Research Article Details

Article ID: A50274
PMID: 35447548
Source: Biomed Pharmacother
Title: Downregulation of hepatic fat accumulation, inflammation and fibrosis by nerolidol in purpose built western-diet-induced multiple-hit pathogenesis of NASH animal model.
Abstract: 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-α) 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-α 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.
DOI: 10.1016/j.biopha.2022.112956

Strategy ID Therapy Strategy Synonyms Therapy Targets Therapy Drugs
S01 Improve insulin resistance insulin sensitizer; insulin resistance; glucose tolerance Biguanide: increases 5-AMP activated protein kinase signaling; SGLT-2 inhibitor; Thiazalidinedione: selective PPAR-γ agonists; GLP-1 agonist Metformin; Empagliflozin; Canagliflozin; Rosiglitazone; Pioglitazone; Liraglutide Details
S03 Anti-fibrosis fibrosis Angiotensin Receptor Blocker (ARB); CCR2/CCR5 antagonist; Thyroid receptor β agonist; PEGylated human FGF21 analogue; Monoclonal antibody to lysyl oxidase-like 2 (LOXL2); Galectin-3 inhibitor; FGF19 variant Losartan; Cenicriviroc; VK-2809; MGL-3196; Pegbelfermin; Simtuzumab; GR-MD-02; NGM282 Details
S04 Anti-oxidative stress oxidative stress α-tocopherol: antioxidant Vitamin E Details
S05 Anti-inflammatory inflammatory Bile acid; TNF-a inhibitor; Dual PPAR-α and -δ agonists; Toll-Like Receptor; (TLR)-4 antagonist; Caspase inhibitor; ASK-1 inhibitor Ursodeoxycholic Acid; Pentoxifylline; Elafibranor; JKB-121; Emricasan; Selonsertib; Details

Target ID Target Name GENE Action Class UniProtKB ID Entry Name
T08 Tumor necrosis factor TNF inhibitor Cytokine P01375 TNFA_HUMAN Details
T10 Caspase-1 CASP1 inhibitor Enzyme P29466 CASP1_HUMAN Details
T18 Acetyl-CoA carboxylase 1 ACACA inhibitor Enzyme Q13085 ACACA_HUMAN Details
T20 Fatty acid synthase FASN inhibitor Enzyme P49327 FAS_HUMAN Details

Diseases ID DO ID Disease Name Definition Class
I13 3146 Lipid metabolism disorder An inherited metabolic disorder that involves the creation and degradation of lipids. http://en.wikipedia.org/wiki/Lipid_metabolism disease of metabolism/ inherited metabolic disorder Details
I05 9352 Type 2 diabetes mellitus A diabetes that is characterized by chronic hyperglycaemia with disturbances of carbohydrate, fat and protein metabolism resulting from defects in insulin secretion, insulin action, or both. A diabetes mellitus that is characterized by high blood sugar, insulin resistance, and relative lack of insulin. http://en.wikipedia.org/wiki/Diabetes, http://en.wikipedia.org/wiki/Diabetes_mellitus_type_2 disease of metabolism/inherited metabolic disorder/ carbohydrate metabolic disorder/glucose metabolism disease/diabetes/ diabetes mellitus Details

Drug ID Drug Name Type DrugBank ID Targets Category Latest Progress
D328 Serine Chemical drug DB00133 SRR Improve insulin resistance Under clinical trials Details
D142 Fructose Chemical drug DB04173 -- Intravenous nutrition drug Under clinical trials Details
D182 Insulin Biological drug DB00030 INSR agonist; CPE modulator&product of -- Under clinical trials Details
D316 S-adenosyl-L-methionine Chemical drug DB00118 GNMT cofactor Antiviral Under clinical trials Details
D094 Cysteamine Chemical drug DB00847 GSS stimulant Renal drug Under clinical trials Details
D095 Cysteamine bitartrate Chemical drug DB00847 -- -- Under clinical trials Details