Schisandrin C enhances cGAS-STING pathway activation and inhibits HBV replication

Zhao, Jia; Xu, Guang; Hou, Xiaorong; Mu, Wenqing; Yang, Hong-Chang; Shi, Wei; Wen, Jincai; Liu, Tingting; Wu, Zhixin; Bai, Jing; Zhang, Ping; Wang, Zhong‐Xia; Xiao, Xiaohe; Zhou, Wenjun; Bai, Zhaofang; Zhan, Xiaoyan

doi:10.1016/j.jep.2023.116427

Cited by 20 publications

(9 citation statements)

References 41 publications

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“…One hour after gavage on the seventh day, the experimental group was injected with DMXAA (25 mg/kg) intraperitoneally, and the control group was injected with an equal amount of the excipient intraperitoneally. After 4 h of the action of DMXAA, the mice were collected in serum and the intraperitoneal lavage fluid, which was tested for the relevant factor indexes [7]. EF dissolution method: 5% DMSO + 5% Tween-80 + 90% saline.…”

Section: Dmxaa-induced In Vivo Experimentsmentioning

confidence: 99%

“…Upon receiving the signal, STING undergoes dimerization and translocate from the endoplasmic reticulum to the Golgi. STING can recruit TBK1, and TBK1 can provide a docking site for IRF3, which recruits IRF3 by binding to the positively charged surface of IRF3 while phosphorylating IRF3 [7,8]. Assembly of the STING-TBK1-IRF3 complex to form a functional STING signalosome also represents typical activation of cGAS-STING signalling pathway [9].…”

Section: Introductionmentioning

confidence: 99%

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Flavonoid extracted from Epimedium attenuate cGAS‐STING‐mediated diseases by targeting the formation of functional STING signalosome

Wang,

Xu,

Wen

et al. 2024

Immunology

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Hyperactivation of the cyclic‐GMP‐AMP synthase (cGAS)–stimulator of interferon genes (STING) signalling pathway has been shown to be associated with the development of a variety of inflammatory diseases, and the discovery of an inhibitor of the cGAS‐STING signalling pathway holds great promise in the therapeutic interventions. Epimedium flavonoid (EF), a major active ingredient isolated from the medicinal plant Epimedium, has been reported to have good anti‐inflammatory activity, but its exact mechanism of action remains unclear. In the present study, we found that EF in mouse bone marrow‐derived macrophages (BMDMs), THP‐1 (Tohoku Hospital Pediatrics‐1) as well as in human peripheral blood mononuclear cells (hPBMC) inhibited the activation of the cGAS‐STING signalling pathway, which subsequently led to a decrease in the expression of type I interferon (IFN‐β, CXCL10 and ISG15) and pro‐inflammatory cytokines (IL‐6 and TNF‐α). Mechanistically, EF does not affect STING oligomerization, but inhibits the formation of functional STING signalosome by attenuating the interaction of interferon regulatory factor 3 (IRF3) with STING and TANK‐binding kinase 1 (TBK1). Importantly, in vivo experiments, EF has shown promising therapeutic effects on inflammatory diseases mediated by the cGAS‐STING pathway, which include the agonist model induced by DMXAA stimulation, the autoimmune inflammatory disease model induced by three prime repair exonuclease 1 (Trex1) deficiency, and the non‐alcoholic steatohepatitis (NASH) model induced by a pathogenic amino acid and choline deficiency diet (MCD). To summarize, our study suggests that EF is a potent potential inhibitor component of the cGAS‐STING signalling pathway for the treatment of inflammatory diseases mediated by the cGAS‐STING signalling pathway.

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Section: Dmxaa-induced In Vivo Experimentsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Flavonoid extracted from Epimedium attenuate cGAS‐STING‐mediated diseases by targeting the formation of functional STING signalosome

Wang,

Xu,

Wen

et al. 2024

Immunology

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“…However, these findings are currently limited to cell-based experimental models, thus, confirmation of the independent anti-HBV activity of sophocarpine in in vivo is still lacking. Furthermore, the specific molecular mechanisms through which sophocarpine counteracts HBV infection, including its potential involvement in established anti-HBV pathways such as liver X receptor pathways ( Zeng et al, 2020 ), AMPK-ULK1 pathway ( Wang et al, 2021d ), and the cGAS-STING pathway ( Zhao et al, 2023 ), have not been identified. Therefore, further investigations are warranted to address these pertinent issues.…”

Section: Pharmacological Activitiesmentioning

confidence: 99%

A review on the pharmacology, pharmacokinetics and toxicity of sophocarpine

Wei,

Xiao,

et al. 2024

Front. Pharmacol.

