Alqahtani Yahya S
Department of Pharmaceutical Chemistry, College of Pharmacy, Najran University, Najran, Saudi Arabia.
Steroids. 2021 Aug;172:108857. doi: 10.1016/j.steroids.2021.108857. Epub 2021 May 1.
Natural product is a well-known source of bioactive compounds. Herein, a steroidal compound stigmasta-7,22-diene-3-one (stigmastadienone) has been isolated from Isodon rugosus. The potency of isolated compound has been tested for several in-vitro targets. The acetyl and butyrylcholinesterase assays were performed using Ellman's procedure. For the in-vitro antidiabetic potential, α-glucosidase inhibitory assay was performed. Similarly, the cyclo and lipoxygenase pathways were studied to find its potential role in the management of inflammation and analgesia. The 2,2-diphenyl-1-picrylhydrazyl (DPPH), 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) and hydrogen peroxide (HO) assays were performed for the antioxidant potentials. Docking studies were performed against acetylcholinesterase, cyclooxygenase and lipoxygenase targets. In anticholinesterase assays, stigmastadienone exhibited half-maximal inhibitory concentration (IC) values of 13.52 and 11.53 μg/ml for acetyl and butyrylcholinesterase respectively. The observed IC values for that of galantamine were 6.07 and 4.42 μg/ml for acety and butyrylcholinesterase respectively. In inhibiting α-glucosidase enzyme, the compound showed mediocre IC of 109.40 μg/ml compared to the standard acarbose (7.60 μg/ml). The stigmastadienone proved to be an excellent inhibitor of cyclooxygenase 2 (COX-2) and 5-lipoxygenase (5-LOX) attaining IC values of 4.72 and 3.36 μg/ml respectively. The standard drugs IC values for COX-2 (celecoxib) and 5-LOX (montelukast) were 3.81 and 2.74 μg/ml respectively. The enzymatic activities of stigmastadienone were also supplemented with antioxidant results, specifically it was more dominant against DPPH and ABTS free radicals. Docking studies showed that only the carbonyl oxygen is able to form hydrogen bond interaction with the residues. In conclusions, the stigmastadienone has been isolated from Isodon rugosus for the first time. Moreover, the compound has been evaluated for several biochemical pathways which suggest its pharmacological role on the explored targets.
天然产物是生物活性化合物的著名来源。在此，从皱叶香茶菜中分离出一种甾体化合物豆甾-7,22-二烯-3-酮（豆甾二烯酮）。已对分离出的化合物针对多个体外靶点的效力进行了测试。使用埃尔曼方法进行乙酰胆碱酯酶和丁酰胆碱酯酶测定。对于体外抗糖尿病潜力，进行了α-葡萄糖苷酶抑制测定。同样，研究了环氧化酶和脂氧合酶途径，以发现其在炎症和镇痛管理中的潜在作用。进行了2,2-二苯基-1-苦基肼（DPPH）、2,2'-联氮-双-（3-乙基苯并噻唑啉-6-磺酸）（ABTS）和过氧化氢（HO）测定以评估抗氧化潜力。针对乙酰胆碱酯酶、环氧化酶和脂氧合酶靶点进行了对接研究。在抗胆碱酯酶测定中，豆甾二烯酮对乙酰胆碱酯酶和丁酰胆碱酯酶的半数抑制浓度（IC）值分别为13.52和11.53μg/ml。加兰他敏对乙酰胆碱酯酶和丁酰胆碱酯酶的观察到的IC值分别为6.07和4.42μg/ml。在抑制α-葡萄糖苷酶方面，与标准阿卡波糖（7.60μg/ml）相比，该化合物显示出中等的IC值，为109.40μg/ml。豆甾二烯酮被证明是环氧化酶2（COX-2）和5-脂氧合酶（5-LOX）的优秀抑制剂，IC值分别为4.72和3.36μg/ml。COX-2（塞来昔布）和5-LOX（孟鲁司特）的标准药物IC值分别为3.81和2.74μg/ml。豆甾二烯酮的酶活性也得到了抗氧化结果的补充，具体而言，它对DPPH和ABTS自由基的作用更显著。对接研究表明，只有羰基氧能够与残基形成氢键相互作用。总之，首次从皱叶香茶菜中分离出豆甾二烯酮。此外，已对该化合物在多个生化途径方面进行了评估，这表明其在探索的靶点上具有药理作用。
