centre d'Agrobiotechnologie et Bioingénierie, Unité de Recherche Labellisée CNRST (Centre AgroBiotech-URL-CNRST-05), Université Cadi Ayyad, Marrakesh 40000, Morocco
- Laboratory of Agro-Food, Biotechnologies and Valorization of Plant Bioresources (AGROBIOVAL), Department of Biology, Faculty of Science Semlalia, Cadi Ayyad University (UCA), Marrakesh 40000, Morocco
| | - Abderrahman Chait
- Laboratory of Pharmacology, Neurobiology, Anthropobiology and Environment, Faculty of Sciences Semlalia, Cadi Ayyad University, Marrakesh 40000, Morocco
| |
Collapse
|
45
|
Ticinesi A, Nouvenne A, Cerundolo N, Parise A, Meschi T. Accounting Gut Microbiota as the Mediator of Beneficial Effects of Dietary (Poly)phenols on Skeletal Muscle in Aging. Nutrients 2023; 15:nu15102367. [PMID: 37242251 DOI: 10.3390/nu15102367] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/24/2023] [Revised: 05/14/2023] [Accepted: 05/16/2023] [Indexed: 05/28/2023] Open
Abstract
Sarcopenia, the age-related loss of muscle mass and function increasing the risk of disability and adverse outcomes in older people, is substantially influenced by dietary habits. Several studies from animal models of aging and muscle wasting indicate that the intake of specific polyphenol compounds can be associated with myoprotective effects, and improvements in muscle strength and performance. Such findings have also been confirmed in a smaller number of human studies. However, in the gut lumen, dietary polyphenols undergo extensive biotransformation by gut microbiota into a wide range of bioactive compounds, which substantially contribute to bioactivity on skeletal muscle. Thus, the beneficial effects of polyphenols may consistently vary across individuals, depending on the composition and metabolic functionality of gut bacterial communities. The understanding of such variability has recently been improved. For example, resveratrol and urolithin interaction with the microbiota can produce different biological effects according to the microbiota metabotype. In older individuals, the gut microbiota is frequently characterized by dysbiosis, overrepresentation of opportunistic pathogens, and increased inter-individual variability, which may contribute to increasing the variability of biological actions of phenolic compounds at the skeletal muscle level. These interactions should be taken into great consideration for designing effective nutritional strategies to counteract sarcopenia.
Collapse
Affiliation(s)
- Andrea Ticinesi
- Department of Medicine and Surgery, University of Parma, Via Antonio Gramsci 14, 43126 Parma, Italy
- Microbiome Research Hub, University of Parma, Parco Area delle Scienze 11/1, 43124 Parma, Italy
- Geriatric-Rehabilitation Department, Azienda Ospedaliero-Universitaria di Parma, Via Antonio Gramsci 14, 43126 Parma, Italy
| | - Antonio Nouvenne
- Microbiome Research Hub, University of Parma, Parco Area delle Scienze 11/1, 43124 Parma, Italy
- Geriatric-Rehabilitation Department, Azienda Ospedaliero-Universitaria di Parma, Via Antonio Gramsci 14, 43126 Parma, Italy
| | - Nicoletta Cerundolo
- Geriatric-Rehabilitation Department, Azienda Ospedaliero-Universitaria di Parma, Via Antonio Gramsci 14, 43126 Parma, Italy
| | - Alberto Parise
- Geriatric-Rehabilitation Department, Azienda Ospedaliero-Universitaria di Parma, Via Antonio Gramsci 14, 43126 Parma, Italy
| | - Tiziana Meschi
- Department of Medicine and Surgery, University of Parma, Via Antonio Gramsci 14, 43126 Parma, Italy
- Microbiome Research Hub, University of Parma, Parco Area delle Scienze 11/1, 43124 Parma, Italy
- Geriatric-Rehabilitation Department, Azienda Ospedaliero-Universitaria di Parma, Via Antonio Gramsci 14, 43126 Parma, Italy
