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Journal of Ethnopharmacology

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Review

Botany, traditional uses, phytochemistry and biological activities ofcardamom [Elettaria cardamomum (L.) Maton] – A critical reviewKaliyaperumal Ashokkumara,∗, Muthusamy Murugana, M.K. Dhanyaa, Thomas D. Warkentinba Cardamom Research Station, Kerala Agricultural University, Pampadumpara, Idukki, 685553, Kerala, IndiabDepartment of Plant Sciences, College of Agriculture and Bioresources, University of Saskatchewan, Saskatoon, SK, S7N 5A8, Canada

A R T I C L E I N F O

Keywords:CardamomBotanyPhytochemicalsEssential oilTraditional and pharmacological applications

A B S T R A C T

Ethnopharmacological relevance: Small cardamom [Elettaria cardamomum (L.) Maton. (Family: Zingiberaceae)]capsules (fruits) have been used for traditional medicine applications including for the control of asthma, teethand gum infections, cataracts, nausea, diarrhea, as well as cardiac, digestive and kidney disorders. The versatileuse of cardamom capsules has several other beneficial health effects that are relevant in light of traditional andmodern pharmaceutical perspectives.Aim of the study: This review aims to provide a critical and comprehensive evaluation of the traditional andcurrent medical uses of E. cardamomum, and compare these applications with modern research studies. Thiscritical review also discusses the botanical distribution, phytochemical constituents and biological activities ofcardamom capsule extracts and essential oil.Materials and methods: An online survey was conducted of the traditional uses, phytochemical composition, andpharmacological applications of cardamom essential oil (CEO) and extracts. Pertinent data were obtained fromseveral electronic scientific databases (Science Direct, Elsevier, Web of Science, PubMed, Springer, ACS pub-lications, Taylor and Francis, Wiley On-line Library and Google Scholar), and additional information was ob-tained from textbooks and local prints and scripts.Results: Cardamom fruits (capsules) are used widely as a spice and flavoring ingredient in foods, and are oftenrecognized for their beneficial health properties. They are also used in fragrances. Phytochemical analyses havedescribed important chemical constituents of cardamom including carbohydrates, proteins, minerals, lipids,essential oils, flavonoids, terpenoids and carotenoids. CEO has several biological roles including antioxidant,antidiabetic, antibacterial, anticancer, gastro-protective and insecticidal activities.Conclusion: The widespread availability and recommendation of synthetic compounds for addressing humanhealth have several side effects besides higher costs. Hence, examining natural bioactive compounds is im-perative. This review investigates and presents the pertinent information on cardamom and its traditional uses,as well as potential pharmacological properties of CEO and extracts. Additional research studies are needed tounderstand the mechanism of action of bioactive constituents.

1. Introduction

Elettaria cardamomum (L.) Maton is commonly known as smallcardamom, green cardamom, or true cardamom and is grown in India,Guatemala, Sri Lanka, Nepal, Indonesia, Costa Rica, Mexico andTanzania (Garg et al., 2016). In India, cardamom is cultivated in alti-tudes ranging from 900 to 1400m above msl (mean sea level) coveringthree southern Indian states (Kerala, Karnataka and Tamil Nadu). InKerala, it is cultivated mainly in the Indian Cardamom Hills covering anarea of 1050 square kilometers designated as Cardamom Hill Reserves,(Madhusoodanan et al., 2002). The botanical name of cardamom,

Elettaria cardamomum, originated from the Tamil word “Elettari” whichrefers to the seeds of cardamom (Mahindru, 1982).

In general, the cardamoms are the capsules of dried fruits in dif-ferent genera of the Zingiberaceae family, primarily Elettaria, Amomumand Aframomum. Among them, Elettaria cardamomum (L.) Maton is mostimportant and is grown predominantly in southern India (Govindarajanet al., 1982). The false cardamom, large cardamom, or black cardamomfrom the allied genus Amomum is native to Nepal, Sikkim, Bengal andsoutheast Asian countries. African cardamom, which is botanicallyknown as Aframomum danielli (Hook.f.) K. Schum., is native to southeast Africa especially in Tanzania, Cameroon, Madagascar and Guinea

https://doi.org/10.1016/j.jep.2019.112244Received 4 March 2019; Received in revised form 16 September 2019; Accepted 16 September 2019

∗ Corresponding author.E-mail address: biotech.ashok@gmail.com (K. Ashokkumar).

Journal of Ethnopharmacology 246 (2020) 112244

Available online 18 September 20190378-8741/ © 2019 Published by Elsevier B.V.

T

(Govindarajan et al., 1982; Adegoke et al., 1998). Small cardamom isextensively cultivated in Nepal and Sikkim and to a limited extent withthe large cardamom (Amomum subulatum Roxb.). However, interna-tional trade is now limited to Asian countries as far as small and largecardamom are concerned because of high prices. Worldwide, car-damom is recognized as the “queen of spices” for its pleasant aroma andtaste, and is the third most expensive spice after saffron and vanilla.

For centuries, cardamom capsules have been used for culinary andtraditional medicine applications including controlling asthma, teethand gum infections, digestive and kidney disorders (Hamzaa et al.,2012; Saeed et al., 2014), cataracts, nausea, diarrhea and cardiac dis-orders (Gilani et al., 2008; Khan et al., 2011). The essential oil andother bioactive metabolites accumulated in cardamom capsules con-tribute to their characteristic aroma and utility as a functional food,pharmaceutical, and nutraceutical (Hamzaa et al., 2012). The essentialoil (EO) content of cardamom capsules varies from 6 to 14% dependingupon the type and processing methods (Menon, 2000). EO of cardamomcapsules possess predominantly monoterpene constituents, such as 1,8-cineole, α-pinene, α-terpineol, linalool, linalyl acetate and nerolidoland the ester constituent α-terpinyl acetate (Kaskoos et al., 2006;Yashin et al., 2017; Ashokkumar et al., 2019b), all of which havetherapeutic benefits including antioxidant, anticancer, antidiabetic,anti-inflammatory, antifungal, antiviral and gastroprotective activities(Nirmala, 2000; Marongiu et al., 2004; Hamzaa et al., 2012; Winarsiet al., 2014). Recent reports claimed that flavonoids, terpenoids, an-thocyanins, alkaloids and other phenolic constituents from cardamomwere being used for controlling cardiovascular, pulmonary, kidney andlung associated disorders (Vaidya and Rathod, 2014). The aim of thisreview is to highlight the main phytochemicals and beneficial effects ofcardamom essential oil (CEO) and extracts on human health.

2. Botany

Small cardamom (Elettaria cardamomum L. Maton), belongs to theZingiberaceae family. The basic chromosome number x= 12 and2n=48 indicates its balanced tetraploid nature (Madhusoodananet al., 2002). The habitat and field view of the cardamom plant is shownin Fig. 1. Cardamom is an herbaceous perennial plant that grows 2–5min height, with underground rhizomes and is propagated by vegetativedivision of rhizomes. The aerial stem is formed by encircling the leafsheaths. The leaves are 30–35 cm long and 7–10 cm wide, lanceolatewith acuminate tip and dark green in colour. Tillers emerge from theaxils of underground stems. Most of the vegetative buds are producedduring monsoon periods (Murugan et al., 2016). Inflorescences arisefrom the rhizomes as a panicle possessing a long cane-like pedunclehaving nodes and internodes. Normally, 2–4 panicles emerge from theswollen base of tillers and certain cultivars have panicles with multiplebranches. Flowers of most cardamom types and varieties are white withthe central lip streaked with pink (Telja et al., 2006). The flowers are

bisexual, irregular and cross-pollination is most common. The labellumis oval and indistinctly 3 lobed. The calyx is tubular, split about ¼ of itslength on one side and shortly 3 toothed. The corolla is unequally threelobed with the larger one at the posterior side. The fertile stamen isunited without connective appendages, but prolonged into a short crest.The crest is positioned above or below the stigma. Anthers are twolobed, adnate to the filament and dehisce vertically. The size of pollengrains varies from 75 to 120 μm in diameter. The stigma is funnelshaped with cilia around a small cavity. The ovary is inferior, trilocularwith axial placentation and ovules are numerous in each carpel. An-thesis typically starts at 3.30 am and continues until 7.30 am, themaximum pollen bursting occurs between 5.30 am and 6.30 am(Prameshwar and Venugopal, 1974).

