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Kaushik H, Sharma R, Kumar A. Natural products against resistant bacterial infections: A systematic literature review. THE MICROBE 2025; 6:100247. [DOI: 10.1016/j.microb.2025.100247] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 03/04/2025]
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Banjan B, Raju R, Keshava Prasad TS, Abhinand CS. Computational identification of potential bioactive compounds from Triphala against alcoholic liver injury by targeting alcohol dehydrogenase. Mol Divers 2025; 29:623-638. [PMID: 38743308 DOI: 10.1007/s11030-024-10879-9] [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: 03/14/2024] [Accepted: 04/15/2024] [Indexed: 05/16/2024]
Abstract
Alcoholic liver injury resulting from excessive alcohol consumption is a significant social concern. Alcohol dehydrogenase (ADH) plays a critical role in the conversion of alcohol to acetaldehyde, leading to tissue damage. The management of alcoholic liver injury encompasses nutritional support and, in severe cases liver transplantation, but potential adverse effects exist, and effective medications are currently unavailable. Natural products with their potential benefits and historical use in traditional medicine emerge as promising alternatives. Triphala, a traditional polyherbal formula demonstrates beneficial effects in addressing diverse health concerns, with a notable impact on treating alcoholic liver damage through enhanced liver metabolism. The present study aims to identify potential active phytocompounds in Triphala targeting ADH to prevent alcoholic liver injury. Screening 119 phytocompounds from the Triphala formulation revealed 62 of them showing binding affinity to the active site of the ADH1B protein. Promising lipid-like molecule from Terminalia bellirica, (4aS, 6aR, 6aR, 6bR, 7R, 8aR, 9R, 10R, 11R, 12aR, 14bS)-7, 10, 11-trihydroxy-9-(hydroxymethyl)-2, 2, 6a, 6b, 9, 12a-hexamethyl-1, 3, 4, 5, 6, 6a, 7, 8, 8a, 10, 11, 12, 13, 14b-tetradecahydropicene-4a-carboxylic acid showed high binding efficiency to a competitive ADH inhibitor, 4-Methylpyrazole. Pharmacokinetic analysis further confirmed the drug-likeness and non-hepatotoxicity of the top-ranked compound. Molecular dynamics simulation and MM-PBSA studies revealed the stability of the docked complexes with minimal fluctuation and consistency of the hydrogen bonds throughout the simulation. Together, computational investigations suggest that (4aS, 6aR, 6aR, 6bR, 7R, 8aR, 9R, 10R, 11R, 12aR, 14bS)-7, 10, 11-trihydroxy-9-(hydroxymethyl)-2, 2, 6a, 6b, 9, 12a-hexamethyl-1, 3, 4, 5, 6, 6a, 7, 8, 8a, 10, 11, 12, 13, 14b-tetradecahydropicene-4a-carboxylic acid from the Triphala formulation holds promise as an ADH inhibitor, suggesting an alternative therapy for alcoholic liver injury.
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Affiliation(s)
- Bhavya Banjan
- Centre for Integrative Omics Data Science, Yenepoya (Deemed to be University), Mangalore, 575018, India
| | - Rajesh Raju
- Centre for Integrative Omics Data Science, Yenepoya (Deemed to be University), Mangalore, 575018, India
| | - Thottethodi Subrahmanya Keshava Prasad
- Center for Systems Biology and Molecular Medicine (CSBMM), Yenepoya Research Centre, Yenepoya (Deemed to be University), Deralakatte, Mangalore, Karnataka, 575018, India
| | - Chandran S Abhinand
- Center for Systems Biology and Molecular Medicine (CSBMM), Yenepoya Research Centre, Yenepoya (Deemed to be University), Deralakatte, Mangalore, Karnataka, 575018, India.
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Neelab, Zeb A, Jamil M. Milk thistle protects against non-alcoholic fatty liver disease induced by dietary thermally oxidized tallow. Heliyon 2024; 10:e31445. [PMID: 38818175 PMCID: PMC11137523 DOI: 10.1016/j.heliyon.2024.e31445] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/09/2024] [Revised: 05/10/2024] [Accepted: 05/15/2024] [Indexed: 06/01/2024] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD) is a chronic condition caused by several factors including thermally oxidized tallow. Various strategies have been considered to ameliorate NAFLD. However, the role of milk thistle (MT) in ameliorating NAFLD caused by thermally oxidized tallow has not been reported. The purpose of this study was to evaluate the ability of milk thistle to protect rabbits from the toxicity of oxidized tallow (OT). The rabbits were given OT and an extract of MT. The composition of MT was analyzed using HPLC-DAD, and tallow samples were studied using GC-MS. The study also examined liver histology, antioxidant levels, liver-related inflammatory markers, and serum lipid profile. The results showed that the major components of the MT extract were silybin B, formononetin-glucuronic acid, proanthocyanidin B1, silychristin B, silydianin, and isosilybin A. The group given OT showed elevated lipid profiles, lower antioxidant status, higher levels of hepatic inflammatory markers, and lower levels of anti-inflammatory markers. This group also had higher fat storage in the liver compared to the control or treatment groups. However, when MT was supplemented, the pro-inflammatory cytokines (IL-1, IL-4, IL-6, and TNF-α) and antioxidant status (CAT, SOD, GSH-Px, GSH, and TBARS) of the liver returned to normal. This suggests that MT extract is an excellent source of hepatoprotective compounds. It protects the liver by increasing antioxidant enzymes, decreasing pro-inflammatory cytokines, and increasing anti-inflammatory markers.
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Affiliation(s)
- Neelab
- Department of Biotechnology, University of Malakand, Chakdara, Pakistan
| | - Alam Zeb
- The Bioactive Lab, Center for Desert Agriculture, King Abdullah University of Science and Technology, Thuwal, Kingdom of Saudi Arabia
- Department of Biochemistry, University of Malakand, Chakdara, Pakistan
| | - Muhammad Jamil
- Department of Surgery, Timergara Teaching Hospital, Timergara, Pakistan
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Barreiro Carpio M, Valdes-Pena MA, Molina DA, Espinoza Cabello SEJ, Sialer Guerrero CA, Cribillero G, Vargas Coca KF, Icochea E. Evaluation of commercial doses of a feed additive and silymarin on broiler performance with and without CCl 4-induced liver damage. Poult Sci 2024; 103:103567. [PMID: 38417302 PMCID: PMC10909905 DOI: 10.1016/j.psj.2024.103567] [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: 11/27/2023] [Revised: 02/07/2024] [Accepted: 02/14/2024] [Indexed: 03/01/2024] Open
Abstract
Improving productive performance is a daily challenge in the poultry industry. Developing cost-effective additives and strategies that improve performance in antibiotic-free poultry production is critical to maintaining productivity and efficiency. This study evaluates the influence of a commercially available phytogenic feed additive (CA-PFA, that comprises silymarin, betaine and curcumin extracts as main ingredients) and silymarin on commercial broilers' productive performance and liver function with and without carbon tetrachloride (CCl4)-induced liver damage. The experiment was conducted in a completely randomized design, with six treatments, eight replicates, and eight birds per replicate in 18 one-day-old male broilers (Cobb Vantress 500) each; under a 3 × 2 factorial arrangement (3 diets x 2 levels of CCl4, 0 and 1 mL/kg body weight orally). The experimental treatments included 3 diets, commercially recommended doses of CA-PFA (500 mg/kg of feed; this dose provides 70 mg/kg of silymarin, besides the other active ingredients included in the formulation), silymarin (250 mg/kg of feed, containing 28% of active ingredient; this dose provides 70 mg/kg of silymarin as active ingredient) and an additive-free basal diet as a control. A standard commercial silymarin was used as a reference due to its well-known and extensively studied hepatoprotective properties that can mitigate the negative effects of CCl4 in the liver. The data were analyzed as a 2-way ANOVA, and the means showing significant (P ≤ 0.05) differences were then compared using the Post-Hoc Tukey HSD test. No interaction was detected between factors. Exposure to CCl4 had a noticeable detrimental effect on alertness, productive performance, and liver function of broilers without a significant increase in mortality. Including CA-PFA in the diet improved productive performance compared to the basal diet from day 21 to the end of the trial, on day 42. While no influence in feed intake was detected for any treatment, CA-PFA improved body weight gain (BWG) and feed conversion ratio (FCR) significantly (P < 0.05) from day 21 to the end of the trial in healthy and CCl4-exposed birds. The results show that CA-PFA supplementation improves performance parameters in broilers with and without CCl4-induced liver damage, when compared to a basal diet and the addition of a standard commercial silymarin product.
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Affiliation(s)
- Mabel Barreiro Carpio
- R&D Department, Ilender Perú S.A., Lima, Peru; Department of Chemistry, NC State University, Raleigh, NC.
| | - M Alejandro Valdes-Pena
- R&D Department, Ilender Perú S.A., Lima, Peru; Department of Chemistry, NC State University, Raleigh, NC
| | | | | | | | - Giovanna Cribillero
- School of Veterinary Medicine, Universidad Nacional Mayor de San Marcos, San Borja, Lima, Peru; Department of Poultry Science, Mississippi State University, Mississippi State, MS
| | - Katherine F Vargas Coca
- School of Veterinary Medicine, Universidad Nacional Mayor de San Marcos, San Borja, Lima, Peru
| | - Eliana Icochea
- School of Veterinary Medicine, Universidad Nacional Mayor de San Marcos, San Borja, Lima, Peru
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Atteia HH. A combination of silymarin and garlic extract enhances thyroid hormone activation and body metabolism in orally intoxicated male rats with atrazine: Impact on hepatic iodothyronine deiodinase type 1. PESTICIDE BIOCHEMISTRY AND PHYSIOLOGY 2024; 199:105801. [PMID: 38458692 DOI: 10.1016/j.pestbp.2024.105801] [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: 09/18/2023] [Revised: 12/31/2023] [Accepted: 01/19/2024] [Indexed: 03/10/2024]
Abstract
Atrazine is a widely applied herbicide to improve crop yield and maintain general health. It has been reported to impair thyroid function and architecture in experimental animals. Alterations in thyroid hormones disrupt normal body function and metabolism. Silymarin, a hepatoprotective flavonolignan, was found to improve thyroid function and body metabolism. Additionally, garlic displays several protective effects on body organs. Therefore, this study explored the prophylactic impact of natural compounds comprising silymarin and garlic extract on disrupted thyroid function, hepatic iodothyronine deiodinase type 1, and metabolic parameters in atrazine-intoxicated male rats. We found that daily pre- and co-treatment of atrazine-intoxicated male rats with silymarin (100 mg/kg, p.o) and/or garlic extract (10 mg/kg, p.o) significantly improved thyroid activation and hepatic functionality as evidenced by the re-establishment of T3, T3/T4, and TSH values as well as ALT and AST activities. Interestingly, individual or concurrent supplementation of the atrazine group with silymarin and garlic extract prevented the down-regulation in hepatic iodothyronine deiodinase type 1. These effects were coupled with the repletion of serum and hepatic antioxidants and the amelioration of lipid peroxidation. In addition, current natural products markedly alleviated weight gain, dyslipidemia, hyperglycemia, glucose intolerance, and insulin resistance. Notably, a cocktail of silymarin and garlic extract exerted superior protection against atrazine-triggered deterioration of thyroid, hepatic, and metabolic functioning to individual treatments. Present findings pinpoint the prophylactic and synergistic influence of silymarin and garlic extract combinatorial regimen on thyroid activation and body metabolism via enhancing antioxidant potential, maintaining hepatic function, and iodothyronine deiodinase type 1.
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Affiliation(s)
- Hebatallah Husseini Atteia
- Department of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Tabuk, Tabuk, Saudi Arabia; Department of Biochemistry, Faculty of Pharmacy, Zagazig University, 44519 Zagazig, Sharkia Gov., Egypt.
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Li Y, Yang X, Bao T, Sun X, Li X, Zhu H, Zhang B, Ma T. Radix Astragali decoction improves liver regeneration by upregulating hepatic expression of aquaporin-9. PHYTOMEDICINE : INTERNATIONAL JOURNAL OF PHYTOTHERAPY AND PHYTOPHARMACOLOGY 2024; 122:155166. [PMID: 37918281 DOI: 10.1016/j.phymed.2023.155166] [Citation(s) in RCA: 6] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/17/2023] [Revised: 10/09/2023] [Accepted: 10/24/2023] [Indexed: 11/04/2023]
Abstract
BACKGROUND The therapeutic efficacy of liver injuries heavily relies on the liver's remarkable regenerative capacity, necessitating the maintenance of glycose/lipids homeostasis and oxidative eustasis during the recovery process. Astragali Radix, an herbal tonic widely used in China and many other countries, is believed to have many positive effects, including immune stimulation, nourishing, antioxidant, liver protection, diuresis, anti-diabetes, anti-cancer and expectorant. Astragali Radix is widely integrated into hepatoprotective formulas as it is believed to facilitate liver regeneration. Nevertheless, the precise molecular pharmacological mechanisms underlying this hepatoprotective effect remain elusive. PURPOSE To investigate the improving effects of Astragali Radix on liver regeneration and the underlying mechanisms. METHODS A mouse model of 70% partial hepatectomy (PHx) was employed to investigate the impact of Radix Astragali decoction (HQD) on liver regeneration. HQD was orally administered for 7 days before the PHx procedure and throughout the experiment. N-acetylcysteine (NAC) was used as a positive control for liver regeneration. Liver regeneration was assessed by evaluating the liver-to-body weight ratio (LW/BW) and the expression of representative cell proliferation marker proteins. Oxidative stress and glucose metabolism were analyzed using biochemical assays, Western blotting, dihydroethidium (DHE) fluorescence, and periodic acid-Schiff (PAS) staining methods. To understand the role of AQP9 as a potential molecular target of HQD in promoting liver regeneration, td-Tomato-tagged AQP9 transgenic mice (AQP9-RFP) were employed to determine the expression pattern of AQP9 protein. AQP9 knockout mice (AQP9-/-) were used to assess the specific targeting of AQP9 in the promotion of liver regeneration by HQD. RESULTS HQD significantly upregulated hepatic AQP9 expression, alleviated liver injury and promoted liver regeneration in wild-type (AQP9+/+) mice after 70% PHx. However, the beneficial impact of HQD on liver regeneration was absent in AQP9 gene knockout (AQP9-/-) mice. Moreover, HQD facilitated the uptake of glycerol by hepatocytes, enhanced gluconeogenesis, and concurrently reduced H2O2 content and oxidative stress levels in AQP9+/+ but not AQP9-/- mouse livers. Additionally, main active substance of Radix Astragali, astragaloside IV (AS-IV) and cycloastragenol (CAG), demonstrated substantial upregulation of AQP9 expression and promoted liver regeneration in AQP9+/+ but not AQP9-/- mice. CONCLUSION This study is the first to demonstrate that Radix Astragali and its main active constituents (AS-IV and CAG) improve liver regeneration by upregulating the expression of AQP9 in hepatocytes to increase gluconeogenesis and reduce oxidative stress. The study revealed novel molecular pharmacological mechanisms of Radix Astragali and provided a promising therapeutic target of liver diseases.
