Johnson SL et al. (2020) Plant Foods Hum Nutr "Equol, a Blood-Brain Barrier Permeable Gut Microbial Metabolite of Dietary Isoflavone Daidzein, Exhibits Neuroprotective Effects against Neurotoxins Induced Toxicity in Human Neuroblastoma SH-SY5Y Cells and Caenorhabditis elegans."

Ma H, Seeram NP, Vattem DA, Johnson SL, Park HY, Grammas P

[Plant Foods Hum Nutr, 2020]

Emerging data support that plant food based isoflavones have ameliorating effects on a variety of neurodegenerative diseases including Parkinson's disease (PD). Our previous investigation revealed that dietary isoflavones including genistein (GEN), daidzein (DAI), and equol (EQL; a gut microbial metabolite of DAI) showed promising blood-brain barrier permeability and anti-neuroinflammatory activity in murine microglial BV2 cells. However, the neuroprotective effects of EQL against neurotoxins induced toxicity in PD related models remains unclear. Herein, EQL, along with GEN and DAI, were evaluated for their cytoprotective effect in a non-contact co-culture model with LPS-BV2-conditioned media and human neuroblastoma SH-SY5Y cells. In addition, their neuroprotective effects against PD related neurotoxins including 6-hydroxydopamine (6-OHDA) and 1-methyl-4-phenylpyridinium (MPP⁺) induced cytotoxicity were evaluated in SH-SY5Y cells. Furthermore, EQL was evaluated for its neuroprotective effects against MPP⁺ induced neurotoxicity using in vivo PD model including Caenorhabditis elegans lifespan assay. DAI (10M) and EQL (10 and 20M) showed cytoprotective effects by decreasing LPS-BV2-conditioned media induced cytotoxicity in SH-SY5Y cells by 29.2, 32.4 and 27.2%, respectively. EQL (10 and 20M) also showed neuroprotective effects by decreasing 6-OHDA and MPP⁺ induced cytotoxicity in SH-SY5Y cells by 30.6-34.5 and 17.9-18.9%, respectively. Additionally, data from the in vivo assay supported EQL's neuroprotective effect as it increases survival of C. elegans exposed to MPP⁺ from 72 to 108h. Our findings support a growing body of evidence of the neuroprotective effects of dietary isoflavones and further studies are warranted to elucidate their mechanisms of action.

Khatri V et al. (2015) J Dig Dis "Brugia malayi cystatin therapeutically ameliorates dextran sulfate sodium induced colitis in mice."

Tarnekar A, Amdare N, Reddy MV, Goswami K, Khatri V

[J Dig Dis, 2015]

OBJECTIVE: Helminth immunomodulation in host has been shown to have therapeutic implications in inflammatory bowel diseases. Herein we have evaluated the therapeutic effect of Brugia malayi recombinant cystatin (rBmCys) in a dose dependent manner on dextran sulfate sodium (DSS)-induced colitis in mice. METHODS: Anti-inflammatory activity of rBmCys on mice peritoneal exudate cells was initially checked in in vitro. BALB/c mice were fed 5% DSS for 7days to induce ulcerative colitis. Colitis mice were treated intraperitoneally (i.p.) with rBmCys (10, 25 or 50g/dose) on day 1, 3 and 5 of the DSS administration. Disease severity was assessed by evaluation of disease activity index (DAI), macroscopic and histopathological scores of colon and myeloperoxidase activity in colonic mucosa. Cytokine profiles were measured in sera and in cultured splenocytes of treated mice followed by stimulation with rBmCys. RESULTS: rBmCys showed anti-inflammatory activity in in vitro. Treatment of DSS colitis with rBmCys in mice ameliorated the overall disease severity as reflected from the significant reduction in the weight loss, DAI, mucosal edema, colon damage and myeloperoxidase activity of the colonic mucosa. While the mRNA expression of IFN-, TNF-, IL-5, IL-6 and IL-17 was down-regulated, the IL-10 expression was up-regulated in the splenocytes of colitis mice treated with rBmCys. The amelioration effect in DSS-colitis was in a dose dependent manner. CONCLUSIONS: The results of this study indicate the anti-inflammatory potential of rBmCys and provide evidential support for this protein to be used as a promising therapeutic agent in ulcerative colitis. This article is protected by copyright. All rights reserved.