Inhibitory Effects of Cucurbitane-Type Triterpenoids from Momordica charantia Fruit on Lipopolysaccharide-Stimulated Pro-Inflammatory Cytokine Production in Bone Marrow-Derived Dendritic Cells

Abstract

The bitter melon, Momordica charantia L., was once an important food and medicinal herb. Various studies have focused on the potential treatment of stomach disease with M. charantia and on its anti-diabetic properties. However, very little is known about the specific compounds responsible for its anti-inflammatory activities. In addition, the in vitro inhibitory effect of M. charantia on pro-inflammatory cytokine production by lipopolysaccharide (LPS)-stimulated bone marrow-derived dendritic cells (BMDCs) has not been reported. Phytochemical investigation of M. charantia fruit led to the isolation of 15 compounds (1−15). Their chemical structures were elucidated spectroscopically (one- and two-dimensional nuclear magnetic resonance) and with electrospray ionization mass spectrometry. The anti-inflammatory effects of the isolated compounds were evaluated by measuring the production of the pro-inflammatory cytokines interleukin IL-6, IL-12 p40, and tumor necrosis factor α (TNF-α) in LPS-stimulated BMDCs. The cucurbitanes were potent inhibitors of the cytokines TNF-α, IL-6, and IL-12 p40, indicating promising anti-inflammatory effects. Based on these studies and in silico simulations, we determined that the ligand likely docked in the receptors. These results suggest that cucurbitanes from M. charantia are potential candidates for treating inflammatory diseases.

Ethnopharmacological Value and Biological Activities via Antioxidant and Anti-Protein Denaturation Activity of Morinda lucida Benth and Momordica charantia L. Leaves Extracts from Benin

“…These authors [ 43 ] also established that M. lucida extracts attenuated systemic inflammation (with fever) induced by LPS in rats and upregulated the anti-inflammatory cytokine, IL-10. Another study [ 44 , 45 ] demonstrated that cucurbitane-type triterpenoids compounds isolated from M. charantia could inhibit the production of IL-6 in LPS-stimulated bone marrow-derived dendritic cells, and the authors attributed these anti-inflammatory effects to interactions of hydrogen bonds between the protein residues and hydroxyl groups and sugar rings of triterpenoids compounds.…”

<em>Momordica charantia</em> extract modulates inflammatory response in human lymphocytes via suppression of TNF-α

“…IL-6 is a pro-inflammatory cytokine readily produced in cases of infections and tissue injuries (28) . Cao (29) demonstrated that cucurbitane-type triterpenoids compounds isolated from the fruit of M. charantia with IC 50 values of 0.028 to 1.962 µM could inhibit the production of IL-6 in LPS-stimulated bone marrow-derived dendritic cells, and the authors attributed these effects to interactions of hydrogen bonds between the protein residues and hydroxyl groups and sugar rings of triterpenoids compounds, which were visualized by molecular docking. Another study showed that the expression of IL-6 in adipose tissues and brown adipose tissues of diet-induced obese mice was lower in animals fed with the fruit of M. charantia in the concentrations of 2% and 5% (30) , the authors associated these results to the improvement of insulin resistance and fat deposition in the rodent model.…”

Acetylcholinesterase inhibition studies of alkaloid components from Crinum asiaticum var. sinicum plants: In vitro assessments by molecular docking and molecular dynamics simulations

“…The general procedures were carried out similarly to those cited in previous papers with slight modi cations [42,23,27]. Biological and chemical reagents were obtained from Sigma (Missouri, USA).…”