董 偉,黃小英,湯喜蘭,李秋香,趙國(guó)巍,梁新麗*,楊 明
植物精油對(duì)心血管疾病作用的研究進(jìn)展
董 偉1,黃小英1,湯喜蘭2,李秋香1,趙國(guó)巍1,梁新麗1*,楊 明1
1. 江西中醫(yī)藥大學(xué) 現(xiàn)代中藥制劑教育部重點(diǎn)實(shí)驗(yàn)室,江西 南昌 330004 2. 江西科技師范大學(xué)藥學(xué)院,江西 南昌 330013
心血管疾病是心臟和血管方面相關(guān)的疾病,包括高血壓、高脂血癥、血栓栓塞、冠心病和心力衰竭等。心血管疾病嚴(yán)重危害人類健康,是全球范圍內(nèi)造成死亡的最主要原因。維護(hù)心血管系統(tǒng)健康的關(guān)鍵因素是對(duì)疾病的預(yù)防。植物精油及其部分成分能舒張血管、降血壓、抗心肌缺血、預(yù)防和改善動(dòng)脈粥樣硬化、抗血小板聚集以及抗心律失常,從而對(duì)心血管系統(tǒng)具有保護(hù)作用。植物精油有益于人體的心血管系統(tǒng),但需要更多的臨床研究和安全性研究的證據(jù)。
植物精油;心血管疾??;高血壓;心肌缺血;動(dòng)脈粥樣硬化;血小板聚集;心律失常
心血管疾病是心臟和血管的疾病,包括高血壓、高脂血癥、血栓栓塞、冠心病和心力衰竭等。心血管疾病嚴(yán)重危害人類健康,是全球范圍內(nèi)造成死亡的最主要原因。根據(jù)世界衛(wèi)生組織的數(shù)據(jù),每年有超過(guò)1700萬(wàn)人(占全球死亡人數(shù)的31%)死于心血管疾病。隨著心血管疾病診斷人數(shù)的增加,預(yù)計(jì)2030年前的死亡人數(shù)將達(dá)到2330萬(wàn)[1]。流行病學(xué)研究表明,某些因素與心血管疾病的發(fā)生有明顯關(guān)聯(lián)。這些因素包括高血壓、高膽固醇血癥、糖尿病、炎癥、致動(dòng)脈粥樣硬化的飲食以及血液中過(guò)量自由基等因素導(dǎo)致的氧化應(yīng)激;運(yùn)動(dòng)缺乏、肥胖和凝血增加也起到了一定作用。近幾十年來(lái),人們?cè)絹?lái)越多地研究替代療法,特別是植物療法和膳食補(bǔ)充劑來(lái)治療心血管疾病。植物精油是芳香植物產(chǎn)生的復(fù)雜次生代謝產(chǎn)物,具有強(qiáng)烈的氣味,具有抑菌、抗衰老、抗哮喘等作用[2-5]。研究顯示植物精油具有心臟保護(hù)作用,含有抗心血管疾病的活性化合物,可以通過(guò)影響血管舒張、降低心率和降低血壓來(lái)改善心血管系統(tǒng),在促進(jìn)心血管系統(tǒng)健康方面起了一定作用。本文總結(jié)了植物精油在降低心血管疾病風(fēng)險(xiǎn)方面的作用及現(xiàn)狀,為開發(fā)治療如高血壓、心絞痛、動(dòng)脈粥樣硬化等心血管疾病新的功能性產(chǎn)品提供研究思路和建議。
高血壓通常極大地增加其他心血管事件包括心肌梗死、卒中和充血性心力衰竭的風(fēng)險(xiǎn)。近69%的首次心臟病發(fā)作、7%的首次卒中和74%的充血性心力衰竭患者患有高血壓。研究表明,降低血壓可以降低心血管事件的發(fā)生率[6]。
研究顯示植物精油以及所含成分對(duì)-硝基--精氨酸甲酯(-nitro--arginine methyl ester,-NAME)所致慢性高血壓大鼠[7-8]、脫氧皮質(zhì)酮所致高血壓大鼠[9-10]和自發(fā)性高血壓大鼠有降壓作用[11]。植物精油誘導(dǎo)血管擴(kuò)張通常是由于直接舒張血管引起的。植物精油iv可引起正常大鼠劑量相關(guān)性雙相低血壓和心動(dòng)過(guò)緩[12-13],降低收縮壓、舒張壓、平均動(dòng)脈壓和心率[14]。1-硝基-2-苯基乙烷[13]、香芹酚[8]、香茅醇[15]、丁香酚[10]等精油中所含的成分iv可直接舒張血管平滑肌引起正常大鼠產(chǎn)生低血壓反應(yīng)。
在體外實(shí)驗(yàn)中植物精油可舒張預(yù)收縮的離體動(dòng)脈環(huán)。如艷山姜(Pers.) Burtt. et Smith精油[7]、阿育魏實(shí)Sprague精油[16]以濃度相關(guān)性地方式抑制苯腎上腺素(phenylephrine,PHE)和KCl誘導(dǎo)的內(nèi)皮完整和內(nèi)皮剝離大鼠離體主動(dòng)脈環(huán)的收縮,鉀通道阻斷劑不影響松弛作用[7],亞甲基藍(lán)和-NAME不影響舒張血管作用[16]。
