Search Results (272)

Cinnamic acid, an organic acid naturally occurring in plants of the Cinnamomum genus, has been highly valued for its medicinal properties in numerous ancient Chinese texts. This article reviews the chemical composition, pharmacological effects, and various applications of cinnamic acid and its derivatives reported in publications from 2016 to 2025, and anticipates their potential in medical and industrial fields. This review evaluates studies in major scientific databases, including Web of Science, PubMed, and ScienceDirect, to ensure a comprehensive analysis of the therapeutic potential of cinnamic acid. Through systematic integration of existing knowledge, it has been revealed that cinnamic acid has a wide range of pharmacological activities, including anti-tumor, antibacterial, anti-inflammatory, antidepressant and hypoglycemic effects. Additionally, it has been shown to be effective against a variety of pathogens such as Staphylococcus aureus, Pseudomonas aeruginosa, and foodborne Pseudomonas. Cinnamic acid acts by disrupting cell membranes, inhibiting ATPase activity, and preventing biofilm formation, thereby demonstrating its ability to act as a natural antimicrobial agent. Its anti-inflammatory properties are demonstrated by improving oxidative stress and reducing inflammatory cell infiltration. Furthermore, cinnamic acid enhances metabolic health by improving glucose uptake and insulin sensitivity, showing promising results in improving metabolic health in patients with diabetes and its complications. This systematic approach highlights the need for further investigation of the mechanisms and safety of cinnamic acid to substantiate its use as a basis for new drug development. Particularly in the context of increasing antibiotic resistance and the search for sustainable, effective medical treatments, the study of cinnamic acid is notably significant and innovative. Full article

Type I collagen is a major protein in animals, and its hydrolyzed products, collagen peptides, have wide-ranging applications. This article reviews collagen peptides’ preparation methods, biological activities, and application progress in the fields of food, cosmetics, and medicine. By employing various extraction and hydrolysis methods, collagen peptides with different molecular weights can be obtained, and their biological activities are closely related to their molecular weight and amino acid sequence. Studies have revealed that collagen peptides possess a variety of biological activities, including antioxidant, hematopoietic promotion, osteogenic differentiation promotion, antihypertensive, and anti-diabetic effects. In the food industry, their antioxidant and hypoglycemic properties have opened new avenues for the development of healthy foods; in the cosmetics field, the moisturizing, anti-aging, and repair functions of collagen peptides are favored by consumers; in the medical field, collagen peptides are used in wound dressings, drug carriers, and tissue engineering scaffolds. Looking to the future, the development of green and efficient preparation technologies for collagen peptides and in-depth research into the relationship between their structure and function will be important research directions. The multifunctional properties of collagen peptides provide a broad prospect for their further application in the health industry. Full article

Background/Objectives: In the context of diabetes, a multifactorial metabolic disorder with significant clinical implications, the present study investigates the hypoglycemic effects of a synthetic sulfonamide (S) administered individually and in combination with Salvia officinalis extract, compared to metformin as a standard therapeutic agent. Methods: An in vivo model of experimentally induced diabetes using alloxan was applied to Wistar female rats, divided into six experimental groups, including a healthy control group and a diabetes-induced, untreated group. Plasma concentrations of metformin and sulfonamide were quantified by high-performance liquid chromatography. The plasma steady-state concentrations of the pharmaceutical agents and their correlation with hypoglycemic effect were evaluated. Results: The combination of the synthetic sulfonamide (S) with Salvia officinalis extract resulted in the greatest reduction in blood glucose level (average value of 50.2%) compared to S (40.6%) or metformin (36.4%). All treatments demonstrated statistically significant differences in blood glucose levels compared to the diabetes-induced untreated group (p < 0.05). Pharmacokinetic analysis revealed a larger volume of distribution for the synthetic sulfonamide S (23.92 ± 8.40 L) compared to metformin (16.07 ± 5.60 L), consistent with its physicochemical properties. No significant correlation was found between plasma drug levels and glycemic response (p > 0.05). Conclusions: Our findings support the potential of combining standard therapeutic agents with natural alternatives such as Salvia officinalis to achieve improved glycemic control through complementary mechanisms. To the best of our knowledge, this is the first in vivo study to evaluate the combined effects of a sulfonylurea-type compound and Salvia officinalis extract in a diabetic animal model. Full article

