Contents lists available at ScienceDirect Journal of Ethnopharmacology journal homepage: www.elsevier.com/locate/jethpharm Curcuma longa L. ameliorates asthma control in children and adolescents: A randomized, double-blind, controlled trial Gabriel Manarin a , Daniela Anderson a , Jorgete Maria e Silva a , Juliana da Silva Coppede b , Persio Roxo-Junior a , Ana Maria Soares Pereira b , Fabio Carmona a,* a Department of Pediatrics, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, Brazil b Department of Plant Biotechnology, University of Ribeirao Preto, Ribeirao Preto, Brazil ARTICLE INFO Keywords: Asthma Pediatrics Curcumin Turmeric Zingiberaceae ABSTRACT Ethnopharmacological relevance: Roots of Curcuma longa L. are used as medicine for millennia. They possess several pharmacological properties, including anti-inflammatory action, and can be suitable for asthma treat- ment. Aim of the study: We aimed to test the hypothesis that, in children and adolescents with persistent asthma, the administration of powdered roots of C. longa for 6 months, in addition to standard treatment, compared to placebo, will result in better disease control. Patients and methods: We conducted a randomized, double-blind, placebo-controlled, phase II clinical trial. Patients were randomly assigned to receive 30 mg/kg/day of C. longa for 6 months, or placebo. Data were collected prospectively. All patients were categorized for asthma severity and control according to GINA-2016 and underwent pulmonary function tests. Results: Overall, both groups experienced amelioration of their frequency of symptoms and interference with normal activity, but no differences were found between the two treatment groups. However, patients receiving C. longa experienced less frequent nighttime awakenings, less frequent use of short-acting β-adrenergic agonists, and better disease control after 3 and 6 months. Conclusion: The powdered roots of C. longa led to less frequent nighttime awakenings, less frequent use of short- acting β-adrenergic agonists, and better disease control after 3 and 6 months, when compared to placebo. 1. Introduction Asthma is a highly prevalent chronic inflammatory disease whose main characteristics are bronchial hyper-responsiveness, variable lim- itation of air flow, and airway remodeling. Symptoms include episodes of wheezing, dyspnea, and cough (Global Initiative for Asthma, 2016). The disease leads to significant morbidity worldwide, and its pre- valence is increasing in the last 20 years. The treatment for asthma aims at controlling inflammation in the long term, while keeping symptoms at minimum and ameliorating the lung function. The main drugs used for long-term control are: inhaled corticosteroids and inhaled long-acting beta-adrenergic agonists (LAβAA). Oral corticosteroids and short-acting beta-adrenergic agonists (SAβAA) are used for asthma attacks. Although most patients experi- ence good disease control, many patients do not (Global Initiative for Asthma, 2016). In addition, chronic exposure to corticosteroids can cause serious adverse effects, especially in children. Therefore, new, safe and effective drugs for asthma are needed. Curcuma longa L. (turmeric, Zingiberaceae) is a perennial plant, extensively grown in Asia and tropical countries, like Brazil. Roots of C. longa have been used for millennia as medicine for many purposes, including respiratory diseases (Jagetia and Aggarwal, 2007) and, more specifically, asthma (WHO, 1999). However, its traditional use for asthma lacks scientific validation. The characteristic yellow, golden color is due to the presence of curcuminoids [curcumin (75–81%), demethoxycurcumin (15–19%), and bisdemethoxycurcumin (2.2–6.6%)] (Patil et al., 2009). There is evidence that the mixture of curcuminoids is more effective than each one alone (Balaji and Chempakam, 2010). Curcumin possessed several biological activities, including: anti-inflammatory, antibacterial, anti- viral, antifungal, antioxidant, wound healing, among many others (Jagetia and Aggarwal, 2007). Curcumin modulates the inflammatory response and release of cytokines by suppressing nuclear factor kappa-B (NF-κB) activation, through inhibition of phosphorylation and https://doi.org/10.1016/j.jep.2019.111882 Received 30 October 2018; Received in revised form 9 April 2019; Accepted 11 April 2019 * Corresponding author. Department of Pediatrics, Avenida dos Bandeirantes, S/N, Campus Universitario, Monte Alegre, Ribeirao Preto, SP, CEP 14149-900, Brazil. E-mail address: carmona@fmrp.usp.br (F. Carmona). Journal of Ethnopharmacology 238 (2019) 111882 Available online 13 April 2019 0378-8741/ © 2019 Published by Elsevier B.V. T