The protective effect of carnosic acid on dextran sulfate sodium-induced colitis based on metabolomics and gut microbiota analysis

Accumulating evidence suggests that the gut microbiota plays an important role in the pathogenesis of inflammatory bowel disease(IBD).Carnosic acid(CA)is a major antioxidant component of rosemary and sage.Herein,we investigated the protective effects of dietary CA on dextran sodium sulfate(DSS)-induced colitis mouse model with an emphasis on its impact on the composition and metabolic function of gut microbiota.We found that CA effectively attenuated DSS-stimulated colitis in mice,as evidenced by reduced disease activity index(DAI),and systemic and colonic inflammation.Additionally,CA restored microbial diversity and improved the composition of gut microbiota in DSS-treated mice.Moreover,Spearman’s correlation coefficient showed a significant correlation between the fecal metabolites and the gut microbiota species.Changes in gut microbiota and the correlated metabolites might partially explain CA’s anti-inflammatory effects against colitis.Future clinical trials are needed to determine the therapeutic effects and mechanisms of CA on IBD in humans.

A Concise Approach to the Synthesis of Carnosic Acid Type Diterpenes

vinyl-8,11,13-podocatriene 8, which is a model of Carnosic acid type diterpenes, has been synthesized by an expeditious convergent synthetic approach.

Cancer combination therapy with carnosic acid

Carnosic acid(CA)is a natural phenolic diterpene mainly occurring in some species of the Lamiaceae family.Numerous studies described the cytotoxicity of CA towards different types of cancer both in vitro and in vivo.Particularly,the influence of CA in combination with other drugs,vitamins or natural products through affecting various targets has raised interest.Current experimental in vivo data suggested that CA may cooperate with clinically used anticancer drugs promoting their activity against cancer.From this point of view,CA gained importance,because it may alter pharmacodynamic profiles of various agents in the case of their co-administration,and thereby,act in a potentially synergistic manner,which can provide a basis for potential applications of CA in the management of cancer.In the present review,we give an overview of CA as well as CA co-treatment regimens with a special focus on cancer.In this context,the role of CA as an adjuvant treatment alternative is highlighted.

Synergism between Carnosic Acid and Arsenic Trioxide on Induction of Acute Myeloid Leukemia Cell Apoptosis Is Associated with Modulation of PTEN/Akt Signaling Pathway

Objective： To investigate the synergistic effects of carnosic acid （CA） with arsenic trioxide （As203） on proliferation and apoptosis in HL-60 human myeloid leukemia cells, and the major cellular signaling pathway involved in these effects. Methods： HL-60 cellular proliferation was measured by 3-（4,5-dimethylthiazol-2-yl）- 2,5-diphenyltetrazolium bromide （MTF） analysis. Cell cycle distribution and apoptosis were monitored by flow cytometry. The activation of casepase-9, Bcl-2-associated agonist of cell death （BAD）, p-BAD, p27, phosphatase and tensin homolog deleted on chromosome ten （PTEN）, Akt, p-Akt was assessed by Western blot analysis. The expression of PTEN mRNA was tested by reverse transcription polymerase chain reaction （RT-PCR） analysis. Results： CA reduced HL-60 cell viability in a dose- and time-dependent manner, and induced G1 arrest and apoptosis. Moreover, CA upregulated PTEN expression, blocked the Akt signaling pathway, subsequently inhibited phosphorylation of BAD, reactivated caspase-9, and elevated levels of p27. CA also augmented these effects of As203. Conclusion： CA might be a novel candidate of the combination therapy for leukemia treatment; these effects were apparently associated with the modulation of PTEN/Akt signaling pathway.

