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Amyloid-beta induced neurotoxicity has been identified as a major cause of Alzheimer's disease. Acorus tatarinowii Schott is one of the most frequently used Chinese herbs for Alzheimer's disease treatment. However, the effects of Acorus tatarinowii Schott on amyloid-beta mediated nerve cell damage remains unknown. In the present study, neuronal differentiated PC12 cells were used as a model to evaluate the effects of A. tatarinowii Schott extract (ATSE) against Abeta25-35 induced neurotoxicity. The results showed pretreatment with ATSE significantly protected PC12 cells from Abeta25-35 induced cell death, lactate dehydrogenase release, DNA damage, mitochondrial dysfunction and cytochrome c release from mitochondria. In addition, pretreatment with ATSE also significantly inhibited Abeta25-35 induced caspase-3 activation and reactive oxygen species generation in PC12 cells. These observations suggested that ATSE protects PC12 cells from amyloid-beta induced neurotoxicity.

P-Glycoprotein (P-gp), an ATP-binding cassette transporter, plays an important role in multidrug resistance (MDR). α-Asarone and β-asarone, bioactive cis-trans isomers found in Acorus tatarinowii Schott, were tested for their potential ability to modulate the expression and function of P-gp in Caco-2 cells. MTT assays revealed that both α-asarone and β-asarone significantly enhanced the vincristine-induced cytotoxicity to cells. β-Asarone was the most potent. Flow cytometry showed that α- and β-asarone increased Rhodamine 123 (Rh123) uptake and inhibited Rh123 efflux in Caco-2 cells in a concentration-dependent manner. Furthermore, P-gp expression and P-gp mRNA in cells were decreased by exposure to α- and β-asarone. In addition, β-asarone increased the inhibition of P-gp activity in cells more than α-asarone. Thus, α- and β-asarone effectively reversed MDR by inhibiting P-gp function and expression.

Acorus calamus (Sweet flag) has a long history of use and has numerous traditional and ethnomedicinal applications. Since ancient times, it has been used in various systems of medicines such as Ayurveda, Unani, Siddha, Chinese medicine, etc. for the treatment of various aliments like nervous disorders, appetite loss, bronchitis, chest pain, colic, cramps, diarrhea, digestive disorders, flatulence, gas, indigestion, rheumatism, sedative, cough, fever, bronchitis, inflammation, depression, tumors, hemorrhoids, skin diseases, numbness, general debility and vascular disorders. Various therapeutic potentials of this plant have been attributed to its rhizome. A number of active constituents from leaves, rhizomes and essential oils of A. calamus have been isolated and characterized. Of the constituents, alpha and beta-asarone are the predominant bioactive components. Various pharmacological activities of A. calamus rhizome such as sedative, CNS depressant, anticonvulsant, antispasmodic, cardiovascular, hypolipidemic, immunosuppressive, anti-inflammatory, cryoprotective, antioxidant, antidiarrheal, antimicrobial, anticancer and antidiabetic has been reported. Genotoxicity and mutagenecity of beta and alpha-asarone is reported, which limits their use at high dosage. Though A. calamus has been used since ancient times, many of its uses are yet to be scientifically validated. In the present review an attempt has been made to explore traditional uses and pharmacological properties of A. calamus., (Copyright © 2013 Elsevier GmbH. All rights reserved.)

Acorus calamus L., a tall, perennial, grass-like monocot plant from the Acoraceae family, is a well-known plant in Indian traditional medicines for centuries. It is a highly valued herb as it acts as a rejuvenator for brain and nervous system. It is a main medhya drug, which has the property of improving the memory power and intellect. Rhizomes of the plant are widely used in the treatment of number of ailments such as epilepsy, mental ailments, chronic diarrhoea, dysentery, fever, abdominal tumours, kidney and liver troubles, and rheumatism. A. calamus leaves, rhizomes and its essential oil possess many biological activities such as antispasmodic, carminative and are compiled in a simple approach in this review. This review presents a pragmatic description that deals with chemical constituents, toxicology, ethnobotany and pharmacological properties of A. calamus for easy and better understanding of the outstanding medicinal potential of this very special plant and sirens for its conservation.

Background: Ischemic hypoxic brain injury often causes irreversible brain damage. The lack of effective and widely applicable pharmacological treatments for ischemic stroke patients may explain a growing interest in traditional medicines. β-Asarone, which has significant pharmacological effects on the central nervous system (CNS), was used in the prevention of cerebral ischemia in this paper., Methods: The right middle cerebral artery occlusion model was used in the study. The effects of β-Asarone on mortality rate, neurobehavior, grip strength, lactate dehydrogenase, glutathione content, Lipid peroxidation, glutathione peroxidase activity, glutathione reductase activity, catalase activity, Na⁺-K⁺-ATPase activity and glutathione S transferase activity in a rat model were studied respectively., Results: β-Asarone significantly improved the neurological outcome after cerebral ischemia and reperfusion in terms of neurobehavioral function in rats. Meanwhile, supplementation of β-Asarone significantly boosted the defense mechanism against cerebral ischemia via increasing antioxidants activity related to lesion pathogenesis. Restoration of the antioxidant homeostasis in the brain after reperfusion may help the brain recover from ischemic injury., Conclusions: These experimental results suggest that complement β-Asarone is protective against cerebral ischemia in specific way. The administration of β-Asarone could reduce focal cerebral ischemic/reperfusion injury. The Mechanism of β-Asarone in protection of cerebral ischemia was via increasing antioxidants activity related to lesion pathogenesis.

Four essential oils from the leaf (P23) and rhizomes (P19, P22, P24) of Acorus calamus L., collected from various parts of Nepal, were obtained by hydrodistillation and analyzed by GC-MS. From a total of 61 peaks, 57 compounds were identified among the four essential oils accounting for 94.3%, 96.2%, 97.6%, and 94.1% of the oils, respectively. All of the essential oils were dominated by (Z)-asarone (78.1%-86.9%). The essential oils also contained (E)-asarone (1.9%-9.9%) and small amounts of gamma-asarone (2.0-2.3%), (Z)-methyl isoeugenol (1.5-2.0%), and linalool (0.2-4.3%). Allelopathic testing of the rhizome oil showed inhibition of seed germination of Lactuca sativa and Lolium perenne with IC50 values of 450 and 737 microg/mL, respectively. The rhizome essential oil demonstrated stronger seedling growth inhibition of L. perenne than of L. sativa, however. The rhizome oil also showed notable brine shrimp lethality (LC50 = 9.48 microg/mL), cytotoxic activity (92.2% kill on MCF-7 cells at 100 microg/mL), and antifungal activity against Aspergillus niger (MIC = 19.5 microg/mL).

