Ethnobotanical survey and phytochemistry of medicinal plants used in the management of HIV/AIDS in Eastern Uganda.

Currently, highly active antiretroviral therapy is unable to cure HIV/AIDS because of HIV latency. This study aimed at documenting medicinal plants used in the management of HIV/AIDS in Eastern Uganda so as to identify phytochemicals with HIV latency reversing potential. An ethnobotanical survey was conducted across eight districts in Eastern Uganda. Traditional medicine practitioners were interviewed using semi-structured questionnaires. Qualitative and quantitative phytochemical tests were respectively, performed to determine the presence and quantity of phytochemicals in frequently mentioned plant species. Data were analysed and presented using descriptive statistics and Informant Consensus Factor (ICF). Twenty-one plant species from fourteen plant families were reported to be used in the management of HIV/AIDS. Six plant species with the highest frequency of mention were: Zanthoxylum chalybeum, Gymnosporia senegalensis, Warbugia ugandensis, Leonatis nepetifolia, Croton macrostachyus and Rhoicissus tridentata. Qualitative phytochemical analysis of all the six most frequently mentioned plant species revealed the presence of flavonoids, tannins, terpenoids, alkaloids and phenolics. Quantitative analysis revealed the highest content of flavonoids in L. nepetifolia (20.4 mg/g of dry extract) while the lowest content was determined in C. macrostachyus (7.1 mg/g of dry extract). On the other hand, the highest content of tannins was observed in L. nepetifolia. (199.9 mg/g of dry extract) while the lowest content was found in R. tridentata. (42.6 mg/g of dry extract). Medicinal plants used by traditional medicine practitioners in Eastern Uganda to manage HIV/AIDS are rich in phytochemicals including flavonoids and tannins. Further studies to evaluate the HIV-1 latency reversing ability of these phytochemicals are recommended to discover novel molecules against HIV/AIDS.

Acute and subacute toxicity profile of ethanolic stem bark extract of Albizia coriaria Welw. ex Oliv. in Wistar albino rats.

Albizia coriaria (Fabaceae) crude extracts are key ingredients of several licensed and unlicensed herbal products in East Africa. However, there is limited and often contradicting information regarding its toxicity. We therefore evaluated the acute and subacute toxicity of the ethanolic stem bark extract of A. coriaria in mature healthy Wistar albino rats following Lorke's method and OECD guidelines 407. The LD50 of the ethanolic stem bark extract of A. coriaria was 2000 mg/kg. The acute toxicity signs observed included piloerection, hyperventilation, lethargy, and loss of righting reflex. There was a significant increase in aspartate aminotransferase, alkaline phosphatase, red blood cells and haemoglobin in rats after 28 days at the dose of 500 mg/kg. Histological analyses revealed multifocal random parenchymal necrosis and scattered periportal mononuclear inflammatory cells infiltration in the liver, interstitial nephritis in the kidney and multifocal lymphoid accumulation in the peribronchiolar and perivascular lung tissue at 500 mg/kg. The ethanolic stem bark of A. coriaria was therefore moderately toxic to the rats when administered in a single high oral dose within 24 h. The extract caused a dose dependent toxicity with significant damage to the kidney, liver and lung tissues at a dose of 500 mg/kg after 28 days. Herbal medicines containing A. coriaria extracts should be consumed cautiously due to likelihood of toxicity particularly at higher doses greater than 500 mg/kg.

New Insights into HIV Life Cycle, Th1/Th2 Shift during HIV Infection and Preferential Virus Infection of Th2 Cells: Implications of Early HIV Treatment Initiation and Care.

The theory of immune regulation involves a homeostatic balance between T-helper 1 (Th1) and T-helper 2 (Th2) responses. The Th1 and Th2 theories were introduced in 1986 as a result of studies in mice, whereby T-helper cell subsets were found to direct different immune response pathways. Subsequently, this hypothesis was extended to human immunity, with Th1 cells mediating cellular immunity to fight intracellular pathogens, while Th2 cells mediated humoral immunity to fight extracellular pathogens. Several disease conditions were later found to tilt the balance between Th1 and Th2 immune response pathways, including HIV infection, but the exact mechanism for the shift from Th1 to Th2 cells was poorly understood. This review provides new insights into the molecular biology of HIV, wherein the HIV life cycle is discussed in detail. Insights into the possible mechanism for the Th1 to Th2 shift during HIV infection and the preferential infection of Th2 cells during the late symptomatic stage of HIV disease are also discussed.

