Effect of Shorea robusta resin extract in 3-nitropropionic acid-induced Huntington’s disease symptoms in Sprague-Dawley rats

Chirag Patel , Khushboo Thakur, Lalita Shagond, Sanjeev Acharya, Ketan Ranch, Sai HS. Boddu


Background and purpose: Huntington’s disease (HD) is a neurodegenerative disease characterized by neuronal death in the striatum. Asiatic acid is an active component of Shorea robusta (Dipterocarpaceae) plants with neuroprotective activity and is considered an acceptable therapeutic candidate for different neurodegenerative diseases. In the present study, the beneficial pharmacological action of Shorea robusta resin extract (SRRE) was assessed in 3-nitropropionic acid (3-NP)-induced HD in rats.

Experimental approach: The neuroprotective effect of SRRE (285.7 and 666.7 mg/kg, p.o., 14 days) was studied in 3-NP (10 mg/kg)-induced rats by measuring body weight, behavioral parameters including neurological scoring, motor coordination, spatial memory, and depression-like behavior, neuro-biochemical parameters (gamma-aminobutyric acid and acetylcholinesterase), and oxidative stress parameter in the brain. Histopathology of the rat’s brain was also studied.

Findings/Results: SRRE treatment (285.7 mg/kg and 666.7 mg/kg) substantially restored body weight, motor coordination, and mitochondrial enzyme complex I function and improved memory impairment as compared to 3-NP-treated rats. Furthermore, SRRE treatment significantly restored the antioxidant enzyme activity in brain tissue and ameliorated the histopathological changes induced by 3-NP.

Conclusion and implications: The neuroprotective effect of SRRE on 3-NP-induced HD in rats was mediated by a reduction in oxidative stress which may favor the usefulness of Shorea robusta in HD.


Asiatic acid; Brain tissue; Huntington’s disease; Neurodegenerative disease; 3-Nitropropionic acid; Shorea robusta.

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Dabrowska M, Olejniczak M. Gene therapy for Huntington’s disease using targeted endonucleases. Methods Mol Biol. 2020;2056:269-284. DOI: 10.1007/978-1-4939-9784-8_17.

Paulson HL, Albin RL,. Huntington’s disease: clinical features and routes to therapy. In: Lo DC, Hughes RE, editors Neurobiology of Huntington's disease: applications to drug discovery. Boca Raton, Florida: CRC Press/Taylor & Francis; 2011. pp. 1-65.PMID: 21882418.

Caron NS, Dorsey ER, Hayden MR. Therapeutic approaches to Huntington disease: from the bench to the clinic. Nat Rev Drug Discov. 2018;17(10): 729-750. DOI: 10.1038/nrd.2018.133.

Mehan S, Monga V, Rani M, Dudi R, Ghimire K. Neuroprotective effect of solanesol against 3-nitropropionic acid-induced Huntington’s disease-like behavioral, biochemical, and cellular alterations: Restoration of coenzyme-Q10-mediated mitochondrial dysfunction. Indian J Pharmacol. 2018;50(6):309-319. DOI: 10.4103/ijp.IJP_11_18.

Hussain R, Zubair H, Pursell S, Shahab M. Neurodegenerative diseases: regenerative mechanisms and novel therapeutic approaches. Brain Sci. 2018;8(9):177,1-37. DOI: 10.3390/brainsci8090177.

Karthika C, Chitra M, Radhika K. Protective activity of Shorea robusta leaf against oxidative stress in rats. Int J Pharm Sci Res. 2013;4(12):4754-4757. DOI: 10.13040/IJPSR.0975-8232.4(12).4754-57.

Wani TA, Kumar D, Prasad R, Verma PK, Sardar KK, Tandan SK, et al. Analgesic activity of the ethanolic extract of Shorea robusta resin in experimental animals. Indian J Pharmacol. 2012;44(4):493-499. DOI: 10.4103/0253-7613.99322.