內(nèi)皮是一層高度專門化的管腔血管層,主要通過(guò)釋放內(nèi)皮衍生的血管擴(kuò)張劑如一氧化氮(nitric oxide,NO)和前列環(huán)素在血管舒張中起關(guān)鍵作用。植物精油的血管舒張功能可能與內(nèi)皮依賴性途徑有關(guān),如內(nèi)皮-精氨酸/NO途徑或內(nèi)皮環(huán)氧化酶途徑[2]。研究顯示丁香羅勒L.精油[10]、香薷狀刺蕊草Benth.[14]對(duì)內(nèi)皮完整的主動(dòng)脈有明顯的舒張作用,其作用機(jī)制可能是通過(guò)NO依賴途徑實(shí)現(xiàn)。薤白Bunge精油及其主要成分二甲基二硫醚對(duì)PHE的內(nèi)皮完整離體大鼠肺動(dòng)脈環(huán)收縮有舒張作用,在去除血管內(nèi)皮后可被消除,其舒張作用有賴于血管內(nèi)皮的完整性;動(dòng)脈舒張通過(guò)蛋白激酶A依賴的一氧化氮合酶(nitric oxide synthase,NOS)磷酸化和NO信號(hào)轉(zhuǎn)導(dǎo)等機(jī)制引起[17]。
植物精油舒張血管也可能不依賴于內(nèi)皮通路,其也可通過(guò)阻斷血管平滑肌膜上的電壓門控型鈣通道而舒張血管?;囊拜風(fēng).精油的血管舒張作用似乎是非內(nèi)皮依賴性的,舒張作用在去除內(nèi)皮后持續(xù)存在;但鈣通道阻滯劑預(yù)處理后減弱了這種作用,提示血管舒張是通過(guò)抑制L型鈣離子通道和激活肌漿/內(nèi)質(zhì)網(wǎng)Ca2+-ATP酶泵介導(dǎo)的[18]。Jowitt精油iv會(huì)誘發(fā)劑量相關(guān)性低血壓和心動(dòng)過(guò)速,該作用不受-NAME或吲哚美辛的影響,但在阿托品使用后部分減少;其對(duì)離體動(dòng)脈環(huán)也有舒張作用,這些作用主要是通過(guò)阻斷鈣離子通道介導(dǎo)的[19]。1,8-桉葉素是姚金娘科植物藍(lán)桉Labill.的主要成分,被發(fā)現(xiàn)可以抑制細(xì)胞鈣離子內(nèi)流,舒張離體動(dòng)脈,降低主動(dòng)脈壓[20]。其可降低長(zhǎng)期接觸尼古丁所致高血壓大鼠的收縮壓,并拮抗尼古丁所致的脂質(zhì)過(guò)氧化水平升高[21]。
抑制ACE活性是治療高血壓的方法之一,研究顯示Schumach. & Thonn.精油等植物精油[22-23]具有抑制ACE舒張血管的作用,這可能是這些精油舒張血管、預(yù)防高血壓的原因。分子對(duì)接顯示精油所含的匙葉桉油烯醇與ACE的結(jié)合親和力最好,最低結(jié)合能為?31.4 kJ/mol[23]。
心肌梗死是一種嚴(yán)重的心血管疾病,以缺血/再灌注損傷為特征。研究表明對(duì)器官造成損害的主要因素不是缺血本身而是再灌注。在再灌注期間,自由基的過(guò)度生成導(dǎo)致氧化應(yīng)激和急性炎癥反應(yīng)。心肌梗死后,炎癥過(guò)程導(dǎo)致包括(tumor necrosis factor-α,TNF-α)、轉(zhuǎn)化生長(zhǎng)因子-β和白細(xì)胞介素(interleukin,IL)在內(nèi)的各種細(xì)胞因子的釋放可導(dǎo)致心肌壞死、細(xì)胞凋亡、纖維化、心力衰竭、非梗死區(qū)心肌肥厚,最終導(dǎo)致心臟重構(gòu)[24]。艷山姜精油[25]、賀蘭山丁香Hemsl. var.Ma et S. Q. Zhou精油[26]對(duì)異丙腎上腺素(isoproterenol,ISO)、冠狀動(dòng)脈結(jié)扎誘導(dǎo)的大鼠心肌梗死以及H2O2誘導(dǎo)的大鼠心肌細(xì)胞死亡有保護(hù)作用。
薰衣草Mill.精油可通過(guò)抑制炎癥和心肌梗死,對(duì)抗氧化應(yīng)激,從而發(fā)揮心臟保護(hù)作用[24]。姜黃L.精油可降低缺血/再灌注大鼠模型左心室缺血面積和內(nèi)皮細(xì)胞誘導(dǎo)的炎癥,并減少黏附因子如E-選擇素和細(xì)胞間黏附分子-1的表達(dá),減少了炎癥細(xì)胞與內(nèi)皮細(xì)胞的黏附[27]。
植物精油中的成分如香芹酚[25]能保護(hù)心肌細(xì)胞缺血/再灌注損傷,可明顯縮小心肌梗死面積,對(duì)心肌缺血具有潛在的治療作用。香芹酚的心肌保護(hù)作用可能與其通過(guò)激活絲裂原活化蛋白激酶/細(xì)胞外信號(hào)調(diào)節(jié)激酶和蛋白激酶B/NOS信號(hào)通路而發(fā)揮抗氧化和抗凋亡作用有關(guān)。此外,精油中的萜類成分如α-蒎烯[29]、諾卡酮[30]具有抗炎、抗氧化的作用,對(duì)ISO誘導(dǎo)的心肌梗死中血脂異常、心肌內(nèi)脂質(zhì)積累和脂質(zhì)代謝改變有明顯的保護(hù)作用。
