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Zhu Y, Jia Y, Zhang E. Oxidative stress modulation in alcohol-related liver disease: From chinese botanical drugs to exercise-based interventions. Front Pharmacol 2025; 16:1516603. [PMID: 40351443 PMCID: PMC12062749 DOI: 10.3389/fphar.2025.1516603] [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: 10/24/2024] [Accepted: 03/10/2025] [Indexed: 05/14/2025] Open
Abstract
Alcohol-related liver disease (ALD) is a chronic liver injury caused by long-term excessive alcohol consumption, with complex and multifaceted pathological mechanisms. Research indicates that oxidative stress (OS), inflammatory responses, and lipid metabolic disturbances induced by alcohol and its metabolites are primary contributors to hepatocyte injury, positioning OS as a key target in ALD treatment. The main non-pharmacological treatment for ALD is alcohol abstinence, while medical treatment primarily relies on Western pharmacological interventions. However, recent research has increasingly highlighted the potential of Chinese botanical drugs in improving histological features and modulating signaling pathways associated with OS in ALD, underscoring the therapeutic potential of traditional Chinese herb medicine. Despite these promising findings, the precise mechanisms and effects of these extracts remain incompletely understood, and potential side effects must be considered. Therefore, a comprehensive analysis of herbal extracts with therapeutic effects is essential to optimize clinical administration and ensure safe, effective treatment. This review focuses on OS as a central theme, categorizing Chinese botanical drugs into six major groups-flavonoids, polyphenols, terpenoids, alkaloids, saponins, and anthraquinones-all widely used in traditional Chinese herb medicine. The review provides an overview of their botanical characteristics and therapeutic actions in the context of ALD, offering insights into OS regulation and exploring their potential as treatments for ALD. Notably, physical exercise shares overlapping mechanisms with botanical drugs in regulating OS. Combining two strategies could offer a promising integrative treatment for ALD, though further research is needed to confirm their synergistic benefits and optimize clinical applications.
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Affiliation(s)
| | | | - Enming Zhang
- School of Sports Medicine and Physical Therapy, Beijing Sport University, Beijing, China
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Yuan M, Wan Y, Wang Y, Li S, Tang J, Liang X, Tan X, Yi S, Wei X, Li X, Guo L, Guo Y. Ursodeoxycholic acid grafted chitosan oligosaccharide self-assembled micelles with enhanced oral absorption and antidiabetic effect of oleanolic acid. Food Chem 2025; 470:142708. [PMID: 39752745 DOI: 10.1016/j.foodchem.2024.142708] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/18/2024] [Revised: 11/26/2024] [Accepted: 12/28/2024] [Indexed: 01/29/2025]
Abstract
Oleanolic acid (OA) is a food-derived bioactive component with antidiabetic activity, but its water solubility and oral bioavailability are notably restricted. In this study, to overcome these limitations, ursodeoxycholic acid-modified chitosan oligosaccharide (UCOS) was synthesized to encapsulate OA in self-assembled nanomicelles (UCOS-OA). The encapsulation efficiency and drug loading of UCOS-OA were 86 % and 11 %, respectively. UCOS-OA exhibited enhanced gastrointestinal stability and prolonged intestinal retention time when compared with free OA, resulting in a 10.6-fold increase in oral bioavailability. The enhanced antidiabetic activity of UCOS-OA was confirmed in the type 2 diabetes mellitus mice model, as it significantly improved glycolipid metabolism disorders and mitigated liver injury. Furthermore, UCOS-OA ameliorated the dysbiosis of gut microbiota and fecal metabolites. In conclusion, UCOS serves as an effective polymeric carrier for encapsulating OA, thereby improving its bioavailability and antidiabetic activity. This work provides valuable insights for the advancement of oral delivery systems for bioactive compounds.
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Affiliation(s)
- Minghao Yuan
- State Key Laboratory of Southwestern Chinese Medicine Resources, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, Sichuan, China; School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, Sichuan, China
| | - Yan Wan
- State Key Laboratory of Southwestern Chinese Medicine Resources, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, Sichuan, China; School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, Sichuan, China
| | - Yulu Wang
- State Key Laboratory of Southwestern Chinese Medicine Resources, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, Sichuan, China; School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, Sichuan, China
| | - Sihui Li
- State Key Laboratory of Southwestern Chinese Medicine Resources, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, Sichuan, China; School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, Sichuan, China
| | - Jiamei Tang
- State Key Laboratory of Southwestern Chinese Medicine Resources, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, Sichuan, China; School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, Sichuan, China
| | - Xue Liang
- State Key Laboratory of Southwestern Chinese Medicine Resources, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, Sichuan, China; School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, Sichuan, China
| | - Xin Tan
- State Key Laboratory of Southwestern Chinese Medicine Resources, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, Sichuan, China; School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, Sichuan, China
| | - Sirui Yi
- State Key Laboratory of Southwestern Chinese Medicine Resources, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, Sichuan, China; School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, Sichuan, China
| | - Xiaohang Wei
- State Key Laboratory of Southwestern Chinese Medicine Resources, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, Sichuan, China; School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, Sichuan, China
| | - Xiaohong Li
- State Key Laboratory of Southwestern Chinese Medicine Resources, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, Sichuan, China; School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, Sichuan, China
| | - Li Guo
- State Key Laboratory of Southwestern Chinese Medicine Resources, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, Sichuan, China; School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, Sichuan, China.
| | - Yiping Guo
- State Key Laboratory of Southwestern Chinese Medicine Resources, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, Sichuan, China; School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, Sichuan, China.
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Dong YW, Qu HX, Wang YQ, Qi JJ, Wei HK, Sun BX, Sun H, Liang S. Oleanolic acid improves the in vitro developmental competence of early porcine embryos by reducing oxidative stress and ameliorating mitochondrial function. Anim Biosci 2025; 38:431-443. [PMID: 39210793 PMCID: PMC11917446 DOI: 10.5713/ab.24.0307] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/08/2024] [Accepted: 08/13/2024] [Indexed: 09/04/2024] Open
Abstract
OBJECTIVE Oleanolic acid (OA) is a pentacyclic triterpenoid with antioxidant activity that can be an effective scavenger of free radicals in cells. This study was designed to investigate the effects of OA on porcine early embryo developmental competence in vitro and its possible mechanisms of action. METHODS In the present study, parthenogenetically activated porcine embryos were used as models to assess the effects of OA on the in vitro developmental capacity of early porcine embryos in vitro. Zygotic genome activation, mitochondrial function, oxidative stress, cell proliferation and apoptosis in early porcine embryos were examined after supplementing the culture medium with 5 μM OA. RESULTS The results showed that 5 μM OA supplementation not only significantly increased the blastocyst diameter in early embryos on day 6 but also increased the total cell number of blastocysts. Furthermore, OA supplementation increased the blastocyst proliferation rate and decreased blastocyst apoptosis. Moreover, OA supplementation significantly increased the proportion of embryos that developed to the 4-cell stage after 48 h of in vitro culture and upregulated the expression of genes associated with zygotic genome activation (DPPA2 and ZSCAN4). Notably, OA alleviated oxidative stress by reducing the intracellular levels of reactive oxygen species and increasing the intracellular levels of reduced glutathione at the 4-cell stage and increased the activities of superoxide dismutase and catalase. Concurrently, OA significantly increased the mitochondrial membrane potential and intracellular adenosine 5'-triphosphate content. CONCLUSION These results suggest that OA promotes the in vitro developmental competence of parthenogenetically activated porcine embryos by reducing oxidative stress and improving mitochondrial function during in vitro culture and that OA may contribute to the efficiency of in vitro embryo production.
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Affiliation(s)
- Yan-Wei Dong
- Department of Animals Sciences, College of Animal Sciences, Jilin University, Changchun130062, China
| | - He-Xuan Qu
- Department of Animals Sciences, College of Animal Sciences, Jilin University, Changchun130062, China
| | - Yan-Qiu Wang
- Department of Animals Sciences, College of Animal Sciences, Jilin University, Changchun130062, China
| | - Jia-Jia Qi
- Department of Animals Sciences, College of Animal Sciences, Jilin University, Changchun130062, China
| | - Hua-Kai Wei
- Department of Animals Sciences, College of Animal Sciences, Jilin University, Changchun130062, China
| | - Bo-Xing Sun
- Department of Animals Sciences, College of Animal Sciences, Jilin University, Changchun130062, China
| | - Hao Sun
- Department of Animals Sciences, College of Animal Sciences, Jilin University, Changchun130062, China
| | - Shuang Liang
- Department of Animals Sciences, College of Animal Sciences, Jilin University, Changchun130062, China
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Tu J, Kang M, Zhao Q, Xue C, Bi C, Dong N. Oleanolic acid improves antioxidant capacity and the abundance of Faecalibacterium prausnitzii in the intestine of broilers. Poult Sci 2024; 103:104340. [PMID: 39520757 PMCID: PMC11585868 DOI: 10.1016/j.psj.2024.104340] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/11/2024] [Revised: 08/28/2024] [Accepted: 09/14/2024] [Indexed: 11/16/2024] Open
Abstract
This study investigated the effect of dietary oleanolic acid (OA) addition on broiler intestinal morphology, intestinal antioxidant capacity, changes in cecum microbiota, and the relationship between microbiota and antioxidant capacity. A total of 288 Arbor Acres broilers at 1-day-old broilers were reared, and they were randomly divided into four groups. The control and experimental groups were fed the basal diet and the basal diet supplemented with 50, 100, and 150 mg/kg OA for a total of 42 d respectively. The results showed that OA does not affect the performance of broiler chickens. The OA supplementation increased the ratio between jejunum villus height and crypt depth (P < 0.05). The expression of antioxidant enzymes (GSH-PX and CAT) and antioxidant-related genes (HO-1, NQO1, Nrf2, and CAT) was significantly increased in the jejunum and cecum (P < 0.05). In addition, jejunal T-AOC activity (P < 0.05) and cecum antioxidant-related gene GPX-1 expression (P < 0.01) were significantly increased. The expression of oxidation-related genes (NOX and ROMO1) was significantly down-regulated in both jejunum and cecum (P < 0.05). The addition of 150 mg/kg of OA increased the relative abundance of potentially beneficial bacteria and Faecalibacterium prausnitzii was significantly and positively correlated with the expression levels of antioxidant-related genes. In conclusion, the addition of OA to the diet may improve the intestinal antioxidant capacity and modulate the intestinal microbiota of broilers. Moreover, OA improved intestinal antioxidant capacity by increasing the relative abundance of F. prausnitzii.
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Affiliation(s)
- Jianing Tu
- Laboratory of Molecular Nutrition and Immunity, College of Animal Science and Technology, Northeast Agricultural University, Harbin, 150030, PR China
| | - Mingxuan Kang
- Laboratory of Molecular Nutrition and Immunity, College of Animal Science and Technology, Northeast Agricultural University, Harbin, 150030, PR China
| | - Qianwen Zhao
- Laboratory of Molecular Nutrition and Immunity, College of Animal Science and Technology, Northeast Agricultural University, Harbin, 150030, PR China
| | - Chenyu Xue
- Laboratory of Molecular Nutrition and Immunity, College of Animal Science and Technology, Northeast Agricultural University, Harbin, 150030, PR China
| | - Chongpeng Bi
- Laboratory of Molecular Nutrition and Immunity, College of Animal Science and Technology, Northeast Agricultural University, Harbin, 150030, PR China
| | - Na Dong
- Laboratory of Molecular Nutrition and Immunity, College of Animal Science and Technology, Northeast Agricultural University, Harbin, 150030, PR China.
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Wang K, Xu X, Shan Q, Ding R, Lyu Q, Huang L, Chen X, Han X, Yang Q, Sang X, Peng M, Hao M, Cao G. Integrated gut microbiota and serum metabolomics reveal the protective effect of oleanolic acid on liver and kidney-injured rats induced by Euphorbia pekinensis. Phytother Res 2024; 38:4877-4892. [PMID: 36426741 DOI: 10.1002/ptr.7673] [Citation(s) in RCA: 8] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/18/2022] [Revised: 09/16/2022] [Accepted: 10/02/2022] [Indexed: 11/27/2022]
Abstract
Euphorbia pekinensis (EP) is a commonly used Chinese medicine treating edema with potential hepatorenal toxicity. However, its toxic mechanism and prevention are remained to be explored. Oleanolic acid (OA) is a triterpene acid with potential hepatorenal protective activities. We investigated the protective effect and potential mechanism of OA on EP-induced hepatorenal toxicity. In this study, rats were given total diterpenes from EP (TDEP, 16 mg/kg) combined with OA (10, 20, 40 mg/kg) by gavage for 4 weeks. The results showed that TDEP administration could lead to a 3-4-fold increasement in hepatorenal biochemical parameters with histopathological injuries, while OA treatment could ameliorate them in a dose-dependent manner. At microbial and metabolic levels, intestinal flora and host metabolism were perturbed after TDEP administration. The disturbance of bile acid metabolism was the most significant metabolic pathway, with secondary bile acids increasing while conjugated bile acids decreased. OA treatment can improve the disorder of intestinal flora and metabolic bile acid spectrum. Further correlation analysis screened out that Escherichia-Shigella, Phascolarctobacterium, Acetatifactor, and Akkermansia were closely related to the bile acid metabolic disorder. In conclusion, oleanolic acid could prevent hepatorenal toxicity induced by EP by regulating bile acids metabolic disorder via intestinal flora improvement.
