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Journal of Future Foods
CrossMark Journalof
Journal ofFuture
FutureFoods
Foods 4-1
4-1 (2024)
(2024) 37-47
37–47
CrossMark Journal of Future Foods 4-1 (2024) 37-47
journalhomepage:
journal homepage:http://www.keaipublishing.com/en/journals/journal-of-future-foods
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Plant based metabolomics: a future prospective and


Plant based metabolomics: a future prospective and
versatile tool for metabolite databases of Curcuma longa
versatile tool for metabolite databases of Curcuma longa
Shuvendhu Guptaaa, Amrat Pal Singhaa, Gurpreet Singhbb, Xianting Dingcc, Alok Sharmaa,a,*
Shuvendhu
a Gupta , Amrat Pal Singh , Gurpreet Singh , Xianting Ding , Alok Sharma *
Department of Pharmacognosy, ISF College of Pharmacy, Moga 142001, India
b
a
Pharmaceutical Chemistry,
Department of Pharmacognosy, ISF
ISF College of College of Pharmacy,
Pharmacy, Moga
Moga 142001, 142001, India
India
cb
School of Biomedical
Department Engineering,
of Pharmaceutical Med-X Research
Chemistry, Institute,
ISF College Shanghai
of Pharmacy, Jiao142001,
Moga Tong University,
India Shanghai 200030, China
c
School of Biomedical Engineering, Med-X Research Institute, Shanghai Jiao Tong University, Shanghai 200030, China

ARTICLE INFO ABSTRACT


ARTICLE INFO ABSTRACT
Article history: Sophisticated analytical instruments are used for quality evaluation and scientific validation to compliance the
Article
Receivedhistory:
19 October 2022 Sophisticated
market analytical
demands. instruments
Recently, aredemand
increase in Curcuma
used forofquality longa has
evaluation andledscientific
to a highvalidation to compliance
swing in small and medium the
Received 19in revised 202230 October 2022
Octoberform market
food demands.
industry. TheRecently,
present increase
review isindevoted
demandto Curcuma
ofan in-depthlonga has led toona metabolite
information high swing database of C.
in small and longa
medium
Accepted in
Received 23revised
November
form2022
30 October 2022 food industry.
from different The presenttechniques
analytical review is such
devoted to an in-depth information
as high-performance thin-layeronchromatography
metabolite database of C. liquid
(HPTLC), longa
Available 23
Accepted Online 15 May2022
November 2023 from different analytical techniques gassuchchromatography-mass
as high-performancespectrometry
thin-layer chromatography (HPTLC), liquid
chromatography-mass spectrometry, and nuclear magnetic resonance.
Available Online 15 May 2023 chromatography-mass spectrometry, gas chromatography-mass spectrometry andstructure
nuclear activity
magneticrelationship,
resonance.
This work highlights different extraction methods, phytochemistry along with
Keywords: This work highlights
nutritional profiling, different extraction
market viability andmethods,
pharmacology of C. longa.
phytochemistry alongThewith structure of
bioactives C. longa
activity relationship,
depends
Curcuma
Keywords:longa nutritional
on profiling,
various factors market
such viability
as plants growth,andtemperature,
pharmacology of C. longa.
humidity, The collection,
soil type, of C. longa
bioactives drying depends
and extraction
Curcuma
Omics longa
approaches on various factors suchcan
as plants growth, temperature, humidity,
process. These factors contribute in quality evaluation of thesoil
food type, collection,ifdrying
supplements need toandbe extraction
included.
Omics approachesmethod
Multidisciplinary process.
The These factors
introduction canapproaches
of omics contribute can
in quality
helpfulevaluation
to explore of thethe food and
quality supplements if need
identification to be included.
of potential lead of
Multidisciplinary
Quality control method Thelonga.
C. introduction of omics
The results approaches
could play ancan helpfulrole
essential to explore
in the the
areaquality and identification
of food-phyto of potentialFurther,
based profiling. lead of
Quality control
Metabolomics C. longa. Thetechniques
metabolomics results could play anan
may provide essential
analyticalrole in theby
platform area of food-phyto
combination based“omics”
of different profiling.
dataFurther,
sources
Metabolomics metabolomics
for techniques
future research to foodmayand provide products.platform by combination of different “omics” data sources
an analytical
herbal based
© 2024 Beijing
for future research to food Academy
and herbalofbased
Foodproducts.
Sciences. Publishing services by Elsevier B.V. on behalf of KeAi
© 2024 Beijing
© 2024 Academy
Academy of
Communications Food
ofCo.,
Food Sciences.
Sciences.
Ltd. This is anPublishing
Publishing
open accessservices
articleby
services Elsevier
byunder
Elsevier B.V. on
on behalf
behalf of
B.V.BY-NC-ND
the CC KeAi
oflicense
KeAi
Communications
Communications Co., Co., Ltd.
Ltd. This
This is
is an
an open
open access
access article
article under
under the
the CC
CC BY-NC-ND
BY-NC-ND license
(http://creativecommons.org/licenses/by-nc-nd/4.0/). license
(http://creativecommons.org/licenses/by-nc-nd/4.0/).
(http://creativecommons.org/licenses/by-nc-nd/4.0/).

