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Liu XJ, Ye-er-tai YLY, Jia YB, Wu CH, Wang XX, Yang KM, Yao X, Ling JH. Runchangningshen paste activates NLRP6 inflammasome-mediated autophagy to stimulate colonic mucin-2 secretion and modulates mucosal microbiota in functional constipation. World J Gastroenterol 2025; 31:102256. [PMID: 40061589 PMCID: PMC11886036 DOI: 10.3748/wjg.v31.i9.102256] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/13/2024] [Revised: 12/06/2024] [Accepted: 01/02/2025] [Indexed: 02/18/2025] Open
Abstract
BACKGROUND Runchangningshen paste (RCNSP) is a paste made of four medicinal and edible homologous Chinese medicine mixed with honey. It is known for its ability to nourish yin and blood as well as to loosen the bowel to relieve constipation. The pathophysiology of functional constipation (FC) is associated with a reduction in mucin-2 (MUC2) secretion and microbial dysbiosis. AIM To investigate the underlying mechanism of RCNSP against FC through MUC2 and the gut mucosal microbiota. METHODS Ultra-performance liquid chromatography tandem mass spectrometry characterized RCNSP composition to elucidate the material basis of action. FC model was induced via loperamide gavage (16 mg/kg) twice daily for 7 days. Applying defecation function and gastrointestinal motility to assess constipation severity. Hematoxylin and eosin and Alcian blue-periodic acid-schiff staining analyzed colonic mucosal morphology. Transmission electron microscope was used to observe the ultrastructure of goblet cells (GCs). Immunofluorescence colocalization, quantitative PCR, and western blot assessed the impact of RCNSP on gene and protein expression within the NLRP6/autophagy pathway. 16S rDNA was employed to sequence the gut mucosal microbiota. RESULTS RCNSP contained 12 components with potential laxative effects. It enhanced defecation function, accelerated gastrointestinal motility, and maintained colonic mucosal integrity. RCNSP treatment significantly increased GC abundance and MUC2 production while preserving GC ultrastructure. At the molecular level, RCNSP enhanced the colocalized expression of key regulatory proteins and modulated mRNA and protein expressions in the NLRP6/autophagy pathway. Through 16S rDNA sequencing analysis, RCNSP significantly altered the mucosal microbiota composition. Specifically, it increased beneficial bacterial strains while reducing harmful ones. Simultaneously, RCNSP reduced butyrate-producing bacteria like Proteobacteria, Enterobacteriaceae, Blautia, and Eubacterium and decreased hydrogen sulfide-producing species, such as Prevotellaceae. It also reduced bile acid-inhibiting species, such as g_Eubacter_coprostanoligenes_group and Erysipelotrichaceae while increasing bile acid-producing species, such as Colidextribacter. CONCLUSION Our findings suggested that RCNSP ameliorated constipation through a dual mechanism: It stimulated colonic MUC2 secretion by activating NLRP6 inflammasome-mediated autophagy and modulated the composition of the mucosal microbiota.
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Affiliation(s)
- Xue-Jiao Liu
- Department of Gastroenterology, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai 200021, China
| | - Ye-li-ya Ye-er-tai
- Department of Gastroenterology, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai 200021, China
| | - Yue-Bo Jia
- Department of Gastroenterology, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai 200021, China
| | - Chen-Heng Wu
- Department of Gastroenterology, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai 200021, China
| | - Xiang-Xiang Wang
- School of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China
| | - Ke-Ming Yang
- Department of Gastroenterology, Shenzhen Traditional Chinese Medicine Hospital, Shenzhen 518033, Guangdong Province, China
| | - Xuan Yao
- Guangdong Shaxi Pharmaceutical Co., Ltd, Zhongshan 528471, Guangdong Province, China
| | - Jiang-Hong Ling
- Department of Gastroenterology, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai 200021, China
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Luo Z, Li Q, He S, Liu S, Lei R, Kong Q, Wang R, Liu X, Wu J. Berberine sensitizes immune checkpoint blockade therapy in melanoma by NQO1 inhibition and ROS activation. Int Immunopharmacol 2024; 142:113031. [PMID: 39217888 DOI: 10.1016/j.intimp.2024.113031] [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: 04/09/2024] [Revised: 07/31/2024] [Accepted: 08/25/2024] [Indexed: 09/04/2024]
Abstract
Unprecedented progress in immune checkpoint blockade (ICB) therapy has been made in cancer treatment. However, the response to ICB therapy is limited to a small subset of patients. The development of ICB sensitizers to improve cancer immunotherapy outcomes is urgently needed. Berberine (BBR), a well-known phytochemical compound isolated from many kinds of medicinal plants such as Berberis aristata, Coptis chinensis, and Phellondendron chinense Schneid, has shown the ability to inhibit the proliferation, invasion and metastasis of cancer cells. In this study, we investigated whether BBR can enhance the therapeutic benefit of ICB for melanoma, and explored the underlying mechanisms involved. The results showed that BBR could sensitize ICB to inhibit tumor growth and increased the survival rate of mice. Moreover, BBR stimulated intracellular ROS production partially by inhibiting NQO1 activity, which induced immunogenic cell death (ICD) in melanoma, elevated the levels of damage-associated molecular patterns (DAMPs), and subsequently activated DC cells and CD8 + T cells in vitro and in vivo. In conclusion, BBR is a novel ICD inducer. BBR could enhance the therapeutic benefit of ICB for melanoma. These effects were partially mediated through the inhibition of NQO1 and ROS activation.
