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Ethnopharmacological Relevance: Acorus tatarinowii Rhizoma, a traditional Chinese medicine known for open the orifices and transform phlegm, is used in the treatment of brain disorders. The essential oil of Acorus tatarinowii Rhizoma (EOAT) has demonstrated neuroprotective properties clinically. However, research into its effect on Olfactory Dysfunction (OD) remains limited., Aim of the Study: This study aimed to investigate the effects and mechanisms of sniffing EOAT on improving olfactory function in a 3-Methylindole (3-MI)-induced OD mouse model., Materials and Methods: The research involved intraperitoneal injection of 3-MI to induce OD in mice. The effects of EOAT treatment were assessed on olfactory function, olfactory bulb (OB) pathology, inflammatory factors, olfactory marker protein (OMP), microglial activation, and related pathway proteins and mRNA., Results: Based on the GC-MS analysis results of EOAT and network pharmacology studies, we predicted 18 targets associated with the treatment of OD. SLC6A3, MAOB, DRD1, and PTGS2 were identified as the core targets of EOAT against OD. Molecular docking and KEGG enrichment results indicated that EOAT may exert anti-inflammatory effects by acting on the core target PTGS2, with its anti-inflammatory mechanism possibly related to the PI3K/Akt signaling pathway. Subsequent animal experiments confirmed that inhalation of EOAT significantly increased the body weight of OD model mice, shortened the foraging time, enhanced the expression of OMP in OB, reduced damage to the OB cells, and improved olfactory function. Meanwhile, EOAT significantly alleviated the inflammatory response in OB of OD model mice, inhibited the activation of microglial cells, and suppressed the expression of PI3K/Akt signaling pathway proteins and mRNA., Conclusion: EOAT inhalation could improve olfactory function in 3-MI-induced OD model. The underlying mechanism may be related to the modulation of the PI3K/Akt signaling pathway., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Ethnopharmacological Relevance: Acori graminei Rhizoma is a commonly used traditional Chinese medicine for treating TD, with its main component being calamus volatile oil. Volatile Oil from Acori graminei Rhizoma (VOA)can protect nerve cells and alleviate learning and memory disorders. However, the mechanism of anti-tic of VOA is still unclear., Aim of the Study: We aimed to explore the effects of Volatile Oil from Acori Tatarinowii Rhizoma (VOA) on striatal dopaminergic and glutamatergic systems and synaptic plasticity of rats with Tic Disorder (TD), as well as its pharmaceutical mechanism against TD., Materials and Methods: This study involved 48 (three-week-old) Sprague Dawley (SD) rats, which were randomly divided into two primary groups: Control (8) and TD (40). Rats in the TD group were injected intraperitoneally with 3,3-iminodipropionitrile (IDPN) to construct the TD rat model. They were divided into five subgroups: Model, Tiapride, VOA-high, VOA-medium, and VOA-low (N = 8). After modeling, VOA was administrated to rats in the VOA groups through gavage (once/day for four consecutive weeks), while rats in the blank control and model groups received normal saline of the same volume. The animals' behavioral changes were reflected using the stereotypic and motor behavior scores. After interferences, patterns of striatal neurons and the density of dendritic spines were investigated using H&E and Golgi staining, and the ultrastructure of striatal synapses was examined using Transmission Electron Microscopy (TEM). Furthermore, Ca 2+ content was determined using the Ca 2+ detector, and Dopamine (DA) and Glutamate (GLU) contents in serum and striatum were detected through ELISA. Finally, DRD1, DRD2, AMPAR1, NMPAR1, DAT, VMAT2, CAMKⅡ, and CREB expression in the striatum was detected using Quantitative real-time PCR (qRT-PCR), Western Blotting (WB) and Immunohistochemical (IHC) methods., Results: Compared to rats in the blank control and model groups, rats in the VOA groups showed lower stereotypic behavior scores. Furthermore, rats in the VOA groups exhibited relieved, neuron damage and increased quantities of neuronal dendrites and dendritic spines Additionally, based on TEM images show that, the VOA groups showed a clear synaptic structure and increased amounts of postsynaptic dense substances and synaptic vesicles. The VOA groups also exhibited reduced Ca 2+ contents, and upregulation of DRD1, DRD2, DAT, AMPAR1, and NMPAR1 and downregulation of VMAT-2, CAMKⅡ, and CREB in the striatum., Conclusions: In summary, VOA could influence synaptic plasticity by tuning the dopaminergic and glutamatergic systems, thus relieving TD., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Ethnopharmacological Relevance: India's ancient texts, the Charak