Molecular Analysis of Clerodendrum formicarum Effects in Painful Diabetic  Neuropathy in Rat

Ghislain Loubano-Voumbi; Mor Diaw; Valentin Ouedraogo; Abdou Khadir Sow; Aïssatou Seck; Luc Magloire Anicet Boumba; Abdoulaye Ba; Abdoulaye Samb

doi:10.4236/wjns.2015.54023

Home > Journals > Biomedical & Life Sciences > WJNS

World Journal of Neuroscience > Vol.5 No.4, August 2015

Molecular Analysis of Clerodendrum formicarum Effects in Painful Diabetic Neuropathy in Rat ()

Ghislain Loubano-Voumbi^1*, Mor Diaw¹, Valentin Ouedraogo¹, Abdou Khadir Sow¹, Aïssatou Seck¹, Luc Magloire Anicet Boumba², Abdoulaye Ba¹, Abdoulaye Samb¹

¹Laboratory of Physiology and Functional Exploration, Faculty of Medicine of Pharmacy and Odontology, Cheikh Anta Diop University of Dakar, Dakar, Senegal.
²Laboratory of Molecular Biology of the Loandjili Hospital Pointe, Noire, Republic of Congo.

DOI: 10.4236/wjns.2015.54023 PDF HTML XML 5,251 Downloads 5,694 Views Citations

Abstract

The pathophysiology of diabetic neuropathic pain is due to primarily metabolic and vascular factors. There is an increase in sorbitol and fructose, glycated end products, reactive oxygen species and activation of protein kinase C in the diabetic state. All these factors lead to direct damage to the nerves. Taking effective clinical management of neuropathic pain is based on a pharmacological treatment that has shown their limits and many side effects. The hypothesis of central sensitization inhibited by Clerodendrum formicarum, an African pharmacopoeia plant used to treat headaches, arthritis, epilepsy and chronic pain could act on astrocytes and microglial cells. The objective of this work is to study the effect of Clerodendrum formicarum (100, 150 and 200 mg/kg body weight) on astrocytes and microglial cells in a model of diabetic neuropathic pain induced by alloxan monohydrate (150 mg/kg). We noted a suppression of mechanical allodynia and mechanical hyperalgesia respectively by the Von Frey filaments test and the pressure test on the paw by the Clerodendrum formicarumextracts (ECF) at different doses from 2 h at the first injection of the ECF. After 5 days of treatment, we expressed by Western Blot bands of different proteins and by quantitative RT-PCR, we determined inhibition of the expression of GFAP, CD11b and isoforms 1 and 2 of cyclooxygenase. These results suggest that ECF inhibits the activation of astrocytes, microglial cells and cyclooxygenase signaling pathway.

Keywords

Clerodendrum formicarum, Astrocytes, Microglial Cells, Diabetic Neuropathy Pain, Cyclooxygenase

Share and Cite:

Loubano-Voumbi, G. , Diaw, M. , Ouedraogo, V. , Sow, A. , Seck, A. , Boumba, L. , Ba, A. and Samb, A. (2015) Molecular Analysis of Clerodendrum formicarum Effects in Painful Diabetic Neuropathy in Rat. World Journal of Neuroscience, 5, 258-269. doi: 10.4236/wjns.2015.54023.

Conflicts of Interest

The authors declare no conflicts of interest.