| |
Collapse
|
46
|
Kaur N, Dey P. Bacterial exopolysaccharides as emerging bioactive macromolecules: from fundamentals to applications. Res Microbiol 2023; 174:104024. [PMID: 36587857 DOI: 10.1016/j.resmic.2022.104024] [Citation(s) in RCA: 52] [Impact Index Per Article: 26.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/03/2022] [Accepted: 12/26/2022] [Indexed: 12/31/2022]
Abstract
Microbial exopolysaccharides (EPS) are extracellular carbohydrate polymers forming capsules or slimy coating around the cells. EPS can be secreted by various bacterial genera that can help bacterial cells in attachment, environmental adaptation, stress tolerance and are an integral part of microbial biofilms. Several gut commensals (e.g., Lactobacillus, Bifidobacterium) produce EPS that possess diverse bioactivities. Bacterial EPS also has extensive commercial applications in the pharmaceutical and food industries. Owing to the structural and functional diversity, genetic and metabolic engineering strategies are currently employed to increase EPS production. Therefore, the current review provides a comprehensive overview of the fundamentals of bacterial exopolysaccharides, including their classification, source, biosynthetic pathways, and functions in the microbial community. The review also provides an overview of the diverse bioactivities of microbial EPS, including immunomodulatory, anti-diabetic, anti-obesity, and anti-cancer properties. Since several gut microbes are EPS producers and gut microbiota helps maintain a functional gut barrier, emphasis has been given to the intestinal-level bioactivities of the gut microbial EPS. Collectively, the review provides a comprehensive overview of microbial bioactive exopolysaccharides.
Collapse
Affiliation(s)
- Navneet Kaur
- Department of Biotechnology, Thapar Institute of Engineering and Technology, Patiala, Punjab, India.
| | - Priyankar Dey
- Department of Biotechnology, Thapar Institute of Engineering and Technology, Patiala, Punjab, India.
| |
Collapse
|
47
|
Kwon C, Ediriweera MK, Kim Cho S. Interplay between Phytochemicals and the Colonic Microbiota. Nutrients 2023; 15:nu15081989. [PMID: 37111207 PMCID: PMC10145007 DOI: 10.3390/nu15081989] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/14/2023] [Revised: 04/08/2023] [Accepted: 04/18/2023] [Indexed: 04/29/2023] Open
Abstract
Phytochemicals are natural compounds found in food ingredients with a variety of health-promoting properties. Phytochemicals improve host health through their direct systematic absorption into the circulation and modulation of the gut microbiota. The gut microbiota increases the bioactivity of phytochemicals and is a symbiotic partner whose composition and/or diversity is altered by phytochemicals and affects host health. In this review, the interactions of phytochemicals with the gut microbiota and their impact on human diseases are reviewed. We describe the role of intestinal microbial metabolites, including short-chain fatty acids, amino acid derivatives, and vitamins, from a therapeutic perspective. Next, phytochemical metabolites produced by the gut microbiota and the therapeutic effect of some selected metabolites are reviewed. Many phytochemicals are degraded by enzymes unique to the gut microbiota and act as signaling molecules in antioxidant, anti-inflammatory, anticancer, and metabolic pathways. Phytochemicals can ameliorate diseases by altering the composition and/or diversity of the gut microbiota, and they increase the abundance of some gut microbiota that produce beneficial substances. We also discuss the importance of investigating the interactions between phytochemicals and gut microbiota in controlled human studies.
