Rapid identifying of COX-2 inhibitors from turmeric (Curcuma longa) by bioaffinity ultrafiltration coupled with UPLC-Q Exactive-Orbitrap-MS and zebrafish-based in vivo validation. Bioorganic chemistry Turmeric (Curcuma longa), a typical source with recognized anti-inflammatory activity, is one such medicine-food homology source, yet its anti-inflammatory mechanisms and specific component combinations remain unclear. In this study, a net fishing method combining bio-affinity ultrafiltration and ultra-high performance liquid chromatography-mass spectrometry (AUF-LC/MS) was employed and 13 potential COX-2 inhibitors were screened out from C. longa. 5 of them (C1, 17, 20, 22, 25) were accurately isolated and identified. Initially, their IC values were measured (IC of C1, 17, 20, 22 and 25 is 55.08, 48.26, 29.13, 111.28 and 150.48 μM, respectively), and their downregulation of COX-2 under safe concentrations (400, 40, 120, 50 and 400 μM for C1, 17, 20, 22 and 25, respectively) was confirmed on RAW 264.7 cells. Further, in transgenic zebrafish (Danio rerio), significant anti-inflammatory activity at safe concentrations (15, 3, 1.5, 1.5 and 3 μg/mL for C1, 17, 20, 22 and 25, respectively) were observed in a dose-dependent manner. More importantly, molecular docking analysis further revealed the mode of interaction between them and the key active site residues of COX-2. This study screened out and verified unreported COX-2 ligands, potentially accelerating the discovery of new bioactive compounds in other functional foods. 10.1016/j.bioorg.2024.107357

Hypoglycemic and hypolipidemic effects of rutin on hyperglycemic rats. Sun Chen,Wang Li,Sun Jing,Wang Zheng,Tang Zhishu Journal of traditional Chinese medicine = Chung i tsa chih ying wen pan OBJECTIVE:To study the effects of rutin on serum glucose and lipid levels in hyperglycemic rats. METHODS:Male Wistar rats were subjected to intraperitoneal streptozotocin injections and a high-sugar, high-fat diet to establish a hyperglycemic and hyperlipidemic model. The model was considered to be successfully established in rats with fasting blood sugar (FBS) ≥ 11.1 mmol/L. The study included 6 groups with 10 rats each: a blank control group, a model group, a metformin group, and groups on large, medium and small doses of rutin. The groups received intraperitoneal streptozotocin or normal saline for 21 d. FBS, serum lipids, serum insulin, insulin sensitivity index (ISI), and levels of catalase (CAT), glutathione peroxidase (GSH-Px), superoxide dismutase (SOD) and malondialdehyde (MDA) levels were evaluated in all rats. Pancreatic tissue samples were harvested to observe structural changes in islet cells. RESULTS:Large, medium, and small doses of rutin were associated with significantly reduced FBS (P < 0.05), and increased levels of ISI, CAT, GSH-Px and SOD, as well as decreased MDA (P < 0.05). Rutin administration was also related with reduced total cholesterol, triglycerides and low density lipoprotein chesterol, as well as increased high density lipoprotein chesterol (P < 0.05). Histologic evaluation revealed rutin induced repair of damaged islet cells. CONCLUSION:In diabetic rat models, rutin can significantly reduce FBS and blood lipids, improve anti-oxidant activity, increase insulin sensitivity, and induce repair of damaged islet cells. 10.19852/j.cnki.jtcm.2020.04.012

Effect of vanillic acid on ischemia-reperfusion of isolated rat heart: Hemodynamic parameters and infarct size assays. Dianat Mahin,Hamzavi Gholam Reza,Badavi Mohammad,Samarbaf-zadeh Alireza Indian journal of experimental biology Vanillic acid is an oxidized form of vanillin produced during the conversion of vanillin to ferulic acid and has free radical scavenging, antioxidant and anti-inflammatory properties. In this study, we investigated the effects of vanillic acid on hemodynamic parameters and infarct size in ischemia-reperfusion of isolated rat heart. Adult male Sprague Dawley rats were randomly divided into control and treatment groups (n = 10). The treatment groups were administered vanillic acid 5, 10 and 20 mg/kg orally for 10 days, then the hearts isolated and were exposed to 30 min ischemia and 1 h reperfusion, using langendorff apparatus. The effects of vanillic acid, on left ventricular developed pressure (LVDP), LV end diastolic pressure (LVEDP), LV pressure (LVP), peak rate of rise and fall of LVP (±dp/dt), coronary flow (CF), rate pressure product (RPP) and infarct size were examined. Rats administered with vanillic acid (10 and 20 mg/kg), displayed significantly improved recovery of LVEDP, RPP, LVDP, LVP and ± dp/dt as compared to control group. There was also significant beneficial effect of these two doses to reduce infarct size. Our results suggest that vanillic acid can effectively improve ventricular function and reduce infarct size in ischemia-reperfusion of isolated rat heart.

