| dc.description.abstract | Cancer has become a key public health affliction worldwide. Recent studies have
shown that genetic factors cause only 5–10% of all human cancers, while the rest are
caused by lifestyle. Epidemiological and clinical studies have shown that chronic
inflammatory diseases predispose individuals to various types of cancer. An estimated
20 % of all cancer related deaths globally arise from primary infections and
inflammation. Current treatments for cancer include radiotherapy, chemotherapy,
surgery, hormone, immune and targeted therapies. However, the efficacy of these
treatments is constrained by their unexpected detrimental effects on other non-target
tissues, development of multi-drug resistant cancer cell lines and high cost. Medicinal
plants are increasingly attracting attention of researchers as a source of
complementary and alternative therapies to mitigate cancer morbidity and mortality.
Plants have been reported to contain bioactive phytochemicals with anti-infective
properties against chronic diseases, including inflammation and cancer. In the current
study the air-dried roots bark and leaves of Fagaropsis angolensis were pulverized
into fine powders. The plant materials were then exhaustively extracted with 50%
CH3OH in CH2Cl2 (v/v) at room temperature by cold solvent percolation. Separation
was carried out using column chromatography on silica gel as the stationary matrix
and eluted with gradients of n-hexane, EtOAc and MeOH. The resultant fractions
were then purified using finer silica gel by recurrent column chromatography,
Sephadex LH 20 and Chromatotron to afford a total of five compounds including two
new norhopane derivatives; 3β,6β,22-trihydroxy-7β,11α-di[(4-hydroxybenzoyl)oxy]21αH-24-norhopa-4(23)-ene
(42)
and
3β,6β,22-trihydroxy-7β-[(4-
hydroxybenzoyl)oxy]-21αH-24-norhopa-4(23)-ene (43) together with the known
norhopane,
3β,6β,11α-trihydroxy-7β-[(4-hydroxybenzoyl)oxy]-24-norhopa-
4(23),17(21)-diene (44) and a norneohopane, (21α-H)-24-norneohopa-4(23), 22(29)diene-3β,6β,7β-triol
7-caffeate
(30)
from
the
root
bark.
The
leaves
afforded
a
reported
flavone,
tachrosin
(45).
Their
structure
elucidation
was
achieved
by
detailed
1D
and
2D
NMR,
HRESI-MS,
FT-IR
and UV
spectra
for
the newly
described
compounds
and
by
comparison of these data with those of correlated compounds in the published
literature. Resazurin reduction assay was used to evaluate the cytotoxicity of
compound 46, with doxorubicin as reference anticancer drug. Compound 46 displayed
minimal activity since the cell viability was more than 70 % against drug sensitive
CCRF-CEM. Owing to the risk associated with chronic inflammation to initiation,
promotion and progression of carcinogenesis, compounds 42 – 45 were assessed for
their anti-inflammatory activity by quantifying the levels of cytokines Interleukin-1β
(IL-1β), Interleukin-2 (IL-2), Granulocyte-macrophage colony-stimulating factor
(GM-CSF) and Tumor necrosis factor-alpha (TNF-α) in lipopolysaccharide (LPS)
stimulated peripheral blood mononuclear cells (PBMCs). All tested compounds
decreased secretion of IL-1β and TNF-α. Compounds 43 and 45 clearly decreased
secretion of IL-2, GM-CSF and TNF-α in comparison with the reference drug
ibuprofen. The findings from this study revealed that F. angolensis contains
significant amounts of hopane-type triterpenoid derivatives with potential to
downregulate pro-inflammatory biomarkers and further provide a scientific rationale
for using the plant in Kenyan folk medicine as anti-pain solution. | en_US |