Sanjayan KP, Partho PD. Influence of asiatic acid, a triterpenoid from Shores robusta, on the feeding and enzyme activity of Oxya fuscovittata (Insecta, Orthoptera). J Appl Entomol. 1993;115(1-5):506-510. DOI: 10.1111/j.1439-0418.1993.tb00420.x.

Krishnamurthy RG, Senut MC, Zemke D, Min J, Frenkel MB, Greenberg EJ, et al. Asiatic acid, a pentacyclic triterpene from Centella asiatica, is neuroprotective in a mouse model of focal cerebral ischemia. J Neurosci Res. 2009;87(11):2541-2550. DOI: 10.1002/jnr.22071.

Lee KY, Bae ON, Serfozo K, Hejabian S, Moussa A, Reeves M, et al. Asiatic acid attenuates infarct volume, mitochondrial dysfunction, and matrix metalloproteinase-9 induction after focal cerebral ischemia. Stroke. 2012;43(6):1632-1638.DOI: 10.1161/STROKEAHA.111.639427.

Mook-Jung I, Shin JE, Yun SH, Huh K, Koh JY, Park HK, et al. Protective effects of asiaticoside derivatives against beta-amyloid neurotoxicity. J Neurosci Res. 1999;58(3):417-425.PMID: 10518115.

Lee MK, Kim SR, Sung SH, Lim D, Kim H, Choi H, et al. Asiatic acid derivatives protect cultured cortical neurons from glutamate-induced excitotoxicity. Res Commun Mol Pathol Pharmacol. 2000;108(1-2):75-86.PMID: 11758977.

Clemency BM, Varughese R, Gonzalez-Rojas Y, Morse CG, Phipatanakul W, Koster DJ, et al. Efficacy of inhaled ciclesonide for outpatient treatment of adolescents and adults with symptomatic COVID-19: a randomized clinical trial. JAMA Intern Med. 2022;182(1):42-49. DOI: 10.1001/jamainternmed.2021.6759.

Sharma K. Phytoconstituents: isolation and characterization from root bark of Shorea robusta plant. Int J Pharmacogn Phytochem Res. 2014;6(4):991-995.

Patel C, Patel P, Sarkar D, Bulsara J, Soni A, Kiran I, et al. Neuroprotective effect of lutein in scopolamine-induced Alzheimer’s disease in mice and zebrafish. Rev Bras Farmacogn. 2021;31:762–771. DOI: 10.1007/s43450-021-00202-0.

Danduga RCSR, Dondapati SR, Kola PK, Grace L, Tadigiri RVB, Kanakaraju VK. Neuroprotective activity of tetramethylpyrazine against 3-nitropropionic acid induced Huntington’s disease-like symptoms in rats. Biomed Pharmacother. 2018;105:1254-1268. DOI: 10.1016/j.biopha.2018.06.079.

Tung VWK, Burton TJ, Quail SL, Mathews MA, Camp AJ. Motor performance is impaired following vestibular stimulation in ageing mice. Front Aging Neurosci. 2016;8:12,1-10. DOI: 10.3389/fnagi.2016.00012.

Locchi F, Dall’Olio R, Gandolfi O, Rimondini R. Water T-maze, an improved method to assess spatial working memory in rats: pharmacological validation. Neurosci Lett. 2007;422(3):213-216.DOI: 10.1016/j.neulet.2007.06.023.

Can A, Dao DT, Arad M, Terrillion CE, Piantadosi SC, Gould TD. The mouse forced swim test. J Vis Exp. 2012;59:e3638,1-5. DOI: 10.3791/3638.

Kola PK, Akula A, NissankaraRao LS, Danduga RCSR. Protective effect of naringin on pentylenetetrazole (PTZ)-induced kindling; possible mechanisms of antikindling, memory improvement, and neuroprotection. Epilepsy Behav. 2017;75: 114-126. DOI: 10.1016/j.yebeh.2017.07.011.

