Total extract and standardized fraction from the stem bark of Butea monosperma have osteoprotective action: evidence for the nonestrogenic osteogenic effect of the standardized fraction.
The aim of this study was to determine the skeletal effects of Butea total extract (BTE) and its acetone soluble fraction (ASF) from Butea monosperma, which is rich in methoxyisoflavones, in ovariectomized (OVx) rats, a model for postmenopausal bone loss.
BTE (1.0 g kg d) and ASF (100 mg kg d) were given orally for 12 weeks to adult OVx rats. The sham-operated and ovariectomy + vehicle groups served as controls. Bone mineral density, osteoid formation (mineral apposition rate and bone formation rate), bone microarchitecture, and bone turnover/resorption markers were studied. Phytoestrogens in rats given BTE and ASF were analyzed by high-performance liquid chromatography. One-way analysis of variance was used to test significance of effects.
OVx rats treated with either BTE or ASF exhibited increased bone mineral density in trabecular bones and improved trabecular microarchitecture compared with the ovariectomy + vehicle group. ASF treatment was more efficient than BTE treatment in maintaining trabecular microarchitecture. Serum osteocalcin and urinary type 1 collagen levels in OVx rats treated with either BTE or ASF were significantly lower than those of the ovariectomy + vehicle group. ASF treatment led to increased mineral apposition rate and bone formation rate compared with ovariectomy + vehicle, whereas BTE had no such effect. In the uterotropic assay, BTE was mildly estrogenic in adult OVx rats. In immature rats, BTE exhibited both estrogenicity and antiestrogenicity. ASF had neither uterine estrogenicity nor antiestrogenicity. Analysis of phytoestrogens revealed significant enrichment of cladrin, isoformononetin, and medicarpin in ASF over BTE.
Derived from B monosperma, ASF at a 10-fold lower dose than that of BTE was effective in preventing OVx-induced bone loss and stimulated new-bone formation.
Pandey R, Gautam AK, Bhargavan B, Trivedi R…
Greater Skeletal Gains in Ovary Intact Rats at Maturity Are Achieved by Supplementing a Standardized Extract of Butea monosperma Stem Bark that Confers Better Bone Conserving Effect following Ovariectomy and Concurrent Treatment Withdrawal.
With a longitudinally designed study, we tested whether an acetone soluble fraction (ASF) from the stem bark of Butea monosperma resulted in maximizing bone gain in rats during growth and maturation and thus protected against osteopenia following ovariectomy (OVx) with concomitant treatment withdrawal. Female rats at weaning were given ASF (100 mg/kg/d) or vehicle for 12 weeks, and baseline skeletal parameters (micro-CT) and total plasma antioxidant status (TAS) were measured. At this stage, one group was OVx and the other group was sham operated. Vehicle group (untreated) after OVx was given E2 or continued with vehicle (OVx control). ASF group after OVx was given vehicle (ASF withdrawn, ASFW). After another 12 weeks, all groups were killed and various skeletal parameters were determined. ASF resulted in substantially better skeletal parameters and higher plasma TAS over control at maturity. Rats treated with ASF before OVx had reduced rates of bone loss compared to OVx control. Twelve weeks after OVx, the ASFW group exhibited better trabecular microarchitectural preservation, bone turnover profiles, increased cortical deposition, and biomechanical strength over the OVx control, and the effects were comparable to OVx + E2 group. ASF supplementation during skeletal growth could maximize bone accrual and could confer increased resistance to post-OVx osteopenia despite treatment withdrawal.
Srivastava K, Khan K, Tyagi AM, Khan MP…
Evid Based Complement Alternat Med 2013
PMID: 23710224 | Free Full Text
O-methoxy substitutions of free phenolic hydroxyl groups of the most abundant soy isoflavones (genistein and daidzein) enhance the lipophilicity, metabolic stability, and uterine safety, thus improving pharmacokinetic/metabolic stability profiles of genistein and daidzein and, consequently, enhance the pharmacodynamic effect (in vivo potency) [12, 13]. In our phytopharmacological evaluation program, aimed at discovering effective alternative strategy for reducing the risk of developing postmenopausal osteopenia, we showed that a standardized fraction (an acetone soluble fraction, ASF) made from the stem bark of Butea monosperma contained four methoxyisoflavones: cajanin (7-methoxy genistein), medicarpin (a methoxypterocarpan with cyclized genistein ring structure), isoformononetin (7-methoxy daidzein), and cladrin (3′4,-dimethoxy daidzein) at percent concentration of 0.061, 0.019, 0.007, and 0.003, respectively . Each one of these, when administered to female rats for four weeks after weaning resulted in increased BMD, bone strength, and bone formation rate with varying efficacy. In vitro, all four compounds stimulated osteoblast function more potently than genistein and daidzein by different modes of action [15–17]. These observations prompted us to hypothesize that the presence of these methoxyisoflavones in the ASF could synergistically augment peak bone mass accrual in female rats at maturity that will confer a superior bone conserving ability after surgical menopause (due to ovariectomy, OVx) even as the treatment is withdrawn.