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AbouSamra MM. Liposomal nano-carriers mediated targeting of liver disorders: mechanisms and applications. J Liposome Res 2024; 34:728-743. [PMID: 38988127 DOI: 10.1080/08982104.2024.2377085] [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: 04/18/2024] [Revised: 06/12/2024] [Accepted: 07/02/2024] [Indexed: 07/12/2024]
Abstract
Liver disorders present a significant global health challenge, necessitating the exploration of innovative treatment modalities. Liposomal nanocarriers have emerged as promising candidates for targeted drug delivery to the liver. This review offers a comprehensive examination of the mechanisms and applications of liposomal nanocarriers in addressing various liver disorders. Firstly discussing the liver disorders and the conventional treatment approaches, the review delves into the liposomal structure and composition. Moreover, it tackles the different mechanisms of liposomal targeting including both passive and active strategies. After that, the review moves on to explore the therapeutic potentials of liposomal nanocarriers in treating liver cirrhosis, fibrosis, viral hepatitis, and hepatocellular carcinoma. Through discussing recent advancements and envisioning future perspectives, this review highlights the role of liposomal nanocarriers in enhancing the effectiveness and the safety of liver disorders and consequently improving patient outcomes and enhances life quality.
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Affiliation(s)
- Mona M AbouSamra
- Pharmaceutical Technology Department, National Research Centre, Giza, Egypt
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Zhang Z, Chang R, Yue Q, Liu B, Li Z, Yuan Y, Liang S, Li Y. Nanoparticle delivery systems of functional substances for precision nutrition. ADVANCES IN FOOD AND NUTRITION RESEARCH 2024; 112:51-88. [PMID: 39218508 DOI: 10.1016/bs.afnr.2024.05.008] [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: 09/04/2024]
Abstract
Foodborne functional substances have received much attention for their functional benefits in health and disease. However, these substances are easily affected by the adverse environment during production, transportation, or storage. They will also be damaged by the gastric environment and limited by the mucosal barrier after entering the human body, thus affecting the bioavailability of functional substances in the body. The construction of nanoparticle delivery systems is helpful to protect the biological activity of functional substances and improve their solubility, stability, and absorption of substances. Responsive delivery systems help control the release of functional substances in specific environments and targeted sites to achieve nutritional intervention, disease prevention, and treatment. In this chapter, the main types of foodborne functional substances and their commonly used delivery systems were reviewed, and the application of delivery systems in precision nutrition was described from the aspects of environmental stimuli-responsive delivery systems, site-specific delivery systems, and disease-targeted delivery systems.
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Affiliation(s)
- Ziyi Zhang
- Research Center of Food Colloids and Delivery of Functionality, College of Food Science and Nutritional Engineering, China Agricultural University, Beijing, P.R. China
| | - Ruxin Chang
- Research Center of Food Colloids and Delivery of Functionality, College of Food Science and Nutritional Engineering, China Agricultural University, Beijing, P.R. China
| | - Qing Yue
- Research Center of Food Colloids and Delivery of Functionality, College of Food Science and Nutritional Engineering, China Agricultural University, Beijing, P.R. China
| | - Bin Liu
- Key Laboratory of Precision Nutrition and Food Quality, Department of Nutrition and Health, China Agricultural University, Beijing, P.R. China
| | - Zekun Li
- Research Center of Food Colloids and Delivery of Functionality, College of Food Science and Nutritional Engineering, China Agricultural University, Beijing, P.R. China
| | - Yu Yuan
- Research Center of Food Colloids and Delivery of Functionality, College of Food Science and Nutritional Engineering, China Agricultural University, Beijing, P.R. China
| | - Shuang Liang
- Key Laboratory of Precision Nutrition and Food Quality, Department of Nutrition and Health, China Agricultural University, Beijing, P.R. China
| | - Yuan Li
- Research Center of Food Colloids and Delivery of Functionality, College of Food Science and Nutritional Engineering, China Agricultural University, Beijing, P.R. China.