Diabetes mellitus (DM) is frequent in kidney transplant recipients (KTRs), reducing graft and patient survival. In recent years, hypoglycemic agents have been approved for chronic kidney disease (CKD) patients, such as sodium glucose co-transporter type 2 inhibitors (SGLT2is), glucagon-like peptide-1 receptor agonists (GLP1RAs), and nonsteroidal mineralocorticoid receptor antagonists (ns-MRAs), such as finerenone. Several studies demonstrated the ability of these drugs to reduce cardiovascular (CV) events and kidney disease progression in diabetic CKD patients. In this review, we will describe their use in KTRs with type 2 DM or post-transplant diabetes mellitus (PTDM), focusing on the potential positive effects. In particular, we will report literature data from observational studies, meta-analyses, and clinical trials. Based on their mechanism of actions, these drugs may balance the negative effects of immunosuppressive therapy on metabolic balance, reducing the risk of PTDM and CV events, that remain the first cause of death in KTRs. Generally, SGLT2is and GLP1RAs appear to be safe and efficacious in KTRs, and no interaction with immunosuppressive drugs or an increased risk of rejection has been reported. Regarding finerenone, no literature data are available and only one clinical trial is ongoing. In conclusion, although the 2022 KDIGO guidelines recommend caution in KTRs, the last meeting in Vienna on PTDM encourages their use in this population. Full article

Objectives: The anticancer effects of PI3Kα inhibitors (PI3Ki) are constrained by their hyperglycemic side effects, while the efficacy of conventional hypoglycemic agents, such as insulin, metformin, and SGLT-2 inhibitors, in mitigating PI3Ki-induced hyperglycemia remains suboptimal. Dorzagliatin, a novel glucokinase activator, has been approved in China for the management of hyperglycemia, offering a promising alternative. This study aims to investigate the pharmacokinetic properties and potential mechanisms of drug interactions of dorzagliatin in the regulation of PI3K-induced hyperglycemia. Methods: Plasma concentrations of WX390, BYL719, and Dorz in mice were measured using high performance liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis. Pharmacokinetic (PK) parameters and PK/PD models were derived by using Phoenix WinNonlin 8.3.5 software. Blood glucose levels at various time points and tumor volume changes over a four-week period were assessed to explore the interactions when PI3Ki were combined with dorzagliatin. Results: The results indicated that, compared to the Dorz group, the combination groups (Dorz + BYL719, Dorz + WX390) exhibited increases in ${\mathrm{A}\mathrm{U}\mathrm{C}}_{0\to t}$ of dorzagliatin by 41.65% and 20.25%, and in C_max by 33.48% and 13.32%, respectively. In contrast, co-administration of these PI3Ki with dorzagliatin resulted in minimal increase in their plasma exposure. The combination therapy group (Dorz+BYL719) exhibited superior antitumor efficacy compared to the BYL719 group. Conclusions: Our findings indicate that the drug–drug interactions (DDIs) between dorzagliatin and multiple PI3Ki (including WX390 and BYL719) may partially account for the enhanced antitumor efficacy observed in the combination therapy group compared to PI3Ki monotherapy. This interaction may be explained by the inhibition of P-glycoprotein (P-gp) and the pharmacological mechanism of dorzagliatin regarding the activation of insulin regulation. Full article

Diabetic kidney disease (DKD), a well-characterized microvascular complication associated with the progression of diabetes mellitus, has been identified as the leading etiological factor contributing to the global burden of end-stage kidney disease (ESKD). Historically, DKD research has predominantly centered on glomerular mechanisms; however, recent studies have increasingly emphasized the critical role of tubular dysfunction. Extensive evidence has elucidated the key pathological drivers of tubular injury in DKD, encompassing metabolic dysregulation, pro-inflammatory signaling pathways, diverse cellular stress responses, and epithelial–mesenchymal transition (EMT). Furthermore, emerging mechanistic studies reveal that autophagic flux impairment and epigenetic memory formation collaboratively drive cellular senescence in DKD. Regarding the treatment of DKD, various hypoglycemic drugs, as well as hypotensive drugs, and microcirculatory improvers have garnered significant attention. Recently, stem cell-based interventions and precision gene editing techniques have unveiled novel therapeutic paradigms for DKD, fundamentally expanding the treatment arsenal beyond conventional pharmacotherapy. This review synthesizes updated insights into the pathogenesis of tubular injury in DKD and highlights promising therapeutic strategies for managing this condition. Full article