動(dòng)脈粥樣硬化是一種動(dòng)脈內(nèi)膜膽固醇沉積過(guò)多的慢性炎癥性疾病,與氧化應(yīng)激和內(nèi)皮功能障礙有關(guān)。高脂血癥是引起肥胖、糖尿病、心血管疾病等代謝癥候群的重要因素。高脂血癥是最常見的血脂異常形式,按照脂質(zhì)類型分為高膽固醇血癥、高三酰甘油血癥、高膽固醇和高三酰甘油混合型高脂血癥,被認(rèn)為是心血管疾病,特別是動(dòng)脈粥樣硬化的一個(gè)非常危險(xiǎn)的因素[31]。研究發(fā)現(xiàn),膽固醇改變了血管的結(jié)構(gòu)和功能,其在血管壁內(nèi)生成并干擾內(nèi)皮功能,導(dǎo)致內(nèi)皮損傷、斑塊、阻塞和栓子[32]。
植物精油有調(diào)血脂作用。酸橙(Christm.) Swingle精油、大蒜L.精油、洋蔥L.精油、迷迭香Linn.精油可以降低高脂血癥大鼠血清總膽固醇(total cholesterol,TC)、三酰甘油(triacylglycerol,TG)、低密度脂蛋白膽固醇(low density lipoprotein cholesterin,LDL-C)水平,從而降低肥胖預(yù)防動(dòng)脈粥樣硬化形成[33-34]。此外研究發(fā)現(xiàn)植物精油中所含成分香葉醇[35]、桃金娘烯醛[36]、油酰胺[37]能顯著降低血漿TC、TG、脂肪酸、LDL-C水平和動(dòng)脈粥樣硬化指數(shù)。
動(dòng)脈粥樣硬化是由血管和炎癥細(xì)胞之間復(fù)雜的相互作用引起的。傳統(tǒng)上認(rèn)為它是一種內(nèi)膜炎癥性疾病,以內(nèi)皮功能障礙、炎性細(xì)胞募集、脂質(zhì)氧化和泡沫細(xì)胞形成為特征。內(nèi)皮損傷和功能障礙被認(rèn)為是動(dòng)脈粥樣硬化形成的基礎(chǔ),它通過(guò)由內(nèi)向外的信號(hào)觸發(fā)血管炎癥和脂質(zhì)攝取[38]。單核細(xì)胞與受損內(nèi)皮層黏附增加是動(dòng)脈粥樣硬化形成的關(guān)鍵早期因素。在炎癥條件下,活化的血管內(nèi)皮細(xì)胞上特異性細(xì)胞黏附分子的表達(dá)增加,從而增加單核細(xì)胞黏附。
五味子(Turcz.) Baill.精油通過(guò)選擇性抑制基質(zhì)金屬蛋白酶9的表達(dá),抑制TNF-α誘導(dǎo)的人主動(dòng)脈平滑肌細(xì)胞HASMCs遷移,提示其具有潛在的抗動(dòng)脈粥樣硬化活性[39]。在動(dòng)脈粥樣硬化過(guò)程中,單核細(xì)胞在動(dòng)脈粥樣硬化斑塊的形成、穩(wěn)定和破裂過(guò)程中起重要作用。牛至L.精油具有抗炎作用,使氧化低密度脂蛋白(oxidized low-density lipoprotein,ox-LDL)激活的人急性THP-1單核細(xì)胞促炎性因子TNF-α、IL-1β和IL-6合成減少,抗炎性因子IL-10合成增加[40]。植物精油中的倍半萜化合物β-欖香烯[41]、反式石竹烯[42]、鼠尾草酚[42]能抑制炎性因子的產(chǎn)生,阻止單核細(xì)胞與內(nèi)皮細(xì)胞的黏附,增加斑塊的穩(wěn)定性,抑制動(dòng)脈粥樣硬化發(fā)展。
LDL氧化在動(dòng)脈粥樣硬化形成中起重要作用,其與其經(jīng)典受體的親和力由于氧化而降低。相反,它被巨噬細(xì)胞中的清道夫分子吸收,因此形成了泡沫細(xì)胞,這些泡沫細(xì)胞在增加血管內(nèi)皮下脂肪層方面起重要作用。研究顯示檸檬精油及其成分γ-松油烯可以有效地減緩LDL的氧化[43]??颬amp.精油中由于含有豐富的抗氧化劑,可通過(guò)減少氧化甾醇的形成來(lái)改善肝臟脂質(zhì)代謝,其可能通過(guò)LDL氧化和上調(diào)低密度脂蛋白受體(low density lipoprotein receptor,LDLR)而具有抗動(dòng)脈粥樣硬化作用[44]。千金子精油、艷山姜精油對(duì)高脂血癥和動(dòng)脈粥樣硬化有改善作用,對(duì)ox-LDL誘導(dǎo)的人臍靜脈內(nèi)皮細(xì)胞、人主動(dòng)脈內(nèi)皮細(xì)胞損傷的內(nèi)皮有保護(hù)作用,減輕ox-LDL誘導(dǎo)的凋亡所致的細(xì)胞損傷[45-46];可通過(guò)提高超氧化物歧化酶、過(guò)氧化氫酶和谷胱甘肽過(guò)氧化物酶的活性,增加谷胱甘肽的水平,降低丙二醛的含量,改善氧化應(yīng)激[46]。此外,精油中的酚類物質(zhì)如百里香酚、丁香酚、百里醌[47-48],具有較強(qiáng)的抗氧化性能;可以改變LDL顆粒對(duì)LDLR的親和力[47]。香茅醛是一種主要由植物次生代謝產(chǎn)生的單萜類化合物,可通過(guò)誘導(dǎo)NOS的調(diào)節(jié)抑制NO的產(chǎn)生,并減少環(huán)氧酶的表達(dá)減少前列腺素的釋放,從而改善內(nèi)皮功能障礙,阻止動(dòng)脈粥樣硬化的發(fā)展[49]。
