Genus Boswellia as a new candidate for neurodegenerative disorders

Document Type: Review Article

Authors

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

Abstract

Neurodegenerative diseases, characterized by progressive loss of neurons, share common mechanisms such as apoptotic cell death, mitochondrial dysfunction, inflammation, and oxidative stress. Genus Boswellia is a genus in the Burseraceae family. It comprises several species traditionally used for treatment of chronic inflammatory diseases, cerebral edema, chronic pain syndrome, gastrointestinal diseases, tumors, as well as enhancing intelligence. Many studies have been carried out to discover therapeutic approaches for neurodegenerative diseases such as Alzheimer’s diseases, Parkinson’s disease, Huntington’s disease, multiple sclerosis and amyotrophic lateral sclerosis, stroke, and concomitant cognitive deficits. However, no curative treatment has been developed. This paper provides an overview of evidence about the potential of the Boswellia species and their main constituents, boswellic acids, as modulators of several mechanisms involved in the pathology of the neurodegenerative diseases. In vitro, animal, and clinical studies have confirmed that Boswellia species contain bioactive components that may enhance cognitive activity and protect against neurodegeneration. They exert the beneficial effects via targeting multiple pathological causes by antioxidative, anti-inflammatory, antiamyloidogenic, and anti-apoptotic properties. The Boswellia species, having neuroprotective potential, makes them a promising candidate to cure or prevent the neurodegenerative disorders. 

Keywords


1.    Ayoobi F, Shamsizadeh A, Fatemi I, Vakilian A, Allahtavakoli M, Hassanshahi G, et al. Bio-effectiveness of the main flavonoids of Achillea millefolium in the pathophysiology of neurodegenerative disorders-a review. Iran J Basic Med Sci 2017; 20:604-612.
2.    Durães F, Pinto M, Sousa E. Old drugs as new treatments for neurodegenerative diseases. Pharmaceuticals 2018; 11:44.
3.    Finkel T. Signal transduction by reactive oxygen species. J Cell Biol 2011; 194:7-15.
4.    Winner B, Kohl Z, Gage FH. Neurodegenerative disease and adult neurogenesis. Eur J Neurosci 2011; 33:1139-1151.
5.    Shirooie S, Nabavi SF, Dehpour AR, Belwal T, Habtemariam S, Argüelles S, et al. Targeting mTORs by omega-3 fatty acids: a possible novel therapeutic strategy for neurodegeneration?. Pharmacol Res 2018; 135:37-48.
6.    Mertens M, Buettner A, Kirchhoff E. The volatile constituents of frankincense–a review. Flavour Fragr J 2009; 24:279-300.
7.    Morikawa T, Matsuda H, Yoshikawa M. A review of anti-inflammatory terpenoids from the incense gum resins frankincense and myrrh. J Oleo Sci 2017; 66:805-814.
8.    Siddiqui M. Boswellia serrata, a potential antiinflammatory agent: an overview. Indian J Pharm Sci 2011; 73:255-261.
9. Farshchi A, Ghiasi G, Farshchi S, Malek Khatabi P. Effects of Boswellia papyrifera gum extract on learning and memory in mice and rats. Iran J Basic Med Sci 2010; 13:9-15.
10.     Hamidpour R, Hamidpour S, Hamidpour M, Shahlari M. Frankincense (乳香 Rǔ Xiāng; Boswellia species): from the selection of traditional applications to the novel phytotherapy for the prevention and treatment of serious diseases. J Tradit Complement Med 2013; 3:221-226.
11.    Takahashi M, Sung B, Shen Y, Hur K, Link A, Boland CR, et al. Boswellic acid exerts antitumor effects in colorectal cancer cells by modulating expression of the let-7 and miR-200 microRNA family. Carcinogenesis 2012; 33:2441-2449.
12.    Basch E, Boon H, Heerema TD, Foppo I, Hashmi S, Hasskarl J, et al. Boswellia: An evidence-based systematic review by the natural standard research collaboration. J Herb Pharmacother 2004; 4:63-83.
13.    Rijkers T, Ogbazghi W, Wessel M, Bongers F. The effect of tapping for frankincense on sexual reproduction in Boswellia papyrifera. J Appl Ecol 2006; 43:1188-1195.
