Effect of Hydroethanolic Extract of Citrus Aurantium Leaves and Magnesium Sulfate in Mice Model of Vincristine-Induced Neuropathy Citrus aurantium and Magnesium in Vincristine-Induced neuropathy
Iranian Journal of Pharmaceutical Sciences,
Vol. 18 No. 1 (2022),
15 January 2022
,
Page 9-17
https://doi.org/10.22037/ijps.v18.41358
Abstract
Neuropathic pain due to vincristine administration is an important dose limiting adverse effect with no definite efficient treatment. Citrus aurantium possesses multiple therapeutic potentials and is commonly used in traditional medicine. This study investigate the possible effects of the hydroethanolic extract of C. aurantium (CA) leaves and magnesium sulfate (MgSO4) as a known analgesic in vincristine-induced peripheral neuropathy (VIN). Vincristine was administered intraperitoneally (IP) to establish peripheral neuropathy in mice. Effects of CA (50,100 and 150 mg/kg, IP) and MgSO4 (50, 75 and 100 mg mg/kg, IP) were assessed on pain threshold performed by hot plate test. Moreover, the serum levels of total antioxidant capacity (TAC) and malondialdehyde (MDA) were assayed. Administration of CA (100 and 150 mg/kg) showed significant (p<0.001) decrease in responses to pain. In addition, MgSO4 in high dose of 100 mg/kg could alleviate the neuropathic symptoms. The result of biochemical tests exerted high TAC level in all CA treated groups (p<0.01 in 50 mg/kg and p<0.001 for 100 and 150 mg/kg). MDA level was decreased significantly (p<0.001) by CA (100 and 150 mg/kg) and MgSO4 (100 mg/kg). However the combination of low dose of CA and MgSO4 exerted no efficient antinociceptive effect. According to the results, it can be concluded that MgSO4 and CA, in an effective dose range, can be effective in controlling the neuropathic pain followed by vincristine, possibly through the modulation of antioxidant balance directed by CA or the NMDA and calcium receptor blocking properties of MgSO4.
Keywords:
- Citrus aurantium,
- Hot plate,
- Magnesium sulfate,
- Mice,
- Neuropathy,
- Vincristine.
How to Cite
Bohlool Habibi, Tahereh Eteraf Oskouei, Haleh Vaez, Abbas delazar, & Pouria Amani. (2022). Effect of Hydroethanolic Extract of Citrus Aurantium Leaves and Magnesium Sulfate in Mice Model of Vincristine-Induced Neuropathy: Citrus aurantium and Magnesium in Vincristine-Induced neuropathy. Iranian Journal of Pharmaceutical Sciences, 18(1), 9–17. https://doi.org/10.22037/ijps.v18.41358
References
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[24] Weng HR, Cordella JV, Dougherty PM. Changes in sensory processing in the spinal dorsal horn accompany vincristine-induced hyperalgesia and allodynia. Pain (2003) 103 (1): 131-138.
[25] Muthuraman A, Singh N. Attenuating effect of hydroalcoholic extract of Acorus calamus in vincristine-induced painful neuropathy in rats. J. Natural Med. (2011) 65 (3-4): 480-487.
[26] ] Jibira Y, Boakye-Gyasi E, Kofi Mensah Abotsi W, Amponsah IK, Adongo DW, Woode E. Hydroethanolic Stem Bark Extract of Burkea africana Attenuates Vincristine-Induced Peripheral Neuropathy in Rats. Adv. Pharmacol. Pharmaceutic. Sci. (2020) 2020: 7232579.
[27] Areti A, Yerra VG, Naidu V, Kumar A. Oxidative stress and nerve damage: role in chemotherapy induced peripheral neuropathy. Redox Biol. (2014) 2: 289-295.
[28] Ellouze I, Mathieu F, Lebrihi A, Abderrabba M. Chemical composition and biological activities of various alimentary preparations of Citrus aurantium leaves. J. Chem. Pharmaceutic. Res. (2015) 7 (6): 966-971.
