摘""要:沉香[Aquilaria"sinensis"(Lour.)"Gilg]是来源于瑞香科沉香属或拟沉香属含有树脂的木材。其中,沉香精油(agarwood"essential"oil,"AEO)是沉香主要的功能活性组分,在神经保护作用方面具有良好效果,常被用来舒缓身心,缓解焦虑、抑郁和治疗失眠。大量研究表明,AEO的化学组成主要包括色酮类、倍半萜类、芳香族类、脂肪酸类以及其他化合物,其中2-(2-苯乙基)色酮和倍半萜类化合物是其特征组分。然而,AEO尚无明确的规范分级及质量检测标准,品质参差不齐,极大影响沉香产业的发展。AEO功效与其化学成分组成有着密切关联。从不同的原料(品种、产地、造香方式及时间)和不同的提取方法(水蒸气蒸馏、超临界流体二氧化碳萃取、有机溶剂萃取法)得到的AEO的化学成分及含量存在较大的差异。因此,建立健全AEO规范分级和质量检测标准,揭示AEO的化学成分与原料和提取方法之间的内在联系将是未来的研究方向。此外,由于人们对沉香的需求量不断增加,沉香属野生种群数量迅速下降,造成野生资源枯竭。但随着人工种植和人工诱导方法的推广,沉香产量有了很大的提高,为AEO的进一步研究提供了研究基础。本文综述了不同来源AEO的化学成分及其在神经保护作用方面的应用前景,并分析了目前AEO研究存在的问题。
关键词:沉香;精油;生物活性;神经保护;研究进展中图分类号:Q949.761.1;R284.1""""""文献标志码:A
Research"Progress"on"Chemical"Components"of"Agarwood"Essential"Oil"and"Application"in"Neuroprotective"Effects
HUANG"Xiaobing1,"LIU"Jin2,"LU"Hanjin1,2,"YANG"Shengtao1*,"LI"Jihua1,2*
1."Agricultural"Products"Processing"Research"Institute,"Chinese"Academy"of"Tropical"Agricultural"Sciences"/"Key"Laboratory"of"Tropical"Crop"Products"Processing,"Ministry"of"Agriculture"and"Rural"Affairs,"Zhanjiang,"Guangdong"524001,"China;"2."College"of"Food"Science,"Fujian"Agriculture"and"Forestry"University,"Fuzhou,"Fujian"350002,"China
Abstract:"Aquilaria"sinensis"(Lour.)"Gilg"is"a"resin"containing"wood"in"the"genus"Aquilaria"or"Gyrinops."Among"them,"agarwood"essential"oil"(AEO)"is"the"main"functional"active"component"of"agarwood,"which"has"good"neuroprotective"effect"and"is"often"used"to"soothe"the"body"and"mind,"relieve"anxiety"and"depression,"and"treat"insomnia."A"large"number"of"studies"have"shown"that"the"chemical"composition"of"AEO"mainly"includesnbsp;chromones,"sesquiterpenoids,"aromatics,"fatty"acids"and"other"compounds,"among"which"2-(2-phenethyl)"chromone"and"sesquiterpenoids"are"the"characteristic"components."However,"there"is"no"clear"standard"for"AEO"classification"and"quality"testing,"and"the"quality"of"AEO"is"uneven,"which"greatly"affects"the"development"of"agarwood"industry."The"efficacy"of"AEO"is"closely"related"to"its"chemical"composition."The"chemical"composition"and"content"of"AEO"obtained"from"different"raw"materials"(species,"origin,"induction"methods"and"time)"and"different"extraction"methods"(hydro-distillation,"supercritical"fluid"carbon"dioxide"extraction,"solvent"extraction)"are"quite"different."Therefore,"it"will"be"the"direction"of"future"research"to"establish"a"sound"grading"and"quality"testing"standard"of"AEO,"and"reveal"the"internal"relationships"of"the"chemical"composition"of"AEO"with"the"raw"materials"and"extraction"methods."In"addition,"due"to"the"increasing"demand"for"agarwood,"the"wild"population"of"agarwood"species"has"declined"rapidly,"resulting"in"the"depletion"of"wild"resources."However,"with"the"popularization"of"artificial"cultivation"and"induction"methods,"the"yield"of"agarwood"has"been"greatly"improved,"which"provides"a"research"basis"for"further"research"on"AEO."This"article"reviews"the"chemical"components"of"AEO"from"different"sources"and"their"application"prospects"in"neuroprotective"effects,"and"analyzes"the"problems"existing"in"the"current"research"of"AEO.
Keywords:"Aquilaria"sinensis;"essential"oil;"biological"activity;"neuroprotective;"research"advances
DOI:"10.3969/j.issn.1000-2561.2024.07.016
沉香[Aquilaria"sinensis"(Lour.)"Gilg]是一种含有树脂的木材,形成于瑞香科沉香属(拟沉香属)的沉香树。沉香树是一种名贵热带作物,主要分布于我国海南、广东、广西、云南和福建等地。近年来,海南作为我国沉香的主要产区,高度重视沉香产业的发展,制定了《海南省沉香产业发展规划(2018—2025)》,大力扶持沉香产业发展,要将沉香产业培育成海南的“第四棵树”,预计到2025年,海南沉香产业将实现综合收入200亿元。沉香树的独特之处在于,健康的树木不生产沉香,但当树体受到外界破坏时,会激活自身的防御机制,从而产生深棕色的树脂,即沉香。作为一种著名的芳香中药,沉香已被列入《中国药典》,也是日本、印度等国的传统名贵药材。因其同时具有龙涎香和檀香的香味,享有“百香之王”的美誉,在佛教、印度教、伊斯兰教以及其他宗教仪式中被用作熏香。
