Acetylcholinesterase (AChE) inhibitory activity-guided fractionation of Angelica gigas led to isolation and identification of a new coumarin, peucedanone (12), and isolation of 11 known coumarins. Among them, decursinol (1) represented the highest inhibitory activity toward AChE in vitro. The correlation of the inhibitory activities of the coumarins toward AChE with their chemical structures was studied.

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Background and Purpose An urgent need exists to develop therapies for stroke which have high efficacy, long therapeutic time windows and acceptable toxicity. We undertook preclinical investigations of a novel therapeutic approach involving supplementation with carnosine, an endogenous pleiotropic dipeptide. Methods Efficacy and safety of carnosine treatment was evaluated in rat models of permanent or transient middle cerebral artery occlusion. Mechanistic studies used primary neuronal/astrocytic cultures and ex vivo brain homogenates. Results Intravenous treatment with carnosine exhibited robust cerebroprotection in a dose-dependent manner, with long clinically-relevant therapeutic time windows of 6 h and 9 h in transient and permanent models, respectively. Histological outcomes and functional improvements including motor and sensory deficits were sustained at 14 d post-stroke onset. In safety and tolerability assessments, carnosine did not exhibit any evidence of adverse effects or toxicity. Moreover, histological evaluation of organs, complete blood count, coagulation tests and the serum chemistry did not reveal any abnormalities. In primary neuronal cell cultures and ex vivo brain homogenates, carnosine exhibited robust anti-excitotoxic, antioxidant, and mitochondria protecting activity. Conclusion In both permanent and transient ischemic models, carnosine treatment exhibited significant cerebroprotection against histological and functional damage, with wide therapeutic and clinically relevant time windows. Carnosine was well tolerated and exhibited no toxicity. Mechanistic data show that it influences multiple deleterious processes. Taken together, our data suggest that this endogenous pleiotropic dipeptide is a strong candidate for further development as a stroke treatment.

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Alzheimer's disease (AD) is the most common cause of senile dementia in later life. Whereas several neurotransmitter systems are known to be involved and depleted in AD, the cholinergic system still receives the greatest attention by far. This is particularly true with regards to pharmacotherapy research and development 2) due to the involvement of the cholinergic system in learning and memory processing.