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Flacourtia jangomas is a plant used for centuries in Brazil, China, India, and the Malaya Peninsula to treat conditions such as diabetes, asthma, anaemia, and diarrhoea. Despite its therapeutic and economic benefits, the plant has not been popular among farmers due to its limited yield and lack of knowledge about its potential. Targeting PPARγ agonists is a promising approach for discovering and developing effective drugs to treat type 2 diabetes. Due to the activation of the PPARγ through PPARγ agonists, target genes implicated in inflammation, adipogenesis, lipid metabolism, and glucose metabolism are transcriptionally regulated. This study analysed the curated datasets of F. jangomas to identify the binding conformations of the phytoconstituents with different T2DM targets through molecular docking, molecular dynamics, and ADMET prediction approach. To determine the most favourable binding conformations of phytoconstituents that bind with the PPARγ receptors, density functional theory and principal component analysis were performed. The study reveals that the phytoconstituents of F. jangomas can act as PPARγ agonists and could be used to design and optimise the potential antidiabetic agents inspired by natural products. These findings provide a promising approach towards developing effective antidiabetic drugs. [ABSTRACT FROM AUTHOR]

Diabetes, a chronic metabolic disease, has become a severe health problem worldwide. According to the latest data from the International Diabetes Federation (IDF), there were 537 million diabetic mellitus (DM) patients worldwide in 2021, expected to increase to 783 million by 2045. Over 90% of people with diabetes have type 2 diabetes, which is driven by socio-economic, demographic, environmental, and genetic factors. Diabetes is still a major global health issue, with prevalence rates rising all across the world. This not only imposes a significant burden on healthcare systems but also impacts the quality of life of affected individuals and their families. Therefore, there is a continuous high demand worldwide to develop novel, more effective, and easily affordable medications against diabetes. This paper illustrates the in-vitro antidiabetic activity and probable binding mechanism prediction of phytoconstituents of Allamanda cathartica against type 2 diabetes molecular targets. Through the application of bioactivity score prediction, molecular docking, and ADMET prediction approach, the potential and selective phytoconstituents with the highest binding affinity and lower toxicity were gained from the curated datasets. Further molecular dynamics simulations and DFT calculations were carried out to identify the favorable binding conformations when the top-scored phytoconstituents bind with the PPAR γ receptors compared to the rosiglitazone. Compound AC2 interacts with the PPAR γ proteins by forming seven hydrogen bonds with the amino acid residues Phe282, His449, Tyr327, His323, and Ser289. The ligand was bound to the protein during the simulation since none of the complex conformations was unstable, and no unfolding or folding occurred. Our results provided an approach to further design and optimize the natural product-inspired small druglike molecules as potential antidiabetic agents. This study highlighted that the phytoconstituents of Allamanda cathartica have antidiabetic potential through the binding of PPAR γ , α -amylase and α -glucosidase proteins that can be further explored for novel antidiabetic drug development. The ethyl acetate extract of A. cathartica displayed significant α -amylase inhibition compared to other fractions, reaching its peak inhibition at a concentration of 4 mg/mL. The organic extract prominently inhibited the enzyme α -glucosidase compared to other fractions, with maximal inhibition observed at a concentration of 4 mg/mL. Phytoconstituents of Allamanda cathartica have shown antidiabetic potential through the binding of PPAR γ , α -amylase, GLP-1 and α -glucosidase proteins Compound AC2 (1-deoxy-d-mannitol) interacts with the PPAR γ proteins through the formation of 7 hydrogen bonds with the residues Phe282, His449, Tyr327, His323 and Ser289, while compound AC31 (Phytol) forms two hydrogen bonds with His323 and Tyr473 amino acid residues. Compounds AC28 (Octanoic acid) show a better binding affinity for GLP-1 target protein. Compounds AC34 (Quercetin) and AC23 (Kaempferol) show excellent binding affinity for α -amylase and α -glucosidase enzymes. [ABSTRACT FROM AUTHOR]

Capsicum annuum L., commonly known as chili pepper, is used as an important spice globally and as a crude drug in many traditional medicine systems. The fruits of C. annuum have been used as a tonic, antiseptic, and stimulating agent, to treat dyspepsia, appetites, and flatulence, and to improve digestion and circulation. The article aims to critically review the phytochemical and pharmacological properties of C. annuum and its major compounds. Capsaicin, dihydrocapsaicin, and some carotenoids are reported as the major active compounds with several pharmacological potentials especially as anticancer and cardioprotectant. The anticancer effect of capsaicinoids is mainly mediated through mechanisms involving the interaction of Ca2+‐dependent activation of the MAPK pathway, suppression of NOX‐dependent reactive oxygen species generation, and p53‐mediated activation of mitochondrial apoptosis in cancer cells. Similarly, the cardioprotective effects of capsaicinoids are mediated through their interaction with cellular transient receptor potential vanilloid 1 channel, and restoration of calcitonin gene‐related peptide via Ca2+‐dependent release of neuropeptides and suppression of bradykinin. In conclusion, this comprehensive review presents detailed information about the traditional uses, phytochemistry, and pharmacology of major bioactive principles of C. annuum with special emphasis on anticancer, cardioprotective effects, and plausible toxic adversities along with food safety. [ABSTRACT FROM AUTHOR]