川芎嗪通过AMPK/NF-κB和Nrf-2/HO-1途径减轻过敏性气道炎症和氧化应激的实验研究

目的 本研究旨在探讨川芎嗪对过敏性炎症反应和氧化应激的影响,并探讨其机制是否与AMPK/NF-κB和Nrf-2/HO-1信号通路有关.方法 用组织化学染色来观察小鼠肺组织病理学改变;小鼠支气管肺泡灌洗液(bronchoalveolar lavage fluid,BALF)中炎症细胞数量用Diff-quik染色法检测;用...     

Perindopril Ameliorates Hepatic Ischemia Reperfusion Injury Via Regulation of NF-κB-p65/TLR-4, JAK1/STAT-3, Nrf-2, and PI3K/Akt/mTOR Signaling Pathways

Hepatic ischemia reperfusion (IR) is an inevitable clinical problem for surgical procedures such as liver transplantation and liver resection. This study was designed to evaluate the protective effect of perindopril (PER) against hepatic IR injury. Thirty-two rats were used and randomly allocated into four groups. Sham control group was subjected to sham operation and received saline only, IR group was subjected to IR and received vehicle, PER group was pretreated with PER (one milligram per kilogram per day i.p. for 10 consecutive days), and IR+PER group was pretreated with PER then subjected to IR. Liver function biomarkers (aspartate aminotransferase and alanine aminotransferase), oxidative stress (glutathione, malondialdehyde, myeloperoxidase, and superoxide dismutase) and inflammation markers (tumor necrosis factor-alpha, interferon-gamma, and inteleukin-10 [IL-10]), mRNA expression of NF-κB-p65 and TLR-4, as well as protein expression of JAK1, STAT-3, PI3K, mTOR, Akt, and Nrf-2 were investigated concomitantly with histopathological examination. The results indicated that, hepatic IR induced a significant alteration in liver function biomarkers and structure, oxidative stress, and inflammation. At the molecular level, up-regulation of NF-κB-p65, TLR-4, JAK1, and STAT-3 concomitantly with down-regulation of Nrf-2, IL-10, PI3K, Akt, and mTOR were observed. These disturbances were alleviated by pretreatment of IR rats with PER in concomitant with hepatic structural improvement. Conclusively, the protective effect of PER presumably may be relevant to its ability to reduce oxidative stress, ameliorate the inflammatory processes, and modify the related signaling pathways. Anat Rec, 2019. © 2019 American Association for Anatomy Anat Rec, 303:1935–1949, 2020. © 2019 American Association for Anatomy     

Aster yomena suppresses LPS-induced cyclooxygenase-2 and inducible nitric oxide synthase expression

Inflammation is a pathological process that is known to be involved in numerous diseases. Microbial infection or tissue injury activates inflammatory responses, resulting in the induction of proinflammatory proteins including cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS). Aster yomena is used in traditional Korean remedies to treat cough, asthma, and insect bites. Here, we investigated the effects of A. yomena extract (EAY) on the expression of COX-2 and iNOS induced by LPS. EAY inhibited NF-κB activation and IκBα degradation induced by LPS. EAY suppressed LPS-induced COX-2 and iNOS expression which are the target genes regulated through NF-κB activation in macrophages. EAY also suppressed LPS-induced nitrite production. These results suggest that EAY has the potential to be developed as a potent anti-inflammatory drug.     

Anti-inflammatory effects of embelin in A549 cells and human asthmatic airway epithelial tissues

Objective: Allergic asthma is the most common type in asthma, which is defined as a chronic inflammatory disease of the lung. In this study, we investigated whether embelin (Emb), the major component of Ardisia japonica BL. (AJB), exhibits anti-inflammatory effects on allergic asthma via inhibition of NF-κB activity using A549 cells and asthmatic airway epithelial tissues.

Methods: Inflammation was induced in A549 cells, a human airway epithelial cell line, by IL-1β (10?ng/ml) treatment for 4?h. The effects of Emb on NF-κB activity and COX-2 protein expression in inflamed airway epithelial cells and human asthmatic airway epithelial tissues were analyzed via western blot. The secretion levels of NF-κB-mediated cytokines/chemokines, including IL-4, 6, 9, 13, TNF-α and eotaxin, were measured by a multiplex assay.

