Xylocarpin H, a Limonoid of Xylocarpus granatum, Produces Antidepressant-Like Activities in Mice

Xi Yin¹, Xin Li², Yaoguang Hao², Yiwen Zhao², Jinghong Zhou², Haishui Shi^3*

¹Department of Functional Region of Diagnosis, Fourth Hospital of Hebei Medical University, Shijiazhuang, China.
²College of Basic Medicine, Hebei Medical University, Shijiazhuang, China.
³Department of Biochemistry and Molecular Biology, College of Basic Medicine, Hebei Medical University, Shijiazhuang, China.

DOI: 10.4236/jbbs.2015.511050                

Abstract

Major depression is a common psychiatric disorder worldwide that imposes a substantial health burden on society. Currently available antidepressants do not meet the clinical needs. Here, we report that Xylocarpin H, a limonoid of Xylocarpus granatum, has antidepressant-like effects in mouse forced swimming and tail suspension tests, two validated models of depression. 7-day oral administration of Xylocarpin H resulted in dose-dependent decreases immobility duration within the dose range of 15 - 50 mg/kg. Xylocarpin H dose-dependently increases the time spent in the central zone at doses of 5 - 50 mg/kg in locomotion activity test. In addition, 7-day treatment Xylocarpus H at 15 and 50 mg/kg doses significantly decreases levels of serum corticosterone and adrenocorticotropic hormone (ACTH) following the acute stress of forced swimming test. Furthermore, these effective doses of Xylocarpin H do not affect locomotor activity and levels of serum corticosterone and ACTH in the absence of stress. In summary, the present study, for the first time, demonstrates that Xylocarpin H exerts antidepressant-like effects in mouse behavioral models of depression, likely by inhibiting HPA axis systems. These data provide primarily basis for developing Xylocarpin H as a novel antidepressant candidate for the treatment of depression and stress related disorders.

Keywords

Depression, Xylocarpin H, Tail Suspension Test, Forced Swimming Test, Hypothalamic-Pituitary-Adrenal Axis

Conflicts of Interest

The authors declare no conflicts of interest.

