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Current Psychopharmacology

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ISSN (Print): 2211-5560
ISSN (Online): 2211-5579

Research Article

Co-administration of Saffron and Chamomile Give Additive Effects of Antidiabetic and Antioxidant Activity with In vivo Augmentation of Brain BDNF, Acetylcholine Levels and Cognitive Functions in Streptozotocininduced Diabetic Rats

Author(s): Saara Ahmad*, Asra Khan, Saiqa Tabassum, Zehra Batool, Saad Bilal Ahmed, Saima Khaliq, Akash Kumar Ahuja, Amrah Hashmi, Hamna Rafiq and Saida Haider

Volume 11, Issue 1, 2022

Published on: 30 November, 2021

Article ID: e060921196196 Pages: 14

DOI: 10.2174/2211556010666210906153253

Price: $65

Abstract

Background: Diabetes mellitus refers to comorbidities associated with reduced release of the brain-derived neurotropic factor and disruption in the metabolism of neurotransmitters leading to depression and cognitive impairment. Allopathic medications are available for the treatment of diabetes, but there is no cure and multiple adverse effects adhere to it. The therapeutic effects of co-administered chamomile with saffron may reverse diabetes and its complications. Co-administration of chamomile and saffron is effective against diabetes and related complications.

Methods: The present study sought to test the hypothesis, conducted on eighty Sprague-Dawley rats randomly divided into eight groups (n=10), including healthy controls, diabetic controls, methanolic extract treatment groups and water decoction treatment groups with respective dosage once a day for two weeks. The dose of a single herb group in methanolic extract and water decoction was saffron 10 mg/kg and chamomile 30 mg/kg, while co-administered groups received both herbs in half doses, saffron 5 mg/kg and chamomile 15 mg/kg. Two widely used tests for the assessment of memory (elevated plus maze and novel object recognition) were used to assess the mood and memory (cognitive) performance after the treatment.

Results: It was observed that all treatment groups exhibited antidiabetic effects with improved mood and enhanced memory, high antioxidant profile, increased brain-derived neurotropic factor and acetylcholine concentration. However, the effects were greater in the co-administered groups of saffron and chamomile, especially the combined water decoction group.

Conclusion: The study provides the successful results of co-administration of chamomile and saffron to alleviate diabetes and related complications.

Keywords: Acetylcholine, antioxidant profile, brain derived neurotropic factor, chamomile, cognition, diabetes mellitus, saffron.

