Research on the potential mechanism of Huashi Baidu Recipe against novel coronavirus pneumonia(COVID-19)by network pharmacology and molecular docking technology

Objective:Use network pharmacology to explore the anti-COVID-19 mechanism of Huashi Baidu Recipe,supplemented by molecular docking verification.Methods:Thorugh databases such as TCMSP,GeneCard,String,and software such as Cytoscape,AutoDockVina,network relationships was established,and the binding ability of active ingredients and targets is calculated through molecular docking,and biological function enrichment analysis was conducted.Result:The ingredients in Huashi Baidu Recipe that had strong affinity with SARS-CoV-23CL hydrolase(3CLpro)and angiotensin converting enzyme 2(ACE2)receptors include Quercetin,Baicalein,Astragaloside IV,Wogonin and other ingredients;25 active ingredients which obtained by screening had strong affinity with targets such as IL6,IL1B,NOS2 and CCL2.The biological function enrichment analysis mainly focused on Th17,Th1 and Th2 cell differentiation,NF-κB,MAPK,TNF,IL-17signaling pathway,etc.Conclusion:The active ingredients of Huashi Baidu Recipe may inhibit the infection and replication of SARS-CoV-2 virus,regulate RAS system’balance,inhibit excessive immune inflammatory response,and prevent inflammatory storm from appearing to fight COVID-19.

Potential mechanism of Xuanfei Baidu Formula in treating new coronavirus pneumonia based on network pharmacology and molecular docking

Objective:To investigate the molecular mechanism of antiviral effect of Xuanfei Baidu Formula in the treatment of coronavirus disease 2019(COVID-19),and to provide reference for the twreatment of COVID-19 with traditional Chinese medicine.Methods:Traditional Chinese Medicine Systems Pharmacology(TCMSP)was employed to search the effective active component and targets of Xuanfei Baidu Formula.Databases,GeneCards etc.were employed to obtain the relevant target genes of COVID-19 and intersect with the targets of Xuanfei Baidu Formula to obtain the therapeutic targets.The therapeutic targets were uploaded to the STRING database to obtain protein interaction(PPI)information,and Cytoscape was utilized to construct drug-target-disease networks,high-confidence PPI networks for target proteins,and active-target-pathway networks.GO,gene ontology,functional analysis and KEGG(Kyoto Encyclopedia of Genes and Genomes)pathway enrichment analysis of potential targets of action were performed using the R package in Bioconductor.The main active components were molecular docking technology with 3C-like protease(3CLPro)and angiotensin-cinverting enzyme2(ACE2)and key targets of SARS-CoV-2,respectively.Results:A total of 99 effective active ingredients of Xuanfei Baidu Formula were selected,of which 22 active ingredients acting on COVID-19 could act on COVID-19 through 52 potential targets.Enrichment yielded 1,364 biological process entries and 22 KEGG pathways in GO,involving paths such as IL-17,JAK-STAT,MAPK,NF-κB,PI3K-Akt,Th1 and Th2 cell differentiation,Th17 cell differentiation,T cell receptor,vascular endothelial growth factor(VEGF)and Salmonella infection.Molecular docking technology results revealed that active components such as luteolin,beta-sitostero,formononetin,and shinpterocarpin in Xuanfei Baidu Formula embraced satisfactory binding to 3CLPro and ACE2,and also had good binding to core targets.Conclusion:Xuanfei Baidu Formula inhibits viral invasion and viral replication mainly by binding to ACE2 and 3CLPro receptors of SARS-CoV-2 through flavonoids and phytosterols,and may play a role in the treatment of COVID-19 by regulating key targets such as IL6,MAPK3,MAPK1,IL1β,CCL2,EGFR,and NOS2 after virus infection of cells,exerting anti-cytokine storm,anti-oxidation,and regulating the body's immunity.