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Affiliation(s)
- Zhuyu Luo
- Department of Dermatology, Huashan Hospital, Fudan University, Shanghai 200040, China
| | - Qiao Li
- Department of Dermatology, Huashan Hospital, Fudan University, Shanghai 200040, China
| | - Shan He
- Department of Dermatology, Huashan Hospital, Fudan University, Shanghai 200040, China
| | - Suqing Liu
- Department of Dermatology, Huashan Hospital, Fudan University, Shanghai 200040, China
| | - Rui Lei
- Department of Dermatology, Huashan Hospital, Fudan University, Shanghai 200040, China
| | - Qing Kong
- Department of Dermatology, Huashan Hospital, Fudan University, Shanghai 200040, China
| | - Ruilong Wang
- Department of Dermatology, Huashan Hospital, Fudan University, Shanghai 200040, China
| | - Xiao Liu
- Department of Dermatology, Huashan Hospital, Fudan University, Shanghai 200040, China.
| | - Jinfeng Wu
- Department of Dermatology, Huashan Hospital, Fudan University, Shanghai 200040, China.
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Varga K, Paszternák A, Kovács V, Guczogi A, Sikur N, Patakfalvi D, Bagaméry F, Szökő É, Tábi T. Differential Cytoprotective Effect of Resveratrol and Its Derivatives: Focus on Antioxidant and Autophagy-Inducing Effects. Int J Mol Sci 2024; 25:11274. [PMID: 39457058 PMCID: PMC11509103 DOI: 10.3390/ijms252011274] [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: 09/21/2024] [Revised: 10/14/2024] [Accepted: 10/19/2024] [Indexed: 10/28/2024] Open
Abstract
Numerous beneficial effects of resveratrol were reported; however, its pharmacological profile is contradictious. Previously, we have demonstrated that resveratrol has a dose-dependent cytoprotective effect and the essential role of autophagy induction was demonstrated. Resveratrol suffers from unfavorable pharmacokinetics, hindering its clinical use. Our aim was to study the cytoprotective effect of resveratrol derivatives to better understand structure-activity relationships that may facilitate the development of compounds with better druglike characteristics. Serum-deprivation-induced caspase activation, free radical generation, mitochondrial membrane depolarization and autophagy were detected in the presence of resveratrol analogs with different oxidation states on mouse embryonal fibroblasts. Distinct cytoprotective mechanisms of the examined compounds were revealed. Monomethyl resveratrol had similar potency to resveratrol (EC50: 85.3 vs. 84.2 μM); however, autophagy induction was not essential for its cytoprotective effect. Oxyresveratrol was found to be a strong antioxidant that can induce direct cytoprotection rather than autophagy. Trimethyl-resveratrol, lacking free hydroxyl groups, induced damage that was too significant and hardly compensated by the activation of cytoprotective machineries, and caspase activation was reduced by only 24.5%. Based on our results, methylation of resveratrol reduces its antioxidant activity, while autophagy induction can still contribute to its cytoprotective effect. The introduction of an additional hydroxyl group, however, augments the antioxidant properties, inducing cytoprotection without autophagy induction.
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Affiliation(s)
- Kamilla Varga
- Department of Pharmacodynamics, Semmelweis University, 4 Nagyvárad tér, H-1089 Budapest, Hungary; (K.V.); (A.P.); (N.S.); (F.B.); (É.S.)
