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Hepatoprotective Diterpenoids Isolated from Andrographis paniculata

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DOI: 10.4236/cm.2012.33022    4,484 Downloads   8,667 Views   Citations

ABSTRACT

Andrographis paniculata (Burm.f.) Nees (Acanthaceae), a plant widely used as traditional herbal medicine in many countries, has drawn attention of the researchers in recent years. Its major constituents are diterpenoids and flavonoids. This article reviews the anti-hepatotoxic effects of A. paniculata extract and derivative compounds, such as andrographolide, the major active compound, most studied for its bioactivities. Neoandrographolide shows anti-inflammatory and anti-hepatoxic properties. 14-deoxy-11,12-didehydroandrographolide and 14-deoxyabdrographolide have immunostimulatory, anti-atherosclerotic, and anti-hepatotoxic activities. The hepatoprotective activities include (1) inhibiting carbontetrachloride (CCl4), tert-butylhydroperoxide (t-BHP)-induced hepatic toxicity, (2) acting as cytochrome P450 enzymes (CYPs) inducers, (3) modulating glutathione (GSH) content, (4) influence glutathione S-transferase (GSTP) activity and phosphatidylinositol-3-kinase/Akt (PI3k/Akt) pathway, (5) synergistic effect with anti-cancer drugs induced apoptosis contributing to the bioactivities of A. paniculata extracts and isolated bioactive compounds. The articles reviewed suggest that the above compounds could be candidates for research and development as potential hepatoprotective drugs.

Conflicts of Interest

The authors declare no conflicts of interest.

Cite this paper

W. Chao and B. Lin, "Hepatoprotective Diterpenoids Isolated from Andrographis paniculata," Chinese Medicine, Vol. 3 No. 3, 2012, pp. 136-143. doi: 10.4236/cm.2012.33022.

