Int J Pharm Pharm Sci, Vol 9, Issue 2, 1-11Review Article


CINNAMOMUM GENUS: A REVIEW ON ITS BIOLOGICAL ACTIVITIES

MADHU KATYAYANI BALIJEPALLI1*, AYUBA SUNDAY BURU2, Raghavendra sakirolla2, MALLIKARJUNA RAO PICHIKA2

1Faculty of Medicine, MAHSA University, Kuala Lumpur, Malaysia, 2International Medical University, Kuala Lumpur, Malaysia
Email: madhu@mahsa.edu.my

Received: 08 Feb 2016 Revised and Accepted: 07 Dec 2016

ABSTRACT

The objective of this review is to systematically appraise the literature available to date on biological activities (in vitro and in vivo) of extracts and constituents from Cinnamomum. An extensive review of the literature available in various recognised databases including PubMed, Google Scholar and Scopus on the biological activities of various species of the Cinnamomum were undertaken. The literature provided information on biological activities of the species of the genus Cinnamomum. Crude extracts and constituents from about 30 species of Cinnamomum displayed significant antibacterial, antifungal, antiseptic, antiviral, anti-inflammatory, antipyretic, antioxidant, chemopreventive, cytotoxic, antidiabetic, hypolipidemic, antispasmodic, antiulcer, antiplatelet, anodyne, choleretic, immunostimulant, anaesthetic and sedative activities. Essential oil, aqueous/alcoholic extracts, cinnamaldehyde and proanthocyanidins were reported to be mainly responsible for biological activities displayed by most of the plants. Plants of Cinnamomum genus possess a wide spread of biological activities validating their use in traditional medicine. However, most of the available references lack information on active constituents, doses, duration of the treatment, storage conditions and positive controls for examining biological activities. The molecular mechanisms involved in eliciting biological activities were not comprehensively elucidated. Investigations to prove the safe use of these plants in traditional medicine are very limited. Thus, more studies on identification of bioactive constituents and their molecular mechanisms are needed. In addition, given that various species of Cinnamomum are being widely used in traditional medicine and culinary purposes, their main therapeutic aspects, toxicity, and adverse effects warrant further investigation in the future.

Keywords: Cinnamomum, Biological activities, Ethnomedicinal uses, Bioactive constituents

© 2017 The Authors. Published by Innovare Academic Sciences Pvt Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4. 0/)
DOI: http://dx.doi.org/10.22159/ijpps.2017v9i2.11156

INTRODUCTION

In rural areas of the developing countries all over the world, plants have been used in the treatment of numerous human diseases for thousands of years and are the primary source of medicine [1]. The secondary metabolites produced by plants has been proven to possess various biological activities and was templates for the development of novel drugs.

There are a number of scientific reports on the use of medicinal plants and their secondary metabolites for the treatment of a wide array of diseases. Few natural products from plants have been recorded in pharmacopoeias. Cinnamomum is one such genus which has been extensively used for the treatment of wide-array of disorders in various traditional systems of medicine including western herbal medicine.

Apart from the wide array of medicinal uses of the genus Cinnamomum, the inner barks of the many species, commonly known as cinnamon, is used as a spice for cooking purposes across the world. In Ayurvedic medicine [2], cinnamon is being used for the common cold, cough, diabetes, fever, flatulence, indigestion, sinusitis and sore throat. Also it is a component of, herbal toothpaste to reduce the incidence of dental caries; chair a spiced black tea beverage consumed widely in India and in Yogi Bhajan's "Yogi Tea", used as a general tonic tea for a varied range of symptoms including digestive disorders, blood purification, and immunostimulation and as an antiparasitic. Ayurvedic physicians prescribe cinnamon for people with a "kapha dosha," an Ayurvedic term used to define a body type described by cold, heavy, slow functioning and wet.

Cinnamon is being prescribed in traditional Chinese medicine (TCM) for cold, diarrhoea, asthma, as an appetiser; to strengthen the uterus and increase fertility in women [2].

In Europe [2], cinnamon is used as a warming herb for the treatment of ailments associated with "cold". Cinnamon bark is approved by German health authorities (Commission E) for its use as an antispasmodic for mild gastrointestinal spasms, an appetiser, and for digestive disorders such as indigestion, bloating and gas.