早在古印度和中国古代就有通过芳香疗法舒缓身心、预防疾病的做法[1]。现代药理学认为,芳香植物精油可通过芳香物质调节人体自主神经系统、中枢神经系统和内分泌系统,影响人的情绪、生理状态和行为[2-4]。因此,芳香(熏香)疗法常被用作治疗慢性疼痛、抑郁、焦虑、失眠等神经系统疾病的辅助治疗[5-9]。此外,沉香精油(AEO)还具有抗氧化、抗菌、抗炎、净化空气、放松和镇静的功效[10-11]。AEO功效与其化学成分有着密切关联。而从不同的原料(品种、产地、造香方式及时间)和不同的提取方法得到的AEO的化学成分存在较大的差异。AEO常用的提取方法有水蒸气蒸馏(hydro-distillation,"HD)、超临界流体二氧化碳萃取(supercritical"fluid"carbon"dioxide"extraction,"SFE)、有机溶剂萃取法(solvent"extraction,"SE)、亚临界流体萃取、纤维素酶辅助萃取、微波萃取法等[12-13]。其中,以HD和SFE方法最为常用。
此外,随着人们对沉香的需求量不断增加,沉香属野生种群数量迅速下降,造成野生资源枯竭。2004年起,沉香属物种被列入《濒危野生动植物种国际贸易公约》附录Ⅱ名单。然而,随着广泛的人工种植和人工诱导方法的推广,沉香产量有了很大的提高,为AEO的进一步研究提供了研究基础。本文旨在系统综述AEO的化学成分及影响因素,分析AEO目前存在的问题及其在神经保护作用方面的应用前景。
研究表明,AEO的主要化学成分包括(2-苯乙基)色酮类、倍半萜类、芳香族类、脂肪酸类等化学成分[12,"14],具有治疗喘息、胃痛、呕吐、腰膝虚冷、止咳和缓解风湿等作用[10]。其中倍半萜类和色酮类是AEO的特征组分,对AEO的气味和功能活性具有显著影响[15-16]。
1.1""色酮类
2-(2-苯乙基)色酮及其衍生物是在显色酮的C-2位置取代苯乙基片段合成的一类化合物[17],已发现有240个不同的亚基[18]。作为沉香的特征组分之一,2-(2-苯乙基)色酮具有抑菌、抗炎、抗肿瘤、神经保护以及乙酰胆碱酯酶、酪氨酸酶和葡萄糖苷酶抑制作用[19-22]。杨洋[23]从沉香中分离的色酮类化合物具有乙酰胆碱酯酶抑制活性。此外,研究发现2-(2-苯乙基)色酮衍生物可通过抑制炎症因子的过量表达[24-25],调控STAT1/3和ERK1/2信号通路[26],抑制脂多糖诱导RAW264.7巨噬细胞中的炎症介质的产生,以达到抗炎效果。值得注意的是,HD法提取的AEO中不含2-(2-苯乙基)色酮,然而超临界流体二氧化碳萃取(SFE)和微波辅助萃取得到的AEO通常含有2-(2-苯乙基)色酮类化合物。
1.2""倍半萜类
作为沉香的另一种特征组分,倍半萜是一种由3个异戊二烯组成的天然萜类化合物,在抑菌、抗氧化[27]、抗炎[28]、抗肿瘤[29]等方面有良好效果。从AEO分离得到的倍半萜类对金黄色葡萄球菌和青枯雷尔氏菌活性有显著抑制作用,抑制圈直径分别为(12.35±0.11)"mm和(16.90±0.09)"mm[30]。此外,沉香的倍半萜成分在中枢神经系统、呼吸系统、消化系统等中具有良好的药理功效和生物活性[31]。杨洋[23]还发现从沉香中分离的倍半萜类同样具有乙酰胆碱酯酶抑制活性。
1.3""芳香族类
芳香族化合物也是AEO的重要组成部分,通常被认为是AEO中香气的主要来源。据报道,在加热的沉香或AEO中可以检测到更多的芳香族物质。TAKAMATSU等[32]发现沉香中的2-(2-苯乙基)色酮加热后会裂解产生小分子量芳香族化合物。
1.4""脂肪酸类
脂肪酸在沉香和AEO的化学成分及活性研究中提及较少。有研究表明在健康的白木香中正十六酸和油酸的含量高达59%,而在经损伤形成的沉香中脂肪酸成分减少,倍半萜类和2-(2-苯乙
基)色酮类化合物明显增加。由此可推断,AEO中的脂肪酸含量越低,其品质越高[33]。
AEO的主要成分包括倍半萜类、色酮类、芳香族类和脂肪酸类。其中,倍半萜类化合物和(2-苯乙基)色酮类化合物分别作为AEO的主要组成成分和特征功能成分,与AEO的品质和营养健康功效存在密切关系。然而,不同的品种、产地、树龄、结香方式及时间和提取方法对AEO的化学组成有很大的影响(表1)。如HD提取的AEO中,最主要的成分为倍半萜类化合物,通常不含色酮类化合物,而利用SFE得到的AEO中倍半萜类和色酮含量较高,成分也相对更丰富。但由于尚无学者针对沉香品种、结香方式和提取方法对沉香组成及功能活性的影响进行全面系统的分析研究,难以判定影响AEO品质的核心决定性因素。因此,本文综述了目前不同品种、结香方式和提取方式对AEO的化学组成的影响,可为进一步的系统性研究提供研究依据。
2.1""品种
目前,沉香属植物有22种,拟沉香属植物有7种,市售沉香的主要品种有马来沉香(A."malaccensis)、白木香沉香(A."sinensis)、厚叶沉香(A."crassna)等。研究表明从不同品种、产地的沉香提取得到的AEO成分有明显差异[37-39]。由表1可知,中国产的白木香沉香的芳香族化合物普遍较高,精油留香较为持久、气味幽香。同时,可以发现3种不同品种、产地的沉香中主要成分为倍半萜类化合物,其相对含量较高。此外,虫蛀法得到的AEO中的脂肪酸化合物含量较高,并能用乙醇萃取得到色酮类化合物。同时,在采用HD提取的AEO中,只有马来沉香[37]和白木香沉香变种“Chi-Nan”的AEO中含有少量的2-(2-苯乙基)色酮[42]。由此可见,不同品种沉香提取得到的AEO的化学成分存在明显差异性。然而,目前对不同物种精油的化学成分尚未进行全面系统的比较,难以区分其优劣。
2.2""结香方式
野生沉香是沉香树受到外界力量伤害产生的,比如风、雨、闪电、昆虫等。由于形成周期较长,野生沉香资源不断减少,再加上市场对沉香的需求不断增长,造成了天然沉香价格居高不下[43]。为此,国家鼓励发展沉香种植和推广人工诱导结香技术,生产人工沉香。人工结香技术主要包括物理创伤法、化学诱导法、微生物法以及通体结香技术。人工结香技术中的物理方法是在沉香树受到外部物理创伤后结香,如砍伤、打洞、打钉、树干断裂和火烙。化学方法是用甲酸、乙烯利、氯化钠、氯化铁、过氧化氢等各种溶液诱导沉香树体产生沉香。生物方法则是通过接种微生物诱导结香。通过打洞法获得的沉香主要由倍半萜类为主,并且含有白木香醛、对甲氧基苄基丙酮等沉香特征性成分。而砍伤法结香的AEO中则以脂肪酸类为主[44]。向盼等[45]对不同打洞结香法所产沉香挥发性成分进行分析,发现火烙打洞法所产沉香比冷铁打洞法和常规打洞法所产沉香质量好。陈品品等[35]比较了不同方法获得的AEO的化学成分,发现真菌接种法形成的AEO中2-(2-苯乙基)色素的含量是烧凿钻法形成的AEO的2倍。此外,LIU等[34]发现沉香通体结香技术(Agar-WIT)诱导6个月的AEO提取率远高于其他3种方法(植菌法、火钻法和砍伤法)诱导12个月以上的AEO提取率,并且由Agar-WIT诱导的AEO中含有更多的芳香成分。综上所述,不同的沉香诱导方法对AEO的提取率和化学成分有显著影响,而Agar-WIT是目前最具有竞争力的诱导技术,即可以缩短诱导生产沉香所需的时间,又可以得到较高品质的沉香和AEO。此外,Agar-WIT是当前中国以及其他生产沉香的国家应用最广泛的人工诱导技术,已应用于中国及东南亚国家超过45万株沉香树[46]。
2.3""提取方法
