Sulforaphane Protects against High Cholesterol‐Induced Mitochondrial Bioenergetics Impairments, Inflammation, and Oxidative Stress and Preserves Pancreatic β‐Cells Function

Abstract

Cholesterol plays an important role in inducing pancreatic β-cell dysfunction, leading to an impaired insulin secretory response to glucose. This study aimed to determine the protective effects of sulforaphane, a natural isothiocyanate Nrf2-inducer, against cholesterol-induced pancreatic β-cells dysfunction, through molecular and cellular mechanisms involving mitochondrial bioenergetics. Sulforaphane prevented cholesterol-induced alterations in the coupling efficiency of mitochondrial respiration, improving ATP turnover and spare capacity, and averted the impairment of the electron flow at complexes I, II, and IV. Sulforaphane also attenuated the cholesterol-induced activation of the NFκB pathway, normalizing the expression of pro- and anti-inflammatory cytokines. In addition, it also inhibited the decrease in sirtuin 1 expression and greatly increased Pgc-1α expression in Min6 cells. Sulforaphane increased the expression of antioxidant enzymes downstream of the Nrf2 pathway and prevented lipid peroxidation induced by cholesterol. The antioxidant and anti-inflammatory properties of sulforaphane and its ability to protect and improve mitochondrial bioenergetic function contribute to its protective action against cholesterol-induced pancreatic β-cell dysfunction. Our data provide a scientifically tested foundation upon which sulforaphane can be developed as nutraceutical to preserve β-cell function and eventually control hyperglycemia.

Association of NF-E2 Related Factor 2 (Nrf2) and inflammatory cytokines in recent onset Type 2 Diabetes Mellitus

“…Moreover, Nrf2 knockout mice are found to be highly prone to oxidative and inflammatory insults 42 , 43 . Few studies demonstrated that, insulin secretion was inhibited in pancreatic β-cells due to cytokine and glucose insult and restored by Nrf2 activation 10 , 44 . These results are consistent with our present findings that, Nrf2 activator showed an impact on insulin secretion process via Nrf2 signaling cascade 10 .…”

Sulforaphane-Loaded Ultradeformable Vesicles as A Potential Natural Nanomedicine for the Treatment of Skin Cancer Diseases

“…The attention given to this natural compound is constantly growing due to its multiple pharmacological activities. It has been demonstrated that sulforaphane is effective in brain and neuronal injury with neuroprotective effects [1,2]; in renal [3,4] and liver damage models [5]; in hyperglycemia and β-cell damage [6]; and in damage to the heart, cardiac cells, and other tissues [7]. Sulforaphane is mostly characterized by its potent anticancer activity.…”

The Glucosinolates, A Sulphur Glucoside Family of Mustard Phytochemicals With Diverse Biomedical Application

“…Leukemia [87,124,[175][176][177][178][179] Prostate cancer [91,95,[180][181][182] non-small cell lung cancer cells [107,183,184] Pancreatic cancer [165,[185][186][187] Breast cancer [92, 93, 101-103, 105, 108, 109, 188-195] Bladder cancer [169,[196][197][198][199][200][201] Ovarian cancer [99] HepG2 Carcinoma Cells [202][203][204][205][206] Gastric cancer [207,208] Squamous cell carcinoma [209,210] Nasopharangeal cancer [211] Melanoma [212] Glioma [173,[213][214][215] Colon cancer [110,216,217] Lung cancer [218,219]...…”