By Dr. Nancy Maurya
Contribution participating in the INPST 2018 Science Communication Awards contest.
Neurodegeneration: An age related issue
Neurodegeneration in different forms has been an increasing health concern worldwide as the population ages and hence it has been attracting the attention of many researchers. Examples of neurodegenerative disorders include Alzheimer’s disease (AD), Parkinson’s disease (PD), etc. along with retinal neurodegenerations like age-related macular degeneration (AMD) and glaucoma. AD is irreversible brain disorder occurring due to amyloid plaque formation that is characterized by gradual loss of memory and thinking ability, while PD is a motor system affecting disease involving neuronal death due to Lewy bodies’ formation. AMD involves gradual loss of central vision due to death of macular cells of the retina while glaucoma the infamous ‘Silent thief of vision’, involves increase in the intra-ocular pressure leading to slowly progressing, permanent blindness that begins from the peripheral vision loss. The underlying causes of all these diseases are quite similar like age, oxidative stress, genetic predisposition etc. They all seem quite related to each other with common mechanism of pathogenesis, however, complete understanding of these diseases is still under research. For instance, it is quite well known fact that AD involves β-Amyloid aggregates (plaques) which is the main causative protein in its pathology but role of this protein in ocular disorders like glaucoma is still elusive. β-Amyloid has however, been suggested to be playing an important role in pathogenesis of this ocular disorder by many scientific groups.
What is β-Amyloid?
β-Amyloid, an amorphous fibrous protein molecule, is found to be expressing in brain, retina, trabecular meshwork of the eye, skin and many other organs and tissues. Its formation occurs from a transmembrane precursor called Amyloid Precursor Protein (APP) due to activity of β-secretase enzyme instead of α-secretase . There occurs an imbalance between the formation and clearance of this protein  and due to its tendency to form large insoluble aggregates with itself and with other cellular proteins, it accumulates intra- and extracellularly to form senile plaques, the characteristic feature of AD . Also, it acts as an inflammatory stimulator for the microglial cells . Thus, it is considered the main culprit in pathogenesis of AD. It is not just AD, but many other neuronal degenerations where β-Amyloid is reported to play significant role such as, neuroblastoma, prion diseases, glaucoma, PD . Hence, it becomes quite obvious that by preventing its formation or enhancing its clearance or slowing down its formation, prevention of all these diseases can be done. Further, if this prevention is mediated by some readily available plant products (like phytochemicals), then all these deteriorating diseases could be easily curbed, without actually undergoing any special treatment or taking medicines that may have side effects.
Phytochemicals: If any health elixir exists, phytochemicals must definitely be its ingredients!
Over a thousand year or two, phytochemicals present in medicinal herbs and spices are commonly used in Asia and are bringing substantial health benefits. These food additives not only give more flavors, aromas and colors but also act as agents that can prevent or even stop age related neuro-degenerative process. Each plant species is the source of many specific bioactive-compounds called phytochemicals which act as anti-oxidants, anti-inflammatory agents, and nutrients . Phytochemicals are sub-grouped in to many classes on the basis of their chemical structure such as stilbenes, carotenoids, essential oils, flavonoids, alkaloids, polyphenols etc. Common kitchen and household products like spices (turmeric, red chilli, black pepper, nutmeg, cloves, cardamom, cinnamon, coriander seeds, asafetida, fennel seeds, cumin seeds etc.) and essential oils obtained from clove, ginger, eucalyptus, neem, orange, rosemary, etc. have been reported to have variety of health benefits due to presence of phytochemicals.
What do common spices and essential oils do to β-Amyloid?
Upon considering their specific activity towards β-Amyloid in neurodegenerative disorders, many facts and figures come in to picture. For instance, it has been reported that turmeric containing curcuminoids (mixture of curcumin, demethoxycurcumin and bisdemethoxycurcumin) have acetylcholinesterase inhibitory and memory enhancing property and thus can be very effective in AD treatment . Another study done with laboratory grown cells shows that curcumin downregulates presenilin 1 protein that participates in generation of β-Amyloid . Curcumin is also reported to have anti-oxidative stress and anti-inflammatory activity along with having ability to induce structural changes in the β-Amyloid aggregates . Not only laboratory controlled experiments, but certain studies like the one involving non-demented elderly Asian subjects is a good evidence to support the notion that curcumin is good for brain function as it resulted in better cognitive performance among the subjects’ group that very often consumed turmeric containing ‘curry’ . Talking about other spices then it is well established that in addition to suppressing inflammatory pathways, cinnamon, zingiber, those belonging to pepper family and others inhibit acetylcholinesterase and aggregation of β-Amyloid . Piperine from black pepper and curcumin and related compounds have also been identified as low molecular weight compounds that can cross the blood brain barrier and exhibit anti-β-secretase activity . A research group in year 2016 reported presence of a large number of natural β-secretase inhibitors in extracts from cardamom, turmeric, long pepper, betel, Sichuan pepper, white turmeric etc. . Thus, there are numerous herbs and spices that are loaded with phytochemicals having anti-amyloidogenic activity like green tea, cinnamon, sage, ginger, ginseng and many more to count that have very high therapeutic potency against AD .