与其他植物精油一样,AEO同样拥有多种提取方法。目前,AEO的提取采用HD、SFE、SE以及其他的辅助方法。其中,HD使用水作为溶剂,安全无毒,设备简单,操作简易[47],是现如今工业生产中采用最多的方法,具有应用广、适用性强、普遍性高的特点。水蒸气蒸馏法[48]虽然优点很多,但同时也存在不可忽视的缺点,例如,与水同为极性的精油组分难以回收;提取温度过高和时间过长。过高的提取温度会破坏精油组分中热敏性物质;而过长的蒸煮时间可能导致精油中关键组分发生变化,以影响精油的品质。有机溶剂萃取法[49]适用于挥发性、热敏性及不稳定的芳香化合物,可弥补HD的不足之处。同时,根据相似相溶原则,SE萃取一些极性较小的挥发油成分时,产率相对较低,并且有机溶剂具有一定的毒性,有机溶剂的残留也会影响精油的质量。此外,通过有机溶剂萃取的精油外观、香气等品质相对较差。SFE是新兴提取技术的代表,近年来发展迅速。该技术的特点是在超临界状态下,通过改变压力和温度以调节超临界流体的溶解能力[50-51]。根据相似相溶原理将组织中的不同化合物依次扩散到溶剂中,最终以减压、升温等手段将超临界流体转变为气体释放,从而得到萃取物。该过程可以在常温下进行,同时最终萃取物无溶剂残留,即解决了HD高温影响AEO中热敏成分损失问题,也避免了有机试剂残留。
从表1可以看出,不同提取方法得到的AEO化合物组成差异很大。采用HD提取AEO的提取率较低,一般为0.1%~0.5%,但倍半萜的相对含量较高,芳香族化合物的相对含量较低,这可能是由于在HD中持续高温导致AEO挥发损失所致。值得注意的是,不同溶剂提取的AEO组成不同,即使用HD法,利用95%乙醇辅助提取,能提取出更多的芳香族和色酮类化合物。在相同溶剂的不同提取方法中,微波辅助提取方法产生的AEO的得率和物质种类较高,分别为1.32%和70种,其中反映精油品质的倍半萜类物质和芳香族物质分别为19种和20种,明显高于水浴回流法、索氏提取法和超声辅助萃取法3种方法[41]。采用HD、纤维素酶酶解辅助HD、内生真菌发酵液浸泡辅助HD、微波辅助HD、微波结合内生真菌发酵液浸泡辅助HD等5种方法提取马来沉香中的AEO,发现5种提取方法获得的AEO中主要成分均为倍半萜类化合物,4种辅助提取方法均能提高精油总量,其中用纤维素酶的酶解辅助法提高最多,其次为微波结合内生真菌发酵液浸泡[38]。
相比之下,采用SFE提取AEO的提取率较HD有较高提升,可达0.8%~5.0%。此外,由于超临界流体的溶解度强,色酮类化合物更容易被提取出。戴伟杰等[52]采用HD、SFE和连续相变法提取AEO,发现连续相变提取AEO得率最高,为1.42%。而李响等[53]对SFE萃取AEO的工艺进行优化后,可以使得AEO的提取率达到1.89%。陈品品等[35]利用SFE提取不同结香方式下的AEO,共鉴定出以色酮类、倍半萜类和芳香族类为主要成分的59种化合物。其中,色酮类化合物有3个,相对总含量达54.59%(植菌法结香)和29.45%(火钻法结香)。田程飘等[36]对HD和SFE提取AEO的成分进行对比研究,HD提取AEO中主要成分为倍半萜类(68.68%),SFE萃取的AEO主要成分为倍半萜类(23.78%)和色酮类(29.42%)。王健松等[54]比较了SFE和亚临界萃取法得到AEO的差异,结果表明这2种提取方法的AEO主要成分基本相同,但相对含量存在差异。总的来讲,SFE萃取得到的AEO中倍半萜类和色酮含量较高,成分也相对更丰富。可见,在实际生产应用中,应根据所需的AEO类型选择合适的提取方法。
快节奏的现代生活和工作压力,导致越来越多群体出现失眠、抑郁、焦虑等负面情绪,甚至诱发严重精神性疾病。《健康中国行动(2019—2030)》数据调查显示,我国失眠患者已达3.5亿,抑郁症终身患病率为12%~20%,严重者可诱发自杀。WHO报告指出,当前抑郁症已成为我国第二大疾病,预计到2030年将位列世界疾病负担的首位[55]。我国药典指出沉香具有行气止痛、温中止呕、纳气平喘等功效[56]。在陶弘景所著《名医别录》中更是将沉香列为上品[57],有“药中黄金”之称。我国自古以来都有运用闻香、熏香等方法的香薰(芳香)疗法缓解神经疲劳和焦虑情绪的习惯,而AEO是芳香疗法中常用精油之一。研究表明,AEO具有抗炎、抗菌、抗氧化、抗肿瘤、抗焦虑、抗抑郁、促进睡眠以及治疗中枢神经退行性障碍等多种功效(表2)。此外,传统中医认为AEO具有舒缓身心的作用[58],可当作安神油、助眠油、定香油等使用,可缓解压力、焦虑,治疗失眠、抑郁和其他精神障碍疾病[59]。同时,现代药理学研究表明,沉香中含有倍半萜类、色酮类、芳香族类等活性化合物,对中枢神经系统具有积极效辅助治疗果[60-61]。因此,AEO对神经保护方面的作用是目前沉香研究的主要方向,具有良好的应用前景。
3.1""抗焦虑
随着生活节奏的不断加快和工作压力的提高,越来越多人长期处于焦虑的精神状态,进一步发展将形成神经性障碍。焦虑的原因有很多,一般认为焦虑障碍是由于调节焦虑过程中神经递质出现紊乱,导致中枢神经系统功能障碍,继而引发焦虑障碍,如γ-氨基丁酸(GABA)和单胺类神经递质减少等。因此,临床上常将苯二氮卓类药物(BDZ)、5-羟色胺再摄取抑制剂(SSRIs)和5-羟色胺-去甲肾上腺素再摄取抑制剂(SNRIs)作为临床治疗焦虑障碍的药物[69-70]。苯二氮卓类药物的抗焦虑作用是通过与GABA受体结合后,促进GABA与其受体相互结合,从而降低神经兴奋性,缓解焦虑症状。而SSRIs和SNRIs则是通过抑制5-HT和去甲肾上腺素的再摄取来发挥抗焦虑作用。在治疗长期焦虑症患者时,药物的副作用问题是经常被提及的问题。因此,人们更喜欢采用长期有效的非药物治疗方法,如心理咨询、放松疗法、针灸疗法以及芳香(香薰)疗法等[71]。其中,芳香疗法作为一种外治方法,是利用植物精油中的芳香气味和本身所富含的大量活性物质,经由嗅闻和皮肤吸收,到达神经系统和血液循环,疏通筋络,舒缓身心[72]。利用香薰或嗅闻精油的方式来缓解焦虑症状,与药物治疗相比具有副作用少、无耐药性等特点[73]。如图1所示,其主要作用机制是精油以嗅闻形式经鼻腔进入神经系统和血液循环,并通过nNOS-CREB、NRG1/ErbB4、Sirt1/Nrf2/HO-1等信号通路调节γ-氨基丁酸、5-羟色胺、多巴胺等神经递质的含量及表达水平,从而有效改善焦虑症状[74-75]。
慢性约束应激(chronic"restraint"stress,"CRS)是一种常用的诱导心理和生理应激反应的方法,可引起神经系统和内分泌系统的一系列行为和生理变化,最终诱导焦虑的产生[76]。LEE等[77]利用反复约束应激造成海马氧化损伤动物模型,发现沉香可有效抑制细胞中活性氧和促炎细胞因子及应激激素的释放,对神经系统具有显著保护作用。WANG等[9]采用十字高架迷宫(EPM)、光暗探索(LDE)和开阔场(OF)等一系列行为学试验方法,并通过检测抑制应激诱导小鼠焦虑症状来判断其抗焦虑活性。结果显示,AEO给药组能够剂量依赖性地改善小鼠的焦虑症状,并显著增加EPM实验中小鼠张开双臂的时间、距离和进入时间;在LDE试验中增加了小鼠在光室中的停留时间;40"mg/kg"AEO的效果与2.5"mg/kg地西泮(阳性药物)相当。以上结果证明AEO具有显著改善焦虑症状的作用。弓宝等[78]采用香薰试验发现AEO能有效提高焦虑和抑郁模型动物的海马体中对谷氨酸系统代谢、谷氨酸受体和囊泡谷氨酸转运蛋白的表达,表现出显著地抗焦虑和抗抑郁作用,且其作用机制可能与调控神经递质分泌、受体及转运体蛋白的表达有关,这与WANG等[79]
得到的吸入AEO对于焦虑症和抑郁症有很大缓解作用的结果一致。值得关注的是,布格呋喃(buagafuran)是一种抗广泛性焦虑障碍的Ⅰ类新药物,它是通过从沉香中分离的沉香呋喃类化合物进行结构修饰而获得的。在多种动物试验中布格呋喃显示出抗焦虑作用,并且毒副作用低,目前已经完成了二期临床试验[80]。以上说明从沉香中分离得到的AEO和一些单体化合物及其衍生物具有潜在的抗焦虑活性,是开发抗焦虑预防保健品和药物的良好来源。
3.2""抗抑郁
抑郁症是一种常见的心理障碍,会伴有焦虑、睡眠障碍等不同程度的心理和躯体症状,且有反复发作的倾向,其发病率正在逐年上升,已经成为一个严峻的社会问题,全世界约有15%~18%的人受到抑郁症的困扰。据WHO预测,到2030年,抑郁症将超过心脑血管疾病成为人类第一大疾病[81]。抑郁症的发病机制与多种因素有关,脑内单胺能神经(如5-HT、NA)功能低下可能是抑郁症的病因之一。目前临床使用的抗抑郁药主要有单胺再摄取抑制剂、单胺氧化酶抑制剂等,但数据表明约有一半的抑郁症患者在首次用药治疗后无明显效果,在后续用药治疗中同样收效甚微[82]。因此,寻找挖掘天然、高效、低毒的抗抑郁药仍是需要攻克的难关。
