Abstract
Thiazolidinediones, an antidiabetic drug, promote bone loss and provoke fractures, suggesting a protective role of phytoestrogens rich herbal supplement along with rosiglitazone. The aqueous methanol extract (AME) of Trifolium resupinatum L. var. minus Boiss. (Fabaceae) and defatted AME (DAME) protective effects were assessed against rosiglitazone (Ros) inducing osteoporosis in type 2 diabetic male rats. The bioactive extract was investigated for its phenolics. Eighty male Albino rats (10/group) were used; G1: control, G2: diabetic rats + Ros (10 mg/kgbw/d for 30 days; Ros-rats), G3-G5 and G6-G8: Ros-rats + AME or DAME (24, 12, 6 mg/kgbw/d, each). OPG, RANKL and β2- microglobulin serum levels, femur BMD (Dexa) and OC, COL and ACP5 osteogenic genes mRNA (qRT-PCR) were evaluated. Phenolics were isolated and characterized by chromatographic, chemical and spectral techniques. Their HPLC profiling was also analyzed. Ros-rats + DAME (24 mg/kgbw) revealed the most significant effects on bone biomarkers. It modulated OPG (ng mL-1), RANKL (pg mL-1) and β2- microglobulin (μg mL-1) serum levels with 2.46 ± 0.44, 96.640 ± 06.12, 0.22 ± 0.04, compared to those of Ros--rats (1.62 ± 0.26, 162.42 ± 11.34, 0.46 ± 0.05), respectively. Also, it improved BMD (mg cm-2) of proximal, distal and total femur bones (102.8 ± 8.6, 104.6 ± 10.2, 106.0 ± 9.2), compared to Ros-rats (82.3± 6.4, 81.2 ± 7.2, 82.1 ± 4.8), respectively and up-regulated OC & COL and down-regulated ACP5 expressions. From DAME, 12 phenolics were identified and HPLC profiling showed major phenolics; chlorogenic acid > formononetin> quercetin> pseudobaptigenin. DAME in combination therapy with rosiglitazone provides protective effect on bone, possibly due to its phenolics.
Highlights
Natural products, plant extracts containing phenolics, are being explored for their protective effects against a variety of disease and disorders, including osteoporosis
The aqueous methanol extract (AME) of Trifolium resupinatum L. var. minus Boiss. (Fabaceae) and defatted AME (DAME) protective effects were assessed against rosiglitazone (Ros) inducing osteoporosis in type 2 diabetic male rats
Administration of rosiglitazone to male rats caused significant increase in serum RANKL and β2-microglobulin levels associated with significant decrease in serum OPG level in comparison with the healthy control rats
Summary
Plant extracts containing phenolics, are being explored for their protective effects against a variety of disease and disorders, including osteoporosis. Flavonoids have been reported to improve bone mineral density (BMD) and bone formation (Ma et al, 2008; Weaver, 2012). Isoflavones are a group of flavonoids called phytoestrogens that structurally resemble endogenous estrogens. It has been found to apply prospective health benefits in hormone dependent and age-related diseases, including cancer, cardiovascular disease, menopausal symptoms and osteoporosis (Wu et al, 2003). The major constituents reported from the genus Trifolium are flavonoids, mainly isoflavones (Kazakov et al, 1973; Oleszek et al, 2007; Janda et al, 2009; Sabudak and Guler, 2009; Kicel and Wolbiś, 2012; Dabkevičienė et al, 2012), in addition to limited amount of fatty acids, clovamids, triterpenes, cyanogenic glucosides and phenolic acids
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
