Search Results (740)

Background/Objectives: Wound healing proceeds in a timely and sequential manner through four well-defined phases: hemostasis, inflammation, proliferation, and remodeling. To explore the therapeutic efficacy and underlying mechanism of a novel monoacylglycerol lipase (MAGL) inhibitor (designated as MAGL11), a diabetic mouse model of skin wounds was established. Methods: Wound healing progression was assessed via gross observation, while histological analyses (including HE staining and Masson staining) were conducted to evaluate tissue repair. Additionally, proteomic analysis and in vitro experiments were employed to validate the therapeutic effects and clarify the molecular mechanism of MAGL11. Results: In vivo studies revealed that treatment with MAGL11 significantly accelerated wound closure in diabetic mice. Compared with the control group, MAGL11-treated wounds exhibited notably increased granulation tissue formation and collagen deposition, which was accompanied by a distinct anti-inflammatory effect. Results from proteomic profiling and in vitro experiments further demonstrated that MAGL11 exerted its pro-healing effects by promoting the activation of the Rap1/PI3K/Akt signaling pathway. Specifically, MAGL11 enhanced the migration and chemotaxis of fibroblasts (NIH3T3), human umbilical vein endothelial cells (HUVECs), and keratinocytes (HaCaT) while simultaneously inhibiting cellular apoptosis—all of which collectively contributed to improved wound healing. Conclusions: These findings suggest that MAGL11 holds promise as a potential candidate for diabetic wound therapy, primarily through its ability to promote angiogenesis, fibroblast activation, and epithelial regeneration. Full article

Type 2 diabetes mellitus (T2DM) can be traditionally treated by edible and medicinal species rich in flavonoids and triterpenoids known for their metabolic benefits. Cucumis prophetarum L. has shown antioxidant and antidiabetic properties in decoction extracts. Since solvent polarity strongly influences the extraction of secondary metabolites, this study investigated the hydroalcoholic extracts of C. prophetarum L. to explore their chemical composition and insulin-sensitizing potential. Hydroalcoholic extracts from the leaf, stem, and root of C. prophetarum L. were analyzed by UV-Vis spectroscopy, ATR-FTIR, and UHPLC-ESI-QqTOF–MS/MS to profile their secondary metabolites. The insulin-sensitizing potential of each extract was assessed using an in vitro model of palmitic-acid-induced insulin resistance in L6 skeletal muscle cells, followed by Western blot analysis of key insulin-signaling proteins. Flavonoid glycosides such as apigenin-C,O-dihexoside, apigenin-malonylhexoside, and luteolin-C,O-dihexoside were abundant in leaf and stem extracts, while cucurbitacins predominated in the root. MTT assay confirmed that hydroalcoholic stem and root extracts of C. prophetarum L. were non-cytotoxic to L6 myotubes, whereas the leaf extract reduced viability only at higher concentrations. Oil Red O staining revealed a pronounced decrease in lipid accumulation following stem and root extract treatment. Consistently, the stem extract enhanced insulin signaling through the activation of the IRS-1/PI3K/Akt pathway, while the root extract primarily modulated the AMPK–mTOR pathway. Importantly, both extracts promoted GLUT4 translocation to the plasma membrane, highlighting their complementary mechanisms in restoring insulin sensitivity. Hydroalcoholic extracts of C. prophetarum L. alleviate insulin resistance through multiple molecular mechanisms, with bioactivity and composition differing markedly from previously reported in the decoctions, which highlight a promising source of insulin-sensitizing phytochemicals and underscore the importance of solvent selection in maximizing therapeutic potential. Full article

