Alkaloids are a type of natural compound possessing different pharmacological activities. Natural products, including alkaloids, which originate from plants, have emerged as potential protective agents against neurodegenerative disorders (NDDs) and chronic inflammations. A wide array of prescription drugs are used against these conditions, however, not free of limitations of potency, side effects, and intolerability. In the context of personalized medicine, further research on alkaloids to unravel novel therapeutic approaches in reducing complications is critical. In this review, a systematic survey was executed to collect the literature on alkaloids and their health complications, from which we found that majority of alkaloids exhibit anti-inflammatory action via nuclear factor-κB and cyclooxygenase-2 (COX-2), and neuroprotective interaction through acetylcholinesterase (AChE), COX, and β-site amyloid precursor protein activity. In silico ADMET and ProTox-II-related descriptors were calculated to predict the pharmacological properties of 280 alkaloids isolated from traditional medicinal plants towards drug development. Out of which, eight alkaloids such as tetrahydropalmatine, berberine, tetrandrine, aloperine, sinomenine, oxymatrine, harmine, and galantamine are found to be optimal within the categorical range when compared to nicotine. These alkaloids could be exploited as starting materials for novel drug synthesis or, to a lesser extent, manage inflammation and neurodegenerative-related complications.

Diabetes is a metabolic disorder of high blood sugar levels which leads to various chronic health-related complications. The digestive enzymes α-amylase and α-glucosidase play a major role in the hydrolysis of starch to glucose; hence, inhibiting these enzymes is considered an important strategy for the treatment of diabetes. Medicinal plants such as Bergenia ciliata, Mimosa pudica, and Phyllanthus emblica are commonly used in traditional remedies due to their numerous health benefits. This study aimed to determine the phytochemicals as well as TPC and TFC contents in these plant extracts along with their antioxidant and enzyme inhibitory activity against α-glucosidase and α-amylase. The ethyl acetate extracts of selected plants have shown higher TPC and TFC contents. The aqueous extract of B. ciliata (IC₅₀: 16.99±2.56μg/mL) and ethyl acetate extract of P. emblica (IC₅₀: 11.98±0.36μg/mL) and M. pudica (IC₅₀: 21.39±3.76μg/mL) showed effective antioxidant activities. Furthermore, ethyl acetate extract of B. ciliata showed significant inhibitory activity against α-amylase and α-glucosidase with IC₅₀ values of 38.50±1.32μg/mL and 3.41±0.04μg/mL, respectively. Thus, secondary metabolites of these medicinal plants can be repurposed as effective inhibitors of digestive enzymes.

Inhibiting α‐glucosidase, a key enzyme in carbohydrate hydrolysis, can potentially control diabetes mellitus. Although commercially available drugs effectively lower blood glucose levels to mitigate hyperglycemia, their associated gastrointestinal side effects necessitate the exploration of explicit inhibitors with minimal side effects. We studied a library of 80 secondary metabolites ascribed to their antidiabetic properties and screened the most potent inhibitors using a comprehensive in silico approach, including molecular docking, DFT study, MD simulation, PCA, MMPBSA calculation, and pharmacokinetic analysis. Scolopianate A and ponasterone A emerged as potent α‐glucosidase inhibitors, forming hydrogen bonds with the catalytic diad and exhibiting prominent binding affinities of −8 kcal/mol. Further analyses encompassed significant reactivity at the catalytic site and stable protein‐ligand complexes, as asserted by 100 ns RMSD, RMSF, R_g, SASA, H‐bond, and PCA‐based free energy landscape analysis. The subsequent analysis of MMPBSA indicating a higher binding free energy of these compounds compared to reference ligand, acarbose further strengthened the validity of these findings. Furthermore, drug‐like behavior and favorable ADMET profiles affirmed scolopianate A and ponasterone A as robust α‐glucosidase inhibitors. These findings highlight their promise for future drug development targeting α‐glucosidase inhibition in diabetes management; however, more research needs to be conducted.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant (B.1.1.529) underwent a substantial number of alterations, and the accompanying structural mutations in the spike protein prompted questions about the virus’s propensity to evade the antibody neutralization produced by prior infection or vaccination. New mutations in SARS-CoV-2 have raised serious concerns regarding the effectiveness of drugs and vaccines against the virus; thus, identifying and developing potent antiviral medications is crucial to combat viral infections. In the present study, we conducted a detailed in silico investigation that involves molecular docking, density functional (DFT) analysis, molecular dynamics (MD) simulations, and pharmacological analysis followed by an in vitro study with the spike protein. Among fifty terpenes screened, cryptotanshinone and saikosaponin B2 were found to be potent S1-RBD spike protein inhibitors, displaying considerable hydrogen bond interactions with key binding site residues, significant binding affinity, and high reactivity attributed to band gap energy. In addition, 100 ns molecular dynamics (MD) simulations further substantiated these findings, showcasing the stability of the compounds within a biological environment. With favorable pharmacokinetic properties and a low half inhibitory concentration (IC₅₀) of 86.06 ± 1.56 μM, cryptotanshinone inhibited S1-RBD of the SARS-CoV-2 Omicron variant. Our findings account for in-depth research on cryptotanshinone as a SARS-CoV-2 inhibitor.

Obesity remains a global health concern, and inhibiting human pancreatic lipase (EC3.1.1.3), a key enzyme in dietary fat breakdown and absorption, is an effective therapeutic approach. However, current lipase inhibitors such as orlistat are often associated with adverse gastrointestinal side effects and poor patient compliance. As a safer and multifunctional alternative, we investigated a library of naturally derived polyphenols known for their enzyme inhibitory activity and metabolic benefits, including anti-inflammatory effects, enhanced insulin sensitivity, and modulation of gut microbiota—offering a synergistic approach to obesity management. This study explores the dynamic and mechanistic inhibitory potential of polyphenol-based HPL inhibitors through an extensive in silico approach, aiming to identify explicit, low-toxicity inhibitors that serve as multi-benefit scaffolds for next-generation anti-obesity therapeutics. Significant binding affinity and interactions with a catalytic triad (SER 152, HIS 263, and ASP 176) of HPL through molecular docking, alongside higher MM/GBSA values of − 53.29, − 52.76, and − 53.37 kcal/mol, identified (-)-epigallocatechin-3-O-p-coumarate, (+)-catechin-3-O-gallate, and (−)-epicatechin-3-O-(3’-O-methyl gallate), respectively, as potent leads. The DFT study and molecular dynamics simulation affirmed the strong reactivity of these compounds in the catalytic site of HPL and a stable protein-ligand complex over 100 ns. FEL, PCA, and DCCM analysis also demonstrated these protein-ligand complexes’ stable dynamic behavior and conformational changes. Additionally, post-simulation MMPBSA analysis revealed higher binding free energies of − 59.46, − 56.54, and − 48.48 kcal mol⁻¹ for these complexes, indicating the formation of thermodynamically more stable complexes. Their favorable ADMET and drug-likeness pharmacokinetic properties further support their potential as effective HPL inhibitors with the potential for obesity control. The finding highlights (−)-epigallocatechin-3-O-p-coumarate, (+)-catechin-3-O-gallate, and (−)-epicatechin-3-O-(3’-O-methyl gallate) as promising low-toxicity, multi-benefit candidates for obesity management, paving the way for next-generation plant-based therapeutics. AbstractSection Graphical abstract