Background: Obesity is a growing global health concern associated with numerous comorbidities and high medication burden. This study aimed to evaluate the impact of low- and very-low-calorie diets (LCD/VLCD), combined with intensive lifestyle changes, on comorbidities and medication use in hospitalized patients with class II and III obesity. Methods: A retrospective cohort study was conducted using medical records of patients hospitalized for 3–6 months at a specialized obesity hospital in Brazil. Prescription data for antihypertensive, hypoglycemic, and lipid-lowering drugs were compared at admission, 3, and 6 months. Descriptive statistics, chi-squared tests, and t-tests were used to compare medication use and weight change over time. Results: Among 246 patients, the proportion of those using antihypertensives decreased from 74.4% at admission to 44.7% at 6 months (p < 0.02), with significant reductions also observed at 3 months (p < 0.001). Hypoglycemic prescriptions also declined at 3 months (p = 0.01), but not significantly at 6 months. Lipid-lowering medication use showed no significant changes. Average weight loss was 11% at 3 months and 21.3% at 6 months. Conclusions: Hospitalization with LCD/VLCD and lifestyle therapy was associated with a short-term reduction in medication burden, especially antihypertensives, supporting the potential of inpatient multidisciplinary strategies for severe obesity management. Full article

The genus Clinopodium L. (Lamiaceae) comprises perennial herbaceous plants known for their diverse pharmacological properties. Clinically, these plants are mainly used for the treatment of various hemorrhagic disorders. This review systematically summarizes the research progress on the chemical composition, pharmacological activity, quality control, toxicity, and pharmacokinetics of the genus Clinopodium by searching Google Scholar, Scopus-Elsevier, Wiley, Springer, Taylor & Francis, Medline, Web of Science, CNKI, Weipu, Wanfang, and other academic databases over the last decade (March 2015–February 2025). To date, more than one hundred and thirty structurally diverse secondary metabolites have been isolated and identified from this genus, including flavonoids, triterpenoid saponins, diterpenoid glycosides, lignans, and phenylpropanoids. In addition, numerous volatile oil constituents have been identified in over forty species of the genus Clinopodium. Crude extracts and purified compounds exhibit a variety of pharmacological activities, including hemostatic, anti-myocardial cell injury, cardiovascular protective, anti-inflammatory, antimicrobial, antitumor, hypoglycemic, and insecticidal properties. However, current quality assessment protocols in the genus Clinopodium are limited to flavonoid- and saponin-based evaluations in C. chinense (Benth.) O. Kuntze and C. gracile (Benth.) O. Matsum. Further research is needed to elucidate the pharmacological mechanisms, toxicity, and possible interactions with other drugs. Therefore, the genus Clinopodium has a wide range of biologically active compounds with potential applications in drug development for hemostasis and cardiovascular protection. Nevertheless, there is also an urgent need to establish standardized methodologies to address uncertainties concerning the safety and efficacy of injectable extracts or compounds. Full article

Ivermectin (IVM) is a macrolide antiparasitic drug, and Metformin (MET) is a biguanide oral hypoglycemic drug. Studies have shown that both of them have obvious anti-tumor effects, but there have been no reports on the combined treatment of Canine breast tumors. This report aimed to investigate the effectiveness and the possible mechanism of drug combination on Canine breast cancers. Mouse breast tumor cells (4T1) and canine breast tumor cells (CMT-1211) were, respectively, treated with IVM, MET, and their combination, and then cell viability was assessed. After that, transcriptomic analysis was performed to study the action pathway of the drug combination with regard to its anti-tumor effects. Reactive oxygen species (ROS) levels were detected by flow cytometry, and autophagosome formation was observed by transmission electron microscopy (TEM). Immunofluorescence detected the cytoplasmic translocation of LC3B and P62 into the nucleus. Western blot detected the protein expressions of LC3B, P62, Beclin1, Bcl-2, p-PI3K, p-AKT, and p-mTOR. Our transcriptomic analysis showed that the combination of IVM and MET regulated the expression of autophagy-related genes and pathways, including the PI3K/AKT/mTOR signaling pathway. Our in vitro experiments showed that the combination of two drugs had a considerably significant effect on cytotoxicity, ROS levels, and the formation of autophagosomes compared to each drug alone. Meanwhile, the in vivo experiments showed that IVM combined with MET had an obvious inhibitory effect on tumor growth in canine breast tumor xenografts. This study concluded that IVM with MET activated autophagy, which killed breast cancer cells by inhibiting the activation of the PI3K/AKT/mTOR pathway and promoting the excessive accumulation of ROS. It offers a theoretical foundation for the synergistic effects of MET and IVM to suppress breast cancer cell activity. Full article

