Biotransformation differences of ginsenoside compound K mediated by the gut microbiota from diabetic patients and healthy subjects

Many natural products can be bio-converted by the gut microbiota to influence pertinent efficiency.Ginsenoside compound K(GCK)is a potential anti-type 2 diabetes(T2D)saponin,which is mainly bio-transformed into protopanaxadiol(PPD)by the gut microbiota.Studies have shown that the gut microbiota between diabetic patients and healthy subjects are significantly different.Herein,we aimed to characterize the biotransformation of GCK mediated by the gut microbiota from diabetic patients and healthy subjects.Based on 16S rRNA gene sequencing,the results indicated the bacterial profiles were considerably different between the two groups,especially Alistipes and Parabacteroides that increased in healthy subjects.The quantitative analysis of GCK and PPD showed that gut microbiota from the diabetic patients metabolized GCK slower than healthy subjects through liquid chromatography tandem mass spectrometry(LC-MS/MS).The selected strain A.finegoldi and P.merdae exhibited a different metabolic capability of GCK.In conclusion,the different biotransformation capacity for GCK may impact its anti-diabetic potency.

Determination of ginsenoside compound K in human plasma by liquid chromatography–tandem mass spectrometry of lithium adducts

Ginsenoside compound K(GCK), the main metabolite of protopanaxadiol constituents of Panax ginseng, easily produces alkali metal adduct ions during mass spectrometry particularly with lithium. Accordingly, we have developed a rapid and sensitive liquid chromatography–tandem mass spectrometric method for analysis of GCK in human plasma based on formation of a lithium adduct. The analyte and paclitaxel(internal standard) were extracted from 50 m L human plasma using methyl tertbutyl ether. Chromatographic separation was performed on a Phenomenex Gemini C18 column(50 mm 2.0 mm; 5 μm) using stepwise gradient elution with acetonitrile–water and 0.2 mmol/L lithium carbonate at a flow rate of 0.5 m L/min. Detection was performed in the positive ion mode using multiple reaction monitoring of the transitions at m/z 629-449 for the GCK-lithium adduct and m/z 860-292 for the adduct of paclitaxel. The assay was linear in the concentration range 1.00–1000 ng/m L(r^2>40.9988)with intra- and inter-day precision of ±8.4% and accuracy in the range of 4.8% to 6.5%. Recovery,stability and matrix effects were all satisfactory. The method was successfully applied to a pharmacokinetic study involving administration of a single GCK 50 mg tablet to healthy Chinese volunteers.

Ginsenoside metabolite compound K alleviate collegen-induced arthritis through impairing dendritic cells function

OBJECTIVE Ginsenoside metabolite compound K(CK)is a degradation product of ginsenoside in the intestine by bacteria.The anti-inflammatory and immunomodulatory activities of CK have been reported.This study investigated whether CK exerted its immunoregulatory effect through modulation of dendritic cells(DCs)function.METHODS In vivo,severity of collegen-induced arthritis(CIA),T cells and DCs subsets,phenotype of DC were assayed by flow cytometry,CCL19 and CCL21 level in lymph nodes assayed by ELISA.In vitro,bone marrow-derived DCs from normal mice were matured with lipopolysaccharide and treated with CK for 48 h.In vivo,bone marrow-derived DCs were generated from CIA mice before and 2 weeks into CK treatment.DCs were analyzed for migration,phenotype and T-cell stimulatory capacity.RESULTS CK alleviated the severity of CIA,decreased pD Cs and mo-DCs,increased na?ve T cells in CIA mice lymph nodes,and suppressed CCL21 expression in lymph nodes.CK suppressed DCs migration induced by CCL21 and T cells-stimulatory capability of DC,down-regulated LPS-induced expression of CD80,CD86,MHCII and CCR7 on DCs.CONCLUSION This study elucidated the novel immunomodulatory property of CK via impairing function of DCs in priming T cells activation.These results provide an interesting novel insight into the potential mechanism by which CK contribute to the restoration of immunoregulation in autoimmune conditions.

Transformation of Compound K from Saponins in Leaves of Panax notoginseng by Immobilized β-Glucanase

Objective To prepare an active anti-tumor component,compound K(C-K),from saponins in leaves of Panax notoginseng(SLPN) using immobilized β-glucanase.Methods Two entrapments,alginate gel-1(Alg 1) and alginate gel-2(Alg 2),were evaluated for their ability to immobilize β-glucanase.The amount and purity of C-K obtained from the transformation process were analyzed by HPLC,and the immobilizing parameters were optimized.Results β-Glucanase can be immobilized and reused with either of the entrapment.However,using Alg 1 resulted in higher enzyme activity than Alg 2.The optimal concentration of the immobilized enzyme was 10%;The optimal crosslinking time was 4–6 h;and the optimal concentration of the crosslinking agent was 6%– 7%.Conclusion Immobilized β-glucanase shows sustained enzyme activity,good ethanol tolerance,and was reusable for the preparation of C-K from SLPN.