Protective Effects of Isolated Curcumin From Curcuma longa on Key Enzymes Involved in the Insulin Signaling Pathway and Digestive and Metabolic Enzymes Associated With Obesity, Type 2 Diabetes, and Hypertension

Abstract

This study explores the potential of curcumin (CUR), extracted from Curcuma longa, in combating obesity and Type 2 diabetes. Obesity and Type 2 diabetes were induced in rats through a high-fat and high-fructose diet (HFFD), and CUR, after purification and characterization by Fourier transform infrared spectroscopy (FTIR) and ultraviolet (UV) spectroscopy, was administered for 3 months via gastric gavage. The results show that CUR supplementation activates the insulin signaling pathway in a dose-dependent manner, leading to improved insulin sensitivity. Specifically, administering CUR at a daily dose of 100 mg/kg significantly reduces the activities of protein tyrosine phosphatase (PTP1B) and dipeptidyl peptidase-4 (DPP-4) by 43% and 45%, respectively, in obese and Type 2 diabetic rats compared to untreated obese rats. Furthermore, CUR effectively inhibits lipase and α-amylase activities at both the serum and intestinal levels. In obese rats, CUR administration reduces glycogen phosphorylase (GP) activity by 35% and enhances glycogen synthase (GS) activity by 78%, leading to a substantial increase in hepatic glycogen content. Additionally, CUR also led to a 21% reduction in food intake and a 12% decrease in water consumption. These changes contributed to significant reductions in the blood sugar and glycosylated hemoglobin (HbA1c) levels, with decreases of 59% and 53%, respectively. Additionally, administering CUR at a dose of 100 mg/kg body weight reduced thiobarbituric acid reactive substances (TBARSs), hydrogen peroxide (H₂O₂), and total oxidant status (TOS) in obese and diabetic rats, with reductions of 49%, 59%, and 58%, respectively. Furthermore, CUR demonstrates a strong regulatory effect on the levels of low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and total cholesterol (TC). Overall, these results underscore the CUR potential for treating and preventing diabetes and obesity.

Keywords: curcumin; diabetes; insulin signalization pathway; key enzyme; obesity.

Figure 1

Fourier transform infrared (FTIR) and absorbance spectra of purified curcumin. Our results show a similarity with the literature, confirming that our compound is pure.

Figure 2

Evaluation of CUR ingestion on lipase activity in the small intestine and serum and body weight of obese rats. The results of this study demonstrate that the ingestion of CUR significantly inhibited the activities of all three enzymes, suggesting its potential role in regulating lipid digestion and absorption. The values are presented as mean ± SD for each group of five animals. Statistical significance is indicated as follows: ⁣^∗p < 0.05 when comparing to controls; ^αp < 0.05 when comparing to obese rats; ^©p < 0.05 when comparing to obese rats treated with CUR₅₀; ^#p < 0.05 when comparing to obese rats treated with CUR₁₀₀; ^βp < 0.05 when comparing to obese rats treated with the combination CUR₁₅₀; and ^¥p < 0.05 when comparing to obese rats treated with the combination CUR₁₀₀ and Glu.

Figure 3

Effect of CUR ingestion on intestinal maltase, sucrase, and α-amylase activities of obese rats is depicted. Curcumin strongly inhibits the activity of polysaccharide hydrolysis, resulting in an antihyperglycemic effect. Statistical analyses are provided in Figure 2.

Figure 4

Effect of curcumin on key insulin signaling enzymes in rats with Type 2 diabetes, such as DPP-4 and PTP1B, was investigated. Our results demonstrate that their administration potentially inhibits the activity of DPP-4 and PTP1B, consequently affecting insulin signaling. Statistical analyses are provided in Figure 2.

Figure 5

Liver GS and GP activities, as well as liver glycogen rates in obese rats treated with CUR at different doses, are presented. Curcumin administration promotes glycogen biosynthesis by inducing GS and inhibiting GP. Statistical analyses are provided in Figure 2.

Figure 6

Effect of Type 2 diabetes and CUR on liver glucose anabolism enyme activities (G6P and FBP) and catabolism (HK and PK). Curcumin ingestion by obese rats induces catabolism and suppresses glycemic anabolism. Statistical analyses are provided in Figure 2.

Figure 7

Levels of oxidative stress indices, such as H₂O₂ and TBARS levels in the serum of rats with obesity and Type 2 diabetes. Curcumin ingestion was found to protect against oxidative stress, as evidenced by the suppression of the levels of these two indices compared to obese individuals not treated with curcumin. Statistical analyses are provided in Figure 2.

Figure 8

Levels of glucose and glycated hemoglobin in the serum of obese rats with Type 2 diabetes were measured. Our results indicate that obesity significantly increases these two indices. However, administration of curcumin in obese rats significantly reduced blood sugar and HbA1c levels. Statistical analyses are provided in Figure 2.

Figure 9

Effect of CUR administration in obese rats with Type 2 diabetes on systolic blood pressure. The results of this study clearly show that the ingestion of CUR at a dose of 100–150 mg/kg is effective in preventing hypertension. Statistical analyses are provided in Figure 2.