Elamin Khaled M, Kishimoto Naoki, Kawahara Teppei, Idris Elbashir Sara Mustafa, Yasutake Tae, Wada Mikiyo, Hitora Yuki, Kordofani Maha, Osman Wadah, Elbashir Mustafa Idris, Misumi Shogo
Global Center for Natural Products Research, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan.
Department of Environmental and Molecular Health Sciences, Faculty of Medical and Pharmaceutical Sciences, Kumamoto University, Kumamoto, Japan.
Front Pharmacol. 2025 Aug 6;16:1587128. doi: 10.3389/fphar.2025.1587128. eCollection 2025.
HIV-1 infection remains a major health challenge, especially in resource-limited settings such as Sudan, where traditional medicine is widely practiced for managing infectious diseases, including HIV/AIDS. In this study, we selected ten Sudanese medicinal plants traditionally used to treat immune-related and infectious diseases. The selection was based on ethnobotanical reports and local knowledge of HIV/AIDS-related treatments. Crude extracts were prepared using either absolute methanol or 50% ethanol via maceration, resulting in a total of 20 extracts. The extracts were then screened for HIV-1 latency reversal using a luciferase reporter assay in TZM-bl cells. The 50% ethanolic extract of showed the highest LTR activation (EC = 3.75 μg/mL) with no significant cytotoxicity observed. Bioactivity-guided fractionation of the extract led to the isolation of gnidilatidin, a daphnane-type diterpenoid, using ultrahigh-performance liquid chromatography coupled with high-resolution mass spectrometry (UHPLC-HRMS). Gnidilatidin demonstrated potent latency-reversing activity (EC = 5.49 nM in J-Lat 10.6 cells) and downregulated CD4 and CXCR4, suggesting enhanced inhibition of HIV-1 entry. This study supports the ethnopharmacological relevance of and validates its traditional use. It also identifies gnidilatidin as a promising lead compound for HIV-1 latency-reversal-based strategies. Further studies are needed to optimize its pharmacological profile and further elucidate its therapeutic potential, particularly as part of an optimized combination regimen with combination antiretroviral therapy (cART).
HIV-1感染仍然是一项重大的健康挑战，尤其是在苏丹等资源有限的地区，在那里传统医学被广泛用于治疗包括HIV/AIDS在内的传染病。在本研究中，我们挑选了10种苏丹药用植物，这些植物传统上用于治疗免疫相关疾病和传染病。选择这些植物是基于民族植物学报告以及对HIV/AIDS相关治疗的当地知识。通过浸渍法使用无水甲醇或50%乙醇制备粗提物，共得到20种提取物。然后在TZM-bl细胞中使用荧光素酶报告基因检测法对提取物进行HIV-1潜伏逆转筛选。[植物名称]的50%乙醇提取物显示出最高的长末端重复序列（LTR）激活（半数有效浓度[EC]=3.75μg/mL），且未观察到明显的细胞毒性。通过超高效液相色谱与高分辨率质谱联用（UHPLC-HRMS）对[植物名称]提取物进行生物活性导向分离，得到了瑞香烷型二萜类化合物瑞香狼毒素。瑞香狼毒素表现出强大的潜伏逆转活性（在J-Lat 10.6细胞中的EC=5.49 nM），并下调了CD4和CXCR4，表明对HIV-1进入的抑制作用增强。本研究支持了[植物名称]的民族药理学相关性，并验证了其传统用途。它还确定瑞香狼毒素是基于HIV-1潜伏逆转策略的一种有前景的先导化合物。需要进一步研究以优化其药理特性，并进一步阐明其治疗潜力，特别是作为与联合抗逆转录病毒疗法（cART）优化联合方案的一部分。