References

[1] F. J. Gonzalez, “The Molecular Biology of Cytochrome P450s,” Pharmacological Reviews, Vol. 40, No. 4, 1988, pp. 243-288.
[2] P. K. Singha, S. Roy and S. Dey, “Protective Activity of Andrographolide and Arabinogalactan Proteins from Andrographis paniculata Nees. against Ethanol Induced Toxicity in Mice,” Journal of Ethnopharmacology, Vol. 111, No. 1, 2007, pp. 13-21. doi:10.1016/j.jep.2006.10.026
[3] J. D. Hayes, J. U. Flanagan and I. R. Jowsey, “Glutathione Transferases,” Annual Review of Pharmacology and Toxicology, Vol. 45, 2005, pp. 51-88. doi:10.1146/annurev.pharmtox.45.120403.095857
[4] M. Iwanari, M. Nakajima, R. Kizu, K. Hayakawa and T. Yokoi, “Induction of CYP1A1, CYP1A2 and CYP1B1 mRNAs by Nitropolycyclic Aromatic Hydrocarbons in Various Human Tissue Derived Cells: Chemical-, Cytochrome p450 Isoforms-, and Cell Specific Differences,” Archives of Toxicology, Vol. 76, No. 5-6, 2002, pp. 287- 298. doi:10.1007/s00204-002-0340-z
[5] P. J. Wedlund, “The CYP2C19 Enzyme Polymorphism,” Pharmacology, Vol. 61, No. 3, 2000, pp. 174-183. doi:10.1159/000028398
[6] T. Shimada, H. Yamazaki, M. Mimura, Y. Inui and F. P. Guengerich, “Interindividual Variations in Human Liver Cytochrome P450 Enzymes Involved in the Oxidation of Drugs, Carcinogens and Toxic Chemicals: Studies with Liver Microsomes of 30 Japanese and 30 Caucasians,” Journal of Pharmacology and Experimental Therapeutics Vol. 270, No. 1, 1994, pp. 414-423.
[7] B. Kligler, C. Ulbricht, E. Basch, C. D. Kirkwood, T. R. Abrams, M. Miranda, K. P. Singh Khalsa, M. Giles, H. Boon and J. Woods, “Andrographis paniculata for the Treatment of Upper Respiratory Infection: A Systematic Review by the Natural Standard Research Collaboration,” Explore, Vol. 2, No. 1, 2006, pp. 25-29. doi:10.1016/j.explore.2005.08.008
[8] M. Roxas and J. Jurenka, “Colds and Influenza, a Review of Diagnosis and Conventional, Botanical and Nutritional Considerations,” Alternative Medicine Review, Vol. 12, No. 1, 2007, pp. 25-48.
[9] A. S. Negi, J. K. Kumar, S. Luqman, K. Sbanker, M. M. Gupta and S. P. S. Kbanuja, “Recent Advances in Plant Hepatoprotectives: A Chemical and Biological Profile of Some Important Leads,” Medicinal Research Reviews, Vol. 28, No. 5, 2008, pp. 746-772. doi:10.1002/med.20115
[10] D. D. Caceres, J. L. Hancke, R. A. Burgos and G. K. Wikman, “Prevention of Common Colds with Andrographis paniculata Dried Extract: A Pilot Doudle-Blind Trial,” Phytomedicine, Vol. 4, 1997, pp. 101-104.
[11] H. Y. Cheung , C. S. Cheung and C. K. Kong, “Determination of Bioactive Diterpenoids from Andrographis paniculata by Micellar Electrokinetic Chromatography,” Journal of Chromatography A, Vol. 930, No. 1-2, 2001, pp. 171-176. doi:10.1016/S0021-9673(01)01160-8
[12] T. Matsuda, M. Kuroyanagi, S. Sugiyama, K. Umehara, A. Ueno and K. Nishi, “Cell Differentiation Inducing Diterpenes from Andrographis paniculata Nees,” Chemical & Pharmaceutical Bulletin, Vol. 42, No. 6, 1994, pp. 1216-1225. doi:10.1248/cpb.42.1216
[13] N. Pholphana, N. Rangkadilok, S. Thongnest, S. Ruchirawat, M. Ruchirawat and J. Satayavivad, “Determination and Variation of Three Active Diterpenoids in Andrographis paniculata (Burm.f.) Nees,” Phytochemical Analysis, Vol. 15, No. 6, 2004, pp. 365-371. doi:10.1002/pca.789
[14] P. H. Kishore, M. V. Reddy, M. K. Reddy, D. Gunasekar, C. Caux and B. Bodo, “Flavonoids from Andrographis lineate,” Phytochemistry, Vol. 63, No. 4, 2003, pp. 457- 461. doi:10.1016/S0031-9422(02)00702-1
[15] J. Li, W. Huang, H. Zhang, X. Wang and H. Zhou, “Synthesis of Andrographolide Derivatives and Their TNF- Alpha and IL-6 Expression Inhibitory Activities,” Bioorganic & Medicinal Chemistry Letters, Vol. 17, No. 24, 2007, pp. 6891-6894. doi:10.1016/j.bmcl.2007.10.009
