Author(s): Anand Koppal, Vagdevi H. R, Senthilkumar Sivanesan, Sukumar Ethirajan, Rajagopalan Vijayaraghavan


DOI: 10.52711/0974-360X.2023.00346   

Address: Anand Koppal1, Vagdevi H. R2, Senthilkumar Sivanesan3, Sukumar Ethirajan4, Rajagopalan Vijayaraghavan5
1Assistant Professor, Department of Pharmacology, PES Institute of Medical Sciences and Research Kuppam - 517425 Andhra Pradesh, India.
2Associate Professor, Bapuji College of Allied Health Sciences, Shivamogga - 577222 Karnataka, India.
3Associate Professor, Department of Research and Development, Saveetha Institute of Medical and Technical Sciences, Chennai - 602105, Tamilnadu, India.
4Advisor, Research and Development ,Vpro Biotech Division Arumparthapuram Main Road Puducherry - 605110, India.
5Research Director, Department of Research and Development, Saveetha Institute of Medical and Technical Sciences Chennai - 602105, Tamilnadu, India.
*Corresponding Author

Published In:   Volume - 16,      Issue - 5,     Year - 2023

Objective: The present work evaluated the therapeutic potential of embelin monotherapy, embelin plus levodopa (L-Dopa) combination therapy in rotenone induced Parkinson’s disease (PD) model mice. Scope: Based on several growing evidence, antioxidants can be considered as modifiable factors that eventually decrease the risk of degeneration and progression of PD. Especially anti-oxidants from herbal medicines play vital role against several degenerative diseases. Therefore, we evaluated the neuroprotective effect of embelin and embelin plus L-Dopa therapy in rotenone induced behavioural changes in mice. Methods: Swiss Albino male adult mice were randomly divided into 7 groups. Group-1 (Control) 2mL/kg olive oil by oral route (p.o.), Groups from 2 to 7 were induced with 2.5mg/kg rotenone by intraperitoneal route (i.p.), L-Dopa 7.5mg/kg p.o was administered to Group-3. Group-4 and Group-5 were given 20mg/kg and 40mg/kg embelin p.o. Group 6 and 7 were given embelin p.o. at a dose of 20mg and 40mg/kg respectively along with 7.5mg/kg L-Dopa p.o. Result: Administration of rotenone (2.5mg/kg) for twenty-one days to mice consecutively produced motor incoordination, decreased locomotor activity anxiety like behaviours and bradykinesia. Embelin monotherapy as well as combination therapy of embelin along with L-Dopa significantly decreased the effect of rotenone on behavioural changes and rendered neuroprotection in a dose dependant manner.

Cite this article:
Anand Koppal, Vagdevi H. R, Senthilkumar Sivanesan, Sukumar Ethirajan, Rajagopalan Vijayaraghavan. Therapeutic effect of Embelin and Levodopa combination in Rotenone induced Parkinson’s disease in mice on Neurobehavioral Changes. Research Journal of Pharmacy and Technology 2023; 16(5):2107-4. doi: 10.52711/0974-360X.2023.00346

Anand Koppal, Vagdevi H. R, Senthilkumar Sivanesan, Sukumar Ethirajan, Rajagopalan Vijayaraghavan. Therapeutic effect of Embelin and Levodopa combination in Rotenone induced Parkinson’s disease in mice on Neurobehavioral Changes. Research Journal of Pharmacy and Technology 2023; 16(5):2107-4. doi: 10.52711/0974-360X.2023.00346   Available on:

