Research Article
Volume 8 Issue 8 - 2020
Potential Impact of Ginsenoside Rg1 on Treatment of Paclitaxel-Induced Neuropathic Pain by TNF-α Inhibitory Action
Satbir Kaur1,2 and Arunachalam Muthuraman2,3,4*
1Department of Pharmacology, Chaudhary Devi Lal College of Pharmacy, BD Sharma University of Health Science, Yamuna Nagar, Yamuna Nagar, Haryana, India
2Department of Pharmacology and Toxicology, Akal College of Pharmacy and Technical Education, Research Scholar of IK Gujral Punjab Technical University (Kapurthala), Mastuana Sahib, Sangrur, Punjab, India
3Department of Pharmacology, JSS College of Pharmacy, JSS Academy of Higher Education and Research, Mysuru, Karnataka, India
4Pharmacology Unit, Faculty of Pharmacy, AIMST University, Semeling, Bedong, Kedah Darul Aman, Malaysia
*Corresponding Author: Arunachalam Muthuraman, Pharmacology Unit, Faculty of Pharmacy, AIMST University, Semeling, Bedong, Kedah Darul Aman, Malaysia.
Received: March 25, 2020; Published: July 31, 2020




Abstract

Ginsenoside Rg1 (GRg) is a major bioactive of a ginseng plant. It is a flavonoid type of natural medicine. In this research work investigated to find the therapeutic action of GRg on paclitaxel (PT) associated neuropathic pain and tumor necrosis factor-alpha (TNF-α) regulatory action. The injection of PT (2 mg/kg, i.p.) for 5 days enhances the progression of neuropathic pain. The GRg dose 5 and 10 mg/kg; intravenous (i.v.) and pregabalin (5 mg/kg; i.v.) were administered for 10 consecutive days. The algesic responses were assessed by pinprick and plantar tests in paw dorsal surface; tail-flick test; and tail pinch test. These tests were assessed at days 0, 4, 8, 12 and 16. The biomarker changes i.e. superoxide anion, myeloperoxidase, and TNF-α protein level were estimated in sciatic nerve tissue. Further, the level of TNF-α was estimated in the serum sample and expression of TNF-α proteins studied in sciatic nerve tissue along with changes of histopathology slides. Treatment of GRg and pregabalin ameliorated the chemotherapeutic agent i.e., PT associated pain response with the control of biomarkers changes like superoxide anion, myeloperoxidase, and TNF-α protein levels and histopathological changes. GRg has potential ameliorative actions against PT induced neuropathic pain due to its free radical scavenging, anti-inflammatory; and TNF-α inhibitory actions.

Keywords: Myeloperoxidase; Neuroinflammation; Nociceptive Pain; Pregabalin, Sciatic Nerve; Tumor Necrosis Factor