In western herbal medicine [2], herbalists prescribe cinnamon for diabetes, diarrhoea, indigestion, nausea, toothache, and vomiting. Cinnamon oil is added in a few kinds of toothpaste for its antimicrobial properties and its capacity to reduce halitosis. The major constituent of cinnamon oil is eugenol which is still being widely used as a local anaesthetic and antibacterial agent in dental practice.

To the best of our knowledge, only two review articles focusing on a particular species of genus cinnmaomum were published in the literature. One article [3] reviewed the ethnobotanical uses of cinnamomum species available in Tamilnadu, India. Another article [4] reviewed the phytoconstituents, ethnobotanical and pharmacological uses of Cinnamomum zeylanicum. With the objective of providing an eagle’s eye view on scientific literature available on biological activities of genus Cinnamomum and for the benefit of those who are interested in Natural Products research we herewith made an attempt to review the entire available literature on biological activities of Cinnamomum genus.

In this review article, the scientifically proven biological activities of all the species from the genus Cinnamomum were reported. Literature searches were performed using a keyword ‘cinnamomum’ in the databases; PubMed, Scopus, and Google Scholar (all from inception to August 2016). All the biological studies including ex vivo, in vitro and in vivo studies related to the species of the genus Cinnamomum published in the English language were included.

Biological activities of Cinnamomum species

Species Parts Extracts/Chemical constituents Biological activities References
1.C. Osmo phloem Leaf Essential oil Antifungal [5, 6]
Antidiabetic [7]
Insecticidal [8-10]
Antitermitic [11]
Larvicidal [12, 13]
xanthine oxidase (XOD) inhibitory andanti-hyperuricemic [14]
Treatment of renal interstitial fibroblasts. [15]
Anti-inflammatory [16-19]
Antibacterial [20-22]
Apoptosis in cancer cells. [23]
Affects insulin signalling pathway  [24]
Anxiolytic [25]
Antioxidant [26]
Ethanol extract Tyrosinase inhibitory activity [27]
Water extract Antioxidant wound healing [27]
Twig Essential oil Antioxidant [28]
Water Extract Antihyperglycemic and antioxidant [29]
2.C. camphora leaf Water extract Antimicrobial [30, 31]
Essential oil Acaricidal [32]
Twig Essential oil Anti-inflammatory [33, 34]
Methanol extract Antioxidant [35]
Bark Essential oil Anti-inflammatory [36]
Anticancer [36]
Cytotoxic [37]
Molluscicidal [38]
Antigenotoxic [39]
Hot water extract and essential oil Antimicrobial [40-42]
Repellant and insecticidal [43]
Medium chain acyl-ACP hydrolysis activity [44]
Seed Essential oil Insecticidal [45]
Antioxidant, Anti-inflammatory [46]
3.C. burmannii Leaf Water extractMethanol extract Antioxidant [47]
Antidiabetic [48-50]
Bark Cytotoxic [51]
Inhibition of cytochrome P450 3A4 (CYP3A4) and CYP2D6 [52]
Antibacterial [53]
4.C. zeylanicum Leaf Essential oil Acaricidal [54]
Ameliorative [55]
Antifungal [56-59]
Antioxidant and Antimicrobial [60-64]
Antioxidant [65, 66]
Bark Unknown Spermatogenesis [67]
Essential oil Ovicidal and adulticidal [68]
Antimicrobial [69, 70]
Insecticidal [71-73]
Water extract Cognitive impairment and oxidative stress [74, 75]
Ethanol extractEssential oilChloroform extractWater extract Increase sexuality [76]
Antiasthmatic [77, 78]
Analgesic [79]
Gastroprotective [80]
Insect repellent [81]
Antibacterial and antifungal [82, 83]
Antioxidant [84-86]
Anti-nociceptive and Anti-inflammatory [87, 88]
Antidiabetic [89-93]
Mutagenic [94, 95]
Osteoclastogenesis [96]
Antioxidant and antimutagenic [97]
5.C. parthenoxylon Bark Water extract Hypoglycemic [98]
Wood Hinokenin, Cubebin Antileukaemic [99]
6.C. kanehira Leaf Methanol extract Antioxidant [33, 35]
Ethanol extract Anticancer [100]
Water extract Anti-inflammatory [34]
Twig Essential oil Antibacterial [101]
7.C. cassia Unknown Volatile oil, Cinnamaldehyde Anticancer [102]
Coumarins Anticancer [103]
Leaf Water extract Antioxidant [47, 104-106]
Antimutagenic [107, 108]
Angiogenesis [109]
Ethanol,Water extractEssential oil Antimicrobial [110-117]
Antifungal [118, 119]
Hypouricemic [120]
Stem bark Hexane extract Anticancer [121]
