Tinospora cordifolia received significant attention due to its medicinal and pharmacological properties in the treatment of various diseases.However, despite its well-established reputation for its anti-inflammatory effects, our understanding of the molecular mechanisms underlying these activities remains limited.To address this gap, an extensive literature review and identification of thirteen anti-inflammatory metabolites derived from Tinospora cordifolia was conducted.These metabolites were subjected to pharmacokinetic prediction using SwissADME and Protox II.Molecular docking techniques with DockingPie through PyMOL was also used to investigate their interactions with thirty-two proteins associated with different inflammatory pathways.Among the secondary metabolites tested, there were 14 conformations consisting of 13 proteins and 5 ligands which showed ideal binding affinity.Stigmasterol (11) had the greatest number of acceptable binding affinities among the 5 ligands with MMP-13 (-9.8 kcal/mol), Nf-kb1 (-8.6 kcal/ mol), NIK (-8.2 kcal/mol), IL-17A (-8.2 kcal/mol), and TGF-B (-8.1 kcal/mol), followed by β-sitosterol (2) with COX-1 (-8.8 kcal/mol), LT-B (-8.8 kcal/mol), 15-LOX (-8.4 kcal/mol), and NIK (-8.2 kcal/mol).Then columbin (5) with 5-LOX (-8.5 kcal/mol), MMP-1 (-8.3 kcal/mol), and MMP-8 (-8.2 kcal/mol).Both berberine (3) and 20-hydroxyecdysone (1) are bound to the least number of proteins, namely MMP-2 (-8.9 kcal/mol) and MMP-19 (-8.9 kcal/mol), respectively.Meanwhile, ADMET analysis revealed that berberine (3), magnoflorine (7), menisperine (8), reticuline (10), and stigmasterol (11) are of good oral bioavailability, while β-sitosterol (2), syringin (12), and 20-hydroxyecdysone (1) have undesirable lipophilicity and polarity.Berberine (3), columbamine (4), jatrorrhizine (6), and palmatine ( 9) are predicted to be the most toxic compounds when administered via oral route.While these secondary metabolites exhibited optimal binding affinities, their potential as lead compounds is constrained by their drug-likeness properties, with some of them having violations in XLOGP3, MLOGP, and hydrogen bond following Lipinski's rule of five and Muegge's rule.Therefore, further functionalization and modification are imperative for prospective drug discovery and design.
Gestational diabetes mellitus (GDM) is one of the metabolic disorders of pregnancy that result in shortand long-term adverse outcomes to both the mothers and her offspring.Among the factors linked to GDM susceptibility, genetic variations such as single nucleotide polymorphisms (SNPs) are the most implicated.Several case-control association studies have reported that the G allele of SNP rs10830963 in the melatonin receptor 1B (MTNR1B) is associated with higher GDM risk, however others reported insignificant associations.Previous meta-analyses also showed inconsistent findings.Herein, we performed a comprehensive literature search and meta-analysis to clarify the role of the SNP on GDM risk.Pooled odds ratios (ORs) with 95% CI were calculated to measure the strength of the association.Meta-analysis of the overall population using 11 eligible studies with a total of 4760 GDM cases and 5345 controls revealed significant association with the variant G allele and increased risk of GDM (CC vs. CG: OR = 1.28, 95% CI = 1.17-1.41,P < 0.001; CC vs. GG: OR = 1.92, 95% CI = 1.49-2.49,P < 0.001; C vs. G: OR = 1.30, 95% CI = 1.16-1.46,P < 0.001).In the subpopulation analysis, similar results were observed in Asians (CC vs. CG: OR = 1.26, 95% CI = 1.07-1.49,P = 0.005; CC vs. GG: OR = 1.66, 95% CI = 1.26-2.19,P < 0.001; C vs. G: OR = 1.30, 95% CI = 1.12-1.50,P < 0.001) with notably lower OR for CC vs GG.For the Euro-American population, higher ORs were noted for all the comparison models (CC vs. CG: OR = 1.40, 95% CI = 1.15-1.70,P = 0.005; CC vs. GG: OR = 2.84, 95% CI = 2.05-3.93,P < 0.001; C vs. G: OR = 1.37, 95% CI = 1.19-1.58,P < 0.001).Overall, the results suggest that the MTNR1B SNP rs10830963 is a risk factor for GDM across all populations with increased susceptibility observed among Euro-Americans.
Mangrove-associated fungal endophytes (MFE) produce structurally diverse secondary metabolites with promising pharmaceutical applications.In our effort to search for these valuable fungi, reported herein is our isolation and molecular identification of fungal endophytes associated with mature leaves of the host mangrove Rhizophora mucronata.The isolated MFE were characterized based on their colonial growth on three culture media -potato dextrose agar (PDA), Czapek Dox agar (CDA), and malt extract agar (MEA), and these were grouped into 16 morphospecies.Analysis of the ITS genes confirmed the identities of the isolated mangrove fungal endophytes as belonging to the genera Aspergillus, Cladosporium, Curvularia, Diaporthe, Fusarium, Nigrospora, Penicillium, Pestalotiopsis, and Schizophyllum.Our study showed the species richness of fungal endophytes associated with Philippine mangroves.
