Drug Design, Development and Therapy (Oct 2023)
Polygonum Cuspidatum Alcohol Extract Exerts Analgesic Effects via the MAPK/ERK Signaling Pathway
Abstract
Yan Lan,1,2,* Yu-Kun Zheng,3,* Liu-Yi Wu,3 Zi-Jun Zhou,3 Ruo-Xin Guan,3 Heng Xu,3 Ji-Yuan Tu,3 Xin Gu,3 Rui Wang,3 Nan Jiang,3 Yuan Wu,4 Cheng-Ren Shu,1,2 Zhong-Shi Zhou3 1Department of Pharmacy, Huangshi Central Hospital, Affiliated Hospital of Hubei Polytechnic University, Huangshi, Hubei, People’s Republic of China; 2Hubei Key Laboratory of Kidney Disease Pathogenesis and Intervention, Hubei, People’s Republic of China; 3College of Pharmacy, Hubei University of Chinese Medicine, Wuhan, Hubei, People’s Republic of China; 4Department of Radiation Oncology, Hubei Cancer Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, People’s Republic of China*These authors contributed equally to this workCorrespondence: Cheng-Ren Shu, Department of Pharmacy, Huangshi Central Hospital, NO. 141, Tianjin Road, Huangshi, Hubei, People’s Republic of China, Tel +86-27-13986590438, Email [email protected] Zhong-Shi Zhou, College of Pharmacy, Hubei University of Chinese Medicine, No. 1, Huangjiahu West Road, Hongshan District, Wuhan City, Hubei Province, People’s Republic of China, Tel +86-27-15871745189, Email [email protected]: Traditional Chinese medicine Polygonum cuspidatum (PC) has significant effects on reducing pain. In this study, we investigated the analgesic effects of the alcohol extract of PC on three types of inflammatory pain and explored its mechanism.Methods: Potential targets for the analgesic effects of the main active components of PC alcohol extract were screened by network pharmacology and molecular docking. Three different inflammatory pain mouse models (acetic acid twisting, formalin foot swelling, and xylene ear swelling) were used to study the analgesic effects of PC. The expression of latent signaling pathways in L4-6 spinal cord tissues in formalin foot swelling mice was evaluated using real-time qPCR (RT-qPCR), Western blot (WB), and immunohistochemistry (IHC) analyses.Results: Network pharmacology analysis shows that PC analgesic mechanism is related to the MAPK/ERK signaling pathway. The five main active components of PC have good docking ability with JNK and p38. PC alcohol extract significantly reduced the pain behavior and alleviated inflammatory reactions in three mouse models, inhibited the mRNA and protein phosphorylation levels of JNK, ERK, p38, and CREB in spinal cord tissues.Conclusion: PC alcohol extract can inhibit inflammation and alleviate pain, which is related to its inhibition of the MAPK/ERK signaling pathway in spinal cord. Thus, PC alcohol extract is a promising candidate for pain treatment.Keywords: Polygonum cuspidatum, network pharmacology, MAPK/ERK, analgesic