Dietary carnosic acid and seleno-compounds change concentrations of fatty acids, cholesterol, tocopherols and malondialdehyde in fat and heart of lambs

The aim of the current study was to evaluate the impact of carnosic acid(CA),selenised yeast(^(Y)Se)and selenate(^(VI)Se)supplemented to diets,including fish oil(FO)and rapeseed oil(RO),on the content of fatty acids,total cholesterol(TCh),tocopherols and malondialdehyde in the fat located between the thigh muscles and the heart in lambs.Twenty-four male Corriedale lambs were divided into 4 groups of 6 animals.Animals were fed a diet with FO and RO(the control diet)or experimental diets containing RO,FO and CA with/without Se(as^(Y)Se or^(VI)Se).The experimental diets without/with^(Y)Se or^(VI)Se changed concentrations of fatty acids in the fat and heart compared to the control.All experimental diets increased the levels of c11c14C20:2,c5c8c11c14C20:4,c5c8c11c14c17C20:5 and the sums of long-chain polyunsaturated fatty acids(LPUFA)and conjugated linoleic acid isomers in the fat compared to the control.The experimental diet containing^(Y)Se or^(VI)Se increased the content of Se,TCh,c11c14C20:2,c8c11c14C20:3,c5c8c11c14C20:4,c5c8c11c14c17C20:5,c7c10c13c16c19C22:5,c4c7c10c13c16c19C22:6 and the concentration sum of n-3LPUFA,n-6LPUFA and tocopherols in the heart in comparison with the control diet and the diet containing only CA.Experimental diets reduced the concentration of malon-dialdehyde in the fat and heart in comparison with the control diet.Our dietary intervention has great potential for future practical and commercial implementations.

Antimicrobial effects of carnosic acid,kaempferol and luteolin on biogenic amine production by spoilage and food-borne pathogenic bacteria

Antimicrobial effects of carnosic acid,kaempferol and luteolin on biogenic amine(BA)production by five spoilage(Photobacterium damselae,Proteus mirabilis,Enterobacter cloacea,Pseudomonas luteola and Serratia liquefaciens)and five food-borne pathogenic bacteria(Staphylococcus aureus ATCC29213,Enterococcus faecalis ATCC29212,Escherichia coli ATCC25922,Salmonella Paratyphi A NCTC13 and Yersinia enterocolitica NCTC 11175)were investigated.The formation of ammonia(AMN),trimethylamine(TMA)and BAs by all bacterial strains were observed using ornithine decarboxylase broth.BAs,AMN,and TMA were determined by using high performance liquid chromatography(HPLC)method.The results showed that significant differences were observed(P≤0.05)in formation among spoilage and also food-borne bacteria.The impact of phenolic compounds on AMN,TMA and BAs production was dependent on bacterial strains.When total amount of cadaverine(CAD),putrescine(PUT),histamine(HIS)and tyramine(TYR)was considered,the phenolic compounds presented antimicrobial activity against fish spoliage bacteria and food-borne pathogens following the order;kaempferol>carnosic acid>luteolin.These phenolics have potential to be used as food preservatives.

Regulation effects of rosemary(Rosmarinus officinalis Linn) on hepatic lipid metabolism in OA induced NAFLD rats

OBJECTIVE To highlight the pharmacological effects of rosemary and its active compounds and eluci⁃date its related mechanisms in nonalcoholic fatty liver disease(NAFLD)management both in vitro and in vivo.METHODS In orotic acid induced NAFLD rats model,rats were administrated with 100,200 and 400 mg·kg^-1 rosemary ethanol extract(RO),10,25 and 50 mg·kg^-1 rosemary acid(RA),and 5,10 and 25 mg·kg^-1 carnosic acid(CA)for three weeks respec⁃tively.Sodium oleate induced HepG2 cell model was used to study the regulation effect of rosemary ethanol extract and its main metabolites on fat accumulation.lipid metabolism related gene expression was analyzed by Western blotting and real-time PCR to clarify the specific molecular mechanism of RO,RA and CA in lipid accumulation.RESULTS RO,RA and CA significantly reduced the contents of liver triglyceride(TG),total cholesterol(TC),free fatty acids(FFA)and improved cell hypertrophy,vacuolation,and cell necrosis in liver of orotic acid induced NAFLD model rats.The mecha⁃nism and related pathways of RO and its main metabolites against lipid disorder was related to the up-regulation of the phosphorylation of adenosine 5′-monophosphate(AMP)-activated protein kinase(AMPK)and inhibition of the sterol regu⁃latory element binding protein-1c(SREBP-1c)cracking into the nuclear,following down-regulation of fatty acid synthesis.CONCLUSION The rosemary has effectively function to regulate lipid metabolism through AMPK/SREBP1c signaling pathway.