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Current Pharmaceutical Design


ISSN (Print): 1381-6128
ISSN (Online): 1873-4286

Review Article

Neurotransmitter, Antioxidant and Anti-neuroinflammatory Mechanistic Potentials of Herbal Medicines in Ameliorating Autism Spectrum Disorder

Author(s): Arefeh Kardani, Amin Soltani, Robert D.E. Sewell, Mehrdad Shahrani and Mahmoud Rafieian-Kopaei*

Volume 25 , Issue 41 , 2019

Page: [4421 - 4429] Pages: 9

DOI: 10.2174/1381612825666191112143940

Price: $65


Background: Autism spectrum disorder (ASD) is a neurodevelopmental issue that disrupts behavior, nonverbal communication, and social interaction, impacting all aspects of an individual’s social development. The underlying origin of autism is unclear, however, oxidative stress, as well as serotonergic, adrenergic and dopaminergic systems are thought to be implicated in ASD. Despite the fact that there is no effective medication for autism, current pharmacological treatments are utilized to ameliorate some of the symptoms such as selfmutilation, aggression, repetitive and stereotyped behaviors, inattention, hyperactivity, and sleep disorders.

Methods: In accord with the literature regarding the activity of herbal medicines on neurotransmitter function, we aimed to review the most worthy medicinal herbs possessing neuroprotective effects.

Results: Based on the outcome, medicinal herbs such as Zingiber officinale, Astragalus membranaceu, Ginkgo biloba, Centella asiatica and Acorus calamus, have antioxidant activity, which can influence neurotransmitter systems and are potentially neuroprotective.

Conclusion: Consequently, these herbs, in theory at least, appear to be suitable candidates within an overall management strategy for those on the autism spectrum.

Keywords: Autism spectrum disorder, herbal medicine, inattention, neurotransmitters, nervous system, dopaminergic.

