Theracurmin (Highly Bioavailable Curcumin) Prevents High Fat Diet-Induced Hepatic Steatosis Development in Mice

Abstract

Curcumin, a hydrophobic polyphenol isolated from the Curcuma longa L. plant, has many pharmacological properties, including antioxidant, anti-inflammatory, and chemo-preventive activities. Curcumin has been shown to have potential in preventing nonalcoholic fatty liver disease (NAFLD). However, the low bioavailability of curcumin has proven to be a major limiting factor in its clinical adoption. Theracurmin, a highly bioavailable curcumin that utilizes micronized technology showed improved biological absorbability in vivo. The aim of this study was to investigate the role of theracurmin in modulating hepatic lipid metabolism in vivo. A fatty liver mouse model was produced by feeding mice a high fat diet (HFD; 60% fat) for 12 weeks. We found that treatment for 12 weeks with theracurmin significantly lowered plasma triacylglycerol (TG) levels and reduced HFD-induced liver fat accumulation. Theracurmin treatment lowered hepatic TG and total cholesterol (T-CHO) levels in HFD-fed mice compared to controls. In addition, theracurmin administration significantly reduced lipid peroxidation and cellular damage caused by reactive oxygen species in HFD-fed mice. Overall, these results suggest that theracurmin has the ability to control lipid metabolism and can potentially serve as an effective therapeutic remedy for the prevention of fatty liver.

Therapeutic potential of mitochondrial uncouplers for the treatment of metabolic associated fatty liver disease and NASH

“…developed Theracurmin, which exhibited 30-fold higher absorption than commercially available curcumin [ 122 ]. Moreover, oral administration (150–600 mg/kg active dose) was recently shown to prevent hypertriglyceridemia and hepatic steatosis in high-fat diet-fed mice by reducing hepatic triglyceride content and inhibiting diet-induced lipid peroxidation [ 123 ]. Whether these beneficial effects were due to curcumin-mediated hepatic uncoupling remain to be determined; nonetheless, Theracurmin is currently in clinical trials (UMIN000007361) for the treatment of T2D.…”

The effect of curcumin on hepatic fat content in individuals with obesity

“…Rodent studies have shown that curcumin supplementation can prevent diet‐induced steatosis 16,27‐35 . Only a few rodent studies have examined curcumin as a treatment for established steatosis, also with positive results 36,37 .…”

“…Rodent studies have shown that curcumin supplementation can prevent diet‐induced steatosis. 16 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 Only a few rodent studies have examined curcumin as a treatment for established steatosis, also with positive results. 36 , 37 Randomized controlled trials have been carried out showing a decrease in ultrasound‐assessed HFC in patients diagnosed with steatosis when treating with curcumin.…”

Molecular Mechanisms of Curcumin in the Pathogenesis of Metabolic Dysfunction Associated Steatotic Liver Disease

“…Specifically, the authors found that curcumin was able to block Notch signaling in the liver of rats fed with HFD who developed hepatic steatosis, by the up-regulation of PPARα, (thus increasing FFAs oxidation), and by the down-regulation of lipogenic genes such as FAS and ACC (thus promoting lipids accumulation and hepatic steatosis development and worsening) [49]. Recently, theracurcumin, a more bioavailable synthetic form of curcumin, has been proven to reduce cholesterol levels by targeting both the HMG-CoA reductase and acyl-CoA: cholesterol acyltransferase (ACAT), two enzymes involved in cholesterol synthesis and esterification, respectively [51]. Niemann-pick C1-like 1 (NPC1L1) is a factor that mediates cholesterol absorption playing an important role in the pathogenesis of MASLD [71].…”