Sulforaphane (SFN), a potent nuclear factor erythroid 2-related factor 2 (Nrf2) activator, is present in the species of the Brassicaceae, especially in broccoli sprouts. In this study, the effects of SFN against microglial activation and inflammation, and the potential mechanisms involved, were analyzed. As mitogen-activated protein kinase (MAPK) signaling plays a key role in microglial activation and inflammation, we focused on the role of SFN in regulating the MAPK signaling regulation of the inflammatory and anti-inflammatory cascades in lipopolysaccharide (LPS)-activated microglia. The anti-inflammatory and immunomodulatory effects of SFN were explored by evaluating the expression and secretion of inflammatory proteins, cytokines, nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), and activator protein-1 (AP-1) under pre- and post-treatment conditions. Under the SFN pre- and post-treatment conditions, the MAPK phosphorylation levels were significantly reduced in both acutely and chronically activated microglial cells. SFN also reduced the c-Jun N-terminal kinase (JNK) phosphorylation levels, which subsequently reduced NF-κB and AP-1 signaling. As a result, the expression of the inflammatory mediators (iNOS, COX-2, NO, and PGE2) and proinflammatory cytokines (TNF-α, IL-6, and IL-1β) was decreased. At the same time, SFN increased the expression of Nrf2 and heme oxygenase-1 (HO-1) as well as the production of the anti-inflammatory cytokines IL-10 and IL-4. In conclusion, this study demonstrated that SFN exerts an anti-neuroinflammatory effect on microglia through JNK/AP-1/NF-κB pathway inhibition and Nrf2/HO-1 pathway activation.

The skin is the outermost protective barrier between the internal and external environments in humans. Chronic exposure to ultraviolet (UV) radiation is a major cause of skin aging. UVB radiation penetrates the skin and induces ROS production that activates three major skin aging cascades: matrix metalloproteinase‐ (MMP‐) 1‐mediated aging; MAPK‐AP‐1/NF‐κB‐TNF‐α/IL‐6, iNOS, and COX‐2‐mediated inflammation‐induced aging; and p53‐Bax‐cleaved caspase‐3‐cytochrome C‐mediated apoptosis‐induced aging. These mechanisms are collectively responsible for the wrinkling and photoaging characteristic of UVB‐induced skin aging. There is an urgent requirement for a treatment that not only controls these pathways to prevent skin aging but also avoids the adverse effects often encountered when applying bioactive compounds in concentrated doses. In this study, we investigated the efficacy of genetically modified normal edible rice (NR) that produces the antiaging compound resveratrol (R) as a treatment for skin aging. This resveratrol‐enriched rice (RR) overcomes the drawbacks of R and enhances its antiaging potential by controlling the abovementioned three major pathways of skin aging. RR does not exhibit the toxicity of R alone and promisingly downregulates the pathways underlying UVB‐ROS‐induced skin aging. These findings advocate the use of RR as a nutraceutical for antiaging purposes.

Estrogen deficiency has been well characterized in inflammatory disorders including neuroinflammation. Daidzein, a dietary alternative phytoestrogen found in soy (Glycine max) as primary isoflavones, possess anti‐inflammatory activity, but the effect of its active metabolite Equol (7‐hydroxy‐3‐(4′‐hydroxyphenyl)‐chroman) has not been well established. In this study, we investigated the anti‐neuroinflammatory and neuroprotective effect of Equol in vitro. To evaluate the potential effects of Equol, three major types of central nervous system (CNS) cells, including microglia (BV‐2), astrocytes (C6), and neurons (N2a), were used. Effects of Equol on the expression of inducible nitric oxide synthase (iNOS), cyclooxygenase (COX‐2), Mitogen activated protein kinase (MAPK) signaling proteins, and apoptosis‐related proteins were measured by western blot analysis. Equol inhibited the lipopolysaccharide (LPS)‐induced TLR4 activation, MAPK activation, NF‐kB‐mediated transcription of inflammatory mediators, production of nitric oxide (NO), release of prostaglandin E2 (PGE‐2), secretion of tumor necrosis factor‐α (TNF‐α) and interleukin 6 (IL‐6), in Lipopolysaccharide (LPS)‐activated murine microglia cells. Additionally, Equol protects neurons from neuroinflammatory injury mediated by LPS‐activated microglia through downregulation of neuronal apoptosis, increased neurite outgrowth in N2a cell and neurotrophins like nerve growth factor (NGF) production through astrocytes further supporting its neuroprotective potential. These findings provide novel insight into the anti‐neuroinflammatory effects of Equol on microglial cells, which may have clinical significance in cases of neurodegeneration.

In this study, pharmacophore based 3D QSAR models for human acetylcholinesterase (AChE) inhibitors were generated, with good significance, statistical values (r²_training = 0.73) and predictability (q²_training = 0.67). It was further validated by three methods (Fischer’s test, decoy set and Güner-Henry scoring method) to show that the models can be used to predict the biological activities of compounds without costly and time-consuming synthesis. The criteria for virtual screening were also validated by testing the selective AChE inhibitors. Virtual screening experiments and subsequentin vitroevaluation of promising hits revealed a novel and selective AChE inhibitor. Thus, the findings reported herein may provide a new strategy for the discovery of selective AChE inhibitors. The IC₅₀value of compounds5cand6apresented selective inhibition of AChE without inhibiting butyrylcholinesterase (BChE) at uM level. Molecular docking studies were performed to explain the potent AChE inhibition of the target compounds studies to explain high affinity.

Allyl isothiocyanate (AITC), present in Wasabia japonica (wasabi), is an aliphatic isothiocyanate derived from the precursor sinigrin, which is a glucosinolate present in vegetables of the Brassica family. Traditionally, it has been used to treat rheumatic arthralgia, blood circulation, and pain. This study focuses on its anti-apoptotic activity through the regulation of lipopolysaccharide (LPS)-induced neuroinflammation. Furthermore, we assessed its neuroprotective efficacy, which it achieves through the upregulation of nerve growth factor (NGF) production. Pretreatment with AITC significantly inhibited inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) expression, decreased tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), prostaglandin E2 (PGE2), and nitric oxide (NO) production in activated microglia, and increased the nerve growth factor (NGF) and neurite outgrowth in neuroblastoma cells. AITC inhibited the nuclear factor (NF-κB-mediated transcription by modulating mitogen activated protein kinase (MAPK) signaling, particularly downregulating c-Jun N-terminal kinase (JNK) phosphorylation, which was followed by a reduction in the TNF-α expression in activated microglia. This promising effect of AITC in controlling JNK/NF-κB/TNF-α cross-linking maintains the Bcl-2 gene family and protects neuroblastoma cells from activated microglia-induced toxicity. These findings provide novel insights into the anti-neuroinflammatory effects of AITC on microglial cells, which may have clinical significance in neurodegeneration.