唐小月¹,何璇²,张萌¹,刘郁林³,叶勇¹

• 1:华南理工大学 化学与化工学院 制药工程系，广东 广州 510640
• 2:赣州哈克生物科技有限公司，江西赣州 341008
• 3:江西环境工程职业学院，江西赣州 341000

摘要(Abstract)：

为了有效利用油茶资源，提高茶皂苷元的抗氧化活性，对其进行结构修饰制备了茶皂苷元缩氨基硫脲及其锌配合物，使用紫外光谱（UV）、红外光谱（IR）、元素分析和核磁共振氢谱表征其结构，对合成工艺进行了优化，以DPPH·、ABTS⁺·、·OH清除率为指标评价其抗氧化活性，并与抗氧化调节因子Keap1进行了分子对接，探讨其作用机制。结果表明，优化后的反应条件为：茶皂苷元与硫代氨基脲的量比为1：1.2，冰乙酸为催化剂，温度75℃，反应时间8 h，茶皂苷元缩氨基硫脲产率79.6%，纯度92%；茶皂苷元缩氨基硫脲与二水合醋酸锌的量比为1：0.6，甲醇为溶剂，温度65℃，时间6 h，茶皂苷元缩氨基硫脲锌配合物产率72.1%，纯度90%。对3种自由基的清除能力强于茶皂苷元，与Keap1-Nrf2有显著的相互作用。茶皂苷元缩氨基硫脲及其锌配合物改善了茶皂苷元的活性，可以增强机体的抗氧化能力。

关键词(KeyWords)： 茶皂苷元;缩氨基硫脲;锌配合物;抗氧化活性;分子对接

Abstract:

Keywords:

基金项目(Foundation): 广东省自然科学基金（2018B030315010）；湖南省重点研发项目（2019NK2091）；国家重点研发项目（2019YFD1002300）。