Results: Emb significantly blocked NF-κB activity in IL-1β-treated A549 cells and human asthmatic airway epithelial tissues. COX-2 expression was also reduced in both IL-1β-treated A549 cells and asthmatic tissues Emb application. Emb significantly reduced the secretion of IL-4, IL-6 and eotaxin in human asthmatic airway epithelial tissues by inhibiting activity of NF-κB.

Conclusions: The results of this study suggest that Emb may be used as an anti-inflammatory agent via inhibition of NF-κB and related cytokines.     

RETRACTED: Immunotoxicity activity from various organic solvents extract of Allium genus from South Korea against Aedes aegypti L.

Background: Glucagon-like peptide-1 (GLP-1) and its analogues are reported to exert wide-ranging cardiovascular actions in preclinical and clinical studies. We thus investigated whether the GLP-1 receptor agonist, exendin-4, has inhibitory effects on LPS-stimulated inflammatory response in cardiomyoblasts.

Methods: H9c2 cardiomyoblasts were exposed to LPS and treated with exendin-4. Expressions of proinflammatory mediators were assessed using quantitative real-time PCR. Nuclear localization of NF-κB was examined using immunoblotting. mRNA expression of inducible nitric oxide synthase (iNOS) and nitric oxide (NO) production were evaluated by q PCR and NO assay. Furthermore, anti-apoptotic effect of exendin-4 in LPS-stimulated H9c2 cells was determined using qPCR and immunoblot.

Results: Exposure to LPS increased mRNA expressions of TNF-α, COX-2 and MMP-9 in H9c2 cells. It also caused increases in iNOS mRNA expression and NF-κB nuclear translocation. Exendin-4 dose-dependently downregulated mRNA levels of TNF-α, COX-2 and MMP-9 in LPS-stimulated H9c2 cells. It also reduced NF-κB nuclear translocation. Treatment with exendin-4 showed no effect on LPS-induced apoptosis in H9c2 cells.

Conclusions: Exendin-4 exerts an effect on cardiomyoblast exposed to LPS by inhibiting mRNA expression of inflammatory mediators and suppressing NF-κB activation. These effects are consistent with some of the observed anti-inflammatory properties of exendin-4, as well as its beneficial actions on the cardiovascular system.     

Hesperidin alleviates oxidative stress and downregulates the expressions of proliferative and inflammatory markers in azoxymethane-induced experimental colon carcinogenesis in mice

Objective

Colon cancer is a common malignant neoplasm causing huge morbidity and mortality worldwide. Current therapeutic interventions are unsatisfying, which necessitates novel chemopreventive strategies. The present study was intended to elucidate the chemopreventive efficacy of hesperidin against azoxymethane (AOM)-induced mouse colon carcinogenesis.

Materials and methods

Swiss albino mice were subjected to intraperitoneal injections of AOM once a week for 3 consecutive weeks. Hesperidin treatments were provided in the initiation or post-initiation phases. The number and multiplicity of aberrant crypt foci (ACF), tumor incidence and antioxidant status were determined. Histopathological analyses, proliferating cell nuclear antigen (PCNA) index and modulations in the expression of inflammatory markers such as nuclear factor kappa B (NF-κB), inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) were studied.

Results

Hesperidin treatments significantly inhibited the number and multiplicities of AOM-induced ACF and tumor incidence. Hesperidin reduced oxidative stress parameters and enhanced antioxidant status. A marked decrease in the PCNA index was evident on hesperidin administration. Hesperidin treatments caused a prominent downregulation of NF-κB and its target molecules iNOS and COX-2, thereby combating inflammation.

Conclusion

This study proves the chemopreventive efficacy of hesperidin against the deleterious traits of colon carcinogenesis including accelerated proliferation, inflammation and persistent oxidative stress.     

Eupartoium makinoi suppresses lipopolysaccharide-induced inducible nitric oxide synthase and cyclooxygenase-2 expression

Inflammation is involved in numerous diseases including cancer. Inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) play important roles in the development of certain inflammatory diseases. Eupatorium makinoi, which belongs to a family of Asteraceae plants, is used medicinally in East Asia. We investigated the effects of an ethanol extract of E. makinoi (EEM) on nuclear factor-kappa B (NF-κB) activation and the expression of iNOS and COX-2 with lipopolysaccharide (TLR4 agonist) in murine macrophages. EEM suppressed NF-κB activation and iNOS and COX-2 expression induced by LPS. These results suggest that EEM may regulate TLR4 signalling pathways and this may be a useful strategy for anti-inflammatory therapies.     

