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Acute kidney injury (AKI) is a major side effect of cisplatin, a crucial anticancer agent. Therefore, it is necessary to develop drugs to protect against cisplatin-induced nephrotoxicity. Ojeoksan (OJS), a traditional blended herbal prescription, is mostly used in Korea; however, there are no reports on the efficacy of OJS against cisplatin-induced AKI. To investigate the reno-protective effect of OJS on AKI, we orally administered 50, 100, and 200 mg/kg of OJS to mice 1 h before intraperitoneal injection with 20 mg/kg of cisplatin. OJS inhibited the increase of blood urea nitrogen (BUN) and serum creatinine (SCr) levels and reduced histological changes in the kidney, like loss of brush borders, renal tubular necrosis, and cast formation. Administration of OSJ reduced the levels of pro-inflammatory cytokines, such as interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α. In addition, OJS inhibited the mitogen-activated protein kinase (MAPK) and nuclear factor kappa B (NF-κB) pathways in cisplatin-induced AKI. These results suggest that OJS attenuates cisplatin-induced AKI by downregulating the MAPK and NF-κB pathways. [ABSTRACT FROM AUTHOR]

Microglial activation-mediated neuroinflammation is associated with the pathogenesis of neurodegenerative disorders. Therefore, the management of microglial cell activation and their inflammatory response is an important therapeutic approach for preventing neurodegenerative diseases. Quercus acuta Thunb. (QA) (Fagaceae) is a tree found in Korea, China, and Japan. The current study investigated the anti-neuroinflammatory effects of QA and its mechanism of action in lipopolysaccharide (LPS)-stimulated BV2 microglial cells. Pretreatment with a methanol extract of dried QA stems (QAE) inhibited the production of nitric oxide and proinflammatory cytokines and decreased the expression of inducible nitric oxide synthase, cyclooxygenase-2 in LPS-stimulated BV2 microglial cells. Furthermore, it inhibited the phosphorylation and degradation of inhibitory κBα and decreased the nuclear translocation and phosphorylation of nuclear factor-κB (NF-κB). Moreover, QAE inhibited the phosphorylation of extracellular signal-regulated kinase, p38 and c-Jun N-terminal kinase, which is known as mitogen-activated protein kinase (MAPK). Additionally, QAE treatment increased heme oxygenase-1 (HO-1) expression by activating the nuclear factor erythroid 2-related factor 2 (Nrf2) signaling, thereby ameliorating LPS-induced intracellular hydrogen peroxide production. Finally, it was found that catechin and taxifolin, two phytochemicals of QAE, also reduced the expression of inflammatory mediators. These findings suggest that QA is beneficial for preventing microglia-mediated neuroinflammatory response through the inhibition of NF-κB, MAPK and the activation of Nrf2/HO-1 signaling pathways. [ABSTRACT FROM AUTHOR]

• Icariin is a potential anti-inflammatory drug for treating atherosclerosis, AD, depression, osteoarthritis, and asthma, etc. • It exerted powerful suppression on the proinflammatory signaling, such as NF-κB and MAPKs. • More importantly, it upregulated the anti-inflammatory signaling, such as GR and Nrf2. Herba Epimedii is a famous herb collected from China and Korea. It has been used for impotency, osteoporosis, and amnestic treatment for thousands of years. Icariin, a typical flavonoid compound isolated from Herba Epimedii, was reported as a potential anti-inflammatory drug. Icariside and icaritin are the two metabolites of icariin. Icariin and its metabolites have been used to treat a wide range of inflammatory diseases, such as atherosclerosis, Alzheimer's disease, depression, osteoarthritis, and asthma. They exert powerful suppression of proinflammatory signaling, such as NF-κB and MAPKs. More importantly, they can upregulate anti-inflammatory signaling, such as GR and Nrf2. In this study, we review the therapeutic effects and mechanisms of icariin and its metabolites in inflammatory diseases and provide novel insights into these potential anti-inflammatory drugs. [ABSTRACT FROM AUTHOR]

Abstract: Ethnopharmacological relevance: Extracts of the roots of Scutellaria baicalensis Georgi (Labiatae) have been widely used to relieve fever related to bacterial infection and inflammatory diseases in traditional Korean medicine and have been reported to be effective in brain diseases. These experiments were conducted to examine the effects of oral administration of Scutellaria baicalensis extracts on the rescue of memory impairments induced by chronic cerebral hypoperfusion or chronic lipopolysaccharide (LPS) infusion. In addition, the underlying mechanisms of these effects were investigated. Materials and methods: In the first experiment, chronic cerebral hypoperfusion was induced in male Wister rats by bilateral common carotid artery occlusion (BCCAo). Daily administration of Scutellaria baicalensis extracts was started on 20 day after BCCAo and given for 40 days. A Morris water maze was then used to evaluate the status of the hippocampal-dependent spatial learning and hippocampal mitogen-activated protein kinase (MAPK) signaling was examined in control rats, rats with chronic cerebral hypoperfusion, and rats with chronic cerebral hypoperfusion that was administered Scutellaria baicalensis. In the second experiment, hippocampal microglial activation was induced by chronic infusions of LPS into the fourth ventricle of Fisher-344 rat brains. Daily administration of Scutellaria baicalensis extracts was started on 7 day after the surgery of LPS infusion and given for 32 days. Spatial memory and hippocampal microglial activation was then examined in control rats with an artificial cerebrospinal fluid infusion, rats with chronic LPS infusion, and rats with chronic LPS infusion that were administered Scutellaria baicalensis. Results: Rats that received chronic cerebral hypoperfusion or chronic LPS infusion showed spatial memory impairments relative to their control rats; however, these symptoms were reduced by daily administration of Scutellaria baicalensis. Administration of Scutellaria baicalensis mitigated alterations of hippocampal MAPK signaling by chronic cerebral infusion and microglial activation by chronic LPS infusion. Conclusions: These results indicate that Scutellaria baicalensis may possess therapeutic potential for the prevention of Alzheimer''s disease and vascular dementia. [Copyright &y& Elsevier]

