The pharmacological activities of Cuminum cyminum -A review

Abstract

Phytochemical analysis showed that Cuminum cyminum contained: alkaloid , coumarin, anthraquinone, flavonoid, glycoside, protein, resin, saponin, tannin and steroid. The previous pharmacological studies revealed that Cuminum cyminum exerted antimicrobial, insecticidal, anti-inflammatory, analgesic, antioxidant, anticancer, antidiabetic, antiplatelet aggregation, hypotensive, bronchodilatory, immunological, contraceptive, anti-amyloidogenic, anti-osteoporotic, aldose reductase , alpha-glucosidase and tyrosinase inhibitory effects, protective and central nervous effects. This review highlights the chemical constituents and pharmacological effects of Cuminum cyminum.

Full text

IOSR Journal Of Pharmacy www.iosrphr.org
(e)-ISSN: 2250-3013, (p)-ISSN: 2319-4219
Volume 6, Issue 6 Version. 2 (June 2016), PP. 46-65
46
The pharmacological activities of Cuminum cyminum - A review
Prof Dr Ali Esmail Al-Snafi
Department of Pharmacology, College of Medicine, Thi qar University, Nasiriyah, P O Box 42, Iraq .
Abstract: Phytochemical analysis showed that Cuminum cyminum contained: alkaloid , coumarin,
anthraquinone, flavonoid, glycoside, protein, resin, saponin, tannin and steroid. The previous pharmacological
studies revealed that Cuminum cyminum exerted antimicrobial, insecticidal, anti-inflammatory, analgesic,
antioxidant, anticancer, antidiabetic, antiplatelet aggregation, hypotensive, bronchodilatory, immunological,
contraceptive, anti-amyloidogenic, anti-osteoporotic, aldose reductase , alpha-glucosidase and tyrosinase
inhibitory effects, protective and central nervous effects. This review highlights the chemical constituents and
pharmacological effects of Cuminum cyminum.
Keywords: constituents, pharmacology, Cuminum cyminum.
I. INTRODUCTION
The World Health Organization (WHO) estimates that 4 billion people, 80 percent of the world
population, presently use herbal medicine for some aspect of primary health care(1). Plant showed wide range of
pharmacological activities including antimicrobial, antioxidant, anticancer, hypolipidemic, cardiovascular,
central nervous, respiratory, immunological, anti-inflammatory, analgesic antipyretic and many other
pharmacological effects(2-70).
Phytochemical analysis showed that Cuminum cyminum contained: alkaloid , coumarin,
anthraquinone, flavonoid, glycoside, protein, resin, saponin, tannin and steroid. The previous pharmacological
studies revealed that Cuminum cyminum exerted antimicrobial, insecticidal, anti-inflammatory, analgesic,
antioxidant, anticancer, antidiabetic, antiplatelet aggregation, hypotensive, bronchodilatory, immunological,
contraceptive, anti-amyloidogenic, anti-osteoporotic, aldose reductase , alpha-glucosidase and tyrosinase
inhibitory effects, protective and central nervous effects. This review highlights the chemical constituents and
pharmacological effects of Cuminum cyminum.
II. PLANT PROFILE
Synonyms:
Cuminia cyminum J. F. Gmel., Cuminum aegyptiacum Mérat ex DC., Cuminum hispanicum Mérat ex DC.,
Cuminum odorum Salisb., Cuminum sativum J. Sm., Cyminon longeinvolucellatum St.-Lag(71).
Taxonomic classification:
Kingdom: Plantae; Subkingdom: Viridiplantae; Infrakingdom: Streptophyta; Superdivision: Embryophyta;
Division: Tracheophyta; Subdivision: Spermatophytina; Class: Magnoliopsida; Superorder: Asteranae;
Order: Apiales; Family: Apiaceae; Genus: Cuminum; Species: Cuminum cyminum(72).
Nomenclature and Common names:
The word cumin was derived from the Latin cuminum, which itself was derived from Greek (kyminon)(73). The
common names of the plant were: Arabic: Kamoun, Kamun; Chinese: Ou shi luo, Ma qin (Ma ch'in), Xian
hao, Xiang han qin, Zi ran.; English: Cumin, Roman caraway; French: Cumin, Cumin de Malte, Cumin
blanc, Cumin du Maroc, Faux anis; German: Kreuzkümmel, Römischer Kümmel, Weißer Kreuzkümmel;
Greek: Kimino, Kiminon; India: Jiiraa (Jeera), Zeera (zira, ziira), afed ziiraa (Safed zira), Safed jiiraa (Safaid
jeera); Italian: Cumino; Japanese: Hime unikyoo, Kumin; Portuguese: Cominho; Russian: Kmin, Kmin
rimskii, Kmin tminovyi (Kmin tminovyj); Spanish: Comino; Swedish: Spiskummin(74).
III. DISTRIBUTION
Cumin was native to Egypt and has been cultivated in the Middle East, India, China and Mediterranean
countries for millennia. The plant possibly originated from the Mediterranean area, perhaps Egypt and Syria.
Nowadays it cultivated extensively in Turkey, India, China, Iraq, Libya, and Palestine. In the past, the largest
cumin exporter to the United States was Iran. However, currently Turkey, India and China have provided
alternatives. Now, the major production of cumin was came from India (states of Rajasthan and Gujarat)(75-77).
Description
The plant is a delicate, glabrous annual 10 to 50 cm high. The stem is bifurcated at the base and glabrous. The
leaves are glabrous and finely pinnatifid with oblong-linear tips, of which the lower are mostly doubly trifoliate.

The pharmacological activities of Cuminum cyminum - A review
47
The flowers are in umbels radiating in groups of 3 to 5. The petals are white or red, oblong and deeply bordered
with a long indented tip. The involucral bracts are long and simple. The style is short and turned outward at the
end. The ovary is inferior and 3-Iocular. The fruit is a schizocarp, about 6 mm long and 1.5 mm wide and
crowned with awl-shaped calyx tips. The mericarp is almost round in transverse section, with 5 thread-like,
bristly main ribs and bristly secondary ribs(78).
Traditional uses:
In traditional medicine, cumin was used to treat hoarseness, jaundice, dyspepsia and diarrhoea. Its seeds were
used for stomachic, diuretic, carminative, stimulant, astringent and abortifacient properties(79-80). The oil of
cumin was used in perfumery and as a seasoning in curry powders, soups, stews, sausages, cheeses, pickles,
meats and chutneys(81). In America, Africa and India the drug is used as an abortive and as an emmenagogue. In
Indonesia, it was used in cases of bloody diarrhea and headache (paste is applied to the forehead). It was also
taken orally for rheumatic ailments. In India, cumin was used as an abortifacient, for kidney and bladder stones,
chronic diarrhea, leprosy and eye disease(78). In Unani system of medicine, the fruits of Cuminum cyminum were
used as an astringent, carminative, emmenagogue, for the treatment of corneal opacities, ulcers, boils, styes and
to relieve cough and inflammation(75).
Parts used:
The medicinal parts were the Cumin oil extracted from the ripe fruit and the ripe, dried fruit(78).
Physicochemical characteristics:
Moisture content: 8%, PH: 7.3, total ash: 7.5, acid insoluble ash: 18%, alcohol soluble extractive: 6.58% ,
water soluble extractive: 138% and ether soluble extractive: 11.44 ± 0.20 and 12.36 ± 0.23% in the wet and dry
fruits(73). Crude protein 18.40 ± 0.16 and 19.88 ± 0.20%, crude fibers 21.82 ± 0.13 and 23.57 ± 0.13%, total
carbohydrate 55.58 and 60.05% in the wet and dry fruits respectively(82). Physical properties of the essential
oil of cumin seeds: extraction percentage: 2.3-5.7 %, color: colorless or pale yellow, refractive index (20 ºC):
1.47-1.50, density (20 ºC): 0.90-0.94, alcohol solubility (80% v/v): 1:1.3-1:2, aldehyde percentage (on the basis
of cuminaldehyde): 35-63%, acidity (on the basis of cuminic acid): 0.36-1.8, alcohol percentage (on the basis of
cuminol): 3.5, carbonyl index: 9.32 and steric index: 19.24(83).
Chemical constituents:
Phytochemical analysis showed that Cuminum cyminum contained: alkaloid , anthraquinone, coumarin,
flavonoid, glycoside, protein, resin, saponin, tannin and steroid(73).
Nutrient contents of cumin (in 2 g of seeds) were included: calories 7.50, calories from fat 4.00, calories from
saturated fat 0.28, protein (g) 0.36, carbohydrates (g) 0.88, dietary fibre (g) 0.22, total fat (g) 0.44, saturated fat
(g) 0.04, monounsaturated fat (g) 0.28, polyunsaturated fat (g) 0.06, water (g) 0.16, Ash (g) 0.16, vitamin A (IU)
25.40, vitamin A (RE) 2.54, α-carotenoid (RE) 2.54, beta carotene (μg) 15.24, thiamin – B1(mg) 0.02, niacin –
B3(mg) 0.10, niacin equiv 0.10, vitamin C 0.16, vitamin E alpha equiv 0.02, vitamin E (IU) 0.04, vitamin E
(mg) 0.02, folate(μg) 0.20, vitamin K (μg) 0.11, calcium(mg) 18.62, copper(mg) 0.02, iron(mg) 1.32,
magnesium (mg) 7.32, manganese (mg) 0.06, phosphorus (mg) 9.98, potassium (mg) 35.76, selenium(μg) 0.10,
sodium (mg) 3.36, zinc (mg) 0.10, palmitic acid (g) 0.02, oleic (g) 0.28, linoleic acid (g) 0.06 and omega 6 fatty
acids (g) 0.06(79).
Organic acids (aspartic, citric, malic, tartaric, propionic, ascorbic, oxalic, maleic and fumaric acids) were
isolated from seeds of Cuminum cyminum(84).
Cumin fruits contained 2.5 to 4.5% volatile oil and 10% fixed oil(75). It appeared that the constituents of
Cuminum cyminum essential oil were differ according to the area from which the Cuminum cyminum samples
were taken. The major compounds in the Turkish cumin (Cuminum cyminum) seed oil were cuminaldehyde
(19.25-27.02%), p-mentha-1,3-dien-7-al (4.29-12.26%), p-mentha-1,4-dien-7-al (24.48-44.91%), γ-terpinene
(7.06-14.10%), p-cymene (4.61-12.01%) and β-pinene (2.98-8.90%)(85).
Cuminaldehyde, γ-terpinene, o-cymene, limonene and β-pinene were determined to be the major constituents of
Syrian Cuminum cyminum (86).
The major compounds in cumin essential oil of Egyptian cultivars were cumin aldehyde (35.25%), tetradecene
(12.25%), γ-terpenene (12%), β-ocimene (9.72%), p-mentha-2-en-ol (9%), α-terpinyl acetate (5.32%), α-
terpinolene (3%), lmonine (0.5%), myrcene (0.2%), β-pinene (0.9%) and α-pinene (0.19%)(82).
Tunisian variety of Cuminum cyminum contained cuminlaldehyde (39.48%), gamma-terpinene (15.21%), O-
cymene (11.82%), beta-pinene (11.13%), 2-caren-10-al (7.93%), trans-carveol (4.49%) and myrtenal (3.5%) as
major components(87).
Analysis of the fruit oil of Cuminum cyminum from Delhi showed that the major constituents were
transdihydrocarvone (31.11%), γ-terpinene (23.22%), p-cymene (15.8%), α- phellandrene (12.01%) and p-
menth-2-en-7-ol (3.48%) and cuminlaldehyde constituted only 0.58%(88).
Analysis of cumin oil samples from four different German regions showed that the major compounds in all
samples were monoterpenes beta -pinene, p-cymene, gamma –terpinene, the terpenoid aldehydes, cuminic
aldehyde and the isomeric menthadien carboxaldehydes(89).

