Beneficial Effects and Toxicity Studies of Xian-ling-gu-bao on Bone Metabolism in Ovariectomized Rats
Authors: Jie Song
Rongling Zhong
Liang Feng
Ziqi Shi
Hao Wu
Fang Fang
Qingxiang Zhong
Man Wang
Xiaobin Jia
Jing Wang
Zhongcheng Ke
E Sun
Zhi Xia
Yingjie Wei
Houcai Huang
Journal: Frontiers in Pharmacology (2017)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: OPG/RANKL; XLGB; osteoporosis; ovariectomized rats; toxicity test.
Affiliations: Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese MedicineNanjing, China., Key Laboratory of New Drug Delivery System of Chinese Materia Medica, Jiangsu Province Academy of Chinese MedicineNanjing, China., College of Pharmacy, Anhui University of Chinese MedicineHefei, China., College of Nursing, Huanghai UniversityQingdao, China., Laboratory Animal Center, Jiangsu Province Academy of Chinese MedicineNanjing, China.

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. 

Retracted: No

PubPeer comments:
 This paper reported similar results to those reported by the same group in other papers. However, the materials in those other papers were different materials, and in some cases results were presented that were otherwise unavailable due to  Failure in sample. For details, refer to the images below. ![file] ![file] ,