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The study investigates the potential of Rolipram a phosphodiesterase-4 inhibitor in cognitive deficits induced by streptozotocin (STZ, 3 mg/kg intracerebroventricularly) and natural ageing in mice. Morris water maze (MWM) test was employed to evaluate learning and memory of the animals. Extent of oxidative stress was measured by estimating the levels of brain glutathione (GSH) and thiobarbituric acid reactive species (TBARS). Brain acetylcholinestrase (AChE) activity was also estimated. The brain activity of myeloperoxidase (MPO) was measured as a marker of inflammation. STZ and ageing results in marked decline in MWM performance of the animals, reflecting impairment of learning and memory. STZ treated mice and aged mice exhibited a marked accentuation of AChE activity, TBARS and MPO activity along with fall in GSH level. Further the stained micrographs of STZ treated mice and aged mice indicate pathological changes, severe neutrophilic infiltration and amyloid deposition. Rolipram treatment significantly attenuated STZ induced and age related memory deficits, biochemical and histopathological alterations. The findings demonstrate the potential of Rolipram in memory dysfunctions which may probably be attributed to its anti-cholinesterase, anti-amyloid, anti-oxidative and anti-inflammatory effects. The study concludes that PDE-4 can be explored as a potential therapeutic target in dementia. [ABSTRACT FROM AUTHOR]

Introduction: Ischemia–reperfusion injury (IRI) is the inexplicable aggravation of cellular dysfunction that results in blood flow restoration to previously ischemic tissues. COX mediates the oxidative conversion of AA to various prostaglandins and thromboxanes, which are involved in various physiological and pathological processes. In the pathophysiology of I/R injuries, COX has been found to play an important role. I/R injuries affect most vital organs and are characterized by inflammation, oxidative stress, cell death, and apoptosis, leading to morbidity and mortality. Materials and methods: A systematic literature review of Bentham, Scopus, PubMed, Medline, and EMBASE (Elsevier) databases was carried out to understand the Nature and mechanistic interventions of the Cyclooxygenase modulations in ischemic injury. Here, we have discussed the COX Physiology and downstream signalling pathways modulated by COX, e.g., Camp Pathway, Peroxisome Proliferator-Activated Receptor Activity, NF-kB Signalling, PI3K/Akt Signalling in ischemic injury. Conclusion: This review will discuss the various COX types, specifically COX-1 and COX-2, which are involved in developing I/R injury in organs such as the brain, spinal cord, heart, kidney, liver, and intestine. [ABSTRACT FROM AUTHOR]

Nrf2-mediated activation of antioxidant response element is a central part of molecular mechanisms governing the protective function of phase II detoxification and antioxidant enzymes against carcinogenesis, oxidative stress, and inflammation. Nrf2 is sequestered in the cytoplasm by its repressor, Keap1. We have designed and synthesized novel chalcone derivatives as Nrf2 activators. The potency of these compounds was measured by the expression of Nrf2 dependent antioxidant genes GCLM, NQO1, and HO1 in human lung epithelial cells, while the cytotoxicity was analyzed using MTT assay. In vivo potency of identified lead compounds to activate Nrf2 was evaluated using a mouse model. Our studies showed 2-trifluoromethyl-2′-methoxychalone (2b) to be a potent activator of Nrf2, both in vitro and in mice. Additional experiments showed that the activation of Nrf2 by this compound is independent of reactive oxygen species or redox changes. We have discussed a quantitative structure–activity relationship and proposed a possible mechanism of Nrf2 activation. [ABSTRACT FROM AUTHOR]

Skin aging is caused by exposure to various external factors. Ultraviolet B (UVB) irradiation induces oxidative stress, photoaging, and inflammation in skin cells. Pinus densiflora Sieb. et Zucc. (red pine) has various antimicrobial and antioxidant activities. However, the anti-inflammatory effects of red pine on skin have rarely been reported. The protective effects of malonic acid (MA) isolated from Pinus densiflora were investigated against UVB-induced damage in an immortalized human keratinocyte cell line (HaCaT). MA increased levels of the antioxidant enzymes superoxide dismutase 1 (SOD-1) and heme oxygenase 1 (HO-1) via activation of nuclear factor-erythroid 2-related factor-2 (Nrf2), resulting in a reduction in UVB-induced reactive oxygen species (ROS) levels. Additionally, the inhibition of ROS increased HaCaT cell survival rate. Thus, MA downregulated the expression of ROS-induced nuclear factor-κB, as well as inflammation-related cytokines (interleukin-6, cyclooxygenase-2, and tumor necrosis factor-α). Furthermore, MA significantly suppressed the mitogen-activated protein kinase/activator protein 1 signaling pathway and reduced the expression of matrix metalloproteinases (MMPs; MMP-1, MMP-3, and MMP-9). In contrast, MA treatment increased the expression of collagen synthesis regulatory genes (COL1A1 and COL3A1) via regulation of Smad2/3 signal induction through transforming growth factor-β. In conclusion, MA protected against UVB-induced photoaging via suppression of skin inflammation and induction of collagen biosynthesis. [ABSTRACT FROM AUTHOR]