Curcumin Mediates a Protective Effect Via TLR-4/NF-κB Signaling Pathway in Rat Model of Severe Acute Pancreatitis

Panax notoginseng saponins are extracted from Chinese ginseng— Panax notoginseng Ledeb—and are known to have therapeutic anti-inflammatory effects. However, the precise mechanism behind their anti-inflammatory effects remains relatively unknown. To better understand how Panax notoginseng saponins exert their therapeutic benefit, we tested them in a rat model of severe acute pancreatitis (SAP). Rats received a tail vein injection of Panax notoginseng saponins and were administered 5% sodium taurocholate 2 h later. Pancreatic tissue was then harvested and levels of miR-181b, FSTL1, TREM1, TLR4, TRAF6, IRAK1, p-Akt, p-p38MAPK, NF-κBp65, and p-IκB-α were determined using Western blot and quantitative real-time polymerase chain reaction (qRT-PCR). Enzyme-linked immunosorbent assays were used to determine serum levels of tumor necrosis factor-α (TNF-α), TREM1, interleukin (IL)-6, ACAM-1, IL-8, and IL-12 and DNA-bound levels of NF-KB65 and TLR4 in pancreatic and ileum tissue. Serum levels of lipase and amylase, pancreatic myeloperoxidase (MPO) activity, and pancreatic water content were also measured. Hematoxylin and eosin staining was used for all histological analyses. Results indicated upregulation of miR-181b, but negligible levels of FSTL1, p-p38MAPK, TLR4, TRAF6, p-Akt, IRAK1, TREM1, p-NF-κBp65, and p-IκB-α, as well as negligible DNA-bound levels of NF-KB65 and TLR4. We also observed lower levels of IL-8, IL-6, ACAM-1, TNF-α, MPO, and IL-12 in the Panax notoginseng saponin–treated group when compared with controls. In addition, Panax notoginseng saponin–treated rats had significantly reduced serum levels of lipase and amylase. Histological analyses confirmed that Panax notoginseng saponin treatment significantly reduced taurocholate-induced pancreatic inflammation. Collectively, our results suggest that Panax notoginseng saponin treatment attenuated acute pancreatitis and pancreatic inflammation by increasing miR-181b signaling. These findings suggest that Panax notoginseng saponins have therapeutic potential in the treatment of taurocholate-induced SAP.

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Protective Effect of Tetrandrine on Sodium Taurocholate-Induced Severe Acute Pancreatitis

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2015/129103 ◽

2015 ◽

Vol 2015 ◽

pp. 1-8 ◽

Cited By ~ 3

Author(s):

Xian-lin Wu ◽

Jie-xing Li ◽

Zhen-dong Li ◽

Da-sheng Liu ◽

Su-hong Lu ◽

...

Keyword(s):

Acute Pancreatitis ◽

Free Radical ◽

Bile Duct ◽

Systemic Inflammatory Response Syndrome ◽

Inflammatory Response ◽

Protective Effect ◽

Severe Acute Pancreatitis ◽

Sodium Taurocholate ◽

Multiple Organ ◽

Multiple Organ Dysfunction

Tet is a type of alkaloid extracted fromStephania tetrandra, and it has recently been demonstrated that Tet can protect against inflammation and free radical injury and inhibit the release of inflammatory mediators. The present study was designed to observe the protective effect of Tet on sodium taurocholate-induced severe acute pancreatitis (SAP). The rat model of SAP was induced by retrograde bile duct injection of sodium taurocholate and then treated with Verapamil and Tet. The results showed that Tet can reduce NF-κB activation in pancreas issue, inhibit the SAP cascade, and improve SAP through inducing pancreas acinar cell apoptosis and stabilizing intracellular calcium in the pancreas, thus mitigating the damage to the pancreas. Our study revealed that Tet may reduce systemic inflammatory response syndrome (SIRS) and multiple organ dysfunction syndromes (MODS) to protect against damage, and these roles may be mediated through the NF-κB pathway to improve the proinflammatory/anti-inflammatory imbalance.

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Saikosaponin A-Induced Gut Microbiota Changes Attenuate Severe Acute Pancreatitis through the Activation of Keap1/Nrf2-ARE Antioxidant Signaling

Oxidative Medicine and Cellular Longevity ◽

10.1155/2020/9217219 ◽

2020 ◽

Vol 2020 ◽

pp. 1-19

Author(s):

Jing Li ◽

Jinfeng Han ◽

Juan Lv ◽

Shiji Wang ◽

Lai Qu ◽

...

