Mulberry (Morus alba L.) Fruit Extract Ameliorates Inflammation via Regulating MicroRNA-21/132/143 Expression and Increases the Skeletal Muscle Mitochondrial Content and AMPK/SIRT Activities

Abstract

The Mulberry (Morus alba L.) fruit is a rich source of polyphenolic compounds; most of these are anthocyanins. Obesity is intimately related to low-grade inflammation, with increased pro-inflammatory cytokine secretion and macrophage infiltration in white adipose tissue (WAT). This study investigated whether mulberry fruit extract (ME) has beneficial effects on obesity-induced inflammation and skeletal muscle mitochondrial dysfunction. Sprague-Dawley rats were divided into four groups and fed either a low-fat diet (LFD), high-fat diet (HFD), HFD + 5 g/kg of ME (ME-L), or HFD + 10 g/kg of ME (ME-H) for 14 weeks. ME alleviated dyslipidemia and lipid accumulation, as well as pro-inflammatory cytokine production such as tumor necrosis factor-α (TNF-α), interleukin 6 (IL-6), and monocyte chemoattractant protein 1 (MCP1) in the WAT. ME mitigated nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) phosphorylation and macrophage infiltration in WAT. Notably, microRNA (miR)-21, miR-132, and miR-43 expressions were downregulated in the WAT of the ME groups compared to the HFD group. Moreover, ME increased the mitochondrial size and mitochondrial DNA (mtDNA) content, as well as key genes’ expression related to mitochondrial function, including sirtuin (SIRT)1, peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α), carnitine palmitoyltransferase 1β (CPT-1β), and uncoupling protein 3 (UCP3), and adenosine monophosphate-activated protein kinase (AMPK)/SIRT activities in skeletal muscle. These results suggested that ME might alleviate obesity-induced inflammation and mitochondrial dysfunction by regulating miR-21, miR-132, and miR-43 expression in WAT, and by activating the PGC-1α/SIRT1 pathway in muscle.

Impact of cyanidin 3-<i>O</i>-glucoside on rat micro-and systemic circulation, possibly thorough angiogenesis

“…Anthocyanins, including C3G, were reported to exhibit beneficial effects on skeletal muscle, including increases in mitochondrial content (32) and intracellular glucose uptake. (33) It is thought that oral C3G induces metabolic activation in skeletal muscle; moreover, in the muscle microenvironment, it induces the secretion of pro-angiogenic factors from hypoxic or metabolically active cells.…”

Effect of Acylated and Nonacylated Anthocyanins on Urine Metabolic Profile during the Development of Type 2 Diabetes in Zucker Diabetic Fatty Rats

“…59 Mulberry anthocyanin extract has been reported to regulate mitochondrial function, such as increasing mitochondrial size, energy production, and mitochondrial DNA content in high-fat dietinduced obese rats. 60 H-AAPP decreased formate, suggesting a possible improvement in energy production and mitochondrial function at week 4; this decrease caused by H-AAPP disappeared at week 8, which might indicate that the progression of T2D neutralized the beneficial effect of anthocyanins on the formate production. A high level of urinary glucose in ZDF rats indicates a high level of plasma glucose and/or renal dysfunction.…”

“…Formate could be produced from methanol in the liver by mitochondrial alcohol dehydrogenase, which induces the production of free radicals; alternatively, formate can also be produced by intestinal bacteria . Mulberry anthocyanin extract has been reported to regulate mitochondrial function, such as increasing mitochondrial size, energy production, and mitochondrial DNA content in high-fat diet-induced obese rats . H-AAPP decreased formate, suggesting a possible improvement in energy production and mitochondrial function at week 4; this decrease caused by H-AAPP disappeared at week 8, which might indicate that the progression of T2D neutralized the beneficial effect of anthocyanins on the formate production.…”

HJ11 decoction restrains development of myocardial ischemia-reperfusion injury in rats by suppressing ACSL4-mediated ferroptosis

“…Myocardial I/R surgery was performed on rats of the I/R group, I/R + HJ11-L group, I/R + HJ11-M group, and I/R + HJ11-H group. The following procedure was used: Rats of the four groups were anesthetized by inhalation of 5% isoflurane, and the anesthesia was maintained by inhalation of 2% isoflurane ( Jung et al, 2021 ). After ensuring that the rats did not respond to limb stimulation, they were fixed on the operating table in the supine position.…”