Graphical Abstract
[1]
Warraich HJ, Rana JS. Dyslipidemia in diabetes mellitus and cardiovascular disease. Cardiovasc Endocrinol 2017; 6(1): 27-32.
[http://dx.doi.org/10.1097/XCE.0000000000000120] [PMID: 31646116]
[2]
Doroodgar M, Doroodgar M, Tofangchiha S. Evaluation of relation between HbA1c Level with cognitive disorders and depression in type 2 diabetes mellitus patients. Maced J Med Sci 2019; 7(15): 2462-6.
[http://dx.doi.org/10.3889/oamjms.2019.658] [PMID: 31666848]
[3]
Grotle AK, Stone AJ. Exaggerated exercise pressor reflex in type 2 diabetes: potential role of oxidative stress. Auton Neurosci 2019; 222: 102591.
[http://dx.doi.org/10.1016/j.autneu.2019.102591] [PMID: 31669797]
[4]
Rorbach-Dolata A, Piwowar A. Neurometabolic evidence supporting the hypothesis of increased incidence of type 3 diabetes mellitus in the 21st century. BioMed Res Int 2019; 2019: 1435276.
[http://dx.doi.org/10.1155/2019/1435276] [PMID: 31428627]
[5]
Haider S, Sajid I, Batool Z, et al. Supplementation of taurine insulates against oxidative stress, confers neuroprotection and attenuates memory impairment in noise stress exposed male wistar rats. Neurochem Res 2020; 45(11): 2762-74.
[http://dx.doi.org/10.1007/s11064-020-03127-7] [PMID: 32918662]
[6]
Chan CB, Ahuja P, Ye K. Developing insulin and BDNF mimetics for diabetes therapy. Curr Top Med Chem 2019; 19(24): 2188-204.
[http://dx.doi.org/10.2174/1568026619666191010160643] [PMID: 31660832]
[7]
Eyileten C, Kaplon-Cieslicka A, Mirowska-Guzel D, Malek L, Postula M. Antidiabetic effect of brain-derived neurotrophic factor and its association with inflammation in type 2 diabetes mellitus. J Diabetes Res 2017; 2017: 2823671.
[http://dx.doi.org/10.1155/2017/2823671] [PMID: 29062839]
[8]
Luo C, Ke Y, Yuan Y, et al. A novel herbal treatment reduces depressive-like behaviors and increases brain-derived neurotrophic factor levels in the brain of type 2 diabetic rats. Neuropsychiatr Dis Treat 2016; 12: 3051-9.
[http://dx.doi.org/10.2147/NDT.S117337] [PMID: 27942216]
[9]
Roopan S, Larsen ER. Use of antidepressants in patients with depression and comorbid diabetes mellitus: a systematic review. Acta Neuropsychiatr 2017; 29(3): 127-39.
[http://dx.doi.org/10.1017/neu.2016.54] [PMID: 27776567]
[10]
M Tata A, Velluto L, D'Angelo C, Reale M. Cholinergic system dysfunction and neurodegenerative diseases: cause or effect?. CNS Neurol Disord Drug Targets 2014; 13(7): 1294-303.
[11]
Jope RS. High affinity choline transport and acetylCoA production in brain and their roles in the regulation of acetylcholine synthesis. Brain Res 1979; 180(3): 313-44.
[http://dx.doi.org/10.1016/0165-0173(79)90009-2] [PMID: 394816]
[12]
Wang HR, Woo YS, Bahk WM. Ineffectiveness of nicotinic acetylcholine receptor antagonists for treatment-resistant depression: a meta-analysis. Int Clin Psychopharmacol 2016; 31(5): 241-8.
[http://dx.doi.org/10.1097/YIC.0000000000000128] [PMID: 26982579]
[13]
Strelitz J, Engel LS, Keifer MC. Blood acetylcholinesterase and butyrylcholinesterase as biomarkers of cholinesterase depression among pesticide handlers. Occup Environ Med 2014; 71(12): 842-7.
[http://dx.doi.org/10.1136/oemed-2014-102315] [PMID: 25189163]
[14]
