Therapeutic Effects of Plant Anthocyanin against Alzheimer's Disease and Modulate Gut Health, Short-Chain Fatty Acids.

Alzheimer's disease (AD) is the most common form of dementia and neurogenerative disease (NDD), and it is also one of the leading causes of death worldwide. The number of AD patients is over 55 million according to 2020 Alzheimer's Disease International (ADI), and the number is increasing drastically without any effective cure. In this review, we discuss and analyze the potential role of anthocyanins (ACNs) against AD while understanding the molecular mechanisms. ACNs have been reported as having neuroprotective effects by mitigating cognitive impairments, apoptotic markers, neuroinflammation, aberrant amyloidogenesis, and tauopathy. Taken together, ACNs could be an important therapeutic agent for combating or delaying the onset of AD.

Quercetin Is An Active Agent in Berries against Neurodegenerative Diseases Progression through Modulation of Nrf2/HO1.

Berries are well-known fruits for their antioxidant effects due to their high content of flavonoids, and quercetin is one of the potent bioactive flavonoids. Although oxidative stress is an inevitable outcome in cells due to energy uptake and metabolism and other factors, excessive oxidative stress is considered a pivotal mediator for the cell death and leads to the progression of neurodegenerative diseases (NDDs). Furthermore, oxidative stress triggers inflammation that leads to neuronal cell loss. Alzheimer's, Parkinson's, Huntington's disease, amyotrophic lateral sclerosis, multiple sclerosis, and so on are the main neurodegenerative diseases. Hence, AD and PD are the most affected NDDs and cause the most lethality without any effective cure. Since AD and PD are the most common NDDs, therefore, in this study, we will describe the effect of oxidative stress on AD and PD. Targeting oxidative stress could be a very effective way to prevent and cure NDDs. Thus, the nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO1) are potent endogenous antioxidant modulatory pathways, which also show cytoprotective activities. Modulation of Nrf2/HO1 signaling pathways through a biological approach could be an effective way to treat with NDDs. Quercetin is a natural polyphenol, which protects neurodegeneration, remarkably by suppressing oxidative stress and inflammation. Thus, quercetin could be a very effective agent against NDDs. We will discuss the benefits and challenges of quercetin to treat against NDDs, focusing on molecular biology.

The Anti-Inflammatory Activities of Fermented Curcuma That Contains Butyrate Mitigate DSS-Induced Colitis in Mice.

Inflammatory bowel disease is characterized by a radical imbalance of inflammatory signaling pathways in the gastrointestinal tract, and it is categorized into two diseases, such as Crohn's disease and ulcerative colitis. In this study, we investigated anti-inflammatory activities using fermented Curcuma that contains butyrate (FB). Nitric oxide production in RAW 264.7 cells and the expression of inducible nitric oxide synthase in the intestinal mucosa appears to be enhanced in active ulcerative colitis. Here, the cytotoxicity, physiological activity, and anti-inflammatory efficacy of FB in colitis animals were investigated. To verify the anti-inflammatory effect, this study was conducted using the dextran sulfate sodium (DSS)-induced colitis mice model. As a result, non-toxicity was confirmed, and anti-inflammatory effects were revealed by inducing a reduction of LPS-induced NO production. In the DSS-induced colitis, reduced weight was recovered and a decrease in inflammatory factors Ig-E and TNF-α in the mesenteric lymph node (MLN) and spleen was induced, and it was confirmed to help with the morphological remodeling of the intestine. In conclusion, this paper suggests that FB can help to alleviate intestinal inflammation and to improve the intestinal environment, with the help of morphological remodeling.

Sodium butyrate ameliorates neurotoxicity and exerts anti-inflammatory effects in high fat diet-fed mice.

The prevalence of high-fat diet consumption-related disorders is increasing, and it is often associated with oxidative stress, inflammation, and dysregulation in the brain may lead to neurodegenerative diseases (NDDs). Our study aims to evaluate the neuroprotective effects of sodium butyrate (NaB) on HFD-fed mice. In this study, four-week-old male C57Bl/6NTac mice were divided into three groups; the control group, the HFD group, and the HFD + NaB group where mice received 11 mg/kg body weight of NaB with HFD. Western blotting, reverse transcription-PCR, and ELISA were used for biochemical analysis of brain specimens. We found that NaB restored bodyweight and attenuated P-53, Bcl-2-associated X protein (BAX), and caspase cascades in the brains of HFD-fed mice. In addition. NaB reduced the expressions of proinflammatory cytokines and positively modulated antioxidant biomarkers. NaB treatment upregulated the expression of the growth factor-related factors PPARγ, CREB, and BDNF in the brain tissues of HFD-fed mice. Furthermore, we found that NaB significantly ameliorated glucocorticoid receptor and NLRP3 inflammasome expression. Based on our findings, NaB suppressed apoptotic and inflammatory cytokines and enhanced the expression of endogenous antioxidants in brain tissues of HFD-fed mice. Our data strongly suggests that NaB could be utilized as an effective therapeutic agent for NDDs.

Neuroprotective Effects of Sodium Butyrate through Suppressing Neuroinflammation and Modulating Antioxidant Enzymes.

The discovery of effective therapeutic agents against neurodegenerative diseases (NDDs) remains challenging. Neurotoxicity, inflammations, and oxidative stress are associating factors of NDDs. Sodium butyrate (NaB) is a short-chain fatty acid found in diet and produced in the gut that reportedly protects cancer, inflammation, obesity and so on. Previously, SH-SY5Y cells were studied as in vitro models of cerebral diseases. We have investigated the neuroprotective effects of NaB in SH-SY5Y cells stimulated with TNF-α. The expression of inflammatory mediators, including iNOS, COX-2, and mitogen-activated protein kinases (MAPK) and the apoptotic regulators, including P-53, Bcl-2 associated X (BAX) Protein, and caspase-3 were analyzed by western blot analysis. The anti-apoptotic gene Bcl-2 and the pro-apoptotic gene BAX translocation were also investigated. Our results showed that NaB attenuated cell death and inhibited the NO production and decreased the expression of iNOS and COX-2 in TNF-α-stimulated SH-SY5Y cells. NaB notably ameliorated apoptotic regulatory proteins p-53, Caspase-3 and caspase-1 level, and reversed phosphorylation of extracellular signal-regulated kinases and p-38 proteins. NaB ameliorated Glucocorticoid receptor and NLRP3 inflammasome expressions. NaB also suppressed the BAX nuclear translocation and modulated Nrf-2, HO-1 and MnSOD expression in neuroblastoma cells. In addition, NaB substantially reversed the reactive oxygen species in H2O2 induced SH-SY5Y cells. Altogether, our results suggest that sodium butyrate has potential therapeutic effects against NDDs.