scholarly journals AdipoRon, an Orally Active, Synthetic Agonist of AdipoR1 and AdipoR2 Receptors Has Gastroprotective Effect in Experimentally Induced Gastric Ulcers in Mice

Molecules ◽  
2021 ◽  
Vol 26 (10) ◽  
pp. 2946
Author(s):  
Hubert Zatorski ◽  
Maciej Salaga ◽  
Marta Zielińska ◽  
Kinga Majchrzak ◽  
Agata Binienda ◽  
...  
Keyword(s):  
Mouse Models ◽  
Adenosine Monophosphate ◽  
Underlying Mechanism ◽  
Gastric Ulcers ◽  
Gastric Tissue ◽  
Adiponectin Receptors ◽  
Gastroprotective Effect ◽  
Microscopic Evaluation ◽  
Anti Inflammatory ◽  
Orally Active

Introduction: Adiponectin is a hormone secreted by adipocytes, which exhibits insulin-sensitizing and anti-inflammatory properties and acts through adiponectin receptors: AdipoR1 and AdipoR2. The aim of the study was to evaluate whether activation of adiponectin receptors AdipoR1 and AdipoR2 with an orally active agonist AdipoRon has gastroprotective effect and to investigate the possible underlying mechanism. Methods: We used two well-established mouse models of gastric ulcer (GU) induced by oral administration of EtOH (80% solution in water) or diclofenac (30 mg/kg, p.o.). Gastroprotective effect of AdipoRon (dose 5 and 50 mg /kg p.o) was compared to omeprazole (20 mg/kg p.o.) or 5% DMSO solution (control). Clinical parameters of gastroprotection were assessed using macroscopic (gastric lesion area) and microscopic (evaluation of the gastric mucosa damage) scoring. To establish the molecular mechanism, we measured: myeloperoxidase (MPO), superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPX) activities; glutathione (GSH) level; and IL-1β, adenosine monophosphate-activated protein kinase (AMPK), and phosphorylated AMPK expression in gastric tissue. Results: AdipoRon produced a gastroprotective effect in both GU mouse models as evidenced by significantly lower macroscopic and microscopic damage scores. AdipoRon exhibited anti-inflammatory effect by reduction in MPO activity and IL-1β expression in the gastric tissue. Moreover, AdipoRon induced antioxidative action, as demonstrated with higher GSH levels, and increased SOD and GPX activity. Conclusions: Activation of AdipoR1 and AdipoR2 using AdipoRon reduced gastric lesions and enhanced cell response to oxidative stress. Our data suggest that AdipoR1 and AdipoR2 activation may be an attractive therapeutic strategy to inhibit development of gastric ulcers.

scholarly journals Protective Effects of Anwulignan against HCl/Ethanol-Induced Acute Gastric Ulcer in Mice

2021 ◽  
Vol 2021 ◽  
pp. 1-14
Author(s):  
Jiawei Liu ◽  
Huijiao Lin ◽  
Liwei Yuan ◽  
Dan Wang ◽  
Chunmei Wang ◽  
...  
Keyword(s):  
Gastric Ulcer ◽  
Signaling Pathway ◽  
Interleukin 2 ◽  
Gastrointestinal Diseases ◽  
Interleukin 10 ◽  
Interleukin 4 ◽  
Gastric Ulcers ◽  
Protective Effects ◽  
Gastric Tissue ◽  
Anti Inflammatory