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Affiliation(s)
- Yanghao Li
- School of Medicine & Holistic Integrative Medicine, Department of Pathology and Pathophysiology, Nanjing University of Chinese Medicine, Xianlin Avenue 138, Nanjing, Jiangsu 210023, China
| | - Xu Yang
- School of Medicine & Holistic Integrative Medicine, Department of Pathology and Pathophysiology, Nanjing University of Chinese Medicine, Xianlin Avenue 138, Nanjing, Jiangsu 210023, China
| | - Tiantian Bao
- School of Medicine & Holistic Integrative Medicine, Department of Pathology and Pathophysiology, Nanjing University of Chinese Medicine, Xianlin Avenue 138, Nanjing, Jiangsu 210023, China
| | - Xiaojuan Sun
- School of Medicine & Holistic Integrative Medicine, Department of Pathology and Pathophysiology, Nanjing University of Chinese Medicine, Xianlin Avenue 138, Nanjing, Jiangsu 210023, China
| | - Xiang Li
- School of Medicine & Holistic Integrative Medicine, Department of Pathology and Pathophysiology, Nanjing University of Chinese Medicine, Xianlin Avenue 138, Nanjing, Jiangsu 210023, China
| | - Huilin Zhu
- School of Medicine & Holistic Integrative Medicine, Department of Pathology and Pathophysiology, Nanjing University of Chinese Medicine, Xianlin Avenue 138, Nanjing, Jiangsu 210023, China
| | - Bo Zhang
- School of Medicine & Holistic Integrative Medicine, Department of Pathology and Pathophysiology, Nanjing University of Chinese Medicine, Xianlin Avenue 138, Nanjing, Jiangsu 210023, China.
| | - Tonghui Ma
- School of Medicine & Holistic Integrative Medicine, Department of Pathology and Pathophysiology, Nanjing University of Chinese Medicine, Xianlin Avenue 138, Nanjing, Jiangsu 210023, China.
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Upadhyay R, Tiwari KN. The antiviral potential of Phyllanthus species: a systematic review. Arch Virol 2023; 168:177. [PMID: 37310509 DOI: 10.1007/s00705-023-05802-w] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Grants] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/11/2023] [Accepted: 04/17/2023] [Indexed: 06/14/2023]
Abstract
Viral infections and diseases caused by viruses are worldwide problems. According to a WHO report, three to five million people are chronically infected with hepatitis B virus (HBV), hepatitis C virus (HCV), and human immunodeficiency virus (HIV) each year globally. Since some viruses mutate very quickly, developing antiviral drugs can be a daunting task. Moreover, currently used synthetic drugs are toxic and associated with side effects. Therefore, there is a need to search for alternative natural remedies that have low toxicity, a new mechanism of action, and no major side effects. Phyllanthus plants have traditionally been used to treat viral hepatitis and liver damage in many tropical and subtropical countries worldwide. In this review, we discuss the therapeutic potential of Phyllanthus spp. against HBV, HCV, HIV, herpes simplex virus, and SARS-CoV-2. The inferences from in vitro and in vivo studies and clinical trials validate the use of Phyllanthus in antiviral remedies.
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Affiliation(s)
- Richa Upadhyay
- Department of Botany, Mihir Bhoj PG College, Dadri, G.B. Nagar, 203207, Uttar Pradesh, India
| | - Kavindra Nath Tiwari
- Department of Botany, MMV, Banaras Hindu University, Varanasi, 221005, Uttar Pradesh, India.
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Hsouna AB, Sadaka C, Beyrouthy ME, Hfaiedh M, Dhifi W, Brini F, Saad RB, Mnif W. Immunomodulatory effect of Linalool (Lin) against CCl 4 -induced hepatotoxicity and oxidative damage in rats. Biotechnol Appl Biochem 2023; 70:469-477. [PMID: 35748559 DOI: 10.1002/bab.2371] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/22/2021] [Accepted: 05/01/2022] [Indexed: 11/11/2022]
Abstract
The current study explored the hepatoprotective and immunomodulatory effects of Linalool (Lin) against carbon tetrachloride (CCl4 )-induced toxicity in mice. Four study groups (n = 8 each) were used: (1) a negative control group and (2) a toxicity control group (single dose of CCl4 administered on day 14 as 1 mL/kg of CCL4 in 1% olive oil). Intraperitoneally (i.p.)), and two experimental groups where mice were treated with either (3) Lin (25 mg/kg b.w., orally, daily for 15 days) or (4) pretreated with Lin (25 mg/kg b.w., orally, daily for 14 days) and intoxicated with CCl4 (1 mL/kg of CCL4 in 1% olive oil. i.p.) on day 14. The levels of the anti-inflammatory cytokine interleukin 10 (IL-10), the proinflammatory cytokines TNF-α, IL-6, and TGF-1β, and the histopathology of the liver were assessed. According to our findings, IL-10 concentrations were significantly increased in Lin-treated groups, while other cytokine levels were marked by a considerable decrease in the toxicity model group (CCl4 -treated group). Histopathological examinations of liver tissues showed that the Lin-treated groups had an almost normal structure. The current findings showed that Lin could inhibit CCl4 -induced liver injury in mice, which warrants further investigation of Lin as a potential protective and therapeutic agent against hepatotoxicity.
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Affiliation(s)
- Anis Ben Hsouna
- Department of Life Sciences, Faculty of Sciences of Gafsa, Gafsa, Tunisia.,Laboratory of Biotechnology and Plant Improvement, Centre of Biotechnology of Sfax, Sfax, Tunisia
| | - Carmen Sadaka
- Department of Infectious Diseases, Infection Control, and Employee Health, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
| | | | - Mbarka Hfaiedh
- Research Unit of Active Biomolecules Valorisation, Higher Institute of Applied Biology of Medicine, University of Gabes, Medenine, Tunisia
| | - Wissal Dhifi
- Laboratory of Biotechnology and Valorisation of Bio-GeoRessources, Higher Institute of Biotechnology of Sidi Thabet, University of Manouba, BiotechPole of Sidi Thabet, Ariana, Tunisia
| | - Faical Brini
- Laboratory of Biotechnology and Plant Improvement, Centre of Biotechnology of Sfax, Sfax, Tunisia
| | - Rania Ben Saad
- Laboratory of Biotechnology and Plant Improvement, Centre of Biotechnology of Sfax, Sfax, Tunisia
| | - Wissem Mnif
- Department of Chemistry, Faculty of Sciences and Arts in Balgarn, University of Bisha, Bisha, Saudi Arabia.,ISBST, BVBGR-LR11ES31, University of Manouba, Biotechpole Sidi Thabet, Ariana, Tunisia
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Balkrishna A, Lochab S, Varshney A. Livogrit, a herbal formulation of Boerhavia diffusa, Phyllanthus niruri and Solanum nigrum reverses the thioacetamide induced hepatocellular toxicity in zebrafish model. Toxicol Rep 2022; 9:1056-1064. [PMID: 35571233 PMCID: PMC9097504 DOI: 10.1016/j.toxrep.2022.03.053] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/05/2021] [Revised: 12/16/2021] [Accepted: 03/30/2022] [Indexed: 11/30/2022] Open
Abstract
Research studies in the past years have shown encouraging therapeutic potential of herbal medicines in liver ailments. Livogrit is a well characterized formulation prepared by mixing extracts of plants, Boerhavia diffusa, Phyllanthus niruri and Solanum nigrum in precise ratios. Our study demonstrates the curative role of Livogrit in thioacetamide (TAA) induced zebrafish model of hepatotoxicity. This is a systematic study, wherein we first screened Livogrit for an effective dose and treatment time-course. Once established, we conducted subsequent experiments to compare the hepatoprotective effects of Livogrit with a reference drug, prednisone. We evaluated a wide range of liver function variables including, albumin, AST, bilirubin, creatinine, platelet clotting factor, INR and sodium blood serum to assess the degree of liver dysfunctionality. Results from screening experiments suggested that Livogrit treatment for 14 days at an effective dose (ED3-142 μg/kg) significantly revamped the deviated serum biochemistry. The experiments comparing prednisone and Livogrit demonstrated that the treatment with the herbal formation was more effective against TAA-induced hepatotoxicity. Liver function parameters indicating hepatic dysfunctionality showed better recovery with Livogrit as compared to prednisone. Furthermore, we enumerated a scoring method for assessing degree of liver dysfunctionality based on the values of bilirubin, creatinine and INR. The herbal formulation in comparison to prednisone successfully restored the liver dysfunction index to low risk. The liver cytology showed a decline in the hepatocyte cell death that further corroborated the promising curative potential of Livogrit.
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Affiliation(s)
- Acharya Balkrishna
- Drug Discovery and Development Division, Patanjali Research Institute, NH-58, Haridwar 249405, Uttarakhand, India
- Department of Allied and Applied Sciences, University of Patanjali, Patanjali Yog Peeth, Roorkee-Haridwar Road, Haridwar 249405, Uttarakhand, India
- Patanjali Yog Peeth (UK) Trust, 40 Lambhill Street, Kinning Park, Glasgow G41 1AU, UK
| | - Savita Lochab
- Drug Discovery and Development Division, Patanjali Research Institute, NH-58, Haridwar 249405, Uttarakhand, India
| | - Anurag Varshney
- Drug Discovery and Development Division, Patanjali Research Institute, NH-58, Haridwar 249405, Uttarakhand, India
- Department of Allied and Applied Sciences, University of Patanjali, Patanjali Yog Peeth, Roorkee-Haridwar Road, Haridwar 249405, Uttarakhand, India
- Special Centre for Systems Medicine, Jawaharlal Nehru University, New Delhi, India
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Jiang G, Sun C, Wang X, Mei J, Li C, Zhan H, Liao Y, Zhu Y, Mao J. Hepatoprotective mechanism of Silybum marianum on nonalcoholic fatty liver disease based on network pharmacology and experimental verification. Bioengineered 2022; 13:5216-5235. [PMID: 35170400 PMCID: PMC8974060 DOI: 10.1080/21655979.2022.2037374] [Citation(s) in RCA: 26] [Impact Index Per Article: 8.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2021] [Revised: 01/17/2022] [Accepted: 01/29/2022] [Indexed: 12/12/2022] Open
Abstract
The study aimed to identify the key active components in Silybum marianum (S. marianum) and determine how they protect against nonalcoholic fatty liver disease (NAFLD). TCMSP, DisGeNET, UniProt databases, and Venny 2.1 software were used to identify 11 primary active components, 92 candidate gene targets, and 30 core hepatoprotective gene targets in this investigation, respectively. The PPI network was built using a string database and Cytoscape 3.7.2. The KEGG pathway and GO biological process enrichment, biological annotation, as well as the identified hepatoprotective core gene targets were analyzed using the Metascape database. The effect of silymarin on NAFLD was determined using H&E on pathological alterations in liver tissues. The levels of liver function were assessed using biochemical tests. Western blot experiments were used to observe the proteins that were expressed in the associated signaling pathways on the hepatoprotective effect, which the previous network pharmacology predicted. According to the KEGG enrichment study, there are 35 hepatoprotective signaling pathways. GO enrichment analysis revealed that 61 biological processes related to the hepatoprotective effect of S. marianum were identified, which mainly involved in response to regulation of biological process and immune system process. Silymarin was the major ingredient derived from S. marianum, which exhibited the hepatoprotective effect by reducing the levels of ALT, AST, TC, TG, HDL-C, LDL-C, decreasing protein expressions of IL-6, MAPK1, Caspase 3, p53, VEGFA, increasing protein expression of AKT1. The present study provided new sights and a possible explanation for the molecular mechanisms of S. marianum against NAFLD.
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Affiliation(s)
- Guoyan Jiang
- Department of Emergency, The Third Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Chunhong Sun
- Department of Emergency, The Third Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Xiaodong Wang
- Chongqing Medical and Pharmaceutical College, School of Clinical medicine, Chongqing, China
| | - Jie Mei
- Department of periodontal, Stomatological Hospital of Chongqing Medical University, Chongqing, China
| | - Chen Li
- Department of Biology, Chemistry, Pharmacy, Free University of Berlin, Berlin, Germany
| | - Honghong Zhan
- College of Pharmaceutical Sciences, Southwest University, Chongqing, China
| | - Yixuan Liao
- College of Pharmaceutical Sciences, Southwest University, Chongqing, China
| | - Yongjun Zhu
- Department of Orthopedics, The Ninth People’s Hospital of Chongqing, Chongqing, China
| | - Jingxin Mao
- Chongqing Medical and Pharmaceutical College, School of Clinical medicine, Chongqing, China
- College of Pharmaceutical Sciences, Southwest University, Chongqing, China
- College of Basic Medical Science, Southwest University, Chongqing, China
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Potential Roles and Key Mechanisms of Hawthorn Extract against Various Liver Diseases. Nutrients 2022; 14:nu14040867. [PMID: 35215517 PMCID: PMC8879000 DOI: 10.3390/nu14040867] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/24/2022] [Revised: 02/10/2022] [Accepted: 02/17/2022] [Indexed: 11/16/2022] Open
Abstract
The genus Crataegus (hawthorn), a flowering shrub or tree, is a member of the Rosaceae family and consists of approximately 280 species that have been primarily cultivated in East Asia, North America, and Europe. Consumption of hawthorn preparations has been chiefly associated with pharmacological benefits for cardiovascular diseases, including congestive heart failure and angina pectoris. Treatment with hawthorn extracts can be related to improvements in the complex pathogenesis of various hepatic and cardiovascular disorders. In this regard, the present review described that the presence of hawthorn extracts ameliorated hepatic injury, lipid accumulation, inflammation, fibrosis, and cancer in an abundance of experimental models. Hawthorn extracts might have these promising activities, largely by enhancing the hepatic antioxidant system. In addition, several mechanisms, including AMP-activated protein kinase (AMPK) signaling and apoptosis, are responsible for the role of hawthorn extracts in repairing the dysfunction of injured hepatocytes. Specifically, hawthorn possesses a wide range of biological actions relevant to the treatment of toxic hepatitis, alcoholic liver disease, non-alcoholic fatty liver disease, and hepatocellular carcinoma. Accordingly, hawthorn extracts can be developed as a major source of therapeutic agents for liver diseases.