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Affiliation(s)
- Kuilong Wang
- School of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou, China
| | - Xiaofen Xu
- School of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou, China
| | - Qiyuan Shan
- School of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou, China
| | - Rui Ding
- School of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou, China
| | - Qiang Lyu
- School of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou, China
| | - Lichuang Huang
- School of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou, China
| | - Xinyi Chen
- School of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou, China
| | - Xin Han
- School of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou, China
| | - Qiao Yang
- School of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou, China
| | - Xianan Sang
- School of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou, China
| | - Mengyun Peng
- School of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou, China
| | - Min Hao
- School of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou, China
| | - Gang Cao
- School of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou, China
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Jannus F, Sainz J, Reyes-Zurita FJ. Principal Bioactive Properties of Oleanolic Acid, Its Derivatives, and Analogues. Molecules 2024; 29:3291. [PMID: 39064870 PMCID: PMC11279785 DOI: 10.3390/molecules29143291] [Citation(s) in RCA: 5] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/22/2024] [Revised: 07/10/2024] [Accepted: 07/10/2024] [Indexed: 07/28/2024] Open
Abstract
Natural products have always played an important role in pharmacotherapy, helping to control pathophysiological processes associated with human disease. Thus, natural products such as oleanolic acid (OA), a pentacyclic triterpene that has demonstrated important activities in several disease models, are in high demand. The relevant properties of this compound have motivated re-searchers to search for new analogues and derivatives using the OA as a scaffold to which new functional groups have been added or modifications have been realized. OA and its derivatives have been shown to be effective in the treatment of inflammatory processes, triggered by chronic diseases or bacterial and viral infections. OA and its derivatives have also been found to be effective in diabetic disorders, a group of common endocrine diseases characterized by hyperglycemia that can affect several organs, including the liver and brain. This group of compounds has been reported to exhibit significant bioactivity against cancer processes in vitro and in vivo. In this review, we summarize the bioactive properties of OA and its derivatives as anti-inflammatory, anti-bacterial, antiviral, anti-diabetic, hepatoprotective, neuroprotective, and anticancer agents.
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Affiliation(s)
- Fatin Jannus
- Department of Biochemistry and Molecular Biology I, Faculty of Sciences, University of Granada, Av. Fuentenueva, 18071 Granada, Spain;
| | - Juan Sainz
- Department of Biochemistry and Molecular Biology I, Faculty of Sciences, University of Granada, Av. Fuentenueva, 18071 Granada, Spain;
- Genomic Oncology Area, GENYO, Centre for Genomics and Oncological Research, Pfizer/University of Granada/Andalusian Regional Government, Av. de la Ilustración, 114, PTS, 18016 Granada, Spain
- Instituto de Investigación Biosanitaria IBs.Granada, 18010 Granada, Spain
- Consortium for Biomedical Research in Epidemiology and Public Health (CIBERESP), University of Barcelona, 08908 Barcelona, Spain
| | - Fernando J. Reyes-Zurita
- Department of Biochemistry and Molecular Biology I, Faculty of Sciences, University of Granada, Av. Fuentenueva, 18071 Granada, Spain;
- Instituto de Investigación Biosanitaria IBs.Granada, 18010 Granada, Spain
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Wang Y, Liu K. Therapeutic potential of oleanolic acid in liver diseases. NAUNYN-SCHMIEDEBERG'S ARCHIVES OF PHARMACOLOGY 2024; 397:4537-4554. [PMID: 38294504 DOI: 10.1007/s00210-024-02959-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/21/2023] [Accepted: 01/15/2024] [Indexed: 02/01/2024]
Abstract
Liver-associated diseases affect millions of individuals worldwide. In developed countries, the incidence of viral hepatitis is reducing due to advancements in disease prevention, diagnosis, and treatment. However, with improvements in living standards, the prevalence of metabolic liver diseases, such as non-alcoholic fatty liver disease and alcohol-related liver disease, is expected to increase; notably, this rise in the prevalence of metabolic liver disease can lead to the development of more severe liver diseases, including liver failure, cirrhosis, and liver cancer. The growing demand for natural alternative therapies for chronic diseases has highlighted the importance of studying the pharmacology of bioactive compounds in plants. One such compound is oleanolic acid (OA), a pentacyclic triterpenoid known for its antioxidant, anti-inflammatory, anti-ulcer, antibacterial, antiviral, antihypertensive, anti-obesity, anticancer, anti-diabetic, cardioprotective, hepatoprotective, and anti-neurodegenerative properties. Recent studies have demonstrated that OA treatment can reduce the risk of pathological liver damage, ultimately alleviating liver dysregulation and restoring overall liver function. This review aims to explore the latest research on the biological effects of OA and its derivatives. Notably, it explores the mechanisms of action of these compounds in both in vitro and in vivo research models and, ultimately, highlights OA as a promising candidate for alternative therapies in the treatment and management of chronic liver disease.
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Affiliation(s)
- Yongxin Wang
- Department of Hepatobiliary and Pancreatic Surgery II, General Surgery Center, The First Hospital of Jilin University, Changchun, 130021, China
| | - Kai Liu
- Department of Hepatobiliary and Pancreatic Surgery II, General Surgery Center, The First Hospital of Jilin University, Changchun, 130021, China.
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8
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Rabelo ACS, Andrade AKDL, Costa DC. The Role of Oxidative Stress in Alcoholic Fatty Liver Disease: A Systematic Review and Meta-Analysis of Preclinical Studies. Nutrients 2024; 16:1174. [PMID: 38674865 PMCID: PMC11055095 DOI: 10.3390/nu16081174] [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] [Revised: 04/05/2024] [Accepted: 04/11/2024] [Indexed: 04/28/2024] Open
Abstract
Alcoholic Fatty Liver Disease (AFLD) is characterized by the accumulation of lipids in liver cells owing to the metabolism of ethanol. This process leads to a decrease in the NAD+/NADH ratio and the generation of reactive oxygen species. A systematic review and meta-analysis were conducted to investigate the role of oxidative stress in AFLD. A total of 201 eligible manuscripts were included, which revealed that animals with AFLD exhibited elevated expression of CYP2E1, decreased enzymatic activity of antioxidant enzymes, and reduced levels of the transcription factor Nrf2, which plays a pivotal role in the synthesis of antioxidant enzymes. Furthermore, animals with AFLD exhibited increased levels of lipid peroxidation markers and carbonylated proteins, collectively contributing to a weakened antioxidant defense and increased oxidative damage. The liver damage in AFLD was supported by significantly higher activity of alanine and aspartate aminotransferase enzymes. Moreover, animals with AFLD had increased levels of triacylglycerol in the serum and liver, likely due to reduced fatty acid metabolism caused by decreased PPAR-α expression, which is responsible for fatty acid oxidation, and increased expression of SREBP-1c, which is involved in fatty acid synthesis. With regard to inflammation, animals with AFLD exhibited elevated levels of pro-inflammatory cytokines, including TNF-a, IL-1β, and IL-6. The heightened oxidative stress, along with inflammation, led to an upregulation of cell death markers, such as caspase-3, and an increased Bax/Bcl-2 ratio. Overall, the findings of the review and meta-analysis indicate that ethanol metabolism reduces important markers of antioxidant defense while increasing inflammatory and apoptotic markers, thereby contributing to the development of AFLD.
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Affiliation(s)
- Ana Carolina Silveira Rabelo
- Postgraduate Program in Biological Sciences, Federal University of Ouro Preto, Ouro Preto 35402-163, Brazil
- Department of Biochemistry, Federal University of Alfenas, Alfenas 37130-001, Brazil
| | | | - Daniela Caldeira Costa
- Postgraduate Program in Biological Sciences, Federal University of Ouro Preto, Ouro Preto 35402-163, Brazil
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9
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Hong W, Fu W, Zhao Q, Xue C, Cai W, Dong N, Shan A. Effects of oleanolic acid on acute liver injury triggered by lipopolysaccharide in broiler chickens. Br Poult Sci 2023; 64:697-709. [PMID: 37697900 DOI: 10.1080/00071668.2023.2251119] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/06/2022] [Revised: 06/21/2023] [Accepted: 07/03/2023] [Indexed: 09/13/2023]
Abstract
1. Infectious injury caused by lipopolysaccharide (LPS), a metabolite of gram-negative bacteria, can induce stress responses in animals and is a significant cause of morbidity and mortality in young birds. The purpose of this study was to investigate the effects of dietary supplementation with oleanolic acid (OA) on acute liver injury in broiler chickens challenged with LPS.2. In total, 120 broiler chickens were randomly divided into six groups and fed a basal diet containing 0, 50, 100, or 200 mg/kg OA or 100 mg/kg aureomycin. On d 15, broiler chickens were injected with either LPS or an equivalent volume of normal saline. Six hours after LPS injection, two broiler chicks were randomly selected for sampling in each replicate.3. The results indicated that dietary aureomycin was ineffective in alleviating LSP-associated liver injury, but protected broiler chickens from LPS-induced liver damage. This promoted a significant reduction in the levels of malondialdehyde and an increase in the levels of superoxide dismutase in liver. In addition, OA was found to cause significant reductions in the relative expression of IL-1β, IL-6, and TNF-α in broiler liver tissues, whereas the relative expression of IL-10 was significantly increased.4. In conclusion, oleanolic acid can alleviate oxidative stress and injury in the livers of broiler chickens induced by lipopolysaccharide. Consequently, oleanolic acid has potential utility as a novel anti-inflammatory and antioxidant feed additive.
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Affiliation(s)
- W Hong
- The Laboratory of Molecular Nutrition and Immunity, College of Animal Science and Technology, Northeast Agricultural University, Harbin, P. R. China
| | - W Fu
- The Laboratory of Molecular Nutrition and Immunity, College of Animal Science and Technology, Northeast Agricultural University, Harbin, P. R. China
| | - Q Zhao
- The Laboratory of Molecular Nutrition and Immunity, College of Animal Science and Technology, Northeast Agricultural University, Harbin, P. R. China
| | - C Xue
- The Laboratory of Molecular Nutrition and Immunity, College of Animal Science and Technology, Northeast Agricultural University, Harbin, P. R. China
| | - W Cai
- The Laboratory of Molecular Nutrition and Immunity, College of Animal Science and Technology, Northeast Agricultural University, Harbin, P. R. China
| | - N Dong
- The Laboratory of Molecular Nutrition and Immunity, College of Animal Science and Technology, Northeast Agricultural University, Harbin, P. R. China
| | - A Shan
- The Laboratory of Molecular Nutrition and Immunity, College of Animal Science and Technology, Northeast Agricultural University, Harbin, P. R. China
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10
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Huang X, Chu X, Tian Y, Xue Y, Zhang L, Li J, Hou H, Dong P, Wang J. Preventive effect of salmon sperm DNA on acute carbon tetrachloride-induced liver injury in mice through Nrf2/ARE and mitochondrial apoptosis pathway. Food Sci Nutr 2023; 11:733-742. [PMID: 36789059 PMCID: PMC9922120 DOI: 10.1002/fsn3.3109] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/05/2022] [Revised: 08/14/2022] [Accepted: 10/09/2022] [Indexed: 11/07/2022] Open
Abstract
Liver injury refers to the damage of liver function, which will seriously harm the body's health if it is not prevented and treated in time. Sporadic researches have reported that ingestion of DNA has a hepatoprotective effect, but its effect and mechanism were not clarified. The purpose of this study was to explore the preventive effect and mechanism of salmon sperm DNA on acute liver injury in mice induced by carbon tetrachloride (CCl4). Six-week-old ICR (Institute of Cancer Research) male mice were used to establish a liver injury model by injecting with 4% CCl4, silymarin, and three different concentrations of DNA solutions were given to mice by gavage for 14 days. The histological and pathological changes in the liver were observed. The levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in serum and the levels of oxidative and antioxidant markers such as malondialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and glutathione (GSH) in liver tissue were determined. The levels of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) were detected by enzyme-linked immunosorbent assay (ELISA), and hepatic oxidative stress and apoptosis-related markers were determined by western blotting. The results showed that compared with the model group, the DNA test group significantly improved the liver pathological changes and the level of liver function, regulated liver oxidative stress, reduced hepatocyte apoptosis, and decreased the levels of inflammatory factors such as TNF-α and IL-6. Compared with the silymarin group, the high dose of DNA was even more effective in preventing liver injury. In conclusion, salmon sperm DNA has a potential protective effect against acute liver injury induced by CCl4, which is achieved by regulating the Nrf2/ARE (nuclear factor erythroid 2 (NF-E2)-related factor 2/antioxidant responsive element) oxidative stress pathway and mitochondrial apoptosis pathway.
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Affiliation(s)
- Xinyi Huang
- College of Food Science and EngineeringOcean University of ChinaQingdaoChina
| | - Xu Chu
- College of Food Science and EngineeringOcean University of ChinaQingdaoChina
| | - Yingying Tian
- College of Food Science and EngineeringOcean University of ChinaQingdaoChina
| | - Yuhan Xue
- College of Food Science and EngineeringOcean University of ChinaQingdaoChina
| | - Lei Zhang
- College of Food Science and EngineeringOcean University of ChinaQingdaoChina
| | - Jing Li
- College of Food Science and EngineeringOcean University of ChinaQingdaoChina
| | - Hu Hou
- College of Food Science and EngineeringOcean University of ChinaQingdaoChina
| | - Ping Dong
- College of Food Science and EngineeringOcean University of ChinaQingdaoChina
| | - Jingfeng Wang
- College of Food Science and EngineeringOcean University of ChinaQingdaoChina
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Ethanol Metabolism in the Liver, the Induction of Oxidant Stress, and the Antioxidant Defense System. Antioxidants (Basel) 2022; 11:antiox11071258. [PMID: 35883749 PMCID: PMC9312216 DOI: 10.3390/antiox11071258] [Citation(s) in RCA: 26] [Impact Index Per Article: 8.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/15/2022] [Revised: 06/18/2022] [Accepted: 06/20/2022] [Indexed: 12/12/2022] Open
Abstract
The liver metabolizes ethanol through three enzymatic pathways: alcohol dehydrogenase (ADH), cytochrome p450 (also called MEOS), and catalase. Alcohol dehydrogenase class I (ADH1) is considered the most important enzyme for the metabolism of ethanol, MEOS and catalase (CAT) are considered minor alternative pathways. However, contradicting experiments suggest that the non-ADH1 pathway may have a greater relevance for the metabolism of ethanol than previously thought. In some conditions, ethanol is predominately metabolized to acetaldehyde via cytochrome P450 family 2 (CYP2E1), which is involved in the generation of reactive oxygen species (ROS), mainly through electron leakage to oxygen to form the superoxide (O2•−) radical or in catalyzed lipid peroxidation. The CAT activity can also participate in the ethanol metabolism that produces ROS via ethanol directly reacting with the CAT-H2O2 complex, producing acetaldehyde and water and depending on the H2O2 availability, which is the rate-limiting component in ethanol peroxidation. We have shown that CAT actively participates in lactate-stimulated liver ethanol oxidation, where the addition of lactate generates H2O2, which is used by CAT to oxidize ethanol to acetaldehyde. Therefore, besides its known role as a catalytic antioxidant component, the primary role of CAT could be to function in the metabolism of xenobiotics in the liver.
