Anthocyanin Derived from Purple Sweet Potato Water Extracts Ameliorated Oxidative Stress, Inflammation, Mechanical Allodynia, and Cold Allodynia among Chronic Constriction Injury-Induced Neuropathic Pain in Rats
Keywords:Neuropathic pain, oxidative stress, inflammation, anthocyanins, purple sweet potato
BACKGROUND: Nerve injury leads to multiple events, including oxidative stress, inflammation, and glial cells activation, which all bring about the neuropathic pain condition. Any alternative novel treatment modalities from natural products are thus highly anticipated, given the account that current treatments for neuropathic pain have not generated any satisfactory efficacy.
AIM: This study aims to address the pleiotropic effects of water extracts from the purple sweet potato (PSP) (Ipomoea batatas L.) as an antioxidant, anti-inflammatory, and anti-nociceptive agent to alleviate neuropathic pain behavior.
METHODS: This is a randomized post-test control group design using chronic constriction injury (CCI) rat models. Thirty-two Wistar rats (34 survived until the end of study period) fulfilling the eligible criteria were randomized into either treatment or control group. Treatment group received water extracts of PSP containing 400 mg/kg of body weight/d of anthocyanin for 28 days. Antioxidant activity was evaluated from malondialdehyde (MDA) levels, anti-inflammatory activity was evaluated from prostaglandin E2 (PGE2) levels. Neuropathic pain was assessed from the animal’s behavioral responses toward mechanical and cold allodynia.
RESULTS: The results showed that mean MDA levels of treatment group were significantly lower than control group (0.291 ± 0.046 μmol vs. 0.394 ± 0.057 μmol; p < 0.001). Furthermore, treatment group’s PGE2 levels were also significantly lower than control’s (0.342 ± 0.096 ng/mL vs. 0.431 ± 0.061 ng/mL; p = 0.004). In addition, neuropathic pain behavior comprising mechanical and cold allodynia were significantly milder among treatment group than in the control group during the observation period (p < 0.05).
CONCLUSION: PSP water extracts had been shown to ameliorate oxidative stress, as well as exerted anti-inflammatory and anti-nociceptive effects and was able to suppress neuropathic pain behavior in Wistar rats with peripheral nerve injury.
Plum Analytics Artifact Widget Block
IASP. Pain terms, a current list with definitions and notes on usage. In: Classification of Chronic Pain, Part III. 2nd ed. Seattle: IASP Press; 1994.
Purwata T, Anggraini H, Anwar Y, Amir D, Asnawi C, Rahmawati D, et al. Characteristics of neuropathic pain in Indonesia: A hospital based national clinical survey. Neurol Asia. 2015;20(4):389-94.
Smith BH, Torrance N. Epidemiology of neuropathic pain and its impact on quality of life. Curr Pain Headache Rep. 2012;16(3):191-8. https://doi.org/10.1007/s11916-012-0256-0 PMid:22395856
Ciaramitaro P, Mondelli M, Logullo F, Grimaldi S, Battiston B, Sard A, et al. Traumatic peripheral nerve injuries: Epidemiological findings, neuropathic pain and quality of life in 158 patients. J Peripher Nerv Syst. 2010;15(2):120-7. https://doi. org/10.1111/j.1529-8027.2010.00260.x PMid:20626775
Lustosa AA, Nogueira LT, Pedrosa JI, Teles JB, Campelo V. The impact of leprosy on health-related quality of life. Rev Soc Bras Med Trop. 2011;44(5):621-6. https://doi.org/10.1590/ s0037-86822011000500019 PMid:22031079
Cohen SP, Mao J. Neuropathic pain: Mechanisms and their clinical implications. Br Med J. 2014;348. PMid:24500412
Akkurt HE, Gumus H, Goksu H, Odabasi OF, Yilmaz H. Gabapentin treatment for neuropathic pain in a child with sciatic nerve injury. Case Rep Med. 2015;2015:873157. https://doi. org/10.1155/2015/873157 PMid:26346828
Jo D, Chapman CR, Light AR. Glial mechanisms of neuropathic pain and emerging interventions. Korean J Pain. 2009;22(1):1-15. https://doi.org/10.3344/kjp.2009.22.1.1
Khalil Z, Liu T, Helme RD. Free radicals contribute to the reduction in peripheral vascular responses and the maintenance of thermal hyperalgesia in rats with chronic constriction injury. Pain. 1999;79(1):31-7. https://doi.org/10.1016/s0304-3959(98)00143-2 PMid:9928773
Ma W, Quirion R. Does COX2-dependent PGE2 play a role in neuropathic pain? Neurosci Lett. 2008;437(3):165-9. https://doi. org/10.1016/j.neulet.2008.02.072 PMid:18434017
Oyenihi AB, Ayeleso AO, Mukwevho E, Masola B. Antioxidant strategies in the management of diabetic neuropathy. Biomed Res Int. 2015;2015:15. https://doi.org/10.1155/2015/515042 PMid:25821809
Tsuda M, Tozaki-Saitoh H, Inoue K. P2X4R and P2X7R in neuropathic pain. Wiley Interdiscip Rev Membr Transp Signal. 2012;1(4):513-21. https://doi.org/10.1002/wmts.47
