Effect of Hiwa syrup, a Persian Medicine Product, on Autism Symptoms and in Children with Autism Spectrum Disorders: A Randomized Double-Blinded Clinical Trial

Authors

  • mohsen dayani Department of Traditional Medicine, School of Medicine, Arak University of Medical Sciences, Arak, Iran
  • Mehrdad Karimi Department of Iranian Medicine, Faculty of Iranian Medicine, Tehran University of Medical Sciences, Tehran, Iran
  • Seied Amirhosein Latifi Traditional and Complementary Medicine Research Center, Arak University of Medical Sciences, Arak, Iran
  • Mohammad Bagher Saberi Zafarghandi School of Behavioral Sciences and Mental Health (Tehran Institute of Psychiatry), Iran University of Medical Sciences, Tehran, Iran
  • Mehdi Salehi Traditional and Complementary Medicine Research Center, Department of Traditional Medicine, School of Medicine, Arak University of Medical Sciences, Arak, Iran

DOI:

https://doi.org/10.31661/gmj.v13i.3553

Keywords:

Autism Spectrum Disorder; Eye Contact; Herbal Medicine; Persian Medicine

Abstract

Background: Autism spectrum disorder (ASD) is a complex condition that affects communication, social interaction, and behavior. This study aims to evaluate the effectiveness of a Persian Medicine product, Hiwa syrup, which consists of consisted of apple (Malus domestica Borkh.) fruit, quince (Cydonia Oblonga Mill.) fruit, basil (Ocimum basilicum L.), green cardamom (Elettaria cardamomum), and sandalwood (Santalum album Linn), in ameliorating autism symptoms and extending eye contact duration in children diagnosed with ASD.

Methods: A double-blind randomized clinical trial involved 60 children (3-5 years) with level 1 autism, randomly assigned to intervention and control (placebo) groups. The intervention group received Hiwa syrup for eight weeks alongside routine therapy. Autism status was assessed using Persian version of Gilliam Autism Rating 2nd edition (GARS-2) questionnaire, and eye contact duration in response to auditory stimuli was measured pre and post-intervention. SPSS software version 25.0 was used for data analysis. 

Results: The Hiwa syrup group exhibited a significant decrease in the mean GARS-2 score from  75.03  ± 7.83 to 69.47 ± 5.87 (p=0.01) with a mean difference of 5.56 ± 3.12. This decrease surpassed that of the placebo group. Furthermore, the intervention group showed a significant increase in eye contact duration, from (7.90 ± 3.81 seconds to 9.26 ± 3.21 seconds (p=0.05), with a mean difference of 1.36±1.88 seconds. In contrast, the placebo group exhibited a smaller increase, from (7.50 ± 2.21seconds to 7.83 ± 2.91 seconds (p=0.64), with a mean difference of  0.33 ± 0.48 seconds.

Conclusion:The polyherbal product from Persian Medicine appears to be effective in ameliorating autism symptoms and extending the duration of eye contact in children diagnosed with autism spectrum disorders. Further clinical trials are essential to validate the efficacy of this product in treating autism spectrum disorders.

References

APA, A.P.A., Diagnostic and statistical manual of mental disorders. The American Psychiatric Association, 2013.

Salari, N., et al., The global prevalence of autism spectrum disorder: a comprehensive systematic review and meta-analysis. Italian Journal of Pediatrics, 2022. 48(1): p. 1-16.

Maenner, M.J., et al., Prevalence and characteristics of autism spectrum disorder among children aged 8 years—Autism and Developmental Disabilities Monitoring Network, 11 sites, United States, 2020. MMWR Surveillance Summaries, 2023. 72(2): p. 1.

Senju, A. and M.H. Johnson, Atypical eye contact in autism: models, mechanisms and development. Neuroscience & Biobehavioral Reviews, 2009. 33(8): p. 1204-1214.

Stuart, N., et al., Eye gaze in autism spectrum disorder: a review of neural evidence for the eye avoidance hypothesis. Journal of Autism and Developmental Disorders, 2023. 53(5): p. 1884-1905.

Trevisan, D.A., et al., How do adults and teens with self-declared Autism Spectrum Disorder experience eye contact? A qualitative analysis of first-hand accounts. PloS one, 2017. 12(11): p. e0188446.

Fonger, A.M. and R.W. Malott, Using shaping to teach eye contact to children with autism spectrum disorder. Behavior analysis in practice, 2019. 12: p. 216-221.

Santosh, P.J. and J. Singh, Drug treatment of autism spectrum disorder and its comorbidities in children and adolescents. BJPsych Advances, 2016. 22(3): p. 151-161.

McPheeters, M.L., et al., A systematic review of medical treatments for children with autism spectrum disorders. Pediatrics, 2011. 127(5): p. e1312-e1321.