Frith U, Happé F. Autism spectrum disorder. Curr Biol 2005; 15(19): R786-90.
[] [PMID: 16213805]
Case-Smith J, Arbesman M. Evidence-based review of interventions for autism used in or of relevance to occupational therapy. Am J Occup Ther 2008; 62(4): 416-29.
[] [PMID: 18712004]
Politte LC, Henry CA, McDougle CJ. Psychopharmacological interventions in autism spectrum disorder. Harv Rev Psychiatry 2014; 22(2): 76-92.
[] [PMID: 24614763]
Lord C, Elsabbagh M, Baird G, Veenstra-Vanderweele J. Autism spectrum disorder. Lancet 2018; 392(10146): 508-20.
[] [PMID: 30078460]
Newschaffer CJ, Croen LA, Daniels J, et al. The epidemiology of autism spectrum disorders. Annu Rev Public Health 2007; 28(2): 235-58.
[] [PMID: 17367287]
Fombonne E. Epidemiology of pervasive developmental disorders. Pediatr Res 2009; 65(6): 591-8.
[] [PMID: 19218885]
Coplan J, Jawad AF. Modeling clinical outcome of children with autistic spectrum disorders. Pediatrics 2005; 116(1): 117-22.
[] [PMID: 15995041]
Eldevik S, Hastings RP, Hughes JC, Jahr E, Eikeseth S, Cross S. Meta-analysis of early intensive behavioral intervention for children with autism. J Clin Child Adolesc Psychol 2009; 38(3): 439-50.
[] [PMID: 19437303]
Smith T, Iadarola S. Evidence base update for autism spectrum disorder. J Clin Child Adolesc Psychol 2015; 44(6): 897-922.
[] [PMID: 26430947]
Myers SM, Johnson CP. Management of children with autism spectrum disorders. Pediatrics 2007; 120(5): 1162-82.
[] [PMID: 17967921]
Rogers SJ, Vismara LA. Evidence-based comprehensive treatments for early autism. J Clin Child Adolesc Psychol 2008; 37(1): 8-38.
[] [PMID: 18444052]
Tan M, Parkin JE. Route of decomposition of thiomersal (thimerosal). Int J Pharm 2000; 208(1-2): 23-34.
[] [PMID: 11064208]
Koenig K, Tsatsanis K, Volkmar F. Neurobiology and genetics of autism: a developmental perspective The Development of Autism 81-102
Waterhouse L. Autism overflows: increasing prevalence and proliferating theories. Neuropsychol Rev 2008; 18(4): 273-86.
[] [PMID: 19015994]
Fombonne E. Thimerosal disappears but autism remains. Arch Gen Psychiatry 2008; 65(1): 15-6.
[] [PMID: 18180423]
Lefebvre A, Beggiato A, Bourgeron T, Toro R. Neuroanatomical diversity of corpus callosum and brain volume in autism: meta-analysis, analysis of the autism brain imaging data exchange project, and simulation. Biol Psychiatry 2015; 78(2): 126-34.
[] [PMID: 25850620]
Sugranyes G, Kyriakopoulos M, Corrigall R, Taylor E, Frangou S. Autism spectrum disorders and schizophrenia: meta-analysis of the neural correlates of social cognition. PLoS One 2011; 6(10) e25322
[] [PMID: 21998649]
Curtis LT, Patel K. Nutritional and environmental approaches to preventing and treating autism and attention deficit hyperactivity disorder (ADHD): a review. J Altern Complement Med 2008; 14(1): 79-85.
[] [PMID: 18199019]
Onaolapo OJ, Onaolapo AY. Nutrition in autism spectrum disorders: a review of evidences for an emerging central role in aetiology, expression, and management. AIMS Med Sci 2018; 5(2): 122-44.
Pineles SL, Avery RA, Liu GT. Vitamin B12 optic neuropathy in autism. Pediatrics 2010; 126(4): e967-70.
[] [PMID: 20855389]
Grant WB, Soles CM. Epidemiologic evidence supporting the role of maternal vitamin D deficiency as a risk factor for the development of infantile autism. Dermatoendocrinol 2009; 1(4): 223-8.
[] [PMID: 20592795]
Surén P, Roth C, Bresnahan M, et al. Association between maternal use of folic acid supplements and risk of autism spectrum disorders in children. JAMA 2013; 309(6): 570-7.
[] [PMID: 23403681]
Chez MG, Buchanan CP, Aimonovitch MC, et al. Double-blind, placebo-controlled study of L-carnosine supplementation in children with autistic spectrum disorders. J Child Neurol 2002; 17(11): 833-7.