1. Introduction It is also used to heal wounds and treat infections of skin, eye infections,
1. Introduction It is also used
respiratory to heal
system, wounds
dental andand treat infections
digestive disordersof
[3] skin, eye infections,
. It is also used as a
[3]
1.1 Habit and habitat respiratory
admix system,Indian
to different dentaltraditional
and digestive disorders
ceremonies . It isfunctions
religious also used
[4] as a
.
1.1 Habit and habitat admix to different
Turmeric, Indian traditional
indigenous to India,ceremonies
belongs toreligious
family functions
[4]
.
Zingiberaceae,
Curcuma longa L. also known as turmeric, is one of the blessed Turmeric,
now-a-days indigenous
highly to India,
cultivated belongslike
in countries to family
Sri Lanka,Zingiberaceae,
Indonesia,
Curcuma
spice of Indialonga
and L. alsoinknown
used as turmeric,
different forms asis one of the blessed
a flavouring and now-a-days highly cultivated in countries
Bangladesh, Burma, and Pakistan [5]
. Morelike
thanSri90%Lanka, Indonesia,
of worldwide
spice of India
colouring and asand used
a key in different
ingredient formssystem
in Indian as a flavouring
of medicineand [1,2]
. Bangladesh, Burma, and Pakistanby [5]
. India,
More only.
than 90% of worldwide
[1,2] turmeric consumption is produced Turmeric is a short
colouring
It is one and
of theas ahighly
key ingredient in Indian
recommended as system of medicine
folk medicine in the. turmeric consumption is produced by India, only.
stem perennial with large oblong leaves, while the Turmeric
tubers or is a short
rhizomes
It is one of
Ayurveda, the highlyIndian
a traditional recommended as folk medicine
system of medicine. The herb is in also
the stemoblong
perennial with large oblong leaves, while the
are or ovate or pyriform. The rhizomes aretubers or rhizomes
yellowish brown
Ayurveda,
uses a traditional
in Indian Indianand
homes as spice system
curingofskin
medicine. TheSince
problems. herb ages,
is also it are oblong or ovate or pyriform. The rhizomes are externally.
yellowish brown
from the outside while they are orange in colour, These
usesbeen
has in Indian homes as
extensively spice
used and curing
to enhance theskin problems.
colour Sinceofages,
and flavour food. it from the have
outside while they
rhizomes a pungent bitterare orange
taste in colour, externally.
and characteristic odour[6]. These
has been extensively used to enhance the colour and flavour of food. rhizomes have a pungent bitter taste and characteristic odour[6].
*
Correspondence author at: Department of Pharmacognosy, ISF College of Pharmacy, Moga
*
Correspondence author at: 142001,
Department of Pharmacognosy, ISF College of Pharmacy, Moga
India. 1.2 Market viability
E-mail address: alokalok22@gmail.com
142001, India. (A. Sharma) 1.2 Market viability
E-mail
Peer address:
review alokalok22@gmail.com
under responsibility of KeAi(A. Sharma)
Communications Co., Ltd. Turmeric has rich market viability due to its high medicinal and
Peer review under responsibility of KeAi Communications Co., Ltd.
foodTurmeric has2018,
values. In rich market
turmericviability
productsdue to its
have high medicinal
attracted some of and
the
food values. In 2018, turmeric products have attracted some of the
Publishing services by Elsevier
Publishing services by Elsevier
http://doi.org/10.1016/j.jfutfo.2023.05.003
2772-5669/© 2023 Beijing Academy of Food Sciences. Publishing services by Elsevier B.V. on behalf of KeAi Communications Co., Ltd. This is an open access article under the CC
http://doi.org/10.1016/j.jfutfo.2023.05.003
BY-NC-ND
2772-5669/©license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
2023 Beijing Academy of Food Sciences. Publishing services by Elsevier B.V. on behalf of KeAi Communications Co., Ltd. This is an open access article under the CC
10.1016/j.jfutfo.2023.05.003
BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
2772-5669 © 2024 Beijing Academy of Food Sciences. Publishing services by Elsevier B.V. on behalf of KeAi Communications Co., Ltd. This is an open access article under the
CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
38 Shuvendhu Gupta et al. / Journal of Future Foods 4-1 (2024) 37–47

38 Shuvendhu Gupta et al. / Journal of Future Foods 4-1 (2024) 37-47

highest sales in the United States. According to turmeric supply preparations as a colorant and flavour, spice due to their distinctive
estimates for 2018-2019, were approximately 1.32 lakh tonnes, aroma[9]. Moreover, other parts of the C. longa are posses high in
while only 0.71 lakh tonnes of turmeric was available[1]. According protein, carbohydrates and utilised as in culinary dishes. Curcuma
to global reports, the “International Turmeric Industry” is having species that are edible are high in carbs, proteins, dietary fibre, as well
the potential to increase annually 3.9% between 2020 and 2027. By as vitamins and minerals. Chemically, these species contain sugars,
2027, the production of turmeric is expected to reach 1.5 million fibres, oils, starch and different amino acids. It also contains some of
metric tonnes. A couple of the divisions examined in the paper are essential micro-nutrients such as Fe, Zn, Cu, Mo, Ca, Cr, Mn, Mg, P,
predicted to grow at a rate of 4% on average, reaching more than N, Na and S and vitamins. The rhizomes of C. longa are utilised as a
1 million metric tonnes by the conclusion of the analysis period. In the health food, as well as a dietary supplement, due to the diverse phyto
US size of the turmeric market is forecast to increase at exponentially contituents as demonstrate in Fig. 1[10].
in tonnes per year, whereas China will need 313.8 thousand metric
tonnes of turmeric by 2027, i.e., 7% per year. In 2016, the global
turmeric market was estimated to be worth $3.16 billion. Over the
2020-2027 time-frame, Japan and Canada are expected to expand at
1.2% and 3%, respectively[7]. Curcuminoids
Volatile oil
Fiber
Mineral matter
1.3 Commercial products Fat
Moisture
Since ages, turmeric has been utilised in traditional medicines Carbohydrate
system of India, which combines the therapeutic effects of herbs
with food. C. longa contains curcumin, a yellow-coloured substance
Fig. 1 Phytoconstituents profiling of C. longa.
which have potent therapeutic benefits. Raw turmeric has been
processed to new-value added products so as to have better shelf- Due to high demand and greater importance as medicinal product
life and market values. There is a plethora of value-added goods that the small and medium food industries (SMFI) have shown great
may be developed using turmeric that have a wide commercial appeal interest into the turmeric and related products[11]. Hence the present
as well as health benefits[8]. Table 1 represent the different marketed work aims to provide an update on metabolic work of turmeric,
C. longa base product and their uses. exploring about the quality control, scientific validation, extraction
techniques and offering a comprehensive work on analytical work,
1.4 Nutritional profiling and composition and market viability of C. longa. Besides, our insights are mainly
focus on the quality of food by among various analytical techniques,
The study of medicinal plants is gaining popularity as a way to which is closely related to their metabolites.
verify its use as an alternative food. Turmeric has been extensively
investigated among spices, and there are still a number of edible 2. Materials and methods
Curcuma species to be discovered. Curcuma angustifolia, Curcuma
caulina, Curcuma leucorrhiza, and Curcuma xanthorrhiza rhizomes A thorough search on various electronic literature databases
are high in starch and used in food industries. Rhizomes of conducted for the compilation of information. The keywords
C. aeruginosa, C. amada, C. aromatica, and C. longa are used in food was made in the subsection of i) conventional applications and

