Abstract:
Tuberculosis (TB) is a disease of global importance that affects millions of people.
Approximately a quarter of the world’s population is currently infected with M.
tuberculosis, and about 10% of those infected will develop into active disease,
particularly immune compromised individuals. Helminthiasis is of global health
importance, affecting over 2 billion people mostly in resource-poor countries. Coinfection with tuberculosis (TB) and helminths (worms) is an emerging global public
health concern with both affecting about one-third of the global population. Chronic
infection with helminths can result in impaired immune responses to TB as well as
enhancing failure to TB therapy and BCG vaccination. Antimycobacterial and
anthelmintic activities of the acetone extract and fractions of Psychotria capensis were
evaluated, including their in vitro safety. In addition, the anti-inflammatory and
immunomodulatory effect of the fractions and crude extract of P. capensis were
assessed. Antimycobacterial activity of the extract and fractions was tested against
four non-tuberculous mycobacteria (Mycobacterium smegmatis, M. fortuitum, M.
aurum, M. bovis BCG) and pathogenic M. tuberculosis H37Rv while the Egg Hatch
Assay (EHA) was used for the anthelmintic test on eggs of Haemonchus contortus.
Cytotoxicity was determined against Vero kidney cells while in vitro immune modulation via
cytokine production was determined on activated macrophages. The minimum inhibitory
concentration (MIC) values of the Psychotria capensis acetone extract and fractions
ranged from 39 to 1,250 μg/ml with the crude extract and hexane fraction having the
best MIC values (both 39 μg/ml). In the EHA, the inhibitory concentration (IC50) ranged from
160 to 630 μg/ml with the hexane fraction having the best activity. The hexane and
chloroform fractions were relatively non-toxic with LC50 values of 290 and 248 μg/ml
respectively, while the acetone crude extract (64 μg/ml) and n-butanol fraction (71 μg/ml)
were moderately toxic. The SI values (LC50/MIC) ranged from 0.1 to 7.4 with the hexane
fraction having the highest value against M. smegmatis (7.4). The hexane fraction had the best dual anthelmintic and antimycobacterial activity. This fraction had the best NO
inhibitory activity and was the least cytotoxic, indicating that its activity was not due to
general metabolic toxicity, with 96.54% cell viability. Pro-inflammatory cytokines such as
IL-12p70 were upregulated while IL-10 expression was inhibited by the extracts.
Compounds were detected using GC-MS analysis, and in both the crude acetone
extract and the hexane fraction was the diterpene neophytadiene, which has antiinflammatory and antimicrobial activity. Finding alternative or complementary
approaches to dealing with TB infections by, amongst other things, reducing the
incidence of helminth infestations may lessen the burden of TB, contributing to slowing
the spread of multi-drug resistance.