Mngomezulu Khanyisile, Madlala Paradise, Nkabinde Siphathimandla Authority, Nkabinde Magugu, Ngcobo Mlungisi, Gqaleni Nceba
Traditional Medicine Laboratory, School of Nursing and Public Health, Howard College, University of KwaZulu-Natal, Durban, South Africa.
Africa Health Research Institute (AHRI), Durban, South Africa.
Front Pharmacol. 2025 Jul 2;16:1618187. doi: 10.3389/fphar.2025.1618187. eCollection 2025.
While antiretroviral therapy (ART) has transformed HIV-1 into a manageable chronic illness, its long-term affordability and accessibility remain major challenges in resource-limited settings. Additionally, adverse side effects can compromise treatment adherence and effectiveness. These limitations highlight the need for novel, affordable therapeutic alternatives. In this study, we evaluated the anti-HIV-1 activity of Product Nkabinde (PN), a traditional herbal formulation comprising four plant extracts, and (), to assess their potential as alternative or complementary therapies.
HIV-1 subtype B and subtype C viral stocks were produced by transfecting HEK293T cells with envelope plasmids and an -deficient HIV-1 backbone vector using polyethylenimine. TZM-bl cells were treated with PN and extracts, alone or combined with antiretrovirals (AZT, raltegravir, maraviroc, amprenavir), then infected with the viruses. Viral infectivity was measured using the luciferase assay, and results were validated in peripheral blood mononuclear cells (PBMCs) using HIV-1 p24 ELISA.
The PN extract exhibited a dose-dependent antiviral effect, with the optimal concentration achieving 93% and 96% inhibition of HIV-1 subtype B and C, respectively, in TZM-bl cells, comparable to AZT. In HIV-1 infected PBMCs, treatment with AZT, PN, or resulted in a sustained reduction of p24 antigen levels over 11 days compared to untreated controls. While NL4.3 showed partial inhibition (p24 levels >20,000 pg/mL), strains CM070P.1, YU2, and CM019P.1.2 exhibited consistently low p24 production levels (<20,000 pg/mL), indicating strain-dependent antiviral activity. PN, combined with maraviroc inhibited YU2 replication by 81.3% (p = 0.0361), while combinations with raltegravir and AZT suppressed subtype C strains CM070P.1 and CM019P.1.2 by 98.7% (p = 0.0083) and 99% (p = 0.0428), respectively, compared to either PN or the antiretroviral alone. combined with AZT inhibited NL4.3 by 80.3% (p = 0.0105), and its combinations with maraviroc, raltegravir, and amprenavir suppressed CM070P.1 replication by 87% (p = 0.0093), 86% (p = 0.0168), and 90% (p = 0.0006), respectively, relative to either test agent alone. Fractional inhibitory concentration index (FICI) analysis indicated no synergistic or antagonistic interactions.
Thus, this current data suggests that PN and possess anti-HIV-1 activity.
虽然抗逆转录病毒疗法（ART）已将HIV-1转变为一种可控制的慢性疾病，但其长期可承受性和可及性在资源有限的环境中仍然是重大挑战。此外，不良副作用可能会影响治疗依从性和有效性。这些局限性凸显了对新型、可承受的治疗替代方案的需求。在本研究中，我们评估了由四种植物提取物组成的传统草药配方恩卡宾德产品（PN）以及（此处原文缺失内容）的抗HIV-1活性，以评估它们作为替代或补充疗法的潜力。
通过使用聚乙烯亚胺用包膜质粒和一种缺乏（此处原文缺失内容）的HIV-1骨架载体转染HEK293T细胞来产生HIV-1 B亚型和C亚型病毒株。TZM-bl细胞用PN和（此处原文缺失内容）提取物单独或与抗逆转录病毒药物（齐多夫定、拉替拉韦、马拉维罗、安普那韦）联合处理，然后感染病毒。使用荧光素酶测定法测量病毒感染性，并使用HIV-1 p24 ELISA在外周血单核细胞（PBMC）中验证结果。
PN提取物表现出剂量依赖性抗病毒作用，最佳浓度在TZM-bl细胞中分别对HIV-1 B亚型和C亚型实现了93%和96%的抑制，与齐多夫定相当。在HIV-1感染的PBMC中，与未处理的对照相比，用齐多夫定、PN或（此处原文缺失内容）处理导致p24抗原水平在11天内持续降低。虽然NL4.3显示出部分抑制（p24水平>20,000 pg/mL），但CM070P.1、YU2和CM019P.1.2株表现出持续低水平的p24产生（<20,000 pg/mL），表明存在毒株依赖性抗病毒活性。PN与马拉维罗联合抑制YU2复制达81.3%（p = 0.0361），而与拉替拉韦和齐多夫定联合分别抑制C亚型毒株CM070P.1和CM019P.1.2达98.7%（p = 0.0083）和99%（p = 0.0428），与单独使用PN或抗逆转录病毒药物相比。（此处原文缺失内容）与齐多夫定联合抑制NL4.3达80.3%（p = 0.0105），其与马拉维罗、拉替拉韦和安普那韦联合分别相对于单独的测试剂抑制CM070P.1复制达87%（p = 0.0093）、86%（p = 0.0168）和90%（p = 0.0006）。部分抑制浓度指数（FICI）分析表明没有协同或拮抗相互作用。
因此，目前的数据表明PN和（此处原文缺失内容）具有抗HIV-1活性。