Essential oilHot water extractEthanol extractMethanol extract Immunomodulatory [122, 123]
Anticancer [124]
Antiviral [125]
Antiproliferative [126, 127]
Antioxidant [128-130]
Antiulcerogenic [131]
Antidiabetic [90, 132-138]
Antihyperglycemic and Antihyperlipidemic [139]
Antitumor [140-142]
Antiallergic [143-146]
Anti-inflammatory [147-152]
Antipyretic [153]
Inhibitory activity on nitric oxide production and metalloproteinases-2 and-9 (MMP-2/9] [154, 155]
Stimulation of steroid hormones [156]
Diabetic nephropathy [157]
Insecticidal and larvicidal [68, 158, 159]
Diterpenoids Immunosuppressant activity [160]
Lignans, tetrahydrofuran derivatives, gamma-butyrolactone Anti-inflammatory [161]
Proanthocyanidin oligomers Antihyperglycaemic [162]
Immunosuppressive effect [163]
Shoot Essential oil Antibacterial [164, 165]
Antiestrogenic [166, 167]
Plant Water extractMethanol extractEssential oil Anxiolytic [168, 169]
Stimulates angiogenesis [170, 171]
Xanthine oxidase inhibitor [172-174]
Antiprotozoal [175]
Twig Methanol extract Xanthine oxidase inhibitor [176]
8.C. pauciflorum Leaf Water extract Antioxidant [65]
9.C. tamala Leaf Water extractEssential oilEthanol extract Antioxidant [65]
Gastroprotective [177]
Antidiarrhoeal [178]
Hypoglyceamic [179]
10.C. carolinense Bark Hot water extract Medicinal tea and hot beverage [180]
11.C. philippinense Root Water extractEssential oil Antioxidant, Antiplatelet aggregation and Vasorelaxant [181]
Thromboxane A2 receptor antagonist [182]
12.C. insularimontanum Fruit Essential oil Anti-inflammatory [183]
Leaf Methanol extract Cytotoxic [184]
13.C. verum Unknown Essential oil Antiparasitic [185]
Unknown Unknown extract Inhibition of amyloid fibril formation [186]
Leaf Methanol extractWater extractEssential oil Antioxidant [187-189]
Antimicrobial [61, 110, 190-193]
Ethanol and aqueous extracts Antioxidant, Analgesic [194]
Essential oil Insecticidal [195-197]
Cortex Water extract Bening prostatic hyperplasia [198]
2-Methoxycinnamaldehyde Anticancer [199-203]
Bark Essential oil Antioxidant [188, 204-206]
Cuminaldedhyde Anticancer [207-209]
Water extract Anthelmintic [210]
14.C. loureirii  Unknown Extract Acetylcholinesterase activity [211]
15.C. micranthum Fruit Water extract Anti-inflammatory [34]]
16.C. ketoense Leaf Methanol extract Antiproliferative [212]
Induces caspase-dependent and-independent apoptosis in Hep G2 cells [213]
Anticancer [212, 214, 215]
Stem wood Hot water extract Antitubercular [216]
17.C. longepaniculatum Leaf Volatile oil Anti-inflammatory [217]
Antibacterial [218]
Antihepatoma [219]
18.C. japonicum Bark Procyanidin oligomer-rich extract Hypoglycemic [136]
19.C. pubescens Leaf Methanol extract Platelet-activating factor (PAF) receptor-binding antagonist activity [220]
20.C. altissimum Leaf Methanol extract PAF receptor-binding antagonist activity [220]
21.C. bejolghota Leaf Essential oil Antimicrobial [221]
22.C. griffithii Leaf/twig/root Methanol extract Antiplasmodial [222]
Leaf/Bark Essential oil Antioxidant, Anticholinesterase [223]
23.C. loureirii Leaf Methanol extract Anti-inflammatory [173]
bark
24.C. massoiae Plant Alcohol extract Antihistaminic [224]
25.C. mairei Plant Boiling water extract Mutagenic [225]
26.C. aromaticum Herbs Methylene chloride extract Insecticidal [226]
Water extract Immunotherapy for respiratory allergy [227]
27.C. migao Leaf Essential oil the relaxation effect on smooth muscles [228]
28.C. longa Plant Acetone extract Antioxidant [229]
29.C. rhizome Plant Acetone extract Antioxidant [229]
30.C. laubatii Fruit Spiroacetals Anticancer [230]
31.C. bodineiri Leaf Subamolide A Antioxidant [231]
32.C. impressinervium Water extract Antidiabetic [232]
33.C. glaucescens Essential oil Insecticidal, antifungal, anti aflatoxin and antioxidant [233]
34.C. subaveniu Stem Subamolide A Cytotoxic [231]
35.C. jensenianum Bark Essential oil Antifungal [234]
36.C. iners Stembark Volatile oil Antibacterial [235]
37.C. impressicostatum Stembark Volatile oil Antibacterial [235]
38.C. porrectum Stembark Volatile oil Antibacterial [235]
39.C. altissimum Stembark Water extract Antibacterial [235]
40C. mollissimum Stembark Aporphine alkaloids Antioxidant, Antibacterial [236]