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12
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Khan MW, Zou C, Hassan S, Din FU, Abdoul Razak MY, Nawaz A, Alam Zeb, Wahab A, Bangash SA. Cisplatin and oleanolic acid Co-loaded pH-sensitive CaCO 3 nanoparticles for synergistic chemotherapy. RSC Adv 2022; 12:14808-14818. [PMID: 35702211 PMCID: PMC9109477 DOI: 10.1039/d2ra00742h] [Citation(s) in RCA: 27] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/03/2022] [Accepted: 05/01/2022] [Indexed: 01/06/2023] Open
Abstract
Despite being one of the most potent anticancer agents, cisplatin (CDDP) clinical usage is limited owing to the acquired resistance and severe adverse effects including nephrotoxicity. The current work has offered a unique approach by designing a pH-sensitive calcium carbonate drug delivery system for CDDP and oleanolic acid (OA) co-delivery, with an enhanced tumor efficacy and reduced unwanted effects. Micro emulsion method was employed to generate calcium carbonate cores (CDDP encapsulated) followed by lipid coating along with the OA loading resulting in the generation of lipid-coated cisplatin/oleanolic acid calcium carbonate nanoparticles (CDDP/OA-LCC NPs). In vitro biological assays confirmed the synergistic apoptotic effect of CDDP and OA against HepG2 cells. It was further verified in vivo through the tumor-bearing nude mice model where NPs exhibited enhanced satisfactory antitumor efficacy in contrast to free drug solutions. In vivo pharmacokinetic study demonstrated that a remarkable long circulation time with a constant therapeutic concentration for both drugs could be achieved via this drug delivery system. In addition, the in vivo imaging study revealed that DiR-loaded NPs were concentrated more in tumors for a longer period of time as compared to other peritoneal tissues in tumor bearing mice, demonstrating the site specificity of the delivery system. On the other hand, hematoxylin and eosin (H&E) staining of Kunming mice kidney tissue sections revealed that OA greatly reduced CDDP induced nephrotoxicity in the formulation. Overall, these results confirmed that our pH-sensitive dual loaded drug delivery system offers a handy direction for effective and safer combination chemotherapy.
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Affiliation(s)
- Muhammad Waseem Khan
- Institute of Pharmaceutical Sciences, Khyber Medical University Peshawar Pakistan +92-3459146065
| | - Chenming Zou
- School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology Wuhan Hubei 430030 China
| | - Said Hassan
- Institute of Biotechnology and Microbiology, Bacha Khan University Charsadda Pakistan
| | - Fakhar Ud Din
- Department of Pharmacy, Quaid-I-Azam University Islamabad 45320 Pakistan
| | - Mahaman Yacoubou Abdoul Razak
- Department of Pathophysiology, School of Basic Medicine, Key Laboratory of Education Ministry of China for Neurological Disorders, Tongji Medical College, Huazhong University of Science and Technology Wuhan 430030 China
| | - Asif Nawaz
- Faculty of Pharmacy, Gomal University Dera Ismail Khan Pakistan
| | - Alam Zeb
- Riphah Institute of Pharmaceutical Sciences, Riphah International University Islamabad Pakistan
| | - Abdul Wahab
- Department of Pharmacy, Kohat University of Science and Technology Kohat Pakistan
| | - Sudhair Abbas Bangash
- Faculty of Life Science, Department of Pharmacy, Sarhad University of Science and Information Technology Peshawar Pakistan
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13
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Qian D, Zhou H, Fan P, Yu T, Patel A, O’Brien M, Wang Z, Lu S, Tong G, Shan Y, Wang L, Gao Y, Xiong Y, Zhang L, Wang X, Liu Y, Zhou S. A Traditional Chinese Medicine Plant Extract Prevents Alcohol-Induced Osteopenia. Front Pharmacol 2021; 12:754088. [PMID: 35002697 PMCID: PMC8730326 DOI: 10.3389/fphar.2021.754088] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/05/2021] [Accepted: 11/11/2021] [Indexed: 12/12/2022] Open
Abstract
Traditional Chinese medicine (TCM) has been practiced in the treatment of bone diseases and alcoholism. Chronic excessive alcohol use results in alcohol-induced bone diseases, including osteopenia and osteoporosis, which increases fracture risk, deficient bone repair, and osteonecrosis. This preclinical study investigated the therapeutic effects of TCM herbal extracts in animal models of chronic excessive alcohol consumption-induced osteopenia. TCM herbal extracts (Jing extracts) were prepared from nine Chinese herbal medicines, a combinative herbal formula for antifatigue and immune regulation, including Astragalus, Cistanche deserticola, Dioscorea polystachya, Lycium barbarum, Epimedium, Cinnamomum cassia, Syzygium aromaticum, Angelica sinensis, and Curculigo orchioides. In this study, Balb/c male mice were orally administrated alcohol (3.2 g/kg/day) with/without TCM herbal extracts (0.125 g/kg, 0.25 g/kg, or 0.5 g/kg) by gavage. Our results showed that after 50 days of oral administration, TCM herbal extracts prevented alcohol-induced osteopenia demonstrated by μ-CT bone morphological analysis in young adults and middle-aged/old Balb/c male mice. Biochemical analysis demonstrated that chronic alcohol consumption inhibits bone formation and has a neutral impact on bone resorption, suggesting that TCM herbal extracts (Jing extracts) mitigate the alcohol-induced abnormal bone metabolism in middle-aged/old male mice. Protocatechuic acid, a natural phenolic acid in Jing extracts, mitigates in vivo alcohol-induced decline of alkaline phosphatase (ALP) gene expression in the bone marrow of Balb/c male mice and in vitro ALP activity in pre-osteoblast MC3T3-E1 cells. Our study suggests that TCM herbal extracts prevent chronic excessive alcohol consumption-induced osteopenia in male mice, implying that traditional medicinal plants have the therapeutic potential of preventing alcohol-induced bone diseases.
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Affiliation(s)
- Dongyang Qian
- Department of Orthopedic Surgery, Brigham and Women’s Hospital, Harvard Medical School, Harvard University, Boston, MA, United States
- Department of Orthopedics, The First Affiliated Hospital, Guangzhou Medical University, Guangzhou, China
| | - Hui Zhou
- Jing Brand Research Institute, Jing Brand Co., Ltd., Daye, China
| | - Pan Fan
- Department of Orthopedic Surgery, Brigham and Women’s Hospital, Harvard Medical School, Harvard University, Boston, MA, United States
- Department of Spine Center, Zhongda Hospital, Southeast University Medical School, Nanjing, China
| | - Tao Yu
- Department of Orthopedic Surgery, Brigham and Women’s Hospital, Harvard Medical School, Harvard University, Boston, MA, United States
- Department of Orthopedic Surgery, Tongji Hospital, School of Medicine, Tongji University, Shanghai, China
| | - Anish Patel
- Department of Orthopedic Surgery, Brigham and Women’s Hospital, Harvard Medical School, Harvard University, Boston, MA, United States
| | - Morgan O’Brien
- Department of Orthopedic Surgery, Brigham and Women’s Hospital, Harvard Medical School, Harvard University, Boston, MA, United States
| | - Zhe Wang
- Jing Brand Research Institute, Jing Brand Co., Ltd., Daye, China
| | - Shiguang Lu
- Jing Brand Research Institute, Jing Brand Co., Ltd., Daye, China
| | - Guoqiang Tong
- Jing Brand Research Institute, Jing Brand Co., Ltd., Daye, China
| | - Yimin Shan
- Jing Brand Research Institute, Jing Brand Co., Ltd., Daye, China
| | - Lei Wang
- Jing Brand Research Institute, Jing Brand Co., Ltd., Daye, China
| | - Yuan Gao
- Department of Orthopedic Surgery, Brigham and Women’s Hospital, Harvard Medical School, Harvard University, Boston, MA, United States
- Department of Orthopaedics, Qilu Hospital, Shandong University, Jinan, China
| | - Yuan Xiong
- Department of Orthopedic Surgery, Brigham and Women’s Hospital, Harvard Medical School, Harvard University, Boston, MA, United States
- Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Lily Zhang
- Department of Orthopedic Surgery, Brigham and Women’s Hospital, Harvard Medical School, Harvard University, Boston, MA, United States
| | - Xin Wang
- Department of Neurosurgery, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, United States
| | - Yuancai Liu
- Jing Brand Research Institute, Jing Brand Co., Ltd., Daye, China
- *Correspondence: Shuanhu Zhou, , ; Yuancai Liu,
| | - Shuanhu Zhou
- Department of Orthopedic Surgery, Brigham and Women’s Hospital, Harvard Medical School, Harvard University, Boston, MA, United States
- Harvard Stem Cell Institute, Harvard University, Cambridge, MA, United States
- *Correspondence: Shuanhu Zhou, , ; Yuancai Liu,
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14
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Jia S, Chen Q, Wu J, Yao X, Shao J, Cheng X, Zhang C, Cen D, Wang Y, Shen Z, Shan L, Yao X. Danshensu derivative ADTM ameliorates CCl 4‑induced acute liver injury in mice through inhibiting oxidative stress and apoptosis. Pathol Res Pract 2021; 228:153656. [PMID: 34749210 DOI: 10.1016/j.prp.2021.153656] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/20/2021] [Revised: 10/09/2021] [Accepted: 10/12/2021] [Indexed: 12/21/2022]
Abstract
Previous studies reported a novel danshensu derivative (R)-(3,5,6-Trimethylpyrazinyl) methyl-2-acetoxy-3-(3,4-diacetoxyphenyl) propanoate (ADTM), which conferred cardioprotective, neuroprotective and anti-thrombotic effects. Here we aim to investigate the hepatoprotective effect of ADTM on acute liver injury caused by carbon tetrachloride (CCl4) and the underlying molecular mechanisms. ADTM (30 and 60 mg/kg) was given to mice by gavage for two weeks. At the last day mice were injected with 0.3% CCl4, 10 mL/kg, ip for 24 h. Clinical and histological chemistry assays were performed to assess liver injury. Moreover, hepatic oxidative stress and apoptosis related markers were determined by western blotting. As a result, ADTM significantly protected against CCl4-induced liver injury by the decrease of elevated serum transaminases and liver index, and the attenuation of histopathological changes in mice. In addition, ADTM remarkably alleviated hepatic oxidative stress (MDA contents and SOD activity) and apoptosis. Further studies revealed that ADTM significantly inhibited the CCl4-induced upregulation of Bax/Bcl-2, increased the CCl4-induced decrease of AKT phosphorylation and inhibited the expression level of NF-κB p65 in CCl4-intoxicated mice. These findings suggest that ADTM possesses the potential protective effects against CCl4-induced liver injury in mice by exerting antioxidative stress and antiapoptosis.
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Affiliation(s)
- Shu Jia
- Faculty of Pharmacy, Zhejiang Pharmaceutical College, Ningbo 315100, PR China
| | - Qi Chen
- Ningbo Yinzhou No. 2 Hospital, Ningbo 315100, PR China
| | - Jingyi Wu
- Faculty of Pharmacy, Zhejiang Pharmaceutical College, Ningbo 315100, PR China
| | - Xiaokun Yao
- Faculty of Pharmacy, Zhejiang Pharmaceutical College, Ningbo 315100, PR China
| | - Jingping Shao
- Faculty of Pharmacy, Zhejiang Pharmaceutical College, Ningbo 315100, PR China
| | - Xiaoyan Cheng
- Beijing Center for Physical & Chemical Analysis, Beijing 100050, PR China
| | - Congcong Zhang
- Faculty of Pharmacy, Zhejiang Pharmaceutical College, Ningbo 315100, PR China
| | - Danwei Cen
- Faculty of Pharmacy, Zhejiang Pharmaceutical College, Ningbo 315100, PR China
| | - Yuqiang Wang
- Institute of New Drug Research, Jinan University College of Pharmacy, Guangzhou, PR China
| | - Zhihong Shen
- Ningbo Yinzhou No. 2 Hospital, Ningbo 315100, PR China
| | - Luchen Shan
- Institute of New Drug Research, Jinan University College of Pharmacy, Guangzhou, PR China.
| | - Xiaomin Yao
- Faculty of Pharmacy, Zhejiang Pharmaceutical College, Ningbo 315100, PR China.