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Mohammed HA, Khan RA. Anthocyanins: Traditional Uses, Structural and Functional Variations, Approaches to Increase Yields and Products' Quality, Hepatoprotection, Liver Longevity, and Commercial Products. Int J Mol Sci 2022; 23:2149. [PMID: 35216263 PMCID: PMC8875224 DOI: 10.3390/ijms23042149] [Citation(s) in RCA: 35] [Impact Index Per Article: 11.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/30/2021] [Revised: 02/08/2022] [Accepted: 02/08/2022] [Indexed: 02/06/2023] Open
Abstract
Anthocyanins are water-soluble, colored compounds of the flavonoid class, abundantly found in the fruits, leaves, roots, and other parts of the plants. The fruit berries are prime sources and exhibit different colors. The anthocyanins utility as traditional medicament for liver protection and cure, and importance as strongest plants-based anti-oxidants have conferred these plants products different biological activities. These activities include anti-inflammation, liver protective, analgesic, and anti-cancers, which have provided the anthocyanins an immense commercial value, and has impelled their chemistry, biological activity, isolation, and quality investigations as prime focus. Methods in extraction and production of anthocyanin-based products have assumed vital economic importance. Different extraction techniques in aquatic solvents mixtures, eutectic solvents, and other chemically reactive extractions including low acid concentrations-based extractions have been developed. The prophylactic and curative therapy roles of the anthocyanins, together with no reported toxicity has offered much-needed impetus and economic benefits to these classes of compounds which are commercially available. Information retrieval from various search engines, including the PubMed®, ScienceDirect®, Scopus®, and Google Scholar®, were used in the review preparation. This imparted an outlook on the anthocyanins occurrence, roles in plants, isolation-extraction, structures, biosynthetic as well as semi- and total-synthetic pathways, product quality and yields enhancements, including uses as part of traditional medicines, and uses in liver disorders, prophylactic and therapeutic applications in liver protection and longevity, liver cancer and hepatocellular carcinoma. The review also highlights the integrated approach to yields maximizations to meet the regular demands of the anthocyanins products, also as part of the extract-rich preparations together with a listing of marketed products available for human consumption as nutraceuticals/food supplements.
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Affiliation(s)
- Hamdoon A. Mohammed
- Department of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, Qassim University, Qassim 51452, Saudi Arabia
- Department of Pharmacognosy, Faculty of Pharmacy, Al-Azhar University, Cairo 11371, Egypt
| | - Riaz A. Khan
- Department of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, Qassim University, Qassim 51452, Saudi Arabia
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Tuerxun K, Zhang S, Zhang Y. Downregulation of PITX2 inhibits the proliferation and migration of liver cancer cells and induces cell apoptosis. Open Life Sci 2022; 16:1322-1329. [PMID: 35071766 PMCID: PMC8724353 DOI: 10.1515/biol-2021-0133] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2021] [Revised: 09/01/2021] [Accepted: 09/21/2021] [Indexed: 11/15/2022] Open
Abstract
Paired-like homeodomain 2 (PITX2) functions as a transcription factor to participate in vertebrate embryogenesis, and dysregulated PITX2 expression was associated with the progression of various cancers. The functional role of PITX2 in tumorigenesis of liver cancer remains unknown. Western blot analysis showed that expression levels of PITX2 were enhanced in the liver cancer tissues and cells. siRNAs targeting PITX2 induced downregulation of PITX2 in liver cancer cells. siRNA-induced knockdown of PITX2 decreased liver cancer cell viability and proliferation, while promoting cell apoptosis by increasing cleaved-PARP, cleaved caspase 3, and cleaved caspase 9. The knockdown of PITX2 repressed liver cancer cell migration and invasion. In conclusion, elevated PITX2 expression was associated with liver cancer progression through repression of cell apoptosis and promoting cell proliferation and metastasis, and silencing of PITX2 might serve as a potential therapeutic strategy for the treatment of liver cancer.
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Affiliation(s)
- Kebinuer Tuerxun
- Department of Infection and Liver Disease Center, The First Affiliated Hospital of Xinjiang Medical University, No. 137, Liyushan South Road, Urumqi, Xinjiang, 830054, China
| | - Shufang Zhang
- Department of Infection and Liver Disease Center, The First Affiliated Hospital of Xinjiang Medical University, No. 137, Liyushan South Road, Urumqi, Xinjiang, 830054, China
| | - Yuexin Zhang
- Department of Infection and Liver Disease Center, The First Affiliated Hospital of Xinjiang Medical University, No. 137, Liyushan South Road, Urumqi, Xinjiang, 830054, China
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Sowjanya K, Girish C, Bammigatti C, Prasanna Lakshmi NC. Efficacy of Phyllanthus niruri on improving liver functions in patients with alcoholic hepatitis: A double-blind randomized controlled trial. Indian J Pharmacol 2022; 53:448-456. [PMID: 34975132 PMCID: PMC8764976 DOI: 10.4103/ijp.ijp_540_20] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/02/2022] Open
Abstract
INTRODUCTION: Phyllanthus niruri, a traditional herbal medicine, was found to be hepatoprotective as evidenced by several preclinical and clinical studies. However, to the best of our knowledge, there are no clinical trials available to date to evaluate its efficacy in alcoholic hepatitis. MATERIALS AND METHODS: The present study is a block randomized, double-blind, parallel-arm placebo-controlled trial that was designed to assess the efficacy of P. niruri on the liver and renal function parameters, total oxidant and antioxidant levels in alcoholic hepatitis patients in comparison to placebo over a 4-week period. Patients were screened by CAGE questionnaire, and those with a confirmed diagnosis of mild–moderate alcoholic hepatitis based on laboratory findings and Maddrey's discriminant function score were randomly allocated to treatment and placebo arms. Clinical assessments were done at baseline, 2 weeks, and 4 weeks. A total of 454 patients were screened and 100 eligible patients were recruited for the study, and 71 were analyzed using the modified intention-to-treat approach. RESULTS: Serum levels of liver and renal function parameters failed to demonstrate significant improvement with P. niruri. However, there was a statistically significant increase in the level of total antioxidants with P. niruri (P = 0.034) with an additional appetite stimulant activity (P = 0.03) in 4 weeks. CONCLUSION: A 4-week administration of P. niruri in mild–moderate alcoholic hepatitis patients showed an improvement in the total antioxidant levels with an appetite stimulant activity compared to a placebo.
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Affiliation(s)
- Karri Sowjanya
- Department of Pharmacology, Jawaharlal Institute of Postgraduate Medical Education and Research, Puducherry, India
| | - Chandrashekaran Girish
- Department of Pharmacology, Jawaharlal Institute of Postgraduate Medical Education and Research, Puducherry, India
| | - Chanaveerappa Bammigatti
- Department of Medicine, Jawaharlal Institute of Postgraduate Medical Education and Research, Puducherry, India
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Dargel C, Gräbitz-Bräuer F, Geisler R, Fandrich P, Hannappel Y, Porcar L, Hellweg T. Stable DOPG/Glycyrrhizin Vesicles with a Wide Range of Mixing Ratios: Structure and Stability as Seen by Scattering Experiments and Cryo-TEM. Molecules 2021; 26:molecules26164959. [PMID: 34443547 PMCID: PMC8399256 DOI: 10.3390/molecules26164959] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2021] [Revised: 08/12/2021] [Accepted: 08/13/2021] [Indexed: 11/24/2022] Open
Abstract
Phosphatidylglycerols represent a large share of the lipids in the plasmamembrane of procaryotes. Therefore, this study investigates the role of charged lipids in the plasma membrane with respect to the interaction of the antiviral saponin glycyrrhizin with such membranes. Glycyrrhizin is a natural triterpenic-based surfactant found in licorice. Vesicles made of 1,2-dioleoyl-sn-glycero-3-phospho-rac-(1’-glycerol) (DOPG)/glycyrrhizin are characterized by small-angle scattering with neutrons and X-rays (SANS and SAXS). Small-angle scattering data are first evaluated by the model-independent modified Kratky–Porod method and afterwards fitted by a model describing the shape of small unilamellar vesicles (SUV) with an internal head-tail contrast. Complete miscibility of DOPG and glycyrrhizin was revealed even at a ratio of lipid:saponin of 1:1. Additional information about the chain-chain correlation distance of the lipid/saponin mixtures in the SUV structures is obtained from wide-angle X-ray scattering (WAXS).
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Affiliation(s)
- Carina Dargel
- Physical and Biophysical Chemistry, Bielefeld University, Universitätsstr. 25, 33615 Bielefeld, Germany; (C.D.); (F.G.-B.); (R.G.); (P.F.); (Y.H.)
| | - Friederike Gräbitz-Bräuer
- Physical and Biophysical Chemistry, Bielefeld University, Universitätsstr. 25, 33615 Bielefeld, Germany; (C.D.); (F.G.-B.); (R.G.); (P.F.); (Y.H.)
| | - Ramsia Geisler
- Physical and Biophysical Chemistry, Bielefeld University, Universitätsstr. 25, 33615 Bielefeld, Germany; (C.D.); (F.G.-B.); (R.G.); (P.F.); (Y.H.)
| | - Pascal Fandrich
- Physical and Biophysical Chemistry, Bielefeld University, Universitätsstr. 25, 33615 Bielefeld, Germany; (C.D.); (F.G.-B.); (R.G.); (P.F.); (Y.H.)
| | - Yvonne Hannappel
- Physical and Biophysical Chemistry, Bielefeld University, Universitätsstr. 25, 33615 Bielefeld, Germany; (C.D.); (F.G.-B.); (R.G.); (P.F.); (Y.H.)
| | - Lionel Porcar
- Institut Laue-Langevin, 71 Avenue des Martyrs CS 20156, CEDEX 9, 38042 Grenoble, France;
| | - Thomas Hellweg
- Physical and Biophysical Chemistry, Bielefeld University, Universitätsstr. 25, 33615 Bielefeld, Germany; (C.D.); (F.G.-B.); (R.G.); (P.F.); (Y.H.)
- Correspondence: ; Tel.: +49-0521-106-2055
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Kim JY, Kim M, Kim RY, Park WK, Park YH. A 12-week, randomized, double-blind, placebo-controlled study assessing the efficacy of EGHB010, a standardized extract of Paeoniae radix and Glycyrrhizae radix, in patients with early age-related macular degeneration. ANNALS OF TRANSLATIONAL MEDICINE 2021; 9:541. [PMID: 33987239 PMCID: PMC8105837 DOI: 10.21037/atm-20-4701] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/14/2020] [Accepted: 12/18/2020] [Indexed: 11/06/2022]
Abstract
BACKGROUND EGHB010, a standardized extract of Paeoniae radix and Glycyrrhizae radix, inhibits choroidal neovascularization. The aim of this study is to evaluate the efficacy and safety of EGHB010 on early age-related macular degeneration (AMD) progression inhibition. METHODS The study was designed as a randomized, double-blind, single-center, placebo-controlled study. Subjects were 50 years of age or older, and early AMD satisfied the criteria of more than 15 small (<63 µm) drusen, less than 20 intermediate (≥63, <125 µm) drusen, or pigment abnormalities. For 12 weeks, the treatment group received EGHB010 and the control received the placebo. The main outcomes were changes in macular pigment optical density (MPOD), central macular thickness (CMT), and central choroidal thickness (CCT). Subgroup analysis was performed on subjects with MPOD <0.75 at baseline. RESULTS Forty-eight subjects out of 94 were assigned to the treatment group, and 46 to the control group. At 12 weeks, mean MPOD of the treatment group increased by 0.04±0.27 (P=0.2730), and that of the control group decreased by 0.03±0.21 (P=0.7240), but there was no significant difference between the two groups (P=0.1234). There were no significant differences between the two groups in mean CMT and CCT (P=0.6718 and 0.6608, respectively). In subgroup analysis, there were 39 subjects with MPOD <0.75 in the treatment group and 36 in the control. Mean MPOD of the treatment group significantly increased by 0.09±0.25 (P=0.0218), and there was a significant difference in mean MPOD at 12 weeks between the two groups (P=0.0248). Adverse reactions were similar in both groups, and no subjects had serious adverse events. CONCLUSIONS EGHB010 is expected to increase MPOD when administered to subjects with MPOD <0.75. EGHB010 is worth considering as a substance that inhibits the progression of early AMD.
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Affiliation(s)
- Joo Young Kim
- Department of Ophthalmology and Visual Science, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
- Catholic Institute for Visual Science, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Mirinae Kim
- Department of Ophthalmology and Visual Science, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
- Catholic Institute for Visual Science, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Rae Young Kim
- Department of Ophthalmology and Visual Science, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
- Catholic Institute for Visual Science, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Woo Kyung Park
- Department of Ophthalmology and Visual Science, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
- Catholic Institute for Visual Science, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Young-Hoon Park
- Department of Ophthalmology and Visual Science, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
- Catholic Institute for Visual Science, College of Medicine, The Catholic University of Korea, Seoul, Korea
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Protective effect of Terminalia arjuna against alcohol induced oxidative damage of rat erythrocyte membranes. J Ayurveda Integr Med 2021; 12:330-339. [PMID: 33731264 PMCID: PMC8186002 DOI: 10.1016/j.jaim.2021.02.001] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/09/2020] [Revised: 02/08/2021] [Accepted: 02/11/2021] [Indexed: 12/18/2022] Open
Abstract
Background Alcohol is a widely abused drug with many health implications, mainly caused by the oxidative and nitrosative stress on different body parts. Ayurvedic herbalism authenticates the multiple therapeutic applications of Terminalia arjuna bark due to its rich phytochemical repertoire. Objective To observe the extent of oxidative damage caused to erythrocytes by alcohol and assess the protective ability of T. arjuna bark powder aqueous extract (AETA) against the damage. Materials and methods Wister albino rats were categorized into four groups of eight rats per group; first group (control) was fed with glucose, second group was given alcohol at a dose of 20% v/v; 5g alcohol/kg b. wt/day, third group was co-administered with AETA (0.5 g/kg b. wt/day) and alcohol and the fourth group was kept on bark extract alone. Blood samples were collected and evaluated for different biochemical parameters after the completion of the treatment period. Results Alcohol significantly increased the erythrocyte membrane protein carbonyl and malondialdehyde (MDA) contents, along with a concomitant decrease in the membrane antioxidant status, when compared to the control group. Chromatographic analysis of the alcohol-treated rat erythrocyte membranes revealed altered membrane individual phospholipid contents and fluidity properties. Alcohol-induced morphological changes in the erythrocytes and its effect on decreasing the resistance of hypotonic shock induced by NaCl are evident from the hemolysis curves. However, AETA administration to alcoholic rats beneficially modulated the membrane properties anvd protected erythrocytes from damage. Conclusion Results suggest that AETA protects erythrocytes from alcohol-induced oxidative stress, biophysical, and biochemical changes very effectively.