This study presents a consumer and farmer safety evaluation on the use of four botanical pesticides in pepper berry crop protection. The pesticides evaluated include preparations from clove, tuba root, sweet flag and pyrethrum. Their safety evaluation was based on their active ingredients being eugenol, rotenone, β-asarone and pyrethrins, respectively. Botanical pesticides from Acorus calamus are of possible concern because of the genotoxic and carcinogenic ingredient β-asarone although estimated margins of exposure (MOE) for consumers indicate a low priority for risk management. For the other three botanical pesticides the margin of safety (MOS) between established acute reference doses and/or acceptable daily intake values and intake estimates for the consumer, resulting from their use as a botanical pesticide are not of safety concern, with the exception for levels of rotenone upon use of tuba root extracts on stored berries. Used levels of clove and pyrethrum as botanical pesticides in pepper berry crop production is not of safety concern for consumers or farmers, whereas for use of tuba root and sweet flag some risk factors were defined requiring further evaluation and/or risk management. It seems prudent to look for alternatives for use of sweet flag extracts containing β-asarone., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

The aim of this research was to determine the chemical composition of the essential oil of Acorus calamus rhizomes, its insecticidal activity against the booklouse, (Liposcelis bostrychophila) and to isolate any insecticidal constituents from the essential oil. The essential oil of A. calamus rhizomes was obtained by hydrodistillation and analyzed by GC-FID and GC-MS. A total of 32 components of the essential oil of A. calamus rhizomes was identified and the principal compounds in the essential oil were determined to be α-asarone (50.09%), (E)-methylisoeugenol (14.01%), and methyleugenol (8.59%), followed by β-asarone (3.51%), α-cedrene (3.09%) and camphor (2.42%). Based on bioactivity-guided fractionation, the three active constituents were isolated from the essential oil and identified as methyleugenol, (E)-methylisoeugenol and α-asarone. The essential oil exhibited contact toxicity against L. bostrychophila with an LD50 value of 100.21 µg/cm2 while three constituent compounds, α-asarone, methyleugenol, and (E)-methylisoeugenol had LD50 values of 125.73 µg/cm2, 103.22 µg/cm2 and 55.32 µg/cm2, respectively. Methyleugenol and (E)-methylisoeugenol possessed fumigant toxicity against L. bostrychophila adults with LC50 values of 92.21 μg/L air and 143.43 μg/L air, respectively, while the crude essential oil showed an LC50 value of 392.13 μg/L air. The results indicate that the essential oil of A. calamus rhizomes and its constituent compounds have potential for development into natural fumigants/insecticides for control of the booklice.

Context: Depression is one of the most common psychiatric diseases. Acorus tatarinowii Schott (Araceae) has shown many bioactivities in treatment of senile dementia and epilepsy. However, there is no report on antidepressant-like effects of the essential oil (EO) and its major components on animals under standardized experimental procedures., Objective: This study was designed to investigate the antidepressant properties of EO and asarones from the rhizomes of A. tatarinowii., Materials and Methods: Gas chromatography-mass spectrometry (GC/MS) was used to determine the composition of EO. The forced swimming test (FST), tail suspension test (TST) and open-field test (OFT) were used to evaluate the antidepressant-like effects of EO and asarones. EO [30, 60, 120 or 240 mg/kg, per os (p.o.)], asarones (α-asarone and β-asarone) [5, 10 and 20 mg/kg, intraperitoneal (i.p.)] and imipramine (15 mg/kg, i.p.) were administered at 1 h, 30 min and 30 min before the test, respectively., Results: From the results of GC/MS, it was found that the main components of the EO were α-asarone (9.18%) and β-asarone (68.9%). From the results of FST and TST, the immobility time can be reduced to 166 ± 17 s (p < 0.01) and 146 ± 15 s (p < 0.05) by EO at the dose of 120 mg/kg. Moreover, significant antidepressant-like effects were shown by α-asarone with the immobility time of 178 ± 15 s (p < 0.05) and 159 ± 17 s (p < 0.01) in FST, or 147 ± 12 (p < 0.05) and 134 ± 12 s (p < 0.01) in TST at the dose of 10 and 20 mg/kg. β-Asarone also displayed antidepressant-like effects with an immobility time of 179 ± 18 s (p < 0.05) in FST or 142 ± 14 (p < 0.05) in TST at 20 mg/kg. However, no change in ambulation was observed in the OFT., Conclusion: The results obtained indicate that the EO and asarones from the rhizomes of A. tatarinowii can be considered as a new therapeutic agent for curing depression.

Colorectal cancer is a leading cause of cancer mortality with a complex carcinogenesis that includes reduced cellular senescence. Lamin proteins are decreased in senescing cells, and frequently decreased in malignancies. This study identified a new drug candidate for colorectal cancer that appears to target cell senescence via a lamin protein. β-Asarone (1-propenyl-2,4,5-methoxybenzol) is a compound from the traditional medical herb Acorus calamus Linn. This study tested the in vitro and in vivo effects of β-asarone on colorectal cancer cells by testing cell viability using human colorectal cell lines HT29 and SW480 in MTT assays; tumorigenesis using xenografts in nude mice and a mouse model of colorectal cancer; cell senescence using senescence-associated β-galactosidase activity; and expression of cancer and senescence-related proteins, specifically lamins, Oct-1, p53, p21, and p15, by Western blot. β-Asarone appeared to increase expression of lamin B1, p53, p21, but not lamin A/C. β-Asarone regulates p15 expression by regulation of Oct-1 binding. Collectively, the results suggested that β-asarone inhibits colon cancer formation in vivo and in vitro by inducing senescence. Since β-asarone induced lamin B1 expression, a model is proposed in which β-asarone inhibits colorectal cancer by inducing senescence through lamin B1., (Copyright © 2013. Published by Elsevier GmbH.)