Capsules (fruits) mature completely in about 120 days from flow-ering. The fruits are ellipsoidal or almost spherical, non-dehiscent,fleshy and leathery when dry. The fruit colour is green and turns goldenyellow on ripening and is 1–2 cm in length. Depending upon the gen-otype, each capsule contains 12 to 32 seeds and the ripe seeds are blackand covered with a white mucilaginous coat (Murugan et al., 2016).Cardamom is highly cross-pollinated and depends on honeybees forpollination. Cardamom is classified into three types based on the natureof the panicles namely, Malabar (prostrate panicle), Mysore (erect pa-nicle) and Vazhukka (semi-erect panicle), shown in Fig. 2. The threecardamom types are briefly described below.

(a) Malabar: This type is well suited for lower elevation of 600–1000mabove msl (mean sea level) and plants reach 2–3m height on ma-turity. Panicles are absolutely prostrate (Fig. 2). This type is rela-tively less susceptible to thrips and shoot borer infestation. It canbloom even under low rainfall conditions in Kerala and Tamil Nadu.Cured capsules are generally round and approximately 18mm inlength.

(b) Mysore: This type is adapted to elevation ranging from 900 to1200m above msl. Plants are robust and attain 3–4m height onmaturity. Panicles are completely erect (Fig. 2). It is best adapted toregions in Kerala and Karnataka with well distributed rainfall.Cured capsules are three cornered and ribbed and tend to be slightlylonger than Malabar type, being about 21mm length.

(c) Vazhukka: This type is a natural hybrid between Malabar andMysore types and exhibits intermediate characteristics of both. It iswell adapted to elevations ranging from 900 – 1200m above msl.Plants are robust and panicles are semi-erect (Fig. 2). Capsules arebold, globose or ovoid shape.

A typical photograph of the various botanical features of these threetypes including flower types, androecium, gynoecium, panicles, ma-tured and cured capsules and seeds are presented in Fig. 3.

Fig. 1. Field view and habitat of Elettaria cardamomum (L.) Maton.

K. Ashokkumar, et al. Journal of Ethnopharmacology 246 (2020) 112244

2

3. Traditional uses and ethnopharmacology

Small cardamom capsules have been used since the 4th century BCby Indian Ayurveda doctors and ancient Greek and Roman doctors fortreating various health problems such as bronchitis, asthma and con-stipation (Al-Zuhair et al., 1996; Bisht et al., 2011), cold, cough,diuretic, carminative, teeth and gum infections, urinary and kidneydisorders, congestion of lungs, pulmonary tuberculosis, and irritation ofeyelids (Jafri et al., 2001; Hamzaa et al., 2012; Saeed et al., 2014), andcataracts, nausea, diarrhea and cardiac disorders (Gilani et al., 2008;Khan et al., 2011). In Chinese traditional medicine, cardamom was usedto treat constipation, stomach ache, bladder infections and dysentery inchildren (Kapoor, 1990; Duke et al., 2003). Cardamom has also beenwidely used to treat food poisoning in Ayurveda medicine. Currently,cardamom oils are used in manufacturing of some plant-based handcreams and soaps (Ajmera et al., 2018). Powdered cardamom capsules

mixed with pulverized cloves, ginger and caraway have been used fordigestive ailments (Govil, 1998). Cardamom powder drink is also anantidote for snake and scorpion venom. The consumption of cardamomcapsules reduces inflammation and headaches (Govil, 1998).

Cardamom capsule powder is used for bronchial asthma patientswith excess saliva and mucus in the respiratory tract, and as an ex-cellent cough suppressant. Cardamom tablets can be used for control-ling cold and related symptoms (Nair and Unnikrishnan, 1997). In In-dian traditional medicine, cardamom capsules are considered asexcellent digestive and balancing Kapha, mainly in stomach and lungs.Also, it is useful for pacifying Vata dhosa (https://www.mapi.com/ayurvedic-recipes/spices/cardamom.html). The cardamom seeds arechewed to avoid bad breath, vomiting and indigestion. Cardamomcapsules reduce the caffeine constituent in coffee and the combinationof cardamom and coffee is called ‘gavah’ which is popular in Arabianculture to relieve headaches and stress. Adding two drops of cardamom

Fig. 2. Types of cardamom based on nature of the panicles.

Fig. 3. Botanical features of cardamom.

K. Ashokkumar, et al. Journal of Ethnopharmacology 246 (2020) 112244

3

oil along with two drops of lavender oil to the water in the daily bathcan be used to maintain healthy skin (http://ayurvedicoils.com/tag/ayurvedic-health-benefits-of-cardamom-essential-oil). In Tibetan tradi-tional medicine, cardamom capsules are combined with cinnamon andlong pepper to treat obesity, glycemic imbalance, liver, kidney andheart diseases (https://www.sowawellness.com/2017/10/07/cardamom/). Some people believe that drinking macerated seeds inhot water at night has aphrodisiac potential (http://www.agricultureinindia.net/cultivation/cardamom/cardamom-cultivation-varieties-and-uses-spices-agriculture/15625).

In Kerala and Tamil Nadu, crushed cardamom capsules are boiledwith tea and water to impart a pleasant aroma to tea, which is popu-larly called “Elakkai tea” and which has been used to relieve tirednessdue to over work and depression. Cardamom capsules contain sig-nificant concentration of β-carotene (0.5 μg g-1), (Ashokkumar et al.,2019a). In traditional medicine, consumption of cardamom daily with atablespoon of honey improves the eyesight (Singh and Singh, 1996).However, some people believe that excessive uses of cardamom cap-sules could cause impotency in humans (Nair, 2011).

In Ayurveda, cardamom capsules have been used in many importantpreparations in the form of powders, oils and decoctions, as well asmedicinal fermented beverages like as Arishta and Aasava (Sahadevan,1965). The cardamom preparation, ‘Eladigana’ is commonly used tocure arthritis, congestion and itching. Intake of cardamom increasesurine production. A mixture of medicines known as Ariyau kashayam(six grains including cardamom) is used for curing skin diseases inchildren (Nair, 2011). Huang et al. (1999) examined the effect of car-damom extract on the transdermal-dermal delivery of indometacin andobserved that cardamom oil has enhanced the permeation of in-dometacin significantly in in vitro (rabbit, rat and human) and in vivo(rabbit) situations.

4. Chemical composition

4.1. Proximate and mineral composition

The proximate composition of cured cardamom capsules includescarbohydrate 68.2%, protein 10.6 %, fat 2.4 % and ash 5.3 % (Sontakkeet al., 2018). One hundred g of cured capsules contained calcium(93mg), magnesium (182mg), potassium (124mg), phosphorus(183mg), sulphur (100mg) and iron (13mg) (Sontakke et al., 2018;Ereifej et al., 2015; Murugan et al., 2012). These are essential mineralelements for normal day-to-day physiological activities of humans.Cardamom capsules and leaves contain significant levels of manganese,zinc and copper (Table 1). Ashokkumar et al. (2019a) reported nu-tritionally important metabolites of cardamom capsules that includeflavonoids (catechin, myricetin, quercetin and kaempferol) and car-otenoids (lutein and β-carotene) (Table 1).

