| dc.description.abstract | Catharanthus roseus (L.) G. Don (C. roseus) is a notable anticancer herb possessing high
alkaloid content. Besides, this plant has been also traditionally used as an effective antidiabetic
treatment in many Asian nations, such as Malaysia, India, and Vietnam. Recently,
although some studies have demonstrated the anti-hyperglycemic effect its fractional
extracts and metabolites were done on several animal models, the missing links in
medicinal chemistry of these published compounds have not been connected. The main
purpose of our study is to determine and estimate the anti-hyperglycemic activity of C.
roseus in both computational and experimental aspects. The in silico part of this study
measures the binding affinity of the compounds of C. roseus toward four target proteins
including 11β-HSD1, PTP1B, α-glucosidase, and DPPIV for anti-hyperglycemic effect with
further investigation of the molecular interaction modes inside the protein’s active sites.
Molecular Dynamics (MD) simulation, structure-based virtual screening, and
pharmacophore analysis were done to explain and suggest potent compounds. In
experiment aspect, IC50 of fractional extracts on alpha-glucosidase and alpha-amylase
was carried. Besides, anti-hyperglycemic test on diabetes-induced mice models was also
performed together with toxicity assessment.
The in silico result suggests 8 compounds (com_05, com_07, com_16, com_26, com_27,
com_28, com_46, and com_56) as potent drug candidates for experimental confirmation.
Besides, com_56 (Strictosidine lactam) and com_46 (Mitraphyllline) are supposed to be
two best top-hit ligands with the extremely high docked score. Additionally, 11-β-HSD1
is supposed to be the most suitable receptor for experimental confirmation. The in vitro
result confirmed the α-amylase-inhibitory activity of fractional extracts with the IC50 of
ETH, DCM, EA, and FW extract is 0.102, 0.102, 0.0641 and 0.0301 mg/mL respectively
while α-glucosidase-inhibitory activity of fractional extracts seems not very notable and
the IC50 of most of the case are incapable of evaluating. The in vivo result indicates DCM
and ETH are two extracts resulting in strong anti-hyperglycemic activity on diabetesinduced
mice models. The LD50 of the total extract is higher than 5000 mg/kg bw while
sub-acute toxicity test gives no evidence on long-term treatment of this total extract.
Key words: C. roseus; structure-based virtual screening; anti-hyperglycemic;
pharmacokinetics | en_US |
