Naringin is a dihydroflavonoid compound, a yellowish natural pigment. As there is completely no conjugation btween A ring and B ring, strong UV absorption peaks exist at 282 nm, which let naringin have a variety of biological activities and pharmacological effects, including antiviral, analgesic, sedation, desensitization, anti-allergy,local microcirculation and nutrient supply performance improvement. In recent years, naringin has been found to have obvious effects of regulating glucose and lipid metabolism, anti-inflammatory, anti-oxidative stress and myocardial protection. It can effectively prevent and treat cardiovascular diseases.

Blood glucose metabolism regulation

Scientists randomly divided 30 Type 2 diabetic mice (C57BL / KsJ-db / db mice) into three groups: control group, hesperidin treatment group (standard laboratory + 0.2/kg dosage) and naringin treatment group (standard laboratory +0.2g/kg dosage). After 5 weeks, naringin significantly decreased blood glucose (P<0.05). Compared with control group, the activity of glucokinase (GK) in naringin-treated group and hesperidin-treated group increased by 35% and the synthesis of hepatic glycogen increased obviously while blood sugar decreased by 31% and 20% respectively. While the activities of glucose-6-phosphatase (G-6-P) and phosphoenolpyr-carboxykinase (PEPCK) in the naringin-treated group decreased by 28.19% and 18.92 % (P <0.05). Further study found that naringin also up-regulated the expression of glucose transporter 4 (GLUT4) and GK.mRNA in adipocytes, downregulated the expression of G6P, PEPCK and GLUT2 genes and participated in the regulation of blood glucose.

Lipid metabolism regulation

The researchers randomized the LDL receptor knockout (LDLR-KO) rat to control group, cholesterol (CH) group (CH 1g / kg dosage), lovastatin group(CH 1g/kg+lovastatin 0.2g/kg dosage) and naringin (CH 1g / + naringin 0.2g/kg dosage), after 6 weeks, naringin decreased the TC of plasma and liver(P<0.05). Both treatment groups significantly reduced the activity of 3-hydroxy-3-methylglutaryl-CoA reductase (HMG-CoA-R) based on comparison with high CH group. Not only did naringin reduce HMG-CoA-R activity. but also reduced the activity of cholesterol acyltransferase (ACAT) activity, fatty acid synthase (FAS), phosphatidic acid phosphate (PAP) and carnitine palmitoyl-ansferase (CPT), which significantly decreased the levels of TG, TC and free fatty acids and increased the HDL-C / TC ratio(P<O.05).

Improve insulin resistance

Current studies show that activated PPARy can not only reduce tumor necrosis factor-induced insulin resistance, but also can enhance insulin signal transduction. Animal experiments showed that naringin (0.2g/kg) feeding C57BL/KsJ-db/db mice increased PPA foot expression (P<0.05). However, cell-based experimental studies suggest that naringin (50-100g/ml) pretreated preadipocytes 313-L1 can significantly inhibit its subtype PPAR2 activity (P<0.05). Therefore, the impact of naringin on PPAR may be related to the route of administration and dose.

Antioxidant stress

Twenty male rabbits were randomly divided into 4 groups: control group, high CH group (CH 5 g/kg), probucol treatment group (CH 5 g/kg + probucol 0.5g/kg), naringin treatment group (0.5 g/kg + CH 5 g/kg naringin), after 8 weeks the result showed that naringin could decrease plasma hydrogen peroxide, lipid peroxides concentration levels (P<0.05). Compared with high CH group, naringin group could significantly upregulate the activities of superoxide dismutase, catalase and glutathione peroxidase, and increase their activities. However, probucol only promoted the expression of superoxide dismutase (SOD) mRNA. The study also found that naringin can significantly increase the activities of SOD, CAT and GSH-Px.

Anti-inflammatory effect

The mice were pretreated with naringin (10, 30 and 60 mg/kg) for 1 h, then intraperitoneally injected with lipopolysaccharide (0.3, 20 mg/kg) to induce the expression of inflammatory cytokines, and then cultured the RAW264 .7 macrophages. Results showed naringin inhibited LPS-induced inducible nitric oxide synthase (iNOS), TNF-α, cyclooxygenase-2 (COX-2), interleukin 6 (IL-6) mRNA expression and NF-KB activity in a dose-dependent manner.