WANG等[9]通过现代药理学实验对应激小鼠进行悬尾(TS)和强迫游泳(FS)试验,发现在TS和FS试验中,20"mg/kg和40"mg/kg剂量下的AEO与10"mg/kg的帕罗西汀具有相似的疗效,能显著缩短小鼠不动时间,由此推测AEO具有良好的抗抑郁作用的潜力。汪凤华等[64]在TS和FS实验中,通过观察二十味沉香丸对绝望小鼠的行为变化,同样发现二十味沉香微丸能缩短小鼠的不动时间,缓解小鼠的抑郁症状。此外,黄国尧等[83]将40例抑郁症患者随机分为2组,对照组采用心理指导加抗抑郁药物治疗,治疗组则采用沉香芳香疗法。2组均在此基础上每日点香2次,2周为1个疗程,治疗2个疗程。结果显示,沉香芳香疗法能降低抑郁量表(CES-D)和汉密尔顿抑郁量表(HAMD)评分,治疗组总有效率为85%,对照组总有效率为55%。以上说明芳香疗法能有效改善抑郁症患者的临床症状,具有良好的临床效果。
3.3""促进睡眠
睡眠是一个活跃的过程,主要发生在中枢神经系统及其相关的神经递质和细胞因子。由于这一生理过程涉及多种因素,因此失眠的原因是极其复杂的。目前,失眠的发病机制主要有2种学说:(1)由于应激等因素引起下丘脑-垂体-肾上腺皮质系统(hypothalamic-pituitary-adrenal"cortex"system,"HPA)功能障碍和神经内分泌系统失调;(2)与睡眠-觉醒效应相关的中枢神经递质失调。其中,多巴胺(DA)和去甲肾上腺素(NE)是促进和维持觉醒的神经递质,而5-HT和GABA是具有镇静催眠功能的抑制性神经递质[21]。镇静催眠药物是一类对中枢神经系统具有抑制作用的药物,主要有苯二氮卓类、巴比妥类及其他类药物。此外,长期使用镇静安眠类药物除了存在副作用,还会出现抗药性和成瘾等问题。而沉香和AEO作为一种传统的镇静安眠剂,尚未发现有耐药性[8],可辅助治疗睡眠障碍。
王帅等[65]使用沉香的不同提取物(水提取物、乙醇提取物和精油)协同戊巴比妥钠进行催眠实验发现,与空白组相比,沉香提取物和AEO能显著增加小鼠的睡眠率和延长睡眠时间,并有效缩短小鼠的睡眠潜伏期,说明沉香提取物和AEO具有较强的镇静催眠作用。梁宇等[67]采用正常小鼠和经300"mg/kg"PCPA诱导的失眠小鼠为研究模型,发现吸入沉香能显著促进正常小鼠的睡眠,显著改善失眠小鼠的生活质量和运动能力。雷莉等[68]将120例失眠障碍患者进行随机分组治疗,实验组每晚睡前接受沉香熏蒸,对照组接受不影响睡眠的丙醇熏蒸,发现沉香熏蒸治疗显著改善了失眠障碍患者的睡眠质量,降低了失眠的严重程度,并能改善焦虑、抑郁等情绪障碍。上述研究表明AEO的芳香疗法具有显著的镇静催眠作用,且不良反应少,无明显耐药性,是一种有效的失眠替代治疗方法。
3.4""神经退行性疾病
神经退行性疾病主要是由于神经元和(或)其髓鞘的丧失而出现的神经性功能障碍。其发病机制与多种因素有关,乙酰胆碱被胆碱酯酶快速水解,从而阻断神经信号传递可能是发病的原因之一。杨洋[23]发现从沉香中分离的倍半萜类和色酮类化合物能有效抑制乙酰胆碱酯酶活性。LI等[21]发现从沉香中分离出的69种化合物具有不同程度乙酰胆碱酯酶抑制活性。可见,沉香中含有大量的天然乙酰胆碱酯酶抑制剂,具有治疗神经退行性疾病的潜力。以上研究表明沉香是一种很有前景的神经保护候选药物,其或将成为未来的研究热点。
自20世纪50年代以来,国内外对沉香的化学成分进行了大量研究,发现AEO主要由倍半萜类、色酮类、芳香族类、脂肪酸类等化合物组成。其中,倍半萜类和(2-苯乙基)色酮类作为AEO的特征组分,备受关注。截至目前,从沉香中已经分离并命名了超过210种倍半萜类、240种色酮类化合物。然而,沉香的来源(包括品种、产地、树龄、结香方式及时间)和精油提取方法均会影响AEO的化学组成,同时影响AEO品质质量。因此,沉香精油的化学成分组成具有潜在鉴定沉香真伪和指导AEO提取工艺改进的作用,如在健康的白木香中脂肪酸含量高达59%,而经损伤形成的沉香中脂肪酸成分减少,倍半萜类和2-(2-苯乙基)色酮类化合物明显增加[33];HD得到的AEO中主要为倍半萜类化合物,而SFE得到的AEO中含有更多的(2-苯乙基)色酮类化合物。除此之外,化学成分也可用于鉴别沉香的来源,如白木香变种“Chi"Nan”沉香和普通白木香沉香提取的AEO成分有明显不同。目前,AEO尚无明确的规范分级,市场“云龙混杂”,品质参差不齐,极大地影响着沉香产业的发展。在此背景下,我国应进一步推进沉香及AEO的规范分级和质量检测标准的制定,促进沉香产业高质量发展。
此外,沉香作为一种名贵的香料和重要的中药,除了具有独特的香味外,还具有镇静、安神的传统功效,如今仍是芳香疗法中舒缓身心的常用精油之一,常用于缓解焦虑、抑郁、治疗失眠和中枢退行性疾病等精神障碍。现代药理学认为,AEO可能通过抑制HPA轴过度反应、抑制海马nNOS蛋白水平、降低大脑皮质和海马CRF基因表达、降低血清ACTH和CORT水平以及调节5-HT、DA、NE等神经递质,发挥抗焦虑、抗抑郁、镇静促进睡眠的作用。目前,AEO尚未在国内外得到广泛应用,市场上除了香薰精油产品外,大部分AEO都是作为香水和香氛水的原料。AEO在神经保护作用方面的独特的药理优势尚未被挖掘,这可能与早期AEO价格昂贵以及对其药理疗效和作用机制的研究不够深入有关。值得关注的是,通过多年培育和发展,沉香产业不断扩大且日渐成熟,涉及种植业、加工业和服务业,初步形成全产业链,呈现出良好发展态势和巨大的发展潜力,使得市售AEO的价格大幅度下降且稳定,使AEO的功能活性研究有了更好的物质基础。因此,针对AEO对神经保护功效的科学内涵和应用,探明其功效活性与核心功能因子的研究将是当前研究的重点方向,具有良好的应用前景。同时,本文对AEO化学成分的现有研究进行了初步梳理,希望对未来AEO等级的分类提供一定的参照依据。不足之处在于,目前对各类沉香精油的研究主要是基于化学成分和药理活性的比较研究,尚不足以证明不同来源的沉香木何种更佳,也不足以证明何种AEO提取方式得到的精油中功能活性更好。
参考文献
[1]"GNATTA"J"R,"KUREBAYASHI"L"F"S,"TURRINI"R"N"T,"SILVA"M"J"P"D."Aromatherapy"and"nursing:"historical"and"theoretical"conception[J]."Revista"da"Escola"de"Enfermagem"da"USP,"2016,"50(1):"127-133.
[2]"GONG"M,"DONG"H,"TANG"Y,"HUANG"W,"LU"F."Effects"of"aromatherapy"on"anxiety:"a"meta-analysis"of"randomized"controlled"trials[J]."Journal"of"Affectivenbsp;Disorders,"2020,"274:"1028-1040.
[3]"HINES"S,"STEELS"E,"CHANG"A,"GIBBONS"K."Aromatherapy"for"treatment"of"postoperative"nausea"and"vomiting[J]."Cochrane"Database"of"Systematic"Reviews,"2018(3):"CD007598.
[4]"HWANG"E,"SHIN"S."The"effects"of"aromatherapy"on"sleep"improvement:"a"systematic"literature"review"and"meta-analysis[J]."The"Journal"of"Alternative"and"Complementary"Medicine,"2015,"21(2):"61-68.
[5]"FARRAR"A"J,"FARRAR"F"C."Clinical"aromatherapy[J]."Nursing"Clinics"of"North"America,"2020,"55(4):"489-504.
