Mechanisms exploration of Angelicae Sinensis Radix and Ligusticum Chuanxiong Rhizoma herb-pair for liver fibrosis prevention based on network pharmacology and experimental pharmacologylogy

Wu, Jianzhi; Huang, Guangrui; Xu, Bing; Zhou, Fei; Liu, Runping; Gao, Feng; Ge, Junde; Cai, Yajie; Zheng, Qi; Li, Xiaojiaoyang

doi:10.1016/s1875-5364(21)60026-2

Cited by 15 publications

(14 citation statements)

References 33 publications

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“…Cell damage and inflammatory infiltration in histological changes were determined by evaluating the degree of hepatic injury. H&E scoring was performed as previously described (Wu et al, 2021). Quantification of collagen deposition (the percentage of blue collagen area relative to the total staining area) in Masson's Trichrome staining was conducted using ImageJ software.…”

Section: Histopathology Masson's Trichrome Staining and Immunohistochemistrymentioning

confidence: 99%

Ferulic Acid Ameliorates Hepatic Inflammation and Fibrotic Liver Injury by Inhibiting PTP1B Activity and Subsequent Promoting AMPK Phosphorylation

Xue

Fan

et al. 2021

Front. Pharmacol.

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Chronic inflammation in response to persistent exogenous stimuli or damage results in liver fibrosis, which subsequently progresses into malignant liver diseases with high morbidity and mortality. Ferulic acid (FA) is a phenolic acid widely isolated from abundant plants and exhibits multiple biological activities including anti-oxidant, anti-inflammation and enhancement of immune responses. Adenosine monophosphate-activated protein kinase (AMPK) functions as a critical energy sensor and is regulated through the phosphorylation of liver kinases like LKB1 or dephosphorylation by protein tyrosine phosphatases (PTPs). However, the role of FA in carbon tetrachloride (CCl4)-induced chronic inflammation and liver fibrosis and AMPK activation has not been elucidated. Here we reported that FA ameliorated CCl4-induced inflammation and fibrotic liver damage in mice as indicated by reduced levels of serum liver function enzyme activities and decreased expression of genes and proteins associated with fibrogenesis. Additionally, FA inhibited hepatic oxidative stress, macrophage activation and HSC activation via AMPK phosphorylation in different liver cells. Mechanically, without the participation of LKB1, FA-induced anti-inflammatory and anti-fibrotic effects were abrogated by a specific AMPK inhibitor, compound C. Combining with the results of molecular docking, surface plasmon resonance and co-immunoprecipitation assays, we further demonstrated that FA directly bound to and inhibited PTP1B, an enzyme responsible for dephosphorylating key protein kinases, and eventually leading to the phosphorylation of AMPK. In summary, our results indicated that FA alleviated oxidative stress, hepatic inflammation and fibrotic response in livers through PTP1B-AMPK signaling pathways. Taken together, we provide novel insights into the potential of FA as a natural product-derived therapeutic agent for the treatment of fibrotic liver injury.

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Section: Histopathology Masson's Trichrome Staining and Immunohistochemistrymentioning

confidence: 99%

Ferulic Acid Ameliorates Hepatic Inflammation and Fibrotic Liver Injury by Inhibiting PTP1B Activity and Subsequent Promoting AMPK Phosphorylation

Xue

Fan

et al. 2021

Front. Pharmacol.

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“…After acclimatization for 7 days, mice were randomly divided into five groups (n = 8): (1) control group; (2) CCl 4 group; (3) CCl 4 + SWT low dose (L) group; (4) CCl 4 + SWT medium dose (M) group; (5) CCl 4 + SWT high dose (H) group. Groups (2)–(5) were intragastrically administered with CCl 4 every 3 days for 4 weeks as previously described [ 16 ]. Groups (3)–(5) were intragastrically administered with SWT (L) (5.2 g/kg), SWT (M) (10.4 g/kg) and SWT (H) (20.8 g/kg) daily for 3 weeks after 1-week CCl 4 administration.…”

Section: Methodsmentioning

confidence: 99%

“…Several clinical and preclinical studies reported that SWT effectively decreased gallstones, improved lipid metabolism and relived liver injury [ 14 , 15 ]. We recently documented that the combination of RAS and RLC effectively ameliorated fibrotic liver injury by decreasing BA accumulation and repressing the production of inflammatory cytokines [ 16 ]. Bioactive ingredients of RPA and RRP exhibited hepatoprotective effects as well [ 17 ].…”

Section: Introductionmentioning

confidence: 99%

Si-Wu-Tang ameliorates fibrotic liver injury via modulating intestinal microbiota and bile acid homeostasis

