An ethnopharmacological survey of medicinal plants traditionally used by the BaKalanga people of the Tutume subdistrict in Central Botswana to manage HIV/AIDS, HIV-associated conditions, and other health conditions.

ETHNOPHARMACOLOGICAL RELEVANCE: While access to antiretroviral therapy (ART) continues to improve worldwide, HIV infection and AIDS persist as serious health challenges, particularly in sub-Saharan Africa. Complementary and Alternative Medicines (CAM), as part of indigenous and pluralistic medical systems, are important contributors to primary health care worldwide. However, this knowledge remains relatively undocumented in many parts of sub-Saharan Africa such as the Tutume subdistrict of Central Botswana, where CAM is widely used including potentially for HIV/AIDS and HIV-associated conditions. AIM OF THE STUDY: To explore the extent to which CAM is used by the BaKalanga Peoples of the Tutume subdistrict, we performed an exploratory community-based project to record medicinal plant use from this relatively undocumented region, with a particular focus on species used for management of HIV/AIDS and HIV-associated conditions. MATERIALS AND METHODS: Using the snowball sampling technique, we recruited 13 Traditional Health Practitioners (THPs) and conducted in-depth interviews to explore medicinal plant uses and treatment regimens. Plant specimens were collected and bio-authenticated. RESULTS: We documented 83 plant species used as CAM to treat or manage a variety of conditions including HIV/AIDS, HIV-associated conditions, and other health conditions. Plants from the family Leguminosae were most frequently reported, comprising 21 species (25.3%), followed by 5 from both Euphorbiaceae and Combretaceae families (6.0%). Four plants (4.8%) were used specifically to manage HIV (Lannea edulis (Sond.) Engl. root, Aloe zebrina Baker root, Myrothamnus flabellifolia Welw. whole plant, and Harpagophytum procumbens var. subulobatum (Engl.) tuber), while an additional 7 (8.4%) were reported specifically for treating combinations of HIV-related symptoms. Notably, 25 (30.1%) have not been reported previously as CAM and/or lack reported bioactivity data. CONCLUSIONS: To our knowledge, this is the first detailed ethnobotanical survey of CAM used by the BaKalanga Peoples of the Tutume subdistrict to manage HIV/AIDS and HIV-associated and other health conditions.

The African natural product knipholone anthrone and its analogue anthralin (dithranol) enhance HIV-1 latency reversal.

A sterilizing or functional cure for HIV is currently precluded by resting CD4+ T cells that harbor latent but replication-competent provirus. The "shock-and-kill" pharmacological ap-proach aims to reactivate provirus expression in the presence of antiretroviral therapy and target virus-expressing cells for elimination. However, no latency reversal agent (LRA) to date effectively clears viral reservoirs in humans, suggesting a need for new LRAs and LRA combinations. Here, we screened 216 compounds from the pan-African Natural Product Library and identified knipholone anthrone (KA) and its basic building block anthralin (dithranol) as novel LRAs that reverse viral latency at low micromolar concentrations in multiple cell lines. Neither agent's activity depends on protein kinase C; nor do they inhibit class I/II histone deacetylases. However, they are differentially modulated by oxidative stress and metal ions and induce distinct patterns of global gene expression from established LRAs. When applied in combination, both KA and anthralin synergize with LRAs representing multiple functional classes. Finally, KA induces both HIV RNA and protein in primary cells from HIV-infected donors. Taken together, we describe two novel LRAs that enhance the activities of multiple "shock-and-kill" agents, which in turn may inform ongoing LRA combination therapy efforts.

Biological activity and stability analyses of knipholone anthrone, a phenyl anthraquinone derivative isolated from Kniphofia foliosa Hochst.

Knipholone (1) and knipholone anthrone (2), isolated from the Ethiopian medicinal plant Kniphofia foliosa Hochst. are two phenyl anthraquinone derivatives, a compound class known for biological activity. In the present study, we describe the activity of both 1 and 2 in several biological assays including cytotoxicity against four human cell lines (Jurkat, HEK293, SH-SY5Y and HT-29), antiplasmodial activity against Plasmodium falciparum 3D7 strain, anthelmintic activity against the model organism Caenorhabditis elegans, antibacterial activity against Aliivibrio fischeri and Mycobacterium tuberculosis and anti-HIV-1 activity in peripheral blood mononuclear cells (PBMCs) infected with HIV-1c. In parallel, we investigated the stability of knipholone (2) in solution and in culture media. Compound 1 displays strong cytotoxicity against Jurkat, HEK293 and SH-SY5Y cells with growth inhibition ranging from approximately 62-95% when added to cells at 50 µM, whereas KA (2) exhibits weak to strong activity with 26, 48 and 70% inhibition of cell growth, respectively. Both 1 and 2 possess significant antiplasmodial activity against Plasmodium falciparum 3D7 strain with IC50 values of 1.9 and 0.7 µM, respectively. These results complement previously reported data on the cytotoxicity and antiplasmodial activity of 1 and 2. Furthermore, compound 2 showed HIV-1c replication inhibition (growth inhibition higher than 60% at tested concentrations 0.5, 5, 15 and 50 µg/ml and an EC50 value of 4.3 µM) associated with cytotoxicity against uninfected PBMCs. The stability study based on preincubation, HPLC and APCI-MS (atmospheric-pressure chemical ionization mass spectrometry) analysis indicates that compound 2 is unstable in culture media and readily oxidizes to form compound 1. Therefore, the biological activity attributed to 2 might be influenced by its degradation products in media including 1 and other possible dimers. Hence, bioactivity results previously reported from this compound should be taken with caution and checked if they differ from those of its degradation products. To the best of our knowledge, this is the first report on the anti-HIV activity and stability analysis of compound 2.