Search JIM Advanced Search

Journal of Chinese Integrative Medicine ›› 2012, Vol. 10 ›› Issue (10): 1149-1154.doi: 10.3736/jcim20121012

Previous Articles     Next Articles

Molecular docking of chlorogenic acid, 3,4-di-O-caffeoylquinic acid and 3,5-di-O-caffeoylquinic acid with human serum albumin

Jing Zhou1, Hong-yue Ma1, Xin-sheng Fan1(), Wei Xiao2,3(), Tuan-jie Wang2,3   

  1. 1. Jiangsu Key Laboratory for Traditional Chinese Medicine Formulae Research, College of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210046, Jiangsu Province, China
    2. Jiangsu Kanion Parmaceutical CO. LTD, Lianyungang 222001, Jiangsu Province, China
    3. State Key Laboratory of New-tech for Chinese Medicine Pharmaceutical Process, Lianyungang 222001, Jiangsu Province, China
  • Received:2012-04-13 Accepted:2012-05-18 Online:2012-10-20 Published:2018-10-15
  • Contact: Xin-sheng Fan, Wei Xiao;

Objective: To investigate the mechanism of binding of human serum albumin (HSA) with potential sensitinogen, including chlorogenic acid and two isochlorogenic acids (3,4-di-O-caffeoylquinic acid and 3,5-di-O-caffeoylquinic acid). .

Methods: By using the docking algorithm of computer-aided molecular design and the Molegro Virtual Docker, the crystal structures of HSA with warfarin and diazepam (Protein Data Bank ID: 2BXD and 2BXF) were selected as molecular docking receptors of HSA sites Ⅰ and Ⅱ. According to docking scores, key residues and H-bond, the molecular docking mode was selected and confirmed. The molecular docking of chlorogenic acid and two isochlorogenic acids on sites Ⅰ and Ⅱ was compared based on the above design.

Results: The results from molecular docking indicated that chlorogenic acid, 3,4-di-O-caffeoylquinic acid and 3,5-di-O-caffeoylquinic acid could bind to HSA site Ⅰ by high affinity scores of –112.3, –155.3 and –153.1, respectively. They could bind to site Ⅱ on HSA by high affinity scores of –101.7, –138.5 and –133.4, respectively. In site Ⅰ, two isochlorogenic acids interacted with the key apolar side-chains of Leu238 and Ala291 by higher affinity scores than chlorogenic acid. Furthermore, the H-bonds of isochlorogenic acids with polar residues inside the pocket and at the entrance of the pocket were different from chlorogenic acid. Moreover, the second coffee acyl of isochlorogenic acid occupied the right-hand apolar compartment in the pocket of HSA site Ⅰ. In site Ⅱ, the second coffee acyl of isochlorogenic acid formed the H-bonds with polar side-chains, which contributed isochlorogenic acid to binding with site Ⅱ of HSA.

Conclusion: The isochlorogenic acids with two coffee acyls have higher binding abilities with HSA than chlorogenic acid with one coffee acyl, suggesting that isochlorogenic acids binding with HSA may be sensitinogen.

Key words: plant extracts, chlorogenic acid, isochlorogenic acid, human serum albumin, molecular docking, computer-aided design

Table 1

Docking method validation"

Ligand Protein (PDB ID) Site RMSD MD score Rerank score H bond score Key residues
Warfarin HSA (2BXD) Site Ⅰ 0.47 –108.5 –93.2 –7.7 Tyr150, Arg222, His242
Diazepam HSA (2BXF) Site Ⅱ 0.45 –107.9 –91.5 –1.9 Tyr411
Warfarin HSA (2BXF) Site Ⅱ –112.7 –88.9 –0.1
Diazepam HSA (2BXD) Site Ⅰ –80.7 –67.4 –2.1 Tyr150

Table 2

Docking scores and interaction residues of tested compounds binding to HSA (PDB ID: 2BXD) site Ⅰ"