The service tree (Sorbus domestica L.) fruits are rich in polyphenols, which exhibit promising therapeutic effects on bone health. This review summarizes the potential benefits of polyphenols identified in Sorbus domestica L. fruits, such as chlorogenic acid (CGA), protocatechuic acid (PCA), rutin, epicatechin, and naringin on bone biology and on bone-related diseases, including osteoporosis and diabetes mellitus. Current evidence suggests that the aforementioned polyphenols may modulate osteoblast and osteoclast activity, enhance mineralization, mitigate oxidative stress and inflammation, thereby supporting overall bone health. Specific studies highlight the anabolic and anti-resorptive effects of CGA, the osteoprotective potential of PCA, and the ability of rutin, epicatechin, and naringin to promote osteogenic differentiation and inhibit osteoclastogenesis. Although the exact mechanisms are still unclear, it is believed that these bioactive metabolites can act through a variety of signalling pathways and epigenetic mechanisms. Despite existing preclinical evidence, there is a significant gap in clinical trials evaluating the direct impact of polyphenols mentioned above on bone health in humans. Therefore, further research is needed to confirm their effectiveness in clinical settings. The therapeutic potential of the most common polyphenols from Sorbus domestica L. fruits has been evaluated by available in vitro and in vivo studies, which highlight their promising potential as dietary interventions to prevent bone loss and improve skeletal integrity in metabolic bone diseases. Based on available information, maximum health benefits may be achieved if mature Sorbus domestica L. fruits are consumed approximately two weeks after harvest or as unripe fruit-based fermented products. Full article

Chronic diabetic wounds are characterized by persistent inflammation, impaired angiogenesis, oxidative stress, and defective tissue remodeling, leading to delayed healing. Cordyceps militaris, a medicinal fungus with known anti-inflammatory and antioxidant properties, has shown therapeutic potential in metabolic disorders; however, its role in diabetic wound repair remains unclear. In this study, we evaluated the wound-healing effects of an aqueous extract of C. militaris using in vitro keratinocyte models and a streptozotocin-induced diabetic mouse model. C. militaris treatment significantly accelerated wound closure, improved epidermal regeneration, and enhanced skin barrier integrity. Mechanistically, C. militaris restored HIF-1α and TGF-β1 expression, promoted cell proliferation and fibroblast activation, and increased the expression of matrix metalloproteinases MMP-1 and MMP-2, indicating enhanced extracellular matrix remodeling. In parallel, excessive inflammatory responses were attenuated, as evidenced by reduced IL-6 and TNF-α levels, along with activation of SIRT1/Nrf2/HO-1 antioxidant signaling pathways. Collectively, these findings demonstrate that C. militaris promotes a balanced wound-healing microenvironment and represents a promising natural therapeutic candidate for the treatment of diabetic wounds. Full article

During gastrointestinal digestion, dietary proteins are hydrolyzed into peptides and free amino acids that modulate enteroendocrine function and satiety-related hormone secretion along the gut–brain axis, thereby contributing to obesity prevention. We investigated whey protein concentrate (WPC) as a source of bioactive peptides and evaluated the effects of its digests on cholecystokinin (CCK) secretion in STC-1 enteroendocrine cells by integrating the standardized INFOGEST in vitro digestion protocol, peptidomics (LC–MS/MS), and in silico bioactivity prediction. In STC-1 cells, the <3 kDa intestinal peptide fraction exhibited the strongest CCK stimulation, positioning these low-molecular-weight peptides as promising bioactive components for satiety modulation and metabolic health applications. Peptidomic analysis of this fraction identified short sequences derived primarily from β-lactoglobulin (β-La) and α-lactalbumin (α-La), enriched in hydrophobic and aromatic residues, including neuropeptide-like sequences containing the Glu–Asn–Ser–Ala–Glu–Pro–Glu (ENSAEPE) motif of β-La f(108–114). In silico bioactivity profiling with MultiPep predicted antihypertensive, angiotensin-converting enzyme (ACE)–inhibitory, antidiabetic, dipeptidyl peptidase-IV (DPP-IV)–inhibitory, antioxidant, antibacterial, and neuropeptide-like activities. Overall, digestion of WPC released low-molecular-weight peptides and amino acids that enhanced CCK secretion in vitro; these findings support their potential use in nutritional strategies to enhance satiety, modulate appetite and energy intake, and improving cardiometabolic health. Full article

