Rui Zeng, Yanan Guo, Jingshu Qi, Meng Li, Kai Huang, Yuan Peng, Zhengxin Li, Chenghai Liu
{"title":"丹桃方通过调节肝星状细胞cAMP/PKA/ROCK信号通路减轻肝纤维化和门脉高压症。","authors":"Rui Zeng, Yanan Guo, Jingshu Qi, Meng Li, Kai Huang, Yuan Peng, Zhengxin Li, Chenghai Liu","doi":"10.1016/j.jep.2025.120650","DOIUrl":null,"url":null,"abstract":"<p><strong>Ethnopharmacological relevance: </strong>The Dantao Formula (DTF) consists of Salvia miltiorrhiza Bunge (Danshen) and Prunus persica (L.) Batsch seeds (Taoren), which were the components of promoting circulation and removing stasis in the anti-fibrotic herbal--- Fuzheng Huayu Formula (FZHY). It has demonstrated efficacy in alleviating hepatic fibrosis and portal hypertension (PH); however, its pharmacological mechanisms remain unclear.</p><p><strong>Aim of the study: </strong>The aim is to investigate the effects and molecular mechanisms of DTF on liver fibrosis and PH.</p><p><strong>Materials and methods: </strong>In vivo experiments were evaluated using a CCl<sub>4</sub>-induced mouse model with rivaroxaban (RIVA) as a drug control. PH was assessed by direct puncture method. Fibrosis was assessed by Sirius red staining and hydroxyproline. Network pharmacology analysis predicted the potential molecules or signal mediators. In vitro, an LX-2 cells was activated with ET-1, and Y-33075 used as a drug control. ELISA, Western blot, immunohistochemistry and immunofluorescence were conducted to assess the target expression of ET-1, ENDRA, ROCK, cAMP, PKA, MLC and p-MLC.</p><p><strong>Results: </strong>DTF or RIVA could alleviate liver fibrosis and PH compared to the model group. Network pharmacology analysis suggested that cAMP/PKA/ROCK signaling pathway acted as a key target in DTF. In vivo, DTF or RIVA suppressed ET-1, EDNRA and ROCK expression, enhanced cAMP and PKA expression. In vitro, DTF or Y-33075 attenuated the activation of LX-2 cells induced by ET-1, down-regulated ROCK and p-MLC expression, up-regulated cAMP and PKA expression.</p><p><strong>Conclusions: </strong>DTF alleviates liver fibrosis and PH by regulating the cAMP/PKA/ROCK signaling pathway in activated HSCs.</p>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":" ","pages":"120650"},"PeriodicalIF":5.4000,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Dantao formula alleviates hepatic fibrosis and portal hypertension via modulation of the cAMP/PKA/ROCK signaling pathway in hepatic stellate cells.\",\"authors\":\"Rui Zeng, Yanan Guo, Jingshu Qi, Meng Li, Kai Huang, Yuan Peng, Zhengxin Li, Chenghai Liu\",\"doi\":\"10.1016/j.jep.2025.120650\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Ethnopharmacological relevance: </strong>The Dantao Formula (DTF) consists of Salvia miltiorrhiza Bunge (Danshen) and Prunus persica (L.) Batsch seeds (Taoren), which were the components of promoting circulation and removing stasis in the anti-fibrotic herbal--- Fuzheng Huayu Formula (FZHY). It has demonstrated efficacy in alleviating hepatic fibrosis and portal hypertension (PH); however, its pharmacological mechanisms remain unclear.</p><p><strong>Aim of the study: </strong>The aim is to investigate the effects and molecular mechanisms of DTF on liver fibrosis and PH.</p><p><strong>Materials and methods: </strong>In vivo experiments were evaluated using a CCl<sub>4</sub>-induced mouse model with rivaroxaban (RIVA) as a drug control. PH was assessed by direct puncture method. Fibrosis was assessed by Sirius red staining and hydroxyproline. Network pharmacology analysis predicted the potential molecules or signal mediators. In vitro, an LX-2 cells was activated with ET-1, and Y-33075 used as a drug control. ELISA, Western blot, immunohistochemistry and immunofluorescence were conducted to assess the target expression of ET-1, ENDRA, ROCK, cAMP, PKA, MLC and p-MLC.