4.2. Cardamom essential oil (CEO) and its composition

The yield of the EO from cardamom varied between 0.2% and 8.7%,on a dry basis, depending on the variety, plant parts and extractionmethods used (Table 2). The EO estimation by various methods issummarized in Table 2. The profiling of EO of cardamom seeds sampledfrom southern India predominantly exhibited 1, 8-cineole (28.94%), α-terpinyl acetate (26.7%), α-terpineol (14.6%), sabinene (13.5%), nerol(5.0%) and α-pinene (2.4%), (Ashokkumar et al., 2019b). Sharma et al.(2011) indicated that seeds of cardamom collected across the car-damom growing region of India chiefly contained α-terpinyl acetate, 1,8-cineole and α-terpineol. The EO of cardamom seeds from Guatemala,which is the global leader in cardamom production, possessed α-ter-pinyl acetate, 1, 8-cineole, sabinene, linalyl acetate and linalool as keyconstituents (Singh et al., 2008). The characteristic aroma of cardamomcapsules and seeds is principally developed by a combination of twomajor constituents namely 1, 8- cineole and α-terpinyl acetate (Olivero-

Verbel et al., 2010). The yield and chemical composition of majorcardamom essential oils across growing regions is presented in Table 3.The molecular structures of major essential oil constituents isolatedfrom cardamom are shown in Fig. 4. The yield of minor constituents ofCEO include limonene (2.9%), 4-terpineol (1.4%), α-pinene (1.1%), β-pinene (0.8%), myrcene (0.8%), octanal (0.2%), δ-3-carene (0.4%), p-cymene (0.7%), (E)-nerolidol (0.7%) cis-sabinene hydrate (0.6%), ger-anylacetate (0.3%), cis-sabinene hydrate acetate (0.2%), β-car-yophyllene (0.2%), β-selinene (0.2%), γ-cadinene (0.2%), and trans-li-nalooloxide (0.1%), (Mejdi et al., 2015).

4.3. Cardamom fixed oil and its composition

The composition of oil from cold pressed cardamom seeds pre-dominantly consisted of oleic acid (49.2 g/100 g of oil), palmitic acid(26.4 g/100 g of oil) and linoleic acid (15.2 g/100 g of oil); these alongwith other minor fatty acids are shown in Table 4 (modified from Parryet al., 2006). Among the fatty acids, cardamom oil contains 30.8, 51.3and 17.9 g/100 g of oil of total saturated fatty acids, total mono un-saturated fatty acid and total unsaturated fatty acid, respectively. Thefatty acids and their breakdown products have a major role in several

Table 1Proximate and mineral composition of dry matter basis of cardamom (Elettariacardamomum).

Proximate composition(%)

Capsules Leaves Authors

Carbohydrates (%) 68.2 – Sontakke et al. (2018)Protein (%) 10.6 – Sontakke et al. (2018)Fat (%) 2.4 – Sontakke et al. (2018)Ash (%) 5.3 – Sontakke et al. (2018)Acid insoluble ash (%) 1.76 – Kizhakkayil et al. (2006)Crude fibre (%) 16.3 – Kizhakkayil et al. (2006)Phenols (%) 3.26 – Kizhakkayil et al. (2006)Minerals (mg/100g)Calcium 92.7 – Sontakke et al. (2018)Phosphorus 188.5 – Murugan et al. (2012)Sodium 17.0 – Sontakke et al. (2018)Potassium 124.2 – Sontakke et al. (2018)Iron 12.8 28.4 Sontakke et al. (2018); Murugan

(2011)Copper 0.5 1.9 Murugan et al. (2012); Murugan

(2011)Magnesium 181.5 – Ereifej et al. (2015)Manganese 41.7 26.0 Murugan et al. (2012); Murugan

(2011)Zinc 3.6 0.2 Murugan et al. (2012); Murugan

(2011)Sulphur 100.8 – Murugan et al. (2012)Metabolites (μg/g)FlavonoidsCatechin 281.8 – Ashokkumar et al. (2019a)Myricetin 18.6 – Ashokkumar et al. (2019a)Quercetin 4.9 – Ashokkumar et al. (2019a)Kaempferol 8.7 – Ashokkumar et al. (2019a)Total flavonoids 314.0 – Ashokkumar et al. (2019a)CarotenoidsLutein 2.4 – Ashokkumar et al. (2019a)β-carotene 0.5 – Ashokkumar et al. (2019a)

Table 2Yield of essential oil from cardamom capsules.

echnique or method Oil yield (%) Authors

Steam distillation 0.2–5.6 Subaddarage et al. (1985)Steam distillation 2.6 Sontakke et al. (2018)Hydro-distillation 1.0 Ebru and Zehra (2013)Hydro-distillation 6–14 Menon (2000)Hydro-distillation 4–7 Abbasipour et al. (2011)Hydro-distillation 6–8.7 Leela et al. (2008)

K. Ashokkumar, et al. Journal of Ethnopharmacology 246 (2020) 112244

4

pathogen defense strategies in plants (Kachroo and Kachroo, 2009).Cardamom oil also contains several forms of tocopherols namely, α-tocopherol (10.4mg/kg of oil), γ-tocopherol (4.3mg/kg of oil) and δ-tocopherol (1.6mg/kg of oil) (Parry et al., 2006). Tocopherols whichhave vitamin E activity are also commonly found in oils of sunflower,olive, maize and soybean. Tocopherol is an effective antioxidant(Robertsii et al., 2007), and diets containing vitamin E are linked withlower risk of several types of human cancers such as kidney cancer(Shen et al., 2015), lung cancer (Zhu et al., 2017) and bladder cancer(Wang et al., 2014). Additionally, diets rich in tocopherol resulted in a23% reduction in age related cataracts (Zhang et al., 2015). Therefore,cardamom may play a key role in disease prevention and health pro-motion.

5. Biological effects of CEO and extracts

The CEO and cardamom extracts have various biological effectsincluding antioxidant, antibacterial, anticancer, insecticidal and othermiscellaneous activities that are summarized in Table 5.

Table 3Major essential oil composition of cardamom (Elettaria cardamomum).

Origin Parts Constituents Yield (%) Authors

South India Capsules 1,8-cineole 28.94 Ashokkumar et al.(2019b)

α-terpinylacetate

26.68

α-terpineol 14.58Sabinene 13.50Nerol 5.01α-pinene 2.42

Iran Seeds α-terpinylacetate

36.61 Chegini and Abbasipour(2017)

1,8-cineole 30.42Linalyl acetate 5.79Sabinene 4.85

Guatemala Seeds α-terpinylacetate

36.80 Singh et al. (2008)

1,8-cineole 29.20Linalyl acetate 5.20Sabinene 3.90Linalool 3.10

Costa Rica Seeds α-terpinylacetate

39.31 Noleau et al. (1987)

Linalool 5.91Sabinene 3.78α-terpineol 2.97Geraniol 2.66

Sri Lanka Capsules α-terpinylacetate

74.60 Subaddarage et al.(1985)

Linalool 12.701,8 Cineole 4.40β-terpineol 1.80

Pakistan Leaves 4-terpineol 30.26 Mahmud (2008)1,8-Cineol 25.74α-terpene 9.80Linalool 2.67

Fig. 4. Molecular structure of the major essential oil constituents in Elettaria cardamomum (L.).

Table 4Fatty acid composition of cardamom oil (modified table of Parry et al., 2006).

Fatty acid Lipidnumber

Composition (g/100gof oil)

Category of fatty acid

Myristic acid 14:0 1.5 SaturatedPalmitic acid 16:0 26.4 SaturatedPalmitoleic acid 16:1 1.6 Mono-unsaturatedStearic acid 18:0 2.3 SaturatedOleic acid 18:1 49.2 Mono-unsaturatedLinoleic acid 18:2 15.2 Polyunsaturatedα-Linolenic acid 18:3 2.7 PolyunsaturatedArachidic acid 20:0 0.4 SaturatedEicosenoic acid 20:1 0.5 Polyunsaturated

K. Ashokkumar, et al. Journal of Ethnopharmacology 246 (2020) 112244

5

Table5

Theactiv

ities

ofcardam

omextracts

andessentialo

ilcompo

nents.

