Anti-inflammatory effects of kinins via microglia in the central nervous system

2006 ◽  
Vol 387 (2) ◽  
pp. 167-171 ◽  
Author(s):  
Mami Noda ◽  
Helmut Kettenmann ◽  
Keiji Wada
Keyword(s):  
Biologically Active ◽  
Prostaglandin E ◽  
Active Peptides ◽  
Tnf Α ◽  
Biologically Active Peptides ◽  
Murine Microglia ◽  
Intracellular Ca ◽  
The Central Nervous System ◽  
Microglial Migration ◽  
Anti Inflammatory

Abstract Kinins are important biologically active peptides that are up-regulated after lesions in both the peripheral and central (CNS) nervous systems. Microglia are immune cells in the CNS and play an important role in the defense of the neuronal parenchyma. In cultured murine microglia, bradykinin (BK) induces mobilization of intracellular Ca2+, microglial migration, and increases the release of nitric oxide and prostaglandin E2. On the other hand, BK attenuates lipopolysaccharide-activated TNF-α and IL-1β release. These results suggest that BK functions as a signal in brain trauma and may have an anti-inflammatory role in the CNS.

scholarly journals Processed Scutellaria baicalensis Georgi Extract Alleviates LPS-Induced Inflammatory and Oxidative Stress through a Crosstalk between NF-κB and KEAP1/NRF2 Signaling in Macrophage Cells

2021 ◽  
Vol 11 (13) ◽  
pp. 6055
Author(s):  
Akhtar Ali ◽  
En-Hyung Kim ◽  
Jong-Hyun Lee ◽  
Kang-Hyun Leem ◽  
Shin Seong ◽  
...  
Keyword(s):  
Scutellaria Baicalensis ◽  
Raw 264.7 Cells ◽  
Prostaglandin E ◽  
Scutellaria Baicalensis Georgi ◽  
Anticancer Effects ◽  
Tnf Α ◽  
Clinical Benefits ◽  
Anti Oxidant ◽  
Cox 2 ◽  
Anti Inflammatory

Prolonged inflammation results in chronic diseases that can be associated with a range of factors. Medicinal plants and herbs provide synergistic benefits based on the interaction of multiple phytochemicals. The dried root of Scutellaria baicalensis Georgi and its compounds possess anti-inflammatory, anti-oxidative, and anticancer effects. Processing is a traditional method to achieve clinical benefits by improving therapeutic efficacy and lowering toxicity. In this study, we investigated the anti-inflammatory and anti-oxidant effect of processed Scutellaria baicalensis Georgi extract (PSGE) against lipopolysaccharide (LPS) stimulated RAW 264.7 cells. Data using Griess assay and ELISA showed that PSGE decreased nitric oxide and prostaglandin E2 (PGE2) levels against LPS. PSGE treatment up-regulated 15-hydroxyprostaglandin dehydrogenase (PGDH), while cyclooxygenase (COX)-2 and microsomal prostaglandin E synthase (mPGES)-1 expression did not change. Interestingly, PGE2 inhibition was regulated by prostaglandin catabolic enzyme 15-PGDH rather than COX-2/mPGES-1, enzymes essential for PGE2 synthesis. Additionally, PSGE-suppressed LPS-induced IL-6 and TNF-α production through NF-κB signaling. NF-κB release from an inactive complex was inhibited by HO-1 which blocked IκBα phosphorylation. The ROS levels lowered by PSGE were measured with the H2DCFDA probe. PSGE activated NRF2 signaling and increased antioxidant Hmox1, Nqo1, and Txn1 gene expression, while reducing KEAP1 expression. In addition, pharmacological inhibition of HO-1 confirmed that the antioxidant enzyme induction by PSGE was responsible for ROS reduction. In conclusion, PSGE demonstrated anti-inflammatory and anti-oxidant effects due to NRF2/HO-1-mediated NF-κB and ROS inhibition.

scholarly journals Fisetin inhibits lipopolysaccharide-induced inflammatory response by activating β-catenin, leading to a decrease in endotoxic shock

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Ilandarage Menu Neelaka Molagoda ◽  
Jayasingha Arachchige Chathuranga C Jayasingha ◽  
Yung Hyun Choi ◽  
Rajapaksha Gedara Prasad Tharanga Jayasooriya ◽  
Chang-Hee Kang ◽  
...  
Keyword(s):  
Glycogen Synthase ◽  
Endotoxic Shock ◽  
Inflammatory Activity ◽  
Prostaglandin E ◽  
Necrosis Factor Alpha ◽  
Zebrafish Larvae ◽  
Proinflammatory Mediators ◽  
Tnf Α ◽  
Anti Inflammatory ◽  
Gsk 3Β