膽固醇的蓄積在心血管疾病中起突出的作用,被認(rèn)為是冠狀動(dòng)脈疾病的重要病因,哺乳動(dòng)物中甲羥戊酸通路負(fù)責(zé)膽固醇作為主要最終產(chǎn)物的生物合成。研究顯示植物精油有降膽固醇的作用,高膽固醇血癥受試者每天服用140 mg檸檬草油膠囊(主要含香葉醇和檸檬醛)90 d之后,血清膽固醇水平有效下降[50]。
羥甲基戊二酸單酰輔酶A還原酶(hydroxymethylglutaryl-CoA synthase,HMGCR)是體內(nèi)催化膽固醇合成的關(guān)鍵酶,其活性大小直接影響膽固醇合成的速度和含量的高低[51]。植物精油對(duì)HMGCR有明顯抑制作用[44,48,52-53]。從而降低膽固醇的合成。研究顯示(Miller) N.E. Brown精油抑制HMGCR,降低HMGCR蛋白水平,降膽固醇生成,抑制TG、膽固醇酯和磷脂合成,并減少脂滴的大小和體積[52]。香葉醇可降低小鼠肝臟HMGCR蛋白水平和酶的催化活性,導(dǎo)致肝細(xì)胞膽固醇合成下降[35]。
過(guò)氧化物酶體增殖物激活受體-α(peroxisome proliferator-activated receptor-α,PPAR-α)是一種核激素受體,調(diào)節(jié)與脂質(zhì)代謝和炎癥相關(guān)的基因[54]。PPAR-α通過(guò)影響膽固醇代謝的多個(gè)過(guò)程,包括從頭合成、降解、腸道吸收、膽汁和糞便排泄,成為控制膽固醇穩(wěn)態(tài)的關(guān)鍵開關(guān);抑制PPAR-α可顯著上調(diào)HMGCR的表達(dá),進(jìn)而促進(jìn)膽固醇的生物合成[55]。肝X受體α是配體激活的轉(zhuǎn)錄因子,調(diào)節(jié)脂質(zhì)和膽固醇代謝相關(guān)基因的表達(dá)。研究顯示姜黃精油對(duì)高膽固醇和高脂飼料喂養(yǎng)金黃地鼠模型顯示出抗高脂血癥作用,可能是通過(guò)調(diào)節(jié)PPAR-α、肝X受體α等與調(diào)節(jié)膽固醇穩(wěn)態(tài)和轉(zhuǎn)運(yùn)相關(guān)的基因來(lái)實(shí)現(xiàn)的[56-57]。
LDLR是脂蛋白受體家族的創(chuàng)始成員,介導(dǎo)低密度脂蛋白顆粒內(nèi)吞作用和調(diào)節(jié)膽固醇穩(wěn)態(tài)。LDLR介導(dǎo)的LDL清除是決定循環(huán)中LDL-C水平的主要因素,在動(dòng)脈粥樣硬化形成中起重要作用[58]。研究顯示植物精油的調(diào)血脂作用與其上調(diào)LDLR有關(guān)[53]。香葉醇還增強(qiáng)了編碼LDL和極低密度脂蛋白受體mRNA的表達(dá)[35]。
動(dòng)物細(xì)胞中的脂質(zhì)平衡是由固醇調(diào)節(jié)元件結(jié)合蛋白(sterol regulatory element-binding protein,SREBP)維持的,這是一種膜結(jié)合轉(zhuǎn)錄因子[59]。SREBP-1和SREBP-2是固醇感受器,當(dāng)細(xì)胞膽固醇和氧化型膽固醇水平較低時(shí),SREBP-1和SREBP-2被激活為功能性轉(zhuǎn)錄因子。SREBP-1a和SREBP-1c參與脂肪合成、脂肪酸合成和碳水化合物代謝基因的誘導(dǎo),SREBP2參與膽固醇合成基因的上調(diào)。研究顯示紅松葉精油可抑制SREBP-1c、SREBP-2的表達(dá)以及膽固醇酰基轉(zhuǎn)移酶1和2的水平[53]。
血小板對(duì)于止血、血栓形成以及各種心血管和腦血管疾病的發(fā)作至關(guān)重要。但是,血管中的血小板聚集會(huì)引起血栓形成,并且是各種臨床疾病的病因。血小板活化和聚集的潛在機(jī)制對(duì)于預(yù)防和治療受損血管的失血非常重要。此外,調(diào)節(jié)血小板聚集是預(yù)防失血和治療心血管疾病的主要策略之一[60]。