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Rani J, Dhull SB, Rose PK, Kidwai MK. Drug-induced liver injury and anti-hepatotoxic effect of herbal compounds: a metabolic mechanism perspective. PHYTOMEDICINE : INTERNATIONAL JOURNAL OF PHYTOTHERAPY AND PHYTOPHARMACOLOGY 2024; 122:155142. [PMID: 37913641 DOI: 10.1016/j.phymed.2023.155142] [Citation(s) in RCA: 4] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/29/2023] [Revised: 09/27/2023] [Accepted: 10/10/2023] [Indexed: 11/03/2023]
Abstract
BACKGROUND Drug-induced liver injury (DILI) is the most challenging and thought-provoking liver problem for hepatologists owing to unregulated medication usage in medical practices, nutritional supplements, and botanicals. Due to underreporting, analysis, and identification issues, clinically evaluated medication hepatotoxicity is prevalent yet hard to quantify. PURPOSE This review's primary objective is to thoroughly compare pharmaceutical drugs and herbal compounds that have undergone clinical trials, focusing on their metabolic mechanisms contributing to the onset of liver illnesses and their hepatoprotective effects. METHODS The data was gathered from several online sources, such as PubMed, Scopus, Google Scholar, and Web of Science, using appropriate keywords. RESULTS The prevalence of conventional and herbal medicine is rising. A comprehensive understanding of the metabolic mechanism is necessary to mitigate the hepatotoxicity induced by drugs and facilitate the incorporation or substitution of herbal medicine instead of pharmaceuticals. Moreover, pre-clinical pharmacological research has the potential to facilitate the development of natural products as therapeutic agents, displaying promising possibilities for their eventual clinical implementation. CONCLUSIONS Acetaminophen, isoniazid, rifampicin, diclofenac, and pyrogallol have been identified as the most often reported synthetic drugs that produce hepatotoxicity by oxidative stress, inflammation, apoptosis, and fibrosis during the last several decades. Due to their ability to downregulate many factors (such as cytokines) and activate several enzyme/enzyme systems, herbal substances (such as Gingko biloba extract, curcumin, resveratrol, and silymarin) provide superior protection against harmful mechanisms which induce hepatotoxicity with fewer adverse effects than their synthetic counterparts.
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Affiliation(s)
- Jyoti Rani
- Department of Botany, Chaudhary Devi Lal University, Sirsa 125055, Haryana, India
| | - Sanju Bala Dhull
- Department of Food Science and Technology, Chaudhary Devi Lal University, Sirsa 125055, Haryana, India.
| | - Pawan Kumar Rose
- Department of Energy and Environmental Sciences, Chaudhary Devi Lal University, Sirsa 125055, Haryana, India.
| | - Mohd Kashif Kidwai
- Department of Energy and Environmental Sciences, Chaudhary Devi Lal University, Sirsa 125055, Haryana, India
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Ergin AD, Uner B. Characterization, optimization, and in vitro evaluation of cholesterol-free liposomes. J Drug Deliv Sci Technol 2023; 84:104468. [DOI: 20.https:/doi.org/10.1016/j.jddst.2023.104468] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/30/2025]
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Gohari Mahmoudabad A, Gheybi F, Mehrabi M, Masoudi A, Mobasher Z, Vahedi H, Gharravi AM, Bitaraf FS, Rezayat Sorkhabadi SM. Synthesis, characterization and hepatoprotective effect of silymarin phytosome nanoparticles on ethanol-induced hepatotoxicity in rats. BIOIMPACTS : BI 2023; 13:301-311. [PMID: 37645028 PMCID: PMC10460772 DOI: 10.34172/bi.2023.24128] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/13/2021] [Revised: 06/25/2022] [Accepted: 09/13/2022] [Indexed: 08/31/2023]
Abstract
Introduction Silymarin proved to be a beneficial herbal medicine against many hepatic disorders such as alcoholic liver disease (ALD). However, its application is restricted due to its low bioavailability and consequently decreased efficacy. We herein used a nano-based approach known as "phytosome", to improve silymarin bioavailability and increase its efficacy. Methods Phytosome nanoparticles (NPs) were synthesized using thin film hydration method. NPs size, electrical charge, morphology, stability, molecular interaction, entrapment efficiency (EE %) and loading capacity (LC %) were determined. Moreover, in vitro toxicity of NPs was investigated on mesenchymal stem cells (MSCs) viability using MTT assay. In vivo experiments were performed using 24 adult rats that were divided into four groups including control, ethanol (EtOH) treatment, silymarin/EtOH treatment and silymarin phytosome/EtOH, with 6 mice in each group. Experimental groups were given 40% EtOH, silymarin (50 mg/kg) and silymarin phytosome (200 mg/kg) through the gastric gavage once a day for 3 weeks. Biochemical parameters, containing ALP, ALT, AST, GGT, GPx and MDA were measured before and after experiment to investigate the protective effect of silymarin and its phytosomal form. And histopathological examination was done to evaluate pathological changes. Results Silymarin phytosome NPs with the mean size of 100 nm were produced and were well tolerated in cell culture. These NPs showed a considerable protective effect against ALD through inverting the biochemical parameters (ALP, ALT, AST, GGT, GPx) and histopathological alterations. Conclusion Silymarin phytosomal NPs can be used as an efficient treatment for ALD.