AbstractFisetin is a naturally occurring flavonoid that possesses several pharmacological benefits including anti-inflammatory activity. However, its precise anti-inflammatory mechanism is not clear. In the present study, we found that fisetin significantly inhibited the expression of proinflammatory mediators, such as nitric oxide (NO) and prostaglandin E2 (PGE2), and cytokines, such as interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α), in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages. Additionally, fisetin attenuated LPS-induced mortality and abnormalities in zebrafish larvae and normalized the heart rate. Fisetin decreased the recruitment of macrophages and neutrophils to the LPS-microinjected inflammatory site in zebrafish larvae, concomitant with a significant downregulation of proinflammatory genes, such as inducible NO synthase (iNOS), cyclooxygenase-2a (COX-2a), IL-6, and TNF-α. Fisetin inhibited the nuclear localization of nuclear factor-kappa B (NF-κB), which reduced the expression of pro-inflammatory genes. Further, fisetin inactivated glycogen synthase kinase 3β (GSK-3β) via phosphorylation at Ser9, and inhibited the degradation of β-catenin, which consequently promoted the localization of β-catenin into the nucleus. The pharmacological inhibition of β-catenin with FH535 reversed the fisetin-induced anti-inflammatory activity and restored NF-κB activity, which indicated that fisetin-mediated activation of β-catenin results in the inhibition of LPS-induced NF-κB activity. In LPS-microinjected zebrafish larvae, FH535 promoted the migration of macrophages to the yolk sac and decreased resident neutrophil counts in the posterior blood island and induced high expression of iNOS and COX-2a, which was accompanied by the inhibition of fisetin-induced anti-inflammatory activity. Altogether, the current study confirmed that the dietary flavonoid, fisetin, inhibited LPS-induced inflammation and endotoxic shock through crosstalk between GSK-3β/β-catenin and the NF-κB signaling pathways.

scholarly journals Ketamine’s effect on inflammation and kynurenine pathway in depression: A systematic review

2021 ◽  
pp. 026988112110264
Author(s):  
Emma Kopra ◽  
Valeria Mondelli ◽  
Carmine Pariante ◽  
Naghmeh Nikkheslat
Keyword(s):  
Systematic Review ◽  
Animal Studies ◽  
Bipolar Depression ◽  
Strong Support ◽  
Kynurenine Pathway ◽  
Future Research ◽  
Downstream Effects ◽  
Tnf Α ◽  
The Central Nervous System ◽  
Anti Inflammatory

Background: Ketamine is a novel rapid-acting antidepressant with high efficacy in treatment-resistant patients. Its exact therapeutic mechanisms of action are unclear; however, in recent years its anti-inflammatory properties and subsequent downstream effects on tryptophan (TRP) metabolism have sparked research interest. Aim: This systematic review examined the effect of ketamine on inflammatory markers and TRP–kynurenine (KYN) pathway metabolites in patients with unipolar and bipolar depression and in animal models of depression. Methods: MEDLINE, Embase, and PsycINFO databases were searched on October 2020 (1806 to 2020). Results: Out of 807 initial results, nine human studies and 22 animal studies on rodents met the inclusion criteria. Rodent studies provided strong support for ketamine-induced decreases in pro-inflammatory cytokines, namely in interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α and indicated anti-inflammatory effects on TRP metabolism, including decreases in the enzyme indoleamine 2,3-dioxygenase (IDO). Clinical evidence was less robust with high heterogeneity between sample characteristics, but most experiments demonstrated decreases in peripheral inflammation including in IL-1β, IL-6, and TNF-α. Preliminary support was also found for reduced activation of the neurotoxic arm of the KYN pathway. Conclusion: Ketamine appears to induce anti-inflammatory effects in at least a proportion of depressed patients. Suggestions for future research include investigation of markers in the central nervous system and examination of clinical relevance of inflammatory changes.

scholarly journals Concepts for Biologically Active Peptides

2010 ◽  
Vol 16 (30) ◽  
pp. 3390-3400 ◽  
Author(s):  
Abba J. Kastin ◽  
Weihong Pan
Keyword(s):  
Biologically Active ◽  
Active Peptides ◽  
Biologically Active Peptides
Sign in / Sign up

Export Citation Format

Share Document