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Calamus

Scientific Name(s): Acorus calamus L.
Common Name(s): Calamus, Calamus oil, Rat root, Shi chang pu, Sweet flag, Sweet myrtle, Sweet root, Sweet sedge, Vash vaj

Clinical Overview

Use

Clinical studies are lacking due to concerns of toxicity. Antioxidant, anti-inflammatory, and cardiovascular effects have been described, as well as activities in epilepsy, diabetes, and cancer. However, because of toxicity and lack of clinical trials, no recommendations for use can be made. Use of calamus and its extracts is prohibited in the US.

Dosing

Use of calamus and its extracts is prohibited in the US. Clinical studies that provide information on therapeutic dosages are lacking.

Contraindications

Contraindications have not yet been identified.

Pregnancy/Lactation

Avoid use. Adverse effects (emmenagogue and genotoxic activity) have been documented.

Interactions

None well documented.

Adverse Reactions

Clinical studies are lacking due to concerns of toxicity.

Toxicology

Case reports of toxicity describe nausea and prolonged vomiting (up to 15 hours) and tachycardia. Mutagenicity attributed to various extracts and chemical constituents has been reported.

Scientific Family

  • Araceae (Calamus)

Botany

Calamus is a semi-evergreen, perennial, hairless herb found in damp, swampy areas. It has bright-green sword-shaped leaves with a waxy margin that thicken in the middle. The plant is similar in appearance to the iris and grows to approximately 2 meters tall, with hermaphroditic flowers that are pollinated by insects. The creeping rhizome is pale yellow to pinkish brown on the outside and white to pinkish on the inside. It is native to much of Asia and is also found throughout North America and eastern Europe.1, 2, 3 Synonyms include A. calamus L. var. americanus (Raf.) H.D. Wulff. and Acorus americanus (Raf.) Raf.

History

The fragrant underground portion (the rhizome) has been used medicinally since biblical times. Popular European books on medicinal plants touted calamus as a "wonder drug." However, because of an association between asarones and the development of tumors in animals, the use of calamus and its extracts is prohibited in the US. Maximum limits for beta-asarone content in food and beverages have been set by the European Commission.2, 3, 4, 5 It has been used in traditional medicine for the treatment of digestive disorders and childhood colic. Infusions of the rhizome have been suggested for the treatment of fever, and chewing the rhizome has been said to relieve irritated throats and to remove the odor of tobacco. It is central to the Ayurvedic medical system as an aromatic, stimulant, bitter tonic, and expectorant and has been used as an emmenagogue. The A. calamus used in Ayurvedic medicine has undergone "sodhana," a process of detoxification. It has been used by Native Americans to soothe toothache and headache. Calamus has been promoted on the Internet as a hallucinogen.

The ground rhizome is used as a spice and commercial flavoring in drinks, cosmetics, and toothpastes.

Chemistry

Calamus leaves and rhizomes contain 1.5% to 3.5% of a volatile oil responsible for the plant's characteristic odor and taste. From some types of calamus, a major component of the oil (up to 75%) is beta-asarone. Alpha-asarone has also been identified and exists in both the cis- and trans-isomer forms.6 More than a dozen additional compounds have been identified in the oil and extracts, including saponins, lectins, sesquiterpenoids, lignans, and steroids. Hydrocarbons, carbonyl compounds, alcohols, phenols, furans, and other compounds have also been described. Ethanolic extracts and acetone, hydroalcoholic, and methanolic extracts have been studied and high-pressure liquid chromatography methods for determining asarone content have been published.3, 5, 7, 8, 9

The chemical composition of the plant varies according to geographic location, plant age, climate, species variety, and plant part used.3, 10 The diploid plant grows in North America and is beta-asarone free. The European triploid plant is different chemotype of calamus, with oil containing less than 10% asarone. Indian tetraploid varieties, however, have been found to contain oils that are composed of 96% asarone or less.6

Uses and Pharmacology

Clinical studies are lacking due to concerns of toxicity. (See Toxicology.)

Allergic reactions

Animal data

Down-regulation of immunoglobulin G and immunoglobulin E has been demonstrated in vitro.11 Prevention of mast cell degranulation has been shown in mice,12 and an antihistamine effect was shown in isolated guinea pig tissue.13

Clinical data

Research reveals no clinical data regarding the use of calamus in allergic reactions.