Samhita and Sushruta Samhita, make reference to the traditional medicinal usage of Acorus calamus L. In India and China, it has long been used to cure stomach aches, cuts, diarrhea, and skin conditions. This ability of the rhizome is attributed to its antimicrobial properties. Research studies to date have shown its antimicrobial properties. However, scientific evidence on its mode of action is still lacking., Aim of the Study: Acorus calamus L. rhizome extract and its bioactive fraction exhibits antibacterial effect by modulating membrane permeability and fatty acid composition., Material and Method: The secondary metabolites in the rhizome of A. calamus L. were extracted in hexane using Soxhlet apparatus. The ability of the extract to inhibit multidrug resistant bacterial isolates, namely Bacillus cereus, Escherichia coli, Acinetobacter baumannii, and Pseudomonas aeruginosa were evaluated using checkerboard assay. Further, the extract was purified using thin layer chromatography, gravity column chromatography, and combiflash chromatography. Structure elucidation of the active compound was done using GC-MS, FT-IR, and UV-Vis spectral scan. The mode of action of the bioactive fraction was determined. Bacterial membrane damage was analyzed using SEM, membrane permeability was determined using SYBR green I and PI dye, leakage of cytoplasmic contents were analyzed using Bradford assay and Fehling's reagent. The ability to inhibit efflux pump of A. baumannii was determined using EtBr accumulation assay and β-lactamase inhibition was analyzed using nitrocefin as substrate. Also, the biofilm inhibition of B. cereus was determined using crystal violet dye. Moreover, the effect of the bioactive fraction on the fatty acid profile of the bacterial membrane was determined by GC-FAME analysis using 37 component FAME mix as standard., Results: Acorus calamus L. rhizome hexane extract (AC-R-H) demonstrated broad-spectrum antibacterial activity against all the isolates tested. AC-R-H extract also significantly reduced the MIC of ampicillin against all tested bacteria, indicating its bacterial resistance modulating properties. The assay guided purification determined Asarone as the major compound present in the bioactive fraction (S-III-BAF). S-III-BAF was found to reduce the MIC of ampicillin against Escherichia coli (100-25 mg/mL), Pseudomonas aeruginosa (15-3.25 mg/mL), Acinetobacter baumannii (12.5-1.56 mg/ml), and Bacillus cereus (10-1.25 mg/mL). Further, it recorded synergistic activity with ampicillin against B. cereus (FICI = 0.365), P. aeruginosa (FICI = 0.456), and A. baumannii (FICI = 0.245). The mode of action of S-III-BAF can be attributed to its ability to disturb the membrane integrity, enhance membrane permeability, reduce biofilm formation, and possibly alter the fatty acid composition of the bacterial cell membranes., Conclusion: The bioactive fraction of AC-R-H extract containing Asarone as the active compound showed antibacterial activity and synergistic interactions with ampicillin against the tested bacterial isolates. Such activity can be attributed to the modulation of fatty acids present in bacterial membranes, which enhances membrane permeability and causes membrane damage., Competing Interests: Declaration of competing interest The authors whose names are listed immediately below certify that they have no affiliations with or involvement in any organization or entity with any financial interest (such as honoraria; educational grants; participation in speakers bureaus; membership, employment, consultancies, stock ownership, or other equity interest; and expert testimony or patent-licensing arrangements), or non-financial interest (such as personal or professional relationships, affiliations, knowledge or beliefs) in the subject matter or materials discussed in this manuscript. We (authors) hereby declare the followings: (1) the information in the manuscripts is true, correct and we do not have any conflict of interest, (2) all authors mutually agree that the manuscript is submitted to Journal of Ethnopharmacology, and (3) this work has not been published/submitted or being submitted to another journal., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Ethnopharmacological Relevance: Different plants are used for the treatment of various ailments and Acorus calamus L. is one such plant found in Western Himalaya. Rhizome of this plants has ethnomedicinal significance, as its rhizome is used for curing fever, pain and inflammation. An attempt has been made to alter the phytochemicals and increase its antioxidant property in a sustainable way with the help of mycorrhizal inoculation., Aim of the Study: Study of mycorrhizal (Funneliformis mosseae) impact on the biological activities and phytochemical profile of A. calamus L. rhizome and in silico studies of phytochemicals for