5.1 Anti-viral activity
Both the ethanol and DMSO reconstituted extracts of C. sanguinolenta, (SI = 74.7 and 51.4) and P. febrifugium (SI = 56.3 and 47.5) exhibited the highest SI against HIV-1 PV. C. sanguinolenta is popularly used in malaria treatment, especially in West Africa. C. sanguinolenta is popularly used for treating malaria, bacterial respiratory diseases, hypertension, diarrhoea, urinogenital infections 49 and skin infections 9. There have been very few studies to investigate the antiviral activity of C. sanguinolenta. Cimanga et al. 50 investigated the antiviral activity of cryptolepine, the main alkaloid isolated from C. sanguinolenta against herpes simplex type1, coxsackie B, Semliki forest, poliomyelitis and vesicular stomatitis viruses and did not find any antiviral properties.
Psorospermum species have previously been reported to anti-viral effects 51. Psorospermum febrifugium is widely used in treating various skin infections in Uganda, especially herpes zoster 9–11 which is caused by the varicella zoster virus 52. Extracts of P. febrifugium possess antitumour/anticancer activities 53,54.
The ethanol extract of B. micrantha in this study showed a relatively high antiviral activity against HIV-1. In a similar study in South Africa where B. micrantha is also traditionally used in treating HIV/AIDS by herbalists, the methanol extracts of its roots showed relatively strong antiviral activity against the RNA-dependent-DNA polymerase (RDDP) and RNase H activities of HIV-1 reverse transcriptase (RT) 55,56 B. micrantha contains several phytochemicals especially, flavonoids, 56,57 which are thought to have anti-HIV RT properties 58.
In this study, A. hockii also showed anti-HIV 1 activity. Acacia species are widely used in treating HIV/AIDS in Africa 9. Other species of Acacia such as A. catechu and A. mellifera also possess anti-viral activity against HIV-1. A. catechu suppressed HIV-1 infection in vitro through the inhibition of the viral protease and Tat 59. A. mellifera has potential anti-viral activity against reverse transcriptase in HIV-1 60,61.
The crude ethanol extract E. abyssinica exhibited antiviral activity against HIV-1 with a SI of 11.4 for both extracts. Similarly, Mohammed et al. 62showed the crude alkaloid fractions of E. abyssinica from Sudan to have anti‐HIV‐1 activity, with a corresponding reduction in the viability of mock‐infected MT‐4 cells (CC50 = 53 μM). The antiviral activity was coupled with a 50% protection of the of MT‐4 cells from HIV‐1‐induced cytopathic effects (EC50 ≥ 53 μM), in comparison to the positive control, efavirenz (CC50 = 45 μM and EC50 = 0.003 μM). The crude extracts of E. abyssinica also showed activity against HIV-1 RT (Rukunga et al., 2002). Other Erythrina species have also have anti-HIV-1 activity such as E. lysistemon (IC50 = 11 μg/ml) 63 and E. senegalensis, with in vitro anti-HIV-1 protease activity (IC50 = 4.0 ± 0.1 μM) 64. Erythrina species are widely used across Africa to treat various ailments as reviewed by Fahmy et al. 65. Isoquinoline-type alkaloids in E. abyssinica are thought to be responsible for the cytotoxicity of mock-infected MT-4 cells which inhibit HIV-1 replication by virus adsorption or reverse transcription 66.
The crude hot water extracts of G. senegalensis to possess potential HIV-1 RT activity. Whereas the SI for Z. chalybeum in this study were low, the crude ethanol extracts Z. chalybeum bark exhibited antiviral activity against HIV-1in a separate study in Kenya 60,61. The crude ethanol seed extract of Z. chalybeum also exhibited antiviral activity against the measles virus (Edmonston strain) 67Studies on W. ugandensis against the measles virus found the extracts to be highly toxic to the VERO cell lines used. Similarly, the crude extracts of W. ugandensis have been shown to be highly cytotoxic to the U87.CD4.CXCR4 cell used in this study 42,68.
Since whole plant extracts are complex mixtures of many compounds 19the cytotoxicity and antiviral activity of different crude plant extracts is not necessarily due to the same compound(s). W. ugandensis and A. coriaria are among the most popular and widely used medicinal plant species in Uganda for various aliments 9,11,69,70. Even though the crude extracts of W. ugandensis and A. coriaria were highly cytotoxic, further isolation and testing of specific compounds or fractions may lead to the separation of the toxic compounds from compounds that may be active and less or non-toxic. This is because the cytotoxicity of some plant compounds may mask the antiviral properties of other plant substances. Cos et al. 19 demonstrated this phenomenon by further fractionating a previously inactive ethanol extract of Tithonia diversifolia (SI < 1), to produce a highly active anti-HIV-1 aqueous fraction (SI > 461). Schultz et al. 69 showed the diethyl ether extract of W. ugandensis stem bark, to be strongly cytotoxic to the human lung cells, displaying a CC50 value as low as 0.3 μg/ml, despite the high antiplasmodial activity. In another study however, the methanol, ethanol, ethyl acetate and, diethyl ether extracts of W. ugandensis showed low cytotoxicity to human keratinocyte cells (HaCaT cells) at a concentration > 512 to 256 μg/mL 69. Therefore, the separation of a polar from polar components can increase the chance to find highly active antiviral compounds with low cytotoxicity 19.
5.2 Herb drug interactions and the concurrent use of herbal medicines and ARVs
PLHIV widely use of traditional herbal remedies together with antiretroviral drugs in Uganda 9–11,71. Traditional herbal remedies are usually used because of the perception that they are safe since they are of natural origin 42,72. Herbs can potentially interact with HIV drug metabolising enzymes and other ARV in the body. These interactions could lower the efficacy of the ARV drugs by reducing their plasma concentrations or lead to drug toxicity 73,74, since this aspect is often if not always under looked 72. Additionally, patients do not generally disclose to their health care providers that they are simultaneously using herbs and ARV drugs 9.