Diosgenin Attenuates Cognitive Impairment in Streptozotocin-Induced Diabetic Rats: Underlying Mechanisms

Mahmoudi, Narges; Kiasalari, Zahra; Rahmani, Tayebeh; Sanaierad, Ashkan; Afshin‐Majd, Siamak; Naderi, Gholam Ali; Baluchnejadmojarad, Tourandokht; Roghani, Mehrdad

doi:10.1159/000507398

Cited by 33 publications

(21 citation statements)

References 70 publications

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“…Our preliminary studies found that diosgenin and its derivatives had anti-inflammatory and anti-oxidative stress effects [16][17][18]. The effects and mechanisms of Drug D in AP are still unknown.…”

Section: Discussionmentioning

confidence: 92%

“…Preliminary research in this laboratory found that Diosgenin (Figure 4ai) derivatives had anti-inflammatory and anti-oxidative stress effects [16][17][18]. Here, we tried to explore whether Drug D (one of Diosgenin derivatives) (Figure 4aii) acted as a GSDMD antagonist to protect AP.…”

Section: Drug D Targeting Gsdmd Protects Against L-arginine-induced N...mentioning

confidence: 99%

“…Diosgenin is a kind of natural steroidal sapogenin extracted from Dioscorea zingiberensis, which has excellent anti-inflammatory properties [16][17][18]. A relevant study has shown that dihydrodiosgenin, a diosgenin derive, prevents AP through mitochondrial protection and PI3Kγ/Akt inhibition [19].…”

Section: Introductionmentioning

confidence: 99%

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Drug D, a Diosgenin Derive, Inhibits L-Arginine-Induced Acute Pancreatitis through Meditating GSDMD in the Endoplasmic Reticulum via the TXNIP/HIF-1α Pathway

et al. 2022

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Acute pancreatitis (AP) is one of the most common causes of hospitalization for gastrointestinal diseases, with high morbidity and mortality. Endoplasmic reticulum stress (ERS) and Gasdermin D (GSDMD) mediate AP, but little is known about their mutual influence on AP. Diosgenin has excellent anti-inflammatory and antioxidant effects. This study investigated whether Diosgenin derivative D (Drug D) inhibits L-arginine-induced acute pancreatitis through meditating GSDMD in the endoplasmic reticulum (ER). Our studies were conducted in a mouse model of L-arginine-induced AP as well as in an in vitro model on mouse pancreatic acinar cells. The GSDMD accumulation in ER was found in this study, which caused ERS of acinar cells. GSDMD inhibitor Disulfiram (DSF) notably decreased the expression of GSDMD in ER and TXNIP/HIF-1α signaling. The molecular docking study indicated that there was a potential interaction between Drug D and GSDMD. Our results showed that Drug D significantly inhibited necrosis of acinar cells dose-dependently, and we also found that Drug D alleviated pancreatic necrosis and systemic inflammation by inhibiting the GSDMD accumulation in the ER of acinar cells via the TXNIP/HIF-1α pathway. Furthermore, the level of p-IRE1α (a marker of ERS) was also down-regulated by Drug D in a dose-dependent manner in AP. We also found that Drug D alleviated TXNIP up-regulation and oxidative stress in AP. Moreover, our results revealed that GSDMD-/- mitigated AP by inhibiting TXNIP/HIF-1α. Therefore, Drug D, which is extracted from Dioscorea zingiberensis, may inhibit L-arginine-induced AP by meditating GSDMD in the ER by the TXNIP /HIF-1α pathway.

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Section: Discussionmentioning

confidence: 92%

Section: Drug D Targeting Gsdmd Protects Against L-arginine-induced N...mentioning

confidence: 99%

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Drug D, a Diosgenin Derive, Inhibits L-Arginine-Induced Acute Pancreatitis through Meditating GSDMD in the Endoplasmic Reticulum via the TXNIP/HIF-1α Pathway

et al. 2022

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“…β-Sitosterol attenuates insulin resistance and high fat diet-induced detrimental changes via mediating IRS-1/AKT signaling for the management of T2DM [44]. Diosgenin ameliorates cognitive deficits in T2DM, owing to its amelioration of astrogliosis, inflammation, and oxidative stress [45]. Baicalein (10 −6 and 10 −5 mol/L) regulated glucose uptake, glycolysis, and gluconeogenesis of hepatocytes to treat T2DM [46].…”

Section: Discussionmentioning

confidence: 99%

A Network Pharmacology Approach to Investigate the Mechanism of Erjing Prescription in Type 2 Diabetes

