In this study, the rhizome of Cyperus rotundus L was investigated for its antioxidant and antidiabetic effects using in vitro and in silico experimental models. Its crude extracts (ethyl acetate, ethanol and aqueous) were screened in vitro for their antioxidant activity using ferric-reducing antioxidant power (FRAP) and 1,1-diphenyl-2-picrylhydrazyl (DPPH), as well as their inhibitory effect on α-glucosidase enzyme. Subsequently, the extracts were subjected to Gas Chromatography-Mass Spectrometry (GC-MS) analysis to elucidate their possible bioactive compounds. Furthermore, computational molecular docking of selected phenolic compounds was conducted to determine their mode of α-glucosidase inhibitory activity. The aqueous extract displayed the highest level of total phenolic content and significantly higher scavenging activity in both FRAP and DPPH assays compared to ethyl acetate and ethanol extracts. In FRAP and DPPH assays, IC₅₀ values of aqueous extract were 448.626 µg/mL and 418.74 µg/mL, respectively. Aqueous extract further presented higher α-glucosidase inhibitory activity with an IC₅₀ value of 383.75 µg/mL. GC-MS analysis revealed the presence of the following phenolic compounds: 4-methyl-2-(2,4,4-trimethylpentan-2-yl) phenol, Phenol,2-methyl-4-(1,1,3,3-tetramethylbutyl)- and 1-ethoxy-2-isopropylbenzene. Molecular docking study revealed 1-ethoxy-2-isopropylbenzene formed two hydrogen bonds with the interacting residues in the active site of α-glucosidase enzyme. Furthermore, 4-methyl-2-(2,4,4-trimethylpentan-2-yl) phenol had the lowest binding energy inferring the best affinity for α-glucosidase active site. These results suggest the possible antioxidant and antidiabetic potential of Cyperus rotundus. Communicated by Ramaswamy H. Sarma

A healthy life depends on the availability and the synthesis of amino acids as they are building blocks of proteins and regulators of principal physiological processes in organisms. Contemporary investigations have elucidated amino acids' roles in biological processes, emphasizing their contributions to preventing and treating metabolic disorders. Their structural architecture and nutritional importance elucidate their diverse biological roles, including muscle protein synthesis, immune support, neurological functions, and energy metabolism. Type 2 diabetes mellitus (T2DM), a prevalent metabolic disorder marked by insulin resistance and hyperglycemia, exemplifies a pertinent case for examining the relevance of amino acids in pathological conditions. The alteration of the amino acid profile, particularly high levels of leucine, isoleucine, and valine, is connected with insulin resistance and oxidative stress, which contribute to the progression of T2DM. In contrast, the potential therapeutic benefit of branched chain amino acid (BCAA) has earlier been reported to influence insulin signaling pathways, promote glucose uptake, and decrease inflammatory responses. However, the dosage and combination of amino acid intake through dietary interventions and supplementation may offer promising benefits to improve the management of T2DM effectively. This review investigates the functions of amino acids in normal physiological states, their potential as a diagnostic biomarker, the probable risk of deficiency, and the therapeutic ability for managing and preventing T2DM. Conversely, there is a need to intensively investigate the controversial dual role of BCAA in T2DM, the mechanism of amino acid actions in insulin resistance, the effect of a combination of amino acids, and the dosage limit in diabetic conditions.

Diabetes mellitus (DM) is a complex metabolic disorder characterized by chronic hyperglycemia and associated complications such as cardiovascular disease, nephropathy, retinopathy, neuropathy, and chronic non-healing wounds. Current antidiabetic therapies offer only partial glycemic control and are limited by poor bioavailability, adverse effects, and an inability to prevent disease progression. Plant-derived exosome-like nanoparticles (PENPs) have emerged as a promising class of natural nanocarriers with excellent biocompatibility, low immunogenicity, and intrinsic multi-component bioactivity. However, few reviews have addressed recent progress in PENPs for DM therapy. To capture the recent developments in this area, this review provides a systematic synthesis of recent advances in PENPs for DM therapy, covering plant sources, extraction and purification methods, molecular compositions, and therapeutic mechanisms. Preclinical studies have demonstrated that PENPs can improve hyperglycemia, enhance insulin sensitivity, regulate hepatic lipid metabolism, and promote wound healing by modulating oxidative stress, inflammation, gut microbiota, glucose metabolism, and insulin signaling. Additionally, PENPs have been shown to promote angiogenesis via glycolytic reprogramming. Despite these promising findings, challenges including scalable isolation, standardized physicochemical characterization, and clinical translation remain. Future directions include engineering multifunctional PENPs, establishing Good Manufacturing Practice (GMP)-compliant production, and conducting clinical trials to facilitate their integration into precision therapeutics for diabetes management.