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Luan F, Wu Q, Yang Y, Lv H, Liu D, Gan Z, Zeng N. Traditional Uses, Chemical Constituents, Biological Properties, Clinical Settings, and Toxicities of Abelmoschus manihot L.: A Comprehensive Review. Front Pharmacol 2020; 11:1068. [PMID: 32973492 PMCID: PMC7482509 DOI: 10.3389/fphar.2020.01068] [Citation(s) in RCA: 41] [Impact Index Per Article: 8.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/02/2019] [Accepted: 06/30/2020] [Indexed: 12/14/2022] Open
Abstract
Abelmoschus manihot, an annual herbal flowering plant, is widely distributed throughout eastern Europe and in temperate and subtropical regions of Asia. Its flowers have been traditionally used for the treatment of chronic kidney disease in China. Currently, more than 128 phytochemical ingredients have been obtained and identified from the flowers, seeds, stems, and leaves of A. manihot. The primary components are flavonoids, amino acids, nucleosides, polysaccharides, organic acids, steroids, and volatile oils. A. manihot and its bioactive constituents possess a plethora of biological properties, including antidiabetic nephropathy, antioxidant, antiadipogenic, anti-inflammatory, analgesic, anticonvulsant, antidepressant, antiviral, antitumor, cardioprotective, antiplatelet, neuroprotective, immunomodulatory, and hepatoprotective activities, and have effects on cerebral infarction, bone loss, etc. However, insufficient utilization and excessive waste have already led to a rapid reduction of resources, meaning that a study on the sustainable use of A. manihot is urgent and necessary. Moreover, the major biologically active constituents and the mechanisms of action of the flowers have yet to be elucidated. The present paper provides an early and comprehensive review of the traditional uses, chemical constituents, pharmacological activities, and pharmaceutical, quality control, toxicological, and clinical settings to emphasize the benefits of this plant and lays a solid foundation for further development of A. manihot.
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Affiliation(s)
- Fei Luan
- Department of Clinical Pharmacy, Shaanxi Provincial Hospital of Tuberculosis Prevention and Treatment, Xi'an, China.,Department of Pharmacology, College of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Qianhong Wu
- Department of Clinical Pharmacy, Shaanxi Provincial Hospital of Tuberculosis Prevention and Treatment, Xi'an, China
| | - Yan Yang
- Department of Bioengineering, Zhuhai Campus of Zunyi Medical University, Zhuhai, China
| | - Haizhen Lv
- Department of Clinical Pharmacy, Shaanxi Provincial Hospital of Tuberculosis Prevention and Treatment, Xi'an, China
| | - Daoheng Liu
- Department of Clinical Pharmacy, Shaanxi Provincial Hospital of Tuberculosis Prevention and Treatment, Xi'an, China
| | - Zhaoping Gan
- Department of Clinical Pharmacy, Shaanxi Provincial Hospital of Tuberculosis Prevention and Treatment, Xi'an, China
| | - Nan Zeng
- Department of Pharmacology, College of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, China
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Clinical Evaluation of the Safety and Effectiveness of Heptonica: A Ghanaian Hepatorestorative Polyherbal Product. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE 2020; 2020:9596182. [PMID: 32655671 PMCID: PMC7327574 DOI: 10.1155/2020/9596182] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/17/2020] [Accepted: 06/03/2020] [Indexed: 11/28/2022]
Abstract
The incidence of liver diseases is increasing globally, and many patients in developing countries are resorting to the use of herbal products as treatment. This study was aimed at establishing the safety and effectiveness outcomes for patients with deranged liver panel treated with a Ghanaian finished polyherbal product. The product Heptonica is prepared by CPMR from three medicinal plants: Bidens pilosa, Citrus aurantifolia, and Trema orientalis. Fifty (50) participants with clinical and biochemical signs of liver impairment were purposively recruited and treated for a period of 28 days. Participants received Heptonica at a dose of 30 mL 8 hourly after meals for the treatment period. Clinical and biochemical evaluation (liver panel test, renal function test, haematology, and urinalysis) of subjects for the safety and effectiveness of the product was undertaken at days 0 (baseline), 14, and 28. Compared to the baseline values, Heptonica did not have any untoward effect on renal function, haematological parameters, and urine parameters of subjects. Clinical and liver panel results of the participants also improved compared to the baseline: serum aspartate transaminase (AST) (p < 0.0001), alanine transaminase (ALT) (p < 0.0001), gamma-glutamyltransferase (GGT) (p- 0.0013), total bilirubin (p-0.0136), direct bilirubin (p < 0.0001), total proteins (p-0.0409), and alkaline phosphates (p- 0.0284). Level of albumin showed no significant difference within the study period. The outcome of this study indicates Heptonica has hepatorestorative action with no observable toxicity and can be used with confidence as indicated as a liver tonic.
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Tan SP, Tan ENY, Lim QY, Nafiah MA. Phyllanthus acidus (L.) Skeels: A review of its traditional uses, phytochemistry, and pharmacological properties. JOURNAL OF ETHNOPHARMACOLOGY 2020; 253:112610. [PMID: 31991202 DOI: 10.1016/j.jep.2020.112610] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/23/2019] [Revised: 01/21/2020] [Accepted: 01/21/2020] [Indexed: 06/10/2023]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Phyllanthus acidus (L.) Skeels is not only used for its edible fruits but also used to treat a wide spectrum of diseases such as inflammatory, rheumatism, bronchitis, asthma, respiratory disorder, hepatic diseases and diabetes in India, Asia, the Caribbean region, and Central and South America. This paper aims to discuss the current understanding regarding the traditional uses, phytochemical and pharmacological studies of P. acidus, and their possible research opportunities. MATERIALS AND METHODS All information on P. acidus was collected from various electronic database (ACS, PubMed, Scopus, Web of Science, SciFinder, Science Direct, Google Scholar, Springer, Wiley, Taylor and Mendeley) and also from those published materials (Ph.D. and M.Sc. dissertations and books) by using a combination of various meaningful keywords. RESULTS Phytochemical analyses on barks, leaves, roots and fruits of P. acidus identified triterpene, diterpene, sesquiterpene, and glycosides as predominant classes of bioactive substances found in this plant. P. acidus was reported with various pharmacological activities such as in vivo hepatoprotective and hypoglycemic, in vitro anti-oxidant, α-glucosidase inhibitory, anti-inflammatory and antimicrobial activities. However, none of these studies are with clinical research. Some of the studies were performed with only a single set of experiments or with a high dose of extract, and thus the validity of the experimental data may be questionable. In addition, most of the studies described were without identifying the effective components. Some of the assays were even without a positive control for comparison which makes results questionable. CONCLUSION Although P. acidus has been proven as a valuable medicinal source from its traditional uses. However, the pharmacological experiments conducted were not sufficient to verify its traditional uses. More investigation is required to confirm the traditional claims such as bioassay-guided isolation of bioactive compounds, detailed pharmacological investigations, clinical studies, and its toxicity investigation. Additionally, an experimental design with sufficient data replication, the use of controls and authenticated research materials, and the selection of a rationale dose or concentration for the analysis are keys to providing reproducible experimental data.
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Affiliation(s)
- Siow-Ping Tan
- Department of Physical Science, Faculty of Applied Sciences, Tunku Abdul Rahman University College, 53300, Kuala Lumpur, Malaysia.
| | - Eric Nyak-Yong Tan
- Department of Physical Science, Faculty of Applied Sciences, Tunku Abdul Rahman University College, 53300, Kuala Lumpur, Malaysia.
| | - Qian-Yu Lim
- Department of Physical Science, Faculty of Applied Sciences, Tunku Abdul Rahman University College, 53300, Kuala Lumpur, Malaysia.
| | - Mohd Azlan Nafiah
- Department of Chemistry, Faculty of Science and Mathematics, Universiti Pendidikan Sultan Idris, 35900, Tanjung Malim, Perak, Malaysia.
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Zhang Z, Miao Y, Xu M, Cheng W, Yang C, She X, Geng Q, Zhang Q. TianJiu therapy for α-naphthyl isothiocyanate-induced intrahepatic cholestasis in rats treated with fresh Ranunculus sceleratus L. JOURNAL OF ETHNOPHARMACOLOGY 2020; 248:112310. [PMID: 31629027 DOI: 10.1016/j.jep.2019.112310] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/27/2019] [Revised: 10/07/2019] [Accepted: 10/14/2019] [Indexed: 06/10/2023]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE TianJiu (TJ) therapy, one type of cold moxibustion, applies to specific acupuncture points with herbal patches of hot nature, providing a constant irritant to the skin until the presence of hyperemia and blistering. Traditional and clinical reports suggest that TJ is an effective therapy for the treatment of jaundice with fresh Ranunculus sceleratus L. (RS), in which protoanemonin is one of the main irritant constituents. However, the therapeutic effect of TJ treatment with fresh RS against intrahepatic cholestasis has not been studied in animal experiments. AIM OF THE STUDY Present study was undertaken to investigate the effect of TJ treatment with fresh RS against intrahepatic cholestasis in rats and provide an experimental basis for the underlying mechanism of TJ therapy. MATERIALS AND METHODS Male intrahepatic cholestatic Sprague-Dawley rats induced by 2% α-naphthylisothiocyanate (ANIT, 80 mg/kg B.W.) were treated by TJ therapy with fresh RS. The levels of serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), direct bilirubin (DBIL), total bilirubin (TBIL), total bile acid (TBA), hepatic malondialdehyde (MDA) and nitric monoxide (NO), as well as hepatic body ratio, bile flow and hepatic histopathological assay were measured and evaluated to investigate the therapeutic effect of TJ treatment with fresh RS. Phytochemical analysis of fresh and dried RS was performed by gas chromatography-mass spectrometer (GC-MS). RESULTS After TJ treatment with fresh RS, the abnormally elevated levels of serum AST, ALT, ALP, DBIL, TBIL and TBA, as well as hepatic MDA and NO at 108 h were reduced significantly (versus model group, P < 0.01). The hepatic body ratio, bile flow and hepatic pathological change of cholestatic rats at 108 h in TJ group were restored when compared with those of model group. Thirty-one compounds including lactones, flavonoids and phenolic acids were identified and determined by GC-MS analysis. The content of protoanemonin in fresh RS (9.49%) was about 25-fold higher than that in dried RS (0.38%). CONCLUSIONS TJ treatment with fresh RS exhibited good therapeutic effect on ANIT-induced intrahepatic cholestasis in rats, which may be due to the attenuated oxidative stress in the liver tissue. It is rational for the ancients to choose fresh RS as TJ herbal patches because of its abundant protoanemonin with the character of irritant. The qualitative and quantitative results of GC-MS analysis provided the chemical basis of TJ therapy with fresh RS, which can be regarded as a simple and efficient method for the treatment of cholestasis hepatitis.
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Affiliation(s)
- Zhiyong Zhang
- School of Pharmacy, Anhui Medical University, Hefei, 230032, China
| | - Yiru Miao
- School of Pharmacy, Anhui Medical University, Hefei, 230032, China
| | - Min Xu
- School of Pharmacy, Anhui Medical University, Hefei, 230032, China
| | - Wenming Cheng
- School of Pharmacy, Anhui Medical University, Hefei, 230032, China.
| | - Chuanyan Yang
- School of Pharmacy, Anhui Medical University, Hefei, 230032, China
| | - Xiangjian She
- School of Pharmacy, Anhui Medical University, Hefei, 230032, China
| | - Qianqian Geng
- School of Pharmacy, Anhui Medical University, Hefei, 230032, China
| | - Qunlin Zhang
- School of Pharmacy, Anhui Medical University, Hefei, 230032, China.
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Lin C, Weng M, Chung C, Liang C. The dramatic effect of intravenous glycyrrhizin on acute‐on‐chronic hepatic failure in chronic hepatitis B patients without liver cirrhosis. ADVANCES IN DIGESTIVE MEDICINE 2019. [DOI: 10.1002/aid2.13131] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/15/2023]
Affiliation(s)
- Chien‐Chu Lin
- Department of Internal MedicineFar Eastern Memorial Hospital New Taipei City Taiwan
| | - Meng‐Tzu Weng
- Department of Internal MedicineFar Eastern Memorial Hospital New Taipei City Taiwan
| | - Chen‐Shuan Chung
- Department of Internal MedicineFar Eastern Memorial Hospital New Taipei City Taiwan
| | - Cheng‐Chao Liang
- Department of Internal MedicineFar Eastern Memorial Hospital New Taipei City Taiwan
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Lima IR, Silva IB, Lima RML, Silva TMS, Maia MBS, Leite SP. HEPATOPROTECTIVE EFFICACY OF METHANOLIC EXTRACT OF INDIGOFERA SUFFRUTICOSA (MILL) ON PARACETAMOL-INDUCED LIVER DAMAGE IN MICE. ARQUIVOS DE GASTROENTEROLOGIA 2019; 56:333-338. [PMID: 31721967 DOI: 10.1590/s0004-2803.201900000-62] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/13/2019] [Accepted: 07/23/2019] [Indexed: 11/22/2022]
Abstract
BACKGROUND Indigofera suffruticosa Mill (Fabaceae) is abundant in northeastern Brazil and popularly used in the treatment of infectious and inflammatory processes. Several biological properties, such as anti-inflammatory, anticancer, antitumor, hepatoprotective and low toxicity, are reported for this plant. OBJECTIVE This study investigated hepatoprotective activity and the antioxidant effect of methanolic extract of I. suffruticosa leaves (MEIS) on Swiss albino mice submitted to experimental models of acetaminophen-induced liver injury. METHODS MEIS (50 mg/kg; p.o.) was standardized according to the LD50 and its hepatoprotective property on Swiss albino mice evaluated during a 7-day period. On the eighth day, the acetaminophen-induced hepatic injury was performed. Histomorphometric analysis of liver tissue, antioxidant activity and serum levels of alanine aminotransferase (AST), aspartate aminotransferase (ALT) and bilirubin were measured. RESULTS MEIS (50 mg/kg; p.o.) restored serum enzyme levels and results were close to those of positive control (silymarin) when compared to the negative control. Histopathological and histomorphometric analyzes confirmed MEIS hepatoprotective activity, showing reorganization of structural units of cells, nuclei and sinusoidal capillaries of hepatocytes, reducing the damage on liver tissue and increasing organ regeneration rate. MEIS showed high antioxidant potential at concentrations of 1000 and 500 µg/mL. CONCLUSION This study suggests that MEIS has hepatoprotective activity and high antioxidant potential.