14.    Goyal S. Novel anti-inflammatory topical herbal gels containing Withania somnifera and Boswellia serrata. Int J Pharm Biol Arch 2011; 2: 1087-1094.
15. Ammon H. Boswellic acids and their role in chronic inflammatory diseases. In: Gupta SC, Prasad S, Aggarwal BB, editors.  Anti-inflammatory Nutraceuticals and Chronic Diseases. Springer; 2016. P. 291-327.
16.  Liu J-J, Nilsson A, Oredsson S, Badmaev V, Zhao W-Z, Duan R-D. Boswellic acids trigger apoptosis via a pathway dependent on caspase-8 activation but independent on Fas/Fas ligand interaction in colon cancer HT-29 cells. Carcinogenesis 2002; 23:2087-2093.
17.    Abdel-Tawab M, Werz O, Schubert-Zsilavecz M. Boswellia serrata. Clin Pharmacokinet 2011; 50:349-369.
18.    Syrovets T, Büchele B, Gedig E, Slupsky JR, Simmet T. Acetyl-boswellic acids are novel catalytic inhibitors of human topoisomerases I and IIα. Mol Pharmacol 2000; 58:71-81.
19.    Brookmeyer R, Johnson E, Ziegler-Graham K, Arrighi HM. Forecasting the global burden of Alzheimer’s disease. Alzheimer’s Dement 2007; 3:186-191.
20.    Kumar A, Singh A. A review on Alzheimer’s disease pathophysiology and its management: an update. Pharmacol Rep 2015; 67:195-203.
21.    Serrano-Pozo A, Frosch MP, Masliah E, Hyman BT. Neuropathological alterations in Alzheimer disease. Cold Spring Harb Perspect Med 2011; 1:a006189.
22.     Reddy VS, Bukke S, Dutt N, Rana P, Pandey AK. A systematic review and meta-analysis of the circulatory, erythrocellular and CSF selenium levels in Alzheimer’s disease: A metal meta-analysis (AMMA study-I). J Trace Elem Med Biol 2017; 42:68-75.
23.    Wenk GL. Neuropathologic changes in Alzheimer’s disease: potential targets for treatment. J Clin Psychiatry 2006; 67:3-7.
24.    Yassin N, El-Shenawy S, Mahdy KA, Gouda N, Marrie A, Farrag A, et al. Effect of Boswellia serrata on Alzheimer’s disease induced in rats. J Arab Soc Med Res 2013; 8:1-11.
25.    Ahmed H, Mohamed E, El-Dsoki S. Evidences for the promising therapeutic potential of Boswellia serrata against Alzheimer’s disease: pre-clinical study. Int J Pharm Pharm Sci 2014; 6:384-392.
26.     Ibrahim BMM. Experimental study of the effects of Boswellia serrata and ginger (Zingiber officinale) on Alzheimer’s Disease induced in rats. CU Theses; 2012.
27. Correia SC, Santos RX, Perry G, Zhu X, Moreira PI, Smith MA. Insulin-resistant brain state: the culprit in sporadic Alzheimer’s disease? Ageing Res Rev 2011;10:264-273
28.    Agrawal R, Tyagi E, Shukla R, Nath C. Insulin receptor signaling in rat hippocampus: a study in STZ (ICV) induced memory deficit model. Eur Neuropsychopharmacol 2011; 21:261-273.
29.     Qu Zq, Zhou Y, Zeng Ys, Lin Yk, Li Y, Zhong Zq, et al. Protective effects of a Rhodiola crenulata extract and salidroside on hippocampal neurogenesis against streptozotocin-induced neural injury in the rat. PLoS One 2012; 7:e29641.
30. Salkovic-Petrisic M, Knezovic A, Hoyer S, Riederer P. What have we learned from the streptozotocin-induced animal model of sporadic Alzheimer’s disease, about the therapeutic strategies in Alzheimer’s research. J Neural Transm 2013; 120:233-252.
31. Sun P, Knezovic A, Parlak M, Cuber J, M Karabeg M, Deckert J, et al. Long-term effects of intracerebroventricular streptozotocin treatment on adult neurogenesis in the rat hippocampus. Curr Alzheimer Res 2015;12:772-84.
32.    Beheshti S, Aghaie R. Therapeutic effect of frankincense in a rat model of Alzheimer’s disease. Avicenna J Phytomed 2016; 6: 468-475.