植物精油具有抑制血小板聚集、凝塊收縮、抗血栓形成作用。研究顯示茴香Mill.精油及其主要成分茴香腦[61]、薰衣草精油[62]對(duì)花生四烯酸、膠原蛋白、二磷酸腺苷(adenosine 5′-diphosphate,ADP)和血栓素A2受體激動(dòng)劑U46619誘導(dǎo)的血小板聚集有抑制作用,對(duì)膠原-腎上腺素注射所致小鼠急性血栓形成有抗血栓形成作用。
植物精油中所含的倍半萜類化合物通常具有抗血小板聚集作用[63]。莪術(shù)二酮是莪術(shù)精油的主要倍半萜類化合物之一,具有抗血小板聚集和抗血栓形成作用。莪術(shù)二酮還能抑制血小板活化因子活化的血小板中P-選擇素的表達(dá)[60]。植物精油對(duì)血小板活化因子(platelet-activating factor,PAF)受體結(jié)合有明顯的抑制作用,這與精油中的倍半萜和倍半萜含量有關(guān)[64]。另有研究顯示富含苯丙素類和酚類的精油具有較好的抑制血小板聚集作用[65]。肉桂醛也有抑制血小板聚集、凝塊收縮、抗血栓形成和舒張血管的作用,可能與抑制血栓素A2受體有關(guān)[66]。
心律失常是由心臟協(xié)調(diào)電活動(dòng)變化引起的一種紊亂,是導(dǎo)致猝死的主要原因之一。心律失常表現(xiàn)為脈沖產(chǎn)生異常、傳導(dǎo)障礙或二者都有。心肌細(xì)胞表現(xiàn)出對(duì)細(xì)胞內(nèi)鈣穩(wěn)態(tài)的精細(xì)動(dòng)態(tài)控制。目前發(fā)現(xiàn)植物精油中的萜類化合物法尼醇[67]、橙花醇[68]、香葉醇[69]具有抗心律失常的特性,可降低細(xì)胞內(nèi)Ca2+瞬時(shí)值、鉀電流(k)、L型鈣電流(Ca.L)并且縮短了90%復(fù)極時(shí)的動(dòng)作電位時(shí)程從而降低嚴(yán)重心律失常的發(fā)生率;抑制鈣火花頻率和鈣波的產(chǎn)生,減少受到Ca2+超載影響的心肌細(xì)胞產(chǎn)生活性氧[67];降低心率和收縮力,抑制毒毛旋花苷誘發(fā)的心律失常,但不改變毒毛旋花苷引起的正性肌力變化[68-69]。
目前以植物精油為載體的芳香療法通過(guò)按摩、香薰等使用方式可降低心血管疾病的風(fēng)險(xiǎn),植物精油吸入可以引起副交感神經(jīng)活動(dòng)增加和交感神經(jīng)活動(dòng)減少,產(chǎn)生降壓、鎮(zhèn)靜作用。薰衣草、依蘭(Lam.) Hook. f. & Thomson、蠟菊(Roth) G. Don、馬郁蘭L.和檸檬(L.) Burm. f.等精油通常用來(lái)輔助降低高血壓[6],改善睡眠質(zhì)量[70-71]。此外,雪松醇是從雪松(Roxb. ex D. Don) G. Don精油中提取的純化合物,加熱霧化吸入后可降低心率、收縮壓、舒張壓和呼吸頻率[72]。一項(xiàng)前瞻性臨床研究顯示迷迭香L.精油對(duì)原發(fā)性低血壓患者有升高血壓的作用并改善患者的健康相關(guān)生活質(zhì)量[73]。
心肌梗死不僅會(huì)導(dǎo)致身體問(wèn)題,還會(huì)導(dǎo)致焦慮、疲勞、抑郁、睡眠障礙、睡眠干擾等心理問(wèn)題。吸入天竺葵L'Hér.精油的芳香療法對(duì)心血管重癥監(jiān)護(hù)病房患者植入心臟支架后降低焦慮、提高睡眠質(zhì)量和穩(wěn)定血壓有積極作用[74]。中風(fēng)患者通常參加康復(fù)鍛煉計(jì)劃,如物理治療、職業(yè)治療和/或語(yǔ)言治療。結(jié)合筷子訓(xùn)練的移動(dòng)豆子任務(wù)已被用于中風(fēng)患者優(yōu)勢(shì)手障礙的康復(fù)治療,但其會(huì)增加中風(fēng)患者的心血管反應(yīng)。對(duì)于特質(zhì)焦慮癥狀較高的腦卒中患者,用薰衣草精油和葡萄柚i Macfad.精油刺激嗅覺(jué),可以抑制移動(dòng)豆子任務(wù)過(guò)度的舒張壓升高的心血管系統(tǒng)反應(yīng)[75]。