Ligand MD score Rerank score H bond score Key residues (score)
Chlorogenic acid –112.3 –108.1 –12.8 Tyr150 (–16.4), Arg257 (–14.0), Ala291 (–11.7),Lys199 (–11.5), Gln196 (–9.3), Leu238 (–4.4)
3,4-di-O-Caffeoylquinic acid –155.3 –111.4 –12 Ala291 (–17.0), Arg257 (–16.8), Leu238 (–15.4), Tyr150 (–13.6), Lys199 (–11.5), His242 (–10.7), His288 (–10.1)
3,5-di-O-Caffeoylquinic acid –153.1 –128.4 –13.6 Tyr150 (–19.5), Ser192 (–16.0), Lys199 (–15.5), Lys 195 (–14.9), Leu238 (–13.6), Ala291 (–12.8), Arg257 (–10.0), His242 (–8.9); Arg222 (–5.8)

Figure 1

Molecular docking model (A1-C1) and interaction residues (A2-C2) of chlorogenic acid (A), 3,4-di-O-caffeoylquinic acid (B) and 3,5-di-O-caffeoylquinic acid (C) binding to HSA site Ⅰ Apolar chains were marked in blue; semipolar chains were marked in violet; polar chains were marked in red. The H-bonds were marked in green dash line. HSA: human serum albumin. "

Table 3

Docking scores and interaction residues of tested compounds binding to HSA (PDB ID: 2BXF) site Ⅱ"

Ligand MD score Rerank score H bond score Key residues (score)
Chlorogenic acid –101.7 –90.4 –9.5 Asn391 (–21.6), Leu387 (–14.9), Ile388 (–14.8), Val433 (–13.7), Leu453 (–9.5), Leu430 (–9.1), Arg485 (–7.1), Tyr411 (–6.8), Ser489 (–6.5)
4-di-O-Caffeoylquinic acid –138.5 –101.7 –5.8 Tyr411 (–20.1), Leu387 (–18.1), Asn391 (–17.4), Arg485 (–13.5), Ile388 (–11.7), Val433 (–10.6), Leu453 (–10.2), Ser489 (–9.2), Pro384 (–7.6), Leu430(–7.0)
3,5-di-O-Caffeoylquinic acid –133.4 –91.7 –13.2 Asn391 (–29.3), Leu387 (–15.8), Ile388 (–14.8), Val433 (–14.4), Tyr411 (–11.4), Gln390 (–10.8), Ser489 (–10.7), Arg410 (–10.3), Leu453 (–10.1), Leu430 (–8.8)

Figure 2

Molecular docking model (A1-C1) and interaction residues (A2-C2) of chlorogenic acid (A), 3,4-di-O-caffeoylquinic acid (B) and 3,5-di-O-caffeoylquinic acid (C) binding to HSA site ⅡApolar chains were marked in blue; semipolar chains were marked in violet; polar chains were marked in red. The H-bonds were marked in green dash line. HSA: human serum albumin."