Research progress on the role of gut microbiota dysregulation in the pathogenesis of diabetic nephropathy

There are about over 100 trillion microbial cells in human gut,which affect the nutritional,metabolic,physiological and immune functions of the host.This paper reviews the differences in gut microbiota between patients with diabetic nephropathy(DN)and healthy people.These differences lead to the disorder of symbiotic relationship,which may have induced the progression of DN,as well as targeted interventions to reconstruct the symbiotic relationship.Recent studies have found that endotoxin from intestinal bacteria and a large number of toxic metabolites were produced by fermentation of gut microbiota,such as trimethylamine-N-oxide,indoxyl sulfate and p-cresol sulfate,leading to the disruption of intestinal barrier function.Endotoxin and bacterial metabolites,entering the systemic circulation,were involved in DN progression by mediating inflammatory responses,renin-angiotensin-system and vascular injury.The reduction of some beneficial bacterial metabolites in DN patients,such as short-chain fatty acids,would weak body energy metabolism and destroy glucose homeostasis.In addition,gut microbiota is essential for the conversion of bile acids,and plays an important role in the development of DN by synthesizing secondary bile acids and regulating glucose and metabolic balance through foresaid X receptor(FXR)and G protein-coupled bile acid receptor(TGR5).Animal and clinical studies have revealed that probiotics,prebiotics,fecal microbiota transplantation,and Chinese medicine intervention may have potential therapeutic effects in maintaining a metabolically balanced gut microbiota to reduce the progression of DN,end-stage renal disease and cardiovascular complications.

Discussion on the composing principle of "Qingfei Paidu Decoction"in the treatment of anti-COVID-19 from the theory of syndrome-differentiation of the six meridians in Treatise on Febrile Diseases

The coronavirus disease 2019(COVID-19)was a newly discovered infectious respiratory disease and characterized by wide prevalence,high incidence rate and fast progress and dangerous,which belonged to the category of"cold-wet plague"in TCM.The onset of COVID-19 was caused by pestilence,which mingled with seasonal cold-dampness and invaded the human body when external defensive qi was weak and then leaded to the accumulation of Yang qi.Different from exogenous pathogenic factors transmitted from the external to the internal or followed the transmission law of Wei,Qi,Ying and Xue,the nature of pestilence belonged to the category of pathogenic fire,spreading as soon as possible,from the external to the internal and from the upper and lower part of triple energizer,even to every part.At the very beginning,the pestilence attacked from the Taiyang meridian into the Yangming meridian quickly,or straight into the three Yang meridian,which was called"triple-yang combination of diseases".Manifestations of fever,aversion to cold and pain of body were conformed to the exterior syndrome of Taiyang,as well as manifestations of fullness and discomfort in chest,vomiting and spitting and diarrhea were conformed to the syndrome of half-interior-half-exterior;And symptoms manifested as high fever,faint,and abdominal fullness and constipation were conformed to the syndrome of Yangming;But sometimes,there was cold-dampness surrounding the exterior at the beginning along with intense interior pathogenic fire.Or at the beginning,the exterior factors invaded into three Yin meridians quickly while have not been eliminated,which may lead to the syndrome of inner blocking causing collapse or Jue exhaustion.The most typical syndrome of COVID-19 was triple-yang combination of diseases,which was often seen in mild,moderate and part of severe cases.Hence"Qingfei Paidu Decoction"was prescribed especially for this kind of syndrome.Its accurate efficacy has been proved by that mild cases converting to severe cases in the mobile cabin hospital have been effectively restrained and thus the progression of the disease has blocked.Composition analysis showed that Mahuang decoction with Maxing Shigan decoction was to relieve exterior Taiyang syndrome,Xiaochaihu decoction was for harmonizing half-superficies and half-interior Shaoyang syndrome,and large dose of gypsum was used to clear interior heat of the Yangming meridian,and Shegan Mahuang decoction and Xiaoqinglong plus gypsum decoction was for lowering the adverse qi and resolving fluid,and Wuling San was for warming the triple energizer and transforming qi and draining water."Qingfei Paidu Decoction"was an syncretic innovation of classical prescriptions from Treatise on Febrile Diseases,which was not made up of herbs but multiple concordant prescriptions helping to get twice the result with half the effort,so that the"cold-wet plague"can be quickly discharged.