The pharmacological activities of Cuminum cyminum - A review
48
However, Li and Jiang found that Chinese cumen seed oil contained cuminal (36.31%), cuminic alcohol
(16.92%), γ-terpinene (11.14%), safranal (10.87%), p-cymene (9.85%) and β-pinene (7.75%) as major
components(90).
Thymol (40.65%), γ-terpinene (24.51%), b-pinene (5.38%), a-pinene (3.47%), camphene (2.31%), terpinene- 4
– ol (2.00%), cuminaldehyde (1.79%), a-thujene (1.45%), a-terpinolene (1.17%), myrcene (1.07%), limonene
(1.04%), α-phyllanderene (0.94%), acetoxylinalool (0.57%) and sabinene (0.37%) represented the major
components isolated from cumin essential oils from Kurdistan mountain of Iran(91).
Romeilah et al., isolated 20 compounds from the Cuminum cyminum (seeds) oil including: α-pinene 2.14,
sabinene 1.01, β-pinene 4.89, β-myrcene 1.45, α-terpinene 0.84, p-cymene 1.77, limonene 0.24, -terpinene
1.07, α-terpinolene 0.08, Camphor 0.12, Terpinen-4-ol 0.04, α-terpineol 2.47, geraniol 0.07, geranyl acetate
4.11, β-caryophyllene 3.44, α-phellandrene 1.09, cuminaldehyde 60.01, thymol 2.04, β-farnesene 3.01 and
caryophyllene oxide 6.12(92).
However, Gachkar et al., isolated 32 compounds from Cuminum cyminum oil including: isobutyl isobutyrate
0.8, a-thujene 0.3, a-pinene 29.1, sabinene 0.6 , myrcene 0.2 , d-3-carene 0.2, p-cymene 0.3, limonene 21.5, 1,8-
cineole 17.9, (E)-ocimene 0.1, g -terpinene 0.6, terpinolene 0.3, linalool 10.4, a-campholenal 0.03, trans-
pinocarveole 0.07 , d-terpineole 0.09, terpinene-4-ol 0.5, a-terpineole 3.17, trans-carveole 0.4, cis-carveole 0.07,
geraniol 1.1, linalyl acetate 4.8, methyl geranate 0.2, a-terpinyl acetate 1.3, neryl acetate 0.09, methyl eugenol
1.6, b-caryophyllene 0.2, a-humulene 0.2, spathulenol 0.07, caryophylleneb epoxide 0.1, humulene epoxide II
0.08 and acetocyclohexane dione-2 0.4(93).
49 components were identified in the essential oil constituents of the Cuminum cyminum fruit grown in Delhi,
which represented 99.78% of total detected constituents. The essential oil was characterized by the presence of
monoterpene (79.61%), sesquiterpene (2.66%), aromatic (16.55%) and aliphatic compounds (0.66%). Among
thirty four monoterpenes detected, there were fourteen hydrocarbons (41.28%), twelve alcohols (5.76%), six
keto compounds (31.92%), one aldehyde (0.54%) and two esters (0.11% ). The predominant monoterpene
hydrocarbon was γ-terpinene (23.22%) followed by α-phellandrene (12.01%), α-pinene (1.78%) and α-terpinene
(1.24%). Among twelve monoterpenic alcohols, p-menth-2-en-7-ol (3.48%) was the major alcoholic constituent
and trans-dihydrocarvone (31.11%) was the prominent monoterpenic ketone in the essential oil. The
sesquiterpenes identified in the oil were teresantalol (2.62%) and karvaknol (0.04%). The aromatic compounds
detected were p-cymene (15.87%), 8a-methyl octahydro-2(1H)- naphthalenone, 2-isopropyl-5-methyl phenol, p-
cymen-7-ol, o-cymen-5-ol, p-cymen-3-ol, 6-allyl-4,5-dimethoxy-1,3-benzodioxole and 2,a,8,8-tetramethyl
decahydrocyclopropanal [d] naphthalene. The aliphatic compounds included 1-(1, 2, 3-trimethyl-2- cyclopenten-
1-yl) ethanone, 3-isopropyl phenol, 2-methyl-4-isopropyliden-cyclopentan-1-al, 1-methyl-4-iso propyl-3-
cyclohexen-1-ol, 2-isopropenyl-5-methyl-hex-4-enal, 4-isopropyl cyclohex-1,3-dien-1-yl) methanol, 4-
isopropyl-1-cyclohexen-1-carbaldehyde, hexadecylene oxide and (3,4-dimethyl-2-oxo-cyclopenten-1-yl) acetic
acid(88).
Analysis of the methanolic extract of the fruits of Cuminum cyminum led to the isolation of five terpenic and
steroidal constituents, they were characterized as 1,4,5,8-tetrahydroxynaphthyl geranilan-10ʹ-al 1ʹ-oate, lanost-
5,20 (22)-dien-3α-olyl ndocosanoate, labdan-6α,16,20-triol-16-(10ʹ,11ʹ- dihydroxy anthraquinone-2ʹ-oate),
stigmast-5-en- 3β-O-D-arabinopyranosyl-2ʹ-benzoate and lanost-5,24-dien-3β-ol 3β-O-D- arabinopyronosyl-2ʹ-
noctadec- 9ʹʹ, 12ʹʹ-dienoate(94).
The characteristic odour of cumin was attributed to the presence of sminaldehyde, 1, 3-p-menthadien-7al, 1-4-p-
menthadien-7-al. 14 free amino acids were also isolated from the seeds. While, flavonoid glycosides isolated
from the plant were included apigenin-7-glucoside, luteolin-7-glucoside, luteolin-7-glcuronosyl glucoside,
luteolin and apigenin(95).
Total polypheols in cumin were 4.98± 0.31. (mg GAE/g DW)(96). Phenols (salicylic acid, gallic acid, cinnamic
acid, hydroquinone, resorcinol, P-hydroxybenzoic acid, rutin, coumarine, quercetin) were isolated from seeds of
Cuminum cyminum(84).
However, Cuminum cyminum roots, stems and leaves, and flowers were investigated for their total phenolics,
flavonoids, and tannins contents. In all Cuminum cyminum organs, total phenolics content ranged from 11.8 to
19.2 mg of gallic acid equivalents per gram of dry weight (mg of GAE/g of DW). Among the polyphenols
studied, 13 were identified in roots, 17 in stem and leaves, and 15 in flowers. The major phenolic compound in
the roots was quercetin (26%), whereas in the stems and leaves, p-coumaric, rosmarinic, trans-2-
dihydrocinnamic acids and resorcinol were predominant. In the flowers, vanillic acid was the main compound
(51%)(97).
A total of 19 phenolic compounds were successfully identified during the ripening of cumin seeds. Rosmarinic
acid was the major phenolic acid for the unripe seeds, while, half ripe and full ripe seeds were dominated by p-
coumaric acid(98).