人們普遍認(rèn)為藥用植物比合成藥物更安全,對(duì)人體的危害更小,天然成分相對(duì)于合成化合物毒性更小[76]。植物精油在心血管系統(tǒng)的安全性方面還缺乏更多的研究信息。毒理研究顯示歐薄荷L. subsp.(Thunb.) Briq.精油125~500 μL/kg使大鼠紅細(xì)胞和淋巴細(xì)胞減少,白細(xì)胞和平均細(xì)胞體積無(wú)明顯變化,對(duì)血清低密度脂蛋白、膽固醇、Na+、Ca2+、Cl?、K+、肌酐和尿酸無(wú)明顯影響,不易導(dǎo)致動(dòng)脈粥樣硬化[77]。黃樟油素-2′,3′-氧化物是黃樟素的主要代謝物,存在于多種植物精油當(dāng)中,如八角茴香Hook. f.、肉豆蔻Houtt.和黑胡椒L.等。黃樟油素-2′,3′-氧化物使apoE?/?小鼠內(nèi)皮細(xì)胞受損血管壁脂質(zhì)面積達(dá)59.8%,導(dǎo)致動(dòng)脈粥樣硬化。其通過(guò)激活p75神經(jīng)營(yíng)養(yǎng)素受體(p75 neurotrophin receptor,p75NTR)和IL-8,促進(jìn)斑塊破裂和斑塊中細(xì)胞的凋亡[78]。
植物精油及其成分對(duì)心血管系統(tǒng)的作用分別見表1、2。
表1 植物精油對(duì)心血管系統(tǒng)的作用
續(xù)表1
植物名主要成分實(shí)驗(yàn)和模型作用文獻(xiàn) Aniba rosaeodora (Rosewood) var. amazonica Ducke芳樟醇(87.7%)、α-松油醇(3.1%)、香葉醇(1.2%)雙側(cè)迷走神經(jīng)切斷和迷走神經(jīng)C-纖維傳導(dǎo)阻斷大鼠;PHE誘導(dǎo)的預(yù)收縮的離體胸主動(dòng)脈環(huán)降壓、減慢心率、舒張動(dòng)脈12 香薷狀刺蕊草莪術(shù)烯(46.1%)、二苯甲酮(8.6%)、α-蓽澄茄醇(5.7%)、牻牛兒酮(6.3%)PHE、KCl誘導(dǎo)的預(yù)收縮的離體胸主動(dòng)脈環(huán);雙側(cè)迷走神經(jīng)切斷大鼠舒張動(dòng)脈、降低迷走神經(jīng)切斷術(shù)后大鼠的收縮壓、舒張壓、平均動(dòng)脈壓、心率14 阿育魏實(shí)百里香酚(38.1%)、γ-萜品烯(33.3%)、對(duì)聚傘花烴(23.1%)PHE、KCl誘導(dǎo)的預(yù)收縮的離體胸主動(dòng)脈環(huán)舒張離體動(dòng)脈16 薤白二甲基三硫(34.93%)、二甲基二硫(11.64%)、2,3,5,6-四甲基吡嗪(7.32%)、1,3-二噻烷(7.18%)PHE誘導(dǎo)的預(yù)收縮的離體肺動(dòng)脈環(huán)、大鼠肺動(dòng)脈內(nèi)皮細(xì)胞模型擴(kuò)張肺動(dòng)脈17 荒野蒿匙葉桉葉油醇(10.19%)、β-桉葉醇(4.05%)、對(duì)傘花烴(3.83%)、δ-杜松萜烯(3.67%)、β-蒎烯(2.82%)、氧化石竹烯(2.30%)、salvial-4(14)-en-1-one(2.51%)PHE、KCl誘導(dǎo)的預(yù)收縮的離體胸主動(dòng)脈環(huán)舒張主動(dòng)脈,抑制L型鈣通道、肌漿網(wǎng)鈣泵降低細(xì)胞內(nèi)鈣;抗血小板聚集;抗氧化18 Cymbopogon winterianus香葉醇(40.06%)、香茅醛(27.44%)、香茅醇(10.45%)雙側(cè)迷走神經(jīng)切斷和迷走神經(jīng)C-纖維傳導(dǎo)阻斷大鼠;PHE誘導(dǎo)的預(yù)收縮的腸系膜動(dòng)脈環(huán)劑量相關(guān)性低血壓;舒張離體動(dòng)脈19 Seseli pallasii Besserα-蒎烯(48.2%)、氧化石竹烯(4.3%~4.4%)、香葉烯D(2.9%~4.1%)、檸檬烯(3.3%~3.8%)、匙葉桉葉油醇(3.1%)、β-蒎烯(2.9%~4.6%)PHE誘導(dǎo)的預(yù)收縮的離體腸系膜動(dòng)脈環(huán)舒張主動(dòng)脈,抑制ACE23 薰衣草乙酸芳樟酯、芳樟醇、1,8-桉葉素、薰衣草醇、乙酸薰衣草酯、樟腦、順式-β-羅勒烯、反式-β-羅勒烯、1-松油烯-4-醇、α-松油醇、檸檬烯大鼠左冠狀動(dòng)脈前降支結(jié)扎再灌注模型抗氧化、抗炎、抑制細(xì)胞凋亡、保護(hù)缺血心肌24 乙酸芳樟酯(36.2%)、芳樟醇(33.4%)、1,8-桉葉素(5.8%)、乙酸熏衣草酯(3.0%)花生四烯酸、U46619、膠原和ADP誘導(dǎo)的血小板聚集;凝血酶誘導(dǎo)的凝塊收縮;膠原和腎上腺素誘導(dǎo)的急性肺栓塞模型抑制血小板聚集;抑制凝塊收縮;抑制血栓形成62 賀蘭山丁香α-杜松醇(19.9%)、τ-依蘭油醇(18.5%)、胡椒烯(4.5%)、β-杜松烯(4.37%)和α-依蘭油烯(3.29%)大鼠左冠狀動(dòng)脈前降支結(jié)扎再灌注模型;H2O2誘導(dǎo)的心肌細(xì)胞損傷模型心肌缺血、抗缺氧、抗氧化應(yīng)激、抗血小板聚集作用26 姜黃芳姜黃酮、α-姜黃酮、β-姜黃酮高脂喂養(yǎng)敘利亞倉(cāng)鼠抗高脂血癥的作用;減少氧化應(yīng)激、血小板活化和血管功能障礙56 大鼠左冠狀動(dòng)脈前降支結(jié)扎再灌注模型;THP-1與人內(nèi)皮細(xì)胞EA.hy926 共培養(yǎng)模型減少左心室缺血面積和內(nèi)皮細(xì)胞誘導(dǎo)的炎癥27
