Hesperidin protects against cadmium-induced pancreatitis by modulating insulin secretion, redox imbalance and iNOS/NF-ĸB signaling in rats

Aja, P. M.; Izekwe, F.I.; Famurewa, Ademola C.; Ekpono, E. U.; Nwite, Felix; Igwenyi, I. O.; Awoke, J.N.; Ani, Onyedika Gabriel; Aloke, Chinyere; Obasi, Nwogo Ajuka; Udeh, Kester U.; Ale, B. A.

doi:10.1016/j.lfs.2020.118268

Cited by 38 publications

(12 citation statements)

References 46 publications

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“…Cd also reduced PGE-2 levels. In previous studies, it has been reported that Cd triggers the in ammatory process by stimulating pro-in ammatory cytokines [22,41]. However, CRV is thought to attenuate Cd-induced oxidative stress through its antioxidant properties, thereby reducing p38 MAPK and NF-kB activation.…”

Section: Discussionmentioning

confidence: 99%

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Evaluation of Oxidative Stress, Inflammation, Apoptosis, Oxidative DNA Damage and Metalloproteinases in the Lungs of Rats Treated With Cadmium and Carvacrol

Yeşildağ

Gür

İleritürk

et al. 2021

Preprint

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Background: The potential protective properties of carvacrol (CRV), which possesses various biological and pharmacological properties, against lung toxicity caused by cadmium (Cd), a major environmental pollutant, were investigated in the present study. Methods and Results: In the study, rats were given 25 or 50 mg/kg CRV orally 30 minutes after administrating 25 mg/kg cadmium chloride for seven days. Subsequently, the levels of 8-OHdG, MMP-2, and MMP-9, as well as markers of oxidative stress, inflammation, and apoptosis, were analyzed in the lung tissue of the animals. The results revealed that CRV exhibited antioxidant characteristics and raised SOD, CAT, GPx, and CAT levels and decreased the MDA levels induced by Cd. It also suppressed proinflammatory cytokines by lowering the levels of CRV NF-kB and p38 MAPK, thus exerting an anti-inflammatory effect against Cd. It was found that the levels of Bax, Caspase-3, and cytochrome c increased by Cd were decreased by the application of CRV. CRV also showed an anti-apoptotic effect by increasing Bcl-2 levels. The levels of 8-OHdG, MMP2, and MMP9, which increased with Cd administration, were observed to reduce after treatment with CRV. Conclusions: The results show that CRV has protective properties against Cd-induced lung toxicity.

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Section: Discussionmentioning

confidence: 99%

“…Increasing evidence points to a close relationship between oxidative stress, in ammation, and apoptosis [41]. In the mechanism associated with oxidative stress, Cd decreases mitochondrial membrane potential by disrupting calcium homeostasis.…”

Section: Discussionmentioning

confidence: 99%

Evaluation of Oxidative Stress, Inflammation, Apoptosis, Oxidative DNA Damage and Metalloproteinases in the Lungs of Rats Treated With Cadmium and Carvacrol

Yeşildağ

Gür

İleritürk

et al. 2021

Preprint

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“…Anti-inflammatory Inject 4% sodium taurocholate through puncturing the pancreatic duct (SAP) [98] VEGF, SIRT1/FOXO 1 , ANG I, ANG II Induce microcirculation disturbance Inject 3% sodium taurocholate into the distant end of the common bile duct (SAP) [99] PRA, ANG II, ET, NO Induce microcirculation disturbance Retrograde infusion of 4.0% sodium taurocholate into the pancreatic duct (SAP) [100] MPO, ICAM-1 Enhance microcirculation Inject 4% sodium taurocholate through puncturing the pancreatic duct (SAP) [101] MDA, GSH-px, SOD, IL-1β, IL-10…”

Section: Tablementioning

confidence: 99%

Natural Chinese herbs for the prevention and treatment of acute pancreatitis: a narrative review

Cui

Zhou

et al. 2022

Journal of Pancreatology

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Acute pancreatitis (AP) is a disease characterized by local inflammation in the pancreas, followed by trypsin activation, and may result from multiple etiologies. Approximately 20% of AP can progress to severe acute pancreatitis (SAP), which can lead to systemic inflammatory response syndrome (SIRS) and multiple organ dysfunction syndromes (MODS). SAP mortality rates have remained high in recent years, but there are currently no specific drugs designed to reduce these rates. Clinical studies have shown that patients can reduce the symptoms of the disease and slow down the development of the disease after taking the Chinese medicine decoction. Basic studies have shown that in AP or SAP disease models, the use of Chinese medicine monomers can improve the condition of rates. These natural Chinese herbal products can improve pancreatitis, given their ability to act on multiple targets. However, they have not been widely employed clinically and studied sufficiently and thoroughly. Therefore, this review aimed to summarize the pathophysiological mechanisms underlying pancreatitis and review the potential role of natural Chinese herbs (monomers and decoctions) in clinical and basic research.

