DOI: http://dx.doi.org/10.18203/2319-2003.ijbcp20211011

Effect of xylopic acid on alloxan-induced diabetic neuropathy in rats

Elvis Ofori Ameyaw, Ernest Obese, Du-Bois Asante, Robert P. Biney, Akua A. Karikari, Emmanuel A. Adakudugu, Bright G. Dzotefe, Maddison Adanusa

Abstract


Background: Neuropathic pain is a very disturbing condition commonly found in diabetic patients. This study investigated xylopic acid (XA), the major constituent of Xylopia aethiopica in diabetic neuropathy as well as established possible toxicity of the compound on some selected tissues.

Methods: Diabetes was induced in six groups of male rats with 120 mg/kg alloxan monohydrate. Diabetes was confirmed as a blood glucose level >15 mmol/dl. Neuropathic pain was confirmed on day three post-diabetes induction and treatment with 10 mg/kg, 30 mg/kg or 100 mg/kg xylopic acid, 10 mg/kg glibenclamide, 10 mg/kg morphine, and 10 ml/kg normal saline were initiated and continued for the next 15 days. The effects of the treatments on cold allodynia (cold water at 4°C) and thermal hyperalgesia (hot water at 55 ± 1°C) were evaluated within the duration of treatments. Histology of the liver and kidney, as well as haematological, serum biochemical, and semen analyses, were done after the fifteenth day of the experiment.

Results: Xylopic acid produced significant anti-hyperglycaemic and analgesic effects in the cold allodynia and thermal hyperalgesia tests. Sperm motility, viability and count were significantly restored at 10 mg/kg XA as compared higher doses and negative control. The outcome of haematological analysis revealed a protective effect of XA although histological damage liver and kidney due to alloxan treatment was observable.

Conclusions: Xylopic acid ameliorates diabetic neuropathy in rats and does not exert detrimental effects at low doses.


Keywords


Xylopic acid, Neuropathic pain, Hyperglycaemia, Diabetes

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References


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Martínez‐Navarro M, Maldonado R, Baños JE. Why mu‐opioid agonists have less analgesic efficacy in neuropathic pain? European Journal of Pain. 2019;23(3):435-454.

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Ameyaw EO, Woode E, Boakye-Gyasi E, Abotsi WK, Kyekyeku OJ, Adosraku RK. Anti-allodynic and Anti-hyperalgesic effects of an ethanolic extract and xylopic acid from the fruits of Xylopia aethiopica in murine models of neuropathic pain. Pharmacognosy Research. 2014;6(2):172-9.

Agarwal A, Virk G, Ong C, du Plessis SS. Effect of oxidative stress on male reproduction. The world journal of men's health. 2014;32(1):1-17.

Ragavan B, Krishnakumari S. Effect of T. Arjuna Stem Bark Extract on Histopathology of Liver, Kidney, and Pancreas of Alloxan-Induced Diabetic Rats. African Journal of Biomedical Research. 2006;9:189-197.

Arba S, Adelaiye A, Mshelia L. Histopathological and Biochemical Changes in the Rats Kidney Following Exposure to a Pyrethroid Based Mosquito Coil. Journal of Applied Sciences Research. 2007;3(12):1788-93.

Pickering RJ, Rosado CJ, Sharma A, Buksh S, Tate M, de Haan JB. Recent novel approaches to limit oxidative stress and inflammation in diabetic complications. Clin Translat Immunol. 2018;7(4):e1016.

Li HY, Wu YL, Te Tu S, Hwu CM, Liu JS, Chuang LM. Trends of mortality in diabetic patients in Taiwan: A nationwide survey in 2005–2014. J Formosan Med Association. 2019;118:S83-S89.

Nandini HS, Naik PR. Antidiabetic, antihyperlipidemic, and antioxidant effect of Vincamine, in streptozotocin-induced diabetic rats. European Journal of Pharmacology. 2019;843:233-9.

Shi GJ, Shi GR, Zhou JY, Zhang WJ, Gao CJ, Jiang YP et al. Involvement of growth factors in diabetes mellitus and its complications: a general review. Biomedicine & Pharmacotherapy. 2018;101:510-27.

Kobayashi M, Zochodne DW. Diabetic neuropathy and the sensory neuron: new aspects of pathogenesis and their treatment implications. Journal of Diabetes Investigation. 2018;9(6):1239-54.

Finnerup NB, Haroutounian S, Kamerman P, Baron R, Bennett DL, Bouhassira D et al. Neuropathic pain: an updated grading system for research and clinical practice. Pain. 2016;157(8):1599.

