从榆属植物中分离得到的一种新型黄酮类化合物 6-C-β-d-吡喃葡萄糖基-(2S,3S)-(+)-3',4',5,7-四羟基黄烷酮可减轻去卵巢大鼠骨质疏松症。

A novel flavonoid, 6-C-beta-d-glucopyranosyl-(2S,3S)-(+)-3',4',5,7-tetrahydroxyflavanone, isolated from Ulmus wallichiana Planchon mitigates ovariectomy-induced osteoporosis in rats.

机构信息

Division of Endocrinology, Central Drug Research Institute (Council of Scientific and Industrial Research), Chattar Manzil, Lucknow, India.

出版信息

Menopause. 2010 May-Jun;17(3):577-86. doi: 10.1097/gme.0b013e3181d2ce7f.

DOI:10.1097/gme.0b013e3181d2ce7f

PMID:20393370

Abstract

OBJECTIVE

The aim of this study was to determine the skeletal effect of 6-C-beta-d-glucopyranosyl-(2S,3S)-(+)-3',4',5,7-tetrahydroxyflavanone (GTDF)/Ulmoside A, a new compound isolated from the extract of Ulmus wallichiana in a rat model of postmenopausal bone loss.

METHODS

GTDF (1.0 and 5.0 mg kg d) was given orally to ovariectomized (OVx) rats (180-200 g) for 12 weeks. Sham operated + vehicle, ovariectomy + 17beta-estradiol (2.5 microg kg d), and ovariectomy + vehicle groups served as various controls. Bone mineral density (BMD), trabecular microarchitecture, bone biomechanical strength, levels of bone turnover/resorption markers, uterotropic effect, and plasma pharmacokinetics were studied. One-way analysis of variance was used to test significance of effects.

RESULTS

OVx rats treated with both doses of GTDF exhibited significantly higher BMD in the trabecular (distal femur, proximal tibia, and vertebrae) and cortical (femur shaft) regions compared with the ovariectomy + vehicle group. Micro-CT demonstrated that OVx rats treated with 5.0 mg kg day of GTDF had better bone microarchitectural parameters compared with the ovariectomy + vehicle group. Serum osteocalcin and urinary C-terminal teleopeptide of Type I collagen levels in OVx rats treated with GTDF (at both doses) were significantly lower than those in the ovariectomy + vehicle group. At neither of the two doses did GTDF exhibit uterine estrogenicity. A pharmacokinetic study revealed that GTDF achieved maximum plasma concentration (40.67 ng mL) at approximately 1 hour, indicating its slow absorption. Its absolute bioavailability was found to be 1.04% with a plasma elimination half-life of approximately 5 hours.

CONCLUSIONS

GTDF, a novel compound isolated from U wallichiana extract, improves bone biomechanical quality through positive modifications of BMD and trabecular microarchitecture without a hyperplastic effect on the uterus.

摘要

目的

本研究旨在探讨从梨属植物中分离得到的新化合物 6-C-β-D-吡喃葡萄糖基-(2S,3S)-(+)-3',4',5,7-四羟基黄烷酮（GTDF）/Ulmoside A 对去卵巢骨质疏松大鼠骨骼的影响。

方法

GTDF（1.0 和 5.0 mg·kg-1·d-1）经口给予 180-200 g 去卵巢大鼠 12 周。假手术+载体、去卵巢+17β-雌二醇（2.5 μg·kg-1·d-1）和去卵巢+载体组作为不同的对照组。研究了骨矿物质密度（BMD）、骨小梁微结构、骨生物力学强度、骨转换/吸收标志物水平、子宫生殖效应和血浆药代动力学。采用单因素方差分析检验效应的显著性。

结果

用两种剂量 GTDF 治疗的去卵巢大鼠，其骨小梁（远端股骨、近端胫骨和椎体）和皮质（股骨骨干）区域的 BMD 明显高于去卵巢+载体组。微 CT 显示，用 5.0 mg·kg-1·d-1 的 GTDF 治疗的去卵巢大鼠的骨微结构参数明显优于去卵巢+载体组。GTDF（两种剂量）治疗的去卵巢大鼠的血清骨钙素和尿Ⅰ型胶原 C 端肽水平明显低于去卵巢+载体组。GTDF 既没有在两种剂量下表现出子宫雌激素活性。药代动力学研究表明，GTDF 在大约 1 小时达到最大血浆浓度（40.67 ng·mL-1），表明其吸收缓慢。绝对生物利用度为 1.04%，血浆消除半衰期约为 5 小时。