[16] W. Parichatikanond, C. Suthisisang, P. Dhepakson and A. Herunsalee, “Study of Anti-Inflammatory Activities of the Pure Compounds from Andrographis paniculata (burm.f.) Nees and Their Effects on Gene Expression,” International Immunopharmacology, Vol. 10, No. 11, 2010, pp. 1361-1373. doi:10.1016/j.intimp.2010.08.002
[17] W. W. Chao, Y. H. Kuo, W. C. Li and B. F. Lin, “The Production of Nitric Oxide and Prostaglandin E2 in Peritoneal Macrophages Is Inhibited by Morus alba, Angelica sinensis and Andrographis paniculata Ethyl Acetate Fraction Extracts,” Journal of Ethnopharmacology, Vol. 122, No. 1, 2009, pp. 68-75. doi:10.1016/j.jep.2008.11.029
[18] W. W. Chao, Y. H. Kuo, S. L. Hsieh and B. F. Lin, “Inhibitory Effects of Ethyl Acetate Extract of Andrographis paniculata on NF-κB Trans-Activation Activity and LPS- Induced Acute Inflammation in Mice,” eCAM, Vol. 2011, 2011, p. 254531.
[19] W. W. Chao, Y. H. Kuo and B. F. Lin, “Anti-Inflammatory Activity of New Compounds from Andrographis paniculata by NF-B Trans-Activation Inhibition,” J Journal of Agricultural and Food Chemistry, Vol. 58, No. 4, 2010, pp. 2505-2512. doi:10.1021/jf903629j
[20] W. W. Chao and B. F. Lin, “Isolation and Identification of Bioactive Compounds in Andrographis paniculata (Chuanxinlian),” Chinese Medicine, Vol. 5, 2010, p. 17. doi:10.1186/1749-8546-5-17
[21] R. O. Recknagel, “Carbon Tetrachloride Hepatotoxicity: Status Quo and Future Prospects,” Trends in Pharmacological Sciences Vol. 4, 1983, pp. 129-131. doi:10.1016/0165-6147(83)90328-0
[22] B. R. Choudhury and M. K. Poddar, “Andrographolide and Kalmegh (Andrographis paniculata) Extract: In Vivo and in Vitro Effect on Hepatic Lipid Peroxidation,” Methods & Findings in Experimental & Clinical Pharmacology, Vol. 6, No. 9, 1984, pp. 481-485.
[23] G. F. Rush, J. R. Gorski, M. G. Ripple, J. Sowinski, P. Bugelski and W. R. Hewitt, “Organic Hydroperoxide-Induced Lipid Peroxidation and Cell Death in Isolated Hepatocytes,” Toxicology and Applied Pharmacology, Vol. 78, No. 3, 1985, pp. 473-483. doi:10.1016/0041-008X(85)90255-8
[24] J. Hogberg, S. Orrenius and P. J. O’Brien, “Further Studies on Lipid-Peroxide Formation in Isolated Hepatocytes,” European Journal of Biochemistry, Vol. 59, No. 2, 1975, pp. 449-455. doi:10.1111/j.1432-1033.1975.tb02473.x
[25] A. Kapil, I. B. Koul, S. K. Banerjee and B. D. Gupta, “Antihepatotoxic Effects of Major Diterpenoid Constituents of Andrographis paniculata,” Biochemical Pharmacology Vol. 46, No. 1, 1993, pp. 182-185. doi:10.1016/0006-2952(93)90364-3
[26] G. A. Akowuah, I. Zhari, A. Mariam and M. F. Yam, “Absorption of Andrographolides from Andrographis paniculata and Its Effect on CCl4-Induced Oxidative Stress in Rats,” Food and Chemical Toxicology, Vol. 47, No. 9, 2009, pp. 2321-2326. doi:10.1016/j.fct.2009.06.022
[27] S. S. Handa and A. Sharma, “Hepatoprotective Activity of Andrographolide against Galactosamine and Paracetamol Intoxication in Rats,” Indian Council of Medical Research, Vol. 92, 1990, pp. 284-292.
[28] P. K. Visen, B. Shukla, G. K. Patnaik and B. N. Dhawan, “Andrographolide Protects Rat Hepatocytes against Paracetamol Induced Gamage,” Journal of Ethnopharmacology, Vol. 40, No. 2, 1993, pp. 131-136. doi:10.1016/0378-8741(93)90058-D
[29] J. F. Ye, H. Zhu, Z. F. Zhou, R. B. Xiong, X. W. Wang, L. X. Su and B. D. Luo, “Protective Mechanism of Andrographolide against Carbon Tetrachloride Induced Acute Liver Injury in Mice,” Biological and Pharmaceutical Bulletin, Vol. 34, No. 11, 2011, pp. 1666-1670. doi:10.1248/bpb.34.1666
[30] R. Nagalekshmi, A. Menon, D. K. Chandrasekharan and C. K. K. Nair, “Hepatoprotective Activity of Andrographis paniculata and Swertia Chirayita,” Food and Chemical Toxicology, Vol. 49, No. 12, 2011, pp. 3367-3373. doi:10.1016/j.fct.2011.09.026