1.    Willis AL, Evanoff BA, Lian M, Criswell SR, Racette BA. Geofiguric and ethnic variation in Parkinson disease: a population-based study of US medicare beneficiaries. Neuroepidemiology.2010;34:143-51.
2.    Sahoo S, Doddamani SH, Panigrahi HK. Ayurvedic management of kampavata (Parkinson's disease)-A case study report. Research journal of Pharmacology and Pharmacodynamics. 2020 Oct 1;12(4):147-50.Dawson TM, Dawson VL. Molecular pathways of neurodegeneration in Parkinson's disease. Science. 2003;302(5646):819-22.
3.    Kahale VP, Upadhay PR, Mhaiskar AJ, Shelat PS, Mundhada DR. To Access the Efficacy of Rutin on 6-Hydroxydopamine induced Animal Model of Memory Impairment in Parkinson’s disease. Research J Pharmacology and Pharmacodynamics. 2013;5(6):331-6.
4.    Prasad J, Netam AK, Singh R, Sahu M, Satapathy T, Rao SP, Baghel P, Sahu MK. Therapeutic Approaches for the Management of Parkinson’s Disease. Research Journal of Pharmacology and Pharmacodynamics. 2019 Feb 27;11(1):46-52.
5.    Jankovic J. Parkinson’s disease: clinical features and diagnosis. J Neurol Neurosurg Psychiatry.2008;79:368-76.
6.    Suryawanshi CP, Patil VR, Chaudhari RY, Kale MK, Firake SD, Pimprikar RB, Patil MD, Yeshwante SB, Saindanem DS. Antiparkinsonian Effect of Cassia tora on Oxotremorine Induced Parkinson Methodology. Research Journal of Pharmacy and Technology. 2009;2(4):842-5.
7.    Jankovic J, Stacy M. Medical management of levodopa-associated motor complications in patients with Parkinson’s disease. CNS drugs. 2007 Aug;21(8):677-92.
8.    Goswami-Giri AS. Qualitative and Quantitative analysis of Dopa from Solanum melangena. Asian Journal of Research in Chemistry. 2014 Nov 28;7(11):954-63.
9.    Sherer TB, Betarbet R, Testa CM, Seo BB, Richardson JR, Kim JH, et al. Mechanism of toxicity in rotenone models of Parkinson’s disease. J Neurosci.2003;23:10756-64.
10.    Ronald B Postuma et all. The new definition and diagnostic criteria of Parkinson's disease.2016; 15 (6)P546-548
11.    Lehto S. M, Ruusunen A, Tolmunen T, Voutilainen S, Tuomainen T. P, and Kauhanen J. Dietary zinc intake and the risk of depression in middle-aged men: a 20-year prospective follow-up study. Journal of affective disorder.2013; 150:682-685.
12.    Hill CA, Alexander ML, McCullough LD, Fitch RH. Inhibition of X-linked inhibitor of apoptosis with embelin differentially affects male versus female behavioural outcome following neonatal hypoxia-ischemia in rats. Developmental neuroscience.  2011;33(6):494-504.
13.    Verma R, Nehru B. Effect of centrophenoxine against rotenone-induced oxidative stress in an animal model of Parkinson's disease. Neurochemistry international. 2009 Nov 1;55(6):369-75.
14.    A. K. Meena, Anshul Sinha, M. D. Gupta, A. K. Mangal, G. Reddy, S. C. Verma, M. M. Padhi. Pharmacognostic and Physicochemical Studies of Embelia ribes Burm. f. Fruit used in Ayurvedic Formulations. Research J. Pharm. and Tech 6(6): June 2013; Page 645-648.Pathan, S. A., Iqbal, Z., Zaidi, S. M., Talegaonkar, S., Vohra, D., Jain, G. K., et al. (2009). CNS drug delivery systems: novel approaches. Recent Pat. Drug Deliv. Formul. 3, 71–89. doi: 10.2174/187221109787158355.
15.    Kobaisy M, Cantrell CL, Mims AB, Lax AR, Tellez MR, Osbrink WLA, 2008. Activity of 1, 4-Benzoquinones against formosan subterranean termites (Coptotermes formosanus). Journal of Agricultural and Food Chemistry, 56: 4021-4026
16.    Afzal M, Gupta G, Kazmi I, Rahman M, Upadhyay G, Ahmad K, Imam F, Pravez M, Anwar F. Evaluation of anxiolytic activity of embelin isolated from Embelia ribes. Biomedicine and Aging Pathology. 2012 Apr 1;2(2):45-7.