Beggs S, Trang T, Salter MW. P2X4R+ microglia drive neuropathic pain. Nat Neurosci. 2012;15(8):1068-73. https://doi. org/10.1038/nn.3155 PMid:22837036
Jiang LH. P2X receptor-mediated ATP purinergic signaling in health and disease. Cell Health Cytoskeleton. 2012;4:18. https://doi.org/10.2147/chc.s27196
Erdman JW Jr., Balentine D, Arab L, Beecher G, Dwyer JT, Folts J, et al. Flavonoids and heart health: Proceedings of the ILSI North America flavonoids workshop, May 31-June 1, 2005, Washington, DC. J Nutr. 2007;137(1):718S-37. https://doi. org/10.1093/jn/137.3.718s PMid:17311968
Tall JM, Seeram NP, Zhao C, Nair MG, Meyer RA, Raja SN. Tart cherry anthocyanins suppress inflammation-induced pain behavior in rat. Behav Brain Res. 2004;153(1):181-8. https://doi. org/10.1016/j.bbr.2003.11.011 PMid:15219719
Wang H, Nair MG, Strasburg GM, Booren AM, Gray JI. Novel antioxidant compounds from tart cherries (Prunus cerasus). J Nat Prod. 1999;62(1):86-8. https://doi.org/10.1021/np980268s PMid:9917288
Lee J, Rennaker C, Wrolstad R. Correlation of two anthocyanin quantification methods: HPLC and spectrophotometric methods. Food Chem. 2008;110:782-6. https://doi.org/10.1016/j. foodchem.2008.03.010
Amin B, Abnous K, Motamedshariaty V, Hosseinzadeh H. Attenuation of oxidative stress, inflammation and apoptosis by ethanolic and aqueous extracts of Crocus sativus L. Stigma after chronic constriction injury of rats. An Acad Bras Cienc. 2014;6(4):1821-32. https://doi. org/10.1590/0001-3765201420140067 PMid:25590719
Bhardwaj H, Muthuraman A, Hari K, Navis S. Antioxidative and anti-inflammatory potentials of ambroxol in ameliorating vincristine induced peripheral neuropathic pain in rats. J Neuroinfect Dis. 2016;7(1):7. https://doi. org/10.4172/2314-7326.1000202
Bennett GJ, Xie YK. A peripheral mononeuropathy in rat that produces disorders of pain sensation like those seen in man. Pain. 1988;33(1):87-107. https://doi. org/10.1016/0304-3959(88)90209-6 PMid:2837713
Chanchal SK, Mahajan UB, Siddharth S, Reddy N, Goyal SN, Patil PH, et al. In vivo and in vitro protective effects of omeprazole against neuropathic pain. Sci Rep. 2016;6:30007. https://doi. org/10.1038/srep30007
Kaulaskar S, Bhutada P, Rahigude A, Jain D, Harle U. Effects of naringenin on allodynia and hyperalgesia in rats with chronic constriction injury-induced neuropathic pain. Zhong Xi Yi Jie He Xue Bao. 2012;10(12):1482-9. https://doi.org/10.3736/ jcim20121223 PMid:23257145
Jawi M, Suprapta DN, Subawa AA. Ubi jalar ungu menurunkan kadar MDA dalam darah dan hati mencit setelah aktivitas fisik maksimal. J Vet. 2008;9(2):65-72.
Bakar OA. Pemberian Ekstrak Kulit Terung Ungu Menghambat Peningkatan MDA Dalam Darah Tikus Wistar Yang Diinduksi Aktivitas Fisik Maksimal, Thesis. Denpasar: Universitas Udayana; 2010.
Kelsey NA, Wilkins HM, Linseman DA. Nutraceutical antioxidants as novel neuroprotective agents. Molecules. 2010;15(11):7792- 814. https://doi.org/10.3390/molecules15117792 PMid:21060289
Vendrame S, Klimis-Zacas D. Anti-inflammatory effect of anthocyanins via modulation of nuclear factor-κB and mitogen-activated protein kinase signaling cascades. Nutr Rev. 2015;73(6):348-58. https://doi.org/10.1093/nutrit/nuu066 PMid:26011910
Serafini M, Peluso I, Raguzzini A. International immunonutrition workshop session 1: Antioxidants and the immune system flavonoids as anti-inflammatory agents. Proc Nutr Soc. 2010;69:6.
Kawabata A. Prostaglandin E2 and pain--an update. Biol Pharm Bull. 2011;34(8):1170-3. https://doi.org/10.1248/bpb.34.1170 PMid:21804201
Bhave G, Zhu W, Wang H, Brasier DJ, Oxford GS, Gereau RW. cAMP-dependent protein kinase regulates desensitization of the capsaicin receptor (VR1) by direct phosphorylation. Neuron. 2002;35(4):721-31. https://doi.org/10.1016/ s0896-6273(02)00802-4 PMid:12194871
Jensen TS, Finnerup NB. Allodynia and hyperalgesia in neuropathic pain: Clinical manifestations and mechanisms. Lancet Neurol. 2014;13(9):924-35. https://doi.org/10.1016/ s1474-4422(14)70102-4 PMid:25142459
Tanimoto-Mori S, Nakazato-Imasato E, Toide K, Kita Y. Pharmacologic investigation of the mechanism underlying cold allodynia using a new cold plate procedure in rats with chronic constriction injuries. Behav Pharmacol. 2008;19(1):85-90. https://doi.org/10.1097/fbp.0b013e3282f3d0a3 PMid:18195599
Lippoldt EK, Ongun S, Kusaka GK, McKemy DD. Inflammatory and neuropathic cold allodynia are selectively mediated by the neurotrophic factor receptor GFRalpha3. Proc Natl Acad Sci U S A. 2016;113(16):4506-11. https://doi.org/10.1073/ pnas.1603294113
How to Cite
Copyright (c) 2020 I Putu Eka Widyadharma, Thomas Eko Purwata, Dewa Ngurah Suprapta, A. A. Raka Sudewi (Author)
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.