Chinese Medicine FTZ Recipe Protects against High-Glucose-Induced Beta Cell Injury through Alleviating Oxidative Stress

Abstract

Objective. To investigate the effect of FTZ on high-glucose-induced oxidative stress and underlying mechanisms. Methods. We used a β cell dysfunction and diabetes model that was induced in rats fed a high-fat high-sugar diet (HFHSD) for 6 weeks and injected once with 35 mg/kg streptozocin (STZ). Then, 3 and 6 g/kg of FTZ were administered by gavage for 8 weeks. In addition, an ex vivo model of oxidative stress was induced by stimulating INS-1 cells with 25 mmol/L glucose for 48 h. Result. The levels of fasting blood glucose (FBG) in diabetic model rats were obviously higher than those in the normal group; furthermore with reduced levels of β cells, catalase (CAT), superoxide dismutase (SOD), and Bcl-2 increased lipid peroxide malondialdehyde (MDA) and caspase-3 in the pancreatic tissue of the diabetic model rats. Afterward, the cells were incubated with FTZ-containing serum and edaravone. The 25 mmol/L glucose-induced SOD reduction increased MDA and intracellular ROS. The protein expression level of Mn-SOD and CAT in the model group decreased significantly compared with that in the control group. Conclusion. FTZ treatment significantly improved the alteration in the level of SOD, CAT, Bcl-2, caspase-3, and MDA coupled with β cell dysfunction in diabetic rats. Oxidative stress in INS-1 cells was closely associated with a higher rate of apoptosis, increased production of ROS and MDA, enhanced Bax expression, and caspase-3, -9 activities and markedly decreased protein expression of Mn-SOD and CAT. FTZ-containing serum incubation notably reversed the high-glucose-evoked increase in cell apoptosis, production of ROS and MDA, and Bax protein levels. Furthermore, FTZ stimulation upregulated the expression levels of several genes, including Mn-SOD, CAT, and Bcl-2/Bcl-xl. In addition, FTZ decreased the intracellular activity of caspase-3, -9 in INS-1 cells. FTZ protected β-cells from oxidative stress induced by high glucose in vivo and in vitro. The beneficial effect of FTZ was closely associated with a decrease in the activity of caspase-3, -9 and intracellular production of ROS, MDA, and Bax coupled with an increase in the expression of Mn-SOD, CAT, and Bcl-2/Bcl-xl.

FTZ Ameliorates Diabetic Cardiomyopathy by Inhibiting Inflammation and Cardiac Fibrosis in the Streptozotocin-Induced Model

“…Consistent with a previous study showing that FTZ reduced blood glucose levels in a model of metabolic syndrome [ 14 ], our results demonstrated that treatment with FTZ significantly improved blood glucose levels in T1DM mice. This may be due to the protective effect of FTZ on pancreatic β -cells [ 13 ]. These data indicate that FTZ can regulate blood glucose levels via various mechanisms.…”

“…The diabetic mice were randomly allocated into three groups: control group (Con), diabetes group (DCM), and diabetes + FTZ group (DCM + FTZ). FTZ was diluted in 0.5% carboxymethyl cellulose-Na (CMC-Na) (Tianjin Zhiyuan Chemical Reagent Co., Ltd., Tianjin, China), and 3 g (crude drug)/kg/day FTZ was used for intragastric administration to mice every day [ 13 , 14 ]. The Con group and DCM group were treated with the considerable volume of 0.5% CMC-Na via intragastric administration once a day.…”

“…Fufang Zhenzhu Tiaozhi (FTZ) formula is an effective traditional Chinese prescription established by Professor Jiao Guo under the guidance of her new theory "Tiao Gan Qi Shu Hua Zhuo" for treating glycolipid metabolic disorders, consisting of Ligustri Lucidi Fructus, Coptidis Rhizoma, Cirsii Japonici Herba, Salviae Miltiorrhizae Radix et Rhizoma, Eucommiae Cortex, Notoginseng Radix et Rhizoma, Atractylodes Macrocephala Rhizoma, and Citri Sarcodactylis Fructus [9][10][11][12][13]. Our serial studies have identified the main components and potential targets of FTZ and demonstrated its protective effects in treating hyperlipidemia, diabetes, nonalcoholic fatty liver disease (NAFLD), and aging-induced osteoporosis through regulation of HMG-CoA reductase (HMGCR) and cholesterol 7-alpha hydroxylase (CYP7A1), attenuating insulin resistance, inhibiting the formation and activation of the nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) inflammasome, and modulating sphingolipid, glycerophospholipid, and amino acid metabolisms, respectively [11,[14][15][16].…”

Novel Antioxidant and Hypoglycemic Water-Soluble Polysaccharides from Jasmine Tea

“…The protective capacities of JSP sub-fractions on RIN-m5F cells damaged by high glucose were determined using the procedure of Bei et al ( 2019) with slight modification [17]. RIN-m5F cells were inoculated in a 96-well microplate (100 µL/well) and allowed to attach for 24-48 h (37 • C).…”

Coloured Rice Phenolic Extracts Increase Expression of Genes Associated with Insulin Secretion in Rat Pancreatic Insulinoma β-cells

“…Two different glucose conditions were used; 1) high glucose (25 mM)-induced stress condition (HGSC) to induce glucotoxic stress and; 2) normal glucose (11.1 mM) condition (NGC) to represent a normal β-cell function [48,49]. INS-1E cells were seeded onto six-well plates at a density of 4 x 10 5 cells per well and expanded in culture media and conditions as described in Section 4.3.…”