主 办:北 京 中 医 药 大 学
ISSN 1006-2157 CN 11-3574/R

JOURNAL OF BEIJING UNIVERSITY OF TRADITIONAL CHINESE MEDICINE ›› 2021, Vol. 44 ›› Issue (4): 340-349.doi: 10.3969/j.issn.1006-2157.2021.04.009

• Chinese Medicinal Pharmacology • Previous Articles     Next Articles

Multi-level mechanisms of Chuanlong decoction in treating rheumatic arthritis from the perspective of systems pharmacology*

Jiang Li1,2, Liang Shengnan3, Wang Haiqing4, GuoZihu2,4, Wang Yonghua1,2,4#   

  1. 1 Key Laboratory of Xinjiang Phytomedicine Resource and Utilization, Ministry of Education, Shihezi University, Xinjiang 832000, China;
    2 Collaborative Innovation Center of Qiyao in Mt. Qinling, Shaanxi 712100, China;
    3 School of Chemistry & Pharmacy, Northwest A & F University, Shaanxi 712100, China;
    4 Key Laboratory of Resource Biology and Biotechnology in Western China, Ministry of Education, School of Life Sciences, Northwest University, Shaanxi 712100, China
  • Received:2020-09-29 Published:2021-04-29
  • Contact: Prof. Wang Yonghua, Ph. D., Key Laboratory of Xinjiang Phytomedicine Resource and Utilization, Ministry of Education, Shihezi University, Xinjiang 832002, E-mail: dcpwyh@163.com
  • Supported by:
    National Natural Science Foundation of China (No.U1603285); National Science and Technology Major Project (No. 2019ZX09201004-001)
    Ethical review: Committee of Ethic Review on Medical and Experimental Animals in Jiangsu Kanion Pharmaceutical Co.Ltd. (No. 2020072003)

Abstract: Objective To study the effects and mechanism of Chuanlong Decoction (CLT), a formula containing Chuanshanlong (Rhizoma Dioscorae Nipponicae) as the major ingredient and also a regional featured herb in Mt. Qingling area. Methods The candidate active ingredients of each herb in CLT Decoction were screened by using the Traditional Chinese Medicine System Pharmacology (TCMSP). Potential targets of these compounds were identified with System Drug Target Model (SysDT) and Weighted Ensemble Similarity (WES); a compound-target network was subsequently constructed. Further, network analysis and functional enrichment analysis were used to uncover the biological processes and signal pathways involved in these pharmacological targets. β-sitosterol, the main active ingredient in CLT Decoction, was selected to test in mice in vivo. Chronic inflammation model was established by using Freund's complete adjuvant (0.02 mL/per mouse). Mice were randomly divided into four groups: normal group, model group, β-sitosterol group and dexamethasone group (n=6 in each group for 7-day continuous intervention). The degree of synovial inflammation was measured with HE staining; The mRNA expressions of TNF-α and IL-6 in synovial tissue were detected by using RT-PCR. Results 27 candidate active ingredients in CLT Decoction were screened, and 148 pharmacological targets of arthritis were predicted. Network analysis and enrichment analysis revealed that the main active ingredients in CLT Decoction including diosgenin, β-sitosterol, cyasterone, lonicerin and onychin can regulate bone cellular proliferation, apoptosis, anti-inflammatory and immunosuppression processes via PI3K-AKT, TNF and Toll-like receptor signaling pathways. The results showed that the synovial layer significantly thickened, and that the inflammatory infiltration increased in the model group. After treatment with β-sitosterol and dexamethasone, the severity of synovial inflammation were significantly reduced, and the levels of TNF-α and IL-6 were also reduced compared with the model group (P<0.05). These results were consistent with the system pharmacological prediction results, indicating that the system pharmacological prediction was quite accurate. Conclusion Different herbal medicines in CLT Decoction may have played different roles in mechanism of action in the treatment of RA, mostly involved in TNF-α and Toll-like signaling pathways.

Key words: Qiyao in Mt. Qinling, Chuanlong Decoction, systems pharmacology, arthritis, compatibility of Chinese medicine, verification, mice

CLC Number: 

  • R285.5