[] [PMID: 12585724]
Adams JB, Holloway C. Pilot study of a moderate dose multivitamin/mineral supplement for children with autistic spectrum disorder. J Altern Complement Med 2004; 10(6): 1033-9.
[] [PMID: 15673999]
Mousain-Bosc M, Roche M, Polge A, Pradal-Prat D, Rapin J, Bali JP. Improvement of neurobehavioral disorders in children supplemented with magnesium-vitamin B6. I. Attention deficit hyperactivity disorders. Magnes Res 2006; 19(1): 46-52.
[PMID: 16846100]
Brigandi SA, Shao H, Qian SY, Shen Y, Wu B-L, Kang JX. Autistic children exhibit decreased levels of essential fatty acids in red blood cells. Int J Mol Sci 2015; 16(5): 10061-76.
[] [PMID: 25946342]
Ooi YP, Weng SJ, Jang LY, et al. Omega-3 fatty acids in the management of autism spectrum disorders: findings from an open-label pilot study in Singapore. Eur J Clin Nutr 2015; 69(8): 969-71.
[] [PMID: 25804268]
Bourgeron T. A synaptic trek to autism. Curr Opin Neurobiol 2009; 19(2): 231-4.
[] [PMID: 19545994]
Pardo CA, Eberhart CG. The neurobiology of autism. Brain Pathol 2007; 17(4): 434-47.
[] [PMID: 17919129]
Burgess NK, Sweeten TL, McMahon WM, Fujinami RS. Hyperserotoninemia and altered immunity in autism. J Autism Dev Disord 2006; 36(5): 697-704.
[] [PMID: 16614791]
Rumsey JM, Ernst M. Functional neuroimaging of autistic disorders. Ment Retard Dev Disabil Res Rev 2000; 6(3): 171-9.
[<171:AID-MRDD4>3.0.CO;2-N] [PMID: 10982494]
Kvq L, Nguyễn LTH. The role of beta-adrenergic receptor blockers in Alzheimer’s disease: potential genetic and cellular signaling mechanisms. Am J Alzheimers Dis (Columbia) 2013; 28(5): 427-39.
Lam KS, Aman MG, Arnold LE. Neurochemical correlates of autistic disorder: a review of the literature. Res Dev Disabil 2006; 27(3): 254-89.
[] [PMID: 16002261]
Chauhan A, Chauhan V. Oxidative stress in autism. Pathophysiology 2006; 13(3): 171-81.
[] [PMID: 16766163]
Lorigooini Z, Kobarfard F, Ayatollahi SA. Anti-platelet aggregation assay and chemical composition of essential oil from Allium atroviolaceum Boiss growing in Iran. Int J Biosci 2014; 5(2): 151-6.
Lorigooini Z, Ayatollahi SA, Amidi S, Kobarfard F. Evaluation of anti-platelet aggregation effect of some Allium species. Iran J Pharm Res 2015; 14(4): 1225-31.
[PMID: 26664390]
Malekmohammad K, Sewell RDE, Rafieian-Kopaei M. Antioxidants and atherosclerosis: mechanistic aspects. Biomolecules 2019; 9(8) E301
Solati K, Heidari-Soureshjani S, Pocock L. Effects and mechanisms of medicinal plants on stress hormone (cortisol): A systematic review. World Family Med 2017; 15(9): 117-23.
Amini FG, Rafieian-Kopaei M, Nematbakhsh M, Baradaran A, Nasri H. Ameliorative effects of metformin on renal histologic and biochemical alterations of gentamicin-induced renal toxicity in Wistar rats. J Res Med Sci 2012; 17(7): 621-5.
[PMID: 23798920]
Nasri H. Toxicity and safety of medicinal plants. J Herbmed Pharmacol 2013; 2: 12-9.
Bahmani M, Sarrafchi A, Shirzad H, Rafieian-Kopaei M. Autism: pathophysiology and promising herbal remedies. Curr Pharm Des 2016; 22(3): 277-85.
[] [PMID: 26561063]
Rezapour S, Bahmani M, Afsordeh O, Rafieian R, Sheikhian A. Herbal medicines: a new hope for autism therapy. J Herbmed Pharmacol 2016; 5(3): 89-91.
Sutalangka C, Wattanathorn J. Neuroprotective and cognitive-enhancing effects of the combined extract of Cyperus rotundus and Zingiber officinale. BMC Complement Altern Med 2017; 17(1): 135-40.
[] [PMID: 28253877]
Wattanathorn J, Jittiwat J, Tongun T, Muchimapura S, Ingkaninan K. Zingiber officinale mitigates brain damage and improves memory impairment in focal cerebral ischemic rat. Evid Based Complement Alternat Med 2011; 2011 429505
[] [PMID: 21197427]