Anti-inflammatory effects

Animal data

In animal and in vitro studies, the immunomodulation and anti-inflammatory action of A. calamus extracts was attributed to observed neuroprotective, analgesic, and wound-healing properties. Interference with cytokines (interleukins and tumor necrosis factor-alpha) and immunoglobulins has been demonstrated.14, 15, 16, 17, 18, 19

Clinical data

There are no clinical data regarding the use of calamus for anti-inflammatory effect.

Antimicrobial effects

Animal data

Leaf and rhizome extracts as well as calamus oil have shown antibacterial activity against some human pathogens, including weak activity against Neisseria gonorrhoeae. Older studies report antiviral activity. Antifungal activity against both human and plant pathogens has been demonstrated in vitro.3, 7, 20, 21, 22 Activity against the larvae of insects has been demonstrated in vitro and in animals such as cattle.3, 23, 24, 25

Clinical data

There are no clinical data regarding the antimicrobial activity of calamus.

Cancer

Animal data

Antioxidant activity of A. calamus has been described and may be responsible for observed effects in cancer cell lines. Protection against irradiation-induced DNA strand breaks and chemotherapy-induced hepatotoxicity and nephrotoxicity has been attributed to antioxidant activity.26, 27, 28, 29, 30, 31 Induced senescence in colorectal cancer cells and upregulation of capases have also been described as mechanisms by which the extracts may decrease proliferation and induce apoptosis in cancer cells.32, 33 Activity has been attributed to beta-asarone, sesquiterpenoids, and the lectin content of the plant.3, 9, 34

Clinical data

There are no clinical data regarding the use of calamus in cancer. Both alpha- and beta-asarone have been shown to be mutagenic themselves.3

Cardiovascular effects

Animal data

Extracts of A. calamus show antagonism of the calcium channel and effects on the nitric oxide pathway. Depending on the extraction method and fractions used, vasodilation and constriction and partial depressant effects on coronary flow and heart rate have been demonstrated in rats and in isolated heart studies.35, 36

Clinical data

There are no clinical data regarding the use of calamus in cardiovascular disease.

CNS effects

Animal data

Anticholinesterase activity has been demonstrated in vitro and in animal studies, which may have implications for the management of Alzheimer disease.13, 37 Beta-asarone and extracts of A. calamus exerted antidepressant effects and improved cognitive function in rats with induced stress-related depression.38, 39, 40, 41 Older studies and traditional uses suggest a sedatory effect.3

Clinical data

There are no clinical data regarding the use of calamus in CNS disorders or to support the occurrence of a hallucinogenic effect.

Diabetes

Animal data

A limited amount of research has described the hypoglycemic effects of different fractions of A. calamus extracts. Decreases in blood glucose, inhibition of alpha-glucosidase activity, and enhanced adipocyte differentiation have all been demonstrated in vitro and in animal studies. Beta-asarone, however, has also been shown to exert an inhibitory effect on adipogenesis.3, 42, 43, 44

Clinical data

There are no clinical data regarding the use of calamus in diabetes.

Epilepsy

Animal data

Limited studies in rats have shown that extracts of A. calamus, especially alpha-asarone and purified rhizome extracts, exert an anticonvulsant effect on induced seizures. Possible sites of action are the gamma-aminobutyric acid receptors and sodium channel.31, 45, 46, 47, 48

Clinical data

There are no clinical data regarding the use of calamus in epilepsy.

Other uses

In studies with isolated guinea pig trachea and atria, a crude extract of A. calamus demonstrated a dual inhibition of calcium channels and phosphodiesterase, suggesting a pharmacological basis for its use in disorders of airways in traditional medicine.49 Results of a study in isolated rabbit jejunum suggested that the spasmolytic effect of an extract of A. calamus is mediated through the presence of calcium channel blockade–like constituent(s) concentrated in the n-hexane fraction, providing a strong mechanistic base for its traditional use in GI disorders.50

Dosing

Use of calamus and its extracts is prohibited in the US. Clinical studies that provide information on therapeutic dosages are lacking. Storage of the root leads to a loss in potency.

Pregnancy / Lactation

Avoid use. Adverse effects (emmenagogue and genotoxic activity) have been documented.3, 51

Interactions

Case reports are lacking. Potentiation of calcium channel blockers (eg, amlodipine) and medicines used in epilepsy is possible based on studies in rodents.44, 52 Alpha-asarone and A. calamus extracts may also interfere with the cytochrome P450 enzyme system.53

Adverse Reactions

Clinical studies are lacking. (See Toxicology). Cardiovascular effects, such as hypotension, are possible based on animal studies.

