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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.)

Background: Alzheimer's disease (AD) presently stands as the most prevalent neurodegenerative disease. Existing research underscores the pivotal role of insulin signaling in the progression of AD. Acorus tatarinowii Schott (SCP), a traditional Chinese herbal, is employed for AD treatment in China. The volatile oil of Acorus tatarinowii Schott (SCP-oil) is the active component. However, its impact on AD-associated insulin resistance (AD-IR) remains inadequately investigated., Purpose: This study used network pharmacology and experimental to investigate the effects and mechanisms of SCP-oil on cognitive improvement in AD by inhibiting IR., Materials and Methods: GC-Q/TOF-MS was employed to analyze the chemical composition of SCP-oil, while network pharmacology predicted the targets associated with SCP-oil in treating AD-IR to identify its regulatory mechanism. IR in the brain was simulated by intracerebroventricular streptozotocin administration (ICV-STZ). The neuroprotective and cognitive improvement effects of SCP-oil were assessed using the Morris water maze and hematoxylin and eosin, as well as Nissl staining. The expression levels of Neun and proteins related to p-tau, tau, amyloid-beta (Aβ), apoptosis, and the phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT) pathway were measured using immunohistochemistry and Western blotting, respectively. Dexamethasone (DXM)-induced HT22 cells were used for IR modeling. Chemical analysis determined the glucose consumption rate, and periodic acid Schiff staining was employed to detect glycogen deposition. Western Blots were utilized to investigate the expression of characteristic AD proteins, apoptosis-related proteins, and PI3K/AKT pathway-related proteins. The apoptosis rate was detected by flow cytometry. Reverse validation was further performed using LY294002 to evaluate the pharmacodynamic effects of SCP-oil after PI3K/AKT pathway inhibition., Results: A total of 25 chemical constituents were identified in SCP-oil. The network pharmacology findings indicated that SCP-oil holds the potential to ameliorate IR in the brain by activating the PI3K/AKT pathway, thereby improving AD. SCP-oil significantly improved ICV-STZ-induced cognitive dysfunction and pathological damage, reduced neuronal loss, Aβ deposition, and tau protein hyperphosphorylation, inhibited cell apoptosis, and activated the PI3K/AKT signaling pathway. Neuron loss, Aβ deposition, and tau protein hyperphosphorylation and cell apoptosis were further enhanced following treatment with LY294002, while the PI3K/AKT signaling pathway was further inhibited, and the protective effect of SCP-oil was weakened., Conclusion: SCP-oil exhibited the potential to ameliorate brain IR, inhibiting cell apoptosis by activating the PI3K/AKT signaling pathway, thereby improving learning and memory ability., Competing Interests: Declaration of competing interest All authors disclosed no relevant relationships., (Copyright © 2024. Published by Elsevier GmbH.)

Seven compounds, named β-sitosterol ( 1 ), daucosterol ( 2 ), (+)-pinoresinol-β-D-glucoside ( 3 ), (-)-syringaresinol 4-O-β-D-apiofuranosyl-(1→2)- β-D-glucopyranoside ( 4 ), 4-hydroxybenzoic acid ( 5 ), 2-(3', 4'-dihydroxyphenyl)-1, 3-pepper ring-5-aldehyde ( 6 ) and spinosin ( 7 ) were isolated from the rhizome of Acorus calamus var. angustatus Besser. 3 , 4 , 6 and 7 were isolated from this medicinal plant for the first time. Structures were elucidated by physicochemical properties and extensive spectroscopic analysis, as well as by comparison with literature data. The anti-inflammatory activity and related mechanisms of the seven compounds showed that compounds 1 - 7 all increased the levels of GSH-PX and SOD and decreased the levels of MDA, TNF-α, IL-1β and IL-6. Compound 4 showed the best effect of anti-inflammatory and Beclin-1 inhibition. These results suggest that compound 4 has stronger anti-inflammatory effect and provide preliminary evidence that the mechanism of action of compound 4 in attenuating LPS-induced inflammatory damage may be related to the inhibition of Beclin-1-dependent autophagy.

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.)

This study aims to investigate the effect of essential oil of Acori Tatarinowii Rhizoma on microglial pyroptosis and decipher the underlying mechanism. BV-2 cells were treated with 1 μg·mL~(-1) lipopolysaccharide(LPS) and 10 μmol·L~(-1) nigericin sodium salt for the modeling of pyroptosis. The cells were treated with different doses of essential oil of Acori Tatarinowii Rhizoma, and then the cell viability and apoptosis were examined by the CCK-8 assay and flow cytometry, respectively. The levels of tumor necrosis factor-α(TNF-α), interleukin-1β(IL-1β), and interleukin-18(IL-18) were measured by ELISA. The mRNA levels of nucleotide-binding domain, leucine-rich repeat, and pyrin domain-containing protein 3(NLRP3), apoptosis-associated speck-like protein containing CARD(ASC), and cysteine proteinase-1(caspase-1) were determined by qRT-PCR. The immunofluorescence assay was used to detect the expression of ionized calcium-binding adapter molecule 1(Iba-1) and NLRP3. Western blot was employed to determine the protein levels of B lymphocytoma-2(Bcl-2), Bcl-2 associated X protein(Bax), Iba-1, κB-inhibitor kinase beta(IKKβ), p-IKKβ(Y188), nuclear factor-κB p65(NF-κB p65), p-NF-κB(S536), NLRP3, ASC, caspase-1, cleaved caspase-1, gasdermin D(GSDMD), and GSDMD-N. The results showed that 8, 16, and 32 μg·mL~(-1) essential oil of Acori Tatarinowii Rhizoma increased the viability, increased the expression of Bcl-2/Bax, and reduced the apoptosis of the cells exposed to LPS and nigericin sodium salt. In addition, the essential oil inhibited the expression of Iba-1, lowered the levels of TNF-α, IL-1β, and IL-18, and down-regulated the mRNA levels of NLRP3, ASC, and caspase-1 as well as the protein levels of NLRP3, ASC, caspase-1, p-IKKβ(Y188)/IKKβ, p-NF-κB(S536)/NF-κB p65, cleaved caspase-1, and GSDMD-N. The results indicated that the essential oil of Acori Tatarinowii Rhizoma inhibited the NLRP3 inflammasome-mediated pyroptosis of microglia.

