Bioconversion variation of ginsenoside CK mediated by human gut microbiota from healthy volunteers and colorectal cancer patients

Abstract

Background Ginsenoside CK (GCK) serves as the potential anti-colorectal cancer (CRC) protopanaxadiol (PPD)-type saponin, which could be mainly bio-converted to yield PPD by gut microbiota. Meanwhile, the anti-CRC effects of GCK could be altered by gut microbiota due to their different diversity in CRC patients. We aimed to investigate the bioconversion variation of GCK mediated by gut microbiota from CRC patients by comparing with healthy subjects. Methods Gut microbiota profiled by 16S rRNA gene sequencing were collected from healthy volunteers and CRC patients. GCK was incubated with gut microbiota in vitro. A LC-MS/MS method was validated to quantify GCK and PPD after incubation at different time points. Results The bioconversion of GCK in healthy subjects group was much faster than CRC group, as well as the yield of PPD. Moreover, significant differences of PPD concentration between healthy subjects group and CRC group could be observed at 12 h, 48 h and 72 h check points. According to 16S rRNA sequencing, the profiles of gut microbiota derived from healthy volunteers and CRC patients significantly varied, in which 12 differentially abundant taxon were found, such as Bifidobacterium, Roseburia, Bacteroides and Collinsella. Spearman’s correlation analysis showed bacteria enriched in healthy subjects group were positively associated with the biotransformation of GCK, while bacteria enriched in CRC group displayed non correlation character. Among them, Roseburia which could secrete β-glycosidase showed the strongest positive association with the bioconversion of GCK. Conclusions The bioconversion of GCK in healthy subjects was much faster than CRC patients mediated by gut microbiota, which might alter the anti-CRC effects of GCK.

Ginsenoside compound K inhibits the proliferation, migration and invasion of Eca109 cell via VEGF-A/Pi3k/Akt pathway

“…Ginseng, as a treasure of human pharmaceutical culture, contains a variety of active components, among which ginsenoside is the main bioactive compound in ginseng and has broad implications in human disease [ 16 ]. Ginsenoside CK is a natural diol-type ginsenoside with medicinal activity in vivo [ 17 ]. Studies found that Ginsenoside CK has inhibiting effects on various tumor cells, containing lung cancer, colon cancer, and liver cancer, as well as bone tumor [ 18 – 20 ].…”

Effects of ginsenoside compound K on alleviating colitis via modulating gut microbiota

“…Studies have shown that GC-K can play a bene cial role in colitis by inhibiting IRAK-1 and NF-kB activation [12]. However, the absolute oral bioavailability of GC-K is only about 35% [13], which implied it could interplay with gut microbiota after oral administration [14]. Recently, natural products have been discovered to interplay with gut microbiota in vivo [23,24].…”

“…However, the absolute oral bioavailability of GC-K is only about 35% [13]. GC-K is catalyzed by β-glycosidase only secreted from gut microbiota to generate its metabolite protopanaxadiol in vivo, which implies that GC-K interplays with gut microbiota after oral administration [14]. Furthermore, our previous study found that GC-K could suppress the tumor growth of AOM/DSS-induced colitis-associated CRC through the modulation of gut microbiota, partially by up-regulation of A. muciniphila [9].…”

Ginsenoside Compound K Inhibits the Proliferation, Migration and Invasion of Eca109 cell via VEGF-A/Pi3k/Akt Pathway

“…Ginseng, as a treasure of human pharmaceutical culture, contains a variety of active components, among which ginsenoside is the main bioactive compound in ginseng and has broad implications in human disease [16]. Ginsenoside CK is a natural diol-type ginsenoside with medicinal activity in vivo [17]. Studies found that Ginsenoside CK has inhibiting effects on various tumor cells, containing lung cancer, colon cancer, and liver cancer, as well as bone tumor [18][19][20].…”