References

  1. Backonja MM. “Use of anticonvulsants for treatment of neuropathic pain”. Neurology 59 (2002): S14-S17.
  2. Hung AL., et al. “Targeting cytokines for treatment of neuropathic pain”. Scandinavian Journal of Pain 17 (2017): 287-293.
  3. Yang S., et al. “Role of TNF-TNF receptor 2 signal in regulatory T cells and its therapeutic implications”. Frontiers in Immunology 9 (2018): 784.
  4. Pegoretti V., et al. “Selective modulation of TNF-TNFRs signaling: insights for multiple sclerosis treatment”. Frontiers in Immunology 9 (2018): 925.
  5. Chang R., et al. “Blood-brain barrier penetrating biologic TNF-alpha inhibitor for Alzheimer's disease”. Molecular Pharmaceutics 14 (2017): 2340-2349.
  6. Li D., et al. “Association of Parkinson's disease-related pain with plasma interleukin-1, interleukin-6, interleukin-10, and tumour necrosis factor-alpha”. Neuroscience Letters 683 (2018): 181-184.
  7. Lahat N., et al. “Hypoxia enhances lysosomal TNF-alpha degradation in mouse peritoneal macrophages”. American Journal of Physiology. Cell Physiology 295 (2008): C2-C12.
  8. Shaikh F., et al. “TNF receptor type II as an emerging drug target for the treatment of cancer, autoimmune diseases, and graft-versus-host disease: Current perspectives and in silico search for small molecule binders”. Frontiers in Immunology 9 (2018): 1382.
  9. Kremer M., et al. “A dual noradrenergic mechanism for the relief of neuropathic allodynia by the antidepressant drugs duloxetine and amitriptyline”. Journal of Neuroscience 38 (2018): 9934-9954.
  10. Lu SC., et al. “Tumor necrosis factor-alpha mediated pain hypersensitivity through Ret receptor in resiniferatoxin neuropathy”. Kaohsiung Journal of Medical Sciences 34 (2018): 494-502.
  11. Tsouni P., et al. “Anti-TNF alpha medications and neuropathy”. Journal of the Peripheral Nervous System 20 (2015): 397-402.
  12. Hokama A., et al. “Crohn's disease complicated by IgA vasculitis during tumor necrosis factor-alpha inhibitor therapy”. Polish Archives of Internal Medicine 129 (2019): 283-284.
  13. Marzano AV., et al. “Drug-induced lupus erythematosus”. Giornale Italiano di Dermatologia e Venereologia 149 (2014): 301-309.
  14. Santos JM., et al. “Adenovirus coding for interleukin-2 and tumor necrosis factor alpha replaces lympho depleting chemotherapy in adoptive T cell therapy”. Molecular Pharmaceutics 26 (2018): 2243-2254.
  15. Dexheimer GM., et al. “Calyptranthes grandifolia O. Berg (Myrtaceae) ethanolic extract inhibits TNF-alpha gene expression and cytokine release In vitro”. Molecular Medicine Reports 15 (2017): 2873-2880.
  16. Kim MJ., et al. “Anti-inflammatory effects of grasshopper ketone from Sargassum fulvellum ethanol extract on lipopolysaccharide-induced inflammatory responses in RAW 264.7 cells”. Journal of Microbiology and Biotechnology 29 (2019): 820-826.
  17. Rezaee-Khorasany A., et al. “Effect of saffron (stigma of Crocus sativus L.) aqueous extract on ethanol toxicity in rats: A biochemical, histopathological and molecular study”. Journal of Ethnopharmacology 237 (2019): 286-299.
  18. Ar Rochmah M., et al. “Centella asiatica prevents increase of hippocampal tumor necrosis factor-alpha independently of its effect on brain-derived neurotrophic factor in rat model of chronic stress”. BioMed Research International 2019 (2019): 2649281.
  19. Ran Z., et al. “Curcumin inhibits high glucose induced inflammatory injury in human retinal pigment epithelial cells through the ROSPI3K/AKT/mTOR signaling pathway”. Molecular Medicine Reports 19 (2019): 1024-1031.
  20. Wang ZM., et al. “Green tea polyphenol epigallocatechin-3-gallate inhibits TNF-alpha-induced production of monocyte chemoattractant protein-1 in human umbilical vein endothelial cells”. Cellular Physiology and Biochemistry 33 (2014): 1349-1358.
  21. Zhao J., et al. “Ferulic acid enhances the vasorelaxant effect of epigallocatechin gallate in tumor necrosis factor-alpha-induced inflammatory rat aorta”. The Journal of Nutritional Biochemistry 25 (2014): 807-814.
  22. Kaur S and Muthuraman A. “Therapeutic investigation of galic acid on paclitaxel-induced motor-incoordination in Mus musculus”. Rapports De Pharmacie 4 (2018): 505-509.
  23. Kaur S and Muthuraman A. “Ameliorative effect of gallic acid in paclitaxel-induced neuropathic pain in mice”. Toxicology Reports 6 (2019): 505-513.
  24. Li Y., et al. “Ginsenoside Rf relieves mechanical hypersensitivity, depression-like behavior, and inflammatory reactions in chronic constriction injury rats”. Phytotherapy Research 33(2019): 1095-1103. 
  25. Kaur S and Muthuraman A. “Anti-neuralgesic effect of ginsenoside Rg1 (GRg) in chemotherapy-induced neuropathic pain”. Journal of Pharmaceutical Sciences and Research 10 (2018): 3482-2489.
  26. Kaur S and Muthuraman A. “Role of neuropeptides and ginsenoside Rg1 in peripheral nerve injury-induced neuropathic pain in mice”. EC Pharmacology and Toxicology 8.4 (2020): 65-77.
  27. Kim MK., et al. “Antinociceptive and anti-inflammatory effects of ginsenoside Rf in a rat model of incisional pain”. Journal of Ginseng Research 42 (2018): 183-191.
