{"doi":"10.3389/fphar.2025.1587128","title":"Ethnopharmacological exploration and isolation of HIV-1 latency-reversing agents from Sudanese medicinal plants","abstract":"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 G. kraussiana showed the highest LTR activation (EC 50 = 3.75 μg/mL) with no significant cytotoxicity observed. Bioactivity-guided fractionation of the Gnidia kraussiana 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 50 = 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 G. kraussiana 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).","journal":"Frontiers in Pharmacology","year":2025,"id":536475,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9532,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":299090,"name":"Naoki Kishimoto","orcid":"0000-0002-9401-8118","position":1,"is_corresponding":false},{"id":1421290,"name":"Teppei Kawahara","orcid":"0000-0001-5140-4724","position":2,"is_corresponding":false},{"id":1421803,"name":"Sara Mustafa Idris Elbashir","orcid":null,"position":3,"is_corresponding":false},{"id":1421804,"name":"Tae Yasutake","orcid":null,"position":4,"is_corresponding":false},{"id":1421291,"name":"Mikiyo Wada","orcid":"0000-0001-8126-6692","position":5,"is_corresponding":false},{"id":1421292,"name":"Yuki Hitora","orcid":"0000-0003-4271-2543","position":6,"is_corresponding":false},{"id":1421293,"name":"Maha Kordofani","orcid":"0000-0003-1334-215X","position":7,"is_corresponding":false},{"id":1421294,"name":"Wadah Osman","orcid":"0000-0003-4368-5161","position":8,"is_corresponding":false},{"id":1421805,"name":"Mustafa I. Elbashir","orcid":null,"position":9,"is_corresponding":false},{"id":299092,"name":"Shogo Misumi","orcid":"0000-0002-9465-4720","position":10,"is_corresponding":false},{"id":1421802,"name":"Khaled M. Elamin","orcid":null,"position":0,"is_corresponding":true}],"reference_count":22,"raw_metadata":null,"created_at":"2026-07-19T02:52:05.227140Z","pmid":"40843377","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}