Beneficial Effects and Toxicity Studies of Xian-ling-gu-bao on Bone Metabolism in Ovariectomized Rats

Abstract

Xian-ling-gu-bao (XLGB) is a well-known patented traditional Chinese prescription widely used to treat osteoporosis, osteoarthritis, aseptic bone necrosis, or climacteric syndrome. However, recent reports have suggested that XLGB may cause liver injury in humans. In the present study, we aimed to evaluate the efficacy of XLGB in the prevention of osteoporosis in the zebrafish and ovariectomized (OVX) rats, both of which have been used as osteoporosis models. The safety of XLGB after long-term administration to OVX rats was also assessed. OVX rats were administered by oral gavage 270 mg/kg (recommended daily dose), 1350 mg/kg, and 1800 mg/kg of XLGB for 26 weeks. Bone mineral density, relative bone surface to bone volume, relative bone volume to total volume, trabecular number, mean trabecular thickness, and mean trabecular spacing in OVX rats were examined at the end of the 26-week dosing period. Additionally, OPG and RANKL expression in the femur were determined by western blot and immunohistochemical staining. To evaluate the safety of XLGB, body weight, hematology, serum biochemistry markers related to toxicology, and organ histopathology were determined in each group of OVX rats. Conversely, the zebrafish was treated with prednisolone to induce osteoporosis in the embryo. Disodium etidronate was used as a treatment control. XLGB was shown to be effective in preventing osteoporosis in both the OVX rats and the prednisolone-treated zebrafish. Similarly, XLGB increased OPG protein and decreased RANKL protein in OVX rats. Interestingly, no obvious toxicity was observed in the heart, liver, kidney, small intestine, or stomach at dosages of up to 1800 mg/kg after treating the OVX rats for 26 weeks. XLGB was shown to be very effective in treating osteoporosis in OVX rats. No obvious toxicity or adverse effects developed in OVX rats at dosages up to 1800 mg/kg, which is equivalent to six times the daily-recommended dose. Therefore, XLGB should be considered a good option for the treatment of post-menopausal osteoporosis.

Effect of Black Tea Extract and Thearubigins on Osteoporosis in Rats and Osteoclast Formation in vitro

“…Xian-Ling-Gu-Bao is a well-known traditional Chinese patent medicine, widely used in the treatment of osteoporosis, osteoarthritis, aseptic bone necrosis, and bone fracture ( Cheng et al, 2013 ; Gao et al, 2013 ). The Chinese State Food and Drug Administration has officially approved it for use in Traditional Chinese Medicine ( Wu et al, 2017 ). In the animal experiments, similar with XLGB treatment, BTE and TRs treatment could also ameliorated the level of femoral index and serum biochemical markers, and the effects of BTE and TRs were similar to XLGB.…”

Advances in Chemistry and Bioactivity of Magnoflorine and Magnoflorine-Containing Extracts

“…XLGB capsule is an extensively used remedy in Chinese natural medicine for the treatment of osteoporosis [101]. It has been reported that XLGB shows anti-osteoporosis activity in ovariectomized mice [102,103] and rats with oral dosages at 236 mg/kg/day and 270 mg/kg/day, respectively [47]. Moreover, the dose up to 1800 mg/kg/day showed no serious side effects in ovariectomized rats.…”

“…Moreover, the dose up to 1800 mg/kg/day showed no serious side effects in ovariectomized rats. [47,103]. Dose 0.3 g/kg/day used for experiments was based on the body weight conversion to the clinical effective dose of XLGB used for the prevention of postmenopausal osteoporosis.…”

<p>Baicalin Ameliorates Dexamethasone-Induced Osteoporosis by Regulation of the RANK/RANKL/OPG Signaling Pathway</p>

“…This conclusion is consistent with reported. 45 During the process of osteoporosis, RANKL recognizes and binds to its receptor RANK on the surface of osteoclast precursors, and then recruits the adapter protein TRAF6, thereby leading to sequential activation of NF-κB, MAPK, c-Fos and nuclear factor of activated T cells c1 (NFATc1), which mediate the completion of the osteoclast differentiation process. 46,47 TRAF6 triggers the self-amplification and gene transcription of NFATc1 and induces the differentiation process.…”