INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2023
·
IF 8.2
Ying Wang,Jianbo Yang,Hongyu Jin,Donglin Gu,Qi Wang,Yue Liu,Ke Zan,Jing Fan,Rong Wang,Feng Wei,Shuangcheng Ma
The raw and processed Polygonum multiflorum Thunb (PM) are used to treat different diseases, and PM has also been reported to have hepatotoxic effects. Moreover, mounting evidence indicates that processed PM is less toxic than raw PM. The changes in efficacy and toxicity of PM during the processing are closely related to the changes in chemical composition. Previous studies have mainly focused on the changes of anthraquinone and stilbene glycosides during process. Polysaccharides, as main components of PM, showed many pharmacological effects, but its changes in the processing has been neglected for a long time. In this study, the polysaccharides of PM in the raw (RPMPs) and processed products (PPMPs) were determined and the liver injury model induced by acetaminophen was utilized to evaluate the impact of polysaccharides on the liver. Results showed that the heteropolysaccharides RPMPs and PPMPs both comprised Man, Rha, GlcA, GalA, Glc, Ara and Xyl, but markedly differed in polysaccharide yield, molar ratio of monosaccharide composition and M w . In vivo analysis, results showed that demonstrated that RPMPs and PPMPs both exerted hepatoprotective effects by upregulating antioxidant enzymes and repressing lipid peroxidation. It is noteworthy that the polysaccharide yield of processed PM was seven-fold higher than that of raw PM, so it is speculated that processed PM has better hepatoprotective effects at the same dose of decoction. The present work provides an important foundation for studying the polysaccharide activity of PM and further revealing the processing mechanism of PM. This study also proposed a new hypothesis that the significant increase of polysaccharide content in processed PM may be another reason that the product PM causes less liver injury.
研究领域:
中药学
·
药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
TOXICOLOGY IN VITRO
·
2025
·
IF 2.7
Yuhui Yan,Wenyu Wang,Aiwen Yan,Haonan Zhu,Qiang Meng
Cholestasis, a condition marked by bile acid accumulation in the liver and body systems, leads to liver dysfunction and cirrhosis. Currently, ursodeoxycholic acid (UDCA) and obeticholic acid (OCA) are the only two FDA-approved drugs for Cholestasis. Thus, new therapeutic approaches need to be developed. In this study, we validated the liver-protective properties of β-sitosterol (SIT), a key bioactive element abundant in plants, against hepatic toxicity and cholestasis induced by alpha-naphthylisothiocyanate(ANIT), while elucidating its mechanisms of action both in vivo and in vitro. SIT's FXR activation was confirmed via molecular docking and dual-luciferase assays. In the mechanisms of SIT hepatoprotection, the expression levels of bile salt export pump (Bsep) and multidrug resistance protein2 (Mrp2) which are bile acid efflux transporter, and sulfate transferase 2a1 (Sult2a1) which is a bile acid metabolizing enzyme were all increased by SIT, whereas the expression of uptake transporter sodium taurocholate transporting polypeptide (Ntcp), bile acid synthesis enzyme cholesterol 7α-hydroxylase (Cyp7a1) and oxysterol 12α-hydroxylase (Cyp8b1) was decreased by SIT. In addition, SIT alleviated liver inflammation by suppressing inflammatory factor expression. However, FXR antagonist guggulsterone and FXR siRNA abolished SIT's improvements in liver histology, bile acid transporters, and enzymes. Conclusively, through activating FXR, SIT provides a protective effect against hepatotoxicity and cholestasis. SIT might serve as a new potential therapeutic strategy for the treatment of cholestatic liver diseases.