DISCUSSION

The genus Cinnamomum has been used in various traditional systems of medicine including Indian and traditional Chinese systems of medicine to treat a multitude of disorders, like indigestion, cold, cough, microbial infections. Only 40 out of the approximate 300 Cinnamomum species have been studied in some detail. The leaves and stem barks have been reported to be the main source for biological activities displayed by Cinnamomum species. One of the most widely investigated constituents of Cinnamomum species is essential oil and reported to exhibit a wide array biological activities including antibacterial, antifungal, antioxidant, antidiabetic, antitermitic, anticancer, anticholinesterase, larvicidal, hypouricemic, immunemodulatory and xanthine oxidase inhibitory activities. Very recently, few attempts are being made to isolate the bioactive constituents and to identify the molecular mechanisms. Adfa, M. et al. [99] reported lignans and phenylpropanoids isolated from C. parthenoxylon possess antileukemic activity mediated through apoptosis in human leukaemia HL-60 and U-937 cells. Chang, W. L. et al. [102] reported cinnamaldehyde, a major constituent of Cinnamomum essential oils, exhibit anticancer activity in human oral squamous cell carcinoma HSC-3 cells mediated through apoptosis, induced mitochondrial dysfunction, increased reactive oxygen species (ROS) production and antioxidant actions. Chen, L. et al. [163] reported procyanidin oligomer compounds, cinnamtannin B1, cinnamtannin D1, para meri tannin A1, procyanidin B2 and procyanidin C1 from C. tamla or C. cassia display immune-suppressive effects mediated through significant reduction of IFN-γ and IL-2 in LPS induced splenocytes proliferation model. Chen, T. W. et al. [207] and Yang, S. M. et al. [209] reported cumin aldehyde, a novel anticancer agent, isolated from C. verum exhibited significant anticancer activity in human lung adenocarcinoma A549 cells and human lung squamous cell carcinoma NCI-H520 cells accompanied by down regulations of proliferative control involving apoptosis, both topoisomerase I and II as well as telomerase activities, together with an upregulation of lysosomal vacuolation with increased volumes of acidic compartments. Tsai K. D. et al. [208] reported cumin aldehyde possess anticancer activity in human colorectal adenocarcinoma COLO 205 cells through downregulation of topoisomerases 1 and II. Cheng, B. H. et al. [25] reported linalool from C. osmophloeum essential oil has significant anxiolytic activity in mice model whose action is mediated through a decrease in the mice brain levels of serotonin, dopamine and norepinephrine. He, S. et al. [161] reported six new compounds including one γ-butyrolactone, cinncassin A, two tetrahydrofuran derivatives, cinncassins B and C, two lignans, cinncassins D and E, and one phenyl propanol glucoside, cinnacassoside D possessing anti-inflammatory activity in LPS induced inflammation in BV-2 microglial cells. Kang, B. H. et al. [162] reported proanthocyanidins from C. cassia do exhibit anti-hyperglycemic activity via carbohydrate hydrolyzing enzyme inhibition. Kim, C. R. et al. [211] reported 2, 4-bis (1,1-dimethylethyl) phenol inhibited acetyl cholinesterase activity and ameliorates trimethyl tin-induced cognitive dysfunction in mice. Lee, S. C. et al. [19] reported essential oil from C. osmophloeum kanehira protected endotoxin-induced intestinal injury in mice associated with suppression of toll-like receptor 4(TLR4) and Nod-like receptor family, pyrin domain containing 3 (NLRP3) signalling pathways. Li, L. et al. [218] reported γ-terpinene, α-terpineol, 1,8-cineole isolated from C. longepaniculatum leaf essential oil displayed significant antibacterial activity against Staphylococcus aureus, Escherichia coli and Salmonella enteritidis. Liu, Y. H. et al. [199].