Acorus gramineus has a number of beneficial effects, including protective effects against age-related disorders. In this study, the effects of A. gramineus on testosterone production and andropause symptoms were evaluated. We first treated TM3 mouse Leydig cells, responsible for testosterone production, with A. gramineus aqueous extract at different concentrations. In TM3 cells, the testosterone concentration increased in a concentration-dependent manner compared with those in the control. In addition, at 400 μg/mL extract, the mRNA expression level of the steroidogenic enzyme CYP11A1 was increased. Subsequently, 23-week-old Sprague-Dawley (SD) rats exhibiting an age-related reduction in serum testosterone (approximately 80% lower than that in 7-week-old SD rats) were administered A. gramineus aqueous extract for 8 weeks. Serum total testosterone and free testosterone levels were higher and serum estradiol, prostate-specific antigen levels, and total cholesterol levels were lower in the AG50 group ( A. gramineus aqueous extract 50 mg/kg of body weight/day) than in the OLD (control group). The AG50 group also showed significant elevations in sperm count, grip strength, and mRNA expression of StAR , CYP11A1 , 17β-HSD , and CYP17A1 compared with those in the OLD group. In conclusion, A. gramineus aqueous extract facilitated steroidogenesis in Leydig cells, elevated testosterone levels, lowered serum estradiol and total cholesterol levels, and increased muscle strength and sperm count, thus alleviating the symptoms of andropause. These findings suggest that A. gramineus aqueous extract is a potentially effective therapeutic agent against various symptoms associated with andropause.

Background: Traumatic brain injury (TBI) causes substantial mortality and morbidity globally. Current treatments only alleviate symptoms and do not halt secondary injury progression., Objectives: Evaluate the neuroprotective potential of Acorus calamus Linn. (AC) in a Drosophila melanogaster model of high-impact TBI., Methods: Fruit flies (Drosophila melanogaster) of the Oregon R + strain were administered hydroalcoholic extracts of Acorus calamus Linn. (HAEAC) at concentrations of 25 and 50 µg/mL, 24 h and continuously for 72 h, respectively, following TBI induction. Mortality rate, locomotor function, neurotransmitter levels, and oxidative stress markers were assessed at 24 and 72 h post-injury as outcomemeasures., Results: AC significantly reduced post-TBI mortality and improved locomotor function in a dose-dependent manner. Additionally, AC increased acetylcholinesterase, gamma-aminobutyric acid, serotonin, and dopamine levels while reducing glutamate. It also boosted antioxidant activity (superoxide dismutase, glutathione, and catalase) and lowered markers of oxidative damage (malondialdehyde, nitrite)., Conclusions: AC mitigated behavioral deficits, oxidative damage, and neurotransmitter imbalance in fruit flies after TBI. These findings indicate AC may be more effective than individual drugs for TBI therapy. Further research into its neuroprotective phytochemicals is warranted., 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.)