β-Asarone (BAS), a phenylpropanoid from Acorus calamus Linn., has shown biological effects in the management of cognitive impairment conditions such as Alzheimer's disease. The present paper describes a selective and sensitive liquid chromatography-tandem mass spectrometric method (HPLC-MS/MS) using electrospray ionization source (ESI) for quantification of BAS in rat plasma. Briefly, the plasma samples were pre-treated using a simple solid-phase extraction method. The separation of BAS and the internal standard, caffeine, was achieved on an Agilent Zorbax XDB C(18) column (50 × 2.1 mm i.d., 5 µm) using 0.2 mL/min isocratic mobile phase flow. The detection was performed using an Applied Biosystems Hybrid Q-Trap API 2000 mass spectrometer equipped with an ESI source operated in positive mode. Also, the developed bioanalytical method was validated as per the US FDA bioanalytical guidelines over the concentration range of 9.79-4892.50 ng/mL (r(2) ≥ 0.9951) for BAS from rat plasma. The mean percentage recovery (n = 3) for the low, middle and high quality control samples was 86.92 ± 3.89, 85.30 ± 1.09 and 87.24 ± 4.03%, respectively. The applicability of the validated HPLC-MS/MS method was demonstrated by successful measurement of BAS from plasma following oral administration of Acorus calamus rhizome extracts to three female albino Wistar rats., (Copyright © 2012 John Wiley & Sons, Ltd.)

Fifteen compounds were isolated from the rhizomes of Acorus tatarinowii by means of various chromatographic techniques such as silica gel, ODS, Sephadex LH-20 and preparative HPLC, and their structures were elucidated as tatanone A (1), calamusenone (2), acoronene (3), 2-acetyloxyacoronene (4), acorenone (5), alpha-asarone (6), beta-asarone (7), 1,2-dimethoxy-4-(1'Z-propenyl) benzene (8), methyleugenol (9), asarylaldehyde (10), acoramone (11), gamma-asarone (12), 5-hydroxymethyl-2-furaldehyde (13), galgravin (14) and eudesmin (15) on the basis of spectroscopic data analysis. Compound 1 was a new compound, and compounds 3-5 were separated from Acorus species for the first time.

Anti-Candida potential of Acorus calamus rhizome and its active principle, β-asarone, was evaluated against the human fungal pathogen, Candida albicans. β-Asarone exhibited promising growth inhibitory activity at 0.5mg/ml and it was fungicidal at 8 mg/ml. Time dependant kill curve assay showed that MFC of β-asarone was highly toxic to C. albicans, killing 99.9% inoculum within 120 min of exposure. β-Asarone caused significant inhibition of C. albicans morphogenesis and biofilm development at sub-inhibitory concentrations. Our data indicate that the growth inhibitory activity of β-asarone might be through inhibition of ergosterol biosynthesis. Hemolytic assay showed that β-asarone is non-toxic, even at concentrations approaching MIC value. Our results suggest that β-asarone may be safe as a topical antifungal agent., (Copyright © 2012 Elsevier GmbH. All rights reserved.)

A further phytochemical investigation of the rhizomes of Acorus gramineus afforded three new quinone derivatives (1-3), together with two known compounds (4 and 5). The identification and structural elucidation of these new compounds were based on 1D and 2D NMR (COSY, HMQC, HMBC and NOESY) and MS data. The absolute configurations were established on the basis of their circular dichroism (CD) data. To investigate the anti-neuroinflammatory effects of the isolated compounds (1-5), the nitric oxide (NO) production was evaluated in the lipopolysaccharide-activated microglia cell line, BV-2. Compounds (1-5) were also tested for their cytotoxicity against four human tumor cell lines (A549, SK-OV-3, SK-MEL-2, and HCT-15) in vitro by using the SRB assay.

In the present study, a rapid and repeatable microemulsion electrokinetic chromatography (MEEKC) method was developed for the simultaneous determination of three isomers (α-, β- and γ-asarone) in Acorus tatarinowii by using ionic liquid 1-butyl-3-methylimidazolium hexafluorophosphate ([BMIM]PF(6)) as oil phase. Experimental parameters including the microemulsion compositions (concentrations of surfactant, co-surfactant and oil phase), pH, concentration of borate buffer, capillary temperature and voltage were intensively investigated. Finally, the main compounds in the methanol extract of A. tatarinowii were well separated within 11 min using a running buffer composed of 40 mmol/L sodium dodecyl sulfonate (SDS), 2.0 mol/L n-propanol, 8 mmol/L [BMIM]PF(6) in 10 mmol/L borate buffer of pH 9.5. The developed method was applied to determine the contents of α-, β- and γ-asarone in A. tatarinowii from five different producing areas in China (Anhui, Hebei, Sichuan, Zhejiang and Chongqing). The results indicated that the contents of three asarones are quite different in the investigated A. tatarinowii samples. On the other hand, the MEEKC with ionic liquid as oil phase should be a promising method for the analysis of volatile components especially isomers in medicinal herbs., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Objective: To study the chemical constituents contained in Acorus calamus., Method: The chemical constituents were separated and purified by various chromatographic methods including silica gel, ODS, HPLC and Sephadex LH-20, and their structures were identified on the basis of analysis on spectroscopic data., Result: Ten compounds were separated from A. calamus and identified as 1beta, 4beta, 7alpha-trihydroxyeudesmane (1), bullatantriol (2), teuclatriol (3), threo-1', 2'-dihydroxyasarone (4), erythro-1', 2'-dihydroxyasarone (5), (+)-de-4'-O-methyleudesmin (6), (+)-de-4'-0-methylmagnolin (7), (+)-eudesmin (8), (+)-magnolin (9) and beta-sitosterol (10), respectively., Conclusion: Compounds 1-2,4-9 were separated from this plant for the first time. Specifically, compounds 1-2,6-9 were obtained from Acorus genus for the first time.

Chemical constituents in ethyl acetate and butanol fractions of ethanol extracts from Acorus tatarinowii were separated by column chromatography. Bufo skeletal muscle fatigue model was established to study the anti-fatigue activity of separated compounds. Five compounds were separated and identified by spectroscopic analysis as acoramone(1),cycloartenone(2),2,4,5-trimethoxyl-2'-butoxy-1,2-phenyl propandiol(3),5-hydroxymethyl furfural(4), and 5-butoxymethyl furfural(5). Compound 3 was a new compound, and compounds 2 and 5 were separated from this plant for the first time. Compound 4 exhibited a notable anti-fatigue activity.

