Ligustroflavone ameliorates CCl4-induced liver fibrosis through down-regulating the TGF-β/Smad signaling pathway

Kang, Rong; Tian, Wen; Cao, Wei; Sun, Yang; Zhang, Hui-Nan; Feng, Yixuan; Li, Chen; Li, Zezhi; Li, Xiaoqiang

doi:10.1016/s1875-5364(21)60018-3

Cited by 4 publications

(3 citation statements)

References 34 publications

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“…Collagen is continuously accumulated in liver fibrosis and is composed of 18 kinds of amino acids, among which Hyp is the prevalent amino acid in collagen. Consequently, the determination of Hyp content can reflect the level of liver collagen accumulation, which can then be used to determine the degree of liver fibrosis [ 33 , 34 ]. Compared to the control group, the CCl 4 group had significantly higher Hyp content ( p < 0.001, Fig.…”

Section: Resultsmentioning

confidence: 99%

Rubus chingii Hu. unripe fruits extract ameliorates carbon tetrachloride-induced liver fibrosis and improves the associated gut microbiota imbalance

Zhang

Zhu

et al. 2022

Chin Med

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Background The unripe fruits of Rubus chingii Hu. (“Fu-peng-zi” in Chinese) is a well-known herbal tonic in traditional Chinese medicine (TCM) for tonifying liver and kidney. However, little is known regarding its therapeutic efficacy against liver fibrosis and the underlying mechanism. Methods The current research aims to explore the potential of Rubus chingii Hu. unripe fruits extract (RF) in the treatment of liver fibrosis and explore the underlying mechanism. RF was administered (450 and 900 mg·kg− 1 of body weight per day) orally to male C57BL/6 mice with CCl4-induced liver fibrosis for 3 weeks. The histopathological changes and fibrosis stage in liver tissue were assessed using hematoxylin and eosin (H&E) and Sirius red staining. The distribution of α-SMA and Col1A1 in the liver was analyzed to determine the hepatic stellate cells (HSCs) activation using immunohistochemistry and immunofluorescent analysis. Various biochemical markers in serum (ALT, AST) and liver (Hyp, IL1-β, IL6, TNF-α and MCP-1) were observed to assess the liver’s injury, fibrosis, and inflammation. In liver tissue, fibrosis-associated proteins including α-SMA, TGF-β1, Smad2/3, p-Smad2/3, and Smad4 were detected through a Western blot assay. Pyrosequencing-based analysis of bacterial 16 S ribosomal RNA from variable regions V3–V4 of fecal samples characterized the gut microbiota. Spearman’s rank correlation analysis was performed for the association between altered bacterial genera by RF and pharmacodynamics parameters. Results Three weeks of RF treatment can significantly lower liver inflammatory levels, pathological abnormalities, and collagen fibrous deposition in mice with CCl4-induced liver fibrosis. The expressions of α-SMA and Col1A1 were lowered by RF, while the expression levels of TGF-β/Smads signaling pathway-related proteins, including TGF-β1, p-Smad2/3, and Smad4, were dramatically decreased by RF. The RF treatment significantly increased or reduced 18 different bacterial species, restoring the CCl4-induced gut microbiota imbalance to the normal group’s levels. According to correlation analysis, the bacterial genera Bifidobacterium and Turicibacter were the most significant in restoring CCl4-induced liver fibrosis. Conclusions RF can reduce liver damage and delay the onset of liver fibrosis through modulating TGF-β/Smads signaling pathway. Furthermore, RF’s anti-liver fibrosis effect was related to balancing the gut microbial community, partly attained by increasing Bifidobacterium and Turicibacter in liver fibrosis.

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Section: Resultsmentioning

confidence: 99%

Rubus chingii Hu. unripe fruits extract ameliorates carbon tetrachloride-induced liver fibrosis and improves the associated gut microbiota imbalance

Zhang

Zhu

et al. 2022

Chin Med

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“…These pieces of evidence increase the credibility of Alternanthera brasiliana (L.) Kuntze as antioxidant. Phytoconstituents like Ligustroflavone ( Kang et al, 2021 ), Vitexin ( An et al, 2012 ), Kaempferol ( Park et al, 2006 ), Quercetin ( Zhang et al, 2011 ), Tricin ( Duarte-Almeida et al, 2007 ), Quercetin 3-β-D-glucoside ( Niranjan Panat et al, 2015 ), Isorhamnetin-3-O-robinobioside ( Boubaker et al, 2012 ), Stigmasterol ( Liang et al, 2020 ), β-Sitosterol ( Gupta et al, 2011 ), Ferulic acid ( Graf, 1992 ), p-Coumaric acid ( Kiliç and Yeşiloğlu, 2013 ), 4-Hydroxybenzoic acid ( Velika and Kron, 2012 ), 2,5-Dihydroxybenzoic acid ( Calderón Guzmán et al, 2007 ), Chlorogenic acid ( Sato et al, 2011 ), Dopamine-betaxanthin ( Cai et al, 2003 ), and 3-Methoxytyramine-betaxanthin ( Cai et al, 2003 ) which were earlier reported from Alternanthera brasiliana (L.) Kuntze, may be responsible for its antioxidant property.…”

