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We recently reported that a butanol soluble fraction from the stem of Cassia occidentalis (CSE-Bu) consisting of osteogenic compounds mitigated methylprednisone (MP)-induced osteopenia in rats, albeit failed to afford complete protection thus leaving a substantial scope for further improvement. To this aim, we prepared an oral formulation that was a lipid-based self-nano emulsifying drug delivery system (CSE-BuF). The globule size of CSE-BuF was in the range of 100-180 nm of diluted emulsion and the zeta potential was -28 mV. CSE-BuF enhanced the circulating levels of five osteogenic compounds compared to CSE-Bu. CSE-BuF (50 mg/kg) promoted bone regeneration at the osteotomy site and completely prevented MP-induced loss of bone mass and strength by concomitant osteogenic and anti-resorptive mechanisms. The MP-induced downregulations of miR29a (the positive regulator of the osteoblast transcription factor, Runx2) and miR17 and miR20a (the negative regulators of the osteoclastogenic cytokine RANKL) in bone was prevented by CSE-BuF. In addition, CSE-BuF protected rats from the MP-induced sarcopenia and/or muscle atrophy by downregulating the skeletal muscle atrogenes, adverse changes in body weight and composition. CSE-BuF did not impact the anti-inflammatory effect of MP. Our preclinical study established CSE-BuF as a prophylactic agent against MP-induced osteopenia and muscle atrophy.

Ethnopharmacological Relevance: Cassia occidentalis L., a synonym of Senna occidentalis (belongs to Caesalpiniaceae family) is an annual plant. Pursuing a lead from a folk practice prevalent since the late nineteenth century in Andhra Pradesh, a Southern state of India, of use of Cassia occidentalis leaf and stem for treating patients with fracture and bone diseases, we have not only confirmed its fracture healing activity but also demonstrated efficacy in preventing glucocorticoid-induced osteoporosis (GIO), the commonest form of medication-induced bone loss caused chiefly due to impairment of bone formation., Aim of the Study: In the present work, the effects of extract and fraction of leaf and stem of Cassia occidentalis was investigated in fracture healing and GIO models of rat. The study also aimed to identify osteogenic compounds from this plant., Materials and Methods: Ethanolic extracts from leaf and stem of Cassia occidentalis were prepared and their efficacy tested in rat femur osteotomy (fracture healing) model. Subsequently, a butanolic fraction was prepared and osteogenic efficacy compared with the ethanolic extract, and upon finding the former to be more potent, its osteogenic effect was studied in details in GIO model. Chemical finger-printing and isolation of ten pure compounds were done to assess their osteogenic effect in rat primary osteoblast cultures., Results: Ethanolic extract of stem was more effective than the leaf extract in enhancing bone regeneration at the site of osteotomy. Further, butanolic fraction of the ethanolic extract of stem was more effective than the later in bone regeneration at the femur osteotomy site and in preventing bone loss in GIO model. The mechanism of skeletal preservation involved stimulation of new bone formation and inhibition of bone resorption. As many as six osteogenic compounds were isolated out of which apigenin-6C-glucopyranoside was most effective in vitro., Conclusion: Our study found that a standardized extract of an ethanolic extract and its butanolic fraction from the stem of Cassia occidentalis has osteogenic as well as anti-resorptive effects, resulting in the protection against glucocorticoid-induced bone loss. Our results contribute towards validation of the traditional use of Cassia occidentalis in fracture healing and also suggest its beneficial use in GIO for which clinical trials are warranted., (Copyright © 2019. Published by Elsevier B.V.)

Objectives: This study was undertaken to investigate the effects of a heartwood ethanolic extract (HEE) made from the Dalbergia sissoo on facture healing and in the prevention of pathological bone loss resulting from estrogen deficiency in ovariectomized (Ovx) rats., Methods: Heartwood ethanolic extract (250, 500 and 1000 mg/kg per day) was administered orally immediately next day after drill-hole injury and continued for 2 weeks. Ovx rats received HEE at same doses for 12 weeks and compared with 17-β estradiol (E2; 100 μg/kg for 5 days/week subcutaneously) group. Confocal imaging for fracture healing, micro-architecture of long bones, biomechanical strength, formation of mineralized nodule by bone marrow osteoprogenitor cells, bone turnover markers and gene expression were studied. One-way ANOVA was used to test significance., Key Findings: Heartwood ethanolic extract treatment promoted fracture healing, formation of new bone at the drill-hole site and stimulated osteogenic genes at callus region. HEE administration to the Ovx rats exhibited better micro-architectural parameters at various anatomical positions, better bone biomechanical strength and more osteoprogenitor cells in the bone marrow compared with Ovx + vehicle group. HEE exhibited no uterine estrogenicity., Conclusions: Oral administration of HEE was found to promote fracture healing and exhibited osteoprotective effect by possibly stimulation of osteoblast function., (© 2017 Royal Pharmaceutical Society.)