Phytochemical, Cytotoxicity, and Antimycobacterial Activity Evaluation of Extracts and Compounds from the Stem Bark of Albizia coriaria Welw ex. Oliver.

BACKGROUND: Albizia coriaria Welw ex. Oliver (Fabaceae) is one of the plants used by herbalists in the East Africa community to prepare herbal remedies for the management of symptoms of TB. Despite its widespread use, the antimycobacterial activity of this plant was uninvestigated and there was contradicting information regarding its cytotoxicity. METHODS: Cytotoxicity (MTT), antimycobacterial activity (MABA), and phytochemical screening were conducted on crude extracts (hexane, chloroform, acetone, and methanol) of the stem bark of A. coriaria. Gas chromatography-mass spectrometry (GC-MS) followed by Fourier transform infrared (FTIR) spectroscopy was carried out on the acetone and methanol extracts. The binding affinities and descriptors of pharmacokinetics and toxicity of the identified compounds were predicted using computational modelling software. RESULTS: The cytotoxic concentrations of all extracts were greater than 1000 µg/mL. The minimum inhibitory concentration of both the acetone and methanol extracts was 1250.0 ± 0.0 µg/mL against M. smegmatis, whereas that against M. tuberculosis was 937.0 ± 442.0 µg/mL and 2500.0 ± 0.0 µg/mL, respectively. Hexane and chloroform extracts were not active against both strains. Alkaloids, triterpenes, flavonoids, tannins, and saponins were the predominant phytochemicals present. GC-MS analysis revealed twenty-eight and nineteen compounds in acetone and methanol extracts, respectively. Among these was hydroquinone, which was previously reported to possess antimycobacterial activity. Seven compounds identified through GC-MS analysis had better binding affinities for the mycobacterial ATPase and polyketide synthase-13 than isoniazid and rifampicin. These compounds also showed variable but promising pharmacokinetic properties with minimum toxicity. CONCLUSION: There are phytochemicals in A. coriaria stem bark with potential antimycobacterial activity and acceptable cytotoxicity, which can be further explored and optimized for the development of novel antitubercular drugs.

Traditional Medicinal Uses, Phytoconstituents, Bioactivities, and Toxicities of Erythrina abyssinica Lam. ex DC. (Fabaceae): A Systematic Review.

BACKGROUND: Many studies have been undertaken on the medicinal values of Erythrina abyssinica Lam. ex DC. (Fabaceae). The details, however, are highly fragmented in different journals, libraries, and other publication media. This study was therefore conducted to provide a comprehensive report on its ethnobotany, ethnomedicinal uses, phytochemicals, and the available pharmacological evidence supporting its efficacy and safety in traditional medicine. METHOD: We collected data using a PROSPERO registered systematic review protocol on the ethnobotany, phytochemistry, and ethnopharmacology of Erythrina abyssinica from 132 reports that were retrieved from electronic databases. Documented local names, morphology, growth habit and habitat, ethnomedicinal and nonmedicinal uses, diseases treated, parts used, method of preparation and administration, extraction and chemical identity of isolated compounds, and efficacy and toxicity of extracts and isolated compounds were captured. Numerical data were summarized into means, percentages, and frequencies and presented as graphs and tables. RESULTS: Erythrina abyssinica is harvested by traditional herbal medicine practitioners in East, Central, and South African communities to prepare herbal remedies for various human and livestock ailments. These include bacterial and fungal infections, tuberculosis, malaria, HIV/AIDS, diarrhea, cancer, meningitis, inflammatory diseases, urinary tract infections, wounds, diabetes mellitus, and skin and soft tissue injuries. Different extracts and phytochemicals from parts of E. abyssinica have been scientifically proven to possess anti-inflammatory, antibacterial, antioxidant, antiplasmodial, antiproliferative, antifungal, antimycobacterial, antidiarrheal, anti-HIV 1, antidiabetic, and antiobesity activities. This versatile pharmacological activity is due to the abundant flavonoids, alkaloids, and terpenoids present in its different parts. CONCLUSION: Erythrina abyssinica is an important ethnomedicinal plant in Africa harboring useful pharmacologically active phytochemicals against various diseases with significant efficacies and minimal toxicity to mammalian cells. Therefore, this plant should be conserved and its potential to provide novel molecules against diseases be explored further. Clinical trials that evaluate the efficacy and safety of extracts and isolated compounds from E. abyssinica are recommended.