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Sophocarpine is a natural compound that belongs to the quinolizidine alkaloid family, and has a long history of use and widespread distribution in traditional Chinese herbal medicines such as Sophora alopecuroides L., Sophora flavescens Ait., and Sophora subprostrata. This article aims to summarize the pharmacology, pharmacokinetics, and toxicity of sophocarpine, evaluate its potential pharmacological effects in various diseases, and propose the necessity for further research and evaluation to promote its clinical application. A large number of studies have shown that it has anti-inflammatory, analgesic, antiviral, antiparasitic, anticancer, endocrine regulatory, and organ-protective effects as it modulates various signaling pathways, such as the NF-κB, MAPK, PI3K/AKT, and AMPK pathways. The distribution of sophocarpine in the body conforms to a two-compartment model, and sophocarpine can be detected in various tissues with a relatively short half-life. Although the pharmacological effects of sophocarpine have been confirmed, toxicity and safety assessments and reports on molecular mechanisms of its pharmacological actions have been limited. Given its significant pharmacological effects and potential clinical value, further research and evaluation are needed to promote the clinical application of sophocarpine.

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“…In addition to the aforementioned pharmacological activities, Sch C was also found to have antiviral activity, [89] and experiments showed that Sch C reduced HBeAg, HBcAg, HBsAg and HBV DNA levels in HBV model mice and increased IFN β production and expression of interferon-stimulated genes (IFIT1, ISG15 and CXCL10). In contrast, a study by D. Lee [90] illustrated that Sch C is also effective in hypoglycemia, enhancing insulin secretion in response to high glucose levels, with no toxic effects on INS-1 cells and better effects than gliclazide (positive control), while enhancing glucose uptake.…”

Section: Othersmentioning

confidence: 99%

A Review of Extraction and Purification, Biological Properties, Structure–Activity Relationships and Future Prospects of Schisandrin C: A Major Active Constituent of Schisandra Chinensis

Xu,

Wang,

et al. 2023

Chemistry & Biodiversity

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Since ancient times, China has used natural medicine as the primary way to combat diseases and has a rich arsenal of natural medicines. With the progress of the times, the extraction of bioactive molecules from natural drugs has become the new development direction for natural medicines. Among the numerous natural drugs, Schisandrin C (Sch C), derived from Schisandra Chinensis (Turcz.) Baill. It has excellent potential for development and has been shown to possess various pharmacological properties, including hepatoprotective, antitumor and anti‐inflammatory activities. Based on the biological properties of hepatoprotection, scholars have explored Sch C and its synthetic products in depth; some studies have shown that pentosidine has the effect of improving the symptoms of liver fibrosis and reducing the concentration of alanine transaminase (ALT) and aspartate aminotransferase (AST) in the serum of rats, which is an essential inspiration for the development of anti‐liver fibrosis drugs. But more in vivo and ex vivo studies still need to be included. This paper focuses on Sch C′s extraction and synthesis, biological activities and drug development progress. The future application prospects of Sch C are discussed to perfect its development work further.

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Schisandrin C enhances cGAS-STING pathway activation and inhibits HBV replication

Cited by 20 publications

References 41 publications

Flavonoid extracted from Epimedium attenuate cGAS‐STING‐mediated diseases by targeting the formation of functional STING signalosome

Flavonoid extracted from Epimedium attenuate cGAS‐STING‐mediated diseases by targeting the formation of functional STING signalosome

A review on the pharmacology, pharmacokinetics and toxicity of sophocarpine

A Review of Extraction and Purification, Biological Properties, Structure–Activity Relationships and Future Prospects of Schisandrin C: A Major Active Constituent of Schisandra Chinensis

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