Protective effect of peroxisome proliferator activator receptor (PPAR)-α and -γ ligands against methotrexate-induced nephrotoxicity

Context: The anticancer drug methotrexate (MTX) may cause multi-organ toxicities, including nephrotoxicity.

Objective: To investigate effects of peroxisome proliferator activator receptor (PPAR)-α and -γ agonists; fenofibrate (FEN) and pioglitazone (PIO), in MTX-induced nephrotoxicity in rats.

Methods: Rats were given FEN or PIO (150 or 5?mg/kg/day, respectively) orally for 15 days. MTX was injected as a single dose of 20?mg/kg, i.p. at day 11 of experiment, with or without either PPAR agonists.

Results: MTX induced renal toxicity, assessed by increase in serum urea and creatinine as well as histopathological alterations. MTX caused renal oxidative/nitrosative stress, indicated by decrease in GSH and catalase with increase in malondialdehyde and nitric oxide (NOx) levels. In addition, MTX increased renal level of the pro-inflammatory cytokine; tumor necrosis factor (TNF)-α and up-regulated the expression of both the inflammatory and apoptotic markers; NF-κB and caspase 3. Pre-administration of FEN or PIO to MTX-treated rats improved renal function and reversed oxidative/nitrosative parameters. Interestingly, pre-administration of PIO, but not FEN, decreased renal TNF-α level and NF-κB expression compared to MTX alone. Furthermore, PIO had more significant effect than FEN on reversing MTX-induced renal caspase 3 expression.

Discussion: Both FEN and PIO conferred protection against MTX-induced nephrotoxicity through comparable amelioration of oxidative/nitrosative stress. FEN lacked any effect on TNF-α/NF-κB, which was reflected on its less improvement on renal histopathology and apoptosis.

Conclusion: At indicated dosage, PPAR-γ ligand; PIO shows better improvement of MTX-induced nephrotoxicity compared to PPAR-α ligand; FEN due to differential effect on TNF-α/NF-κB inflammatory pathway.     

Berberis aristata Ameliorates Adjuvant-Induced Arthritis by Inhibition of NF-κB and Activating Nuclear Factor-E2-related Factor 2/hem Oxygenase (HO)-1 Signaling Pathway

The present study was carried out to investigate the anti-arthritic activity of Berberis aristata hydroalcoholic extract (BAHE) in formaldehyde-induced arthritis and adjuvant-induced arthritis (AIA) model. Arthritis was induced by administration of either formaldehyde (2% v/v) or CFA into the subplantar surface of the hind paw of the animal. In formaldehyde-induced arthritis and AIA, treatment of BAHE at doses 50, 100 and 200 mg/kg orally significantly decreased joint inflammation as evidenced by decrease in joint diameter and reduced inflammatory cell infiltration in histopathological examination. BAHE treatment demonstrated dose-dependent improvement in the redox status of synovium (decrease in GSH, MDA, and NO levels and increase in SOD and CAT activities). The beneficial effect of BAHE was substantiated with decreased expression of inflammatory markers such as IL-1β, IL-6, TNF-R1, and VEGF by immunohistochemistry analysis in AIA model. BAHE increased HO-1/Nrf-2 and suppressed NF-κB mRNA and protein expression in adjuvant immunized joint. Additionally, BAHE abrogated degrading enzymes, as there was decreased protein expression of MMP-3 and -9 in AIA. In conclusion, we demonstrated the anti-arthritic activity of Berberis aristata hydroalcoholic extract via the mechanism of inhibition of NF-κB and activation of Nrf-2/HO-1.     