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Affiliation(s)
- Izabela Rangel Lima
- Universidade Federal de Pernambuco, Laboratório de Histomoformetria, Departamento de Histologia e Embriologia Recife, PE, Brasil
| | - Ivanise Brito Silva
- Universidade Federal de Pernambuco, Laboratório de Histomoformetria, Departamento de Histologia e Embriologia Recife, PE, Brasil
| | - Roberta M Leite Lima
- Universidade Federal de Pernambuco, Laboratório de Histomoformetria, Departamento de Histologia e Embriologia Recife, PE, Brasil
| | - Tainá M Santos Silva
- Universidade Federal de Pernambuco, Laboratório de Histomoformetria, Departamento de Histologia e Embriologia Recife, PE, Brasil
| | - Maria B Sousa Maia
- Universidade Federal de Pernambuco, Laboratório de Produtos Naturais e Bioativos, Departamento de Fisiologia e Farmacologia, Brasil
| | - Sônia Pereira Leite
- Universidade Federal de Pernambuco, Laboratório de Histomoformetria, Departamento de Histologia e Embriologia Recife, PE, Brasil
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Lv H, An B, Yu Q, Cao Y, Liu Y, Li S. The hepatoprotective effect of myricetin against lipopolysaccharide and D-galactosamine-induced fulminant hepatitis. Int J Biol Macromol 2019; 155:1092-1104. [PMID: 31712142 DOI: 10.1016/j.ijbiomac.2019.11.075] [Citation(s) in RCA: 36] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/29/2019] [Revised: 10/09/2019] [Accepted: 11/07/2019] [Indexed: 12/25/2022]
Abstract
Fulminant hepatitis (FH) is a severe liver disease characterized by extensive hepatic necrosis, oxidative stress, and inflammation. Myricetin (Myr), a botanical flavonoid glycoside, is recognized to exert antiapoptosis, anti-inflammatory, and antioxidant properties. In the current study, we focused on exploring the protective effects and underlying mechanisms of Myr against lipopolysaccharide (LPS) and D-galactosamine (D-GalN)-induced FH. These data indicated that Myr effectively protected from LPS/D-GalN-induced FH by lowering the mortality of mice, decreasing ALT and AST levels, and alleviating histopathological changes, oxidative stress, inflammation, and hepatic apoptosis. Moreover, Myr could efficiently mediate multiple signaling pathways, displaying not only the regulation of caspase-3/9 and P53 protein, inhibition of toll-like receptor 4 (TLR4)-nuclear factor-kappa B (NF-κB) activation, and -mitogen-activated protein kinase (MAPK), but also the increase of heme oxygenase-1 (HO-1) and nuclear factor-erythroid 2-related factor 2 (Nrf2) expression, as well as induction of AMP-activated protein kinase (AMPK) and acetyl-CoA carboxylase (ACC) phosphorylation in mice with LPS/D-GalN-induced FH. Importantly, our further results in vitro suggested that Myr remarkably attenuated H2O2-triggered hepatotoxicity and ROS generation, activated Keap1-Nrf2/HO-1 and AMPK/ACC signaling pathway. However, Myr-enhanced the expression of HO-1 and Nrf2 protein was reversed by Keap1-overexpression, Nrf2-null and AMPK inhibitor. Meanwhile, Myr-relieved hepatotoxicity excited by H2O2 was blocked by Nrf2-null and AMPK inhibitor. Taken together, Myr exhibits a protective role against LPS/D-GalN-induced FH by suppressing hepatic apoptosis, inflammation, and oxidative stress, likely involving in the regulation of apoptosis-related protein, TLR4-NF-κB/-MAPK and NLRP3 inflammasome, and AMPK-Nrf2/HO-1 signaling pathway.
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Affiliation(s)
- Hongming Lv
- College of Animal Science and Veterinary Medicine, Heilongjiang Bayi Agricultural University, Daqing 163319, Heilongjiang Bayi, China
| | - Beiying An
- Department of Clinical Laboratory, The First Hospital of Jilin University, Changchun 130021, Jilin, China
| | - Qinlei Yu
- Jilin Provincial Animal Disease Control Center, 4510 Xi'an Road, Changchun 130062, China
| | - Yu Cao
- College of Animal Science and Veterinary Medicine, Heilongjiang Bayi Agricultural University, Daqing 163319, Heilongjiang Bayi, China
| | - Yang Liu
- College of Animal Science and Veterinary Medicine, Heilongjiang Bayi Agricultural University, Daqing 163319, Heilongjiang Bayi, China
| | - Shize Li
- College of Animal Science and Veterinary Medicine, Heilongjiang Bayi Agricultural University, Daqing 163319, Heilongjiang Bayi, China.
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Nithyananthan S, Keerthana P, Umadevi S, Guha S, Mir IH, Behera J, Thirunavukkarasu C. Nutrient mixture from germinated legumes: Enhanced medicinal value with herbs-attenuated liver cirrhosis. J Food Biochem 2019; 44:e13085. [PMID: 31646659 DOI: 10.1111/jfbc.13085] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/23/2019] [Revised: 09/12/2019] [Accepted: 10/02/2019] [Indexed: 01/14/2023]
Abstract
Among various food processing strategies, germination and dehulling enhance the nutritional content of the food, and the addition of herbs to this could improve the medicinal value. The milled powders of germinated Macrotyloma uniflorum (horse gram) and Vigna radiata (green gram) were used to make the nutrient mixture. Further, Curcuma longa (turmeric) and Trigonella foenum graecum (fenugreek) were used to improve its medicinal value. The prepared nutrient mixture has high nutritional value, antioxidant potential, and reduced antinutrient factors. Supplementation of nutrient mixture reduced oxidative stress-mediated hepatocyte injury on the CCl4 -induced liver cirrhosis model. Further, histological examination (H&E and Sirius red), matrix metalloproteinase gelatin zymography, and Western blot revealed the management of hepatic stellate cells in an inactive stage thereby reduced cirrhosis. These findings conclude that the supplementation of nutrient mixture formulation protected and effectively prevented liver cirrhosis. PRACTICAL APPLICATIONS: This study has a good impact on nutritional therapy for liver diseases. Many of the chronic liver diseases are associated with severe malnutrition and hypoalbuminemia, which further worsens the condition. This study would emphasize the nutritional therapy to treat such imbalance and enriching the medicinal value of nutrition mixture with herbs could target different pathophysiological changes and provide better defense in liver disease patients. Since this nutrient mixture is from common edible natural resources, it could reach the pharmaceutical industry's attention to the highest production and marketing.
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Affiliation(s)
| | - Pushparaj Keerthana
- Department of Biochemistry and Molecular Biology, Pondicherry University, Puducherry, India
| | - Srinivasan Umadevi
- Department of Biochemistry and Molecular Biology, Pondicherry University, Puducherry, India
| | - Shreyoshi Guha
- Department of Biochemistry and Molecular Biology, Pondicherry University, Puducherry, India
| | - Ishfaq Hassan Mir
- Department of Biochemistry and Molecular Biology, Pondicherry University, Puducherry, India
| | - Jajnasenee Behera
- Department of Biochemistry and Molecular Biology, Pondicherry University, Puducherry, India
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Baradaran A, Samadi F, Ramezanpour SS, Yousefdoust S. Hepatoprotective effects of silymarin on CCl 4-induced hepatic damage in broiler chickens model. Toxicol Rep 2019; 6:788-794. [PMID: 31440455 PMCID: PMC6698800 DOI: 10.1016/j.toxrep.2019.07.011] [Citation(s) in RCA: 35] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/07/2019] [Revised: 07/27/2019] [Accepted: 07/31/2019] [Indexed: 02/07/2023] Open
Abstract
This study was conducted to investigate the hepatoprotective effects of silymarin on CCl4-induced oxidative stress in broiler chickens model. A total of 240 day-old broilers were divided into 4 equal groups (n = 60) composed of a control group (receiving 1 mL/Kg BW saline) and 3 groups treated with silymarin (receiving 100 mg/Kg BW silymarin), CCl4 (receiving 1 mL/Kg BW CCl4), and combination of silymarin + CCl4. Results indicated that silymarin has potential to mitigate the deleterious effects of CCl4 on protein and lipid metabolism. The protective activity of silymarin against CCl4-mediated lipid peroxidation was demonstrated by the lower serum content of MDA, as lipid peroxidation marker. CCl4-induced hepatotoxicity was demonstrated by the elevation of serum contents of ALP, AST, ALT, and GGT enzymes, whereas silymarin decreased serum activity of ALP and AST hepatic enzymes. The CCl4-challenged birds revealed considerable hepatic injures characterized by moderate to severe hepatocellular degeneration around the portal vein, aggregation of inflammatory cells, granulomatosis, cytolytic necrosis, periportal space fibrosis, and sinusoidal dilatation. However, liver damages were amended by the silymarin. In line with molecular study, a remarkable down-regulation was detected in the expression of CAT, GPx, and Mn-SOD hepatic genes in CCl4-challenged birds, whereas silymarin significantly up-regulated aforementioned genes. In general, current study showed that silymarin has potential to alleviate the adverse effects of oxidative stress in poultry farms.
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Affiliation(s)
- A Baradaran
- Department of Animal and Poultry Physiology, Faculty of Animal Science, Gorgan University of Agricultural Sciences and Natural Resources, Gorgan, Iran
| | - F Samadi
- Department of Animal and Poultry Physiology, Faculty of Animal Science, Gorgan University of Agricultural Sciences and Natural Resources, Gorgan, Iran
| | - S S Ramezanpour
- Department of Plant Breeding and Biotechnology, Gorgan University of Agricultural Sciences and Natural Resources, Gorgan, Iran
| | - S Yousefdoust
- Department of Animal and Poultry Physiology, Faculty of Animal Science, Gorgan University of Agricultural Sciences and Natural Resources, Gorgan, Iran
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Ahmad S, Zeb A. Effects of phenolic compounds from aqueous extract of Trifolium repens against acetaminophen-induced hepatotoxicity in mice. J Food Biochem 2019; 43:e12963. [PMID: 31489655 DOI: 10.1111/jfbc.12963] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/02/2019] [Revised: 06/10/2019] [Accepted: 06/11/2019] [Indexed: 12/14/2022]
Abstract
The aqueous extract of Trifolium repens (TR) leaves was analyzed for the phenolic profile using reversed phase HPLC-DAD and administered to mice against acetaminophen-induced hepatoxicity. Twenty-four phenolic compounds were identified and quantified. The highest amounts present were of kaempferol-3-(caffeoyldiglucoside)-7-glucoside (983.7 µg/ml), followed by p-coumaroyl-4-glucoside (905.6 µg/ml) and daidzein-O-sulfate (808.3 µg/ml). The aqueous extract was administered to mice along with acetaminophen at different doses. Acetaminophen was found to significantly alter body weight, serum biochemistry, and hematological indices of mice, which were ameliorated by the co-administration of aqueous extract. Liver histopathological studies revealed that acetaminophen significantly induced toxicity, while TR aqueous extract provides curative functions. Lipid peroxidation and total reduced glutathione in the liver were also normalized by the aqueous extract of TR. The aqueous extract of TR was rich in important phenolic compounds, which can be used as a source of beneficial bioactive compounds with hepato-protective function. PRACTICAL APPLICATIONS: Acetaminophen has been widely used as antipyretic and analgesic. However, the major complication reported is hepatotoxicity. Synthetic or conventional drugs used for hepatic diseases or against hepatotoxicity are insufficient and causes severe side effects. For this purpose, traditional medicinal plants or nutraceuticals are used to decrease in the side effects of different hepatotoxic medicine are demanding. Food and neutraceuticals are rich in important polyphenolic compounds which are the best antioxidants. This study was aimed to evaluate the phenolic composition of aqueous extract of Trifolium repens and its potential protective action against the acetaminophen-induced toxicity in mice. This study showed for the first time that the aqueous extract of TR was protective against the hepatotoxicity induced by acetaminophen.
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Affiliation(s)
- Sultan Ahmad
- Laboratory of Biochemistry, Department of Biotechnology, Faculty of Biological Sciences, University of Malakand, Chakdara, Pakistan
| | - Alam Zeb
- Laboratory of Biochemistry, Department of Biotechnology, Faculty of Biological Sciences, University of Malakand, Chakdara, Pakistan
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Li S, Tan HY, Wang N, Feng Y, Wang X, Feng Y. Recent Insights Into the Role of Immune Cells in Alcoholic Liver Disease. Front Immunol 2019; 10:1328. [PMID: 31244862 PMCID: PMC6581703 DOI: 10.3389/fimmu.2019.01328] [Citation(s) in RCA: 47] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2019] [Accepted: 05/24/2019] [Indexed: 12/12/2022] Open
Abstract
Accumulating clinical and experimental evidences have demonstrated that both innate and adaptive immunity are involved in the pathogenesis of alcoholic liver disease (ALD), in which the role of immunity is to fuel the inflammation and to drive the progression of ALD. Various immune cells are implicated in the pathogenesis of ALD. The activation of innate immune cells induced by alcohol and adaptive immune response triggered by oxidative modification of hepatic constituents facilitate the persistent hepatic inflammation. Meanwhile, the suppressed antigen-presenting capability of various innate immune cells and impaired function of T cells may consequently lead to an increased risk of infection in the patients with advanced ALD. In this review, we summarized the significant recent findings of immune cells participating in ALD. The pathways and molecules involved in the regulation of specific immune cells, and novel mediators protecting the liver from alcoholic injury via affecting these cells are particularly highlighted. This review aims to update the knowledge about immunity in the pathogenesis of ALD, which may facilitate to enhancement of currently available interventions for ALD treatment.
