*4.1.2 Curcumin*

Curcumin, a yellow-pigmented bioactive of *Curcuma longa*, is most commonly used as a dietary spice. Numerous investigations described its pharmacological activities, including antioxidant, lipid-modifying, anti-inflammatory, anti-cancer effects [58]. Oral administration of curcumin (50 mg/kg body weight) synergistically regulated both endogenous and exogenous Nrf2/LXRα pathways in high sucrose diet-induced NAFLD rats [44]. Jazayeri et al. (2019) showed curcumin regulated the PPAR-γ activity, inhibited cyclooxygenase controlled inflammation and improved NAFLD [44, 59]; Curcumin (100 mg/kg body weight) administration for three weeks to methionine and choline-deficient (MCD) diet-fed mice significantly upregulated superoxide dismutase 1 (SOD1), SIRT1 levels and inhibited O-GlcNAcylation pathway [60]. Saadati et al. (2019) conducted a randomized placebo-controlled clinical trial with 52 NAFLD subjects where they showed curcumin (1500 mg) administration for 12 weeks significantly reduced serum cholesterol, glucose and liver fibrosis [61].



**Table1.**

 *Mechanism of action of functional foods against NAFLD.*

#### *Functional Foods for the Management of Non-Alcoholic Fatty Liver Disease DOI: http://dx.doi.org/10.5772/intechopen.96317*

### *4.1.3 Isoflavones*

Isoflavones exhibited an excellent therapeutic effect for NAFLD through de novo lipogenesis via ChREBP and anti-adipogenic Wnt signaling [62]. Genistein derived from soybean is the most investigated isoflavone with higher potency against NAFLD. Genistein supplementation (2 and 4 g/kg diet) for 12 weeks markedly reduced serum and liver lipids and downregulated SREBP-1c, PPAR-γ in NAFLD mice [63]. Genistein significantly suppressed the expression of cyclooxygenase-1 and hepatic thromboxane A2 receptor expression through the thromboxane A2 (TXA2) pathway [46]. Daidzein, a naturally occurring phytoestrogen occurring in soybean and legumes, reduced NAFLD risk and inhibited hepatic fatty acid β-oxidation in high fat supplemented mice [47]. Liu et al. (2017) showed administration of soy isoflavone (10 or 20 mg/kg) to NAFLD animals inhibited fatty acid synthesis. It promoted fat oxidation in the liver by regulating the expression of SREBP-1c and PPARα [64].

### *4.1.4 Resveratrol*

Resveratrol (3, 5, 4′-trihydroxystilbene) is widely present in the skin of grapes, berries and peanuts. Oral administration of resveratrol (50 mg/kg body weight) to high-fat diet (HFD)-induced C57BL/6 J mice reduced inflammation and fibrosis risk by modulating the IκBα-NF-κB and autophagic pathway [48]. Resveratrol by upregulating SIRT1 decreased liver lipogenesis markers and improved lipid metabolism in HFD fed mice [65]. Intragastric administration of resveratrol improved hepatic steatosis mediated by a SIRT1/ATF6-dependent mechanism in HFD fed mice [66]. Theodotou et al. (2019) showed supplementation of trans-resveratrol as a micronized formulation to NAFLD subjects reduced TG accumulation and improved insulin resistance via activation of 5′ adenosine monophosphate-activated protein kinase (AMPK) and SIRT1 [67].

#### **4.2 Proanthocyanidins and flavonoids**

The oligomeric and polymeric components of the flavonoid biosynthetic pathway are proanthocyanidins, also known as condensed tannins. Proanthocyanidins are widely distributed in seeds, fruits, flowers, nuts, barks of several plants and are typically made up of catechin and epicatechin [68]. The number of anti-NAFLD proanthocyanidins published studies is less, but findings are similar to those of other flavonoids (**Figure 2**). The grape seed proanthocyanidins (GSP) exhibited anti-NAFLD effect mainly by lipid-lowering and high antioxidant activities [49]. In another study, GSP suppressed high calorie diet-induced hepatic injury in animals [69]. A significant number of studies demonstrated the hepatoprotective and anti-fibrotic effect of morin in NAFLD models, mainly by modulating the key signaling pathways associated with fibrosis [70]. Administration of polymethoxylated flavones enriched Daoxianyeju extracts (0.2% and 0.5%) to HFD fed mice prevented liver inflammation and steatosis by activating nuclear factor erythroid-2 related factor 2 (Nrf2) signaling [71]. Tannic acid supplementation to the western diet-fed mice for 12 weeks suppressed histone acetyltransferase activity and prevented lipid accumulation [72]. Silybin, also known as silibinin, derived from Silybum (milk thistle) plant extracts in combination with tangeretin (75–150 mg/ kg) showed potent antioxidant, anti-inflammatory and anti-fibrotic activities [73]. Citrus peel extract composed of hesperidin, narirutin, synephrine and tangeretin prevented *in vivo* lipid accumulation and fatty liver development by regulating AMPK activation [74].

*Functional Foods for the Management of Non-Alcoholic Fatty Liver Disease DOI: http://dx.doi.org/10.5772/intechopen.96317*

**Figure 2.** *Significance of functional foods for NAFLD.*
