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They promote Aβ deposition and TAU hyperphosphorylation aggravating and increasing the progression of AD. Moreover, they affect the processing of senile plaques and produce abnormal TAU phosphorylation. CONCLUSION There is no cure for AD but the therapeutic potential of chemokines to control the development of the disease may be a field of study to consider in the future. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.CONTEXT Yokukansan is a traditional Japanese herbal medicine that has an antiallodynic effect in patients with chronic pain. However, the mechanisms by which yokukansan inhibits neuropathic pain are unclear. OBJECTIVE To investigate the molecular effects of yokukansan on neuroinflammation in U373 MG glioblastoma astrocytoma cells, which express a functional high-affinity neurokinin 1 receptor (substance P receptor), and produce interleukin (IL)-6 and IL-8 in response to stimulation by substance P (SP). MATERIALS AND METHODS We assessed the effect of yokukansan on expression of ERK1/2, P38 MAPK, nuclear factor (NF)-κB, and cyclooxygenase-2 (COX-2) in U373 cells by western blot assay. Levels of IL-6 and IL-8 in conditioned medium obtained after stimulation of cells with SP for 24 h were measured by enzyme-linked immunosorbent assay. All experiments were conducted in triplicate. Results were analyzed by one-way ANOVA, and significance was accepted at p less then 0.05. RESULTS Yokukansan suppressed SP-induced production of IL-6 and IL-8 by U373 MG cells, and downregulated SP-induced COX-2 expression. Yokukansan also inhibited phosphorylation of ERK1/2 and p38 MAPK, as well as nuclear translocation of NF-B, induced by SP stimulation of U373 MG cells. CONCLUSION Yokukansan exhibits anti-inflammatory activity by suppressing SP-induced production of IL-6 and IL-8 and downregulating COX-2 expression in U373 MG cells, possibly via inhibition of the activation of signaling molecules, such as ERK1/2, p38 MAPK, and NF-κB. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.BACKGROUND The present study was convened to evaluate the mitigating effects of Asiatic acid (AA), on the changes in carbohydrate metabolism, insulin signaling molecules and renal function markers in streptozotocin (STZ)-nicotinamide (NAD) induced diabetic rats. METHODS AA (20 mg/kg BW) was supplemented orally to the diabetic rats for 42 days. The levels of plasma glucose, hemoglobin (Hb), glycosylated hemoglobin (HbA1c) insulin and renal function markers, carbohydrate metabolic enzymes in the kidney and insulin signaling molecules in skeletal muscle were measured. RESULTS The administration of AA elicited a significant decrease in the levels of plasma glucose, insulin resistance, HbA1c, urea, uric acid, creatinine, glycogen, glycogen synthase, glucose-6-phosphatase, and fructose-1,6-bisphosphatase and a significant increase of body weight development, insulin, Hb, hexokinase, and glycogen phosphorylase and mRNA expressions of insulin signaling molecule like insulin receptor 1, insulin receptor 2 and glucose transporter-4 in the STZ-NAD induced diabetic rats. Further, the protective effect of AA was evidenced by its histological annotation of the kidney tissues. CONCLUSION Hence, this study concluded that AA can protect against renal dysfunction by attenuating carbohydrate metabolic disorder and subsequently enhances glucose utilization and renal function in STZ-NAD-induced diabetic rats. Doxycycline inhibitor Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.BACKGROUND In recent years, many novel alkaloids with anticancer activity are found in China, and some of them are promising for developing anticancer agents. OBJECTIVE This review aims to provide a comprehensive overview of the information about alkaloid anticancer agents disclosed in Chinese patents, and discuss their potential to be developed as anticancer drugs used clinically. METHODS Anticancer alkaloids disclosed in Chinese patents in recent 5 years were presented according to their mode of actions. Their study results published on PubMed, and SciDirect data bases were presented. RESULTS More than one hundred anticancer alkaloids were disclosed in Chinese patents and their mode of action referred to arresting cell cycle, inhibiting protein kinases, affecting DNA synthesis and p53 expression etc. Conclusion Many newly found alkaloids displayed potent anticancer activity both in vitro and in vivo, and some of the anticancer alkaloids acted as protein kinase inhibitors or CDK inhibitors possess potential for developing as novel anticancer agents. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.BACKGROUND Antihypertensive medications may reduce the incidence of cognitive disorders. This may be due to reasons beyond their pure hypotensive effect. This study aimed to systematically review the association between the use of Angiotensin-Receptor Blockers (ARBs)and the incidence of Alzheimer's Disease (AD). METHODS We systematically searched studies reporting the association between ARB use and incidence of AD. RESULTS Ten studies (1 RCT, 2 case-control studies and 7 cohort studies) met the inclusion criteria. When all observational studies (9) were analyzed, ARB use was associated with a reduced risk of incident AD (HR 0.72, 95% CI 0.58-0.88, p less then 0.001). In the only RCT, the decrease in the incidence of AD was also significant (HR= 0.31,95% CI0.14-0.68). CONCLUSION ARB use may reduce the risk of incident AD. This association does not imply causation and further research is required to clarify potential mechanisms. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.AIM To generate and validate predictive models for blood brain permeation (BBB) of CNS molecules using QSPR approach. BACKGROUND Prediction of molecules crossing BBB remain a challenge in drug delivery. Predictive models are designed for evaluation of set of preclinical drugs which may serve as alternatives for determining BBB permeation by experimentation. OBJECTIVE The objective of present study was to generate QSPR models for permeation of CNS molecules across BBB and its validation using existing in-house leads. METHOD The present study envisaged the determination of set of molecular descriptors which are considered significant correlative factors for BBB permeation property. Quantitative Structure Property Relationship (QSPR) approach was followed to describe the correlation between identified descriptors for 45 molecules and highest, moderate and least BBB permeation data. The molecular descriptors were selected based on drug likeness, hydrophilicity, hydrophobicity, polar surface area, etc. of molecules which served highest correlation with BBB permeation.

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