Gastric ulcer is one of the most common gastrointestinal diseases. Anwulignan (AN) is a major active component of Schisandra sphenanthera Rehd. This study was designed to evaluate the protective effect of AN against the acute gastric ulcer induced by HCl/ethanol in mice. The mice were given HCl/ethanol by gavage to establish an acute gastric ulcer model. Then, the serum and gastric tissue samples were taken for biochemical analyses. The results showed that the pretreatment with AN could significantly reduce the gastric ulcer index (GUI) and increase the ulcer inhibition rate, indicating that AN can protect against gastric ulcers. AN showed its antioxidant roles by decreasing the content of reactive oxygen species (ROS), malondialdehyde (MDA), and 8-hydroxydeoxyguanosine (8-OHdG) and increasing the activity of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) and anti-inflammatory roles by decreasing the content of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), interleukin-1β (IL-1β), and myeloperoxidase (MPO) and increasing the content of interleukin-2 (IL-2), interleukin-4 (IL-4), interleukin-10 (IL-10), prostaglandin E2 (PGE2), and nitric oxide (NO) in both serum and gastric tissue. Furthermore, AN also activated the NRF2/ARE signaling pathway and inhibited the MAPK/NF-κB signaling pathway. AN improves the acute gastric ulcer induced by HCl/ethanol in mice, which may be mainly through its antioxidant capacity and anti-inflammatory effect.

scholarly journals Cryptotanshinone ameliorates CUS-induced depressive-like behaviors in mice

2021 ◽  
Vol 12 (1) ◽  
pp. 469-481
Author(s):  
Kaixin Wang ◽  
Qingling Zhai ◽  
Sanwang Wang ◽  
Qiongyu Li ◽  
Jing Liu ◽  
...  
Keyword(s):  
Salvia Miltiorrhiza ◽  
Adenosine Monophosphate ◽  
Underlying Mechanism ◽  
Antidepressant Effect ◽  
Tyrosine Kinase Receptor ◽  
Expression Levels ◽  
Microglial Polarization ◽  
Protein Levels ◽  
Arginase 1 ◽  
Anti Inflammatory

Abstract Objectives Cryptotanshinone (CPT), a natural quinoid diterpene, isolated from Salvia miltiorrhiza, has shown various pharmacological properties. However, its effect on chronic unpredictable stress (CUS)-induced depression phenotypes and the underlying mechanism remain unclear. Therefore, the aim of this study was to investigate whether CPT could exert an antidepressant effect. Methods We investigated the effects of CPT in a CUS-induced depression model and explored whether these effects were related to the anti-inflammatory and neurogenesis promoting properties by investigating the expression levels of various signaling molecules at the mRNA and protein levels. Results Administration of CPT improved depression-like behaviors in CUS-induced mice. CPT administration increased the levels of doublecortin-positive cells and reversed the decrease in the expression levels of brain-derived neurotrophic factor (BDNF)/tyrosine kinase receptor B (TrkB) signaling transduction, as well as the downstream functional proteins, phosphorylated extracellular regulated protein kinases (p-ERK), and cyclic adenosine monophosphate (cAMP)-response element-binding protein levels (p-CREB) in hippocampus. CPT treatment also inhibited the activation of microglia and suppressed M1 microglial polarization, while promoting M2 microglial polarization by monitoring the expression levels of arginase 1 (Arg-1) and inducible nitric oxide synthase (iNOS), and further inhibited the expression of proinflammatory cytokines, including interleukin (IL)-1, IL-6, and tumor necrosis factor-α (TNF-α), and increased the expression of the anti-inflammatory cytokine IL-10 by regulating nuclear factor-κB (NF-κB) activation. Conclusions CPT relieves the depressive-like state in CUS-induced mice by enhancing neurogenesis and inhibiting inflammation through the BDNF/TrkB and NF-κB pathways and could therefore serve as a promising candidate for the treatment of depression.

scholarly journals The Gastroprotective Effect of Naringenin against Ethanol-Induced Gastric Ulcers in Mice through Inhibiting Oxidative and Inflammatory Responses

2021 ◽  
Vol 22 (21) ◽  
pp. 11985
Author(s):  
Wei-Sung Li ◽  
Shih-Chao Lin ◽  
Chien-Hui Chu ◽  
Yu-Kang Chang ◽  
Xiang Zhang ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Inflammatory Responses ◽  
Therapeutic Potential ◽  
Mapk Signaling ◽  
Mitogen Activated Protein Kinase ◽  
Gastric Ulcers ◽  
Gastroprotective Effect ◽  
Tnf Α ◽  
Anti Inflammatory

