Archive of SID Advanced Adv Pharm Bull, 2018, 8(4), 575-590 Pharmaceutical doi: 10.15171/apb.2018.066 Bulletin http://apb.tbzmed.ac.ir Review Article A Review of Herbal Therapy in Multiple Sclerosis Sina Mojaverrostami1* , Maryam Nazm Bojnordi2,3, Maryam Ghasemi-Kasman4 , Mohammad Ali Ebrahimzadeh5 , Hatef Ghasemi Hamidabadi2,6 1 Young Researchers and Elite Club, Behshahr Branch, Islamic Azad University, Behshahr, Iran. 2 Department of Anatomy & Cell Biology, Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, Iran. 3 Cellular and Molecular Research Center, Department of Anatomy & Cell Biology, Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, Iran. 4 Cellular and Molecular Biology Research Center, Health Research Institute, Babol University of Medical Sciences, Babol, Iran. 5 Pharmaceutical Sciences Research Center, School of Pharmacy, Mazandaran University of Medical Sciences, Sari, Iran. 6 Immunogenetic Research Center, Department of Anatomy & Cell Biology, Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, Iran. Article info Abstract Article History: Multiple sclerosis is a complex autoimmune disorder which characterized by demyelination Received: 18 May 2018 and axonal loss in the central nervous system (CNS). Several evidences indicate that some Revised: 30 July 2018 new drugs and stem cell therapy have opened a new horizon for multiple sclerosis Accepted: 15 August 2018 treatment, but current therapies are partially effective or not safe in the long term. Recently, ePublished: 29 November 2018 herbal therapies represent a promising therapeutic approach for multiple sclerosis disease. Here, we consider the potential benefits of some herbal compounds on different aspects of Keywords: multiple sclerosis disease. The medicinal plants and their derivatives; Ginkgo biloba, Multiple sclerosis Zingiber officinale, Curcuma longa, Hypericum perforatum, Valeriana officinalis, Inflammation Vaccinium macrocarpon, Nigella sativa,Piper methysticum, Crocus sativus, Panax ginseng, Demyelination Boswellia papyrifera, Vitis vinifera, Gastrodia elata, Camellia sinensis, Oenothera biennis, Remyelination MS14 and Cannabis sativa have been informed to have several therapeutic effects in MS Herbal therapy patients. Introduction Multiple sclerosis (MS) is an autoimmune disease that reprogramming of glial cells to OPCs …) that improve mostly occurs in young adulthood.1 The etiology of MS myelination.10 Despite the potential benefits of stem cell disease is still not well understood, but both genetic and therapy in the improvement of myelin repair,11 its environmental factors were found to have important roles clinical application has been hampered because of the in MS disease initiation or progression.2 In MS disease, possibility of teratoma formation, cell rejection and inflammatory cells demolish myelin sheath in the CNS ethical problems.12,13 Therefore, there is still a need for which weakens action potential conduction.3 Two developing new drugs which have no or less cardinal properties of MS are acute inflammation that considerable side effects. associated with demyelination and another one is axonal The pathophysiology of MS is not well elucidated, which loss.4 After injury, oligodendrocyte precursor cells makes itsʼ treatment strategy very difficult and (OPCs) which are residing at parenchyma continuously perplexing.14 At the present time, most of the strategies produce myelinating oligodendrocytes.3-5 In addition, in MS treatment are focused on preventing of regarding to the ability of neural stem cells for inflammation in the CNS.15 Interferon beta (IFN-beta) differentiation to OPCs, these stem cells are considered was firstly confirmed as an effective drug for treatment as an important source for remyelination.6-8 These of MS in 1993.16 Afterward, different drugs were endogenous stem cells proliferate, migrate and introduced for curing MS such as glatiramer acetate, differentiate to OPCs after brain injuries. However, natalizumab, alemtuzumab and fingolimod.14 All of these endogenous OPCs can produce myelin and improve mentioned drugs were partially effective and their some aspects of the MS disease, but endogenous repair remarkable adverse effects makes them unsuitable for may fail in long term.7,9 Therefore, several studies have proloned use.17 For example, several studies indicated focused on different approaches (including targeting the adverse effects of IFN-beta consumption including, specific signaling pathways, stem cell therapy, stroke, headache, migraine and depression.17 Until now, suppressing the inflammation process and no absolute treatment has been found for MS, therefore, *Corresponding author: Sina Mojaverrostami, Tel: +98 21 64432348, Fax: 98 21 66419072, Email: [email