Paul Moundipa F
University of Yaounde I, Cameroon
Posters & Accepted Abstracts: J Trop Dis
Statement of the Problem: Khaya grandifoliola (Meliaceae) is used in Cameroonian traditional medicine for the treatment
of jaundice and others liver related diseases. Scientific reports supporting its use in folk medicine have been documented
through laboratory experiments using extract and compounds from stem bark of the plant. Antiviral, hepatoprotective and
anti-inflammatory activities as well as the related molecular mechanisms were investigated.
Methodology: Dried bark powder was extracted in methylene chloride/methanol (v/v) system and separated by flash
chromatography. The hepatoprotective activity of the fractions obtained was tested by assessing their effect against H2O2,
cisplatin and acetaminophen (APAP)-induced hepatotoxicity in HC-04 and L-02 cells line. The antiviral (hepatitis C virus)
activity was assessed by measuring infection and replication rates in Huh-7 cells using subgenomic replicon, HCV-pseudotyped
and HCVcc particles. The anti-inflammatory activity was evaluated against lipopolysaccharide (LPS)-induced inflammation
in raw 264.7 macrophages model. Cell viability was assessed by MTT assay and the chemical composition of the most active
fraction was analyzed by GC-MS, HPLC and NMR.
Findings: Five fractions of different polarities were obtained. One (KgF25), showed the strongest hepatoprotective, antiviral and
anti-inflammatory activities at non-toxic concentration. The hepatoprotective effect of KgF25 was associated to the inhibition
of CYP2E1 expression and c-JNK phosphorylation, and the induction of Mkp-1 expression and nuclear translocation of Nrf2.
This fraction also inhibited HCV infection by mostly targeting entry and replication step. Its antiviral effect was mediated by
the transcriptional up-regulation of hme oxygenase-1 and interferon antiviral response genes. This fraction also showed antiinflammatory
effect through inhibition of nitric oxide production, P38MAP-Kinase and JNK3 enzymes activities and mRNA
expression of iNOS and major pro-inflammatory cytokines (TNF-? and IL-1?). In addition, six compounds exhibited the
aforementioned activities were identified from KgF25.
Conclusion & Significance: These findings demonstrate that K. grandifoliola is a potential source of active ingredients bearing
pharmacological activities.