Naringenin is a major flavanone found in grapes, tangelos, blood oranges, lemons, pummelo, and tangerines. It is known to have anti-inflammatory, antioxidant, anticancer, antimutagenic, antifibrogenic, and antiatherogenic pharmacological properties. This study aims to investigate the anti-inflammatory effects of naringenin in ethanol-induced gastric damage in vivo and ethanol-stimulated KATO III cells in vitro. Our results showed that pretreatment with naringenin significantly protected mice from ethanol-induced hemorrhagic damage, epithelial cell loss, and edema with leucocytes. It reduced gastric ulcers (GU) by suppressing ethanol-induced nuclear factor-κB (NF-κB) activity and decreasing the levels of nitric oxide (NO), malondialdehyde (MDA), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), interleukin-8 (IL-8), and myeloperoxidase (MPO). In addition, pretreatment with naringenin might inhibit the secretion of TNF-α, IL-6, and IL-8, as well as the proteins cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) via the suppression of NF-κB and mitogen-activated protein kinase (MAPK) signaling in ethanol-stimulated stomach epithelial KATO III cells. Together, the results of this study highlight the gastroprotective effect of naringenin in GU of mice by inhibiting gastric secretion and acidity, reducing inflammation and oxidative stress, suppressing NF-κB activity, and restoring the histological architecture. These findings suggested that naringenin has therapeutic potential in the alleviation of ethanol-induced GU.

scholarly journals Duhaldea pterocaula (Franch.) Anderb. Attenuates Nociception and Inflammation via GABAA Receptors

2021 ◽  
Vol 12 ◽  
Author(s):  
Chunli Huang ◽  
Changsheng Dong ◽  
Yanan Zhu ◽  
Yang Yu ◽  
Huizi Jin ◽  
...  
Keyword(s):  
Mouse Models ◽  
Gabaa Receptors ◽  
Inflammatory Pain ◽  
Therapeutic Agent ◽  
Biological Activities ◽  
Folk Medicine ◽  
Underlying Mechanism ◽  
Pharmacological Effects ◽  
Analgesic Effects ◽  
Anti Inflammatory

Duhaldea pterocaula (Franch.) Anderb, also known as Inula pterocaula Franch (I. pterocaula), is a folk medicine of the Yi nationality in China. The Inula plants display various biological activities, including anti-nociceptive and anti-inflammatory properties. I. pterocaula has been traditionally used for the treatment of bronchitis, vasculitis, and dizziness. However, very few studies have been reported on the pharmacology of I. pterocaula. The present study aims to characterize the anti-nociceptive and anti-inflammatory properties of I. pterocaula and explore the underlying mechanism. I. pterocaula was extracted by 95% ethanol and further portioned with petroleum ether, ethyl acetate (EA) and n-butanol, sequentially, to obtain corresponding factions with different polarities. The EA fraction (IPEA) was found to be one of the most effective fractions. It demonstrated potent analgesic effects in both acute and inflammatory pain mouse models, and caused no anti-nociceptive tolerance. Furthermore, IPEA improved the tolerance of mice to morphine. IPEA also showed potent anti-inflammatory effects on LPS-induced septic mice. BIC, a GABAAR antagonist, reversed the effects of IPEA in pain and inflammation models. Collectively, GABAARs play a key role in the pharmacological effects of IPEA. I. pterocaula may be useful as a complementary or alternative therapeutic agent for the treatment of pain and inflammation.

scholarly journals Artemisinin protects against sepsis-associated encephalopathy by activating the AMPK axis in the microglia

2019 ◽  
Author(s):  
Shao-Peng Lin ◽  
Jue-Xian Wei ◽  
Shan Ye ◽  
Jiasong Hu ◽  
Jingyi Bu ◽  
...  
Keyword(s):  
Nuclear Translocation ◽  
Neuronal Damage ◽  
Immunohistochemical Analysis ◽  
Adenosine Monophosphate ◽  
Underlying Mechanism ◽  
Protective Mechanism ◽  
Protective Effects ◽  
Bv2 Cells ◽  
Anti Inflammatory

