Moringa Isothiocyanate Activates Nrf2: Potential Role in Diabetic Nephropathy.

Abstract

Moringa isothiocyanate (MIC-1) is the main active isothiocyanate found in Moringa oleifera, a plant consumed as diet and traditional herbal medicine. Compared to sulforaphane (SFN), MICs are less studied and most work have focused on its anti-inflammatory activity. The purpose of this study is to better understand the Nrf2-ARE antioxidant activity of MIC-1 and its potential in diabetic nephropathy. MIC-1 showed little toxicity from 1.25-5 μM. MIC-1 activated Nrf2-ARE at similar levels to SFN. MIC-1 also increased gene expression of downstream Nrf2 genes NQO1, HO-1, and GCLC. Protein expression of HO-1 and GCLC was elevated in MIC-1-treated cells versus control. MIC-1 suppressed pro-inflammatory cytokines in LPS-stimulated macrophages. MIC-1 reduced levels of reactive oxygen species in high glucose (HG)-treated human renal proximal tubule HK-2 cells. RNA-seq was performed to examine the transcriptome in HK-2 cells exposed to HG with or without MIC-1. Ingenuity Pathway Analysis (IPA) of RNA-seq on HK-2 cells exposed to HG identified TGFβ1 and NQO1 regulation as potentially impacted and treatment of HG-exposed HK-2 cells with MIC-1 reversed the gene expression of these two pathways. Results implicate that the transcriptional regulator TGFβ1 signaling is activated by HG and that MIC-1 can inhibit HG-stimulated TGFβ1 activation. In summary, MIC-1 activates Nrf2-ARE signaling, increases expression of Nrf2 target genes, and suppresses inflammation, while also reducing oxidative stress and possibly TGFβ1 signaling in high glucose induced renal cells. Taken together, it appears that one potential therapeutic strategy for managing DN and is currently under development in clinic is Nrf2 activation.

• Authors: David Cheng, Linbo Gao, Shan Su, Davit Sargsyan, Renyi Wu, Ilya Raskin, Ah-Ng Kong
• Journal: The AAPS journal (AAPS J) Vol. 21 Issue 2 Pg. 31 (02 19 2019) ISSN: 1550-7416 [Electronic] United States
• PMID: 30783799 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antioxidants
• Isothiocyanates
• NF-E2-Related Factor 2
• NFE2L2 protein, human
• Plant Extracts
• Reactive Oxygen Species
• TGFB1 protein, human
• Transforming Growth Factor beta1
• NAD(P)H Dehydrogenase (Quinone)
• NQO1 protein, human
• Glucose

Topics

• Antioxidant Response Elements
• Antioxidants (pharmacology, therapeutic use)
• Diabetic Nephropathies (drug therapy, pathology)
• Drug Evaluation, Preclinical
• Epithelial Cells
• Gene Expression Profiling
• Glucose (metabolism)
• Hep G2 Cells
• Humans
• Isothiocyanates (pharmacology, therapeutic use)
• Kidney Tubules, Proximal (cytology)
• Macrophages
• Moringa (chemistry)
• NAD(P)H Dehydrogenase (Quinone) (metabolism)
• NF-E2-Related Factor 2 (genetics, metabolism)
• Oxidative Stress (drug effects, genetics)
• Plant Extracts (pharmacokinetics, therapeutic use)
• RNA-Seq
• Reactive Oxygen Species (metabolism)
• Seeds (chemistry)
• Signal Transduction (drug effects)
• Transforming Growth Factor beta1 (metabolism)