Background: Depression is a common and complex mental illness that manifests as persistent episodes of sadness, loss of interest, and decreased energy, which might lead to self-harm and suicide in severe cases. Reportedly, depression affects 3.8 % of the world's population and has been listed as one of the major global public health concerns. In recent years, aromatherapy has been widely used as an alternative and complementary therapy in the prevention and treatment of depression; people can relieve anxiety and depression by sniffing plant aromatic essential oils. Acorus tatarinowii and Panax ginseng essential oils in Chang Shen Hua volatile oil (CSHVO) are derived from Acorus tatarinowii and Panax ginseng, respectively, the main medicines in the famous Chinese medicine prescription Kai Xin San (KXS), Then, these oils are combined with the essential oil of Albizia julibrissin flower to form a new Chinese medicine inhalation preparation, CSHVO. KXS has been widely used in the treatment of depression; however, whether CSHVO can ameliorate depression-like behavior, its pharmacological effects, and the underlying mechanisms of action are yet to be elucidated., Study Design and Methods: A rat model of chronic and unpredictable mild stimulation (CUMS) combined with orphan rearing was treated with CSHVO for 4 weeks. Using behavioral tests (sucrose preference, force swimming, tail suspension, and open field), the depression-like degree was evaluated. Concurrently, brain homogenate and serum biochemistry were analyzed to assess the changes in the neurotransmitters and inflammatory and neurotrophic factors. Furthermore, tissue samples were collected for histological and protein analyses. In addition, network pharmacology and molecular docking analyses of the major active compounds, potential therapeutic targets, and intervention pathways predicted a role of CSHVO in depression relief. Subsequently, these predictions were confirmed by in vitro experiments using a corticosterone (CORT)-induced PC12 cell damage model., Results: CSHVO inhalation can effectively improve the weight and depression-like behavior of depressed rats and regulate the expression of inflammatory factors and neurotransmitters. Hematoxylin-eosin, Nissl, and immunofluorescence staining indicated that compared to the model group, the pathological damage to the brain tissues of rats in the CSHVO groups was improved. The network pharmacological analysis revealed that 144 CSHVO active compounds mediate 71 targets relevant to depression treatment, most of which are rich in the cAMP signaling and inflammatory cytokine pathways. Protein-protein interaction analysis showed that TNF, IL6, and AKT are the core anti-depressive targets of CSHVO. Molecular docking analysis showed an adequate binding between the active ingredients and the key targets. In vitro experiments showed that compared to the model group, the survival rate of PC12 cells induced by CSHVO intervention was increased, the apoptosis rate was decreased, and the expression of inflammatory cytokines in the cell supernatant was improved. Western blot analysis and immunofluorescence staining confirmed that CSHVO regulates PC12 cells in the CORT model through the cAMP-PKA-CREB signaling pathway, and pretreatment with PKA blocker H89 eliminates the protective effect of CSHVO on CORT-induced PC12 cells., Conclusions: CSHVO improves CORT-induced injury in the PC12 cell model and CUMS combined with orphan rearing-induced depression model in rats. The antidepressant mechanism of CSHVO is associated with the modulation of the cAMP-PKA-CREB signaling pathway., Competing Interests: Declaration of competing interest The authors declare no competing interests associated with this study., (Copyright © 2024. Published by Elsevier GmbH.)

Growing evidence has demonstrated that gut microbiota could be developed as a therapeutic target due to its contribution to microglia activation in the pathological process of ischemic stroke. Acorus tatarinowii oils (AT oils), which is considered as the active fraction of a traditional Chinese herbal medicine Acorus tatarinowii, exerts various bioactivities and prebiotic effects. However, it remains unclear that the effect of AT oils on inflammatory response after ischemic stroke and whether its underlying mechanism is associated to gut microbiota and the intestinal barrier. In the current study, we aim to investigate the anti-microglial neuroinflammation mechanism of AT oils in a middle cerebral artery occlusion model of ischemic stroke. The compositions of AT oils were identified by GC-MS. Our results demonstrated that AT oils could effectively relieve cerebral infarction, inhibit neuronal apoptosis, degrade the release of pro-inflammatory factors (TNF-α, IL-17, IL-6 and IFN-γ), and mediate the polarization of microglia. Moreover, AT oils restored the composition and the balance of gut microbiota in stroke rats, and reduced abundance of opportunistic genera including Verrucomicrobia, Akkermansia and Tenericutes, as well as increased beneficial bacteria abundance such as Tenericutes and Prevotella_copri. To investigate the role of gut microbiota on AT oils against ischemic stroke, we conducted the fecal microbiota transplantation (FMT) experiments with gut microbiota consumption, which suggested that the depletion of gut microbiota took away the protective effect of AT oils, confirming the importance of gut microbiota in the protective effect of AT oils on ischemic stroke. FMT experiments have demonstrated that AT oils preserved the gut permeability and blood-brain barrier, as well as mediated the microglial phenotype under the intervention of gut microbiota. In summary, AT oils could efficaciously moderate neuronal damage and intervene microglial phenotype by reversing gut microbiota disorder in ischemic stroke rats., Competing Interests: Declaration of Competing Interest The authors confirm that the research was conducted without any existing commercial or financial relationships that could be perceived as a potential conflict of interest., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Due to the presence of several active secondary metabolites, the traditional Indian and Chinese medicinal herb Acorus calamus L. has been utilized for both medical and culinary purposes since ancient times. A recent report has underscored the promising cytotoxic effect of A. calamus leaves extract against non-small cell lung cancer A549 cells. Thus, we want to separate the bioactive substance from the hydromethanolic extract of A. calamus leaves in the current investigation. Thin-layer chromatography was used to separate the compounds and different spectroscopic methods (UV, FTIR, NMR, and LCMS/MS) were used for the structure prediction. α- asarone was found to be the main bioactive compound present and it was isolated from A. calamus leaves extract. It exerted a good cytotoxic effect with an IC 50 value of 21.43 ± 1.27 μM against A549 cells and IC 50 value of 324.12 ± 1.32 μM against WI-38 cells. The induction of apoptosis in A549 cells by α - asarone was reaffirmed by the diverse differential staining methods including DAPI, Acridine Orange/Ethidium Bromide, and Giemsa staining. Additionally, α-asarone induced mitochondrial membrane potential (ΔΨ m ) dissipation with a concomitant increase in the production of ROS. Furthermore, it also increased expressions of caspase-3, caspase-9, caspase-8, DR4, and DR5 genes in A549 cells. In conclusion, α-asarone-induced apoptotic cell death in non-small lung cancer cells (A549) as a result of loss of mitochondrial function, increased ROS production, subsequent activation of an internal and extrinsic caspase pathway, and altered expression of genes controlling apoptosis. As a whole, α - asarone is a plausible therapeutic agent for managing lung cancer. HIGHLIGHTSIsolation of bioactive compound from hydromethanolic leaves extract of Acorus calamus L. by thin layer chromatography.Structural elucidation of the bioactive compound was carried out using different methods like UV analysis, FTIR, NMR, and LC-MS/MS analysis.A plausible mode of action revealed that α-asarone can induce apoptosis in lung cancer cells (A549).Communicated by Ramaswamy H. Sarma.