作者(Author): 唐小月¹,何璇²,张萌¹,刘郁林³,叶勇¹

DOI: 10.3969/j.issn.1003-9015.2021.05.015

参考文献(References)：

• [1] 李穗敏, 杨谦, 赵闯, 等. 光响应茶皂苷元纳米囊的制备及其抗耐药菌活性研究[J]. 高校化学工程学报, 2018, 32(1):193-199. LI S M, YANG Q, ZHAO C, et al. Preparation of photo responsive sapogenin nanocapsules and their inhibiting activity on drug resistant bacteria[J]. Journal of Chemical Engineering of Chinese Universities, 2018, 32(1):193-199.
  [2] 魏婷婷, 崔晓芳, 文旭, 等. 油茶粕中茶皂素纯化方法与抗菌活性研究[J]. 中国油料作物学报, 2011, 33(6):616-621.WEI T T, CUI X F, WEN X, et al. Purification technology and biological activity of theasaponin from Camellia cake[J]. Chinese Journal of Oil Crop Sciences, 2011, 33(6):616-621.
  [3] 唐红枫, 孙茜, 张雨婷, 等. 油茶皂甙的提取及抑菌活性研究[J]. 中国油脂, 2012, 37(2):69-71.TANG H F, SUN Q, ZHANG Y T, et al. Extraction and antibacterial activities of tea saponin[J]. China Oils and Fats, 2012, 37(2):69-71.
  [4] CHATTOPADHYAY P, BESRA S E, GOMES A, et al. Anti-inflammatory activity of tea (Camellia sinensis) root extract[J]. Life Sciences, 2004, 74(15):1839-1849.
  [5] 吕晓玲, 邱松山, 孙晓侠, 等. 油茶总皂苷的抗氧化及清除自由基能力初步研究[J]. 食品科学, 2005, 26(11):66-70.LV X L, QIU S S, SUN X X, et al. Preliminary study on the capability of antioxidation and scavenging free radicals of sasanquasaponins[J]. Food Science, 2005, 26(11):66-70.
  [6] SYR P, CHANDHURI T, VEDASIROMONI J R, et al. Antiinflammatory and antioxidant property of saponins of tea Camellia sinensis (L) O. Kuntze root extract[J]. Phytotherapy Research, 2001, 15(2):174-176.
  [7] YE Y, XING H, CHEN X. Anti-inflammatory and analgesic activities of the hydrolyzed sasanquasaponins from the defatted seeds of Camellia oleifera[J]. Archives of Pharmacal Research, 2013, 36(8):941-951.
  [8] YE Y, FANG F, LI Y. Isolation of the sapogenin from defatted seeds of Camellia oleifera and its neuroprotective effects on dopaminergic neurons[J]. Journal of Agricultural & Food Chemistry, 2014, 62(26):6175-6182.
  [9] YE Y, CHEN X L, XING H T. Hypolipidemic and antioxidant activities of hydrolyzed saponins from defatted seeds of Camellia oleifera Abel[J]. Latin American Journal of Pharmacy, 2013, 32(3):409-417.
  [10] 王延芳. 油茶皂素及其水解产物的分离及降血脂抗氧化活性研究[D]. 广州:华南理工大学, 2012.WANG Y F. Studies on separation of sasanquasaponin and its hydrolyzed products and their hypolipidemic and antioxidant activities[D]. Guangzhou:South China University of Technology, 2012.
  [11] 陈雪兰. 油茶皂苷元的结构修饰及其抗神经退化活性研究[D]. 广州:华南理工大学, 2015.CHEN X L. Studies on structural modifications of sapogenin and their anti-neurodegenerative activities[D]. Guangzhou:South China University of Technology, 2015.
  [12] 杨谦. 光响应茶皂苷元衍生物阳离子脂质体的制备及其抗菌活性研究[D]. 广州:华南理工大学, 2018.YANG Q. Preparation of photoresponsive camelliagenin derivatives cationic liposome and its antibacterial activity[D]. Guangzhou:South China University of Technology, 2018.
  [13] BAVIN E M, REES R J W, ROBSON J M, et al. The tuberculostatic activity of some thiosemicarbazones[J]. The Journal of Pharmacy and Pharmacology, 1950, 2(11):764-772.
  [14] BROCKMAN R W, THOMSON J R, BELL M J, et al. Observations on the antileukemic activity of pyridine-2-carboxaldehyde thiosemicarbazone and thiocarbohydrazone[J]. Cancer Research, 1956, 16(2):167-170.
  [15] LEVINSON W, FARAS A, WOODSON B, et al. Inhibition of RNA-dependent DNA polymerase of Rous sarcoma virus by thiosemicarbazones and several cations[J]. Proceedings of the National Academy of Sciences of the United States of America, 1973, 70(1):164-171.
  [16] NUTTING C M, VAN HERPEN C M L, MIAH A B, et al. Phase II study of 3-AP triapine in patients with recurrent or metastatic head and neck squamous cell carcinoma[J]. Annals of Oncology, 2009, 20(7):1275-1279.
  [17] ALCARAZ R, MUNIZ P, CAVIA M, et al. Thiosemicarbazone-metal complexes exhibiting cytotoxicity in colon cancer cell lines through oxidative stress[J]. Journal of Inorganic Biochemistry, 2020, 206:110993-111003.
  [18] ROSU T, GULEA A, NICOLAE A, et al. Complexes of 3dn metal ions with thiosemicarbazones:synthesis and antimicrobial activity[J]. Molecules, 2007, 12(4):782-796.
  [19] PELOSI G, BISCEGLIE F, BIGNAMI F, et al. Antiretroviral activity of thiosemicarbazone metal complexes[J]. Journal of Medicinal Chemistry, 2010, 53(24):8765-8769.
  [20] ZENG W C, ZHANG Z, GAO H, et al. Characterization of antioxidant polysaccharides from Auricularia auricular using microwave-assisted extraction[J]. Carbohydrate Polymers, 2012, 89(2):694-700.
  [21] ZENG W C, ZHANG Z, GAO H, et al. Chemical composition, antioxidant, and antimicrobial activities of essential oil from pine needle (Cedrus deodara)[J]. Journal of Food Science, 2012, 77(7):824-829.
  [22] 冯慧萍, 李亦聪. 羟自由基与水杨酸反应机理的初探[J]. 光谱实验室, 2009, 26(4):931-938.FENG H P, LI Y C. A preliminary study on the reaction mechanism of hydroxyl radical with salicylic acid[J]. Chinese Journal of Spectroscopy Laboratory, 2009, 26(4):931-938.
  [23] 郭海阳, 莫林兰, 谭海生, 等. 茶皂素的美白功效及其抑菌和抗氧化活性研究[J]. 中国粮油学报, 2020, 35(6):83-89. GUO H Y, MO L L, TAN H S, et al. Whitening effect, antibacterial and antioxidant activities of tea saponin[J]. Journal of Chinese Cereals and Oil Association, 2020, 35(6):83-89.
  [24] REUTER S, GUPTA S C, CHATURVEDI M M, et al. Oxidative stress, inflammation, and cancer:How are they linked?[J]. Free Radical Biology and Medicine, 2010, 49(11):1603-1616.
  [25] ANATOLIOTAKIS N, DEFTEREOS S, BOURAS G, et al. Myeloperoxidase:Expressing inflammation and oxidative stress in cardiovascular disease[J]. Current Topics in Medicinal Chemistry, 2013, 13(2):115-138.
  [26] EMERIT J, EDEAS A, BRICAIRE F. Neurodegenerative diseases and oxidative stress[J]. Biomedicine & Pharmacotherapy, 2004, 58(1):39-46.