Shahgond L, Patel C, Thakur K. Sarkar D, Achaya S, Patel P. Therapeutic potential of probiotics - Lactobacillus plantarum UBLP40 and Bacillus clausii UBBC07 on thioacetamide-induced acute hepatic encephalopathy in rats. Metab Brain Dis.2022;37(1):185-195.DOI: 10.1007/s11011-021-00862-w.

Akhtar M, Pillai K, Vohora D. Effect of thioperamide on oxidative stress markers in middle cerebral artery occlusion model of focal cerebral ischemia in rats. Hum Exp Toxicol. 2008; 27(10):761-767. DOI: 10.1177/0960327108094608.

Patel C, Pande S, Acharya S. Potentiation of anti-Alzheimer activity of curcumin by probiotic Lactobacillus rhamnosus UBLR-58 against scopolamine-induced memory impairment in mice. Naunyn Schmiedebergs Arch Pharmacol. 2020;393(10):1955-196.DOI: 10.1007/s00210-020-01904-3.

Marklund S, Marklund G. Involvement of the superoxide anion radical in the autoxidation of pyrogallol and a convenient assay for superoxide dismutase. Eur J Biochem. 1974;47(3):469-474. DOI: 10.1111/j.1432-1033.1974.tb03714.x.

Saravana Babu C, Kesavanarayanan KS, Kalaivani P, Ranju V, Ramanathan M. A Simple densitometric method for the quantification of inhibitory neurotransmitter gamma-aminobutyric acid (GABA) in rat brain tissue. Chromatogr Res Int. 2011;2011:732409,1-6. DOI: 10.4061/2011/732409.

Ellman GL, Courtney KD, Andres VJ, Feather-stone RM. A new and rapid colorimetric determination of acetylcholinesterase activity. Biochem Pharmacol. 1961;7:88-95. DOI: 10.1016/0006-2952(61)90145-9.

King TE. Preparation of succinate dehydrogenase and reconstitution of succinate oxidase. Meth Enzymol. 1967;10:322-331.DOI: 10.1016/0076-6879(67)10061-X.

Jamwal S, Kumar P. Spermidine ameliorates 3-nitropropionic acid (3-NP)-induced striatal toxicity: possible role of oxidative stress, neuroinflammation, and neurotransmitters. Physiol Behav. 2016;155:180-187. DOI: 10.1016/j.physbeh.2015.12.015.

Zhou R, Wang FEI, Chang M, Yue H, Shi L, Zhao Y. preparation and evaluation of solid dispersion of asiatic acid with PVPK30. Dig J Nanomater Biostructures. 2012;7(3):1015-1020.

Reiner A, Dragatsis I, Dietrich P. Genetics and neuropathology of Huntington’s disease. Int Rev Neurobiol. 2011;98:325-372. DOI: 10.1016/B978-0-12-381328-2.00014-6.

Kumar P, Kumar A. Possible neuroprotective effect of Withania somnifera root extract against 3-nitropropionic acid-induced behavioral, biochemical, and mitochondrial dysfunction in an animal model of Huntington’s disease. J Med Food. 2009;12(3):591-600.DOI: 10.1089/jmf.2008.0028.

Khan A, Jamwal S, Bijjem KR V, Prakash A, Kumar P. Neuroprotective effect of hemeoxygenase-1/glycogen synthase kinase-3β modulators in 3-nitropropionic acid-induced neurotoxicity in rats. Neuroscience. 2015;287:66-77. DOI: 10.1016/j.neuroscience.2014.12.018.

Gao Y, Chu S, Li J, Zhang Z, Yan J, Wen Z, et al. Protopanaxtriol protects against 3-nitropropionic acid-induced oxidative stress in a rat model of Huntington’s disease. Acta Pharmacol Sin. 2015;36(3):311-322. DOI: 10.1038/aps.2014.107.

Borlongan CV, Koutouzis TK, Randall TS, Freeman TB, Cahill DW, Sanberg PR. Systemic 3-nitropropionic acid: behavioral deficits and striatal damage in adult rats. Brain Res Bull. 1995;36(6):549-556.DOI: 10.1016/0361-9230(94)00242-s.