研究领域:
药理学
·
分子生物学
·
肝脏疾病
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Frontiers in Pharmacology
·
2018
·
IF 3.831
Xu Peng,Zhou Hua,Li Ya-Zhuo,Yuan Zhong-Wen,Liu Chang-Xiao,Liu Liang,Xie Ying
Although hepatoprotective properties of silybin are well documented, the clinical therapeutic efficacy is limited by its low bioavailability due to absorption rates, extensive phase II metabolism, and biliary excretion. As our previous study indicated that metabolic enzymes may have limited effects on the pharmacokinetic (PK) behavior of silymarin, here, we intended to increase the oral bioavailability and bio-efficacy of silybin through the inhibition of active efflux. In Caco-2 and transfected MDCKII cell models, flavone baicalein significantly inhibited the efflux of silybin as a BCRP and MRP2 inhibitor. In addition, baicalein reduced the biliary excretion index (BEI) and biliary clearance of silybin conjugates in the sandwich-cultured rat hepatocyte (SCH) model, indicating the inhibition of baicalein in biliary excretion of conjugated silybin metabolites. PK study demonstrated that baicalein significantly increased the area under the curve (AUC) and Cmax of silybin and its conjugates, suggesting enhanced absorption in vivo. Moreover, coadministration of silybin with baicalein boosted the liver protective, antioxidant, and anti-inflammatory effects of silybin in the carbon tetrachloride (CCl4)-induced liver injury model in comparison with silybin given alone. In summary, efflux transporters play a critical role in the low bioavailability of silybin, while inhibition of breast cancer resistance protein (BCRP) and multi-drug resistance protein 2 (MRP2) by baicalein can significantly increase the absorption and bio-efficacy of silybin, which provides a new combination therapeutic approach for the treatment of chronic liver diseases.
研究领域:
药理学
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肝病学
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药物代谢动力学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Food & Function
·
2020
·Vol. 12
·期 1
·191-202
·
IF 4.171
Xiaoting Yu,Ruiying Wang,Bin Lai,Mingqian Tan
In this paper, the protective effect of Auricularia auricula (A. auricula) fermentation broth on the liver and stomach of mice with acute alcoholism was studied. The A. auricula fermentation broth was prepared by adding Bacillus subtilis, lactic acid bacteria, and Saccharomyces cerevisiae to A. auricula solution. The changes of physical and chemical indexes during the fermentation of A. auricula were monitored, and the results showed the content of polysaccharides and protein in the two kinds of fermentation broth after the fermentation was completed. Furthermore, the characteristic structures of active substances such as proteins, polysaccharides and phenolics were found in the A. auricula fermentation by structural analysis. Antioxidant activity test results showed that the A. auricula fermentation broth had a strong ability to scavenge 1,1-diphenyl-2-picrylhydrazyl (DPPH) and hydroxyl radicals. Cell experiments showed that the fermentation broth of A. auricula could significantly enhance the activity of NRK cells and protect NRK cells from H2O2 damage. Animal experiments showed that the A. auricula fermentation broth had protective effects on the liver and stomach of mice with acute alcoholism, and significantly reduced the levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), total cholesterol (TC) and triglycerides (TG) in serum. These results indicated that the A. auricula fermentation broth had protective effects on the liver and stomach of mice with acute alcoholism, and could be used as a potential functional food to prevent liver and stomach damage caused by acute alcoholism.
研究领域:
食品科学
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生物化学
·
医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Foods
·
2025
·Vol. 14
·期 7
·1270
·
IF 5.1
Jiali Tang,Mengyao Zhang,Jiaying Wang,Haijing Zhang,Zhong Wang,Ziteng Lei,Chengtao Wang,Wei Chen
Inflammatory bowel disease (IBD) is a chronic disease influenced by a complex interplay of factors, including genetics, environmental, and gut microbiota. This study aimed to explore the therapeutic potential of the natural polyphenolic compound hydroxytyrosol (HT) in modulating dextran sodium sulfate (DSS)-induced colitis in mice. The findings demonstrate that oral administration of HT significantly alleviated colitis symptoms, as evidenced by a reduction in the disease activity index and improvements in colonic pathology. HT was found to inhibit the release of pro-inflammatory cytokines, enhance antioxidant status, and mitigate oxidative stress. Furthermore, HT contributed to the restoration of the gut barrier by reinstating tight junction proteins, reducing the inflammatory marker lipopolysaccharide (LPS), and suppressing inflammation-related genes. This compound also modulated the NLRP3-Cas-1-GSDMD-IL-1β inflammatory pathway and inhibited the NF-κB (nuclear factor kappa B) pathway, thereby alleviating colitis. Gut microbial analysis revealed that HT enriched the abundance of Bacteroidota and altered the balance between Bacteroidota and Firmicutes in mice. Correlation analysis between bacterial microbiota and inflammatory factors suggested that HT may alleviate colitis by modulating the relative abundance of Alistipes , Bacteroides , and unclassified_f__ Muribaculaceae . These findings underscore the potential of HT as a therapeutic agent in the treatment of colitis.
