Microglial cells are the prime effectors in immune and inflammatory responses of the central nervous system (CNS). During pathological conditions, the activation of these cells helps restore CNS homeostasis. However, chronic microglial activation endangers neuronal survival through the release of various proinflammatory molecules and neurotoxins. Thus, negative regulators of microglial activation have been considered as potential therapeutic candidates to target neurodegeneration, such as that in Alzheimer's and Parkinson's diseases. The rhizome of Ligusticum chuanxiong Hort. (Ligusticum wallichii Franch) has been widely used for the treatment of vascular diseases in traditional oriental medicine. Butylidenephthalide (BP), a major bioactive component from L. chuanxiong, has been reported to have a variety of pharmacological activities, including vasorelaxant, anti-anginal, anti-platelet and anti-cancer effects. The aim of this study was to examine whether BP represses microglial activation. In rat brain microglia, BP significantly inhibited the lipopolysaccharide (LPS)-induced production of nitric oxide (NO), tumour necrosis factor-α and interleukin-1β. In organotypic hippocampal slice cultures, BP clearly blocked the effect of LPS on hippocampal cell death and inhibited LPS-induced NO production in culture medium. These results newly suggest that BP provide neuroprotection by reducing the release of various proinflammatory molecules from activated microglia.
Chronic microglial activation endangers neuronal survival through the release of various pro-inflammatory and neurotoxic factors. As such, negative regulators of microglial activation have been considered as potential therapeutic candidates to reduce the risk of neurodegeneration associated with inflammation. Uncaria rhynchophylla (U. rhynchophylla) is a traditional oriental herb that has been used for treatment of disorders of the cardiovascular and central nervous systems. Hirsutine (HS), one of the major indole alkaloids of U. rhynchophylla, has demonstrated neuroprotective potential. The aim of the present study was to examine the efficacy of HS in the repression of inflammation-induced neurotoxicity and microglial cell activation. In organotypic hippocampal slice cultures, HS blocked lipopolysaccharide (LPS)-related hippocampal cell death and production of nitric oxide (NO), prostaglandin (PG) E2 and interleukin-1β. HS was demonstrated to effectively inhibit LPS-induced NO release from cultured rat brain microglia. The compound reduced the LPS-stimulated production of PGE2 and intracellular reactive oxygen species. HS significantly decreased LPS-induced phosphorylation of the mitogen-activated protein kinases and Akt signaling proteins. In conclusion, HS reduces the production of various neurotoxic factors in activated microglial cells and possesses neuroprotective activity in a model of inflammation-induced neurotoxicity.
Blood stasis syndrome (BSS) in traditional Asian medicine has been considered to correlate with the extent of atherosclerosis, which can be estimated using the cardioankle vascular index (CAVI). Here, the diagnostic utility of CAVI in predicting BSS was examined. The BSS scores and CAVI were measured in 140 stroke patients and evaluated with respect to stroke risk factors. Receiver operating characteristic (ROC) curve analysis was used to determine the diagnostic accuracy of CAVI for the diagnosis of BSS. The BSS scores correlated significantly with CAVI, age, and systolic blood pressure (SBP). Multiple logistic regression analysis showed that CAVI was a significant associate factor for BSS (OR 1.55, P = 0.032) after adjusting for the age and SBP. The ROC curve showed that CAVI and age provided moderate diagnostic accuracy for BSS (area under the ROC curve (AUC) for CAVI, 0.703, P < 0.001; AUC for age, 0.692, P = 0.001). The AUC of the “CAVI+Age,” which was calculated by combining CAVI with age, showed better accuracy (0.759, P < 0.0001) than those of CAVI or age. The present study suggests that the CAVI combined with age can clinically serve as an objective tool to diagnose BSS in stroke patients.
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