The pharmacological activities of Cuminum cyminum - A review
49
IV. PHARMACOLOGICAL EFFECTS
Antimicrobial effect:
Ethanol extracts of seed of Cyminum cuminum were tested for antimicrobial activity in vitro by the
microdilution method. Ethanol extract of seed exhibited antimicrobial activity against biofilm Escherichia
coli(99).
All essential oils, and cuminic aldehyde, were tested, using agar diffusion and serial dilution methods, against
different Gram-positive and Gram-negative bacteria isolated from different sources of food (pork fillet, minced
meat and sausages) and clinical isolates, as well as three different Candida albicans isolates. All cumin oils and
cuminic aldehyde exhibited a considerable inhibitory effect against all the tested organisms, except
Pseudomonas spp(89).
The volatile oil of Cuminum cyminum was active against Staphylococcus epidermidis, S. aureus, S.
haemolyticus, Propionibacterium acnes, Corynebacterium diphtheriae, Erysipelothrix rhusiopathiae, Bacillus
cereus, Clostridium tetani, C. difficile, Escherichia coli, Salmonella typhi, Klebsiella pneumoniae, Vibrio
cholerae, Aeromonas hpydrophila, Mycobacterium tuberculosis and Neisseria gonorrhoeae, Asperigillus niger,
Saccharomyces cerevisae and Colletrotrichum gloeosporioides. The antimicrobial activity induced by
methanolic, hydroalcoholic and aqueous extracts was less that that produced by volatile oils(88).
The essential oil of Bulgarian Cuminum cyminum was active against Aspergillus niger, Bacillus subtilis,
Staphylococcus epidermidis, Saccharomyces cerevisiae and Candida albicans(100).
The inhibitory effect of steam distilled essential oil of cumin fruits was tested against 3 Gram-negative bacteria
(Pseudomonas fluorescens, Escherichia coli, and Serratia marcescens), 4 Gram-positive bacteria
(Staphylococcus aureus, Micrococcus spp., Sarcina spp., and Bacillus subtilis), an acid fast bacterium
(Mycobacterium phlei), and one yeast (Saccharomyces cerevisiae). The results showed that cumin oils
possessed strong antimicrobial activity(101).
The essential oils from seeds of Cuminum cyminum, exerted antifungal activity against Aspergillus flavus(102).
The cumin essential oil showed activity against E. coli, Pseudomonas aeruginosa and Salmonella sp. and their
inhibitory zones were 18, 10 and 23 mm, respectively(103).
The antimicrobial activity of the essential oil of cumin (Cuminum cyminum) seeds was studied against different
strains of microorganisms. Antimicrobial testing showed high activity of the essential Cuminum cyminum oil
against Candida albicans, Aspergillus niger, the Gram positive bacteria Bacillus subtilis and Staphylococcus
epidermidis as well as the yeast (Saccharomyces cerevisiae) (104).
Cuminum cyminum essential oil exhibited strong antimicrobial activity against E. coli, S. aureus and L.
monocytogenes. Complete death time on exposure to Cuminum cyminum oil was 20, 180 and 90 min for E. coli,
S. aureus and L. monocytogenes, respectively(105).
Cuminum cyminum essential oils possessed antifungal activity against Botrytis cinerea, Rhizopus stolonifer and
Aspergillus niger. The incorporation of 750 μl/1 from Cuminum cyminum oils to PDA medium was completely
inhibited the growth of B. cinerea, R. stolonifer and A. niger(106).
The fungicidal activities of p-isopropyl benzaldehyde and p-isopropyl benzoic acid extracted from Cuminum
cyminum were studied against Alternaria solani, Verticillium dahliae, Rhizoctonia cerealis, Alternaria
alternata, Gaeumannomyces graminis, Sclerotinia sclerotiorum, Phytophthora capsici, Thanatephorus
cucumeris, Blumeria graminis [Erysiphe graminis] and Botrytis cinerea. The bioassay results showed that both
compounds had fungicidal activities in vivo and in vitro. P-isopropyl benzaldehyde and p-isopropyl benzoic acid
had better inhibitory effects against Sclerotinia sclerotiorum, and their EC50 were 2.1 and 7.3 mg/l respectively.
In a concentration of 1000 mg/l, the protective effects of p-isopropyl benzaldehyde and p-isopropyl benzoic acid
treatments were higher than 50% against Blumeria graminis. At the same concentration, the control effect of p-
isopropyl benzoic acid treatment was 57.52% against Sclerotinia sclerotiorum, which was comparable to
sumilex treatment(107).
The effectiveness of the essentials oils from cumin (Cuminum cyminum) was studied on the growth of some
bacteria commonly used in the food industry, Lactobacillus curvatus, Lactobacillus sakei, Staphylococcus
carnosus and Staphylococcus xylosus or related to food spoilage Enterobacter gergoviae, Enterobacter
amnigenus. The agar disc diffusion method was used to determine the antibacterial activities of the oils.
Cuminum cyminum essential oils showed an inhibitory effect against all the tested bacteria(108).
The antifungal activities of the essential oils obtained from Hyssopus officinalis, Cuminum cyminum, Thymus
vulgaris and cones of Cupressus arizonica were evaluated against Aspergillus flavus. Different concentrations
of the essential oils on conidial germination and germ tube elongation were determined in vitro. Essential oils
were applied in 5 levels (0, 0.125, 0.25, 0.375 and 0.5%). The results showed that the essential oil of Cuminum
cyminum was more effective in comparison with others(109).
The storage life of the strawberry fruits was increased by the use of Cumin (Cuminum cyminum) essential oils
significantly, because they inhibited the fungi (Botrytis cinerea)(110).

The pharmacological activities of Cuminum cyminum - A review
50
Cuminum cyminum oil exhibited higher antibacterial and antifungal activities with a high effectiveness against
Vibrio spp. strains with a diameter of inhibition zones ranging from 11 to 23 mm, and MIC and MBC values
ranging from (0.078-0.31 mg/ml) to (0.31-1.25 mg/ml) respectively(87).
A great inhibition of Cuminum cyminum essential oil was recorded on Pseudomonas syringae pv.
Syringae(111).
The ranges of minimum inhibitory concentration of Cuminum cyminum oils against several food-borne
pathogens (Staphylococcus aureus, Bacillus cereus, Escherichia coli O157:H7, Salmonella enteritidis and
Listeria monocytogenes) were 0.37-3.0 mg/ml. Moreover, the combination of B. persicum and Cuminum
cyminum essential oils confirmed synergistic and additive activities against the pathogens(112).
The antifungal activity of the volatile parts (at doses from 5 to 20 microl) of the essential oil of fruits of
Cuminum cyminum was tested on dermatophytes and phytopathogens, fungi, yeasts and some new Aspergilli.
Antifungal testing showed that Cuminum cyminum was active on all fungi but in particular on the
dermatophytes, where Trichophyton rubrum was the most inhibited fungus at the lowest dose of 5 µl.
Phytopathogens were less sensitive to the treatment (113).
The chemical composition of essential oils from cumin (Cuminum cyminum), laurel (Laurus nobilis), oregano
(Oreganum onites), rosemary (Rosmarinus officinalis), anise (Pimpinella anisum) and clove (Syzygium
aromaticum) was determined and their antibacterial activities were tested aginst Salmonella typhimurium CCM
5445, Staphylococcus aureus (MRSA) RSKK 95047, Staphylococcus aureus ATCC 6538P, Escherichia coli
ATCC 29998 and Escherichia coli O157:H7 RSKK 232 by two different methods (disc diffusion and agar
dilution). The results showed that oregano essential oil showed the highest inhibition (0.0625-0.125 mg/ml)
effect followed by cumin (0.0625-2.0 mg/ml) and clove (0.25-1.0 mg/ml)(114).
Antibacterial activity of seed extracts of cumin (Cuminum cyminum) was investigated against 10 Gram positive
and Gram negative bacteria. Disc diffusion method was used to test the antibacterial activity. Minimum
inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) were determined by using
standard procedures. The highest inhibition zone of 16.67±0.47 mm was found at 250 mg/ml against
Escherichia coli. On the other hand, the inhibition zones 15.00±0.82 mm for ethanol, 15.33±0.47 for methanol,
and 15.67±0.82 for acetone were recorded against Bacillus subtilis, Sarcina lutea and Klebsiella pneumonia,
respectively. MIC value (20 to 50 mg/ml) and MBC value (40 to 60 mg/ml) were recorded against the studied
bacteria(115).
Antibacterial activity of Cuminum cyminum essential oil was observed against Gram-positive and Gram-
negative bacterial species. The activity was particularly high against the genera Clavibacter, Curtobacterium,
Rhodococcus, Erwinia, Xanthomonas, Ralstonia, and Agrobacterium, which were responsible for plant or
cultivated mushroom diseases worldwide. In general, a lower activity was observed against bacteria belonging
to the genus Pseudomonas(116).
Antimicrobial activities and biofilm-formation preventive properties of Cuminum cyminum essential oils and
chlorhexidine were assessed against Streptococcus mutans and Streptococcus pyogenes. The minimal
bactericidal concentrations (MBC) of the oils and chlorhexidine and microbial decimal reduction time (D value)
were determined. Cuminum cyminum induced mild antibacterial and in vivo biofilm preventive effects (less
than chlorhexidine). In vivo experiments conducted on male and female volunteers who brushed with essential
oil blended toothpastes indicated that lower concentrations of the oils were significantly higher (p<0.001) and
effective during the course of the study as compared to chlorhexidine(117).
The effect of different concentrations of Cuminum cyminum essential oil (0, 15, 30 and 45 µl/100 ml) and nisin
(0, 0.5 and 1.5 µg/ml) combination at different temperatures (10, 25 and 35°C) was studied on growth of
Salmonella typhimurium and Staphylococcus aureus in the brain-heart infusion (BHI) broth model. The
concentrations of 0 µl/100 ml for essential oil and 0 µg/ml for nisin imply the negative control. The growth of S.
typhimurium was significantly decreased by the concentration of essential oil ≥ 30 µl/100 ml in combination
with nisin ≥ 0.5 µg/ml at temperature = 10°C (p<0.05). Also, in combination of the essential oil ≥ 15 µl/100 ml
and nisin ≥ 0.5 µg/ml at temperature ≤ 25°C, the growth of S. aureus was significantly reduced (p<0.05). The
results indicated that the combination of essential oil and nisin inhibited the growth of S. typhimurium and S.
aureus bacteria and there was the possibility of using them as substitutes for chemical food preservatives(118).
The antimicrobial activity of cumin oil against many pathogenic bacteria, showed that E. coli, S. aureus, and S.
faecalis were sensitive to various oil dilutions(119).
The antmicrobial activity of Cuminum cyminum essential oil was evaluated against: Micrococcus luteus LA
2971, Bacillus megaterium NRS, Bacillus brevis FMC 3, Enterococcus faecalis ATCC 15753, Pseudomonas
pyocyaneus DC 127, Mycobacterium smegmatis CCM 2067, Escherichia coli DM, Aeromonas hydrophila
ATCC 7966, Yersinia enterocolitica AU 19, Staphylococcus aureus Cowan 1, Streptococcus faecalis DC 74
bacteria, and Saccharomyces cerevisiae WET 136, Kluvyeromyces fragilis DC 98 fungi). Cuminum cyminum
essential oil (2 µl) exerted antibacterial effect against all the tested microorganisms with MIC ranged from 10-
60mm. While the inhibition zone was higher in the bacteria E. faecalis, it was lowest in E. coli and P.