Table 1
Selected marketed C. longa based formulations.
No. Formulation name Specific use Product benefit
1 Turmeric latte Digestive, immunity Boost your immunity
2 Golden turmeric superfood granula Anti-inflammatory and blood sugar balancing functions Diabetes control
3 Muesli Strengthens and increase immunity Boost energy
4 Golden turmeric superfood oatmeal Balancing functions of the body Immune health
5 Immuniveda turmeric milk mix Immunity enhancer Immunity booster
6 Night beauty balm Antioxidant Skin lightening and antiageing
7 Turmeric noodle Antiinflammatory Staple food
8 Organic honey with turmeric Antioxidant Helps reducing oxidative stress
Lowers bad (low density lipoprotein (LDL))
9 Turmeric peanut butter Anti-lipid cholesterol and increases protective
(high density lipoprotein (HDL) ) cholesterol
10 Turmeric body wash Anti-bacterial Combat acne
11 Turmeric formula Anti inflammatory Antioxidant powerhouse
12 Turmeric and cranberry seed energizing radiance mask Look of skin tone and antioxidant Glow face mask
13 Aloe turmeric juice Antiinflammatory Reduces inflammation
14 Turmeric forte Antioxidant Health supplement
15 Curamin Antiseptic antiinflammatory Pain relief
16 Haldi drops Builds immunity Cold cough and joint pain
Shuvendhu Gupta et al. / Journal of Future Foods 4-1 (2024) 37–47 39

Shuvendhu Gupta et al. / Journal of Future Foods 4-1 (2024) 37-47 39

pharmacology, ii) Metabolomic tools and procedures, iii) a but different species has been reported to contain variety of
comprehensive list of metabolites discovered in C. longa, iv) monoterpene like α-phellandrene, terpinolene, 1,8-cineole, etc[19]. The
exploration and drawbacks of different metabolomics approaches, and health benefits of C. longa oil include cardio-protection, anti-obesity,
v) metabolomics relevance. anti-aging, reduced platelet aggregation and inflammation of joints
etc.
3. Traditional uses and pharmacology of C. longa
5. Phytochemistry
C. longa is used in cough, respiratory problems, anorexia,
rheumatoid arthritis, and oral problems, etc. C. longa has also shown C. longa revealed diverse bioactives which are responsible
good result in some gastrointestinal disorders which includes liver for various pharmacological activities. C. longa rhizome contains
disease, acidity, dyspepsia, ulcers, indigestion, and flatulence [12]. a plethora of bioactives with a unique pharmacological activity.
To treat muscle pain and inflammation induced by injury, a heated C. longa’s components have been linked to 326 different biological
poultice composed of turmeric and slaked lime is applied. It’s activities in total[20]. The bioactives depends on the geographical
considered as an choice of crude drugs on new-borns’ severed regions, temperature and types of soil. C. longa contains diverse
umbilical cords in some parts of rural India. Turmeric’s antimicrobial alkaloids, diterpenes, triterpenoids, polyphenols, sesquiterpenes
characteristics enable it to treat and prevent acne[13]. and sterols. Others ingredients such as carbohydrates, protein, fat,
minerals, and moisture also present in C. longa. Curcumin and
4. Pharmacology of C. longa comprises curcumin I, curcumin II and curcumin III[21]. Additionally,
curcumin’s demethoxy and bisdemethoxy derivatives have been
C. longa has shown plethora of bioactivities in cell-based identified from C. longa. Curcumin melts at 176–177 °C, reacts with
investigations which includes diverse pharmacological activities. In alkali to generate a salt that is reddish-brown in colour. Gas liquid
addition, different animal-based model had been developed to unlock chromatography was used to study the essential oils found in the
its potential in conditions such as inflammation, diabetes, cancer, leaves of C. longa such as linalool, caryophyllene, geraniol, α-pinene,
depression, and neuroprotective[1]. Furthermore, the clinical studies β-pinene and etc. Different bioactive studies revealed the occurrence
have demonstrated the effectiveness of turmeric for the different of phytosterols in C. longa rhizomes such as stigmasterol, b-sitosterol,
medical condition such as irritable bowel syndrome fibrosis and some and stigmast-4-en-3-one, and one monoterpene and terpinene-4-ol[22].
cancers etc.
Curcumin, principal component of turmeric, which was reported
5.1 Bioactive and their activities
in 1815 by Vogel and characterized by Lampe et al. in 1910, which
has been extensively investigated by different researchers against The most researched curcuminoid polyphenols are curcumin,
various disorders[14]. Curcumin help in reduction of levels of lipids and bisdemethoxycurcumin, and de-methoxy curcumin. As curcumin
glucose, reduction of inflammations, slowing the progress of cancer, is not soluble in water, it is extracted using organic solvents[23].
and treating viral infections[14]. It is versatile molecules possessing The further activities and mechanism of metabolites is elaborated
capacity to interact with diverse receptors and targets which include in Fig. 2. Curcumin contains a vast number of compounds which
mdm2, GSK-3β, p53, NF-κB, ERK, Jak etc. In-spite of this, a clear includes curcumin, desmethoxycurcumin, mono-demethoxycurcumin,
molecular mechanism of interaction of curcumin with variety of bisdemethoxycurcumin, dihydrocurcumin, and cyclocurcumin are the
drug targets is still at large[15]. Furthermore, Akt dephosphorylation, primary components as mention in Table 2[24]. Vanillin is produced
inhibition of Bcl-2 and Bcl-X, improvement in cytochrome-C release, when curcumin is oxidised whereas α-phellandrene, sabinene, cineol,
activation of Caspase-3 and suppression of CDK 4 has been also borneol, zingiberene, and sesquiterpenes are reported in the C. longa
reported upon treatment with curcumin[16,17]. Moreover, the studies oil isolated[25].
have highlighted that curcumin has poor oral absorption. Diferuloylmethane or commonly known as curcumin is a
Now-a-days, the various perfumery, pharmaceutical, food and sesquiterpene, molecular formula of C21H20O6 with subatomic mass of
agriculture industries have the increased the demand of essential oils 368.385 g/mol. It has two methoxy and hydroxy substituted aromatic
and their products[18]. The rhizomes of C. longa are rich in essential rings which are connected by seven-membered alkyl chains having an
oil, which is enriched with sesquiterpenoids and has a rich spicy and α,β-unsaturated-hydroxy ketone moiety[23]. The donation of hydrogen
aromatic flavour. α- and β-turmerones are the principal components atom is the primarily of utmost importance for the bioactivity of