Acortatarins A and B have been synthesized via stereoselective spirocyclizations of glycals. Mercury-mediated spirocyclization of a pyrrole monoalcohol side chain leads to acortatarin A. Glycal epoxidation and reductive spirocyclization of a pyrrole dialdehyde side chain leads to acortatarin B. Acid equilibration and crystallographic analysis indicate that acortatarin B is a contrathermodynamic spiroketal with distinct ring conformations compared to acortatarin A.

Objective: To analyze the constituents of volatile oils extracted from Yuan Zhi (Radix Polygalae), Shi Chang Pu (Acorus Tatarinowii), and a mixture of the two herbs., Methods: The volatile oils were extracted using supercritical fluid extraction (SFE) with CO2, and the constituents of the volatile oil extracts were analyzed by gas chromatography-mass spectrometry (GC-MS). The relative content of each component was calculated using peak area normalization., Results: The optimized SFE conditions were 45 MPa at 35 degrees C for 2 h. Twenty-four compounds were identified in the extract from the Yuan Zhi (Radix Polygalae) and Shi Chang Pu (Acorus Tatarinowii) mixture, and six of these had relative contents >1. These compounds were 1,2-dimethoxy-4-(2-propenyl)-benzene; 1,2,3-trimethoxy-5-(2-propenyl)-benzene; beta-asarone; (Z,Z) 9,12-octadecadienoic acid; (Z) 6-octadecenoic acid; and ethyl oleate. Combination of the herbs increased the number of pharmacologically active substances in the extract and decreased the number of compounds with one benzene ring compared with the extracts from the individual herbs., Conclusion: These results indicate there is a synergistic relationship among the compounds in these herbs.

Eight new sesquiterpenes (1-8) and one new norsesquiterpene (9) named calamusins A-I were isolated from the ethanol extract of Acorus calamus rhizomes. The absolute configuration of compound 8 was determined by comparing its experimental and calculated ECD spectra. The absolute configurations of the other compounds were determined from their CD spectra. Furthermore, in in vitro assays, compounds 3, 4, 7, and 9 (10 μM) exhibited weak hepatoprotective activities against APAP-induced HepG2 cell damage.

Aim: To explore the effects of β-asarone from Acorus Tatarinowii Schott on autophagy in an ischemic stroke model of PC12 cells., Methods: The ischemic stroke model of PC12 cells was made by OGD/R (2 h oxygen-glucose deprivation followed by 24 h reperfusion). Drug administration was started 1 h before OGD and last for 3 h. Then the cells were incubated in the drug-free and full culture medium under normoxic conditions for 24 h. After the treatments, Beclin-1, intracellular free calcium concentration ([Ca(2+)](i)) and mitochondrial membrane potential (MMP) were analyzed using flow cytometry. Cell viability was measured using MTT assay. Cell morphology was studied under inverted phase contrast microscope, and autophagosomes were observed under transmission electron microscope., Results: Pretreatment with β-asarone (20, 30, or 45 μg/mL) or the calcium channel antagonist nimodipine (10 μmol/L) significantly increased the cell viability and MMP, and decreased Beclin-1 expression and [Ca(2+)](i) in OGD/R-treated PC12 cells. Under inverted phase contrast microscope, pretreatment with β-asarone or nimodipine dramatically increase the number of cells and improved the cellular morphology. Autophagosomes were found in OGD/R-treated PC12 cells as well as in drug plus OGD/R-treated PC12 cells., Conclusion: β-Asarone protects PC12 cells against OGD/R-induced injury partly due to attenuating Beclin-1-dependent autophagy caused by decreasing [Ca(2+)](i) and increasing MMP.

Ethnopharmacological Relevance: Acorus calamus Linn. (Araceae) is a traditional herbal plant used for centuries to treat various allergic symptoms including asthma and bronchitis., Aim of the Study: The present study was focused to provide a pharmacological basis for the traditional use of Acorus calamus in allergic symptoms using the mast cell-dependent anaphylactic reactions in in vitro and in vivo models., Materials and Methods: Cell viabilities were measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay. Dinitrophenyl-human serum albumin (DNP-HSA) induced β-hexosaminidase and interleukin (IL)-4 productions in IgE-sensitized rat basophilic leukaemia (RBL-2H3) cells were measured by enzymatic assay and enzyme-linked immunosorbent assay (ELISA). Passive cutaneous anaphylaxis (PCA) reaction mouse model was implemented for in vivo studies., Results: Hot water (HW), butylene glycol (BG), hexane (HE) and steam distilled (SD) extracts of Acorus calamus showed different cytoxicity levels evaluated in RBL-2H3 cells. Sub-toxic doses of HW extract suppressed the β-hexosaminidase secretion and IL-4 production significantly and dose dependently in DNP-HSA induced IgE-sensitized RBL-2H3 cells compared to other extracts of Acorus calamus. Further, in vivo studies also revealed that the HW extract significantly inhibited the PCA reaction in mouse compared to the normal control group., Conclusion: HW extract of Acorus calamus most effectively inhibited degranulation and IL-4 secretion in DNP-HSA-stimulated RBL-2H3 cells and also reduced the mast cell-mediated PCA reaction in mouse, providing a therapeutic evidence for its traditional use in ameliorating allergic reactions., (Copyright © 2012. Published by Elsevier Ireland Ltd.)

This investigation was aimed to probe the pharmacological base of medicinal use of Acorus calamus in ischemic heart diseases. Effect on heart parameters was studied in isolated rabbit heart while coronary vasodilator effect was studied in isolated bovine coronary arterial rings, suspended in tissue baths filled with Krebs solution, maintained at 37°C, aerated with carbogen and responses were measured on PowerLab data acquisition system. In Langendorrf's perfused rabbit heart, the crude extract of Acorus calamus (Ac.Cr) at 0.01-10 mg/mL partially suppressed force of ventricular contractions (FVC), heart rate (HR) and coronary flow (CF). The ethylacetate fraction completely suppressed FVC, partially suppressed HR and CF, while the nHexane fraction exhibited similar effect on FVC and HR but increased CF, similar to methacholine and arachidonic acid. In bovine coronary arterial preparations, Ac.Cr caused inhibition of U46619 (20 nM)-precontractions, which was blocked in presence of increasing concentration of K(+) (4.8-20 mM), tetraethylammonium (1 μM) and SKF525A (10 μM), similar to arachidonic acid and methacholine, indicating K(+) channels activation and possible involvement of endothelial-derived hyperpolarizing factor (EDHF). Activity-directed fractionation revealed that EDHF-mediated activity is concentrated in the nHexane fraction. When tested against high K(+), the ethylacetate fraction was found more potent than parent crude extract and nHexane fraction. These data indicate that Ac.Cr mediates coronary vasodilator effect primarily through EDHF, responsible for the increase in CF, while the cardiac depressant effects may be due to the presence of additional cardiac depressant constituent(s), thus provides possible mechanistic basis to its medicinal use in ischemic heart diseases.

