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Research J. Pharm. and Tech. 12(6): June 2019
1
ISSN 0974-3618 (Print) www.rjptonline.org
0974-360X (Online)
RESEARCH ARTICLE
Vanilla- Natural Vs Artificial: A Review
Vijayalakshmi. S , Disalva. X, Chittaranjan Srivastava, Arun A*
School of Hotel and Catering Management, Vels Institute of Science, Technology and Advanced Studies
(VISTAS), Chennai, India
*Corresponding Author E-mail: arunarticle2016@gmail.com
ABSTRACT:
Natural and artificial flavours are identical. Natural flavours made by extracting chemicals from natural
ingredients, artificial flavours are made by creating the same chemical compositions synthetically. The most
popular flavouring compound - Vanilla, can find its application in food and beverage industry, perfume and
pharmaceutical industries. This review features natural vanilla flavouring from the vanilla bean. The extraction
process, chemical constituents and health benefits are emphasised. Culinary uses of vanilla flavouring are
analysed. Production of artificial/synthetic vanillin and its health impact is also highlighted. Food and Drug
Administration rules have been discussed. From this context consumer awareness and understanding are
significant towards the difference between artificial and natural vanilla flavouring and their associated benefits,
which help them to make the right decisions for their well being.
KEYWORDS: Flavour, Natural Vanilla, Artificial Vanillin, Culinary Uses, Health benefits and Impact, Food
and Drug Administration.
INTRODUCTION:
Flavour plays a key role in the acceptance or rejection of
food1. The most popular flavouring compound - Vanilla,
can find its application in food and beverage industry,
perfume and pharmaceutical industries2,3. ‘Vanilla’ is
derived from Spanish, meaning sheath or pod and ‘illa’,
conveys little (i.e.) a vine yielding small pods.
Vanilla pods are macerated and percolated in a solution
of ethanol and water and thus vanilla extract is obtained.
The compounds, oil and aroma in vanilla beans are
extracted from the plant genus planifolia. Vanilla flavour
is an indispensable ingredient in many bakery and
confectionary products, custards, ice creams, and
puddings4.
The objectives of this article are to differentiate between
natural as opposed to artificial vanilla flavour additive.
Culinary uses of vanilla flavour are discussed and also
chemical additives in synthetic vanillin are listed out in
this review.
Received on 12.10.2018 Modified on 17.11.2018
Accepted on 18.12.2018 © RJPT All right reserved
Research J. Pharm. and Tech. 2019; 12(6):
DOI:
Acceptable Daily Intake (ADI) and Food and Drug
Administration rules are mentioned. Also to high light
whether vanillin extracted from nature is safer or
artificial made vanillin is safer.
Natural vanilla flavourings:
Natural Vanilla flavour is obtained from total of 110
species of plant genus Vanilla which belongs to the
family Orchidaceous, a tropical hiking orchid. Vanilla
planifolia and Vanilla tahitensus are two species from
this genus have been approved in most countries,
however because of its pod quality and yield, Vanillus
planifolia is widely recommended. The flavour and
aroma of vanilla extract is due to the presence of vanillin
(4-hydroxy-3-methoxybenzaldehyde). The species of
Vanilla Planifolia having a highest vanillin content
comparatively with the species Vanill tahitensi5
Cultivation of Vanilla:
Indonesia and Madagascar are the largest producers of V.
Planifolia. The influx of Spaniards in Mexico and the
discovery of artificial pollination techniques, V.
planifolia cultivation is possible in many tropical
climates 6.
USA, Germany, France and Netherland are the main
consumers of vanilla. The demand for natural vanillin
increases in the international market year after year.
Vanilla is originated from South East Mexico but above
Research J. Pharm. and Tech. 12(6): June 2019
2
90 per cent of vanilla production comes from the Indian
Ocean Island nations, Indonesia and Madagascar7.
India entered the international vanilla market during a
crisis due to shortage of supply from Madagascar and
resulting price rise. Now in India, vanilla cultivation has
become a major activity for farmers in Tamil Nadu,
Karnataka and Kerala4, 8 and 9.
Types of vanilla beans:
Bourbon-Madagascar, Mexican and Tahitian are the
3major types of vanilla. The Bourbon-Madagascar
vanilla is featured with thin pod, a rich and sweetest
flavour. Mexican vanilla tastes smooth and rich, while
Tahitian vanilla has the thickest and darkest-coloured
pod that’s aromatic with less flavour comparitively10.