Table 2
Major chemical constituents from C. longa.
No. Name of metabolite Pharmacological activity Proposed action
Curcuminoids have to be found the skeleton of two aromatic rings. Some curcuminoids have a
1 Curcuminoids Curcuminoids are key components
1,3-diketone group, at least two keto-enol tautomers. UV-Vis absorption range: 410–430 nm
Terpenoids are the important 62 sesquiterpenoids, 1 monoterpene, 4 norsesquiterpenoids and
2 Terpenoids
bioactives in volatile oil 1 norditerpene reported from C. longa
Turmeric also contain C. longa has for dihydroflavonol glucoside and flavonol glycosides. Flavanonol, flavones, and
3 Flavonoids
flavonoids and their glycosides flavonols, luteolin, apigenin, quercetin, kaempferol, and myricetin were reported by researchers
Others phytocompunds are also Number of other bioactives such as phenols, organic acids, alkaloid, steroids,
4 Others
reported form C. longa polysaccharides also reported from C. longa
40 Shuvendhu Gupta et al. / Journal of Future Foods 4-1 (2024) 37–47
40 Shuvendhu Gupta et al. / Journal of Future Foods 4-1 (2024) 37-47

Fig. 2 Different boactives compounds isolated from C. longa.

curcumin[24]. It also helps in oxidation of curcumin, nucleophilic addition disease model animals is predicted[30].
to the moiety, hydrolysis, degradation, and important enzymatic activities The most frequent tumour of the urinary tract (UT) is bladder
of curcumin[25]. It can act as a hydrophobic reducing agent and suppress cancer, which has the highest morbidity rate of all UT tumours[31].
oxidative stress more effectively. Another important constituent which has been isolated from turmeric
The authors reported that curcumin reduce the growth of SMMC- is curcumol. Curcumol’s antiproliferative activities were studied using
7721 cells through apoptosis via the inhibition of protein like Bax/ a colony formation assay, as well as its proapoptotic effects using an
Bcl-2 significantly[26]. It was also highlighted that curcumin disrupt Annexin V-FITC assay and propidium iodide (PI) staining. The ROS
the spindle micro-assembly through the phosphorylation of cell in bladder cancer cells was measured using the dichlorofluorescein
division cycle 27 (CDC27)[27]. In nutshell, curcumin exert anticancer (DCF) staining method. Curdione’s neuroprotective efficacy in rat
effect by activating programmed cell death and inhibiting the growth focal cerebral ischemia staining was used to verify the size of the
and differentiation of cell[28]. infarcts in the animals. The sham group had no brain damage after 24 h
ar-Turmerone is one of the essential oil components of C. longa. of reperfusion[31]. The middle cerebral artery occlusion (MCAO)
In midbrain slice cultures, ar-turmerone and its analogues suppress group’s infarct area was clearly visible, and curdione drastically
dopaminergic neurodegeneration, most likely through activating Nrf2 reduced infarct sizes from 28.40%−3.01% to 11.50%−1.12%. At 4,
in dopaminergic neurons[29]. The recent studies highlight that A2 is 7, and 14 days following MCAO, similar results were obtained. The
one of the analogues with anti-inflammatory and neuroprotective synthesis of cytokines is primarily inhibited by zingiberene which is
properties. As a result, A2 could be a promising treatment option for thought to provide long term relive from the inflammations[32].
Parkinson’s disease. Because ar-turmerone has antidepressant efficacy
in mice, more research on the in vivo efficacy of A2 in Parkinson’s
Shuvendhu Gupta et al. / Journal of Future Foods 4-1 (2024) 37–47 41