Farombi EO, Abolaji AO, Adetuyi BO, Awosanya O, Fabusoro M. Neuroprotective role of 6-Gingerol-rich fraction of Zingiber officinale (Ginger) against acrylonitrile-induced neurotoxicity in male Wistar rats. J Basic Clin Physiol Pharmacol 2018; 30(3)
Jalsrai A, Grecksch G, Becker A. Evaluation of the effects of Astragalus mongholicus Bunge saponin extract on central nervous system functions. J Ethnopharmacol 2010; 131(3): 544-9.
[] [PMID: 20655376]
Chan W-S, Durairajan SSK, Lu J-H, et al. Neuroprotective effects of Astragaloside IV in 6-hydroxydopamine-treated primary nigral cell culture. Neurochem Int 2009; 55(6): 414-22.
[] [PMID: 19409437]
Zhang H, Pan N, Xiong S, et al. Inhibition of polyglutamine-mediated proteotoxicity by Astragalus membranaceus polysaccharide through the DAF-16/FOXO transcription factor in Caenorhabditis elegans. Biochem J 2012; 441(1): 417-24.
[] [PMID: 21892924]
Cheng CY, Yao CH, Liu BS, Liu CJ, Chen GW, Chen YS. The role of astragaloside in regeneration of the peripheral nerve system. J Biomed Mater Res A 2006; 76(3): 463-9.
[] [PMID: 16315188]
Lu M-C, Yao C-H, Wang S-H, Lai Y-L, Tsai C-C, Chen Y-S. Effect of Astragalus membranaceus in rats on peripheral nerve regeneration: in vitro and in vivo studies. J Trauma 2010; 68(2): 434-40.
[] [PMID: 20154555]
Brinkhaus B, Lindner M, Schuppan D, Hahn EG. Chemical, pharmacological and clinical profile of the East Asian medical plant Centella asiatica. Phytomedicine 2000; 7(5): 427-48.
[] [PMID: 11081995]
Singh S, Gautam A, Sharma A, Batra A. Centella asiatica (L.): a plant with immense medicinal potential but threatened. Int J Pharm Sci Rev Res 2010; 4(2): 9-17.
Tiwari S, Singh S, Patwardhan K, Gehlot S, Gambhir I. Effect of Centella asiatica on mild cognitive impairment (MCI) and other common age-related clinical problems. Dig J Nanomater Biostruct 2008; 3(4): 215-20.
Gray NE, Harris CJ, Quinn JF, Soumyanath A. Centella asiatica modulates antioxidant and mitochondrial pathways and improves cognitive function in mice. J Ethnopharmacol 2016; 180: 78-86.
[] [PMID: 26785167]
Ramesh B, Indi S, Rao K. Studies to understand the effect of Centella asiatica on Aβ (42) aggregation in vitro. Curr Trends Biotechnol Pharm 2010; 4(2): 716-24.
Defillipo PP, Raposo AH, Fedoce AG, et al. Inhibition of cPLA2 and sPLA2 activities in primary cultures of rat cortical neurons by Centella asiatica water extract. Nat Prod Commun 2012; 7(7): 841-3.
[] [PMID: 22908561]
Haleagrahara N, Ponnusamy K. Neuroprotective effect of Centella asiatica extract (CAE) on experimentally induced Parkinsonism in aged Sprague-Dawley rats. J Toxicol Sci 2010; 35(1): 41-7.
[] [PMID: 20118623]
Xu CL, Wang QZ, Sun LM, et al. Asiaticoside: attenuation of neurotoxicity induced by MPTP in a rat model of Parkinsonism via maintaining redox balance and up-regulating the ratio of Bcl-2/Bax. Pharmacol Biochem Behav 2012; 100(3): 413-8.
[] [PMID: 22001429]
Soumyanath A, Zhong YP, Gold SA, et al. Centella asiatica accelerates nerve regeneration upon oral administration and contains multiple active fractions increasing neurite elongation in-vitro. J Pharm Pharmacol 2005; 57(9): 1221-9.
[] [PMID: 16105244]
Zhang X, Wu J, Dou Y, et al. Asiatic acid protects primary neurons against C2-ceramide-induced apoptosis. Eur J Pharmacol 2012; 679(1-3): 51-9.
[] [PMID: 22296759]
Soumyanath A, Zhong Y-P, Henson E, et al. Centella asiatica extract improves behavioral deficits in a mouse model of Alzheimer’s disease: investigation of a possible mechanism of action. Int J Alzheimers Dis 2012; 2012 381974
[PMID: 22506133]
Ferreira-Vieira TH, Guimaraes IM, Silva FR, Ribeiro FM. Alzheimer’s disease: targeting the cholinergic system. Curr Neuropharmacol 2016; 14(1): 101-15.
[] [PMID: 26813123]