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Affiliation(s)
- Arezoo Gohari Mahmoudabad
- Student Research Committee, School of Medicine, Shahroud University of Medical Sciences, Shahroud, Iran
- Department of Medical Nanotechnology, School of Medicine, Shahroud University of Medical Sciences, Shahroud, Iran
| | - Fatemeh Gheybi
- Department of Medical Biotechnology and Nanotechnology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Mohsen Mehrabi
- Department of Medical Nanotechnology, School of Medicine, Shahroud University of Medical Sciences, Shahroud, Iran
| | - Alireza Masoudi
- Department of Pharmacology, School of Medicine, Shahroud University of Medical Sciences, Shahroud, Iran
| | - Zeinab Mobasher
- Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences (TUMS), Tehran, Iran
| | - Hamid Vahedi
- Clinical Research Development Unit, Imam Hossein Hospital, Shahroud University of Medical Sciences, Shahroud, Iran
- Department of Gastroenterology, School of Medicine, Shahroud University of Medical Sciences, Shahroud, Iran
| | - Anneh Mohammad Gharravi
- Tissue Engineering and Stem Cell Research Center, Shahroud University of Medical Sciences, Shahroud, Iran
| | - Fatemeh Sadat Bitaraf
- Department of Medical Biotechnology, School of Medicine, Shahroud University of Medical Sciences, Shahroud, Iran
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Warner JB, Guenthner SC, Hardesty JE, McClain CJ, Warner DR, Kirpich IA. Liver-specific drug delivery platforms: Applications for the treatment of alcohol-associated liver disease. World J Gastroenterol 2022; 28:5280-5299. [PMID: 36185629 PMCID: PMC9521517 DOI: 10.3748/wjg.v28.i36.5280] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/24/2022] [Revised: 08/16/2022] [Accepted: 09/06/2022] [Indexed: 02/06/2023] Open
Abstract
Alcohol-associated liver disease (ALD) is a common chronic liver disease and major contributor to liver disease-related deaths worldwide. Despite its pre-valence, there are few effective pharmacological options for the severe stages of this disease. While much pre-clinical research attention is paid to drug development in ALD, many of these experimental therapeutics have limitations such as poor pharmacokinetics, poor efficacy, or off-target side effects due to systemic administration. One means of addressing these limitations is through liver-targeted drug delivery, which can be accomplished with different platforms including liposomes, polymeric nanoparticles, exosomes, bacteria, and adeno-associated viruses, among others. These platforms allow drugs to target the liver passively or actively, thereby reducing systemic circulation and increasing the ‘effective dose’ in the liver. While many studies, some clinical, have applied targeted delivery systems to other liver diseases such as viral hepatitis or hepatocellular carcinoma, only few have investigated their efficacy in ALD. This review provides basic information on these liver-targeting drug delivery platforms, including their benefits and limitations, and summarizes the current research efforts to apply them to the treatment of ALD in rodent models. We also discuss gaps in knowledge in the field, which when addressed, may help to increase the efficacy of novel therapies and better translate them to humans.