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15
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Yan J, Nie Y, Luo M, Chen Z, He B. Natural Compounds: A Potential Treatment for Alcoholic Liver Disease? Front Pharmacol 2021; 12:694475. [PMID: 34290612 PMCID: PMC8287649 DOI: 10.3389/fphar.2021.694475] [Citation(s) in RCA: 33] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/13/2021] [Accepted: 06/23/2021] [Indexed: 12/12/2022] Open
Abstract
Excessive alcohol intake is a direct cause of alcoholic liver disease (ALD). ALD usually manifests as fatty liver in the initial stage and then develops into alcoholic hepatitis (ASH), fibrosis and cirrhosis. Severe alcoholism induces extensive hepatocyte death, liver failure, and even hepatocellular carcinoma (HCC). Currently, there are few effective clinical means to treat ALD, except for abstinence. Natural compounds are a class of compounds extracted from herbs with an explicit chemical structure. Several natural compounds, such as silymarin, quercetin, hesperidin, and berberine, have been shown to have curative effects on ALD without side effects. In this review, we pay particular attention to natural compounds and developing clinical drugs based on natural compounds for ALD, with the aim of providing a potential treatment for ALD.
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Affiliation(s)
- Junbin Yan
- The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, China.,Key Laboratory of Integrative Chinese and Western Medicine for the Diagnosis and Treatment of Circulatory Diseases of Zhejiang Province, The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, China
| | - Yunmeng Nie
- The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, China
| | - Minmin Luo
- The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, China.,Key Laboratory of Integrative Chinese and Western Medicine for the Diagnosis and Treatment of Circulatory Diseases of Zhejiang Province, The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, China
| | - Zhiyun Chen
- The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, China.,Key Laboratory of Integrative Chinese and Western Medicine for the Diagnosis and Treatment of Circulatory Diseases of Zhejiang Province, The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, China
| | - Beihui He
- The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, China.,Key Laboratory of Integrative Chinese and Western Medicine for the Diagnosis and Treatment of Circulatory Diseases of Zhejiang Province, The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, China
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16
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Bingül İ, Aydın AF, Küçükgergin C, Doğan-Ekici I, Doğru-Abbasoğlu S, Uysal M. The effect of 1,25-dihydroxyvitamin D3 on liver damage, oxidative stress, and advanced glycation end products in experimental nonalcoholic- and alcoholic- fatty liver disease. Turk J Med Sci 2021; 51:1500-1511. [PMID: 33421970 PMCID: PMC8283439 DOI: 10.3906/sag-2007-289] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/28/2020] [Accepted: 01/07/2021] [Indexed: 01/10/2023] Open
Abstract
Background/aim Oxidative stress and advanced glycation end products (AGEs) formation are proposed as effective mechanisms in the pathogenesis of nonalcoholic fatty liver disease (NAFLD) and alcoholic liver disease (ALD). 1,25(OH)2D3 was proposed to have antioxidant, antiinflammatory and antiglycation properties. In this study, the effect of 1,25(OH)2D3 treatment on oxidative stress parameters and AGEs levels together with hepatic histopathology was investigated in high fructose (HFr) or ethanol (EtOH)-treated rats. Materials and methods Rats were treated with fructose (30%) or ethanol (5-20%) in drinking water with and without 1,25(OH)2D3 treatment (5 µg/kg two times a week) for 8 weeks. Insulin resistance (IR), oxidative stress parameters, AGEs, triglyceride (TG), and hydroxyproline (Hyp) levels together with histopathology were investigated in the liver. Results 1,25(OH)2D3 decreased hepatic reactive oxygen species, lipid and protein oxidation products together with histopathological improvements in HFr- and EtOH-treated rats. 1,25(OH)2D3 treatment was observed to decrease significantly serum and hepatic AGEs in HFr group, and hepatic AGEs in EtOH group. Conclusion Our results clearly show that 1,25(OH)2 D3 treatment may be useful in the alleviation of hepatic lesions by decreasing glycooxidant stress in both NAFLD and ALD models created by HFr- and EtOH-treated rats, respectively.
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Affiliation(s)
- İlknur Bingül
- Department of Medical Biochemistry, İstanbul Medical Faculty, İstanbul University, İstanbul, Turkey
| | - A. Fatih Aydın
- Department of Medical Biochemistry, İstanbul Medical Faculty, İstanbul University, İstanbul, Turkey
| | - Canan Küçükgergin
- Department of Medical Biochemistry, İstanbul Medical Faculty, İstanbul University, İstanbul, Turkey
| | - Işın Doğan-Ekici
- Department of Pathology, Acıbadem University Medical Faculty, İstanbul, Turkey
| | - Semra Doğru-Abbasoğlu
- Department of Medical Biochemistry, İstanbul Medical Faculty, İstanbul University, İstanbul, Turkey
| | - Müjdat Uysal
- Retired Prof. Dr., Tayyareci Nurettin Sokak, Bakırkoy, İstanbul, Turkey
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17
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Zhao L, Mehmood A, Yuan D, Usman M, Murtaza MA, Yaqoob S, Wang C. Protective Mechanism of Edible Food Plants against Alcoholic Liver Disease with Special Mention to Polyphenolic Compounds. Nutrients 2021; 13:nu13051612. [PMID: 34064981 PMCID: PMC8151346 DOI: 10.3390/nu13051612] [Citation(s) in RCA: 25] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/07/2021] [Revised: 05/06/2021] [Accepted: 05/08/2021] [Indexed: 12/13/2022] Open
Abstract
Alcoholic liver disease (ALD) is one type of liver disease, causing a global healthcare problem and mortality. The liver undergoes tissue damage by chronic alcohol consumption because it is the main site for metabolism of ethanol. Chronic alcohol exposure progresses from alcoholic fatty liver (AFL) to alcoholic steatohepatitis (ASH), which further lead to fibrosis, cirrhosis, and even hepatocellular cancer. Therapeutic interventions to combat ALD are very limited such as use of corticosteroids. However, these therapeutic drugs are not effective for long-term usage. Therefore, additional effective and safe therapies to cope with ALD are urgently needed. Previous studies confirmed that edible food plants and their bioactive compounds exert a protective effect against ALD. In this review article, we summarized the hepatoprotective potential of edible food plants and their bioactive compounds. The underlying mechanism for the prevention of ALD by edible food plants was as follows: anti-oxidation, anti-inflammation, lipid regulation, inhibition of apoptosis, gut microbiota composition modulation, and anti-fibrosis.
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Affiliation(s)
- Liang Zhao
- Beijing Advance Innovation Center for Food Nutrition and Human Health, Beijing Technology and Business University, Beijing 100048, China; (L.Z.); (A.M.); (M.U.); (C.W.)
- Beijing Engineering and Technology Research Center of Food Additives, School of Food and Health, Beijing Technology and Business University, Beijing 100048, China
| | - Arshad Mehmood
- Beijing Advance Innovation Center for Food Nutrition and Human Health, Beijing Technology and Business University, Beijing 100048, China; (L.Z.); (A.M.); (M.U.); (C.W.)
- Beijing Engineering and Technology Research Center of Food Additives, School of Food and Health, Beijing Technology and Business University, Beijing 100048, China
| | - Dongdong Yuan
- Beijing Advance Innovation Center for Food Nutrition and Human Health, Beijing Technology and Business University, Beijing 100048, China; (L.Z.); (A.M.); (M.U.); (C.W.)
- Beijing Engineering and Technology Research Center of Food Additives, School of Food and Health, Beijing Technology and Business University, Beijing 100048, China
- Correspondence: ; Tel.: +86-10-6898-4547
| | - Muhammad Usman
- Beijing Advance Innovation Center for Food Nutrition and Human Health, Beijing Technology and Business University, Beijing 100048, China; (L.Z.); (A.M.); (M.U.); (C.W.)
- Beijing Engineering and Technology Research Center of Food Additives, School of Food and Health, Beijing Technology and Business University, Beijing 100048, China
| | - Mian Anjum Murtaza
- Institute of Food Science and Nutrition, University of Sargodha, Sargodha 40100, Pakistan;
| | - Sanabil Yaqoob
- Department of Food Science and Technology, University of Central Punjab, Punjab 54590, Pakistan;
| | - Chengtao Wang
- Beijing Advance Innovation Center for Food Nutrition and Human Health, Beijing Technology and Business University, Beijing 100048, China; (L.Z.); (A.M.); (M.U.); (C.W.)
- Beijing Engineering and Technology Research Center of Food Additives, School of Food and Health, Beijing Technology and Business University, Beijing 100048, China
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18
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Han B, Niu D, Wang T, An S, Wang Y, Chen X, Bi H, Xue X, Kang J. Ultrasonic-microwave assisted extraction of total triterpenoid acids from Corni Fructus and hypoglycemic and hypolipidemic activities of the extract in mice. Food Funct 2020; 11:10709-10723. [PMID: 33226385 DOI: 10.1039/d0fo02568b] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
Triterpene acids, the main component of Corni Fructus, could improve diabetes mellitus, for which the underlying hypoglycemic mechanism is still unclear, in patients. In this study, total triterpenoid acids were extracted by ultrasonic-microwave assisted extraction optimized by the response surface methodology. The extract was then purified with an X-5 macroporous resin, and the yield of total triterpenoid acids increased to 281.24 mg g-1 as compared with the 35.71 mg g-1 obtained by unassisted extraction. The contents of five components were determined by ultrafast performance liquid chromatography. In addition, the hypoglycemic and hypolipidemic activities of total triterpenoid acids in diabetic mice induced by streptozotocin and a high fat diet were studied. The results indicated that all parameters (oral glucose tolerance, insulin resistance and liver damage) related to diabetes were significantly improved by total triterpenoid acids. Furthermore, total triterpenoid acids significantly recovered the expression level of AMP-activated protein kinase and its downstream proteins, including acetyl-CoA carboxylase, carnitine palmityltransferase-1, peroxisome proliferator-activated receptor alpha, sterol regulatory element-binding protein 1c and fatty acid synthase. Altogether, total triterpenoid acids could ameliorate hyperlipidemia and hyperglycemia in diabetic mice, probably by activating the AMP-activated protein kinase-peroxisome proliferator-activated receptor signaling pathway and inhibiting the sterol regulatory element-binding protein 1c and fatty acid synthase signaling pathways. Therefore, total triterpene acids, isolated from Corni Fructus which is a prevailing health food, could be a functional food ingredient with therapeutic and commercial values.
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Affiliation(s)
- Binkai Han
- National Engineering Laboratory for Resource Development of Endangered Crude Drugs in Northwest China, The Key Laboratory of Medicinal Resources and Natural Pharmaceutical Chemistry, The Ministry of Education, College of Life Sciences, Shaanxi Normal University, Xi'an, Shaanxi 710119, The People's Republic of China.
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19
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Yang Q, Shu F, Gong J, Ding P, Cheng R, Li J, Tong R, Ding L, Sun H, Huang W, Wang Z, Yang L. Sweroside ameliorates NAFLD in high-fat diet induced obese mice through the regulation of lipid metabolism and inflammatory response. JOURNAL OF ETHNOPHARMACOLOGY 2020; 255:112556. [PMID: 31926984 DOI: 10.1016/j.jep.2020.112556] [Citation(s) in RCA: 29] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/04/2019] [Revised: 12/19/2019] [Accepted: 01/07/2020] [Indexed: 06/10/2023]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Sweroside, an iridoid derived from Traditional Chinese Medicine, is an active component in Swertia pseudochinensis Hara. Swertia pseudochinensis Hara is first recorded in "Inner Mongolia Chinese Herb Medicine"and is considered as a folk medicine for treating hepatitis in northern China. AIM OF THE STUDY This study sought to elucidate the role of sweroside in high fat diet induced obesity and fatty liver by using mouse model and investigated the primary molecular mechanism via transcriptomics analysis. MATERIALS AND METHODS C57BL/6 mice were fed high-fat diet (HFD) for 14 weeks to induce obesity, hyperglycemia, and fatty liver. These mice were subsequently treated with HFD alone or mixed with sweroside (at a daily dosage of 60 mg per kg of BW, 120 mg per kg of BW and 240 mg per kg of BW) for 6 weeks. BW and food intake was monitored weekly. Biochemical and pathological analysis were conducted to investigate the effect of sweroside on NAFLD. RNA-sequence and RT-qPCR analysis were performed to analyze the potential mechanism. RESULTS The mice treated with sweroside were resistant to HFD-induced body weight gain, insulin resistance and hepatic steatosis. Ingenuity pathway analysis (IPA) demonstrated that hepatic gene networks related to lipid metabolism and inflammatory response were down-regulated in the HFD + sweroside group. PPAR-ɑ was located in the center of the hepatic gene network, and the significantly altered genes were CD36 and FGF21, which are related to hepatic inflammation and lipid metabolism. Consistently, upstream-regulators analysis revealed that the main enriched upstream-regulator was PPAR-ɑ. CONCLUSION Our results indicate that sweroside may ameliorate obesity with fatty liver via the regulation of lipid metabolism and inflammatory responses. The beneficial effects of sweroside might be closely associated with the regulation of PPAR-α.