Bourbon Vanilla:
Bourbon vanilla is long and slim pod, with a rich and
sweet flavour. It has a thick, strong vanilla notes and
contain a large quantity of tiny seeds. Bourbon Vanilla is
a generic term for Vanilla planifolia10 and 11.
Mexican vanilla:
The flavour of Mexican vanilla has a mellower, smooth,
quality and a spicy, woody fragrance. Their robust
flavour is great for rich baked goods, sauces, ice cream,
sweet breads, custard, cheesecake and other desserts12.
Tahitian vanilla:
Tahitian vanilla is rare species from France Polynesia.
These beans are more subtle than Madagascar beans
comparatively. Rather than being sweet and strong,
Tahitian vanilla beans are usually blended with ice
creams, custards and fruit-based desserts. Tahitian
vanilla beans are used in cold foods. The essential oil
from Tahitian vanilla beans is blended into perfumes and
soaps and imparted its flavour. Tahitian vanilla beans are
so subtle when added to body fragrances13.
A. Bourbon Vanilla B. Mexican Vanilla C. Tahitian Vanilla
Fig. 1: Types of vanilla beans
A. Bourbon Vanilla Essence B. Mexican Vanilla Essence C.
Tahitian Vanilla Essence
Fig. 2: Types of vanilla essence
Curing of Vanilla beans:
Freshly planted vanilla beans have no flavour or aroma.
The curing of harvested vanilla pods are involved four
steps-
Killing:
Vanilla pods are dipped in hot water (63 to 65oC) for
three minutes and retarded the vegetative tissues growth
of pods. The enzymatic reaction is initiated and the
aroma is developed by killing process. Heating in an
oven and/or exposing the bean in direct sun light are few
other methods to kill the pods.
Sweating:
The pods are wrapped in woollen clothes to maintain the
temperature (4565 °C) of beans and alternate this is
stored in air tight wooden boxes during night. This is
exposed to sun during day time and continued for nearly
10 days. Thus, the moisture is maintained between 60
and 70% by weight.
Drying:
The beans are dried in a wooden rack at room
temperature for three to four weeks that results
considerable reduction of bean weight up to one third
(25 -30%) of the actual. The beans become flexible and
stretchy by drying process.
Conditioning:
The beans are stored in closed boxes for five to six
months and this process is called conditioning. The
processed beans are sorted and graded, bundled and
wrapped in paraffin paper and preserved till the required
quality of bean is achieved, especially flavour and
aroma14.
Constituents and odour of Natural Vanilla:
The compounds present in vanilla extract determine the
aroma. The other non-volatile constituents like tannins,
polyphenols, free amino acids and resins which impart
the aroma to vanilla 15.
An extract contains resins retain aromatic compounds for
longer. Volatile constituents such as acids, ethers,
alcohols, acetals, heterocyclics, phenolics, hydrocarbons,
esters and carbonyls are influencing the aroma and
flavour of vanilla16. Many other compounds- vanillin, p-
hydroxybenzaldehyde, guaiacol, and anise alcohol are
important for the aroma profile of vanilla. Each vanilla
bean only contains around 3% - 5% vanillin by its
volume. However, vanillin signifies for about 25% of the
total flavour and fragrance experience of genuine vanilla
extract and remaining 75% are the organic compounds
found in real vanilla beans. This is the major difference
between extract and essence. But the bean extract
contains three other major components, vanillic acid, 4-
hydroxybenzoic acid, and 4-hydroxybenzaldehyde,
which account for 17 percent (by weight) of the flavor
Research J. Pharm. and Tech. 12(6): June 2019
3
chemicals that make up vanilla17.
In view of various volatile compounds reported in
vanilla extract, vanillin is the single most characteristic
component of flavour. Bioactive properties and because
of advancements in chemistry and pharmacology, most
of the earlier uses of vanilla have given way to
functional uses of vanillin, vanilla’s main constituent3 and
18.
Vanillin 4- hydro benzaldehyde 4-hydroxybenzoic vanillin acid
Fig. 3: Constituents of natural vanilla
Canadian regulations:
According to Food and Drug Regulations (C.R.C., c.
870)19, vanilla extract products are to be
processed/produced from vanilla beans (Vanilla
planifolia or Vanilla tahitensia). In 100 ml of extract, it
must have an amount of soluble substances that
proportional to their natural state available for extract.
Specifically, if the beans contain lesser than 25% water
content, the vanilla extract must consist of at least 10 g
of vanilla beans; if the beans contain more than 25%
water content, the vanilla extract must consist of at least
7.5 g of vanilla beans. Any other colour should not be
found in vanilla extract.