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Affiliation(s)
- Jeffrey Barr Warner
- Department of Medicine, Division of Gastroenterology, Hepatology and Nutrition, University of Louisville School of Medicine, Louisville, KY 40202, United States
- Department of Pharmacology and Toxicology, University of Louisville School of Medicine, Louisville, KY 40202, United States
| | - Steven Corrigan Guenthner
- Department of Medicine, Division of Gastroenterology, Hepatology and Nutrition, University of Louisville School of Medicine, Louisville, KY 40202, United States
| | - Josiah Everett Hardesty
- Department of Medicine, Division of Gastroenterology, Hepatology and Nutrition, University of Louisville School of Medicine, Louisville, KY 40202, United States
| | - Craig James McClain
- Department of Medicine, Division of Gastroenterology, Hepatology and Nutrition, University of Louisville School of Medicine, Louisville, KY 40202, United States
- Alcohol Research Center, University of Louisville School of Medicine, Louisville, KY 40202, United States
- Hepatobiology and Toxicology Center, University of Louisville School of Medicine, Louisville, KY 40202, United States
- Veterans Health Administration, Robley Rex Veterans Medical Center, Louisville, KY 40206, United States
| | - Dennis Ray Warner
- Department of Medicine, Division of Gastroenterology, Hepatology and Nutrition, University of Louisville School of Medicine, Louisville, KY 40202, United States
| | - Irina Andreyevna Kirpich
- Department of Medicine, Division of Gastroenterology, Hepatology and Nutrition, University of Louisville School of Medicine, Louisville, KY 40202, United States
- Department of Pharmacology and Toxicology, University of Louisville School of Medicine, Louisville, KY 40202, United States
- Alcohol Research Center, University of Louisville School of Medicine, Louisville, KY 40202, United States
- Hepatobiology and Toxicology Center, University of Louisville School of Medicine, Louisville, KY 40202, United States
- Department of Microbiology and Immunology, University of Louisville School of Medicine, Louisville, KY 40202, United States
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Németh Z, Csóka I, Semnani Jazani R, Sipos B, Haspel H, Kozma G, Kónya Z, Dobó DG. Quality by Design-Driven Zeta Potential Optimisation Study of Liposomes with Charge Imparting Membrane Additives. Pharmaceutics 2022; 14:1798. [PMID: 36145546 PMCID: PMC9503861 DOI: 10.3390/pharmaceutics14091798] [Citation(s) in RCA: 81] [Impact Index Per Article: 27.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/20/2022] [Revised: 08/23/2022] [Accepted: 08/24/2022] [Indexed: 11/17/2022] Open
Abstract
Liposomal formulations, as versatile nanocarrier systems suitable for targeted delivery, have a highly focused role in the therapy development of unmet clinical needs and diagnostic imaging techniques. Formulating nanomedicine with suitable zeta potential is an essential but challenging task. Formulations with a minimum ±30 mV zeta potential are considered stable. The charge of the phospholipid bilayer can be adjusted with membrane additives. The present Quality by Design-derived study aimed to optimise liposomal formulations prepared via the thin-film hydration technique by applying stearylamine (SA) or dicetyl phosphate (DCP) as charge imparting agents. This 32 fractional factorial design-based study determined phosphatidylcholine, cholesterol, and SA/DCP molar ratios for liposomes with characteristics meeting the formulation requirements. The polynomials describing the effects on the zeta potential were calculated. The optimal molar ratios of the lipids were given as 12.0:5.0:5.0 for the SA-PBS pH 5.6 (optimised sample containing stearylamine) and 8.5:4.5:6.5 for the DCP-PBS pH 5.6 (optimised sample containing dicetyl phosphate) particles hydrated with phosphate-buffered saline pH 5.6. The SA-PBS pH 5.6 liposomes had a vesicle size of 108 ± 15 nm, 0.20 ± 0.04 polydispersity index, and +30.1 ± 1.2 mV zeta potential, while these values were given as 88 ± 14 nm, 0.21 ± 0.02, and -36.7 ± 3.3 mV for the DCP-PBS pH 5.6 vesicles. The prepared liposomes acquired the requirements of the zeta potential for stable formulations.