17.    Chitra M, Sukumar E, Suja V, Devi S. Antitumor, anti-inflammatory and analgesic property of embelin, a plant product. Chemotherapy. 1994;40(2):109-13.
18.    Gupta G, Kazmi I, Afzal M, Upadhyay G, Singh R, Habtemariam S. Antidepressant-like activity of Embelin isolated from Embelia ribes. Phytopharmacology. 2013 Oct 6;4(1):87-95.
19.    Mahendran S, Badami S, Maithili V. Evaluation of antidiabetic effect of embelin from Embelia ribes in alloxan induced diabetes in rats. Biomedicine and Preventive Nutrition. 2011 Jan 1;1(1):25-31.
20.    Chitra M, Shyamala Devi CS, Sukumar E. Antibacterial activity of embelin. Fitoterapia. 2003 Jun 1;74(4):401-3.
21.    Dhadde SB, Nagakannan P, Roopesh M, Kumar SA, Thippeswamy BS, Veerapur VP, Badami S. Effect of embelin against 3-nitropropionic acid-induced Huntington's disease in rats. Biomedicine and Pharmacotherapy. 2016 Feb 1; 77:52-8.
22.    Mahendran S, Thippeswamy BS, Veerapur VP, Badami S. Anticonvulsant activity of embelin isolated from Embelia ribes. Phytomedicine. 2011 Jan 15;18(2-3):186-8.
23.    Joshi R, Kamat JP, Mukherjee T. Free radical scavenging reactions and antioxidant activity of embelin: biochemical and pulse radiolytic studies. Chemico-biological interactions. 2007 Apr 25;167(2):125-34.
24.    Rao SP, Sharma N, Kalivendi SV. Embelin averts MPTP-induced dysfunction in mitochondrial bioenergetics and biogenesis via activation of SIRT1. Biochimica et Biophysica Acta (BBA)-Bioenergetics. 2020 Mar 1;1861(3):148157.
25.    Anand Koppal, Senthilkumar Sivanesan, Vagdevi HR, Sukumar Ethirajan, Rajagopalan Vijayaraghavan. Embelin and levodopa combination therapy mitigates Parkinson's disease complications in mice: In press Indian Journal of Pharmaceutical Education and Research | Vol 55 | Issue 3 | Jul-Sep, 2021
26.    Kavuri S, Sivanesan S, Howell MD, Vijayaraghavan R, Rajadas J. Studies on Parkinson’s-Disease-Linked Genes, Brain Urea Levels and Histopathology in Rotenone Induced Parkinson’s Disease Rat Model. World Journal of Neuroscience. 2020 Nov 6;10(4):216-34.
27.    Rozas G, Guerra MJ, Labandeira-Garcıa JL. An automated rotarod method for quantitative drug-free evaluation of overall motor deficits in rat models of parkinsonism. Brain Research Protocols. 1997 Dec 1;2(1):75-84.
28.    Walf AA, Frye CA. The use of the elevated plus maze as an assay of anxiety-related behavior in rodents. Nature protocols. 2007 Feb;2(2):322-8.
29.    Pêgo JM, Morgado P, Pinto LG, Cerqueira JJ, Almeida OF, Sousa N. Dissociation of the morphological correlates of stress‐induced anxiety and fear. European Journal of Neuroscience. 2008 Mar;27(6):1503-16.
30.    Jaya Preethi P, Padmini K, Srikanth J, Lohita M, Swetha K. Screening Models for CNS Stimulant Drugs: A Review.
31.    Javitch JA, D'amato RJ, Strittmatter SM, Snyder SH. Parkinsonism-inducing neurotoxin, MPTP uptake of the metabolite MPP+ by dopamine neurons explains selective toxicity. Proc. Natl. Acad. Sci. USA.1985;82:2173-7.
32.    Kitamura Y, Shimohama S, Akaike A, Taniguchi T. —Current Perspective—The Parkinsonian Models: Invertebrates to Mammals. The Japanese Journal of Pharmacology. 2000;84(3):237-43.
33.    Thiruchelvam M, Richfield EK, Baggs RB, Tank AW, Cory-Slechta DA. The nigrostriatal dopaminergic system as a preferential target of repeated exposures to combined paraquat and maneb: implications for Parkinson's disease. Journal of Neuroscience. 2000 Dec 15;20(24):9207-14.
34.    Fahn S, Sulzer D. Neurodegeneration and neuroprotection in Parkinson disease. NeuroRx. 2004 Jan 1;1(1):139-54.

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