天然草藥與認知健康

傳統療法的局限性推動了草藥研究

癡呆症是一種神經退行性疾病，會對記憶和學習、執行功能和日常生活活動造成漸進性損傷。全世界有超過4750萬人患有癡呆症，每年有770萬新病例加入癡呆症行列。血管性癡呆（VaD）風險增加可能與肥胖、血壓偏高、心血管疾病和腦血管意外（即“中風”）有關。在工業化國家，VaD佔所有癡呆病例的10%至15%，在世界上欠發達地區佔癡呆病例的30%，是僅次於阿爾茨海默病（AD）的第二種極常見的癡呆症。超過40%的血管性癡呆病例也伴有AD神經退行性病變，代表著極為常見的混合型癡呆類型。

可用的製劑如膽鹼酯酶阻止劑和谷氨酸受體拮抗劑在某些AD病例中可能有幫助，但對抗VaD的效果有限。結果是許多患有VaD的人可能正在使用草藥和其他補充劑以及替代（CAM）方法，如針灸、營養保健品、瑜伽、太極拳和音樂療法。

因為中藥中使用的許多草藥可能對AD和VaD的症狀有潛在的益處，人們已經對它們進行了單獨和不同組合的研究，這些草藥包括銀杏、蛇足石杉、薑黃、人參、三七、假馬齒莧、丹參、藏紅花和茶。以下簡要概述了單一草藥和復合草藥配方的研究，這些研究可能對健康成人和癡呆症患者俱有潛在的認知強化作用。

單一草藥有益但有限

新進的研究結果顯示銀杏萃取可能有助於改善VaD動物模型的學習和記憶。大型安慰劑對照研究和薈萃分析研究符合嚴格的入選標準，強烈支持銀杏萃取可能減慢了被診斷患有AD和VaD的個體的認知、執行功能和行為的退化速度。建議的機制顯示銀杏可能增強大腦功能、改善記憶和認知功能，包括降低促炎性巨噬細胞的活性、改善血流、降低血小板活化因子的活性（降低卒中風險）、降低皮質類固醇的合成和增加葡萄糖的攝取、增強神經乾細胞的增殖、促進腦損傷後的突觸可塑性、減少循環游離膽固醇、減少大腦中β-澱粉樣蛋白前體蛋白的合成。

薑黃（鬱金）已經在中醫、印度和阿育吠陀醫學中被沿用了好幾個世紀，可能用於對抗多種疾病，包括胰腺發炎、關節發炎、癌病和炎性反應、神經退行性疾病和消化系統疾病。動物和體外研究表明，薑黃素的認知增強益處可能基於多種作用機制，包括阻止脂質過氧化、清除活性氧（ROS）和活性氮物質、阻止NF-kB活化及其控制炎性反應的作用。薑黃素還可能直接結合小的β-澱粉樣物質以阻止聚集和形成纖維纏結。在一項為期24個月的隨機臨床試驗中，36名輕度至中度AD患者隨機使用薑黃素（2和4克/天）或安慰劑，兩組在認知和記憶方面有著相似的而非明顯的變化。這些結果的部分原因可能是研究中使用的薑黃素製劑的生物利用度低。

動物研究結果表明，生物活性成分人參可能改善癡呆患者的認知和記憶。人參皂苷Rg5可能降低β-澱粉樣蛋白和膽鹼酯酶的活性，人參皂苷Rg3可能通過增強基因表達來促進β-澱粉樣蛋白肽的降解。人參還可能通過增強血管擴張來降低血壓並改善血液循環。兩項為期12週的開放性試驗顯示，人參可能改善被診斷患有AD的個體的認知。在新近的兩項小型開放性試驗中，每天接受4.5和9克劑量人參的AD患者在認知和記憶方面可能得到了顯著的改善。兩項小型安慰劑對照試驗的結果顯示，三七可能改善大腦的血流量，增強被診斷患有VaD的個體的記憶力。

假馬齒莧（學名：Bacopa monnieri）可能具有神經保護和防氧化的作用，可能用作自由基清除劑，也可能增加大腦的血流量。該草藥被廣泛用於阿育吠陀醫學，用於對抗記憶問題。目前人們正在研究草藥可能增強健康成人和被診斷患有AD的個體的認知能力的功效。