The rhizomes of Acorus tatarinowii Schott and Acorus gramineus Solander are widely used for treating amnesia in traditional Chinese medicine. In contrast, their leaves are usually discarded without their medicinal properties being known. Here, we found that the hot water extract of leaves improved cognition and tau pathology in model mice of frontotemporal dementia, similar to or even better than that of rhizomes. To explore the optimal method of processing, we made three preparations from dried leaves: hot water extract, extraction residue, and non-extracted simple crush powder. Among them, the simple crush powder had the strongest effect on tauopathy in mice. The crush powder also ameliorated Aβ and α-synuclein pathologies and restored cognition in mouse models of Alzheimer's disease and dementia with Lewy bodies. These findings suggest the potential of Acorus tatarinowii / gramineus leaves as a dietary source for dementia prevention and reveal that simple crushing is a better way to maximize their efficacy.

Objective: To investigate the activity of Acorus tatarinowii extracts against dust mites, and to isolate and characterize active ingredient of A. tatarinowii extracts., Methods: The essential oil components were extracted from A. tatarinowii rhizome powder by rotary evaporation with methanol as solvents, followed by petroleum ether extraction and rotary evaporation. The essential oil was mixed with Tween-80 at a ratio of 1:1 and diluted into concentrations of 1.000 00%, 0.500 00%, 0.250 00%, 0.125 00%, 0.062 50% and 0.031 25%, while diluted Tween-80 served as controls. A. tatarinowii essential oil at each concentration (200 μL) was transferred evenly to filter papers containing 100 adult mites, with each test repeated in triplicate, and controls were assigned for each concentration. Following treatment at 25 °C and 75% relative humidity for 24 h, the mean corrected mortality of mites was calculated. The essential oil components were separated by silica gel column chromatography, and the essential oil was prepared in the positive column of medium pressure; and then, each component was collected. Silica gel column chromatography was run with the mobile phase that consisted of petroleum ether solution containing 10% ethyl acetate and pure ethyl acetate, detection wavelength of 254 nm, positive silica gel column as the chromatography column, and room temperature as the column temperature. Each component of the purified A. tatarinowii essential oil was diluted into 1.000 00% for acaricidal tests. The components with less than 100% acaricidal activity were discarded, and the remaining components were diluted into 50% of the previous-round tests for subsequent acaricidal tests. The components with acaricidal activity were subjected to high-performance liquid chromatography, liquid chromatography-mass spectrometry and pulsed-Fourier transform nuclear magnetic resonance spectroscopy. The structure of active monomer compounds was determined by standard spectral library retrieval and literature review., Results: A. tatarinowii essential oil at concentrations of 1.000 00%, 0.500 00%, 0.250 00% and 0.125 00% killed all dust mites, and the corrected mortality was all 100%. Exposure to A. tatarinowii extracts at an effective concentration of 0.062 50% for 24 hours resulted in 94.33% mortality of dust mites. Six components (A to F) were separated using gel column chromatography, and components D and E both showed a 100% acaricidal activity against dust mites at a concentration of 0.50000%. In addition, Component D was identified as isoeugenol methyl ether, and Component E as β-asarinol., Conclusions: The extract of A. tatarinowii essential oil has acaricidal activity, and the isoeugenol methyl ether shows a remarkable acaricidal activity against dust mites.

