Murata Kazuya, Matsumura Shinichi, Yoshioka Yuri, Ueno Yoshihiro, Matsuda Hideaki
Faculty of Pharmacy, Kinki University, 3-4-1 Kowakae, Higashiosaka, Osaka, 577-8502, Japan.
J Nat Med. 2015 Jan;69(1):123-9. doi: 10.1007/s11418-014-0859-3. Epub 2014 Aug 15.
The therapeutic agents for dementia are limited due to the complex system underlying the mechanisms. Taking a preventive point of view, we focused on the inhibition of β-secretase and acetylcholinesterase (AChE). In addition, plant resources including herbs and spices have been widely consumed, and further, may be consumed for a long period over a lifetime. Considering this background, we screened β-secretase and AChE inhibitors from curry spices. Amongst them, curry leaf, black pepper, and turmeric extracts were effective to inhibit β-secretase. Furthermore, black pepper and turmeric extracts were also effective to inhibit AChE. Having these results in hand, we focused on the investigation of β-secretase inhibitors since the inhibitor of this enzyme has not previously been well investigated. As a result, α- and β-caryophyllene, β-caryophyllene oxide (from curry leaf), piperine (from black pepper), curcumin, demethoxycurcumin, and bisdemethoxycurcumin (from turmeric) were successfully identified as low molecular inhibitors. This is the first report to determine α- and β-caryophyllene, β-caryophyllene oxide, and piperine as β-secretase inhibitors. These compounds may pass through the blood brain barrier since their molecular weights are relatively low.
由于痴呆症潜在机制的系统复杂，其治疗药物有限。从预防的角度来看，我们专注于抑制β-分泌酶和乙酰胆碱酯酶（AChE）。此外，包括草药和香料在内的植物资源已被广泛食用，而且可能在一生中长期食用。考虑到这一背景，我们从咖喱香料中筛选β-分泌酶和AChE抑制剂。其中，咖喱叶、黑胡椒和姜黄提取物对抑制β-分泌酶有效。此外，黑胡椒和姜黄提取物对抑制AChE也有效。基于这些结果，我们专注于β-分泌酶抑制剂的研究，因为此前对该酶抑制剂的研究并不充分。结果，α-和β-石竹烯、氧化石竹烯（来自咖喱叶）、胡椒碱（来自黑胡椒）、姜黄素、去甲氧基姜黄素和双去甲氧基姜黄素（来自姜黄）被成功鉴定为低分子抑制剂。这是首次将α-和β-石竹烯、氧化石竹烯和胡椒碱确定为β-分泌酶抑制剂的报告。由于这些化合物的分子量相对较低，它们可能会穿过血脑屏障。
