Diosgenin Protects Against Kidney Injury and Mitochondrial Apoptosis Induced by 3‐MCPD Through the Regulation of ER Stress, Ca²⁺ Homeostasis, and Bcl2 Expression

Abstract

Scope Diosgenin (DIO) is a natural steroid sapogenin presented in various plants. It exerts anti‐oxidant, anti‐inflammatory and anti‐diabetic nephropathy properties. The present study evaluates the intervention effect of DIO on nephrotoxicity induced by food contaminant 3‐chloro‐1, 2‐propanediol (3‐MCPD) in vivo and in vitro. Methods and Results Treatment with DIO (15 mg kg−1 d−1) in Sprague‐Dawley rats for 4‐week relieves kidney injury induced by 3‐MCPD (30 mg kg−1 d−1). In vitro, DIO (2, 6, and 8 µM) alleviates cell injury and apoptosis effectively in human embryonic kidney (HEK293) cells. DIO realizes its protective function via the regulation of endoplasmic reticulum (ER) stress and mitochondrial apoptosis pathway. Blockage of ER stress by 4‐phenylbutyric acid (4‐PBA), a specific ER stress antagonist, inhibits mitochondrial apoptosis, suggesting a connection between mitochondrial apoptosis and ER stress. Furthermore, the study demonstrates that the maintenance of Ca2+ homeostasis and Bcl2 expression, two main targets of ER stress, contributes to the protection role of DIO on mitochondrial‐dependent apoptosis. In addition, DIO relieves the impairment of oxidative phosphorylation. Conclusion This study demonstrates that DIO exerts protective effect against kidney injury, mitochondrial dysfunction, and apoptosis through the inhibition of ER stress and the further maintenance of Ca2+ homeostasis and Bcl2 expression.

WITHDRAWN: GRP75 modulates endoplasmic reticulum-mitochondria coupling and accelerates Ca 2+ -dependent endothelial cells apoptosis in diabetic retinopathy

“…Disruption of ER homeostasis results in accumulation of unfolded and misfolded proteins in the ER, leading to ERS. ERS may cause cell death by inducing Ca 2+ overload, inhibiting protein synthesis and promoting apoptosis [52]. Khaled Elmasry et al…”

Diosgenin exerts an antihypertensive effect in spontaneously hypertensive rats via gut–brain communication

“…3,5,6,27 Diosgenin (as a phytochemical with multiple biological properties) has shown significant protection against various inflammatory and cardiovascular diseases. 13,15 Recent studies also demonstrate that diosgenin ameliorates dextran sulfate sodium (DSS)-induced colitis in mice through the modulation of gut microbiota and the enhancement of SCFA production. 28 Compared with DSS-induced colon injury, diosgenin improved the colon homeostasis through modulating the gut microbiota, including increases in the relative abundance of several probiotic bacteria, and decreases in the pathogenic bacteria.…”

“…Diosgenin is a sapogenin and dietary supplement derived from various plants with anti-thrombosis, anti-inflammatory, antioxidant and anti-cancer properties. 13,14 The beneficial effects of diosgenin have been observed in cardiovascular diseases, metabolic diseases, and inflammation. 13,15,16 Recently, a study found that oral administration of diosgenin prevented changes in monocrotaline-induced pulmonary and cardiac pathophysiology in rats.…”

“…13,14 The beneficial effects of diosgenin have been observed in cardiovascular diseases, metabolic diseases, and inflammation. 13,15,16 Recently, a study found that oral administration of diosgenin prevented changes in monocrotaline-induced pulmonary and cardiac pathophysiology in rats. 15 Moreover, diosgenin ameliorated monocrotaline-induced pulmonary hypertension mediated by alleviating oxidative stress and inflammation.…”

Calcium Signaling Mediates Cell Death and Crosstalk with Autophagy in Kidney Disease

“…Secondly, modulators targeting mitochondrial Ca 2+ mediate apoptotic pathways and may also be treatments for kidney disease therapy (Figure 1). Inhibition of ER stress by 4-phenylbutyric acid (4-PBA) and Diosgenin mitigates ER-associated mitochondrial apoptosis by maintaining Ca 2+ homeostasis and mitochondrial dynamics, which ameliorates 3-MCPD-induced kidney injury [105,106]. In addition, 4-PBA also decreases Porcine Circovirus Type 2 (PCV2) infection-induced apoptosis by decreasing the cytosolic and mitochondrial Ca 2+ load in porcine kidney PK-15 cells [107].…”