[1] Zhang RX, Tang NP, Lin HX, Ma J, Xie C, Chen XY . Allergenicity assessment and comparison between chlorogenic acid and Shuanghuanglian Fenzhenji[J]. Shi Jie Ke Xue Ji Shu Zhong Yi Yao Xian Dai Hua, 2010,12(6):1005-1008
doi: 10.11842/wst.2010.6.[sequence]
张瑞霞, 汤纳平, 林海霞, 马璟, 谢岑, 陈笑艳 . 绿原酸和双黄连粉针剂致敏性比较评价[J]. 世界科学技术中医药现代化, 2010,12(6):1005-1008
doi: 10.11842/wst.2010.6.[sequence]
[2] Bi SY, Yan LL, Sun YT . Study on the binding of chlorogenic acid with human serum albumin by spectroscopy[J]. Hua Xue Fen Xi Ji Liang, 2010,19(2):31-33
毕淑云, 闫丽丽, 孙艳涛 . 光谱法研究绿原酸与人血清白蛋白的相互作用[J]. 化学分析计量, 2010,19(2):31-33
[3] Yang B. The pharmacokinetics and metabolism of 1, 5-dicaffeoylquinic acid in vivo and in vitro. Shenyang: Shenyang Pharmaceutical University. 2005. Chinese.
杨波 . 1,5-二咖啡酰奎宁酸的体内外代谢及药代动力学研究. 沈阳药科大学. 2005.
[4] Liu L, Ma H, Tang Y, Chen W, Lu Y, Guo J, Duan JA . Discovery of estrogen receptor α modulators from natural compounds in Si-Wu-Tang series decoctions using estrogen-responsive MCF-7 breast cancer cells[J]. Bioorg Med Chem Lett, 2012,22(1):154-163
doi: 10.1016/j.bmcl.2011.11.041
[5] Ghuman J, Zunszain PA, Petitpas I, Bhattacharya AA, Otagiri M, Curry S . Structural basis of the drug-binding specificity of human serum albumin[J]. J Mol Biol, 2005,353(1):38-52
doi: 10.1016/j.jmb.2005.07.075 pmid: 16169013
[1] Wan-jun Guo, Yi Wang, Yu Deng, Lin-yan Cheng, Xin Liu, Ruo-fan Xi, Sheng-jie Zhu, Xin-yi Feng, Liang Hua, Kan Ze, Jian-yong Zhu, Dong-jie Guo, Fu-lun Li. Therapeutic effects of the extract of Sancao Formula, a Chinese herbal compound, on imiquimod-induced psoriasis via cysteine-rich protein 61. Journal of Integrative Medicine, 2022, 20(4): 376-384.
[2] Zi-jia Zhang, Wen-yong Wu, Jin-jun Hou, Lin-lin Zhang, Fei-fei Li, Lei Gao, Xing-dong Wu, Jing-ying Shi, Rong Zhang, Hua-li Long, Min Lei, Wan-ying Wu, De-an Guo, Kai-xian Chen, Lewis A. Hofmann, Zhonghua Ci. Active constituents and mechanisms of Respiratory Detox Shot, a traditional Chinese medicine prescription, for COVID-19 control and prevention: network-molecular docking-LC-MSE analysis. Journal of Integrative Medicine, 2020, 18(3): 229-241.
[3] Deng-hai Zhang, Kun-lun Wu, Xue Zhang, Sheng-qiong Deng, Bin Peng. In silico screening of Chinese herbal medicines with the potential to directly inhibit 2019 novel coronavirus. Journal of Integrative Medicine, 2020, 18(2): 152-158.
[4] Chang-quan Ling. Traditional Chinese medicine is a resource for drug discovery against 2019 novel coronavirus (SARS-CoV-2). Journal of Integrative Medicine, 2020, 18(2): 87-88.
[5] Stefania Lamponi, Anna Maria Aloisi, Claudia Bonechi, Marco Consumi, Alessandro Donati, Gemma Leone, Claudio Rossi, Gabriella Tamasi, Luana Ghiandai, Ersilia Ferrini, Paolo Fiorenzani, Ilaria Ceccarelli, Agnese Magnani. Evaluation of in vitro cell and blood compatibility and in vivo analgesic activity of plant-derived dietary supplements. Journal of Integrative Medicine, 2019, 17(3): 213-220.
[6] Supakanya Kumkarnjana, Rutt Suttisri, Ubonthip Nimmannit, Thongchai Koobkokkruad, Chutichot Pattamadilok, Nontima Vardhanabhuti . Anti-adipogenic effect of flavonoids from Chromolaena odorata leaves in 3T3-L1 adipocytes. Journal of Integrative Medicine, 2018, 16(6): 427-434.
[7] Rohitash Jamwal. Bioavailable curcumin formulations: A review of pharmacokinetic studies in healthy volunteers. Journal of Integrative Medicine, 2018, 16(6): 367-374.
[8] Shohini Chakraborty, Nashra Afaq, Neelam Singh, Sukanta Majumdar. Antimicrobial activity of Cannabis sativaThuja orientalis and Psidium guajava leaf extracts against methicillin-resistant Staphylococcus aureus. Journal of Integrative Medicine, 2018, 16(5): 350-357.
[9] Bruno José Martins Da Silva, Amanda Anastácia Pinto Hage, Edilene Oliveira Silva, Ana Paula Drummond Rodrigues. Medicinal plants from the Brazilian Amazonian region and their antileishmanial activity: A review. Journal of Integrative Medicine, 2018, 16(4): 211-222.
[10] Musa Toyin Yakubu, Abdulquadri Funmbi Olutoye. Aphrodisiac activity of aqueous extract of Anthonotha macrophylla P. Beauv. leaves in female Wistar rats. Journal of Integrative Medicine, 2016, 14(5): 400-408.
[11] Nisha Panth, Keshav Raj Paudel, Rajendra Karki. Phytochemical profile and biological activity of Juglans regia. Journal of Integrative Medicine, 2016, 14(5): 359-373.
[12] JiaXia, Li-qunHe, XiaoSu. Interventional mechanisms of herbs or herbal extracts on renal interstitial fibrosis. Journal of Integrative Medicine, 2016, 14(3): 165-173.
[13] Santu Kumar Saha, Sourav Roy, Anisur Rahman Khuda-Bukhsh. Ultra-highly diluted plant extracts of Hydrastis canadensis and Marsdenia condurango induce epigenetic modifications and alter gene expression profiles in HeLa cells in vitro. Journal of Integrative Medicine, 2015, 13(6): 400-411.
[14] Wei Chiang Chan Eric, Kuin Wong Siu. Phytochemistry and pharmacology of ornamental gingers, Hedychium coronarium and Alpinia purpurata: A review. Journal of Integrative Medicine, 2015, 13(6): 368-379.
[15] Rashmi Singh, Shatruhan Sharma, Veena Sharma. Comparative and quantitative analysis of antioxidant and scavenging potential of Indigofera tinctoria Linn. extracts. Journal of Integrative Medicine, 2015, 13(4): 269-278.
Full text



