Apigenin and apigeninidin isolates from the Sorghum bicolor leaf targets inflammation via cyclo-oxygenase-2 and prostaglandin-E2 blockade.

AIM: This study evaluated the anti-inflammatory properties of a species of Sorghum bicolor leaf (SBL) grown in West Africa. METHOD: Cyclo-oxygenase (COX)-2:COX-1 selectivity assay was carried out by plating isolated peripheral blood mononuclear cells in culture medium with specific SBL fractions: crude extract (J), ethyl-acetate (JE) and aqueous (JA); secondary compounds from JE (JE5, JE6, JE7 and JE8); purified (P9) and semi-purified (P8) compounds from JE5 at 5-200 µg/mL for 1 hour. Test compounds and controls ibuprofen (50 µmol/L) and CAY10404 (1 µmol/L; 10 µmol/L) were added to two sets of plates, one without lipopolyshaccharide (LPS) and the other with LPS (1 µg/mL) for 24 hour. COX-2IC50 :COX-1IC50 ratio represented 50% inhibition of the activity of COX-2 to that of COX-1 using ibuprofen as control. In separate experiments the supernatant of P8 and P9-treated fractions of SBL and controls were plated with RAW 264.7 macrophage cells to measure prostaglandin (PG)-E2 production and cell proliferation activity. RESULTS: JA fraction of SBL had the highest ratio of COX-2IC50 :COX-1IC5041.214 whereas JE had the lowest ratio COX-2IC50 :COX-1IC501.161 . Interestingly, JE5 derived from JE showed a ratio of COX-2IC50 :COX-1IC500.495 while P8 derived from JE5 showed a dose-dependent reduction in COX-2IC50 :COX-1IC50 ratio and in PG-E2 production, which was more effective compared to ibuprofen. A dose-dependent reduction in RAW 264.7 macrophage cell proliferation was also observed in P8-treated cells. The phenolic compounds identified in P8 include apigenin and apigeninidin adducts which may explain the exceptional anti-inflammatory activity and efficacy in COX-2 targeting.

Virtualizing the p-ANAPL library: a step towards drug discovery from African medicinal plants.

BACKGROUND: Natural products play a key role in drug discovery programs, both serving as drugs and as templates for the synthesis of drugs, even though the quantities and availabilities of samples for screening are often limitted. EXPERIMENTAL APPROACH: A current collection of physical samples of > 500 compound derived from African medicinal plants aimed at screening for drug discovery has been made by donations from several researchers from across the continent to be directly available for drug discovery programs. A virtual library of 3D structures of compounds has been generated and Lipinski's "Rule of Five" has been used to evaluate likely oral availability of the samples. RESULTS: A majority of the compound samples are made of flavonoids and about two thirds (2/3) are compliant to the "Rule of Five". The pharmacological profiles of thirty six (36) selected compounds in the collection have been discussed. CONCLUSIONS AND IMPLICATIONS: The p-ANAPL library is the largest physical collection of natural products derived from African medicinal plants directly available for screening purposes. The virtual library is also available and could be employed in virtual screening campaigns.