Shuvendhu Gupta et al. / Journal of Future Foods 4-1 (2024) 37-47 41

5.2 Structure activity relationship 5.2.2 Structure-activity relationships (SARS) for different
biological activities
Curcumin is yellow-colored naturally occurring polyphenolic
pigment which is hydrophobic in nature and basic studies of structural Anti-inflammatory action of the curcumin derivative was found
changes and their further activities have been reported majorly. to be associated with the alteration of para-position. The presece of
Curcumin and its derivatives shown to have anti-Parkinson’s, a hydroxy group at the para position is found essential for obtaining
anticancer, glucose lowering, inflammations, anti-bacterial, anti- significant anti-inflammatory activity, while the analogues which are
viral, antioxidant, atherosclerosis and cardiovascular actions such as devoid of OH groups displyed poor or non inflammatory activity[37].
Moreover, curcumin and tetrahydrocurcumin were most active
anti-arrhythmic, anti-hypertensive, and hypolipidemic activity[32]. The
against reactive active species. The increased antioxidant potential
ability of Curcumin and its reported derivatives in various diseases was
of tetrahydrocurcumin boosted antioxidative potential. Both natural
attributed to their potential biological activities. In an experimental study
curcuminoids and tetrahydrocurcuminoids had lower antioxidant
its protective effect against AFB1-induced liver injury was attributed due
activity when one or both methoxy groups were missing. In the lipid
to reduced AFB1-DNA adduct accumulation[33]. peroxidation model, the compound with multiple CH3 groups at ortho
Curcumin activates GPR97 and increased serum-response locations with respect to the phenolic hydroxy groups demonstrated
element-mediated transcription in GPR97 over expressing cells, the best inhibitory action[38]. Compound, on the other hand, was 10
but no response factor-mediated transcription or cAMP-mediated times less active than compound because it had bulkier butyl groups
transcription has been seen. Curcumin and related compounds flanking the phenolic group. The inhibitory effect appears to be
activated both mutant strain of GPR i.e., GPR97(T250A) which do dependent on the presence of hydroxy groups in the phenyl ring. In
not have cleavage at G protein coupled receptors proteolysis site and this bioassay (which bioassay), no other compound showed inhibitory
mutant GPR97(N)[34]. In other study, curcumin was found to be the activity, implying that the unsaturated linker is also involved in the
most potent of the 21 polyphenols tested in increasing HSP70 levels inhibitory activity, Shim et al.[39] found that hydrazinocurcuminoids
in Caco-2 cells without affecting cell viability[35]. derived from eurcurninoids had higher anti-proliferative efficacy than
Curcumin derivatives inhibit α-amino-3-hydroxy-5-methyl-4- curcuminoids in bovine aortic endothelial cells (BAECs). Unlike
curcumin, which suppressed the growth of a variety of epithelial and
isoxazolepropionic acid (AMPA) receptor subunits and affect gating
fibroblast cells without discrimination, hydrazinocurcuminoids were
biophysical properties. Overactivation of AMPA receptors is linked
found to be specific against endothelial cells. The curcuminoids’
to epilepsy, Amyotrophic lateral sclerosis, and strokes. A study was
potencies were ranked 1 > 2 > 3 in order of their potencies. The
conducted and described that curcumin protects cardiac cells from
hydrazinocurcuminoids followed a similar pattern. As a result,
ischemia-reperfusion injury by inhibiting oxidative stress, NF-κB, removing the methoxy groups from the phenyl rings reduced the anti-
and JNK signaling pathways. Curcumin administration, especially angiogenic activity[40].
before the hypoxic challenge, appears to be a promising strategy for
protecting cardiac cells from ischaemia-reperfusion injury injury[36]. 6. Extraction of bioactive compounds from turmeric
In this scenario, the present findings highlight the importance of
timing for treatment outcomes and provide a differential assessment Curcumin is one of the most important chemical constituents
of the degree of protection curcumin can provide through antioxidant reported in C. longa, accounting for 1%−7%. Various studies worked
activity or other mechanisms. on curcumin recovery after performed experiment on different
extraction methods. For the extraction of curcumin, it needs the use
of organic solvents due to its limited solubility in water and solvent.
5.2.1 Commom synthetic routes for curcumin and its analogs
For the efective isolation of curcumin the continuous extraction using
The one structural difference between curcumin analogues soxhlet extractor has been successfully employed[41].
and curcumin is the phenyl ring replacements. The condensation Ultrasound (US), microwave (MW), subcritical water, and
of substituted benzaldehydes with 2,4-pentanedione is the general supercritical CO 2 extraction are the improve methods for the
synthesis approach for this analogue family, as shown in Fig. 3. Boron extraction of curcumin. The key benefits of these technologies are
oxide is employed in this condensation reaction by forming a boron the reductions in extraction time, energy consumption, and residues
complex with 2,4-pentanedione. produced. The efficiency of US was found nearly same as that of
Soxhlet extraction [42]. MW can be used to obtain curcumin-rich
extracts in a similar way to US. The quantity of curcumin obtained
from MW extraction method was found equivalent to the quantity
obtained from Soxhlet extraction, after 2 min of MW irradiation.
Moreover, the recovery efficiency was found superior to the Soxhlet
after only being irradiated for 5 min i.e., 90.7% recovery. Similarly,
other subcritical water extraction tests yielded substantial curcumin
recovery yields. The extraction of curcumin by the super critical fluid
extraction using CO2, using ethanol as a co-solvent and maintain
temperature at 50 °C throughout extraction, 69.4% of curcumin
Demethoxycurcumin Bis-dimethoxycurcumin
was recoverd[43]. Different extraction techniques and conditions of
Fig. 3 General synthetic routes of curcumin and its analogs. C. longa are described in Table 3.
42 Shuvendhu Gupta et al. / Journal of Future Foods 4-1 (2024) 37–47

