Downregulation of hepatic fat accumulation, inflammation and fibrosis by nerolidol in purpose built western-diet-induced multiple-hit pathogenesis of NASH animal model

被引:11
作者
Sabir, Usman [1 ]
Irfan, Hafiz Muhammad [1 ]
Alamgeer [2 ]
Ullah, Aman [3 ]
Althobaiti, Yusuf S. [4 ,5 ]
Alshehri, Fahad S. [6 ]
Niazi, Zahid Rasul [7 ]
机构
[1] Univ Sargodha, Coll Pharm, Dept Pharmacol, POB 40100, Sargodha, Punjab, Pakistan
[2] Univ Punjab, Punjab Univ Coll Pharm, Lahore, Pakistan
[3] Shifa Tameer E Millat Univ, Coll Pharmaceut Sci, Islamabad, Pakistan
[4] Taif Univ, Coll Pharm, Dept Pharmacol & Toxicol, POB 11099, Taif 21944, Saudi Arabia
[5] Taif Univ, Addict & Neurosci Res Unit, Taif, Saudi Arabia
[6] Umm Al Qura Univ, Coll Pharm, Dept Pharmacol & Toxicol, Mecca, Saudi Arabia
[7] Gomal Univ, Fac Pharm, Dera Ismail Khan, Kpk, Pakistan
关键词
Western diet; Non-alcoholic steatohepatitis; Insulin resistance; Inflammation; Nerolidol; LIVER-DISEASE; OXIDATIVE STRESS; FRUCTOSE; TERPENOIDS; STEATOSIS; OBESITY; NAFLD; ASSAY; RATS;
D O I
10.1016/j.biopha.2022.112956
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
Western diet style (fast food), which includes fatty frozen junk food, lard, processed meats, whole-fat dairy foods, cream, mayonnaise, butter, snacks, and fructose, is a primary etiological determinant for developing nonalcoholic steatohepatitis (NASH) worldwide. Here the primary focus is to see the impact of naturally identified essential oil on disease mechanisms developed in an animal model using the same ingredients. Currently, symptomatic therapies are recommended for the management of NASH due to non-availability of specific treatments. Therefore, the present study was designed to evaluate the potential anti-NASH effect of nerolidol in a rat model fed with a purpose-built diet. The diet substantially induced insulin resistance, hepatic steatosis, dyslipidemia, and elevation of liver enzymes in the experimental animals. The levels of liver oxidative stress markers, nitrites (NO2-), serum pro-inflammatory cytokine (TNF-alpha) and hepatic collagen were increased in disease control rats. Nerolidol oral treatment in ascending dose order of 250 and 500 mg/kg substantially reduced the steatosis (macrovesicular and microvesicular), degeneration of hepatocytes, and inflammatory cells infiltration. The amounts of circulatory TNF-alpha and tissue collagen were also reduced at 500 mg/kg dose of nerolidol, expressing its anti-fibrotic effect. The current study described the multiple-hit pathophysiology of NASH as enhanced steatosis, pro-inflammatory markers, and oxidative stress in rats, which resulted in the development of vicious insulin resistance. Nerolidol treatment significantly reduced hepatic lipid accumulation and halted disease progression induced by a hypercaloric diet.
引用
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页数:12
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