Background/Objectives: Plants of the Crassulaceae family have been utilized in traditional medicine because of their medicinal properties. Crassula capitella, an ornamental succulent plant, has not yet received significant attention from physiochemists or pharmacologists. The objective of this study was to investigate the in vitro phytochemical properties and biological activity of methanolic extracts obtained from the leaves (CCLE) and inflorescences (CCIE) of C. capitella. Methods: Phytochemical screening included GC/MS analysis. The in vitro investigation of biological properties includes the assessment of antibacterial activity, utilizing disk diffusion assays and measuring MIC and MBC values for Gram-positive and Gram-negative bacteria. Antioxidant properties were determined through IC50 values in DPPH and ABTS assays. Cytotoxicity properties were evaluated using the MTT assay in MCF-7 and HepG2 cells, along with an analysis of apoptosis gene expression. Additionally, the antidiabetic effects were examined through α-amylase or α-glucosidase inhibition assays. Results: GC/MS analysis revealed distinct differences. CCLE contained more terpenoids such as betulinaldehyde (30.53%) followed by lupeol (19%) and betulin (4.07%), whereas CCIE was rich in fatty acids. The TPC and TFC of CCIE (88.17 mg GAE/g and 57 mg QE/g) were significantly greater than those of CCLE. Compared with CCLE, CCIE exhibited greater antibacterial properties (MIC values of 6.25 µg/mL toward S. aureus), greater antioxidant properties (IC₅₀ values in the DPPH/ABTS assay), antitumor properties (IC₅₀ values of approximately 90–96 µg/mL), and antidiabetic properties (IC₅₀ values of 87–83 µg/mL in the α-amylase/α-glucosidase assay). Both bioactive extracts induced apoptosis in cancer cells by downregulating the expression of the tumorigenesis genes bcl-2 and bcl-xL. Conclusions: The findings provided the first evidence about the evaluated the potential antibacterial, antioxidant, anticancer, and antidiabetic activities of C. capitella, which is attributed to its robust chemical composition and position it as a compelling candidate for further in vivo and sub-clinical applications. Full article

Type 2 diabetes mellitus (T2DM) is characterised by chronic hyperglycaemia and accumulation of advanced glycation end products (AGEs), driving interest in food-derived peptides as safer multifunctional modulators. Coconut milk is a promising source, but its anti-hyperglycaemic and anti-glycation potential remains largely unexplored. Here, proteins from coconut cream, skimmed and insoluble fractions of coconut milk were enzymatically hydrolysed, and the resulting peptides were profiled by nano-ESI-Orbitrap-LC-MS/MS. One hundred and fourteen peptides were identified and screened in silico against α-glucosidase, α-amylase, aldose reductase and the receptor for AGEs (RAGE). Two peptides, MQIFVK and ADVFNPR, showed the most favourable docking scores and physicochemical properties. However, ADVFNPR inhibited all 3 diabetic targets & RAGE. Molecular dynamics analysis showed that both peptides bind stably to the diabetic targets. Both peptides were synthesised and evaluated in vitro. ADVFNPR significantly inhibited α-glucosidase, α-amylase and aldose reductase with lower IC₅₀ values and displayed competitive inhibition kinetics. It also scavenged methylglyoxal, 2,2-diphenyl-1-picrylhydrazyl (DPPH), 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid (ABTS) and superoxide radicals at low EC₅₀ values, and showed low hemolytic activity in human erythrocytes. These findings indicate that coconut milk contains multifunctional peptides with anti-hyperglycaemic, anti-glycation and antioxidant activities that may be further developed as food-derived adjuncts for managing T2DM and glycation-related complications. Full article

