羅光明，黃遠(yuǎn)亮

(1.同濟(jì)大學(xué)，上海 200072；2.同濟(jì)大學(xué)附屬東方醫(yī)院，上海 200120)

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肉蓯蓉松果菊苷藥理作用研究進(jìn)展

羅光明1，黃遠(yuǎn)亮2

(1.同濟(jì)大學(xué)，上海 200072；2.同濟(jì)大學(xué)附屬東方醫(yī)院，上海 200120)

現(xiàn)代藥理學(xué)研究證實(shí)，補(bǔ)益腎陽類傳統(tǒng)中藥肉蓯蓉具有廣泛藥理作用和豐富的化學(xué)成分。肉蓯蓉主要活性成分之一松果菊苷具有神經(jīng)保護(hù)、促進(jìn)新骨形成、抗氧化、抗組織損傷、抗炎等作用，是安全有效的植物雌激素因子。現(xiàn)對(duì)其藥理作用作一簡(jiǎn)要綜述。

肉蓯蓉；松果菊苷

1 肉蓯蓉化學(xué)成分及藥理作用

肉蓯蓉Y. C. Ma(C. deserticola)是一種生長(zhǎng)于干旱和半干旱地區(qū)的藥用植物，在中國(guó)中草藥市場(chǎng)存在四種肉蓯蓉物種：沙漠肉蓯蓉(C. Deserticola)、管花肉蓯蓉(C. Tubulosa)、鹽生肉蓯蓉(C. salsa)、沙蓯蓉(C. sinensis)，通過化學(xué)指紋結(jié)合基因指紋能鑒別和控制肉蓯蓉質(zhì)量。肉蓯蓉屬種是常年寄生草藥，主要分布于陸地和熱荒漠，傳統(tǒng)中醫(yī)主要用作滋補(bǔ)藥，主治腎虛、陽痿、女性不育、白帶異常、子宮不規(guī)則出血過多、老年性便秘等癥狀，故有“沙漠人參”之稱。現(xiàn)代藥理學(xué)研究已經(jīng)證實(shí)肉蓯蓉具有廣泛藥用功能，包括激素樣調(diào)節(jié)作用、通便、免疫調(diào)節(jié)、神經(jīng)保護(hù)、抗氧化、抗細(xì)胞凋亡、抗損傷、抗炎、抗衰老、抗疲勞活性以及促進(jìn)骨的形成[1,2]，還可能具有保護(hù)心臟并能抗心肌缺血性損傷、預(yù)防和治療高血糖、高血脂癥的功能[3-5]。

近年來，人們對(duì)肉蓯蓉的化學(xué)成分進(jìn)行了大量研究，從其中分離出多種化合物，分析鑒定為：揮發(fā)油類、苯乙醇苷(phenylethanoid glycosides，PhGs，主要包含松果菊苷和阿克替甙)、三十烷醇、咖啡酸糖脂、環(huán)烯醚萜類、木脂素類、多羥糖醇、寡糖類、甜菜堿、谷甾醇、胡蘿卜苷、甘露醇、硬脂酸、β-谷固醇、胡蘿卜甙、琥珀酸、多糖類等。其中，PhGs是治療腎虛、抗氧化、神經(jīng)保護(hù)的主要活性成分；半乳糖醇、寡糖類是治療老年性便秘的活性成分；多糖由鼠李糖、木糖、阿拉伯糖、半乳糖濃縮而來，多糖是抗衰老、改善機(jī)體免疫力的活性成分[6-8]。

Nan等[9]又從塔中栽培荒漠肉蓯蓉干燥肉質(zhì)莖的85% 乙醇提取物中分離得到紫丁香苷、去甲基紫丁香苷、松柏苷、芐基葡萄糖苷、煙酰胺、對(duì)羥基苯甲酸、對(duì)羥基苯乙醇、半乳糖醇等17種化合物。沙漠肉蓯蓉中還含有豐富的錳、鉀、鈣、 鎂、鈉等微量元素，在肉蓯蓉不同生長(zhǎng)階段，微量元素含量比例不同[9,10]。

2 松果菊苷(Echinacoside ，ECH)

松果菊苷是沙漠肉蓯蓉主要活性成分之一，從其他藥用植物如密蒙花、紫錐花屬中也能分離出松果菊苷[11, 12]，其具有如下藥理作用。

2.1 神經(jīng)保護(hù)[13-21]

松果菊苷能逆轉(zhuǎn)保護(hù)魚藤酮、中動(dòng)脈閉塞、6-羥多巴胺誘導(dǎo)的多巴胺能神經(jīng)元損傷。短暫接觸松果菊苷,即具有足夠保護(hù)抗魚藤酮損傷過表達(dá)TrkA或 TrkB受體的神經(jīng)元細(xì)胞和非神經(jīng)元細(xì)胞的作用，其機(jī)制與松果菊苷短暫抑制細(xì)胞色素C(cytochrome c)的釋放并激活細(xì)胞凋亡蛋白酶-3(caspase-3)有關(guān)。松果菊苷也能自由穿過血腦屏障，有可能用于治療帕金森病、阿爾茨海默病等神經(jīng)變性疾病及預(yù)防和治療大腦的缺血性疾病。zhao等觀察證實(shí)，口服松果菊苷治療7～14天，帕金森病患者步態(tài)失調(diào)明顯改善。