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Affiliation(s)
- Zsófia Németh
- Faculty of Pharmacy, Institute of Pharmaceutical Technology and Regulatory Affairs, University of Szeged, 6, Eötvös Street, H-6720 Szeged, Hungary
| | - Ildikó Csóka
- Faculty of Pharmacy, Institute of Pharmaceutical Technology and Regulatory Affairs, University of Szeged, 6, Eötvös Street, H-6720 Szeged, Hungary
| | - Reza Semnani Jazani
- Faculty of Pharmacy, Institute of Pharmaceutical Technology and Regulatory Affairs, University of Szeged, 6, Eötvös Street, H-6720 Szeged, Hungary
| | - Bence Sipos
- Faculty of Pharmacy, Institute of Pharmaceutical Technology and Regulatory Affairs, University of Szeged, 6, Eötvös Street, H-6720 Szeged, Hungary
| | - Henrik Haspel
- Department of Applied and Environmental Chemistry, Faculty of Science and Informatics, Institute of Chemistry, University of Szeged, 1, Rerrich Béla Sqare, H-6720 Szeged, Hungary
| | - Gábor Kozma
- Department of Applied and Environmental Chemistry, Faculty of Science and Informatics, Institute of Chemistry, University of Szeged, 1, Rerrich Béla Sqare, H-6720 Szeged, Hungary
| | - Zoltán Kónya
- Department of Applied and Environmental Chemistry, Faculty of Science and Informatics, Institute of Chemistry, University of Szeged, 1, Rerrich Béla Sqare, H-6720 Szeged, Hungary
| | - Dorina Gabriella Dobó
- Faculty of Pharmacy, Institute of Pharmaceutical Technology and Regulatory Affairs, University of Szeged, 6, Eötvös Street, H-6720 Szeged, Hungary
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Mao J, Zhan H, Meng F, Wang G, Huang D, Liao Z, Chen M. Costunolide protects against alcohol-induced liver injury by regulating gut microbiota, oxidative stress and attenuating inflammation in vivo and in vitro. Phytother Res 2022; 36:1268-1283. [PMID: 35084790 DOI: 10.1002/ptr.7383] [Citation(s) in RCA: 24] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/23/2021] [Revised: 12/14/2021] [Accepted: 12/29/2021] [Indexed: 12/17/2022]
Abstract
Costunolide (cos) derived from the roots of Dolomiaea souliei (Franch.), which belongs to the Dolomiaea genus in the family Compositae, exert the anti-inebriation effect mainly by inhibiting the absorption of alcohol in the gastrointestinal tract. However, the protective effect of cos against alcohol-induced liver injury (ALI) remains obscure. The present study was aimed to evaluate the hepatoprotective effects of cos (silymarin was used as positive control) against ALI and its potential mechanisms. MTT was used to examine the effect of cos on the cell viability of L-02 cells. Plasma was separated from blood that used to test the levels of TNF-α, IL-6 and IL-12, and LPS while serum separated from blood which used to detect the level of ALT and AST. Liver tissues were obtained for histopathological examination and western blot analysis. Fresh mice feces samples were collected for the detection of bacterial composition. Cos exhibited protective effect against alcoholic-induced liver injury by regulating gut microbiota capacities (higher relative abundance of Firmicutes and Actinobacteria while lower in Bacteroidetes and Proteobacteria), adjusting oxidative stress (reduced the activities of MDA and ROS while promoted SOD, GSH and GSH-PX in L-02 cells) and attenuating inflammation (decreased the levels of ALT, AST, LPS, IL-6, IL-12 and TNF-α) via LPS-TLR4-NF-κB p65 signaling pathway, which might be an active therapeutic agent for treatment of ALI.
