Xiao Hui-Hui, Sham Tung-Ting, Chan Chi-On, Li Meng-Heng, Chen Xi, Wu Qing-Chang, Mok Daniel Kam-Wah, Yao Xin-Sheng, Wong Man-Sau
State Key Laboratory of Chinese Medicine and Molecular Pharmacology (Incubation), Hong Kong Polytechnic University Shenzhen Research Institute, Shenzhen, China.
Department of Applied Biology and Chemical Technology, Hong Kong Polytechnic University, Hong Kong, China.
Front Pharmacol. 2018 Aug 21;9:932. doi: 10.3389/fphar.2018.00932. eCollection 2018.
The lignan-rich fraction (SWR) of Sambucus Williamsii Ramulus, a folk herbal medicine in China for treatment of bone diseases, has previously reported to exert protective effects on bone without exerting uterotrophic effects in ovariectomized (OVX) mice. The aim of the present study was to identify the potential metabolites and the associated metabolic pathways that contribute to the beneficial effects of SWR on bone . Aged female Sprague Dawley rats (9 months old) were either sham-operated or ovariectomized for 12 weeks, before receiving treatment for another 12 weeks with the following treatment groups ( = 12 each): vehicle (Sham), vehicle (OVX), Premarin (130 μg/kg) or low (57 mg/kg), medium (114 mg/kg), and high (228 mg/kg) doses of SWR. The results showed that SWRH significantly suppressed bone loss, improved bone micro-architecture and increased bone strength on tibia without stimulating uterus weight gain in OVX rats. Premarin exerted similar bone protective effects as SWRH but elicited uterotrophic effects in OVX rats. The metabolic profiles of serum samples were analyzed by using ultra-performance liquid chromatography quadrupole time-of flight mass spectrometry and gas chromatography time-of flight mass spectrometry, and the metabolites that were significantly altered were identified by multivariate statistical analysis. Our study indicated that SWRH effectively restored the changes of 26 metabolites induced by estrogen-deficiency in OVX rats, which related to lipids, amino acids, tryptophan metabolisms, and anti-oxidative system. A subsequent validation showed that the serum level of superoxide dismutase and catalase were indeed up-regulated, while the serotonin level in a tryptophan hydroxylase 1 (TPH1) high expressing cells (rats RBL-2H3 cells) was down regulated after treatment with SWR. The results also suggested that the gut-microbiota may play an important role on the bone protective effects of SWR. The current study provides insight for understanding the unique mechanism of actions of SWR that might be involved in achieving bone protective effects .
接骨木嫩枝富含木脂素的组分（SWR）是中国一种用于治疗骨病的民间草药，此前有报道称其对骨骼具有保护作用，且在去卵巢（OVX）小鼠中不会产生子宫营养作用。本研究的目的是确定有助于SWR对骨骼产生有益作用的潜在代谢产物及相关代谢途径。将老年雌性Sprague Dawley大鼠（9月龄）进行假手术或去卵巢手术12周，然后在接下来的12周内接受以下治疗组的治疗（每组n = 12）：载体（假手术组）、载体（OVX组）、结合雌激素（130 μg/kg）或低（57 mg/kg）、中（114 mg/kg）、高（228 mg/kg）剂量的SWR。结果表明，SWRH能显著抑制OVX大鼠的骨质流失，改善骨微结构并增加胫骨的骨强度，且不会刺激子宫重量增加。结合雌激素在OVX大鼠中发挥了与SWRH相似的骨骼保护作用，但引起了子宫营养作用。使用超高效液相色谱四极杆飞行时间质谱和气相色谱飞行时间质谱分析血清样本的代谢谱，并通过多变量统计分析鉴定出显著改变的代谢产物。我们的研究表明，SWRH有效恢复了OVX大鼠中由雌激素缺乏引起的26种代谢产物的变化，这些变化与脂质、氨基酸、色氨酸代谢和抗氧化系统有关。随后的验证表明，超氧化物歧化酶和过氧化氢酶的血清水平确实上调，而用SWR处理后，色氨酸羟化酶1（TPH1）高表达细胞（大鼠RBL - 2H3细胞）中的血清素水平下调。结果还表明，肠道微生物群可能在SWR的骨骼保护作用中起重要作用。本研究为理解SWR可能参与实现骨骼保护作用的独特作用机制提供了见解。
