1beta-Hydroxyalantolactone

Simultaneous determination of three sesquiterpene lactones from Herba Inula extract in rat plasma by LC/MS/MS and its application to pharmacokinetic study.[Pubmed:22819204]

J Chromatogr B Analyt Technol Biomed Life Sci. 2012 Aug 15;903:40-5.

A rapid and sensitive liquid chromatography-tandem mass spectrometry method has been developed and validated for the determination of 1-acetoxy-6alpha-hydroxyeriolanolide, 1beta-Hydroxyalantolactone and ivangustin from Herba Inula extract in rat plasma. Plasma samples were pretreated by protein precipitation with methanol. Chromatographic separation was accomplished on a TOSOH TSKgel ODS column with mobile phase consisting of methanol and 0.3% formic acid (80:20, v/v). The detection was carried out by multiple-reaction monitoring mode under positive electrospray ionization. The quantification was performed using the transitions of m/z 309.1/185.0 for 1-acetoxy-6alpha-hydroxyeriolanolide, m/z 249.0/231.1 for 1beta-Hydroxyalantolactone and ivangustin and m/z 285.0/193.0 for diazepam, respectively. Calibration curves were linear over the concentration range of 4-800 ng/mL for 1-acetoxy-6alpha-hydroxyeriolanolide, 8-500 ng/mL for 1beta-Hydroxyalantolactone and ivangustin. The limit of detection (LOD) was 1 ng/mL for 1-acetoxy-6alpha-hydroxyeriolanolide, 1.6 ng/mL for 1beta-Hydroxyalantolactone and ivangustin (S/N=3). The intra-day and inter-day precisions (RSD%) for the three compounds were less than 7.8% and 8.6%, and the accuracy (RE%) ranged from -4.6 to 6.8%. The method was successfully applied to pharmacokinetic studies of the three sesquiterpene lactones after oral administration of 300 mg/kg Herba Inula extract to rats, the t((1/2)) of 1-acetoxy-6alpha-hydroxyeriolanolide, 1beta-Hydroxyalantolactone and ivangustin was 9.65+/-1.43, 14.88+/-0.82 and 13.93+/-2.74 (h). The AUC((0-t)) of 1-acetoxy-6alpha-hydroxyeriolanolide, 1beta-Hydroxyalantolactone and ivangustin was 1102.46+/-247.04, 808.92+/-117.53 and 990.35+/-275.49 (ng h/mL), respectively.

1beta-Hydroxyalantolactone, a sesquiterpene lactone from Inula japonica, attenuates atopic dermatitis-like skin lesions induced by 2,4-dinitrochlorobenzene in the mouse.[Pubmed:26017682]

Pharm Biol. 2016;54(3):516-22.

CONTEXT: 1beta-Hydroxyalantolactone (IJ-5) is a sesquiterpene lactone compound isolated from Inula japonica Thunb (Asteraceae). Sesquiterpene lactones have been shown to modulate many processes that influence inflammatory reactions. OBJECTIVE: The present study examines the protective effect of IJ-5 on atopic dermatitis (AD) in a mouse model induced by 2,4-dinitrochlorobenzene (DNCB). MATERIALS AND METHODS: AD-like skin lesions were induced in Balb/c mice by sensitizing once with painting 100 muL of 5% DNCB on their shaved back skin and then challenging with 20 muL of 0.2% DNCB five times on their right ears at 3 d interval starting on day 5 post-sensitization. IJ-5 was administrated intraperitoneally at 10 mg/kg 1 h before each DNCB challenge. RESULTS: IJ-5 treatment attenuated DNCB-induced dermatitis severity and right ear swelling. The serum levels of IgE, IL-4, and IL-6 in IJ-5-treated mice were reduced by 54.7, 56.5, and 53.0%, respectively, while the mRNA levels of TNFalpha, IL-1, IL-4, and IL-6 in back skin lesions of IJ-5-treated mice were reduced by 47.7, 61.5, 57.5, and 58.5%, respectively, compared with untreated controls. Histopathological examination showed that IJ-5 treatment decreased DNCB-induced hypertrophy, hyperkeratosis, and infiltration of inflammatory cells in both ear and back skins. Moreover, IJ-5 suppressed the expression of TNFalpha, IL-1, and IL-6 with IC50 values of 6.58, 9.48, and 7.01 muM, respectively, and inhibited the activation of NF-kappaB pathway in TNFalpha-stimulated HaCat cells. DISCUSSION AND CONCLUSION: The present study demonstrates the protective effects of IJ-5 against AD-like skin inflammation and highlights IJ-5 as a potential therapeutic agent for AD.