Not only spices and herbs, essential oils also have anti-AD effects that have been established using animal models, in vitro culture based studies etc. For instance, rose essential oil has been reported to significantly inhibit AD like symptoms in C. elegans and also suppressed β-Amyloid deposits, decreased its oligomers, thus alleviating cytotoxicity induced by its overexpression . Another phytochemical occurring in many essential oils like those of clove, rosemary, cannabis, milkworts etc. called caryophyllene is also reported to have therapeutic activity against AD as BV-2 microglial cells pre-treated with this compound exhibited lesser production of pro-inflammatory cytokines, COX-2, prostaglandin E2, iNOS, nitric oxide when challenged with β-Amyloid . α- and β-caryophyllene, and β-caryophyllene oxide from curry leaves also act as β-secretase (enzyme involved in β-amyloid synthesis from APP) inhibitors . Eugenol, a component of many essential oils like that of clove, nutmeg, basil, cinnamon, bay leaf etc. has been reported to block β-Amyloid induced Ca2+ uptake in PC12 cells and hence has potent anti-AD effect . A volatile oil obtained from the stems of Chinese five-flavor berry plant (Schisandra chinensis Baill.) also has AD preventive and therapeutic potential . Another rat model based study showed that essential oil of a plant called Shirazi thyme (Zataria multiflora Boiss.) found in Southwestern Asia (Pakistan, Afghanistan, Kashmir) has anti-inflammatory, anti-oxidant and anti-cholinesterase activities that are beneficial in ameliorating β-Amyloid induced cognitive deficits . Coriander essential oil upon inhalation is reported to exhibit anxiolytic and anti-depressant activities along with counteracting oxidative stress in AD, as reported in a rat model based study . Many essential oils have clinical importance due to presence of components that exhibit neuroprotective effects like Blue gum (Eucalyptus globulus), Black cumin (Nigella sativa), Peppermint (Mentha piperita), English lavender (Lavandula angustifolia), Arabian Jasmine (Jasminum sambac) and many more, and they have specific pathological targets like deposition of β-amyloid, oxidative stress, neurofibrillary tangles, etc. . Further, these oils also have protective activity against neurological diseases like anxiety, cognitive hypofunction and depression .
Phytochemicals can protect eyesight
These natural medicinal agents are effective not only in AD but also in neurodegenerative ocular diseases, however, instances of their evident activity have been far less in number than those of AD. Rhone and Basu (2008) suggested that phytochemicals (like lutein, zeaxanthin, resveratrol, green tea catechins etc.) being anti-inflammatory and anti-oxidative stress compounds can also help prevent or delay the progress of common causes of age-related blinding diseases like cataract, glaucoma and macular degeneration . Another study showed withaferin A (found in Indian winter cherry or Ashwagandha) to be a potent treatment of different gliosis-dependent central nervous system traumatic injuries and diseases including retinal gliosis in mouse model . Carotenoids have also been long known to reduce risk of cataracts, age-related macular degeneration (AMD) and photosensitivity diseases . Using palm fruit or its phytonutrient rich fractions like water soluble antioxidants provides protection against many diseases like cataract, AMD etc. . A very recent study suggests protective activity of flavonoids against AMD . Few studies have been done in evaluating the effect of essential oils against retinal diseases. For instance, Recsan et al. (2011) showed in aged rats that essential oils of nutmeg, clove, thyme and pepper can be used as therapeutic agents against AMD . Another rat model-based study showed that rosemary oil or its detergent extract combined with zinc oxide is very much effective against slowly progressing age-related ocular diseases .
All these and many more examples and our own experiences bring us to the conclusion that if we incorporate phytochemicals available naturally in a variety of forms such as spices, herbs and essential oils in our daily diet from an early age, then we can possibly protect ourselves from dementia and vision loss in later stages of life. Thus, maintaining good health and productive life using these amazing natural gifts is not difficult.
- Eteghad SS, Sabermarouf B, Majdi A, Talebi M, Farhoudi M, Mahmoudi J. Amyloid-beta: a crucial factor in Alzheimer’s disease. Medical Principles and Practice. 2014. 24, 1.
- Tarasoff-Conway JM, Carare RO, Osorio RS, et al. Clearance systems in the brain-implications for Alzheimer disease. Nat Rev Neurol. 2015;11(8):457-70.
- Hu Y, Zeng Z, Wang B, Guo S. Trans-caryophyllene inhibits amyloid β (Aβ) oligomer-induced neuroinflammation in BV-2 microglial cells. Int Immunopharmacol. 2017 Oct;51:91-98.
- Maurya N, Agarwal NR. Proceedings of the Nature Research Society, 2, 02006 (2018). doi: 10.11605/j.pnrs.201802006.
- Mirmosayyeb O, Tanhaei A, Sohrabi HR, et al. Possible Role of Common Spices as a Preventive and Therapeutic Agent for Alzheimer’s Disease. Int J Prev Med. 2017;8:5.