</p><p><strong>Results: </strong>DTF or RIVA could alleviate liver fibrosis and PH compared to the model group. Network pharmacology analysis suggested that cAMP/PKA/ROCK signaling pathway acted as a key target in DTF. In vivo, DTF or RIVA suppressed ET-1, EDNRA and ROCK expression, enhanced cAMP and PKA expression. In vitro, DTF or Y-33075 attenuated the activation of LX-2 cells induced by ET-1, down-regulated ROCK and p-MLC expression, up-regulated cAMP and PKA expression.</p><p><strong>Conclusions: </strong>DTF alleviates liver fibrosis and PH by regulating the cAMP/PKA/ROCK signaling pathway in activated HSCs.</p>\",\"PeriodicalId\":15761,\"journal\":{\"name\":\"Journal of ethnopharmacology\",\"volume\":\" \",\"pages\":\"120650\"},\"PeriodicalIF\":5.4000,\"publicationDate\":\"2025-09-26\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of ethnopharmacology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1016/j.jep.2025.120650\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"CHEMISTRY, MEDICINAL\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of ethnopharmacology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1016/j.jep.2025.120650","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CHEMISTRY, MEDICINAL","Score":null,"Total":0}
Dantao formula alleviates hepatic fibrosis and portal hypertension via modulation of the cAMP/PKA/ROCK signaling pathway in hepatic stellate cells.
Ethnopharmacological relevance: The Dantao Formula (DTF) consists of Salvia miltiorrhiza Bunge (Danshen) and Prunus persica (L.) Batsch seeds (Taoren), which were the components of promoting circulation and removing stasis in the anti-fibrotic herbal--- Fuzheng Huayu Formula (FZHY). It has demonstrated efficacy in alleviating hepatic fibrosis and portal hypertension (PH); however, its pharmacological mechanisms remain unclear.
Aim of the study: The aim is to investigate the effects and molecular mechanisms of DTF on liver fibrosis and PH.
Materials and methods: In vivo experiments were evaluated using a CCl4-induced mouse model with rivaroxaban (RIVA) as a drug control. PH was assessed by direct puncture method. Fibrosis was assessed by Sirius red staining and hydroxyproline. Network pharmacology analysis predicted the potential molecules or signal mediators. In vitro, an LX-2 cells was activated with ET-1, and Y-33075 used as a drug control. ELISA, Western blot, immunohistochemistry and immunofluorescence were conducted to assess the target expression of ET-1, ENDRA, ROCK, cAMP, PKA, MLC and p-MLC.
Results: DTF or RIVA could alleviate liver fibrosis and PH compared to the model group. Network pharmacology analysis suggested that cAMP/PKA/ROCK signaling pathway acted as a key target in DTF. In vivo, DTF or RIVA suppressed ET-1, EDNRA and ROCK expression, enhanced cAMP and PKA expression. In vitro, DTF or Y-33075 attenuated the activation of LX-2 cells induced by ET-1, down-regulated ROCK and p-MLC expression, up-regulated cAMP and PKA expression.
Conclusions: DTF alleviates liver fibrosis and PH by regulating the cAMP/PKA/ROCK signaling pathway in activated HSCs.
期刊介绍：
The Journal of Ethnopharmacology is dedicated to the exchange of information and understandings about people''s use of plants, fungi, animals, microorganisms and minerals and their biological and pharmacological effects based on the principles established through international conventions. Early people confronted with illness and disease, discovered a wealth of useful therapeutic agents in the plant and animal kingdoms. The empirical knowledge of these medicinal substances and their toxic potential was passed on by oral tradition and sometimes recorded in herbals and other texts on materia medica. Many valuable drugs of today (e.g., atropine, ephedrine, tubocurarine, digoxin, reserpine) came into use through the study of indigenous remedies. Chemists continue to use plant-derived drugs (e.g., morphine, taxol, physostigmine, quinidine, emetine) as prototypes in their attempts to develop more effective and less toxic medicinals.
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