Aim and Objective:
Maxingyigan (MXYG) decoction is a traditional Chinese medicine (TCM) prescription.
However, how MXYG acts against coronavirus disease 2019 (COVID-19) is not known. We investigated the active ingredients and the therapeutic targets of MXYG decoction against COVID-19.
Methods:
A network pharmacology strategy involving drug-likeness evaluation, prediction of oral bioavailability, network
analyses, and virtual molecular docking were used to predict the mechanism of action of MXYG against COVID-19.
Results:
Thirty-three core COVID-19-related targets were identified from 1023 gene targets through analyses of protein–
protein interactions. Eighty-six active ingredients of MXYG decoction hit by 19 therapeutic targets were screened out by
analyses of a compound–compound target network. Via network topology, three “hub” gene targets (interleukin (IL-6),
caspase-3, IL-4) and three key components (quercetin, formononetin, luteolin) were recognized and verified by molecular
docking. Compared with control compounds (ribavirin, arbidol), the docking score of quercetin to the IL-6 receptor was
highest, with a score of 5. Furthermore, the scores of three key components to SARS-CoV-2 are large as 4, 5, and 5, respectively, which are even better than those of ribavirin at 3. Bioinformatics analyses revealed that MXYG could prevent and
treat COVID-19 through anti-inflammatory and immunity-based actions involving activation of T cells, lymphocytes, and
leukocytes, as well as cytokine–cytokine-receptor interaction, and chemokine signaling pathways.
Conclusion:
The hub genes of COVID-19 helped to reveal the underlying pathogenesis and therapeutic targets of COVID19. This study represents the first report on the molecular mechanism of MXYG decoction against COVID-19.
Obesity is recognized as not only a major contributing factor to cardiovascular diseases but also an independent risk factor for end-stage renal disease. Previous studies have found that Huoxue Qianyang Qutan Recipe (HQQR) could reduce urinary microalbumin in patients with obesity-related hypertension (OBH). However, the renal protective activity of HQQR in OBH and its molecular targets involved remains ambiguous. In this work, we investigate the mechanism of HQQR against OBH-induced early renal damage using integrating network pharmacology and experimental validation-based strategy. First, via network pharmacology, IL-6 is identified as one of the key targets of HQQR against early renal damage in hypertension, and inhibition of inflammation is a crucial process. Second, in in vivo experiments, HQQR can lower blood pressure, lose weight, and restore metabolic abnormalities in OBH rats, which could be associated with the effects on protecting early renal damage. Finally, in the mechanism, HQQR increases SIRT1 mRNA and protein expression consistent with reduction of NF-κB acetylation and suppressed the p65-mediated inflammatory signaling pathway. As a result, HQQR robustly inhibits OBH-induced renal inflammation by reducing IL-6 mRNA and protein levels in the renal tissue and the release of IL-6 in serum of OBH rats. This study aims to provide a multimethod (network pharmacology-animal experiment) and multilevel (component-target-pathway) strategy for the prevention and treatment of OBH-induced target organ damage by traditional Chinese medicine.
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