- Center for Pharmacology and Drug Research & Development, Semmelweis University, 26 Üllői út, H-1085 Budapest, Hungary
| | - Alexandra Paszternák
- Department of Pharmacodynamics, Semmelweis University, 4 Nagyvárad tér, H-1089 Budapest, Hungary; (K.V.); (A.P.); (N.S.); (F.B.); (É.S.)
- Center for Pharmacology and Drug Research & Development, Semmelweis University, 26 Üllői út, H-1085 Budapest, Hungary
| | - Virág Kovács
- Department of Pharmacodynamics, Semmelweis University, 4 Nagyvárad tér, H-1089 Budapest, Hungary; (K.V.); (A.P.); (N.S.); (F.B.); (É.S.)
- Center for Pharmacology and Drug Research & Development, Semmelweis University, 26 Üllői út, H-1085 Budapest, Hungary
| | - Annamária Guczogi
- Department of Pharmacodynamics, Semmelweis University, 4 Nagyvárad tér, H-1089 Budapest, Hungary; (K.V.); (A.P.); (N.S.); (F.B.); (É.S.)
- Center for Pharmacology and Drug Research & Development, Semmelweis University, 26 Üllői út, H-1085 Budapest, Hungary
| | - Noémi Sikur
- Department of Pharmacodynamics, Semmelweis University, 4 Nagyvárad tér, H-1089 Budapest, Hungary; (K.V.); (A.P.); (N.S.); (F.B.); (É.S.)
- Center for Pharmacology and Drug Research & Development, Semmelweis University, 26 Üllői út, H-1085 Budapest, Hungary
| | - Dimitrisz Patakfalvi
- Department of Pharmacodynamics, Semmelweis University, 4 Nagyvárad tér, H-1089 Budapest, Hungary; (K.V.); (A.P.); (N.S.); (F.B.); (É.S.)
- Center for Pharmacology and Drug Research & Development, Semmelweis University, 26 Üllői út, H-1085 Budapest, Hungary
| | - Fruzsina Bagaméry
- Department of Pharmacodynamics, Semmelweis University, 4 Nagyvárad tér, H-1089 Budapest, Hungary; (K.V.); (A.P.); (N.S.); (F.B.); (É.S.)
- Center for Pharmacology and Drug Research & Development, Semmelweis University, 26 Üllői út, H-1085 Budapest, Hungary
| | - Éva Szökő
- Department of Pharmacodynamics, Semmelweis University, 4 Nagyvárad tér, H-1089 Budapest, Hungary; (K.V.); (A.P.); (N.S.); (F.B.); (É.S.)
- Center for Pharmacology and Drug Research & Development, Semmelweis University, 26 Üllői út, H-1085 Budapest, Hungary
| | - Tamás Tábi
- Department of Pharmacodynamics, Semmelweis University, 4 Nagyvárad tér, H-1089 Budapest, Hungary; (K.V.); (A.P.); (N.S.); (F.B.); (É.S.)
- Center for Pharmacology and Drug Research & Development, Semmelweis University, 26 Üllői út, H-1085 Budapest, Hungary
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Zhao L, Duan Y, Li Z, Li J, Li S. Unearthing the Potential Therapeutic Effects of Oxyresveratrol Based on Intrinsic Links between Pharmacological Effects: Implications for the Gut-Liver-Brain Axis. Pharmaceuticals (Basel) 2024; 17:1063. [PMID: 39204169 PMCID: PMC11359039 DOI: 10.3390/ph17081063] [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: 03/19/2024] [Revised: 08/09/2024] [Accepted: 08/11/2024] [Indexed: 09/03/2024] Open
Abstract
Oxyresveratrol is a stilbene compound with a simple chemical structure and various therapeutic potentials. This study summarized and analyzed the multiple pharmacological effects and mechanisms of oxyresveratrol, identifying its prominent performance in neuroprotection, hepatoprotection, and anti-inflammatory activities in the intestines. By integrating the pharmacological effects of oxyresveratrol with insights from the network pharmacology and molecular docking of its interactions with targets linked to gut-liver-brain axis disorders, it has been shown that oxyresveratrol may hold promise for the treatment of gut-liver-brain axis-related disorders. The synergistic effect between various mechanisms has inspired further research and the development of oxyresveratrol's application value.