Background: Crude extracts are easily available and considered safe and cost-effective in comparison with synthetic extracts and are more accessible compared with purified compounds, making them suitable for initial screening and exploratory studies in drug discovery. Introduction: Cucumis sativus and Cucurbita pepo are medicinal plants that belong to the Cucurbitaceae family, commonly known as cucumber and pumpkin, comprising a series of phytochemicals such as chlorophylls, carotenoids, oleanolic acid, saponin, and triterpenoids. Materials and Methods: In this study, an ethanol extract of Cucumis sativus and Cucurbita pepo whole plants was used to assess their hypoglycemic effects in a fasted, fed, glucose-loaded and streptozotocin-induced diabetes model of albino rats followed by Molecular Spectroscopic (FTIR and UV-Vis) analysis. Blood sugar levels were determined from samples collected at different intervals (0, 1, 3, and 4 h). Results and Conclusions: A significant blood glucose reduction was observed as a result of both plants’ extracts, while the greatest reduction was shown by Cucumis sativus. The UV-Vis profile showed several absorption bands ranging from 200 to 800 nm, showing the presence of flavonoids, phenolic compounds, terpenoids, carotenoids, and chlorophyll. The FTIR spectra reveal the presence of carbohydrates, proteins, lipids, and phenolic compounds, which contribute to the extracts’ nutritional and biological value. Further research is needed to determine the active agents and the likely mechanism of action of both the plants regarding their hypoglycemic effects. Full article

Diabetes-related osteoporosis has been known to be a consequence of oxidative stress caused by excessive reactive oxygen species (ROS) production in the tissues. Despite the increase in the number of individuals with diabetes-related osteoporosis year on year, there is still no effective drug that does not induce adverse side effects. Glabridin, which exerts hypoglycemic effects and possesses antioxidant properties, may have beneficial effects in the treatment of diabetes-related osteoporosis. In this study, we aimed to investigate the preventive effects of glabridin in counteracting oxidative stress-induced bone loss and its underlying mechanisms. A diabetic rat model was established by a single intraperitoneal injection of streptozotocin into male Wistar rats. The diabetic rats were orally gavaged daily with glabridin or glyburide for 8 weeks. The presence of diabetes significantly decreased the rats’ tibia length, bone thickness, epiphyseal plate length, and collagen deposition compared to the control rats; in comparison, treatment with glabridin for 8 weeks significantly reversed these effects. In our in vitro study, the treatment of MC3T3-E1 preosteoblasts with glabridin up to 7.5 µM for 48 h showed no cytotoxic effect. However, pretreatment with glabridin significantly prevented oxidative stress-induced inhibition of cell proliferation. In addition, glabridin significantly diminished ROS production, restored antioxidant enzyme activity, and mitigated cellular apoptosis. These effects occurred by stimulating the phosphorylation of Akt, GSK-3β, and P65 NF-ĸB proteins. The above results show that glabridin alleviated oxidative stress-induced bone loss and osteoblast cell apoptosis by modulating the expression of the Akt/NF-ĸB and Akt/GSK-3β pathways. Full article

Background: Metformin is a widely used oral hypoglycemic agent for treating type 2 diabetes. Planarians, with their remarkable regenerative abilities, are frequently employed as model organisms in stem cell and regeneration studies. This study aimed to investigate the effects of metformin on planarian regeneration, focusing on the regeneration of eyespots after amputation. Methods: Regenerating planarians with amputated eyespots were exposed to various concentrations of metformin. The regeneration time of the eyespots was measured to assess the effects of metformin. Subsequently, a 1 mmol/L metformin treatment for 24 h was applied to the planarians, followed by transcriptome analysis to identify differentially expressed genes (DEGs). The gene expression was validated through qPCR. The full-length gene of casein kinase 1α (DjCK1α) was cloned using RACE technology. DjCK1α interference was performed to examine its role in regeneration. Results: Low concentrations of metformin significantly reduced the regeneration time of planarians. Transcriptome analysis identified 113 DEGs, including 61 upregulated and 52 downregulated genes. GO and KEGG enrichment analyses were conducted. Notably, DjCK1α, a key gene involved in regeneration, was selected for further validation. qPCR confirmed that DjCK1α was significantly upregulated. The interference of DjCK1α prolonged the regeneration time of the eyespots of planarians cultured in water, while treatment with metformin did not promote the eyespot regeneration of the DjCK1α-interfered planarians. Conclusions: The results suggest that metformin accelerates planarian eyespot regeneration, potentially through the regulation of DjCK1α. This study provides the first transcriptome-based analysis of drug effects on regeneration in planarians, highlighting the role of metformin in the regeneration process. Full article