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Affiliation(s)
- Jingxin Mao
- College of Pharmaceutical Sciences, Southwest University, Chongqing, China
| | - Honghong Zhan
- College of Pharmaceutical Sciences, Southwest University, Chongqing, China
| | - Fancheng Meng
- College of Pharmaceutical Sciences, Southwest University, Chongqing, China
| | - Guowei Wang
- College of Pharmaceutical Sciences, Southwest University, Chongqing, China
| | - Dan Huang
- College of Pharmaceutical Sciences, Southwest University, Chongqing, China
| | - Zhihua Liao
- School of Life Sciences, Southwest University, Chongqing, China
| | - Min Chen
- College of Pharmaceutical Sciences, Southwest University, Chongqing, China
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Islam A, Mishra A, Siddiqui MA, Siddiquie S. Recapitulation of Evidence of Phytochemical, Pharmacokinetic and Biomedical Application of Silybin. Drug Res (Stuttg) 2021; 71:489-503. [PMID: 34318464 DOI: 10.1055/a-1528-2721] [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: 10/20/2022]
Abstract
Silymarin is a standardized extract obtained from seeds of Silybum marianum (SM) belonging to the family Asteraceae. It is a flavonolignan complex and consists of various compounds like silybin A silybin B, isosilybin A, isosilybin B, silydianin, silychristin and isosilychristin. Silybin is the major active component present in 60-70% of the silymarin extract. It has been used traditionally for the treatment of various liver disorders like cirrhosis, jaundice, and hepatitis. Silymarin possesses antioxidant and anti-inflammatory properties and is responsible for its antitumor activity. Other than hepatoprotective effect SM also possesses renoprotective, anti-diabetic, neuroprotective, hypolipidemic, anti-atherosclerosis and cardioprotective effects. Rather antimicrobial property of silymarin was observed against specific microbes, fungi, and viruses. This manuscript covered recent preclinical and clinical evidence of specific components silybin, responsible for its efficacy and about clinical studies has been conducted so far, which proven it's safety and offers mild effect like nausea, diarrhea and bloating. This review specifically focused on recent updates on its active components therapeutic applications against complicated ailments not covered in earlier reports.
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Affiliation(s)
- Anas Islam
- Faculty of Pharmacy, Integral University, Lucknow, Uttar Pradesh, India
| | - Anuradha Mishra
- Faculty of Pharmacy, Integral University, Lucknow, Uttar Pradesh, India
| | - Md Aftab Siddiqui
- Faculty of Pharmacy, Integral University, Lucknow, Uttar Pradesh, India
| | - Saman Siddiquie
- Faculty of Pharmacy, Integral University, Lucknow, Uttar Pradesh, India
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Xiao F, Gao F, Zhou S, Wang L. The therapeutic effects of silymarin for patients with glucose/lipid metabolic dysfunction: A meta-analysis. Medicine (Baltimore) 2020; 99:e22249. [PMID: 33019400 PMCID: PMC7535778 DOI: 10.1097/md.0000000000022249] [Citation(s) in RCA: 22] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/19/2022] Open
Abstract
BACKGROUND To comprehensively evaluate the treatment efficacy and safety of silymarin for patients with glucose/lipid metabolic dysfunction using a meta-analysis. METHODS A systematic literature search in PubMed, EMBASE and Cochrane Library databases was performed up to October 1, 2019. STATA 13.0 software was used to estimate pooled standardized mean difference (SMD) and 95% confidence interval (95% CI). RESULTS Sixteen studies involving 1358 patients were identified. Overall meta-analysis showed that compared with control, silymarin significantly reduced levels of fasting blood glucose (SMD: -1.27, 95% CI = [-1.78, -0.76]; P < .001), homeostatic model assessment for insulin resistance (SMD: -0.41, 95% CI = [-0.70, -0.12]; P = .005), hemoglobin A1c (SMD: -1.88, 95% CI = [-2.57, -1.20]; P < .001), total cholesterol (SMD: -1.13, 95% CI = [-1.82, -0.77]; P < .001), triglyceride (SMD: -0.37, 95% CI = [-0.69, -0.05]; P = .025), low-density lipoprotein-cholesterol (SMD: -1.30, 95% CI = [-1.93, -0.67]; P < .001), C-reactive protein (SMD: -0.63, 95% CI = [-1.01, -0.27]; P = .001), and increased high-density lipoprotein-cholesterol (SMD: 0.17, 95% CI = [0.05, 0.29]; P = .005), but had no impacts on function indicators of liver and kidney (alanine transaminase, aspartate aminotransferase, creatinine phosphokinase, creatinine) and the complication rate. Subgroup analyses indicated that insulin (which was negative in overall analysis) was significantly decreased in patients undergoing silymarin monotherapy (SMD: -2.03, 95% CI = [-3.03, -1.04]; P = .044) for more than 3 months (SMD: -0.01, 95% CI = [-0.25, -0.24]; P = .035). CONCLUSION Supplementation of silymarin may be effective and safe for the management of diabetes mellitus and hyperlipidemia.