Acorus tatarinowii, a famous traditional Chinese medicine, is used for the clinical treatment of memory impairment and dementia. In this research, AT50, the crude polysaccharide extracted from A. tatarinowii rhizome, significantly improved the memory and learning ability of mice with Alzheimer's disease (AD) and exerted excellent anti-neuroinflammatory effects. More importantly, AT50 returned the levels of NO, TNF-α, IL-1β, PGE-2, and IL-6 in AD mouse brains to normal levels. To identify the active ingredients in AT50, a heteropolysaccharide ATP50-3 was obtained from AT50. Structural analysis indicated ATP50-3 consisted of α-L-Araf-(1→, →2)-α-L-Araf-(1→, →3)-α-L-Araf-(1→, →5)-α-L-Araf-(1→, α-D-Xylp-(1→, →3,4)-β-D-Xylp-(1→, →3)-α-D-Galp-(1→, →3,6)-α-D-Galp-(1→, →6)-4-OAc-α-D-Galp-(1→, →3,4,6)-α-D-Galp-(1→, →4)-α-D-Glcp-(1→, →2,3,6)-β-D-Glcp-(1→, →4,6)-α-D-Manp-(1→, →3,4)-α-L-Rhap-(1→, →4)-α-D-GalpA-(1→, and →4)-α-D-GlcpA-(1 → residues and terminated with Xyl and Ara. Additionally, ATP50-3 significantly inhibited the release of proinflammatory factors in lipopolysaccharide-stimulated BV2 cells. ATP50-3 may be an active constituent of AT50, responsible for its anti-neuroinflammatory effects, with great potential to treat AD., Competing Interests: Declaration of competing interest There are no conflicts of interest to declare., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The development of novel antioxidant compounds with high efficacy and low toxicity is of utmost importance in the medicine and food industries. Moreover, with increasing concerns about the safety of synthetic components, scientists are beginning to search for natural sources of antioxidants, especially essential oils (EOs). The combination of EOs may produce a higher scavenging profile than a single oil due to better chemical diversity in the mixture. Therefore, this exploratory study aims to assess the antioxidant activity of three EOs extracted from Cymbopogon flexuosus, Carum carvi, and Acorus calamus in individual and combined forms using the augmented-simplex design methodology. The in vitro antioxidant assays were performed using DPPH and ABTS radical scavenging approaches. The results of the Chromatography Gas-Mass spectrometry (CG-MS) characterization showed that citral (29.62%) and niral (27.32%) are the main components for C. flexuosus, while D-carvone (62.09%) and D-limonene (29.58%) are the most dominant substances in C. carvi. By contrast, β-asarone (69.11%) was identified as the principal component of A. calamus (30.2%). The individual EO exhibits variable scavenging activities against ABTS and DPPH radicals. These effects were enhanced through the mixture of the three EOs. The optimal antioxidant formulation consisted of 20% C. flexuosus, 53% C. carvi, and 27% A. calamus for DPPHIC50. Whereas 17% C. flexuosus, 43% C. carvi, and 40% A. calamus is the best combination leading to the highest scavenging activity against ABTS radical. These findings suggest a new research avenue for EOs combinations to be developed as novel natural formulations useful in food and biopharmaceutical products., (© 2024. The Author(s).)

Acorus tatarinowii Schott (A. tatarinowii), a well-known traditional Chinese medicinal plant renowned for its high medicinal value, but its mitochondrial genome (mitogenome) is still unexplored. In this study, we meticulously assembled the complete mitochondrial genome of A. tatarinowii using a combination of Illumina short reads and Oxford Nanopore long reads. Our findings revealed that A. tatarinowii possesses a complex chromosomal structural mitogenome, comprising two linear chromosomes and seven circular chromosomes. This mitogenome spans 1.81 Mb in length with a GC content of 38.29 %. Notably, it contained 24 unique mitochondrial core genes, seven unique variable genes, 17 tRNA genes, and three rRNA genes. Analyses of codon usage, most protein-coding genes (PCGs) exhibited a common codon usage preference, with RSCU values greater than 1, and the codon with the highest RSCU value was UAA(End, 1.90). We conducted a thorough analysis of repeat sequences, the distribution of repetitive sequences in nine mitochondrial chromosomes showed distinct patterns. Moreover, we identified 82 and 12 homologous fragments by comparing the sequences of chloroplast and nuclear genomes to the A. tatarinowii mitogenome, respectively. Lastly, We predicted a total of 234 potential RNA editing sites in 28 unique PCGs and discovered that the nad4 gene has been edited the most often, at 26 times. Our results contribute to the enrichment of mitochondrial genome resources for Acoraceae, and the mitogenome also can be used as a reference for other species., 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 © 2023. Published by Elsevier B.V.)

A pair of new guaiane-type sesquiterpene tautomers ( 1 ) was isolated from rhizomes of Acorus calamus . Meanwhile, three pairs of known compounds, including a pair of dihydroflavone glycoside tautomers ( 2 ), a pair of 4-hydroxybenzoic acid ester glycoside tautomers ( 3 ), as well as a pair of secoiridoid glycoside tautomers ( 4 ) were isolated from fruits of Cornus officinalis . Their structures were elucidated by extensive spectroscopic and computational methods. Furthermore, the tautomeric mechanisms were discussed.

Epilepsy is a serious public health problem in the world. At present, over 30% of affected patients remain refractory to currently available treatment. Medicinal plants as pharmaceuticals and healthcare treatments have been frequently used in the management of epilepsy in China for many centuries. Gastrodia elata-Acous tatarinowii (GEAT), as a classic and most commonly used herb pair in traditional Chinese medicine (TCM), has been employed to control seizures for thousands of years. However, the animal experiment data on its anticonvulsant effect is limited in the literature. Thus, this study aimed to reveal the therapeutic actions of GEAT decoction against seizures in mice. UHPLC-MS/MS was performed to analyze the chemical components of GEAT decoction. The mice were given GEAT decoction for 7 days, and MES, PTZ, and 3-MP injection was given 30 min after the last administration. Video monitoring was performed for comparisons. In addition, the PTZ-induced kindling models were conducted to investigate the seizure severity, anxiety and cognitive profile, inflammation, and oxidative stress parameters in mice. The results showed that GEAT decoction dose-dependently protected mice against MES, 3-MP, and PTZ-induced acute seizures. Furthermore, GEAT decoction significantly ameliorated seizure severity, decreased the accumulation of inflammatory mediators TNF-α, IL-1β, and IL-6, mitigated oxidative stress, as well as alleviated anxious-like behavior and cognitive deficits in PTZ-kindled mice. These results suggest that GEAT decoction possesses certain anticonvulsant properties, which might be clinically useful as phytotherapy alone or as an adjunct therapy for the prevention and treatment of seizures and epilepsy., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