Pharmacolog

ical

activ

ities

Stud

yextract/

CEO

Invitro/

Invivo

Target/M

odel

Control(s)

IC50

/Dosage

Results

/Rem

arks

Reference

Antibacterial

activ

ityCE

OIn

vitro

S.aureus

Positiv

e:Amoxicillin

andciprofl

oxacin

MIC:6

.25mg/ml

MBC

:12.5mg/ml

Mod

eratean

tibacterial

activ

ity@

6.25

mg/ml

Grădina

ruet

al.

(201

4)Antibacterial

activ

ity1,8-cineole

Invitro

S.aureus

Positiv

e:Amoxicillin

andciprofl

oxacin

MIC:1

.25–

2.5mg/ml

MBC

:2.5mg/ml

Notew

orthyan

tibacterial

activ

ity@

2.5mg/ml

Grădina

ruet

al.

(201

4)Antibacterial

activ

ityAqu

eous

cardam

omcapsuleextract

Invitro

E.coli,

S.typhia

ndS.

aureus

Positiv

e:Te

tracyclin

eNegative:

Distilledwater

MIC:0

.5–4

.1mg/ml

Inhibitio

nzone

rang

edfrom

12.3

to20

.6mm

with

best

inhibitory

effectagainstS.

aureus

Kaushiket

al.

(201

0)

Antifu

ngal

activ

ityCE

OIn

vitro

Candidaspp.

andS.

cerevisia

ePo

sitiv

e:Amph

otericin

BNegative:

Distilledwater

MIC:0

.048

–0.097

mg/ml

MFC

:6.25–

12.50mg/ml

Inhibitio

nzone

rang

edfrom

13.3

to21

.7mm

with

bestinhibitory

effect@

0.04

8mg/mla

gainstCa

ndida

parapsilosis

Nou

mie

tal.

(201

8)

Cardioprotectiv

eactiv

ityAqu

eous

cardam

omcapsuleextract

Invivo

Wistarm

alealbino

ratsindu

cedby

Isop

rotereno

lPo

sitiv

e:Isop

rotereno

l(ISO)

Negative:

Normal

Salin

e

100mgan

d20

0mg/kg/

oral

for30

days

Treatm

entwith

cardam

omextracts

(100

&20

0mg/

kg)resulte

din

sign

ificant

declineof

arterial

pressure

indices,systolic

arterial

pressure

(SAP),d

iastolic

arterial

pressure

(DAP),m

eanarterial

pressure

(MAP)

andmyo

cardiale

nzym

esthan

control

Goy

alet

al.(20

15)

Antidiabetic

and

hypo

cholesterolemic

activ

ityEtha

nolleaf

extract

Invivo

Allo

xan(120

mg/kg)indu

ced

Spragu

eDaw

leydiab

etic

rats

Negative:

Normal

Salin

eNot

repo

rted

Orala

dministrationof

etha

nolic

leaf

extractfor14

days,d

ecreased

bloo

dglucoselevelfrom

201.7to

102.

8mg/dl.H

owever,d

osean

dpo

sitiv

econtrolw

asno

treported,

itredu

cing

therelia

bilityof

results

Winarsiet

al.

(201

4)

Antidiabetic

activ

ityCa

psule/tablet

Invivo

Eigh

tyov

erweigh

torob

ese

patie

ntswith

type

2diab

etes

Positiv

e:Irisin,a

ndSirtuin1

(SIRT1

)Negative:

Distilled

water

1g/3tim

es/day

for10

weeks

Theresults

ofthistrialp

rovidesclinical

evidence

ontheeff

ectiv

enessan

dsafety

ofcardam

omsupp

lementatio

nin

patie

ntswith

Type

2diab

etes

Agh

asie

tal.

(201

8)

Antidiabetic

activ

ityCa

psule/tablet

Invivo

Obese

wom

enpa

tientswith

pre-

diab

etic

Negative:

Placebo

3g/dfor8weeks

Nosign

ificant

decrease

insystolic

anddiastolic

bloo

dpressure,g

lycemic

indices,an

dserum

lipidsvalues

incardam

oman

dplacebogrou

ps.

Thisstud

yalso

repo

rted

that

3g/da

yof

cardam

omwou

ldbe

alargebu

tno

tun

reason

able

amou

ntto

consum

eas

apa

rtof

thediet.

Fatemeh

etal.

(201

7)

Anti-o

besity

andno

nalcoh

olic

fatty

liver

disease(N

FLD)

Capsule/tablet

Invivo

Overw

eigh

torob

esepa

tientswith

nona

lcoh

olic

fattyliv

erdisease

(NFL

D)

Negative:

Placebo

1g/3

times/day

for12

weeks

Incompa

risonwith

placebo,

cardam

omsign

ificantly

redu

cedtumor

necrosisfactor-alpha

(TNF-α),h

igh

sensitive

c-reactiv

eprotein(hs-CR

P),interleuk

in-6

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degree

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(201

8)

(continuedon

next

page)

K. Ashokkumar, et al. Journal of Ethnopharmacology 246 (2020) 112244

6

5.1. Antioxidant activity

Oxidative stress is a chief factor for induction of several chronic anddegenerative diseases such as diabetes, cancer, immune dysfunctionand Parkinson's (Haliwell, 2000; Metodiewa and Koska, 2000). Anti-oxidants are natural or synthetic compounds that can be used for pre-vention of free radical formation through scavenging and suppressionof chronic and degenerative diseases (Haliwell, 2000). Currently, thereis an increasing interest towards natural antioxidants from herbalsources (Larson, 1988; Velioglu et al., 1998). Cardamom capsules andseeds are rich sources of antioxidant substances that neutralize freeradicals by preventing oxidation of other components. Nair et al. (1998)reported that cardamom capsules have a moderate level of naturalantioxidant properties owing to the presence of phenol compounds suchas quercetin, kaempferol and luteolins. Natural antioxidants arethought to be safer than synthetic forms (Saeed et al., 2014). Likephytonutrients and vitamins, EO of cardamom acts as an antioxidantand helps scavenging free radicals, thus reducing cellular ageing(Nanasombat and Wimuttigosol, 2011; Saeed et al., 2014). However,some of the studies of antioxidant activity based on chemical tests in-cluding DPHH assays no longer have pharmacological relevance. Theirpotential under in vitro and in vivo conditions need to studied for theseeffects to be considered clinically relevant (Harnly, 2017).

5.2. Anticancer activity

The essential oil of cardamom capsules in in vitro studies showedanticarcinogenic effects by inhibiting damage to adult DNA by aflatoxinB1 in a microsomal enzyme intermediated reaction (Hashim et al.,1994). This might be due to bioactive components present in the es-sential oil that have potential anticancer roles. Cardamom oil increasedthe glutathione transferase and acid-soluble sulfhydryl activities andarbitrates the oxidation and detoxification of xenobiotics (Banerjeeet al., 1994). Bhattacharjee et al. (2007) reported that the constituentsof phytochemicals of CEOs such as 1, 8-cineole and limonene demon-strated a protective role against cancer development. Further they saidaqueous cardamom extract could improve the activity of the detox-ifying enzyme glutathione S-transferase and reduce lipid peroxidation.Elguindy et al. (2018) stated that oral administration of CEO at doses of100 and 200mg/kg/day for 26 weeks significantly decreased serumcreatinine and urea, and LDH activity in diethylnitrosamine (DENA)induced oxidative stress in rats. Only a few studies have investigatedthe anticancer potential of cardamom extracts and CEO, and these wereconducted in animal models, not in humans. Hence, future investiga-tions should be focused on the bioactivity of CEO in various clinicalstudies with humans.

