Biotransformation of geniposide by human intestinal microflora on cytotoxicity against HepG2 cells

Khanal, Tilak; Kim, Hyung Gyun; Choi, Jae Ho; Truong, Minh; Kong, Min Jeong; Kang, Mi Jeong; Noh, Kyeumhan; Yeo, Hee Kyung; Ahn, Young Tae; Kang, Wonku; Kim, Dong Hyun; Jeong, Tae Cheon; Jeong, Hye Gwang

doi:10.1016/j.toxlet.2011.12.017

Cited by 37 publications

(26 citation statements)

References 29 publications

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“…GP possesses more potent pharmacological activities than GE, such as choleretic (Shoda et al, ), anti‐inflammatory (Li et al, ; Rajanbabu et al, ), antiapoptosis (Kim, Kim, Lee, Kwak, & Lee, ), antifibrosis (Inao et al, ), treatment of sprain (Chen et al, ), and neuroprotective effects (Li, Li, & Holscher, ). On the other hand, several studies demonstrate that GE causes acute liver injury after oral administration, and GP is responsible for GE‐induced hepatotoxicity (Khanal et al, ; Wei et al, ; Yamano et al, ). To better understand the biological effects and the underlying mechanism of GE and the role of GP, it is essential to study the pharmacokinetic properties of GE and GP after administration of GE.…”

Section: Introductionmentioning

confidence: 99%

A sensitive LC–MS/MS method for simultaneous quantification of geniposide and its active metabolite genipin in rat plasma and its application to a pharmacokinetic study

Shi

Pan

et al. 2017

Biomedical Chromatography

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Genipin (GP), an active metabolite of geniposide (GE), exhibits more potent pharmacological effects than its parent compound. In this paper, a sensitive LC-MS/MS method was developed and fully validated for the simultaneous determination of GE and GP in rat plasma. We found that GP degraded rapidly in rat plasma at room temperature as a result of irreversible binding with the endogenous nucleophiles in plasma. GP was stable when the sample's pH was ≤4.0. The degradation of GP in rat plasma was well prevented by immediate addition of 5% glacial acetic acid to the freshly collected plasma. The detection was performed on a tandem mass spectrometer coupled with electrospray ionization source in negative mode. Quantification was conducted by multiple reaction monitoring of the transitions [M + CH COO] m/z 447.3 → 225.3 for GE and [M - H] m/z 225.2 → 123.1 for GP. The method exhibited high sensitivity (LLOQ 1 ng/mL for GE and 0.2 ng/mL for GP) by selecting the acetate adduct ions as the precursor ions for GE. The robust developed method was successfully applied to a pharmacokinetic study in rats after oral administration of GE.

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Section: Introductionmentioning

confidence: 99%

A sensitive LC–MS/MS method for simultaneous quantification of geniposide and its active metabolite genipin in rat plasma and its application to a pharmacokinetic study

Shi

Pan

et al. 2017

Biomedical Chromatography

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“…In PC12 cells, geniposide induced the PI3 kinase signaling pathway and the expression of anti-apoptotic protein Bcl-2 (Liu et al ., 2009). However, geniposide did not affect apoptotic signaling in HepG2 cells (Khanal et al ., 2012). Genipin induced apoptosis with increased expression of caspase-3 and the pro-apoptotic protein, Bax, in HepG2 cells (Hong and Kim, 2007).…”

Section: Discussionmentioning

confidence: 99%

Protective Effects of Geniposide and Genipin against Hepatic Ischemia/Reperfusion Injury in Mice

Kim

Lee

2013

Biomolecules and Therapeutics

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Geniposide is an active product extracted from the gardenia fruit, and is one of the most widely used herbal preparations for liver disorders. This study examined the cytoprotective properties of geniposide and its metabolite, genipin, against hepatic ischemia/reperfusion (I/R) injury. C57BL/6 mice were subjected to 60 min of ischemia followed by 6 h of reperfusion. Geniposide (100 mg/kg) and genipin (50 mg/kg) were administered orally 30 min before ischemia. In the I/R mice, the levels of serum alanine aminotransferase and hepatic lipid peroxidation were elevated, whereas hepatic glutathione/glutathione disulfide ratio was decreased. These changes were attenuated by geniposide and genipin administration. On the other hand, increased hepatic heme oxygenase-1 protein expression was potentiated by geniposide and genipin administration. The increased levels of tBid, cytochrome c protein expression and caspase-3 activity were attenuated by geniposide and genipin. Increased apoptotic cells in the I/R mice were also significantly reduced by geniposide and genipin treatment. Our results suggest that geniposide and genipin offer significant hepatoprotection against I/R injury by reducing oxidative stress and apoptosis.

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“…Several studies have indicated that probiotics could play immunomodulatory roles in reducing Salmonella colonization in mice and chickens [4, 7, 23, 24]. In addition, intestinal microflora offers ability to convert and then alter bioactivity of herbal compounds [25, 26]. …”

Section: Discussionmentioning

confidence: 99%

Application ofScutellariae radix,Gardeniae fructus, and Probiotics to PreventSalmonella entericaSerovar Choleraesuis Infection in Swine

Chang

Chen

Chiou

et al. 2013

Evidence-Based Complementary and Alternative Medicine

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Salmonella enterica serovar Choleraesuis, a host-adapted pathogen of swine, usually causes septicemia. Lactic acid bacteria (LAB) strains have been widely studied in recent years for their probiotic properties. In this study, a mouse infection model first screened for potential agents against infection, then a pig infection model evaluated effects of LAB strains and herbal plants against infection. Scutellariae radix (SR) and Gardeniae fructus (GF) showed abilities to reduce bacteria shedding and suppressing serum level of TNF-α induced by infection in swine. Bioactivities of SR and GF were enhanced by combining with LAB strains, which alone could speed up the bacteria elimination time in feces and boost immunity of infected pigs. Baicalein and genipin exhibited stronger cytotoxicity than baicalin and geniposide did, as well as prevent Salmonella from invading macrophages. Our study suggests LAB strains as exhibiting multiple functions: preventing infection, enhancing immunity to prepare host defenses against further infection, and adjusting intestinal microbes' enzymatic activity in order to convert herbal compounds to active compounds. The SR/GF-LAB strain mixture holds potential infection-prevention agents supplied as feed additives.

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Biotransformation of geniposide by human intestinal microflora on cytotoxicity against HepG2 cells

Cited by 37 publications

References 29 publications

A sensitive LC–MS/MS method for simultaneous quantification of geniposide and its active metabolite genipin in rat plasma and its application to a pharmacokinetic study

A sensitive LC–MS/MS method for simultaneous quantification of geniposide and its active metabolite genipin in rat plasma and its application to a pharmacokinetic study

Protective Effects of Geniposide and Genipin against Hepatic Ischemia/Reperfusion Injury in Mice

Application ofScutellariae radix,Gardeniae fructus, and Probiotics to PreventSalmonella entericaSerovar Choleraesuis Infection in Swine

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