Synergistic anti-inflammatory activities of a new flavone and other flavonoids from Tephrosia hildebrandtii vatke.

A new flavone, named hildeflavone (1) along with 7 other known flavonoids were isolated from the aerial parts of Tephrosia hildebrandtii Vatke. Their characterisation was based on NMR and MS data analysis. The anti-inflammatory properties of the crude extract, isolated compounds and combination of the compounds were investigated in lipopolysaccharide (LPS)-stimulated peripheral blood mononuclear cells (PBMCs). Treatment of the LPS-stimulated PBMCs with the isolated flavonoids at a concentration of 100 µM significantly reduced the production of interleukins (IL-1ß, IL-2 and IL-6), interferon-gamma (IFN-γ), granulocyte macrophage-colony stimulating factor (GM-CSF) and tumour necrosis factor-alpha (TNF-α). It was also found that the combination of a flavone and flavanones exhibited remarkable synergistic anti-inflammatory effects on the production of the cytokines.[Figure: see text].

Isoflavones from the seedpods of Tephrosia vogelii and pyrazoisopongaflavone with anti-inflammatory effects.

Phytochemical investigation of Tephrosia vogelii seedpods led to the isolation of twelve compounds: vogelisoflavone A (1), vogelisoflavone B (2), isopongaflavone (3), onogenin, luteolin, 4',7-dihydroxy-3'-methoxyflavanone, trans-p-hydroxycinnamic acid, tephrosin, 2-methoxygliricidol, dehydrorotenone, 6a,12a-dehydro-α-toxicarol and pinoresinol. Compounds 1 and 2 are reported as new natural products. Isopongaflavone (3) was structurally modified using hydrazine to pyrazoisopongaflavone (4). These compounds were characterized based on their NMR and HRESIMS data. Further, four compounds (1-4) were evaluated for their anti-inflammatory effects in lipopolysaccharide (LPS)-stimulated peripheral blood mononuclear cells (PBMCs). Treatment of the LPS-stimulated PBMCs with the compounds at a concentration of 100 µM suppressed the secretion of interleukin IL-1ß interferon-gamma (IFN-γ), granulocyte macrophage-colony stimulating factor (GM-CSF) and tumour necrosis factor-alpha (TNF-α).

Anti-inflammatory Flavanones and Flavones from Tephrosia linearis.

Phytochemical analysis of a methanol-dichloromethane (1:1) extract of the aerial parts of Tephrosialinearis led to the isolation of 18 compounds. Seven of these, namely, lineaflavones A-D (1-4), 6-methoxygeraldone (5), 8″-acetylobovatin (6), and 5-hydroxy-7-methoxysaniculamin A (7) are new compounds. The compounds were characterized based on their NMR and HRMSn data. The anti-inflammatory effects of the crude extract and isolated compounds were evaluated by measuring the levels of interleukins (IL-1ß, IL-2, and IL-6), granulocyte-macrophage colony-stimulating factor (GM-CSF), and tumor necrosis factor-α (TNF-α) in lipopolysaccharide (LPS)-stimulated peripheral blood mononuclear cells (PBMCs). The crude extract inhibited the release of all cytokines except IL-1ß, which slightly increased in comparison to the LPS control. All the tested compounds suppressed the production of IL-2, GM-CSF, and TNF-α. Whereas compounds 1, 2, 4-8, 10-15, 17, and 18 decreased production of IL-6, compounds 1, 2, 4, 7, 10, 13-15, and 17 inhibited the release of IL-1ß. It is worth noting that most of the compounds tested showed a superior reduction in cytokines release compared to the reference drug ibuprofen.