Archive of SID Iranian Journal of Basic Medical Sciences ijbms.mums.ac.ir Genus Boswellia as a new candidate for neurodegenerative disorders Arezoo Rajabian 1, HamidReza Sadeghnia 2, 3, Sahar Fanoudi 2, Azar Hosseini 1* 1 Pharmacological Research Center of Medicinal Plants, Mashhad University of Medical Sciences, Mashhad, Iran 2 Department of Pharmacology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran 3 Division of Neurocognitive Sciences, Psychiatry and Behavioral Sciences Research Center, Mashhad University of Medical Sciences, Mashhad A R T I C L E I N F O A B S T R A C T Article type: Neurodegenerative diseases, characterized by progressive loss of neurons, share common Review article stress. Genus Boswellia is a genus in the Burseraceae family. It comprises several species traditionally Article history: Received: Jun 6, 2018 mechanisms such as apoptotic cell death, mitochondrial dysfunction, inflammation, and oxidative Accepted: Sep 28, 2019 gastrointestinal diseases, tumors, as well as enhancing intelligence. Many studies have been carried usedout to fordiscover treatment therapeutic of chronic approaches inflammatory for neurodegenerative diseases, cerebral diseases edema, such chronic as Alzheimer’s pain syndrome, diseases, Keywords: Parkinson’s disease, Huntington’s disease, multiple sclerosis and amyotrophic lateral sclerosis, Alzheimer’s diseases Boswellia paper provides an overview of evidence about the potential of the Boswellia species and their main Cognitive stroke,constituents, and concomitant boswellic acids, cognitive as modulatorsdeficits. However, of several no curative mechanisms treatment involved has been in the developed. pathology This of Neurodegenerative diseases the neurodegenerative diseases. In vitro Neuroprotection species contain bioactive components that may enhance cognitive activity and protect against , animal, and clinical studies have confirmed that Boswellia neurodegeneration.species, having neuroprotective They exert thepotential, beneficial makes effects them via a promising targeting candidatemultiple pathological to cure or prevent causes theby antioxidative,neurodegenerative anti-inflammatory, disorders. antiamyloidogenic, and anti-apoptotic properties. The Boswellia ►Please cite this article as: Rajabian A, Sadeghnia HR, Fanoudi S, Hosseini A. Genus Boswellia as a new candidate for neurodegenerative disorders. Iran J Basic Med Sci 2020; 23:277- 286. doi: 10.22038/IJBMS.2020.35288.8419 Introduction part contains tetracyclic and pentacyclic triterpene Neurodegenerative diseases such as Alzheimer’s acids. Boswellic acids (BAs) are considered the main disease (AD), Parkinson’s disease (PD), Huntington’s biologically active components among the triterpene disease (HD), multiple sclerosis (MS), amyotrophic acids (Figure 1) (8, 14). Frankincense is responsible for lateral sclerosis, and stroke are age-related disorders (1, 2). A number of common pathophysiological features ammatory mechanisms are applied through have been proposed for these diseases, including anti-inflammatoryinhibition of 5-lipo and anti-cancer effects of BAs (15, 16). Theprostaglandin-E anti-infl synthase (mPGES)-1 (17). Other mechanisms includexygenase, suppression cathepsin of nuclear G, and transcription microsomal elevatedloss, and decreasedoxidative/nitrosative neuronal survival stress, (3, 4).mitochondrial Considering dysfunction,limitation of proteineffective misfolding/aggregation, treatments for these diseases,synapse as tumor necrosi there is an urgent need for new strategies using natural factor κB (NF-κB) and pro-inflammatory cytokines such products that act through novel biological targets (5). apoptosis in cancers cellsfactor via (TNFα), activation interleukin of caspase-8 (IL)-1β, and The genus Boswellia belonging to the Burseraceae IL-2,inhibition and IL-6of topoisomerases-I(15, 17). Also, BAs and lead II-alpha to induction (16, 18). of family comprises about 20 species. Species include B. In this review, the therapeutic effects of Boswellia and serrata, B. sacra, B. frereana, B. neglecta, B. microphylla, their major constituents on various neurodegenerative B. papyrifera, B. ogadensis, B. pirottae, B. rivae, B. disease models have been summarized (Figure 2). madagascariensis, B. socotrana, B. popoviana, B. nana, Herein, pharmacological effects of the genus Boswellia B. ameero, B. bullata, B. dioscoridis, B. elongata, and . , and (6, 7). B. ovalifoliolata B. neglectae B. dalzielii 1. Alzheimer’s disease The genus is widespread in dry areas such as Arabia, northeastern coast of Africa, and India (8). The in2. Parkinson’sneurodegenerative disease diseases were classified as follows: species have been useful in traditional medicine for 3. Cognitive dysfunction 4. Multiple