Activated microglia-mediated neuroinflammation plays a key pathogenic role in neurodegenerative diseases, such as Alzheimer’s disease, Parkinson’s disease, multiple sclerosis, and ischemia. Sulforaphane is an active compound produced after conversion of glucoraphanin by the myrosinase enzyme in broccoli (Brassica oleracea var) sprouts. Dietary broccoli extract as well as sulforaphane has previously known to mitigate inflammatory conditions in aged models involving microglial activation. Here, we produced sulforaphane-enriched broccoli sprouts through the pretreatment of pulsed electric fields in order to trigger the biological role of normal broccoli against lipopolysaccharide-activated microglia. The sulforaphane-enriched broccoli sprouts showed excellent potency against neuroinflammation conditions, as evidenced by its protective effects in both 6 and 24 h of microglial activation in vitro. We further postulated the underlying mechanism of action of sulforaphane in broccoli sprouts, which was the inhibition of an inflammatory cascade via the downregulation of mitogen-activated protein kinase (MAPK) signaling. Simultaneously, sulforaphane-enriched broccoli sprouts inhibited the LPS-induced activation of the NF-κB signaling pathway and the secretions of inflammatory proteins (iNOS, COX-2, TNF-α, IL-6, IL-1β, PGE2, etc.), which are responsible for the inflammatory cascades in both acute and chronic inflammation. It also upregulated the expression of Nrf2 and HO-1 in normal and activated microglia followed by the lowered neuronal apoptosis induced by activated microglia. Based on these results, it may exhibit anti-inflammatory effects via the NF-κB and Nrf2 pathways. Interestingly, sulforaphane-enriched broccoli sprouts improved the scopolamine-induced memory impairment in mice through Nrf2 activation, inhibiting neuronal apoptosis particularly through inhibition of caspase-3 activation which could lead to the neuroprotection against neurodegenerative disorders. The present study suggests that sulforaphane-enriched broccoli sprouts might be a potential nutraceutical with antineuroinflammatory and neuroprotective activities.

Resveratrol-enriched rice (RR) was developed using genetic engineering to combine the properties of resveratrol and rice. To evaluate the effect of RR on pruritic skin inflammation in atopic dermatitis (AD)-like skin lesions, we used dinitrochlorobenzene (DNCB)-induced NC/Nga mice and an in vitro 3D skin model. Normal rice (NR), resveratrol, and RR were topically applied to mice dorsal skin, following which the dermatitis index and scratching frequency were calculated. Histological examination was performed by hematoxylin and eosin and immunohistochemistry staining of IL-31 level. The level of immunoglobulin E (IgE) and IL-31 in the serum was determined by enzyme-linked immunosorbent assay (ELISA). The cytotoxicity of RR and the expression levels of pro-inflammatory cytokines were also determined in cultured human keratinocytes and a 3D skin model. RR significantly reduced scratching frequency, decreased the dermatitis severity and trans-epidermal water loss (TEWL) and improved skin hydration in DNCB-induced NC/Nga mice. RR also significantly decreased serum IL-31 and IgE levels and suppressed the production of IL-6 in human keratinocytes and the 3D skin model. Our study indicates that the synergistic effect of rice and resveratrol manifested by the topical application of RR can serve as a potential alternative therapy for chronic skin inflammatory diseases such as AD.

Lespedeza bicolor (LB) is often used in traditional medicine to remove toxins, replenish energy stores, and regulate various symptoms of diabetes. This study aimed to explore the use of LB as a therapeutic to prevent diabetic nephropathy in methylglyoxal (MGO)-treated models in vitro and in vivo. Western blotting, immunostaining, and biochemical assays were used to obtain several experimental readouts in renal epithelial cells (LLC-PK1) and BALB/c mice. These include: production of reactive oxygen species (ROS), formation of advanced glycation end-products (AGEs), expression of receptor for advanced glycation end-products (RAGE), apoptotic cell death, glucose levels, fatty acid and triglyceride levels, expression of pro-inflammatory cytokines IL-1β and TNF-α, glyoxalase 1 (Glo1), and nuclear factor erythroid 2-related factor 2 (Nrf2). Pretreatment with LB significantly reduced MGO-induced cellular apoptosis, intracellular production of ROS, and formation of AGEs to ameliorate renal dysfunction in vitro and in vivo. Interestingly, administering LB in MGO-treated cells and mice upregulated the expression of Nrf2 and Glo1, and downregulated the expression of IL-1β and TNF-α. Moreover, LB reduced MGO-induced AGE accumulation and RAGE expression in the kidneys, which subsequently reduced AGE-RAGE interactions. Overall, LB ameliorates renal cell apoptosis and corrects renal dysfunction in MGO-treated mice. These findings extend our understanding of the pathogenic mechanism of MGO-induced nephrotoxicity and regulation of the AGE/RAGE axis by Lespedeza bicolor.

Our studies indicate that PUL ameliorates atopic dermatitis-like symptoms by suppressing the proinflammatory cytokines and immune stimuli in both in vitro and in vivo animal models. Therefore, these data suggest that PUL might be an effective natural resource for the treatment of AD.

Pyrus ussuriensis Maxim, a pear commonly known as “Sandolbae” in Korea, is used as a traditional herbal medicine for asthma, cough, and fever in Korea, China, and Japan. P. ussuriensis Maxim leaves (PUL) have therapeutic effects on atopic dermatitis (AD). However, there are no reports on the efficacy of specific components of PUL. In the present study, activity-guided isolation of PUL was used to determine the compounds with potent activity. Astragalin was identified as the major component of the chloroform-soluble fraction of PUL (PULC) using High-performance liquid chromatography (HPLC) analysis. Astragalin and PULC were tested in vitro and in vivo for their effects against AD. PULC and astragalin dose-dependently inhibited the production of nitric oxide (NO) in mouse macrophage (RAW 264.7) cells, and interleukin (IL)-6 and IL-1β in tumor necrosis factor (TNF-α)/interferon γ (IFNγ) induced HaCaT cells. In the AD mice model, PULC and astragalin application significantly reduced dermatitis severity, scratching behavior, and trans-epidermal water loss (TEWL) when compared to that of 2, 4-dinitrochlorobenzene-treated NC/Nga mice. Additionally, they normalized skin barrier function by decreasing immunoglobulin E (IgE) levels in the serum. Filaggrin and involucrin protein levels were normalized by PULC treatment in HaCaT cells and skin lesions. These results indicate that PULC and astragalin ameliorate AD-like symptoms by alleviating both pro-inflammatory cytokines and immune stimuli in vitro and in vivo in animal models. Therefore, PULC and astragalin might be effective therapeutic agents for the treatment of AD.