References

[1]	Murray, C.C.J.L. and Lopez, A.D. (1998) The Global Burden of Disease, 1990-2020. Nature Medicine, 4, 1241-1243. http://dx.doi.org/10.1038/3218
[2]	Szafranski, T. (2014) Herbal Remedies in Depression—State of the Art. Psychiatria Polska, 48, 59-73. http://dx.doi.org/10.12740/PP/23981
[3]	De Smet, P.A. (2002) Herbal Remedies. New England Journal of Medicine, 347, 2046-2056. http://dx.doi.org/10.1056/NEJMra020398
[4]	Ye, L., Hu, Z.P., Du, G.Y., Zhang, J.Z., Dong, Q.J., Fu, F.H. and Tian, J.W. (2012) Antidepressant-Like Effects of the Extract from Cimicifuga foetida L. Journal of Ethnopharmacology, 144, 683-691. http://dx.doi.org/10.1016/j.jep.2012.10.013
[5]	Zhang, L., Xu, T.Y., Wang, S., Yu, L.Q., Liu, D.X., Zhan, R.Z. and Yu, S.Y. (2012) Curcumin Produces Antidepressant Effects via Activating MAPK/ERK-Dependent Brain-Derived Neurotrophic Factor Expression in the Amygdala of Mice. Behavioural Brain Research, 235, 67-72. http://dx.doi.org/10.1016/j.bbr.2012.07.019
[6]	Zhu, W.L., Shi, H.S., Wei, Y.M., Wang, S.J., Sun, C.Y., Ding, Z.B. and Lu, L. (2012) Green Tea Polyphenols Produce Antidepressant-Like Effects in Adult Mice. Pharmacological Research, 65, 74-80. http://dx.doi.org/10.1016/j.phrs.2011.09.007
[7]	Lakshmi, V. and Gupta, P. (2008) An Overview of the Genus Xylocarpus. Natural Product Research, 22, 1197-1224. http://dx.doi.org/10.1080/14786410701654909
[8]	Shen, L.R., Guo, D., Yu, Y.M., Yin, B.W., Zhao, L., Shi, Q.W., Wang, Y.L. and Huo, C.H. (2009) Chemical Constituents of Plants from the Genus Xylocarpus. Chemistry & Biodiversity, 6, 1293-1308. http://dx.doi.org/10.1002/cbdv.200800025
[9]	Tundis, R., Loizzo, M.R. and Menichini, F. (2014) An Overview on Chemical Aspects and Potential Health Benefits of Limonoids and Their Derivatives. Critical Reviews in Food Science and Nutrition, 54, 225-250. http://dx.doi.org/10.1080/10408398.2011.581400
[10]	Roy, A. and Saraf, S. (2006) Limonoids: Overview of Significant Bioactive Triterpenes Distributed in Plants Kingdom. Biological and Pharmaceutical Bulletin, 29, 191-201. http://dx.doi.org/10.1248/bpb.29.191
[11]	Lakshmi, V., Srivastava, S., Mishra, S.K., Srivastava, M.N., Srivastava, K. and Puri, S.K. (2012) Antimalarial Activity in Xylocarpus granatum (Koen). Natural Product Research, 26, 1012-1015. http://dx.doi.org/10.1080/14786419.2010.535000
[12]	Misra, S., Verma, M., Mishra, S.K., Srivastava, S., Lakshmi, V. and Misra-Bhattacharya, S. (2011) Gedunin and Photogedunin of Xylocarpus granatum Possess Antifilarial Activity against Human Lymphatic Filarial Parasite Brugia malayi in Experimental Rodent Host. Parasitology Research, 109, 1351-1360. http://dx.doi.org/10.1007/s00436-011-2380-x
[13]	Zhou, Z.F., Taglialatela-Scafati, O., Liu, H.L., Gu, Y.C., Kong, L.Y. and Guo, Y.W. (2014) Apotirucallane Protolimonoids from the Chinese Mangrove Xylocarpus granatum Koenig. Fitoterapia, 97, 192-197. http://dx.doi.org/10.1016/j.fitote.2014.06.009
[14]	Cui, J.X., Wu, J., Deng, Z.W., Proksch, P. and Lin, A.W. (2007) Xylocarpins A-I, Limonoids from the Chinese Mangrove Plant Xylocarpus granatum. Journal of Natural Products, 70, 772-778. http://dx.doi.org/10.1021/np060622j
[15]	Sarker, S.D., Uddin, S.J., Shilpi, J.A., Rouf, R., Ferdous, M.E. and Nahar, L. (2007) Neuropharmacological Properties of Xylocarpus moluccensis. Fitoterapia, 78, 107-111. http://dx.doi.org/10.1016/j.fitote.2006.09.029
[16]	Charlton, B.G. and Ferrier, I.N. (1989) Hypothalamo-Pituitary-Adrenal Axis Abnormalities in Depression: A Review and a Model. Psychological Medicine, 19, 331-336. http://dx.doi.org/10.1017/S003329170001237X
[17]	Sapolsky, R.M. (2000) Glucocorticoids and Hippocampal Atrophy in Neuropsychiatric Disorders. Archives of General Psychiatry, 57, 925-935. http://dx.doi.org/10.1001/archpsyc.57.10.925
[18]	Gu, X., Zhou, Y., Wu, X., Wang, F., Zhang, C.Y., Du, C., Shen, L., Chen, X., Shi, J., Liu, C. and Ke, K. (2014) Antidepressant-Like Effects of Auraptenol in Mice. Scientific Reports, 4, 4433. http://dx.doi.org/10.1038/srep04433
[19]	Shi, H.S., Zhu, W.L., Liu, J.F., Luo, Y.X., Si, J.J., Wang, S.J., Xue, Y.X., Ding, Z.B., Shi, J. and Lu, L. (2012) PI3K/Akt Signaling Pathway in the Basolateral Amygdala Mediates the Rapid Antidepressant-Like Effects of Trefoil Factor 3. Neuropsychopharmacology, 37, 2671-2683. http://dx.doi.org/10.1038/npp.2012.131
[20]	Pan, J.Y., Chen, S.L., Li, M.Y., Li, J., Yang, M.H. and Wu, J. (2010) Limonoids from the Seeds of a Hainan Mangrove, Xylocarpus granatum. Journal of Natural Products, 73, 1672-1679. http://dx.doi.org/10.1021/np100395w
