Baicalein stimulates fibroblast growth factor 21 expression by up-regulating retinoic acid receptor-related orphan receptor α in C2C12 myotubes

FGF21 as Modulator of Metabolism in Health and Disease

“…Furthermore, the knockdown of RORα prevented the augmentation of FGF21 and up-regulation of CHOP in response to baicalein in C2C12 cells. Collectively, these results suggest that baicalein stimulates the ER stress response and FGF21 expression through a RORα-dependent mechanism in C2C12 myotubes, and indicates the potential of baicalein as an effective anti-obesity therapy via its ability to enhance FGF21 production (Hirai et al, 2019). Other reports have shown that the hepatic expression of FGF21 is either regulated positively or negatively by glucocorticoid receptor (GR) (Patel et al, 2015), cAMP-responsive element-binding protein H (CREBH) (Lee et al, 2017), carbohydrate response element-binding protein (ChREBP) (Iizuka et al, 2009), PPARγ (Moyers et al, 2007; Wang et al, 2008), farnesoid X receptor (FXR) (Cyphert et al, 2012), and liver X receptor (LXR) (Archer et al, 2012; Uebanso et al, 2012) under various conditions.…”

“…Moreover, several researchers have speculated that FGF21 expression is regulated by RARβ (Wang et al, 2010, p. 21; Berry et al, 2012; Tsuchiya et al, 2012; Li et al, 2013). This is because the metabolic effect of the RARb ligand, retinoic acid, on body weight loss and glucose/lipid metabolism are similar to FGF21, this has been recently demonstrated in vitro in C2C12 (Hirai et al, 2019) but has not yet been confirmed in vivo . Retinoic acid receptor-related orphan receptor (ROR) α has been implicated in various physiological functions, including the immune system, inflammation, and circadian rhythms.…”

Natural products as modulators of retinoic acid receptor-related orphan receptors (RORs)

“…Increase of RORa transcriptional activity 191 and Rora/RORA expression 191,192 Increased expression of RORa target genes (e.g. BMAL1, Fgf21) 191,192 Decreased expression of RORgt 193,194 Decrease of proinammatory cytokines (e.g. IL-17) 193,194 Decrease in Th17 cell differentiation 193,194 Protection from liver damage in rodents 194 Cardiac glycosides Uscharin, calcein, calotropin, digoxigenin, dihydroouabain, strophanthidine…”

Prospects of circadian clock in joint cartilage development

“…145,146 Certain natural medicine, such as Baicalein and Berberine, have been able to stimulate the expression of FGF21 by regulating the clock molecules in the liver and brown adipose tissue, thereby increasing the heat production and reducing body weight. 147,148 FGF23 is a considerable site for phosphate metabolism. Circadian rhythmic variation of FGF23 is positively correlated with PTH in serum 149,150 and skeleton.…”

“…This reveals a potential therapeutic target for the precaution of obesity 145,146 . Certain natural medicine, such as Baicalein and Berberine, have been able to stimulate the expression of FGF21 by regulating the clock molecules in the liver and brown adipose tissue, thereby increasing the heat production and reducing body weight 147,148 …”