Chemical profiling and investigation of molecular mechanisms underlying anti-hepatocellular carcinoma activity of extracts from Polygonum perfoliatum L

Xiaolong Tang; Lin Liu; Yan Li; Siyu Hao; Yueshui Zhao; Xu Wu; Mingxing Li; Yu Chen; Shuai Deng; Shuang Gou; Dan Cai; Meijuan Chen; Xiaobing Li; Yuhong Sun; Li Gu; Wanping Li; Fang Wang; Zhuo Zhang; Lei Yao; Jing Shen; Zhangang Xiao; Fukuan Du

doi:10.1016/j.biopha.2023.115315

Chemical profiling and investigation of molecular mechanisms underlying anti-hepatocellular carcinoma activity of extracts from Polygonum perfoliatum L

Biomed Pharmacother. 2023 Oct:166:115315. doi: 10.1016/j.biopha.2023.115315. Epub 2023 Aug 12.

Authors

Xiaolong Tang¹, Lin Liu², Yan Li³, Siyu Hao², Yueshui Zhao², Xu Wu², Mingxing Li², Yu Chen², Shuai Deng², Shuang Gou², Dan Cai², Meijuan Chen⁴, Xiaobing Li⁴, Yuhong Sun⁴, Li Gu⁴, Wanping Li⁴, Fang Wang⁴, Zhuo Zhang⁴, Lei Yao⁵, Jing Shen⁶, Zhangang Xiao⁷, Fukuan Du⁸

Affiliations

¹ Laboratory of Molecular Pharmacology, Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou 646600, Sichuan, China; Cell Therapy & Cell Drugs of Luzhou Key Laboratory, Luzhou 646000, Sichuan, China; South Sichuan Institute of Translational Medicine, Luzhou 646600, Sichuan, China; The Key Laboratory for Human Disease Gene Study of Sichuan Province and Department of Laboratory Medicine, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu 610072, China; Research Unit for Blindness Prevention of Chinese Academy of Medical Science (2019RU026), Sichuan Academy of Medical Sciences, Chengdu 610072, China.
² Laboratory of Molecular Pharmacology, Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou 646600, Sichuan, China; Cell Therapy & Cell Drugs of Luzhou Key Laboratory, Luzhou 646000, Sichuan, China; South Sichuan Institute of Translational Medicine, Luzhou 646600, Sichuan, China.
³ Laboratory of Molecular Pharmacology, Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou 646600, Sichuan, China; Public Center of Experimental Technology, Southwest Medical University, Luzhou 646000, Sichuan, China.
⁴ Laboratory of Molecular Pharmacology, Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou 646600, Sichuan, China.
⁵ The Key Laboratory for Human Disease Gene Study of Sichuan Province and Department of Laboratory Medicine, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu 610072, China; Research Unit for Blindness Prevention of Chinese Academy of Medical Science (2019RU026), Sichuan Academy of Medical Sciences, Chengdu 610072, China.
⁶ Laboratory of Molecular Pharmacology, Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou 646600, Sichuan, China; Cell Therapy & Cell Drugs of Luzhou Key Laboratory, Luzhou 646000, Sichuan, China; South Sichuan Institute of Translational Medicine, Luzhou 646600, Sichuan, China. Electronic address: crystal_stray@126.com.
⁷ Laboratory of Molecular Pharmacology, Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou 646600, Sichuan, China; Cell Therapy & Cell Drugs of Luzhou Key Laboratory, Luzhou 646000, Sichuan, China; South Sichuan Institute of Translational Medicine, Luzhou 646600, Sichuan, China; Department of Oncology, Affiliated Hospital of Southwest Medical University, Luzhou 646600, Sichuan, China. Electronic address: xzg555898@hotmail.com.
⁸ Laboratory of Molecular Pharmacology, Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou 646600, Sichuan, China; Cell Therapy & Cell Drugs of Luzhou Key Laboratory, Luzhou 646000, Sichuan, China; South Sichuan Institute of Translational Medicine, Luzhou 646600, Sichuan, China. Electronic address: adublg@126.com.

PMID: 37579693
DOI: 10.1016/j.biopha.2023.115315

Abstract

Polygonum perfoliatum L. is an herbal medicine that has been extensively used in traditional Chinese medicine to treat various health conditions ranging from ancient internal to surgical and gynecological diseases. Numerous studies suggest that P. perfoliatum extract elicits significant anti-tumor, anti-inflammatory, anti-bacterial, and anti-viral effects. Nevertheless, the underlying mechanisms of its anti-liver cancer effects remain poorly understood. Our study suggests that P. perfoliatum stem extract (PPLA) has a favorable safety profile and exhibits a significant anti-liver cancer effect both in vitro and in vivo. We identified that PPLA activates the cGMP-PKG signaling pathway, and key regulatory genes including ADRA1B, PLCB2, PRKG2, CALML4, and GLO1 involved in this activation. Moreover, PPLA modulates the expression of genes responsible for the cell cycle. Additionally, we identified four constituents of PPLA, namely taxifolin, myricetin, eriodictyol, and pinocembrin, that plausibly act via the cGMP-PKG signaling pathway. Both in vitro and in vivo experiments confirmed that PPLA, along with its constituting compounds taxifolin, myricetin, and eriodictyol, exhibit potent anti-cancer activities and hold the promise of being developed into therapeutic agents.

Keywords: Hepatocellular carcinoma; Molecular docking simulation; Polygonum perfoliatum L..

MeSH terms

Anti-Inflammatory Agents / chemistry
Carcinoma, Hepatocellular* / drug therapy
Humans
Liver Neoplasms* / drug therapy
Plant Extracts / chemistry
Plant Extracts / pharmacology
Plant Extracts / therapeutic use
Plants, Medicinal*
Polygonum* / chemistry

Substances

Anti-Inflammatory Agents
Plant Extracts