The pharmacological properties of plant polysaccharides are reviewed and original experimental data on the properties of water-soluble polysaccharides isolated from Acorus calamus L. are presented. The possibility of using plant (in particular, Acorus calamus) polysaccharides to increase the effectiveness of anticancer treatment of transferred tumors and to reduce the toxic effects of cytostatic treatment on the normal cells of blood, liver, and epithelium of thin intestine in experimental animals has been demonstrated.

Anticonvulsant property of Acorus calamus is known. Since combination therapy can lower the dose of individual drug and dose related toxicities, in this study, the effect of co-administration of hydroalcoholic extract of A. calamus (HAEAC) on conventional antiepileptic drugs (AEDs), sodium valproate and carbamazepine was determined using pentylenetetrazole-induced seizures model in rats. On combining the subanticonvulsant doses of HAEAC with sodium valproate and carbamazepine, greater protection as compared to either drug alone was observed. This was not related to change in levels of the AEDs. Thus, the results further substantiate anticonvulsant effect of HAEAC and suggest a potential for add on therapy with AEDs.

Contact toxicities of Acorus calamus L. (Arales: Araceae) extracts obtained from four published extraction methods: soakage, soxhlet, ultrasonic and supercritical fluid CO₂ (SFE-CO₂), were compared in this study. Under the given extraction conditions, SFE-CO₂ extract exhibited the highest contact toxicity against S. zeamais of the four methods. With the SFE-CO₂ method, extraction temperature, pressure, time and the amount of EtOH (the extraction solvent) were identified as having a significant effect on the extract. Orthogonal experiments showed that the optimal extraction parameters were: temperature--55°C, pressure--35 MPa, time--40 min and EtOH--150 mL per 200 g of dry powder. Under these conditions, the yield was 4.12% and the LD₅₀ of the extract against S. zeamais after 96 h of treatment was 27.26 µg cm⁻². β-asarone was the dominant component of the extract derived from the SFE-CO₂ method, accounting for 24.39% of the extract. These results may contribute to the designing of large-scale production processes for obtaining A. calamus extract, which proves to be an effective alternative for the control of stored product insect pests.

The radioprotecting activity of Acorus calamus extract after whole body exposure of mice to lethal and sub-lethal doses of γ-irradiation in terms of radiation induced mortality and damages to cellular DNA and tissue antioxidant levels were studied. A. calamus extract (250 mg/kg body weight) was orally administered to mice 1 h prior to whole body γ-radiation exposure. The antioxidant levels in the tissue homogenates of brain, liver and kidney of the irradiated mice were determined and cellular DNA damage was monitored by comet assay. Effect of administration of the extract on survival of the animals exposed to acute lethal dose of 10 Gy whole body γ-radiations was also monitored. Administration of the extract significantly increased the activities of major enzymes of the antioxidant defense system specially SOD, catalase and GPx and levels of GSH in 2, 6 and 10 Gy irradiated mice and decreased the formation MDA. The extract also decreased DNA strand breaks. The survival rate was found to be increased up to 5%. These studies highlight the role of A. calamus extract as good source of natural radioprotecting agent and its therapeutic implications for radiation-induced injuries., (Copyright © 2010 Elsevier GmbH. All rights reserved.)

In this study, supercritical fluid extraction (SFE) was used to extract essential oil from Acorus tatarinowii Schott under the pressure of 25 MPa and temperature of 35°C. Two (E)- and (Z)-diastereomers of α-asarone and β-asarone were separated and purified by high-speed counter-current chromatography (HSCCC) with a two-phase solvent system composed of n-hexane-ethyl acetate-methanol-water (1:0.2:1:0.3, v/v). The separation yielded a total of 39 mg of α-asarone and 463 mg of β-asarone from 1.0 g of essential oil in one-step separation with the purity of 98.9 and 99.1%, respectively, as determined by HPLC. The chemical structures of these compounds were identified by EI-MS, (1)H-, and (13)C-NMR., (Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Hydro-distilled essential oils extracted from three commercially important aromatic plants were analysed by capillary gas chromatography-flame ionization detector and gas chromatography/quadrupole mass spectrometry and subjected to antifungal activity. Fifteen compounds, which accounted for 97.8% of Acorus calamus root oil composition have been identified. Besides the major constituent (Z)-asarone (81.1-92.4%), (Z)-methyl isoeugenol (1.8-2.1%), (Z)-isoelemicin (1.2-1.3%), (E)-asarone (1.0-2.6%), (E)-methyl isoeugenol (0.2-0.4%), (Z)-β-ocimene (0.2-0.4%), elemicin (0.2-0.3%), linalool (0.1-0.9%) and kessane (t-0.2%) were identified. Monoterpenes constituted the main fraction of Origanum vulgare essential oil attaining 90.5% of the total oil composition. p-Cymene (10.3%) was the major component of the monoterpene hydrocarbon fraction while thymol (53.2%) and carvacrol (3.9%) were the most abundant oxygenated monoterpenes among the 33 identified constituents. Cinnamomum tamala leaf oil contained (E)-cinnamaldehyde as the principal component. Quantitative variations in (Z)-cinnamaldehyde (5.8-7.1%), linalool (6.4-8.5%) and (E)-cinnamyl acetate (4.7-5.2%) were significant. The antifungal activity of the hydro-distilled essential oils of A. calamus, O. vulgare and C. tamala were evaluated against Aspergillus flavus and Aspergillus niger. Disc diffusion method was used for the determination of the inhibitory effect. O. vulgare essential oil exhibited the highest activity. Moreover, all three essential oils inhibit the growth of A. flavus and A. niger.