Collapse
Affiliation(s)
- Chohee Kwon
- Department of Environmental Biotechnology, Graduate School of Industry, Jeju National University, Jeju 63243, Republic of Korea
| | - Meran Keshawa Ediriweera
- Department of Biochemistry and Molecular Biology, Faculty of Medicine, University of Colombo, Colombo 008, Sri Lanka
| | - Somi Kim Cho
- Department of Environmental Biotechnology, Graduate School of Industry, Jeju National University, Jeju 63243, Republic of Korea
- Interdisciplinary Graduate Program in Advanced Convergence Technology and Science, Jeju National University, Jeju 63243, Republic of Korea
| |
Collapse
|
48
|
Ajzashokouhi AH, Rezaee R, Omidkhoda N, Karimi G. Natural compounds regulate the PI3K/Akt/GSK3β pathway in myocardial ischemia-reperfusion injury. Cell Cycle 2023; 22:741-757. [PMID: 36593695 PMCID: PMC10026916 DOI: 10.1080/15384101.2022.2161959] [Citation(s) in RCA: 19] [Impact Index Per Article: 9.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/14/2022] [Revised: 12/14/2022] [Accepted: 12/16/2022] [Indexed: 01/04/2023] Open
Abstract
The PI3K/Akt/GSK3β pathway is crucial in regulating cardiomyocyte growth and survival. It has been shown that activation of this pathway alleviates the negative impact of ischemia-reperfusion. Glycogen synthase kinase-3 (GSK3β) induces apoptosis through stimulation of transcription factors, and its phosphorylation has been suggested as a new therapeutic target for myocardial ischemia-reperfusion injury (MIRI). GSK3β regulatory role is mediated by the reperfusion injury salvage kinase (RISK) pathway, and its inhibition by Akt activation blocks mitochondrial permeability transition pore (mPTP) opening and enhances myocardial survival. The present article discusses the involvement of the PI3K/Akt/GSK3β pathway in cardioprotective effects of natural products against MIRI.Abbreviations: Akt: protein kinase B; AMPK: AMP-activated protein kinase; ATP: adenosine triphosphate; Bad: bcl2-associated agonist of cell death; Bax: bcl2-associated x protein; Bcl-2: B-cell lymphoma 2; CK-MB: Creatine kinase-MB; CRP: C-reactive-protein; cTnI: cardiac troponin I; EGCG: Epigallocatechin-3-gallate; Enos: endothelial nitric oxide synthase; ER: endoplasmic reticulum; ERK ½: extracellular signal‑regulated protein kinase ½; GSK3β: glycogen synthase kinase-3; GSRd: Ginsenoside Rd; GSH: glutathione; GSSG: glutathione disulfide; HO-1: heme oxygenase-1; HR: hypoxia/reoxygenation; HSYA: Hydroxysafflor Yellow A; ICAM-1: Intercellular Adhesion Molecule 1; IKK-b: IκB kinase; IL: interleukin; IPoC: Ischemic postconditioning; IRI: ischemia-reperfusion injury; JNK: c-Jun N-terminal kinase; Keap1: kelch-like ECH-associated protein- 1; LDH: lactate dehydrogenase; LVEDP: left ventricular end diastolic pressure; LVP: left ventricle pressure; LVSP: left ventricular systolic pressure; MAPK: mitogen-activated protein kinase; MDA: malondialdehyde; MIRI: myocardial ischemia-reperfusion injury; MnSOD: manganese superoxide dismutase; mPTP: mitochondrial permeability transition pore; mtHKII: mitochondria-bound hexokinase II; Nrf-1: nuclear respiratory factor 1; Nrf2: nuclear factor erythroid 2-related factor; NO: nitric oxide; PGC-1α: peroxisome proliferator‑activated receptor γ coactivator‑1α; PI3K: phosphoinositide 3-kinases; RISK: reperfusion injury salvage kinase; ROS: reactive oxygen species; RSV: Resveratrol; SOD: superoxide dismutase; TFAM: transcription factor A mitochondrial; TNF-α: tumor necrosis factor-alpha; VEGF-B: vascular endothelial growth factor B.
