Kayu manis Leaves
Cinnamomum verum J.S. Presl
Lauraceae
Figure 1 : Cinnamomum verum. (a) Whole plant; (b) leaves arrangement; (c) adaxial and abaxial leaf surfaces; (d) flower; (e) fruit. (Photos courtesy of Centre for Herbal Standardization, 2018)
DEFINITION
Kayu manis leaves consist of the powder of dried leaves of Cinnamomum verum J.S. Presl (Lauraceae).
SYNONYM
Camphorina cinnamomum (L.) Farw., Cinnamomum alexei Kosterm., Cinnamomum aromaticum J. Graham., Cinnamomum barthii Lukman., Cinnamomum bengalense Lukman., Cinnamomum biafranum Lukman., Cinnamomum bonplandii Lukman., Cinnamomum boutonii Lukman., Cinnamomum capense Lukman., Cinnamomum carolinense var. oblongum Kaneh., Cinnamomum cayennense Lukman., Cinnamomum commersonii Lukman., Cinnamomum cordifolium Lukman., Cinnamomum decandollei Lukman., Cinnamomum delessertii Lukman., Cinnamomum ellipticum Lukman., Cinnamomum erectum Lukman., Cinnamomum humboldtii Lukman., Cinnamomum karrouwa Lukman., Cinnamomum leptopus A. C. Sm., Cinnamomum leschenaultia Lukman., Cinnamomum madrassicum Lukman., Cinnamomum maheanum Lukman., Cinnamomum maheanum var. karrouwa Lukman., Cinnamomum mauritianum Lukman., Cinnamomum meissneri Lukman., Cinnamomum ovatum Lukman., Cinnamomum pallasii Lukman., Cinnamomum pleei Lukman., Cinnamomum pourretii Lukman., Cinnamomum regelii Lukman., Cinnamomum roxburghii Lukman., Cinnamomum sieberi Lukman., Cinnamomum sonneratii Lukman., Cinnamomum vaillantii Lukman., Cinnamomum variabile Lukman., Cinnamomum wolkensteinii Lukman., Cinnamomum zeylanicum Blume., Cinnamomum zeylanicum var. cassia Meisn., Cinnamomum zeylanicum var. cordifolium Hayne., Cinnamomum zeylanicum var. foeniculaceum Meisn., Cinnamomum zeylanicum var. inodorum Meisn., Cinnamomum zeylanicum var. microphyllum Meisn., Cinnamomum zollingeri Lukman., Laurus cinnamomum L [ 1 ].
VERNACULAR NAMES
Ceylon cinnamon, cinnamon, cinnamon tree or true cinnamon (English); kayu manis (Malay); xi lan rou gui (Chinese); lavangapattai, karuvapattai (Tamil) [ 2 , 3 , 4 ]
CHARACTER
| Colour | Brownish-green |
| Odour | Strongly aromatic [2] |
| Taste | Characteristic |
IDENTIFICATION
Plant Morphology
C. verum is a evergreen tree grows up to 18 m tall. Trunk is stout, low-branching, up to 60 cm in diameter; buttresses 60 cm tall, 70 cm deep, thin, light pinkish-brown; stem bark about 10 mm thick, strongly aromatic; the stem bark on young shoots is smooth and pale brown, on mature branches and stems rough, dark brown or brownish-grey; wood of mature trees varies from light brownish-grey to grey or yellowish-brown, without markings, more or less lustrous and faintly scented. Leaves opposite, somewhat variable in form and size, strongly aromatic; petiole 1-2 cm long, grooved on upper surface; blade ovate to elliptical, 5-25 cm x 3-10 cm, conspicously 3-veined, or 5-veined, base rounded, apex acuminate, glabrous, coriaceous, shiny dark green. Inflorescence consisting of lax axillary or terminal panicles up to 10 cm long or longer; peduncle creamy white, softly hairy, 5-7 cm long. Flowers small, 3 mm in diameter, with foetid smell, pale yellow, subtended by small ovate hairy bract; perianth 8 mm long, silky hairy, with short campanulate tube and 6 persistent tepals about 3 mm long; fertile stamens 9, in 3 whorls, with 2 small glands at the base of the stamens of the third whorl; a fourth innermost whorl consists of 3 staminodes; filaments hairy, stout; anthers 4- or 2-celled; ovary superior, 1-celled, with a single ovule, style short. Fruit 1-seeded berry, ellipsoidal to ovoid, 1-2 cm long, black when ripe, surrounded by the enlarged perianth at the base. Roots moderately deep and extensive; seedling root growth is initially rapid, with formation of a well-developed taproot followed by numerous spreading laterals [ 5 ].
