Epiprogoitrin

Stereoselective pharmacokinetic study of epiprogoitrin and progoitrin in rats with UHPLC-MS/MS method.[Pubmed:32416341]

J Pharm Biomed Anal. 2020 May 7;187:113356.

An accurate and precise liquid chromatography-electrospray ionization-tandem mass spectrometry (LC-ESI-MS/MS) method was developed and validated for the pharmacokinetic study of Epiprogoitrin and progoitrin, a pair of epimers that can be deglycosylated to epigoitrin and goitrin, respectively. These analytes were administered intravenously or intragastrically to male Sprague-Dawley rats, and the influence of 3(R/S)-configuration on the pharmacokinetics of both epimers in rat plasma was elucidated. The analytes and an internal standard (i.e., sinigrin) were resolved by LC-MS/MS on a reverse-phase ACQUITY UPLC HSS T3 column equilibrated and eluted with acetonitrile and water (0.1 % formic acid) at a fl ow rate of 0.3mL/min. Quantitation was achieved by applying the multiple reaction monitoring mode, in the negative ion mode, at transitions of m/z 388 --> 97 and m/z 358 --> 97 for the epimers and sinigrin, respectively. The method demonstrated good linearity over the concentration range of 2-5000ng/mL (r > 0.996). The lower limit of quantification for Epiprogoitrin and progoitrin was 2ng/mL. The interday and intraday accuracy and precision were within +/-15 %. The extraction recovery, stability, and matrix effect were demonstrated to be within acceptable limits. The validated method was thus successfully applied for the pharmacokinetic study of both the epimers. After the rats received the same oral dose of the epimers, the pharmacokinetic profiles were similar. The maximum plasma concentration (Cmax) and AUC values of Epiprogoitrin were a bit higher than those of progoitrin, whereas the pharmacokinetic behaviours of the epimers were obviously different upon intravenous administration. The Cmax and AUC values of Epiprogoitrin were approximately three-fold higher than those of progoitrin, and the half-life of progoitrin was much shorter than that of Epiprogoitrin. The oral bioavailability of progoitrin was 20.1 %-34.1 %, which is three times higher than that of Epiprogoitrin.

Antiviral activity of Isatidis Radix derived glucosinolate isomers and their breakdown products against influenza A in vitro/ovo and mechanism of action.[Pubmed:31918015]

J Ethnopharmacol. 2020 Apr 6;251:112550.

ETHNOPHARMACOLOGICAL RELEVANCE: Isatidis Radix, the sun-dried roots of Isatis indigotica Fortune ex Lindl., is one of the most usually used traditional Chinese medicines. For centuries, the herb has been employed in clinical practice for treatment of virus infection and inflammation. However, its active ingredients remain unclear. AIM OF THE STUDY: In the present study, the anti-influenza virus activity of Epiprogoitrin, progoitrin, epigoitrin and goitrin, the Isatidis Radix derived glucosinolate isomers and their breakdown products, was firstly evaluated in vitro and in ovo and their mechanism of action was investigated. MATERIALS AND METHODS: Epiprogoitrin, progoitrin, epigoitrin and goitrin were isolated from Isatidis Radix by chiral separation. In vitro and in ovo evaluations were performed on Madin-Darby canine kidney (MDCK) cells and embryonated eggs respectively, both using protocols including prevention, treatment and virus neutralization. Hemagglutination (HA) and neuraminidase (NA) inhibition assays were performed for further understanding of the antiviral mechanism. RESULTS: Isatidis Radix derived glucosinolate isomers and their breakdown products all exhibited dose-dependent inhibition effect against influenza A virus (H1N1) without toxicity. The antiviral potency of the components was in the order of progoitrin > goitrin > epigoitrin > Epiprogoitrin. The attachment of the constituents to the viral envelope conduced to the mechanism of their antiviral action without disturbing viral adsorption or budding. CONCLUSION: Taken together, these results are promising for further development of Isatidis Radix and may contribute an adjunct to pharmacotherapy for influenza virus infection.

Separation and Quantification of Four Main Chiral Glucosinolates in Radix Isatidis and Its Granules Using High-Performance Liquid Chromatography/Diode Array Detector Coupled with Circular Dichroism Detection.[Pubmed:29844266]

Molecules. 2018 May 29;23(6). pii: molecules23061305.

As chemical drugs, separation and quantification of the specific enantiomer from the chiral compounds in herbal medicines are becoming more important. To clarify the chemical characterization of chiral glucosinolates-the antiviral active ingredients of Radix Isatidis, an optimized efficient method of HPLC-UV-CD was developed to simultaneously separate and quantify the four main chiral glucosinolates: progoitrin, Epiprogoitrin, and R,S-goitrin. The first step was to determine progoitrin, Epiprogoitrin, and R,S-goitrin using HPLC-UV, and then determine the R-goitrin and S-goitrin by coupling with CD detection. Subsequently, through the linear relations between anisotropy factor (g factor) and the percent optical purity of R-goitrin, the contents of R-goitrin and S-goitrin from the R,S-goitrin mixture were calculated separately. Furthermore, the chemical composition features of the four chiral glucosinolates in 37 samples from crude drugs, decoction pieces, and granules of R. Isatidis were conducted. The total content of the four glucosinolates was obviously higher in crude drugs, and the variance character of each glucosinolate contents was different. In summary, the accurate measurement method reported here allows for better control of the internal quality of R. Isatidis and its granules and provides a powerful approach for the analysis of other chiral components in traditional Chinese medicines.