Culinary Uses of Vanilla:
The most significant flavouring component in many
baked items and custards is found vanilla that adds its
taste. Vanilla is adding creaminess in sauces, balancing
sweetness in desserts, and also adding flavour to tea,
toning or masking bitterness and acidity20. Vanilla
extract is not only delicious in many bakery products and
other includes beverages like milkshakes, flavouring
drinks and yogurt for a better flavour. Vanilla exhibits
antioxidant and antimicrobial activity thus acting as a
food preservative21 and 22.
Health Benefits of Vanilla Extract:
Vanilla bean extract is richer when compare to the
artificial and they are not only for their aroma and taste,
but these beans in fact have unbelievable health benefits.
Helps to treat infection:
The active compounds present in the plant Vanilla
such as vanillin and Isoeugenol known to have anti-
filarial property23.
Antioxidant activity:
Antioxidants found in natural vanilla extract are
vanillic acid and vanillin, that protects the body from
harmful components, such as free radicals and toxins.
These antioxidants are used to preserve food and
health supplements as nutraceuticals22.
Antimicrobial activity:
The active ingredients of the vanilla extract in
Vanilla planifolia are flavonoid and alkaloid in
nature. All the parts of this plant can be a potential
source for evolving newer antimicrobial
compounds24.
Anti-inflammatory activity:
Vanilla extract has anti-inflammatory abilities and
preserves liver health25.
Antinociceptive effect:
A study conducted by Vanillin is known to have
antinociceptive agent26.
The Problem with Natural Vanilla Production:
Vanilla is a very difficult to cultivate as basically it
requires 600 hands for pollination to produce one kg of
cured beans. The processing of the beans involves
crucial and time consuming to evaluate their aroma and
inspect the quality of each bean27. Farmer’s income is
escalating from vanilla by attaining valuable
certifications such as organic, fair-trade, and Rainforest
Alliance Certification. Perhaps it is difficult to plant
more orchids since their area of farms are often quite
miniature and the maturation process takes four years for
the vines28.
Hence food markets face a huge shortage of the vanilla.
Food makers, meanwhile, are confronting skyrocketing
costs for natural vanilla29. To meet the growing demand,
food brands have to introduce synthetic vanillin to the
market.
Synthetic Vanillin:
Synthetic vanillin is an alternate and chemical form for
natural vanilla which is made from petrochemicals and
by products from the paper industry. This synthetic
vanillin is a nature identical vanilla. It is commonly used
to reduce production costs. Since it’s cheap, available
everywhere and vanilla flavoured over-the-counter
medicines, beverages, and cookies are found. Thus
synthetic vanillin is able to satisfy the demands of the
vanillin consumers2 and 30.
Both natural and synthetic vanilla contains the same
major flavour chemical, vanillin. Natural vanilla has a
much richer mouth feel and aroma compared with
‘vanilla essence’ or ‘synthetic vanilla’ as it only contains
Research J. Pharm. and Tech. 12(6): June 2019
4
synthetically derived ‘vanillin’ hence the lack of diverse
flavours28.
There are two types of synthetic vanillin- 1. lignin-based
and guaiacol based. The lignin-based vanillin is made
from wood pulp, has a richer flavour. The guaiacol based
vanillin is more cost effective flavour to the shortage of
vanilla flavouring31.
Synthetic Vanillin Contains Chemical Additives:
Synthetic vanillin flavouring is due to its chemical,
lignin vanillin which mimics the flavour of natural
extract from real vanilla. The first commercial synthesis
of vanillin starts with the more readily available natural
compound is eugenol. Lignin vanillin is obtained from
wastes produced in the paper manufacturing industry.
Some vanilla flavouring also contains glycerine or a
glycol base32 and 18.
Ethyl Vanillin:
Ethyl vanillin is also an artificial chemical that tastes like
vanilla. Ethyl vanillin, or 3-ethoxy-4-
hydroxybenzaldehyde, is 3-4 times as potent as vanillin
and can be used to increase the aroma and flavour of an
extract. Ethyl vanillin is a chemically synthesized
flavouring agent related to vanillin or artificial vanilla. It
is three times as strong as artificial vanillin and acts as
an imitation vanilla. In the preparation of edible flavour,
ethyl vanillin can be used instead of vanillin. Ethyl
vanillin appears as a white to light yellow needle crystal
or crystalline powder. It has an aroma similar to vanilla
beans, but it is more concentrated than vanillin. Ethyl
vanillin can be used to flavouring chocolates, candies,
biscuits, beverages and ice creams33.