Smith BH, Raja SN. NeuPSIG: investing in solutions to the growing global challenge of neuropathic pain. 2017

Binder A, Baron R. The pharmacological therapy of chronic neuropathic pain. Deutsches Ärzteblatt International. 2016;113(37):616.

Yan YY, Li CY, Zhou L, Ao LY, Fang WR, Li YM. Research progress of mechanisms and drug therapy for neuropathic pain. Life Sciences. 2017;190:68-77.

Martínez‐Navarro M, Maldonado R, Baños JE. Why mu‐opioid agonists have less analgesic efficacy in neuropathic pain? European Journal of Pain. 2019;23(3):435-454.

Mangaiarkkarasi A, Rameshkannan S, Ali RM. Effect of gabapentin and pregabalin in the rat model of taxol induced neuropathic pain. Journal of clinical and diagnostic research: JCDR. 2015;9(5):FF11.

Famuyiwa FG, Ayoola MD, Famuyiwa SO, Aladesanmi AJ. Hyperglycaemia Lowering Effect of Kaurane Diterpenoids from the Fruits of Xylopia aethiopica (A. Dunal) Rich. International Journal of Medicinal Plants and Natural Products. 2018;4(3):11-9.

Abarikwu SO, Ogunlaja A, Otuechere CA, Gideon O. Effect of ethanolic extract from seeds or pods of Xylopia aethiopica (Dunal) A. Rich (Annonaceae) on the testicular function of adult male rats. Indian Journal of Clinical Biochemistry. 2017;32(4):420-8.

Fetse JP, Kofie W, Adosraku RK. Ethnopharmacological importance of Xylopia aethiopica (Dunal) A. Rich (Annonaceae)-A review. Journal of Pharmaceutical Research International. 2016;1-21.

Woode E, Ameyaw EO, Ainooson GK, Abotsi W, Gyasi E, Kyekyeku J. Analgesic effects of an ethanol extract of the fruits of Xylopia aethiopica and xylopic acid in murine models of pain: possible mechanism (s). Pharmacologia. 2013;4(4):285-300.

Ameyaw EO, Koffuor GA, Asare KK, Konja D, Du-bois A, Kyei S et al. Cryptolepine, an indoloquinoline alkaloid, in the management of diabetes mellitus and its associated complications. Journal of intercultural ethnopharmacology. 2016;5(3):263.

Zemjanis R. Collection and evaluation of semen. Diagnostic and therapeutic technique in animal reproduction. 1970;2:467-523.

Rohilla A, Ali S. Alloxan-Induced Diabetes: Mechanisms and Effects. International Journal of Research in Pharmaceutical and Biomedical Sciences. 2012;(2229):819-23.

Bhatti R, Rawal S, Singh J, Ishar M. Effect of Aegle marmelos leaf extract treatment on diabetic neuropathy in rats: a possible involvement of α2 adrenoceptors. International Journal of Pharmacy and Pharmaceutical Sciences. 2012;4(3):1-5.

Elsner M, Rohilla A, Ali S. Importance of the GLUT2 glucose transporter for pancreatic beta cell toxicity of alloxan. Diabetologia. 2002;1542-9.

Cavaletti G, Cavalletti E, Oggioni N, Sottani C, Minoia C, D'Incalci M et al. Distribution of paclitaxel within the nervous system of the rat after repeated intravenous administration. 2000;21(3):389-93.

Zieglgänsberge W, Berthele A, Tölle T. Understanding neuropathic pain. CNS Spectr. 2005;10(4):298-308.

Campbell J, Meyer R. Mechanisms of Neuropathic Pain. Neuron. 2006;52(1):77-92.

Ameyaw EO, Woode E, Boakye-Gyasi E, Abotsi WK, Kyekyeku OJ, Adosraku RK. Anti-allodynic and Anti-hyperalgesic effects of an ethanolic extract and xylopic acid from the fruits of Xylopia aethiopica in murine models of neuropathic pain. Pharmacognosy Research. 2014;6(2):172-9.

Agarwal A, Virk G, Ong C, du Plessis SS. Effect of oxidative stress on male reproduction. The world journal of men's health. 2014;32(1):1-17.

Ragavan B, Krishnakumari S. Effect of T. Arjuna Stem Bark Extract on Histopathology of Liver, Kidney, and Pancreas of Alloxan-Induced Diabetic Rats. African Journal of Biomedical Research. 2006;9:189-197.

Arba S, Adelaiye A, Mshelia L. Histopathological and Biochemical Changes in the Rats Kidney Following Exposure to a Pyrethroid Based Mosquito Coil. Journal of Applied Sciences Research. 2007;3(12):1788-93.