Abstract: Ethnopharmacological relevance: The aerial parts of the plant Physalis alkekengi L. var. franchetii (PA) are traditionally used in folk medicine to treat cough, middle ear infection, sore throat, abscesses, and urinary problems. However, the cellular mechanisms underlying PA''s possible anti-inflammatory effects are unknown. Materials and methods: We examined the effect of a methanol extract of PA on the production of nitric oxide (NO), inducible NO synthase (iNOS), cyclooxygenase (COX)-2, tumor necrosis factor (TNF)-α, and interleukin (IL)-6. We also examined the extract''s effect on the activity of IκBα, mitogen-activated protein kinases (MAPKs) and STAT1 in macrophages stimulated by lipopolysaccharide (LPS) or LPS/interferon-γ (IFN-γ). We further fractioned the extract into chloroform and water to investigate which fraction possessed anti-inflammatory activity. Results: We found that the PA methanol extract significantly reduced the production of NO, iNOS, COX-2, TNF-α, and IL-6. The extract also inhibited LPS-induced IκBα degradation and MAPK activation as well as LPS/IFN-γ-induced STAT1 activation, effects observed at a higher concentration than that required to suppress iNOS. The chloroform fraction possessed the anti-inflammatory activity of PA by inhibiting the expression of iNOS, TNF-α and IL-6 through downregulation of IκBα degradation and MAPK activation. Conclusion: Our findings indicate that the PA methanol extract contains different anti-inflammatory compounds, some of which suppressed iNOS expression and some of which inhibited IκBα degradation and MAPK activity. Further research is warranted to identify these anti-inflammatory components of PA and validate its use in animal studies. [Copyright &y& Elsevier]

Abstract: Prodigiosin was isolated from marine bacteria Hahella chejuensis which has been recently discovered from Marado, Cheju Island, Republic of Korea. Immunosuppressive properties have been reported for prodigiosin members such as undecylprodigiosin, metacycloprodigiosin, prodigiosin and its synthetic analogue PNU156804 (PNU). However, the effect of this agent on macrophage function has not been characterized in detail. In the present study, we examined the effects of prodigiosin on the production of inflammatory cytokines and nitric oxide (NO) in lipopolysaccharide (LPS)-activated murine macrophage. When thioglycollate-elicited macrophages pre-exposed to prodigiosin (1–100 ng/ml) were stimulated with LPS, pretreatment with prodigiosin resulted in the inhibition of NO production and inducible nitric oxide synthase (iNOS) protein and mRNA expression in a concentration-dependent manner. In contrast, the production of pro-inflammatory cytokines such as tumor necrosis factor-α (TNF-α), interleukin-1 (IL-1) and IL-6 was not altered. Inhibition of iNOS protein expression appears to be at the transcriptional level, since prodigiosin decreased LPS-induced NF-κB activity through preventing the degradation of IkBα, with significant inhibition achieved following pretreatment with prodigiosin. However, prodigiosin did not exert any effect on AP-1 activity. Prodigiosin blocked phosphorylation of p38 mitogen-activated protein kinase (MAPK) and c-Jun NH2-terminal kinase (JNK), but not that of extracellular signal-regulated kinase 1/2 (ERK 1/2). These results indicate that the inhibition of these signaling molecules expression was correlated with the reduced production of NO in macrophages. Taken together, the present data suggest that prodigiosin reduces NO production and iNOS expression by inhibiting LPS-triggered p38 MAPK and JNK phosphorylation and NF-κB activation, thereby implicating a mechanism by which prodigiosin may exert its immunosuppressive effects. [Copyright &y& Elsevier]

Juglans mandshurica Maxim., a traditional folk medicinal plant, is widely distributed in Korea and China. In our previous study, we isolated a new phenylpropanoid compound, 4-((1R,2R)-3-hydroxy-1-(4-hydroxyphenyl)-1-methoxypropan-2-yl)-2-methoxyphenol (HHMP), from J. mandshurica. In the present study, we evaluated the anti-inflammatory activity of HHMP on lipopolysaccharide (LPS)-stimulated RAW 264.7 cells and zebrafish larvae. HHMP significantly inhibited LPS-induced nitric oxide (NO) and prostaglandin E2 production in a dose-dependent manner. Moreover, HHMP treatment considerably suppressed LPS-induced expression of inducible nitric oxide synthase and cyclooxygenase-2. We also demonstrated the mechanisms of HHMP inhibition of inflammatory responses in LPS-stimulated RAW 264.7 cells via Western blot analysis and immunofluorescence staining. Furthermore, HHMP significantly inhibited NO production in LPS-stimulated zebrafish larvae. Consequently, we established that HHMP significantly inhibited the LPS-induced activation of NF-κB and MAPK and the nuclear translocation of p65 in RAW 264.7 cells. Taken together, our findings demonstrate the effect of HHMP on LPS-induced inflammatory responses in vitro and in vivo, suggesting its potential to be used as a natural anti-inflammatory agent. [ABSTRACT FROM AUTHOR]