續(xù)表1
植物名主要成分實(shí)驗(yàn)和模型作用文獻(xiàn) 酸橙檸檬烯(42.35%),γ-松油烯(15.44%)、β-蒎烯(12.57%)、α-蒎烯(3.12%)、乙酸橙酯(2.2%)和檜烯(2.12%)高脂飼料喂養(yǎng)大鼠抗氧化,降低LDL水平33 五味子—主動(dòng)脈平滑肌細(xì)胞抑制腫瘤TNF-α誘導(dǎo)的血管平滑肌細(xì)胞遷移39 牛至反式水合檜烯(45.21%)、百里香酚(24.10%)、香芹酚(7.99%)ox-LDL激活的THP-1單核細(xì)胞模型促炎因子TNF-α、IL-1β和IL-6合成減少,抗炎因子IL-10的產(chǎn)生增加40 魁蒿1,8-桉葉素(20.1%)、反式石竹烯(16.3%)、1-檸檬烯(12.6%)、苯酚(7.5%)和莰烯(7.5%)肝源性HepG2細(xì)胞降低膽固醇44 Nigella sativa L.對(duì)傘花烴(3.81%)、對(duì)叔丁基鄰苯二酚(4.28%)、(+)-trans,trans-5-caranol(7.83%)、4-松油醇(10.55%)、百里香醌(13.53%)和百里香酚(31.98%)動(dòng)脈粥樣硬化飼料喂養(yǎng)Wistar大鼠降膽固醇、抗氧化48 Lippia alba 月桂烯酮(30.4%)、1,8-桉葉素(21.4%)、月桂烯(11.0%)、檜烯(4.3%)、右旋大根香葉烯(3.2%)HepG2細(xì)胞、非肝源性細(xì)胞A549濃度范圍內(nèi)降低膽固醇52 紅松Pinus koraiensis Siebold et Zuccarini 龍腦(21.11%)、D-檸檬烯(21.01%)、α-蒎烯(16.74%)和冰片(11.52%)HepG2細(xì)胞促進(jìn)LDLR的表達(dá),降低SREBP-1、-2、HMGCR的表達(dá);抑制HACA T1、2和LDL-氧化活性53 茴香茴香腦(75.83%)、檸檬烯(5.67%)、甲基胡椒酚(4.56%)花生四烯酸、膠原、ADP和血栓素A2激動(dòng)劑U46619誘導(dǎo)的血小板聚集;凝塊收縮實(shí)驗(yàn);血小板活性檢測(cè);膠原和腎上腺素誘導(dǎo)的急性肺栓塞模型;PHE、KCl誘導(dǎo)的預(yù)收縮的胸主動(dòng)脈環(huán)抑制血小板聚集;抑制凝血酶誘導(dǎo)的凝塊回縮;抗血栓形成;舒張離體動(dòng)脈61 Ocotea quixos (Lam.) Kosterm. 反式肉桂醛(27.8%)、肉桂酸甲酯(21.6%)、苯甲醛(3.1%)、檸檬烯(8.1%)、α-蒎烯(3.1%)、p-cymene(4.8%)、芳樟醇(3.2%)、4-松油醇(2.2%)、α-松油醇(2.9%)花生四烯酸、U46619、ADP、佛波酯、膠原誘導(dǎo)的血小板聚集;凝血酶誘導(dǎo)的凝塊收縮;膠原和腎上腺素誘導(dǎo)的急性肺栓塞模型;U46619誘導(dǎo)的預(yù)收縮的離體胸主動(dòng)脈環(huán)抑制血小板聚集;抗血栓形成;舒張離體動(dòng)脈66 Hedychium coronariumJ. Koening1,8-桉葉素(22.68%)、β-蒎烯(14.78%)、β-石竹烯(12.95%)、β-松油醇(7.90%)、α-蒎烯(7.10%)松油酮(4.45%)ADP、膠原誘導(dǎo)的血小板聚集試驗(yàn)抑制血小板聚集79
表2 植物精油成分對(duì)心血管系統(tǒng)的作用
心血管系統(tǒng)健康的關(guān)鍵因素是對(duì)疾病的預(yù)防。大量研究顯示大多數(shù)植物精油及其部分成分對(duì)心血管系統(tǒng)的保護(hù)作用,能舒張血管、降血壓、抗心肌缺血、預(yù)防和改善動(dòng)脈粥樣硬化、抗血小板聚集以及抗心律失常。因此,它們可能成為抑制和/或治療心血管疾病的候選藥物。盡管許多研究報(bào)告了植物精油對(duì)心血管系統(tǒng)的作用及其可能作用機(jī)制,但這些研究絕大多數(shù)為體外和動(dòng)物研究?,F(xiàn)有的臨床報(bào)道或研究?jī)H限于植物精油作為芳香療法,對(duì)高血壓、心肌梗死等進(jìn)行輔助治療,缺乏臨床的直接應(yīng)用的證據(jù)以及在心血管系統(tǒng)安全性方面的信息。因此,還需要更多研究來(lái)進(jìn)一步確定植物精油對(duì)人體有益于人體心血管系統(tǒng),特別是有心血管危險(xiǎn)因素患者心血管系統(tǒng)的機(jī)制。