  28. Kilic FS., et al. “Pregabalin attenuates carrageenan-induced acute inflammation in rats by inhibiting proinflammatory cytokine levels”. The Eurasian Journal of Medicine 50 (2018): 156-159.
  29. Brito AMS., et al. “Antiallodynic activity of leflunomide is partially inhibited by naltrexone and glibenclamide and associated with reduced production of TNF-alpha and CXCL-1”. European Journal of Pharmacology 818 (2018): 17-25.
  30. Parvathy SS., et al. “Matrix metalloproteinase inhibitor COL-3 prevents the development of paclitaxel-induced hyperalgesia in mice”. Medical Principles and Practice 22 (2013): 35-41.
  31. Erichsen HK and Blackburn-Munro G. “Pharmacological characterisation of the spared nerve injury model of neuropathic pain”. Pain 98 (2002): 151-161.
  32. Hargreaves K., et al. “A new and sensitive method for measuring thermal nociception in cutaneous hyperalgesia”. Pain 32 (1988): 77-88.
  33. D'Amour FE and Smith DL. “A method for determining loss of pain sensation”. The Journal of Pharmacology and Experimental Therapeutics 72 (1941): 74-79.
  34. Takagi H., et al. “A modification of Haffner's method for testing analgesics”. Japanese Journal of Pharmacology 16 (1966): 287-294.
  35. Muthuraman A., et al. “Protective effect of Acorus calamus L. in rat model of vincristine induced painful neuropathy: an evidence of anti-inflammatory and anti-oxidative activity”. Food and Chemical Toxicology 49 (2011): 2557-2563.
  36. Muthuraman A. and Singh N. “Neuroprotective effect of saponin rich extract of Acorus calamus L. in rat model of chronic constriction injury (CCI) of sciatic nerve-induced neuropathic pain”. Journal of Ethnopharmacology 142 (2012): 723-731.
  37. Wang HD., et al. “Superoxide anion from the adventitia of the rat thoracic aorta inactivates nitric oxide”. Circulation Research 82 (1998): 810-818.
  38. Patriarca P., et al. “Interference of myeloperoxidase with the estimation of superoxide dismutase activity”. The Journal of Laboratory and Clinical Medicine 90 (1977): 289-294.
  39. Grisham MB., et al. “Effects of nitric oxide synthase inhibition on the pathophysiology observed in a model of chronic granulomatous colitis”. Journal of Pharmacology and Experimental Therapeutics 271 (1994): 1114-1121.
  40. Lowry OH., et al. “Protein measurement with the Folin phenol reagent”. The Journal of Biological Chemistry 193 (1951): 265-275.
  41. Krinke GJ., et al. “Experience with examination of the spinal cord and peripheral nervous system (PNS) in mice: A brief overview”. Experimental and Toxicologic Pathology 66 (2014): 277-280.
  42. Masocha W. “Paclitaxel-induced hyposensitivity to nociceptive chemical stimulation in mice can be prevented by treatment with minocycline”. Scientific Reports 4 (2014):6719.
  43. Bie B., et al. “An overview of the cannabinoid type 2 receptor system and its therapeutic potential”. Current Opinion in Anesthesiology 31 (2018): 407-414.
  44. Siau C., et al. “Paclitaxel- and vincristine-evoked painful peripheral neuropathies: loss of epidermal innervation and activation of Langerhans cells”. Experimental Neurology 201 (2006): 507-514.
  45. Toma W., et al. “Effects of paclitaxel on the development of neuropathy and affective behaviors in the mouse”. Neuropharmacology 117 (2017): 305-315.
  46. Zhang H., et al. “Dorsal root ganglion infiltration by macrophages contributes to paclitaxel chemotherapy-induced peripheral neuropathy”. The Journal of Pain 17 (2016): 775-786.
  47. Farah MH., et al. “Reduced BACE1 activity enhances clearance of myelin debris and regeneration of axons in the injured peripheral nervous system”. Journal of Neuroscience 31 (2011): 5744-5754.
  48. Hong X., et al. “Disruption of protein neddylation with MLN4924 attenuates paclitaxel-induced apoptosis and microtubule polymerization in ovarian cancer cells”. Biochemical and Biophysical Research Communications 508 (2019): 986-990.
  49. Kamei J., et al. “Rikkunshito prevents paclitaxel-induced peripheral neuropathy through the suppression of the nuclear factor kappa B (NFkappaB) phosphorylation in spinal cord of mice”. PLoS One 12 (2017): e0171819.
  50. Nadipelly J., et al. “Effect of certain trimethoxy flavones on paclitaxel - induced peripheral neuropathy in mice”. Integrative Medicine Research 7 (2018): 159-167.
  51. Gui Y., et al. “Icariin, a flavonoid with anti-cancer effects, alleviated paclitaxel-induced neuropathic pain in a SIRT1-dependent manner”. Molecular Pain 14 (2018): 1744806918768970.
  52. Liu HP., et al. “Ellagic acid alleviates inflammatory pain and paclitaxel-induced neuropathic pain in murine models”. International Journal of Clinical and Experimental Medicine 9 (2016): 12514-12520.
  53. Tang F., et al. “Inhibition of TNF-alpha-mediated NF-kappaB activation by ginsenoside rg1 contributes the attenuation of cardiac hypertrophy induced by abdominal aorta coarctation”. Journal of Cardiovascular Pharmacology 68 (2016): 257-264.
Citation: Satbir Kaur and Arunachalam Muthuraman. “Potential Impact of Ginsenoside Rg1 on Treatment of Paclitaxel-Induced Neuropathic Pain by TNF-α Inhibitory Action”. EC Pharmacology and Toxicology 8.8 (2020): 90-103.