Collapse
Affiliation(s)
| | - Ramin Rezaee
- International UNESCO Center for Health-Related Basic Sciences and Human Nutrition, Mashhad University of Medical Sciences, Mashhad, Iran
- Applied Biomedical Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Navid Omidkhoda
- Department of Clinical Pharmacy, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Gholamreza Karimi
- Department of Pharmacodynamics and Toxicology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran
- Pharmaceutical Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran
| |
Collapse
|
49
|
Phytochemical Profile, Antioxidant, Antimicrobial and Cytoprotective Effects of Cornelian Cherry (Cornus mas L.) Fruit Extracts. Pharmaceuticals (Basel) 2023; 16:ph16030420. [PMID: 36986519 PMCID: PMC10058959 DOI: 10.3390/ph16030420] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/20/2023] [Revised: 03/04/2023] [Accepted: 03/08/2023] [Indexed: 03/12/2023] Open
Abstract
Cornus mas L. is characterized by an increased quantity of bioactive compounds, namely polyphenols, monoterpenes, organic acids, vitamin C and lipophilic compounds such as carotenoids, being anciently used in the treatment of various diseases. This paper’s objectives were to characterize the phytochemical profile of Cornus mas L. fruits and to evaluate the in vitro antioxidant, antimicrobial and cytoprotective effects on renal cells exposed to gentamicin. As such, two ethanolic extracts were obtained. The resulting extracts were used to assess the total polyphenols, flavonoids and carotenoids through spectral and chromatographic methods. The antioxidant capacity was assessed using DPPH and FRAP assays. Due to the high content of phenolic compounds analyzed in fruits and the results obtained regarding antioxidant capacity, we decided to further use the ethanolic extract to investigate the in vitro antimicrobial and cytoprotective effects on renal cells stressed with gentamicin. The antimicrobial activity was assessed using agar well diffusion and broth microdilution methods, with great results regarding Pseudomonas aeruginosa. The cytotoxic activity was assessed using MTT and Annexin-V assays. According to the findings, extract-treated cells had a higher cell viability. However, at high concentrations, viability was shown to decline, most likely due to the extract and gentamicin’s additive effects.
Collapse
|
50
|
Sharma R, Singh S, Tewari N, Dey P. A toxic shrub turned therapeutic: The dichotomy of Nerium oleander bioactivities. Toxicon 2023; 224:107047. [PMID: 36706925 DOI: 10.1016/j.toxicon.2023.107047] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/26/2022] [Revised: 01/20/2023] [Accepted: 01/24/2023] [Indexed: 01/26/2023]
Abstract
Nerium oleander L. is a medicinal plant, used for the treatment of cancers and hyperglycemia across the world, especially in Indian sub-continent, Turkey, Morocco, and China. Although clinical studies supporting its pharmacological effects remain critically underexplored, accidental and intentional consumption of any part of the plant causes fatal toxicity in animals and humans. While the polyphenolic fraction of oleander leaves has been attributed to its pre-clinical pharmacological activities, the presence of diverse cardiac glycosides (especially oleandrin) causes apoptosis to cancer cells in vitro and results in clinical signs of oleander poisoning. Thus, the dual pharmacological and toxicological role of oleander is a perplexing dichotomy in phytotherapy. The current investigative review, therefore, intended to analyze the intrinsic and extrinsic factors that likely contribute to this conundrum. Especially by focusing on gut microbial diversity, abundance, and metabolic functions, oleander-associated pharmacological and toxicological studies have been critically analyzed to define the dual effects of oleander. Electronic databases were extensively screened for relevant research articles (including pre-clinical and clinical) related to oleander bioactivities and toxicity. Taxonomic preference was given to the plant N. oleander L. and synonymous plants as per 'The World Flora Online' database (WCSP record #135196). Discussion on yellow oleander (Cascabela thevetia (L.) Lippold) has intentionally been avoided since it is a different plant. The review indicates that the gut microbiota likely plays a key role in differentially modulating the pharmacological and toxicological effects of oleander. Other factors identified influencing the oleander bioactivities include dose and mode of treatment, cardiac glycoside pharmacokinetics, host-endogenous glycosides, plant material processing and phytochemical extraction methods, plant genotypic variations, environmental effects on the phytochemical quality and quantity, gene expression variations, host dietary patterns and co-morbidity, etc. The arguments proposed are also relevant to other medicinal plants containing toxic cardiac glycosides.
Collapse
Affiliation(s)
- Rajat Sharma
- Department of Biotechnology, Thapar Institute of Engineering and Technology, Patiala, Punjab, India.
| | - Swati Singh
- Department of Zoology, University of North Bengal, Siliguri, West Bengal, India.
| | - Nisha Tewari
- Department of Biotechnology, Thapar Institute of Engineering and Technology, Patiala, Punjab, India.
| | - Priyankar Dey
- Department of Biotechnology, Thapar Institute of Engineering and Technology, Patiala, Punjab, India.
| |
Collapse
|