[21]	Cui, J., Ouyang, J., Deng, Z. and Lin, W. (2008) Structure Elucidation of an Unprecedented Alkaloid and a New Limonoid from Xylocarpus granatum. Magnetic Resonance in Chemistry, 46, 894-897. http://dx.doi.org/10.1002/mrc.2273
[22]	Wu, J., Zhang, S., Bruhn, T., Xiao, Q., Ding, H. and Bringmann, G. (2008) Xylogranatins F-R: Antifeedants from the Chinese Mangrove, Xylocarpus granatum: A New Biogenetic Pathway to Tetranortriterpenoids. Chemistry, 14, 1129- 1144. http://dx.doi.org/10.1002/chem.200700663
[23]	Krishnan, V. and Nestler, E.J. (2010) Linking Molecules to Mood: New Insight into the Biology of Depression. American Journal of Psychiatry, 167, 1305-1320. http://dx.doi.org/10.1176/appi.ajp.2009.10030434
[24]	Tian, J., Zhang, F., Cheng, J., Guo, S., Liu, P. and Wang, H. (2014) Antidepressant-Like Activity of Adhyperforin, a Novel Constituent of Hypericum perforatum L. Scientific Reports, 4, 5632. http://dx.doi.org/10.1038/srep05632
[25]	Lutter, M., Sakata, I., Osborne-Lawrence, S., Rovinsky, S.A., Anderson, J.G., Jung, S., Birnbaum, S., Yanagisawa, M. Elmquist, J.K., Nestler, E.J. and Zigman, J.M. (2008) The Orexigenic Hormone Ghrelin Defends against Depressive Symptoms of Chronic Stress. Nature Neuroscience, 11, 752-753. http://dx.doi.org/10.1038/nn.2139
[26]	Zhu, W.L., Shi, H.S., Wei, Y.M., Wang, S.J., Sun, C.Y., Ding, Z.B. and Lu, L. (2012) Green Tea Polyphenols Produce Antidepressant-Like Effects in Adult Mice. Pharmacological Research, 65, 74-80. http://dx.doi.org/10.1016/j.phrs.2011.09.007
[27]	Schatzberg, A.F., Keller, J., Tennakoon, L., Lembke, A., Williams, G., Kraemer, F.B., Sarginson, J.E., Lazzeroni, L.C. and Murphy, G.M. (2014) HPA Axis Genetic Variation, Cortisol and Psychosis in Major Depression. Molecular Psychiatry, 19, 220-227. http://dx.doi.org/10.1038/mp.2013.129
[28]	Antonijevic, I. (2008) HPA Axis and Sleep: Identifying Subtypes of Major Depression. Stress, 11, 15-27. http://dx.doi.org/10.1080/10253890701378967
[29]	Birmaher, B., Dahl, R.E., Perel, J., Williamson, D.E., Nelson, B., Stull, S., Kaufman, J., Waterman, G.S., Rao, U., Nguyen, N., Puig-Antich, J. and Ryan, N.D. (1996) Corticotropin-Releasing Hormone Challenge in Prepubertal Major Depression. Biological Psychiatry, 39, 267-277. http://dx.doi.org/10.1016/0006-3223(95)00177-8
[30]	Marais, L., van Rensburg, S.J., van Zyl, J.M., Stein, D.J. and Daniels, W.M. (2008) Maternal Separation of Rat Pups Increases the Risk of Developing Depressive-Like Behavior after Subsequent Chronic Stress by Altering Corticosterone and Neurotrophin Levels in the Hippocampus. Neuroscience Research, 61, 106-112. http://dx.doi.org/10.1016/j.neures.2008.01.011
[31]	Liu, J., Qiao, W., Yang, Y., Ren, L., Sun, Y. and Wang, S. (2012) Antidepressant-Like Effect of the Ethanolic Extract from Suanzaorenhehuan Formula in Mice Models of Depression. Journal of Ethnopharmacology, 141, 257-264. http://dx.doi.org/10.1016/j.jep.2012.02.026
[32]	Ohgi, Y., Futamura, T., Kikuchi, T. and Hashimoto, K. (2013) Effects of Antidepressants on Alternations in Serum Cytokines and Depressive-Like Behavior in Mice after Lipopolysaccharide Administration. Pharmacology Biochemistry and Behavior, 103, 853-859. http://dx.doi.org/10.1016/j.pbb.2012.12.003
[33]	Kronenberg, G., Kirste, I., Inta, D., Chourbaji, S., Heuser, I., Endres, M. and Gass, P. (2009) Reduced Hippocampal Neurogenesis in the GR(+/-) Genetic Mouse Model of Depression. European Archives of Psychiatry and Clinical Neuroscience, 259, 499-504. http://dx.doi.org/10.1007/s00406-009-0036-y
[34]	Khalid, S.A., Duddeck, H. and Gonzalez-Sierra, M. (1989) Isolation and Characterization of an Antimalarial Agent of the Neem Tree Azadirachta indica. Journal of Natural Products, 52, 922-926. http://dx.doi.org/10.1021/np50065a002
[35]	Toume, K., Kamiya, K., Arai, M.A., Mori, N., Sadhu, S.K., Ahmed, F. and Ishibashi, M. (2013) Xylogranin B: A Potent Wnt Signal Inhibitory Limonoid from Xylocarpus granatum. Organic Letters, 15, 6106-6109. http://dx.doi.org/10.1021/ol4029995
[36]	Wisutsitthiwong, C., Buranaruk, C., Pudhom, K. and Palaga, T. (2011) The Plant Limonoid 7-Oxo-Deacetoxygedunin Inhibits RANKL-Induced Osteoclastogenesis by Suppressing Activation of the NF-κB and MAPK Pathways. Biochemical and Biophysical Research Communications, 415, 361-366. http://dx.doi.org/10.1016/j.bbrc.2011.10.073
[37]	Lakshmi, V., Mishra, V. and Palit, G. (2014) A New Gastroprotective Effect of Limonoid Compounds Xyloccensins X and Y from Xylocarpus molluccensis in Rats. Natural Products and Bioprospecting, 4, 277-283. http://dx.doi.org/10.1007/s13659-014-0034-2