3-methylquercetin and kaempferide

Vitiligo is a long-term skin disease characterized by the loss of pigment in the skin. The current therapeutic approaches are limited. Although the anti-vitiligo mechanisms of Vernonia anthelmintica (L.) remain ambiguous, the herb has been broadly used in Uyghur hospitals to treat vitiligo. The overall objective of the present study aims to identify the potential lead compounds from Vernonia anthelmintica (L.) in the treatment of vitiligo via an oral route as well as the melanogenic mechanisms in the systematic approaches in silico of admetSAR and substructure-drug-target network-based inference (SDTNBI).. The results showed that the top 5 active compounds with a relatively higher bioavailability that interacted with 23 therapeutic targets were identified in Vernonia anthelmintica (L.) using admetSAR and SDTNBI methods. Among these compounds, Isorhamnetin and Kaempferide, which are methyl-flavonoids, performed 1st and 2nd. Isorhamnetin and Kaempferide significantly increased the expression of melanin-biosynthetic genes (MC1R, MITF, TYR, TYRP1 and DCT) and the tyrosinase activity in B16F10 cells. Isorhamnetin and Kaempferide significantly increased the mRNA-expression of melanin-biosynthetic genes (MC1R, MITF, TYR, TYRP1 and DCT), the protein level of MITF and the tyrosinase activity. Based on the SDTNBI method and experimental verification, Isorhamnetin and Kaempferide effectively increased melanogenesis by targeting the MC1R-MITF signaling pathway, MAPK signaling pathway, PPAR signaling pathway (PPARA, PPARD, PPARG), arachidonic acid metabolism pathway (ALOX12, ALOX15, CBR1) and serotonergic synapses (ALOX12, ALOX15) in the treatment of vitiligo from a network perspective.. We identified the melanogenic activity of the methyl-flavonoids Isorhamnetin and Kaempferide, which were successfully predicted in a network pharmacological analysis of Vernonia anthelmintica (L.) by admetSAR and SDTNBI methods.

Topics: Animals; Cell Line, Tumor; Gene Expression Regulation; Kaempferols; Melanins; Melanoma, Experimental; Mice; Plant Extracts; Quercetin; Structure-Activity Relationship; Up-Regulation; Vernonia; Vitiligo

To establish an HPLC-MS/MS method for the analysis of quercetin, kaempferid and isorhamnetin in rats plasma and study its pharmamacokinetics after an intragastrical administration of Hippophae rhamnoides extracts. Five healthy male Sprague-Dawley (SD) rats were given single doses of H. rhamnoides extracts (quercetin 26.35 mg x kg(-1), kaempferid 4.040 mg x kg(-1), isorhamnetin 31.37 mg x kg(-1)), and then their orbital sinus blood samples were collected at different time points. The drug plasma concentration of the three flavonoids was determined by HPLC-MS/MS method. After that, the main pharmacokinetics parameters were calculated by using Kinetica 5. 0. 11 software. The methodological test showed that the linear concentration ranges of quercetin, kaempferid and isorhamnetin were 7.500-600.0 μg x L(-1) (R2 = 0.998 5), 1.000-80.00 μg x L(-1) (R2 = 0.998 5 ) and 10.00-800.0 μg x L(-1) (R2 = 0.998 0), respectively. The inner and inter-days precisions were both less than 14.0%. The plasma samples showed a good stability and consistency with the requirement of biological sample analysis after the samples were frozen once and placed at - 20 degrees C for 15 d and room temperature for 6 h and the treated analytes were placed at -20 degrees C for 24 h. For quercetin, the pharmacokinetic parameter t(½β), AUC(0-∞), MRT(0.∞), C.(max) and T(max) were (113.3 ± 19.37) min, (12 542.14 ± 3 504.05) μg x h x L(-1), (119.6 ± 13.29) h, (164.6 ± 27.33) μg x L(-1) and (5.199 ± 0.840 3) h, respectively. For kaempferid, the pharmacokinetic parameters t(½β), AUC(0-t), MRT(0-∞), C(max) and T(max) were (79.85 ± 17.15) min, (934.51 ± 94.59) μg x h x L(-1), (81.50 ± 13.75) h, (80.15 ± 14.24) μg x L(-1) and (3.827 ± 0.902 7) h, respectively. For isorhamnetin, the pharmacokinetic parameters t1,2,, AUC(0-t), MRT(0-∞), C(max) and T(max) were (118.3 ± 20.73) min, (26 067.77 ± 4 124.60) μg x h x L(-1), (129.0 ± 16.30) h, (269.6 ± 29.32) μg x L(-1) and (6.513 ± 1.450) h, respectively. The HPLC-MS/MS analysis method established in this study was proved to be sensitive and accurate and could be applied in the pharmacokinetic study of quercetin, kaempferid and isorhamnetin in rat plasma.

Topics: Animals; Chromatography, High Pressure Liquid; Drugs, Chinese Herbal; Hippophae; Kaempferols; Male; Quercetin; Rats; Rats, Sprague-Dawley; Tandem Mass Spectrometry

Polygonum aviculare L. (Common Knotrgrass) (Polygonaceae Juss.) is an annual from which pharmacopoeial (Ph. Eur.) plant material Polygoni avicularis herba is obtained. Although its main active constituents are flavonoids and its standardization is based on their total content, no profound qualitative analysis has been performed, yet. The use of hyphenated analytical methods: UHPLC-DAD coupled with ion trap or time of flight mass detectors together with acidic hydrolysis products analysis allowed for a comprehensive determination of flavonoid composition. Among dominating compounds, myricetin, kaempferol, isorhamnetin and kaempferide glucuronides, which were not previously reported in P. avicularis herba, were discovered. The developed method can be used as a suitable tool for a more insightful, metabolome-based standardization of flavonoid rich pharmacopoeial plant material -P. avicularis herba.

Topics: Chromatography, High Pressure Liquid; Flavonoids; Glucuronides; Kaempferols; Mass Spectrometry; Plant Extracts; Polygonum; Quercetin