Microscopy
Powdered material consists of epidermal cells; fragments of parenchyma, paracytic stomata found attached to epidermal cells; brachysclereid found isolated; fibres; group of spiral and annular vessels; simple multicellular trichome; mucilage cell.
Figure 2 : Microscopic characters of C. verum leaves powder of 0.355 mm size. (a) Epidermis (magnification 50x); (b) cluster of brachysclereid (magnification 50x); (c) stomata (arrow) attached to parenchyma (magnification 50x); (d) brachyscelereid (arrow) (magnification 50x); (e) fibres (arrow) (magnification 50x); (f) a group of spiral vessels (magnification 50x); (g) fragment of spiral vessel (arrow) (magnification 50x); (h) annular vessel (magnification 50x); (i) multicellular trichome (magnification 50x); (j) oil cell (magnification 50x). [Scale bars: a–j = 20 µm]
Chemical Tests
Observation of solution after treatment with reagent:
| Test for the presence of steroids | Bluish green |
Thin Layer Chromatography (TLC)
Figure 3 : TLC chromatogram of eugenol (S), ethanol extract of C. verum dried leaves (L) observed under (a) visible light and (b) UV at 366 nm after derivatisation.
| Test solution | Weigh about 1.0 g of C. verum dried leaves powder of 0.355 mm size in 50 mL of conical flask. Add 10 mL of ethanol. Sonicate the mixture for 15 min at room temperature. Filter the mixture with Whatman no.1 filter paper into flat bottom flask. Dry off the filtrate by using rotary evaporator at 60°C and 150 mbar. Then, reconstitute the extract with 10 mL of methanol, mix well. Use the filtrate as the test solution. |
| Standard solution | Dissolve eugenol standard [CAS no.: 97-53-0] in methanol to produce concentration 1.0 mg/mL. Vortex standard for 10 s before use. |
| Stationary phase | HPTLC Silica gel 60 F254, 10 x 10 cm |
| Mobile phase | Toluene : ethyl acetate, (28 : 8) (v/v) |
| Application |
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| Development distance | 8 cm |
| Drying | Air drying |
| Detection |
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High Performance Liquid Chromatography (HPLC)
| Test solution | Weigh about 1.0 g of C. verum dried leaves powder of 0.355 mm size in 100 mL of conical flask. Add 10 mL of ethanol. Sonicate the mixture for 15 min. The mixture was then centrifuged and supernatant was collected. | ||||||||||||||||||
| Standard solution | Dissolve eugenol standard [CAS no.: 97-53-0] in ethanol to produce a standard concentration of 0.25 mg/mL. Vortex standard for 10 s at room temperature before use. | ||||||||||||||||||
| Chromatographic system |
Detector: 280 nmColumn: C18 (3.5 µm, 4.6 mm I.D x 150 mm,) (Zorbax SB-C18 if necessary) Column oven temperature: 25˚C Flow rate: 1 mL/min Injection volume: 10 µL |
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| Mobile Phase (gradient mode) |
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| System suitability requirement |
Perform at least five replicate injections of the standard solutions (0.25 mg/mL). The requirements of the system suitability parameters are as follow:
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| Acceptance criteria |
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(a)
(b)
Figure 4 : Whole HPLC chromatogram of (a) eugenol standard solution (0.25 mg/mL) at tr = 10.148 min and (b) ethanol extract of C. verum dried leaves powder showing peak corresponding to eugenol standard solution at tr = 10.136 min.
(a)
(b)
Figure 5 : HPLC chromatogram highlighting the elution region of (a) eugenol standard solution (0.25 mg/mL) at tr = 10.148 min and (b) ethanol extract of C. verum dried leaves powder showing peak corresponding to eugenol standard solution at tr = 10.136 min.
Figure 6 : UV spectrum of eugenol standard solution (0.25 mg/mL) and ethanol extract of C. verum dried leaves powder.
