A nutraceutical composition containing diosmin and hesperidin has osteogenic and anti-resorptive effects and expands the anabolic window of teriparatide

被引：19

作者：

Bhattacharyya, Sharmistha ^{[1
]}

Pal, Subhashis ^{[2
]}

Mohamed, Riyazuddin ^{[3
]}

Singh, Priya ^{[2
]}

Chattopadhyay, Sourav ^{[4
]}

China, Shyamsundar Pal ^{[2
]}

Porwal, Konica ^{[2
]}

Sanyal, Sabyasachi ^{[4
]}

Gayen, Jiaur R. ^{[3
]}

Chattopadhyay, Naibedya ^{[2
]}

机构：

[1] CSIR Cent Drug Res Inst, Div Endocrinol, DBT BIOcare, Lucknow 226031, Uttar Pradesh, India

[2] CSIR, Cent Drug Res Inst, Div Endocrinol, Lucknow 226031, Uttar Pradesh, India

[3] CDRI CSIR, Div Pharmaceut, Lucknow 226031, Uttar Pradesh, India

[4] CSIR CDRI, Div Biochem, Lucknow 226031, Uttar Pradesh, India

来源：

BIOMEDICINE & PHARMACOTHERAPY | 2019年 / 118卷

关键词：

Nutraceutical; Parathyroid hormone; Bone regeneration; Osteoporosis; Estrogen receptors; Sclerostin; PARATHYROID-HORMONE; POSTMENOPAUSAL OSTEOPOROSIS; BONE MASS; OSTEOBLASTIC DIFFERENTIATION; VENOUS THROMBOEMBOLISM; RALOXIFENE THERAPY; DOUBLE-BLIND; ESTROGEN; RECEPTOR; SCLEROSTIN;

D O I：

10.1016/j.biopha.2019.109207

中图分类号：

R-3 [医学研究方法]; R3 [基础医学];

学科分类号：

1001 ;

摘要：

A combination of diosmin and hesperidin (9:1 ratio) is marketed as a dietary supplement/nutraceutical for cardiovascular health. We studied the skeletal effect of this combination (90% diosmin and 10% hesperidin, henceforth named as DH). We showed that a) in rats with femur osteotomy, DH stimulated callus bone regeneration, b) in growing rats, DH promoted peak bone mass achievement and c) in OVX rats rendered osteopenic, DH completely restored femur trabecular bones and strength along with the increases in surface referent bone formation and serum osteogenic marker. Furthermore, DH suppressed bone resorption in OVX rats as well as in OVX rats treated with teriparatide (human parathyroid hormone 1-34) but did not affect the osteoanabolic effect of teriparatide. These data suggested that DH could prolong the anabolic window of teriparatide. To understand the mechanism of DH action, we performed pharmacokinetic studies and observed that upon its oral administration the only circulating metabolites was diosmetin (the aglycone form of diosmin) while none of the two input flavanones were detectable. Accordingly, subsequent experiments with diosmetin revealed that it was a selective estrogen receptor-beta agonist that stimulated osteoblast differentiation and suppressed sclerostin the anti-osteoblastogenic Wnt antagonist. Taken together, our study defined a positive skeletal effect of DH.

引用

页数：11

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