As a part of our ongoing search for bioactive constituents from natural Korean sources, the investigation of rhizomes of Acorus gramineus afforded five new lignans, named ligraminols A-E (1-5), together with seven known ones (6-12). The structures of 1-5 were determined by a combination of 1D and 2D NMR, HRMS, CD, and enzymatic hydrolysis. Compounds 1-12 were tested for their antiproliferative activities toward a panel of human-derived normal and cancer cell lines. Moreover, compounds 1-12 were evaluated for their inhibitory activities on nitric oxide production in an activated murine microglial cell line.

A first total synthesis of acortatarins A, B, and an enantiomer of the proposed structure of acortatarin B is described by using readily available d-sugars. This convergent total synthesis revealed the revision of the absolute configuration of acortatarin A and structural revision of acortatarin B. The key steps involved are regioselective epoxide opening with deprotonated 2,5-disubstituted pyrrole and spiroketalization., (© 2011 American Chemical Society)

The study investigates the protective effect of Acorus calamus L. (AC) in vincristine-induced painful neuropathy. Vincristine (75μg/kg, i.p. for 10 consecutive days) was administered to induce painful neuropathy in rats. Various tests were performed to assess the degree of painful neuropathy at different days i.e., 0, 1, 7, 14, and 21st day. Sciatic nerve TNF-α, superoxide anion generation, total calcium, and myeloperoxidase activity level were also estimated after 21st day of study. Hydro-alcoholic extract of AC (HAE-AC, 100 and 200mg/kg, p.o.) and pregabalin (10mg/kg, p.o.) were administered for 14 consecutive days. Vincristine significantly induced neuropathic pain manifested in the terms of thermal hyperalgesia and allodynia (increase in hind paw licking, lifting or jumping from hot plate); mechanical hyperalgesia (increase in left hind paw lifting duration in pin-prick test) and allodynia (left hind paw withdrawal reflexes to non-noxious stimuli in Von Frey test); and sciatic functional index (analysis of footprints of the feet) along with rise in the levels of various biochemicals. HAE-AC attenuated vincristine induced behavioral, and biochemical changes comparable to that of pregabalin (positive control). HAE-AC attenuated vincristine induced painful neuropathy, which may be attributed to its multiple effects including anti-oxidative, anti-inflammatory, and calcium inhibitory actions., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

The purification of a MeOH extract from the rhizome of Acorus gramineus (Araceae) using column chromatography furnished two new stereoisomers of phenylpropanoid, acoraminol A (1) and acoraimol B (2). It also furnished 17 known phenolic compounds, β-asarone (3), asaraldehyde (4), isoacoramone (5), propioveratrone (6), (1'R,2'S)-1',2'-dihydroxyasarone (7), (1'S,2'S)-1',2'-dihydroxyasarone (8), 3',4'-dimethoxycinnamyl alcohol (9), 3',4',5'-trimethoxycinnamyl alcohol (10), kaempferol 3-methyl ether (11), 2-[4-(3-hydroxypropyl)-2-methoxyphenoxy]-1,3-propanediol (12), hydroxytyrosol (13), tyrosol (14), (2S,5S)-diveratryl-(3R,4S)-dimethyltetrahydrofuran (15), (7S,8R)-dihydrodehydrodiconiferyl alcohol (16), 7S,8S-threo-4,7,9,9'-tetrahydroxy-3,3'-dimethoxy-8-O-4'-neolignan (17), 7S,8R-erythro-4,7,9,9'-tetrahydroxy-3,3'-dimethoxy-8-O-4'-neolignan (18), and dihydroyashsbushiketol (19). The structures of the new compounds were elucidated by analysis of spectroscopic data including 1D and 2D NMR data. The absolute configurations of 1 and 2 were determined using the convenient Mosher ester procedure. Compounds 5-19 were isolated for the first time from this plant source. The isolated compounds were tested for cytotoxicity against four human tumor cell lines in vitro using a Sulforhodamine B (SRB) bioassay.

The constituents and antimicrobial activity of the essential oil from Acorus calamus were analysed. Methyl isoeugenol and cyclohexanone were identified as the major constituents of the essential oil. The essential oil was tested for antimicrobial activity against bacteria and yeast, and has shown strong antibiotic activities against most of the tested microbes, except Escherichia coli. The hexane extract has shown a similar pattern of antimicrobial activity as the essential oil. Methyl isoeugenol, the most abundant constituent in the essential oil, has also shown similar antimicrobial activity, except against Bacillus subtilis. The essential oil as well as the hexane extract and methyl isoeugenol have shown antimicrobial activity against Propionibacterium acne, which is known to be involved in acne vulgaris.

The present study was designed to investigate the attenuating potential of hydroalcoholic extract of Acorus calamus in vincristine-induced neuropathic pain in rats. Vincristine (50 μg/kg, i.p. for 10 consecutive days) was administered to induce neuropathic pain in rats. Hot plate, plantar, Randall-Selitto and von Frey hair tests were performed to assess the degree of thermal and mechanical hyperalgesia and mechanical allodynia, respectively, at different time intervals, viz., 0, 1, 3, 6, 9, 12, 15, 18 and 21 days. Tissue myeloperoxidase, superoxide anion and total calcium levels were determined after day 21to assess biochemical alterations. Histopathological evaluations were also performed. Hydroalcoholic extract of Acorus calamus (HAE-AC, 100 and 200 mg/kg, p.o.) and pregabalin (10 mg/kg, p.o.) were administered for 14 consecutive days. Vincristine significantly induced peripheral neuropathic pain, manifested in thermal and mechanical hyperalgesia and mechanical allodynia, along with rises in the levels of superoxide anion, total calcium and myeloperoxidase activity. Moreover, significant histological changes were also observed. HAE-AC attenuated vincristine-induced development of painful behavioural, biochemical and histological changes in a dose-dependent manner comparable to that of pregabalin, serving as positive control. Acorus calamus prevented vincristine-induced neuropathic pain, which may be attributed to its anti-oxidative, anti-inflammatory, neuroprotective and calcium inhibitory actions, among others.