[29] Suntar I, Khan H, Patel S, Celano R, Rastrelli L. An Overview on Citrus aurantium L.: Its Functions as Food Ingredient and Therapeutic Agent. Oxid. Med. Cell Longev. (2018) 2018: 7864269.
[30] Azhdarzadeh F, Hojjati M. Chemical Composition and Antimicrobial Activity of Leaf, Ripe and Unripe Peel of Bitter Orange (Citrus aurantium) Essential Oils. Nutr. Food Sci. Res. (2016) 3 (1): 43-50.
[31] Kim JA, Park HS, Kang SR, Park KI, Lee DH, Nagappan A, et al. Suppressive effect of flavonoids from Korean Citrus aurantium L. on the expression of inflammatory mediators in L6 skeletal muscle cells. Phytother. Res. (2012) 26 (12): 1904-1912.
[32] Choi BK, Kim TW, Lee DR, Jung WH, Lim JH, Jung JY, et al. A polymethoxy flavonoids-rich Citrus aurantium extract ameliorates ethanol-induced liver injury through modulation of AMPK and Nrf2-related signals in a binge drinking mouse model. Phytother. Res (2015) 29 (10): 1577-1584.
[33] Ulugol A, Aslantas A, Ipci Y, Tuncer A, Hakan Karadag C, Dokmeci I. Combined systemic administration of morphine and magnesium sulfate attenuates pain-related behavior in mononeuropathic rats. Brain Res. (2002) 943 (1): 101-104.
[34] Bordi F, Quartaroli M. Modulation of nociceptive transmission by NMDA/glycine site receptor in the ventroposterolateral nucleus of the thalamus. Pain (2000) 84 (2-3): 213-224.
[35] Bujalska M, Malinowska E, Makulska-Nowak H, Gumułka SW. Magnesium ions and opioid agonist activity in streptozotocin-induced hyperalgesia. Pharmacol. (2008) 82 (3): 180-186.
[36] Li M, Zhao X, Zhang L, Niu X, Guo T, Yang B, et al. Effects and safety of magnesium sulfate on propofol-induced injection pain, a meta-analysis of randomized controlled trials. Int. J. Clin. Exp. Med. (2015) 8 (5): 6813-6821.
[37] Begon S, Pickering G, Eschalier A, Dubray C. Magnesium increases morphine analgesic effect in different experimental models of pain. Anesthesiology (2002) 96 (3): 627-632.
[2] Mendell JR, Sahenk Z. Clinical practice. Painful sensory neuropathy. N. Engl. J. Med (2003) 348 (13): 1243-1255.
[3] Wolf S, Barton D, Kottschade L, Grothey A, Loprinzi C. Chemotherapy-induced peripheral neuropathy: prevention and treatment strategies. Eur. J. cancer (2008) 44 (11): 1507-1515.
[4] Madsen ML, Due H, Ejskjær N, Jensen P, Madsen J, Dybkær K. Aspects of vincristine-induced neuropathy in hematologic malignancies: a systematic review. Cancer Chemother. Pharmacol. (2019) 84 (3): 471-485.
[5] Hu L-Y, Mi W-L, Wu G-C, Wang Y-Q, Mao-Ying Q-L. Prevention and Treatment for Chemotherapy-Induced Peripheral Neuropathy: Therapies Based on CIPN Mechanisms. Curr. Neuropharmacol. (2019) 17 (2): 184-196.
[6] Lee G, Kim SK. Therapeutic Effects of Phytochemicals and Medicinal Herbs on Chemotherapy-Induced Peripheral Neuropathy. Molecules (2016) 21 (9): 1252.
[7] Noh H, Yoon SW, Park B. A Systematic Review of Herbal Medicine for Chemotherapy Induced Peripheral Neuropathy. Evid. Based Complement. Alternat. Med. (2018) 2018: 6194184.