[31] K. Jarukamjorn, K. Donin, C. Makejaruskul, T. Laha, S. Daodee, P. Pearaksa and B. Sripanidkulchai, “Impact of Andrographis paniculata Crude Extract on Mouse Hepatic Cytochrome P450 Enzymes,” Journal of Ethno-pharmacology, Vol. 105, No. 3, 2006, pp. 464-467. doi:10.1016/j.jep.2005.11.024
[32] A. Jaruchotikamol, J. Kanokwan, S. T. S. Wanna, K. Yuki and N. Nobuo, “Strong Synergistic Induction of CYP1A1 Expression by Andrographolide plus Typical CYP1A Inducers in Mouse Hepatocytes,” Toxicology and Applied Pharmacology, Vol. 224, No. 2, 2007, pp. 156-162. doi:10.1016/j.taap.2007.07.008
[33] W. Chatuphonprasert, K. Jarukamjorn, S. Kondo and N. Nemoto, “Synergistic Increases of Metabolism and Oxidation Reduction Genes on Their Expression after Combined Treatment with a CYP1A Inducer and Androgra-pholide,” Chemico-Biological Interactions, Vol. 182, No. 2-3, 2009, pp. 233-238. doi:10.1016/j.cbi.2009.09.001
[34] D. Pekthong, H. Martin, C. Abadie, A. Bonet, B. Heyd, G. Mantion and L. Richert, “Differential Inhibition of Rat and Human Hepatic Cytochrome P450 by Andrographis paniculata Extract and Andrographolide,” Journal of Ethnopharmacology, Vol. 115, No. 3, 2008, pp. 432-440. doi:10.1016/j.jep.2007.10.013
[35] D. Pekthong, N. Blanchard, C. Abadie, A. Bonet, B. Heyd, G. Mantion, A. Berthelot, L. Richert and H. Martin, “Effects of Andrographis paniculata Extract and Androgra-pholide on Hepatic Cytochrome P450 mRNA Expression and Monooxygenase Activities after in Vivo Administration to Rats and in Vitro in Rat and Human Hepatocyte Cultures,” Chemico-Biological Interactions, Vol. 179, No. 2-3, 2009, pp. 247-255.
[36] K. Jarukamjorn, S. Kondo, W. Chatuphonprasert, T. Sakuma, Y. Kawasaki and N. Nemoto, “Gender-Associated Modulation of Ineucible CYP1A1 expression by Andro-grapholide in Mouse Liver,” European Journal of Pharmaceutical Sciences, Vol. 39, No. 5, 2010, pp. 394-401. doi:10.1016/j.ejps.2010.01.009
[37] J. P. Ooi, M. Kuroyanagi, S. F. Sulaiman, T. S. T. Muhammad and M. L. Tan, “Andrographolide and 14-Deoxy-11, 12-Didehydroandrographolide Inhibit Cytochtome P450s in HepG2 Hepatoma Cells,” Life Sciences, Vol. 88, No. 9-10, 2011, pp. 447-454. doi:10.1016/j.lfs.2010.12.019
[38] Y. Pan, B. A. Abd-Rashid, Z. Ismail, R. Ismail, J. W. Mak, P. C. K. Pook, H. M. Er and C. E. Ong, “In Vitro Determination of the Effect of Andrographis Paniculata Extracts and Andrographolide on Human Hepatic Cytochrome P450 Activities,” Journal of Natural Medicines, Vol. 65, No. 3-4, 2011, pp. 440-447. doi:10.1007/s11418-011-0516-z
[39] W. Chatuphonprasert, T. Remsungnen, N. Nemoto and K. Jarukamjorn, “Different AhR Binding Sites of Diterpenoid Ligands from Andrographis Paniculata Caused Differential CYP1A1 Induction in Primary Culture in Mouse Hepatocytes,” Toxicology in Vitro, Vol. 25, No. 8, 2011, pp. 1757-1763. doi:10.1016/j.tiv.2011.09.004
[40] F. Qiu, X. L. Hou, K. Takahashi, L. X. Chen, J. Azuma and N. Kang, “Andrographolide Inhibits the Expression and Metabolic Activity of Cytochrome P450 3A4 in the Modified Caco-2 Cells,” Journal of Ethnopharmacology, Vol. 141, No. 2, 2012, pp. 709-713. doi:10.1016/j.jep.2011.09.002
[41] S. Kondo, W. Chatuphonprasert, A. Jaruchotikamol, T. Sakuma and N. Nemoto, “Cellular Glutathione Content Modulates the Effect of Andrographolide on -Naphtho- flavone Induced CYP1A1 mRNA Expression in Mouse Hepatocytes,” Toxicology, Vol. 280, No. 1-2, 2011, pp. 18- 23. doi:10.1016/j.tox.2010.11.002
[42] Y. Pan, B. A. Abd-Rashid, Z. Ismail, R. Ismail, J. W. Mak, P. C. K. Pook, H. M. Er and C. E. Ong, “In Vitro Modulatory Effects of Andrographis paniculata, Centella asiatica and Orthosiphon stamineus on Cytochrome P450 2C19 (CYP2C19),” Journal of Ethnopharmacology, Vol. 133, No. 2, 2011, pp. 881-887. doi:10.1016/j.jep.2010.11.026