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Affiliation(s)
- Sha Li
- Li Ka Shing Faculty of Medicine, School of Chinese Medicine, The University of Hong Kong, Hong Kong, China
| | - Hor-Yue Tan
- Li Ka Shing Faculty of Medicine, School of Chinese Medicine, The University of Hong Kong, Hong Kong, China
| | - Ning Wang
- Li Ka Shing Faculty of Medicine, School of Chinese Medicine, The University of Hong Kong, Hong Kong, China
| | - Yigang Feng
- Guanghua School of Stomatology, Sun Yat-sen University, Guangzhou, China
| | - Xuanbin Wang
- Laboratory of Chinese Herbal Pharmacology, Laboratory of Wudang Local Chinese Medicine Research, Oncology Center, Renmin Hospital, Hubei University of Medicine, Shiyan, China
| | - Yibin Feng
- Li Ka Shing Faculty of Medicine, School of Chinese Medicine, The University of Hong Kong, Hong Kong, China
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Natural products in licorice for the therapy of liver diseases: Progress and future opportunities. Pharmacol Res 2019; 144:210-226. [PMID: 31022523 DOI: 10.1016/j.phrs.2019.04.025] [Citation(s) in RCA: 182] [Impact Index Per Article: 30.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/21/2019] [Revised: 04/18/2019] [Accepted: 04/21/2019] [Indexed: 12/16/2022]
Abstract
Liver diseases related complications represent a significant source of morbidity and mortality worldwide, creating a substantial economic burden. Oxidative stress, excessive inflammation, and dysregulated energy metabolism significantly contributed to liver diseases. Therefore, discovery of novel therapeutic drugs for the treatment of liver diseases are urgently required. Licorice is one of the most commonly used herbal drugs in Traditional Chinese Medicine for the treatment of liver diseases and drug-induced liver injury (DILI). Various bioactive components have been isolated and identified from the licorice, including glycyrrhizin, glycyrrhetinic acid, liquiritigenin, Isoliquiritigenin, licochalcone A, and glycycoumarin. Emerging evidence suggested that these natural products relieved liver diseases and prevented DILI through multi-targeting therapeutic mechanisms, including anti-steatosis, anti-oxidative stress, anti-inflammation, immunoregulation, anti-fibrosis, anti-cancer, and drug-drug interactions. In the current review, we summarized the recent progress in the research of hepatoprotective and toxic effects of different licorice-derived bioactive ingredients and also highlighted the potency of these compounds as promising therapeutic options for the treatment of liver diseases and DILI. We also outlined the networks of underlying molecular signaling pathways. Further pharmacology and toxicology research will contribute to the development of natural products in licorice and their derivatives as medicines with alluring prospect in the clinical application.
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Maithani M, Raturi R, Gupta V, Bansal P. Assessment of compliance level of ICH guidelines for organic volatile impurities in common ayurvedic hepatic formulations. JOURNAL OF COMPLEMENTARY & INTEGRATIVE MEDICINE 2019; 16:/j/jcim.ahead-of-print/jcim-2018-0159/jcim-2018-0159.xml. [PMID: 30870142 DOI: 10.1515/jcim-2018-0159] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/04/2018] [Accepted: 10/07/2018] [Indexed: 11/15/2022]
Abstract
Background Herbal medicines have been used in the treatment of liver diseases for a long time. In recent years, the use of herbal medicines for protection from other strong antibiotics as well as drugs that can damage the liver during their metabolism in liver and for treatment of liver diseases has increased all over the world. It is important to mention that a number of organic solvents are used at different stages of extraction/formulation development for these traditional preparations in industries/pharmacies. In addition, some of these solvents possess established carcinogenic properties and may enter the formulation as residual solvents. Hence as per ICH guidelines it is mandatory to keep the level of these solvents up to permissible limits. There has been a lot of hue and cry that ayurvedic formulations available in the market are not properly standardized for their quality due to lack of stringent regulations and standards from regulatory authorities. Therefore the aim of present work was to assess the compliance of ICH guidelines for level of organic volatile impurities in common marketed ayurvedic hepatic formulations. Methods In this study, 25 ayurvedic herbal formulations available as OTC product have been assessed for presence of residual solvents using gas chromatography with flame ionization detector. Results This study on 25 fast moving hepatic formulations in the market reflects that no residual solvents were detected in any of the formulations however if present were within prescribed permissible limits of ICH guidelines. The data was also subjected to statistical analysis (F-test and t-test at 95% confidence level). Conclusions Results indicate the safety of these hepatic formulations with respect to residual solvents. In addition presents a simple, linear, specific, accurate, precise and rugged gas chromatographic method for estimation of residual solvents.
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Affiliation(s)
- M Maithani
- Multidisciplinary Research Unit, University Centre of Excellence in Research, Baba Farid University of Health Sciences, Faridkot, India
| | - R Raturi
- Multidisciplinary Research Unit, University Centre of Excellence in Research, Baba Farid University of Health Sciences, Faridkot, India
| | - V Gupta
- Multidisciplinary Research Unit, University Centre of Excellence in Research, Baba Farid University of Health Sciences, Faridkot, India
| | - P Bansal
- Multidisciplinary Research Unit, University Centre of Excellence in Research, Baba Farid University of Health Sciences, Faridkot, India
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Daliu P, Santini A, Novellino E. A decade of nutraceutical patents: where are we now in 2018? Expert Opin Ther Pat 2018; 28:875-882. [PMID: 30484340 DOI: 10.1080/13543776.2018.1552260] [Citation(s) in RCA: 79] [Impact Index Per Article: 11.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/27/2022]
Abstract
INTRODUCTION In the last 10 years, nutraceuticals have grown in interest to researchers, industry, and consumers and are now familiar in the collective imagination as a tool for preventing the onset of a disease. Often nutraceuticals are confused with biologically active phytochemicals/botanicals which can have health benefits. This is a misunderstanding however as the term nutraceutical refers to a product that must have a beneficial effect on health proven by clinical testing. Areas covered: A search has been performed on both recent patents and the literature regarding nutraceuticals focusing on the beneficial and proven health effects on pathological conditions to give an overview of the state-of-the-art developments in this area. Patents and literature data addressing specific pathological conditions are discussed. Expert opinion: Nutraceuticals represent a challenge for the future of drug-based pharmacotherapy, and, at the same time, are a powerful tool for the prevention of chronic disease. They are not proposed as an alternative to drugs, but instead, can be helpful to complement a pharmacological therapy and prevent the onset of chronic diseases in subjects who do not qualify for conventional pharmacological treatment.
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Affiliation(s)
- Patricia Daliu
- a Department of Pharmacy , University of Napoli Federico II , Napoli , Italy
| | - Antonello Santini
- a Department of Pharmacy , University of Napoli Federico II , Napoli , Italy
| | - Ettore Novellino
- a Department of Pharmacy , University of Napoli Federico II , Napoli , Italy
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Kim NH, Heo JD, Rho JR, Yang MH, Jeong EJ. The Standardized Extract of Limonium tetragonum Alleviates Chronic Alcoholic Liver Injury in C57Bl/6J Mice. Pharmacogn Mag 2018; 14:58-63. [PMID: 29576702 PMCID: PMC5858243 DOI: 10.4103/pm.pm_44_17] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/06/2017] [Revised: 03/14/2017] [Indexed: 11/06/2022] Open
Abstract
Background: In traditional folk medicine, Limonium tetragonum is used in the treatment of uterine hemorrhage, tinnitus, and oligomenorrhea. Objective: This study aimed to identify the therapeutic effect of L. tetragonum EtOAc extract (EALT) on liver of mice with chronic alcohol poisoning. Materials and Methods: C57BL/6J mice were administered 100 mg/kg of EALT with a single binge ethanol/Lieber-DeCarli liquid diet for 8 weeks. Results: The chronic-binge ethanol diet induced a significant increase in liver marker enzyme activities. Coadministration of EALT reversed the elevation of serum total cholesterol and triglyceride as well as aspartate aminotransferase and alanine aminotransferase due to chronic alcohol consumption. Histologic findings including markedly attenuated fat accumulation in hepatocytes were observed in EALT-treated mice. EALT supplementation prevented alcoholic liver injury through attenuation of inflammatory mediators such as toll-like receptor-4, cytochrome P4502E1, and cyclooxygenase-2, and inflammatory cytokine interleukin-6. Conclusion: Results provided direct experimental evidence for the hepatoprotective effect of EALT in the NIAAA mouse model. Therapeutic attempts with the L. tetragonum extract might be useful in the management of alcoholic liver disease. SUMMARY
Halophyte Limonium tetragonum has recently been of interest in Korea for its nutritional value and salty taste which made it an ideal vegetable Phytochemical analysis of L. tetragonum EtOAc extract (EALT) resulted in nine compounds including catechins and myricetin glycosides as main components Administration of EALT for 8 weeks showed hepatoprotective effect on Lieber-DeCarli diet-fed mouse model A significant decrease in liver marker enzymes and inflammatory mediators was also detected. Abbreviations used: EALT: L. tetragonum EtOAc extract; TC: Total cholesterol; TG: Triglyceride; ROS: Reactive oxygen species; CYP2E1: Cytochrome P4502E1; TLR-4: Toll-like receptor-4; COX-2: Cyclooxygenase-2.
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Affiliation(s)
- Na-Hyun Kim
- Gyeongnam Department of Environment and Toxicology, Korea Institute of Toxicology, Gyeongnam 52834, Republic of Korea
| | - Jeong-Doo Heo
- Gyeongnam Department of Environment and Toxicology, Korea Institute of Toxicology, Gyeongnam 52834, Republic of Korea
| | - Jung-Rae Rho
- Department of Oceanography, Kunsan National University, Jeonbuk 54150, Republic of Korea
| | - Min Hye Yang
- College of Pharmacy, Pusan National University, Busan 46241, Republic of Korea
| | - Eun Ju Jeong
- Department of Agronomy and Medicinal Plant Resources, Gyeongnam National University of Science and Technology, Jinju 52725, Republic of Korea
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Zhang W, Dong Z, Chang X, Zhang C, Rong G, Gao X, Zeng Z, Wang C, Chen Y, Rong Y, Qu J, Liu Z, Lu Y. Protective effect of the total flavonoids from Apocynum venetum L. on carbon tetrachloride-induced hepatotoxicity in vitro and in vivo. J Physiol Biochem 2018. [DOI: 10.1007/s13105-018-0618-0] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
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Dočkalová H, Horký P, Zeman L, Skládanka J. Influence of milk thistle pressed parts on rats liver histology. POTRAVINARSTVO 2018. [DOI: 10.5219/864] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/18/2022] Open
Abstract
Milk thistle (Silybum marianum) is one of the best known and very often used herbs with positive effect on liver. The aim of this article was to study influence of addition of milk thistle pressed parts in feed ration on liver histology and weight increase of laboratory rats. The experiment was tested by 15 pieces of laboratory rats divided into 3 groups (A, B, C). The rats in first group (A) hade feed ration with addition of 10% milk thistle pressed parts, second group (B) hade feed ration with 20% and control group (C) hade feed ration without addition of milk thistle pressed parts. The silymarin content of pressed milk thistle seed was 26.2 mg/g. The aim of this article is to study influence of addition of milk thistle pressed parts in feed ration on liver histology and weight increase of laboratory rats. The hypothesis is that the feeding addition - milk thistle seed pressed parts has positive effect on weight performance and liver histology. Does the feeding addition have any effect on these health indicators? Does feeding of milk thistle seed pressed parts have any sense? In results, the groups with addition of milk thistle had significant bigger average gain increases than the control group. Histological results vary considerably among groups of rats. All rats in the control group had dystrophic liver with sinusoidal congestion. In most rats of the group A, the dystrophy was minimal without congestion. On the other hand, most of rats of the group B had liver dystrophy caused by large droplets steatosis with congestion. All rats in control group C were found to have significant dystrophy caused by steatosis. The results indicate rats receiving the addition of milk thistle pressed parts in their feed had a lower incidence of liver steatosis due to the hepatoprotective effects of silymarin.
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St. John TM. Chronic Hepatitis. Integr Med (Encinitas) 2018. [DOI: 10.1016/b978-0-323-35868-2.00021-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
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Wu JS, Li YF, Li YY, Dai Y, Li WK, Zheng M, Shi ZC, Shi R, Wang TM, Ma BL, Liu P, Ma YM. Huangqi Decoction Alleviates Alpha-Naphthylisothiocyanate Induced Intrahepatic Cholestasis by Reversing Disordered Bile Acid and Glutathione Homeostasis in Mice. Front Pharmacol 2017; 8:938. [PMID: 29311939 PMCID: PMC5742571 DOI: 10.3389/fphar.2017.00938] [Citation(s) in RCA: 39] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/23/2017] [Accepted: 12/11/2017] [Indexed: 12/13/2022] Open
Abstract
Intrahepatic cholestasis is a serious symptom of liver disorders with limited therapies. In this study, we investigated the efficacy of Huangqi decoction (HQD), a two-herb classic traditional Chinese medicine (TCM), in the treatment of alpha-naphthylisothiocyanate (ANIT)-induced intrahepatic cholestasis in mice. HQD treatment ameliorated impaired hepatic function and tissue damage. A metabolomics study revealed that the endogenous metabolites significantly affected by HQD were related to bile acid (BA) biosynthesis and glutathione metabolism pathways. HQD treatment decreased the intrahepatic accumulation of cytotoxic BAs, normalized serum BA levels, and increased biliary and urinary BA excretion. Additionally, HQD restored the hepatic glutathione content and suppressed reactive oxygen species (ROS) in cholestatic mice. Protein and gene analysis revealed that HQD increased the expression of the hepatic metabolizing enzymes cytochrome P450 (CYP) 2B10 and UDP glucuronosyltransferase family 1 member A1 (UGT1A1), as well as multidrug resistance-associated protein 2 (Mrp2), Mrp3, and Mrp4, which play crucial roles in BA homeostasis. Further, HQD increased the protein expression of glutamate-cysteine ligase, which is involved in the synthesis of glutathione. Importantly, HQD increased the nuclear expression of nuclear factor-E2-related factor-2 (Nrf2). In conclusion, HQD protects against intrahepatic cholestasis by reversing the disordered homeostasis of BAs and glutathione.