References

[1]	Barrett, A.M., Lucero, M.A., Le, T., Robinson, R.L., Dworkin, R.H. and Chappell, A.S. (2007) Epidemiology, Public Health Burden, and Treatment of Diabetic Peripheral Neuropathic Pain: A Review. Pain Medicine, 8, S50-S62. http://dx.doi.org/10.1111/j.1526-4637.2006.00179.x
[2]	Miranda-Massari, J.R., Gonzalez, M.J., Jimenez, F.J., Allende-Vigo, M.Z. and Duconge, J. (2011) Metabolic Correction in the Management of Diabetic Peripheral Neuropathy: Improving Clinical Results beyond Symptom Control. Current Clinical Pharmacology, 6, 260-273. http://dx.doi.org/10.2174/157488411798375967
[3]	Patel, N., Mishra, V., Patel, P. and Dikshit, R.K. (2014) A Study of the Use of Carbamazepine, Pregabalin and Alpha Lipoic Acid in Patients of Diabetic Neuropathy. Journal of Diabetes & Metabolic Disorders, 13, 62. http://dx.doi.org/10.1186/2251-6581-13-62
[4]	Dodda, D. and Ciddi, V. (2014) Plants Used in the Management of Diabetic Complications. Indian Journal of Pharmaceutical Sciences, 76, 97-106.
[5]	Raafat, K. and Samy, W. (2014) Amelioration of Diabetes and Painful Diabetic Neuropathy by Punicagranatum L. Extract and Its Spray Dried Biopolymeric Dispersions. Evidence-Based Complementary and Alternative Medicine, 2014, 180495. http://dx.doi.org/10.1155/2014/180495
[6]	Shaikh, A.S. and Somani, R.S. (2010) Animal Models and Biomarkers of Neuropathy in Diabetic Rodents. Indian Journal of Pharmacology, 42, 129-134. http://dx.doi.org/10.4103/0253-7613.66833
[7]	Ziegler, D., Sohr, C.G. and Nourooz-Zadeh, J. (2004) Oxidative Stress and Antioxidant Defense in Relation to the Severity of Diabetic Polyneuropathy and Cardiovascular Autonomic Neuropathy. Diabetes Care, 27, 2178-2183. http://dx.doi.org/10.2337/diacare.27.9.2178
[8]	Ali, M.S., Ahmed, Z., Ali, M.I. and Ngoupayo, J. (2010) Formadienoate A and B: Two New Long Chained Feruloyl Esters from Clerodendrum formicarum Gürke (Lamiaceae) of Cameroon. Natural Product Communications, 5, 919-922.
[9]	Tauseef, S., Ali, M.S., Ahmed, A., Ali, M.I., Ahmed, Z., Sherwani, S.K., Ahmed, G., Onocha, A.O., Ngoupayo, J., Kamdem Waffo, A.F. and Tauseef, F. (2013) In Vitro Antioxidant Activity Analysis of Five Medicinally Important Plants. Journal of Pharmacognosy and Phytochemistry, 2, 183-188.
[10]	Zimmermann, M. (1983) Ethical Guidelines for Investigations of Experimental Pain in Conscious Animals. Pain, 16, 109-110. http://dx.doi.org/10.1016/0304-3959(83)90201-4
[11]	Orman, M.A., Berthiaume, F., Androulakis, L.P. and Ierapetritou, M.G. (2011) Advanced Stoichiometric Analysis of Metabolic Networks of Mammalian Systems. Critical Reviews? in Biomedical Engineering, 39, 511-534. http://dx.doi.org/10.1615/CritRevBiomedEng.v39.i6.30
[12]	Sun, W., Miao, B., Wang, X.-C., Duan, J.-H., Ye, X., Han, W.-J., Wang, W.-T., Luo, C. and Hu, S.-J. (2012) Gastrodin Inhibits Allodynia and Hyperalgesia in Painful Diabetic Neuropathy Rats by Decreasing Excitability of Nociceptive Primary Sensory Neurons. PLoS ONE, 7, e39647. http://dx.doi.org/10.1371/journal.pone.0039647
[13]	Flatters, S.J. and Bennett, G.J. (2004) Ethosuximide Reverses Paclitaxel- and Vincristine-Induced Painful Peripheral Neuropathy. Pain, 109, 150-161. http://dx.doi.org/10.1016/j.pain.2004.01.029
[14]	Stohr, T., Krause, E. and Selve, N. (2006) Lacosamide Displays Potent Antinociceptive Effects in Animal Models for Inflammatory Pain. European Journal of Pain, 10, 241-249. http://dx.doi.org/10.1016/j.ejpain.2005.04.002
