• Shanshan Jia, Hua Luo, Xinkui Liu, Xiaotian Fan, Zhihong Huang, Shan Lu, Liangliang Shen, Siyu Guo, Yingying Liu, Zhenzhong Wang, Liang Cao, Zeyu Cao, Xinzhuang Zhang, Wei Zhou, Jingyuan Zhang, Jialin Li, Jiarui Wu, and Wei Xiao.
• Department of Clinical Chinese Pharmacy, School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, 100102, China. Electronic address: cristielove@163.com.
• J Ethnopharmacol. 2021 Jun 12; 273: 113871.

Ethnopharmacological RelevanceReduning injection (RDNI) is a patented Traditional Chinese medicine that contains three Chinese herbal medicines, respectively are the dry aboveground part of Artemisia annua L., the flower of Lonicera japonica Thunb., and the fruit Gardenia jasminoides J.Ellis. RDNI has been recommended for treating Coronavirus Disease 2019 (COVID-19) in the "New Coronavirus Pneumonia Diagnosis and Treatment Plan".Aim Of The StudyTo elucidate and verify the underlying mechanisms of RDNI for the treatment of COVID-19.MethodsThis study firstly performed anti-SARS-CoV-2 experiments in Vero E6 cells. Then, network pharmacology combined with molecular docking was adopted to explore the potential mechanisms of RDNI in the treatment for COVID-19. After that, western blot and a cytokine chip were used to validate the predictive results.ResultsWe concluded that half toxic concentration of drug CC50 (dilution ratio) = 1:1280, CC50 = 2.031 mg crude drugs/mL (0.047 mg solid content/mL) and half effective concentration of drug (EC50) (diluted multiples) = 1:25140.3, EC50 = 103.420 μg crude drugs/mL (2.405 μg solid content/mL). We found that RDNI can mainly regulate targets like carbonic anhydrases (CAs), matrix metallopeptidases (MMPs) and pathways like PI3K/AKT, MAPK, Forkhead box O s and T cell receptor signaling pathways to reduce lung damage. We verified that RDNI could effectively inhibit the overexpression of MAPKs, PKC and p65 nuclear factor-κB. The injection could also affect cytokine levels, reduce inflammation and display antipyretic activity.ConclusionRDNI can regulate ACE2, Mpro and PLP in COVID-19. The underlying mechanisms of RDNI in the treatment for COVID-19 may be related to the modulation of the cytokine levels and inflammation and its antipyretic activity by regulating the expression of MAPKs, PKC and p65 nuclear factor NF-κB.Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.

40 keywords...

hide…