The pharmacological activities of Cuminum cyminum - A review
51
pyocyaneus. Among the fungi, the inhibition zone against K. fragilis was higher than S. cerevisiae. In combined
application of Cuminum cyminum essential oil (2 µl) and gentamicin antibiotics discs, a synergistic effect in P.
pyocyaneus and A. hydrophila, an antagonistic effect in other bacteria were noted (120).
The antimicrobial effects of garlic, bay, black pepper, origanum, orange, thyme, tea tree, mint, clove, and cumin
essential oils were studied against Listeria monocytogenes AUFE 39237, Escherichia coli ATCC 25922,
Salmonella enteritidis ATCC 13076, Proteus mirabilis AUFE 43566, Bacillus cereus AUFE 81154,
Saccharomyces uvarum UUFE 16732, Kloeckera apiculata UUFE 10628, Candida albicans ATCC 10231,
Candida oleophila UUPP 94365, and Metschnikowia fructicola UUPP 23067. Thyme, origanum, clove, and
orange essential oils were the most inhibitory against bacteria and yeasts. Cumin, tea tree, and mint oils
inhibited the yeasts actively(121).
The activity of cumin seed essential oil and alcoholic extract against Klebsiella pneumoniae ATCC 13883 and
clinical K. pneumoniae isolates was studied by evaluating the effect of subminimum inhibitory concentrations
(sub-MICs) on cell morphology, capsule expression and urease activity. Growth of K. pneumoniae strains
exposed to sub-MICs of Cuminum cyminum extracts resulted in cell elongation and repression of capsule
expression. Urease activity was decreased(122).
The effects of the essential oils (EOs) of Cuminum cyminum on growth and aflatoxins production by A.
parasiticus was evaluated. Minimal inhibitory concentrations (MICs) and minimal fungicidal concentrations
(MFCs) of the EOs were determined. Determination of aflatoxin (AFB1, AFB2, AFG1, and AFG2) production
was performed by immunoaffinity column extraction using reverse phase-high performance liquid
chromatography. Cuminum cyminum oil exhibited strong activity (MIC90: 1.6; MFC: 3.5 mg/ml) against A.
parasiticus. Aflatoxin production was inhibited at 0.25 mg/ml of Cuminum cyminum (123).
Chloroformic and isoamyl alcohol extracts of Cuminum cyminum were investigated for their in vitro
antibacterial activity against six human bacterial pathogens. The antibacterial activity was evaluated and based
on the zone of inhibition using agar disc diffusion method. The tested bacterial strains were included
Streptococcus pyogenes, Staphylococcus epidermidis, Klebsiella pneumonia, Staphylococcus aurues, Serratia
marcesnces, and Pseudomonas aeruginosa. Chloroform and isoamyl alcohol extracts of Cuminum cyminum had
significant effect against P. aeruginosa, S. marcesnces and S. pyogenes(124).
The potential of Cuminum cyminum (cumin) seed essential oil (EO) (as a plant based shelf life enhancer) was
studied against fungal and aflatoxin contamination and lipid peroxidation. The EO showed efficacy as a
preservative in food systems (stored wheat and chickpeas). The minimum inhibitory concentration and
minimum aflatoxin inhibitory concentration of EO were 0.6 and 0.5 μl/ml respectively. The EO showed toxicity
against a broad spectrum of food borne fungi. The antifungal action of EO on ergosterol content in the plasma
membrane of A. flavus was determined. As a fumigant in food systems, the EO provided sufficient protection of
food samples against fungal association without affecting seed germination. In view of the antifungal and
antiaflatoxigenic nature, free radical scavenging potential and efficacy in food system, cumin seed EO may be
able to provide protection of food commodities against quantitative and qualitative losses, thereby enhancing
their shelf life(125).
The in vitro antifungal activities of essential oil from Cuminum cyminum were studied against C. albicans
ATCC 14053, C. dubliniensis ATCC CD60, C. glabrata ATCC 90030, C. krusei ATCC 6258 and C.
parapsilosis ATCC 22019. Cuminum cyminum oil had a broad-spectrum antifungal activity against different
pathogenic Candida species. Inhibition zone values were ranged from 7 to 50mm against the tested organisms.
The best minimal inhibitory concentration (MIC) of Cuminum cyminum oil was recorded against C. albicans
and C. dubliniensis (289 mg/l)(126).
The antifungal activity of cumin oil was evaluated on mycelia growth of 90 fungal isolates (eighty-seven
species and 3 species varieties belonging to 32 genera). The agar-well diffusion method was used to evaluate
fungal growth inhibition at a concentration of 100%. Cumin oil was highly effective against all the isolates of
tested fungi. It was completely inhibited mycelial growth of all fungi when added to solid medium(127).
The effect of Cuminum cyminum essential oil was studied in the growth and FUM1 gene expression of
fumonisin-producing Fusarium verticillioides strains isolated from maize. FUM1 transcript levels were
quantified using a reverse transcription-polymerase chain reaction (RT-PCR) protocol. Minimum inhibitory
concentration (MIC) values of Cuminum cyminum oil against F. verticillioides strains varied from 0.195 to
0.781 µl/ml (mean MIC value: 0.461 µl/ml) indicating 54.5% of the fungal strains were inhibited at 0.390 µl/ml.
PCR analysis of FUM1 gene expression revealed that DNA fragment of 183 bp was amplified in all the isolates
of F. verticillioides before treatment with Cuminum cyminum essential oil. Based on RT-PCR analyses,
reduction in the expression of fumonisin biosynthetic genes was significant only for FUM1 gene (p<0.05), while
no effect was observed on ITS gene(128).
The essential oils of Cuminum cyminum showed antiviral activities against herpes simplex virus 1 (HSV-1)
using cytopathicity (CPE) assay. At concentration of 1000 µg the antiviral activity reached 91.60 ± 1.93(129).