In the present study, we report herein the isolation of cadinane-type sesquiterpenoid, tatarinowin A (ACH-6), and pentadecanoic acid (ACH-8) from petroleum ether extract of rhizome of Acorus calamus L. (Acoraceae) along with 6 other known compounds in this species. It is pertinent to mention here that this is the first report to stain these compounds in which dereplication approach based on GC-MS was applied to target unknown compounds ACH-6 and ACH-8 in A. calamus L. Derelpication approaches based on GC-MS is very useful technique in the area of drug discovery and have eminence potential to identify known and unknown compounds present in extracts of medicinal important plants. This technique can be used to expedite the process of purification of unknown compounds from different matrixes. The isolated compounds were identified with the help of inbuilt library search which reveals the presence of 17 known and 4 unknown compounds. Further, the structure elucidation of all isolated compounds was done using spectroscopy techniques. Also, the structure of ACH-6 was further confirmed by using the single-crystal X-ray diffraction technique.

Acorus tatarinowii Schott ( A. tatarinowii ) is a natural medicinal plant. It plays an indispensable role in the treatment of diseases by the empirical medicine system and has achieved remarkable curative effects. A. tatarinowii is often used to treat various diseases, such as depression, epilepsy, fever, dizziness, heartache, stomachache, etc. More than 160 compounds of different structural types have been identified in A. tatarinowii , including phenylpropanoids, terpenoids, lignans, flavonoids, alkaloids, amides, and organic acids. These bioactive ingredients make A. tatarinowii remarkable for its pharmacological effects, including antidepressant, antiepileptic, anticonvulsant, antianxiety, neuroprotective, antifatigue, and antifungal effects, improving Alzheimer's disease, and so on. It is noteworthy that A. tatarinowii has been widely used in the treatment of brain diseases and nervous system diseases and has achieved satisfactory therapeutic effects. This review focused on the research publications of A. tatarinowii and aimed to summarize the advances in the botany, traditional uses, phytochemistry, and pharmacology, which will provide a reference for further studies and applications of A. tatarinowii .

Noroviruses (NVs) are a major cause of foodborne diseases worldwide. The rhizomes of Acorus gramineus (AGR) have been used as a traditional medicinal plant and a food additive. In this study, AGR and its bioactive components-α-asarone and β-asarone-showed significant antiviral activities against murine NV (MNV) with pre-treatment, with more than two log reductions in viral plaques. They also demonstrated strong inhibition on binding to A- and O-type saliva by the recombinant P domain derived from human NV (HuNV) GII.4. Both α- and β-asarones also inhibited the binding of the P domain to the receptor at 0.125-1 mM in a concentration-dependent manner and induced a marked reduction in T m , suggesting that they may reduce structural stability and block receptor binding by the P domain. In simulated digestive conditions, the AGR extract, α-asarone, or β-asarone further showed a significant reduction of MNV plaques by 1.5-2.8 logs. The asarones show a potential for development as a scaffold for anti-NV agents.

Acorus calamus is a perennial aromatic medicinal plant from the Acorusaceae family, known for its pharmaceutical and medicinal value. A combined chemical, biochemical, and molecular study was conducted to evaluate the differential accumulation of volatile organic compounds (VOCs) in rhizomes and leaves of A. calamus essential oil. Here, we performed VOC profiling and transcriptome-based identification and functional characterization of terpene synthase (TPS) genes. A total of 110 VOCs were detected from the rhizomes and leaves of A. calamus, and some VOCs showed significant differences between them. The further transcriptome-based analysis led to the identification of six putative TPSs genes. In phylogenetic analysis, three TPSs belonged to the TPS-g clade, one to each of the TPS-a, TPS-c, and TPS-e clades. The heterologous E. coli-based expression of recombinant TPSs identified three genes (AcTPS3, AcTPS4, and AcTPS5) as bifunctional linalool/nerolidol synthase. The correlation of TPS gene expression and VOC metabolite profiles supported the function of these genes in A. calamus. Our findings provide a roadmap for future efforts to enhance the molecular mechanisms of terpene biosynthesis and our understanding of Acorus-insect interactions., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: Alzheimer's disease places a heavy economic burden to healthcare systems around the world. However, the effective treatments are still lacking. Traditional Chinese medicines (TCM) of Schisandra chinensis and Acorus tatarinowii Schott have the pharmacological effects of sedation and neuroprotection and have been clinically proven to be effective in the treatment of AD. However, their main anti-Alzheimer's compounds and functional mechanisms remain unclear., Purpose: To elucidate the main therapeutic components and possible mechanisms of Sc-At in AD using a comprehensive strategy combining metabolomics and network pharmacology., Methods: First, the UPLC-QTOF/MS method was used to identify the main chemical constituents of Schisandra chinensis and Acorus tatarinowii Schott alcohol extracts in vitro and in vivo . Secondly, the theoretical active ingredients, targets, and pathways of Sc-At for AD treatment were predicted by network pharmacology methods. Finally, plasma metabolomics were detected by UPLC-QTOF/MS to analyze the differential metabolites and metabolic pathways related to Sc-At. Based on the analyses above, the anti-AD mechanism of Sc-At was explored., Results: A total of 95 chemical components were identified in Sc-At extracts in vitro , and 34 prototype drug components were detected in rat plasma; network pharmacology screening identified 14 drug components in line with the principle of Lipinski, of which 10 were present for in vitro drug composition analysis. For these 10 components, 58 AD disease targets were predicted, and 85 AD-related KEGG signaling pathways were enriched. Six core biomarkers of Sc-At ( cis -8,11,14,17-eicosatetraenoic acid, prostaglandin H2, sphingosine 1-phosphate, enol-phenylpyruvate, 3-methoxytyrosine, and pristanoyl-CoA) were regulated to a normal state during the treatment of AD., Conclusion: The mechanism of Sc-At for the treatment of AD can be achieved by the effect of the 10 compounds of Sc-At on TNF, MAPK8, MAPK14, PTGS1, and other targets, thereby affecting arachidonic acid metabolism, neurotransmitters, and sphingolipid metabolism., Competing Interests: There are no conflicts to declare., (Copyright © 2022 Jian Chen et al.)