[1] Wei-xiong Liang. Problems-solving strategies in clinical treatment guideline for traditional Chinese medicine and integrative medicine. Journal of Chinese Integrative Medicine, 2008, 6(1): 1-4
[2] Zhao-guo Li. Discussion on English translation of commonly used sentences in traditional Chinese medicine: part one. Journal of Chinese Integrative Medicine, 2008, 6(1): 107-110
[3] Jun Hu, Jian-ping Liu. Non-invasive physical treatments for chronic/recurrent headache. Journal of Chinese Integrative Medicine, 2008, 6(1): 31
[4] Xue-mei Liu, Qi-fu Huang, Yun-ling Zhang, Jin-li Lou, Hong-sheng Liu, Hong Zheng. Effects of Tribulus terrestris L. saponion on apoptosis of cortical neurons induced by hypoxia-reoxygenation in rats. Journal of Chinese Integrative Medicine, 2008, 6(1): 45-50
[5] . Uniform requirements for manuscripts submitted to biomedical journals: Writing and editing for biomedical publication (Chinese version, part two). Journal of Chinese Integrative Medicine, 2010, 8(11): 1001-1005
[6] Daniel Weber, Janelle M Wheat, Geoffrey M Currie. Inflammation and cancer: Tumor initiation, progression and metastasis,and Chinese botanical medicines. Journal of Chinese Integrative Medicine, 2010, 8(11): 1006-1013
[7] Hong Liu , Guo-liang Zhang, Li Shen , Zhen Zeng, Bao-luo Zhou, Cheng-hai Liu, Guang Nie . Application and evaluation of a pseudotyped virus assay for screening herbs for anti-H5Nl avian influenza virus. Journal of Chinese Integrative Medicine, 2010, 8(11): 1036-1040
[8] Zhao-guo Li . A discussion of English translation of 1995 and 1997 Chinese National Standards of Traditional Chinese Medical Terminologies for Clinical Diagnosis and Treatment. Journal of Chinese Integrative Medicine, 2010, 8(11): 1090-1096
[9] Rui Jin, Bing Zhang. A complexity analysis of Chinese herbal property theory: the multiple formations of herbal property (Part 1). Journal of Chinese Integrative Medicine, 2012, 10(11): 1198-1205
[10] Hui-min Liu, Xian-bo Wang, Yu-juan Chang, Li-li Gu. Systematic review and meta-analysis of randomized controlled trials of integrative medicine therapy for treatment of chronic severe hepatitis. Journal of Chinese Integrative Medicine, 2012, 10(11): 1211-1228