Perng, D. S. et al. [200, 201], Tsai K. D. et al. [202] and Wong Y. H. et al. [203] reported 2-methoxycinnamaldehyde exhibited anticancer activity in human lung squamous cell carcinoma NCI-H520 cells, hepatocellular carcinoma Hep 3B cells, human colorectal adenocarcinoma COLO 205 cells and human lung adenocarcinoma A549 cells through targeting topoisomerase I and II. Manson, F. F. et al. [236] reported five aporphine alkaloids; N-methyl-1,2,10-trimethoxyaprophine, N-methylhernagine, N-methylhemovine, hernagine and hernovine; showed significant antibacterial and antioxidant activities. Ngoc, T. M. et al. [103] reported a new coumarin derivative, coumacasia possessing significant growth inhibitory effects in two human cancer cell lines, HL-60 and A-549. Song, X. et al. [219] reported safrole from C. longepaniculatum exhibited anti-hepatoma effect mediated through apoptosis. Williams A. R. et al. [210] reported trans-cinnamaldehyde and A-and B-type proanthocyanidins obtained from C. verum exhibited anthelmintic activity. Yan Y. M. et al. [157] reported sesquiterpenoids may be responsible for anti-diabetic nephropathy displayed by C. cassia bark. Yang, F. et al. [38] reported linalool obtained from C. camphora leaf extracts exhibited molluscicidal activity against Oncomelania hupensis and inhibits infection of schistosoma japonicum. Zeng, J. et al. [160] reported diterpenoids isolated from C. aromaticum possess immunosuppressive effect.

CONCLUSION

In this review, we summarised the existing studies on the biological activities of Cinnamomum genus. Only 40 out of available 300 Cinnamomum species were scientifically investigated for biological activities which implies that there is a huge potential for researchers to explore further the potential biological activities of Cinnamomum species because majority of the species have been used for various purposes in different traditional systems of medicine and as a food ingredient all over the world for a quite long time. C. verum, C. cassia, C. zeylanicum, C. camphora and C. osmophloeum are the only five species that have been somewhat thoroughly investigated in the identification of potential biological activities, bioactive constituents and molecular mechanisms. Also, the majority of the studies have been concentrated on essential oil and aqueous/alcohol extracts of leaves and stem barks with the main focus on validating the uses of Cinnamomum in various traditional systems of medicine. Detailed studies were performed only on two bioactive compounds namely 2-methoxycinnamaldehyde and cumin aldehyde for their anticancer activity in various human cancer cells. Based on the published results in the literature, these two compounds have exhibited promising effects and could be good leads in anticancer drug discovery. However, further studies have to be carried out to assess the bioavailability, toxicity, drug-like properties, in vivo efficacy and molecular targets. Also, there is an opportunity for the medicinal chemists to look at structure-activity relationship studies on these two compounds.

CONFLICTS OF INTERESTS

Declared none

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