Maw, S.S. and C. Haga, Effectiveness of cognitive, developmental, and behavioural interventions for Autism Spectrum Disorder in preschool-aged children: A systematic review and meta-analysis. Heliyon, 2018. 4(9).

Bang, M., et al., Herbal medicine treatment for children with autism spectrum disorder: a systematic review. Evidence-Based Complementary and Alternative Medicine, 2017. 2017.

Whitehouse, A.J., Complementary and alternative medicine for autism spectrum disorders: Rationale, safety and efficacy. Journal of Paediatrics and child health, 2013. 49(9): p. E438-E442.

Rezapour, S., et al., Herbal medicines: a new hope for autism therapy. Journal of Herbmed Pharmacology, 2016. 5(3): p. 89-91.

DeFilippis, M., The use of complementary alternative medicine in children and adolescents with autism spectrum disorder. Psychopharmacology bulletin, 2018. 48(1): p. 40.

Golsorkhi, H., M. Kamalinejad, and M. Dadmehr, The Useful Diet and Medicinal Plants for ADHD from the Viewpoint of Traditional Persian Medicine. International Journal of Pediatrics, 2022. 10(3): p. 15547-15551.

Tefagh, S., et al., Effect of Ustukhuddus Alavi, a multi-herbal product, on the cognitive performance of adolescent female students. Journal of Ethnopharmacology, 2022. 288: p. 114971.

Motaharifard, M.S., et al., Effect of sweet almond syrup versus methylphenidate in children with ADHD: A randomized triple-blind clinical trial. Complementary therapies in clinical practice, 2019. 36: p. 170-175.

Akhondian1ABCDEF, J., A. Parsa2ABCDE, and H. Rakhshande2BG, The effect of Nigella sativa L.(black cumin seed) on intractable pediatric seizures. Med Sci Monit, 2007. 13(12): p. 559.

Samadi, S.A. and R. McConkey, The utility of the Gilliam autism rating scale for identifying Iranian children with autism. Disability and rehabilitation, 2014. 36(6): p. 452-456.

Gilliam, J.E., Gilliam autism rating scale: GARS 2. 2006: Pro-ed.

Adriaenssens, N., Using an Elicited Orienting Response and Respondent Conditioning to Increase Eye Contact in Response to a Name Call in Children with Autism. 2019.

Editorial board. PDR for herbal medicines. Montvale: Medical Economics Company Pub, 2000.

Amerizadeh, A., et al., Cardiovascular effects of Cydonia oblonga Miller (quince). Evidence‐Based Complementary and Alternative Medicine, 2022. 2022(1): p. 3185442.

Patocka, J., et al., Malus domestica: A review on nutritional features, chemical composition, traditional and medicinal value. Plants, 2020. 9(11): p. 1408.

Aminian, A.R., R. Mohebbati, and M.H. Boskabady, The effect of Ocimum basilicum L. and its main ingredients on respiratory disorders: An experimental, preclinical, and clinical review. Frontiers in pharmacology, 2022. 12: p. 805391.

Izadi, B., et al., The effect of green cardamom on blood pressure and inflammatory markers among patients with metabolic syndrome and related disorders: A systematic review and meta‐analysis of randomized clinical trials. Phytotherapy Research, 2023. 37(2): p. 679-688.

Teixeira da Silva, J.A., et al., Sandalwood: basic biology, tissue culture, and genetic transformation. Planta, 2016. 243: p. 847-887.

Chan, A.S., S.L. Sze, and Y.M. Han, An intranasal herbal medicine improves executive functions and activates the underlying neural network in children with autism. Research in Autism Spectrum Disorders, 2014. 8(6): p. 681-691.

Elangovan, P., et al., Efficacy of Siddha Therapeutics on Mantha Sanni (Autism Spectrum Disorder) Among Pediatric Patients: An Interventional Non-randomized Open-Label Clinical Trial. Cureus, 2023. 15(10).

Aqili‐Khurasani, Makhzan‐al‐Adviyah (The Storehouse of Medicaments). 2001, Tehran: Bavardaran publication;[Persian].

Hakim Moumen SM. Tohfeh al-Momenin. Tehran: Nashr. Shahr; 2008.

Anushiravani, M., et al., Depression from the perspective of modern and Persian medicine. Electronic Physician, 2018. 10(2): p. 6372.

Shaharzani, M., Tibb‐e Akbari (Persian). 2007.

Aliabadi, S., L. Alvyar, and Z. Zendehboodi, The association of hot/cold status of temperament with depression and hopelessness scores in females. Current Traditional Medicine, 2021. 7(4): p. 584-587.

Torkmannejad Sabzevari, M., et al., The relationship between different temperaments and postpartum depression in health centers in Sabzevar, 2017. The Iranian Journal of Obstetrics, Gynecology and Infertility, 2018. 21(6): p. 64-70.