Mineur YS, Cahuzac EL, Mose TN, et al. Interaction between noradrenergic and cholinergic signaling in amygdala regulates anxiety- and depression-related behaviors in mice. Neuropsychopharmacology 2018; 43(10): 2118-25.
[http://dx.doi.org/10.1038/s41386-018-0024-x] [PMID: 29472646]
[15]
Schubert M, Gautam D, Surjo D, et al. Role for neuronal insulin resistance in neurodegenerative diseases. Proc Natl Acad Sci USA 2004; 101(9): 3100-5.
[http://dx.doi.org/10.1073/pnas.0308724101] [PMID: 14981233]
[16]
Kleinridders A, Cai W, Cappellucci L, et al. Insulin resistance in brain alters dopamine turnover and causes behavioral disorders. Proc Natl Acad Sci USA 2015; 112(11): 3463-8.
[http://dx.doi.org/10.1073/pnas.1500877112] [PMID: 25733901]
[17]
Selivanov VA, Votyakova TV, Pivtoraiko VN, et al. Reactive oxygen species production by forward and reverse electron fluxes in the mitochondrial respiratory chain. PLOS Comput Biol 2011; 7(3): e1001115.
[http://dx.doi.org/10.1371/journal.pcbi.1001115] [PMID: 21483483]
[18]
Mani V, Jaafar SM, Azahan NSM, et al. Ciproxifan improves cholinergic transmission, attenuates neuroinflammation and oxidative stress but does not reduce amyloid level in transgenic mice. Life Sci 2017; 180: 23-35.
[http://dx.doi.org/10.1016/j.lfs.2017.05.013] [PMID: 28501482]
[19]
David DJ, Gourion D. Antidepressant and tolerance: determinants and management of major side effects. Encephale 2016; 42(6): 553-61.
[http://dx.doi.org/10.1016/j.encep.2016.05.006] [PMID: 27423475]
[20]
Bailey CJ, Day C. Metformin: its botanical background. Pract Diabetes Int 2004; 21(3): 115-7.
[http://dx.doi.org/10.1002/pdi.606]
[21]
Yeung KSHM, Hernandez M, Mao JJ, Haviland I, Gubili J. Herbal medicine for depression and anxiety: a systematic review with assessment of potential psycho-oncologic relevance. Phytother Res 2018; 32(5): 865-91.
[http://dx.doi.org/10.1002/ptr.6033] [PMID: 29464801]
[22]
Franco EPD, Contesini FJ, Lima da Silva B, et al. Enzyme-assisted modification of flavonoids from Matricaria chamomilla: antioxidant activity and inhibitory effect on digestive enzymes. J Enzyme Inhib Med Chem 2020; 35(1): 42-9.
[http://dx.doi.org/10.1080/14756366.2019.1681989] [PMID: 31656110]
[23]
Ortiz MI, Fernández-Martínez E, Soria-Jasso LE, et al. Isolation, identification and molecular docking as cyclooxygenase (COX) inhibitors of the main constituents of Matricaria chamomilla L. extract and its synergistic interaction with diclofenac on nociception and gastric damage in rats. Biomed Pharmacother 2016; 78: 248-56.
[http://dx.doi.org/10.1016/j.biopha.2016.01.029] [PMID: 26898449]
[24]
Mao JJ, Xie SX, Keefe JR, Soeller I, Li QS, Amsterdam JD. Long-term chamomile (Matricaria chamomilla L.) treatment for generalized anxiety disorder: A randomized clinical trial. Phytomedicine 2016; 23(14): 1735-42.
[http://dx.doi.org/10.1016/j.phymed.2016.10.012] [PMID: 27912875]
[25]
Moshiri M, Vahabzadeh M, Hosseinzadeh H. Clinical applications of saffron (Crocus sativus) and its constituents: a review. Drug Res (Stuttg) 2015; 65(6): 287-95.
[PMID: 24848002]
[26]
Hosseini A, Razavi BM, Hosseinzadeh H. Pharmacokinetic properties of saffron and its active components. Eur J Drug Metab Pharmacokinet 2018; 43(4): 383-90.
[http://dx.doi.org/10.1007/s13318-017-0449-3] [PMID: 29134501]
[27]
