Simultaneous Determination of Glycyrrhizin Metabolites Formed by the Incubation of Glycyrrhizin with Rat Feces by Semi-micro High-Performance Liquid Chromatography

Okamura, Nobuyuki; Miyauchi, Hidetoshi; Choshi, Tominari; Ishizu, Tomoko; Yagi, Akira

doi:10.1248/bpb.26.658

Cited by 13 publications

(10 citation statements)

References 16 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In humans no glycyrrhizic acid was detected in plasma following an oral dose of 100–800 mg. In rats glycyrrhizic acid plasma levels were only detectable after high oral doses of 50–500 mg/kg, demonstrating low oral bioavailability (4% after 200 mg/kg) [46]. It also induces apoptosis in several cancer cell lines such as human hepatoma (HLE), promyelotic leukemia (HL-60) and stomach cancer (KATO III) and prostate cancer cell lines (DU-145 and LNCaP) [47]–[49].…”

Section: Introductionmentioning

confidence: 99%

Glycyrrhizic Acid Suppresses the Development of Precancerous Lesions via Regulating the Hyperproliferation, Inflammation, Angiogenesis and Apoptosis in the Colon of Wistar Rats

Khan

Lateef

et al. 2013

PLoS ONE

View full text Add to dashboard Cite

BackgroundColon carcinogenesis is a multistep process and it emanates from a series of molecular and histopathological alterations. Glycyrrhizic acid (GA) is a natural and major pentacyclic triterpenoid glycoside of licorice roots extracts. It has several pharmacological and biological properties such as anti-inflammatory, anti-viral, and anti-cancer. In the present study, we investigated the chemopreventive potential of GA against 1,2-dimethyhydrazine (DMH)-induced precancerous lesions i.e., aberrant crypt foci (ACF) and mucin depleted foci (MDF), and its role in regulating the hyperproliferation, inflammation, angiogenesis and apoptosis in the colon of Wistar rats.MethodsAnimals were divided into 5 groups. In group III, IV and V, GA was administered at the dose of 15 mg/kg b. wt. orally while in group II, III and IV, DMH was administered subcutaneously in the groin at the dose of 20 mg/kg b.wt once a week for first 5 weeks and animals were euthanized after 9 weeks.ResultsGA supplementation suppressed the development of precancerous lesions and it also reduced the infiltration of mast cells, suppressed the immunostaining of Ki-67, NF-kB-p65, COX-2, iNOS and VEGF while enhanced the immunostaining of p53, connexin-43, caspase-9 and cleaved caspase-3. GA treatment significantly attenuated the level of TNF-α and it also reduced the depletion of the mucous layer as well as attenuated the shifting of sialomucin to sulphomucin.ConclusionOur findings suggest that GA has strong chemopreventive potential against DMH-induced colon carcinogenesis but further studies are warranted to elucidate the precise mechanism of action of GA.

show abstract

Section: Introductionmentioning

confidence: 99%

Glycyrrhizic Acid Suppresses the Development of Precancerous Lesions via Regulating the Hyperproliferation, Inflammation, Angiogenesis and Apoptosis in the Colon of Wistar Rats

Khan

Lateef

et al. 2013

PLoS ONE

View full text Add to dashboard Cite

show abstract

“…Determination of GZ and GA in biological samples by HPLC has been reported by several authors [17], [18]. In the current study, phenol red in intestinal perfusate was determined simultaneously with GZ and/or GA.…”