研究领域:
免疫学
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消化病学
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微生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Frontiers in Veterinary Science
·
2025
·
IF 2.9
Baili Lu,Jiayu He,Shirou Pan,Junhao Wei,Bingxin Li,Nan Cao,Yunmao Huang,Yunbo Tian,Ngai Cheong,Ying Chen,Danning Xu,Wanyan Li
Atractylodes macrocephala Koidz. (AMK) and its purified polysaccharide fraction (PAMK) are known for their antioxidant, anti-inflammatory, and hepatoprotective properties, showing potential benefits for poultry liver health. This study simulated hepatic oxidative stress in late-laying hens, a physiological stage characterized by increased metabolic demands and reactive oxygen species (ROS) generation, without exogenous hepatotoxic agents. Hens were randomly assigned to three groups: control (basal diet), AMK (basal diet + 15 g/kg AMK), and PAMK (basal diet + 400 mg/kg PAMK). Both AMK and PAMK significantly reduced serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities compared to control. Notably, PAMK showed superior efficacy, decreasing malondialdehyde (MDA) levels by 35.29% vs. 32.87% in AMK, and more effectively increasing antioxidant enzymes superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px). Histopathological analysis revealed better-preserved liver structure and less inflammatory infiltration in PAMK-fed hens. Mechanistically, both treatments upregulated Nrf2 and downstream antioxidant genes, with stronger activation observed in the PAMK group. In vitro, PAMK reduced H2O2-induced ROS accumulation and apoptosis in primary embryonic chicken hepatocytes, effects that were attenuated by the Nrf2 inhibitor ML385. In conclusion, PAMK exerts superior hepatoprotective effects compared to crude AMK by modulating the Nrf2 pathway, mitigating oxidative stress, apoptosis, and autophagy. Future research should evaluate PAMK's long-term safety, synergistic potential with other natural antioxidants, and cost-effectiveness in poultry production.
研究领域:
兽医学
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动物营养学
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分子生物学
·
氧化应激
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天然药物药理学
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家禽生理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
·
2024
·
IF 5.7
Li Hao,Yulian Ding,Yan Fan,Qiaoji Tian,Yang Liu,Yueting Guo,Jian Zhang,Hu Hou
The development of food-derived antihyperuricemic substances is important for alleviating hyperuricemia (HUA) and associated inflammation. Here, novel peptides fromThunnus albacares (TAP) with strong antihyperuricemic activity were prepared. TAP was prepared by alkaline protease (molecular weight <1000 Da), with an IC50 value of xanthine oxidase inhibitory activity of 2.498 mg/mL, and 5 mg/mL TAP could reduce uric acid (UA) by 33.62% in human kidney-2 (HK-2) cells (P < 0.01). Mice were fed a high-purine diet and injected with potassium oxonate to induce HUA. Oral administration of TAP (600 mg/kg/d) reduced serum UA significantly by 42.22% and increased urine UA by 79.02% (P < 0.01) via regulating urate transporters GLUT9, organic anion transporter 1, and ATP-binding cassette subfamily G2. Meantime, TAP exhibited hepatoprotective and nephroprotective effects, according to histological analysis. Besides, HUA mice treated with TAP showed anti-inflammatory activity by decreasing the levels of toll-like receptor 4, nuclear factors-κB p65, NLRP3, ASC, and Caspase-1 in the kidneys (P < 0.01). According to serum non-targeted metabolomics, 91 differential metabolites between the MC and TAP groups were identified, and purine metabolism was considered to be the main pathway for TAP alleviating HUA. In a word, TAP exhibited strong antihyperuricemic activity both in vitro and in vivo.