利益沖突 所有作者均聲明不存在利益沖突
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Research progress on effect of essential oils on cardiovascular diseases
DONG Wei1, HUANG Xiao-ying1, TANG Xi-lan2, Li Qiu-xiang1, ZHAO Guo-wei1, LIANG Xin-li1, YANG Ming1
1. Key Laboratory of Modern Preparation of Traditional Chinese Medicine, Ministry of Education, Jiangxi University of Traditional Chinese Medicine, Nanchang 330004, China 2. School of Pharmacy, Jiangxi Science & Technology Normal University, Nanchang 330013, China
Cardiovascular diseases are a group of disorders of heart and blood vessels, and include hypertension, hyperlipidemia, thromboembolism, coronary artery disease and heart failure. Cardiovascular diseases are a serious threat to human health and a leading cause of mortality worldwide. The key to a healthy cardiovascular system is the prevention of illness. Essential oils and some of components are able to signi?cantly promote the cardiovascular system and can lead to vasorelaxation, hypotension, prevention and improvement of atherosclerosis, anti-platelet aggregation and anti-arrhythmia. Essential oils are beneficial to the cardiovascular system, but more evidence from clinical trials is necessary to confirm these results in humans.
essential oils; cardiovascular diseases; hypertension; myocardial ischemia; atherosclerosis; platelet aggregation; arrhythmia
R282.710.5
A
0253 - 2670(2021)24 - 7668 - 12
10.7501/j.issn.0253-2670.2021.24.030
2021-06-06
國(guó)家自然科學(xué)基金資助項(xiàng)目(82060733);國(guó)家自然科學(xué)基金資助項(xiàng)目(81960732);江西省自然科學(xué)基金資助項(xiàng)目(20181BAB215041);江西省科技廳重大科技研發(fā)專項(xiàng)(20194ABC28009);江西中醫(yī)藥大學(xué)現(xiàn)代中藥制劑教育部重點(diǎn)實(shí)驗(yàn)室開放基金資助項(xiàng)目(TCM-201911)
董 偉,講師,主要從事中藥藥效物質(zhì)基礎(chǔ)研究。Tel: (0791)87118658 E-mail: sober96@foxmail.com
梁新麗 Tel: (0791)87118658 E-mail: paln7@163.com
[責(zé)任編輯 崔艷麗]