Abstract
Objectives: The presence of drug-resistant HIV is a major global concern and warrants the development of novel anti-virals as alternative and inexpensive therapy. In the current study, potentially drug-resistant HIV was isolated and previously unreported anti-viral activity of Jatropha curcas Linn. leaf extracts was assessed. Methods: HIV isolation was done using in vitro micro co-culture methods followed by drug susceptibility assays to determine resistance to Zidovudine (AZT), Lamivudine (3TC) and Stavudine (d4T). Soxhlet apparatus was used for extraction of metabolites from leaves of Jatropha curcas Linn. and Methanolic and Aqueous Extracts were chosen for further study. Secondary metabolites were detected by High-Performance Thin Layer Chromatography and in vitro cytotoxicity established by MTT assay. The extracts were then used in post- and pre-infection studies by measuring inhibition of HIV replication to determine anti-viral activity. Results: Seven HIV isolates were obtained (isolation rate: 23.33%) with drug IC50 values ranging from 0.001418- 82.73 μM AZT, 2.645-15.35 μM 3TC and 18.55-66.23 μM d4T. Tannins, Flavonoids, Saponins were detected in Aqueous Extract and Flavonoids, Saponins in Methanolic Extract. The CC50 values were 32.07 mg/mL and 35.5 mg/ mL for Aqueous and Methanolic Extracts respectively. Anti-viral activity was evaluated by inhibition of HIV replication as determined by HIV p24 antigen ELISA. Post-infection (4 isolates) interaction studies showed IC50 values ranging from 0.0255-0.4137 mg/mL and 0.00073-0.1278 mg/mL for Aqueous and Methanolic Extracts respectively and preinfection (1 isolate) interaction studies showed 100% inhibition by Methanolic and 97.19% inhibition by Aqueous Extract at 25 mg/mL each. Conclusions: HIV isolates potentially resistant to AZT/3TC/d4T were obtained and Jatropha curcas Linn. leaf extracts showed effective anti-viral and probable entry inhibition activity against potentially drug-resistant HIV, which has not been reported earlier. The study indicates that Jatropha curcas Linn. is a good candidate for anti-HIV therapy with further research.
Highlights
People living with HIV/AIDS often choose traditional or complementary and alternative medicine to complement or replace conventional treatment
Thirty samples were processed for Peripheral Blood Mononuclear Cells (PBMC) co-cultivation from which seven HIV isolates were obtained giving an isolation rate of 23.33%
The phenotypic drug resistance was determined by calculating the fold increase in IC50 values of the drugs against the HIV isolates compared with reported IC50 values against a standard strain of HIV (HIV-1IIIB) [19]
Summary
People living with HIV/AIDS often choose traditional or complementary and alternative medicine to complement or replace conventional treatment. The presence of multi-drug or even multiclass resistance in HIV warrants the need to explore additional means to combat HIV and provide further justifications for the need of alternative and complementary medicines in the treatment of HIV/ AIDS. It is not surprising that the activity of these traditional medicines against HIV can be scientifically analysed to deduce the role of natural plant products in their anti-HIV activities. A number of medicinal plants have been reported to have anti-HIV properties [1]. Over the past two decades, substantial progress has been made in research on the natural products possessing anti-HIV activity. A variety of secondary metabolites obtained from natural origin showed moderate to good anti-HIV activity [2]
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