Bergenin inhibits palmitic acid-induced pancreatic β-cell inflammatory death via regulating NLRP3 inflammasome activation

Lei, Donghong; Sun, Yuan; Liu, Jie; Chi, Jianxiu

doi:10.21037/atm-22-3781

Cited by 5 publications

(4 citation statements)

References 44 publications

(56 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Apart from OS, inflammation and ERS have been demonstrated to be the significant factors for β-cell decline in T2DM 55 . In line with the previous study 29 , upregulated expression of the pro-inflammatory cytokines, TNF-α and IL-6, was observed in PA-induced MIN6 cells compared to normal cells. Significantly, 1,25(OH) 2 D 3 treatment reduced the expression of TNF-α and IL-6 in PA-induced MIN6 cells.…”

Section: Discussionsupporting

confidence: 92%

“…3c), suggesting the rescue of β-cell dysfunction. Inflammation has been demonstrated to be closely linked with β cell dysfunction, and PA can induce the release of pro-inflammatory mediators, such as tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) [29]. As expected, PA-induced MIN6 cells had higher expression of TNF-α and IL-6 mRNAs than control cells, which were markedly reversed by 1,25(OH) 2 D 3 pretreatments (2 and 4 nM) in a dose-dependent way (p < 0.05; ▶Fig.…”

Section: Vitamin D Mitigates Pancreatic β-Cell Impairment In Vitromentioning

confidence: 99%

See 1 more Smart Citation

Vitamin D Alleviates Type 2 Diabetes Mellitus by Mitigating Oxidative Stress-Induced Pancreatic β-Cell Impairment

Liu,

Zhang,

Shi

et al. 2023

Exp Clin Endocrinol Diabetes

View full text Add to dashboard Cite

Objective Type 2 diabetes mellitus (T2DM) is a common metabolic disorder with rising incidence worldwide. This study explored the anti-T2DM role of vitamin D, thereby providing novel therapeutic strategies. Methods C57BL/6 J mice and MIN6 cells were used to induce in vivo T2DM and damaged β-cell models, respectively. Body weights, fasting blood glucose, and fasting insulin were measured in mice. Oral glucose tolerance test (OGTT) and insulin tolerance test (ITT) were conducted on mice. Lipid indices (TG, TC, LDL-C, and HDL-C) were detected in mouse serum. Hematoxylin-eosin staining was used to evaluate pancreatic tissue injury. ELISA was used to assess insulin and oxidative stress (OS) markers (MDA, GSH, and SOD) in mice and MIN6 cells. Production of ROS was detected in islet β-cells and MIN6 cells. Cell viability and apoptosis were evaluated using CCK-8 and flow cytometry, respectively. QRT-PCR and western blotting were used to detect pro-inflammatory factors (TNF-α and IL-6) and endoplasmic reticulum stress (ERS) markers (CHOP and GRP78), respectively. Results Vitamin D reduced body weights, fasting blood glucose, and insulin and ameliorated glucose tolerance and insulin sensitivity in T2DM mice. Besides, vitamin D decreased serum TG, TC, LDL-C, and increased HDL-C in T2DM mice. Vitamin D inhibited pancreatic histopathological injury, cell apoptosis, OS, and β-cell decline in T2DM mice. Moreover, vitamin D alleviated cell death, insufficient insulin secretion, inflammation, OS, and ERS in damaged MIN6 cells. Notably, N-acetyl-L-cysteine (an OS inhibitor) enhanced these effects of vitamin D. Conclusions Vitamin D relieved T2DM symptoms by alleviating OS-induced β-cell impairment.

show abstract

Section: Discussionsupporting

confidence: 92%

Section: Vitamin D Mitigates Pancreatic β-Cell Impairment In Vitromentioning

confidence: 99%

Vitamin D Alleviates Type 2 Diabetes Mellitus by Mitigating Oxidative Stress-Induced Pancreatic β-Cell Impairment

Liu,

Zhang,

Shi

et al. 2023

Exp Clin Endocrinol Diabetes

View full text Add to dashboard Cite

show abstract

“…But other protein targets are implicated in the mechanism of action. Previous studies also suggested the binding of bergenin to the proteins NLRP3 (NOD-like receptor family-pyrin domain containing 3) inflammasome [129], antiapoptotic protein B-Cell Lymphoma 2 (Bcl-2) [130], enzyme galectin-3 [131] and several other proteins [132][133][134][135].…”

Section: Polyphenols and Flavonoidsmentioning

confidence: 94%

Traditional Uses, Pharmacology and Phytochemistry of the Medicinal Plant Flueggea virosa (Roxb. ex Willd.) Royle