藏紅花（學名：Crocus sativus）在中醫中被用作抗抑鬱藥、解痙劑和抗羊癲瘋的藥。含有藏紅花素的提取物可能具有防氧化和抗血小板特性，並已被證實可能改善癡呆動物模型的學習和記憶。在一項為期22週的雙盲隨機臨床試驗中，隨機每天向AD患者提供30毫克藏紅花和10毫克膽鹼酯酶阻止劑多奈哌齊，兩組在認知方面都可能表現出相當的改善，而藏紅花可能具有更好的耐受性。在為期16週的雙盲試驗中，接受藏紅花的AD患者的反應可能明顯優於安慰劑組。

茶（學名：Camellia sinensis）被廣泛用於保健，它含有表沒食子兒茶素沒食子酸酯（EGCG），具有由控制炎性反應的效果介導的神經保護作用，可能將其用作自由基清除劑等。經常喝茶的人可能會降低患AD的風險。兩項前瞻性研究發現，老年人經常喝綠茶可能與患認知障礙和癡呆的風險相對較低有關。

針對癡呆症人群的單一草藥研究的結果可能受到個體臨床試驗的樣本量小、方法學質量較差和研究持續時間較短的限制。此外，許多單一草藥的生物活性成分的血漿濃度可能太低以至於不能起到有益的效果，這表明觀察到的認知改善可能與兩種或更多種生物活性成分之間的協同相互作用有關。中醫和其他亞洲醫學系統通常採用草藥組合，可能導致離散的生物活性成分之間的協同性相互作用，這可能更有效地對付複雜的病因，如AD和VaD病症。近來，一種稱為“系統到系統分析”的新型研究方法已被應用於草藥配方中復合協同相互作用的研究。

複合草藥配方的前景

針對VaD的複合草藥配方的研究較少。雖然有些研究顯示出了好的結果，但研究成果的意義可能受到研究規模較小和方法學缺陷的限制。2012年針對VaD患者的複合草藥配方研究的系統評價報告稱，與常規使用的藥或安慰劑相比，研究的大多數配方可能使認知功能得到顯著的改善。其中4項研究表明，與傳統藥劑相比，草藥與常規藥劑相結合可能提高認知功能，然而，這些研究結果的意義可能受到嚴重的方法學缺陷的限制。新近的一項薈萃分析包括對被診斷患有VaD的個體進行的24項隨機臨床試驗（均在中國進行）。在亞組分析中，與吡拉西坦（10項研究）或安慰劑（3項研究）相比，複合中草藥干預可能顯著地增強了認知功能。與使用吡拉西坦療法的個體相比，接受草藥療法的個體在日常生活活動方面可能得到了更大的改善。但是，與上述研究一樣，研究結果的意義可能也受到方法缺陷的限制。

持續努力開發針對血管性癡呆的複合草藥配方

為了應對上述挑戰，十多年來，中國醫學科學院與西悉尼大學之間正在進行合作，共同開髮用於對抗VaD的標準化複合草藥製劑。這個名叫SLT的配方包含銀杏（學名：Ginkgo biloba）、人參（學名：Panax ginseng）和藏紅花（學名：Crocus sativus）萃取的標準化製劑。

通過一系列的動物研究確定生物活性成分的理想比例和SLT的理想劑量。臨床前試驗證實癡呆動物模型的學習和記憶、神經病理標誌物和防氧化活動可能得到了顯著的改善。在撰寫本文時，正在進行大規模的III期研究，以確定針對被診斷患有VaD個體的效果。臨床前試驗的累積結果證實了SLT的許多可能的腦血管益處，包括局灶性腦缺血/再灌注損傷面積減少、血小板聚集減少和自由基清除活性增加。

使用SLT療法或安慰劑的個體可能具有相同的不良反應風險。在為期1週的小型隨機對照試驗中，16名隨機接受SLT療法的健康成年人的工作記憶可能得到了改善。在一項小型的II期研究中，被診斷可能患有VaD的個體隨機接受SLT療法後，在認知功能方面可能得到了顯著的改善，一些個體可能表現出與記憶、聽覺和言語處理相關的腦部區域的血流量增加。針對325名可能患有VsD的個體進行的第二個為期12個月的II期研究可能發現了類似的認知改善，這兩項II期研究均報告了SLT相關的嚴重不良事件。在撰寫本文時，正在進行兩項多中心III期試驗。在確認III期研究成果之前，SLT可能成為VsD的基於依據的草藥療法，VsD是一種目前尚無有效療法的神經退行性疾病。

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