Anti-neuralgesic Effect of Ginsenoside Rg1 (GRg) in Chemotherapy-Induced Neuropathic Pain Satbir Kaur 1 , Arunachalam Muthuraman 2,3,4, * Abstract Ginsenoside Rg1 (GRg) is a natural bioactive flavonoid compound. It has potential action on the neuronal system and it prevents neurodegenerative disorders. The present study is focused to explore their role of GRgin paclitaxel-induced neuropathic pain. Neuropathic pain was induced by administration of paclitaxel dose 2 mg/kg, i.p. for 5 consecutive days in mice. The ginsenoside Rg1 (5 and 10 mg/kg; i.v.) and pregabalin (5 mg/kg; i.v.) were administered for 10 consecutive days. The neuralgic sensations were assessed by various pain assessment tests like acetone drop, pinprick, plantar, tail flick, and tail pinch test. All tests were performed on variable time intervals i.e., 0, 4, 8, 12 and 16 th day. The tissue biomarker changes i.e., thiobarbituric acid reactive substances (TBARS), reduced glutathione (GSH), superoxide anion, calcium, myeloperoxidase, and TNF-α level were estimated in sciatic nerve tissue. Treatment of GRg and pregabalin attenuated the paclitaxel- induced pain sensitivity in a dose-dependent manner along with tissue biomarkers changes. GRg has potential neuroprotective actions against paclitaxel-induced neuropathic pain due to its anti-oxidant; anti-inflammatory; and regulation of cytosolic calcium ion concentration. Keywords: Allodynia, Ginsenoside, Hyperalgesia, Myeloperoxidase, Paclitaxel, Sciatic nerve. INTRODUCTION Neuropathic pain is a progressive neurodegenerative disorder. It occurs due to the damage of central and peripheral neuronal tissue. It produces the unpleasant painful sensation and sometimes it induces the lack of sensation [1]. The treatment of neuropathic pain is complicated due to the involvement of multiple pathophysiological mechanism and complexity of drug prescription. The conventional medicines are treated the neuropathic pain by symptomatic manner. There are some common medicines are used to treat the neuropathic pain such as narcotic; anti-depressants; and anti-epileptic drugs. Even though, these approaches are not satisfactory for the management of neuropathic pain due to its potential side effects; lack of efficacy in certain neuropathic pain and cost-effectiveness. Therefore, alternative medicines are essential for the treatment of neuropathic pain. Numerous reports revealed that herbal medicine has a promising role in the prevention of neuropathic pain and their progress. In addition, it has neuroprotective action along with lacks of adverse effects for chronic usage; and low cost. Paclitaxel is one of the natural anti-cancer agents and it is used for the treatment of breast cancer; lung cancer; and ovarian cancer. However, it causes serious adverse effects on host neurological system leads to cause the peripheral neuropathic pain. The mechanism of paclitaxel-induced neuropathic pain is the prevention of tubulin polymerization; calcium ion accumulation; raising the inflammatory cytokines including TNF-α, and activation of myeloperoxidase enzyme [2-4]. Experimentally, the administration of PT is documented to produce the neuropathic pain in rodents as well as in human [5-6]. The plant extracts are documented to prevents the progress of neuropathic pain-like Acorus calamus; Artemisia dracunculus; Butea monosperma; Citrullus colocynthis; Curcuma longa; Crocus sativus; Elaeagnus angustifolia; Ginkgo biloba; Mitragyna speciosa; Momordica charantia; Nigella sativa; Ocimum sanctum; Phyllanthus amarus; and Salvia officinalis [7]. In addition, plant-derived constituents i.e., celastrol [8], liquiritigenin [9], epigallocatechin gallate [10], tocotrienol [11], lycopene [12], thymoquinone [13], and resveratrol [14] are also produce the anti-nociceptive action. Ginsenosides is one of the saponins type steroidal glycosides and it belongs from family of Sapindaceae. The treatment of ginsenosides Rg 5 and Rh 3 ameliorates the scopolamine-induced memory deficits [15]; multiple sclerosis and Parkinson's disease [16-17]; and ischemic stroke in human [18-19]. Thus, the role of ginsenosides in neuropathic pain remains to be explored. Therefore, the present study designed to evaluate the role of GRg in paclitaxel-induced neuropathic pain in mice. MATERIALS AND METHODS Animals About 20-25 g and age of 10-month-old disease free male Swiss albino mice were used for the evaluation of GRg in paclitaxel- induced neuropathic pain in mice. Animals were kept at standard laboratory diet, temperature (65-75 °F; ~18-23 °C) and humidity (40-60 %) condition. The complete animal experimental protocol including acclimatized period, all the animals were kept in 12 hours light-dark cycles. The animals were allowed accessing the standard laboratory diet and water ad libitum. The experimental protocol was approved by the Institutional Animal Ethics Committee (IAEC; No.: ATRC/09/I4). And, maintaining of animals was followed as per the guidelines of the Committee for the Purpose of Control and Supervision of Experiments on Animals (CPCSEA), Ministry of Environment and Forest, Government of India. Drugs and Chemicals Ginsenoside Rg1 (GRg: Purity ≥ 98 %) was obtained from Pioneer Enterprise Mumbai, Maharashtra, India. And, GRg dose was prepared with 50 mM of phosphate buffer. The paclitaxel injection was purchased from Bristol-Mayer Squipp, Mumbai. Sulfanilamide and 1,1,3,3-tetramethoxy propane were procured from Sisco Research Laboratories, Mumbai. Thiobarbituric acid and nitro blue tetrazolium (NBT) was procured from Sigma Aldrich Mumbai. Rat TNF-alpha ELISA kit was purchased from RayBio, Inc., USA. The remaining chemical reagents were obtained from S.D. Fine Chemicals, Mumbai, India with the analytical grade. Satbir Kaur et al /J. Pharm. Sci. & Res. Vol. 10(12), 2018, 3482-2489 3482 1 Department of Pharmacology, Chaudhary Devi Lal College of Pharmacy, BD Sharma University of Health Science, Yamuna Nagar-135003, Haryana, India. 2 Department of Pharmacology and Toxicology, Akal College of Pharmacy & Technical Education, Research scholar of IK Gujral Punjab Technical University (Kapurthala), Mastuana Sahib, Sangrur-147001, Punjab, India. 3 Department of Pharmacology, JSS College of Pharmacy, JSS Academy of Higher Education and Research, Mysuru-570 015, Karnataka, India. 4 Pharmacology Unit, Faculty of Pharmacy, AIMST University, Semeling, 08100 Bedong, Kedah Darul Aman, Malaysia.