their anti-inflammatory property., Materials and Methods: F. mosseae was mass multiplied by single spore culture and then A. calamus rhizomes were inoculated with it. Antioxidant potential of rhizome extract was observed by DPPH and FRAP assays and the phytochemical profiling was done with GC-MS analysis. For observing antimicrobial activity disc diffusion method was employed. Dominant phytochemicals α-asarone and monolinolein TMS were chosen for molecular docking studies against four receptors (4COX, 2AZ5, 5I1B, 1ALU)., Results: There was increase in antioxidant activity of rhizome extract after mycorrhizal inoculation. However, no change in antimicrobial activity was observed in the plant after mycorrhizal inoculation. The comparison in phytochemicals was observed by GC-MS analysis which showed qualitative and quantitative variation in biochemical content in plants. The phytochemical, α-asarone and monolinolein TMS showed highest docking score and least binding energy against 1ALU and 4COX respectively for anti-inflammatory activity., Conclusion: Medicinal plants are potential source of antioxidants which can be increased by mycorrhizal inoculation without addition of chemical fertilizers and also results in altering the phytochemical composition., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Ethnopharmacology Relevance: As a traditional folk medicine, Acorus tatarinowii Schott was used to treat digestive diseases, such as diarrhea, which may be related to Candida albicans infection; however according to literature surveys, there have been few studies of A. tatarinowii focusing on its antimicrobial activity, and almost all describe investigations using crude extracts or fractions., Aim of the Study: The aims of the current study were to isolate and identify antifungal fractions of A. tatarinowii based on their antifungal activity, explore the preliminary mechanism of 60% ethanol elution (AT60) by metabonomics, and evaluate the antifungal activity of AT60 in vivo and in vitro, to provide natural resources against fungal infections., Materials and Methods: As a pilot evaluation of activity, A. tatarinowii fractions and compounds with antifungal bioactivity were isolated by bioactive-guided column chromatography, and identified by LC-QTOF-MS/MS and NMR spectroscopy. The antifungal effects of the active ingredients against resistant C. albicans were evaluated by in vivo and in vitro colony forming unit assays. The mechanism underlying the activity of AT60 against C. albicans was explored using an LC-QTOF-based metabonomics approach and fluorescence microscopy imaging., Results: AT60 showed better activity against C. albicans than the same dose of the first line antifungal drugs, fluconazole and itraconazole (positive control drugs). Subsequent phytochemical investigation of AT60 identified twenty-five known compounds, six of which were isolated: asaraldehyde (7), 1-(2,4,5-trimethoxyphenyl)-1,2-propanediol (12), α-asarone (14), β-asarone (15), γ-asarone (18), acotatarone C (19). Further, the compounds α-asarone (14) and acotatarone C (19) may be responsible for the antifungal activity, and exhibit synergistic effects. Metabonomics analysis indicated that AT60 can inhibit biofilm formation by regulating the C. albicans protein kinase C pathway., Conclusions: Our results show that A. tatarinowii has potent bioactivity against C. albicans in vitro and in vivo, and can be considered an antifungal botanic agent., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Ethnopharmacological Relevance: Acorus gramineus rhizoma (AGR) is the dry rhizome of Acorus gramineus Solander from the family Araceae that has been used as sedative, analgesic, diuretic, digestive and antifungal agent., Aim of the Study: To evaluate the no-observed-adverse-effect level (NOAEL) and the toxicity of AGR, following repeated oral administration to rats for 13 weeks., Materials and Methods: AGR was administered by oral gavage to groups of rats (10 per group, each sex) at doses of 0 (control), 25, 74, 222, 667, or 2,000mg/kg/day, 5 times per week for 13 weeks. Mortality, clinical signs, body weights, food consumption, hematology, serum chemistry, urinalysis, vaginal cytology, sperm motility, sperm morphology, organ weights, gross and histopathological findings were compared between control and AGR groups., Results: No mortality or remarkable clinical signs were observed during this 13-week study. No adverse effects on body weight, food consumption, urinalysis, hematology, serum chemistry, organ weights, gross lesion, histopathology, vaginal cytology, sperm motility or deformity were observed in any of the male or female rats treated with AGR., Conclusions: On the basis of these results, the NOAEL of AGR is determined to be 2,000mg/kg/day for male and female rats., (Copyright © 2016. Published by Elsevier Ireland Ltd.)

