Ursolic acid ameliorates CCl4‐induced liver fibrosis through the NOXs/ROS pathway

Gan, D.; Zhang, Wang; Huang, Chia-Chi Flora; Chen, Jiang; He, Wenhua; Wang, Anjiang; Li, Bimin; Zhu, Xuan

doi:10.1002/jcp.26541

Cited by 53 publications

(33 citation statements)

References 28 publications

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“…These results were also confirmed with animal experiments. Injection of NOX4 bioinhibitors into CCl 4 -induced liver fibrosis in mice reversed the progression of liver fibrosis [ 40 ]. Here, we used NOX4 knockout mice to better understand the role of NOX4 in the development of liver fibrosis in vivo.…”

Section: Discussionmentioning

confidence: 99%

Ursolic acid reverses liver fibrosis by inhibiting interactive NOX4/ROS and RhoA/ROCK1 signalling pathways

Wan

Luo

Huang

et al. 2020

Aging

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Liver fibrosis is the reversible deposition of extracellular matrix (ECM) and scar formation after liver damage by various stimuli. The interaction between NOX4/ROS and RhoA/ROCK1 in liver fibrosis is not yet clear. Ursolic acid (UA) is a traditional Chinese medicine with anti-fibrotic effects, but the molecular mechanism underlying these effects is still unclear. We investigated the interaction between NOX4/ROS and RhoA/ROCK1 during liver fibrosis and whether these molecules are targets for the anti-fibrotic effects of UA. First, we confirmed that UA reversed CCl4-induced liver fibrosis. In the NOX4 intervention and RhoA intervention groups, related experimental analyses confirmed the decrease in CCl4-induced liver fibrosis. Next, we determined that the expression of NOX4 and RhoA/ROCK1 was decreased in UA-treated liver fibrotic mice. Furthermore, RhoA/ROCK1 expression was decreased in the NOX4 intervention group, but there was no significant change in the expression of NOX4 in the RhoA intervention group. Finally, we found that liver fibrotic mice showed a decline in their microbiota diversity and abundance, a change in their microbiota composition, and a reduction in the number of potential beneficial bacteria. However, in UA-treated liver fibrotic mice, the microbiota dysbiosis was ameliorated. In conclusion, the NOX4/ROS and RhoA/ROCK1 signalling pathways are closely linked to the development of liver fibrosis. UA can reverse liver fibrosis by inhibiting the NOX4/ROS and RhoA/ROCK1 signalling pathways, which may interact with each other.

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Section: Discussionmentioning

confidence: 99%

Ursolic acid reverses liver fibrosis by inhibiting interactive NOX4/ROS and RhoA/ROCK1 signalling pathways

Wan

Luo

Huang

et al. 2020

Aging

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“…The outstanding findings in this paper are that the anti-liver-fibrosis Chinese medicine UA also has a certain improvement effect on the intestinal microbiota disorder during liver fibrosis. Our group has previously confirmed that UA can protect liver tissue and reverse liver fibrosis in an animal model of liver fibrosis induced by CCl 4 37 . In addition, our previous experiments also found that UA can reduce intestinal damage and protect intestinal integrity during liver fibrosis.…”

Section: Discussionmentioning

confidence: 65%

Ursolic acid improves the bacterial community mapping of the intestinal tract in liver fibrosis mice

Wan

Huang

2020

Preprint

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ABSTRACTLiver fibrosis often appears in chronic liver disease, with extracellular matrix (ECM) deposition as the main feature. Due to the presence of the liver-gut axis, the destruction of intestinal homeostasis is often accompanied by the development of liver fibrosis. The inconsistent ecological environment of different intestinal sites may lead to differences in the microbiota. The traditional Chinese medicine Ursolic acid (UA) has been proven to protect the liver from fibrosis. We investigated the changes in the microbiota of different parts of the intestine during liver fibrosis and the effect of UA on these changes based on high-throughput sequencing technology. Sequencing results suggest that the diversity and abundance of intestinal microbiota decline and the composition of the microbiota is disordered, the potentially beneficial Firmicutes bacteria are reduced, and the pathways for functional prediction are changed in the ilea and anal faeces of liver fibrosis mice compared with normal mice. However, in UA-treated liver fibrosis mice, these disorders improved. It is worth noting that the bacterial changes in the ilea and anal faeces are not consistent. In conclusion, in liver fibrosis, the microbiota of different parts of the intestines have different degrees of disorder, and UA can improve this disorder. This may be a potential mechanism for UA to achieve anti-fibrosis. This study provides theoretical guidance for the UA targeting of intestinal microbiota for the treatment of liver fibrosis.

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“…A derivative of oleanolic acid has shown antifibrotic effects in rat livers [52]. Ursolic acid has shown to exhibit anti-fibrotic effects in the liver of mice and rats [53][54][55][56].…”

Section: Discussionmentioning

confidence: 99%

Decreased overall mortality rate with Chinese herbal medicine usage in patients with decompensated liver cirrhosis in Taiwan

Tsai

Yang

Chen

et al. 2020

BMC Complement Med Ther

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Background: Liver cirrhosis is one of the main causes of the morbidity and mortality in liver diseases. Chinese herbal medicine (CHM) has long been used for the clinical treatment of liver diseases. This study was designed to explore the usage frequency and prescription patterns of CHM for patients with decompensated liver cirrhosis and to evaluate the long-term effects of CHM on overall mortality. Methods: Two thousand four hundred sixty-seven patients with decompensated liver cirrhosis (ICD-9-CM code: 571.2, 571.5, and 571.6) diagnosed between 2000 and 2009 in Taiwan were identified from the registry for catastrophic illness patients. Of these, 149 CHM users and 298 CHM non-users were matched for age, gender, and Charlson comorbidity index score. The chi-squared test, paired Student's t-test, Cox proportional hazard model, and Kaplan-Meier method were applied for various comparisons between these groups of patients. Results: CHM-treated patients showed a lower overall mortality risk compared with non-treated patients (Multivariable: p < 0.0001; HR: 0.54, 95% CI: 0.42-0.69). The cumulative incidence of overall mortality was lower in the CHM-treated group (stratified log-rank test, p = 0.0002). The strongest CHM co-prescription pattern-Yin-Chen-Hao-Tang (YCHT) → Long-Dan-Xie-Gan-Tang (LDXGT) had the highest support, followed by Zhi-Zi (ZZ) → Yin-Chen-Wu-Ling-San (YCWLS) and Bai-Hua-She-She-Cao (BHSSC) → Da-Huang (DaH). Conclusion: CHM, as adjunct therapy, might decrease the risk of overall mortality in patients with decompensated liver cirrhosis. CHM co-prescription patterns and network analysis showed that comprehensive herbal medicines have a protective role against liver fibrosis. Further studies are required to enhance the knowledge of safety and efficacy of CHM in patients with decompensated liver cirrhosis.

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Ursolic acid ameliorates CCl4‐induced liver fibrosis through the NOXs/ROS pathway

Cited by 53 publications

References 28 publications

Ursolic acid reverses liver fibrosis by inhibiting interactive NOX4/ROS and RhoA/ROCK1 signalling pathways

Ursolic acid reverses liver fibrosis by inhibiting interactive NOX4/ROS and RhoA/ROCK1 signalling pathways

Ursolic acid improves the bacterial community mapping of the intestinal tract in liver fibrosis mice

Decreased overall mortality rate with Chinese herbal medicine usage in patients with decompensated liver cirrhosis in Taiwan

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