The pharmacological activities of Cuminum cyminum - A review
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V. INSECTICIDAL EFFECTS
The electrophysiological, behavioural (repellency, irritancy) and toxic effects of the of Cuminum cyminum
essential oils was studied against Anopheles gambiae strain (Kisumu). Aldehydes elicited the strongest
responses and monoterpenes the weakest responses in electroantennogram (EAG) trials. However, EAG
responses did not correlate consistently with results of behavioral assays. In behavioral and toxicity studies,
several of the single compounds exhibited repellency, irritancy or toxicity in An. gambiae; however, the activity
of essential oils did not always correlate with activity expected from the major components. The biological
activity of essential oils appeared complex, suggesting interactions between individual compounds and the
insect. Data also indicated that the three effects appeared independent, suggesting that repellency mechanism(s)
may differ from mechanisms of irritancy and toxicity(130).
Fumigant activity of essential oil vapours distilled from cumin was recorded against the eggs of two stored-
product insects, the confused flour beetle, Tribolium confusum, and the Mediterranean flour moth, Ephestia
kuehniella. The exposure to vapours of essential oils resulted in 100% mortality of the eggs at a concentration
of 98.5 μl cumin essential oil/l air(131-132).
Antidiabetic effect:
The orally administered seed powder (2 g/kg) lowered the blood glucose levels in hyperglycaemic rabbits(133).
The Antidiabetic effects of cumin seed, was examined in streptozotocin induced diabetic rats. An eight week
dietary regimen containing cumin powder (1.25%) was found to be remarkably beneficial, as indicated by
reduction in hyperglycaemia and glucosuria. This was also accompanied by improvement in body weights of
diabetic animals. Dietary cumin also countered other metabolic alterations as revealed by lowered blood urea
level and reduced excretions of urea and creatinine by diabetic animals(134).
Cuminaldehyde and cuminol were identified as potent insulinotrophic components. Cuminaldehyde and cuminol
(25 μg/ml) showed 3.34- and 3.85-fold increased insulin secretion, respectively. The insulinotrophic action of
both components was glucose-dependent and due to the closure of the ATP-sensitive K (K⁺-ATP) channel and
the increase in intracellular Ca²⁺ concentration. An inhibitor of insulin secretion with potent β-cell protective
action was also isolated from the same petroleum ether fraction. The authors concluded that Cuminum cyminum
was able to lower blood glucose without causing hypoglycaemia or β-cell burn out(135).
The effect of methanolic extract of seeds of Cuminum cyminum (CC) on diabetes, oxidative stress and formation
of advanced glycated end products (AGE) were investigated compared with glibenclamide. In vitro studies
indicated that CC inhibited free radicals and AGE formation. Treatment of streptozotocin-diabetic rats with CC
and glibenclamide for 28 days induced a reduction in blood glucose, glycosylated hemoglobin, creatinine, blood
urea nitrogen and improved serum insulin and glycogen (liver and skeletal muscle) content when compared to
diabetic control rats. Significant reductions in renal oxidative stress and AGE were observed with CC when
compared to diabetic control and glibenclamide. CC and glibenclamide also improved antioxidant status in
kidney and pancreas of diabetic rats. Diabetic rats showed increase in rat tail tendon collagen, glycated collagen,
collagen linked fluorescence and reduction in pepsin digestion(136).
The role of Cuminum cyminum supplementation on the plasma and tissue lipids was studied in alloxan diabetic
rats. Oral administration of 0.25 g/kg body weight of Cuminum cyminum for 6 weeks to diabetic rats resulted in
significant reduction in blood glucose and an increase in total haemoglobin and glycosylated haemoglobin. It
also prevented a decrease in body weight. Cuminum cyminum treatment also resulted in a significant reduction
in plasma and tissue cholesterol, phospholipids, free fatty acids and triglycerides. Histological observations
demonstrated significant fatty changes and inflammatory cell infiltrates in diabetic rat pancreas, but
supplementation with Cuminum cyminum to diabetic rats significantly reduced the fatty changes and
inflammatory cell infiltrates. Moreover, Cuminum cyminum supplementation was found to be more effective
than glibenclamide in the treatment of diabetes mellitus(137).
VI. ANTICANCER EFFECT
At a concentration of 0.1 microl/ml, oil of Cuminum cyminum destructed Hela cells by 79%(119).
Cancer chemopreventive potentials of different doses of a cumin seed-mixed diet were evaluated against
benzo(α)pyrene [B(α)P]-induced forestomach tumorigenesis and 3-methylcholanthrene (MCA)-induced uterine
cervix tumorigenesis. Results showed a significant inhibition of stomach tumor burden by cumin. Tumor
burden was 7.33 ± 2.10 in the B(α)P-treated control group, whereas it reduced to 3.10 ± 0.57 (p<0.001) by a
2.5% dose and 3.11 ± 0.60 (p<0.001) by a 5% dose of cumin seeds. Cervical carcinoma incidence, compared
with the MCA-treated control group (66.67%), reduced to 27.27% (p<0.05) by a diet of 5% cumin seeds and to
12.50% (p<0.05) by a diet of 7.5% cumin seeds. The effect of 2.5 and 5% cumin seed-mixed diets was also
examined on carcinogen/xenobiotic metabolizing phase I and phase II enzymes, antioxidant enzymes,
glutathione content, lactate dehydrogenase (LDH), and lipid peroxidation in the liver of Swiss albino mice.
Levels of cytochrome P-450 (cyt P-450) and cytochrome b5 (cyt b5) were significantly augmented (p<0.05) by

The pharmacological activities of Cuminum cyminum - A review
53
the 2.5% dose of cumin seed diet. The levels of cyt P-450 reductase and cyt b5 reductase were increased ( from
p<0.05 to p<0.01) by both doses of cumin. Among the phase II enzymes, glutathione S-transferase specific
activity increased (p<0.005) by the 5% dose, whereas that of DT-diaphorase increased significantly (p<0.05) by
both doses used (2.5 and 5%). In the antioxidant system, significant elevation of the specific activities of
superoxide dismutase (p<0.01) and catalase (p<0.05) was observed with the 5% dose of cumin. The activities of
glutathione peroxidase and glutathione reductase remained unaltered by both doses of cumin. The level of
reduced glutathione measured as nonprotein sulfhydryl content was elevated ( from p<0.05 to p<0.01) by both
doses of cumin. Lipid peroxidation measured as formation of MDA production showed significant inhibition
(p<0.05 to p<0.01) by both doses of cumin. LDH activity remained unaltered by both doses of cumin. The
results were strongly suggested the cancer chemopreventive potentials of cumin seed and could be attributed to
its ability to modulate carcinogen metabolism(138).
Cumin seeds also augmented the levels of carcinogen/xenobiotic metabolizing phase I enzymes, cytochrome
P-450 (cyt P-450) and cytochrome b5 (cyt b5), the levels of cyt P-450 reductase and cyt b5 reductase, and the
phase II enzymes, such as glutathione-S-transferase and DT-diaphorase. These results, in addition to antioxidant
effects, strongly suggest the cancer chemopreventive potential of cumin seed, which attributed to its ability to
modulate carcinogen metabolism. Cumin seeds also decreased significantly the incidence of both B[a]P-induced
neoplasia and 3'MeDAB induced hepatomas in Wistar rats(79, 139).
VII. ANTIOXIDANT EFFECTS
The antioxidant capacity of cumin by ABTS and DPPH assays was3.26 ± 0.29 and2.16 ± 0.06 (mmol TE/g
DW) respectively(140).
The antioxidant activity of cumin was studied. The oil showed higher antioxidant activity compared with that of
BHT and BHA. The cumin essential oil exhibited a dose-dependent scavenging of DPPH radicals and 5.4
microg of the oil was sufficient to scavenge 50% of DPPH radicals/ml(119).
Antioxidant activity of essential oils was evaluated by DPPH radical scavenging assay, radical inhibition of
Cuminum cyminum essential oils was 83.59% , the scavenging activities of the essential oil was increased with
the increased of the essential oil concentrations(129).
It appeared that the full ripe seeds were richer on polyphenols and condensed tannin than unripe ones, and
consequently exhibited higher antioxidant activities. However, the unripe seeds had a higher total flavonoid
content compared to those of half ripe and full ripe ones. The comparison of two extraction methods, the
soxhlet extracts contained the greatest amount of polyphenols and flavonoids, while maceration samples
exhibited higher antiradical and bleaching power assay. Total phenolic contents and IC50 values in cumin seed
during their maturation allowed to conclude that antioxidant activity does not depend only on the high content of
total phenolics but also on the phenolic composition(98).
The antioxidant activities of β-pinene, p-cymene, γ-terpinene, cuminaldehyde and cumin oils (cumin
oleoresin/COR, cumin essential oil/CEO, distillation residue/DR and distillate condensed from cold trap/CT)
were investigated in the present study. IC50 values and kinetics rates were used to evaluate the efficiency of
tested samples in scavenging the alkyl peroxyl radical generated in the β-carotene-linoleic acid system and the
2,2-diphenyl-1-picrylhydrazyl radical (DPPH). In kinetic approach, antioxidant activities of tested samples
were expressed as the rate of β-carotene bleaching (R(β-carotene)) and DPPH scavenging (R(DPPH)),
respectively. The order of antioxidant activities of cumin oils was DR=COR>CEO>CT. γ-Terpinene exhibited
lower R (β-carotene) value and the lowest IC50(β-carotene) value, which indicated the stronger response in alkyl
peroxyl radical scavenging. The R2(DPPH) values for γ-terpinene, followed by DR and COR, showed high
response in scavenging DPPH, with IC50 values of 22.73, 6.72, 8.53mg/ml, respectively. γ–terpinene appeared
the most efficient antioxidant compounds in cumin oils(141).
Thiobarbituric acid reactive substances (TBARS) assay was used to evaluate the lipid peroxidation of Cuminum
cyminum extract. The extract also produced significant lipid peroxidation inhibition in comparison with known
antioxidant ascorbic acid in both rat liver and brain(142).
The antioxidant activities of Cuminum cyminum essential oils and acetone extracts obtained from the three
organs were assessed using four tests [1,1-diphenyl-2-picrylhydrazyl (DPPH), β-carotene/linoleic acid, reducing
power, and chelating power assays]. The acetone extract of flowers was strongly effective as a DPPH radical
scavenger, lipid peroxidation inhibitor, and reducing agent, with IC50 values of 4, 32, and 8 μg/ml, respectively.
Moreover, the acetone extract of stems and leaves showed the highest chelating power. However, the essential
oils exhibited moderate activities in the different tests(97).
Two complementary assays were used to assess the antioxidant activity of cumin and caraway methanolic and
acetonic seed extracts: the DPPH free radical scavenging assay and the β-carotene bleaching assay. Both cumin
and caraway seed extracts were able to neutralize free radicals over a period of 60 min in the DPPH assay, with
most of the neutralization occurring quickly within the first 30s. The steady state was reached within 10min, and
it appeared that the acetonic extracts of both seeds had less antioxidant activity than the methalonic extracts. The