研究领域:
营养学
·
分子生物学
·
食品科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
PHYTOTHERAPY RESEARCH
·
2025
·
IF 6.3
Yanfang Zheng,Jiaying Chen,Ying Zhang,Huaying Guan,Shan Deng,Dennis Chang,Yitao Wang,JinJian Lu,Xian Zhou,Qin Xie,Jianyuan Song,Mingqing Huang
Gut microbiota and bile acid metabolism play crucial roles in the progression of nonalcoholic fatty liver disease (NAFLD). Early evidence demonstrates that Ginsenoside Re (Re) possesses pharmacological effects on NAFLD, but its mechanisms of action are not well understood. This study aimed to investigate the hepatic protective effects of Re in NAFLD and elucidate relevant mechanisms. The effects of Re treatments (10, 20, or 40 mg/kg) against high-fat diet-induced NAFLD were initially tested on male C57BL/6 mice. Then, a separate mouse group received Re with or without antibiotics to confirm the regulatory role of microbiota in the effect of Re. Finally, another group of mice received fecal microbiota transplantation (FMT) from the initial experiment of NAFLD mice to further investigate the mechanistic role of gut microbiota. Re significantly improved liver function by reducing hepatic lipid accumulation, injury and hepatocyte steatosis, and inflammation. The liver protection was mediated by the regulation of gut microbiota as evidenced by restored intestinal barrier integrity, normalized Firmicutes/Bacteroidota ratio, enhanced abundances of Adlercreutzia equolifaciens , and reduced Faecalibaculum rodentium . Following that, Re reduced total and primary bile acids and downregulated bile acid synthesis genes and proteins such as farnesoid X receptor and cytochrome P450 family 7 subfamily A member 1. The co-administration of antibiotic cocktail counteracted the effect of Re against NAFLD. Further, the results obtained from the FMT animal study confirmed that Re's liver protective effects were at least partly driven by the regulation of gut microbiota. Re modulated bile salt hydrolase-related microbial genera to alter bile acid synthesis pathways, thereby inhibiting NAFLD progression.
研究领域:
药理学
·
代谢组学
·
微生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
FOOD AND CHEMICAL TOXICOLOGY
·
2012
·
IF 2.999
Hua-Zhong Ying,Yue-Huan Liu,Bing Yu,Zhi-Yuan Wang,Jia-Na Zang,Chen-Huan Yu
Dietary quercetin is highly abundant in edible plants, which possesses a wide range of pharmacological properties. This study was to investigate hepatoprotective effects of quercetin in the nonalcoholic steatohepatitis (NASH) gerbils induced by a high-fat diet (HFD), and to evaluate its regulatory mechanism on hepatic inflammatory response. The gerbils were fed with HFD for 28 days to induce NASH. From 15th day to 28th day, the treated drugs were given daily to each animal, respectively. The lipid profiles and biochemical markers were determined at the end of the experiment. The expressions of Sirt1, NF-κB p65 and iNOS were detected by immunohistochemistry and Western blot analysis. The results showed that oral administration of quercetin at doses of 30–60 mg/kg to hyperlipidemia rats for 14 days were highly effective in decreasing the levels of serum total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), alanine aminotransferase (ALT) and aspartate aminotransferase (AST). It could decrease lipid accumulation in the hepatocytes, and reduce serum levels of pro-inflammatory cytokines TNF-α and IL-6 via regulating the expressions of Sirt1, NF-κB p65 and iNOS. Thus, dietary quercetin had significant therapeutic benefits and could be explored as a potential promising candidate for the prevention of NASH.
