2. Academic Validation
  3. The combination of Schisandrin C and Luteolin synergistically attenuates hepatitis B virus infection via repressing HBV replication and promoting cGAS-STING pathway activation in macrophages

The combination of Schisandrin C and Luteolin synergistically attenuates hepatitis B virus infection via repressing HBV replication and promoting cGAS-STING pathway activation in macrophages

  • Chin Med. 2024 Mar 18;19(1):48. doi: 10.1186/s13020-024-00888-z.
Zhixin Wu # 1 2,  Xiaomei Zhao # 2,  Ruisheng Li # 3,  Xinru Wen 2,  Ye Xiu 2,  Minjuan Long 1 2,  Junjie Li 2,  Xiuqin Huang 2,  Jincai Wen 2,  Xu Dong 2,  Yingjie Xu 2,  Zhaofang Bai 4 5,  Xiaoyan Zhan 6 7,  Xiaohe Xiao 8 9 10
Affiliations

Affiliations

  • 1 School of Pharmacy, Hunan University of Traditional Chinese Medicine, Changsha, 410208, China.
  • 2 Department of Hepatology, The Fifth Medical Center of Chinese PLA General Hospital, Beijing, 100039, China.
  • 3 Research Institute of Department of Infectious Diseases, 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. baizf2008@hotmail.com.
  • 5 National Key Laboratory of Kidney Diseases, Beijing, China. baizf2008@hotmail.com.
  • 6 Department of Hepatology, The Fifth Medical Center of Chinese PLA General Hospital, Beijing, 100039, China. xyzhan123@163.com.
  • 7 National Key Laboratory of Kidney Diseases, Beijing, China. xyzhan123@163.com.
  • 8 School of Pharmacy, Hunan University of Traditional Chinese Medicine, Changsha, 410208, China. Pharmacy_302@126.com.
  • 9 Department of Hepatology, The Fifth Medical Center of Chinese PLA General Hospital, Beijing, 100039, China. Pharmacy_302@126.com.
  • 10 National Key Laboratory of Kidney Diseases, Beijing, China. Pharmacy_302@126.com.
  • # Contributed equally.
PMID: 38500179 DOI: 10.1186/s13020-024-00888-z
Abstract

Background: HBV Infection can result in severe liver diseases and is one of the primary causes of liver cell carcinoma-related mortality. Liuwei Wuling tablet (LWWL) is a traditional Chinese medicine formula, with a protecting liver and decreasing Enzyme activity, usually used to treat chronic hepatitis B with NAs in clinic. However, its main active ingredients and mechanism of action have not been fully investigated. Hence, we aimed to screen the active ingredient and effective ingredient combinations from Liuwei Wuling tablet to explore the anti-herpatitis B virus activity and mechanism.

Methods: Analysis and screening of effective Antiviral components in LWWL by network pharmacology, luteolin (Lut) may be a compound with significant Antiviral activity. The mechanism of Antiviral action of Lut was also found by Real-Time PCR detection and western blotting. Meanwhile, we established a co-culture model to investigate the Antiviral mechanism of Schisandrin C (SC), one of the main active components of Schisandra chinensis fructus (the sovereign drug of LWWL). Next, HBV-infected mice were established by tail vein injection of pAAV-HBV1.2 plasmid and administered continuously for 20 days. And their Antiviral capacity was evaluated by checking serum levels of HBsAg, HBeAg, levels of HBV DNA, and liver levels of HBcAg.

Results: In this study, we conducted network pharmacology analysis on LWWL, and through in vitro experimental validation and data analysis, we found that luteolin (Lut) possessed obviously anti-HBV activity, inhibiting HBV replication by downregulating hepatocyte nuclear factor 4α (HNF4α) via the ERK pathway. Additionally, we established a co-culture system and proved that SC promoted activation of cGAS-STINIG pathway and IFN-β production in THP-1 cells to inhibit HBV replication in HepG2.2.15 cells. Moreover, we found the combination of SC and Lut shows a greater effect in inhibiting HBV compared to SC or Lut alone in HBV-infected mice.

Conclusion: Taken together, our study suggests that combination of SC and Lut may be potential candidate drug for the prevention and treatment of chronic hepatitis B.

Keywords

Co-culture; Combination therapy; HBV; Liuwei Wuling tablets; Luteolin; Schisandrin C.

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