Ultra-diluted Toxicodendron Pubescens Attenuates Pro-inflammatory Cytokines and ROS- Mediated Neuropathic Pain in Rats

Overview

Journal Sci Rep

Specialty Science

Date 2018 Sep 12

PMID 30202036

Citations 3

Authors

Shital Magar

Deepika Nayak

Umesh B Mahajan

Kalpesh R Patil

Sachin D Shinde

Sameer N Goyal

Shivang Swaminarayan

Chandragouda R Patil

Shreesh Ojha

Chanakya Nath Kundu

Affiliations

Soon will be listed here.

Abstract

Despite the availability of multiple therapeutic agents, the search for novel pain management of neuropathic pain is still a challenge. Oxidative stress and inflammatory signaling are prominently involved in clinical manifestation of neuropathic pain. Toxicodendron pubescens, popularly known as Rhus Tox (RT) is recommended in alternative medicines as an anti-inflammatory and analgesic remedy. Earlier, we reported anti-inflammatory, anti-arthritic and immunomodulatory activities of Rhus Tox. In continuation, we evaluated antinociceptive efficacy of Rhus Tox in the neuropathic pain and delineated its underlying mechanism. Initially, in-vitro assay using LPS-mediated ROS-induced U-87 glioblastoma cells was performed to study the effect of Rhus Tox on reactive oxygen species (ROS), anti-oxidant status and cytokine profile. Rhus Tox decreased oxidative stress and cytokine release with restoration of anti-oxidant systems. Chronic treatment with Rhus Tox ultra dilutions for 14 days ameliorated neuropathic pain revealed as inhibition of cold, warm and mechanical allodynia along with improved motor nerve conduction velocity (MNCV) in constricted nerve. Rhus Tox decreased the oxidative and nitrosative stress by reducing malondialdehyde (MDA) and nitric oxide (NO) content, respectively along with up regulated glutathione (GSH), superoxide dismutase (SOD) and catalase activity in sciatic nerve of rats. Notably, Rhus Tox treatment caused significant reductions in the levels of tumor necrosis factor (TNF-α), interleukin-6 (IL-6) and interleukin-1β (IL-1β) as compared with CCI-control group. Protective effect of Rhus Tox against CCI-induced sciatic nerve injury in histopathology study was exhibited through maintenance of normal nerve architecture and inhibition of inflammatory changes. Overall, neuroprotective effect of Rhus Tox in CCI-induced neuropathic pain suggests the involvement of anti-oxidative and anti-inflammatory mechanisms.

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References

Freire M, Guimaraes J, Gomes Leal W, Pereira A . Pain modulation by nitric oxide in the spinal cord. Front Neurosci. 2009; 3(2):175-81. PMC: 2751623. DOI: 10.3389/neuro.01.024.2009. View

Piccinelli A, Neder Morato P, Barbosa M, Croda J, Sampson J, Kong X . Limonene reduces hyperalgesia induced by gp120 and cytokines by modulation of IL-1 β and protein expression in spinal cord of mice. Life Sci. 2016; 174:28-34. DOI: 10.1016/j.lfs.2016.11.017. View

Kandhare A, Raygude K, Ghosh P, Ghule A, Bodhankar S . Neuroprotective effect of naringin by modulation of endogenous biomarkers in streptozotocin induced painful diabetic neuropathy. Fitoterapia. 2012; 83(4):650-9. DOI: 10.1016/j.fitote.2012.01.010. View

Singh A, Kumar S, Vinayak M . Recent development in antihyperalgesic effect of phytochemicals: anti-inflammatory and neuro-modulatory actions. Inflamm Res. 2018; 67(8):633-654. DOI: 10.1007/s00011-018-1156-5. View

Goecks C, Horst A, Moraes M, Scheid T, Kolberg C, Bello-Klein A . Assessment of oxidative parameters in rat spinal cord after chronic constriction of the sciatic nerve. Neurochem Res. 2012; 37(9):1952-8. DOI: 10.1007/s11064-012-0815-0. View