33.    Bensky D, Gamble A, Kaptchuk TJ. Chinese herbal medicine: materia medica. Eastland Press Seattle; 2004.
34.    Jeon S, Hur J, Jeong HJ, Koo B-S, Pak SC. SuHeXiang Wan essential oil alleviates amyloid beta induced memory impairment through inhibition of tau protein phosphorylation in mice. Am J Chin Med 2011; 39:917-932.
35.    den Brok MG, van Dalen JW, van Gool WA, Moll van Charante EP, de Bie RM, Richard E. Apathy in Parkinson’s disease: a systematic review and meta‐analysis. Mov Disord 2015; 30:759-769.
36.    Yuan H, Zhang ZW, Liang LW, Shen Q, Wang XD, Ren SM, et al. Treatment strategies for Parkinson’s disease. Neurosci Bull 2010; 26:66-76.
37.    Gaki GS, Papavassiliou AG. Oxidative stress-induced signaling pathways implicated in the pathogenesis of Parkinson’s disease. Neuromolecular Med 2014; 16:217-230.
38.    Kazmi S, Kafami L, Ebrahimi A, Jameie B, Joghataiee MT. The effects of Boswellia resin extract on dopaminergic cell line, SK-N-SH, against MPP+-induced neurotoxicity. Basic Clin Neurosci 2011; 3:16-21.
39.    Baudry M, Bi X. Learning and memory: an emergent property of cell motility. Neurobiol Learn Mem 2013; 104:64-72.
40.     Colciago A, Casati L, Negri-Cesi P, Celotti F. Learning and memory: steroids and epigenetics. J Steroid Biochem Mol Biol 2015; 150:64-85.
41.    Gallistel CR, Balsam PD. Time to rethink the neural mechanisms of learning and memory. Neurobiol Learn Mem 2014; 108:136-144.
42.    Bliss TV, Collingridge GL. A synaptic model of memory: long-term potentiation in the hippocampus. Nature. 1993; 361:31-39.
43.     Kandel ER, Schwartz JH, Jessell TM, Jessell MBT, Siegelbaum S, Hudspeth AJ. Principles of neural science. McGraw-hill New York; 2000.
44.    Martin SJ, Grimwood PD, Morris RG. Synaptic plasticity and memory: an evaluation of the hypothesis. Annu Rev Neurosci 2000; 23:649-711.
45.    Whitlock JR, Heynen AJ, Shuler MG, Bear MF. Learning induces long-term potentiation in the hippocampus. Science 2006; 313:1093-1097.
46. Arlt S. Non-Alzheimer’s disease-related memory impairment and dementia. Dialogues Clin Neurosci 2013; 15:465-473.
47.    Hosseini SM, Esfandiari E, Alaei H. Effects of frankincense aqueous extract during gestational period on increasing power of learning and memory in adult offsprings.  J Isfahan Med School 2004; 21:16-20.
48.    Hosseini Sharifabad M, Esfandiary E. A morphometeric study on CA3 hippocampal field in young rats following maternal administration of Boswellia serrata resin during gestation. Iran J Basic Med Sci 2007; 10:176-182.
49.    Sharifabad MH, Esfandiary E. The effects of maternal administration of boswellia gum resin (Frankincense) during lactation on stereological parameters of rat hippocampus. J Isfahan Med School 2012; 29:1-9.
50. Beheshti S, Shakakomi AG, Ghaedi K, Dehestani H. Frankincense upregulates the hippocampal calcium/calmodulin kinase II-α during development of the rat brain and improves memory performance. Int J Dev Neurosci 2018; 69:44-48.
51.    Kang H, Sun LD, Atkins CM, Soderling TR, Wilson MA, Tonegawa S. An important role of neural activity-dependent CaMKIV signaling in the consolidation of long-term memory. Cell 2001; 106:771-783.
52. Petersen JD, Chen X, Vinade L, Dosemeci A, Lisman JE, Reese TS. Distribution of postsynaptic density (PSD)-95 and Ca2+/calmodulin-dependent protein kinase II at the PSD. J Neurosci 2003; 23:11270-11278.
53.    Lisman J, Schulman H, Cline H. The molecular basis of CaMKII function in synaptic and behavioural memory. Nat Rev Neurosci 2002; 3:175-190.