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Affiliation(s)
- Qiaoling Yang
- The MOE Key Laboratory of Standardization of Chinese Medicines and the SATCM Key Laboratory of New Resources and Quality Evaluation of Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China; Department of Pharmacy, Shanghai Children's Hospital, Shanghai Jiao Tong University, Shanghai, 200040, China; Department of Diabetes Complications & Metabolism, Institute of Diabetes Center, Beckman Research Institute, City of Hope National Medical Center, Duarte, CA, USA
| | - Fangfang Shu
- The MOE Key Laboratory of Standardization of Chinese Medicines and the SATCM Key Laboratory of New Resources and Quality Evaluation of Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China; Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China
| | - Junting Gong
- The MOE Key Laboratory of Standardization of Chinese Medicines and the SATCM Key Laboratory of New Resources and Quality Evaluation of Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China
| | - Ping Ding
- The MOE Key Laboratory of Standardization of Chinese Medicines and the SATCM Key Laboratory of New Resources and Quality Evaluation of Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China
| | - Rongrong Cheng
- The MOE Key Laboratory of Standardization of Chinese Medicines and the SATCM Key Laboratory of New Resources and Quality Evaluation of Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China; Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China
| | - Jinmei Li
- The MOE Key Laboratory of Standardization of Chinese Medicines and the SATCM Key Laboratory of New Resources and Quality Evaluation of Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China
| | - Renchao Tong
- The MOE Key Laboratory of Standardization of Chinese Medicines and the SATCM Key Laboratory of New Resources and Quality Evaluation of Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China
| | - Lili Ding
- The MOE Key Laboratory of Standardization of Chinese Medicines and the SATCM Key Laboratory of New Resources and Quality Evaluation of Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China; Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China; Department of Diabetes Complications & Metabolism, Institute of Diabetes Center, Beckman Research Institute, City of Hope National Medical Center, Duarte, CA, USA
| | - Huajun Sun
- Department of Pharmacy, Shanghai Children's Hospital, Shanghai Jiao Tong University, Shanghai, 200040, China
| | - Wendong Huang
- Department of Diabetes Complications & Metabolism, Institute of Diabetes Center, Beckman Research Institute, City of Hope National Medical Center, Duarte, CA, USA
| | - Zhengtao Wang
- The MOE Key Laboratory of Standardization of Chinese Medicines and the SATCM Key Laboratory of New Resources and Quality Evaluation of Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China
| | - Li Yang
- The MOE Key Laboratory of Standardization of Chinese Medicines and the SATCM Key Laboratory of New Resources and Quality Evaluation of Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China; Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China.
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20
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Hosny S, Sahyon H, Youssef M, Negm A. Oleanolic Acid Suppressed DMBA-Induced Liver Carcinogenesis through Induction of Mitochondrial-Mediated Apoptosis and Autophagy. Nutr Cancer 2020; 73:968-982. [PMID: 32519911 DOI: 10.1080/01635581.2020.1776887] [Citation(s) in RCA: 29] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
Phytochemicals appeared as a rich source of efficient and safe agents against many diseases like cancer. Various herbal sources are rich in oleanolic acid (OA). The scope of this study was to assess the biochemical and molecular mechanisms implicated in the ameliorative potency of OA against DMBA-induced liver carcinogenesis. Forty-eight male albino mice were assigned randomly to five groups (eight mice each) as follows: control healthy group, olive oil group, OA group, DMBA group, and DMBA with OA. Apoptosis, autophagy, inflammation, proliferation, and angiogenesis were investigated in the tissue samples. Histopathological examination was carried out as well as liver enzymes activity and other hepatic antioxidant and inflammatory biomarkers. The treatment with OA effectively suppressed the DMBA-initiated liver carcinogenesis via modulation of antioxidant status, induction of apoptosis and autophagy through modulating the expression of Caspase-3, Bcl-2 and Beclin-1, inhibiting angiogenesis (VEGF), proliferation (PCNA), and improved liver function and histological picture with a reduction in AFP level. Additionally, OA applies its antitumor effects by inhibition of proinflammatory transcription factor NF-κB and inflammatory markers (TNF-α and Cox-2) associated with DMBA administration. The present study shows that OA treatment efficiently suppressed the DMBA-initiated liver carcinogenesis through induction of mitochondrial-mediated apoptosis and autophagy and modulating inflammation.
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Affiliation(s)
- Samar Hosny
- Chemistry Department, Biochemistry Division, Faculty of Science, Mansoura University, Mansoura, Egypt
| | - Heba Sahyon
- Chemistry Department, Faculty of Science, Kafrelsheikh University, Kafrelsheikh, Egypt
| | - Magdy Youssef
- Chemistry Department, Biochemistry Division, Faculty of Science, Mansoura University, Mansoura, Egypt
| | - Amr Negm
- Chemistry Department, Biochemistry Division, Faculty of Science, Mansoura University, Mansoura, Egypt.,Department of Chemistry, College of Science, King Faisal University, Al-Ahasa, Saudi Arabia
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21
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Sen A. Prophylactic and therapeutic roles of oleanolic acid and its derivatives in several diseases. World J Clin Cases 2020; 8:1767-1792. [PMID: 32518769 PMCID: PMC7262697 DOI: 10.12998/wjcc.v8.i10.1767] [Citation(s) in RCA: 49] [Impact Index Per Article: 9.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/12/2020] [Revised: 03/27/2020] [Accepted: 05/01/2020] [Indexed: 02/05/2023] Open
Abstract
Oleanolic acid (OA) and its derivatives are widely found in diverse plants and are naturally effective pentacyclic triterpenoid compounds with broad prophylactic and therapeutic roles in various diseases such as ulcerative colitis, multiple sclerosis, metabolic disorders, diabetes, hepatitis and different cancers. This review assembles and presents the latest in vivo reports on the impacts of OA and OA derivatives from various plant sources and the biological mechanisms of OA activities. Thus, this review presents sufficient data proposing that OA and its derivatives are potential alternative and complementary therapies for the treatment and management of several diseases.
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Affiliation(s)
- Alaattin Sen
- Department of Molecular Biology and Genetics, Faculty of Life and Natural Sciences, Abdullah Gul University, Kayseri 38080, Turkey
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22
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Antioxidant, anti-inflammatory and anti-fibrotic effects of Boswellia serrate gum resin in CCl 4-induced hepatotoxicity. Exp Ther Med 2019; 19:1313-1321. [PMID: 32010304 PMCID: PMC6966228 DOI: 10.3892/etm.2019.8353] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/14/2018] [Accepted: 10/11/2019] [Indexed: 12/14/2022] Open
Abstract
The present study aims to investigate the potential antioxidant, anti-inflammatory and anti-fibrotic effects of Boswellia serrate (BS) gum resin against carbon tetrachloride (CCl4)-induced liver damage. Four groups consisting of eight rats each were designated: Group I, normal healthy control; group II, CCl4-induced liver fibrosis; group III, CCl4-induced liver fibrosis followed by BS treatment daily for two weeks; and group IV, CCl4-induced liver fibrosis followed by silymarin treatment daily for two weeks. Expression of tumor necrosis factor-α (TNF-α) and nuclear factor κB (NF-κB), interleukin-6 (IL-6), transforming growth factor-β (TGF-β) and cyclooxygenase-2 (COX-2) were assessed, in addition to histopathological and fibrotic changes in liver tissues isolated from the rats. BS significantly ameliorated CCl4-induced increases in serum aspartate (AST) and alanine transaminase (ALT) levels, reduced lactate dehydrogenase (LDH) activities in addition to restoring total bilirubin, triglyceride and albumin levels. BS treatment also alleviated oxidative stress and improved total antioxidant capacity in the liver, and reduced the expression of TNF-α, NF-κB, TGF-β, IL-6 and COX-2. On a histopathological level, BS treatment also exhibited antifibrotic activity. In conclusion, these findings suggest that BS contains potentially hepatoprotective effects against CCl4-induced liver injury via its antioxidant, anti-inflammatory and antifibrotic characteristics.
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23
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Khan MW, Zhao P, Khan A, Raza F, Raza SM, Sarfraz M, Chen Y, Li M, Yang T, Ma X, Xiang G. Synergism of cisplatin-oleanolic acid co-loaded calcium carbonate nanoparticles on hepatocellular carcinoma cells for enhanced apoptosis and reduced hepatotoxicity. Int J Nanomedicine 2019; 14:3753-3771. [PMID: 31239661 PMCID: PMC6554709 DOI: 10.2147/ijn.s196651] [Citation(s) in RCA: 54] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/03/2018] [Accepted: 03/19/2019] [Indexed: 12/19/2022] Open
Abstract
Background: Cisplatin (CDDP), a widely used chemotherapeutic agent against hepatocellular carcinoma (HCC), faces severe resistance and hepatotoxicity problems which can be alleviated through combination therapy. Purpose: The objective of this study was to develop a pH-dependent calcium carbonate nano-delivery system for the combination therapy of CDDP with oleanolic acid (OA). Methods: A microemulsion method was employed to generate lipid coated cisplatin/oleanolic acid calcium carbonate nanoparticles (CDDP/OA-LCC NPs), and the loading concentration of CDDP and OA was measured by atomic absorption spectroscopy and HPLC respectively.Transmission electron microscopy (TEM) was used to examine the nanoparticles morphology while its pH dependent release characteristics were investigated through in vitro release study. Cellular uptake was examined through a fluorescence microscopy. Apoptotic assays and western blot analysis were conducted to explore the synergistic apoptotic effect of OA on CDDP against HCC cells. The hepatoprotective of OA for CDDP was evaluated through H&E staining. Results: TEM analysis revealed nanoparticles spherical shape with an average particle size of 206±15 nm, and the overall entrapment efficiency was 63.70%±3.9%. In vitro drug release study confirmed the pH-dependent property of the formulation, with the maximum CDDP release of 70%±4.6% at pH 5.5, in contrast to 28%±4.1% CDDP release at pH 7.4. Annexin V-FITC/PI assay and cell cycle analysis confirmed that CDDP and OA synergistically promoted greater HepG2 cells apoptosis for the CDDP/OA-LCC NPs as compared to their individual free drug solutions and NPs-treated groups. Western blot analysis also proved that CDDP/OA-LCC NPs induced the apoptosis by enhancing the proapoptotic protein expressions through downregulating P13K/AKT/mTOR pathway and upregulating p53 proapoptotic pathway. OA helped CDDP to overcome the resistance by downregulating the expression of proteins like XIAP, Bcl-2 via NF-κB pathway. OA also significantly alleviated CDDP-induced hepatotoxicity as evident from the decreased alanine transaminase, aspartate transaminase levels and histochemical evaluation. The possible mechanism may be related to the Nrf-2 induction via its antioxidant mechanism to maintain the redox balance and reduction in CYP2E1 activity which can lead to ROS-mediated oxidative stress. Conclusion: These results suggest that CDDP/OA-LCC NPs have promising applications for co-delivering CDDP and OA to synergize their anti-tumor activity against HCC and to utilize OA’s protective effect against CDDP-induced hepatotoxicity.
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Affiliation(s)
- Muhammad Waseem Khan
- School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, People's Republic of China
| | - Pengxuan Zhao
- School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, People's Republic of China
| | - Asifullah Khan
- State Key Laboratory of Natural Medicines and Department of Pharmaceutics, China Pharmaceutical University, Nanjing 210009, People's Republic of China
| | - Faisal Raza
- State Key Laboratory of Natural Medicines and Department of Pharmaceutics, China Pharmaceutical University, Nanjing 210009, People's Republic of China
| | - Shahid Masood Raza
- School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, People's Republic of China
| | - Muhammad Sarfraz
- School of Basic Medical Sciences, Henan University, Kaifeng, Henan 475001/475004, People's Republic of China
| | - Yan Chen
- School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, People's Republic of China
| | - Minsi Li
- School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, People's Republic of China
| | - Tan Yang
- School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, People's Republic of China
| | - Xiang Ma
- School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, People's Republic of China
| | - Guangya Xiang
- School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, People's Republic of China
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24
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Liu J, Lu YF, Wu Q, Xu SF, Shi FG, Klaassen CD. Oleanolic acid reprograms the liver to protect against hepatotoxicants, but is hepatotoxic at high doses. Liver Int 2019; 39:427-439. [PMID: 30079536 DOI: 10.1111/liv.13940] [Citation(s) in RCA: 39] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/06/2018] [Revised: 07/14/2018] [Accepted: 07/27/2018] [Indexed: 12/13/2022]
Abstract
Oleanolic acid (OA) is a triterpenoid that exists widely in fruits, vegetables and medicinal herbs. OA is included in some dietary supplements and is used as a complementary and alternative medicine (CAM) in China, India, Asia, the USA and European countries. OA is effective in protecting against various hepatotoxicants, and one of the protective mechanisms is reprogramming the liver to activate the nuclear factor erythroid 2-related factor 2 (Nrf2). OA derivatives, such as CDDO-Im and CDDO-Me, are even more potent Nrf2 activators. OA has recently been shown to also activate the Takeda G-protein-coupled receptor (TGR5). However, whereas a low dose of OA is hepatoprotective, higher doses and long-term use of OA can produce liver injury, characterized by cholestasis. This paradoxical hepatotoxic effect occurs not only for OA, but also for other OA-type triterpenoids. Dose and length of time of OA exposure differentiate the ability of OA to produce hepatoprotection vs hepatotoxicity. Hepatotoxicity produced by herbs is increasingly recognized and is of global concern. Given the appealing nature of OA in dietary supplements and its use as an alternative medicine around the world, as well as the development of OA derivatives (CDDO-Im and CDDO-Me) as therapeutics, it is important to understand not only that they program the liver to protect against hepatotoxic chemicals, but also how they produce hepatotoxicity.