PURITY TESTS
The purity tests, except foreign matter test are based on C. verum dried leaves powder of 0.355 mm particle size.
| Foreign Matter |
| Not more than 2% |
| Ash Contents | |
| Total ash | Not more than 6% |
| Acid-insoluble ash | Not more than 1% |
| Water soluble ash | Not less than 0.5% |
| Loss on Drying |
| Not more than 13% |
| Extractive Values | |
| Water-soluble extracts | |
| Hot method | Not less than 15% |
| Cold method | Not less than 13% |
| Ethanol-soluble extracts | |
| Hot method | Not less than 13% |
| Cold method | Not less than 6% |
SAFETY TESTS
The safety tests are based on C. verum dried leaves powder of 0.355 mm particle size.
| Heavy Metals | |
| Arsenic | Not more than 5.0 mg/kg |
| Mercury | Not more than 0.5 mg/kg |
| Lead | Not more than 10.0 mg/kg |
| Cadmium | Not more than 0.3 mg/kg |
| Microbial Limits | |
| Total bacterial count | Not more than 105cfu/g |
| Total yeast and mould count | Not more than 104 cfu/g |
| Bile-tolerant gram negative | Not more than 104 cfu/g |
| Specific Pathogens | |
| Salmonella spp. | Absent in 25 g |
| Escherichia coli | Absent in 1 g |
| Staphylococcus aureus | Absent in 1 g |
| Pseudomonas aeruginosa | Absent in 1 g |
CHEMICAL CONSTITUENTS
Essential oil of C. verum leaves was found to contain sesquiterpenoids (e.g α-amorphene, α-muurolene, α-pinene, caryophyllenol, caryophyllene oxide, α-phyllandrene, α-santalene, α-selinene, α-cadinol, α-copaene, α-humulene, α-thujene, α-n-hexylcinnamaldehyde, α-guaiol, nerolidol, (E)-caryophyllene, (E)-β-farnesene, g-cadinene, aromadendrene, β-eudesmol, clovene, humulene epoxide II, carophyllene, valencene, spathulenol, eugenol, iso-eugenol, δ-cadinene, gurjunene, bicyclogermacrene, terpenes (e.g. α-terpeneol, α-terpinene, α-terpineol, terpinolene, phytol, camphene, verbenone, β-bisabolene, limonene, β-caryophyllene, β-caryophyllene oxide, camphor, β-myrcene, β-oplopenone, β-pinene, camphene, geraniol, β-phellandrene, copaene, γ-elemene, γ-terpinene, linalool, myrcene, (E,E)-α-farnesene), (Z)-citral, 1,8-cineole, (E)-β-ocimene, O-cymene, sabinene, safrole, p-cymene, borneol, citronellal, eucalyptol, ledene, methyl eugenol, trans-carveol, trans-pinocarveol, nerol, calacorene, eudesma-4,11-diene), aldehydes (e.g. cinnamaldehyde, (E)-cinnamaldehyde, (Z)-cinnamaldehyde, (Z)-3-hexanal (E)-cinnamic aldehyde, O-methoxycinnamaldehyde, trans-cinnamaldehye, benzaldehyde, benzenepropanal, hexanal), alcohols (e.g. (E)-cinnamyl alcohol, (E)-cinnamyl acetate, (E)-isoeugenol, (E)-2-hexenol, (Z)-3-hexanol, 1-hexen-3-ol, (E)-nerolidol, elemol, 2-phenyl ethyl alcohol, cinnamyl alcohol, cadinol, valerenol, nonanol, (Z)-β-ocimene, hexanol, n-hexan-2-ol, nonanol, terpinene-4-ol), esters (e.g. hexenyl acetate, (E)-2-hexenyl acetate, (Z)-methylcinnamate, benzyl benzoate, cinnamyl acetate, bornyl acetate, linalyl acetate, phenylethyl benzoate, phenyletyl-n-decanoate, allo-ocimene), organic acids (e.g. hexadecenoic acid, (Z)-cinnamic acid), ketones (e.g. humuladienone, piperitone) [ 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 ].
Methanol extract of C. verum leaves was found to contain aldehydes (e.g. cinnamaldehyde), sesquiterpenoids (e.g. eugenol) and organic acids (e.g. pentadecanoic acid, cis-vaccenic acid) [ 16 ].
MEDICINAL USES
Uses described in folk medicine, not supported by experimental or clinical data
Traditionally, the leafy branches is used for joint pains and mental health [ 2 ].
Biological and pharmacological activities supported by experimental data
Antioxidant activity
Essential oil of C. verum leaves exhibited 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging activity with 50% inhibition concentration (IC50) value of 0.245 µg/mL compared to eugenol (IC50 = 1.258 µg/mL), butylhydroxytoluene (BHT) (IC50 = 4.407 µg/mL) and butylated hydroxyanisole (BHA) (IC50 = 1.12 µg/mL) using DPPH assay [ 17 ].
Essential oil of C. verum leaves exhibited hydroxyl radical scavenging activity with 50% inhibition concentration (IC50) value of 0.046 µg/mL compared to eugenol (IC50 = 0.055 µg/mL) and quercetin (IC50 = 4.61 µg/mL) using deoxyribose assay [ 17 ].