Sanaie, S., et al., Evaluating the Relationship between Sleep Quality and Temperament in Older Adults: Data from Tabriz Older People Survey (TOPS). Traditional and Integrative Medicine, 2022: p. 369-374.

Ahwazi, A., Kamel-al-Sanaeh (arabic) 1. 2008.

Jorjani, S., zakhireh Kharazmshahi (persian). 2012.

Dayani, M., et al., Investigating the Temperament of Autism Spectrum Patients from the Perspective of Persian Medicine. Complementary Medicine Journal, 2023. 13(3): p. 39-46.

Zhang, Y., et al., Does an apple a day keep away diseases? Evidence and mechanism of action. Food Science & Nutrition, 2023.

Tripathi, S. and P. Mitra Mazumder, Comprehensive investigations for a potential natural prophylaxis—A cellular and murine model for apple cider vinegar against hydrogen peroxide and scopolamine induced oxidative stress. Drug Development Research, 2022. 83(1): p. 105-118.

Lobo, A.R. and S. Satish, An investigation on anti-depressant activity of fresh fruit juice of Malus domestica in experimental animal models. Int. J. Res. Pharm. Pharm. Sci, 2019. 4(1): p. 19-23.

Sakhri, F.Z., et al., Behavioral and neurological improvement by Cydonia oblonga fruit extract in chronic immobilization stress rats. Phytotherapy Research, 2021. 35(4): p. 2074-2084.

Moghaddam, A. and A. Kianmehr, The protective effect of Quince (Cydonia oblonga Miller) leaf extract on locomotor activity and anxiety-like behaviors in a ketamine model of schizophrenia. Arak Medical University Journal, 2016. 19(5): p. 31-41.

Gomaa, A.A., et al., Terpenoid-rich Elettaria cardamomum extract prevents Alzheimer-like alterations induced in diabetic rats via inhibition of GSK3β activity, oxidative stress and pro-inflammatory cytokines. Cytokine, 2019. 113: p. 405-416.

Abu-Taweel, G.M., Cardamom (Elettaria cardamomum) perinatal exposure effects on the development, behavior and biochemical parameters in mice offspring. Saudi journal of biological sciences, 2018. 25(1): p. 186-193.

Rabbani, M., S.E. Sajjadi, and A. Vaezi, Evaluation of anxiolytic and sedative effect of essential oil and hydroalcoholic extract of Ocimum basilicum L. and chemical composition of its essential oil. Research in pharmaceutical sciences, 2015. 10(6): p. 535.

Mostafapour, P., M. Asle-Rousta, and M. Rahnema, Anxiolytic and antidepressant effects of Basil (Ocimum basilicum L.) hydro-alcoholic extract in male rats exposed to chronic restraint stress. SSU_Journals, 2018. 25(11): p. 887-896.

Singh, V., P. Krishan, and R. Shri, Improvement of memory and neurological deficit with Ocimum basilicum L. extract after ischemia reperfusion induced cerebral injury in mice. Metabolic brain disease, 2018. 33: p. 1111-1120.

Mohankumar, A., et al., East Indian sandalwood (Santalum album L.) oil confers neuroprotection and geroprotection in Caenorhabditis elegans via activating SKN-1/Nrf2 signaling pathway. RSC advances, 2018. 8(59): p. 33753-33774.

Y. Liang, J.H.H., and H. Song,, Clinical study on treatment of autism with Suhe Ditan decoction combined with acupuncture. For all Health, 2015. 9(20): p. 314.

DeFilippis, M., Depression in children and adolescents with autism spectrum disorder. Children, 2018. 5(9): p. 112.

Liu, Y., et al., Antioxidant interventions in autism spectrum disorders: A meta-analysis. Progress in Neuro-Psychopharmacology and Biological Psychiatry, 2022. 113: p. 110476.

Siniscalco, D., et al., Inflammation and neuro-immune dysregulations in autism spectrum disorders. Pharmaceuticals, 2018. 11(2): p. 56.

Matrisciano, F. and G. Pinna, Functional food and nutrition for the management of autism spectrum disorders and schizophrenia. Book: Functional Foods and Mental Health Publisher. Food Science, Publisher 9781708767006, 2019.

Alahmadi, B.A., Polyphenols as bioactive food components in relation to autism spectrum disorders: An overview of the literature. Journal of Complementary Medicine Research, 2023. 14(3): p. 180-180.

Adams, J.B., et al., Effect of a vitamin/mineral supplement on children and adults with autism. BMC pediatrics, 2011. 11: p. 1-30.

Bjørklund, G., et al., The role of vitamins in autism spectrum disorder: what do we know? Journal of molecular neuroscience, 2019. 67: p. 373-387.

Published

2024-10-09

Issue

Section

Original Article