[8] Weisskopf A, Fuller DQ. Citrus Fruits: Origins and Development. Smith C (Ed.) In: Encyclopedia of Global Archaeology. Springer New York, New York (2014) 1479-1483.
[9] Mannucci C, Calapai F, Cardia L, Inferrera G, D’Arena G, Di Pietro M, et al. Clinical Pharmacology of Citrus aurantium and Citrus sinensis for the Treatment of Anxiety. Evid. Based Complement. Alternat. Med. (2018) 2018: 3624094.
[10] Forouzanfar F, Hosseinzadeh H. Medicinal herbs in the treatment of neuropathic pain: a review. Iran J. Basic Med. Sci. (2018) 21 (4): 347-358.
[11] Kandhare AD, Raygude KS, Ghosh P, Ghule AE, Bodhankar SL. Neuroprotective effect of naringin by modulation of endogenous biomarkers in streptozotocin induced painful diabetic neuropathy. Fitoterapia (2012) 83 (4): 650-659.
[12] Khettal B, Kadri N, Tighilet K, Adjebli A, Dahmoune F, Maiza-Benabdeslam F. Phenolic compounds from Citrus leaves: antioxidant activity and enzymatic browning inhibition. J. Complement. Integr. (2017) 14 (1).
[13] Lagha-Benamrouche S, Madani K. Phenolic contents and antioxidant activity of orange varieties (Citrus sinensis L. and Citrus aurantium L.) cultivated in Algeria: Peels and leaves. Indust. Crop. Prod. (2013) 50: 723-730.
[14] Karthikeyan V, Karthikeyan J. Citrus aurantium (Bitter Orange): A Review of its Traditional Uses, Phytochemistry and Pharmacology. Int. j. discov. herb. res. (2014) 4 (4): 766-772.
[15] Parsons CG. NMDA receptors as targets for drug action in neuropathic pain. Eur. J. Pharmacol. (2001) 429 (1): 71-78.
[16] Geisler S, Doan RA, Strickland A, Huang X, Milbrandt J, DiAntonio A. Prevention of vincristine-induced peripheral neuropathy by genetic deletion of SARM1 in mice. Brain (2016) 139 (Pt 12): 3092-3108.
[17] González V, Pelissier T, Cazanga V, Hernández A, Constandil L. Magnesium Salt, a Simple Strategy to Improve Methadone Analgesia in Chronic Pain: An Isobolographic Preclinical Study in Neuropathic Mice. Front. Pharmacol. (2020) 11 (566).
[18] Xie H, Chen Y, Du K, Wu W, Feng X. Puerarin alleviates vincristine-induced neuropathic pain and neuroinflammation via inhibition of nuclear factor-κB and activation of the TGF-β/Smad pathway in rats. Int. Immunopharmacol. (2020) 89: 107060.
[19] Eddy NB, Leimbach D. Synthetic analgesics. II. Dithienylbutenyl- and dithienylbutylamines. J. Pharmacol. Exp. Ther. (1953) 107 (3): 385.
[20] Satoh K. Serum lipid peroxide in cerebrovascular disorders determined by a new colorimetric method. Int. J. Clinic. chem. (1978) 90 (1): 37-43.
[21] Chrzczanowicz J, Gawron A, Zwolinska A, de Graft-Johnson J, Krajewski W, Krol M, et al. Simple method for determining human serum 2,2-diphenyl-1-picryl-hydrazyl (DPPH) radical scavenging activity - possible application in clinical studies on dietary antioxidants. Clinic. Chem. Lab. Med. (2008) 46 (3): 342-349.
[22] Muthuraman A, Jaggi AS, Singh N, Singh D. Ameliorative effects of amiloride and pralidoxime in chronic constriction injury and vincristine induced painful neuropathy in rats. Eur. J. Pharmacol. (2008) 587 (1-3): 104-111.