Acorus tatarinowii Schott is a traditional Chinese medicine used to treat memory and cognitive dysfunction. Because of their efficacy and lower toxic effects, research on α- and β-asarone, the phytoconstituents, has attracted attention owing to their remarkable pharmacological activities. Silver ion coordination complexation high-speed counter-current chromatography was used to separate these isomers from A. tatarinowii extract, coupled with accelerated solvent extraction. Accelerated solvent extraction parameters were investigated with single-factor and orthogonal testing. A two-phase solvent system composed of n-hexane-ethyl acetate-ethanol-water (2:1:2:1, v/v) with 0.50 mol/L silver ions was selected for separation. From 2.0 g crude extract, 1.4 g of β-asarone and 0.09 g of α-asarone were obtained with purities over 98% by sequential sample loading in 20 h. The isolated compounds were identified by electrospray ionization mass spectrometry, 1 H and 13 C NMR. Silver ions significantly increased the separation factor and retention of the stationary phase. The chromatographic behavior indicated that cis-configuration was more strongly complexed with the silver ion. This was further demonstrated with the help of computational analysis. In conclusion, the established method could be employed to separate other cis-trans or E/Z isomers that form coordination complexes., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest., (Copyright © 2021. Published by Elsevier B.V.)

Background-Alzheimer's disease (AD) is a multifactorial, progressive, neurodegenerative disease that is characterized by memory loss, personality changes, and a decline in cognitive function. While the exact cause of AD is still unclear, recent studies point to lifestyle, diet, environmental, and genetic factors as contributors to disease progression. The pharmaceutical approaches developed to date do not alter disease progression. More than two hundred promising drug candidates have failed clinical trials in the past decade, suggesting that the disease and its causes may be highly complex. Medicinal plants and herbal remedies are now gaining more interest as complementary and alternative interventions and are a valuable source for developing drug candidates for AD. Indeed, several scientific studies have described the use of various medicinal plants and their principal phytochemicals for the treatment of AD. This article reviews a subset of herbs for their anti-inflammatory, antioxidant, and cognitive-enhancing effects. Methods-This article systematically reviews recent studies that have investigated the role of neuroprotective herbs and their bioactive compounds for dementia associated with Alzheimer's disease and pre-Alzheimer's disease. PubMed Central, Scopus, and Google Scholar databases of articles were collected, and abstracts were reviewed for relevance to the subject matter. Conclusions-Medicinal plants have great potential as part of an overall program in the prevention and treatment of cognitive decline associated with AD. It is hoped that these medicinal plants can be used in drug discovery programs for identifying safe and efficacious small molecules for AD.

The Asian traditional medicinal plant Acorus calamus and its component α-asarone exhibited various biological activities, such as antiinflammation and antioxidant effects. In the present study, we investigated the in vitro effects of A. calamus extract and α-asarone on oxidative stress- and endoplasmic reticulum (ER) stress-induced cell death in hippocampal HT22 cells. A. calamus extract and α-asarone both significantly suppressed cell death induced by the oxidative stress inducer l-glutamate and ER stress inducer tunicamycin. A. calamus extract and α-asarone also significantly reduced reactive oxygen species (ROS) production induced by l-glutamate. Moreover, A. calamus extract and α-asarone suppressed the phosphorylation of protein kinase RNA-like ER kinase (PERK) induced by tunicamycin. These results suggest that A. calamus extract and α-asarone protect hippocampal cells from oxidative stress and ER stress by decreasing ROS production and suppressing PERK signaling, respectively. α-Asarone has potential as a potent therapeutic candidate for neurodegenerative diseases, including Alzheimer's disease., (© The Author(s) 2021. Published by Oxford University Press on behalf of Japan Society for Bioscience, Biotechnology, and Agrochemistry.)

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.)

α-Asarone and β-asarone are reported as bioactive constituents of Acorus calamus . Phase I metabolism of asarone isomers results in a multiple spectrum of genotoxic metabolites. Thus, the question arises whether structural analogues of the known phase I metabolites also naturally occur in A. calamus -based food products. A liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed and validated for three product classes, herbal infusions, alcoholic beverages, and food supplements. High asarone contents were detected in herbal infusions (total mean 9.13 mg/kg, n = 8) and food supplements (total mean 14.52 mg/kg, n = 6); hence, these food products can highly contribute to human exposure to genotoxic asarone derivatives. Also, the occurrence of asarone oxidation products found in food and food supplements has to be taken under consideration because data on toxicity is limited so far.