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Affiliation(s)
- Lijuan Zhao
- School of Pharmacy, Hunan University of Chinese Medicine, Changsha 410208, China; (L.Z.); (Y.D.); (J.L.)
- Hunan Engineering Technology Research Center for Bioactive Substance Discovery of Chinese Medicine, Changsha 410208, China;
- Hunan Province Sino-US International Joint Research Center for Therapeutic Drugs of Senile Degenerative Diseases, Changsha 410208, China
- College of Biology and Food Engineering, Huaihua University, Huaihua 418000, China
| | - Yan Duan
- School of Pharmacy, Hunan University of Chinese Medicine, Changsha 410208, China; (L.Z.); (Y.D.); (J.L.)
- Hunan Engineering Technology Research Center for Bioactive Substance Discovery of Chinese Medicine, Changsha 410208, China;
- Hunan Province Sino-US International Joint Research Center for Therapeutic Drugs of Senile Degenerative Diseases, Changsha 410208, China
| | - Zhaoxing Li
- Hunan Engineering Technology Research Center for Bioactive Substance Discovery of Chinese Medicine, Changsha 410208, China;
- Hunan Province Sino-US International Joint Research Center for Therapeutic Drugs of Senile Degenerative Diseases, Changsha 410208, China
- School of Pharmacy, China Pharmaceutical University, Nanjing 210009, China
| | - Juan Li
- School of Pharmacy, Hunan University of Chinese Medicine, Changsha 410208, China; (L.Z.); (Y.D.); (J.L.)
- Hunan Engineering Technology Research Center for Bioactive Substance Discovery of Chinese Medicine, Changsha 410208, China;
- Hunan Province Sino-US International Joint Research Center for Therapeutic Drugs of Senile Degenerative Diseases, Changsha 410208, China
| | - Shunxiang Li
- School of Pharmacy, Hunan University of Chinese Medicine, Changsha 410208, China; (L.Z.); (Y.D.); (J.L.)
- Hunan Engineering Technology Research Center for Bioactive Substance Discovery of Chinese Medicine, Changsha 410208, China;
- Hunan Province Sino-US International Joint Research Center for Therapeutic Drugs of Senile Degenerative Diseases, Changsha 410208, China
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Zhu H, Zhou X, Shen C, Ao Z, Cao X, Song C, Mehmood MA, Wu T, Mei J, He M, Ma Y, Wang N. Bacillus licheniformis-based intensive fermentation of Tibetan tea improved its bioactive compounds and reinforced the intestinal barrier in mice. Front Microbiol 2024; 15:1376757. [PMID: 38933031 PMCID: PMC11199413 DOI: 10.3389/fmicb.2024.1376757] [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: 01/26/2024] [Accepted: 05/21/2024] [Indexed: 06/28/2024] Open
Abstract
Tibetan tea changes during microorganism fermentation. Research on microorganisms in Tibetan tea has focused on their identification, while studies on the influence of specific microorganisms on the components and health functions of Tibetan tea are lacking. Bacillus licheniformis was inoculated into Tibetan tea for intensive fermentation, and the components of B. licheniformis-fermented tea (BLT) were detected by liquid chromatography with tandem mass spectrometry (UHPLC-TOF-MS), and then the effects of BLT on intestinal probiotic functions were investigated by experiments on mice. The results revealed the metabolites of BLT include polyphenols, alkaloids, terpenoids, amino acids, and lipids. Intensified fermentation also improved the antioxidant capacity in vivo and the protective effect on the intestinal barrier of Tibetan tea. In addition, the enhanced fermentation of Tibetan tea exerted intestinal probiotic effects by modulating the relative abundance of short-chain fatty acid-producing bacteria in the intestinal flora. Therefore, intensive fermentation with B. licheniformis can improve the health benefits of Tibetan tea.
