Screening of Iridoids and Seco-iridoids in Gentianaceae Family against Liver corrective Targets using Molecular Docking studies


Rajasekaran Aiyalu1, Karthikeyan Lakshmanan1, Hari Baskar Balasubramanian1, Arivukkarasu Ramasamy2*

1The Tamilnadu Dr. M.G.R. Medical University, Chennai, Tamil Nadu, India.

2Associate Professor, KMCH College of Pharmacy, Coimbatore, Tamil Nadu, India 641048

*Corresponding Author E-mail:



In this study we confirmed the hepatoprotective properties of the phytoconstituents Swertiamarin, Sweroside, Amarogentin, Gentiopicroside present in Gentianaceae family mainly the Iridoids and Seco-iridoids using molecular docking. This technique is used to check the interaction of phytoconstituents with hepatoprotective targets such as 1JEN -  Human-S-Adenosyl methionine decarboxylase, 2OOL - Human sperimidine synthase, 2PO2 - Crystal structure of the alpha subunit of human-S-Adenosyl methionine Synthetase II, 1JBQ - Structure of human cystathionoine beta synthase a unique pyridoxal 5’ phosphate dependent heme protein, 2AZT - Crystal structure  of H 176 N mutant of human glycine N-Methyl transferase, 2OBV - Crystal  structure of the human-S-Adenosyl methionine  synthase-I in complex with the product, 1093 - Methionine adenosyl transferase complexed with ATP and a  L-Methionine analogues. Among the screened four phytoconstituents Sweroside exhibited best affinity against IJBQ with maximum binding energy of -38.97 and Gentio Picroside exhibit -30.53 with 1O93 target. Amarogentin also showed least affinity of 69.13 with 1JEN and JBQI. Thus, the present study provided the scientific validation for hepatoprotective activity of selected Iridoids and Secoiridoids.


KEYWORDS: Gentianaceae, Iridoids, Sweroside, Molecular docking, FRED.




Human beings are exposed environmental pollutants, chemicals, drugs, and virus infiltration collectively referred to as xenobiotics which are causing serious health problems. Liver is the major site of xenobiotic metabolism and its injury leads to loss of defense mechanism. Swertiamarin a secoiridoid glycoside was found to contain a major constituent of the Enicostemma axillare produced significant hepatoprotective activity against d-GalN induced hepatotoxicity[1]. Sweroside was reported to possess anti-hepatitis property[2]. Eustomoside, eustoside, eustomorusside, and desoxyeustomoside are some of the seco-iridoids in Gentianaceae family[3]. Gentiopicroside and Sweroside are isolated from Swertia franchetiana[4]. Anti-inflammatory and antinociceptive activity of iridoid glucosides of Veronica anagallis were reported[5].


Gentiana asclepiadea L extracts had been reported for the treatment of carbon tetrachloride-induced liver injury. The hepatoprotective activity is mainly due to the phytoconstituents sweroside, swertiamarin and gentiopicrin which are present in high concentrations[6]. Iridoids of Senburiside III and Senburiside IV from Swertia franchetiana (Gentianaceae) in Tibetan Folk Medicine used for treatment for hepatitis and cholecystitis[7]. From this docking studies the hepatoprotective activity of iridoids and secoiridoids was due to the interaction with the above mentioned seven hepatoprotective targets.




Chem Draw ultra is the industry standard structure, drawing suite for the serious chemist to draw accurate, chemically-aware structures for use in database queries, preparation of publication-quality graphics, and entry for modeling and other programs that require an electronic description of molecules and reactions as well as advanced prediction tools and full Web integration using Chem Draw AxtiveX/plugin. Chem Draw Ultra is the gold standard for chemical drawing, publication and query preparation The structures are drawn and saved as mol file and further used for docking with FRED software.



Fig 1: Chemdraw protocol



The protein Data Bank (PDB)[8] is a repository for the 3D structural data for biomolecules, such as proteins and nucleic acids. The PDB is overseen by an organization called the Worldwide Protein Data Bank, wwPDB. PDB is the main element in areas of structural biology, such as structural genomics. Most major scientific journals such as the NIH in the USA, now require scientists to submit their structure data to the PDB. If the contents of the PDB are thought of as primary data, then there are hundreds of derived (i.e., secondary) database that categorize the data differently.