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Affiliation(s)
- Jie Liu
- Key Laboratory for Basic Pharmacology of Ministry of Education and Joint International Research Laboratory of Ethnomedicine, Zunyi Medical University, Zunyi, China.,Department of Pharmacology, Toxicology and Therapeutics, School of Medicine, University of Kansas, Kansas City, Kansas
| | - Yuan-Fu Lu
- Key Laboratory for Basic Pharmacology of Ministry of Education and Joint International Research Laboratory of Ethnomedicine, Zunyi Medical University, Zunyi, China
| | - Qin Wu
- Key Laboratory for Basic Pharmacology of Ministry of Education and Joint International Research Laboratory of Ethnomedicine, Zunyi Medical University, Zunyi, China
| | - Shang-Fu Xu
- Key Laboratory for Basic Pharmacology of Ministry of Education and Joint International Research Laboratory of Ethnomedicine, Zunyi Medical University, Zunyi, China
| | - Fu-Guo Shi
- Key Laboratory for Basic Pharmacology of Ministry of Education and Joint International Research Laboratory of Ethnomedicine, Zunyi Medical University, Zunyi, China
| | - Curtis D Klaassen
- Department of Pharmacology, Toxicology and Therapeutics, School of Medicine, University of Kansas, Kansas City, Kansas
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25
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Zhao N, Guo FF, Xie KQ, Zeng T. Targeting Nrf-2 is a promising intervention approach for the prevention of ethanol-induced liver disease. Cell Mol Life Sci 2018; 75:3143-3157. [PMID: 29947925 PMCID: PMC11105722 DOI: 10.1007/s00018-018-2852-6] [Citation(s) in RCA: 35] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/21/2018] [Revised: 05/18/2018] [Accepted: 06/06/2018] [Indexed: 02/07/2023]
Abstract
Alcoholic liver disease (ALD) remains to be a worldwide health problem. It is generally accepted that oxidative stress plays critical roles in the pathogenesis of ALD, and antioxidant therapy represents a logical strategy for the prevention and treatment of ALD. Nuclear factor erythroid-derived 2-like 2 (NFE2L2 or Nrf-2) is essential for the antioxidant responsive element (ARE)-mediated induction of endogenous antioxidant enzymes such as heme oxygenase 1 (HO-1) and glutamate-cysteine ligase [GCL, the rate-limiting enzyme in the synthesis of glutathione (GSH)]. Activation of Nrf-2 pathway by genetic manipulation or pharmacological agents has been demonstrated to provide protection against ALD, which suggests that targeting Nrf-2 may be a promising approach for the prevention and treatment of ALD. Herein, we review the relevant literature about the potential hepatoprotective roles of Nrf-2 activation against ALD.
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Affiliation(s)
- Ning Zhao
- Institute of Toxicology, School of Public Health, Shandong University, 44 Wenhua West Road, Jinan, 250012, Shandong, China
| | - Fang-Fang Guo
- Department of Pharmacy, Qilu Hospital of Shandong University, 107 Wenhua West Road, Jinan, 250012, Shandong, China
| | - Ke-Qin Xie
- Institute of Toxicology, School of Public Health, Shandong University, 44 Wenhua West Road, Jinan, 250012, Shandong, China
| | - Tao Zeng
- Institute of Toxicology, School of Public Health, Shandong University, 44 Wenhua West Road, Jinan, 250012, Shandong, China.
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26
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Liu YC, Wang HM, Zeng XH. Research progress of active compounds and pharmacological effects in Akebia trifoliata (Thunb) koidz stems. ACTA ACUST UNITED AC 2018. [DOI: 10.1088/1755-1315/185/1/012034] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
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27
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Liu Y, Wen PH, Zhang XX, Dai Y, He Q. Breviscapine ameliorates CCl4‑induced liver injury in mice through inhibiting inflammatory apoptotic response and ROS generation. Int J Mol Med 2018; 42:755-768. [PMID: 29717768 PMCID: PMC6034936 DOI: 10.3892/ijmm.2018.3651] [Citation(s) in RCA: 45] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/28/2017] [Accepted: 04/05/2018] [Indexed: 01/06/2023] Open
Abstract
Acute liver injury is characterized by fibrosis, inflammation and apoptosis, leading to liver failure, cirrhosis or cancer and affecting the clinical outcome in the long term. However, no effective therapeutic strategy is currently available. Breviscapine, a mixture of flavonoid glycosides, has been reported to have multiple biological functions. The present study aimed to investigate the effects of breviscapine on acute liver injury induced by CCl4 in mice. C57BL/6 mice were subjected to intraperitoneal injection with CCl4 for 8 weeks with or without breviscapine (15 or 30 mg/kg). Mice treated with CCl4 developed acute liver injury, as evidenced by histological analysis, Masson trichrome and Sirius Red staining, accompanied with elevated levels of alanine aminotransferase and aspartate aminotransferase. Furthermore, increases in pro‑inflammatory cytokines, chemokines and apoptotic factors, including caspase‑3 and poly(ADP ribose) polymerase‑2 (PARP‑2), were observed. Breviscapine treatment significantly and dose‑dependently reduced collagen deposition and the fibrotic area. Inflammatory cytokines were downregulated by breviscapine through inactivating Toll‑like receptor 4/nuclear factor-κB signaling pathways. In addition, co‑administration of breviscapine with CCl4 decreased the apoptotic response by enhancing B‑cell lymphoma-2 (Bcl‑2) levels, while reducing Bcl‑2‑associated X protein, apoptotic protease activating factor 1, caspase‑3 and PARP activity. Furthermore, CCl4‑induced oxidative stress was blocked by breviscapine through improving anti‑oxidants and impeding mitogen‑activated protein kinase pathways. The present study highlighted that breviscapine exhibited liver‑protective effects against acute hepatic injury induced by CCl4 via suppressing inflammation and apoptosis.
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Affiliation(s)
- Yu Liu
- Department of Hepatobiliary Surgery, Beijing Chao-Yang Hospital Affiliated to Capital University of Medical Science, Beijing 100000, P.R. China
| | - Pei-Hao Wen
- Department of Hepatobiliary Surgery, Beijing Chao-Yang Hospital Affiliated to Capital University of Medical Science, Beijing 100000, P.R. China
| | - Xin-Xue Zhang
- Department of Hepatobiliary Surgery, Beijing Chao-Yang Hospital Affiliated to Capital University of Medical Science, Beijing 100000, P.R. China
| | - Yang Dai
- Department of Hepatobiliary Surgery, Beijing Chao-Yang Hospital Affiliated to Capital University of Medical Science, Beijing 100000, P.R. China
| | - Qiang He
- Department of Hepatobiliary Surgery, Beijing Chao-Yang Hospital Affiliated to Capital University of Medical Science, Beijing 100000, P.R. China
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28
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Mir SM, Sahu BD, Koneru M, Kuncha M, Jerald MK, Ravuri HG, Kanjilal S, Sistla R. Supplementation of oat ( Avena sativa L.) extract abates alcohol-induced acute liver injury in a mouse model. Nutr Res 2018; 54:80-92. [DOI: 10.1016/j.nutres.2018.04.002] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/24/2017] [Revised: 03/26/2018] [Accepted: 04/02/2018] [Indexed: 02/08/2023]
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29
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Zhang Y, Wang C, Yu B, Jiang JD, Kong WJ. Gastrodin Protects against Ethanol-Induced Liver Injury and Apoptosis in HepG2 Cells and Animal Models of Alcoholic Liver Disease. Biol Pharm Bull 2018; 41:670-679. [DOI: 10.1248/bpb.b17-00825] [Citation(s) in RCA: 24] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
Affiliation(s)
- Yong Zhang
- Department of Virology, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College
| | - Can Wang
- State Key Laboratory of Bioactive Natural Products and Function, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College
| | - Bin Yu
- Department of Virology, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College
| | - Jian-Dong Jiang
- State Key Laboratory of Bioactive Natural Products and Function, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College
| | - Wei-Jia Kong
- Department of Virology, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College
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30
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Li J, Yang C, Zhang S, Liu S, Zhao L, Luo H, Chen Y, Huang W. Ginsenoside Rg1 inhibits inflammatory responses via modulation of the nuclear factor‑κB pathway and inhibition of inflammasome activation in alcoholic hepatitis. Int J Mol Med 2018; 41:899-907. [PMID: 29207044 PMCID: PMC5752168 DOI: 10.3892/ijmm.2017.3297] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/11/2016] [Accepted: 11/16/2017] [Indexed: 12/11/2022] Open
Abstract
Ginsenoside Rg1 (G‑Rg1) is an active ingredient of Panax ginseng, which has previously been reported to attenuate alcohol‑induced hepatic damage; however, the underlying mechanisms remain largely unknown. The present study aimed to investigate the protective effects of G‑Rg1 on alcohol‑induced cell injury in vitro and on a rat model of alcoholic hepatitis in vivo. For the in vitro model, L‑O2 cells were incubated with ethanol in the presence or absence of G‑Rg1. For the in vivo model, rats were administered ethanol by intragastric injection and were treated with G‑Rg1, or dexamethasone as a control. The results indicated that serum biochemical parameters, including alanine aminotransferase, aspartate aminotransferase and total bilirubin, as well as the expression of nuclear factor (NF)‑κB pathway‑associated inflammatory cytokines, including interleukin (IL)‑6, tumor necrosis factor‑α and IL‑1β, were elevated in response to alcohol; however, they were significantly decreased by G‑Rg1 treatment. Furthermore, NF‑κB pathway activation was reduced by treatment with G‑Rg1. G‑Rg1 also decreased oxidative stress by inhibiting cytochrome P450 2E1 expression and reactive oxygen species production, and promoting glutathione peroxidase expression. Furthermore, G‑Rg1 inhibited the expression levels of caspase‑3 and ‑8, which may be associated with decreased hepatocyte apoptosis. These data suggested that G‑Rg1 may protect hepatocytes against alcohol‑induced injury, through preventing excessive inflammation and hepatocellular apoptosis.
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Affiliation(s)
- Jiajun Li
- Department of Infectious Diseases and
| | | | - Shu Zhang
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, P.R. China
| | - Shu Liu
- Department of Infectious Diseases and
| | | | - Huan Luo
- Department of Infectious Diseases and
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31
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Nepali S, Ki HH, Lee JH, Cha JY, Lee YM, Kim DK. Triticum aestivum sprout-derived polysaccharide exerts hepatoprotective effects against ethanol-induced liver damage by enhancing the antioxidant system in mice. Int J Mol Med 2017; 40:1243-1252. [PMID: 28849040 DOI: 10.3892/ijmm.2017.3095] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/14/2017] [Accepted: 07/28/2017] [Indexed: 11/05/2022] Open
Abstract
Triticum aestivum sprout-derived polysaccharide (TASP) has anti-diabetic properties, but no information is available in regards to its protective effect against ethanol-induced hepatic injury. This study aimed to investigate the mechanism behind the protective role of TASP against ethanol-induced liver injury in vivo. Male C57BL/6 mice were administered ethanol with or without TASP for 10 consecutive days by oral gavage. Silymarin was administered in the same manner as a positive control. TASP reduced ethanol-induced hepatic lipid accumulation and serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels. TASP also prevented glutathione (GSH) depletion and increased the superoxide dismutase (SOD) in liver tissue. In addition, TASP significantly inhibited ethanol-induced cytochrome P450 2E1 (CYP2E1) activation, and upregulated the expressions of nuclear factor erythroid 2-related factor 2 (Nrf2) and hemeoxygenase-1 (HO-1), and downregulated NADPH oxidase genes in ethanol fed mice. Furthermore, the upregulation of Nrf2 was found to be regulated by a phosphatidylinositol 3-kinase (PI3K)/Akt pathway. TASP also attenuated hepatic injury by modulation of caspase-3 and apoptosis-associated mitochondrial proteins including B-cell lymphoma-2 (Bcl-2) and Bcl-2-associated X (Bax) in liver tissues of mice. The study demonstrated that TASP treatment protects against ethanol-induced hepatic injury via multiple pathways by inhibiting steatosis and improving antioxidant marker levels during hepatic injury. Such properties provide a basis for therapeutic agents against alcohol-induced liver injury.
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Affiliation(s)
- Sarmila Nepali
- Department of Immunology and Institute of Medical Sciences, Medical School, Chonbuk National University, Jeonju, Jeonbuk 54907, Republic of Korea
| | - Hyeon-Hui Ki
- Department of Immunology and Institute of Medical Sciences, Medical School, Chonbuk National University, Jeonju, Jeonbuk 54907, Republic of Korea
| | - Ji-Hyun Lee
- Department of Immunology and Institute of Medical Sciences, Medical School, Chonbuk National University, Jeonju, Jeonbuk 54907, Republic of Korea
| | - Ji-Yun Cha
- Department of Oriental Pharmacy, College of Pharmacy and Wonkwang-Oriental Medicine Research Institute, Wonkwang University, Iksan, Jeonbuk 54538, Republic of Korea
| | - Young-Mi Lee
- Department of Oriental Pharmacy, College of Pharmacy and Wonkwang-Oriental Medicine Research Institute, Wonkwang University, Iksan, Jeonbuk 54538, Republic of Korea
| | - Dae-Ki Kim
- Department of Immunology and Institute of Medical Sciences, Medical School, Chonbuk National University, Jeonju, Jeonbuk 54907, Republic of Korea
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32
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Li WF, Wang P, Li H, Li TY, Feng M, Chen SF. Oleanolic acid protects against diabetic cardiomyopathy via modulation of the nuclear factor erythroid 2 and insulin signaling pathways. Exp Ther Med 2017; 14:848-854. [PMID: 28673009 DOI: 10.3892/etm.2017.4527] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/28/2015] [Accepted: 01/20/2017] [Indexed: 12/12/2022] Open
Abstract
Oleanolic acid (OL) is a pentacyclic triterpene compound used for the treatment of hepatitis, liver fibrosis and liver cirrhosis. In China, there is no published research on the effect or biological utilization of OL on liver diseases. The aim of the present study was to investigate the protective effects of OL against diabetic cardiomyopathy and its possible mechanism. A rat model of diabetes was established using streptozotocin and the effect of OL on diabetic cardiomyopathy (DCM) was evaluated. The results demonstrated that OL significantly reversed the DCM-induced changes to body weight, heart rate, echocardiography and hemodynamics, phosphorylated-glycogen synthase (GS) and glycogen phosphorylase (GP) activity in diabetic rats (all P<0.01). Treatment of diabetic rats with OL significantly inhibited oxidative stress and activated heme oxygenase (HO)-1/nuclear factor erythroid 2 (Nrf2) signaling in a rat model of diabetes (both P<0.01). The results of the present study indicate that OL protects against DCM through the HO-1/Nrf2 and insulin modulating GS/GP signaling pathways.