Fig. 4: Ethyl vanillin
Health Impact of Synthetic vanillin:
A negligible amounts of neurotoxins contained in
vanillin are capable of killing brain cells24. Ethyl vanillin
cause allergic34 and can irritate the eyes, skin, and the
respiratory tract33.
Acceptable Daily Intake:
The widely industrially produced vanillin is ingested in
the form of bakery foods and hot and cold beverages.
Remaining is used externally as soaps, perfumes etc.
Acceptable Daily Intake (ADI) of vanillin in form of
food and beverage is worldwide and it implies that
almost every human. An ADI of 10 mg/kg has been
approved by FAO/WHO and EU. For a 70 kg person, the
ADI is 700 mg vanillin that corresponds to minimum
700 g chocolate, or 7000 g of ice cream35.
Food and Drug Administration rules:
Natural vanilla is been a main source for dairy products
like ice cream and yogurt for decades. According to
Food and Drug Administration rules in the United States,
declare that vanilla ice cream must get its flavour from
natural vanilla. If it is flavoured partially or through
some other source, the company should label vanilla
flavoured or “artificial vanilla” on the package, a likely
turnoff to consumers36.
Analysis of vanilla Compounds:
Vanillin is a chief constituent of vanilla extract, a
flavouring ingredient which is been used in food
products and drinks. Analysis of vanilla Compounds
in vanilla extracts and model vanilla ice cream mixes
using novel technology has been studied37.
Liquid chromatographic method has been used to
quantify coumarin, vanillin, and ethyl vanillin in
vanilla extract38.
RPLC method for the characterization of vanilla
extract, a key component in food, has been
established39.
HPTLC method has been proposed to determine the
vanillin in three different food samples such as
vanilla essence, custard powder and vanilla flavoured
ice cream40.
CONCLUSION:
Vanilla has a very versatile flavouring agent and is
popular worldwide. It is found in all our confectionery
products like ice cream, candies, cakes, and cookies.
Vanilla also improves perception of sweetness and other
flavours. Natural vanilla extract is obtained by curing
vanilla beans. Vanilla substitutes are actually nature-
identical artificial vanillin (i.e.) synthetic vanillin
derivatives synthesized on multi-ton scale from guaiacol
or lignin extracts, which can be isolated from wood pulp
or petroleum by products. The distinction between
natural and artificial vanillin is the source of chemicals.
The synthetic chemicals in artificial vanilla flavour
generally cost less to produce than finding natural
sources of vanilla. Vanillin extracted from nature is safer
than artificially made nature identical vanillin. On the
whole, artificial vanilla tends to be cheaper, but the
health impact is to be considered.
Research J. Pharm. and Tech. 12(6): June 2019
5
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Parkinson’s disease (PD) is the second-most common neurodegenerative chronic disease affecting both cognitive performance and motor functions in aged people. Yet despite the prevalence of this disease, the current therapeutic options for the management of PD can only alleviate motor symptoms. Research has explored novel substances for naturally derived antioxidant phytochemicals with potential therapeutic benefits for PD patients through their neuroprotective mechanism, targeting oxidative stress, neuroinflammation, abnormal protein accumulation, mitochondrial dysfunction, endoplasmic reticulum stress, neurotrophic factor deficit, and apoptosis. The aim of the present study is to perform a comprehensive evaluation of naturally derived antioxidant phytochemicals with neuroprotective or therapeutic activities in PD, focusing on their neuropharmacological mechanisms, including modulation of antioxidant and anti-inflammatory activity, growth factor induction, neurotransmitter activity, direct regulation of mitochondrial apoptotic machinery, prevention of protein aggregation via modulation of protein folding, modification of cell signaling pathways, enhanced systemic immunity, autophagy, and proteasome activity. In addition, we provide data showing the relationship between nuclear factor E2-related factor 2 (Nrf2) and PD is supported by studies demonstrating that antiparkinsonian phytochemicals can activate the Nrf2/antioxidant response element (ARE) signaling pathway and Nrf2-dependent protein expression, preventing cellular oxidative damage and PD. Furthermore, we explore several experimental models that evaluated the potential neuroprotective efficacy of antioxidant phytochemical derivatives for their inhibitory effects on oxidative stress and neuroinflammation in the brain. Finally, we highlight recent developments in the nanodelivery of antioxidant phytochemicals and its neuroprotective application against pathological conditions associated with oxidative stress. In conclusion, naturally derived antioxidant phytochemicals can be considered as future pharmaceutical drug candidates to potentially alleviate symptoms or slow the progression of PD. However, further