54.    Khalaj-Kondori M, Sadeghi F, Hosseinpourfeizi MA, Shaikhzadeh-Hesari F, Nakhlband A, Rahmati-Yamchi M. Boswellia serrata gum resin aqueous extract upregulatesBDNF but not CREB expression in adult male rat hippocampus. Turk J Med Sci 2016; 46:1573-1578.
55.    Mahmoudi A, Hosseini-Sharifabad A, Monsef-Esfahani HR, Yazdinejad AR, Khanavi M, Roghani A, et al. Evaluation of systemic administration of Boswellia papyrifera extracts on spatial memory retention in male rats J Nat Med 2011;65:519-525.
56.    Begin M, Langlois M, Lorrain D, Cunnane S. Thyroid function and cognition during aging. Curr Gerontol Geriatr Res 2008; 2008:474868.
57.    Miller KJ, Parsons TD, Whybrow PC, Van Herle K, Rasgon N, Van Herle A, et al. Verbal memory retrieval deficits associated with untreated hypothyroidism. J Neuropsychiatry Clin Neurosc 2007; 19:132-136.
58. Paz-Baruch N, Leikin M, Leikin R. Visual processing and attention abilities of general gifted and excelling in mathematics students. , Charles University in Prague, Faculty of Education; ERME, Feb 2015, Prague, Czech Republic. pp.1046-1051.
59.     Hosseini M, Hadjzadeh MA-R, Derakhshan M, Havakhah S, Rassouli FB, Rakhshandeh H, et al. The beneficial effects of olibanum on memory deficit induced by hypothyroidism in adult rats tested in Morris water maze. Arch Pharm Res 2010; 33:463-468.
60. Bejar C, Wang R-H, Weinstock M. Effect of rivastigmine on scopolamine-induced memory impairment in rats. Eur J Pharmacol 1999; 383:231-240.
61.    Hosseinzadeh H, Ramezani M, Akhtar Y, Ziaei T. Effects Boswellia carterii gum resin fractions on intact memory and hyoscine-induced learning impairments in rats performing the Morris water maze task. J Medicinal Plants 2010; 2:95-101.
62.    Mahboubi M, Taghizadeh M, Talaei SA, Firozeh SMT, Rashidi AA, Tamtaji OR. Combined administration of Melissa officinalis and Boswellia serrata extracts in an animal model of memory. Iran J Psychiatry Behav Sci. 2016; 10:e681.
63.    Czerniawski J, Miyashita T, Lewandowski G, Guzowski JF. Systemic lipopolysaccharide administration impairs retrieval of context–object discrimination, but not spatial, memory: evidence for selective disruption of specific hippocampus-dependent memory functions during acute neuroinflammation. Brain Behav Immun 2015; 44:159-166.
64.    Kranjac D, McLinden KA, Deodati LE, Papini MR, Chumley MJ, Boehm GW. Peripheral bacterial endotoxin administration triggers both memory consolidation and reconsolidation deficits in mice. Brain Behav Immun 2012; 26:109-121.
65. Lehnardt S, Massillon L, Follett P, Jensen FE, Ratan R, Rosenberg PA, et al. Activation of innate immunity in the CNS triggers neurodegeneration through a Toll-like receptor 4-dependent pathway. Proc Natl Acad Sci 2003; 100:8514-8519.
66.    Zhao M, Zhou A, Xu L, Zhang X. The role of TLR4-mediated PTEN/PI3K/AKT/NF-κB signaling pathway in neuroinflammation in hippocampal neurons. Neuroscience 2014; 269:93-101.
67.    Beheshti S, Karimi B. Frankincense improves memory retrieval in rats treated with lipopolysaccharide. J Herbmed Pharmacol 2016; 5: 12-16.
68.    Dodrill CB. Neuropsychological effects of seizures. Epilepsy Behav 2004; 5:21-24.
69.    Babb TL. Axonal growth and neosynaptogenesis in human and experimental hippocampal epilepsy. Adv Neurol 1997; 72:45-51.
70.    Portavella M, Vargas J, Torres B, Salas C. The effects of telencephalic pallial lesions on spatial, temporal, and emotional learning in goldfish. Brain Res Bull 2002; 57:397-399.
71. Jalili C, Salahshoor M, Pourmotabbed A, Moradi S, Roshankhah S, Darehdori AS, et al. The effects of aqueous extract of Boswellia serrata on hippocampal region CA1 and learning deficit in kindled rats. Res Pharm Sci 2014; 9:351-358.
