Application Of Serum Pharmacochemistry Of Chinese Medicine (Ⅳ)

AimAs one of the subjects of studies on Liu Wei Di Huang Wan,this work is focusing on the main effective compounds in vivo and the metabolic process of Liu Wei Di Huang Wan,based on the previous serum pharmacochemistry studies on the formula.MethodUsing classical separating method and prep-HPLC, the constituents absorbed into blood after oral administration of Liu Wei Di Huang Wan were separated and identified. The replenishing kidney activity of these constituents was evaluated on the rat model of kidney-yin deficiency induced by hydrocortisone. And then, the activity of stimulating osteoblast proliferation of some constituents were observed by method of primary cell culture of Wistar neonate rats. At last, the pharmacokinetics parameters were obtained to explore the in vivo metabolic process of these constituents.Result1 In the study, 11 constituents absorbed into blood were separated and identified. Compound 1 was identified as 5-hydroxymethyl-2-furoic acid (5-HMFA), compound 2 was morroniside, compound 3 was 2-hydroxyacetophenone-4-O- glucopyranuronoside, compound 4 was sweroside, compound 5 was loganin, compound 6 was 4-methoxyl-5-sulphoacetophenone -2-O-glucopyranuronoside, compound 7 was peoniflorin, compound 8 was 2,4-dihydroxyacetophenone, compound 9 was the metabolite of paeonol and being separated, compound 10 was the original compound of Fructus corni and being separated, and compound 11 was paeonol.2 The body weight, heart rate, thymus index, spleen index, the activity of SOD and GSH-PX, plasma viscosity, FT₄, T, E₂/T, ALP of kidney-yin deficiency rat model were downregualted by 5-HMFA, Mix.(mixture containing morroniside, sweroside and loganin) and paeonol. Consequently, these five compounds were proved to be the effective compoundsof Liu Wei Di Huang Wan on replenish kidney.3 The osteoblast proliferation was increased obviously by the mixture containing morroniside, sweroside and loganin with the dose of 5x10 g*mL .4 The pharmacokinetics parameters of 5-HMFA, loganin, paeonol and 2,4-dihydroxyacetophenone after oral administration of Liu Wei Di Huang Wan were obtained, and all of these four compounds were rapidly absorbed and distributed , and eliminated slowly with larger AUC.ConclusionIn the study, the constituents absorbed into blood after oral administration of methanol extraction of Liu Wei Di Huang Wan were separated and identified. Besides, the effective compounds with replenishing kidney and antiosteoporosis activities were identified and their pharmacokinetics parameters were elucidated. This study will definately contributes to the development of modern drug delivery system of Liu Wei Di Huang Wan.