Apigenin Alleviates Liver Fibrosis by Inhibiting Hepatic Stellate Cell Activation and Autophagy via TGF-β1/Smad3 and p38/PPARα Pathways

Ji, Jie; Yu, Qiang; Dai, Weiqi; Wu, Liwei; Jiao, Feng; Zheng, Yuanyuan; Li, Yan; Guo, Chuanyong

doi:10.1155/2021/6651839

Cited by 33 publications

(22 citation statements)

References 67 publications

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“…This natural flavone has been shown to exert therapeutic effects in neurological disorders and CVD [17]. Other studies showed that apigenin has hepatoprotective, antidepressant, anticancer and antihypertensive effects; it is also able to prevent autoimmune myocarditis, atherogenesis and asthma and induces beneficial action against osteoporosis, type 2 diabetes mellitus and pancreatitis [69][70][71][72][73][74][75][76][77][78][79][80]. Importantly, in addition to the involvement of apigenin in inflammation modulation, mRNA splicing regulation, cell cycle arrest and regulation of apoptosis [81], most of these findings support the hypothesis that the beneficial effects of apigenin are also attributed to its capacity to counteract oxidative stress, which is known to be a key component of many diseases, including cardiovascular, pulmonary, neurodegenerative diseases, cancer and metabolic disorders [82].…”

Section: Broad-spectrum Antioxidant Activity Of Apigenin With a Main Focus On Dysmetabolic Conditionsmentioning

confidence: 99%

Current Status and Future Perspectives on Therapeutic Potential of Apigenin: Focus on Metabolic-Syndrome-Dependent Organ Dysfunction

et al. 2021

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Metabolic syndrome and its associated disorders such as obesity, insulin resistance, atherosclerosis and type 2 diabetes mellitus are globally prevalent. Different molecules showing therapeutic potential are currently available for the management of metabolic syndrome, although their efficacy has often been compromised by their poor bioavailability and side effects. Studies have been carried out on medicinal plant extracts for the treatment and prevention of metabolic syndrome. In this regard, isolated pure compounds have shown promising efficacy for the management of metabolic syndrome, both in preclinical and clinical settings. Apigenin, a natural bioactive flavonoid widely present in medicinal plants, functional foods, vegetables and fruits, exerts protective effects in models of neurological disorders and cardiovascular diseases and most of these effects are attributed to its antioxidant action. Various preclinical and clinical studies carried out so far show a protective effect of apigenin against metabolic syndrome. Herein, we provide a comprehensive review on both in vitro and in vivo evidence related to the promising antioxidant role of apigenin in cardioprotection, neuroprotection and renoprotection, and to its beneficial action in metabolic-syndrome-dependent organ dysfunction. We also provide evidence on the potential of apigenin in the prevention and/or treatment of metabolic syndrome, analysing the potential and limitation of its therapeutic use.

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Section: Broad-spectrum Antioxidant Activity Of Apigenin With a Main Focus On Dysmetabolic Conditionsmentioning

confidence: 99%

Current Status and Future Perspectives on Therapeutic Potential of Apigenin: Focus on Metabolic-Syndrome-Dependent Organ Dysfunction

et al. 2021

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“…Studies have shown that Quercetin inhibits liver steatosis and fibrosis induced by cadmium chloride by down-regulating the transcription of mi R-21 [20] . Apigenin alleviates hepatic fibrosis by inhibiting hepatic stellate cell activation and autophagy through TGF-β1/Smad3 and p38 /PPAR pathways [21] . Throug h network pharmacology analysis,20 core targets such as Akt1, PIK3R1, EGFR, PPARA, IGF1R, INSR, MAPK14, TNF, PPARG, and BRAF of Mongolian medicine scabiosa against hepatic fibrosis were obtained.…”

Section: Go Function Analysismentioning

confidence: 99%

Exploring the Therapeutic Mechanism of the Mongolian Medicine Scabiosa Against Hepatic Fibrosis Based on UHPLC-TOF-MS/MS Combined with Network Pharmacological Methods and Experimental Verification