72.    Jalili C, Salahshoor MR, Moradi S, Pourmotabbed A, Motaghi M. The therapeutic effect of the aqueous extract of Boswellia serrata on the learning deficit in kindled rats. Int J Prev Med 2014; 5:563-568.
73.    Burger C. Region-specific genetic alterations in the aging hippocampus: implications for cognitive aging. Front Aging Neurosci 2010; 2:140.
74.    Hosseini-Sharifabad M, Kamali-Ardakani R, Hosseini-Sharifabad A. Beneficial effect of Boswellia serrata gum resin on spatial learning and the dendritic tree of dentate gyrus granule cells in aged rats. Avicenna J Phytomed 2016; 6: 189-197.
75.    Taghizadeh M, Maghaminejad F, Aghajani M, Rahmani M. The effect of tablet containing Boswellia serrata and Melisa officinalis extract on older adults’ memory: A randomized controlled trial. Arch Gerontol Geriatr 2018; 75: 146-150.
76.     Noseworthy JH, Lucchinetti C, Rodriguez M, Weinshenker BG. Multiple sclerosis. New Engl J Med 2000; 343:938-952.
77. Lopez YP, Kenis G, Rutten BP, Myint AM, Steinbusch HW, van den Hove DL. Quinolinic acid-immunoreactivity in the naïve mouse brain. J Chem Neuroanat 2016; 71:6-12.
78.    Sundaram G, Brew BJ, Jones SP, Adams S, Lim CK, Guillemin GJ. Quinolinic acid toxicity on oligodendroglial cells: relevance for multiple sclerosis and therapeutic strategies. J Neuroinflammation 2014; 11:204.
79.    Rahimi VB, Askari VR, Mehrdad A, Sadeghnia HR. Boswellia serrata has promising impact on glutamate and quinolinic acid-induced toxicity on oligodendroglia cells: in vitro study. Acta Pol Pharm 2017; 74:1803-1811.
80.    Chiaravalloti ND, DeLuca J. Cognitive impairment in multiple sclerosis. The Lancet Neurol 2008; 7:1139-1151.
81.    Mirhosseini G, Tehranipour M, Shahri NM. The synergistic effects of mixture extract Portulaca olerace, Urtica Dioica, Boswellia serrate on multiple sclerosis in rats. J Gorgan Univ Med Sci 2018; 21:57-61.
82.    Sedighi B, Pardakhty A, Kamali H, Shafiee K, Hasani BN. Effect of Boswellia papyrifera on cognitive impairment in multiple sclerosis. Iran J Neurol 2014; 13:149-153.
83. Majdinasab N, Siahpush A, Mousavinejad SK, Malayeri A, Sajedi SA, Bizhanzadeh P. Effect of Boswellia serrata on cognitive impairment in multiple sclerosis patients. J Herb Med 2016; 6: 119-127.
84.    Miniño AM, Murphy SL, Xu J, Kochanek KD. Deaths: final data for 2008. Natl Vital Stat Rep. 2011; 59:1-126.
85.    Della-Morte D, Guadagni F, Palmirotta R, Testa G, Caso V, Paciaroni M, et al. Genetics of ischemic stroke, stroke-related risk factors, stroke precursors and treatments. Pharmacogenomics 2012;13:595-613.
86. Mahajan S, Kashyap R, Sood B, Jaret P, Mokta J, Kaushik N, et al. J Assoc Physicians India 2004;52:699-702.
87.    Lai TW, Zhang S, Wang YT. Excitotoxicity and stroke: identifying novel targets for neuroprotection. Prog Neurobiol 2014; 115:157-188.
88.    Chamorro Á, Dirnagl U, Urra X, Planas AM. Neuroprotection in acute stroke: targeting excitotoxicity, oxidative and nitrosative stress, and inflammation. Lancet Neurol 2016; 15:869-881.
89.    Assimopoulou A, Zlatanos S, Papageorgiou V. Antioxidant activity of natural resins and bioactive triterpenes in oil substrates. Food Chem 2005; 92:721-727.
90.    Sadeghnia HR, Arjmand F, Ghorbani A. Neuroprotective effect of Boswellia serrata and its active constituent acetyl 11-keto-β-boswellic acid against oxygen-glucose-serum deprivation-induced cell injury. Acta Pol Pharm 2017; 74:911-920.