Glycemic control disorders, including insulin resistance (IR) and type 2 diabetes (T2D), represent a major global health challenge. Although existing therapeutic strategies demonstrate effectiveness regarding glycemic control and reduction in diabetes-associated mortality, they are often associated with limited patient tolerance and adherence. Consequently, there is growing interest in natural bioactive compounds that may support glycemic regulation while potentially posing a lower risk of adverse effects in ongoing therapy. The objective of this review is to evaluate the potential of selected natural substances in the context of blood glucose regulation. The analysis encompasses data from in vitro, in vivo, and clinical studies on compounds such as mannoheptulose, β-carotene, resveratrol, steviol glycosides, and curcumin. These agents have demonstrated the ability to modulate key metabolic pathways, enhance tissue insulin sensitivity, reduce oxidative stress, and support pancreatic β-cell function. Particularly promising effects have been observed when some of these compounds are combined with conventional antidiabetic medications, such as metformin. The review also highlights relevant molecular mechanisms, including activation of the AMP-activated protein kinase (AMPK) pathway, increased expression of glucose transporter type 4 (GLUT4), and modulation of gene expression related to insulin sensitivity. Despite encouraging findings, further clinical research is necessary to determine optimal dosages, therapeutic protocols, and the long-term safety of these substances in human populations. Natural bioactive compounds may thus represent a valuable adjunct to current strategies for managing glycemic disorders. Full article

Diabetes mellitus represents one of the main health challenges worldwide, characterized by hyperglycemia and long-term serious microvascular and macrovascular complications. Marine organisms are a promising reservoir of bioactive metabolites for developing effective antidiabetic therapies with fewer side effects. The sea urchin Tripneustes gratilla (T. gratilla) is widely distributed in the Red Sea, with limited reports of its pharmacological activities and chemical characterization. In this study, a nanosuspension formulation of T. gratilla extract (T. gratilla-NS) was developed to enhance the bioavailability of its bioactive constituents. This study investigated the antidiabetic potential of T. gratilla extract through an integrated approach encompassing chemical profiling of the extract, assessment of its alcoholic extract for in vitro inhibitory effects on α-amylase and α-glucosidase, and in vivo evaluation of T. gratilla-NS in an alloxan-induced diabetic rat model. We found that the alcoholic extract showed potent inhibitory action toward α-amylase with IC₅₀ 5.31 ± 0.05 µg/mL and moderate inhibitory activity toward α-glucosidase with IC₅₀ 21.36 ± 0.06 µg/mL. T. gratilla-NS significantly increased insulin levels, reduced blood glucose levels, and restored pancreatic damage. Furthermore, it enhanced the levels of superoxide dismutase and total antioxidant capacity with a concomitant decrease in malondialdehyde concentration in pancreatic tissue. The observed activities could be attributed to a wide array of diverse compounds, terpenes, mainly sesquiterpenes, diterpenes, steroids, and polyunsaturated fatty acids detected by GC-MS, compounds with a phenolic nucleus equal to 54.26 ± 1.27 mg. GAE/g of extract. This research highlights the dual role of T. gratilla-NS in combating diabetes and subsequently attenuating its associated complications. Full article

Spearmint phytochemicals exhibit remarkable antidiabetic, antioxidant, and broad pharmacological activities. In vitro organ cultures offer an efficient and sustainable platform for enhancing the production of these bioactive metabolites, although optimized media and cultivation strategies are essential to maximize yields. Here, four Murashige and Skoog (MS) medium variants and three cultivation systems—agar-solidified, static-liquid (L), and agitated-liquid (LA)—were evaluated to assess phenolics, antioxidant capacity, antidiabetic potential, and metabolic biochemical markers in in vitro-grown spearmint shoots. Half-strength MS (MS/2) consistently produced the highest antioxidant activity and accumulation of phenolics and sugars across all systems. The MS/2–L combination markedly boosted antioxidant responses, increasing 2,2-diphenyl-1-picrylhydrazyl (DPPH) values up to 27-fold and ferric reducing antioxidant power (FRAP) values tenfold relative to full-strength MS. Antioxidant capacity strongly correlated with total phenolics, flavonoids, rosmarinic acid, antidiabetic activity, and carbohydrate levels. Lipid peroxidation analysis further revealed that shoots cultured under LA conditions showed the highest level of malondialdehyde (MDA) accumulation, whereas MSN/2 (half-strength nitrogen) consistently yielded the lowest MDA levels across all cultivation systems. Collectively, these results highlight the strong influence of nutrient availability and culture system on the metabolic performance of in vitro-grown spearmint. In conclusion, nutrient limitation combined with liquid cultivation effectively enhances antioxidant metabolite accumulation, providing valuable criteria for the future design and optimization of scalable bioreactor systems. Full article