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Affiliation(s)
- Hui Zhu
- College of Bioengineering, Sichuan University of Science and Engineering, Zigong, China
- Sichuan Province Engineering Technology Research Center of Liquor-Making Grains, Yibin, China
| | - Xiaoli Zhou
- College of Bioengineering, Sichuan University of Science and Engineering, Zigong, China
- Sichuan Province Engineering Technology Research Center of Liquor-Making Grains, Yibin, China
| | | | | | | | | | - Muhammad Aamer Mehmood
- College of Bioengineering, Sichuan University of Science and Engineering, Zigong, China
- Sichuan Province Engineering Technology Research Center of Liquor-Making Grains, Yibin, China
- Department of Bioinformatics and Biotechnology, Government College University Faisalabad, Faisalabad, Pakistan
| | - Tao Wu
- School of Food and Biological Engineering, Xihua University, Chengdu, China
| | - Jie Mei
- Sichuan Jixiang Tea Co., Ltd., Ya'an, China
| | - Manli He
- Laboratory Animal Center, Southwest Medical University, Luzhou, China
| | - Yi Ma
- College of Bioengineering, Sichuan University of Science and Engineering, Zigong, China
- Sichuan Province Engineering Technology Research Center of Liquor-Making Grains, Yibin, China
| | - Ning Wang
- College of Bioengineering, Sichuan University of Science and Engineering, Zigong, China
- Sichuan Province Engineering Technology Research Center of Liquor-Making Grains, Yibin, China
- Luzhou Laojiao Co. Ltd., Luzhou, China
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Shi YR, Hao WW, Zhang EX, Wang ZH, Li L. Role of autophagy in pathogenesis of ulcerative colitis. Shijie Huaren Xiaohua Zazhi 2023; 31:1022-1028. [DOI: 10.11569/wcjd.v31.i24.1022] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/27/2023] [Revised: 11/18/2023] [Accepted: 11/27/2023] [Indexed: 12/28/2023] Open
Abstract
Ulcerative colitis is a chronic idiopathic inflammatory disease involving the colorectal mucosa. It is characterized by recurrent attacks, such as abdominal pain, diarrhea, mucus, and purulent stool. At present, the pathogenesis of ulcerative colitis is not fully understood. Most scholars generally believe that the pathogenesis of ulcerative colitis is affected by genetic susceptibility, environmental factors, immune system disorders, microflora and intestinal microflora disorders, and other factors. In recent years, the concept of autophagy has gradually attracted the attention of the scientific community, and more and more scholars have begun to study the pathogenesis of ulcerative colitis on the basis of autophagy theory. This review will give an overview of cellular autophagy and discuss its role in the pathogenesis of ulcerative colitis.
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Affiliation(s)
- Yi-Rong Shi
- Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai 200120, China
| | - Wei-Wei Hao
- Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai 200120, China
| | - Er-Xin Zhang
- Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai 200120, China
| | - Zhu-Huan Wang
- Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai 200120, China
| | - Le Li
- Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai 200120, China
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Wang Y, Hong C, Wu Z, Li S, Xia Y, Liang Y, He X, Xiao X, Tang W. Resveratrol in Intestinal Health and Disease: Focusing on Intestinal Barrier. Front Nutr 2022; 9:848400. [PMID: 35369090 PMCID: PMC8966610 DOI: 10.3389/fnut.2022.848400] [Citation(s) in RCA: 19] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/04/2022] [Accepted: 02/07/2022] [Indexed: 12/14/2022] Open
Abstract
The integrity of intestinal barrier determines intestinal homeostasis, which could be affected by various factors, like physical, chemical, and biological stimuli. Therefore, it is of considerable interest and importance to maintain intestinal barrier function. Fortunately, many plant polyphenols, including resveratrol, could affect the health of intestinal barrier. Resveratrol has many biological functions, such as antioxidant, anti-inflammation, anti-tumor, and anti-cardiovascular diseases. Accumulating studies have shown that resveratrol affects intestinal tight junction, microbial composition, and inflammation. In this review, we summarize the effects of resveratrol on intestinal barriers as well as the potential mechanisms (e.g., inhibiting the growth of pathogenic bacteria and fungi, regulating the expression of tight junction proteins, and increasing anti-inflammatory T cells while reducing pro-inflammatory T cells), and highlight the applications of resveratrol in ameliorating various intestinal diseases.
