Anti-proliferative Activity of Labdane Diterpenes Isolated from Polyalthia cerasoides and their Molecular Interaction Studies.

BACKGROUND: Polyalthia cerasoides is well known for its therapeutic effects and is extensively used by the tribal people of South India and Africa to treat infertility, toothache, inflammation, rheumatism, fever, and to combat stress. OBJECTIVE: In the present research, the anti-proliferative potential of two bioactive compounds isolated from the stem bark of P. cerasoides (Roxb.) Bedd. of the Annonaceae family was investigated. METHODS: The dried stem bark was powdered and subjected to extraction using methanol and further partitioned using petroleum ether. Yellow viscous oil was isolated from the petroleum ether fraction using column and preparative thin-layer chromatography. The chromatographic fractions were characterized using GC-MS. The anti-proliferative effect of the isolated compounds was assessed against HepG2 Cells using MTT- Cytotoxicity test. Furthermore, comparative in-silico docking studies were performed to predict the binding pattern of isolated molecules individually, as well as simultaneously with α, ß-tubulin, a critical protein involved in the molecular mechanism of microtubule formation. RESULTS: GC-MS analysis of yellow viscous oil from petroleum fraction confirmed the presence of two labdane diterpenes that were identified as 12E-3,4-Seco-labda-4(18),8(17),12,14-tetraen-3-oic acid, and methyl harvadate C by mass fragmentation analysis. The MTT-cytotoxicity assay showed the dose-dependent cytotoxic effect on HepG2 Cells. The comparative docking studies of the isolated compounds exhibited strong interactions with the α, ß-tubulin protein. CONCLUSION: The prominent anti-proliferative effect exhibited by the isolated compounds, along with effective binding to α, ß-tubulin protein, encourages their future utilization as prominent anti-cancer molecules.

Atheroprotective effect of novel peptides from Porphyridium purpureum in RAW 264.7 macrophage cell line and its molecular docking study.

OBJECTIVE: To explore the atherogenic foam cell prevention efficiency of two dipeptides purified from Porphyridium purpureum on RAW 264.7 cell line and to study its molecular interaction through molecular docking. RESULT: P. purpureum consists of 29.9% protein and 2.98% phycoerythrin on a dry weight basis. The two dipeptides namely of Histidine-Glutamic acid (HE) and Glycine-Proline (GP) isolated from the total protein and purified phycoerythrin of P. purpureum respectively, were evaluated for atherogenic foam cell prevention capacity in RAW 264.7 cell line. The IC5O values of peptides were found to be 91.2 ± 1.81 µg/ml (GP), 103.3 ± 4.8 µg/ml (HE) in MTT assay. The two peptides reduce the foam cell formation, intracellular lipid accumulation (cholesterol and triglycerides) and the secretion of TNF-α and IL-6 which are inflammatory cytokines in RAW 264.7 cell line at non-cytotoxic concentrations. A molecular interaction study proposed the binding pose for GP and HE peptides targeting the scavenging receptors CD36, SRA1, and Map Kinase p38 (a protein mediator). CONCLUSIONS: The cell line and molecular docking study indicated that among the two dipeptides, peptide GP has the highest atherogenic foam cell prevention efficiency.