Chinese Journal of Tissue Engineering Research ›› 2024, Vol. 28 ›› Issue (28): 4516-4521.doi: 10.12307/2024.456

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Semen cuscutae in the treatment of osteoarthritis: network pharmacology analysis and experimental validation

Zhang Tiandong1, Peng Qingping1, Liu Huan2, Feng Jianguo3, Yi Qian4, Huang Wenhua1, 5   

  1. 1School of Integrated Traditional Chinese and Western Medicine, Southwest Medical University, Luzhou 646000, Sichuan Province, China; 2Department of Physiology, School of Basic Medical Science, Southwest Medical University, Luzhou 646000, Sichuan Province, China; 3Department of Orthopedics, The Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University, Luzhou 646000, Sichuan Province, China; 4Department of Anesthesiology, the Affiliated Hospital of Southwest Medical University, Luzhou 646000, Sichuan Province, China; 5Guangdong Engineering Research Center for Translation of Medical 3D Printing Application, Guangdong Provincial Key Laboratory of Digital Medicine and Biomechanics, National Key Discipline of Human Anatomy, Southern Medical University, Guangzhou 510515, Guangdong Province, China
  • Received:2023-07-03 Accepted:2023-08-21 Online:2024-10-08 Published:2023-11-27
  • Contact: Huang Wenhua, Professor, School of Integrated Traditional Chinese and Western Medicine, Southwest Medical University, Luzhou 646000, Sichuan Province, China; Guangdong Engineering Research Center for Translation of Medical 3D Printing Application, Guangdong Provincial Key Laboratory of Digital Medicine and Biomechanics, National Key Discipline of Human Anatomy, Southern Medical University, Guangzhou 510515, Guangdong Province, China
  • About author:Zhang Tiandong, Master candidate, Physician, School of Integrated Traditional Chinese and Western Medicine, Southwest Medical University, Luzhou 646000, Sichuan Province, China
  • Supported by:
    Special Support Project for High-level Talents (Zhong Shizhen Team) of Southwest Medical University, No. 02061648361 (to HWH); National Key Research and Development Program of China, No. 2022YFB4600600 (to HWH); National Natural Science Foundation of China, No. 32271181 (to HWH); Luzhou Science and Technology Plan Project, No. 2021-JYJ-71 (to YQ); Sichuan Science and Technology Joint Innovation Special Project, No. 2022YFS0609 (to YQ); Natural Science Foundation of Sichuan Province, No. 22NSFSC3871 (to YQ)

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Abstract: BACKGROUND: Semen cuscutae has the effect of tonifying the liver and kidney system and benefiting the essence. The main pathogenesis of osteoarthritis is deficiency of the liver and kidneys. Therefore, it is hypothesized that there is a link between semen cuscutae and osteoarthritis.
OBJECTIVE: To explore the potential relationship between osteoarthritis and semen cuscutae and validate the mechanism of semen cuscutae based on the network pharmacology and molecular docking analysis.
METHODS: First, the active ingredients and targets of semen cuscutae were screened in TCMSP, and the genes related to osteoarthritis were collected in the disease databases GeneCard’s, OMIM and TTD. The intersected genes were taken and then subjected to a series of analyses and screened for hub genes. Through the enrichment analysis of hub genes, the pathway of semen cuscutae acting on osteoarthritis was selected. The role of hub genes was verified by molecular docking. Therefore, the appropriate active ingredients of semen cuscutae were selected for experimental verification.
RESULTS AND CONCLUSION: There were 11 active ingredients of semen cuscutae, 66 intersection target genes of semen cuscutae and osteoarthritis, and 12 hub genes, including tumor necrosis factor, interleukin 1B, TP53, RAC-alpha serine/threonine protein kinase (AKT1), vascular endothelial growth factor A, matrix metalloproteinase 9, prostaglandin peroxidase 2, cystatinase 3, epidermal growth factor, peroxisome proliferator-activated receptor gamma, interleukin 10, vascular cell adhesion factor 1. After the enrichment analysis of the hub genes, the classical inflammatory pathway, nuclear factor-κB signaling pathway, was selected for subsequent validation of semen cuscutae to alleviate osteoarthritic inflammation. Through the results obtained after molecular docking of each active ingredient and the hub gene of the pathway prostaglandin peroxidase 2, sesamin with the highest affinity was selected for subsequent cell experiments, and the experimental results confirmed that sesamin, the active ingredient of semen cuscutae, could reduce the expression of cyclooxygenase 2 by inhibiting the nuclear factor-κB signaling pathway induced by interleukin-1β. To conclude, sesamin, the active ingredient of semen cuscutae, reduces the expression of cyclooxygenase 2 by inhibiting the nuclear factor-κB signaling pathway induced by interleukin-1β, thereby improving inflammation in osteoarthritis and expanding the therapeutic effect of semen cuscutae in osteoarthritis.

Key words: semen cuscutae, osteoarthritis, sesamin, nuclear factor-κB signaling pathway, cyclooxygenase 2, network pharmacology, molecular docking, inflammation

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