{"title":"黑纹小螺杆菌富含甾体皂苷的部分通过调节脂质代谢和炎症减轻斑马鱼和小鼠的脂肪性肝炎。","authors":"Swati Katoch, Jyoti Chhimwal, Damanpreet Singh, Dinesh Kumar, Vikram Patial","doi":"10.1016/j.phymed.2025.156368","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Non-alcoholic steatohepatitis (NASH) has become a serious public health concern with high global prevalence. The lack of safe and efficient treatment for the condition demands exploring new therapeutic solutions.</p><p><strong>Purpose: </strong>In the present study, we investigated the protective efficacy of picrosides-rich fraction (PF) from Picrorhiza kurroa against steatohepatitis and revealed the molecular mechanism of action.</p><p><strong>Methods: </strong>PF was prepared and characterized using UPLC analysis. Initially, the efficacy of PF was studied on the zebrafish model of NASH. Further, a Methionine and Choline-Deficient (MCD) diet-induced NASH model in mice was employed to evaluate the hepatoprotective efficacy of PF by utilizing biochemical, histopathological and molecular studies.</p><p><strong>Results: </strong>The UPLC analysis revealed the presence of 29.11% and 29.86% picroside I and II in the PF, respectively. In the zebrafish model of NASH, PF treatment reduced the hepatic lipid accumulation and modulated the expressions of lipogenic, inflammatory, oxidative, and cellular stress genes. Further, in MCD diet-induced NASH in mice, PF treatment showed a significant improvement in body weights and serum liver injury markers. Reduced degenerative changes and fibrous tissue was observed in the PF-treated groups. The downregulated expression of Srebp1c, Cd36, Fas, Chrebp, Pparγ, and Hnf4α showed anti-lipogenic potential of PF treatment. NASH development followed oxidative stress, mitochondrial dysfunction, and inflammation in the liver of mice. However, PF treatment encouraged mitochondrial biogenesis by upregulating Pgc1α, Tfam, and Nrf2 expressions. The elevated levels of NFκB, TNFα, IL6, TGFβ, and αSMA were also restored by PF, advocating its anti-inflammatory and anti-fibrogenic effect.</p><p><strong>Conclusion: </strong>The present study revealed that PF ameliorate the progression of NASH by increasing mitochondrial biogenesis and decreasing lipogenesis, hepatic inflammation, and fibrosis.</p>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"137 ","pages":"156368"},"PeriodicalIF":6.7000,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Picrosides-rich fraction from Picrorhiza kurroa attenuates steatohepatitis in zebrafish and mice by modulating lipid metabolism and inflammation.\",\"authors\":\"Swati Katoch, Jyoti Chhimwal, Damanpreet Singh, Dinesh Kumar, Vikram Patial\",\"doi\":\"10.1016/j.phymed.2025.156368\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Non-alcoholic steatohepatitis (NASH) has become a serious public health concern with high global prevalence. The lack of safe and efficient treatment for the condition demands exploring new therapeutic solutions.</p><p><strong>Purpose: </strong>In the present study, we investigated the protective efficacy of picrosides-rich fraction (PF) from Picrorhiza kurroa against steatohepatitis and revealed the molecular mechanism of action.</p><p><strong>Methods: </strong>PF was prepared and characterized using UPLC analysis. Initially, the efficacy of PF was studied on the zebrafish model of NASH. Further, a Methionine and Choline-Deficient (MCD) diet-induced NASH model in mice was employed to evaluate the hepatoprotective efficacy of PF by utilizing biochemical, histopathological and molecular studies.</p><p><strong>Results: </strong>The UPLC analysis revealed the presence of 29.11% and 29.86% picroside I and II in the PF, respectively. In the zebrafish model of NASH, PF treatment reduced the hepatic lipid accumulation and modulated the expressions of lipogenic, inflammatory, oxidative, and cellular stress genes. Further, in MCD diet-induced NASH in mice, PF treatment showed a significant improvement in body weights and serum liver injury markers. Reduced degenerative changes and fibrous tissue was observed in the PF-treated groups. The downregulated expression of Srebp1c, Cd36, Fas, Chrebp, Pparγ, and Hnf4α showed anti-lipogenic potential of PF treatment. NASH development followed oxidative stress, mitochondrial dysfunction, and inflammation in the liver of mice. However, PF treatment encouraged mitochondrial biogenesis by upregulating Pgc1α, Tfam, and Nrf2 expressions. The elevated levels of NFκB, TNFα, IL6, TGFβ, and αSMA were also restored by PF, advocating its anti-inflammatory and anti-fibrogenic effect.