Abstract Background and purpose: Artemisinin has been in use as an anti-malarial drug for almost half a century in the world. There is growing evidence that artemisinin also possesses potent anti-inflammatory and immunoregulatory properties. However, the efficacy of artemisinin treatment in sepsis-associated encephalopathy (SAE) remains unknown. Here, we evaluate the possible protective effects and explore the underlying mechanism of action of artemisinin on SAE. Methods: Male C57BL/6mice were pretreated with either vehicle or artemisinin, and then injected with LPS to establish an animal model of SAE. The cognitive function was then assessed using the Morris water maze. Neuronal damage and neuroinflammation in the hippocampus were evaluated by immunohistochemical analysis. Additionally, the protective mechanism of artemisinin was determined in vitro. Results: The results showed that artemisinin preconditioning attenuated LPS-induced cognitive impairment, neural damage, and microglial activation in the mouse brain. Luminex liquid chip revealed that artemisinin could inhibit the pro-inflammatory cytokines and chemokines induced by LPS in the BV2 microglia cells. Meanwhile, artemisinin suppressed the migratory ability of BV2 cells. Western blot demonstrated that artemisinin promoted adenosine monophosphate-activated protein kinaseα1 (AMPKα1) expression and suppressed nuclear translocation of NF-κB. Furthermore, knock-down of AMPKα1 markedly abolished the anti-inflammatory effects of artemisinin when exposed to LPS. Conclusion: Artemisinin is a potential therapeutic agent for SAE, and its effect was probably mediated by the activation of AMPKα1signalling pathway in microglia.

HG-9-91-01 Attenuates Murine Experimental Colitis by Promoting Interleukin-10 Production in Colonic Macrophages Through the SIK/CRTC3 Pathway

2021 ◽  
Author(s):  
Yong Fu ◽  
Gailing Ma ◽  
Yuqian Zhang ◽  
Wenli Wang ◽  
Tongguo Shi ◽  
...  
Keyword(s):  
Mononuclear Cells ◽  
Experimental Colitis ◽  
Underlying Mechanism ◽  
Interleukin 10 ◽  
Camp Response Element Binding ◽  
Cellular Level ◽  
Trinitrobenzene Sulfonic Acid ◽  
Murine Colitis ◽  
Anti Inflammatory

Abstract Background Interleukin-10 (IL-10) is a potent immunoregulatory cytokine that plays a pivotal role in maintaining mucosal immune homeostasis. As a novel synthetic inhibitor of salt-inducible kinases (SIKs), HG-9-91-01 can effectively enhance IL-10 secretion at the cellular level, but its in vivo immunoregulatory effects remain unclear. In this study, we investigated the effects and underlying mechanism of HG-9-91-01 in murine colitis models. Methods The anti-inflammatory effects of HG-9-91-01 were evaluated on 2, 4, 6-trinitrobenzene sulfonic acid (TNBS)-, dextran sulfate sodium–induced colitis mice, and IL-10 knockout chronic colitis mice. The in vivo effector cell of HG-9-91-01 was identified by fluorescence-activated cell sorting and quantitative real-time polymerase chain reaction. The underlying mechanism of HG-9-91-01 was investigated via overexpressing SIKs in ANA-1 macrophages and TNBS colitis mice. Results Treatment with HG-9-91-01 showed favorable anticolitis effects in both TNBS- and DSS-treated mice through significantly promoting IL-10 expression in colonic macrophages but failed to protect against IL-10 KO murine colitis. Further study indicated that HG-9-91-01 markedly enhanced the nuclear level of cAMP response element-binding protein (CREB)-regulated transcription coactivator 3 (CRTC3), whereas treatment with lentiviruses encoding SIK protein markedly decreased the nuclear CRTC3 level in HG-9-91-01–treated ANA-1 macrophages. In addition, intracolonic administration with lentiviruses encoding SIK protein significantly decreased the nuclear CRTC3 level in the lamina propria mononuclear cells and ended the anti-inflammatory activities of HG-9-91-01. Conclusions We found that HG-9-91-01 promoted the IL-10 expression of colonic macrophages and exhibited its anticolitis activity through the SIK/CRTC3 axis, and thus it may represent a promising strategy for inflammatory bowel disease therapy.

