2. Academic Validation
  3. Schisandrin C enhances cGAS-STING pathway activation and inhibits HBV replication

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

  • J Ethnopharmacol. 2023 Mar 29;116427. doi: 10.1016/j.jep.2023.116427.
Jia Zhao 1,  Guang Xu 2,  Xiaorong Hou 3,  Wenqing Mu 4,  Huijie Yang 4,  Wei Shi 4,  Jincai Wen 4,  Tingting Liu 4,  Zhixin Wu 4,  Jun Bai 5,  Ping Zhang 6,  Zhongxia Wang 4,  Xiaohe Xiao 7,  Wenjun Zou 8,  Zhaofang Bai 9,  Xiaoyan Zhan 10
Affiliations

Affiliations

  • 1 School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, China; Department of Hepatology, The Fifth Medical Center of Chinese PLA General Hospital, Beijing, 100039, China; School of Pharmacy, North Sichuan Medical College, Nanchong, 637000, China.
  • 2 Department of Hepatology, The Fifth Medical Center of Chinese PLA General Hospital, Beijing, 100039, China; School of Traditional Chinese Medicine, Capital Medical University, Beijing, 100069, China.
  • 3 School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, China; Department of Hepatology, The Fifth Medical Center of Chinese PLA General Hospital, Beijing, 100039, China.
  • 4 Department of Hepatology, The Fifth Medical Center of Chinese PLA General Hospital, Beijing, 100039, China.
  • 5 Department of Neurosurgery, General Hospital of Chinese People Liberty Army, Beijing, 100853, China.
  • 6 Department of Pharmacy, Medical Supplies Center of PLA General Hospital, Beijing, 100039, China.
  • 7 China Military Institute of Chinese Materia, The Fifth Medical Center of Chinese PLA General Hospital, Beijing, 100039, China. Electronic address: pharmacy_302@126.com.
  • 8 School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, China. Electronic address: zouwenjun@163.com.
  • 9 Department of Hepatology, The Fifth Medical Center of Chinese PLA General Hospital, Beijing, 100039, China; China Military Institute of Chinese Materia, The Fifth Medical Center of Chinese PLA General Hospital, Beijing, 100039, China. Electronic address: baizf2008@hotmail.com.
  • 10 Department of Hepatology, The Fifth Medical Center of Chinese PLA General Hospital, Beijing, 100039, China. Electronic address: xyzhan123@163.com.
PMID: 37001770 DOI: 10.1016/j.jep.2023.116427
Abstract

Ethnopharmacological relevance: Schisandra Chinensis (Turcz.) Baill. is a long-term used traditional Chinese medicine with the functions of tonifying the kidney and calming the heart, tonifying qi and engendering fluid. It can be used to treat insomnia and dreaminess, spermatorrhea, coughs, as well as liver and kidney deficiency of Yin or Yang Syndrome. Modern pharmacological studies have shown that Schisandra Chinensis regulates host immunity and exhibits anti-cancer, Antiviral and liver-protecting effects. However, the specific mechanism by which Schisandra Chinensis modulates Antiviral immunity is unknown.

Aim of the study: We sought to explore the therapeutic effect of the active components of Schisandra Chinensis on anti-viral immunity and further investigate the underlying mechanism.

Materials and methods: Immunoblotting, quantitative Real-Time PCR, enzyme-linked immunosorbent assay, immunofluorescence, and immunoprecipitation were used to investigate the effect of schisandrin C (SC), one of the most abundant and biologically active components of Schisandra Chinensis, on the activation of cGAS-STING signaling pathway and the underlying mechanism. In addition, CMA-mediated STING activation and hydrodynamic injection-mediated HBV-replicating mouse model were used to investigate the effect of SC on the activation of STING signaling pathway and its Antiviral effect in vivo.

Results: SC promoted cGAS-STING pathway activation, accompanied by increased production of interferon β (IFN β) and downstream gene expression. Moreover, SC also exerted anti-HBV effects, reducing HBeAg, HBcAg, HBsAg, and HBV DNA levels in hydrodynamic injection-mediated HBV-replicating mouse model and elevating the production of IFN β and expression of interferon-stimulated genes (IFIT1, ISG15, and CXCL10). Mechanistically, SC could facilitate the interaction between TANK-binding kinase 1 (TBK1) and STING, which is important for IRF3 phosphorylation and production of IFN β.

Conclusions: Our study confirmed that SC enhances cGAS-STING pathway activation and inhibits HBV replication, as well as provides clues for chronic hepatitis B and other infectious diseases treated by SC.

Keywords

HBV; IFN β; Schisandra chinensis; Schisandrin C; TBK1; cGAS-STING pathway.

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