[15]	Bang, S., Yoo, S., Yang, T.J., Cho, H., Kim, Y.G. and Hwang, S.W. (2010) Resolvin D1 Attenuates Activation of Sensory Transient Receptor Potential Channels Leading to Multiple Anti-Nociception. British Journal of Pharmacology, 161, 707-720. http://dx.doi.org/10.1111/j.1476-5381.2010.00909.x
[16]	Livak, K.J. and Schmittgen, T.D. (2001) Analysis of Relative Gene Expression Data Using Real-Time Quantitative PCR and the 2?ΔΔCT Method. Methods, 25, 402-408. http://dx.doi.org/10.1006/meth.2001.1262
[17]	Ta, L.E., Bieber, A.J., Carlton, S.M., Loprinzi, C.L., Low, P.A., et al. (2010) Transient Receptor Potential Vanilloid 1 Is Essential for Cisplatin-Induced Heat Hyperalgesia in Mice. Molecular Pain, 6, 15. http://dx.doi.org/10.1186/1744-8069-6-15
[18]	Sebai, H., Selmi, S., Rtibi, K., Souli, A., Gharbi, N. and Sakly, M. (2013) Lavender (Lavandula stoechas L.) Essential Oils Attenuate Hyperglycemia and Protect against Oxidative Stress in Alloxan-Induced Diabetic Rats. Lipids in Health and Disease, 12, 189. http://dx.doi.org/10.1186/1476-511X-12-189
[19]	Clarke, C.B., Suter, M.R. and Gosselin, R.-D. (2013) Cellules gliales et douleur chronique: Du laboratoire à l’espoir clinique. Revue Médicale Suisse, 392, 1342-1345.
[20]	Homs, J., Pagès, G., Ariza, L., Casas, C., Chillón, M., Navarro, X. and Bosch, A. (2014) Intrathecal Administration of IGF-I by AAVrh10 Improves Sensory and Motor Deficits in a Mouse Model of Diabetic Neuropathy. Molecular Therapy—Methods & Clinical Development, 1, Article No. 7. http://dx.doi.org/10.1038/mtm.2013.7
[21]	Milligan, E.D. and Watkins, L.R. (2009) Pathological and Protective Roles of Glia in Chronic Pain. Nature Reviews Neuroscience, 10, 23-36. http://dx.doi.org/10.1038/nrn2533
[22]	Tesfaye, S., Boulton, A.J.M., Dyck, P.J., Freeman, R., Horowitz, M., Kempler, P., Lauria, G., Malik, R.A., Spallone, V., Vinik, A., Bernardi, L. and Valensi, P. (2010) Diabetic Neuropathies: Update on Definitions, Diagnostic Criteria, Estimation of Severity, and Treatments. On behalf of the Toronto Diabetic Neuropathy Expert Group. Diabetes Care, 33, 2285-2293.
[23]	Islam, M.S. (2013) Animal Models of Diabetic Neuropathy: Progress since 1960s. Journal of Diabetes Research, 2013, Article ID: 149452.
[24]	Tracy, J.A. and Dyck, P.J.B. (2008) The Spectrum of Diabetic Neuropathies. Physical Medicine and Rehabilitation Clinics of North America, 19, 1-26. http://dx.doi.org/10.1016/j.pmr.2007.10.010
[25]	Callaghan, B.C., Cheng, H., Stables, C.L., Smith, A.L. and Feldman, E.L. (2012) Diabetic Neuropathy: Clinical Manifestations and Current Treatments. The Lancet Neurology, 11, 521-534. http://dx.doi.org/10.1016/S1474-4422(12)70065-0
[26]	Hoke, A. (2012) Animal Models of Peripheral Neuropathies. Neurotherapeutics, 9, 262-269. http://dx.doi.org/10.1007/s13311-012-0116-y
[27]	O’Brien, P.D., Sakowsk, S.A.I., Eva, L. and Feldman, E.L. (2014) Mouse Models of Diabetic Neuropathy. ILAR Journal, 54, 259-272. http://dx.doi.org/10.1093/ilar/ilt052
[28]	Nadig, P.D., Revankar, R.R., Dethe, S.M., Narayanswamy, S.B. and Aliyar, M.A. (2012) Effect of Tinospora cordifolia on Experimental Diabetic Neuropathy. Indian Journal of Pharmacology, 44, 580-583. http://dx.doi.org/10.4103/0253-7613.100380
[29]	Davidson, E., Coppey, L., Lu, B., Arballo, V., Calcutt, N.A., Gerard, C. and Yorek, M. (2010) The Roles of Streptozotocin Neurotoxicity and Neutral Endopeptidase in Murine Experimental Diabetic Neuropathy. Experimental Diabetes Research, 2009, Article ID: 431980.
[30]	Shakher, J. and Stevens, M.J. (2011) Update on the Management of Diabetic Polyneuropathies. Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy, 4, 289-305.