42 Shuvendhu Gupta et al. / Journal of Future Foods 4-1 (2024) 37-47

Table 3
Different extraction techniques and conditions of C. longa.
Extraction method Experiment condition Experiment observations
Solvents: different solvents were considered for the extraction of curcumin
Solvent extraction 30−60 °C, 1 h
by various scientist; Observation: highest yield observe in ethanol
Soxhlet method shown a higher curcumin extraction as compares to others;
Soxhlet extraction 65 °C, 1−2 days
Observation: required higher temperature for longer time
22–65 °C
Ultrasound-assisted extraction Observation: yield value under optimized conditions was higher
30 min−8 h
Solid; solvent ratio 120–430 W,
Microwave-assisted extraction Observation: showed reduction in time with higher precision
particles screened through sieve 10–44, 2 450 MHz
Some of enzyme assisted extraction α-amylase, glucoamylase a Observation: α-amylase and glucoamylase increased the yields of curcumin
Enzyme-assisted extraction
pH 3.0–6.5, incubation: 3–12 h, extraction: 4–16 h under optimum conditions
Observation: changes in porosity and hardness of turmeric affect the curcumin
Pressurized liquid extraction 110–170 °C, 1 000–2 500 kPa, particle size 0.5–2.0 mm, 5–25 min
extraction process
Supercritical fluid extraction 50 °C, 30 MPa, CO2: 5 mL/min, 60 min static, 300 min dynamic Observation: curcumin yield was obtained significantly higher
Ionic liquids-based extraction Room temperature, 10–90 min, drug solvent ratio: 1:30 (m/V) Observation: the curcuminoids yield in was 6.14%

7. Metabolomic studies as bicyclo-3-heptene, 2-isopropenyl-5-isopropyl7,7-dimethyl,


xylopropamine,1-(3,3-dimethyl-but-1-ynyl)-1,2-dimethyl-3-
Metabolic fingerprinting and metabolomics highlighted a variety methylenecyclopropane, 3,7-dimethyl etc. Further, Ghosh et al. [47]
of sophisticated analytica instruments, such as high performance stated that TR1, TR2, TR3, and TR5 genotypes with high rhizome oil
thin layer chromatography-mass spectroscopy (HPTLC-MS), yields of 2.1%, 1.7%, 1.6%, and 1.5%, respectively, were regarded
liquid chromatography (LC), mass spectrometry (MS), nuclear elite clones possessing turmerone as the predominant constituent of
magnetic resonance (NMR), Fourier transform-infrared spectroscopy rhizome essential oil, as well as all desirable elements[47].
(FT-IR) and, gas chromatography (GC)-MS and ultra-performance Singh et al.[21] examined the composition of extract and essential
liquid chromatography-mass spectrometry (UPLC-MS). In oil obtained from the dried and fresh C. longa rhizomes using GC-MS.
order to facilitate compound analysis using a greater variety of The primary components obtained from the fresh rhizomes were
metabolome perspectives, multi-hyphenated techniques including ar-turmerone, α-turmerone, and β-turmerone while the dried rhizome
GC-high-resolution time-of-flight mass spectrometry, The ultra-high contains a lesser amount of active metabolites i.e., ar-turmerone,
performance liquid chromatography-quadrupole time-of-flight mass santalene, and ar-curcumene. While further investigation by Tang et al.[48]
spectrometry (UHPLC/Q-TOF-MS), and GC coupled to time-of-flight using GC-MS fingerprint analysis to distinguish the rhizomes of
mass spectrometry (TOF-MS) have been progressively integrated with C. longa from different origins and identified different components
the technologies that are frequently employed for global metabolome such as turmerone, arturmerone, and zingibere.
investigations[44].
For the study of Curcuma species, various analytical methods
7.2 Detection using HPTLC technique
have been developed. The majority of the methods employed
advanced and hyphenated chromatographic methods such as HPTLC, HPTLC is now become one of the most accepted
HPLC, UPLC, GC-MS, and LC-MS. Authentication of Curcuma chromatographic techniques for identification and quality control
species has been reported using UV-visible, infrared, Raman, of herbal and food products. The identification of adulterants using
and NMR spectroscopy [45]. NMR spectroscopy may be utilised to the compression method through available biomarkers will help in
analyse both primary and secondary metabolites simultaneously differentiation of different species and their adulterants[48]. Moreover,
in a variety of plant samples [46]. Advanced NMR techniques has these methods are quality tool for isolation and identification of
become a valuable tool for generating fingerprint of the natural medicinally important metabolites. The data generated will also help
molecules. Principal component analysis (PCA), partial least to identify various location for agricultural development for turmeric.
squares-discriminant analysis (PLS-DA) and orthogonal projections In the different experimented documents, the variety C. longa of
to latent structures discriminant analysis (OPLS-DA) contributing in obtained from Erode (Tamilnadu) found superior to the other regions
metabolites present in the natural products. which make it suitable for cultivation of highly quality curcumin
species[49]. The analysis of ethanolic extract of C. longa, performed by
7.1 Metabolites of C. longa detected using GC-MS technique research group[50], showed the quantifiable amount of curcumin from
the dried rhizomes i.e., 1.5% of total content. Moreover, the content
The metabolites in C. longa were identified, seprated and
variation of 70% and 16%, due to environmental and genotype
characterized by using analytical techniques. Several other
investigations have also demonstrated the plant’s diversity, containing variation, in the yield of curcuminoids from the rhizomes of curcumin
secondary metabolites of various types, particularly steroids and was disclosed by[50]. Furthermore, Ayer et al.[51] highlighted the effects
alkaloids[44]. The GC-MS study of methanolic extract of rhizomes of of hybridization and introgression on the yield metabolites from the
C. longa led to the identification of bioactive compounds such species of Curcuma.
Shuvendhu Gupta et al. / Journal of Future Foods 4-1 (2024) 37–47 43

