Gut microbiota-mediated metabolism of Panax notoginseng saponins and its role in pharmacokinetics and pharmacodynamics

Panax notoginseng saponins(PNS)are a class of effective ingredients in Notoginseng Radix et Rhizoma,a well-known herbal medicine called San-Qi in Chinese.After oral administration,PNS inevitably interacts with gut microbiota,and thus affect the pharmacokinetic profiles and pharmacological effects.To date,studies concering gut microbiota-mediated metabolism of PNS have not been reviewed systematically.Herein,we outline the metabolic profiles of Panax notoginseng saponins mediated by gut microbiota,as well as its role in the pharmacokinetics and pharmacodynamics on the basis of reported data.The metabolic pathways of primary saponins are proposed,and step-by-step deglycosylation is found to be the primary degradation pathways of PNS mediated by gut microbiota.Specific microorganisms and enzymes involved in the metabolic processes were summarized.Gut microbiota is deeply involved in the metabolism of PNS,affects the pharmacokinetic profiles,and produces a series of active metabolites.These metabolites were documented to play an essential role in the efficacy of the parent compounds.Future studies should focus on strengthening the real-world evidence,defining the interaction between gut microbiota and PNS,and developing the strategy for modulating gut microbiota to enhance the bioavailability and efficacy of PNS.These information would be useful for further research and clinical application of PNS.

The potential application of the traditional Chinese herb Exocarpium Citri grandis in the prevention and treatment of COVID-19

Huajuhong(Exocarpium Citri grandis,ECG)is a traditional Chinese herbal medicine and has been used for the treatment of respiratory diseases for hundreds of years.Recently,ECG has been listed in a traditional Chinese medicine formula in the Guidelines for the Diagnosis and Treatment of Coronavirus Disease 2019(sixth edition)in China.To date,the effect and mechanism of ECG against respiratory diseases have not been systematically reviewed.In this paper,the researchers summarized the effects of ECG and its pharmacologically active compound naringin in functioning as an antitussive and expectorant,improving lung function,alleviating acute lung injury,attenuating pulmonary fibrosis,and enhancing antiviral immune response,so as to provide a reference for its clinical application in the prevention and treatment of multiple respiratory diseases,including coronavirus disease 2019.

Role of community-based active case finding in screening tuberculosis in Yunnan province of China

Background:The barriers to access diagnosis and receive treatment,in addition to insufficient case identification and reporting,lead to tuberculosis(TB)spreads in communities,especially among hard-to-reach populations.This study evaluated a community-based active case finding(ACF)strategy for the detection of tuberculosis cases among high-risk groups and general population in China between 2013 and 2015.Methods:This retrospective cohort study conducted an ACF in ten communities of Dongchuan County,located in northeast Yunnan Province between 2013 and 2015;and compared to 136 communities that had passive case finding(PCF).The algorithm for ACF was:1)screen for TB symptoms among community enrolled residents by home visits,2)those with positive symptoms along with defined high-risk groups underwent chest X-ray(CXR),followed by sputum microscopy confirmation.TB incidence proportion and the number needed to screen(NNS)to detect one case were calculated to evaluate the ACF strategy compared to PCF,chi-square test was applied to compare the incidence proportion of TB cases'demography and the characteristics for detected cases under different strategies.Thereafter,the incidence rate ratio(IRR)and multiple Fisher's exact test were applied to compare the incidence proportion between general population and high-risk groups.Patient and diagnostic delays for ACF and PCF were compared by Wilcoxon rank sum test.Results:A total of 97521 enrolled residents were visited with the ACF cumulatively,12.3%were defined as highrisk groups or had TB symptoms.Sixty-six new TB patients were detected by ACF.There was no significant difference between the cumulative TB incidence proportion for ACF(67.7/100000 population)and the prevalence for PCF(62.6/100000 population)during 2013 to 2015,though the incidence proportion in ACF communities decreased after three rounds active screening,concurrent with the remained stable prevalence in PCF communities.The cumulative NNS were 34,39 and 29 in HIV/AIDS infected individuals,people with positive TB symptoms and history of previous TB,respectively,compared to 1478 in the general population.The median patient delay under ACF was 1 day(Interquartile range,IQR:0-27)compared to PCF with 30 days(IQR:14-61).Conclusions:This study confirmed that massive ACF was not effective in general population in a moderate TB prevalence setting.The priority should be the definition and targeting of high-risk groups in the community before the screening process is launched.The shorter time interval of ACF between TB symptoms onset and linkage to healthcare service may decrease the risk of TB community transmission.Furthermore,integrated ACF strategy in the National Project of Basic Public Health Service may have long term public health impact.

Common mechanism of Citrus Grandis Exocarpium in treatment of chronic obstructive pulmonary disease and lung cancer

Objective:"Same treatment for different diseases"is a unique treatment strategy in traditional Chinese medicine.Two kinds of malignant respiratory diseases endanger human health-chronic obstructive pulmonary disease(COPD)and lung cancer.Citrus Grandis Exocarpium(Huajuhong in Chinese,HJH),a famous herbal,is always applied by Chinese medicine practitioners to dispersion the lung to resolve phlegm based on"syndrome differentiation and treatment"theory.However,the common mechanism for HJH’s treatment of COPD and lung cancer is not clear.Methods:In this study,based on network pharmacology and molecular docking technology,the common mechanism of HJH in the treatment of COPD and lung cancer was studied.The active ingredients and related targets of HJH were integrated from TCMSP,BATMAN-TAM,STP,and Pubchem databases.The standard names of these targets were united by Uni Prot database.Targets of COPD and lung cancer were enriched through Gene Cards,NCBI(Gene),Therapeutic Target Database,and Dis Ge NET(v7.0)databases.Then the intersection targets of HJH and diseases were obtained.The STRING network and the Cytoscape 3.7.2 were used to construct PPI network,the DAVID database was used to perform GO and KEGG analysis.Then Cytoscape 3.6.1 was used to build"ingredient-target-signal pathway"network.Finally,Auto Dock 1.5.6 software was used to perform molecular docking of key proteins and molecules.Results:Eleven active ingredients in HJH were obtained by searching the database,corresponding to 184 HJH-COPD-lung cancer targets intersection.The results of biological network analysis showed that naringenin,the active component in HJH,could mainly act on target proteins such as AKT1,EGFR.Then through positive regulation of vasoconstriction and other biological processes,naringenin could regulate estrogen signaling pathway,VEGF signaling pathway,HIF-1 signaling pathway,Erb B signaling pathway,PI3K-Akt signaling pathway to play an important role in the treatment of both COPD and lung cancer.Conclusion:Network pharmacology was employed to systematically investigate the active ingredients and targets of HJH in treatment of COPD and lung cancer.And then,the common pharmacodynamic network of HJH for the two malignant respiratory diseases was firstly described.Furthermore,naringenin was proved to strongly bind with AKT1 and EGFR.It may provide the scientific basis for understanding the"Same treatment for different diseases"strategy in traditional Chinese medicine and inspirit subsequent drug discovery for COPD,lung cancer and other malignant lung diseases.