[23] Dworkin RH, O'Connor AB, Audette J, Baron R, Gourlay GK, Haanpää ML, et al. Recommendations for the pharmacological management of neuropathic pain: an overview and literature update. Mayo Clin. Proc. (2010) 85 (3 Suppl): S3-S14.
[24] Weng HR, Cordella JV, Dougherty PM. Changes in sensory processing in the spinal dorsal horn accompany vincristine-induced hyperalgesia and allodynia. Pain (2003) 103 (1): 131-138.
[25] Muthuraman A, Singh N. Attenuating effect of hydroalcoholic extract of Acorus calamus in vincristine-induced painful neuropathy in rats. J. Natural Med. (2011) 65 (3-4): 480-487.
[26] ] Jibira Y, Boakye-Gyasi E, Kofi Mensah Abotsi W, Amponsah IK, Adongo DW, Woode E. Hydroethanolic Stem Bark Extract of Burkea africana Attenuates Vincristine-Induced Peripheral Neuropathy in Rats. Adv. Pharmacol. Pharmaceutic. Sci. (2020) 2020: 7232579.
[27] Areti A, Yerra VG, Naidu V, Kumar A. Oxidative stress and nerve damage: role in chemotherapy induced peripheral neuropathy. Redox Biol. (2014) 2: 289-295.
[28] Ellouze I, Mathieu F, Lebrihi A, Abderrabba M. Chemical composition and biological activities of various alimentary preparations of Citrus aurantium leaves. J. Chem. Pharmaceutic. Res. (2015) 7 (6): 966-971.
[29] Suntar I, Khan H, Patel S, Celano R, Rastrelli L. An Overview on Citrus aurantium L.: Its Functions as Food Ingredient and Therapeutic Agent. Oxid. Med. Cell Longev. (2018) 2018: 7864269.
[30] Azhdarzadeh F, Hojjati M. Chemical Composition and Antimicrobial Activity of Leaf, Ripe and Unripe Peel of Bitter Orange (Citrus aurantium) Essential Oils. Nutr. Food Sci. Res. (2016) 3 (1): 43-50.
[31] Kim JA, Park HS, Kang SR, Park KI, Lee DH, Nagappan A, et al. Suppressive effect of flavonoids from Korean Citrus aurantium L. on the expression of inflammatory mediators in L6 skeletal muscle cells. Phytother. Res. (2012) 26 (12): 1904-1912.
[32] Choi BK, Kim TW, Lee DR, Jung WH, Lim JH, Jung JY, et al. A polymethoxy flavonoids-rich Citrus aurantium extract ameliorates ethanol-induced liver injury through modulation of AMPK and Nrf2-related signals in a binge drinking mouse model. Phytother. Res (2015) 29 (10): 1577-1584.
[33] Ulugol A, Aslantas A, Ipci Y, Tuncer A, Hakan Karadag C, Dokmeci I. Combined systemic administration of morphine and magnesium sulfate attenuates pain-related behavior in mononeuropathic rats. Brain Res. (2002) 943 (1): 101-104.
[34] Bordi F, Quartaroli M. Modulation of nociceptive transmission by NMDA/glycine site receptor in the ventroposterolateral nucleus of the thalamus. Pain (2000) 84 (2-3): 213-224.
[35] Bujalska M, Malinowska E, Makulska-Nowak H, Gumułka SW. Magnesium ions and opioid agonist activity in streptozotocin-induced hyperalgesia. Pharmacol. (2008) 82 (3): 180-186.
[36] Li M, Zhao X, Zhang L, Niu X, Guo T, Yang B, et al. Effects and safety of magnesium sulfate on propofol-induced injection pain, a meta-analysis of randomized controlled trials. Int. J. Clin. Exp. Med. (2015) 8 (5): 6813-6821.
[37] Begon S, Pickering G, Eschalier A, Dubray C. Magnesium increases morphine analgesic effect in different experimental models of pain. Anesthesiology (2002) 96 (3): 627-632.
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