Mulberry Anthocyanin Extract Ameliorates Oxidative Damage in HepG2 Cells and Prolongs the Lifespan of Caenorhabditis elegans through MAPK and Nrf2 Pathways

Abstract

Mulberry anthocyanins possess many pharmacological effects including liver protection, anti-inflammation, and anticancer. The aim of this study was to evaluate whether mulberry anthocyanin extract (MAE) exerts beneficial effects against oxidative stress damage in HepG2 cells and Caenorhabditis elegans. In vitro, MAE prevented cytotoxicity, increased glucose consumption and uptake, and eliminated excessive intracellular free radicals in H2O2-induced cells. Moreover, MAE pretreatment maintained Nrf2, HO-1, and p38 MAPK stimulation and abolished upregulation of p-JNK, FOXO1, and PGC-1α that were involved in oxidative stress and insulin signalling modulation. In vivo, extended lifespan was observed in C. elegans damaged by paraquat in the presence of MAE, while these beneficial effects were disappeared in pmk-1 and daf-16 mutants. PMK-1 and SKN-1 were activated after exposure to paraquat and MAE suppressed PMK-1 activation but enhanced SKN-1 stimulation. Our findings suggested that MAE recovered redox status in HepG2 cells and C. elegans that suffered from oxidative stress, which might be by targeting MAPKs and Nrf2.

Dietary Anthocyanins: A Review of the Exercise Performance Effects and Related Physiological Responses

“…For many years, benefits were attributed to the anthocyanins scavenging free radicals by B ring hydroxyl groups and conjugated double bonds. However, anthocyanins also affect signalling pathways (Qin et al, 2012), particularly the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway (Cimino et al, 2013;Yan et al, 2017). Nrf2 is a transcription factor regulating gene expression of antioxidant proteins.…”

A mixture of mulberry and silk amino acids protected against D‑galactosamine induced acute liver damage by attenuating oxidative stress and inflammation in HepG2 cells and rats

“…Mulberry extract may act as an antioxidant to reduce oxidative stress and improve inflammation as shown in other studies (6)(7)(8). Silk amino acids have been reported to improve glucose metabolism by increasing insulin secretion and pancreatic β-cell mass, even in type 1 diabetes (21,22), suggesting that they have the potential to improve the recovery of damaged cells.…”

“…Mulberry (Morus alba L.) fruits contain anthocyanins, which have anti-oxidant and anti-inflammation properties. Mulberry fruit extracts have been reported to protect against liver damage caused by tetrachloride, lipopolysaccharide, and oxidative stress (2,6,7). In addition, mulberry extracts improve alcohol-induced steatosis by alleviating gut microbiota (4).…”

Daily Consumption of an Anthocyanin-Rich Extract Made From New Zealand Blackcurrants for 5 Weeks Supports Exercise Recovery Through the Management of Oxidative Stress and Inflammation: A Randomized Placebo Controlled Pilot Study

“…Although still unknown and hence of interest, a potential underlying mechanism could include the ability of anthocyanins, through their putative chemical electrophilic properties (78), to mediate changes in cell redox perturbations that result in the up-regulation of adaptive anti-inflammatory responses [e.g., involving IL-10, (50)] and, as we observed in this study with an improved resolution of TNFα and enhanced IL-10 levels following 5 weeks of BAE consumption. This notion is supported by a number of cell studies (23,24,79) that show that anthocyanin-induced increases in cellular antioxidant enzyme systems involve redox-initiated transcription of nrf2/ARE. It is also feasible there is a relationship between oxidative stress-driven nrf2/ARE transcription and the expression of anti-inflammatory mediators, such as TNFα and IL-10 (80), which regulates cell redox homeostasis to favor an antiinflammatory/antioxidant cellular microenvironment.…”

“…Similarly, nutritional intervention studies by others (19)(20)(21) reveal that the consumption of blackcurrant anthocyanins exhibit cardiac and eye health as well as alleviating oxidative stress in both physiological and disease scenarios. Anthocyanins have been shown to reduce cellular oxidative damage and inflammation through a number of cellular mechanisms, including the upregulation of cellular cyclic adenosine monophosphate responsive element driven upregulation of reduced glutathione content (22), nuclear redox factor/antioxidant responsive element (nrf2/ARE)-induced antioxidant enzyme expression, e.g., superoxide dismutase, catalase (23,24), and down-regulation of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and activator protein-1 (AP-1)-induced inflammation (25)(26)(27). Therefore, the improved lifestyle health benefits from consuming foods rich in anthocyanins appear to involve the activation of different cellular pathways that contribute to a dynamic cellular antioxidant/anti-inflammatory microenvironment capable of responding to redox fluctuation caused by various physiological (e.g., exercise) or pathophysiological (e.g., atherosclerosis) events.…”