Nitric oxide regulates stretch-induced proliferation in C2C12 myoblasts

Mechanical stretch of skeletal muscle activates nitric oxide (NO) production and is an important stimulator of satellite cell proliferation. Further, cyclooxygenase (COX) activity has been shown to promote satellite cell proliferation in response to stretch. Since COX-2 expression in skeletal muscle can be regulated by NO we sought to determine if NO is required for stretch-induced myoblast proliferation and whether supplemental NO can counter the effects of COX-2 and NF-κB inhibitors. C2C12 myoblasts were cultured for 24 h, then switched to medium containing either the NOS inhibitor, l-NAME (200 μM), the COX-2 specific inhibitor NS-398 (100 μM), the NF-κB inhibiting antioxidant, PDTC (5 mM), the nitric oxide donor, DETA-NONOate (10–100 μM) or no supplement (control) for 24 h. Subgroups of each treatment were exposed to 1 h of 15% cyclic stretch (1 Hz), and were then allowed to proliferate for 24 h before fixing. Proliferation was measured by BrdU incorporation during the last hour before fixing, and DAPI stain. Stretch induced a twofold increase in nuclear number compared to control, and this effect was completely inhibited by l-NAME, NS-398 or PDTC (P < 0.05). Although DETA-NONOate (10 μM) did not affect basal proliferation, the NO-donor augmented the stretch-induced increase in proliferation and rescued stretch-induced proliferation in NS-398-treated cells, but not in PDTC-treated cells. In conclusion, NO, COX-2, and NF-κB are necessary for stretch-induced proliferation of myoblasts. Although COX-2 and NF-κB are both involved in basal proliferation, NO does not affect basal growth. Thus, NO requires the synergistic effect of stretch in order to induce muscle cell proliferation.     

孕酮抑制大鼠脑损伤后炎症反应诱导的神经细胞凋亡

目的:研究孕酮(progesterone,PROG)对大鼠脑损伤后皮质COX-2、iNOS、NF-κB和caspase-3表达的影响,以探讨PROG脑保护作用的可能机制。方法:雄性SD大鼠45只,随机分为假手术组、脑损伤组和PROG治疗组,按照改良的Feeney自由落体损伤装置制作大鼠脑损伤模型。PROG治疗组伤后1,6h腹腔注射PROG16mg/kg,各组于伤后24h取材。用免疫组织化学法及免疫蛋白印迹法,观察大鼠皮质COX-2、iNOS、NF-κB和caspase-3的免疫阳性细胞数和蛋白表达水平变化。结果:与假手术组大鼠相比,脑损伤组大鼠皮质COX-2、iN-OS、NF-κB和caspase-3阳性细胞数和蛋白表达水平较假手术组COX-2、iNOS、NF-κB和caspase-3显著增加(P0.05);PROG治疗组与脑损伤组比较,大鼠皮质COX-2、iNOS、NF-κB和caspase-3阳性细胞数和蛋白表达水平明显减少(P0.05)。结论:PROG可通过抑制NF-κB的活化,阻断NF-κB和iNOS自身强化的炎症反应过程,降低COX-2、caspase-3的表达,抑制脑损伤后的炎症反应和细胞凋亡,从而发挥脑保护作用。     

Hepatoprotective effect of parthenolide in rat model of nonalcoholic fatty liver disease

Context: The active ingredients of traditional medical herbs have been the focus of scientific interests.

Objective: This study was designed to explore the mechanisms of actions of parthenolide on nonalcoholic fatty liver disease (NAFLD).

Materials and methods: Thirty-five male Wistar rats were fed high-fat diet (HFD) for eight weeks with or without an intraperitoneal injection of parthenolide to develop NAFLD. Liver triacylglycerol (TG), total antioxidant capacity (TAC), total oxidative status (TOS), thiobarbituric acid reactant substances (TBARs), total thiol groups and tumor necrosis factor alpha (TNF-α) and cytochrome P4502E1 (CYP2E1) levels as well as liver ALT, AST and catalase activities were determined. In addition, quantitative real-time PCR was performed to obtain hepatic gene expression levels of TNF-α, CYP2E1 and nuclear factor-κB (NF-κB).

Results: HFD caused a significant weight gain and increased liver TG content as well as alteration in ALT and AST activities, which were attenuated after administration of parthenoide (p?p?κB and CYP2E1 at the both gene expression and protein levels were found associated with necroinflammatory changes in histopathological observations and were abrogated almost completely after parthenolide treatment. Oxidative and inflammatory changes observed in HFD fed rats were indicative of NAFLD, which were suppressed with parthenolide treatment.

Conclusions: Based on these results, parthenolide might be a candidate agent for preventing NAFLD due to its anti-inflammatory and anti-oxidative potency.     