Toxicology

The Swedish Poisons Information Centre reported 30 cases of acute intoxication related to A. calamus abuse from 2003 through 2006 that involved nausea and prolonged vomiting (up to 15 hours) as well as tachycardia.4 Acute toxicity tests in mice showed piloerection, decreased mobility, increasing respiratory distress, unconsciousness, and death. Long-term toxicity studies report the development of tumors and thrombosis in rat heart chambers. The median lethal dose in mice was reported to be 417 mg/kg (oral) to 900 mg/kg.14

The primary toxicological concern focuses on the carcinogenic effects of asarone. Both alpha- and beta-asarone showed mutagenicity in most studies.3

Feeding studies conducted from the late 1960’s provided evidence of the mutagenic potential of this compound.2, 3, 6

Index Terms

  • Acorus americanus (Raf.) Raf
  • Araceae calamus L. var. americanus (Raf.) H.D. Wulff

References

1. USDA, NRCS. 2014. The PLANTS Database (http://plants.usda.gov, 29 May 2014). National Plant Data Center, Baton Rouge, LA 70874-4490 USA.
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3. Rajput SB, Tonge MB, Karuppayil SM. An overview on traditional uses and pharmacological profile of Acorus calamus Linn. (sweet flag) and other Acorus species. Phytomedicine. 2014;21(3):268-276.24200497
4. Björnstad K, Helander A, Hultén P, Beck O. Bioanalytical investigation of asarone in connection with Acorus calamus oil intoxications. J Anal Toxicol. 2009;33(9):604-609.20040135
5. Widmer V, Schibli A, Reich E. Quantitative determination of beta-asarone in calamus by high-performance thin-layer chromatography. J AOAC Int. 2005;88(5):1562-1567.16386010
6. Gholkar MS, Mulik MB, Laddha KS. Fate of β-asarone in Ayurvedic sodhana process of vacha. J Ayurveda Integr Med. 2013;4(1):19-22.23741157
7. Kim WJ, Hwang KH, Park DG, et al. Major constituents and antimicrobial activity of Korean herb Acorus calamus. Nat Prod Res. 2011;25(13):1278-1281.21707379
8. Du Z, Clery RA, Hammond CJ. Volatiles from leaves and rhizomes of fragrant Acorus spp. (Acoraceae). Chem Biodivers. 2008;5(6):887-895.18618386
9. Hao ZY, Liang D, Luo H, et al. Bioactive sesquiterpenoids from the rhizomes of Acorus calamus. J Nat Prod. 2012;75(6):1083-1089.22671987
10. Kumari R, Singh S, Agrawal SB. Response of ultraviolet-B induced antioxidant defense system in a medicinal plant, Acorus calamus. J Environ Biol. 2010;31(6):907-911.21506474
11. Shi GB, Wang B, Wu Q, et al. Evaluation of the wound-healing activity and anti-inflammatory activity of aqueous extracts from Acorus calamus L. Pak J Pharm Sci. 2014;27(1):91-95.24374458
12. Kim DY, Lee SH, Kim WJ, et al. Inhibitory effects of Acorus calamus extracts on mast cell-dependent anaphylactic reactions using mast cell and mouse model. J Ethnopharmacol. 2012;141(1):526-529.22366435
13. Vijayapandi P, Annabathina V, SivaNagaSrikanth B, et al. In vitro anticholinergic and antihistaminic activities of Acorus calamus Linn. leaves extracts. Afr J Tradit Complement Altern Med. 2012;10(1):95-101.24082330
14. Khan MA, Islam MT. Analgesic and cytotoxic activity of Acorus calamus L., Kigelia pinnata L., Mangifera indica L. and Tabernaemontana divaricata L. J Pharm Bioallied Sci. 2012;4(2):149-154.22557926
15. Belska NV, Guriev AM, Danilets MG, et al. Water-soluble polysaccharide obtained from Acorus calamus L. classically activates macrophages and stimulates Th1 response. Int Immunopharmacol. 2010;10(8):933-942.20483383
16. Kim H, Han TH, Lee SG. Anti-inflammatory activity of a water extract of Acorus calamus L. leaves on keratinocyte HaCaT cells. J Ethnopharmacol. 2009;122(1):149-156.19146941
