Schisantherin A ameliorates liver fibrosis through TGF-β1mediated activation of TAK1/MAPK and NF-κB pathways in vitro and in vivo

Wang, Haili; Che, Jin-Ying; Chen, Kai; Zhuang, Wenyue; Li, He; Sun, Jia; Chen, Jianguang; Wang, Chunmei

doi:10.1016/j.phymed.2021.153609

Cited by 62 publications

(23 citation statements)

References 41 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Consequently, Sch B is provided with therapeutic potential against LF through activation of PPARγ [182] . Schisantherin A (SCA) ameliorated TAA and HSC-T6-induced activation of TGF-β1 in LF cells in mice, probably by inhibiting TGF-β1-mediated TAK1/MAPK and signaling pathways to suppress the activation and inflammatory response of HSCs [183] . Pentoxifylline may ameliorate LF by inhibiting MAPK as well as TGF-β/Smad signal pathways [245] .…”

Section: Schisandra Related Small Moleculementioning

confidence: 99%

Small-molecule natural products for reversing liver fibrosis based on modulation of HSCs activation: an update

Zheng

Yang

Luo

et al. 2022

Preprint

View full text Add to dashboard Cite

Liver fibrosis (LF) is a trauma repair process carried out by the liver in response to various acute and chronic liver injuries, featured by excessive proliferation as well as abnormal dismissal of extracellular matrix as the main pathological features, and its continuous development will deteriorate into cirrhosis, liver cancer as well as other illnesses. The occurrence of LF is closely related to Hepatic stellate cells (HSCs) stimulation, and intervention in HSCs proliferation is expected to reverse LF. Plant-based small molecule drugs have anti-LF effects, and their mechanisms of action are related to anti-inflammation, anti-oxidative stress, as well as inhibition of abnormal accumulation of extracellular matrix. Consequently, new agents for HSCs will be required to furnish a possible curative response. Small-molecule natural products might be attractive for LF therapy. That is because they not only have the effect against HSCs, but also have excellent qualities such as low toxic side effects and easy availability from the perspective of safety and cost. In this review, we provide an updated review of the signal transduction pathways involved in HSCs and small-molecule natural products targeting HSCs reported in the past 3 years at home and abroad, with the aim of providing new ideas for the development of plant-based small molecule drugs targeting HSCs to reverse LF.

show abstract

Section: Schisandra Related Small Moleculementioning

confidence: 99%

Small-molecule natural products for reversing liver fibrosis based on modulation of HSCs activation: an update

Zheng

Yang

Luo

et al. 2022

Preprint

View full text Add to dashboard Cite

show abstract

“…[44,45] Alternatively, activated TGF-β can activate the mitogen-activated protein kinase (MAPK) signaling pathways. [46][47][48][49] For example, the activator-binding domain of the Ras protein is catalyzed to convert to Ras-GTP, then binds to C-Raf-1 and phosphorylates MAPK kinase (MEK/MKK). This triggers extracellular regulated protein kinase 1/2 (ERK1/2), further upregulating Smad expression.…”

Section: Pathogenesis Of Organ Fibrosismentioning

confidence: 99%

Periplaneta americana (Insecta: Blattodea) and organ fibrosis: A mini review

et al. 2022

View full text Add to dashboard Cite

Fibrosis is the end stage of many chronic inflammatory diseases and eventually leads to organ failure. Periplaneta americana (P. americana) is referred to as “the product of flesh and blood” in traditional Chinese medicine and has a wide range of therapeutic effects. Owing to the growing interest in this insect for its application in the treatment of tissue injury-healing disorders that induce organ fibrosis, it has attracted the interest of researchers. A literature search was performed using core collections of electronic databases, such as PubMed, Web of Science, China National Knowledge Infrastructure, and Wanfang, using the keywords given below and terms such as pharmacological and biochemical details of this insect. P. americana extracts presented a wide range of therapeutic and biological activities, including antifibrotic, antiinflammatory, antioxidative, and tissue repair activities. Emerging evidence suggests that P. americana extracts may improve scarring, pulmonary fibrosis, liver fibrosis, and kidney fibrosis through the regulation of fibroblast activation, cytokine secretion, and deposition of fibrin, indicating the potential role of P. americana as a therapeutic option for organ fibrosis. P. americana is a potential therapeutic agent for treating fibrosis. Further studies are required for a more in-depth characterization of the antifibrogenic mechanism of P. americana prior to its clinical application in the treatment of organ fibrosis. (Fig. 1).

show abstract

“…et Wils, and it has a variety of pharmacological effects (14). Studies have shown that STA has an ameliorative effect on liver injury caused by a variety of conditions and can protect liver function (15)(16)(17)(18). A recent study has shown that STA induces apoptosis and has anti-tumor activity (19).…”

Section: Original Articlementioning

confidence: 99%

Influence of schisantherin A on the pharmacokinetics of lenvatinib in rats and its potential mechanism

Cui¹,

Ma²,

Liu³

et al. 2022

J Gastrointest Oncol

View full text Add to dashboard Cite

Background: Lenvatinib (LEN) is approved as first-line therapy for advanced hepatocellular carcinoma (HCC). Schisantherin A (STA) can exert hepatoprotective and anti-tumor effects. The clinical combination of LEN and STA is very common, especially for patients with advanced HCC, but the effect of STA on the pharmacokinetics of LEN is unclear. This study aimed to investigate the effects of STA on the pharmacokinetics of LEN in rats and explore its potential mechanism.Methods: Male Sprague-Dawley (SD) rats were orally administered different doses of STA or vehicle control for 7 consecutive days, and 1.2 mg/kg of LEN was given on day 7. The messenger RNA (mRNA) and protein expression levels in the intestines and liver were investigated by reverse transcription quantitative polymerase chain reaction (RT-qPCR) and western blot.Results: It was revealed that STA increased the oral bioavailability of LEN. The area under the curve from time 0 to infinity (AUC 0-∞ ) and maximum plasma concentration (C max ) of LEN after co-administration with STA (20 mg/kg) increased by 54.3% (3,396.73±989.35 vs. 5,240.03±815.49 μg/L/h) and 54.8% (490.64±124.20 vs. 759.66±152.75 μg/L), respectively. The clearance decreased from 0.38±0.12 to 0.23±0.04 L/h/kg, and the apparent volume of distribution (Vz) decreased from 10.83±3.19 to 6.35±1.38 L/kg in the presence of 20 mg/kg STA. In addition, the expression of P-glycoprotein (P-gp) mRNA and protein in the intestines was markedly decreased.Conclusions: This study showed that STA increased the bioavailability of LEN, probably due to inhibition of P-gp in the intestine, thereby increasing systemic absorption of LEN. Thus, there is an interaction between the two drugs, and careful monitoring must be conducted when they are used in combination.

show abstract

Schisantherin A ameliorates liver fibrosis through TGF-β1mediated activation of TAK1/MAPK and NF-κB pathways in vitro and in vivo

Cited by 62 publications

References 41 publications

Small-molecule natural products for reversing liver fibrosis based on modulation of HSCs activation: an update

Small-molecule natural products for reversing liver fibrosis based on modulation of HSCs activation: an update

Periplaneta americana (Insecta: Blattodea) and organ fibrosis: A mini review

Influence of schisantherin A on the pharmacokinetics of lenvatinib in rats and its potential mechanism

Contact Info

Product

Resources

About