Babbar S, Marier J, Mouksassi M, Beliveau M, Vanhove G, Chanda S . Pharmacokinetic analysis of capsaicin after topical administration of a high-concentration capsaicin patch to patients with peripheral neuropathic pain. Ther Drug Monit. 2009; 31(4):502-10. DOI: 10.1097/FTD.0b013e3181a8b200. View

Patel D, Ansari I, Kachchhi Y, Patel R, Patil K, Jadhav R . Toxicodendron pubescens retains its anti-arthritic efficacy at 1M, 10M and CM homeopathic dilutions. Homeopathy. 2012; 101(3):165-70. DOI: 10.1016/j.homp.2012.02.007. View

Naziroglu M, Dikici D, Dursun S . Role of oxidative stress and Ca²⁺ signaling on molecular pathways of neuropathic pain in diabetes: focus on TRP channels. Neurochem Res. 2012; 37(10):2065-75. DOI: 10.1007/s11064-012-0850-x. View

Kim H, Park S, Zhou J, Taglialatela G, Chung K, Coggeshall R . Reactive oxygen species (ROS) play an important role in a rat model of neuropathic pain. Pain. 2004; 111(1-2):116-24. DOI: 10.1016/j.pain.2004.06.008. View

10.

Jia S, Zhang Y, Yu J . Antinociceptive Effects of Isosakuranetin in a Rat Model of Peripheral Neuropathy. Pharmacology. 2017; 100(3-4):201-207. DOI: 10.1159/000478986. View

11.

Cohen S, Mao J . Neuropathic pain: mechanisms and their clinical implications. BMJ. 2014; 348:f7656. DOI: 10.1136/bmj.f7656. View

12.

Moron M, Depierre J, Mannervik B . Levels of glutathione, glutathione reductase and glutathione S-transferase activities in rat lung and liver. Biochim Biophys Acta. 1979; 582(1):67-78. DOI: 10.1016/0304-4165(79)90289-7. View

13.

Tsuda M, Koizumi S, Kita A, Shigemoto Y, Ueno S, Inoue K . Mechanical allodynia caused by intraplantar injection of P2X receptor agonist in rats: involvement of heteromeric P2X2/3 receptor signaling in capsaicin-insensitive primary afferent neurons. J Neurosci. 2000; 20(15):RC90. PMC: 6772519. View

14.

Shubayev V, Myers R . Upregulation and interaction of TNFalpha and gelatinases A and B in painful peripheral nerve injury. Brain Res. 2000; 855(1):83-9. DOI: 10.1016/s0006-8993(99)02321-5. View

15.

Sudoh Y, Desai S, Haderer A, Sudoh S, Gerner P, Anthony D . Neurologic and histopathologic evaluation after high-volume intrathecal amitriptyline. Reg Anesth Pain Med. 2004; 29(5):434-40. DOI: 10.1016/j.rapm.2004.06.008. View

16.

Jadhav H, Chaudhari G, Patil D, Jadhav R, Reddy N, Shirkhedkar A . Standardization of homeopathic mother tincture of Toxicodendron pubescens and correlation of its flavonoid markers with the biological activity. Homeopathy. 2016; 105(1):48-54. DOI: 10.1016/j.homp.2015.08.003. View

17.

Naik A, Tandan S, Dudhgaonkar S, Jadhav S, Kataria M, Prakash V . Role of oxidative stress in pathophysiology of peripheral neuropathy and modulation by N-acetyl-L-cysteine in rats. Eur J Pain. 2005; 10(7):573-9. DOI: 10.1016/j.ejpain.2005.08.006. View

18.

Attal N . Pharmacologic treatment of neuropathic pain. Acta Neurol Belg. 2001; 101(1):53-64. View

19.

Fisher P, Scott D . A randomized controlled trial of homeopathy in rheumatoid arthritis. Rheumatology (Oxford). 2001; 40(9):1052-5. DOI: 10.1093/rheumatology/40.9.1052. View

20.

Patil K, Mohapatra P, Patel H, Goyal S, Ojha S, Kundu C . Pentacyclic Triterpenoids Inhibit IKKβ Mediated Activation of NF-κB Pathway: In Silico and In Vitro Evidences. PLoS One. 2015; 10(5):e0125709. PMC: 4418667. DOI: 10.1371/journal.pone.0125709. View