Yuan¹,

Ren²,

Li³

et al. 2021

Preprint

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Objective To systematically elucidate the chemical composition of Mongolian medicine scabiosa, explore its key targets and related pathways by network p harmacology, and further clarify its against hepatic fibrosis mechanism through experiments. Methods The Mongolian medicine scabiosa was determined by UHPLC -TOF-MS/MS and its components were analyzed; The intersection of Mongolian medicine scabiosa was screened in the Swiss target prediction database to obtain the against hepatic fibrosis target of Mongolian Medicine Scabiosa. The protein interaction was analyzed through a string database, and the GO function and KEGG path way were analyzed on the Metascape platform. Meanwhile, we selected the PI3K/Akt and PI3K, Akt, p-Akt, p38 and p-p38 targets in MAPK signaling pathway for v erification. The mechanism against hepatic fibrosis of Mongolian medicine scabiosa was verified by in vitro and in vivo experiments. Results A total of 120 chemical constituents were identified, including flavonoids, alkaloids, coumarins, terpenoids, phenols, and fatty acids. According to the prediction, there are 63 against hepatic fibrosis targets, including 20 core targets. GO enrichment analysis involves three aspects: biological process (BP), cell component (CC), and molecular function (MF). KEGG enrichment results show that PI3K/Akt, EGFR, Rap1, HIF-1, Ras, MAPK are significant pathways. In the in vivo experiment, Mongolian medicine scabiosa can significantly reduce serum biochemical indexes ( P< 0.05), hydroxyproline ( P< 0.05); Masson staining showed that the proliferation of abnormal fibrous tissue w as reduced, and the infiltration of inflammatory cells was reduced, which improved the fibrotic liver tissue; RT-qPCR results showed that the expression of α-SMA, c ollagen, PI3K, Akt, p38 mRNA decreased( P< 0.05). The results of Western blot showed that compare with the model group, the Mongolian medicine scabiosa could i nhibit the expression of markers of hepatic fibrosis α-SMA, collagen, PI3K, Akt, p-Akt, p38,p-p38decreased( P< 0.01); In the in vitro experiment, MTT results showe d that the inhibition rate of serum containing Mongolian medicine scabiosa on HSC-T6 was the highest at 24 hours; Western blot results showed that compared with t he control group, the protein expression levels of α-SMA, collagen, PI3K, Akt, p-Akt, p38,p-p38 in high, medium and low dose groups were significantly decreased

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“…APG inhibits the proliferation of hepatocellular carcinoma cells via up- or down-regulating miRNA molecules and their target genes ( Wang et al, 2021 ). Further, a study reported the role of APG in inhibiting hepatic stellate cell activation and autophagy via the TGF-1/Smad3 and p38/PPAR pathways, which may help to reduce liver fibrosis ( Ji et al, 2021 ).…”

Section: Introductionmentioning

confidence: 99%

The role of serotonergic and catecholaminergic systems for possible antidepressant activity of apigenin

Al-Yamani¹,

Asdaq²,

Alamri

et al. 2022

Saudi Journal of Biological Sciences

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Background and objective Although, the anti-depressant like effects of apigenin (APG) are documented in the literature, the underlying mechanism for exerting such an effect is still not clear. In this research, an attempt was made to determine the possible role of APG for antidepressant activity through serotonergic and catecholaminergic systems using standardized animal models. Materials and methods The antidepressant property of APG was determine by involving tail suspension (TST) and modified forced swimming tests (MFST). The effect of APG was evaluated at 25 and 50 mg/kg. In mechanistic models, animals were pretreated with catecholaminergic and serotonergic antagonists prior to administration of APG. The results obtained were statistically analyzed to determine the level of significance. Results The period of immobility in both models (TST and MFST) was significantly reduced by APG (25 and 50 mg/kg). The best therapetuic dose of APG (50 mg/kg) was selected for the mechanistic study. The anti-immobility effect of APG declined to a significant extent upon pretreatment with catecholaminergic antagonists (α-methyl-para-tyrosine methyl ester; SCH 23390; sulpiride; phentolamine) and serotonergic inhibitors ( p -clorophenylalanine-methyl-ester; ondansetron) in both TST and MFST models. The antidepressant benefits of apigenin were only modestly reversed when rats were given propranolol. Conclusions The findings suggest that APG's antidepressant effect is mediated by the α-adrenergic, dopaminergic and 5-HT3 serotonergic receptors.

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Apigenin Alleviates Liver Fibrosis by Inhibiting Hepatic Stellate Cell Activation and Autophagy via TGF-β1/Smad3 and p38/PPARα Pathways

Cited by 33 publications

References 67 publications

Current Status and Future Perspectives on Therapeutic Potential of Apigenin: Focus on Metabolic-Syndrome-Dependent Organ Dysfunction

Current Status and Future Perspectives on Therapeutic Potential of Apigenin: Focus on Metabolic-Syndrome-Dependent Organ Dysfunction

Exploring the Therapeutic Mechanism of the Mongolian Medicine Scabiosa Against Hepatic Fibrosis Based on UHPLC-TOF-MS/MS Combined with Network Pharmacological Methods and Experimental Verification

The role of serotonergic and catecholaminergic systems for possible antidepressant activity of apigenin

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