Kumar P, Kumar A. Effect of lycopene and epigallocatechin-3-gallate against 3-nitropropionic acid induced cognitive dysfunction and glutathione depletion in rat: a novel nitric oxide mechanism. Food Chem Toxicol. 2009;47(10):2522-2530. DOI: 10.1016/j.fct.2009.07.011.

Lagoa R, Lopez-Sanchez C, Samhan-Arias AK, Gañan CM, Garcia-Martinez V, Gutierrez-Merino C. Kaempferol protects against rat striatal degeneration induced by 3-nitropropionic acid. J Neurochem. 2009;111(2):473-487. DOI: 10.1111/j.1471-4159.2009.06331.x.

Kumar P, Kumar A. Protective effect of hesperidin and naringin against 3-nitropropionic acid induced Huntington’s like symptoms in rats: possible role of nitric oxide. Behav Brain Res. 2010;206(1):38-46. DOI: 10.1016/j.bbr.2009.08.028.

Kumar P, Kumar A. Possible role of sertraline against 3-nitropropionic acid induced behavioral, oxidative stress and mitochondrial dysfunctions in rat brain. Prog Neuropsychopharmacol Biol Psychiatry. 2009;33(1):100-108. DOI: 10.1016/j.pnpbp.2008.10.013.

Pérez-De La Cruz V, González-Cortés C, Pedraza-Chaverrí J, Maldonado PD, Andrés-Martínez L, Santamaría A. Protective effect of S-allylcysteine on 3-nitropropionic acid-induced lipid peroxidation and mitochondrial dysfunction in rat brain synaptosomes. Brain Res Bull. 2006;68(5):379-383. DOI: 10.1016/j.brainresbull.2005.09.013.

Binienda ZK, Ali SF. Neuroprotective role of L-carnitine in the 3-nitropropionic acid induced neurotoxicity. Toxicol Lett. 2001;125(1-3):67-73. DOI: 10.1016/s0378-4274(01)00415-5.

Tadros MG, Khalifa AE, Abdel-Naim AB, Arafa HMM. Neuroprotective effect of taurine in 3-nitropropionic acid-induced experimental animal model of Huntington’s disease phenotype. Pharmacol Biochem Behav. 2005;82(3):574-582. DOI: 10.1016/j.pbb.2005.10.018.

Kumar P, Padi SSV, Naidu PS, Kumar A. Effect of resveratrol on 3-nitropropionic acid-induced biochemical and behavioural changes: possible neuroprotective mechanisms. Behav Pharmacol. 2006;17(5-6):485-492. DOI: 10.1097/00008877-200609000-00014.

Brouillet E, Jacquard C, Bizat N, Blum D. 3-Nitropropionic acid: a mitochondrial toxin to uncover physiopathological mechanisms underlying striatal degeneration in Huntington’s disease. J Neurochem. 2005;95(6):1521-1540. DOI: 10.1111/j.1471-4159.2005.03515.x.

Kim GW, Copin JC, Kawase M, Chen SF, Sato S, Gobbel GT, et al. Excitotoxicity is required for induction of oxidative stress and apoptosis in mouse striatum by the mitochondrial toxin, 3-nitropropionic acid. J Cereb Blood Flow Metab. 2000; 20(1):119-129. DOI: 10.1097/00004647-200001000-00016.

Kumar P, Kalonia H, Kumar A. Possible GABAergic mechanism in the neuroprotective effect of gabapentin and lamotrigine against 3-nitropropionic acid induced neurotoxicity. Eur J Pharmacol. 2012;674(2-3):265-274. DOI: 10.1016/j.ejphar.2011.11.030.

Kumar P, Kumar P, Khan A, Deshmukh R, Sharma PL. Role of neurosteroids in experimental 3-nitropropionic acid induced neurotoxicity in rats. Eur J Pharmacol. 2014;723:38-45. DOI: 10.1016/j.ejphar.2013.11.036.


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