17. Muthuraman A, Singh N. Neuroprotective effect of saponin rich extract of Acorus calamus L. in rat model of chronic constriction injury (CCI) of sciatic nerve-induced neuropathic pain. J Ethnopharmacol. 2012;142(3):723-731.22706151
18. Muthuraman A, Singh N, Jaggi AS. Protective effect of Acorus calamus L. in rat model of vincristine induced painful neuropathy: an evidence of anti-inflammatory and anti-oxidative activity. Food Chem Toxicol. 2011;49(10):2557-2563.21756962
19. Jain N, Jain R, Jain A, Jain DK, Chandel HS. Evaluation of wound-healing activity of Acorus calamus Linn. Nat Prod Res. 2010;24(6):534-541.20182947
20. Cybulska P, Thakur SD, Foster BC, et al. Extracts of Canadian first nations medicinal plants, used as natural products, inhibit Neisseria gonorrhoeae isolates with different antibiotic resistance profiles. Sex Transm Dis. 2011;38(7):667-671.21301385
21. Ghosh M. Antifungal properties of haem peroxidase from Acorus calamus. Ann Bot. 2006;98(6):1145-1153.17056613
22. Rajput SB, Karuppayil SM. β-asarone, an active principle of Acorus calamus rhizome, inhibits morphogenesis, biofilm formation and ergosterol biosynthesis in Candida albicans. Phytomedicine. 2013;20(2):139-142.23123225
23. Liu XC, Zhou LG, Liu ZL, Du SS. Identification of insecticidal constituents of the essential oil of Acorus calamus rhizomes against Liposcelis bostrychophila Badonnel. Molecules. 2013;18(5):5684-5696.23676474
24. Ghosh S, Sharma AK, Kumar S, et al. In vitro and in vivo efficacy of Acorus calamus extract against Rhipicephalus (Boophilus) microplus. Parasitol Res. 2011;108(2):361-370.20886235
25. Sharma PR, Sharma OP, Saxena BP. Effect of sweet flag rhizome oil (Acorus calamus) on hemogram and ultrastructure of hemocytes of the tobacco armyworm, Spodoptera litura (Lepidoptera: Noctuidae). Micron. 2008;39(5):544-551.17826115
26. Sandeep D, Nair CK. Protection of DNA and membrane from γ-radiation induced damage by the extract of Acorus calamus Linn.: an in vitro study. Environ Toxicol Pharmacol. 2010;29(3):302-307.21787617
27. Sandeep D, Nair CK. Protection from lethal and sub-lethal whole body exposures of mice to gamma-radiation by A. calamus L.: Studies on tissue antioxidant status and cellular DNA damage. Exp Toxicol Pathol. 2012;64(1-2):57-64.20605086
28. Sandeep D, Krishnan Nair CK. Amelioration of cisplatin-induced nephrotoxicity by extracts of Hemidesmus indicus and Acorus calamus. Pharm Biol. 2010;48(3):290-295.20645815
29. Kumari R, Agrawal SB, Singh S, Dubey NK. Supplemental ultraviolet-B induced changes in essential oil composition and total phenolics of Acorus calamus L. (sweet flag). Ecotoxicol Environ Saf. 2009;72(7):2013-2019.19321203
30. Ilaiyaraja N, Khanum F. Amelioration of alcohol-induced hepatotoxicity and oxidative stress in rats by Acorus calamus. J Diet Suppl. 2011;8(4):331-345.22432772
31. Hazra R, Ray K, Guha D. Inhibitory role of Acorus calamus in ferric chloride-induced epileptogenesis in rat. Hum Exp Toxicol. 2007;26(12):947-953.18375638
32. Liu L, Wang J, Shi L, et al. β-asarone induces senescence in colorectal cancer cells by inducing lamin B1 expression. Phytomedicine. 2013;20(6):512-520.23357361
33. Zou X, Liu SL, Zhou JY, Wu J, Ling BF, Wang RP. Beta-asarone induces LoVo colon cancer cell apoptosis by up-regulation of caspases through a mitochondrial pathway in vitro and in vivo. Asian Pac J Cancer Prev. 2012;13(10):5291-5298.23244151
34. Bains JS, Dhuna V, Singh J, Kamboj SS, Nijjar KK, Agrewala JN. Novel lectins from rhizomes of two Acorus species with mitogenic activity and inhibitory potential towards murine cancer cell lines. Int Immunopharmacol. 2005;5(9):1470-1478.15953573
