Camel milk protein hydrosylate alleviates hepatic steatosis and hypertension in high fructose-fed rats

Abstract

Context: Camel milk is used in traditional medicine to treat diabetes mellitus hypertension and other metabolic disorders.

Objective: This study evaluated the antisteatotic and antihypertensive effects of camel milk protein hydrolysate (CMH) in high fructose (HF)-fed rats and compared it with the effects afforded by the intact camel milk protein extract (ICM).

Materials and methods: Adult male Wistar rats were divided into 6 groups (n = 8 each) as 1) control, 2) ICM (1000 mg/kg), 3) CMH (1000 mg/kg), 4) HF (15% in drinking water), 5) HF (15%) + ICM (1000 mg/kg), and 6) HF (15%) + CMH (1000 mg/kg). All treatments were given orally for 21 weeks, daily.

Results: Both ICM and CMH reduced fasting glucose and insulin levels, serum and hepatic levels of cholesterol and triglycerides, and serum levels of ALT and AST, angiotensin II, ACE, endothelin-1, and uric acid in HF-fed rats. In addition, both ICM and CMH reduced hepatic fat deposition in the hepatocytes and reduced hepatocyte damage. This was associated with an increase in the hepatic activity of AMPK, higher PPARα mRNA, reduced expression of fructokinase C, SREBP1, SREBP2, fatty acid synthase, and HMG-CoA-reductase. Both treatments lowered systolic and diastolic blood pressure. However, the effects of CMH on all these parameters were greater as compared to ICM.

Discussion and conclusions: The findings of this study encourage the use of CMH in a large-scale population and clinical studies to treat metabolic steatosis and hypertension.

Keywords: Metabolic disorder; NAFLD; angiotensin; blood pressure; hyperglycaemia; hyperlipidaemia; liver.

Figure 1.

Histological sections of the livers of all groups of rats as stained by the haematoxylin and eosin (H&E). (A–C) were taken from control, intact camel milk (ICM), and camel milk hydrosylate (CMH)-treated rats, respectively, and showing normal liver structure with intact rounded hepatocytes (long arrow) radiating from the central vein (CV) and normally appeared sinusoids (short arrow). (D) was taken from high fructose (HF)-fed rat and showed increased fat droplet deposition of all sizes, including large (long arrow), medium (short arrow), and small vacuoles (arrowhead). The sinusoids were hardly seen. (E) was taken from HF + ICM-treated rats and showed much improvement in the structure of the hepatocytes with an obvious reduction in the fatty vacuolation and normally appeared hepatocytes (long arrow) and sinusoids (short arrow). However, some cytoplasmic lipid accumulation is still seen in some hepatocytes (curved arrow). (F) was taken from HF + CMH and showed almost normal hepatic architecture with no fat accumulation and normal hepatocytes (long arrow) and sinusoids (short arrow) structures.

Figure 2.

Hepatic levels of ROS (A), MDA (B), SOD (C), and GSH (D) in all groups of rats. Data are presented as mean ± SD for n = 8 rats/group. Values are considered significantly different at p < 0.05. ^a: significantly different as compared to control rats, ^b: significantly different as compared to intact camel milk (ICM)-treated rats. ^c: significantly different as compared to camel milk hydrosylate (CMH)-treated rats. ^d: significantly different as compared to high fructose (HF)-fed rats, and ^e: significantly different as compared to HF + ICM-treated rats.

Figure 3.

Serum levels of ALT (A), AST (B), and uric acid (C), as well hepatic protein levels of fructokinase C (D) in all groups of rats. Data are presented as mean ± SD for n = 8 rats/group. Values are considered significantly different at p < 0.05. Values are considered significantly different at p < 0.05. ^a: significantly different as compared to control rats, ^b: significantly different as compared to intact camel milk (ICM)-treated rats. ^c: significantly different as compared to camel milk hydrosylate (CMH)-treated rats. ^d: significantly different as compared to high fructose (HF)-fed rats, and ^e: significantly different as compared to HF + ICM-treated rats.

Figure 4.

Serum levels of ACE (A), ET-1 (B), and ANG II (C), as well as the systolic and diastolic blood pressures (SBP/DBP) (D) in all groups of rats. Data are presented as mean ± SD for n = 8 rats/group. Values are considered significantly different at p < 0.05. Values are considered significantly different at p < 0.05. ^a: significantly different as compared to control rats, ^b: significantly different as compared to intact camel milk (ICM)-treated rats. ^c: significantly different as compared to camel milk hydrosylate (CMH)-treated rats. ^d: significantly different as compared to high fructose (HF)-fed rats, and ^e: significantly different as compared to HF + ICM-treated rats.

Figure 5.

Protein levels of AMPK/p-AMPK (A) and mRNA levels of SREBP1, SREBP2 (B), PPARα, FAS, and HMGCoAR (C) in all groups of rats. Data are presented as mean ± SD for n = 8 rats/group. Values are considered significantly different at p < 0.05. Values are considered significantly different at p < 0.05. ^a: significantly different as compared to control rats, ^b: significantly different as compared to intact camel milk (ICM)-treated rats. ^c: significantly different as compared to camel milk hydrosylate (CMH)-treated rats. ^d: significantly different as compared to high fructose (HF)-fed rats, and ^e: significantly different as compared to HF + ICM-treated rats.

Figure 6.

A graphical abstract demonstrating the protective effect of the camel milk hydrosylate (CMH) against high fructose diet-induced hypertension, hyperglycaemia, and non-alcoholic fatty liver disease (NAFLD). All steps are assumed to occur in the liver tissue. The mechanisms include 1) downregulating the hepatic fructokinase C enzyme, which results in suppressing the production of glucose, fatty acids, and uric acid; 2) upregulating antioxidants; 3) activating AMPK and PPARα, which inhibits lipogenesis by suppressing SREBP1/2 and activating and fatty acids oxidation, respectively; and 4) inhibiting the production of ANG II possibly by downregulating endothelin-1 (ET-1) and angiotensin-converting enzyme (ACE). TGs: triglycerides; CHOL: cholesterol, ROS: reactive oxygen species; CPT1/2: carnitine palmitoyltransferase I/2.