sclerosis arthritis, cerebral edema, chronic pain syndrome, 5. Central nervous system trauma and brain ischemia treatmentgastrointestinal of inflammatory disease, tumors, diseases, and including for enhancing asthma, memory and learning function (9-11). Frankincense, Methods oleo-gum resins obtained from the genera Boswellia, is To prepare this review, an online search was performed composed of essential oil (5-9%), mucopolysaccharides by using some databases, including PubMed, Google (20-23%), and resin (60%) (12, 13). The resinous Scholar, Science Direct, and Scopus. This review mainly *Corresponding author: Azar Hosseini. Pharmacological Research Center of Medicinal Plants, Mashhad University of Medical Sciences, Mashhad, Iran. Tel: +98- 38002283; Email: [email protected] www.SID.ir Rajabian et al. Boswellia in neurodegenerative diseases Archive of SID Figure 1. Chemical structure of main constituents of genus Boswellia brain and serum levels of AChE, C-reactive protein of genus Boswellia and its main active constituents, (CRP), nuclear factor kappa-light-chain-enhancer of focusesAKBA, onon neurodegenerativethe therapeutic/or diseasespharmaceutical (such aseffects AD, activated B cells (NF-kB), monocyte chemoattractant PD, MS, and cerebral ischemia). The search terms suppressed while brain ACh and Bcl-2 were elevated. “Neurocognitive”, “Neurodegenerative”, “Neurological protein-1 (MCP-1), and leukotriene B4 (LTB4)B. serrata were includeddisorders”, “Neuropharmacology”, “Alzheimer’s disease”, “Learning”,“Parkinson’s “Memory”, disease”, “Multiple sclerosis”, “Cerebral ischemia”, “Boswellia”, The(25). data Also represented, co-administration preventing ofefficacy ginger of (Zingiber officinaleagainst neuro-inflammatory and B.apoptosis serrata (45insults and 3. The B. serrata Alzheimer’sand “AKBA (3-acetyl-11-keto-β-boswellic disease acid)” and ginger, 108 improved and 216 histopathologic mg/kg) and changes and also Alzheimer’s disease is the most common type of behavior90 mg/kg) stress in rats tests, treated including with activityAlCl cage, rotarod, neurodegenerative dementia in older people (19). It T- maze, as well as restoring ACh and AChE levels in brain homogenate (26). Recent evidence revealed that in plaques and hyper-phosphorylation of tau protein insulin resistance and metabolic dysfunction play an is characterized by amyloid-beta (Aβ) accumulation important role in the pathology of sporadic Alzheimer’s and neurofibrillary tangles induce neuron and synapse disease (sAD) (27). Intracerebral-ventricular injection formingloss and neurofibrillarygross degeneration tangles in (20). the Aβtemporal aggregation lobe, nitrosoureido)-D-glucopyranose) is applied to mimic cingulate gyrus (21). The pathological alterations cause ofsAD streptozotocin(28). STZ -induced (STZ, insulin2- deoxy-2-(3-(methyl-3- resistance causes parietalprogressive lobe, memory as well loss,as parts cognitive of the impairment frontal cortex and and the several features characterizing AD including oxidative inabilitysynaptic todysfunction, perform daily andactivities senile (21, 22).plaque-induced Aβ toxicity, stress, neuroinflammation, and dysfunctions in adult cholinergic dysfunction, oxidative damage, apoptosis, neurogenesis that are followed by progressive deficitsB. pathogenesis AD (21, 23). The possible prophylactic and carteriin learning could and have memory therapeutic (29-31). effects A onstudy STZ- explored induced inflammationtherapeutic effects have ofbeen B. serrata postulated using to an be animal involved model in whethermemory impairment.aqueous extract The evaluation of frankincense of learning from using AD induced by AlCl3 passive avoidance task (PAT) indicated that chronic standardized medicine, (17 and mg/kg B. serrata for 4 weeks, orally) were assessed.day) were In given this forstudy, 2 weeks rivastigmine before AlCl(0.33 mg/kg/day),administration as administration of aqueous extract of frankincense (50 to rats. The results revealed that(45 activity and 90 mg/kg/of rats mg/kg,manner 42(32). days) SuHeXiang improved Wan memory (SHXW) in is rats a traditional receiving increased, while the duration taken by rats to reach food STZChinese (1.5 medicinemg/kg/2 μl/side,comprising i.c.v.) Liquidambar in a time-dependent orientalis, in the T-maze test decreased. According to biochemical Saussurea lappa, Aquilaria agallocha, Santalum album, analysis, treatment with B. serrate led to elevation of B. carteri, Eugenia caryophyllata, Cyperus rotundus, acetylcholine (ACh) levels while acetylcholine esterase (AChE) activity was suppressed in brain homogenates. been used orally for the treatment of seizures, infantile Styrax benzoin, and Dryobalanops aromatica that has plaques reduced in the hippocampus (24). In a preclinical