The pharmacological activities of Cuminum cyminum - A review
54
methanolic and acetonic extracts of cumin showed slightly higher neutralization ability than the respective
extracts from caraway within three minutes of assay initiation (57.0 and 52.4% for cumin and 44.7 and 39.5%
for caraway(143).
The effect of Cuminum cyminum was investigated on alcohol and thermally oxidized oil induced
hyperlipidaemia. The results showed increased activity of aspartate transaminase (AST), alkaline phosphatase
(ALP) and gamma glutamyl transferase (GGT) and increased levels of cholesterol, triglycerides and
phospholipids in the plasma of rats given alcohol, thermally oxidized oil and alcohol+ thermally oxidized oil
when compared with the normal control group. The levels of tissue (liver and kidney) cholesterol and
triglycerides were increased significantly in rats groups given alcohol, thermally oxidized oil and alcohol+
thermally oxidized oil when compared with the normal control rats. The levels were decreased when cumin was
given along with alcohol and thermally oxidized oil. The level of phospholipids decreased significantly in the
liver and kidney of groups given alcohol, thermally oxidized oil and alcohol+ thermally oridized oil when
compared with the normal control rats. The level increased when cumin was administered along with alcohol
and thermally oxidized oil. The activity of phospholipase A and C increased significantly in the liver of groups
given alcohol, thermally oxidized oil and alcohol+ thermally oxidized oil when compared with the normal
control rats, whereas the activity was decreased with the cumin treatment. The results indicate that cumin can
decrease the lipid levels in alcohol and thermally oxidized oil induced hepatotoxicity(144).
VIII. ANTIINFLAMMATORY AND ANALGESIC EFFECTS
Acetic-acid induced writhing, hot plate, Carrageenan-induced paw oedema and Cotton-pellet granuloma
methods were used for evaluation of analgesic and anti-inflammatory effects of Cuminum cyminum extracts (
200 and 500 mg/kg for aqueous and ethanolic extract). Both the aqueous and ethanolic extracts showed highly
significant analgesic activity in Acetic-acid induced writhing, while the ethanolic extracts were effective in hot
plate method. Both the aqueous and ethanolic extracts showed significant anti-inflammatory activity in
Carrageenan-induced paw oedema and Cotton-pellet granuloma models when compared to the control
group(145).
The anti-inflammatory effects of cumin essential oil (CuEO), in lipopolysaccharide- (LPS-) stimulated
RAW 264.7 cells and the underlying mechanisms were investigated. Mitochondrial-respiration-dependent 3-
(4,5-dimethylthiazol-2-yl)- 2,5-diphenyl tetrazolium (MTT) reduction assay demonstrated that CuEO did not
exhibit any cytotoxic effect at the employed concentrations (0.0005–0.01%). Real-time PCR tests showed that
CuEO significantly inhibited the mRNA expressions of inducible nitric oxide synthase (iNOS), cyclooxygenase
(COX-2), interleukin- (IL-) 1, and IL-6. Moreover, western blotting analysis revealed that CuEO blocked LPS-
induced transcriptional activation of nuclear factor-kappa B (NF-κB) and inhibited the phosphorylation of
extracellular signal regulated kinase (ERK) and c-Jun N-terminal kinase (JNK). The results revealed that CuEO
exerted anti-inflammatory effects in LPS-stimulated RAW264.7 cells via inhibition of NF-κB and mitogen-
activated protein kinases ERK and JNK signaling(146).
The potential anti-nociceptive and anti-inflammatory activities of the fruit essential oil of Cuminum
cyminum has been evaluated in chemical (formalin test) and thermal (tail-flick test) models of nociception and
formalin model of acute inflammation in rats and mice. The essential oil at the doses ranging between 0.0125
and 0.20 ml/kg exhibited a significant and dose-dependent analgesic effect in both model of chronic and
inflammatory pain. However, the essential oil was devoid of anti-inflammatory activity. Moreover, the essential
oil had no analgesic effect in tail flick test as a model of acute pain(147).
The antiinflammatory activity of cumin volatile oil was investigated in carrageenan-induced rat paw oedema.
The volatile oil showed dose–dependent inhibition of rat paw oedema, at dose of 0.1ml/kg, ip, when compared
to control group. The activity was comparable with that of the standard drug, diclofenac sodium(75).
The methanolic extract of Cuminum cyminum inhibited lipoxygenase (LOX) activity. Activity-guided
screening of the Cuminum cyminum crude extracts helped the identification and isolation of cuminaldehyde as a
15-LOX inhibitor. The enzyme kinetics analysis suggested cuminaldehyde to be a competitive inhibitor and the
IC 50 value derived from LB plots is 1.370 μM(148).
IX. CENTRAL NERVOUS EFFECT
The effect of the fruit essential oil of Cuminum cyminum on the epileptiform activity induced by
pentylenetetrazol (PTZ) was evaluated using intracellular technique. The results demonstrated that extracellular
application of the essential oil of Cuminum cyminum (1% and 3%) dramatically decreased the frequency of
spontaneous activity induced by PTZ in a time and concentration dependent manner. In addition it showed
protection against pentylenetetrazol-induced epileptic activity by increasing the duration, decreasing the
amplitude of after hyperpolarization potential (AHP) following the action potential, the peak of action potential,
and inhibition of the firing rate(149).