protected] ©2018 The Authors. This is an Open Access article distributed under the terms of the Creative Commons Attribution (CC BY), which permits unrestricted use, distribution, and reproduction in any medium, as long as the original authors and source are cited. No permission is required from the authors or the publishers. www.SID.ir ArchiveMojaverrostami of etSID al. trying to find a completely effective and safe treatment is by MS patients for ameloriating the severity of still ongoing. disease.27 The beneficial effects of CHM in MS disease Use of complementary and alternative medicine is occured by reduction of the severity of MS disease; (CAM), in particular herbal remedies have noticeably including antioxidative properties, anti-apoptotic risen in MS patients over the last decades.18,19 Herbal effects, anti-inflammatory properties and promoting the therapy is known as a helpful strategy for curing the differentiation of local stem cells to myelin producing different disorders from ancient to the present time.20 cells.28 MS patients usually use CAM, and medicinal Previous studies reported that medicinal plants have plants as a member of this family plays a crucial role to several therapeutic effects in different disorders such as cure MS and itsʼ associated symptoms.29 Different cancers, diabetes and neurodegenerative diseases.21,22 herbal medicines are recommended for MS patients, but Recently, a growing number of findings have indicated the understanding of their efficacy is not well that some herbal compounds improve myelin repair and described. In this review; we will discuss some of lead to suppression of inflammation.23,24 Also, there are herbal compounds beneficial effects on MS disease many studies that reported the anti-inflammatory and (Table 1 and Table 2). We conducted a search for all antioxidant effects of medicinal plants, as well as other English language articles in Google Scholar, Science helpful properties which make them as a natural, safe Direct, Scopus, PubMed and Medline for medicinal and reliable remedy for treatment of neurodegenerative plants, that have been used for their therapeutic diseases.25,26 Perivious studies have indicated that MS potentials in MS disease, studies which their patients are interested in using herbal medicines to publication dates from January 1960 to April 2018 were control their disease symptoms.26 For example in used. China, Chinese herbal medicine (CHM) is widely used Table1. Summary of herbal medicines used in the treatment of Multiple sclerosis Author Duration Plant Design of study Dosage Number Effects Ref (Country) of study Clinical trial-Double- Treatment with ginkgo extract Johnson et al 240 mg/day of ginkgo 22 MS blind, placeo- 4 weeks relieved fatigue with no adverse 34 (USA) extract patients controlled effect in MS patients Clinical trial-Double- Improvement of the cognitive Lovera et al 240 mg/day of ginkgo 38 MS Ginkgo biloba blind, placeo- 12 weeks performance were reported in 37 (USA) extract patients controlled treated group Clinical trial-Double- Brochet et al 240 and 360 mg/day of 104 MS ginkgolide B was not an effective blind, placeo- 1 week 180 (France) ginkgolide B patients treatment for exacerbations of MS controlled Ginger extract ameliorated EAE Zingiber Jafarzadeh et EAE model of MS in 200 and 300 mg/kg ginger 24 4 weeks severity and modulated the 43 officinale al (Iran) mice extract expression of IL-27, IL-33 Curcumin decreased the Xie et al EAE model of MS in 100 and200 mg/kg 21 2 weeks inflammation and the severity of 53 (Japan) rats curcumin extract EAE Natarajan Curcumin decreased CNS EAE model of MS in 50 and 100 µg curcumin in and Bright - 4 weeks inflammation and demyelination 54 Curcuma longa SJL/J mice 25 µl DMSO / day (USA) also,decreased the severity of EAE Treatment with polymerized Mohajeri et al EAE model of MS in nano-curcumin decreased the 12.5 mg/kg of curcumin 20 17 days 23 (Iran) rats severity of EAE and increased the remyelination Treatment with co-supplemented Double blind, 18–21 g/day Evening Firouzi et al 100 MS C. sativa and evening primrose oils randomized clinical primrose oil and C. 24 weeks 158 (Iran) patients decreased the clinical score in MS trial sativa oils Oenothera patients biennis Treatment with colchicine and Double blind, Horrobin 14 MS evening primrose oil improved randomized clinical - 24 weeks 159 (Canada) patients manual dexterity test and clinical trial score in MS patients In-vitro study on Treatment with H. perforatum Hypericum Naziroglu et 20 μM/ml H. perforatum 9 MS neutrophils of MS - indicated the protective effects on 69 perforatum al (Turkey) for 2 hours patients patients oxidative stress in MS patients Double blind, clinical Treatment with cranberry