研究领域:
药理学
·
肝病学
·
营养学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
PHARMAZIE
·
2022
·
IF 1.515
Zhou Huiping,Peng Yuxuan,Liu Hongyun,Li Xiaohui,Mei Wenqiu,Li Hao,Xu Kangyan,Hu Meichun,She Tonghui
As a common vegetable, Momordica charantia (M. charantia), also known as bitter melon, has the pharmacological activity of reducing blood sugar and body fat. This experiment explored the effect of M. charantia on the mice liver by adding freeze-dried M. charantia
to the feed intake of high-fat diet mice. Among the three groups of normal diet mice (Control), high-fat diet mice fed with lyophilized bitter melon powder (BM) and single high-fat diet mice (HFD), it was seen that the body weight of BM mice did not change apparently (p>0.05), while the
body weight of HFD mice increased significantly (p<0.01). Serum triglycerides, total cholesterol, high density lipoprotein cholesterol (HDL-C), Low density lipoprotein cholesterol (LDL-C) of HFD mice was significantly higher than those of Control and BM mice (p<0.01). The results of
RT-PCR and Western blot showed that the transcription and protein expression levels of acetyl-CoA carboxylases alpha (ACACA) and fatty acid synthase (FASN) genes in HFD mice were significantly increased (p<0.01), while BM administration could reduce the transcription and expression of these
two genes (p<0.01). It is concluded that M. charantia powder alleviates the lipid metabolism disorder of liver in HFD mice via downregulating ACACA and FASN both in the transcription and protein expression levels, and thus exhibits protective effects for the liver.
研究领域:
营养学
·
药理学
·
分子生物学
✓ 已验证
DOI
高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
·
2024
·
IF 5.7
Jiamin Dang,Ting Cai,Yuanrong Tuo,Siwang Peng,Jing Wang,Aiying Gu,Jialu Li,Long Ding,Shuangkui Du,Liying Wang
This study aimed to investigate the effects of corn gluten-derived soluble epoxide hydrolase (sEH) inhibitory peptides on nonalcoholic fatty liver fibrosis induced by a high-fat diet and carbon tetrachloride in mice. Mice treated with corn peptides at doses of 500 or 1000 mg/kg/d for 4 weeks exhibited reduced sEH activity in serum and liver, enhanced lipid metabolism, and decreased lipid accumulation and oxidative stress. Corn peptides effectively downregulated the mRNA levels of Pro-IL-1β, Pro-IL-18, NOD-like receptor protein 3 (NLRP3), ASC, Pro-caspase-1, Caspase-1, and GSDMD in the liver. This hepatoprotective effect of corn peptides by inhibiting NLRP3 inflammasome activation was further validated in H2O2-induced HepG2 cells. Moreover, corn peptides restored the composition of the gut microbiota and promoted short-chain fatty acid production. This study provides evidence that corn-derived sEH inhibitory peptides have hepatoprotective activity against nonalcoholic fatty liver fibrosis by suppressing NLRP3 inflammasome activation and modulating gut microbiota.
研究领域:
营养学
·
肝病学
·
微生物学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Food & Function
·
2023
·Vol. 14
·期 7
·3051-3066
·
IF 6.1
Qingqing Wang,Zihou Liu,Rui Wang,Run Li,Xiaoru Lian,Yanquan Yang,Jiao Yan,Zhiqi Yin,Guangji Wang,Jianguo Sun,Ying Peng
Ginkgo biloba extract (GBE) is a common dietary supplement used by people with dyslipidaemia worldwide to reduce the risk of cardiovascular disease. Many studies have found that GBE itself has a variety of pharmacological activities. However, the role of GBE as an adjunct to conventional therapy with chemical drugs remains controversial. Therefore, this study explored the additional benefits of GBE in the treatment of hyperlipidaemia with statins in terms of both pharmacodynamics and pharmacokinetics. A hyperlipidaemia model was established by feeding rats a high-fat diet for a long time. The animals were treated with atorvastatin only, GBE only, or a combination of atorvastatin and GBE. The results showed that statins combined with GBE could significantly improve the blood lipid parameters, reduce the liver fat content, and reduce the size of adipocytes in abdominal fat. The effect was superior to statin therapy alone. In addition, the combination has shown additional liver protection against possible pathological liver injury or statin-induced liver injury. A lipidomic study showed that GBE could regulate the abnormal lipid metabolism of the liver in hyperlipemia. When statins are combined with GBE, this callback effect introduced by GBE on endogenous metabolism has important implications for resistance to disease progression and statin resistance. Finally, in the presence of GBE, there was a significant increase in plasma statin exposure. These results all confirmed that GBE has incremental benefits as a dietary supplement of statin therapy for dyslipidaemia.
研究领域:
药理学
·
药代动力学
·
代谢
·
心血管疾病
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）