Miquelianin, a main functional flavonoid of lotus leaf, induces thermogenic signature via p38‐PINK1‐PARKIN‐mediated mitophagy and mimicking NRF2 signaling during brown adipocyte differentiation

Abstract

Adipocytes thermogenesis is an important mechanism for increasing energy expenditure. Here, screening of thermogenic activators (Sirt1 and Ucp1) investigated in C3H10T1/2 cells revealed ethanol extract of lotus leaf (LLE) may exert higher activity compared with that of the other 11 ingredients. UPLC‐MS/MS analysis showed that miquelianin was identified as the main flavonoid compounds in LLE (12.8%) and therefore deserves further investigation. The results in C3H10T1/2 cells revealed miquelianin promoted lipolysis, enhanced thermogenic programming (Sirt1, Ppargc1a, Prdm16, Cox7a, Nrf1, Cox2, and Ucp1), and induced brown‐like adipocyte formation (Fgf21, Cd137, Tmem26, Tbx1, Cd40, and Cited1). Moreover, miquelianin increased mitochondrial abundance, mitochondrial membrane potential, and NAD+/NADH ratio, suggesting its potential in mitochondria activity. We also observed that miquelianin improved mitochondrial quality by the establishment of mitochondrial dynamics (Mfn1, Mfn2, Opa1, Drp1, and Fis1) and subsequent suppression of autophagy. Chemical inhibition experiment revealed miquelianin may trigger browning via p38‐PINK1‐PARKIN‐mediated mitophagy. Furthermore, in ML385‐treated cells, NRF2, HMOX1, TFAM, and UCP1 were compromised by miquelianin treatment, suggesting that NRF2 signaling is necessary during miquelianin‐induced mitochondria biogenesis. Together, our findings demonstrate that miquelianin may induce browning and mitochondria thermogenic programing by suppressing mitophagy via p38‐PINK1‐PARKIN and mimicking NRF2 signaling.

Quercetin as one of the most abundant represented biological valuable plant components with remarkable chemoprotective effects - A review

“…Miquelianin (quercetin 3- O -glucuronide) is a primary functional flavonoid found in lotus leaves. It possesses anti-inflammatory, anti-atherogenic, and antioxidant properties, and by dissipating energy, it may be utilized as a new food raw material or nutritional supplement in weight loss products [ 72 ]. This flavonoid is derived from Hypericum perforatum L., and in vivo, pharmacological studies have demonstrated its antidepressant properties [ 73 ].…”

Sea Buckthorn Flavonoid Extracted by High Hydrostatic Pressure Inhibited IgE-Stimulated Mast Cell Activation through the Mitogen-Activated Protein Kinase Signaling Pathway

“…In ovariectomized mice, quercitrin decreased the expression of p-INK, p-ERK, and p-p38 to blunt the MAPK signaling pathways [48]. Similarly, the crucial flavonoid from lotus leaf can mediate brown-adipocyte differentiation and thermogenic via inhibiting the p38 MAPK signal pathway [49]. Chung et al [50] found that quercetin could markedly inhibit the IgE-antigen complex that stimulates phosphorylation of the p38, ERK, and JNK proteins.…”

Mitophagy suppression by miquelianin‐rich lotus leaf extract induces ‘beiging’ of white fat via AMPK/DRP1‐PINK1/PARKIN signaling axis

“…Determination of NADH content, NAD + content and NAD + / NADH ratio A NAD + /NADH Quantification Kit (Beyotime) was used for the determination of NADH content, NAD + content and NAD + /NADH ratio according to our previous report. 11…”