Oleanolic acid (OA) is a natural pentacyclic triterpenoid with reported hypoglycemic, hepatoprotective, antidiabetic, and anti-inflammatory activities. However, its limited aqueous solubility restricts its formulation and potential biomedical applications. To address this limitation, we designed a hydrophilic OA derivative, 1a, by introducing an amino acid fragment at the C-28 position. We established a reverse-phase high-performance liquid chromatography (HPLC)-based method to measure the octanol–water partition coefficient (Log P_ow) of OA and 1a. Under neutral conditions, 1a showed a markedly reduced Log P_ow value (2.91 ± 0.02) compared with OA (4.30 ± 0.01), confirming substantially improved hydrophilicity. The biological compatibility of OA and 1a was further evaluated using in vitro human islet cultures. Both compounds maintained high islet viability (approximately 90%). In addition, islets pre-treated with 1a exhibited viability, purity, and insulin expression levels comparable to those observed with OA treatment, indicating that the C-28 modification preserved OA’s biological properties while improving solubility. Overall, this proof-of-concept study demonstrates that C-28 amino-functionalization can improve the physicochemical properties of OA without compromising its compatibility with human islets. The HPLC-based Log P_ow method established here provides a practical analytical tool for future structure–activity investigations of OA derivatives, and the improved solubility of 1a may facilitate its use in human islet preparation workflows. Full article

Background: Diabetes mellitus is a multifactorial disease characterized by complex metabolic dysfunctions and chronic complications induced by hyperglycaemia. The design of multitarget ligands, capable of simultaneously controlling different pathogenic processes, was proposed as a promising approach to identify novel antidiabetic drugs endowed with improved efficacy. Methods: (5-Arylidene-4-oxothiazolidin-3-yl)alkanoic acid derivatives 1a–g and 2a–g were synthesized as potential multitarget antidiabetic agents. They were tested in vitro as inhibitors of both human recombinant AKR1B1 and PTP1B, and kinetic studies and molecular docking simulations for both enzymes were performed. Their effects on cellular glucose uptake, insulin signalling, and mitochondrial potential were assayed in cultures of murine C2C12 myocytes. A lipid accumulation assay was performed in HepG2 liver cells. The effects on high glucose-induced sorbitol accumulation were evaluated in lens HLE and retinal MIO-M1 cells. Results: All compounds displayed excellent AKR1B1 inhibitory activity (IC₅₀ 0.03–0.46 μM 1a–g; IC₅₀ 0.48–6.30 μM 2a–g); 1g and 2e–g also appreciably inhibited PTP1B at micromolar concentrations. Propanoic derivatives 2e–g significantly stimulated glucose uptake in C2C12 myocytes, in an insulin-independent way, reduced lipid accumulation in HepG2 liver cells, and caused hyperpolarization of C2C12 mitochondria at 10 μM concentration. Derivative 2e significantly reduced sorbitol accumulation in both HLE and MIO-M1 cells at a 5 μM concentration. Conclusions: The results reported here provided new insights into the mechanisms of action and structure/activity relationships of 4-thiazolidinone derivatives, underscoring the capability of compounds 2e–g of eliciting insulin-mimetic effects independent of hormone signalling. Among them, compound 2e also proved to inhibit AKR1B1-dependent sorbitol accumulation and, thus, emerged as a promising multitarget agent that can be considered for further investigations. Full article