Shuvendhu Gupta et al. / Journal of Future Foods 4-1 (2024) 37-47 43

7.3 UV-visible spectrophotometer the authors performed all the analytical parameters and confirmed
method for the simultaneous analysis[58].
The spectrophotometric approach is a straightforward and In an another study, the author performed to separated and
widely used method for determining curcumin in a variety of sample identified 15 phenolic compounds from C. longa and resulted
matrices. Kotra et al. [52] compare the curcumin content by both described that ethanolic extract of is having significant amount of
spectrophotometric and HPLC methods in which spectrophotometric curcumin along with essential phenoliic compounds which could be
method was found better to that of HPLC method. The ethyl acetate responsible for antidiabetic activity[59].
was used as appropriate solvent for the analysis because only few Sahu et al.[60] illustrate a method for separation of curcumin,
millilitre of the extract prepared in EtOAc were sufficient to produce bisdemethoxycurcumin, demethoxycurcumin, and metanil yellow
desirable results. Moreover, the biodegradability and environmental by reversed-phase HPLC (RP-HPLC) method. In another study,
harmless of the solvent made it a best choice for carrying out the a simple method was developed and validated with different
examination. extracts of turmeric. Seperation of curcuminoid such as curcumin,
In a study performed by Pundarikakshudu et al.[53], the curcumin desmethoxycurcumin, bisdesmethoxycurcumin was performed
and berberine were quantified simultaneously from methanolic extract in the extracts, The result showed that method is robust in term
of Berberis aristata and C. longa. In another study, curcuminoids of all required parameters and was could be applied used for the
content in C. xanthorrhiza was found much lower than in C. longa[54]. analysis of turmeric analysis [61]. Table 4 mention the different
Curcumin showed considerable inhibitory effect on β-hematin detection techniques for the identification of selected metabolites
formation with efficiency of 78.8% compared 91.8% of aqueous from C. longa.
solution and 10.7% for inactive dimethyl sulfoxide solvent.
Table 4
Different detection techniques for the identification of selected metabolites
7.4 IR spectroscopy from C. longa.
Technique of Molecular
FT-IR spectroscopy in association of PLS-DA analysis serves No.
detection
Name of metabolite Plant part
weight
as potential method for determining the concentration of curcumin ar-Turmerone Rhizome 216
from the Curcuma species. Rohman and co-workers[54] developed α-Turmerone Rhizome 218
a rapid and reliable FTIR based method in which required no β-Turmerone Rhizome 218
sample preparation and at the same time no solvent was required Cineole Rhizome 154

for sample introduction. The distinguishment of the characteristic ar-Curcumene Rhizome 202
α-Zingeberene Rhizome 204
IR peaks of different components is quite difficult due to variety of
β-Bisabolene Rhizome 204
components present in the extract varies a lot[55]. However, more
Glyerol Rhizome 308
detailed study and applying bio-markers based IR studies can yield Mallic acid Rhizome 350
good information regarding the qualification and quantification of Fructose Rhizome 569
components present in the sample. The near IR region coupled with Glucose Rhizome 569
multivariant statistical analysis has yielded valuable information 1,2-Cyclohexanediol,1-methyl-4-(1-
Leaf and peel 172.1
about the different curcuminoids from different 34 samples. In the methylethenyl)
1 GCMS
trans,trans-Octa-2,4-dienyl acetate Rhizome 168.1
NIR spectra two distinctive absorption band of curcuminoids was
Phenol,2-methoxy-3-(2-propenyl)- Wood extract 164
observed i.e., between 1 700 and 2 300–2 320 nm. The amount
Isopropyl-4-methyl-1-pentyn-3-ol Leaf and stem 140
of curcuminoids in a turmeric sample was measured using the 9-Tetradecadiyne Leaves 190
PLS approach. Moreover, the characteristic absorption bands Naphthalene,5-butyl-1,2,3,4-tetrahydro- Rhizome 188
have helped in the predication of active metabolites from the Pentanone,4-mercapto-4-methyl- Rhizome 132
powders of curcumin species, C. longa and C. xanthorrhiza [56]. 1,2-Cyclohexanediol, 1-methyl-4-(1-
Rhizome 220
Moreover, spectra feature of turmeric was also enhanced and methylethenyl)
Bicyclo(2.2.1)hept-2-ene,2,3-dimethyl- Leaf 122
transformed into other form of spectra correction using mean centring
4-Ethylphenethylamine Stem 149
(MC) algorithm by[57]. Despite the fact that this technique is quick
E-11-Tetradecenoic acid Rhizome 226
and non-destructive, a powerful PLS model requires a large number 2-Nonen-4-yn-1-ol, (Z) Rhizome 154
of samples from many sources. Despite this, because of its speed, IR 3-Cyclohexen-1-one,3,5,5-trimethyl- Rhizome 138
spectroscopy is a good choice for quality control in the food industry.
Curcumin Rhizome 368.38
Demethoxycurcumin Rhizome 338.4
7.5 HPLC analysis Alanine Rhizome 89.09
Methionine Rhizome 149.21
HPLC is one of the favourable instrument for analysis of Threonine Rhizome 119.1
2 NMR
curcumin. The mobile phase columns and different wavelengths Lysine Rhizome 146.1
was used by various scientist for the identification of bioactives in β-Glucose Rhizome 180.1
C. longa. In a study, a microparticle formulation containing C. longa Fructose Rhizome 180.1

and P. nigrum extracts a method was developed and validated for the Sucrose Rhizome 180.1

presence of the presence of piperine and curcumin. In that experiment Xanthorrhizol Rhizome 218.3
44 Shuvendhu Gupta et al. / Journal of Future Foods 4-1 (2024) 37–47