Bailly

2024

Future Pharmacology

View full text Add to dashboard Cite

The white berry bush, officially Flueggea virosa (Roxb. ex Willd.) Royle is a medicinal plant distributed throughout tropical areas and traditionally used in Africa, India and China. Root decoctions are used to treat abdominal pain, whereas extracts from the aerial parts serve to treat liver and urinary diseases, inflammatory pathologies and diabetes, among other pathologies. Plant extracts have revealed antiparasitic, antimicrobial, antiepilepsy, antidiabetic, anticancer and analgesic effects. Three main categories of phytochemicals were isolated from F. virosa: polyphenols, with the lead product bergenin; terpenoids, such as the flueggenoids and related podocarpane-type diterpenoids; and many alkaloids derived from securinine and norsecurinine. A remarkable feature of S. virosa is the production of norsecurinine oligomers, including macromolecular tetramers and pentamers, such as fluevirosinines. The most potent anticancer alkaloid in the family is the dimeric indolizidine flueggine B, which was identified as a potential binder to α/β-tubulin dimer, which is a known target for securinine. This review highlights the diversity of phytochemicals identified from S. virosa and the potential therapeutic benefits of dimeric alkaloids. Studies are encouraged to further investigate the therapeutic properties of the lead compounds but also define and finesse the nutritional profile of the edible fruit.

show abstract

“…An array of different pharmaceuticals and nutriceuticals afford protection in pancreatic β-cells via the suppression of the NLRP3 inflammasome [ 176 , 177 , 178 ]. Although not investigated in pancreatic β-cells, melatonin suppresses the NLRP3 inflammasome in different cell types across the body [ 179 ], indicating another aspect to melatonin’s potential utility in T1DM treatment, as well as from locally produced pancreatic melatonin.…”

Section: Treatment Implicationsmentioning

confidence: 99%

Type I Diabetes Pathoetiology and Pathophysiology: Roles of the Gut Microbiome, Pancreatic Cellular Interactions, and the ‘Bystander’ Activation of Memory CD8+ T Cells

Anderson¹

2023

IJMS

View full text Add to dashboard Cite

Type 1 diabetes mellitus (T1DM) arises from the failure of pancreatic β-cells to produce adequate insulin, usually as a consequence of extensive pancreatic β-cell destruction. T1DM is classed as an immune-mediated condition. However, the processes that drive pancreatic β-cell apoptosis remain to be determined, resulting in a failure to prevent ongoing cellular destruction. Alteration in mitochondrial function is clearly the major pathophysiological process underpinning pancreatic β-cell loss in T1DM. As with many medical conditions, there is a growing interest in T1DM as to the role of the gut microbiome, including the interactions of gut bacteria with Candida albicans fungal infection. Gut dysbiosis and gut permeability are intimately associated with raised levels of circulating lipopolysaccharide and suppressed butyrate levels, which can act to dysregulate immune responses and systemic mitochondrial function. This manuscript reviews broad bodies of data on T1DM pathophysiology, highlighting the importance of alterations in the mitochondrial melatonergic pathway of pancreatic β-cells in driving mitochondrial dysfunction. The suppression of mitochondrial melatonin makes pancreatic β-cells susceptible to oxidative stress and dysfunctional mitophagy, partly mediated by the loss of melatonin’s induction of PTEN-induced kinase 1 (PINK1), thereby suppressing mitophagy and increasing autoimmune associated major histocompatibility complex (MHC)-1. The immediate precursor to melatonin, N-acetylserotonin (NAS), is a brain-derived neurotrophic factor (BDNF) mimic, via the activation of the BDNF receptor, TrkB. As both the full-length and truncated TrkB play powerful roles in pancreatic β-cell function and survival, NAS is another important aspect of the melatonergic pathway relevant to pancreatic β-cell destruction in T1DM. The incorporation of the mitochondrial melatonergic pathway in T1DM pathophysiology integrates wide bodies of previously disparate data on pancreatic intercellular processes. The suppression of Akkermansia muciniphila, Lactobacillus johnsonii, butyrate, and the shikimate pathway—including by bacteriophages—contributes to not only pancreatic β-cell apoptosis, but also to the bystander activation of CD8+ T cells, which increases their effector function and prevents their deselection in the thymus. The gut microbiome is therefore a significant determinant of the mitochondrial dysfunction driving pancreatic β-cell loss as well as ‘autoimmune’ effects derived from cytotoxic CD8+ T cells. This has significant future research and treatment implications.

show abstract

Bergenin inhibits palmitic acid-induced pancreatic β-cell inflammatory death via regulating NLRP3 inflammasome activation

Cited by 5 publications

References 44 publications

Vitamin D Alleviates Type 2 Diabetes Mellitus by Mitigating Oxidative Stress-Induced Pancreatic β-Cell Impairment

Vitamin D Alleviates Type 2 Diabetes Mellitus by Mitigating Oxidative Stress-Induced Pancreatic β-Cell Impairment

Traditional Uses, Pharmacology and Phytochemistry of the Medicinal Plant Flueggea virosa (Roxb. ex Willd.) Royle

Type I Diabetes Pathoetiology and Pathophysiology: Roles of the Gut Microbiome, Pancreatic Cellular Interactions, and the ‘Bystander’ Activation of Memory CD8+ T Cells

Contact Info

Product

Resources

About