Methanol extract of C. verum dried leaves exhibited 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging activity with 50% inhibition concentration (IC50) value of 100.2 ± 0.42 µg/mL compared to vitamin C (IC50 = 30.23 ± 0.12 µg/mL) using DPPH assay [ 18 ].
Methanol extract of C. verum dried leaves exhibited metal chelating capacity with with 50% inhibition concentration (IC50) value of 98.5 ± 0.15 µg/mL compared to EDTA (IC50 = 50.98 ± 0.17 µg/mL) using iron metal chelating assay [ 18 ].
Antimicrobial activity
Essential oil of C. verum leaves (1000 ppm) showed antibacterial activity against Gram-positive bacteria Bacillus cereus with inhibition zone (IZ) of 43.3 mm diameter compared to ampicillin (IZ = 31.4 mm) using disc diffusion method [ 13 ].
Essential oil of C. verum leaves (1000 ppm) showed antibacterial activity against Gram-positive bacteria Staphylococcus aureus with inhibition zone (IZ) of 26.1 mm diameter compared to ampicillin (IZ = 29.5 mm) using disc diffusion method [ 13 ].
Essential oil of C. verum leaves (1000 ppm) showed antibacterial activity against Gram-negative bacteria Pseudomonas aeruginosa with inhibition zone (IZ) of 25.7 mm diameter compared to ampicillin (IZ = 24.3 mm) using disc diffusion method [ 13 ].
Human pancreatic amylase inhibitory activity
Isopropanol extract of C. verum dried leaves showed human pancreatic amylase inhibitory activity with 50% inhibition concentration (IC50) value of 1.0 µg/mL compared to acarbose (IC50 = 10.5 µg/mL) using chromogenic 3,5-dinitrosalicylic acid (DNSA) assay [ 19 ].
Clinical studies
Information and data have not been established.
SAFETY INFORMATION
Preclinical studies (Toxicology studies)
Acute oral toxicity.
Oral single dose acute toxicity study on female Sprague Dawley rats (aged between 8 and 12 weeks old) using aqueous extract of C. verum leaves showed no toxic effect on the parameters observed, including behaviours, body weight, food and water intake. All rats were observed for 14 days prior to necropsy. No death was found throughout the study period. Necropsy revealed no significant abnormality but several histological lesions were found. Approximate lethal dose (LD50) is less than 2,000 mg/kg body weight [20].
Others (Adverse reactions, contraindications, side effects, warning, precautions)
Information and data have not been established.
DOSAGE
Information and data have not been established.
STORAGE
Store below 30°C. Protect from light and moisture.
REFERENCES
- The plant list. [Internet] Cinnamomum verum. Version 1.1; [cited on 1st September 2018]. Available from: http://www.theplantlist.org/tpl1.1/record/kew-2721692.
- Quattrocchi UFLS. CRC world dictionary of medicinal and poisonous plants: common names, scientific names, eponyms, synonyms, and etymology. Vol. III E-L. United States: CRC Press. 2012; p.259-260.
- Burkill IH. A dictionary of the economic product of the Malay Peninsula. Vol. 1. London: Published on behalf of the Governments of the Straits Settlements and Federated Malay States by the Crown Agents for the Colonies. 1935; p.556-558.
- Government of India Ministry of Health & Family Welfare Department of Ayush New Delhi. The Ayurvedic Pharmacopoeia of India. Part I, Volume VI, First Edition. India: Department of Ayush New Delhi. 20118:151-152.
- [Internet] M. Flach, J.S. Siemonsma. Cinnamomum verumJ.S. Presl; [cited on 30th September 2014]. Available from:
http://proseanet.org/prosea/e-prosea_detail.php?frt=&id=570. - Chakraborty A, Sankaran V, Ramar M, Chellapan DR. Chemical analysis of leaf essential oil of Cinnamomum verum from Palni hills, Tamil Nadu. Journal of Chemical and Pharmaceutical Sciences. 2015;8(3):476-479.
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- Li Y, Kong D, Lin X, Xie Z, Bai M, Huang S, Nian H, Wu H. Quality evaluation for essential oil of Cinnamomum verum leaves at different growth stages based on GC-MS, FTIR and Microscopy. Food Analytical Methods. 2016;9:202-212.
- Singh G, Maurya S, deLampasona MP, Catalan CAN. A comparison of chemical, antioxidant and antimicrobial studies of cinnamon leaf and bark volatile oils, oleoresins and their constituents. Food and Chemical Toxicology. 2007;45:1650-1661.
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