well-designed clinical studies are required to evaluate the protective and therapeutic benefits of phytochemicals as promising drugs in the management of PD. 1. Introduction Parkinson’s disease (PD) is a common progressive chronic neurodegenerative movement disorder that increases with age. PD prevalence is 315 per 100 000 persons of all ages in the Western world; this prevalence is expected to double by the year 2030, increasing mortality, morbidity, and socioeconomic burden worldwide [1]. The clinical symptoms commonly associated with PD disorder include bradykinesia, resting tremor, postural instability, rigidity, depression, and anxiety [2]. The important hallmarks of PD are progressive loss or damage of dopaminergic neurons in the substantia nigra pars compacta (SNpc) and dopamine (DA) depletion in the striatum (ST), which is associated with the motor impairments of PD [3]. In addition to the neuropathological process affecting dopaminergic and nondopaminergic systems, other pathological processes are also seen in Alzheimer’s disease (AD) affecting cholinergic dysfunction and serotonergic, glutamatergic, and noradrenergic pathways associated with dopaminergic neuronal death and/or DA system dysfunction. People with PD also experience nonmotor symptoms such as sleep disturbance, cognitive changes, autonomic dysfunction, altered mood, depression, fatigue, and pain [4, 5]. PD is described as a synucleinopathy, as accumulation of misfolded α-synuclein becomes a central feature of Lewy bodies, which are an important pathological hallmark of PD. Moreover, α-synuclein appears to be linked to both sporadic and familial forms of the disease and carries unique importance in the etiology of PD [6]. Interestingly, α-synuclein accumulation has been broadly linked to several neurotoxin pathways, including posttranslational modifications, neuroinflammation, oxidative stress, mitochondrial dysfunction, altered mitochondrial morphology, synaptic dysfunction, phospholipids, induced endoplasmic reticulum (ER) stress, and metal ions [7]. The age-related failure of antioxidant defense system and overproduction of ROS exacerbate oxidative stress in the brain; these events may play a role of misfolded α-synuclein initiating aging process in PD [8, 9]. Currently, levodopa (L-dopa) is the most effective therapy for the early-stage motor symptoms of PD, but it is not considered a cure for PD [10]. Bradykinesia and rigidity respond best, whereas tremor may be only slightly reduced. Problems with balance and other symptoms may not be alleviated at all. However, L-dopa is not effective in relieving neuronal loss, nonmotor symptoms, or Lewy pathology. Over time, patients require higher doses of L-dopa, which are associated with increased side effects such as dyskinesia [11]. Anticholinergic drugs may help control rigidity and tremor in approximately 50% of cases, and the antiviral agent amantadine also seems to diminish motor symptoms [3]. Deep brain stimulation (DBS) and DA-based medications are also used to treat various neurologic motor symptoms with disease progression [12]. Hence, it is critical to develop new therapeutic approaches to prevent neuronal loss and nonmotor symptoms and to prevent the accumulation of α-synuclein aggregation or Lewy pathology in the brain. Moreover, only symptomatic treatment options are available for PD; none slow or prevent progressive neuronal loss in the dopaminergic system [13, 14]. Herbal preparation and phytochemicals isolated from plant food have been proposed as “herbal medicine” for the treatment of PD [15]. Myriad phytochemicals from nature have been documented as potential molecules, drug leads, and phytochemical formulations in treating several inflammatory disorders [16, 17]. Likewise, extensive pharmacological reports have demonstrated the effectiveness of phytochemicals in treating dementia, depression, and neurodegenerative disorders (NDDs) [18]. Biologically active phytochemicals produced in plants are of clinical importance as primary and secondary metabolites for the antioxidant defense mechanism against various stress-related disorders and other pathogenic conditions [19]. The therapeutic and beneficial effects of these phytochemicals provide nutrition for normal living cells, fight disease-causing agents, strengthen the immune system, and act as antioxidants [20]. Plant products and their bioactive phytochemicals can efficiently scavenge oxygen free radicals and boost the cellular antioxidant defense system and related molecules, thereby protecting cells from oxidative damage [20, 21]. Several findings indicate that these antioxidant phytochemicals have confirmed neuritogenic potential, reconstructing synaptic connectivity by restoring the loss of neuronal processes [22–25]. In fact, various preclinical reports have described a number of natural pharmacological candidates that can coactivate the antioxidant defense system and neurotrophic factor-mediated cell survival systems [26–31], suggesting that these phytochemicals have therapeutic potential for