The pharmacological activities of Cuminum cyminum - A review
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The memory-enhancing and antistress activities of Cuminum cyminum were studied in rats. Antistress
activity was evaluated by inducing stress via forced swimming and the urinary vanillylmandelic acid (VMA)
and ascorbic acid were estimated as biomarkers. Memory-enhancing activity was studied by conditioned
avoidance response using Cook's pole climbing apparatus in normal and scopolamine-induced amnestic rats.
Daily administration of cumin at doses of 100, 200, and 300 mg/kg bw, 1h prior to induction of stress, it
inhibited the stress-induced urinary biochemical changes in a dose-dependent manner without altering the levels
in normal control groups. The cognition, as determined by the acquisition, retention, and recovery in rats, was
observed to be dose-dependent. The extract also produced significant lipid peroxidation inhibition in
comparison with known antioxidant ascorbic acid in both rat liver and brain(142).
The effects of fruit essential oil (FEO) of Cuminum cyminum on acquisition and expression of
morphine tolerance and dependence were investigated in mice. Animals were rendered dependent on morphine
using the established method in which morphine (50, 50, 75 mg/kg; sc) was injected three times daily for 3
days. FEO (0.001, 0.01, 0.1, 0.5, 1 and 2%; 5 ml/kg, ip) or Tween-80 (5 ml/kg, ip) were given 60 min prior to
each morphine injection (for acquisition) or the last injection of morphine on test day (for expression). Morphine
tolerance was measured by tail-flick before and after administration of a single dose of morphine (50 mg/kg, sc)
in test day (4th day). Morphine dependence was also evaluated by counting the number of jumps after injection
of naloxone (5 mg/kg, ip) on the test day. The results showed that Cumin FEO, only at the dose of 2%,
significantly attenuated the development of morphine tolerance (p<0.01) and dependence (p<0.05). It was
significantly effective on expression of morphine tolerance (1 and 2%) and dependence (0.5, 1 and 2%) in a
dose-dependent manner. Accordingly, the essential oil of Cuminum cyminum ameliorated the morphine
tolerance and dependence in mice(150).
The effects of Cuminum cyminum fruit essential oil (FEO) on the acquisition and expression of
morphine-induced conditioned place preference (CPP) was studied in mice. CPP was induced by subcutaneous
injection of morphine (5mg/kg) in 3 days conditioning schedule. Intraperitoneal administration of Cumin FEO
(0.001%, 0.01%, 0.1%, 0.5%, 1% and 2%; 5 ml/kg) or Tween-80 (0.5%, 5 ml/kg) did not show any conditioning
effects. Administration of Cumin FEO (0.001-2%, 5 ml/kg; ip), 60 min before test on day 5 (expression)
decreased the conditioning scores at the doses of 1% and 2% while ip injection of Cumin FEO (0.001-2%, 5
ml/kg), 60 min before morphine injection (5mg/kg, sc) during 3 days of conditioning session (acquisition)
significantly resulted in decrement of rewarding properties of morphine at the doses of 0.1%, 0.5%, 1% and 2%
in dose-dependent manner(151).
The inhibitory effects of the Cuminum cyminum essential oil on the fibrillation of α-SN, which was a
critical process in the pathophysiology of several neurodegenerative diseases, especially Parkinson's disease,
was investigated. Analysis of different fractions from the total extract, identified cuminaldehyde as the active
compound involved in the antifibrillation activity. In comparison with baicalein, a well-known inhibitor of α-SN
fibrillation, cuminaldehyde showed the same activity in some aspects and a different activity on other
parameters influencing α-SN fibrillation. The presence of spermidine, an α-SN fibrillation inducer, dominantly
enforced the inhibitory effects of cuminaldehyde even more intensively than baicalein. Furthermore, the results
from experiments using preformed fibrils and monobromobimane-labeled monomeric protein also suggested
that cuminaldehyde prevents α-SN fibrillation even in the presence of seeds, having no disaggregating impact on
the preformed fibrils. Structural studies showed that cuminaldehyde stalls protein assembly into β-structural
fibrils, which might be achieved by the interaction with amine groups through its aldehyde group as a Schiff
base reaction. This assumption was supported by FITC labeling efficiency assay. In addition, cytotoxicity assays
on PC12 cells showed that cuminaldehyde is a nontoxic compound, treatment with cuminaldehyde throughout
α-SN fibrillation showed no toxic effects on the cells(152).
X. EFFECT ON PLATELET FUNCTION
Extract of cumin inhibited arachidonate-induced platelet aggregation. It also inhibited thromboxane
B2 production from exogenous (14C) arachidonic acid (AA) in washed platelets, in addition, a simultaneous
increase in the formation of lipoxygenase-derived products was also observed(153).
XI. HYPOTESIVE EFFECT
The anti-hypertensive potential of standardized aqueous extract of Cuminum cyminum seeds and its
role in arterial endothelial nitric oxide synthase expression, inflammation, and oxidative stress were evaluated in
renal hypertensive rats. Renal hypertension was induced by the two-kidney one-clip (2K/1C) method in rats.
Systolic blood pressure (SBP), plasma nitrate/nitrite, carotid–eNOS, renal–TNF-α, IL-6, Bax, Bcl-2, thioredoxin
1 (TRX1), and thioredoxin reductase 1 (TRXR1) mRNA expressions were studied to demonstrate the anti-
hypertensive action of Cuminum cyminum. Cuminum cyminum seed was administered orally (200 mg/kg bw)
for a period of 9 weeks, it improved plasma nitric oxide and decreased the systolic blood pressure in
hypertensive rats. It also up-regulated the gene expression of eNOS, Bcl-2, TRX1, and TRXR1; and down-

The pharmacological activities of Cuminum cyminum - A review
56
regulated Bax, TNF-α, and IL-6. The data revealed that Cuminum cyminum seeds augment endothelial functions
and ameliorate inflammatory and oxidative stress in hypertensive rats(154).
XII. HYPOLIPIDEMIC AND WEIGHT REDUCTION EFFECTS
The hypocholesterolemic effect of methanolic extract of Cuminum cyminum (MCC) was evaluated in
ovariectomized (OVX) rats. MCC 1000 mg/kg and estradiol benzoate equivalent to 0.15 mg/kg of estradiol were
administered to OVX rats per orally for 10 weeks. The results indicated that estradiol as well as MCC protected
OVX rats against increased cholesterol levels due to ovariectomy, MCC was better than estradiol(155).
The effect of cumin powder on body composition and lipid profile was studied in overweight and
obese women in a randomized clinical trial. 88 overweight/obese women were randomly assigned into two
groups. The experimental group was given 3 g/day cumin powder with yogurt at two meals for 3 months. The
same amount of yogurt without cumin powder was prescribed for the control group. All patients received
nutrition counseling for weight loss in a similar manner. Anthropometric and biochemical parameters were
determined before and after the intervention. Cumin powder reduced serum levels of fasting cholesterol,
triglyceride, and LDL and increased HDL. Weight, BMI, waist circumference, and fat mass were also
significantly reduced. However, it exerted no effect on FBS and fat-free mass(156).
The effects of cumin extract supplementation on oxLDL, paraoxanase 1 activity, FBS, total cholesterol,
triglycerides, High density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C),
apolipoprotein A1 (Apo A1), and apolipoprotein B (Apo B) were studied in the patients with
hypercholesterolemia. The results demonstrated that there was a significant decrease in the level of oxLDL after
receiving cumin. Paraoxonase and arylesterase activities increased in serum after taking cumin extract.
Paraoxanase 1 (PON1) played a protective role against the oxidative modification of plasma lipoproteins and
hydrolyzes lipid peroxides in human atherosclerotic lesions (157).
The effects of Cuminum cyminum intake on weight loss and metabolic profiles among overweight
subjects was studied by a randomized double-blind placebo-controlled clinical trial which conducted among 78
overweight subjects (male, n = 18; female, n = 60) aged 18-60 years old. Participants were randomly assigned
into three groups to receive: (1) Cuminum cyminum capsule (n = 26); (2) orlistat 120 capsule (n = 26) and (3)
placebo (n = 26) three times a day for 8 weeks. Anthropometric measures and fasting blood samples were taken
at baseline and after 8 weeks of intervention. Consumption of the Cuminum cyminum and orlistat120 resulted in
a similar significant decrease in weight (-1.1 ± 1.2 and -0.9 ± 1.5 compared with placebo 0.2 ± 1.5 kg,
respectively, p = 0.002) and BMI (-0.4 ± 0.5 and -0.4 ± 0.6 compared with placebo 0.1 ± 0.6 kg/m(2),
respectively, p = 0.003). In addition, Cuminum cyminum L., compared with orlistat and placebo, led to a
significant reduction in serum insulin levels (-1.4 ± 4.5 vs. 1.3 ± 3.3 and 0.3 ± 2.2 µIU/ml, respectively, p =
0.02), HOMA-B (-5.4 ± 18.9 vs. 5.8 ± 13.3 and 1.0 ± 11.0, respectively, p = 0.02) and a significant rise in
QUICKI (0.01 ± 0.01 vs. -0.005 ± 0.01 and -0.004 ± 0.01, respectively, p = 0.02)(158).
XIII. GASTROINTESTINAL EFFECT
The stomach of pentobarbitone-anesthetized rats was perfused at 0.15 ml/min with aqueous extracts of
cumin or acetylcholine (1 microgram/ml or 10 micrograms/ml solutions, in 40 min blocks, twice in each
experiment bracketed by saline perfusions. The acid content in the samples was estimated by titration with 0.1N
NaOH with phenolphthalein as indicator. Cumin increased stomach acid secretion from 0.08 to 0.02. (p <
0.05)(159).
The antiulcer activity of the aqueous extracts of leaves of dried fruits of cumin against the diclofenac sodium
induced stomach ulceration has been studied in rats in comparison with omeprazole. Cumin extract accelerated
the healing process to different extents. Healing activity of the aqueous extracts of combination of piper betel
and cumin was found to be beter than healing activity of aqueous extracts of cumin and piper betel alone.
Aqueous extract also enhance gastric mucin protection and regeneration(160).
The effect of aqueous extract of Cuminum cyminum seeds (ACCS) was studied against diarrhoea on albino
rats. The animals were divided into five groups and the control group was given 2% acacia suspension, the
standard group with loperamide (3 mg/kg) or atropine sulphate (5mg/kg) and three test groups administered
orally with 100, 250 and 500 mg/kg of ACCS. The antidiarrhoeal effect was investigated by castor oil induce
diarrhoea model, prostaglandin E2 (PGE2) induced enteropooling model and intestinal transit by charcoal meal
test. The ACCS showed significant (p< 0.001) inhibition in frequency of diarrhoea, defecation time delaying,
secretion of intestinal fluid as well as intestinal propulsion as compared to control. The graded doses of the
tested extract showed dose dependent protection against diarrhea(161).
Protective effects:
The effect of Cuminum cyminum (Cumin) on kidney exposed to profenofos was evaluated in female
swiss albino mice. The results showed that cumin was effective in normalizing the uric acid and creatinine
level(162).

