Integrating lipidomics and gut microbiota to study the anti-hyperlipidemia effect of Sargentodoxae Caulis extract

Background:Sargentodoxae Caulis(SC)is the vine stem of Sargentodoxa Cuneata(Oliv.)Rehd.&E.H.Wilson in C.S.Sargent,and it in traditional Chinese medicine has been known for promoting blood circulation and removing blood stasis as recorded in the ancient book“Illustrated Classics of Materia Medica”.It has been used effectively to treat blood stasis too in modern clinical practice.However,the anti-hyperlipidemia effect of SC is not fully understood.This paper aims at exploring the use of SC stems to improve the balance of blood lipids in the body,and its new role in treating hyperlipidemia.Methods:The effects of SC extract on hyperlipidemia were explored by combining lipidomics and gut microbiota.Secondly,we explored the potential mechanism of SC in treating hyperlipidemia by pathway analysis.Results:The results showed that the stem extract of SC could restore the physiological and biochemical indices of hyperlipidemia in mice,as well as repair the morphological and structural damage to tissues.Compared to the Model group,the SC extract significantly reduced the liver index,epididymal fat index,and Lee’s index.It also significantly decreased serum levels of total cholesterol,triglycerides,low-density lipoprotein cholesterol,peroxisome proliferator-activated receptor gamma(PPAR-γ),D-lactate,and free fatty acids,while significantly increasing the relative content of peroxisome proliferator-activated receptor alpha(PPAR-α).These changes were statistically significant.Non-targeted lipidomics,based on LC-MS,were utilized to investigate the lipid metabolism characteristics in serum,liver,and epididymal fat of the subjects.It was observed that,compared to the blank group,the Model group exhibited significant changes primarily in glycerol lipids and glycerophospholipids.The treatment group also displayed alterations in these lipids.A total of 38,81,and 27 differential lipids were identified in serum,liver,and epididymal fat samples,respectively.Among these,14 common differential lipids were found in both serum and liver samples,and their KEGG enrichment pathways were largely consistent.Among them,the sphingolipid signaling pathway and the glycerophospholipid metabolic pathway were identified as key metabolic pathways that were regulated.Our gut microbiota analysis revealed that SC diminishes the abundance of Actinobacteria by altering the cecal flora in mice.Conclusion:This alteration leads to the downregulation of genes involved in triglyceride metabolism,which in turn changes lipid processing and reduces triglyceride levels.Consequently,SC effectively combats hyperlipidemia.Notably,SC impacts key metabolic pathways,including the sphingolipid signaling and glycerophospholipid metabolism.These findings underscore SC’s therapeutic potential,positioning it as a promising alternative for reducing the health risks associated with hyperlipidemia.

Effects of “Caulis Sargentodoxae Formula” on Experimental Endometriosis in Rat

Objective To study the drug effects of ＂Caulis Sargentodoxae Formula＂ which dears away heat and blood clot on experimental endometriosis in rat, and to compare this effect with Danazol＇s effects. Method The model of endometriosis rat was induced by transplanting with endometrium surgically The rats were divided into 6 groups randomly： the non-treatment group, the castrate group, Danazol group（80 mg/kg）, ＂Caulis Sargentodoxae Formula＂ group （110 g/kg）, the medium dose group（77.5 g/kg） and the low dose group（55 g/kg）. After 3 weeks＇ treatment, the volume ofendometrium was detected by cutting the rats＇ belly open, drawing the materials from endometrium for tissue section, and doing the quantity analysis of endometrium by semiautomatic image analysis machine.Results There was no significant difference of the endometrium volumes between the low dose group and the non-treatment group（P〉O.05）, other groups＇ endometrium volumes were significantly lower than those of the non-treatment group（P〈0. 05）. And apart from the low dose group, all other groups＇ heights of the endometrium epithelia were significantly lower than that of the non-treatment group（p〈0.01）. Conclusion ＂Caulis Sargentodoxae Formula＂ can refrain the growth of the endometrium, and the effects are better than that of Danazol＇s.

Caulis Sargentodoxae Prescription Inhibits Angiogenesis-related Cytokines in a Rat Endometriosis Model

Background:To determine the efficacy of the Caulis Sargentodoxae prescription,which is an empirical formula of Chinese herbs and has definite curative effects on endometriosis.Methods:The Caulis Sargentodoxae prescription on the growth of ectopic endometria was studied with a rat endometriosis(EMS)model.The EMS model was established by autoplastic transplantation.To study the curative effects of Chinese medicine on EMS in comparison with western medicine,gestrinone and an angiogenesis inhibitor were introduced.The rats were randomly divided into seven groups:normal group,model group,ovariectomized group,gestrinone(western medicine)group,Caulis Sargentodoxae prescription(Chinese medicine)group,apatinib(inhibitor)group,and combination(Chinese medicine+inhibitor)group.After administration for 21 days,the growth inhibitory rates of ectopic endometria in the treatment groups were evaluated,and the levels of vascular endothelial growth factor(VEGF)and VEGF receptor-2(VEGFR2)were detected by ELISA in the serum and peritoneal fluid,as well as in the ectopic endometrial tissues by real-time polymerase chain reaction and Western blotting.Results:The growth inhibitory rates of ectopic endometria in the treatment groups were significantly higher(P<0.05).In the Caulis Sargentodoxae prescription group,the levels of angiogenesis-related factors,including VEGF and VEGFR2,were reduced in the serum and peritoneal fluid compared with the model group(P<0.05).In addition,the positive expression of VEGF and VEGFR2 in ectopic endometria significantly decreased in the Caulis Sargentodoxae prescription group both at mRNA and protein levels.Conclusions:VEGF and VEGFR2 levels in the serum and peritoneal fluid can be used as a clinical reference for endometriotic pathogenesis and treatment,and the Caulis Sargentodoxae prescription has reliable therapeutic effects on EMS for its target-action ability to decrease angiogenesis.