Keyword(s):

Oxidative Stress ◽

Acute Pancreatitis ◽

Gut Microbiota ◽

Severe Acute Pancreatitis ◽

Rat Model ◽

Inflammatory Responses ◽

Standard Diet ◽

Microbiota Composition ◽

Serum Lipase ◽

Saikosaponin A

Objective. Severe acute pancreatitis (SAP) is a serious and life-threatening disease associated with multiple organ failure and a high mortality rate and is accompanied by distinct oxidative stress and inflammatory responses. Saikosaponin A has strong antioxidant properties and can affect the composition of gut microbiota. We sought to determine the effects of Saikosaponin A interventions on SAP by investigating the changes of gut microbiota and related antioxidant signaling. Methods. A SAP model was established in Sprague-Dawley (SD) rats through the injection of sodium taurocholate into the biliopancreatic duct and confirmed by elevated levels of serum lipase and amylase. The model was fed a standard diet either with saline solution or with Saikosaponin A. Fecal microbiota transplantation (FMT) from Saikosaponin A-induced rats into the rat model was performed to test the effects of gut microbiota. The composition of gut microbiota was analyzed by using 16S rRNA gene sequencing. We measured apoptotic status, inflammatory biomarkers, and Keap1-Nrf2-ARE ((Kelch-like ECH-associated protein 1) nuclear factor erythroid 2-related factor 2-antioxidant response element) antioxidant signaling. Results. Saikosaponin A intervention attenuated SAP lesions and reduced the levels of serum amylase and lipase, oxidative stress, and inflammatory responses by reducing pathological scores and affecting the serum level of oxidative and inflammatory factors. Meanwhile, the expression of Keap1-Nrf2-ARE was increased. Saikosaponin A intervention improved microbiota composition by increasing the relative abundance of Lactobacillus and Prevotella species. FMT resulted in similar results as those caused by the Saikosaponin A intervention, suggesting Saikosaponin A may exert its function via the improvement of gut microbiota composition. Conclusions. Saikosaponin A-induced gut microbiota changes attenuate SAP progression in the rat model and may be a potential natural drug for adjuvant treatment of SAP. Further work is needed to clear up the points.

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The possible protective effect of Nano-Selenium on the endocrine and exocrine pancreatic functions in a rat model of acute pancreatitis

Journal of Trace Elements in Medicine and Biology ◽

10.1016/j.jtemb.2020.126480 ◽

2020 ◽

Vol 60 ◽

pp. 126480 ◽

Cited By ~ 3

Author(s):

Elshymaa A. Abdel-Hakeem ◽

Heba A. Abdel-Hamid ◽

Sara Mohamed Naguib Abdel Hafez

Keyword(s):

Acute Pancreatitis ◽

Protective Effect ◽

Rat Model

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Hsp70/Bmi1-FoxO1-SOD Signaling Pathway Contributes to the Protective Effect of Sound Conditioning against Acute Acoustic Trauma in a Rat Model

Neural Plasticity ◽

10.1155/2020/8823785 ◽

2020 ◽

Vol 2020 ◽

pp. 1-22

Author(s):

Guoxia Zhu ◽

Yongxiang Wu ◽

Yang Qiu ◽

Keyong Tian ◽

Wenjuan Mi ◽

...

Keyword(s):

Protective Effect ◽

Signaling Pathway ◽

Rat Model ◽

Molecular Mechanisms ◽

Outer Hair Cell ◽

Acoustic Trauma ◽

Auditory Brainstem Responses ◽

Ultrastructural Changes ◽

Ganglion Neurons ◽

Acute Acoustic Trauma

Sound conditioning (SC) is defined as “toughening” to lower levels of sound over time, which reduces a subsequent noise-induced threshold shift. Although the protective effect of SC in mammals is generally understood, the exact mechanisms involved have not yet been elucidated. To confirm the protective effect of SC against noise exposure (NE) and the stress-related signaling pathway of its rescue, we observed target molecule changes caused by SC of low frequency prior to NE as well as histology analysis in vivo and verified the suggested mechanisms in SGNs in vitro. Further, we investigated the potential role of Hsp70 and Bmi1 in SC by targeting SOD1 and SOD2 which are regulated by the FoxO1 signaling pathway based on mitochondrial function and reactive oxygen species (ROS) levels. Finally, we sought to identify the possible molecular mechanisms associated with the beneficial effects of SC against noise-induced trauma. Data from the rat model were evaluated by western blot, immunofluorescence, and RT-PCR. The results revealed that SC upregulated Hsp70, Bmi1, FoxO1, SOD1, and SOD2 expression in spiral ganglion neurons (SGNs). Moreover, the auditory brainstem responses (ABRs) and electron microscopy revealed that SC could protect against acute acoustic trauma (AAT) based on a significant reduction of hearing impairment and visible reduction in outer hair cell loss as well as ultrastructural changes in OHCs and SGNs. Collectively, these results suggested that the contribution of Bmi1 toward decreased sensitivity to noise-induced trauma following SC was triggered by Hsp70 induction and associated with enhancement of the antioxidant system and decreased mitochondrial superoxide accumulation. This contribution of Bmi1 was achieved by direct targeting of SOD1 and SOD2, which was regulated by FoxO1. Therefore, the Hsp70/Bmi1-FoxO1-SOD signaling pathway might contribute to the protective effect of SC against AAT in a rat model.

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