</p><p><strong>Conclusion: </strong>The present study revealed that PF ameliorate the progression of NASH by increasing mitochondrial biogenesis and decreasing lipogenesis, hepatic inflammation, and fibrosis.</p>\",\"PeriodicalId\":20212,\"journal\":{\"name\":\"Phytomedicine\",\"volume\":\"137 \",\"pages\":\"156368\"},\"PeriodicalIF\":6.7000,\"publicationDate\":\"2025-02-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Phytomedicine\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1016/j.phymed.2025.156368\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2025/1/2 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q1\",\"JCRName\":\"CHEMISTRY, MEDICINAL\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Phytomedicine","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1016/j.phymed.2025.156368","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/1/2 0:00:00","PubModel":"Epub","JCR":"Q1","JCRName":"CHEMISTRY, MEDICINAL","Score":null,"Total":0}
Picrosides-rich fraction from Picrorhiza kurroa attenuates steatohepatitis in zebrafish and mice by modulating lipid metabolism and inflammation.
Background: Non-alcoholic steatohepatitis (NASH) has become a serious public health concern with high global prevalence. The lack of safe and efficient treatment for the condition demands exploring new therapeutic solutions.
Purpose: In the present study, we investigated the protective efficacy of picrosides-rich fraction (PF) from Picrorhiza kurroa against steatohepatitis and revealed the molecular mechanism of action.
Methods: PF was prepared and characterized using UPLC analysis. Initially, the efficacy of PF was studied on the zebrafish model of NASH. Further, a Methionine and Choline-Deficient (MCD) diet-induced NASH model in mice was employed to evaluate the hepatoprotective efficacy of PF by utilizing biochemical, histopathological and molecular studies.
Results: The UPLC analysis revealed the presence of 29.11% and 29.86% picroside I and II in the PF, respectively. In the zebrafish model of NASH, PF treatment reduced the hepatic lipid accumulation and modulated the expressions of lipogenic, inflammatory, oxidative, and cellular stress genes. Further, in MCD diet-induced NASH in mice, PF treatment showed a significant improvement in body weights and serum liver injury markers. Reduced degenerative changes and fibrous tissue was observed in the PF-treated groups. The downregulated expression of Srebp1c, Cd36, Fas, Chrebp, Pparγ, and Hnf4α showed anti-lipogenic potential of PF treatment. NASH development followed oxidative stress, mitochondrial dysfunction, and inflammation in the liver of mice. However, PF treatment encouraged mitochondrial biogenesis by upregulating Pgc1α, Tfam, and Nrf2 expressions. The elevated levels of NFκB, TNFα, IL6, TGFβ, and αSMA were also restored by PF, advocating its anti-inflammatory and anti-fibrogenic effect.
Conclusion: The present study revealed that PF ameliorate the progression of NASH by increasing mitochondrial biogenesis and decreasing lipogenesis, hepatic inflammation, and fibrosis.
期刊介绍：
Phytomedicine is a therapy-oriented journal that publishes innovative studies on the efficacy, safety, quality, and mechanisms of action of specified plant extracts, phytopharmaceuticals, and their isolated constituents. This includes clinical, pharmacological, pharmacokinetic, and toxicological studies of herbal medicinal products, preparations, and purified compounds with defined and consistent quality, ensuring reproducible pharmacological activity. Founded in 1994, Phytomedicine aims to focus and stimulate research in this field and establish internationally accepted scientific standards for pharmacological studies, proof of clinical efficacy, and safety of phytomedicines.
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