5.3. Cytotoxic activity

Cardamom capsule extracts considerably enhanced the cytotoxiceffects of natural killer cells and indicated their anticancer potential(Majdalawieh and Carr, 2010). According to Raksamiharja et al.(2012), CEO enhanced the amount of lymphocyte, CD4+ and CD8+ indoxorubicin treated rats in a dose dependent manner. Additionally,Elguindy et al. (2016) reported that cardamom essential oil or geraniol(200mg/kg) decreased the level of TNF, IL-1 and NF-κB in diethylni-trosamine induced rats. These researchers also showed that CEO was animmune stimulant agent for chemotherapy. Even though the safety ofcardamom extracts and CEO was indicated, the use of cell lines basedonly on in vitro assays limits the pharmacological relevance of thisoutcome.

5.4. Antimicrobial and antibacterial activity

The EO of cardamom has robust antibacterial effects against variousfood-borne microorganisms (Kubo et al., 1991). Growth of MorgenellaTa

ble5(continued)

Pharmacolog

ical

activ

ities

Stud

yextract/

CEO

Invitro/

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Target/M

odel

Control(s)

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Results

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arks

Reference

Insecticidal

activ

ity(O

vipo

sitio

ndeterrence)

CEO

Invivo

Femalead

ultof

Callosobruchus

maculatus

Negative:

Distilledwater

LC50:3

5.7,

49.98,

57.12,

and64

.26mg/mlfor

48h

Results

show

edthat

numberof

eggs

laid

byC.

maculatus

females

intreatm

ents57

.12an

d64

.26mg/

mlfor

48hwas

sign

ificantly

lower

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doses(35.7an

d49

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tsign

ificantly

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e.

Abb

asipou

ret

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(201

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,Minim

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LC50

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IC50,Inhibitory

con-

centratio

n.

K. Ashokkumar, et al. Journal of Ethnopharmacology 246 (2020) 112244

7

morganii was moderately inhibited by the application of cardamom oil(Shakila et al., 1996). CEO (10mg/ml) showed antibacterial activityagainst S. aureus, E. coli, S. typhi, Streptococcus mutans and C. albicans(Abdullah et al., 2018), Bacillus pulmilus and Listeria monocytogenes(Bano et al., 2016). Hence, CEO could play a vital role in developingsafe and novel antibiotics in modern medicine. According to Mejdi et al.(2015), CEO has potential broad-spectrum antibacterial and antifungalactivities that could be used to prevent damage from food-borne pa-thogens and food spoilage organisms. The majority of studies focusingon the antibacterial activity of cardamom extracts and CEO have beenconducted using the disc diffusion method (Grădinaru et al.,2014;Kaushik et al., 2010), however given its inherent limitations, themethod needs to be supplemented by the more relevant MIC assay (VanVuuren, 2008).

5.5. Insecticidal activity

The development of bioactive constituents that are less persistentwill be beneficial to both farmers and the environment. Exploitation ofnatural products such as EOs are being considered as substitutes tochemical pesticides due to their low toxicity effect on non-target or-ganisms and their lower persistence in the environment. Therefore, EOof cardamom could be used as a stored grain protectant by killing ordisturbing various life stages of insect pests (including Sitophilus zeamaisand Trilobium castaneum) attacking wheat, through direct interactionand fumigant action (Huang et al., 2000). Chegini and Abbasipour(2017) evaluated insecticidal activity of CEO against various stages(egg, 2nd larval instars and adults) of tomato leaf minor (Tuta absoluta)and noticed that CEO has LC50% (lethal concentration, 50%) values foreggs, larvae and adults as 351.19, 7.88 and 1.55 μl L-1, respectively andobserved that CEO has high potential for controlling T. absoluta, par-ticularly under protected situations. Thus far, only one study has in-vestigated the insecticidal activity of CEO, so additional research isrequired in this promising application.

5.6. Miscellaneous activity

Recently, CEO has been extracted and commercially used in thefood industry as a flavoring agent in bread, cakes, curry powder andpickles. Capsules and volatile oils of cardamom are being used as fla-voring constituents in various types of foods, including alcoholic andnon-alcoholic beverages, frozen desserts, candies, puddings, bakedgoods, condiments, gravies and meat products. Cardamom oil is alsomixed with massage oil, perfumes and lotions, because of its soothingproperties (Madhusoodanan et al., 2002).

Three CEO components (α- pinene, β- pinene and α- terpineol) hadsynergistic effects with 1, 8-cineole and enhanced the penetration ofindometacin. Hence, addition of CEO in ointments and lotions in-creased the absorption of medicines through the skin. Al-Zuhair et al.(1996) observed that CEO has antispasmodic action through receptorblockage, in addition to diuretic properties. Lahlou et al. (2002) as-sessed the cardiovascular activity of CEO 1,8-cineole in animal ex-perimental studies and observed intravenous bolus injections of0.3–10mg/kg (1,8-cineole) stimulated dose dependent decline in aorticpulse pressure. Elkomy et al. (2015) proposed that the administration ofgentamicin along with powdered cardamom at 100mg/kg and 20mg/kg had noteworthy protection of rat kidneys.

6. Conclusion

In the present review, we summarize the knowledge on botany,ethnobotanical and traditional uses, phytochemistry and pharmacolo-gical activities of E. cardamomum, which has been widely used to treatseveral illnesses in ancient and modern India. According to the classicalIndian medical treatises, E. cardamomum has been traditionally used totreat teeth and gum infections, asthma, nausea, diarrhea, digestive,

kidney disorders and others. Over a very long history, E. cardamomumhas been demonstrated to be reliable, and now it is important to un-derstand whether modern pharmacological studies on E. cardamomumare available to assess the traditional uses. We demonstrate that some ofthe modern in vitro and in vivo pharmacological studies have confirmedthe traditional use of E. cardamomum.

Based on the currently available information, more than 100 sec-ondary metabolites have been isolated from E. cardamomum, and ofthese 1, 8-cineole is an most important active compound, which showedantitumor, anti-inflammatory and cardiovascular activities.Furthermore, cardamom extracts and CEO has been extensively ex-plored for their beneficial constituents (Table 5). However, gaps exist inthe scientific studies on E. cardamomum, and we have provided re-commendations of several topics that should have priority for detailedinvestigations.

Firstly, based on the currently available phytochemistry reports, theinvestigations on the structural characterization of metabolites in E.cardamomum capsules are very limited. Thus, in-depth investigations ofstructural identification and purification of the bioactive metabolitesfrom cardamom is essential.

Secondly, the essential oil of cardamom loses it flavor rapidly uponstoring under normal ambience/environment. The change in the aromaor flavor can also cause changes in the constituents of its phytochem-icals. Yet very little research has been conducted on maintaining theshelf-life quality of CEO.

Thirdly, insufficient pharmacological studies have been conductedon cardamom. Some biological activity studies were performed usingvery high dosage concentrations, some were lacking in comparison withstandard positive and negative controls, and others lacked determina-tion of MIC values, possibly leading to false positive results.

Fourthly, previous pharmacological investigations were mostly fo-cused on the CEO and organic fractions of crude extracts with littleattention on the aqueous extracts; we need to give attention to its tra-ditional usage. Likewise, comprehensive placebo-controlled anddouble-blind clinical trials are required to evaluate efficacy and safety.

Fifthly, although E. cardamomum possesses various potential ther-apeutic effects on antioxidant, anti-inflammatory, antidiarrheal, antic-ancer, cytotoxic and cardio-protective activities, these studies wereperformed only in animal and cell models and clinical investigations inhumans have rarely been implemented. Hence, future investigationshould be focused on the bioactivity of CEO in various clinical studieswith humans. Such research will benefit future pharmaceutical appli-cations of CEO.