In a two-microelectrode voltage clamp with Xenopus laevis oocytes, a petroleum ether extract of Acorus calamus rhizomes enhanced the GABA-induced chloride current through GABA(A) receptors of the α₁β₂γ(2S) subtype by 277% ± 9.7% (100 μg/mL). β-Asarone (1), (+)-dioxosarcoguaiacol (2), (+)-shyobunone (3), and (+)-preisocalamenediol (4) were subsequently identified as main active principles through HPLC-based activity profiling and targeted isolation. The compounds induced maximum potentiation of the chloride current ranging from 588% ± 126% (EC₅₀: 65.3 ± 21.6 μM) (2) to 1200% ± 163% (EC(50): 171.5 ± 34.6 μM) (1), whereas (-)-isoshyobunone (5) and (-)-acorenone (6) exhibited weak GABA(A) modulating properties (5: 164% ± 42.9%; EC₅₀: 109.4 ± 46.6 μM and 6: 241% ± 23.1%; EC₅₀: 34.0 ± 6.7 μM). The relative configuration of 2 was established as 4R*8S*10R* by NOESY experiments and conformational analysis.

Three novel sesquinlignans, tatanans A (1), B (2), and C (3), have been isolated from the rhizomes of Acorus tatarinowii Schott. Their structures were established by spectroscopic techniques and single-crystal X-ray analysis. Tatanans A-C potently increase GK enzymatic activity with EC(1.5) values in the range of 0.16-1.85 μM. The potent GK activity and unique structural features of tatanans make them promising leads for therapeutic development of antihyperglycemic drugs.

The present study was aimed to investigate the possible interaction of the standardized extract of Acorus calamus (AC) with Cytochrome P450 enzyme, quantitative determination of the α-asarone in the AC rhizome was performed by RP-HPLC method. In vitro interaction of the plant extract was evaluated by CYP450-carbon monoxide complex (CYP450-CO) assay. Effect on individual isoforms such as CYP3A4 and CYP2D6 isozymes were analyzed through fluorescence product formation and respective IC(50) values were determined. CYP450-CO assay showed moderate interaction potential. Extract showed higher IC(50) values (46.84±1.83-32.99±2.21 μg/ml) comparing to the standard inhibitors and lower IC(50) value than α-asarone (65.16±2.37-42.15±2.45 μg/ml)., (Copyright © 2010 Elsevier B.V. All rights reserved.)

This study was designed to investigate the therapeutic potential of hydroalcoholic extracts of Acorus calamus (AC) in tibial and sural nerve transection (TST)-induced neuropathic pain in rats. The hot plate, paw heat allodynia, acetone drop, and pinprick tests were performed to assess the degree of heat hyperalgesia, heat and cold allodynia, and mechanical hyperalgesia, respectively, at different time intervals, i.e., day 0, 1, 3, 6, 9, 12, 15, 18, and 21. The tissue superoxide anion and total calcium were measured as markers of oxidative stress. Tissue myeloperoxidase activity was measured as a specific marker of inflammation. Histopathological evaluation was also performed in the nervous tissue to assess the axonal degeneration. Pregabalin served as positive control in this study. TST in rats significantly induced thermal hyperalgesia and allodynia, mechanical hyperalgesia, and increased the levels of superoxide anion, total calcium, and myeloperoxidase (MPO) activity. Moreover significant histological changes were also observed. Oral administration of AC hydroalcoholic extract (100 and 200 mg/kg for 14 days) attenuated TST-induced behavioral, biochemical, and histological changes. Acorus calamus has ameliorative potential in TST-induced painful neuropathy, and this effect may be attributed to its multiple actions including anti-inflammatory, antioxidant, and neuroprotective actions.

To develop a environment friendly control measure against cattle tick, Rhipicephalus (Boophilus) microplus, medicinally important plants were identified and extracts were prepared. Twelve 95% ethanolic, thirteen 50% hydroethanolic and nine hot water extracts were prepared and tested against laboratory reared homogenous colony of R. (B.) microplus. Amongst the 34 extracts, 26 extracts showed no mortality within 72 h of application while 12.0 ± 4.9% to 35.0 ± 9.6% mortality of treated ticks was recorded in other extracts. Of the effective extracts, the extract prepared from rhizome of Acorus calamus proved highly efficacious and 100% final mortality within 14 DPT was recorded. The LC85 value of the extract was determined as 11.26. In vivo experiments confirmed the efficacy of the extract up to 42%, and repeat application was required after 7 DPT. The extract was found safe and no reaction was observed when animals were treated with 50% of the concentration, which was five times of the concentration used for in vivo studies. The possibility of using the extract for the control of cattle tick is discussed.

Objective: To probe into the therapeutic effect of perfume stimulating olfaction with volatile oil of Acorus Gramineus on the Alzheimer's disease (AD) rat., Methods: Totally 50 adult SD rats, male,weighing 300 +/- 10 g, were randomly divided into 5 groups, normal group (group A), olfactory nerve severing model group (group B), AD model group (group C), AD model plus perfume stimulation group (group D), AD model olfactory nerve severing plus perfume stimulation group (group E), 10 rats in each group. After perfume stimulation, Morris maze test was conducted for valuating the learning and memory ability; Malondaldehyde (MDA) content, and superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities in the brain, and the brain weight were detected., Results: Compared with the AD model group, the average escape latency and swimming distance in 6 days were significantly shorter than those in the group A, B, D (P < 0.01), with no significant differences between the group C and the group E (P > 0.05); Compared with the group A, B and D, MDA content in the group C significantly increased (P < 0.01), and SOD and GSH-Px activities significantly decreased (P < 0.01), and brain weight/body weight decreased significantly in the group C (P < 0.01), with no significant differences between the group C and the group E (P > 0.05)., Conclusion: Perfume stimultating olfaction with volatile oil of Acorus Gramineus can significantly increase the learning-memory ability, decrease MDA content and increase SOD and GSH-Px activities and weight of brain in AD rats.

A novel cadinane sesquiterpene with a propan-2-ylidene, named (1R,4R,6S,10R)-1-hydroxy-7(11)-cadinen-5,8-dione (1), and a new sesquiterpene, named (2R,6R,7S,9S)-1(10),4-cadinadiene-2,9-diol (2), were isolated from the ethanol extract of the rhizome of Acorus calamus L. Their structures were elucidated on the basis of spectroscopic data including NMR spectroscopy and X-ray crystallography. The absolute configurations of compounds 1 and 2 were confirmed by comparison of their experimental optical rotations with those obtained from theoretical calculations at the B3LYP/6-311+G (d) level of theory., (© Georg Thieme Verlag KG Stuttgart · New York.)