- Ahmed T, Gilani AH. Inhibitory effect of curcuminoids on acetylcholinesterase activity and attenuation of scopolamine-induced amnesia may explain medicinal use of turmeric in Alzheimer’s disease. Pharmacology Biochemistry and Behavior. 2009. 91(4): 554-559.
- Yoshida H, Okumura N, Nishimura Y, Kitagishi Y, Matsuda S. Turmeric and curcumin suppress presenilin 1 protein expression in Jurkat cells. Exp Ther Med. 2011;2(4):629-632.
- Mithu VS, Sarkar B, Bhowmik D, et al. Curcumin alters the salt bridge-containing turn region in amyloid β(1-42) aggregates. J Biol Chem. 2014;289(16):11122-31.
- Ng TP, Chiam PC, Lee T, Chua HC, Lim L, Kua EH. Curry consumption and cognitive function in the elderly. Am J Epidemiol. 2006 Nov 1;164(9):898-906.
- Murata K, Matsumura S, Yoshioka Y, Ueno Y, Matsuda H. Screening of β-secretase and acetylcholinesterase inhibitors from plant resources. J Nat Med. 2015. 69(1):123-9.
- Matsumura S, Murata K, Yoshioka Y, Matsuda H. Search for β-Secretase Inhibitors from Natural Spices. Nat Prod Commun. 2016. 11(4):507-10.
- Hügel HM. Brain Food for Alzheimer-Free Ageing: Focus on Herbal Medicines. Adv Exp Med Biol. 2015;863:95-116.
- Zhu S, Li H, Dong J, Yang W, Liu T, Wang Y, Wang X, Wang M, Zhi D. Rose Essential Oil Delayed Alzheimer’s Disease-Like Symptoms by SKN-1 Pathway in C. elegans. J Agric Food Chem. 2017. 65(40):8855-8865.
- Irie Y1, Keung WM. Rhizoma acori graminei and its active principles protect PC-12 cells from the toxic effect of amyloid-beta peptide. Brain Res. 2003. 963(1-2):282-9.
- Yang B, Liu B, Liu Y, Han H, Kuang H. Cognitive enhancement of volatile oil from the stems of Schisandra chinensis Baill. in Alzheimer’s disease rats. Can J Physiol Pharmacol. 2018. 96(6):550-555.
- Majlessi N, Choopani S, Kamalinejad M, Azizi Z. Amelioration of amyloid β-induced cognitive deficits by Zataria multiflora Boiss. essential oil in a rat model of Alzheimer’s disease. CNS Neurosci Ther. 2012. 18(4):295-301.
- Cioanca O, Hritcu L, Mihasan M, Trifan A, Hancianu M. Inhalation of coriander volatile oil increased anxiolytic-antidepressant-like behaviors and decreased oxidative status in beta-amyloid (1-42) rat model of Alzheimer’s disease. Physiol Behav. 2014. 131:68-74.
- Ayaz M, Sadiq A, Junaid M, Ullah F, Subhan F, Ahmed J. Neuroprotective and Anti-Aging Potentials of Essential Oils from Aromatic and Medicinal Plants. Front Aging Neurosci. 2017. 9:168.
- Rhone M, Basu A. Phytochemicals and age-related eye diseases. Nutr Rev. 2008. 66(8):465-72.
- Bargagna-Mohan P, Paranthan RR, Hamza A, et al. Withaferin A targets intermediate filaments glial fibrillary acidic protein and vimentin in a model of retinal gliosis. J Biol Chem. 2010. 285(10):7657-69.
- Mayne ST. Beta-carotene, carotenoids, and disease prevention in humans. FASEB J. 1996. 10(7):690-701.
- Wattanapenpaiboon N, Wahlqvist MW. Phytonutrient deficiency: the place of palm fruit. Asia Pac J Clin Nutr. 2003. 12(3):363-8.
- Gopinath B, Liew G, Kifley A, Flood VM, Joachim N, Lewis JR, Hodgson JM, Mitchell P. Dietary flavonoids and the prevalence and 15-y incidence of age-related macular degeneration. Am J Clin Nutr. 2018. 108(2):381-387.
- Recsan Z, Pagliuca G, Piretti MV, Penzes LG, Youdim KA, Raymond C. Noble & Stanley G. Deans. Effect of Essential Oils on the Lipids of the Retina in the Ageing Rat: A Possible Therapeutic Use. Journal of Essential Oil Research Volume 9, 1997 – Issue 1: 53-56.
- Organisciak DT, Darrow RM, Rapp CM, Smuts JP, Armstrong DW, Lang JC. Prevention of retinal light damage by zinc oxide combined with rosemary extract. Mol Vis. 2013;19:1433-45.
Keywords: spicy-flavored and colorful platter, health of brain and eyesight, age-related macular degeneration, eugenol, piperine, curcuminoids, turmeric, phytochemicals, β-amyloid, Alzheimer’s disease (AD), glaucoma, neurodegeneration.
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