the treatment of oxidative stress-mediated NDDs, especially PD. Thus, therapeutic approaches targeting oxidative stress, α-synuclein accumulation, neuroinflammation, and mitochondrial dysfunction may hold great promise as a cure for PD. Numerous antioxidant phytochemicals have displayed potentially neuroprotective properties by targeting several mechanisms beyond those mentioned above. Phytochemicals are biologically active compounds that usually correspond to the secondary metabolites present in plants like alkaloids, flavonoids, and terpenoids [32]. Many epidemiological studies have suggested a proportional relationship between consumption of a diet rich in antioxidant phytochemicals and improved health outcomes, including reduced risk for AD, PD, and other NDDs [33–35]. Other epidemiological studies have associated the consumption of various food groups and beverages such as fruits, vegetables, tea, and coffee with reduced risk of development of PD [36, 37]. Recent research on the dietary intake of phenolic phytochemicals has been presented in several European countries, with results showing that the average intake is 820 mg/day in Spain, 1193 mg/day in France, and 1756.5 mg/day in Poland. The main dietary sources of the total polyphenols in Spain and France are fruits and nonalcoholic beverages (principally coffee and tea). In Spain, fruits accounted for 44% and nonalcoholic beverages for 23% of total polyphenol intake, whereas in France fruit accounted for only 17% and nonalcoholic beverages for 55%. Considered individually, the main source of total dietary polyphenols is food with 18% and 44% of contribution in Spain and France, respectively. In Spain, olives and olive oils are also important sources of polyphenols, accounting for 11% of the total polyphenol intake. Nonalcoholic beverages were the main food contributors to polyphenol intake in Poland and accounted for fully 67% of the total polyphenol intake due to high consumption of coffee and tea. The third main contributor to total polyphenol intake is chocolate, whereas fruits accounted for a lower percentage of intake [38–40]. In the present study, we describe the phytochemicals present in dietary sources, using chrysin, vanillin, ferulic acid (FA), thymoquinone (TQ), ellagic acid (EA), caffeic acid (CA), epigallocatechin-3-gallate (EGCG), theaflavin (TF), and other plant-derived antioxidant phytochemicals (asiatic acid (AA) and α- and β-asarone) as examples and discuss their beneficial neuroprotective effects and relevance to potential treatment strategies of PD. Importantly, phytochemicals have thus far been investigated primarily in both cellular and rodent experimental studies for their potential benefits in brain metabolism; these studies have provided some encouraging results indicating antioxidant, anti-inflammatory, and cognitive enhancing effects of these phytochemicals coupled with a wide range of tolerability [41, 42]. Additionally, phytochemicals also have been confirmed to reduce mitochondrial dysfunction and inhibit formation of α-synuclein accumulation-induced oxidative stress and inflammatory responses [43, 44]. Several studies have also provided evidence that the antioxidant activity of some phytochemicals can activate nuclear factor E2-related factor 2 (Nrf2)/antioxidant response element (ARE) signaling pathways. Furthermore, phytochemicals contribute to the activation of the phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) and extracellular signal-regulated kinase (ERK) pathways and inhibit nuclear factor kappa B (NF-κB) pathways [22, 45]. Similarly, a number of studies have suggested that phytochemicals confer neuroprotection in experimental parkinsonism by reducing oxidative stress and mitochondrial dysfunction and fostering degradation of α-synuclein toxic species through activation of autophagy [46–48]. This study provides information about the neuroprotective properties and mechanisms of action of recently discovered naturally derived phytochemicals that target oxidative stress and neurodegeneration through cellular- and molecular-level changes in the progression of PD. In addition, we explore Nrf2/ARE and autophagy signaling-related pharmacological mechanisms. Moreover, we highlight some potentially neuroprotective active derivatives of antioxidant phytochemicals and phytochemical-based nanodelivery systems that fight pathological conditions associated with aging-related oxidative stress. The sources and chemical structures of phytochemicals are presented in Figure 1.
... It is the primary component of the extract of the vanilla bean and it is a principle flavor compound used in numerous foods (Quyen et al., 2016). Vanillin being a powerful antioxidant biophenol is often used as a flavoring and fragrance agent in foods, beverages, and pharmaceuticals (Vijayalakshmi et al., 2019). Besides this, it is also used as a food preserving agent, due to its antimicrobial, anti-mold, anti-yeast, and antioxidant activities (Ciriminna et al., 2019). ...
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