Vascular endothelium protection

Human umbilical vein endothelial cells (HUVECs) were pretreated with naringin (10, 25, 50 ug/mL) for 4 hours and then induced by high glucose (glucose 33 mmol/mL) for 48 hours. Compared with the control group (glucose l1 mmol/mL), naringin medium dose group (25g/mL) significantly inhibited THP-1 cells adhesion to high glucose-induced HUVECs; In naringin group the inhibitory rates of intercellular adhesion molecule expression were 23%, 40% and 57%, respectively. The inhibitory rates of expression of adhesion molecules on vascular endothelial cells were 19%, 37% and 70%, respectively. The inhibitory rates on reactive oxygen were l8% , 38%, 45% respectively. The inhibitory rates of nuclear factor kBp65 were 23%, 42%, 70% respectively (P<0.05). Therefore, naringin may effectively protect against hyperglycemia induced vascular endothelial damage.

Vascular smooth muscle cell proliferation inhibition


Scientists isolated and cultured rat smooth muscle cells (VSMCs) and pretreated with naringin (0, 10, 20 and 100 u mol/L) for 24 h, then added lysolecithin(0, 10, 20 and 100 u mol/L). The results showed that naringin (100 umol/L) could significantly inhibit the mitosis induced by lysophosphatidylcholine in VSMCs with the inhibition rates of (34 ± 5)% and (35 ± 5)% (P: 0.01). VSMCs were induced by naringin (0, 75, 100, 125 and 150 u mol/L) for 12 h and then stimulated with mitogen-stimulated enzymes. It was found that the naringin-treated cells resulted in significant dose-dependent growth inhibition. In pathway inhibitor studies, specific inhibitors of the extracellular signal regulated kinase (ERK), which prevent naringin-dependent p21WAFI expression, suggest that naringin mediates inhibition of cell proliferation and decreases Cyclins. In addition, naringin treatment increased Ras and Raf activation, and transfected cells with dominant negative RAS and Raf mutant genes inhibited nafingin-induced ERK activity and p21WAFI expression, and finally naringin induced a decrease in cell proliferation with cells Cyclin also abolishes the presence of the RasN17 and RatS621A mutant genes.

Myocardium protection

Rats were pretreated with naringin (10, 20, 40 mg/kg) for 56 days and then injected with isoproterenol (85 mg/kg) for 2 days (24 hours). Compared with the control group, naringin group prevented isoprenaline-induced cardiac hypertrophy; decreased blood glucose, serum iron, uric acid, serum and cardiac glycosylated protein, increased plasma iron binding capacity, plasma protein and albumin/globulin ratio; increased cardiac Na/K ATP phosphatase activity, decreased the activities of Mg ATP and Ca2 + ATP phosphatase, and scavenged free radicals and NO at a dose of 50-500 umol/L (P<0.05). Further research found naringin also increased myocardial mitochondrial antioxidant enzyme (SOD, CAT) peroxidase, glutathione S-transferase (GST) activity and antioxidant substances (glutathione, Reduced glutathione) (P<0.05) .Therefore, naringin could regulate myocardial mitochondrial energy metabolism and scavenge free radicals by regulating the biological activity of cardiomyocyte enzymes, thereby maintaining the steady-state and normal glycoproteins of myocardial cells, and ultimately achieve myocardial protection.

Anti-cardiomyocyte genotoxic effects

The rats were pretreated with naringin (50, 250 and 500 mg/kg) for 1 hour, and then daunorubicin (1 mg/kg) was injected intraperitoneally to induce cardiomyocyte injury. It was found that naringin (20 mmol/L) could clear 95% of daunorubicin-induced free radicals and thus significantly inhibit the DNA damage induced by cardiomyocytes.

Conclusion

In summary, naringin has preventive and therapeutic effects on cardiovascular diseases, including cardiovascular diseases related to atherosclerosis, diabetes and myocardial cytotoxicity injury, and its protective mechanism on cardiovascular diseases is mainly related to its effect on cell enzymology, which provides a basis for improving oxidative stress, inflammatory injury, vascular lesions and myocardial energy metabolism. It can be used to prevent and treat cardiovascular diseases.