Spirodela polyrhiza (L.) Sch. ethanolic extract inhibits LPS-induced inflammation in RAW264.7 cells

Objective: Spirodela polyrhiza (L.) Sch. is widely used in Korean traditional medicine. No previous work has investigated in detail the anti-inflammatory activities of S. polyrhiza or assessed in vitro their potential underlying mechanism(s). We assessed the effects of S. polyrhiza ethanolic extract (SPEE) on the production of inflammatory mediators in lipopolysaccharide (LPS)-stimulated RAW264.7 cells and investigated some potential underlying mechanisms. Additionally, we performed simultaneous determination of seven flavonoids in S. polyrhiza by high-performance liquid chromatography (HPLC)-photodiode array (PDA).

Materials and methods: RAW264.7 cells were subjected to 5, 10, 20, and 50 μg/mL of SPEE for 1 h then treated with LPS for 24 h. Production of namely nitric oxide (NO), prostaglandin E₂ and cytokine levels were measured by the Griess reagent and ELISA, respectively. To investigate the underlying mechanisms of the anti-inflammatory activities of SPEE, expression of NO synthase (iNOS), cyclooxygenase-2 (COX-2), and nuclear factor-kappa B (NF-κB) proteins were evaluated by western blot analysis. HPLC analysis was performed using a Gemini C₁₈ column at 40°C and PDA detection at 340 nm.

Results: SPEE treatment significantly inhibited the LPS-induced production of NO, prostaglandin E₂, interleukin-6, and tumor necrosis factor-α and inhibited the expression of iNOS and COX-2 via attenuation of NF-κB p65 expression. The contents of the seven flavonoids in S. polyrhiza range from 0.25 to 8.77 mg/g.

Conclusions: These results indicate that the anti-inflammatory activity of SPEE may be NF-κB p65 signaling. Also, the method will help to improve quality control of S. polyrhiza.     

Beta-naphthoflavone inhibits LPS-induced inflammation in BV-2 cells via AKT/Nrf-2/HO-1-NF-κB signaling axis

Numerous studies have shown that over-activation of microglia could cause neuroinflammation and release pro-inflammatory mediators, which could result in neurodegenerative diseases, like Parkinson’s disease, Alzheimer’s disease etc. Beta-naphthoflavone (BNF) has anti-oxidant and anti-inflammatory effects in borderline tissues, but BNF has not been reported the effect associated with neuroinflammation. Therefore, the purpose of this experiment is to inquiry the impact and mechanism of BNF on neuroinflammation. The results indicated that BNF significantly inhibited the production of pro-inflammatory mediators (inducible nitric-oxide synthase (iNOS), Cyclooxygenase-2 (COX-2), tumor necrosis factor-α (TNF-α) andinterleukin-6 (IL-6)) in LPS-exposed BV-2 cells. Analysis of western blot results found that BNF accelerated the activation of AKT/Nrf-2/HO-1 signaling pathway and suppressed NF-κB pathway activation. Further study showed that BNF inhibited activation of NF-κB pathway via promoting HO-1, and SnPP IX (a HO-1 inhibitor) could inhibit anti-inflammatory function of BNF. We also found that BNF reduced the apoptosis rate of Human neuroblastoma cells (SHSY5Y) and mouse hippocampal neuron cell line (HT22) by inhibiting release of inflammatory mediators in LPS-exposed BV2 cells. In a word, our results suggested that BNF could inhibit inflammatory response via AKT/Nrf-2/HO-1-NF-κB signaling axis in BV-2 cells and exerts neuroprotective impact via inhibiting the activation of BV2 cells.     

Dioscorin Pre-treatment Protects A549 Human Airway Epithelial Cells from Hydrogen Peroxide-Induced Oxidative Stress

Hydrogen peroxide (H₂O₂) is a highly reactive oxygen species involved in lung and bronchial epithelium injury. Increased H₂O₂ levels have been reported in expired breath condensates of patients with inflammatory airway diseases such as chronic obstructive pulmonary disease. Protecting airway epithelial cells from oxidative stress is an important task in the prevention and management of airway diseases. Previous studies demonstrate that yam (Dioscorea batatas Decne) has antioxidant and anti-trypsin activities. This study evaluated the validity of dioscorin in vitro. The results showed that dioscorin attenuated the alteration of H₂O₂ on G2/M cell cycle arrest. This might be associated with the activation of IκB and subsequent inactivation of NF-κB. Furthermore, dioscorin suppressed IL-8 secretion and reduced changes of adhesion molecule expressions in H₂O₂-injured A549 cells. These results help in understanding the potential of traditional Chinese herbal medicine as treatment for airway inflammatory diseases.     