The pharmacological activities of Cuminum cyminum - A review
57
Depression in growth, hepatotoxicity and nephrotoxicity were observed in rats that had been given
paracetamol at 500 mg/kg orally for 4 weeks. These findings were accompanied by leucopenia, macrocytic
normochromic anemia and alterations of serum aspartate aminotransferase, alanine aminotransferase and
alkaline phosphatase activities and concentrations of cholesterol, urea and other serum constituents. Serum
bilirubin did not change. In rats given the mixture of paracetamol 500 mg/ kg plus 6% Cuminum cyminum fruit
for 4 weeks, the recovery of paracetamol hepatotoxicity was evidenced by increase in body weight, absence of
hepatocellular fatty vacuolation and significant improvement of serbiochemical and hematological
parameters(163).
The effects of cumin on sperm quality and testicular tissue was evaluated following experimentally
induced copper poisoning (copper sulphate 100 mg/kg ) in mice. Cuminum cyminum was used at dose of
1 mg/kg. The results showed that sperm concentration, motility and viability in copper group were
significantly decreased at weeks 4 and 6, and severe degenerative changes were observed in testicular tissues in
comparison with the control group. In cumin treated group, significant improvement in the sperm count, motility
and viability, and normal architecture in most seminiferous tubules with organized epithelium was observed
compared to the copper group(164).
Bronchodilatory effects:
The relaxant effects of the macerated and aqueous extracts of Cuminum cyminum (0.25, 0.5, 0.75 and
1.0 g%) was investigated on the tracheal chains of guinea pig in comparison with saline and theophylline (0.25,
0.5, 0.75, and 1.0 mM) In Group 1 experiments (contracted by KCl) only the last two concentrations of
theophylline and the highest concentration of macerated extract showed significant relaxant effect compared to
that of saline (p<0.001 and p<0.05 for theophylline and macerated extract respectively). The effects of the last
two concentrations of theophylline in this group were significantly greater than those of the macerated and
aqueous extracts (p<0.001). However, in Group 2 experiments (contracted by methacholine) both the extracts
and theophylline showed concentration-dependent relaxant effect compared to that of saline (p<0.05 to
p<0.001). The effects of the two last concentrations of both extracts were significantly lower than those of
theophylline in Group 2 experiments (p<0.05 to p<0.001). In Group 3 (non-incubated, contracted by
methacholine) the extracts of Cuminum cyminum did not show any relaxant effect of tracheal chains. The
relaxant effects of macerated and aqueous extracts in Groups 1 and 3 were significantly lower than those of
Group 2 (p<0.05 to p<0.001)(165).
Immunological effect:
The health modulating effects and immunomodulatory properties of Cuminum cyminum were
evaluated using flowcytometry and ELISA in normal and immune-suppressed animals. Cuminum cyminum
stimulated the T cells and Th1 cytokines expression in normal animals. Swiss albino mice subjected to
Cyclosporine-A induced immune-suppression were dosed orally with Cuminum cyminum (25, 50, 100 and 200
mg/kg) on consecutive days. The results showed that administration significantly increased T cells (CD4 and
CD8) count and Th1 predominant immune response in a dose dependent manner, suggesting
immunomodulatory activity through modulation of T lymphocytes expression. In restraint stress induced
immune-suppressed animals, Cuminum cyminum countered the depleted T lymphocytes, decreased the elevated
corticosterone levels and size of adrenal glands and increased the weight of thymus and spleen(166).
Contraceptive effect:
The contraceptive efficacy of Cuminum cyminum isolated fractions (CcFr) was investigated in male
albino rats. Oral dose of CcFr 50 mg/rat/day for 60 days revealed no significant changes in body weight, while
marked abnormalities in spermatogenesis were observed with decreased counts (P ≤ 0.001) in round spermatids,
preleptotene spermatocytes and secondary spermatocytes. Cross sectional surface area of Sertoli cells as well as
number of mature Leydig cell were decreased significantly (p≤0.001). Testicular as well as accessory sex organ
biochemical parameters were significantly changed (p≤0.001). Sperm motility, density and morphology were
resulted in 100% negative fertility. Testosterone levels were declined significantly. The authors concluded that
Cuminum cyminum inhibited spermatogenesis in rats and can be acting as herbal male contraceptive(167).
Anti-amyloidogenic effect:
The active anti-amyloidogenic compounds of the cumin oil was studied. After fractionation, the
highest inhibitory effect was observed in the toluene-ethyl acetate part of the oil. Gas chromatography-mass
spectrometry (GC-MS) analysis of this fraction indicated that eight compounds were predominantly present in
the fraction. Two compounds including terpinolene and limonene (having very similar chemical structures)
inhibited fibrillation. PC12 cells (derived from a transplantable rat pheochromocytoma) were affected by HEWL
fibrils, whereas the inhibited forms of fibrils in the presence of terpinolene led to higher levels of viability, as
appeared by 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT), lactate dehydrogenase
(LDH) and flow cytometry assays. Molecular local docking analysis suggested a site of interaction for

The pharmacological activities of Cuminum cyminum - A review
58
terpinolene in the flexible cleft of the protein. This interaction site was close to tryptophan -62 and -63 and two
other hydrophobic residues in the hot spot regions of the protein(168).
Anti-osteoporotic effect:
The anti-osteoporotic activity of Cuminum cyminum was evaluated in rats. Adult Sprague-Dawley rats
were bilaterally ovariectomized (OVX) and randomly assigned to 3 groups. Additional animals were sham
operated. OVX and sham control groups were orally administered with vehicle while the other two OVX groups
were administered 0.15 mg/kg estradiol and 1 g/kg of methanolic extract of Cuminum cyminum fruits (MCC) in
two divided doses for 10 weeks. At the end of the study blood, bones and uteri of the animals were collected.
Serum was evaluated for calcium, phosphorus, alkaline phosphatase and tartarate resistant acid phosphatase.
Bone density, ash density, mineral content and mechanical strength of bones were evaluated. Scanning electron
microscopic (SEM) analysis of bones (tibia) was performed. MCC (1 g/kg, po) significantly reduced urinary
calcium excretion and significantly increased calcium content and mechanical strength of bones in comparison
to OVX control. It showed greater bone and ash densities and improved microarchitecture of bones in SEM
analysis. Unlike estradiol it did not affect body weight gain and weight of atrophic uterus in OVX animals.
MCC prevented ovariectomy-induced bone loss in rats with no anabolic effect on atrophic uterusl(169).
Aldose reductase and alpha-glucosidase inhibitory effects:
The inhibitory activity of Cuminum cyminum seed oil component was evaluated against lens aldose
reductase and alpha-glucosidase isolated from Sprague-Dawley male rats and compared with quercitrin as an
aldose reductase inhibitor and acarbose as an alpha-glucosidase inhibitor. The biologically active constituent of
Cuminum cyminum seed oil was characterized as cuminaldehyde by various spectral analyses. The IC50 value of
cuminaldehyde is 0.00085 mg/ml against aldose reductase and 0.5 mg/ml against alpha-glucosidase.
Cuminaldehyde was about 1.8 and 1.6 times less inhibitory than quercitin and acarbose, respectively(170).
Tyrosinase inhibitory effect:
Cuminaldehyde was identified as a potent mushroom tyrosinase monophenol monooxygenase inhibitor.
It inhibited the oxidation of L-3,4-dihydroxyphenylalanine (L-DOPA) by mushroom tyrosinase with an ID50 of
7.7 g/ml (0.05 mM). Its oxidized analogue, cumic acid (p-isopropylbenzoic acid), also inhibited this oxidation
with an ID50 of 43 g/ml (0.26 mM). These two inhibitors affected mushroom tyrosinase activity in different
ways(171).
Effect on erythrocyte hemolysis:
The effect of methanolic and acetonic seed extracts of Cumin (Cuminum cyminum) was studied on on
human erythrocyte hemolysis in comparison with caraway. Both seed extracts were able to protect erythrocytes
from hemolysis. Methanolic cumin extract showed higher percentage of protection than caraway(143).
Side effect and toxicity:
Health risks or side effects following the proper administration of designated dierapeutic dosages are
not recorded(78). The LD50 of essential oils in mice was 0.59 ml/kg(77). Cuminum cyminum fruits were fed to
male Wistar rats at 2% or 10% of standard diet for 6 weeks. A mixture (5% Cuminum cyminum fruits + 5% T.
vulgaris leaves) was also fed to rats for a similar period. Diets containing 2% Cuminum cyminum fruits, was not
toxic to rats. Impairment of growth and enterohepatonephropathy were observed in the rats fed a diet containing
10% Cuminum cyminum fruits. These changes were also recorded in the rats fed the mixture of the 2 plants and
were accompanied by leukopenia, anemia and increases in serum AST activity and urea and by decreased total
protein and albumin levels(172).
Acute and subchronic toxicity of cumin essential oil were studied in a 30 day oral toxicity study in rats. A
17.38% decrease in WBCs count, and 25.77%, 14.24%, and 108.81% increase in hemoglobin concentration,
hematocrit, and platelet count respectively, were noted. LDL/HDL ratio was reduced to half(119).
Dose:
Daily dosage: The average single dose is 300 to 600 mg of drug (equivalent to 5 - 10 fruits). However,
cumin was used both internally and externally in ground form and as a pressed oil(78).
XIV. CONCLUSION
This review discuss the chemical constituent, pharmacological and therapeutic effects of Cuminum cyminum as
promising herbal drug because of its safety and effectiveness.
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