Overall, E. cardamomum appears to be both a nutraceutical and afunctional food, with regular consumption of cardamom capsuleshaving potential to protect humans from various chronic diseases. Thepresence of biologically active molecules such as 1, 8-cineole, α-ter-pinyl acetate, α-terpineol and sabinene as major components in car-damom oil can serve as a new potential natural source, which can beused in the food, aroma, cosmetics and pharmaceutical domains. In thefuture, studies are needed on the bioavailability and pharmacokineticsof E. cardamomum to search for the metabolites responsible for its ac-tivities. Thus far, the available pharmacological studies are insufficientto assess the ethnobotanical uses. Further research should be conductedto expand the medical application of E. cardamomum.

Author contributions

K.A and M.M conceptualized the manuscript. K.A. wrote themanuscript, M.M. and M.K.D. collected and reviewed the literature onthe chemical composition and biological activities. T.W. contributed tothe manuscript editing. All authors approved the final version.

Conflicts of interest

The authors have no conflict of interest.

K. Ashokkumar, et al. Journal of Ethnopharmacology 246 (2020) 112244

8

Acknowledgements

We thank Mrs. Surya Raj for reference checking and Dr. ArjunPandian, PRIST Deemed University-Thanjavur, for technical assistanceto draw the molecular structures of major constituents of cardamomessential oil. The authors also thank five anonymous reviewers for theirdetailed suggestions for improving the manuscript.

References

Abbasipour, H., Mahmoudvand, M., Rastegar, F., Hosseinpour, M.H., 2011. Fumiganttoxicity and oviposition deterrency of the essential oil from cardamom, Elettariacardamomum, against three stored-product insects. J. Insect Sci. 11, 165. https://doi.org/10.1673/031.011.16501.

Abdullah, Asghar, A., Butt, M.S., Shahid, M., Huang, Q., 2018. Evaluating the anti-microbial potential of green cardamom essential oil focusing on quorum sensinginhibition of Chromobacterium violaceum. J. Food Sci. Technol. 54, 2306–2315.

Adegoke, G.O., Rao, L.J.M., Shankaracharya, N.B., 1998. A comparison of the essentialoils of Aframomum danielli (Hook.f.) K. Schum. and Amomum subulatum Roxb. FlavourFragrance J. 13, 349–352.

Aghasi, M., Ghazi-Zahedi, S., Koohdani, F., Siassi, F., Nasli-Esfahani, E., Keshavarz, A.,Qorbani, M., Khoshamal, H., Salari-Moghaddam, A., Sotoudeh, G., 2018. The effectsof green cardamom supplementation on blood glucose, lipids profile, oxidative stress,sirtuin-1 and irisin in type 2 diabetic patients: a study protocol for a randomizedplacebo-controlled clinical trial. BMC Complement Altern. Med. 18, 18. https://doi.org/10.1186/s12906-017-2068-6.

Ajmera, P., Singh, A., Chauhan, Sharma, L., Singh, M., 2018. Cardamom crop productionand harvesting: a review. Int. J. Food Sci. Nutr. 3, 174–178.

Al-Zuhair, H., El-Sayeh, B., Ameen, H.A., Al-Shoora, H., 1996. Pharmacological studies ofcardamom oil in animals. Pharmacol. Res. 34, 79–82.

Ashokkumar, K., Murugan, M., Dhanya, M.K., Surya, R., Kamaraj, D., 2019b.Phytochemical variations among four distinct varieties of Indian cardamom Elettariacardamomum (L.) Maton. Nat. Prod. Res. https://doi.org/10.1080/14786419.2018.1561687.

Ashokkumar, K., Pandian, A., Murugan, M., Dhanya, M.K., Sathyan, T., Sivakumar, P.,Surya, R., Warkentin, T.D., 2019a. Profiling bioactive flavonoids and carotenoids inselect south Indian spices and nuts. Nat. Prod. Res. https://doi.org/10.1080/14786419.2018.1557179.

Banerjee, S., Sharma, R., Kale, R.K., Rao, A.R., 1994. Influence of certain essential oils oncarcinogen-metabolising enzymes. Nutr. Cancer 21, 263–269.

Bano, S., Ahmad, N., Sharma, A.K., 2016. Phytochemical screening and evaluation ofantimicrobial and antioxidant activity of Elettaria cardamomum (Cardamom). JApplied Natural Sci 8, 1966–1970.

Bhattacharjee, S., Rana, T., Sengupta, A., 2007. Inhibition of lipid peroxidation and en-hancement of GST activity by cardamom and cinnamon during chemically inducedcolon carcinogenesis in Swiss albino mice. Asian Pac. J. Cancer Prev. APJCP 8,578–582.

Bisht, V.K., Negi, J.S., Bhandari, A.K., Sundriyal, R.C., 2011. Amomum subulatum Roxb:traditional, phytochemical and biological activities-An overview. Afr. J. Agric. Res. 6,5386–5390.

Chegini, S.G., Abbasipour, H., 2017. Chemical composition and insecticidal effects of theessential oil of cardamom, Elettaria cardamomum on the tomato leaf miner, Tuta ab-soluta. Toxin Rev. 36, 12–17.

Daneshi-Maskooni, M., Keshavarz, S.A., Qorbani, M., Mansouri, S., Alavian, S.M., Badri-Fariman, M., Jazayeri-Tehrani, S.A., Sotoudeh, G., 2018. Green cardamom increasesSirtuin-1 and reduces inflammation in overweight or obese patients with non-alco-holic fatty liver disease: a double-blind randomized placebo-controlled clinical trial.Nutr. Metab. 15, 63. https://doi.org/10.1186/s12986-018-0297-4.

Duke, J.A., Bogenschutz-Godwin, M.J., deCellier, J., Duke, P.K., 2003. Elettaria carda-momum (L.) Maton (Zingiberaceae) cardamom, malabar or Mysore cardamom. In:CRC Handbook of Medicinal Spices. CRC Press, Washington DC, pp. 159.

Ebru, K.S., Zehra, F.K., 2013. Essential oil composition of Elettaria cardamomum Maton. J.Appl. Biol. Sci. 7, 42–45.

Elguindy, N.M., Yacouta, G.A., El Azab, E.F., 2018. Amelioration of DENA-induced oxi-dative stress in rat kidney and brain by the essential oil of Elettaria cardamomum.Beni-Seuf Univ J Appl Sci. 7, 299–305.

Elguindy, N.M., Yacouta, G.A., El Azab, E.F., Maghraby, H.K., 2016. Chemoprotectiveeffect of Elettaria cardamomum against chemically induced hepatocellular carcinomain rats by inhibiting NF-κB, oxidative stress, and activity of ornithine decarboxylase.South Afr. J. Bot. 105, 251–258.

Elkomy, A., Aboubakr, M., Elsawaf, N., 2015. Renal protective effect of cardamom againstnephrotoxicity induced by gentamicin in rats. Benha Veterinary Med J 29, 100–105.

Ereifej, K.I., Feng, H., Rababah, T.M., Tashtoush, S.H., Al-U’datt, M.H., Al-Rabadi, G.J.,Torley, P., Alkasrawi, M., 2015. Microbial status and nutritional composition ofspices used in food preparation. Food Nutr. Sci. 6, 1134–1140.

Fatemeh, Y., Siassi, F., Rahimi, A., Koohdani, F., Doostan, F., Qorbani, M., Sotoudeh, G.,2017. The effect of cardamom supplementation on serum lipids, glycemic indices andblood pressure in overweight and obese pre-diabetic women: a randomized con-trolled trial. J. Diabetes Metab. Disord. 16, 40. https://doi.org/10.1186/s40200-017-0320-8.

Garg, G., Sharma, S., Dua, A., Mahajan, R., 2016. Antibacterial potential of polyphenolrich methanol extract of cardamom (Amomum subulatum). J Innovative Biol 3,271–275.