Ethnopharmacological Relevance: The radix of Acorus calamus L. (AC) is widely used in diabetes therapies in traditional folk medicine from America and Indonesia, and we have previously reported that the ethyl acetate fraction of AC (ACE) acts as an antidiabetic through insulin sensitizing, insulin releasing and alpha-glucosidase inhibitory activities. The present study is designed to investigate the effects and molecular mechanisms of ACE on glucagon-like peptide-1 (GLP-1) expression and secretion related to its hypoglycemic effects., Materials and Methods: The hypoglycemic effect of ACE (100mg/kg, i.g.) was confirmed by testing blood glucose levels or via oral glucose tolerance test (OGTT) in streptozotocin (STZ) induced hyperglycemic mice, db/db diabetic mice and diet-induced obese (DIO) mice. Plasma insulin, GLP-1 levels and intestinal GLP-1 related gene expression were determined in STZ-induced and db/db diabetic mice. The in vitro effects of ACE (12.5μg/ml) on the expression and secretion of GLP-1 were detected in NCI-H716 intestinal L-cells, and the correlation between ACE and molecules in the Wnt signaling pathway was further explored., Results: ACE (100mg/kg) significantly lowered fasting blood glucose in STZ-induced and db/db diabetic mice and improved the OGTT in DIO mice. Insulin releasing and islet protective effects, along with the increased secretion of GLP-1, were observed. The expression of proglucagon gene (gcg) and post-translational processing gene prohormone convertase 3 (pc3) and the GLP-1 content in the culture medium of L-cells notably increased after the ACE treatment (12.5μg/ml). At the same time, β-catenin nuclear translocation occurred, and its downstream protein cyclin D1 was activated, showing the involvement of Wnt signaling., Conclusions: ACE might activate Wnt signaling to increase the gene expression of gcg and pc3 and exert incretin effects, including insulinotropic and islet protection, to lower blood glucose levels via elevated GLP-1 secretion either directly or indirectly., (Copyright © 2015. Published by Elsevier Ireland Ltd.)

Ethnopharmacological Relevance: Acorus tatarinowii Schott (Shi Chang Pu) belongs to the family of Acoraceae. The plant is used as an important herb for prolonging life many years in traditional Chinese medicine. It is an ancient herbal tonic nutriment and can be used as anti-fatigue medicine. However, the effects of Acorus tatarinowii Schott on the endurance exercise in relation to central nervous system have not yet been clarified. In this study, the effects of Acorus tatarinowii Schott on treadmill running endurance, 5-HT concentrations, TPH2, 5-HT1B expression in the dorsal raphe of exercised rats were investigated., Materials and Methods: Sixty adult male Sprague-Dawley rats were randomly divided into six groups: the normal group, the exercise group, the exercise and the rhizomes of Acorus tatarinowii Schott (ATS)(1mg/kg)-treated group, the exercise and ATS (10mg/kg)-treated group, the exercise and ATS (100mg/kg)-treated group, the exercise and caffeine (10mg/kg)-treated group. The effects of Acorus tatarinowii Schott on endurance exercise were determined by the time to exhaustion during treadmill exercise. The detection of 5-HT concentrations in the dorsal raphe was performed by HPLC analysis. The levels of TPH2, 5-HT1A and 5-HT1B expression were measured by western blot analysis and real-time PCR., Results: We found Acorus tatarinowii Schott could prolong the time to exhaustion in treadmill exercise and suppress the exercise-induced increase of 5-HT synthesis, TPH2 mRNA and protein expression and prevent the exercise-induced decrease of 5-HT1B mRNA and protein expression in the dorsal raphe. Acorus tatarinowii Schott was as effective as caffeine in prolonging the exhaustion time in treadmill running and in decreasing the exercise-induced increase of 5-HT synthesis and TPH2 mRNA and protein expression and in preventing the exercise-induced decrease of 5-HT1B mRNA and protein expression in the dorsal raphe., Conclusions: The results indicated that the effects of Acorus tatarinowii Schott in inhibiting the exercise-induced synthesis of 5-HT and TPH2 expression and in preventing the exercise-induced decrease of 5-HT1B expression in the dorsal raphe might be the anti-fatigue mechanism of Acorus tatarinowii Schott., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