Vanillin modulates activities linked to dysmetabolism in psoas muscle of diabetic rats. Scientific reports Skeletal muscles are important in glucose metabolism and are affected in type 2 diabetes (T2D) and its complications. This study investigated the effect of vanillin on redox imbalance, cholinergic and purinergic dysfunction, and glucose-lipid dysmetabolism in muscles of rats with T2D. Male albino rats (Sprague-Dawley strain) were fed 10% fructose ad libitum for 2 weeks before intraperitoneally injecting them with 40 mg/kg streptozotocin to induce T2D. Low (150 mg/kg bodyweight (BW)) and high (300 mg/kg BW) doses of vanillin were orally administered to diabetic rats. Untreated diabetic rats and normal rats made up the diabetic control (DC) and normal control (NC) groups, respectively. The standard antidiabetic drug was metformin. The rats were humanely put to sleep after 5 weeks of treatment and their psoas muscles were harvested. There was suppression in the levels of glutathione, activities of SOD, catalase, ENTPDase, 5'Nucleotidase and glycogen levels on T2D induction. This was accompanied by concomitantly elevated levels of malondialdehyde, serum creatine kinase-MB, nitric oxide, acetylcholinesterase, ATPase, amylase, lipase, glucose-6-phosphatase (G6Pase), fructose-1,6-biphophastase (FBPase) and glycogen phosphorylase activities. T2D induction further resulted in the inactivation of fatty acid biosynthesis, glycerolipid metabolism, fatty acid elongation in mitochondria and fatty acid metabolism pathways. There were close to normal and significant reversals in these activities and levels, with concomitant reactivation of the deactivated pathways following treatment with vanillin, which compared favorably with the standard drug (metformin). Vanillin also significantly increased muscle glucose uptake ex vivo. The results suggest the therapeutic effect of vanillin against muscle dysmetabolism in T2D as portrayed by its ability to mitigate redox imbalance, inflammation, cholinergic and purinergic dysfunctions, while modulating glucose-lipid metabolic switch and maintaining muscle histology. 10.1038/s41598-021-98158-7

Network pharmacology analysis and experimental verification of the antithrombotic active compounds of trichosanthis pericarpium (Gualoupi) in treating coronary heart disease. Journal of ethnopharmacology ETHNOPHARMACOLOGICAL RELEVANCE:Trichosanthis pericarpium (TP; Gualoupi, pericarps of Trichosanthes kirilowii Maxim) has been used in traditional Chinese medicine (TCM) to reduce heat, resolve phlegm, promote Qi, and clear chest congestion. It is also an essential herbal ingredient in the "Gualou Xiebai" formula first recorded by Zhang Zhongjing (from the Eastern Han Dynasty) in the famous TCM classic "Jin-Guì-Yào-Lüe" for treating chest impediments. According to its traditional description, Gualou Xiebai is indicated for symptoms of chest impediments, which correspond to coronary heart diseases (CHD). AIM OF THE STUDY:This study aimed to identify the antithrombotic compounds in Gualoupi for the treatment of CHD. MATERIALS AND METHODS:A CHD rat model was established with a combination of high-fat diet and isoproterenol hydrochloride (ISO) administration via subcutaneous multi-point injection in the back of the neck. This model was used to evaluate the antithrombotic effect of two mainstream cultivars of TP ("HaiShi GuaLou" and "WanLou") by analyzing the main components and their effects. Network pharmacology, molecular docking-based studies, and a zebrafish (Danio rerio) thrombosis model induced by phenylhydrazine was used to validate the antithrombosis components of TP. RESULTS:TP significantly reduced the body weight of the CHD rats, improved myocardial ischemia, and reduced collagen deposition and fibrosis around the infarcted tissue. It reduced thrombosis in a dose-dependent manner and significantly reduced inflammation and oxidative stress damage. Cynaroside, isoquercitrin, rutin, citrulline, and arginine were identified as candidate active TP compounds with antithrombotic effects. The key potential targets of TP in thrombosis treatment were initially identified by molecular docking-based analysis, which showed that the candidate active compounds have a strong binding affinity to the potential targets (protein kinase C alpha type [PKCα], protein kinase C beta type [PKCβ], von Willebrand factor [vWF], and prostaglandin-endoperoxide synthase 1 [PTGS1], fibrinogen alpha [Fga], fibrinogen beta [Fgb], fibrinogen gamma [Fgg], coagulation factor II [F2], and coagulation factor VII [F7]). In addition, the candidate active compounds reduced thrombosis, improved oxidative stress damage, and down-regulated the expression of thrombosis-related genes (PKCα, PKCβ, vWF, PTGS1, Fga, Fgb, Fgg, F2, and F7) in the zebrafish model. CONCLUSION:Cynaroside, isoquercitrin, rutin, citrulline, and arginine were identified as the active antithrombotic compounds of TP used to treat CHD. Mechanistically, the active compounds were found to be involved in oxidative stress injury, platelet activation pathway, and complement and coagulation cascade pathways. 10.1016/j.jep.2024.118158