44 Shuvendhu Gupta et al. / Journal of Future Foods 4-1 (2024) 37-47

Table 4 (Continued) fields with a primary utilization as spice and food supplement,
Technique of Molecular worldwide. The quality assessment of turmeric via UV, FTIR, 1H
No. Name of metabolite Plant part
detection weight NMR, and HPLC were used to create a metabolomic fingerprint. The
Eucalyptol Rhizome 154.2
differences and similarities between 30 samples were determined
Betaine Rhizome 117.1
using PCA and hierarchical clustering analysis (HCA). The findings
α-Glucose Rhizome 180.1
indicated that UV could be used as a simple and quick alternative to
Choline Rhizome 257.2
HPLC, FTIR. The metabolic variability between samples was more
Fumarate Rhizome 116
visible in the essential oils/fatty acid[66].
β-Pinene Rhizome 136.23
The bioactives variation and quality of the herbal products
β-Myrcene Rhizome 136.2
containing metabolites of turmeric was conducted in UK wherein the
3 HPLC α-Phellandrene Rhizome 136.2
quality difference was assessed at various stages. Nearly, 72 samples
β-Linalool Rhizome 154.2
were analysis using proton-NMR studies and their metabolic variation
Borneol Rhizome 154.2
Curcumin Rhizome 368.38
was identified using PCA and HPTLC [67]. Crude powders from
4
UPLC/
Demethoxycurcumin Rhizome 338.4
turmeric, intermediate products and commercial products, results
Q-TOF
Bisdemethoxycurcumin Rhizome 308.3 showed a significant variation in the chemical composition of turmeric
finished products, particularly those containing turmeric extracts.
In experiments and clinical trials, chemical variability will lead to
8. Application of metabolomics
inconsistent results and uncertain efficacy. As a result, standardisation
Isolation from an extract is complicated because of presence of of chemical ingredients in turmeric products is required. Products
containing turmeric extract were analysed and various curcuminoids
hundreds of chemical constituents and there content in low amount.
were detected by direct analysis in real time (DART) atmospheric
Recently, metabolomics has become now an inspirational tool for
pressure ionisation. In another study, molecular ions of curcuminoids
the identification and analysis of diverse metabolites from extract.
in C. longa were efficiently detected and a method was developed for
Sophisticated analytical tools are considered to systematically quantification of curcuminoids by using UPLC-MS/MS[68].
interpret the bioactives for identification and quality control of Different analytical techniques such as UV-visible, FTIR, NMR,
herbal drugs. The latest research in natural products, selection of chromatographic techniques and hyphenated chromatographic
instruments and data interpretation supported the scientific evidence techniques were employed for quality assement of curcumin
in natural plant metabolomics. The study and quality evaluation products. However, the distinguishment of metabolites using FTIR
of medications generated from natural products have been aided was quite difficult but other techniques such as NMR has been
by the use of metabolomics, a potent tool [62]. In a recent study, successfully employed. For, the clinical trials, pharmacokinetics and
interrogate the metabolomes of 5 Curcuma reported UPLC-tandem pharmacodynamics studies, chemical variability lead to inconsistent
mass spectrometry (UPLC-MS/MS). The result highlight nearly 432 results and uncertain efficacy. Hence, identification of chemical
compounds in C. longa products would be in future requirement[69].
metabolites were identified in C. longa and other species and also
revealed that C. longa have a higher presence of phenolic acids,
amino acid derivatives, and flavonoids which are associated with the 8.2 Discovery of new molecules
curcumin biosynthesis pathway. This study show a new insights into
Curcumin was discovered by Vogel and Pelletier around
Curcuma and other species metabolomics for the development of two centuries ago from C. longa[70]. Several chemists speculated
future functional based foods products[63]. about the structure of curcumin in the decades that followed the
discovery. It is now known that turmeric reported more than
8.1 Quality controls 235 secondary metabolites that are made up of 109 sesquiterpenes and
68 monoterpenes, as well as three Curcuminoid molecules that have
Identifing bioactives from C. longa is an essential in food, been identified through chromatographic methods and MS. Curcumin
cosmetics and pharmaceutical industry. Still, C. longa has some of (the primary curcuminoid), DMC, and bisdemethoxycurcumin, all of
issue such as water solubility, chemical instability, photo degradation, which are other components of C. longa, appear to possess a variety
metabolic degradation and low bioavailability. Whereas, analytical of medicinal properties. Cyclocurcumin, a 4th molecule that, in the
instruments has capacity to resolve these challenges and recently absence of the α-, β-unsaturated β-diketone motif, is not considered
various researchers performed successfully. Moreover, metabolite a Curcuminoid but a curcumin analogue, is recently discovered to
profiling can be used to verify the authenticity of a collection of be present in the rhizome at a much lower concentration but with
materials[64]. This profiling can be implemented from cultivation, some intriguing medicinal properties [71]. The active ingredient in
collection, harvesting extraction and method of separation. Curcuma species has been identified as curcuminoids.. Curcumin,
Curcuminoids, which are bioactive chemicals, are important demethoxycurcumin, and bisdemethoxycurcumin are the three types
components of C. longa’s therapeutic efficacy, and products with high of curcuminoids, with curcumin having the highest concentration[72].
curcuminoids are favoured for formulation [65]. As a result, HPLC- To differentiate phyto components and or bioactives utilised
based quality control systems that are dependent on a single active/ in natural medicines, metabolomic analysis employing GC-MS,
marker chemical may not be adequate. The roots and rhizome of LC-MS, or NMR spectroscopy might be used. These approaches can
C. longa, offers a wide application to both medical and economic also be used to differentiate between types gathered from diverse
Shuvendhu Gupta et al. / Journal of Future Foods 4-1 (2024) 37–47 45

Shuvendhu Gupta et al. / Journal of Future Foods 4-1 (2024) 37-47 45

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