[43] K. T. Chang, C. K. Lii, C. W. Tsai, A. J. Yang and H. W. Chen, “Modulation of the Expression of the ? Class of Glutathione S-Transferase by Andrographis paniculata Extracts and Andrographolide,” Food and Chemical Toxicology, Vol. 46, No. 3, 2008, pp. 1079-1088. doi:10.1016/j.fct.2007.11.002
[44] C. Y. Lu, C. C. Li, C. K. Lii, H. T. Yao, K. L. Liu, C. W. Tsai and H. W. Chen, “Andrographolide Induced Pi Class of Glutathione S-Transferase Gene Expression via PI3K/ AKt Pathway in Rat Primary Hepatocytes,” Food and Chemical Toxicology, Vol. 49, No. 1, 2011, pp. 281-289. doi:10.1016/j.fct.2010.10.030
[45] L. Yang, D. Wu, K. Luo, S. Wu and P. Wu, “Andrographolide Enhances 5-Fluorouracil-Induced Apoptosis via Cas-pase-8 Dependent Mitochondrial Pathway Involving p53 Participation in Hepatocellular Carcinoma (SMMC-7721) Cells,” Cancer Letters, Vol. 276, No. 2, 2009, pp. 180-188. doi:10.1016/j.canlet.2008.11.015
[46] D. N. Roy, G. Sen, K. D. Chowdhury and T. Biswas, “Combination Therapy with Andrographolide and D-Penicillamine Enhanced Therapeutic Advantage over Monotherapy with D-Penicillamine in Attenuating Fibrogenic Response and Cell Death in the Periportal Zone of Liver in Rats during Copper Toxicosis,” Toxicology and Applied Pharmacology, Vol. 250, No. 1, 2011, pp. 54-68. doi:10.1016/j.taap.2010.09.027
[47] T. Y. Lee, K. C. Lee and H. H. Chang, “Modulation of the Cannabinoid Receptors by Andrographolide Attenuates Hepatic Apoptosis Following Bile Duct Ligation in Rats with Fibrosis,” Apoptosis, Vol. 15, No. 8, 2010, pp. 904-914. doi:10.1007/s10495-010-0502-z
[48] J. Zhou, C. N. Ong, G. M. Hur and H. M. Shen, “Inhibition of the JAK-STAT3 Pathway by Andrographolide Enhances Chemosensitivity of Cancer Cells to Doxorubicin,” Biochemical Pharmacology, Vol. 79, No. 9, 2010, pp. 1242-1250. doi:10.1016/j.bcp.2009.12.014
[49] D. N. Roy, S. Mandal, G. Sen, S. Mukhopadhyay and T. Biswas, “14-Deoxyandrographolide Desensitizes Hepatocytes to Tumour Necrosis Factor-Alpha Induced Apoptosis through Calcium Dependent Tumour Necrosis Factor Receptor Superfamily Member 1A Release via the NO/cGMP Pathway,” British Journal of Pharmacology, Vol. 160, No. 7, 2010, pp. 1823-1843. doi:10.1111/j.1476-5381.2010.00836.x
[50] L. Ji, K. Shen, P. Jiang, G. Morahan and Z. Wang, “Critical Roles of Cellular Glutathione Homeostasis and JNK Activation in Andrographolide Mediated Apoptotic Cell Death in Human Hepatoma Cells,” Molecular Carcinogenesis, Vol. 50, No. 8, 2011, pp. 580-591. doi:10.1002/mc.20741
[51] G. Tiegs, J. Hentschel and A. Wendel, “A T Cell Dependent Experimental Liver Injury in Mice Inducible by Concanavalin A,” The Journal of Clinical Investigation, Vol. 90, No. 1, 1992, pp. 196-203. doi:10.1172/JCI115836
[52] Z. L. Wang, X. H. Wu, L. F. Song, Y. S. Wang, X. H. Hu, Y. F. Luo, Z. Z. Chen, J. Ke, X. D. Peng, C. M. He, W. Zhang, L. J. Chen and Y. Q. Wei, “Phosphoinostide 3 Kinase Gamma Inhibitor Ameliorates Concanavalin A Induced Hepatic Injury in Mice,” Biochemical and Biophysical Research Communications, Vol. 386, No. 4, 2009, pp. 569-574. doi:10.1016/j.bbrc.2009.06.060
[53] D. H. Adams, C. Ju, S. K. Ramaiah, J. Uetrecht and H. Jaeschke, “Mechanisms of Immune Mediated Liver Injury,” Toxicological Sciences, Vol. 115, No. 2, 2010, pp. 307-321. doi:10.1093/toxsci/kfq009
[54] G. Shi, Z. Zhang, R. Zhang, X. Zhang, Y. Lu, J. Yang, D. Zhang, Z. Zhang, X. Li and G. Ning, “Protective Effect of Andrographolide against concanavalin A Induced Liver Injury,” Naunyn-Schmiedeberg’s Archives of Pharmacology, Vol. 385, No. 1, 2012, pp. 69-79. doi:10.1007/s00210-011-0685-z

  
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