Based on original scientific perspective and efficient computational algorithms, FRED is an accurate and fast docking program, typically processing 3 ligands in a second. For each, FRED exhaust exhaustively examines all possible poses with in the protein active site, filtering for shape complementarity and pharmacophoric features before selecting a single pose based upon a consensus of scoring functions. Ligands are then scored and ranked with a choice of structure-based or ligand-based scoring functions. When using a well-chosen set of conformers FRED predicts binding modes quite well. FRED is considered as a good docking engine for structure based Virtual screening.


This OEDocking distribution contains three primary command line programs for docking molecules.

·       Fred Docks multi conformer molecules using an exhaustive search algorithm.

·       Uses the structure of a target protein to dock and score molecules.

·       Uses one structure of the target protein.

·       Can utilize multiple processors via MPI on supported platforms



Step1: Load the receptor molecule using "MOLECULE" option.

Step2: Select a specific place in the receptor molecule using "BOX” option.

Step3: To find the flexible way for drug in the receptor molecule using "TWEAK "option.

Step4: To find the mutable residues in the receptor molecule using "SHAPE" option.

Step5: The Docking value obtains by using the "TRIAL DOCKING" option

Step6: Using "FINISH" option quit the FRED program.



Fig 2: Flow chart of docking procedure used in FRED software.


Fig 3: Loading of Molecule mol File in FRED



Table 1 shows the binding affinity of Swertiamarin, Sweroside, Amarogentin, Gentio picroside, glycosides with seven liver corrective targets 1JEN-Human-S-Adenosyl methionine decarboxylase, 2OOL-Human sperimidine synthase, 2PO2-Crystal structure of the alpha subunit of human-S-Adenosyl methionine Synthetase II, 1JBQ-Structure of human cystathionoine beta synthase a unique pyridoxal 5’ phosphate dependent heme protein, 2AZT-Crystal structure  of H 176 N mutant of human glycine N-Methyl transferase, 2OBV-Crystal  structure of the human-S-Adenosyl methionine  synthase-I in complex with the product, 1093-Methionine adenosyl transferase complexed with ATP and a  L-Methionine analogues. Swertiamarin had shown best affinity with 2PO2 of -28.91. Sweroside had shown best affinity with 1JBQ of -38.97. Gentiopicroside shows no valid poses for the 2OOL, 2AZT, 2OBV. Amarogentin revealed no valid poses for 2OOL also weak affinity with 2PO2.


Table 1: Binding Affinity of Iridoid Glycosides with seven liver corrective targets

Target Enzymes

Binding Affinity (KJ/Mol)

Swertia marin

Swero side


Gentiopicro side





































Fig 4: Binding affinity – Swertiamarin


Fig 5: Binding affinity - Sweroside


Fig 6: Binding affinity - Amarogentin


Fig 7: Binding affinity - Gentiopicroside



It can be concluded from the results that iridoid glycosides, Swertiamarin, Sweroside, Amarogentin, Gentio picroside present in Gentianaceae family proved the scientific validation for hepatoprotective activity using in-silico methods.



The author Dr. R. Arivukkarasu whole heartedly thank Dr. A. Thamaraiselvan, Head, Department of Chemistry, Thiyagarajar college, Madurai, Tamilnadu, 625009. The authors are thankful to Chairman and Secretary of Kovai Medical Centre Research and Educational Trust, Tamilnadu for providing facilities necessary for carrying out the work.



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2.        Zhou J. Bioactive glycosides from Chinese medicines. Memórias do Instituto Oswaldo Cruz. 1991; 86:231-4.

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4.        Cheng Hui-yun et al., Separation and preparation of Gentiopicroside and Sweroside from the Extracts of Swertia franchetiana H.Smith by HSCCC. Medicinal Plant. 2010; 1(10):38-40.

5.        Esra Kupeli et al., Bioassay-guided isolation of iridoid glucosides with antinociceptive and anti-inflammatory activities from Veronica anagallis-aquatica L. Journal of Ethnopharmacology; 2005 102:170–176.

6.        Mihailović V et al., Hepatoprotective effects of Gentiana asclepiadea L. extracts against carbon tetrachloride induced liver injury in rats. Food and Chemical Toxicology. 2013; 52:83-90.

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8.        The Protein Data Bank H.M. Berman, J et al., Nucleic Acids Research. 2000; 28:235-242.






Received on 14.05.2019           Modified on 21.06.2019

Accepted on 30.07.2019         © RJPT All right reserved

Research J. Pharm. and Tech. 2019; 12(12): 5735-5738.

DOI: 10.5958/0974-360X.2019.00992.2