<p>The Protective Effects of Cryptochlorogenic Acid on β-Cells Function in Diabetes in vivo and vitro via Inhibition of Ferroptosis</p>

Abstract

Purpose: Mulberry leaf extract has exerted better antidiabetic activities, while the effects of major active components in mulberry leaf extract are still unclear. Cryptochlorogenic acid (CCA) as the major active component in mulberry leaf extracts was investigated herein. Materials and Methods: Rats were treated with 50mg/kg streptozotocin for the establishment of diabetic model in vivo, and cells were treated with 33.3 mM glucose for the establishment of cell model in vitro. HE staining assay was performed for observation of pancreatic pathology and aldehyde fuchsin staining assay for examining islet cell numbers. The iron content was detected via Perls staining assay with iron assay kit (ab83366). The malondialdehyde (MDA), glutathione (GSH) and oxidized glutathione (GSSG) were detected by corresponding kits. Real-time quantitative polymerase chain reaction (RT-qPCR) was performed for assessment of gene level and Western blot for measurement of protein expression level. The cell survival was detected via CCK-8 assay. Results: The blood glucose level, iron content, accumulation of lipid peroxides and islet injury in diabetic model were all improved by CCA via a concentration-dependent manner. CCA functions via inhibition of ferroptosis by activation of cystine/glutamate transporter system (XC − )/glutathione peroxidase 4(GPX4)/Nrf2 and inhibition of nuclear receptor coactivator 4 (NCOA4) in diabetes. Conclusion: CCA exerted excellent antidiabetic effects via inhibition of ferroptosis, so it may be a promising agent for diabetes therapy, providing a new avenue for diabetes treatment.

Naringenin alleviates myocardial ischemia/reperfusion injury by regulating the nuclear factor-erythroid factor 2-related factor 2 (Nrf2) /System xc-/ glutathione peroxidase 4 (GPX4) axis to inhibit ferroptosis

“…In addition, Nrf2 is a key protein to maintain iron homeostasis. The activation of Nrf2 can increase ferritin, an iron storage protein, and activated the antioxidant system that supplements the antioxidant function of GPX [ 29 ]. In addition, NAR and trimetazidine have protective effects on oxidative stress and myocardial injury at the distal end of acute kidney injury via Nrf 2 regulation [ 30 ].…”

Dihydrotanshinone I inhibits human glioma cell proliferation via the activation of ferroptosis

“…GSH and GSSG constitute an important cellular antioxidant system that provides a reducing environment for the reduction of oxidative substances. GPX4 is an important regulator of ferroptosis, the absence of which causes a sharp increase in GSSG, leading to a reduction in the GSH/GSSG ratio ( 39 ) GSH and GSSG constitute a critical cellular antioxidant system and provide a reducing environment to reduce oxidative species. The loss of GPX4 activity can cause a drastic increase in GSSG, leading to a decrease in the GSH/GSSG ratio and ultimately ferroptosis ( 30 ).…”

Ferroptosis and Its Potential Role in Metabolic Diseases: A Curse or Revitalization?

“…Bilirubin may protect the islet by raising GPX4, upregulating Nrf2/HO-1 and chelating iron to interdict ferroptosis (Yao et al, 2020). Cryptochlorogenic acid (CCA), the active constituent of the mulberry leaf, was reported to target some major regulators (system Xc-GPX4, Nrf2 and NCOA4) to inhibit ferroptosis in a concentration-dependent manner in a diabetic model (Zhou, 2020). Similarly, in T2DM, a natural iron chelator, quercetin, may also exert a positive effect to reverse pancreatic iron deposition as an inhibitor of ferroptosis (Li D. et al, 2020).…”