松果菊苷還可能通過逆轉(zhuǎn)線粒體功能及細(xì)胞凋亡、抗TNF-α(腫瘤壞死因子α)誘導(dǎo)的人神經(jīng)母細(xì)胞瘤細(xì)胞凋亡、促進(jìn)血管性癡呆鼠腦中膽堿能神經(jīng)遞質(zhì)水平等途徑發(fā)揮明顯的神經(jīng)保護(hù)效應(yīng)，可用于干預(yù)神經(jīng)變性疾病。松果菊苷能選擇性逆轉(zhuǎn)線粒體功能和細(xì)胞凋亡，而對(duì)線粒體形態(tài)沒有影響。

2.2 骨保護(hù)

松果菊苷具有雌激素樣的作用。Yang等[22]用松果菊苷治療給藥12周，股骨礦物質(zhì)密度、微結(jié)構(gòu)、生物力學(xué)特性得到改善；松果菊苷還顯著增加骨保護(hù)素(OPG)水平，并降低血清核因子κB配體受體活化劑水平，而對(duì)子宮、乳腺無不良反應(yīng)；松果菊苷能通過增加OPG/RANKL的比例有效安全預(yù)防鼠卵巢切除術(shù)后骨質(zhì)疏松并抑制骨吸收，是一類新的植物雌激素，是治療雌激素缺乏誘導(dǎo)的絕經(jīng)后骨質(zhì)疏松較有前景的草藥[23]。Li等[24]研究證實(shí)，0.01～10nmol/L松果菊苷即能明顯增加成骨細(xì)胞系MC3T3-E1的增殖、堿性磷酸酶(alkaline phosphatase，ALP)活性、I型膠原含量、骨鈣素(osteocalcin，OCN)水平，增加了成骨細(xì)胞礦化，它主要增加OPG/RNKL比例促進(jìn)骨形成。Tm等[25]則研究證實(shí)，肉蓯蓉提取物對(duì)培養(yǎng)的成骨細(xì)胞增殖、遷移無任何影響，也不影響骨誘裂，但增加了ALP、骨形態(tài)發(fā)生蛋白-2(bone morphogenetic proteins-2，BMP-2)、骨橋蛋白(osteopontin，OPN )的mRNA表達(dá)和骨的礦化 ，并能預(yù)防卵巢切除鼠的骨丟失，推斷松果菊苷可能是治療骨質(zhì)疏松的骨形成因子。

2.3 抗損傷、抗氧化

松果菊苷能保護(hù)急性肺損傷，用于治療急性呼吸窘迫綜合征[26]，也能保護(hù)由四氯化碳引起的急性鼠肝損傷。經(jīng)松果菊苷治療后，肝的組織病理學(xué)損傷和凋亡的肝細(xì)胞數(shù)明顯好轉(zhuǎn)，可能主要與抗氧化效應(yīng)有關(guān)[27]。松果菊苷還可能通過上調(diào)TTGF-B促進(jìn)腸上皮細(xì)胞增殖，阻止細(xì)胞死亡而改善黏膜組織修復(fù)[28]。

2.4 抗炎、護(hù)膚、抗衰老

松果菊苷可有效預(yù)防硫酸葡聚糖鈉誘導(dǎo)的鼠大腸炎，臨床用于治療炎性腸病[29]。松果菊苷通過誘導(dǎo)II期細(xì)胞保護(hù)能力而具有持久的皮膚保護(hù)效應(yīng)[30]。松果菊苷能激發(fā)細(xì)胞從G1期進(jìn)入S期和G2期，保護(hù)細(xì)胞免受DNA損傷可能是其抗衰老的機(jī)制[31]。

3 結(jié)語

人們還進(jìn)行了大量松果菊苷藥物代謝動(dòng)力學(xué)研究，建立和驗(yàn)證了在動(dòng)物血漿中檢測(cè)松果菊苷濃度的方法，具有高度選擇性、敏感性、可重復(fù)性[32]，并且易獲得高純度松果菊苷，完全能滿足實(shí)驗(yàn)研究及臨床治療需要[33]。肉蓯蓉及其主要活性成分松果菊苷更廣泛的藥理作用及臨床應(yīng)用有待進(jìn)一步研究證實(shí)。

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(責(zé)任編輯：魏 曉)

2014-04-29

羅光明(1971-)，同濟(jì)大學(xué)博士研究生，研究方向?yàn)榭谇簧镝t(yī)學(xué)及轉(zhuǎn)化醫(yī)學(xué)。

R285

A

1673-2197(2014)17-0058-03