Section: Determination Of Gz Ga and Phenol Red In Collected Samples mentioning

confidence: 54%

The Disposition of Diammonium Glycyrrhizinate and Glycyrrhetinic Acid in the Isolated Perfused Rat Intestine and Liver

et al. 2008

View full text Add to dashboard Cite

The major component of liquorice root extract, glycyrrhizinate (GZ), has been formulated as an injection for the treatment of hepatitis. If given orally, GZ has poor bioavailability and is catalysed to glycyrrhetinic acid (GA) by intestinal bacteria. GA is subsequently responsible for significant side effects. This study was conducted to clarify the relationship between GZ and GA absorption and bioavailability. GZ and GA absorption were investigated using the in situ single pass isolated perfused intestine (IPI). Hepatic disposition was investigated using isolated perfused liver (IPL) and in vivo biliary excretion models. The apparent permeability and absorption rate constants in the IPI for GZ were 0.36 +/- 0.31 cm/min and 0.35 +/- 0.33 min (-1), while those for GA were 5.73 +/- 0.11 cm/min and 1.53 +/- 0.05 min (-1), respectively. The hepatic extraction ratios of unbound GZ and GA in the IPL were 0.22 +/- 0.01 and 0.44 +/- 0.15, respectively. Seven hours after intra-portal venous injection in vivo, the cumulative biliary excretion ratio for GZ was 96 %. There was negligible biliary excretion of unchanged GA during the same period. It was apparent in all models used that in the absence of intestinal bacteria GZ was not metabolised to GA, or vice versa. Hence, GZ can be absorbed unchanged from the intestine provided it has sufficient time and is protected from intestinal bacteria. This opens up the possibility that the use of pharmaceutical carrier systems or similar formulation approaches may allow effective oral administration of therapeutic levels of GZ without the side effects associated with GA.

show abstract

“…[15][16][17] To elucidate the role of glycyrrhiza in DKT, the influence of glycyrrhiza and glycyrrhiza constituents on the activity of sennoside A metabolism was investigated using mouse feces. HPLC methods for the determination of sennoside A in rhubarb have been developed.…”

Section: Resultsmentioning

confidence: 99%

High-Performance Liquid Chromatographic Determination and Metabolic Study of Sennoside A in Daiokanzoto by Mouse Intestinal Bacteria

Takayama

Matsui

Kobayashi

et al. 2011

CHEMICAL & PHARMACEUTICAL BULLETIN

Self Cite

View full text Add to dashboard Cite

Daiokanzoto (DKT, combination of rhubarb and glycyrrhiza), a Kampo medicine, is clinically effective for constipation. Sennoside A is well known to induce diarrhea. Sennoside A is a prodrug that is transformed into an active metabolite, rheinanthrone, by intestinal bacteria. In this study, we investigated the effects of glycyrrhiza on the activity of sennoside A metabolism in intestinal bacteria using mouse feces. A high-performance liquid chromatography (HPLC) method for the determination of sennoside A in incubation mixture of DKT with mouse feces was established. The retention time of sennoside A was 9.26±0.02 min with a TSKgel ODS-80TsQA column by linear gradient elution using a mobile phase containing aqueous phosphoric acid and acetonitrile and detection at 265 nm. We found that the activity of sennoside A metabolism in intestinal bacteria was significantly accelerated when glycyrrhiza, liquiritin or liquiritin apioside coexisted with sennoside A, whereas that of glycyrrhizin was not altered. This method is applicable for determination of the activity of sennoside A metabolism by anaerobic incubation of DKT with mouse feces.

show abstract

Simultaneous Determination of Glycyrrhizin Metabolites Formed by the Incubation of Glycyrrhizin with Rat Feces by Semi-micro High-Performance Liquid Chromatography

Cited by 13 publications

References 16 publications

Glycyrrhizic Acid Suppresses the Development of Precancerous Lesions via Regulating the Hyperproliferation, Inflammation, Angiogenesis and Apoptosis in the Colon of Wistar Rats

Glycyrrhizic Acid Suppresses the Development of Precancerous Lesions via Regulating the Hyperproliferation, Inflammation, Angiogenesis and Apoptosis in the Colon of Wistar Rats

The Disposition of Diammonium Glycyrrhizinate and Glycyrrhetinic Acid in the Isolated Perfused Rat Intestine and Liver

High-Performance Liquid Chromatographic Determination and Metabolic Study of Sennoside A in Daiokanzoto by Mouse Intestinal Bacteria

Contact Info

Product

Resources

About