Ancient Herbal Formula Mahuang Lianqiao Chixiaodou Decoction Protects Acute and Acute-on-Chronic Liver Failure via Inhibiting von Willebrand Factor Signaling

Jiacheng Lin; Qihua Ling; Liang Yan; Bowu Chen; Fang Wang; Yihan Qian; Yueqiu Gao; Qian Wang; Hailong Wu; Xuehua Sun; Yanjun Shi; Xiaoni Kong

doi:10.3390/cells11213368

Ancient Herbal Formula Mahuang Lianqiao Chixiaodou Decoction Protects Acute and Acute-on-Chronic Liver Failure via Inhibiting von Willebrand Factor Signaling

Cells. 2022 Oct 25;11(21):3368. doi: 10.3390/cells11213368.

Authors

Jiacheng Lin¹, Qihua Ling², Liang Yan³, Bowu Chen¹, Fang Wang¹, Yihan Qian¹, Yueqiu Gao¹, Qian Wang², Hailong Wu⁴, Xuehua Sun¹, Yanjun Shi⁵, Xiaoni Kong¹

Affiliations

¹ Central Laboratory, Department of Liver Diseases, ShuGuang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
² Department of Emergency Internal Medicine, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
³ Department of General Practice, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
⁴ Shanghai Key Laboratory of Molecular Imaging, Shanghai University of Medicine and Health Sciences, Shanghai 201318, China.
⁵ Abdominal Transplantation Center, General Surgery, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200025, China.

Abstract

Background: Acute liver failure (ALF) and acute-on-chronic liver failure (ACLF) are characterized by systemic inflammation and high mortality, but there is no effective clinical treatment. As a classic traditional Chinese medicine (TCM) formula, MaHuang-LianQiao-ChiXiaoDou decoction (MHLQD) has been used clinically for centuries to treat liver diseases.

Methods: The LPS/D-GalN-induced ALF mice model and the CCl₄+LPS/D-GalN-induced ACLF mice model were used to observe the therapeutic effects of MHLQD on mice mortality, hepatocytes death, liver injury, and immune responses.

Results: MHLQD treatment significantly improved mice mortality. Liver injury and systemic and hepatic immune responses were also ameliorated after MHLQD treatment. Mechanistically, proteomic changes in MHLQD-treated liver tissues were analyzed and the result showed that the thrombogenic von Willebrand factor (VWF) was significantly inhibited in MHLQD-treated ALF and ACLF models. Histological staining and western blotting confirmed that VWF/RAP1B/ITGB3 signaling was suppressed in MHLQD-treated ALF and ACLF models. Furthermore, mice treated with the VWF inhibitor ADAMTS13 showed a reduced therapeutic effect from MHLQD treatment.

Conclusions: Our study indicated that MHLQD is an effective herbal formula for the treatment of ALF and ACLF, which might be attributed to the protection of hepatocytes from death via VWF/RAP1B/ITGB3 signaling.

Keywords: acute liver failure; acute-on-chronic liver failure; herbal therapy; traditional Chinese medicine; von Willebrand factor.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Acute-On-Chronic Liver Failure* / drug therapy
Animals
Drugs, Chinese Herbal* / pharmacology
Drugs, Chinese Herbal* / therapeutic use
Lipopolysaccharides
Mice
Proteomics
Signal Transduction
von Willebrand Factor* / drug effects
von Willebrand Factor* / metabolism

Substances

Drugs, Chinese Herbal
Lipopolysaccharides
von Willebrand Factor
Mahuang Lianqiao Chixiaodou Decoction

Grants and funding

This research was funded by the National Natural Science Foundation of China (82070633 and 81873582 to X.K., 82004321 to Q.L., 31870905 to H.W., 82074336 to X.S., 82074156 to Q.W.), the Program of Shanghai Academic/Technology Research Leader (20XD1403700) to X.K., and the Budgetary project of Shanghai University of Traditional Chinese Medicine (2020LK050) to L.Y.