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“…Hesperidin is a plant flavonoid from citrus fruits with an emerging therapeutic potential against several disease conditions such as diabetes and other metabolic syndromes [ 28 – 31 ]. We demonstrated most recently in our lab that hesperidin could markedly increase insulin level in cadmium-induced pancreatitis in rats [ 32 ], thus opening a new horizon for the use of hesperidin in therapeutically modulating metabolic dysregulations caused by several endocrine disruptor chemicals (EDC) that find their way into the body system. In this present study, using in silico molecular docking techniques, we investigated whether one of the molecular mechanisms of BPA endocrine disruption is through its binding with FGF-21, α-amylase, and α-glucosidase and if hesperidin could interfere with this binding, thus ameliorating metabolic dysregulations elicited by BPA.…”

Section: Introductionmentioning

confidence: 99%

Hesperidin abrogates bisphenol A endocrine disruption through binding with fibroblast growth factor 21 (FGF-21), α-amylase and α-glucosidase: an in silico molecular study

Aja

Awoke

Agu

et al. 2022

Journal of Genetic Engineering and Biotechnology

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Background Fibroblast growth factor 21 (FGF-21), alpha-amylase, and alpha-glucosidase are key proteins implicated in metabolic dysregulations. Bisphenol A (BPA) is an environmental toxicant known to cause endocrine dysregulations. Hesperidin from citrus is an emerging flavonoid for metabolic diseases management. Through computational approach, we investigated the potentials of hesperidin in abrogating BPA interference in metabolism. The 3D crystal structure of the proteins (FGF-21, α-amylase, and α-glucosidase) and the ligands (BPA and hesperidin) were retrieved from the PDB and PubChem database respectively. Using Autodock plugin Pyrx, molecular docking of the ligands and individual proteins were performed to ascertain their binding affinities and their potentials to compete for the same binding site. Validation of the docking study was considered as the ability of the ligands to bind at the same site of each proteins. The docking poses were visualized using UCSF Chimera and Discovery Studio 2020, respectively to reveal each of the protein-ligands interactions within the binding pockets. Using SwissAdme and AdmeSar servers, we further investigated hesperidin’s ADMET profile. Hesperidin used was purchased commercially. Results Hesperidin and BPA competitively bound to the same site on each protein. Interestingly, hesperidin had greater binding affinities (Kcal/mol) − 5.80, − 9.60, and − 9.60 than BPA (Kcal/mol) − 4.40, − 7.20, − 7.10 for FGF-21, α-amylase, and α-glucosidase respectively. Visualizations of the binding poses showed that hesperidin interacted with stronger bonds than BPA within the proteins’ pockets. Although hesperidin violated Lipinski rule of five, this however can be optimized through structural modifications. Conclusions Hesperidin may be an emerging natural product with promising therapeutic potentials against metabolic and endocrine derangement.

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Hesperidin protects against cadmium-induced pancreatitis by modulating insulin secretion, redox imbalance and iNOS/NF-ĸB signaling in rats

Cited by 38 publications

References 46 publications

Evaluation of Oxidative Stress, Inflammation, Apoptosis, Oxidative DNA Damage and Metalloproteinases in the Lungs of Rats Treated With Cadmium and Carvacrol

Evaluation of Oxidative Stress, Inflammation, Apoptosis, Oxidative DNA Damage and Metalloproteinases in the Lungs of Rats Treated With Cadmium and Carvacrol

Natural Chinese herbs for the prevention and treatment of acute pancreatitis: a narrative review

Hesperidin abrogates bisphenol A endocrine disruption through binding with fibroblast growth factor 21 (FGF-21), α-amylase and α-glucosidase: an in silico molecular study

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