PubMed Indexed Article


EC Pharmacology and Toxicology
LC-UV-MS and MS/MS Characterize Glutathione Reactivity with Different Isomers (2,2' and 2,4' vs. 4,4') of Methylene Diphenyl-Diisocyanate.

PMID: 31143884 [PubMed]

PMCID: PMC6536005


EC Pharmacology and Toxicology
Alzheimer's Pathogenesis, Metal-Mediated Redox Stress, and Potential Nanotheranostics.

PMID: 31565701 [PubMed]

PMCID: PMC6764777


EC Neurology
Differences in Rate of Cognitive Decline and Caregiver Burden between Alzheimer's Disease and Vascular Dementia: a Retrospective Study.

PMID: 27747317 [PubMed]

PMCID: PMC5065347


EC Pharmacology and Toxicology
Will Blockchain Technology Transform Healthcare and Biomedical Sciences?

PMID: 31460519 [PubMed]

PMCID: PMC6711478


EC Pharmacology and Toxicology
Is it a Prime Time for AI-powered Virtual Drug Screening?

PMID: 30215059 [PubMed]

PMCID: PMC6133253


EC Psychology and Psychiatry
Analysis of Evidence for the Combination of Pro-dopamine Regulator (KB220PAM) and Naltrexone to Prevent Opioid Use Disorder Relapse.

PMID: 30417173 [PubMed]

PMCID: PMC6226033


EC Anaesthesia
Arrest Under Anesthesia - What was the Culprit? A Case Report.

PMID: 30264037 [PubMed]

PMCID: PMC6155992


EC Orthopaedics
Distraction Implantation. A New Technique in Total Joint Arthroplasty and Direct Skeletal Attachment.

PMID: 30198026 [PubMed]

PMCID: PMC6124505


EC Pulmonology and Respiratory Medicine
Prevalence and factors associated with self-reported chronic obstructive pulmonary disease among adults aged 40-79: the National Health and Nutrition Examination Survey (NHANES) 2007-2012.

PMID: 30294723 [PubMed]

PMCID: PMC6169793


EC Dental Science
Important Dental Fiber-Reinforced Composite Molding Compound Breakthroughs

PMID: 29285526 [PubMed]

PMCID: PMC5743211


EC Microbiology
Prevalence of Intestinal Parasites Among HIV Infected and HIV Uninfected Patients Treated at the 1o De Maio Health Centre in Maputo, Mozambique

PMID: 29911204 [PubMed]

PMCID: PMC5999047


EC Microbiology
Macrophages and the Viral Dissemination Super Highway

PMID: 26949751 [PubMed]

PMCID: PMC4774560


EC Microbiology
The Microbiome, Antibiotics, and Health of the Pediatric Population.

PMID: 27390782 [PubMed]

PMCID: PMC4933318


EC Microbiology
Reactive Oxygen Species in HIV Infection

PMID: 28580453 [PubMed]

PMCID: PMC5450819


EC Microbiology
A Review of the CD4 T Cell Contribution to Lung Infection, Inflammation and Repair with a Focus on Wheeze and Asthma in the Pediatric Population

PMID: 26280024 [PubMed]

PMCID: PMC4533840


EC Neurology
Identifying Key Symptoms Differentiating Myalgic Encephalomyelitis and Chronic Fatigue Syndrome from Multiple Sclerosis

PMID: 28066845 [PubMed]

PMCID: PMC5214344


EC Pharmacology and Toxicology
Paradigm Shift is the Normal State of Pharmacology

PMID: 28936490 [PubMed]

PMCID: PMC5604476


EC Neurology
Examining those Meeting IOM Criteria Versus IOM Plus Fibromyalgia

PMID: 28713879 [PubMed]

PMCID: PMC5510658


EC Neurology
Unilateral Frontosphenoid Craniosynostosis: Case Report and a Review of the Literature

PMID: 28133641 [PubMed]

PMCID: PMC5267489


EC Ophthalmology
OCT-Angiography for Non-Invasive Monitoring of Neuronal and Vascular Structure in Mouse Retina: Implication for Characterization of Retinal Neurovascular Coupling

PMID: 29333536 [PubMed]

PMCID: PMC5766278


EC Neurology
Longer Duration of Downslope Treadmill Walking Induces Depression of H-Reflexes Measured during Standing and Walking.