Gomisin A decreases the LPS-induced expression of iNOS and COX-2 and activation of RIP2/NF-κB in mouse peritoneal macrophages

Gomisin A (GA), a lignan component contained in the fruit of Schisandra chinensis Baillon, improves hepatic cell degeneration, vasodilatory activity and insulin sensitivity. These effects also impact the immune system, including various inflammatory mediators and cytokines. In this study, the anti-inflammatory effect of GA on lipopolysaccharide-stimulated mouse peritoneal macrophages was studied. Pretreatment with GA attenuated the expression of receptor-interacting protein 2 (RIP2) and IκB kinase-β (IKK-β) as well as IKK-β phosphorylation. The activation of nuclear factor-kappa B (NF-κB) in the nucleus, the phosphorylation of IκBα and degradation of IκBα in the cytosol were suppressed by GA. GA decreased the production and mRNA expression of the inflammatory cytokines tumor necrosis factor-alpha (TNF-α) and interleukin (IL)-6. In addition, expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) and production of nitric oxide were decreased by pretreatment with GA. In conclusion, these results show that the anti-inflammatory properties of GA potentially result from the inhibition of COX-2, iNOS, IL-6, TNF-α and NO through the down-regulation of RIP2 and NF-κB activation. These results impact the development of potential health products for preventing and treating inflammatory diseases.     

Anti-Inflammatory Mechanism of a Folk Herbal Medicine,Duchesnea indica (Andr) Focke at RAW264.7 Cell Line

This study is to explore the anti-inflammatory mechanism of the ethanol extract of Duchesnea indica (Andr) Focke. An inflammatory cellular model was established by addition of lipopolysaccharide (LPS) on RAW264.7 cell line. The cellular secretion of TNF-α, IL-1β, IL-6, NO and IL-10 in supernatant, mRNA expression of TNF-α, COX-2, iNOS and HO-1, protein expression of COX-2 and HO-1, and activation of NF-κB were assayed by ELISA, the Griess method, real-time quantitative PCR, and Western blot and immunocytochemistry method, respectively. The ethanol extract of D. indica not only reduced production of pro-inflammatory cytokines and mediators and blocked NF-κB activation, but also slightly promoted release of the anti-inflammatory mediator HO-1 and suppressed IL-10 secretion. In conclusion, the anti-inflammatory effects of the extract of D. indica are attributed to the suppression of pro-inflammatory cytokines and mediators by blocking NF-κB activation. The extract of D. indica can also slightly promote HO-1 production to reduce inflammation.     

Inhibition of visfatin alleviates sepsis-induced intestinal damage by inhibiting Hippo signaling pathway

Background

The aim of this study is to investigate role of Visfatin, one of the pro-inflammatory adipokines, in sepsis-induced intestinal injury and to clarify the potential mechanism.

Methods

C57BL/6 mice underwent cecal ligation and puncture (CLP) surgery to establish sepsis model in vivo. Intestinal epithelial cells were stimulated with LPS to mimic sepsis-induced intestinal injury in vitro. FK866 (the inhibitor of Visfatin) with or without XMU-MP-1 (the inhibitor of Hippo signaling) was applied for treatment. The expression levels of Visfatin, NF-κB and Hippo signaling pathways-related proteins were detected by western blot or immunohistochemistry. The intestinal cell apoptosis and intestinal injury were investigated by TUNEL staining and H&E staining, respectively. ELISA was used to determine the production of inflammatory cytokines.

Results

The expression of Visfatin increased in CLP mice. FK866 reduced intestinal pathological injury, inflammatory cytokines production, and intestinal cell apoptosis in sepsis mice. Meanwhile, FK866 affected NF-κB and Hippo signaling pathways. Additionally, the effects of FK866 on inflammatory response, apoptosis, Hippo signaling and NF-κB signaling were partly abolished by XMU-MP-1, the inhibitor of Hippo signaling. In vitro experiments also revealed that FK866 exhibited a protective role against LPS-induced inflammatory response and apoptosis in intestinal cells, as well as regulating NF-κB and Hippo signaling, whereas addition of XMU-MP-1 weakened the protective effects of FK866.

Conclusion

In short, this study demonstrated that inhibition of Visfatin might alleviate sepsis-induced intestinal injury through Hippo signaling pathway, supporting a further research on Visfatin as a therapeutic target.