肉苁蓉松果菊苷药理作用研究进展

罗光明，黄远亮

(1.同济大学，上海 200072；2.同济大学附属东方医院，上海 200120)



肉苁蓉松果菊苷药理作用研究进展

罗光明1，黄远亮2

(1.同济大学，上海 200072；2.同济大学附属东方医院，上海 200120)

现代药理学研究证实，补益肾阳类传统中药肉苁蓉具有广泛药理作用和丰富的化学成分。肉苁蓉主要活性成分之一松果菊苷具有神经保护、促进新骨形成、抗氧化、抗组织损伤、抗炎等作用，是安全有效的植物雌激素因子。现对其药理作用作一简要综述。

肉苁蓉；松果菊苷

1 肉苁蓉化学成分及药理作用

肉苁蓉Y. C. Ma(C. deserticola)是一种生长于干旱和半干旱地区的药用植物，在中国中草药市场存在四种肉苁蓉物种：沙漠肉苁蓉(C. Deserticola)、管花肉苁蓉(C. Tubulosa)、盐生肉苁蓉(C. salsa)、沙苁蓉(C. sinensis)，通过化学指纹结合基因指纹能鉴别和控制肉苁蓉质量。肉苁蓉属种是常年寄生草药，主要分布于陆地和热荒漠，传统中医主要用作滋补药，主治肾虚、阳痿、女性不育、白带异常、子宫不规则出血过多、老年性便秘等症状，故有“沙漠人参”之称。现代药理学研究已经证实肉苁蓉具有广泛药用功能，包括激素样调节作用、通便、免疫调节、神经保护、抗氧化、抗细胞凋亡、抗损伤、抗炎、抗衰老、抗疲劳活性以及促进骨的形成[1,2]，还可能具有保护心脏并能抗心肌缺血性损伤、预防和治疗高血糖、高血脂症的功能[3-5]。

近年来，人们对肉苁蓉的化学成分进行了大量研究，从其中分离出多种化合物，分析鉴定为：挥发油类、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、环烯醚萜类、木脂素类、多羟糖醇、寡糖类、甜菜碱、谷甾醇、胡萝卜苷、甘露醇、硬脂酸、β-谷固醇、胡萝卜甙、琥珀酸、多糖类等。其中，PhGs是治疗肾虚、抗氧化、神经保护的主要活性成分；半乳糖醇、寡糖类是治疗老年性便秘的活性成分；多糖由鼠李糖、木糖、阿拉伯糖、半乳糖浓缩而来，多糖是抗衰老、改善机体免疫力的活性成分[6-8]。

Nan等[9]又从塔中栽培荒漠肉苁蓉干燥肉质茎的85% 乙醇提取物中分离得到紫丁香苷、去甲基紫丁香苷、松柏苷、苄基葡萄糖苷、烟酰胺、对羟基苯甲酸、对羟基苯乙醇、半乳糖醇等17种化合物。沙漠肉苁蓉中还含有丰富的锰、钾、钙、 镁、钠等微量元素，在肉苁蓉不同生长阶段，微量元素含量比例不同[9,10]。

2 松果菊苷(Echinacoside ，ECH)

松果菊苷是沙漠肉苁蓉主要活性成分之一，从其他药用植物如密蒙花、紫锥花属中也能分离出松果菊苷[11, 12]，其具有如下药理作用。

2.1 神经保护[13-21]

松果菊苷能逆转保护鱼藤酮、中动脉闭塞、6-羟多巴胺诱导的多巴胺能神经元损伤。短暂接触松果菊苷,即具有足够保护抗鱼藤酮损伤过表达TrkA或 TrkB受体的神经元细胞和非神经元细胞的作用，其机制与松果菊苷短暂抑制细胞色素C(cytochrome c)的释放并激活细胞凋亡蛋白酶-3(caspase-3)有关。松果菊苷也能自由穿过血脑屏障，有可能用于治疗帕金森病、阿尔茨海默病等神经变性疾病及预防和治疗大脑的缺血性疾病。zhao等观察证实，口服松果菊苷治疗7～14天，帕金森病患者步态失调明显改善。

松果菊苷还可能通过逆转线粒体功能及细胞凋亡、抗TNF-α(肿瘤坏死因子α)诱导的人神经母细胞瘤细胞凋亡、促进血管性痴呆鼠脑中胆碱能神经递质水平等途径发挥明显的神经保护效应，可用于干预神经变性疾病。松果菊苷能选择性逆转线粒体功能和细胞凋亡，而对线粒体形态没有影响。

2.2 骨保护

松果菊苷具有雌激素样的作用。Yang等[22]用松果菊苷治疗给药12周，股骨矿物质密度、微结构、生物力学特性得到改善；松果菊苷还显著增加骨保护素(OPG)水平，并降低血清核因子κB配体受体活化剂水平，而对子宫、乳腺无不良反应；松果菊苷能通过增加OPG/RANKL的比例有效安全预防鼠卵巢切除术后骨质疏松并抑制骨吸收，是一类新的植物雌激素，是治疗雌激素缺乏诱导的绝经后骨质疏松较有前景的草药[23]。Li等[24]研究证实，0.01～10nmol/L松果菊苷即能明显增加成骨细胞系MC3T3-E1的增殖、碱性磷酸酶(alkaline phosphatase，ALP)活性、I型胶原含量、骨钙素(osteocalcin，OCN)水平，增加了成骨细胞矿化，它主要增加OPG/RNKL比例促进骨形成。Tm等[25]则研究证实，肉苁蓉提取物对培养的成骨细胞增殖、迁移无任何影响，也不影响骨诱裂，但增加了ALP、骨形态发生蛋白-2(bone morphogenetic proteins-2，BMP-2)、骨桥蛋白(osteopontin，OPN )的mRNA表达和骨的矿化 ，并能预防卵巢切除鼠的骨丢失，推断松果菊苷可能是治疗骨质疏松的骨形成因子。

2.3 抗损伤、抗氧化

松果菊苷能保护急性肺损伤，用于治疗急性呼吸窘迫综合征[26]，也能保护由四氯化碳引起的急性鼠肝损伤。经松果菊苷治疗后，肝的组织病理学损伤和凋亡的肝细胞数明显好转，可能主要与抗氧化效应有关[27]。松果菊苷还可能通过上调TTGF-B促进肠上皮细胞增殖，阻止细胞死亡而改善黏膜组织修复[28]。

2.4 抗炎、护肤、抗衰老

松果菊苷可有效预防硫酸葡聚糖钠诱导的鼠大肠炎，临床用于治疗炎性肠病[29]。松果菊苷通过诱导II期细胞保护能力而具有持久的皮肤保护效应[30]。松果菊苷能激发细胞从G1期进入S期和G2期，保护细胞免受DNA损伤可能是其抗衰老的机制[31]。

3 结语

人们还进行了大量松果菊苷药物代谢动力学研究，建立和验证了在动物血浆中检测松果菊苷浓度的方法，具有高度选择性、敏感性、可重复性[32]，并且易获得高纯度松果菊苷，完全能满足实验研究及临床治疗需要[33]。肉苁蓉及其主要活性成分松果菊苷更广泛的药理作用及临床应用有待进一步研究证实。

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(责任编辑：魏 晓)

2014-04-29

罗光明(1971-)，同济大学博士研究生，研究方向为口腔生物医学及转化医学。

R285

A

1673-2197(2014)17-0058-03