Geographical authenticity evaluation of Mentha haplocalyx by LIBS coupled with multivariate analyzes

Mentha haplocalyx(mint)is a significant traditional Chinese medicine(TCM)listed in the Catalogue of’Medicinal and Food Homology’,therefore,its geographical origins(GOs)are critical to the medicinal and food value.Laser-induced breakdown spectroscopy(LIBS)is an advanced analytical technique for GOs certification,due to the fast multi-elemental analysis requiring minimal sample pretreatment.In this study,LIBS data of sampled mint from five GOs were investigated by LIBS coupled with multivariate statistical analyzes.The spectral data was analyzed by two chemometric algorithms,i.e.principal component analysis(PCA)and least squares support vector machines(LS-SVM).Specifically,the performance of LS-SVM with least kernel and radial basis function(RBF)kernel was explored in sensitivity and robustness tests.Both LS-SVM algorithms exhibited excellent performance of classification in sensitive test and good performance(a little inferior)in robustness test.Generally,LS-SVM with linear kernel equally outperformed LS-SVM based on RBF kernel.The result indicated the potential for future applications in herbs and food,especially for in situ GOs applications of TCM authenticity rapidly.

Characteristic chemical profile of Juhe Fang extract with lipid-lowering properties

Objective:The objective of this study was to verify the lipid-lowering effect of Juhe Fang extract(JHFE)and to determine its characteristic chemical profile in vitro and in vivo.Methods:A hyperlipidemia model was established by feeding mice a high-fat diet(HFD).After treatment for 30 days,serum total cholesterol(TC),triglyceride(TG),high-density lipoprotein cholesterol(HDL-C)and low-density lipoprotein cholesterol(LDL-C)levels were measured with an automatic biochemistry analyzer.The components from JHFE obtained from in vivo and in vitro experiments were investigated using an UPLC-Q Exactive-Orbitrap MS/MS.Results:The TC,TG,and LDL-C in the serum significantly decreased and the HDL-C significantly increased after JHFE treatment.A total of 95 compounds from JHEF including 15 phenolic acids(PA),4 phenylethanoid glycosides(PG),24 flavonoids(F),14 triterpenoids(T),10 diterpenoid glycosides(D),18 alkaloids(A)and 10 others(O)were identified.Trigonelline was discovered for the first time in a herbal medicine of Juhe Fang.Furthermore,68 compounds were identified in vivo including 28 prototype compounds and 40 metabolites.The metabolic characteristics of these components were revealed including identification of new metabolites of 4-hydroxyphenyl ethyl-8-O-[a-L-arabinopyranosyl-(1/6)]-b-D-glucopyranoside(PEG)and lirinidine.A total of 43 components from JHFE were absorbed and/or metabolized.The contribution rate of each type of chemical component from JHFE to its lipidlowering effect from high to low were A,F,PG,PA,D and T.Conclusion:The results of this study showed that JHFE demonstrated a significant lipid-lowering effect in a high-fat diet(HFD)-induced hyperlipidemia mouse model.Specific types of PA,PG,F,D,T and A formed the pharmaceutical architecture of the lipid-lowering effect of JHFE.This study should prove useful for clarifying the components responsible for the lipid-lowering effect of JHFE and provide a basis for precision quality control research.

Research progress on mechanism of Chinese material medica in preventing and treating insulin resistance and type 2 diabetes mellitus

Insulin resistance(IR)is a significant feature and one of the basic links in the pathogenesis of type 2 diabetes mellitus(T2DM).Chinese material medica(CMM)has promoted the development of traditional Chinese medicine due to its definite clinical efficacy in the treatment of IR and T2DM.However,owing to the fact that the mechanism of CMM is characterized by“multiple components and multiple targets”,which has not been effectively interpreted,result in the scientificity of clinical efficacy with CMM is controversial.Therefore,this article summarized the mechanisms of CMM and its main active components in improving IR and preventing and treating T2DM,whose aim is to provide valuable reference for the research mechanism on the treatment of IR and T2DM.

