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Functional improvement and immune-inflammatory cytokines profile of ischaemic stroke patients after treatment with boswellic acids: a randomized, double-blind, placebo-controlled, pilot trial

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Abstract

Ischaemic stroke represents one of the main causes of disability. According to the broad investigations, it is widely assumed that the contribution of inflammatory mediators is strongly involved in its pathogenesis. Hence, it seems that stroke treatment needs more efficient and inflammatory-targeted compounds to modulate inflammatory-related pathways. Such strategies paved the way to achieve better clinical outcomes along with conventional therapies. Boswellic acids (BAs), the main bioactive compounds of Boswellia sp. resin; are triterpenoids with well-documented anti-inflammatory properties. Compared with NSAIDs, BAs cross blood–brain barrier yet they do not cause serious gastrointestinal adverse effects. Considering BAs anti-inflammatory features, we conducted a randomized double-blind placebo-controlled pilot trial of these compounds as a supplementary therapy. This trial randomized 80 ischaemic stroke patients (40–80-years old) with a 4–20 score according to the National Institutes of Health Stroke Scale (NIHSS), within 72 h of neurological sign onset, in 1-month follow-up period. We assessed NIHSS as primary and plasma levels of TNF-α, IL-1α, IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12p70, IFN-γ, IP-10, MCP-1, 8-isoprostane, and PGE2 as secondary outcomes. According to NIHSS evaluation, patients who were allocated to BA group had a significant recovery in neurological function during the 1-month follow-up, compared with the placebo. The levels of plasma inflammatory markers were significantly decreased in BA group after 7 days of intervention in TNF-α, IL-1β, IL-6, IL-8, and PGE2. As a preliminary controlled trial in ischaemic stroke, BAs could improve clinical outcome in the early phases of stroke along with promising changes in plasma inflammatory factors.

Clinical trial registrationhttps://www.irct.ir Unique identifier: IRCT20170315033086N5. IRCT is a primary registry in the WHO registry network (https://www.who.int/ictrp/network/primary/en/)

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Acknowledgements

This study was granted by Shahid Beheshti University of Medical Sciences (SBMU) (number: 0308/25030-95/11/11). Our study benefited greatly from the efforts and critical comments of Mr. Hamid Fatemi. We would like to thank all stroke patients and Imam Hossein Hospital and Imam Khomeini Hospital Complex staffs specially Ms. Fatemeh Abbasi, and Ms. Mahnaz Varedi, chief nurses of stroke ward in the study centers for their cooperation. We are also grateful to Dr. Nahid Beladi Moghadam, Dr. Farhad Assarzadegan, Dr. Omid Hessami for their help. The authors wish to thank Pars Teb Lab staffs and Dr. Ali Kharaziyan for performing all routine laboratory tests. We also would like to thank all staff members of the IPD CRO Department for their cooperation and critical notes in this study.

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Authors and Affiliations

  1. Department of Clinical Biochemistry, School of Medicine, Shahid Beheshti University of Medical Sciences (SBMU), Tehran, 1985717443, Iran

    Somayeh Mahmoodi Baram, Saeed Karima, Somayeh Shateri, Shima Rajaei & Meisam Mahdavi

  2. Iranian Center of Neurological Research, Neuroscience Institute, Tehran University of Medical Sciences, Tehran, Iran

    Abbas Tafakhori, Sina Gharahje, Samaneh Kabiri & Maryamosadat Hosseinizadeh

  3. Department of Epidemiology and Biostatistics, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran

    Akbar Fotouhi

  4. Department of Neurology, Imam Hossein Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran

    Behnam Safarpour Lima, Seyed Hossein Aghamiri, Behnam Mansouri & Shima Zare Shahamati

  5. Neurology Department, Roozbeh Hospital, Tehran University of Medical Sciences, Tehran, Iran

    Vajiheh Aghamollaii

  6. HealthWeX Clinical Research Ltd. Co., Tehran, Iran

    Hessam Sepasi Tehrani & Amir Taher Alborzi

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  1. Somayeh Mahmoodi Baram
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  2. Saeed Karima
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Correspondence to Saeed Karima.

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All procedures involving human participants were carried out under Shahid Beheshti University of Medical Sciences (SBMU) ethics committee approval and supervision (Reference number: IR.SBMU.MSP.REC.1395.409) and were compatible with Good Clinical Practice guidelines which is in association with the International Council for Harmonization (ICH) dated November 9, 2016 and the 1964 Helsinki Declaration, its later amendments or comparable ethical standards.

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Baram, S.M., Karima, S., Shateri, S. et al. Functional improvement and immune-inflammatory cytokines profile of ischaemic stroke patients after treatment with boswellic acids: a randomized, double-blind, placebo-controlled, pilot trial. Inflammopharmacol 27, 1101–1112 (2019). https://doi.org/10.1007/s10787-019-00627-z

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