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Affiliation(s)
- Youxia Wang
- College of Animal Science, South China Agricultural University, Guangzhou, China
| | - Changming Hong
- College of Animal Science, South China Agricultural University, Guangzhou, China
| | - Zebiao Wu
- College of Animal Science, South China Agricultural University, Guangzhou, China
| | - Shuwei Li
- Animal Breeding and Genetics Key Laboratory of Sichuan Province, Sichuan Animal Science Academy, Chengdu, China
- Livestock and Poultry Biological Products Key Laboratory of Sichuan Province, Sichuan Animtech Feed Co., Ltd., Chengdu, China
| | - Yaoyao Xia
- College of Animal Science, South China Agricultural University, Guangzhou, China
| | - Yuying Liang
- College of Animal Science, South China Agricultural University, Guangzhou, China
| | - Xiaohua He
- College of Animal Science, South China Agricultural University, Guangzhou, China
| | - Xinyu Xiao
- College of Animal Science, South China Agricultural University, Guangzhou, China
| | - Wenjie Tang
- Animal Breeding and Genetics Key Laboratory of Sichuan Province, Sichuan Animal Science Academy, Chengdu, China
- Livestock and Poultry Biological Products Key Laboratory of Sichuan Province, Sichuan Animtech Feed Co., Ltd., Chengdu, China
- *Correspondence: Wenjie Tang
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Lapaquette P, Bizeau JB, Acar N, Bringer MA. Reciprocal interactions between gut microbiota and autophagy. World J Gastroenterol 2021; 27:8283-8301. [PMID: 35068870 PMCID: PMC8717019 DOI: 10.3748/wjg.v27.i48.8283] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/18/2021] [Revised: 09/09/2021] [Accepted: 12/08/2021] [Indexed: 02/06/2023] Open
Abstract
A symbiotic relationship has set up between the gut microbiota and its host in the course of evolution, forming an interkingdom consortium. The gut offers a favorable ecological niche for microbial communities, with the whole body and external factors (e.g., diet or medications) contributing to modulating this microenvironment. Reciprocally, the gut microbiota is important for maintaining health by acting not only on the gut mucosa but also on other organs. However, failure in one or another of these two partners can lead to the breakdown in their symbiotic equilibrium and contribute to disease onset and/or progression. Several microbial and host processes are devoted to facing up the stress that could alter the symbiosis, ensuring the resilience of the ecosystem. Among these processes, autophagy is a host catabolic process integrating a wide range of stress in order to maintain cell survival and homeostasis. This cytoprotective mechanism, which is ubiquitous and operates at basal level in all tissues, can be rapidly down- or up-regulated at the transcriptional, post-transcriptional, or post-translational levels, to respond to various stress conditions. Because of its sensitivity to all, metabolic-, immune-, and microbial-derived stimuli, autophagy is at the crossroad of the dialogue between changes occurring in the gut microbiota and the host responses. In this review, we first delineate the modulation of host autophagy by the gut microbiota locally in the gut and in peripheral organs. Then, we describe the autophagy-related mechanisms affecting the gut microbiota. We conclude this review with the current challenges and an outlook toward the future interventions aiming at modulating host autophagy by targeting the gut microbiota.
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Affiliation(s)
- Pierre Lapaquette
- UMR PAM A 02.102, University Bourgogne Franche-Comté, Agrosup Dijon, Dijon 21000, France
| | - Jean-Baptiste Bizeau
- Eye and Nutrition Research Group, Centre des Sciences du Goût et de l'Alimentation, AgroSup Dijon, CNRS, INRAE, Université Bourgogne Franche-Comté, Dijon 21000, France
| | - Niyazi Acar
- Eye and Nutrition Research Group, Centre des Sciences du Goût et de l'Alimentation, AgroSup Dijon, CNRS, INRAE, Université Bourgogne Franche-Comté, Dijon 21000, France
| | - Marie-Agnès Bringer
- Eye and Nutrition Research Group, Centre des Sciences du Goût et de l'Alimentation, AgroSup Dijon, CNRS, INRAE, Université Bourgogne Franche-Comté, Dijon 21000, France
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Likhitwitayawuid K. Oxyresveratrol: Sources, Productions, Biological Activities, Pharmacokinetics, and Delivery Systems. Molecules 2021; 26:4212. [PMID: 34299485 PMCID: PMC8307110 DOI: 10.3390/molecules26144212] [Citation(s) in RCA: 33] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/16/2021] [Revised: 07/05/2021] [Accepted: 07/08/2021] [Indexed: 12/18/2022] Open
Abstract
Oxyresveratrol has recently attracted much research attention due to its simple chemical structure and diverse therapeutic potentials. Previous reviews describe the chemistry and biological activities of this phytoalexin, but additional coverage and greater accessibility are still needed. The current review provides a more comprehensive summary, covering research from 1955 to the present year. Oxyresveratrol occurs in both gymnosperms and angiosperms. However, it has never been reported in plants in the subclass Sympetalae, and this point might be of both chemotaxonomic and biosynthetic importance. Oxyresveratrol can be easily obtained from plant materials by conventional methods, and several systems for both qualitative and quantitative analysis of oxyresveratrol contents in plant materials and plant products are available. Oxyresveratrol possesses diverse biological and pharmacological activities such as the inhibition of tyrosinase and melanogenesis, antioxidant and anti-inflammatory activities, and protective effects against neurological disorders and digestive ailments. However, the unfavorable pharmacokinetic properties of oxyresveratrol, including low water solubility and poor oral availability and stability, have posed challenges to its development as a useful therapeutic agent. Recently, several delivery systems have emerged, with promising outcomes that may improve chances for the clinical study of oxyresveratrol.
