Lipase immobilization on magnetic cellulose microspheres for rapid screening inhibitors from traditional herbal medicines
Lipase immobilization on magnetic cellulose microspheres for rapid screening inhibitors from traditional herbal medicines
复制标题
脂肪酶固定在磁性纤维素微球上用于快速筛选传统草药中的抑制剂
DOI：
10.1016/j.talanta.2021.122374
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发表时间：
2021-04-02
期刊：
影响因子：
6.1
通讯作者：
Shi, Yan-Ping
中科院分区：
文献类型：
--
作者：
Liu, Jia;Zhang, Hai-Xia;Shi, Yan-Ping
随着肥胖症发病率的急剧上升，从传统中草药中筛选脂肪酶抑制剂作为治疗肥胖症的药物具有重要意义。目前用于治疗肥胖症的脂肪酶抑制剂存在毒性和脱靶效应的缺陷。因此，迫切需要从传统中草药中寻找更安全、有效、靶向性更强的抗肥胖药物。本工作以氨基功能化磁性纤维素微球为载体，通过共价键合的方式固定脂肪酶。通过红外光谱、透射电子显微镜和X射线衍射对载体进行了表征。与游离脂肪酶相比，固定化脂肪酶具有较宽的pH和温度耐受范围，较好的pH稳定性、热稳定性、贮存稳定性和重复使用性。通过对固定化脂肪酶动力学性能的研究，计算出固定化脂肪酶的米氏常数为2.05mM，对奥利司他的抑制常数为40.74 μ M。最后，将建立的筛选策略应用于7种中草药中脂肪酶抑制剂的筛选，筛选出具有显著抑制活性的山楂。综上所述，我们新建立的方法不仅为从传统草药中高效发现新型减肥药物开发了平台，而且为成功探索传统草药未被发现的药用价值奠定了坚实的基础。
With a dramatic increase in the incidence of obesity, it is significant to screen lipase inhibitors from traditional herbal medicines as drugs to treat obesity. Lipase inhibitors currently used to treat obesity possess the defects of toxicity and off-target effects. Thus, there is an urgent need to explore more safe, effective and targeted anti-obesity drugs from traditional herbal medicines. In this work, amino functionalized magnetic cellulose microsphere was employed as a novel support to immobilize lipase through covalent bonding. Characterizations from fourier transform infrared spectroscopy, transmission electron microscopy and X-ray diffraction demonstrated the successful preparation of the support. In comparison with the free lipase, the immobilized lipase manifested the excellent properties of a wider range for pH and temperature endurance, better pH, thermal, storage stability and reusability. Through investigating the kinetics performances of the immobilized lipase, the Michaelis-Menten constant was calculated to be 2.05 mM and its inhibition constant for orlistat was ascertained to be 40.74 mu M. Eventually, the established strategy was applied to screen lipase inhibitors from 7 traditional herbal medicines and Crataegus pinnatifida Bunge was screened out due to its significant lipase inhibitory activity. To sum up, our newly established method not only developed a platform for efficiently discovering novel anti-obesity drugs from traditional herbal medicines, but also laid a solid foundation for successfully exploring undiscovered medicinal value of the traditional herbal medicines.