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Affiliation(s)
- Fengyan Xiao
- College of Chinese Medicine, Jilin Agricultural Science and Technology College, Jilin City
| | - Feng Gao
- College of Chinese Medicine, Jilin Agricultural Science and Technology College, Jilin City
- YanBian Han Gong Fang Health Products Limited Company, YanBian City
| | - Shengxue Zhou
- College of Chinese Medicine, Jilin Agricultural Science and Technology College, Jilin City
| | - Lina Wang
- School of Pharmacy, Jilin Pharmaceutical College, Jilin City, Jilin Province, China
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Rai A, Gill M, Kinra M, Shetty R, Krishnadas N, Rao CM, Sumalatha S, Kumar N. Catechin ameliorates depressive symptoms in Sprague Dawley rats subjected to chronic unpredictable mild stress by decreasing oxidative stress. Biomed Rep 2019; 11:79-84. [PMID: 31338194 DOI: 10.3892/br.2019.1226] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/08/2019] [Accepted: 06/10/2019] [Indexed: 12/13/2022] Open
Abstract
Catechin is an active ingredient of green tea. It is reported to inhibit corticosteroid-induced anxiety and depression-like symptoms. Considering the complex nature of depression, effects of catechin need to be studied in a clinically relevant depression model. The present study was designed to explore the antidepressant effect of catechin in Sprague Dawley rats subjected to chronic unpredictable mild stress (CUMS). Animals were subjected to CUMS and treated with (+)-catechin (50 mg/kg) or escitalopram (10 mg/kg) orally; a CUMS control and a vehicle control that was not exposed to CUMS were also established. Various stressors were applied daily in an unpredictable manner for 8 weeks achieve CUMS. Sucrose preference test were performed after 4 and 8 weeks and forced swim tests (FSTs) were conducted at weeks 4, 6 and 8. At the end of week 8, animals were sacrificed and the brain homogenate was studied for antioxidant parameters. Compared with the vehicle control, animals of the CUMS control group showed a significant decrease in sucrose intake. Catechin and escitalopram treatment significantly improved the sucrose intake compared with the CUMS control. A similar trend was observed in the FSTs, where catechin and escitalopram treatment significantly reduced the immobility time, and antioxidant parameters, including catalase, glutathione and superoxide dismutase levels were recovered in treated animals compared with the CUMS control. Thus, it was concluded that catechin reverses CUMS-induced depression in rats by ameliorating oxidative stress, which may help to develop a novel treatment for major depressive disorder.
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Affiliation(s)
- Amita Rai
- Department of Pharmacology, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal, Karnataka 576104, India.,Ecron Acunova Ltd., Manipal, Karnataka 576104, India
| | - Meghna Gill
- Department of Pharmacology, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal, Karnataka 576104, India
| | - Manas Kinra
- Department of Pharmacology, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal, Karnataka 576104, India
| | | | - Nandakumar Krishnadas
- Department of Pharmacology, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal, Karnataka 576104, India
| | - C Mallikarjuna Rao
- Department of Pharmacology, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal, Karnataka 576104, India
| | - Suhani Sumalatha
- Department of Anatomy, Kasturba Medical College, Manipal Academy of Higher Education, Manipal, Karnataka 576104, India
| | - Nitesh Kumar
- Department of Pharmacology, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal, Karnataka 576104, India
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