Anti-obesity and Gut Microbiota Modulation Effect of Astragalus Polysaccharides Combined with Berberine on High-Fat Diet-Fed Obese Mice

Objective To investigate whether astragalus polysaccharides(APS)combined with berberine(BBR)can reduce high-fat diet(HFD)-induced obesity in mice.Methods Except for normal mice,32 HFD-induced obese mice were randomized into HFD,APS(1,000 mg/kg APS),BBR(200 mg/kg BBR),and APS plus BBR(1,000 mg/kg APS plus 200 mg/kg BBR)groups,respectively.After 6-week treatment(once daily by gavage),the obesity phenotype and pharmacodynamic effects were evaluated by histopathological examination of epididymal fat,liver,and colon using hematoxylin-eosin staining and serum biochemical analyses by an automated chemistry analyzer.The feces were collected at the 12 th week,and taxonomic and functional profiles of gut microbiota were analyzed by 16S ribosomal ribonucleic acid(16S rRNA)sequencing.Results Compared with HFD group,the average body weight of APS plus BBR group was decreased(P<0.01),accompanied with the reduced fat accumulation,enhanced colonic integrity,insulin sensitivity and glucose homeostasis(P<0.05 or P<0.01).Importantly,APS combined with BBR treatment was more effective than APS or BBR alone in improving HFD-induced insulin resistance(P<0.05 or P<0.01).16S rRNA sequence-based analysis of fecal samples demonstrated that APS combined with BBR treatment exhibited a better impact on HFD-induced gut microbiota dysbiosis,exclusively via the enriched abundances of Bacteroides,which corresponded to the large increase of predicted bacterial genes involved in carbohydrate metabolism.Conclusion APS combined with BBR may synergistically reduce obesity and modulate the gut microbiota in HFD-fed mice.

Gut microbiota: a potential target for insulin resistance and type 2 diabetes mellitus

Insulin resistance(IR)runs through the whole process of occurrence and development of type 2 diabetes mellitus.Gut microbiota is the largest micro-ecosystem in human body,which has an important influence on the metabolism of material and energy.Recent studies have shown that besides genetic and islet dysfunction,disorders of the gut microbiota induced by dietary imbalance may lead to IR,which influence health.Here,we reviewed the research status of the correlation between IR and gut microbiota,and summarized the relationship between IR and gut microbiota,metabolites of gut microbiota and IR,and possible mechanism of gut microbiota participating in IR,which provides theoretical basis and literature reference for the treatment of IR and type 2 diabetes mellitus by gut microbiota regulation.

Novel phthalimides regulating PD-1/PD-L1 interaction as potential immunotherapy agents

Programmed cell death 1(PD-1)/programmed cell death ligand 1(PD-L1)have emerged as one of the most promising immune checkpoint targets for cancer immunotherapy.Despite the inherent advantages of small-molecule inhibitors over antibodies,the discovery of small-molecule inhibitors has fallen behind that of antibody drugs.Based on docking studies between small molecule inhibitor and PD-L1 protein,changing the chemical linker of inhibitor from a flexible chain to an aromatic ring may improve its binding capacity to PD-L1 protein,which was not reported before.A series of novel phthalimide derivatives from structure-based rational design was synthesized.P39 was identified as the best inhibitor with promising activity,which not only inhibited PD-1/PD-L1 interaction(IC_(50)=8.9 nmol/L),but also enhanced killing efficacy of immune cells on cancer cells.Co-crystal data demonstrated that P39 induced the dimerization of PD-L1 proteins,thereby blocking the binding of PD-1/PD-L1.Moreover,P39 exhibited a favorable safety profile with a LD_(50)>5000 mg/kg and showed significant in vivo antitumor activity through promoting CD8^(+)T cell activation.All these data suggest that P39 acts as a promising small chemical inhibitor against the PD-1/PD-L1 axis and has the potential to improve the immunotherapy efficacy of T-cells.