Curcumin supplementation mitigates NASH development and progression in female Wistar rats

Abstract

Curcumin, a naturally occurring plant polyphenolic compound, may have beneficial effects in nonalcoholic steatohepatitis (NASH) development. We examined whether curcumin supplementation could be used in both prevention and treatment of NASH with fibrosis. Female Wistar rats were provided ad libitum access to a “western diet” (WD) high in fat (43% kcal), sucrose (29% kcal), and cholesterol (2% w/v), as well as 15% fructose drinking water. Intraperitoneal CC14 injections (0.5 mL/kg) were also administered at weeks 1, 2, 4, and 6 to accelerate development of a NASH with fibrosis phenotype. Rats were randomized to four groups (n = 9–12/group) and fed ad libitum: (1) WD for 8‐weeks (8WD), (2) WD enriched with curcumin for 8‐weeks (8WD+C; 0.2% curcumin, BCM‐95, DolCas Biotech) to assess prevention, (3) WD for 12‐weeks (12WD), (4) WD for 8‐weeks followed by 4‐weeks WD+C (12WD+C) to assess treatment. Curcumin prevention (8WD vs. 8WD+C) attenuated (P < 0.05) histological liver inflammation, molecular markers of fibrosis (Col1a1 mRNA) and a serum marker of liver injury (AST). Curcumin treatment (12WD vs. 12WD+C) reduced (P < 0.05) hepatocellular inflammation, steatosis, NAFLD Activity Scores, and serum markers of liver injury (AST, ALP). Moreover, curcumin treatment also increased hepatic pACC/ACC, ApoB100, and SOD1 protein, and decreased hepatic FGF‐21 levels; whereas, curcumin prevention increased hepatic glutathione levels. Both curcumin prevention and treatment reduced molecular markers of hepatic fibrosis (Col1a1 mRNA) and inflammation (TNF‐α, SPP1 mRNA). Curcumin supplementation beneficially altered the NASH phenotype in female Wistar rats, particularly the reversal of hepatocellular inflammation.

Curcuminoids plus piperine improve nonalcoholic fatty liver disease: A clinical trial

“…It has been reported that the prevalence of NAFLD rise to 50% in patients with dyslipidemia and to 90% in diabetic patients . The association between NAFLD and metabolic syndrome and thus with obesity, insulin resistance, impaired glucose tolerance, dyslipidemia, and ultimately, increased risk of morbidity and mortality related to the liver and cardiovascular disease (CVD), have been reported by several studies . Pathogenesis of NAFLD is complex and is incompletely understood but it has been reported that it is a reversible condition .…”

“…2 The association between NAFLD and metabolic syndrome and thus with obesity, insulin resistance, impaired glucose tolerance, dyslipidemia, and ultimately, increased risk of morbidity and mortality related to the liver and cardiovascular disease (CVD), have been reported by several studies. 1,3,[5][6][7][8][9] Pathogenesis of NAFLD is complex and is incompletely understood but it has been reported that it is a reversible condition. 4,10 However, there are no efficient and accessible FDA-approved pharmacological treatments for NAFLD.…”

“…4,10 However, there are no efficient and accessible FDA-approved pharmacological treatments for NAFLD. 1 Therefore, good metabolic control through dietary modification and increased physical activity is always the first line of recommended treatment but it is not often fully efficacious in reversing the diseases especially at advanced stages. 6,8,11 Hence, novel treatments to control or slow the progression of NAFLD are urgently needed.…”

Curcuma longaandTrigonella foenum graecum‐enriched nutrient mixture from germinatedMacrotyloma uniflorumandVigna radiateameliorate nonalcoholic fatty liver diseases in rats

“…The onset of direct hepatocyte injury releases such markers into the bloodstream and indicates the abnormality of the liver and is noticed to be elevated in rats fed with the MCD diet (Hadizadeh et al, ). The co‐ and pre‐administration of the nutrient mixture to steatosis rats resulted in the decrease of all of these markers, indicating the role of the nutrient mixture as a hepatoprotective agent by reducing the damage done to the hepatocytes by other metabolic factors (Cunningham et al, ; Kargulewicz et al, ).…”

Effect of curcumin supplementation on serum expression of select cytokines and chemokines in a female rat model of nonalcoholic steatohepatitis

“…Limited evidence also suggests that curcumin may have anti-steatotic [10] and anti-fibrotic effects on the liver [11, 12]. To this end, we recently evaluated the prophylactic and therapeutic potential of a turmeric extract/curcumin supplement, BCM-95 ® , in a rat model of NAFLD/NASH [13]. In that study/model, we found that curcumin supplementation was partially effective in preventing the development of liver disease and more effective in mitigating its progression.…”