Objective: To evaluate the therapeutic potential of coumarin-loaded chitosan nanoparticles (CNNPs) in managing high-fructose diet-induced diabetes and associated complications.

Methods: CNNPs were synthesized using an ionic gelation method with chitosan coating and characterized. Rats with a high-fructose diet-induced diabetes were treated with coumarin and CNNPs (30, 70, and 100 mg/kg) for 6-12 weeks. Metabolic, inflammatory, oxidative stress, organ function, and cardiovascular parameters were assessed, and qRT-PCR studies were carried out for measuring the mRNA expression of glucose transporter-4 (GLUT-4), sirtuin-1 (S1RT1), pyrin domain containing-3 (NLRP3), sterol regulatory element binding protein 1c (SREBP-1c), forkhead box O3 (FOXO3), and endothelial nitric oxide synthase (eNOS) genes.

Results: Nanoparticle characterization revealed a Z-average size of 510.8 nm with a +14 mV zeta potential. CNNP treatment was more effective than coumarin, normalizing glycemic markers (glycosylated hemoglobin, serum insulin, and fasting blood glucose), and lipid profiles (total cholesterol, low-density lipoprotein cholesterol, triglycerides, and high-density lipoprotein cholesterol). Significant improvements were also seen in adipokines (adiponectin, chemerin, and leptin), inflammatory cytokines (interleukin-6 and tumor necrosis factor-a), and oxidative stress markers (catalase, superoxide dismutase and malonaldehyde). In addition, both treatments significantly upregulated the gene expression of S1RT1, GLUT-4, and eNOS, and downregulated FOXO3, SREBP-1c, and NLRP3. Histopathological studies confirmed that CNNPs ameliorated diabetes-induced structural abnormalities in major organs.

Conclusions: CNNPs demonstrate improved bioavailability and therapeutic efficacy, offering a promising strategy for managing high-fructose diet-induced metabolic dysfunction and its complications.

Objective: To evaluate the cardioprotective effects of sinomenine using the ischemia/reperfusion (I/R) rat model.

Methods: Wistar rats were randomly divided into 6 groups: group I with reperfusion, group II perfused with sinomenine, group III perfused with 5-hydroxydecanoate (5-HD), group IV perfused with 5-HD+sinomenine, group V perfused with L-nitro arginine methyl ester (L-NAME), group VI perfused with L-NAME+sinomenine. Myocardial ischemia was induced by interrupting the aortic blood supply for 30 min, followed by reperfusion (55 min). Cardiac, hepatic, antioxidant, and inflammatory parameters were assessed. Additionally, endothelin, tissue factor, platelet-activating factor, plasminogen activator inhibitor, plasma fibrinogen, and thromboxane B2 were also analyzed.

Results: Administration of 5-HD or L-NAME, used as the selective antagonist of mitoKATP and NO system, respectively, resulted in significantly increased levels of premature ventricular complexes, lactate dehydrogenase, ventricular fibrillation, ventricular tachycardia, and arrhythmia intensity (P<0.05). In contrast, sinomenine significantly reduced the level of troponin I, lactate dehydrogenase, creatine kinase, and creatine kinase MB compared to the 5-HD group and the L-NAME group (P<0.05). Additionally, sinomenine significantly reduced malondialdehyde level and enhanced the levels of superoxide dismutase, glutathione peroxidase, catalase, and glutathione/glutathione disulfide ratio (P<0.05). It also significantly suppressed the levels of endothelin-1, platelet-activating factor, tissue factor, plasminogen activator inhibitor 1, thromboxane B2, and plasma fibrinogen (P<0.05).

Conclusions: These results suggest that sinomenine exhibits significant cardioprotection effects against I/R-induced cardiac injury in rats.

Objective: To investigate the therapeutic adjuvant potential of fucoidan in cervical cancer and to evaluate its efficacy in combination with immunotherapy.

Methods: Fucoidan extracted from Fucus vesiculosus was dissolved in phosphate buffered saline and used to treat TC-1 cervical cancer cells in vitro as well as tumor-bearing C57BL/6 mice in vivo. Mice were divided into four groups: the vehicle control group, the mRNA therapy-alone group, the fucoidan-only group, and the combination group. MAPK signaling proteins (p-ERK, T-ERK, p-p38) were analyzed by Western blotting assays. T cell surface markers and intracellular cytokines in splenocytes were assessed by flow cytometry, and plasma cytokine levels were measured by ELISA.

Results: Fucoidan decreased the p-ERK/T-ERK ratio and p-p38. Fucoidan combined with mRNA therapy did not significantly affect CD4+ T-cell activation but reduced CD8+ T-cell activation compared with mRNA therapy alone. MCP-1 and IFN-γ were significantly reduced in the combination therapy group compared with mRNA therapy alone, while IL-6, TNF-α, perforin, and granzyme B did not show significant changes between the two groups.

Conclusions: These findings suggest that fucoidan could inhibit excessive T cell activation and cytokine production by suppressing MAPK p-p38 protein expression.

Objective: To evaluate the antidiabetic effects of manool in streptozotocin-induced diabetic rats and HepG2 cells.

Methods: Diabetes was induced in Wistar rats using streptozotocin and nicotinamide, and animals were treated with two doses of manool (1 and 2 mg/kg). Biochemical, oxidative stress, apoptotic, and inflammatory parameters were assessed, followed by histopathology of the pancreas. Expression of key marker genes in the liver and pancreas was analyzed via qRT-PCR. Catalase and superoxide dismutase activities, malondialdehyde level, and glucose consumption were examined in vitro.

Results: Manool significantly reduced fasting glucose level, improved insulin levels, and restored glucokinase and Ki67 expression in rats with diabetes. It also enhanced antioxidant defense, upregulated insulin signaling, activated the mTOR pathway, and promoted β-cell regeneration via increased expression of Pdx1, MAFA, Ngn3, and Ins1 in a dose-dependent manner. However, manool suppressed JAK/STAT pathway only at a higher dose of 2 mg/kg. Histopathological study showed near-normal islet architecture in manool-treated diabetic rats.

Conclusions: Manool exerts antidiabetic effects by modulating oxidative stress, inflammation, β-cell regeneration, and insulin sensitivity in diabetic rats. However, further pharmacological and clinical investigations are required before confirming its therapeutic applicability.

Objective: To investigate the influence and underlying mechanisms of imrecoxib on liver damage in rats with type 2 diabetes mellitus (T2DM).

Methods: A rat model of T2DM was established by a high-fat diet and streptozotocin administration. Rats were then treated with imrecoxib 10, 20, or 40 mg/kg for 5 weeks. Body weight and fasting blood glucose levels were measured. The analysis included serum liver function, blood lipid profiles, and the levels of inflammatory factors in the rats. Liver tissue histology was evaluated using hematoxylin and eosin staining. Western blotting was conducted to measure the liver expression of proteins such as AKT, PI3K, NF-κB, p-AKT, p-PI3K, and p-NF-κB.

Results: Rats treated with imrecoxib showed a greater weight gain compared to untreated diabetic rats. Compared to untreated diabetic rats, imrecoxib at all three doses reduced alanine aminotransferase, aspartate aminotransferase, triglycerides, cholesterol, tumor necrosis factor-α, interleukin (IL)-6, and IL-1β, and significantly increased the levels of IL-10 and IL-4. In imrecoxib-treated rats, the expression levels of AKT, PI3K, p-AKT, and p-PI3K were higher in comparison to the diabetes group, whereas the expression of p-NF-κB was lower.

Conclusions: Imrecoxib could alleviate hepatic damage in T2DM rats by modulating PI3K/AKT/NF-κB signaling.