Rossignol DA, Frye RE. The use of medications approved for Alzheimer’s disease in autism spectrum disorder: a systematic review. Front Pediatr 2014; 2(87): 87.
[PMID: 25202686]
Mukherjee PK, Kumar V, Houghton PJ. Screening of Indian medicinal plants for acetylcholinesterase inhibitory activity. Phytother Res 2007; 21(12): 1142-5.
[] [PMID: 17639556]
Ariffin F, Heong Chew S, Bhupinder K, Karim AA, Huda N. Antioxidant capacity and phenolic composition of fermented Centella asiatica herbal teas. J Sci Food Agric 2011; 91(15): 2731-9.
[] [PMID: 21987075]
Orhan IE. Centella asiatica (L.) Urban: from traditional medicine to modern medicine with neuroprotective potential. Evid Based Complement Alternat Med 2012; 2012 946259
[] [PMID: 22666298]
Castillo MA, Urdaneta KE, Semprún-Hernández N, et al. Speech-stimulating substances in autism spectrum disorders. Behav Sci (Basel) 2019; 9(6): 60.
[] [PMID: 31212856]
Fatemi SH, Halt AR, Stary JM, Kanodia R, Schulz SC, Realmuto GR. Glutamic acid decarboxylase 65 and 67 kDa proteins are reduced in autistic parietal and cerebellar cortices. Biol Psychiatry 2002; 52(8): 805-10.
[] [PMID: 12372652]
Awad R, Levac D, Cybulska P, Merali Z, Trudeau VL, Arnason JT. Effects of traditionally used anxiolytic botanicals on enzymes of the gamma-aminobutyric acid (GABA) system. Can J Physiol Pharmacol 2007; 85(9): 933-42.
[] [PMID: 18066140]
Wanasuntronwong A, Tantisira MH, Tantisira B, Watanabe H. Anxiolytic effects of standardized extract of Centella asiatica (ECa 233) after chronic immobilization stress in mice. J Ethnopharmacol 2012; 143(2): 579-85.
[] [PMID: 22841896]
Wanakhachornkrai O, Pongrakhananon V, Chunhacha P, et al. Neuritogenic effect of standardized extract of Centella asiatica ECa233 on human neuroblastoma cells. BMC Complement Altern Med 2013; 13: 204-11.
[] [PMID: 23915016]
Xu Y, Cao Z, Khan I, Luo Y. Gotu Kola (Centella Asiatica) extract enhances phosphorylation of cyclic AMP response element binding protein in neuroblastoma cells expressing amyloid beta peptide. J Alzheimers Dis 2008; 13(3): 341-9.
[] [PMID: 18431001]
Omar NS, Zakaria ZAC, Mian TS, Ngah WZW, Mazlan M. Centella asiatica modulates neuron cell survival by altering caspase-9 pathway. J Med Plants Res 2011; 5(11): 2201-9.
Neha B, Honey J, Ranjan B, Mukesh B. Pharmacognostical and preliminary phytochemical investigation of Acorus calamus linn. Asian J Pharmac Res 2012; 2(1): 39-42.
Jayaraman R, Anitha T, Joshi VD. Analgesic and anticonvulsant effects of Acorus calamus roots in mice. Int J Pharm Tech Res 2010; 2(1): 552-5.
Esfandiari E, Ghanadian M, Rashidi B, Mokhtarian A, Vatankhah AM. The effects of Acorus calamus L. in preventing memory loss, anxiety, and oxidative stress on lipopolysaccharide-induced neuroinflammation rat models. Int J Prev Med 2018; 9: 85.
[] [PMID: 30450168]
Geng Y, Li C, Liu J, et al. Beta-asarone improves cognitive function by suppressing neuronal apoptosis in the beta-amyloid hippocampus injection rats. Biol Pharm Bull 2010; 33(5): 836-43.
[] [PMID: 20460763]
Lim HW, Kumar H, Kim BW, et al. β-Asarone (cis-2,4,5-trimethoxy-1-allyl phenyl), attenuates pro-inflammatory mediators by inhibiting NF-κB signaling and the JNK pathway in LPS activated BV-2 microglia cells. Food Chem Toxicol 2014; 72: 265-72.
[] [PMID: 25066769]
Shukla PK, Khanna VK, Ali MM, Maurya RR, Handa SS, Srimal RC. Protective effect of acorus calamus against acrylamide induced neurotoxicity. Phytother Res 2002; 16(3): 256-60.
[] [PMID: 12164272]
Shukla PK, Khanna VK, Ali MM, Maurya R, Khan MY, Srimal RC. Neuroprotective effect of Acorus calamus against middle cerebral artery occlusion-induced ischaemia in rat. Hum Exp Toxicol 2006; 25(4): 187-94.