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Affiliation(s)
- Kittisak Likhitwitayawuid
- Department of Pharmacognosy and Pharmaceutical Botany, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok 10330, Thailand
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Qiyusanlong Formula Induces Autophagy in Non-Small-Cell Lung Cancer Cells and Xenografts through the mTOR Signaling Pathway. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE 2021; 2021:5575453. [PMID: 34093717 PMCID: PMC8164545 DOI: 10.1155/2021/5575453] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 02/25/2021] [Revised: 04/01/2021] [Accepted: 04/16/2021] [Indexed: 11/30/2022]
Abstract
Objective Qiyusanlong (QYSL) formula has been used in the clinic for more than 20 years and has been proved to have pronounced efficacy in the treatment of non-small-cell lung cancer (NSCLC). This work aims to evaluate the molecular mechanism of QYSL formula action on NSCLC, specifically in relation to autophagy induction. Methods In vitro, CCK-8 was used to detect the effect of QYSL serum on cell viability in A549 cells. In vivo, A549 cells were implanted subcutaneously in nude mice to establish a xenograft model. TUNEL staining was used to measure cell apoptosis and TEM to observe the autophagy-related morphological changes in vitro and in vivo. Western blotting, RT-qPCR, and immunofluorescence were used to measure autophagy-related proteins. In addition, rapamycin (an inhibitor of mTOR and inducer of autophagy) and MHY1485 (an activator of mTOR and inhibitor of autophagy) were used to determine whether QYSL-induced autophagy was regulated by the mTOR pathway. Results QYSL serum inhibited the cell viability of A549 cells in a concentration‐dependent manner. In vivo, the QYSL formula inhibited xenograft growth. The QYSL formula promoted apoptosis in A549 cells and induced autophagosome formation in vitro and in vivo. In addition, the QYSL formula downregulated the expression of mTOR and p62, while it upregulated the expression of ATG-7 and Beclin-1 and increased the LC3-II/LC3-I ratio. QYSL serum inhibited p-mTOR in a similar manner to rapamycin while reducing the activating effects of MHY1485 on p-mTOR. Conclusion The QYSL formula has anti-lung cancer effects and promotes autophagy through the mTOR signaling pathway.
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Oxyresveratrol Ameliorates Dextran Sulfate Sodium-Induced Colitis in Rats by Suppressing Inflammation. Molecules 2021; 26:molecules26092630. [PMID: 33946346 PMCID: PMC8124641 DOI: 10.3390/molecules26092630] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/02/2021] [Revised: 04/28/2021] [Accepted: 04/28/2021] [Indexed: 12/13/2022] Open
Abstract
Colitis causes destruction of the intestinal mucus layer and increases intestinal inflammation. The use of antioxidants and anti-inflammatory agents derived from natural sources has been recently highlighted as a new approach for the treatment of colitis. Oxyresveratrol (OXY) is an antioxidant known to have various beneficial effects on human health, such as anti-inflammatory, antibacterial activity, and antiviral activity. The aim of this study was to investigate the therapeutic effect of OXY in rats with dextran sulfate sodium (DSS)-induced acute colitis. OXY ameliorated DSS-induced colitis and repaired damaged intestinal mucosa. OXY downregulated the expression of pro-inflammatory cytokine genes (TNF-α, IL-6, and IL-1β) and chemokine gene MCP-1, while promoting the production of anti-inflammatory cytokine IL-10. OXY treatment also suppressed inflammation via inhibiting cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) expression in the colon, as well as the activity of myeloperoxidase (MPO). OXY exhibited anti-apoptotic effects, shifting the Bax/Bcl-2 balance. In conclusion, OXY might improve DSS-induced colitis by restoring the intestinal mucus layer and reducing inflammation within the intestine.
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