[6]"FORRESTER"L"T,"MAAYAN"N,"ORRELL"M,"SPECTOR"A"E,"BUCHAN"L"D,"SOARES-WEISER"K."Aromatherapy"for"dementia[J]."Cochrane"Database"of"Systematic"Reviews,"2014,"25(2):"CD003150.
[7]"TAKEMOTO"H,"ITO"M,"SHIRAKI"T,"YAGURA"T,"HONDA"G."Sedative"effects"of"vapor"inhalation"of"agarwood"oil"and"spikenard"extract"and"identification"of"their"active"components[J]."Journal"of"Natural"Medicines,"2008,"62:"41-46.
[8]"WANG"S,"WANG"C,"PENG"D,"LIU"X,"WU"C,"GUO"P,"WEI"J."Agarwood"essential"oil"displays"sedative-hypnotic"effects"through"the"GABAergic"system[J]."Molecules,"2017,"22(12):"2190.
[9]"WANG"S,"WANG"C,"YU"Z,"WU"C,"PENG"D,"LIU"X,"LIU"Y,"YANG"Y,"GUO"P,"WEI"J."Agarwood"essential"oil"ameliorates"restrain"stress-induced"anxiety"and"depression"by"inhibiting"HPA"axis"hyperactivity[J]."International"Journal"of"Molecular"Sciences,"2018,"19(11):"3468.
[10]"CHHIPA"H,"CHOWDHARY"K,"KAUSHIK"N."Artificial"production"of"agarwood"oil"in"Aquilaria"sp."by"fungi:"a"review[J]."Phytochemistry"Reviews,"2017,"16(5):"835-860.
[11]"HASHIM"Y"Z"H-Y,"KERR"P"G,"ABBAS"P,"MOHD"SALLEH"H."Aquilaria"spp."(agarwood)"as"source"of"health"beneficial"compounds:"a"review"of"traditional"use,"phytochemistry"and"pharmacology[J]."Journal"of"Ethnopharmacology,"2016,"189(2):"331-360.
[12]"田程飘."广西沉香的化学成分分析及生物活性研究[D]."南宁:"广西民族大学,"2020.TIAN"C"P."Analysis"of"chemical"constituents"and"biological"activities"of"Guangxi"agarwood[D]."Nanning:"Guangxi"University"for"Nationalities,"2020."(in"Chinese)
[13]"CHAMUTPONG"S,"CHEN"C"J,"CHAIPRATEEP"E"O."Optimization"ultrasonic–microwave-assisted"extraction"of"phenolicnbsp;compounds"from"Clinacanthus"nutans"using"response"surface"methodology[J]."Journal"of"Advanced"Pharmaceutical"Technology"amp;"Research,"2021,"12(2):"190.
[14]"ABDUL"KADIR"F"A,"AZIZAN"K"A,"OTHMAN"R."Datasets"of"essential"oils"from"naturally"formed"and"synthetically"induced"Aquilaria"malaccensis"agarwoods[J]."Data"in"Brief,"2020,"28:"104987.
[15]"LI"W,"YANG"Y,"DONG"W,"WANG"H,"KONG"F,"CAI"C,"MEI"W,"DAI"H."Dimeric"2-(2-phenylethyl)"chromones"from"the"agarwood"of"Aquilaria"crassna"in"Laos[J]."Fitoterapia,"2019,"133:"12-16.
[16]"杨德兰,"梅文莉,"杨锦玲,"曾艳波,"戴好富."GC-MS分析4种奇楠沉香中致香的倍半萜和2-(2-苯乙基)色酮类成分[J]."热带作物学报,"2014,"35(6):"1235-1243.YANG"D"L,"MEI"W"L,"YANG"J"L,"ZENG"Y"B,"DAI"H"F."GC-MS"analysis"of"the"fragrant"sesquiterpenes"and"2-(2-Phenylethyl)"chromone"derivatives"in"four"types"of"agarwood"“Qi-Nan”[J]."Chinese"Journal"of"Tropical"Crops,"2014,"35(6):"1235-1243."(in"Chinese)
[17]"TAKAMATSU"S,"ITO"M."Factors"affecting"2-(2-phenylethyl)"chromones"in"artificial"agarwood[J]."Journal"of"Natural"Medicines,"2021,"76(1):"321-330.
[18]"CHEN"L,"CHEN"H,"CAI"C,"YUAN"J,"GAI"C,"LIU"S,"MEI"W,"DAI"H."Seven"new"2-(2-phenethyl)"chromone"derivatives"from"agarwood"of"Aquilaria"walla[J]."Fitoterapia,"2023,"165:"105421.
[19]"DONG"W"H,"WANG"H,"GUO"F"J,"MEI"W"L,"CHEN"H"Q,"KONG"F"D,"LI"W,"ZHOU"K"B,"DAI"H"F."Three"new"2-(2-phenylethyl)"chromone"derivatives"of"agarwood"originated"from"Gyrinops"salicifolia[J]."Molecules,"2019,"24(3):"576.
[20]"YU"Z,"WANG"C,"ZHENG"W,"CHEN"D,"LIU"Y,"YANG"Y,"WEI"J."Anti-inflammatory"5,6,7,8-tetrahydro-2-(2-"phenylethyl)"chromones"from"agarwood"of"Aquilaria"sinensis[J]."Bioor ganic"Chemistry,"2020,"99:"103789.
[21]"LI"W,"CHEN"H"Q,"WANG"H,"MEI"W"L,"DAI"H"F."Natural"products"in"agarwood"and"Aquilaria"plants:"chemistry,"biological"activities"and"biosynthesis[J]."Natural"Product"Reports,"2021,"38(3):"528-565.
[22]"MI"C"N,"YUAN"J"Z,"ZHU"M"M,"YANG"L,"WEI"Y"M,"WANG"H,"LONG"W"X,"MEI"W"L,"DAI"H"F."2-(2-phen ylethyl)"chromone"derivatives:"promising"α-glucosidase"inhibitors"in"agarwood"from"Aquilaria"filaria[J]."Phytochemistry,"2021,"181:"112578.
[23]"杨洋."柯拉斯那沉香中2-(2-苯乙基)色酮聚合物的分离鉴定及其生物活性研究[D]."大庆:"黑龙江八一农垦大学,"2017.YANG"Y."Isolation"and"identification"of"2-(2-phenethyl)"chromone"polymers"from"agarwood"of"Aquilaria"crassna"as"well"as"their"bioactivities[D]."Daqing:"Heilongjiang"Bayi"Agricultural"University,"2017."(in"Chinese)
[24]"HUO"H,"GU"Y,"SUN"H,"ZHANG"Y,"LIU"W,"ZHU"Z,"SHI"S,"SONG"Y,"JIN"H,"ZHAO"Y,"TU"P,"LI"J."Anti-inflammatory"2-(2-phenylethyl)"chromone"derivatives"from"Chinese"agarwood[J]."Fitoterapia,"2017,"118:"49-55.
[25]"HUO"H,"ZHU"Z,"SONG"Y,"SHI"S,"SUN"J,"SUN"H,"ZHAO"Y,"ZHENG"J,"FERREIRA"D,"ZJAWIONY"J"K,"TU"P,"LI"J."Anti-inflammatory"dimeric"2-(2-Phenylethyl)"chromones"from"the"resinous"wood"of"Aquilaria"sinensis[J]."Journal"of"Natural"Products,"2018,"81(3):"543-553.
[26]"ZHU"Z,"GU"Y,"ZHAO"Y,"SONG"Y,"LI"J,"TU"P."GYF-17,"a"chloride"substituted"2-(2-phenethyl)-chromone,"suppresses"LPS-induced"inflammatory"mediator"production"in"RAW 264.7"cells"by"inhibiting"STAT1/3"and"ERK1/2"signaling"pathways[J]."International"Immunopharmacology,"2016,"35:"185-192.
[27]"DAHHAM"S,"TABANA"Y,"IQBAL"M,"AHAMED"M,"EZZAT"M,"MAJID"A,"MAJID"A."The"anticancer,"antioxidant"and"antimicrobial"properties"of"the"sesquiterpene"β-cary op hyllene"from"the"essential"oil"of"Aquilaria"crassna[J]."Molecules,"2015,"20(7):"11808-11829.