[] [PMID: 16696294]
Werneke U, Turner T, Priebe S. Complementary medicines in psychiatry: review of effectiveness and safety. Br J Psychiatry 2006; 188(2): 109-21.
[] [PMID: 16449696]
Smith TC, Ryan MA, Smith B, et al. Complementary and alternative medicine use among US Navy and Marine Corps personnel. BMC Complement Altern Med 2007; 7(1): 16.
[] [PMID: 17506899]
Brunello N, Racagni G, Clostre F, Drieu K, Braquet P. Effects of an extract of Ginkgo biloba on noradrenergic systems of rat cerebral cortex. Pharmacol Res Commun 1985; 17(11): 1063-72.
[] [PMID: 3003764]
Hadjiivanova ChI, Petkov VV. Effect of Ginkgo biloba extract on beta-adrenergic receptors in different rat brain regions. Phytother Res 2002; 16(5): 488-90.
[] [PMID: 12203273]
Wu W-R, Zhu X-Z. Involvement of monoamine oxidase inhibition in neuroprotective and neurorestorative effects of Ginkgo biloba extract against MPTP-induced nigrostriatal dopaminergic toxicity in C57 mice. Life Sci 1999; 65(2): 157-64.
[] [PMID: 10416821]
Ramassamy C, Clostre F, Christen Y, Costentin J. Prevention by a Ginkgo biloba extract (GBE 761) of the dopaminergic neurotoxicity of MPTP. J Pharm Pharmacol 1990; 42(11): 785-9.
[] [PMID: 1982302]
Weichel O, Hilgert M, Chatterjee SS, Lehr M, Klein J. Bilobalide, a constituent of Ginkgo biloba, inhibits NMDA-induced phospholipase A2 activation and phospholipid breakdown in rat hippocampus. Naunyn Schmiedebergs Arch Pharmacol 1999; 360(6): 609-15.
[] [PMID: 10619176]
Klein J, Chatterjee SS, Löffelholz K. Phospholipid breakdown and choline release under hypoxic conditions: inhibition by bilobalide, a constituent of Ginkgo biloba. Brain Res 1997; 755(2): 347-50.
[] [PMID: 9175905]
Nooshinfar E, Lashgari R, Haghparast A, Sajjadi S. NMDA receptors are involved in Ginkgo extract-induced facilitation on memory retention of passive avoidance learning in rats. Neurosci Lett 2008; 432(3): 206-11.
[] [PMID: 18191327]
Droy-Lefaix MT. Effect of the antioxidant action of Ginkgo biloba extract (EGb 761) on aging and oxidative stress. Age (Omaha) 1997; 20(3): 141-9.
[] [PMID: 23604306]
Huguet F, Tarrade T. α 2-adrenoceptor changes during cerebral ageing. The effect of Ginkgo biloba extract. J Pharm Pharmacol 1992; 44(1): 24-7.
[] [PMID: 1350623]
Takuma K, Hoshina Y, Arai S, et al. Ginkgo biloba extract EGb 761 attenuates hippocampal neuronal loss and cognitive dysfunction resulting from chronic restraint stress in ovariectomized rats. Neuroscience 2007; 149(2): 256-62.
[] [PMID: 17869007]
Hasanzadeh E, Mohammadi MR, Ghanizadeh A, et al. A double-blind placebo controlled trial of Ginkgo biloba added to risperidone in patients with autistic disorders. Child Psychiatry Hum Dev 2012; 43(5): 674-82.
[] [PMID: 22392415]
Niederhofer H. First preliminary results of an observation of Ginkgo Biloba treating patients with autistic disorder. Phytother Res 2009; 23(11): 1645-6.
[] [PMID: 19274699]
Kim JY, Son MJ, Son CY, et al. Environmental risk factors and biomarkers for autism spectrum disorder: an umbrella review of the evidence. Lancet Psychiatry 2019; 6(7): 590-600.
[] [PMID: 31230684]
Abrahams BS, Geschwind DH. Advances in autism genetics: on the threshold of a new neurobiology. Nat Rev Genet 2008; 9(5): 341-55.
[] [PMID: 18414403]
Rabiei Z, Bigdeli M, Lorigooini Z. A review of medicinal herbs with antioxidant properties in the treatment of cerebral ischemia and reperfusion. Majallah-i Danishgah-i Ulum-i Pizishki-i Babul 2015; 17(12): 45-76.
Ghanizadeh A, Akhondzadeh S, Hormozi M, Makarem A, Abotorabi-Zarchi M, Firoozabadi A. Glutathione-related factors and oxidative stress in autism, a review. Curr Med Chem 2012; 19(23): 4000-5.
[] [PMID: 22708999]

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