Sillapachaiyaporn Chanin, Rangsinth Panthakarn, Nilkhet Sunita, Moungkote Nuntanat, Chuchawankul Siriporn
Program in Clinical Biochemistry and Molecular Medicine, Department of Clinical Chemistry, Faculty of Allied Health Sciences, Chulalongkorn University, Bangkok 10330, Thailand.
Department of Transfusion Medicine and Clinical Microbiology, Faculty of Allied Health Sciences, Chulalongkorn University, Bangkok 10330, Thailand.
Pharmaceuticals (Basel). 2021 Oct 31;14(11):1115. doi: 10.3390/ph14111115.
Human immunodeficiency virus type-1 (HIV-1) infection causes acquired immunodeficiency syndrome (AIDS). Currently, several anti-retroviral drugs are available, but adverse effects of these drugs have been reported. Herein, we focused on the anti-HIV-1 activity of Roxb. (CA) extracted by hexane (CA-H), ethyl acetate (CA-EA), and methanol (CA-M). The in vitro HIV-1 protease (PR) and HIV-1 reverse transcriptase (RT) inhibitory activities of CA extracts were screened. CA-M potentially inhibited HIV-1 PR (82.44%) comparable to Pepstatin A (81.48%), followed by CA-EA (67.05%) and CA-H (47.6%), respectively. All extracts exhibited moderate inhibition of HIV-1 RT (64.97 to 76.93%). Besides, phytochemical constituents of CA extracts were identified by GC-MS and UPLC-HRMS. Fatty acids, amino acids, and terpenoids were the major compounds found in the extracts. Furthermore, drug-likeness parameters and the ability of CA-identified compounds on blocking of the HIV-1 PR and RT active sites were in silico investigated. Dihydroergocornine, 3β,6α,7α-trihydroxy-5β-cholan-24-oic acid, and 6β,11β,16α,17α,21-Pentahydroxypregna-1,4-diene-3,20-dione-16,17-acetonide showed strong binding affinities at the active residues of both HIV-1 PR and RT. Moreover, antioxidant activity of CA extracts was determined. CA-EA exhibited the highest antioxidant activity, which positively related to the amount of total phenolic content. This study provided beneficial data for anti-HIV-1 drug discovery from CA extracts.
人类免疫缺陷病毒1型（HIV-1）感染会导致获得性免疫缺陷综合征（AIDS）。目前，有几种抗逆转录病毒药物可供使用，但这些药物的不良反应已有报道。在此，我们重点研究了用己烷（CA-H）、乙酸乙酯（CA-EA）和甲醇（CA-M）提取的罗汉果提取物（CA）的抗HIV-1活性。筛选了CA提取物的体外HIV-1蛋白酶（PR）和HIV-1逆转录酶（RT）抑制活性。CA-M对HIV-1 PR具有潜在抑制作用（82.44%），与胃蛋白酶抑制剂A（81.48%）相当，其次是CA-EA（67.05%）和CA-H（47.6%）。所有提取物对HIV-1 RT均表现出中等程度抑制（64.97%至76.93%）。此外，通过气相色谱-质谱联用（GC-MS）和超高效液相色谱-高分辨质谱（UPLC-HRMS）鉴定了CA提取物的植物化学成分。脂肪酸、氨基酸和萜类化合物是提取物中发现的主要化合物。此外，还通过计算机模拟研究了CA鉴定化合物的类药参数以及它们阻断HIV-1 PR和RT活性位点的能力。二氢麦角碱、3β,6α,7α-三羟基-5β-胆烷-24-酸和6β,11β,16α,17α,21-五羟基孕甾-1,4-二烯-3,20-二酮-16,17-丙酮化物在HIV-1 PR和RT的活性残基处均表现出很强的结合亲和力。此外，还测定了CA提取物的抗氧化活性。CA-EA表现出最高的抗氧化活性，这与总酚含量呈正相关。本研究为从CA提取物中发现抗HIV-1药物提供了有益数据。