Gilani, A.H., Jabeen, Q., Khan, A., Shah, J., 2008. Gut modulatory, blood pressure low-ering, diuretic and sedative activities of cardamom. J. Ethnopharmacol. 115,463–472.

Govil, J.N., 1998. Glimpses in Plant Research. Vol. XII. Current Concepts ofMultidiscipline Approach to the Medicinal Plants (Part I). Today and Tomorrow’sPrinters, New Delhi.

Govindarajan, V.S., Shanthi, N., Raghuveer, K.G., Lewis, Y.S., Stahl, W.H., 1982.Cardamom - production, technology, chemistry, and quality. Crit. Rev. Food Sci.Nutr. 16, 229–326.

Goyal, S.N., Sharma, C., Mahajan, U.B., Patil, C.R., Agarwal, Y.O., Kumari, S., Arya, D.S.,Ojha, S., 2015. Protective effects on cardamom in isoproterenol induced myocardialinfraction in rats. Int. J. Mol. Sci. 16, 27457–27469.

Grădinaru, A.C., Aprotosoaie, A.C., Trifan, A., Șpac, A., Brebu, M., Miron, A., 2014.Interactions between cardamom essential oil and conventional antibiotics againstStaphylococcus aureus clinical isolates. Farmacia 62, 1214–1222.

Halliwell, B., 2000. The antioxidant paradox. Lancet 355, 1179–1180.Hamzaa, R., Osman, N., 2012. Using of coffee and cardamom mixture to ameliorate

oxidative stress induced in γ-irradiated rats. Biochem. Anal. Biochem. 1, 113–119.Harnly, J., 2017. Antioxidant methods. J. Food Compos. Anal. 64, 145–146.Hashim, S., Aboobaker, V.S., Madhubala, R., Bhattacharya, R.K., Rao, A.R., 1994.

Modulatory effects of essential oils from spices on the formation of DNA adduct byaflatoxin B1 in vitro. Nutr. Cancer 21, 169–175.. http://ayurvedicoils.com/tag/ayurvedic-health-benefits-of-cardamom-essential-oil http://www.agricultureinindia.net/cultivation/cardamom/cardamom-cultivation-varieties-and-uses-spices-agriculture/15625 https://www.mapi.com/ayurvedic-recipes/spices/cardamom.html https://www.sowawellness.com/2017/10/07/cardamom/.

Huang, Y., Lam, S.L., Ho, S.H., 2000. Bioactivities of essential oil from Elettaria carda-momum (L.) Maton to Sitophilus zeamais mostschulsky and Tribolium castaneum.Herbst J Stored Products Res 36, 167–171.

Huang, Y.B., Fang, J.Y., Hung, C.H., Wu, P.C., Tsai, Y.H., 1999. Cyclic monoterpene ex-tract from cardamom oil as a skin permeation enhancer for indometacin; in vitro andin vivo studies. Biol. Pharm. Bull. 22, 642–646.

Jafri, M.A., Farah, Javed, K., Singh, S., 2001. Evaluation of the gastric antiulcerogeniceffect of large cardamom (fruits of Amomum subulatum Roxb). J. Ethnopharmacol. 75,89–94.

Jamal, A., Kalim, J., Aslama, M., Jafri, M.A., 2006. Gastroprotective effect of cardamom,Elettaria cardamomum Maton. fruits in rats. J. Ethnopharmacol. 103, 149–153.

Kachroo, A., Kachroo, P., 2009. Fatty Acid-derived signals in plant defense. Annu. Rev.Phytopathol. 47, 153–176.

Kapoor, L.D., 1990. Handbook of Ayurvedic Medicinal Plants. CRC Press, Boca Raton, pp.p172.

Kaskoos, R.A., Ali, M., Kapoor, R., Akhtar, M.M.S., Mir, S.R., 2006. Essential oil com-position of the fruits of Eletteria cardamomum. J Essent Oil Bear Pl 9, 81–84.

Kaushik, P., Goyal, P., Chauhan, A., Chauhan, G., 2010. In Vitro evaluation of anti-bacterial potential of dry fruit extracts of Elettaria cardamomum Maton (ChhotiElaichi). Iran. J. Pharm. Res. (IJPR) 9 (3), 287–292.

Khan, A.U., Khan, Q.J., Gilani, A.H., 2011. Pharmacological basis for the medicinal use ofcardamom in asthma. Bangladesh J. Pharmacol. 6, 34–37.

Kizhakkayil, J., Thomas, E., Zachariah, T.J., Syamkumar, S., Sasikumar, B., 2006. Acomparative quality appraisal of exported cardamoms of India, Sri Lanka andGuatemala. Nat. Product. Radiance 5, 361–365.

Kubo, I., Himejima, M., Murari, H., 1991. Antimicrobial activity of flavour components ofCardamom. J. Agric. Food Chem. 39, 1984–1986.

Lahlou, S., Figuiredo, A.F., Magalhaes, P.J.C., Leal-Cardoso, J.H., 2002. Cardiovasculareffects of 1,8-cineole, a terpenoid oxide present in many plant essential oils, innormotensive rats. Can. J. Physiol. Pharmacol. 80, 1125–1131.

Larson, R.A., 1988. The antioxidants of higher plants. Phytochemistry (Oxf.) 27, 969–978.Leela, N.K., Prasath, D., Venugopal, M.N., 2008. Essential oil composition of selected

cardamom genotypes at different maturity levels. Indian J. Hortic. 65 (3), 366–369.Madhusoodanan, K.J., Pradeep Kumar, K., Ravindran, P.N., 2002. Chapter 2: botany, crop

improvement and biotechnology of cardamom. In: Ravindran, P.N., Madhusoodanan,K.J. (Eds.), Cardamom - the Genus Elettaria (Medicinal and Aromatic Plants IndustrialSeries). CRC Press, Taylor and Francis Group, London, United Kingdom, pp. 11–68.

Mahindru, S.N., 1982. Spices in Indian Life, 6500 B.C.-1950 A.D.: A Comprehensive andCritical Narration about the Role of Spices in Indian Life. Sultanchand & Sons, NewDelhi.

Mahmud, S., 2008. Composition of essential oil of Elettaria cardamomum Maton leaves.Pak. J. Sci. 60, 111–114.

Majdalawieh, A.F., Carr, R.I., 2010. In vitro investigation of the potential im-munomodulatory and anti-cancer activities of black pepper (Piper nigrum) and car-damom (Elettaria cardamomum). J. Med. Food 13, 371–381.

Marongiu, B., Piras, A., Procedda, S., 2004. Comparative analysis of the oil and CO2extract of Elettaria cardamomum (L) Maton. J. Agric. Food Chem. 52, 6278–6282.

Mejdi, S., Emira, N., Ameni, D., Guido, F., Mahjoub, A., Al-sieni, M., Al-sieni, A., 2015.Chemical composition and antimicrobial activities of Elettaria cardamomum L.(Maton) essential oil: a high activity against a wide range of food borne and medicallyimportant bacteria and fungi. J. Chem. Biol. Phys. Sci. 6, 248–259.

Menon, N.A., 2000. Studies on the volatiles of cardamom (Elleteria cardamomum). J. FoodSci. Technol. 37, 406–408.

Metodiewa, D., Koska, C., 2000. Reactive oxygen species and reactive nitrogen species:relevance to cyto (neuro) toxic events and neurologic disorders an overview.Neurotox. Res. 1, 197–233.

Murugan, M., 2011. Factors and Patterns of Pesticide Usage and Sustainability ofCardamom Elettaria Cardamomum L Maton in Indian Cardamom Hills. Ph.D ThesisSubmitted to the National Institute of Advanced Studies. Indian Institute of Sciencecampus, Bangalore, pp. 198.