[28]"MA"C"T,"LY"T"L,"LE"T"H"V,"TRAN"T"V"A,"KWON"S"W,"PARK"J"H."Sesquiterpene"derivatives"from"the"agarwood"of"Aquilaria"malaccensis"and"their"anti-inflammatory"effects"on"NO"production"of"macrophage"RAW"264.7"cells[J]."Phytochemistry,"2021,"183:"112630.
[29]"HUANG"X"L,"CAI"D,"GAO"P,"WANG"J"G,"CHENG"Y"X."Aquilariperoxide"A,"a"sesquiterpene"dimer"from"agarwood"of"Aquilaria"sinensis"with"dual"antitumor"and"antimalarial"effects[J]."Journal"of"Organic"Chemistry,"2023,"88(13):"8352-"8359.
[30]"WANG"H"N,"DONG"W"H,"HUANG"S"Z,"LI"W,"KONG"F"D,"WANG"H,"WANG"J,"MEI"W"L,"DAI"H"F."Three"new"sesquiterpenoids"from"agarwood"of"Aquilaria"crassna[J]."Fitoterapia,"2016,"114:"7-11.
[31]"王云云,"侯文成,"魏建和,"刘洋洋."沉香中倍半萜类化合物与生物活性研究进展及其质量标志物预测分析[J]."中草药,"2022,"53(4):"1191-1209.WANG"Y"Y,"HOU"W"C,"WEI"J"H,"LIU"Y"Y."Research"progress"onnbsp;sesquiterpenoids"in"Aquilariae"Lignum"Resinatum"and"their"biological"activities"and"predictive"analysis"on"quality"marker[J]."Chinese"Traditional"and"Herbal"Drugs,"2022,"53(4):"1191-1209."(in"Chinese)
[32]"TAKAMATSU"S,"ITO"M."Agarotetrol:"a"source"compound"for"low"molecular"weight"aromatic"compounds"from"agarwood"heating[J]."Journal"of"Natural"Medicines,"2019,"73(3):"685.
[33]"CHEN"H,"YANG"Y,"XUE"J,"WEI"J,"ZHANG"Z,"CHEN"H."Comparison"of"compositions"and"antimicrobial"activities"of"essential"oils"from"chemically"stimulated"agarwood,"wild"agarwood"and"healthy"Aquilaria"sinensis"(Lour.)"gilg"trees[J]."Molecules,"2011,"16(6):"4884-4896.
[34]"LIU"Y,"CHEN"H,"YANG"Y,"ZHANG"Z,"WEI"J,"MENG"H,"CHEN"W,"FENG"J,"GAN"B,"CHEN"X,"GAO"Z,"HUANG"J,"CHEN"B,"CHEN"H."Whole-tree"agarwood-inducing"technique:"an"efficient"novel"technique"for"producing"high-qu al ity"agarwood"in"cultivated"Aquilaria"sinensis"trees[J]."Molec ules,"2013,"18(3):"3086-3106.
[35]"陈品品,"陈日忠,"吴辉煌,"林文忠,"马晓娟,"刘靓,"庄卫东."白木香不同结香方法所得沉香的精油成分分析[J]."热带生物学报,"2019,"10(2):"190-196.CHEN"P"P,"CHEN"R"Z,"WU"H"H,"LIN"W"Z,"MA"X"J,"LIU"L,"ZHUANG"W"D."Analysis"of"components"of"essential"oil"of"agarwood"from"Aquilaria"sinensis"induced"by"different"methods[J]."Journal"of"Tropical"Biology,"2019,"10(2):"190-196."(in"Chinese)
[36]"田程飘,"宋雅玲,"许海棠,"牛思琪,"吴志鸿,"申利群."超临界和水蒸气蒸馏提取沉香精油成分分析及抗氧化、抑菌活性对比研究[J]."中国中药杂志,"2019,"44(18):"4000-4008.TIAN"C"P,"SONG"Y"L,"XU"H"T,"NIU"S"Q,"WU"Z"H,"SHEN"L"Q."Composition"analysis,antioxidative"and"antibacterial"activities"comparison"of"agarwood"oils"extracted"by"supercriticalnbsp;and"steam"distillation[J]."China"Journal"of"Chinese"materia"medica,"2019,"44(18):"4000-4008."(in"Chinese)
[37]"韩恰恰,"杨思惠,"陈晓颖,"钟兆健,"周欣,"章卫民,"高晓霞."沉香挥发油化学组成分析及比较[J]."中药材,"2019,"42(7):"1566-1571.HAN"Q"Q,"YANG"S"H,"CHEN"X"Y,"ZHONG"Z"J,"ZHOU"X,"ZHANG"W"M,"GAO"X"X."Analysis"and"comparison"of"chemical"composition"of"volatile"oil"from"agarwood[J]."Journal"of"Chinese"Medicinal"Materials,"2019,"42(7):"1566-1571."(in"Chinese)
[38]"易润青,"陈兴静,"杨思惠,"黄圆圆,"高晓霞,"陈晓颖."不同水蒸气蒸馏辅助方法对马来沉香挥发油化学组成的影响[J]."广东药科大学学报,"2019,"35(2):"193-198.YI"R"Q,"CHEN"X"J,"YANG"S"H,"HAUNG"Y"Y,"GAO,"X"X,"CHEN"X"Y."Study"on"the"effect"of"different"auxiliary"methods"of"steam"distillation"on"the"chemical"composition"of"volatile"oil"of"Aquilaria"malaccensis[J]."Journal"of"Guangdong"Pharmaceutical"University,"2019,"35(2):"193-198."(in"Chinese)
[39]"THUY"D"T"T,"TUYEN"T"T,"THUY"T"T"T,"MINH"P"T"H,"TRAN"Q"T,"LONG"P"Q,"NGUYEN"D"C,"BACH"L"G,"CHIEN"N"Q."Isolation"process"and"compound"identification"of"agarwood"essential"oils"from"Aquilaria"crassna"cultivated"at"three"different"locations"in"Vietnam[J]."Processes,"2019,"7:"432.
[40]"PENPUN"W,"NAPAPORN"T,"JUREE"C."Chemical"constituents"and"antimicrobial"activity"of"essential"oil"and"extracts"of"heartwood"of"Aquilaria"crassna"obtained"from"water"distillation"and"supercritical"fluid"carbon"dioxide"extraction[J]."Silpakorn"University"Science"and"Technology"Journal,"2009,"3(1):"25-33.
[41]"耿天佑."沉香精油的提取与生物活性研究[D]."重庆:"西南大学,"2020.GENG"T"Y."Study"on"extraction"and"biological"activity"of"agarwood"essential"oil[D]."Chongqing:"Southwest"University,"2020."(in"Chinese)
[42]"王雅丽,"李薇,"曾军,"董文化,"戴好富,"梅文莉."栽培奇楠沉香精油中致香成分的GC-MS分析[J]."中国热带农业,"2021(1):"90-97.WANG"Y"L,"LI"W,"ZENG"J,"DONG"W"H,"DAI"H"F,"MEI"W"L."GC-MS"analysis"of"the"fragrant"constituents"in"cultivated"“Qi-Nan”"agarwood"essential"oil[J]."China"Tropical"Agriculture,"2021(1):"90-97."(in"Chinese)
[43]"YANG"Y,"ZHU"J,"WANG"H,"GUO"D,"WANG"Y,"MEI"W,"PENG"S,"DAI"H."Systematic"investigation"of"the"R2R3-"MYB"gene"family"in"Aquilaria"sinensis"reveals"a"transcrip tional"repressor"AsMYB054"involved"in"2-(2-phenylethyl)"chromone"biosynthesis[J]."International"Journal"of"Biological"Macromolecules,"2023,"244:"125302.