Mutagenic properties of water soluble polysaccharides (WSPS) extracted from Acorus calamus L. have been studied. Neither a single intravenous injection nor a course intraperitoneal introduction of WSPS in a dose of 1/2 LD50 to mice of the CBA/CaLac line increases the level of cytogenetic disorders in the bone marrow cells. The investigation of WSPS by means of the somatic mosaicism test showed that the given dose of WSPS does not increase the rate of mutant spots on Drosophila wings.

A new cadinane-type sesquiterpenoid, tatarinowin A (1), two phenylpropanoids, tatarinoids A (2) and B (3), and a trinorlignan, tatarinoid C (4), along with 15 known compounds including two pairs of mixtures were isolated from the rhizome of Acorus tatarinowii. The absolute configurations of 1-4 were established by computation of specific rotation values. The isolated compounds were evaluated for their cAMP regulatory activity by the AlphaScreen assay.

The rhizome of Acorus tatarinowii is a well-known traditional Chinese medicine. Our extensive investigation on this plant material afforded two new compounds, including a cadinane-type sesquiterpenoid and a pyrazine derivative, along with seven known compounds. The structures of the new compounds, tatarinowin B and tatarinine A, were elucidated as 2-oxocadinan-1(10),3-dien-5-ol (1) and 2-(3',4'-dihydroxy-1'-butylenyl)-5-(2'',3'',4''-trihydroxybutyl)-pyrazine (2), respectively, by means of spectral methods.

Acortatarins A (1) and B (2), two novel spiroalkaloids with a naturally unusual morpholine motif, were isolated from the rhizome of Acorus tatarinowii. Their structures with absolute configuration were determined by spectroscopic methods, X-ray diffraction analysis, and Mosher's method. Importantly, compound 1 could significantly inhibit reactive oxygen species production in high-glucose-stimulated mesangial cells in a dose- and time-dependent manner.

Ethnopharmacological Relevance: The radix of Acorus calamus L. (AC) is widely used in the therapy of diabetes in traditional folk medicine of America and Indonesia, and we previously reported the insulin sensitizing activity of the ethyl acetate fraction of AC (ACE)., Aim of the Study: To investigate the insulin releasing and alpha-glucosidase inhibitory activity of ACE in vitro and in vivo., Materials and Methods: Insulin releasing and alpha-glucosidase inhibitory effects of different fractions from AC were detected in vitro using HIT-T15 cell line and alpha-glucosidase enzyme. Furthermore, effects of ACE orally on serum glucose were detected in fasted and glucose/amylum challenged normal mice., Results: AC and ACE increased insulin secretion in HIT-T15 cells as gliclazide did. As in vivo results, ACE (400 and 800 mg/kg) significantly decreased fasting serum glucose, and suppressed the increase of blood glucose levels after 2g/kg glucose loading in normal mice. In addition, ACE as a mixed-type inhibitor inhibited alpha-glucosidase activity in vitro with an IC(50) of 0.41 microg/ml, and 100mg/kg of it clearly reduced the increase of blood glucose levels after 5 g/kg amylum loading in normal mice., Conclusions: Apart from its insulin sensitizing effect, ACE may have hypoglycemic effects via mechanisms of insulin releasing and alpha-glucosidase inhibition, and thus improves postprandial hyperglycemia and cardiovascular complications., (Copyright (c) 2009 Elsevier Ireland Ltd. All rights reserved.)

Three new sesquiterpenes, 1 beta,7 alpha(H)-cadinane-4 alpha,6 alpha,10 alpha-triol (1), 1 alpha,5 beta-guaiane-10 alpha-O-ethyl-4 beta,6 beta-diol (2), and 6 beta,7 beta(H)-cadinane-1 alpha,4 alpha, 10 alpha-triol ( 3), together with 25 known ones, were isolated from the rhizome of Acorus calamus L. Their chemical structures were established on the basis of interpretation of spectroscopic data and comparison with those of the related known compounds., ((c) Georg Thieme Verlag KG Stuttgart . New York.)

Administration of commonly used anticancer drug cisplatin [cis-diamminedichloroplatinum (II)] at pharmacologically relevant concentrations (12 mg/kg body weight) resulted in severe renal toxicity as evidenced from histopathological observations and biochemical alterations in the renal tissue. The extracts of medicinal plants Hemidesmus indicus L. (Apocynaceae) and Acorus calamus L. (Araceae) protected the renal tissue effectively from cisplatin-induced toxicity. Treatment of cisplatin-administered animals with the plant extracts could prevent the drug-induced oxidative damage in the renal tissue as evidenced from the decreased levels of lipid peroxidation and enhanced activities of the antioxidants in the renal tissue. Cisplatin treatment increased serum urea level to 41.3 +/- 2.86 mg/dL and administration of the extracts of H. indicus and A. calamus brought down the level to 34.54 +/- 0.37 and 30.12 +/- 0.95 mg/dL, respectively. Serum creatinine levels were increased to 1.1 +/- 0.02 mg/dL following cisplatin administration, and treatment with extracts of H. indicus and A. calamus brought this down to 0.76 +/- 0.09 and 0.61 +/- 0.06 mg/dL, respectively. The histopathological observations indicated that treatment with the H. indicus and A. calamus extracts restored the cisplatin-induced structural alterations in the renal tissue.

Asarone is a molecule found in certain plants such as Acorus calamus, the root of which is used in traditional medicine to treat diabetes. We determined the molecular mechanism underlying the anti-diabetic activity of asarone. Treatment of asarone significantly inhibited the differentiation of 3T3-L1 preadipocytes through suppression of expression of the transcription factors, CCAAT/enhancer binding protein-alpha and peroxisome proliferator activated receptor-gamma, which activate adipogenesis. Intracellular triglyceride levels were reduced by asarone in a dose-dependent manner and asarone treatment stimulated the phosphorylation of hormone-sensitive lipase. Together, the present findings indicate that asarone inhibits adipogenesis by down-regulation of PPARgamma and C/EBPalpha and reduces lipid accumulation by stimulation of lipolysis through an increase in hormone-sensitive lipase activity.