[31]	Zychowska, M., Rojewska, E., Pilat, D. and Mika, J. (2015) The Role of Some Chemokines from the CXC Subfamily in a Mouse Model of Diabetic Neuropathy. Journal of Diabetes Research, 2015, Article ID: 750182. http://dx.doi.org/10.1155/2015/750182
[32]	Rocha-González, E.I., Ramírez-Aguilar, M., Granados-Soto, V., Reyes-García, J.G., Torres-López, J.E., Huerta-Cruz, J.C. and Navarrete, A. (2014) Antineuropathic Effect of 7-Hydroxy-3,4-Dihydrocadalin in Streptozotocin-Induced Diabetic Rodents. BMC Complementary and Alternative Medicine, 14, 129. http://dx.doi.org/10.1186/1472-6882-14-129
[33]	Chen, S.-R., Samoriski, G. and Pan, H.-L. (2009) Antinociceptive Effects of Chronic Administration of Uncompetitive NMDA Receptor Antagonists in a Rat Model of Diabetic Neuropathic Pain. Neuropharmacology, 57, 121-126. http://dx.doi.org/10.1016/j.neuropharm.2009.04.010
[34]	Wattanathorn, J., Thiraphatthanavong, P., Muchimapura, S., Thukhammee, W., Lertra, K. and Suriharn, B. (2015) The Combined Extract of Zingiber officinale and Zea Mays (Purple Color) Improves Neuropathy, Oxidative Stress, and Axon Density in Streptozotocin Induced Diabetic Rats. Evidence-Based Complementary and Alternative Medicine, 2015, Article ID: 301029. http://dx.doi.org/10.1155/2015/301029
[35]	Rondón, L.J., Privat, A.M., Daulhac, L., Davin, N., Mazur, A., Fialip, J., Eschalier, A. and Courteix, C. (2010) Magnesium Attenuates Chronic Hypersensitivity and Spinal Cord NMDA Receptor Phosphorylation in a Rat Model of Diabetic Neuropathic Pain. The Journal of Physiology, 588, 4205-4215. http://dx.doi.org/10.1113/jphysiol.2010.197004
[36]	Schreiber, A.K., Nones, C.F.M., Reis, R.C., Chichorro, J.G. and Cunha, J.M. (2015) Diabetic Neuropathic Pain: Physiopathology and Treatment. World Journal of Diabetes, 6, 432-444. http://dx.doi.org/10.4239/wjd.v6.i3.432
[37]	Kohno, T., Ji, R.R., Ito, N., Allchorne, A.J., Befort, K., Karchewski, L.A. and Woolf, C.J. (2005) Peripheral Axonal Injury Results in Reduced Mu Opioid Receptor Pre- and Post-Synaptic Action in the Spinal Cord. Pain, 117, 77-87. http://dx.doi.org/10.1016/j.pain.2005.05.035
[38]	Kehlet, H., Jensen, T.S. and Woolf, C.J. (2006) Persistent Postsurgical Pain: Risk Factors and Prevention. The Lancet, 367, 1618-1625. http://dx.doi.org/10.1016/S0140-6736(06)68700-X
[39]	Kellogg, A.P., Cheng, H.T. and Pop-Busui, R. (2008) Cyclooxygenase-2 Pathway as a Potential Therapeutic Target in Diabetic Peripheral Neuropathy. Current Drug Targets, 9, 68-76. http://dx.doi.org/10.2174/138945008783431691
[40]	Basbaum, A.I., Bautista, D.M., Scherrer, G. and Julius, D. (2009) Cellular and Molecular Mechanisms of Pain. Cell, 139, 267-284. http://dx.doi.org/10.1016/j.cell.2009.09.028
[41]	Ackermann, P.W. and Hart, D.A. (2013) Influence of Comorbidities: Neuropathy, Vasculopathy, and Diabetes on Healing Response Quality. Advances in Wound Care, 2, 410-421. http://dx.doi.org/10.1089/wound.2012.0437
[42]	Yagihashi, S., Mizukami, H. and Sugimoto, K. (2010) Mechanism of Diabetic Neuropathy: Where Are We Now and Where to Go? Journal of Diabetes Investigation, 2, 18-32. http://dx.doi.org/10.1111/j.2040-1124.2010.00070.x
[43]	Farmer, K.L., Li, C. and Dobrowsky, R.T. (2012) Diabetic Peripheral Neuropathy: Should a Chaperone Accompany Our Therapeutic Approach? Pharmacological Reviews, 64, 880-900. http://dx.doi.org/10.1124/pr.111.005314
[44]	Bouquet, A. (1969) Féticheurs et médecine traditionnelles du Congo (Brazzaville). Mémoires O.R.S.T.O.M., No. 36, 282 p.