Autoimmune disease (AD) is a breakdown of self-tolerance by the immune system and has a variety of clinical manifestations and complications across all organ systems. One of the targets for treatment of AD aims at reducing inflammation and upregulating factors that eliminate autoreactive cells. Intermittent fasting (IF) has recently gained popularity as a dietary intervention for weight management, but has also been found to interact and positively interfere with pathways involved in the pathophysiology of AD. Methods include searching in the PubMed and Google Scholar databases for reviews and clinical trials studying any relationships between AD and IF. The search results have identified a variety of anti-inflammatory effects IF has on the immune system that can potentially reduce AD severity and several trials specifically studying IF’s effects on type I diabetes (T1D), systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), inflammatory bowel disease (IBD), and multiple sclerosis (MS). Based on the findings, IF has potential anti-inflammatory effects that could assist with decreasing AD severity. Future directions include studies to further determine safety and efficacy of IF with AD, broader investigations to include IF’s impact on a wide variety of ADs, an ideal time frame of how long patients should remain on IF, and any potential interactions IF may have on current drug therapies used to treat AD. This review also aims to encourage more human studies of IF and its application to AD given that many of these results are largely from in vitro, cellular and molecular, and animal studies. Full article

The Belamcanda chinensis (L.) Redouté is a perennial herb belong to the genus Belamcanda, primarily found in China, but with additional distribution in North Korea, South Korea, Japan, and India. The rhizomes of B. chinensis have a long history of use as a traditional herbal medicine in China, one that is recognized for its effects in clearing heat, in detoxifying and eliminating phlegm, and in soothing the throat. In this review, we conducted a comprehensive search across several databases, both Chinese and international, using the primary keyword Belamcanda chinensis paired with a relevant research area (e.g., chemical composition, pharmacology). The databases included Sci-Finder, ScienceDirect, PubMed, China National Knowledge Infrastructure, Wiley, Springer Baidu Scholar and Research Gate, as well as domestic materia medica. We illustrated the chemical structures using ChemBioDraw Ultra 22.0 software. There are more than 10 proprietary Chinese medicines already on the market that consist of or originate from B. chinensis. More than 200 natural products have been isolated and identified from B. chinensis, including iridal-type triterpenoids, flavonoids, phenolics, quinones, sesquiterpenes, and polysaccharides. Modern pharmacological studies indicate that both crude extracts and monomeric compounds exhibit anti-inflammatory, anti-tumor, antioxidant, neuroprotective and anti-diabetic activities, with potential regulatory pathways. Additionally, B. chinensis demonstrates toxicity to fish, mollusks and arthropods. Clinical studies have shown that formulas containing B. chinensis as the main ingredient have a good therapeutic effect on respiratory diseases. In summary, B. chinensis presents promising prospects for application in medicine, functional food, cosmetics and agriculture. Therefore, we have reviewed the chemical composition, pharmacological activities (both in vivo and in vitro), structure–activity relationships, toxicity and clinical application of B. chinensis over the past 40 years, aiming to provide a theoretical basis for the subsequent comprehensive utilization of the plants. Full article

Saffron (Crocus sativus L.), known as the world’s most valuable spice, has long been appreciated for its culinary, medicinal, and cultural significance. In recent years, increasing scientific attention has been directed toward its unique phytochemical profile and wide-ranging therapeutic potential. This review provides a comprehensive synthesis of current evidence regarding saffron’s chemical composition, molecular mechanisms of action, pharmacological activities, and safety aspects. The stigmas of saffron contain a rich array of bioactive constituents, notably crocin, crocetin, picrocrocin, and safranal, which collectively contribute to its antioxidant, anti-inflammatory, immunomodulatory, cardioprotective, hepatoprotective, neuroprotective, anti-obesity, antidiabetic, and anticancer properties. Evidence from in vitro and in vivo models, as well as clinical studies, suggests that saffron primarily exerts its beneficial effects through the modulation of oxidative stress, apoptosis, autophagy, lipid metabolism, and the regulation of key molecular pathways, including the NF-κB, PI3K/Akt/mTOR, and Nrf2/HO-1 pathways. Furthermore, recent advances in nanotechnology-based formulations have demonstrated improved bioavailability and enhanced therapeutic efficacy, thereby opening up promising avenues for clinical applications. While saffron is generally regarded as safe, challenges remain concerning its high cost, limited availability, and variability in quality due to geographic and environmental factors. Collectively, the accumulated body of evidence highlights saffron as a promising natural agent for the prevention and management of chronic diseases. However, further translational and large-scale clinical investigations are needed to fully establish its therapeutic value and optimize its integration into modern pharmacological and nutraceutical strategies. Full article