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Affiliation(s)
- Wei-Fang Li
- Department of Geriatric Endocrinology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, P.R. China
| | - Peng Wang
- Department of Epidemiology, College of Public Health, Zhengzhou University, Zhengzhou, Henan 450001, P.R. China
| | - Hua Li
- Department of Geriatric Endocrinology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, P.R. China
| | - Tian-Yi Li
- Department of Geriatric Endocrinology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, P.R. China
| | - Ming Feng
- Department of Geriatric Endocrinology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, P.R. China
| | - Su-Fang Chen
- Department of Geriatric Endocrinology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, P.R. China
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Gao Y, Chu S, Shao Q, Zhang M, Xia C, Wang Y, Li Y, Lou Y, Huang H, Chen N. Antioxidant activities of ginsenoside Rg1 against cisplatin-induced hepatic injury through Nrf2 signaling pathway in mice. Free Radic Res 2016; 51:1-13. [PMID: 27931128 DOI: 10.1080/10715762.2016.1234710] [Citation(s) in RCA: 66] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Oxidative stress is mainly caused by reactive oxygen species (ROS). The damage causes a net stress on normal organs, leading to a gradual loss of vital physiological function. ROS, such as free radicals, represent a class of molecules which are derived from the metabolism of oxygen and exist inherently. However, excessive produced ROS can damage all aerobic organisms. Ginseng is one of the most commonly used alternative herbal medicines, also as a traditional Chinese medicine. The aim of this study is to investigate the antioxidant potential function of ginsenoside Rg1 against cisplatin-caused hepatic damage. Male mice were treated with cisplatin to induce oxidative stress to mimic the side effect of anti-cancer drug cisplatin. Ginsenoside Rg1 effectively prevented against cisplatin-induced hepatotoxicity, alleviating histological lesions. Antioxidant functions of Rg1 were restrained by the activation of p62-Keap1-Nrf2 signaling pathway, simultaneously accompanied with expression of protein products. Accumulative p62 and increased activation of JNK in hepatocytes promoted the activation of Nrf2. For the other, degradation of Nrf2 was guided by tyrosine phosphorylation, ubiquitin, and Keap1. In summary, Rg1 prevents hepatotoxicity mainly by inhibiting the binding of Keap1 and Nrf2, partly by p62 accumulation, and more importantly by increasing the production of antioxidative proteins associated to Nrf2. Pharmacological activation of Nrf2 is an effective way in combating against liver injury.
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Affiliation(s)
- Yan Gao
- a State Key Laboratory of Bioactive Substances and Functions of Natural Medicines , Institute of Materia Medica Chinese Academy of Medical Sciences and Peking Union Medical College , Beijing , China
| | - Shifeng Chu
- b College of Pharmacy , Hunan University of Chinese Medicine , Changsha , China
| | - Qianhang Shao
- a State Key Laboratory of Bioactive Substances and Functions of Natural Medicines , Institute of Materia Medica Chinese Academy of Medical Sciences and Peking Union Medical College , Beijing , China
| | - Meijin Zhang
- a State Key Laboratory of Bioactive Substances and Functions of Natural Medicines , Institute of Materia Medica Chinese Academy of Medical Sciences and Peking Union Medical College , Beijing , China
| | - Congyuan Xia
- a State Key Laboratory of Bioactive Substances and Functions of Natural Medicines , Institute of Materia Medica Chinese Academy of Medical Sciences and Peking Union Medical College , Beijing , China
| | - Yingying Wang
- a State Key Laboratory of Bioactive Substances and Functions of Natural Medicines , Institute of Materia Medica Chinese Academy of Medical Sciences and Peking Union Medical College , Beijing , China
| | - Yueting Li
- c Beijing Hospital of Integrated Traditional and Western Medicine , Beijing , China
| | - Yuxia Lou
- d Tianjin University of Traditional Chinese Medicine , Tianjin , China
| | - Huiyong Huang
- b College of Pharmacy , Hunan University of Chinese Medicine , Changsha , China
| | - Naihong Chen
- a State Key Laboratory of Bioactive Substances and Functions of Natural Medicines , Institute of Materia Medica Chinese Academy of Medical Sciences and Peking Union Medical College , Beijing , China.,b College of Pharmacy , Hunan University of Chinese Medicine , Changsha , China
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Abd-ElSalam HAH, Al-Ghobashy MA, Al-Shorbagy M, Nassar N, Zaazaa HE, Ibrahim MA. Correlation of In Vivo and In Vitro Assay Results for Assessment of Free Radical Scavenging Activity of Green Tea Nutraceuticals. J Food Sci 2016; 81:C1707-15. [PMID: 27275932 DOI: 10.1111/1750-3841.13362] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2016] [Revised: 04/26/2016] [Accepted: 05/13/2016] [Indexed: 12/27/2022]
Abstract
Green tea (GT)-derived catechins; epigallocatechin gallate (EGCG) in particular are commonly used nutraceuticals for their free-radical scavenging activity (FRSA). The influence of photodegradation on the protective power of GT nutracenticals against oxidative stress was thoroughly explored. Photodegradation of GT extracts was carried out and monitored using orthogonal stability-indicating testing protocol; in vitro and in vivo assays. Total polyphenol content (TPC) and FRSA were determined spectrophotometrically while EGCG was selectively monitored using SPE-HPLC. In vivo assessment of photodegraded samples was investigated via measuring a number of biomarkers for hepatic oxidative stress and apoptosis (caspase-3, inducible nitric oxide synthase, nitric oxide, mitogen-activated protein kinase, glutathione, thiobarbituric acid reactive substances, nuclear factor kappa beta, and nuclear factor erythroid 2-related factor) as well as liver damage (alanine transaminase and aspartate transaminase) in serum of rats previously subjected to oxidative stress. Results showed complete degradation of EGCG in photodegraded green tea samples with no correlation with either TPC or FRSA. On the other hand, in vivo assay results revealed not only loss of activity but formation of harmful pro-oxidants. Photostability was found crucial for the protective effect of GT extract against lead acetate insult. Results confirmed that careful design of quality control protocols requires correlation of chemical assays to bioassays to verify efficacy, stability, and most importantly safety of nutraceuticals.
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Affiliation(s)
| | - Medhat A Al-Ghobashy
- Bioanalysis Research Group, Faculty of Pharmacy, Cairo Univ, Egypt.,Analytical Chemistry Dept., Faculty of Pharmacy, Cairo Univ, Egypt
| | | | - Noha Nassar
- Pharmacology and Toxicology Dept., Faculty of Pharmacy, Cairo Univ, Egypt
| | - Hala E Zaazaa
- Analytical Chemistry Dept., Faculty of Pharmacy, Cairo Univ, Egypt
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Long C, Yang J, Yang H, Li X, Wang G. Attenuation of renal ischemia/reperfusion injury by oleanolic acid preconditioning via its antioxidant, anti‑inflammatory, and anti‑apoptotic activities. Mol Med Rep 2016; 13:4697-704. [PMID: 27082705 DOI: 10.3892/mmr.2016.5128] [Citation(s) in RCA: 34] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/16/2015] [Accepted: 01/20/2016] [Indexed: 12/13/2022] Open
Abstract
Ischemia/reperfusion (I/R)‑associated acute kidney injury is a major clinical problem in both native and transplanted kidneys. Renal I/R, and subsequent renal injury, may be attributed to oxidative stress, inflammation, and apoptosis. Oleanolic acid (OA) is a natural product, which possesses antioxidant, anti‑inflammatory, and anti‑apoptotic activities. The present study aimed to examine the effects of OA preconditioning on renal I/R and the possible underlying mechanisms. In a renal I/R model, rats were administered OA (12.5, 25 and 50 mg/kg) for 15 consecutive days prior to bilateral renal I/R induction. Serum samples and kidneys were then collected and stored for subsequent determination. The results of the present study demonstrated that OA significantly and dose‑dependently attenuated I/R‑induced renal damage. OA prevented renal I/R injury, as evidenced by decreased levels of blood urea nitrogen, creatinine, kidney injury molecule‑1 and lactate dehydrogenase. In addition, OA defended against oxidative stress, as reflected by decreased levels of methane dicarboxylic aldehyde, increased activities of superoxide dismutase, catalase and glutathione peroxidase, and increased glutathione (GSH) levels. Levels of proinflammatory cytokines, interferon‑γ, interleukin (IL)‑6) and myeloperoxidase, were also reduced by OA, whereas the anti‑inflammatory cytokine IL‑10 was increased. Furthermore, OA prevented I/R‑induced apoptotic cell death, and prevented decreases in the mRNA expression levels of nuclear factor erythroid 2‑related factor 2 (Nrf2) and γ‑glutamylcysteine ligase (GCLc). Conversely, buthionine sulphoximine attenuated the protective effects of OA on renal I/R injury. These results indicated that OA preconditioning may prevent I/R‑induced renal damage via antioxidant, anti‑inflammatory, and anti‑apoptotic activities. Stabilization of Nrf2/GCLc signaling and subsequent maintenance of the GSH pool is critical for the protective effects of OA against renal I/R injury. The present study reported a novel therapeutic strategy for the treatment of renal I/R injury.
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Affiliation(s)
- Chengmei Long
- Graduate Faculty, Medical College of Nanchang University, Nanchang, Jiangxi 330006, P.R. China
| | - Jinran Yang
- Department of Organ Transplantation, Jiangxi Provincial People's Hospital, Nanchang, Jiangxi 330006, P.R. China
| | - Hua Yang
- Department of Organ Transplantation, Jiangxi Provincial People's Hospital, Nanchang, Jiangxi 330006, P.R. China
| | - Xinchang Li
- Department of Organ Transplantation, Jiangxi Provincial People's Hospital, Nanchang, Jiangxi 330006, P.R. China
| | - Gongxian Wang
- Department of Urology, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, P.R. China
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Chen LY, Chen Q, Cheng YF, Jin HH, Kong DS, Zhang F, Wu L, Shao JJ, Zheng SZ. Diallyl trisulfide attenuates ethanol-induced hepatic steatosis by inhibiting oxidative stress and apoptosis. Biomed Pharmacother 2016; 79:35-43. [DOI: 10.1016/j.biopha.2016.01.009] [Citation(s) in RCA: 31] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/29/2015] [Revised: 01/10/2016] [Accepted: 01/13/2016] [Indexed: 12/26/2022] Open
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Han KH, Hashimoto N, Fukushima M. Relationships among alcoholic liver disease, antioxidants, and antioxidant enzymes. World J Gastroenterol 2016; 22:37-49. [PMID: 26755859 PMCID: PMC4698500 DOI: 10.3748/wjg.v22.i1.37] [Citation(s) in RCA: 62] [Impact Index Per Article: 6.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/24/2015] [Revised: 06/25/2015] [Accepted: 09/02/2015] [Indexed: 02/06/2023] Open
Abstract
Excessive consumption of alcoholic beverages is a serious cause of liver disease worldwide. The metabolism of ethanol generates reactive oxygen species, which play a significant role in the deterioration of alcoholic liver disease (ALD). Antioxidant phytochemicals, such as polyphenols, regulate the expression of ALD-associated proteins and peptides, namely, catalase, superoxide dismutase, glutathione, glutathione peroxidase, and glutathione reductase. These plant antioxidants have electrophilic activity and may induce antioxidant enzymes via the Kelch-like ECH-associated protein 1-NF-E2-related factor-2 pathway and antioxidant responsive elements. Furthermore, these antioxidants are reported to alleviate cell injury caused by oxidants or inflammatory cytokines. These phenomena are likely induced via the regulation of mitogen-activating protein kinase (MAPK) pathways by plant antioxidants, similar to preconditioning in ischemia-reperfusion models. Although the relationship between plant antioxidants and ALD has not been adequately investigated, plant antioxidants may be preventive for ALD because of their electrophilic and regulatory activities in the MAPK pathway.
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Oleanolic Acid Attenuates Insulin Resistance via NF-κB to Regulate the IRS1-GLUT4 Pathway in HepG2 Cells. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE 2015; 2015:643102. [PMID: 26843885 PMCID: PMC4710921 DOI: 10.1155/2015/643102] [Citation(s) in RCA: 55] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 10/10/2015] [Revised: 12/09/2015] [Accepted: 12/15/2015] [Indexed: 12/16/2022]
Abstract
The aim of our study is to elucidate the mechanisms of oleanolic acid (OA) on insulin resistance (IR) in HepG2 cells. HepG2 cells were induced with FFA as the insulin resistance model and were treated with OA. Then the glucose content and the levels of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) were analyzed. Moreover, protein expression of nuclear factor kappa B (NF-κB), insulin receptor substrate 1(IRS1), and glucose transporter 4 (GLUT4) in cells treated with OA were measured by Western blot analysis. Additionally, IRS1 protein expression exposed to OA was detected after using pyrrolidine dithiocarbamate (PDTC).Our results revealed that OA decreased the glucose content in HepG2 cells in vitro. Moreover, OA reduced the levels of TNF-α and IL-6 and upregulated IRS1 and GLUT4 protein expression. Furthermore, OA also reduced NF-κB protein expression in insulin-resistant HepG2 cells. After blocking NF-κB, the expression of IRS1 protein had no obvious changes when treated with OA. OA attenuated insulin resistance and decreased the levels of TNF-α and IL-6. Meanwhile, OA decreased NF-κB protein expression and upregulated IRS1 and GLUT4 protein expression. Therefore, regulating the IRS1-GLUT4 pathway via NF-κB was the underlying mechanism of OA on insulin resistance.