Lopresti AL, Drummond PD. Saffron (Crocus sativus) for depression: a systematic review of clinical studies and examination of underlying antidepressant mechanisms of action. Hum Psychopharmacol 2014; 29(6): 517-27.
[http://dx.doi.org/10.1002/hup.2434] [PMID: 25384672]
[28]
Bankova V. Recent trends and important developments in propolis research. Evid Based Complement Alternat Med 2005; 2(1): 29-32.
[http://dx.doi.org/10.1093/ecam/neh059] [PMID: 15841275]
[29]
Nazari Parchestani Z, Rafieirad M. The effect of herniarin on anxiety‎ behaviors and depression following‎ chronic cerebral ischemia‎ hypoperfusion in male rats. Experim Animal Biol 2021; 9(3): 93-103.
[30]
Qin T, Fang F, Song M, Li R, Ma Z, Ma S. Umbelliferone reverses depression-like behavior in chronic unpredictable mild stress-induced rats by attenuating neuronal apoptosis via regulating ROCK/Akt pathway. Behav Brain Res 2017; 317: 147-56.
[http://dx.doi.org/10.1016/j.bbr.2016.09.039] [PMID: 27646771]
[31]
Liu J, Fang Y, Yang L, Qin X, Du G, Gao X. A qualitative, and quantitative determination and pharmacokinetic study of four polyacetylenes from Radix Bupleuri by UPLC-PDA-MS. J Pharm Biomed Anal 2015; 111: 257-65.
[http://dx.doi.org/10.1016/j.jpba.2015.04.002] [PMID: 25912847]
[32]
Meng S, Cao J, Feng Q, Peng J, Hu Y. Roles of chlorogenic Acid on regulating glucose and lipids metabolism: a review. Evid Based Complement Alternat Med 2013; 2013: 801457.
[http://dx.doi.org/10.1155/2013/801457] [PMID: 24062792]
[33]
Murtaza G, Karim S, Akram MR, et al. Caffeic acid phenethyl ester and therapeutic potentials. BioMed Res Int 2014; 2014: 145342.
[http://dx.doi.org/10.1155/2014/145342] [PMID: 24971312]
[34]
Demmig-Adams B, López-Pozo M, Stewart JJ, Adams WW III. Zeaxanthin and lutein: Photoprotectors, anti-inflammatories, and brain food. Molecules 2020; 25(16): 3607.
[http://dx.doi.org/10.3390/molecules25163607] [PMID: 32784397]
[35]
Salehi B, Venditti A, Sharifi-Rad M, et al. The therapeutic potential of apigenin. Int J Mol Sci 2019; 20(6): 1305.
[http://dx.doi.org/10.3390/ijms20061305] [PMID: 30875872]
[36]
Abdalla FH, Schmatz R, Cardoso AM, et al. Quercetin protects the impairment of memory and anxiogenic-like behavior in rats exposed to cadmium: possible involvement of the acetylcholinesterase and Na(+),K(+)-ATPase activities. Physiol Behav 2014; 135: 152-67.
[http://dx.doi.org/10.1016/j.physbeh.2014.06.008] [PMID: 24952260]
[37]
Ghafarzadeh S, Hobbenaghi R, Tamaddonfard E, Farshid AA, Imani M. Crocin exerts improving effects on indomethacin-induced small intestinal ulcer by antioxidant, anti-inflammatory and anti-apoptotic mechanisms. Vet Res Forum 2019; 10(4): 277-84.
[PMID: 32206222]
[38]
Christodoulou E, Kadoglou NP, Kostomitsopoulos N, Valsami G. Saffron: a natural product with potential pharmaceutical applications. J Pharm Pharmacol 2015; 67(12): 1634-49.
[http://dx.doi.org/10.1111/jphp.12456] [PMID: 26272123]
[39]
Rezaee R, Hosseinzadeh H. Safranal: from an aromatic natural product to a rewarding pharmacological agent. Iran J Basic Med Sci 2013; 16(1): 12-26.
[PMID: 23638289]
[40]
Shewale PB, Patil RA, Hiray YA. Antidepressant-like activity of anthocyanidins from Hibiscus rosa-sinensis flowers in tail suspension test and forced swim test. Indian J Pharmacol 2012; 44(4): 454-7.
[http://dx.doi.org/10.4103/0253-7613.99303] [PMID: 23087504]
[41]