[44]"刘洋洋."通体结香技术产沉香的质量特征研究[D]."北京:"北京协和医学院,"2018.LIU"Y"Y."Research"on"quality"characteristics"of"agarwood"produced"by"whole-tree"agarwood-inducing"technique[D]."Beijing:"Peking"Union"Medical"College,"2018."(in"Chinese)
[45]"向盼,"梅文莉,"杨锦玲,"廖格,"姜北,"戴好富."不同打洞结香法所产沉香挥发性成分的GC-MS分析[J]."热带作物学报,"2016,"37(7):"1413-1418.XIANG"P,"MEI"W"L,"YANG"J"L,"LIAO"G,"JIANG"B,"DAI"H"F."GC-MS"analysis"of"volatile"constituents"from"agarwood"produced"by"holing"methods[J]."Chinese"Journal"of"Tropical"Crops,"2016,"37(7):"1413-1418."(in"Chinese)
[46]"何欣,"张燕,"孟慧,"魏建和,"吕菲菲,"刘培卫,"李浩凌,"陈波,"黄良明,"杨云."通体结香技术处理30"d产沉香的品质监测[J]."中国现代中药,"2022,"24(6):"1074-1082.HE"X,"ZHANG"Y,"MENG"H,"WEI"J"H,"LYU"F"F,"LIU"P"W,"LI"H"L,"CHEN"B,"HUANG"M"L,"YANG"Y."Quality"monitoring"of"agarwood"produced"by"whole-tree"agarwood-ind ucing"technique"(Agar-WIT)"within"30"days[J]."Modern"Chinese"Medicine,"2022,"24(6):"1074-1082."(in"Chinese)
[47]"ŘEBíČKOVá"K,"BAJER"T,"ŠILHA"D,"VENTURA"K,"BAJEROVá"P."Comparison"of"chemical"composition"and"biological"properties"of"essential"oils"obtained"by"hydrodistillation"and"steam"distillation"of"Laurus"nobilis"L[J]."Plant"Foods"for"Human"Nutrition,"2020,"75(4):"495-504.
[48]"AYUB"M"A,"CHOOBKAR"N,"HANIF"M"A,"ABBAS"M,"AIN"Q"U,"RIAZ"M,"GARMAKHANY"A"D."Chemical"composition,"antioxidant,"and"antimicrobial"activities"of"P."roxburghii"oleoresin"essential"oils"extracted"by"steam"distillation,"superheated"steam,"and"supercritical"fluid"CO2"extraction[J]."Journal"of"Food"Science,"2023,"88(6):"2425-2438.
[49]"权春梅,"周光姣,"朱勇,"张兴."精油提取方法及芍花精油的研究进展[J]."广州化工,"2016,"44(20):"16-17.QUAN"C"M,"ZHOU"G"J,"ZHU"Y,"ZHANG"X."Extracting"method"of"essential"oil"and"research"progress"on"essential"oil"of"the"peony"flower[J]."Guangzhou"Chemical"Industry,"2016,"44(20):"16-17."(in"Chinese)
[50]"张艳东,"张艳俊,"李腾飞."植物精油的提取及其生理活性研究进展[J]."食品研究与开发,"2023,"44(9):"203-210.ZHANG"Y"D,"ZHANG"Y"J,"LI"T"F."Plant"essential"oil"extraction"and"physiological"activities[J]."Food"Research"and"Development,"2023,"44(9):"203-210."(in"Chinese)
[51]"GRAJZER"M,"WIATRAK"B,"GĘBAROWSKI"T,"MATK OWSKI"A,"GRAJETA"H,"RóJ"E,"KULMA"A,"PRESCHA"A."Chemistry,"oxidative"stability"and"bioactivity"of"oil"extracted"from"Rosa"rugosa"(Thunb.)"seeds"by"supercritical"carbon"dioxide[J]."Food"Chemistry,"2021,nbsp;335:"127649.
[52]"戴伟杰,"李一峰,"陈志韶,"郑仲沐,"阚启鑫,"曹庸."不同溶剂及提取方式对沉香精油成分的影响[J]."药物评价研究,"2022,"45(8):"1597-1607.DAI"W"J,"LI"Y"F,"CHEN"Z"S,"ZHENG"Z"M,"QUE"Q"X,"CAO"Y."Effects"of"different"solvent"and"extraction"methods"on"components"of"agarwood"essential"oil[J]."Drug"Evaluation"Research,"2022,"45(8):"1597-1607."(in"Chinese)
[53]"李响,"王卫飞,"周瑢,"杨博,"王永华."超临界二氧化碳萃取沉香精油的工艺优化[J]."食品工业科技,"2014,"35(20):"307-312.LI"X,"WANG"W"F,"ZHOU"R,"YANG"B,"WANG"Y"H."Supercritical"CO2"fluid"extraction"of"the"essential"oil"from"Chinese"eaglewood[J]."Science"and"Technology"of"Food"Industry,"2014,"35(20):"307-312."(in"Chinese)
[54]"王健松,"李远彬,"王羚郦,"罗珊,"陈嘉丽,"盛楠,"温炳权,"杨良,"赖小平."超临界和亚临界提取的沉香精油的气相色谱-质谱联用分析[J]."时珍国医国药,"2017,"28(5):"1082-"1085.WANG"J"S,"LI"Y"B,"WANG"L"L,"LUO"S,"CHEN"J"L,"SHENG"N,"WEN"B"Q,"YANG"L,"LAI"X"P."GC-MS"analysis"on"supercritical"CO2"fluid"and"subcritical"fluid"extractions"of"agarwood"essential"oils[J]."Lishizhen"Medicine"and"Materia"Medica"Research,"2017,"28(5):"1082-1085."(in"Chinese)
[55]"World"Health"Organization."Depression"and"other"commonmental"disorders:"global"health"estimates"[M/OL]."Geneva:"WHO,"2017.
[56]"国家药典委员会."中华人民共和国药典[M]."北京:"中国医药科技出版社,"2020.Chinese"Pharmacopoeia"Commission."Pharmacopoeia"of"People’s"Republic"of"China[M]."Beijing:"China"Medical"Science"and"Technology"Press,"2020."(in"Chinese)
[57]"霍会霞."沉香的化学成分分析及抗动脉粥样硬化作用机制研究[D]."北京:"北京中医药大学,"2019.HUO"H"X."Analysis"of"chemical"constituents"of"Agarwood"and"research"on"mechanism"of"anti-atherosclerosis"action"[D]."Beijing:"Beijing"University"of"Chinese"Medicine,"2019."(in"Chinese)
[58]"TIAN"C"P,"YAO"X"D,"LU"J"H,"SHEN"L"Q,"WU"A"Q."GC-MS"fingerprints"of"essential"oils"from"agarwood"grown"in"wild"and"artificial"environments[J]."Trees-Structure"and"Function,"2021,"35(6):"2105-2117.
[59]"KAO"W"Y,"HSIANG"C"Y,"HO"S"C,"HO"T"Y,"LEE"K"T."Novel"serotonin-boosting"effect"of"incense"smoke"from"Kynam"agarwood"in"mice:"the"involvement"of"multiple"neuroactive"pathways[J]."Journal"of"Ethnopharmacology,"2021,"275:"114069.
[60]"JUAN"L,"JIAN"Y,"CHAO"J,"JUNHUI"Z,"YUYANG"Z,"HUANG"L."Volatile"organic"compound"and"endogenous"phyto hormone"characteristics"during"callus"browning"in"Aquilaria"sinensis[J]."Industrial"Crops"and"Products,"2021,"168:"113605.
[61]"NAEF"R."The"volatile"and"semi-volatile"constituents"of"agarwood,"the"infected"heartwood"of"Aquilaria"species:"a"review[J]."Flavour"and"Fragrance"Journal,"2011,"26(2):"73-87.
[62]"MIYOSHI"T,"ITO"M,"KITAYAMA"T,"ISOMORI"S,"YAMASHITA"F."Sedative"effects"of"inhaled"benzylacetone"and"structural"features"contributing"to"its"activity[J]."Biological"and"Pharmaceutical"Bulletin,"2013,"36(9):"1474-1481.
[63]"OKUGAWA"H,"UEDA"R,"MATSUMOTO"K,"KAWAN IS HI"K,"KATO"A."Effects"of"agarwood"extracts"on"the"central"nervous"system"in"mice[J]."Planta"Medica,"1993,"59(1):"32-36.