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Liu Z, Dou W, Zheng Y, Wen Q, Qin M, Wang X, Tang H, Zhang R, Lv D, Wang J, Zhao S. Curcumin upregulates Nrf2 nuclear translocation and protects rat hepatic stellate cells against oxidative stress. Mol Med Rep 2015; 13:1717-24. [PMID: 26676408 DOI: 10.3892/mmr.2015.4690] [Citation(s) in RCA: 41] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/25/2015] [Accepted: 11/25/2015] [Indexed: 02/01/2023] Open
Abstract
The present study aimed to investigate the protective role of curcumin against oxidative stress in rat hepatic stellate cells (HSCs)-T6, and to determine the possible underlying mechanisms. HSC-T6 cells were divided into three groups: Negative control group, oxidant-treated group and curcumin-treated group. Flow cytometry and spectrophotometry were used to measure the production of reactive oxygen species (ROS), and the levels of malondialdehyde (MDA) and glutathione (GSH). Immunocytochemistry and a radioimmunoassay were used to determine the expression of smooth muscle α-actin (α-SMA) and the secretion of extracellular matrix (ECM) molecules. In addition, western blotting and immunocytochemistry were used to determine the expression levels of nuclear factor-erythroid 2-related factor (Nrf2). Treatment with glucose oxidase (GO) significantly stimulated the formation of ROS and increased the production of MDA, as compared with the control cells; however, the production of GSH was only slightly increased. In addition, treatment with GO significantly promoted the expression of α-SMA and the secretion of ECM molecules. Conversely, treatment with curcumin significantly decreased the levels of ROS and MDA, and significantly increased the levels of GSH. Curcumin significantly inhibited the expression of α-SMA and decreased the secretion of ECM molecules. Furthermore, treatment with curcumin significantly increased the nuclear expression levels of Nrf2. These results indicated that curcumin may protect rat HSCs against oxidative stress and inhibit the GO-induced activation and secretion of ECM molecules in vitro. These effects were mediated by the upregulation of Nrf2 nuclear translocation.
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Affiliation(s)
- Zhenxiong Liu
- Department of Gastroenterology, Tangdu Hospital, Fourth Military Medical University, Xi'an, Shaanxi 710038, P.R. China
| | - Weijia Dou
- Department of Gastroenterology, Tangdu Hospital, Fourth Military Medical University, Xi'an, Shaanxi 710038, P.R. China
| | - Yuanyuan Zheng
- Department of Gastroenterology, 180 Military Hospital, Quanzhou, Fujian 362000, P.R. China
| | - Qinsheng Wen
- Department of Gastroenterology, Tangdu Hospital, Fourth Military Medical University, Xi'an, Shaanxi 710038, P.R. China
| | - Ming Qin
- Department of Gastroenterology, Tangdu Hospital, Fourth Military Medical University, Xi'an, Shaanxi 710038, P.R. China
| | - Xuxia Wang
- Department of Gastroenterology, Tangdu Hospital, Fourth Military Medical University, Xi'an, Shaanxi 710038, P.R. China
| | - Hua Tang
- Department of Gastroenterology, Tangdu Hospital, Fourth Military Medical University, Xi'an, Shaanxi 710038, P.R. China
| | - Rong Zhang
- Department of Gastroenterology, Tangdu Hospital, Fourth Military Medical University, Xi'an, Shaanxi 710038, P.R. China
| | - Dandan Lv
- Department of Gastroenterology, Tangdu Hospital, Fourth Military Medical University, Xi'an, Shaanxi 710038, P.R. China
| | - Jingjie Wang
- Department of Gastroenterology, Tangdu Hospital, Fourth Military Medical University, Xi'an, Shaanxi 710038, P.R. China
| | - Shuguang Zhao
- Department of Gastroenterology, Tangdu Hospital, Fourth Military Medical University, Xi'an, Shaanxi 710038, P.R. China
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Lu C, Zhang F, Xu W, Wu X, Lian N, Jin H, Chen Q, Chen L, Shao J, Wu L, Lu Y, Zheng S. Curcumin attenuates ethanol-induced hepatic steatosis through modulating Nrf2/FXR signaling in hepatocytes. IUBMB Life 2015; 67:645-58. [DOI: 10.1002/iub.1409] [Citation(s) in RCA: 61] [Impact Index Per Article: 6.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/20/2015] [Accepted: 07/20/2015] [Indexed: 12/20/2022]
Affiliation(s)
- Chunfeng Lu
- Department of Pharmacology; College of Pharmacy, Nanjing University of Chinese Medicine; Nanjing Jiangsu Province China
- Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica; Nanjing University of Chinese Medicine; Nanjing Jiangsu Province China
| | - Feng Zhang
- Department of Pharmacology; College of Pharmacy, Nanjing University of Chinese Medicine; Nanjing Jiangsu Province China
- Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica; Nanjing University of Chinese Medicine; Nanjing Jiangsu Province China
| | - Wenxuan Xu
- Department of Pharmacology; College of Pharmacy, Nanjing University of Chinese Medicine; Nanjing Jiangsu Province China
- Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica; Nanjing University of Chinese Medicine; Nanjing Jiangsu Province China
| | - Xiafei Wu
- Department of Pharmacology; College of Pharmacy, Nanjing University of Chinese Medicine; Nanjing Jiangsu Province China
- Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica; Nanjing University of Chinese Medicine; Nanjing Jiangsu Province China
| | - Naqi Lian
- Department of Pharmacology; College of Pharmacy, Nanjing University of Chinese Medicine; Nanjing Jiangsu Province China
- Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica; Nanjing University of Chinese Medicine; Nanjing Jiangsu Province China
| | - Huanhuan Jin
- Department of Pharmacology; College of Pharmacy, Nanjing University of Chinese Medicine; Nanjing Jiangsu Province China
- Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica; Nanjing University of Chinese Medicine; Nanjing Jiangsu Province China
| | - Qin Chen
- Department of Pharmacology; College of Pharmacy, Nanjing University of Chinese Medicine; Nanjing Jiangsu Province China
- Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica; Nanjing University of Chinese Medicine; Nanjing Jiangsu Province China
| | - Lianyun Chen
- Department of Pharmacology; College of Pharmacy, Nanjing University of Chinese Medicine; Nanjing Jiangsu Province China
- Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica; Nanjing University of Chinese Medicine; Nanjing Jiangsu Province China
| | - Jiangjuan Shao
- Department of Pharmacology; College of Pharmacy, Nanjing University of Chinese Medicine; Nanjing Jiangsu Province China
| | - Li Wu
- Department of Pharmacology; College of Pharmacy, Nanjing University of Chinese Medicine; Nanjing Jiangsu Province China
| | - Yin Lu
- Department of Pharmacology; College of Pharmacy, Nanjing University of Chinese Medicine; Nanjing Jiangsu Province China
- Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica; Nanjing University of Chinese Medicine; Nanjing Jiangsu Province China
| | - Shizhong Zheng
- Department of Pharmacology; College of Pharmacy, Nanjing University of Chinese Medicine; Nanjing Jiangsu Province China
- Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica; Nanjing University of Chinese Medicine; Nanjing Jiangsu Province China
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Madlala HP, Van Heerden FR, Mubagwa K, Musabayane CT. Changes in Renal Function and Oxidative Status Associated with the Hypotensive Effects of Oleanolic Acid and Related Synthetic Derivatives in Experimental Animals. PLoS One 2015; 10:e0128192. [PMID: 26046776 PMCID: PMC4457832 DOI: 10.1371/journal.pone.0128192] [Citation(s) in RCA: 33] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/18/2014] [Accepted: 04/24/2015] [Indexed: 01/06/2023] Open
Abstract
Purpose The triterpene oleanolic acid (OA) is known to possess antihypertensive actions. In the present study we to compared the effects of the triterpene on mean arterial blood pressure (MAP) and kidney function following acute administration in normotensive animals with those of its related oleanane synthetic derivatives (brominated oleanolic acid, Br-OA and oleanolic acid methyl ester, Me-OA). We also used experimental models of hypertension to further explore the effects of sub-chronic oral OA treatment and evaluated influences on oxidative status. Methods OA was extracted from dried flower buds of Syzygium aromaticum using a previously validated protocol in our laboratory. Me-OA and Br-OA were synthesized according to a method described. Rats were supplemented with lithium chloride (12 mmol L-1) prior to experimentation in order to raise plasma lithium to allow measurements of lithium clearance and fractional excretion (FELi) as indices of proximal tubular Na+ handling. Anaesthetized animals were continuously infused via the right jugular with 0.077M NaCl. MAP was measured via a cannula inserted in the carotid artery, and urine was collected through a cannula inserted in the bladder. After a 3.5 h equilibration, MAP, urine flow, electrolyte excretion rates were determined for 4 h of 1 h control, 1.5 h treatment and 1.5 h recovery periods. OA, Me-OA and Br-OA were added to the infusate during the treatment period. We evaluated sub-chronic effects on MAP and kidney function in normotensive Wistar rats and in two animal models of hypertension, spontaneously hypertensive rats (SHR) and Dahl salt-sensitive (DSS) rats, during 9-week administration of OA (p.o.). Tissue oxidative status was examined in these animals at the end of the study. Increasing evidence suggests that and renal function disturbances and oxidative stress play major roles in the pathogenesis of hypertension. Results Acute infusion OA and oleanane derivatives displayed qualitatively similar effects in decreasing MAP and increasing urinary Na+ outputs. The drugs increased the FENa and FELi without influencing GFR indicating that at least part of the overall natriuretic effect involved proximal tubular Na+ reabsorption. Sub-chronic OA administration (p.o.) also elicited hypotensive responses in Wistar, DSS and SHR rats. The MAP lowering effect was more marked in hypertensive animals and were positively correlated with increased urinary Na+ excretion. Compared with respective control rats, OA treatment reduced malondialdehyde (MDA, a marker of lipid peroxidation) and increased activities of antioxidant enzymes; superoxide dismutase and glutathione peroxidase in hepatic, cardiac and renal tissues. Conclusions OA and oleanane derivatives have similar effects on MAP, kidney function and oxidative stress. The amelioration of oxidative stress and blood pressure lowering effects by OA are more marked in hypertensive animals and correlated with an increased urinary Na+ output. Novelty of the Work The results of this study are novel in that they show 1) a correlation between blood pressure reduction and increased urinary Na+ excretion by OA, 2) a more marked MAP reduction in hypertensive animals and 3) a drug-induced decrease in proximal tubule Na+ reabsorption. The results may also be clinically relevant because OA is effective via oral administration.
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Affiliation(s)
- Hlengiwe Pretty Madlala
- School of Laboratory Medicine and Medical Sciences, College of Health Sciences, University of KwaZulu-Natal, Durban, South Africa
| | - Fanie Retief Van Heerden
- School of Chemistry and Physics, College of Science, Engineering and Agriculture, University of KwaZulu-Natal, Pietermaritzburg, South Africa
| | - Kanigula Mubagwa
- Department of Cardiovascular Sciences, Faculty of Medicine, Katholieke Universiteit Leuven, Leuven, Belgium
| | - Cephas Tagumirwa Musabayane
- School of Laboratory Medicine and Medical Sciences, College of Health Sciences, University of KwaZulu-Natal, Durban, South Africa
- * E-mail:
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Molecular docking of potential inhibitors for influenza H7N9. COMPUTATIONAL AND MATHEMATICAL METHODS IN MEDICINE 2015; 2015:480764. [PMID: 25861376 PMCID: PMC4377397 DOI: 10.1155/2015/480764] [Citation(s) in RCA: 27] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/17/2014] [Revised: 02/22/2015] [Accepted: 02/22/2015] [Indexed: 01/06/2023]
Abstract
As a new strain of virus emerged in 2013, avian influenza A (H7N9) virus is a threat to the public health, due to its high lethality and pathogenicity. Furthermore, H7N9 has already generated various mutations such as neuraminidase R294K mutation which could make the anti-influenza oseltamivir less effective or ineffective. In this regard, it is urgent to develop new effective anti-H7N9 drug. In this study, we used the general H7N9 neuraminidase and oseltamivir-resistant influenza virus neuraminidase as the acceptors and employed the small molecules including quercetin, chlorogenic acid, baicalein, and oleanolic acid as the donors to perform the molecular docking for exploring the binding abilities between these small molecules and neuraminidase. The results showed that quercetin, chlorogenic acid, oleanolic acid, and baicalein present oseltamivir-comparable high binding potentials with neuraminidase. Further analyses showed that R294K mutation in neuraminidase could remarkably decrease the binding energies for oseltamivir, while other small molecules showed stable binding abilities with mutated neuraminidase. Taken together, the molecular docking studies identified four potential inhibitors for neuraminidase of H7N9, which might be effective for the drug-resistant mutants.
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Domitrović R, Rashed K, Cvijanović O, Vladimir-Knežević S, Škoda M, Višnić A. Myricitrin exhibits antioxidant, anti-inflammatory and antifibrotic activity in carbon tetrachloride-intoxicated mice. Chem Biol Interact 2015; 230:21-9. [DOI: 10.1016/j.cbi.2015.01.030] [Citation(s) in RCA: 141] [Impact Index Per Article: 14.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/15/2014] [Revised: 01/02/2015] [Accepted: 01/24/2015] [Indexed: 12/14/2022]
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Camer D, Huang XF. Comment on: Oleanolic acid co-administration alleviates ethanol-induced hepatic injury via Nrf-2 and ethanol-metabolizing modulation (sic) in rats. Chem Biol Interact 2014; 223:116. [DOI: 10.1016/j.cbi.2014.09.008] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/02/2014] [Revised: 09/09/2014] [Accepted: 09/10/2014] [Indexed: 01/06/2023]
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