Diabetes mellitus is the eighth leading health challenge globally, and its management has become a major concern. Research is now focusing on naturally derived organic compounds that can reduce the activity of enzymes involved in carbohydrate and lipid metabolism to manage Type 2 diabetes. The present study combines in vitro and in silico methods to determine the radical‐scavenging ability and enzyme‐inhibitory capacity of pure isoleucine, lysine and serine. Antioxidant capacity was determined using the DPPH, hydroxyl radical scavenging assay and the ferric reducing antioxidant power (FRAP) assay. The inhibitory effect of α‐amylase and α‐glucosidase assays was assessed, while their kinetic mode of inhibition was determined using the Michaelis–Menten model and complemented with the Lineweaver–Burk plot. Molecular docking and molecular dynamics were performed to evaluate the binding stability and flexibility of the complexes formed by these enzymes with amino acids. Toxicity prediction and drug‐likeness profiling were also performed to predict their safety and drug‐like behaviour. In antioxidant assays, the amino acids showed increased radical‐scavenging activity in the DPPH and hydroxyl radical assays, but weak reducing power in the FRAP assay. In vitro, isoleucine, lysine and serine showed maximum inhibitions of 72.6%, 72.92% and 76.76%, respectively, against α‐amylase. In the α‐glucosidase assay, isoleucine, lysine and serine also demonstrated maximum inhibitory effects of 43.57%, 43.66% and 46.55%, respectively. The kinetic behaviour analysis suggested that acarbose, lysine and serine inhibited α‐amylase via a mixed inhibition, whereas isoleucine was noncompetitive. In α‐glucosidase, isoleucine, lysine and serine showed mixed inhibition, while acarbose exhibited competitive inhibition. Molecular docking and molecular dynamics simulation analyses showed that acarbose exhibited the strongest affinities, stability and flexibility toward α‐amylase and α‐glucosidase, while isoleucine, lysine and serine displayed weaker affinities and stability. The toxicity prediction provides a variable acute oral toxicity and organ‐specific toxicity alert on isoleucine, lysine and serine, with favourable drug‐likeness properties. These results revealed that isoleucine, lysine and serine affect multiple pathways relevant to diabetes. This supports their potential as nutraceuticals for managing Type 2 diabetes if it is deeply explored. Further animal studies are required to determine their efficiency and safety in vital organs under physiological conditions.

Diabetes mellitus is a chronic metabolic disease characterized by insufficient insulin production or action, resulting in impaired blood glucose regulation. Insulin therapy remains critical for managing diabetes; however, it is conventionally administered through regular subcutaneous injections. This invasive route is associated with pain, discomfort, and complications, imposes significant physical and psychological burdens on patients, and adversely affects long‐term adherence. As the global prevalence of diabetes continues to increase, the development of alternative insulin delivery methods has become increasingly urgent. Oral insulin delivery offers a promising alternative by mimicking endogenous insulin secretion via the hepatic portal pathway. However, this approach has significant gastrointestinal barriers, such as enzymatic degradation, variable pH, and low permeability, which can delay effective absorption. Recent advances in nanotechnology have emerged as transformative approaches to overcome these challenges, leveraging advanced nanomaterials for insulin protection, enhanced absorption, and targeted delivery. The present review critically evaluates the recent advancements in nanomaterials used for oral insulin delivery, focusing on GI barriers and highlighting key preclinical and clinical developments.