K. Ashokkumar, et al. Journal of Ethnopharmacology 246 (2020) 112244

9

Murugan, M., Dhanya, M.K., Deepthy, K.B., Preethy, T.T., Aswathy, T.S., Sathyan, T.,Manoj, V.S., 2016. Compendium on Cardamom, second ed. Kerala AgriculturalUniversity, Cardamom Research Station, Pampadumpara, pp. 66.

Murugan, M., Panigrahy, B.K., Shetty, P.K., Subbiah, A., Ravi, R., 2012. Effect of heavymetal and nutrient uptake by soils in Indian cardamom hills. J. Soil Sci. Environ.Manag. 3, 196–206.

Nair, K.P.P., 2011. The agronomy and economy of cardamom (Elettaria cardamomum M.):the “queen of spices”. In: Agronomy and Economy of Black Pepper and Cardamom;the King and Queen of Spices, pp. 109–366. https://doi.org/10.1016/C2011-0-04238-2.

Nair, P.R.S., Unnikrishnan, G., 1997. Evaluation of Medicinal Values of Cardamom Aloneand in Combination with Other Spices in Ayurvedic System of Medicine-Project (PartI and II), vol.51. Government Ayurveda College, Trivandrum, Kerala, India, pp. 46.

Nair, S., Nagar, R., Gupta, R., 1998. Antioxidant phenolics and flavonoids in commonIndian foods. J. Assoc. Phys. India 46, 708–710.

Nanasombat, S., Wimuttigosol, P., 2011. Antimicrobial and antioxidant activity of spiceessential oils. Food Sci Biotechnol 20, 45–53.

Nirmala, M.A., 2000. Studies on the volatile of cardamom (Elettaria cardamomum). J.Food Sci. Technol. 37, 406–408.

Noleau, I., Toulemonde, B., Richard, H., 1987. Volatile constituents of cardamom(Elettaria cardamomum) cultivated in Costa Rica. Flavour Fragrance J. 2, 123–127.

Noumi, E., Snoussi, M., Alreshidi, M.M., Rekha, P.D., Saptami, K., Caputo, L., De Martino,L., Souza, L.F., Msaada, K., Mancini, E., Flamini, G., Al-sieni, A., De Feo, V., 2018.Chemical and biological evaluation of essential oils from cardamom species.Molecules 23, e2818. https://doi.org/10.3390/molecules23112818.

Olivero-Verbel, J., González-Cervera, T., Guette-Fernandez, J., Jaramillo-Colorado, B.,Stashenko, E., 2010. Chemical composition and antioxidant activity of essential oilsisolated from Colombian plants. Braz J Pharmacogn 20, 568–574.

Parry, J., Hao, Z., Luther, M., Su, L., Zhou, K., Yu, L., 2006. Characterization of cold-pressed onion, parsley, cardamom, mullein, roasted pumpkin, and milk thistle seedoils. J. Am. Oil Chem. Soc. 83, 847–854.

Prameswar, N.S., Venugopal, R., 1974. Study of flowering and anthesis in cardamom(Elettaria cardamomum Maton). Mysore J. Agric. Sci. 6 (3), 356–361.

Rahman, T., Rahman, K.A., Rajia, S., Alamgir, M., Khan, M.T.H., Choudhuri, M.S.K.,2008. Evaluation of antidiarrhoeal activity of cardamom (Elettaria cardamomum) onmice models. Orient Pharm Exp Med 8, 130–134.

Raksamiharja, R., Sy, K., Zulharini, M.S., Novarina, A., Sasmito, E., 2012. Elettaria car-damomum distillate increases cellular immunity in doxorubicin treated rats. Indones JCancer Chemoprev 3, 437–443.

Robertsii, L., Oates, J., Linton, M., Fazio, S., Meador, B., Gross, M., Shyr, Y., Morrow, J.,2007. The relationship between dose of vitamin E and suppression of oxidative stressin humans. Free Radic. Biol. Med. 43, 37–46.

Saeed, A., Sultana, B., Anwar, F., Mushtaq, M., Alkharfy, K.M., Gilani, A.H., 2014.Antioxidant and antimutagenic potential of seeds and pods of green cardamom(Elettaria cardamomum). Int. J. Pharm. 10, 461–469.

Sahadevan, P.C., 1965. Cardamom. Farm Bulletin No. 4. Department of Agriculture,Kerala, India, pp. 90.

Shakila, R.J., Vasundhara, T.S., Rao, D.V., 1996. Inhibitory effect of spices on in vitrohistamine production and histidine decarboxylase activity of Morganella morganii andon the biogenic amine formation in mackerel stored at 30 degrees C. Z. Lebensm.Unters. Forsch. 203, 71–76.

Sharma, S., Sharma, J., Kaur, G., 2011. Therapeutic uses of Elettaria cardamomum. Int JDrug Formul Res 2, 102–108.

Shen, C., Huang, Y., Yi, S., Fang, Z., Li, L., 2015. Association of vitamin E intake withreduced risk of kidney cancer: a meta-analysis of observational studies. Med. Sci.Monit. 21, 3420–3426.

Singh, G., Kiran, S., Marimuthu, P., Isidorov, V., Vinogorova, V., 2008. Antioxidant andantimicrobial activities of essential oil and various oleoresins of Elettaria carda-momum (seeds and pods). J. Sci. Food Agric. 88, 280–289.

Singh, V.B., Singh, K., 1996. Spices. New Age International Ltd., New Delhi, India, pp.253.

Sontakke, M.D., Syed, H.M., Sawate, A.R., 2018. Studies on extraction of essential oilsfrom spices (Cardamom and Cinnamon). Int J Chem Studies 6, 2787–2789.

Subaddarage, J., Sarath, K., Vellupillai, P.E., Errol, R.J., 1985. Some studies on the effectof maturity and storage on the chlorophyll content and essential oils of the cardamomfruit (Elettaria cardamomum). J. Sci. Food Agric. 36, 491–498.

Telja, R., Olavl, L., Roberto, Q., 2006. Small cardamom-precious for people, harmful formountain forests. Possibilities for sustainable cultivation in the east Usambaras,Tanzania. Mt. Res. Dev. 26, 131–137.

Vaidya, A., Rathod, M., 2014. An in vitro study of the immunomodulatory effects of Pipernigrum (black pepper) and Elettaria cardamomum (cardamom) extracts using a murinemacrophage cell line. Int J Res Formal Appl Nat Sci 8, 18–27.

Van Vuuren, S.F., 2008. Antimicrobial activity of South African medicinal plants. J.Ethnopharmacol. 119, 462–472.

Velioglu, Y.S., Mazza, G., Gao, L., Oomah, B.D., 1998. Antioxidant activity and totalphenolics in selected fruits, vegetables and grain products. J. Agric. Food Chem. 46,4113–4117.

Wang, Y.Y., Wang, X.L., Yu, Z.J., 2014. Vitamin C and E intake and risk of bladder cancer:a meta-analysis of observational studies. Int. J. Clin. Exp. Med. 7, 4154–4164.

Winarsi, H., Sasongko, N.D., Purwanto, A., Nuraeni, I., 2014. Effect of cardamom leavesextract as antidiabetic, weight lost and hypocholesterolemic to alloxan-inducedSprague Dawley diabetic rats. Int Food Res J 21, 2253–2261.

Yashin, A., Yashin, Y., Xia, X., Nemzer, B., 2017. Antioxidant activity of spices and theirimpact on human health: a review. Antioxidants 6, 70.

Zhang, Y., Jiang, W., Xie, Z., Wu, W., Zhang, D., 2015. Vitamin E and risk of age-relatedcataract: a meta-analysis. Public Health Nutr. 18, 2804–2814.

Zhu, Y.J., Bo, Y.C., Liu, X.X., Qiu, C.G., 2017. Association of dietary vitamin E intake withrisk of lung cancer: a dose-response meta-analysis. Asia Pac. J. Clin. Nutr. 26,271–277.

K. Ashokkumar, et al. Journal of Ethnopharmacology 246 (2020) 112244

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