Park SH, Sim YB, Han PL, Lee JK, Suh HW. Antidepressant-like effect of Kaempferol and Quercitirin, Isolated from Opuntia ficus-indica var. saboten. Exp Neurobiol 2010; 19(1): 30-8.
[http://dx.doi.org/10.5607/en.2010.19.1.30] [PMID: 22110339]
[42]
Dhingra D, Bansal Y. Antidepressant-like activity of beta-carotene in unstressed and chronic unpredictable mild stressed mice. J Funct Foods 2014; 7: 425-34.
[http://dx.doi.org/10.1016/j.jff.2014.01.015]
[43]
Elango P, Asmathulla S, Kavimani S. Lycopene treatment transposed antidepressant-like action in rats provoked to chronic mild stress. Biomed Pharmacol J 2019; 12(2): 981-8.
[http://dx.doi.org/10.13005/bpj/1725]
[44]
Liang Y, Yang X, Zhang X, et al. Antidepressant-like effect of the saponins part of ethanol extract from SHF. J Ethnopharmacol 2016; 191: 307-14.
[http://dx.doi.org/10.1016/j.jep.2016.06.044] [PMID: 27321411]
[45]
Yang Z, Scott CA, Mao C, Tang J, Farmer AJ. Resistance exercise versus aerobic exercise for type 2 diabetes: a systematic review and meta-analysis. Sports Med 2014; 44(4): 487-99.
[http://dx.doi.org/10.1007/s40279-013-0128-8] [PMID: 24297743]
[46]
Samarghandian S, Azimi-Nezhad M, Samini F. Ameliorative effect of saffron aqueous extract on hyperglycemia, hyperlipidemia, and oxidative stress on diabetic encephalopathy in streptozotocin induced experimental diabetes mellitus. BioMed Res Int 2014; 2014: 920857.
[http://dx.doi.org/10.1155/2014/920857] [PMID: 25114929]
[47]
Geromichalos GD, Lamari FN, Papandreou MA, et al. Saffron as a source of novel acetylcholinesterase inhibitors: molecular docking and in vitro enzymatic studies. J Agric Food Chem 2012; 60(24): 6131-8.
[http://dx.doi.org/10.1021/jf300589c] [PMID: 22655699]
[48]
Misra HP, Fridovich I. The role of superoxide anion in the autoxidation of epinephrine and a simple assay for superoxide dismutase. J Biol Chem 1972; 247(10): 3170-5.
[http://dx.doi.org/10.1016/S0021-9258(19)45228-9] [PMID: 4623845]
[49]
Gwarzo MY, Ahmadu JH, Ahmad MB, Dikko AU. Serum glucose and malondialdehyde levels in alloxan induced diabetic rats supplemented with methanolic extract of Tacazzea apiculata. Int J Biomed Sci 2014; 10(4): 236-42.
[PMID: 25598753]
[50]
Hestrin S. The reaction of acetylcholine and other carboxylic acid derivatives with hydroxylamine, and its analytical application. J Biol Chem 1949; 180(1): 249-61.
[http://dx.doi.org/10.1016/S0021-9258(18)56740-5] [PMID: 18133390]
[51]
Ellman GL, Courtney KD, Andres V Jr, Feather-Stone RM. A new and rapid colorimetric determination of acetylcholinesterase activity. Biochem Pharmacol 1961; 7(2): 88-95.
[http://dx.doi.org/10.1016/0006-2952(61)90145-9] [PMID: 13726518]
[52]
Haider S, Saleem S, Perveen T, et al. Age-related learning and memory deficits in rats: role of altered brain neurotransmitters, acetylcholinesterase activity and changes in antioxidant defense system. Age (Dordr) 2014; 36(3): 9653.
[http://dx.doi.org/10.1007/s11357-014-9653-0] [PMID: 24771014]
[53]
Haider S, Tabassum S, Perveen T. Scopolamine-induced greater alterations in neurochemical profile and increased oxidative stress demonstrated a better model of dementia: A comparative study. Brain Res Bull 2016; 127: 234-47.
[http://dx.doi.org/10.1016/j.brainresbull.2016.10.002] [PMID: 27725168]
[54]
