Abstract:
ETHNOPHARMACOLOGICAL RELEVANCE : The Natal gwarri or Natal ebony (Euclea natalensis A.DC.) is a deciduous tree found widespread throughout southern Africa, especially in Kwazulu-Natal and the southern cost. It has been widely used by indigenous communities such as the Zulus, Tsongas and Vendas for symptoms related to
tuberculosis (TB). The decoctions made from the plant parts are administered for chest diseases to treat
complications such as chest pains, bronchitis, pleurisy and asthma. TB is prevalent in immune-compromised
patients and it is evident that TB-drugs cause hepatotoxicity. The objective of the present study was therefore to
evaluate the antimycobacterial activity of the ethanolic extract of E. natalensis against TB and its
hepatoprotective and immunomodulatory activities.
MATERIALS AND METHODS : The antimycobacterial, antioxidant, hepatoprotective, immunomodulatory activity and
cytotoxicity of the ethanolic extract of the shoots of E. natalensis were determined in vitro. The mechanism of
action of the antituberculosis activity was determined by investigating the inhibitory effect on mycothiol
disulfide reductase enzyme. Furthermore, the acute, sub-acute toxicity (50–2000 mg/kg) and antimycobacterial
effect (300 mg/kg) of E. natalensis shoot extract were investigated in Balb/c mice. Hepatoprotective activity of
the extract (50–150 mg/kg) was evaluated on isoniazid and rifampicin (50 mg/kg; i.p.) induced hepatic damage
in a rat model.
RESULTS : The minimum inhibitory concentration of the extract was found to be 125 µg/ml against
Mycobacterium tuberculosis. The extracts 50% inhibitory concentration (IC50) against 1,1-diphenyl-2-
picrylhydrazyl (DPPH) free radical was found to be 22.55 µg/ml. The plant showed a hepatoprotective effect
(50% at 12.5 µg/ml) and the ability to increase T-helper 1 cell cytokines; Interleukin 12, Interleukin 2 and
Interferon α by up to 12 fold and the ability to decrease the T-helper 2 cell cytokine Interleukin 10 4 fold when
compared to baseline cytokine production. No cellular toxicity was observed in primary peripheral blood
mononuclear cells (PBMC's) and two secondary cell lines; U937 monocytes and Chang liver cells (a derivative of
the HepG2 cell line). During mechanistic studies, the extract showed a 50% inhibition of mycothiol reductase
activity at 38.62 µg/ml. During the acute and sub-acute studies, E. natalensis exhibited no toxic effect and the
50% lethal dose (LD50) was established to be above 2000 mg/kg. The extract was able to reduce the
mycobacterial load (1.5-fold reduction) in infected mice. Isoniazid and rifampicin caused significant hepatic
damage in rats, and the extract was able to reduce the toxicity by 15% and 40% at 50 and 150 mg/kg
respectively.
CONCLUSION : The present study supports the traditional usage of the plant against tuberculosis symptoms. The
study showed the ability of E. natalensis shoot extract to inhibit mycobacterial growth, stimulate an appropriate
immune response and have a hepatic protective effect. Due to the extract's significant results for hepatoprotective,
immunomodulatory effects and antimycobacterial activity, it may prove to be effective to serve as an
adjuvant for TB-patients.