35. Shah AJ, Gilani AH. Aqueous-methanolic extract of sweet flag (Acorus calamus) possesses cardiac depressant and endothelial-derived hyperpolarizing factor-mediated coronary vasodilator effects. J Nat Med. 2012;66(1):119-126.21826570
36. Shah AJ, Gilani AH. Blood pressure-lowering and vascular modulator effects of Acorus calamus extract are mediated through multiple pathways. J Cardiovasc Pharmacol. 2009;54(1):38-46.19528816
37. Oh MH, Houghton PJ, Whang WK, Cho JH. Screening of Korean herbal medicines used to improve cognitive function for anti-cholinesterase activity. Phytomedicine. 2004;11(6):544-548.15500267
38. Dong W, Li M, Yang D, Lu R. Two new sesquiterpenes from Acorus calamus. Planta Med. 2010;76(15):1742-1745.20419623
39. Geng Y, Li C, Liu J, et al. Beta-asarone improves cognitive function by suppressing neuronal apoptosis in the beta-amyloid hippocampus injection rats. Biol Pharm Bull. 2010;33(5):836-843.20460763
40. Tripathi AK, Singh RH. Experimental evaluation of antidepressant effect of vacha (Acorus calamus) in animal models of depression. Ayu. 2010;31(2):153-158.22131703
41. Sundaramahalingam M, Ramasundaram S, Rathinasamy SD, Natarajan RP, Somasundaram T. Role of Acorus calamus and alpha-asarone on hippocampal dependent memory in noise stress exposed rats. Pak J Biol Sci. 2013;16(16):770-778.24498829
42. Si MM, Lou JS, Zhou CX, et al. Insulin releasing and alpha-glucosidase inhibitory activity of ethyl acetate fraction of Acorus calamus in vitro and in vivo. J Ethnopharmacol. 2010;128(1):154-159.20051258
43. Wu HS, Li YY, Weng LJ, Zhou CX, He QJ, Lou YJ. A fraction of Acorus calamus L. extract devoid of beta-asarone enhances adipocyte differentiation in 3T3-L1 cells. Phytother Res. 2007;21(6):562-564.17335118
44. Wu HS, Zhu DF, Zhou CX, et al. Insulin sensitizing activity of ethyl acetate fraction of Acorus calamus L. in vitro and in vivo. J Ethnopharmacol. 2009;123(2):288-292.19429374
44. Zaugg J, Eickmeier E, Ebrahimi SN, Baburin I, Hering S, Hamburger M. Positive GABA(A) receptor modulators from Acorus calamus and structural analysis of (+)-dioxosarcoguaiacol by 1D and 2D NMR and molecular modeling. J Nat Prod. 2011;74(6):1437-1443.21563811
46. Wang ZJ, Levinson SR, Sun L, Heinbockel T. Identification of both GABAA receptors and voltage-activated Na(+) channels as molecular targets of anticonvulsant α-asarone. Front Pharmacol. 2014;5:40.24653701
47. Katyal J, Sarangal V, Gupta YK. Interaction of hydroalcoholic extract of Acorus calamus Linn. with sodium valproate and carbamazepine. Indian J Exp Biol. 2012;50(1):51-55.22279941
48. Bhat SD, Ashok BK, Acharya RN, Ravishankar B. Anticonvulsant activity of raw and classically processed vacha (Acorus calamus Linn.) rhizomes. Ayu. 2012;33(1):119-122.23049196
49. Shah AJ, Gilani AH. Bronchodilatory effect of Acorus calamus (Linn.) is mediated through multiple pathways. J Ethnopharmacol. 2010;131(2):471-477.19528816
50. Gilani AU, Shah AJ, Ahmad M, Shaheen F. Antispasmodic effect of Acorus calamus Linn. is mediated through calcium channel blockade. Phytother Res. 2006;20(12):1080-1084.17009206
51. Ernst E. Herbal medicinal products during pregnancy: are they safe? BJOG. 2002;109(3):227-235.11950176
52. Singh BK, Pillai KK, Kohli K, Haque SE. Isoproterenol-induced cardiomyopathy in rats: influence of Acorus calamus Linn.: A. calamus attenuates cardiomyopathy. Cardiovasc Toxicol. 2011;11(3):263-271.21695526
53. Pandit S, Mukherjee PK, Ponnusankar S, Venkatesh M, Srikanth N. Metabolism mediated interaction of α-asarone and Acorus calamus with CYP3A4 and CYP2D6. Fitoterapia. 2011;82(3):369-374.21062640

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