CDP840. A prototype of a novel class of orally active anti-Inflammatory phosphodiesterase 4 inhibitors

2002 ◽  
Vol 12 (11) ◽  
pp. 1451-1456 ◽  
Author(s):  
R.P. Alexander ◽  
G.J. Warrellow ◽  
M.A.W. Eaton ◽  
E.C. Boyd ◽  
J.C. Head ◽  
...  
Keyword(s):  
Phosphodiesterase 4 ◽  
Phosphodiesterase 4 Inhibitors ◽  
Anti Inflammatory ◽  
Orally Active

scholarly journals Dibenzoylthiamine Has Powerful Antioxidant and Anti-Inflammatory Properties in Cultured Cells and in Mouse Models of Stress and Neurodegeneration

Biomedicines ◽  
2020 ◽  
Vol 8 (9) ◽  
pp. 361
Author(s):  
Margaux Sambon ◽  
Anna Gorlova ◽  
Alice Demelenne ◽  
Judit Alhama-Riba ◽  
Bernard Coumans ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Neurodegenerative Diseases ◽  
Cell Line ◽  
Mouse Models ◽  
Cultured Cells ◽  
Therapeutic Potential ◽  
Motor Dysfunction ◽  
Oxidative Stress Marker ◽  
Bv2 Cells ◽  
Anti Inflammatory

Thiamine precursors, the most studied being benfotiamine (BFT), have protective effects in mouse models of neurodegenerative diseases. BFT decreased oxidative stress and inflammation, two major characteristics of neurodegenerative diseases, in a neuroblastoma cell line (Neuro2a) and an immortalized brain microglial cell line (BV2). Here, we tested the potential antioxidant and anti-inflammatory effects of the hitherto unexplored derivative O,S-dibenzoylthiamine (DBT) in these two cell lines. We show that DBT protects Neuro2a cells against paraquat (PQ) toxicity by counteracting oxidative stress at low concentrations and increases the synthesis of reduced glutathione and NADPH in a Nrf2-independent manner. In BV2 cells activated by lipopolysaccharides (LPS), DBT significantly decreased inflammation by suppressing translocation of NF-κB to the nucleus. Our results also demonstrate the superiority of DBT over thiamine and other thiamine precursors, including BFT, in all of the in vitro models. Finally, we show that the chronic administration of DBT arrested motor dysfunction in FUS transgenic mice, a model of amyotrophic lateral sclerosis, and it reduced depressive-like behavior in a mouse model of ultrasound-induced stress in which it normalized oxidative stress marker levels in the brain. Together, our data suggest that DBT may have therapeutic potential for brain pathology associated with oxidative stress and inflammation by novel, coenzyme-independent mechanisms.

Anti-inflammatory, analgesic activity, and toxicity of Pituranthos scoparius stem extract: An ethnopharmacological study in rat and mouse models

2020 ◽  
Vol 258 ◽  
pp. 112936 ◽  
Author(s):  
Ahlem Karbab ◽  
Kamel Mokhnache ◽  
Soraya Ouhida ◽  
Noureddine Charef ◽  
Farida Djabi ◽  
...  
Keyword(s):  
Mouse Models ◽  
Analgesic Activity ◽  
Stem Extract ◽  
Anti Inflammatory

scholarly journals Flaxseed orbitides, linusorbs, inhibit LPS-induced THP-1 macrophage inflammation

RSC Advances ◽  
2020 ◽  
Vol 10 (38) ◽  
pp. 22622-22630
Author(s):  
Xian-Guo Zou ◽  
Youn Young Shim ◽  
Jae Youl Cho ◽  
Deok Jeong ◽  
Jian Yang ◽  
...  
Keyword(s):  
Inflammatory Response ◽  
Cyclic Peptides ◽  
Underlying Mechanism ◽  
Anti Inflammatory

Linusorbs (flax orbitides) are a family of plant cyclic peptides. We investigate the anti-inflammatory activities of two different linusorbs ([1–9-NaC]-linusorb B2 and [1–9-NaC]-linusorb B3) and the underlying mechanism of this inflammatory response.

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