Section: Introductionmentioning

confidence: 99%

The Genus Alternanthera: Phytochemical and Ethnopharmacological Perspectives

et al. 2022

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Ethnopharmacological relevance: The genus Alternanthera (Amaranthaceae) comprises 139 species including 14 species used traditionally for the treatment of various ailments such as hypertension, pain, inflammation, diabetes, cancer, microbial and mental disorders.Aim of the review: To search research gaps through critical assessment of pharmacological activities not performed to validate traditional claims of various species of Alternanthera. This review will aid natural product researchers in identifying Alternanthera species with therapeutic potential for future investigation.Materials and methods: Scattered raw data on ethnopharmacological, morphological, phytochemical, pharmacological, toxicological, and clinical studies of various species of the genus Alternanthera have been compiled utilizing search engines like SciFinder, Google Scholar, PubMed, Science Direct, and Open J-Gate for 100 years up to April 2021.Results: Few species of Alternanthera genus have been exhaustively investigated phytochemically, and about 129 chemical constituents related to different classes such as flavonoids, steroids, saponins, alkaloids, triterpenoids, glycosides, and phenolic compounds have been isolated from 9 species. Anticancer, antioxidant, antibacterial, CNS depressive, antidiabetic, analgesic, anti-inflammatory, and immunomodulator effects have been explored in the twelve species of the genus. A toxicity study has been conducted on 3 species and a clinical study on 2 species.Conclusions: The available literature on pharmacological studies of Alternanthera species reveals that few species have been selected based on ethnobotanical surveys for scientific validation of their traditional claims. But most of these studies have been conducted on uncharacterized and non-standardized crude extracts. A roadmap of research needs to be developed for the isolation of new bioactive compounds from Alternanthera species, which can emerge out as clinically potential medicines.

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“…TGF-β is considered to be the strongest pro-brosis factor that can activate hepatic stellate cells and promote liver brosis. TGF-β plays a pro-brosis role mainly through the TGF/Smad signaling pathway [9] . Smads protein is the only known intracellular kinase substrate of TGF-β receptor, and is the key downstream protein of TGF-β signaling transmembrane into the nucleus, regulating the transcription of nuclear target genes, thereby exerts the biological effects of TGF-β [8][9][10] .…”

Section: Introductionmentioning

confidence: 99%

Protective Effects and Mechanisms of Babao Dan Capsules on ANIT-Induced Intrahepatic Cholestasis Liver Disease in Mice

Mao

Liu

Huang

et al. 2021

Preprint

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Background Babao Dan(BBD), as a traditional Chinese medicine, is widely used in a variety of diseases, especially chronic liver diseases. The aim of this study is to observe the effects and possible mechanisms of Babao Dan(BBD) Capsules on α-Naphthyl isothiocyanate (ANIT) - induced intrahepatic cholestasis liver disease in mice. Methods Fifteen mice were randomly divided into three groups: control group, model group, and treatment group, with five in each group. Except for the mice in the control group, the mice in the other two groups were gavaged with a 1% α-Naphthyl isothiocyanate (ANIT) olive oil solution, and cholestasis models were established at a dose of 100 mg/Kg. Meanwhile, at the same time point, the control group was gavaged with the same amount of olive oil. After modeling, the control group, the model group and the treatment group were gavaged with the same amount of saline, saline and BBD saline suspension once daily for 10 days, respectively. On the 10th day, we took the blood preparation and liver samples, then we detected serum levels of liver function indexes(TBA, TBil, DBil, ALT, AST, ALP, GGT), liver fibrosis indexes(HA, LN, PC-Ⅲ, C-Ⅳ). Hepatic pathological examinations were observed by hematoxylin and eosin staining(HE), Masson staining and picric acid-Sirius red staining. The protein expression of TGF-β1 and Smad3 were detected by immunohistochemistry. The level of mRNA expression of TGF-β1 and Smad3 were detected by RT-PCR. Results Compared with the control group, serum levels of liver function indexes(TBA, TBil, DBil, ALT, AST, ALP, GGT) and liver fibrosis indexes(HA, LN, PC-Ⅲ, C-Ⅳ) in the model group were significantly increased (P < 0.01).Similarly, compared with control group, in the model group, HE staining showed that hepatocyte swelling, hepatocellular necrosis and destroyed hepatic lobular structure; Masson staining showed that a large amount of blue collagen fibers deposited in the liver tissue, forming fibrous septa and pseudolobule; Picric acid-Sirius red staining showed that type Ⅰ collagen and type Ⅲ collagen in liver tissue increased significantly, the total area of collagen increased significantly. The protein expression of TGF-β1 and Smad3 were significantly up-regulated; the mRNA expression of TGF-β1 and Smad3 was significantly up-regulated. Compared with the model group, the above indexes in treatment group were significantly decreased(P < 0.01). Conclusions Babao Dan(BBD) has significant therapeutical effects on intrahepatic cholestasis liver disease by inhibiting TGF-β/Smad signaling pathway.

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Ligustroflavone ameliorates CCl4-induced liver fibrosis through down-regulating the TGF-β/Smad signaling pathway

Cited by 4 publications

References 34 publications

Rubus chingii Hu. unripe fruits extract ameliorates carbon tetrachloride-induced liver fibrosis and improves the associated gut microbiota imbalance

Rubus chingii Hu. unripe fruits extract ameliorates carbon tetrachloride-induced liver fibrosis and improves the associated gut microbiota imbalance

The Genus Alternanthera: Phytochemical and Ethnopharmacological Perspectives

Protective Effects and Mechanisms of Babao Dan Capsules on ANIT-Induced Intrahepatic Cholestasis Liver Disease in Mice

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