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Affiliation(s)
- Jia-Sheng Wu
- Department of Pharmacology, School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Yi-Fei Li
- Department of Pharmacology, School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Yuan-Yuan Li
- Department of Pharmacology, School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Yan Dai
- Department of Pharmacology, School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Wen-Kai Li
- Department of Pharmacology, School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Min Zheng
- Department of Pharmacology, School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Zheng-Chun Shi
- Department of Pharmacology, School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Rong Shi
- Department of Pharmacology, School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Tian-Ming Wang
- Department of Pharmacology, School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Bing-Liang Ma
- Department of Pharmacology, School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Ping Liu
- Key Laboratory of Liver and Kidney Diseases (Ministry of Education), Institute of Liver Diseases, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Yue-Ming Ma
- Department of Pharmacology, School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai, China.,Shanghai Key Laboratory of Compound Chinese Medicines, Shanghai University of Traditional Chinese Medicine, Shanghai, China
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37
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Darvishi-Khezri H, Salehifar E, Kosaryan M, Karami H, Alipour A, Shaki F, Aliasgharian A. The impact of silymarin on antioxidant and oxidative status in patients with β-thalassemia major: A crossover, randomized controlled trial. Complement Ther Med 2017; 35:25-32. [DOI: 10.1016/j.ctim.2017.08.007] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/08/2017] [Revised: 08/06/2017] [Accepted: 08/07/2017] [Indexed: 02/08/2023] Open
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Ali M, Khan T, Fatima K, Ali QUA, Ovais M, Khalil AT, Ullah I, Raza A, Shinwari ZK, Idrees M. Selected hepatoprotective herbal medicines: Evidence from ethnomedicinal applications, animal models, and possible mechanism of actions. Phytother Res 2017; 32:199-215. [PMID: 29047177 PMCID: PMC7167792 DOI: 10.1002/ptr.5957] [Citation(s) in RCA: 70] [Impact Index Per Article: 8.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/08/2017] [Revised: 08/30/2017] [Accepted: 09/26/2017] [Indexed: 02/06/2023]
Abstract
Insight into the hepatoprotective effects of medicinally important plants is important, both for physicians and researchers. Main reasons for the use of herbal medicine include their lesser cost compared with conventional drugs, lesser undesirable drug reactions and thus high safety, and reduced side effects. The present review focuses on the composition, pharmacology, and results of experimental trials of selected medicinal plants: Silybum marianum (L.) Gaertn., Glycyrrhiza glabra, Phyllanthus amarus Schumach. & Thonn., Salvia miltiorrhiza Bunge., Astragalus membranaceus (Fisch.) Bunge, Capparis spinosa (L.), Cichorium intybus (L.), Solanum nigrum (L.), Sapindus mukorossi Gaertn., Ginkgo biloba (L.), Woodfordia fruticosa (L.) Kurz, Vitex trifolia (L.), Schisandra chinensis (Turcz.) Baill., Cuscuta chinensis (Lam.), Lycium barbarum, Angelica sinensis (Oliv.) Diels, and Litsea coreana (H. Lev.). The probable modes of action of these plants include immunomodulation, stimulation of hepatic DNA synthesis, simulation of superoxide dismutase and glutathione reductase to inhibit oxidation in hepatocytes, reduction of intracellular reactive oxygen species by enhancing levels of antioxidants, suppression of ethanol-induced lipid accumulation, inhibition of nucleic acid polymerases to downregulate viral mRNA transcription and translation, free radical scavenging and reduction of hepatic fibrosis by decreasing the levels of transforming growth factor beta-1, and collagen synthesis in hepatic cells. However, further research is needed to identify, characterize, and standardize the active ingredients, useful compounds, and their preparations for the treatment of liver diseases.
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Affiliation(s)
- Muhammad Ali
- Department of Biotechnology, Quaid-i-Azam University Islamabad, Islamabad, 45320, Pakistan
| | - Tariq Khan
- Department of Biotechnology, Quaid-i-Azam University Islamabad, Islamabad, 45320, Pakistan.,Department of Biotechnology, University of Malakand Chakdara Dir (L)-18000, Khyber Pakhtunkhwa, Pakistan
| | - Kaneez Fatima
- Department of Biotechnology, Quaid-i-Azam University Islamabad, Islamabad, 45320, Pakistan
| | - Qurat Ul Ain Ali
- Department of Biotechnology, Quaid-i-Azam University Islamabad, Islamabad, 45320, Pakistan
| | - Muhammad Ovais
- Department of Biotechnology, Quaid-i-Azam University Islamabad, Islamabad, 45320, Pakistan
| | - Ali Talha Khalil
- Department of Biotechnology, Quaid-i-Azam University Islamabad, Islamabad, 45320, Pakistan
| | - Ikram Ullah
- Department of Biotechnology, Quaid-i-Azam University Islamabad, Islamabad, 45320, Pakistan
| | - Abida Raza
- National Institute of Laser and Optronics, Nilore, 45650, Pakistan
| | - Zabta Khan Shinwari
- Department of Biotechnology, Quaid-i-Azam University Islamabad, Islamabad, 45320, Pakistan
| | - Muhammad Idrees
- Hazara University Mansehra, Khyber Pakhtunkhwa, 21120, Pakistan.,Center for Applied Molecular Biology (CAMB), University of the Punjab, Lahore, 53700, Pakistan
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39
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Xu L, Sheng T, Liu X, Zhang T, Wang Z, Han H. Analyzing the hepatoprotective effect of the Swertia cincta Burkillextract against ANIT-induced cholestasis in rats by modulating the expression of transporters and metabolic enzymes. JOURNAL OF ETHNOPHARMACOLOGY 2017; 209:91-99. [PMID: 28734962 DOI: 10.1016/j.jep.2017.07.031] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/17/2016] [Revised: 07/15/2017] [Accepted: 07/18/2017] [Indexed: 06/07/2023]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Swertia cincta Burkill was traditionally used for treating jaundice and various types of chronic and acute hepatitis in Yunnan and Tibet in China for hundreds of years. This study aims to investigate the protective effect of S. cincta Burkill (ESC) extract on alpha-naphthylisothiocyanate (ANIT)-induced hepatotoxicity and cholestasis in rats. MATERIALS AND METHODS Crude extracts were prepared using 90% ethanol and by vacuum drying. We utilized an ultra-high-performance liquid chromatography coupled with electrospray ionization quadrupole time-of-flight tandem mass spectrometry (UHPLC/Q-TOF-MS) system to conduct a phytochemical analysis of the active components of ESC. Liver function was evaluated by measuring the serum levels of enzymes and components and by analyzing the liver histology. We also measured the expression of bile metabolism-related transporters and metabolic enzymes at both protein and mRNA levels to elucidate the underlying mechanisms. RESULTS ESC analysis using an UHPLC/Q-TOF-MS revealed eight compounds. Oral administration of ESC to ANIT-treated rats can significantly reduce the increases in serum levels of ALT, AST, ALP, TBIL, and TBA. It can also improve liver pathology and bile flow. Western blot and qRT-PCR analyses showed that ESC upregulated the protein and mRNA expression of Fxr, Ntcp, Bsep, Cyp7a1, Mrp2, and Mdr2. CONCLUSION ESC could alleviate liver injury by reducing enzyme activities of serums, improving liver pathology and bile flow. The protective mechanism was associated with regulation of the expression of hepatic transporters and metabolic enzymes.
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Affiliation(s)
- Lili Xu
- Institute of Traditional Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai 201210, China; Institute of Science, Technology and Humanities, Shanghai University of Traditional Chinese Medicine, Shanghai 201210, China.
| | - Tingting Sheng
- Experiment Center for Teaching and Learning, Shanghai University of Traditional Chinese Medicine, Shanghai 201210, China; School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai 201210, China.
| | - Xiaolong Liu
- Institute of Traditional Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai 201210, China.
| | - Tong Zhang
- Experiment Center for Teaching and Learning, Shanghai University of Traditional Chinese Medicine, Shanghai 201210, China; School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai 201210, China.
| | - Zhengtao Wang
- Institute of Traditional Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai 201210, China.
| | - Han Han
- Experiment Center for Teaching and Learning, Shanghai University of Traditional Chinese Medicine, Shanghai 201210, China; Institute of Traditional Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai 201210, China.
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Chester K, Paliwal S, Khan W, Ahmad S. UPLC-ESI-MS/MS and HPTLC Method for Quantitative Estimation of Cytotoxic Glycosides and Aglycone in Bioactivity Guided Fractions of Solanum nigrum L. Front Pharmacol 2017; 8:434. [PMID: 28729835 PMCID: PMC5498608 DOI: 10.3389/fphar.2017.00434] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/05/2017] [Accepted: 06/16/2017] [Indexed: 11/13/2022] Open
Abstract
Solanum nigrum L., is traditionally used for the management of the various liver disorders. Investigating the effect of polarity based fractionation of S. nigrum for its hepatoprotective effect on Hep G2 cells in vitro to provide base of its activity by quantifying in steroidal glycosides responsible for hepatoprotective potential. A new UPLC-ESI-MS/MS method following a high performance thin layer chromatography (HPTLC) has been developed and validated for quantification of steroidal glycosides and aglycone (solasonine, solamargine, and solasodine, respectively). The in vitro antioxidant potential, total phenolics, and flavonoid content were also determined in different fractions. The newly developed UPLC-ESI-MS/MS and HPTLC methods were linear (r2 ≥ 0.99), precise, accurate, and showing recovery more than 97%. The n-butanol enriched fraction of S. nigrum berries was found to be the most potent hepatoprotective fraction against all other fractions as it showed significantly (p < 0.01) better in vitro anti-oxidant potential than other fractions. Quantification by both methods revealed that, content of steroidal glycosides and aglycones are more than 20% in n-butanol fraction as compared to other fractions. The screened steroidal glycoside n-butanol enriched fraction underwent bioefficacy studies against D-galactosamine and H2O2 induced toxicity in HepG2 cell line showing significant (p < 0.05) liver protection. However, developed method can be used for the quality control analysis with respect to targeted metabolites and it can be explored for the pharmacokinetic and pharmacodynamic analysis in future.
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Affiliation(s)
| | | | - Washim Khan
- Bioactive Natural Product Laboratory, Department of Pharmacognosy and Phytochemistry, Faculty of Pharmacy, Jamia Hamdard UniversityNew Delhi, India
| | - Sayeed Ahmad
- Bioactive Natural Product Laboratory, Department of Pharmacognosy and Phytochemistry, Faculty of Pharmacy, Jamia Hamdard UniversityNew Delhi, India
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41
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Adebayo AH, Ashano EE, Yakubu OF, Okubena O. Pro-inflammatory and toxicological evaluation of Hepacare ® in mice. J Taibah Univ Med Sci 2017; 12:313-323. [PMID: 31435257 PMCID: PMC6695049 DOI: 10.1016/j.jtumed.2017.02.004] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/12/2016] [Revised: 02/10/2017] [Accepted: 02/12/2017] [Indexed: 11/18/2022] Open
Abstract
Objectives Hepacare® is a widely marketed herbal formulation in Nigeria for treating chronic liver ailments. This study evaluated the safety, as well as pro-inflammatory and genotoxicity effects, of Hepacare® in mice. Methods The effect of the formulation was estimated in a 28-day study where 25 mice were divided into five groups, and Hepacare® was orally administered at 250, 500, 750 and 2500 mg/kg body weight. The biochemical and haematological parameters were determined, organ weights were estimated and histopathology was also conducted. mRNA expression of the pro-inflammatory cytokines, TNF-α and IL-6 was estimated by RT-PCR in acute toxicity experiments. Results The LD50 was calculated at 3807.89 mg/kg body weight in mice. There was a significant increase (p < 0.05) in the ALP activity in the 750 mg/kg treated group, while the 2500 mg/kg group exhibited significant increases in their AST, ALT, ALP, total bilirubin and total protein levels compared with the control group. However, there was a significant dose related increase in monocytes counts in the groups treated with 750 and 2500 mg/kg. There was no significant difference (p > 0.05) in TNF-α and IL-6 mRNA expression in the genotoxicity studies in all of the treatment groups compared with the control. However, several hepatic and nephro-pathological derangements were observed in the groups treated with higher doses of the formulation. Conclusions The study established that the herbal formulation may not induce significant pro-inflammatory toxic responses and genotoxic effects, but prolonged intake of higher doses may cause severe biochemical and clinical abnormalities.
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Affiliation(s)
- Abiodun H Adebayo
- Department of Biological Sciences, College of Science and Technology, Covenant University, Ota, Nigeria
| | - Efejiro E Ashano
- Department of Biological Sciences, College of Science and Technology, Covenant University, Ota, Nigeria
| | - Omolara F Yakubu
- Department of Biological Sciences, College of Science and Technology, Covenant University, Ota, Nigeria
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42
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Shirani M, Raeisi R, Heidari-Soureshjani S, Asadi-Samani M, Luther T. A review for discovering hepatoprotective herbal drugs with least side effects on kidney. J Nephropharmacol 2017. [DOI: 10.15171/npj.2017.03] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022] Open
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43
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Tlili N, Feriani A, Saadoui E, Nasri N, Khaldi A. Capparis spinosa leaves extract: Source of bioantioxidants with nephroprotective and hepatoprotective effects. Biomed Pharmacother 2017; 87:171-179. [PMID: 28056421 DOI: 10.1016/j.biopha.2016.12.052] [Citation(s) in RCA: 41] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/24/2016] [Revised: 12/01/2016] [Accepted: 12/14/2016] [Indexed: 01/15/2023] Open
Abstract
Capparis spinosa, Capparidaceae, is largely distributed all over the Mediterranean Basin and is traditionally used to treat many illnesses, such as liver and kidney diseases. The aim of the current study was to explore the antioxidant, nephroprotective and hepatoprotective effects of methanolic extract of Capparis spinosa leaves (MECS) associated with its phytochemical content. The levels of total phenolics, flavonoids and condensed tannins were 23.37mgGAE/g, 9.05mgQE/g and 9.35mgTAE/g, respectively. HPLC analysis revealed nine compounds, namely rutin, resveratrol, coumarin, epicatechin, luteolin, catechin, kaempferol, vanillic acid and gallic acid. The MECS showed interesting antioxidant capacity. The MECS-treatment significantly reduced the increased plasma levels of creatinine, urea and uric acid, reduced the elevated MDA levels, significantly reduced the antioxidant enzyme activities and restored the kidney damage, provoked by cisplatin-treatment. Furthermore, MECS-treatment significantly prevented the increase in serum ALT, AST and LDH levels in acute liver damage induced by CCl4, decreased the amount of hepatic malondialdehyde (MDA) formation and elevated the activities of SOD, CAT and GPx, and restored liver injury. This study supports the traditionally use of C. spinosa to cure kidney and liver diseases. The obtained results highlighted the possible use of C. spinosa as a source of phytochemical with important biological advantages.