The food industry generates the largest number of valuable by-products. The recovery of compounds such as fatty acids and polyphenols with notorious biological properties from biowaste is a new challenge in the circular economy scenario, as they represent value-added starting materials for the preparation of functional foods, food supplements, cosmetics and over-the-counter drugs. Less commonly explored are industrial wastewaters, which return to the nearby water streams without adequate treatment. Distillation wastewater (DWW) from the essential oils or agro-food industries may represent a valuable source of bioactive compounds to be valorized. In this work, DWW from rosemary was treated with different resins through dynamic and static adsorption/desorption approaches, for the recovery of phenolic compounds including rosmarinic acid. The most effective methodology, selected according to total phenolic and rosmarinic acid contents, as well as antioxidant activity evaluation, was applied to sage, thyme and oregano DWWs. The procedure provides several advantages compared with conventional separation processes, as it involves the lower consumption of reagents/solvents, low operational costs, ease of handling, and simplicity of scale-up. The results of this work highlight a fast and sustainable procedure for the recovery of rosmarinic acid and other phenolics (caffeic acid derivatives and flavonoid glycosides) from DWWS, thus affording a fraction with antioxidant and hypoglycemic activities. Full article

Diabetes mellitus has become a major public health problem due to aspects such as an alarming increase in prevalence, the morbidity and mortality associated with its complications and, not least, the economic burden. SGLT2 inhibitors are a relatively new but valuable class of drugs that demonstrated multifaceted effects in addition to hypoglycemic action. Moreover, these drugs demonstrated cardiovascular and renal benefits, even in individuals without diabetes, being recommended by current guidelines to patients with a history of cardiovascular disease, or at high risk for it, as well as to patients with chronic kidney disease. The prescription of this class of drugs is limited by the risk of urogenital infections, despite their multiple demonstrated benefits. Data regarding the prevalence of SGLT2 inhibitors associated with urogenital infections depend on several factors related to the study carried out and to other additional conditions that could precipitate such infections. While SGLT2 inhibitors have a well-established association with the risk of genital infections, the association with urinary tract infections remains controversial and uncertain. This review will be focused on urogenital infections associated with the administration of SGLT2 inhibitors, highlighting their prevalence, risk factors, mechanisms involved, clinical relevance and particularities of management. Full article

Background: Astrocytes play a key role in the inflammatory process accompanying various neurological diseases. Extracellular ATP accompanies inflammatory processes in the brain, but its effect on lipid mediators (oxylipins) in astrocytes remains elusive. Metformin is a hypoglycemic drug with an anti-inflammatory effect that has been actively investigated in the context of therapy for neuroinflammation, but its mechanisms of action are not fully elucidated. Therefore, we aimed to characterize the effects of ATP on inflammatory markers and oxylipin profiles; determine the dependence of these effects on the adaptation of astrocytes to high glucose levels; and evaluate the possibility of modulating ATP effects using metformin. Methods: We estimated the ATP-mediated response of primary rat astrocytes cultured at normal (NG, 5 mM) and high (HG, 22.5 mM) glucose concentrations for 48 h before stimulation. Cell responses were assessed by monitoring changes in the expression of inflammatory markers (TNFα, IL-6, IL-10, IL-1β, iNOS, and COX-2) and the synthesis of oxylipins (41 compounds), assayed with ultra-high-performance liquid chromatography and tandem mass spectrometry (UPLC-MS/MS). Intracellular pathways were assessed by analyzing the phosphorylation of p38; ERK MAPK; transcription factors STAT3 and NF-κB; and the enzymes mediating oxylipin synthesis, COX-1 and cPLA2. Results: The stimulation of cells with ATP does not affect the expression of pro-inflammatory markers, increases the activities of p38 and ERK MAPKs, and activates oxylipin synthesis, shifting the profiles toward an increase in anti-inflammatory compounds (PGD2, PGA2, 12-HHT, and 18-HEPE). The ATP effects are reduced in HG astrocytes. Metformin potentiated ATP-induced oxylipin synthesis (11-HETE, PGD2, 12-HHT, 15-HETE, 13-HDoHE, and 15-HETrE), which was predominantly evident in NG cells. Conclusions: Our data provide new evidence showing that ATP induces the release of anti-inflammatory oxylipins, and metformin enhances these effects. These results should be considered in the development of anti-inflammatory therapeutic approaches aimed at modulating astrocyte function in various pathologies. Full article