Leaves of Dalbergia sissoo is known to have protective actions against postmenopausal bone loss in rat. In this study, we have evaluated the fracture healing properties of ethanolic extract (EE) of Dalbergia sissoo leaves. To observe the fracture healing property in the drill-hole injury model, we randomly divided total 32 adult female Sprague Dawley rats (180±200g) into 4 groups: (i) Control operated group; (ii) EE (250mg/kg/day); (iii) EE (500mg/kg/day) and (iv) EE (1000mg/kg/day). The right femora were fractured at the mid-diaphysis region and each group of rats received their respective treatment for 15days. Ethanol extract dose dependently induced bone regeneration at the fracture site assessed by fluorochrome labeling. All of three doses, 250mg/kg/day dose significantly increased bone volume fraction, trabecular thickness, trabecular number, and connectivity density and decreased trabecular separation in bone. Furthermore, the extract induced the expression of osteogenic genes including BMP-2, BMP-4, RunX-2 and COL-1 compared to the control group. The EE improved fracture healing much earlier (day 15) than the normal healing process, as assessed by the increased callus volumes and mineralized nodule formation. This extract is found beneficial in fracture healing of rat., (Copyright © 2016 Elsevier Masson SAS. All rights reserved.)

Objective: Dalbergiphenol (DGP) is a neoflavonoid isolated from heartwood of Dalbergia sissoo. Effects of DGP on skeletal health remain to be elucidated. The objective of the present study was to investigate the biological effects of DGP on bone loss in ovariectomized mice., Methods: Adult BALB/c mice were ovariectomized and administered DGP (1 and 5  mg/kg/d) or 17β-estradiol (E2) orally for 6 weeks. The sham group and the ovariectomy (OVX) + vehicle group served as controls. Eight female BALB/c mice were taken for each group. Uterine estrogenicity, bone microarchitecture, biomechanical strength, new bone formation (based on bone formation rate and mineral apposition rate), and skeletal expression of osteogenic and resorptive gene markers were studied., Results: OVX resulted in a marked increase in body weight and a decrease in femoral and vertebral trabecular bone volume that were prevented by DGP or E2 treatment. DGP treatment increased bone biomechanical strength and new bone formation rate in ovariectomized mice, comparable with E2 treatment. However, increase in uterine weight and estrogenicity were observed in E2-treated ovariectomized mice, but not in response to DGP treatment. Treatment with DGP increased messenger RNA expression of runt-related transcription factor 2, osterix, and collagen type I, and decreased messenger RNA expression of tartrate-resistant acid phosphatase and the osteoprotegerin-to-receptor activator of nuclear factor-κB ligand ratio in the femur of ovariectomized mice., Conclusions: Overall findings suggest that DGP treatment can effectively prevent OVX-induced increase in bone loss and decrease in bone strength possibly by increasing osteoblastic activities and by decreasing osteoclastic activities.

The present study was undertaken to investigate and rationalize the in vitro antiosteoporotic activity of neoflavonoids, isolated from Dalbergia sissoo heartwood. Neoflavonoids were isolated using extensive column chromatography and identified as dalsissooal (1) a new compound and cearoin (2), dalbergin (3), 4-methoxy dalbergion (4), dalbergiphenol (5), dalbergichromene (6), methyl dalbergin (7) and latinone (8) as known compounds by comparison their spectroscopic data with those reported in the literature. Among the screened compounds, compounds 1, 3, 5-8 significantly increased proliferation as assessed by alkaline phosphatase activity and mineralization in calvarial osteoblast cells., (Copyright © 2014 Elsevier Ltd. All rights reserved.)