Xue

Ding

et al. 2021

Chin Med

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Background Fibrotic liver injury is a progressive scarring event, which may permanently affect liver function and progress into devastating end-stage liver diseases due to the absence of effective therapies. Si-Wu-Tang (SWT), a traditional Chinese medicine formula used in clinic to treat gynecological disorders for centuries, has been investigated in recent preliminary findings for its role in alleviating chronic liver diseases. Here we aim to elucidate the therapeutic effects and possible mechanisms of SWT against fibrotic liver injury. Methods UHPLC-MS/MS was performed to investigate the chemical characterization of SWT. After intragastrically administered with carbon tetrachloride (CCl4) every 3 days for 1-week, C57BL/6 mice were orally administered with SWT (5.2, 10.4 and 20.8 g/kg) once daily for 3 weeks along with CCl4 challenge. Liver function was determined by the measurement of serum biomarkers, hematoxylin and eosin (H&E) and Masson’s trichrome staining. Intestinal inflammatory infiltration and the disruption of intestinal barrier were examined by H&E and E-cadherin immunohistochemical staining. The microbial composition of intestinal content was determined by 16S rRNA sequencing. Serum bile acids (BAs) profiling was analyzed by LC–MS/MS. Simultaneously, the expression of genes of interest was determined by qPCR and western blot. Results SWT exhibited remarkable therapeutic effects on CCl4-induced liver fibrosis, as indicated by improved collagen accumulation in livers, intestinal barrier injury and hepatic and intestinal inflammatory response. Results of 16S rRNA sequencing revealed that SWT treatment strikingly restructured intestinal microbiota in fibrotic mice by increasing the relative abundances of Bacteroides and Lachnoclostridium and decreasing the relative abundances of Alistipes and Rikenellaceae. UHPLC-MS/MS data suggested that SWT altered the composition of BAs in circulation as evidenced by increased unconjugated BAs like cholic acid and chenodeoxycholic acid but decreased conjugated BAs including taurocholic acid and taurodeoxycholic acid, compared to that in CCl4 mice. Notably, SWT efficiently improved the imbalance of BA homeostasis in livers caused by CCl4 via activating farnesoid X receptor (FXR)-fibroblast growth factor 15 enterohepatic and FXR-small heterodimer partner hepatic pathways. Conclusion SWT decreased inflammatory response, reconstructed gut microbiota-mediated BA homeostasis as well as activated FXR pathways, which eventually protected against CCl4-induced fibrotic liver injury.

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“…Ligusticum attenuates hyperhomocysteinemia-induced Alzheimer-like pathologies in rats ( Zhang et al, 2021 ) and acts against focal cerebral ischemia ( Gu et al, 2020 ). Moreover, Ligusticum alleviates acute lung injury ( Jiang et al, 2021 ), prevents liver fibrosis ( Wu et al, 2021 ), and has an anti-tumor effect ( Zhong et al, 2021 ).…”

Section: Pharmacological Effects On the Active Ingredients Of Buyang ...mentioning

confidence: 99%

A Review of Traditional Chinese Medicine, Buyang Huanwu Decoction for the Treatment of Cerebral Small Vessel Disease

Sun

Wang

et al. 2022

Front. Neurosci.

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Cerebral small vessel disease (CSVD) is often referred to as “collaterals disease” in traditional Chinese medicine (TCM), and commonly includes ischemic and hemorrhagic CSVD. TCM has a long history of treating CSVD and has demonstrated unique efficacy. Buyang Huanwu Decoction (BHD) is a classical TCM formula that has been used for the prevention and treatment of stroke for hundreds of years. BHD exerts its therapeutic effects on CSVD through a variety of mechanisms. In this review, the clinical and animal studies on BHD and CSVD were systematically introduced. In addition, the pharmacological mechanisms, active components, and clinical applications of BHD in the treatment of CSVD were reviewed. We believe that an in-depth understanding of BHD, its pharmacological mechanism, disease-drug interaction, and other aspects will help in laying the foundation for its development as a new therapeutic strategy for the treatment of CSVD.

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Mechanisms exploration of Angelicae Sinensis Radix and Ligusticum Chuanxiong Rhizoma herb-pair for liver fibrosis prevention based on network pharmacology and experimental pharmacologylogy

Cited by 15 publications

References 33 publications

Ferulic Acid Ameliorates Hepatic Inflammation and Fibrotic Liver Injury by Inhibiting PTP1B Activity and Subsequent Promoting AMPK Phosphorylation

Ferulic Acid Ameliorates Hepatic Inflammation and Fibrotic Liver Injury by Inhibiting PTP1B Activity and Subsequent Promoting AMPK Phosphorylation

Si-Wu-Tang ameliorates fibrotic liver injury via modulating intestinal microbiota and bile acid homeostasis

A Review of Traditional Chinese Medicine, Buyang Huanwu Decoction for the Treatment of Cerebral Small Vessel Disease

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