PMID: 31032493 [PubMed]

PMCID: PMC6483108


EC Microbiology
Onchocerciasis in Mozambique: An Unknown Condition for Health Professionals.

PMID: 30957099 [PubMed]

PMCID: PMC6448571


EC Nutrition
Food Insecurity among Households with and without Podoconiosis in East and West Gojjam, Ethiopia.

PMID: 30101228 [PubMed]

PMCID: PMC6086333


EC Ophthalmology
REVIEW. +2 to +3 D. Reading Glasses to Prevent Myopia.

PMID: 31080964 [PubMed]

PMCID: PMC6508883


EC Gynaecology
Biomechanical Mapping of the Female Pelvic Floor: Uterine Prolapse Versus Normal Conditions.

PMID: 31093608 [PubMed]

PMCID: PMC6513001


EC Dental Science
Fiber-Reinforced Composites: A Breakthrough in Practical Clinical Applications with Advanced Wear Resistance for Dental Materials.

PMID: 31552397 [PubMed]

PMCID: PMC6758937


EC Microbiology
Neurocysticercosis in Child Bearing Women: An Overlooked Condition in Mozambique and a Potentially Missed Diagnosis in Women Presenting with Eclampsia.

PMID: 31681909 [PubMed]

PMCID: PMC6824723


EC Microbiology
Molecular Detection of Leptospira spp. in Rodents Trapped in the Mozambique Island City, Nampula Province, Mozambique.

PMID: 31681910 [PubMed]

PMCID: PMC6824726


EC Neurology
Endoplasmic Reticulum-Mitochondrial Cross-Talk in Neurodegenerative and Eye Diseases.

PMID: 31528859 [PubMed]

PMCID: PMC6746603


EC Psychology and Psychiatry
Can Chronic Consumption of Caffeine by Increasing D2/D3 Receptors Offer Benefit to Carriers of the DRD2 A1 Allele in Cocaine Abuse?

PMID: 31276119 [PubMed]

PMCID: PMC6604646


EC Anaesthesia
Real Time Locating Systems and sustainability of Perioperative Efficiency of Anesthesiologists.

PMID: 31406965 [PubMed]

PMCID: PMC6690616


EC Pharmacology and Toxicology
A Pilot STEM Curriculum Designed to Teach High School Students Concepts in Biochemical Engineering and Pharmacology.

PMID: 31517314 [PubMed]

PMCID: PMC6741290


EC Pharmacology and Toxicology
Toxic Mechanisms Underlying Motor Activity Changes Induced by a Mixture of Lead, Arsenic and Manganese.

PMID: 31633124 [PubMed]

PMCID: PMC6800226


EC Neurology
Research Volunteers' Attitudes Toward Chronic Fatigue Syndrome and Myalgic Encephalomyelitis.

PMID: 29662969 [PubMed]

PMCID: PMC5898812


EC Pharmacology and Toxicology
Hyperbaric Oxygen Therapy for Alzheimer's Disease.

PMID: 30215058 [PubMed]

PMCID: PMC6133268


News and Events


April Issue Release

We always feel pleasure to share our updates with you all. Here, notifying you that we have successfully released the April issue of respective journals and the latest articles can be viewed on the current issue pages.

Submission Deadline for upcoming Issue

Ecronicon delightfully welcomes all the authors around the globe for effective collaboration with an article submission for the upcoming issue of respective journals. Submissions are accepted on/before May 04, 2021.

Certificate of Publication

Ecronicon honors with a "Publication Certificate" to the corresponding author by including the names of co-authors as a token of appreciation for publishing the work with our respective journals.

Best Article of the Issue

Editors of respective journals will always be very much interested in electing one Best Article after each issue release. The authors of the selected article will be honored with a "Best Article of the Issue" certificate.

Certifying for Review

Ecronicon certifies the Editors for their first review done towards the assigned article of the respective journals.

Latest Articles

The latest articles will be updated immediately on the articles in press page of the respective journals.

Immediate Assistance

The prime motto of this team is to clarify all the queries without any delay or hesitation to avoid the inconvenience. For immediate assistance on your queries please don't hesitate to drop an email to editor@ecronicon.uk