Liaquat L, Ahmad S, Sadir S, et al. Development of AD like symptoms following co-administration of AlCl3 and D-gal in rats: A neurochemical, biochemical and behavioural study. Pak J Pharm Sci 2017; 30(2(Suppl.)(Suppl. 2): 647-53.
[PMID: 28650335]
[55]
Faridi S, Delirezh N, Abtahi Froushani SM. Beneficial effects of hydroalcoholic extract of saffron in alleviating experimental autoimmune diabetes in C57bl/6 mice. Iran J Allergy Asthma Immunol 2019; 18(1): 38-47.
[http://dx.doi.org/10.18502/ijaai.v18i1.629] [PMID: 30848572]
[56]
Benfante R, Di Lascio S, Cardani S, Fornasari D. Acetylcholinesterase inhibitors targeting the cholinergic anti-inflammatory pathway: a new therapeutic perspective in aging-related disorders. Aging Clin Exp Res 2021; 33(4): 823-34.
[http://dx.doi.org/10.1007/s40520-019-01359-4] [PMID: 31583530]
[57]
Nunes PV, Nascimento CF, Kim HK, et al. Low brain-derived neurotrophic factor levels in post-mortem brains of older adults with depression and dementia in a large clinicopathological sample. J Affect Disord 2018; 241: 176-81.
[http://dx.doi.org/10.1016/j.jad.2018.08.025] [PMID: 30125821]
[58]
Fathimoghadam H, Farbod Y, Ghadiri A, Fatemi R. Moderating effects of crocin on some stress oxidative markers in rat brain following demyelination with ethidium bromide. Heliyon 2019; 5(2): e01213.
[http://dx.doi.org/10.1016/j.heliyon.2019.e01213] [PMID: 30815598]
[59]
Kianbakht S, Mozafari K. Effects of saffron and its active constituents, crocin and safranal, on prevention of indomethacin induced gastric ulcers in diabetic and nondiabetic rats. Faslnamah-i Giyahan-i Daruyi 2009; 8(5)(Suppl.): 30-8.
[60]
Danciu C, Zupko I, Bor A, et al. Botanical therapeutics: Phytochemical screening and biological assessment of chamomile, parsley and celery extracts against a375 human melanoma and dendritic cells. Int J Mol Sci 2018; 19(11): 3624.
[http://dx.doi.org/10.3390/ijms19113624] [PMID: 30453564]
[61]
Cvetanović A, Švarc-Gajić J, Zeković Z, et al. Comparative analysis of antioxidant, antimicrobiological and cytotoxic activities of native and fermented chamomile ligulate flower extracts. Planta 2015; 242(3): 721-32.
[http://dx.doi.org/10.1007/s00425-015-2308-2] [PMID: 25976264]
[62]
Al-Ismail KM. ATAaowaaeocf, anise seeds and dill seeds. J Sci Food Agric 2004; 84: 173-8.
[63]
Bhaskaran N, Shukla S, Kanwal R, Srivastava JK, Gupta S. Induction of heme oxygenase-1 by chamomile protects murine macrophages against oxidative stress. Life Sci 2012; 90(25-26): 1027-33.
[http://dx.doi.org/10.1016/j.lfs.2012.05.019] [PMID: 22683429]
[64]
Sanati S, Razavi BM, Hosseinzadeh H. A review of the effects of Capsicum annuum L. and its constituent, capsaicin, in metabolic syndrome. Iran J Basic Med Sci 2018; 21(5): 439-48.
[PMID: 29922422]
[65]
Dourado NS, Souza CDS, de Almeida MMA, et al. Neuroimmunomodulatory and neuroprotective effects of the flavonoid apigenin in in vitro models of neuroinflammation associated with Alzheimer’s disease. Front Aging Neurosci 2020; 12: 119.
[http://dx.doi.org/10.3389/fnagi.2020.00119] [PMID: 32499693]
[66]
Khan H, Marya , Amin S, Kamal MA, Patel S. Flavonoids as acetylcholinesterase inhibitors: Current therapeutic standing and future prospects. Biomed Pharmacother 2018; 101: 860-70.
[http://dx.doi.org/10.1016/j.biopha.2018.03.007] [PMID: 29635895]

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