91.    Rajabian A, Boroushaki MT, Hayatdavoudi P, Sadeghnia HR. Boswellia serrata Protects Against Glutamate-Induced Oxidative Stress and Apoptosis in PC12 and N2a Cells. DNA Cell Biol 2016; 35:666-679.
92.    Al-Harrasi A, Ali L, Ceniviva E, Al-Rawahi A, Hussain J, Hussain H, et al. Antiglycation and antioxidant activities and HPTLC analysis of Boswellia sacra Oleogum resin: the sacred frankincense. Trop J Pharm Res 2013; 12:597-602.
93.    Afsar V, Reddy YM, Saritha K. In vitro antioxidant activity and anti-inflammatory activity of methanolic leaf extract of Boswellia serrata. Int J Life Sc Bt & Pharm Res 2012; 4:15-23.
94.    Forouzanfar F, Hosseinzadeh H, Ebrahimzadeh Bideskan A, Sadeghnia HR. Aqueous and ethanolic extracts of Boswellia serrata protect against focal cerebral ischemia and reperfusion injury in rats. Phytother Res 2016; 30:1954-1967.
95.    Rahnema M. Effect of treatment with aqueous extracts of Boswellia serrata on blood-brain barrier permeability and brain edema in experimental model of stroke in rats. Qom Univ Med Sci J 2017; 11: 56-65.
96.    Kirste S, Treier M, Wehrle SJ, Becker G, Abdel‐Tawab M, Gerbeth K, et al. Boswellia serrata acts on cerebral edema in patients irradiated for brain tumors: A prospective, randomized, placebo‐controlled, double‐blind pilot trial. Cancer 2011; 117:3788-3795.
97.    Moein P, Abbasi Fard S, Asnaashari A, Baratian H, Barekatain M, Tavakoli N, et al. The effect of Boswellia Serrata on neurorecovery following diffuse axonal injury. Brain Inj 2013; 27:1454-1460.
98.    Sheykhiyeh Golzardi Mahshid, Rezaenejad Rezvan, Kachouei Emadeddin Y, Siahposht-Khachaki Ali.  Neuroscience J Shefaye Khatam 2018; 6:64.
99.    Ding Y, Chen M, Wang M, Wang M, Zhang T, Park J, et al. Neuroprotection by acetyl-11-keto-β-boswellic acid, in ischemic brain injury involves the Nrf2/HO-1 defense pathway. Sci Rep 2014; 4:7002-7010.
100. Ding Y, Chen M, Wang M, Li Y, Wen A. Post treatment with 11-keto-β-boswellic acid ameliorates cerebral ischemia-reperfusion injury: Nrf2/HO-1 pathway as a potential mechanism. Mol Neurobiol 2015; 52:1430-1439.
101. Sayed AS, El Sayed NSED. Co-administration of 3-acetyl-11-keto-beta-boswellic acid potentiates the protective effect of celecoxib in lipopolysaccharide-induced cognitive impairment in mice: possible implication of anti-inflammatory and antiglutamatergic pathways. J Mol Neurosci 2016; 59:58-67.
102. Bishnoi M, Patil C, Kumar A, Kulkarni SK. Co-administration of acetyl-11-keto-β-boswellic acid, a specific 5-lipoxygenase inhibitor, potentiates the protective effect of COX-2 inhibitors in kainic acid-induced neurotoxicity in mice. Pharmacology 2007; 79:34-41.
103. Ding Y, Qiao Y, Wang M, Zhang H, Li L, Zhang Y, et al. Enhanced neuroprotection of acetyl-11-keto-β-boswellic acid (AKBA)-loaded O-carboxymethyl chitosan nanoparticles through antioxidant and anti-inflammatory pathways. Mol Neurobiol 2016; 53:3842-3853.
104. Sayed AS, Gomaa IEO, Bader M, El Sayed NSED. Role of 3-acetyl-11-keto-beta-boswellic acid in counteracting LPS-induced neuroinflammation via modulation of miRNA-155. Mol Neurobiol 2018; 55:5798-5808.
105. Bishnoi M, Patil C, Kumar A, Kulkarni S. Protective effects of nimesulide (COX Inhibitor), AKBA (5-LOX Inhibitor), and their combination in aging-associated abnormalities in mice. Methods Find Exp Clin Pharmacol 2005; 27:465-470.