Wang

Chu

et al. 2021

Evidence-Based Complementary and Alternative Medicine

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Erjing prescription (EJP) was an ancient formula that was recorded in the General Medical Collection of Royal Benevolence of the Song Dynasty. It has been frequently used to treat type 2 diabetes mellitus (T2DM) in the long history of China. The formula consists of Lycium barbarum L. and Polygonatum sibiricum F. Delaroche with a ratio of 1 : 1. This study aimed to identify the potential effects and mechanisms of EJP treatment T2DM. The target proteins and possible pathways of EJP in T2DM treatment were investigated by the approach of network pharmacology and real-time PCR (RT-PCR). 99 diabetes-related proteins were regulated by 56 bioactive constituents in EJP in 26 signal pathways by Cytoscape determination. According to GO analysis, 606 genes entries have been enriched. The PPI network suggested that AKT1, EGF, EGFR, MAPK1, and GSK3β proteins were core genes. Among the 26 signal pathways, the PI3K-AKT signal pathway was tested by the RT-PCR. The expression level of PI3K p85, AKT1, GSK3β, and Myc mRNA of this pathway was regulated by EJP. The study based on network pharmacology and RT-PCR analysis revealed that the blood sugar level was regulated by EJP via regulating the PI3K-AKT signal pathway. Plenty of new treatment methods for T2DM using EJP were provided by network pharmacology analysis.

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“… 10 It has also been shown to treat successfully cardiovascular diseases such as Type 2 diabetes and neurodegenerative diseases. 11 Studies have shown that diosgenin can reduce cognitive impairment, 12 aortic vascular dysfunction, 13 and kidney damage in streptozotocin‐induced diabetic rats. 14 Diosgenin can alleviate testicular injury in streptozotocin diabetic rats by reducing apoptotic oxidative stress and inflammation, 15 and inhibits renal tubular epithelial fibrosis induced by high glucose (HG) through the epithelial–mesenchymal transition pathway.…”

Section: Introductionmentioning

confidence: 99%

Diosgenin protects retinal pigment epithelial cells from inflammatory damage and oxidative stress induced by high glucose by activating AMPK/Nrf2/HO‐1 pathway

Yang

Gao

2022

Immunity Inflam & Disease

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Introduction Diosgenin is a natural steroidal compound with reported antidiabetic and many other protective properties. This study aimed to explore the protective effect of diosgenin on high‐glucose (HG)‐induced retinal pigment epithelial cells. Methods HG‐induced ARPE‐19 cells were considered as a cell model of diabetic retinopathy (DR). The viability and apoptosis of ARPE‐19 cells induced by HG treated with either diosgenin or Compound C (CC; dorsomorphin) were detected by Cell Counting Kit‐8 assay and flow cytometric analysis. The expression of apoptosis‐related proteins, inflammation‐related proteins, and AMPK/Nrf2/HO‐1 pathway‐related proteins was detected by western blotting. The levels of inflammatory cytokines and detection of oxidative stress indexes were performed using the appropriate assay kits. The messenger RNA expression of inflammatory cytokines was detected by real‐time quantitative polymerase chain reaction. Results There was no obvious effect of diosgenin on the viability of ARPE‐19 cells and the viability of ARPE‐19 cells was significantly reduced after HG induction. However, diosgenin increased the viability, inhibited the apoptosis, and reduced the inflammatory response and oxidative stress of ARPE‐19 cells induced by HG. In addition, diosgenin could activate the AMPK/Nrf2/HO‐1 pathway. CC, an AMPK inhibitor, could reverse the above changes caused by diosgenin treatment in ARPE‐19 cells induced by HG. Conclusions Diosgenin could protect ARPE‐19 cells from inflammatory damage and oxidative stress induced by HG, by activating the AMPK/Nrf2/HO‐1 pathway.

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Diosgenin Attenuates Cognitive Impairment in Streptozotocin-Induced Diabetic Rats: Underlying Mechanisms

Cited by 33 publications

References 70 publications

Drug D, a Diosgenin Derive, Inhibits L-Arginine-Induced Acute Pancreatitis through Meditating GSDMD in the Endoplasmic Reticulum via the TXNIP/HIF-1α Pathway

Drug D, a Diosgenin Derive, Inhibits L-Arginine-Induced Acute Pancreatitis through Meditating GSDMD in the Endoplasmic Reticulum via the TXNIP/HIF-1α Pathway

A Network Pharmacology Approach to Investigate the Mechanism of Erjing Prescription in Type 2 Diabetes

Diosgenin protects retinal pigment epithelial cells from inflammatory damage and oxidative stress induced by high glucose by activating AMPK/Nrf2/HO‐1 pathway

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