[64]"汪凤华,"李东勳,"王日康."二十味沉香微丸对绝望小鼠行为及海马5-HT系统的影响[J]."中成药,"2019,"41(12):"3029-3032.WANG"F"H,"LI"D"X,"WAMG"R"K."Effects"of"twenty"kinds"of"Agarwood"pellets"on"behavior"and"5-HT"system"in"hippocampus"of"desperate"mice[J]."Chinese"Traditional"Patent"Medicine,"2019,"41(12):"3029-3032."(in"Chinese)
[65]"王帅,"周岳,"马富超,"张泉洋,"刘洋洋,"弓宝,"郭鹏,"魏建和."通体沉香对小鼠催眠和自主活动抑制作用[J]."国际药学研究杂志,"2016,"43(6):"1082-1087.WANG"S,"ZHOU"Y,"MA"F"C,"ZHANG"Q"Y,"LIU"Y"Y,"GONG"B,"GUO"P,"WEI"J"H."Effect"of"agarwood"produced"by"whole-tree"agarwood-inducing"technique"on"hypnotic"and"spontaneous"activity"inhibition"of"mice[J]."Journal"of"International"Pharmaceutical"Research,"2016,"43(6):"1082-1087."(in"Chinese)
[66]"侯金良,"张媛媛,"张浩,"耿希文,"李自发,"齐冬梅,"邓华亮,"魏盛."沉香片剂小鼠口鼻吸入给药抗焦虑和催眠功效实验研究[J]."山东中医药大学学报,"2021,"45(1):"113-119.HOU"J"L,"ZHANG"Y"Y,"ZHANG"H,"GENG"X"W,nbsp;LI"Z"F,"QI"D"M,"DENG"H"L,"WEI"S."Experimental"study"on"antianxiety"and"hypnotic"effects"of"aquilariae"lignum"resinatum"tablet"on"mice"by"oral"and"nasal"inhalation[J]."Journal"of"Shandong"University"of"Traditional"Chinese"Medicine,"2021,"45(1):"113-119."(in"Chinese)
[67]"梁宇,"孔德文,"周启蒙,"赵晓悦,"于子茹,"王静蓉,"李改云,"杜冠华."沉香气体吸入给药通过影响神经递质调节小鼠睡眠的作用研究[J]."中药药理与临床,"2019,"35(6):"71-77.LAING"Y,"KONG"D"W,"ZHOU"Q"M,"ZHAO"X"Y,"YU"Z"R,"WANG"J"R,"LI"G"Y,"DU"G"H."Effect"of"agarwood"gas"on"the"sleep"of"mice"by"regulating"neurotransmitters[J]."Pharmacology"and"Clinics"of"Chinese"Materia"Medica,"2019,"35(6):"71-77."(in"Chinese)
[68]"雷莉,"张婷,"高东,"黄庆玲."沉香熏香疗法对失眠障碍患者的临床疗效研究[J]."中风与神经疾病杂志,"2019,"36(7):"609-612.LEI"L,"ZHANG"T,"GAO"D,"HUANG"Q"L."The"clinical"effect"of"aromatherapy"of"best"agarwood"production"in"patients"with"insomnia[J]."Journal"of"Apoplexy"and"Nervous"Diseases,"2019,"36(7):"609-612."(in"Chinese)
[69]"BANDELOW"B,"SHER"L,"BUNEVICIUS"R,"HOLLAN D ER"E,"KASPER"S,"ZOHAR"J,"MöLLER"H-J."Guidelines"for"the"pharmacological"treatment"of"anxiety"disorders,"obsess ive–compulsive"disorder"and"posttraumatic"stress"disorder"in"primary"care[J]."International"Journal"of"Psychiatry"in"Clinical"Practice,"2012,"16(2):"77-84.
[70]"DELL'OSSO"B,"BUOLI"M,"BALDWIN"D"S,"ALTAMURA"A"C."Serotonin"norepinephrine"reuptake"inhibitors"(SNRIs)"in"anxiety"disorders:"a"comprehensive"review"of"their"clinical"efficacy[J]."Human"Psychopharmacology:"Clinical"and"Experimental,"2010,"25(1):"17-29.
[71]"ERRINGTON-EVANS"N."Acupuncture"for"anxiety[J]."CNS"Neuroscience"amp;"Therapeutics,"2012,"18(4):"277-284.
[72]"吴亚妮."精油香气抗焦虑作用的代谢组学研究[D]."上海:"上海交通大学,"2013.WU"Y"N."Metabolomics"research"on"anxiolytic"effect"of"aerial"of"essential"oils[D]."Shanghai:"Shanghai"Jiao"Tong"University,"2013."(in"Chinese)
[73]"ZHANG"N,"YAO"L."Anxiolytic"effect"of"essential"oils"and"their"constituents:"a"review[J]."Journal"of"Agricultural"and"Food"Chemistry,"2019,"67(50):"13790-13808.
[74]"袁付丽."基于代谢组学和网络药理学的栀子抗焦虑作用机制研究[D]."北京:"北京中医药大学,"2021.YUAN"F"L."Research"on"anxiolytic"mechanism"of"Gardenia"jasminoides"ellis"based"on"metabolomics"and"network"pharmacology[D]."Beijing:"Beijing"University"of"Chinese"Medicine,"2021."(in"Chinese)
[75]"DANG"R,"WANG"M,"LI"X,"WANG"H,"LIU"L,"WU"Q,"ZHAO"J,"JI"P,"ZHONG"L,"LICINIO"J,"XIE"P."Edaravone"ameliorates"depressive"and"anxiety-like"behaviors"via"Sirt1/Nrf2/HO-1/Gpx4"pathway[J]."Journal"of"Neuroinflammation,"2022,"19(1):"41.
[76]"LIU"W"Z,"ZHANG"W"H,"ZHENG"Z"H,"ZOU"J"X,"LIU"X"X,"HUANG"S"H,"YOU"W"J,"HE"Y,"ZHANG"J"Y,"WANG"X"D,"PAN"B"X."Identification"of"a"prefrontal"cortex-to-amygdala"pathway"for"chronic"stress-induced"anxiety[J]."Nature"Communications,"2020,"11(1):"2221.
[77]"LEE"H"Y,"LEE"J"S,"KIM"H"G,"KIM"W"Y,"LEE"S"B,"CHOI"Y"H,"SON"C"G."The"ethanol"extract"of"Aquilariae"lignum"ameliorates"hippocampal"oxidative"stress"in"a"repeated"restraint"stress"mouse"model[J]."BMC"Complementary"and"Alternative"Medicine,"2017,"17(1):"397.
[78]nbsp;弓宝,"王灿红,"吴玉兰,"刘洋洋,"魏建和."沉香熏香吸入抗焦虑、抗抑郁作用及其机制研究[J]."中国中药杂志,"2023,"48(4):"1023-1031.GONG"B,"WANG"C"H,"WU"Y"L,"LIU"Y"Y,"WEI"J"H."Anxiolytic"and"antidepressant"effects"of"agarwood"inhalation"and"its"mechanism"[J]."China"Journal"of"Chinese"Materia"Medica,"2023,"48(4):"1023-1031."(in"Chinese)
[79]"WANG"C,"GONG"B,"LIU"Y,"CHEN"D,"WU"Y,"WEI"J."Agarwood"essential"oil"inhalation"exerts"antianxiety"and"antidepressant"effects"via"the"regulation"of"Glu/GABA"system"homeostasis[J]."Biomedical"Reports,"2023,"18(2):"16.
[80]"刘倩,"王东辉,"李春,"吕岱,"王维君,"郭积玉."α-沉香呋喃衍生物的合成及中枢神经系统活性[J]."中国药物化学杂志,"2003,"13(3):"125-130.LIU"Q,"WANG"D"H,"LI"C,"LYU"D,"WANG"W"J,"GUO"J"Y."Synthesis"and"CNS"activities"of"α-agarofuran"derivatives[J]."Chinese"Journal"of"Medicinal"Chemistry,"2003,"13(3):"125-130."(in"Chinese)
[81]"MALHI"G"S,"MANN"J"J."Depression[J]."Lancet,"2018,"392(10161):"2299-2312.
[82]"RUBERTO"V"L,"JHA"M"K,"MURROUGH"J"W."Pharmacological"treatments"for"patients"with"treatment-resistant"depression[J]."Pharmaceuticals,"2020,"13(6):"116.
[83]"黄国尧."沉香香熏改善抑郁状态的临床研究[D]."济南:"山东中医药大学,"2016.HUANG"G"Y."The"clinical"research"of"tambac"incense"improving"depressive"state[D]."Jinan:"Shandong"University"of"Traditional"Chinese"Medicine,"2016."(in"Chinese)