Chitosan nanoparticles (CSNPs) are promising vehicles for targeted and controlled drug release. Recognized for their biodegradability, biocompatibility, low toxicity, and ease of production, CSNPs represent an effective approach to drug delivery. Encapsulating drugs within nanoparticles (NPs) provides numerous benefits compared to free drugs, such as increased bioavailability, minimized toxic side effects, improved delivery, and the incorporation of additional features like controlled release, imaging agents, targeted delivery, and combination therapies with multiple drugs. Keys parameters in nanomedicines are drug loading content and drug loading efficiency. Most current NP systems struggle with low drug loading, presenting a significant challenge to the field. This review summarizes recent research on developing CSNPs with high drug loading capacity, focusing on various synthesis strategies. It examines CSNP systems using different materials and drugs, providing details on their synthesis methods, drug loadings, encapsulation efficiencies, release profiles, stability, and applications in drug delivery. Additionally, the review discusses factors affecting drug loading, providing valuable guidelines for future CSNPs’ development.

Dipeptidyl peptidase IV (DPP-IV) is an enzyme responsible for the degradation of the incretin hormone glucagon-like peptide-1 (GLP-1). DPP-IV plays a significant role in regulating blood glucose levels by modulating the activity of GLP-1. In the context of diabetes, DPP-IV inhibitors effectively block the activity of DPP-IV, hence mitigating the degradation of GLP-1. This, in turn, leads to an extension of GLP-1’s duration of action, prolongs gastric emptying, enhances insulin sensitivity, and ultimately results in the reduction of blood glucose levels. Nonetheless, reported adverse events of DPP-IV inhibitors on T2DM patients make it essential to understand the activity and mechanism of these drugs, particularly viewed from the perspective of finding the effective and safe add-on medicinal plants, to be implemented in clinical practice. This review is intended to bring forth a thorough overview of plants that work by reducing DPP-IV activity, from computational technique, enzymatic study, animal experiments, and studies in humans. The articles were searched on PubMed using “Plants”, “DPP-IV”, “DPP-IV inhibitor”, “GLP-1”, “Type 2 diabetes”, “diabetes”, “in silico”, “in vitro”, “in vivo”, “studies in human”, “clinical study” as the query words, and filtered for ten years of publication period. Eighteen plants showed inhibition against DPP-IV as proven by in silico, in vitro, and in vivo studies; however, only ten plants were reported for efficacy in clinical studies. Several plant-based DPP-IV inhibitors, eg, Allium sativum, Morus Alba, Curcuma longa, Pterocarpus marsupium, and Taraxacum officinale, have established their functional role in inhibiting DPP-IV and have proven their effectiveness through studies in humans earning them a prominent place in therapeutic discovery.

Context: The development of emerging viral diseases like SARS-CoV-2 has underlined the critical need for new antiviral medicines. Many of the discovered inhibitors have off-target effects or toxicity issues, but no single lead chemical has been found as a powerful SARS-CoV-2 inhibitor. Small-molecule metabolites from human blood, for example, have been demonstrated to exhibit biological action, such as anti-inflammatory or antiviral properties, but have not been reported as pharmacophore-based drug discovery models. Aims: To evaluate the feasibility of employing pharmacophore models of small-molecule metabolites taken from human blood as a lead discovery method for SARS-CoV-2 inhibitors. Methods: A total of six small-molecule metabolites from human blood were utilized to construct a pharmacophore model, which was then used to simulate the interaction's stability for the top two-rank ligands with the best interactions using molecular docking and molecular dynamics. Results: The area under the curve value of the pharmacophore model created using the best pairwise alignments approach was 0.576, indicating that it is suitably validated as a model. The pharmacophore model was utilized for virtual screening, followed by molecular docking, yielding 75 hits. An investigation of the molecular dynamics of two top-rank hits (ZINC000085567845 and ZINC000085567870) revealed a stable interaction with the SARS-CoV-2 spike protein. Conclusions: Finally, the pharmacophore model developed was capable of discovering lead compounds with the potential as SARS-CoV-2 spike protein inhibitors.

Objective: The purpose of this study was to determine the structural-based molecular interactions between flavonoids contained in Acalypha indica L. and caspase-3 by molecular docking and molecular dynamics (MD) simulations. Methods: In a computer simulation, ten flavonoids contained in A. indica L. were evaluated for caspase-3 using the X-ray crystal structure of human caspase-3 (PDB ID 1NME). The AutoDock 4.2 software was used to study molecular docking, and MD simulations were done with GROMACS v2018. Results: The results of molecular docking identified the top four compounds, namely nicotiflorin, naringenin, hesperetin, and kaempferol, with docking scores of-6.81,-6.45,-6.33, and-6.10 kcal/mol, respectively. According to the MD simulation results, nicotiflorin was most effective in stabilizing the complex with caspase-3, with a total energy (ΔGbind, MM-PBSA) of-96.315 kcal/mol. Conclusion: This study showed that nicotiflorin was the flavonoid in A. indica L. that activated caspase-3 the best.

Background: Roselle (Hibiscus sabdariffa L.) calyces have been used in traditional medicine as diuretics, mild laxatives, and antihypertensive agents but to date, a comprehensive study of its pharmacological activity and safety has not been conducted. Aims of the study: The current study aims to provide a comprehensive evaluation of the antihypertensive efficacy and toxicity profile of Roselle (H. sabdariffa L.) calyces extract. Utilizing animal models, the investigation assessed the dose-dependent pharmacological effects and safety of H. sabdariffa L. Results: The findings indicate that the extract exerts a significant antihypertensive effect at a dose of 250 mg/kg body weight (BW), lowering systolic and diastolic blood pressures by 10.12% and 11.63%, respectively. Ethyl acetate fractions administered at 112.5 mg/kg BW demonstrated greater efficacy than n-hexane and aqueous fractions, suggesting that the active compounds likely possess semi-polar properties. Acute toxicity testing yielded an LD₅₀ of 8.75 g/kg BW for male rats and 7.5 g/kg BW for female rats, classifying the extract as slightly toxic. The sub-chronic toxicity study shows that H. sabdariffa L. demonstrates an effect on bodyweight and urea levels in male and female rats, while the change in the blood parameters, creatinine level, and the liver index was only observed in female rats. Conclusions: These data suggest that H. sabdariffa L. extract exhibits therapeutic promise but should be administered cautiously, preferably at doses lower than 250 mg/kg BW, due to potential toxicity.