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Affiliation(s)
- Nizar Tlili
- Laboratoire de biochimie, Faculté des Sciences de Tunis, Université Tunis El-Manar, 2092 Tunis, Tunisie; Institut National de Recherches en Génie Rural, Eaux et Forêts, Université de Carthage, BP 10, Ariana 2080, Tunisie.
| | - Anouar Feriani
- Unité de Biochimie Macromoléculaire et Génétique, Faculté des Sciences de Gafsa, cité Zarroug, Université de Gafsa, 2112 Gafsa, Tunisie; Laboratoire d'Ecophysiologie Animale, Faculté des Sciences de Sfax, Tunisia
| | - Ezzeddine Saadoui
- Institut National de Recherches en Génie Rural, Eaux et Forêts, Université de Carthage, BP 10, Ariana 2080, Tunisie
| | - Nizar Nasri
- Laboratoire de biochimie, Faculté des Sciences de Tunis, Université Tunis El-Manar, 2092 Tunis, Tunisie
| | - Abdelhamid Khaldi
- Institut National de Recherches en Génie Rural, Eaux et Forêts, Université de Carthage, BP 10, Ariana 2080, Tunisie
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Naturally Occurring Nrf2 Activators: Potential in Treatment of Liver Injury. OXIDATIVE MEDICINE AND CELLULAR LONGEVITY 2016; 2016:3453926. [PMID: 28101296 PMCID: PMC5215260 DOI: 10.1155/2016/3453926] [Citation(s) in RCA: 88] [Impact Index Per Article: 9.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 06/17/2016] [Revised: 11/08/2016] [Accepted: 11/28/2016] [Indexed: 12/26/2022]
Abstract
Oxidative stress plays a major role in acute and chronic liver injury. In hepatocytes, oxidative stress frequently triggers antioxidant response by activating nuclear erythroid 2-related factor 2 (Nrf2), a transcription factor, which upregulates various cytoprotective genes. Thus, Nrf2 is considered a potential therapeutic target to halt liver injury. Several studies indicate that activation of Nrf2 signaling pathway ameliorates liver injury. The hepatoprotective potential of naturally occurring compounds has been investigated in various models of liver injuries. In this review, we comprehensively appraise various phytochemicals that have been assessed for their potential to halt acute and chronic liver injury by enhancing the activation of Nrf2 and have the potential for use in humans.
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Pinchuk SV, Vasilevich IB, Kvacheva ZB, Volotovski ID. The effect of quercetin on hepatic differentiation of human adipose-derived mesenchymal stem cells. ACTA ACUST UNITED AC 2016. [DOI: 10.1134/s1990519x16050102] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
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46
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Chiu HW, Hua KF. Hepatoprotective Effect of Wheat-Based Solid-State Fermented Antrodia cinnamomea in Carbon Tetrachloride-Induced Liver Injury in Rat. PLoS One 2016; 11:e0153087. [PMID: 27046059 PMCID: PMC4821531 DOI: 10.1371/journal.pone.0153087] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/22/2015] [Accepted: 03/23/2016] [Indexed: 12/21/2022] Open
Abstract
Antrodia cinnamomea (A. cinnamomea) is an indigenous medical fungus in Taiwan and has multiple biological functions, including hepatoprotective and immune-modulatory effects. Currently, the commercially available A. cinnamomea are mainly liquid- and solid-state fermented A. cinnamomea. However, the hepatoprotective effect of solid-state fermented A. cinnamomea has never been reported. Here we evaluate the ability of air-dried, ground and non-extracted wheat-based solid-state fermented A. cinnamomea (WFAC) to protect against carbon tetrachloride (CCl4)-induced hepatic injury in vivo. The results showed that oral administration of WFAC dose dependently (180, 540 and 1080 mg/kg) ameliorated the increase in plasma aspartate aminotransferase and alanine aminotransferase levels caused by chronic repeated CCl4 intoxication in rats. WFAC significantly reduced the CCl4-induced increase in hepatic lipid peroxidation levels and hydroxyproline contents, as well as reducing the spleen weight and water content of the liver. WFAC also restored the hepatic soluble protein synthesis and plasma albumin concentration in CCl4-intoxicated rats, but it did not affect the activities of superoxide dismutase, catalase, or glutathione peroxidase. In addition, a hepatic morphological analysis showed that the hepatic fibrosis and necrosis induced by CCl4 were significantly ameliorated by WFAC. Furthermore, the body weights of control rats and WFAC-administered rats were not significantly different, and no adverse effects were observed in WFAC-administered rats. These results indicate that WFAC is a nontoxic hepatoprotective agent against chronic CCl4-induced hepatic injury.
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Affiliation(s)
- Huan-Wen Chiu
- Department of Biotechnology and Animal Science, National Ilan University, Ilan, Taiwan
| | - Kuo-Feng Hua
- Department of Biotechnology and Animal Science, National Ilan University, Ilan, Taiwan
- Department of Pathology, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan
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Thomford NE, Awortwe C, Dzobo K, Adu F, Chopera D, Wonkam A, Skelton M, Blackhurst D, Dandara C. Inhibition of CYP2B6 by Medicinal Plant Extracts: Implication for Use of Efavirenz and Nevirapine-Based Highly Active Anti-Retroviral Therapy (HAART) in Resource-Limited Settings. Molecules 2016; 21:molecules21020211. [PMID: 26891286 PMCID: PMC6273559 DOI: 10.3390/molecules21020211] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/23/2015] [Revised: 01/25/2016] [Accepted: 02/02/2016] [Indexed: 12/22/2022] Open
Abstract
Highly active antiretroviral therapy (HAART) has greatly improved health parameters of HIV infected individuals. However, there are several challenges associated with the chronic nature of HAART administration. For populations in health transition, dual use of medicinal plant extracts and conventional medicine poses a significant challenge. There is need to evaluate interactions between commonly used medicinal plant extracts and antiretroviral drugs used against HIV/AIDS. Efavirenz (EFV) and nevirapine (NVP) are the major components of HAART both metabolized by CYP2B6, an enzyme that can potentially be inhibited or induced by compounds found in medicinal plant extracts. The purpose of this study was to evaluate the effects of extracts of selected commonly used medicinal plants on CYP2B6 enzyme activity. Recombinant human CYP2B6 was used to evaluate inhibition, allowing the assessment of herb-drug interactions (HDI) of medicinal plants Hyptis suaveolens, Myrothamnus flabellifolius, Launaea taraxacifolia, Boerhavia diffusa and Newbouldia laevis. The potential of these medicinal extracts to cause HDI was ranked accordingly for reversible inhibition and also classified as potential time-dependent inhibitor (TDI) candidates. The most potent inhibitor for CYP2B6 was Hyptis suaveolens extract (IC50 = 19.09 ± 1.16 µg/mL), followed by Myrothamnus flabellifolius extract (IC50 = 23.66 ± 4.86 µg/mL), Launaea taraxacifolia extract (IC50 = 33.87 ± 1.54 µg/mL), and Boerhavia diffusa extract (IC50 = 34.93 ± 1.06 µg/mL). Newbouldia laevis extract, however, exhibited weak inhibitory effects (IC50 = 100 ± 8.71 µg/mL) on CYP2B6. Launaea taraxacifolia exhibited a TDI (3.17) effect on CYP2B6 and showed a high concentration of known CYP450 inhibitory phenolic compounds, chlorogenic acid and caffeic acid. The implication for these observations is that drugs that are metabolized by CYP2B6 when co-administered with these herbal medicines and when adequate amounts of the extracts reach the liver, there is a high likelihood of standard doses affecting drug plasma concentrations which could lead to toxicity.
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Affiliation(s)
- Nicholas E Thomford
- Division of Human Genetics, Department of Pathology & Institute of Infectious Disease and Molecular Medicine, Faculty of Health Sciences, University of Cape Town, Anzio Road, Observatory, Cape Town 7925, South Africa.
- School of Medical Sciences, University of Cape Coast, Cape Coast, PMB, Ghana.
| | - Charles Awortwe
- Division of Clinical Pharmacology, Faculty of Medicine and Health Sciences, University of Stellenbosch, Cape Town 7602, South Africa.
| | - Kevin Dzobo
- International Center for Genetic Engineering and Biotechnology (ICGEB), Cape Town component, Faculty of Health Sciences, University of Cape Town, Anzio Road, Observatory, Cape Town 7925, South Africa.
- Division of Medical Biochemistry, Faculty of Health Sciences, University of Cape Town, Anzio Road, Observatory, Cape Town 7925, South Africa.
| | - Faustina Adu
- School of Medical Sciences, University of Cape Coast, Cape Coast, PMB, Ghana.
| | - Denis Chopera
- Division of Medical Virology, Department of Pathology & Institute of Infectious Disease and Molecular Medicine, Faculty of Health Sciences, University of Cape Town, Anzio Road, Observatory, Cape Town 7925, South Africa.
| | - Ambroise Wonkam
- Division of Human Genetics, Department of Pathology & Institute of Infectious Disease and Molecular Medicine, Faculty of Health Sciences, University of Cape Town, Anzio Road, Observatory, Cape Town 7925, South Africa.
| | - Michelle Skelton
- Division of Human Genetics, Department of Pathology & Institute of Infectious Disease and Molecular Medicine, Faculty of Health Sciences, University of Cape Town, Anzio Road, Observatory, Cape Town 7925, South Africa.
| | - Dee Blackhurst
- Division of Chemical Pathology, Department of Pathology & Institute of Infectious Disease and Molecular Medicine, Faculty of Health Sciences, University of Cape Town, Anzio Road, Observatory, Cape Town 7925, South Africa.
| | - Collet Dandara
- Division of Human Genetics, Department of Pathology & Institute of Infectious Disease and Molecular Medicine, Faculty of Health Sciences, University of Cape Town, Anzio Road, Observatory, Cape Town 7925, South Africa.
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Kim MS, Ong M, Qu X. Optimal management for alcoholic liver disease: Conventional medications, natural therapy or combination? World J Gastroenterol 2016; 22:8-23. [PMID: 26755857 PMCID: PMC4698510 DOI: 10.3748/wjg.v22.i1.8] [Citation(s) in RCA: 39] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/28/2015] [Revised: 07/07/2015] [Accepted: 11/13/2015] [Indexed: 02/06/2023] Open
Abstract
Alcohol consumption is the principal factor in the pathogenesis of chronic liver diseases. Alcoholic liver disease (ALD) is defined by histological lesions on the liver that can range from simple hepatic steatosis to more advanced stages such as alcoholic steatohepatitis, cirrhosis, hepatocellular carcinoma and liver failure. As one of the oldest forms of liver injury known to humans, ALD is still a leading cause of liver-related morbidity and mortality and the burden is exerting on medical systems with hospitalization and management costs rising constantly worldwide. Although the biological mechanisms, including increasing of acetaldehyde, oxidative stress with induction of cytochrome p450 2E1, inflammatory cytokine release, abnormal lipid metabolism and induction of hepatocyte apoptosis, by which chronic alcohol consumption triggers serious complex progression of ALD is well established, there is no universally accepted therapy to prevent or reverse. In this article, we have briefly reviewed the pathogenesis of ALD and the molecular targets for development of novel therapies. This review is focused on current therapeutic strategies for ALD, including lifestyle modification with nutrition supplements, available pharmacological drugs and new agents that are under development, liver transplantation, application of complementary medicines, and their combination. The relevant molecular mechanisms of each conventional medication and natural agent have been reviewed according to current available knowledge in the literature. We also summarized efficacy vs safety on conventional and herbal medicines which are specifically used for the prevention and treatment of ALD. Through a system review, this article highlighted that the combination of pharmaceutical drugs with naturally occurring agents may offer an optimal management for ALD and its complications. It is worthwhile to conduct large-scale, multiple centre clinical trials to further prove the safety and benefits for the integrative therapy on ALD.
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Novel Investigations of Flavonoids as Chemopreventive Agents for Hepatocellular Carcinoma. BIOMED RESEARCH INTERNATIONAL 2015; 2015:840542. [PMID: 26858957 PMCID: PMC4695650 DOI: 10.1155/2015/840542] [Citation(s) in RCA: 49] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 09/02/2015] [Accepted: 10/19/2015] [Indexed: 12/16/2022]
Abstract
We would like to highlight the application of natural products to hepatocellular carcinoma (HCC). We will focus on the natural products known as flavonoids, which target this disease at different stages of hepatocarcinogenesis. In spite of the use of chemotherapy and radiotherapy in treating HCC, patients with HCC still face poor prognosis because of the nature of multidrug resistance and toxicity derived from chemotherapy and radiotherapy. Flavonoids can be found in many vegetables, fruits, and herbal medicines that exert their different anticancer effects via different intracellular signaling pathways and serve as antioxidants. In this review, we will discuss seven common flavonoids that exert different biological effects against HCC via different pathways.
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Song X, Yin S, Huo Y, Liang M, Fan L, Ye M, Hu H. Glycycoumarin ameliorates alcohol-induced hepatotoxicity via activation of Nrf2 and autophagy. Free Radic Biol Med 2015; 89:135-46. [PMID: 26169726 DOI: 10.1016/j.freeradbiomed.2015.07.006] [Citation(s) in RCA: 53] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/19/2014] [Revised: 06/24/2015] [Accepted: 07/07/2015] [Indexed: 02/06/2023]
Abstract
Licorice, a traditional Chinese medicine, has been used to treat various diseases, including liver disease, for centuries. However, the chemical basis and biological mechanisms underlying the biological functions of licorice remain elusive. The purpose of the current study was to test the hepatoprotective effect of glycycoumarin (GCM), a representative coumarin in licorice, using animal models of both chronic and acute alcoholic liver injury. C57BL/6J mice were used to evaluate the hepatoprotective effect of GCM on liver injury induced by either chronic or acute ethanol exposure. AML-12 and HepG2 cells were utilized to determine the functional role of Nrf2 in the hepatoprotective effect of GCM and to decipher the mechanisms of GCM-induced Nrf2 activation. We found that treatment with GCM leads to a significant reduction in hepatotoxicity in response to either chronic or acute ethanol exposure. Further mechanistic investigations reveal that activation of Nrf2 via the p38 pathway and induction of autophagy by GCM contribute to its hepatoprotective activity. In addition, we demonstrate that p62 upregulation by a transcriptional mechanism also contributes to Nrf2 activation via a positive feedback loop. Our study has identified GCM as a novel active ingredient that contributes to the hepatoprotective activity of licorice.
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Affiliation(s)
- Xinhua Song
- Department of Nutrition and Health, College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100083, China
| | - Shutao Yin
- Department of Nutrition and Health, College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100083, China
| | - Yazhen Huo
- Department of Nutrition and Health, College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100083, China
| | - Min Liang
- Department of Nutrition and Health, College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100083, China
| | - Lihong Fan
- College of Veterinary Medicine, China Agricultural University, Beijing 100193, China
| | - Min Ye
- State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China.
| | - Hongbo Hu
- Department of Nutrition and Health, College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100083, China.
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