Ethnopharmacological Relevance: Acorus tatarinowii Schott (AT), belong to the family Araceae, is perennial herbaceous plant mainly present in China, Japan and India. The rhizomes of AT have been used as a famous traditional Chinese medicine for the treatment of central nervous system related diseases., Aim of the Study: A selective, accurate and sensitive method using gas chromatography-mass spectroscopy (GC-MS) for the simultaneous determination and pharmacokinetic study of β-asarone, α-asarone, elemicin and cis-methyl isoeugenol in rat plasma was developed and validated., Materials and Methods: The GC-MS system was operated under selected ion monitoring (SIM) mode. The samples were prepared by protein precipitation with acetonitrile after being spiked with an internal standard (1-naphthol). The GC separation was achieved on a DB-1701 column (60 m × 0.25 mm ID, and 0.25 µm film thickness)., Results: The current GC/MS assay was validated for linearity, intra-day and inter-day precisions, accuracy, extraction recovery and stability. The analyte calibration curves were linear over a wide concentration range and the lowest limit of quantifications (LLOQ) were 5.53 ng/mL (β-asarone), 6.50 ng/mL (α-asarone), 3.10 ng/mL (elemicin) and 7.60 ng/mL (cis-methyl isoeugenol). After oral administration 0.9 g /Kg of AT rhizomes, the maximum plasma concentration (Cmax) was 2508.6±498.7 ng/mL for β-asarone, 257.5±37.1 ng/mL for α -asarone, 345.5±33.4 ng/mL for elemicin and 452.7±59.1 ng/mL for cis-methyl isoeugenol, respectively. The time to reach the maximum plasma concentration (Tmax) was 1.42±0.18 h for β-asarone, 1.58±0.19 h for α -asarone, 1.67±0.24 h for elemicin and 1.75±0.38 h for cis-methyl isoeugenol, respectively., Conclusion: This paper described a simple, sensitive and validated GC-MS method for simultaneous determination of four phenylpropanoids in rat plasma after oral administration of the essential oil of AT rhizomes and investigated on their pharmacokinetics studies as well., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

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.)

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.)

Unlabelled: Acorus calamus L. (AC), family Araceae, have been used in the Indian and Chinese systems of medicine for hundreds of years. The radix of AC is widely used in the therapy of diabetes in traditional folk medicine of America and Indonesia., Aim of the Study: To investigate the insulin sensitizing activity and antidiabetic effects of the ethyl acetate fraction of AC (ACE)., Materials and Methods: Glucose consumption mediated by insulin was detected in L6 rat skeletal muscle cells. Diabetes and its complications related indexes were monitored after orally administrating to genetically obese diabetic C57BL/Ks db/db mice daily for 3 weeks., Results: ACE (12.5 and 25 microg/ml) increased glucose consumption mediated by insulin in L6 cells (p<0.05 and p<0.01). In db/db mice, ACE (100 mg/kg) significantly reduced serum glucose, triglyceride, reinforce the decrease of total cholesterol caused by rosiglitazone (at least p<0.05), and markedly reduced free fatty acid (FFA) levels and increased adiponectin levels (p<0.01 and p<0.05) as rosiglitazone did (p<0.05 and p<0.001). Serum insulin was decreased but not significantly. In addition, ACE decreased the intake of food and water, and did not increase body weight gain whereas rosiglitazone did., Conclusions: Owing to the ability of insulin sensitizing, ACE has the potential to be useful for the treatment of diabetes and cardiovascular complications without body weight gain.