Spectroscopic analysis of HPLC-purified 7.3-kD Acorus tatarinowii Schott root polysaccharide ASP2-1 (FT-IR, NMR) revealed respective monosaccharide proportions of glucose: galactose: arabinose: xylose: galacturonic acid: mannose: rhamnose: glucuronic acid:fucose of 49.1:16.0:11.6:10.2:5.3:2.9:2.2:1.7:0.8. In vitro, ASP2-1 inhibited osteoclastogenesis-associated bone resorption, RANKL-induced osteoclastogenesis and F-actin ring formation and suppressed osteoclastogenesis-associated gene expression (e.g., TRAP, OSCAR, Atp6v0d2, αV, β3, MMP9 and CtsK) as shown via RT-PCR. ASP2-1-treated RANKL-stimulated bone marrow-derived macrophages exhibited decreased levels of NFATc1 and c-Fos mRNAs and corresponding transcription factor proteins, elevated expression of negative NFATc1 regulators (Mafb, IRF8, Bcl6) and reduced their upstream negative regulator (Blimp1) expression. ASP2-1 inhibition of NFATc1 expression involved PLCγ2-Ca 2+ oscillation-calcineurin axis suppression, reflecting suppression of RANKL-induced PLCγ2 activation (and associated Ca 2+ oscillation) and calcineurin catalytic subunit PP2BAα expression without inhibiting NF-κB and MAPKs activation or phosphorylation. Staining (H&E, TRAP) and micro-CT assays revealed ASP2-1 attenuated bone destruction and osteoclast over-activation and improved tibia micro-architecture in a murine LPS-induced bone loss model. Thus, ASP2-1 may alleviate inflammatory bone loss-associated diseases., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Our previous study has indicated that a crude polysaccharide derived from Acorus tatarinowii, AT50, remarkably improves learning and memory in scopolamine-induced amnesic mice and prevents the release of inflammatory mediators. To further explore the bioactive constituents of AT50, a novel polysaccharide (ATP50-3) was purified, and its anti-neuroinflammatory effects and underlying mechanisms were investigated. ATP50-3 significantly reduced abnormal elevation of inflammatory mediators in lipopolysaccharide (LPS)-induced proinflammatory BV2 cells in vitro and inhibited the activation of nuclear factor kappa B (NF-κB). Moreover, ATP50-3 down-regulated LPS-induced protein levels of Toll-like receptor 4 (TLR4), myeloid differentiation primary response protein (MyD88), p-PI3K (phosphoinositide 3-kinase), and p-Akt (protein kinase B). Further experiments demonstrated that TAK242 (a TLR4 inhibitor) and LY294002 (a PI3K inhibitor) remarkably augmented ATP50-3's down-regulation on LPS-induced proinflammatory mediators. Importantly, ATP50-3 provided neuroprotection against neuroinflammation-induced neurotoxicity in primary cortical and hippocampal neurons by mitigating overproduction of reactive oxygen species and damage to the mitochondrial membrane potential (MMP). Taken together, our findings suggest that ATP50-3 exerts anti-neuroinflammatory and neuroprotective effects through modulation of TLR4-mediated MyD88/NF-κB and PI3K/Akt signaling pathways., (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.)

Extracts or active components from Acorus gramineus Aiton (EAAGA) have been clinically used for cognition impairment more than hundreds of years and are still used in modern times in China and elsewhere worldwide. Previous studies reported that EAAGA improves cognition impairment in animal models. Here, we conducted a preclinical systematic review to assess the current evidence of EAAGA for cognition impairment. We searched 7 databases up until June 2019. Methodological quality for each included studies was accessed according to the CAMARADES 10-item checklist. The primary outcome measures were neurobehavioral function scores evaluated by the Morris water maze test, electrical Y-maze test, step-down test, radial eight-arm maze test, and step-through test. The secondary outcome measures were mechanisms of EAAGA for cognition function. Finally, 34 studies involving 1431 animals were identified. The quality score of studies range from 1 to 6, and the median was 3.32. Compared with controls, the results of the meta-analysis indicated EAAGA exerted a significant effect in decreasing the escape latency and error times and in increasing the length of time spent in the platform quadrant and the number of platform crossings representing learning ability and memory function (all P < 0.01). The possible mechanisms of EAAGA are largely through anti-inflammatory, antioxidant, antiapoptosis activities, inhibition of neurotoxicity, regulating synaptic plasticity, protecting cerebrovascular, stimulating cholinergic system, and suppressing astrocyte activation. In conclusion, EAAGA exert potential neuroprotective effects in experimental cognition impairment, and EAAGA could be a candidate for cognition impairment treatment and further clinical trials., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2020 Yan Li et al.)

BACKGROUND Acori Tatarinowii Rhizoma (ATR), a traditional Chinese herbal medicine, is used to treat Alzheimer's disease (AD), which is a worldwide degenerative brain disease. The aim of this study was to identify the potential mechanism and molecular targets of ATR in AD by using network pharmacology. MATERIAL AND METHODS The potential targets of the active ingredients of ATR were predicted by PharmMapper, and the targets of Alzheimer's disease were searched by DisGeNET. All screened genes were intersected to obtain potential targets for the active ingredients of ATR. The protein-protein interaction network of possible targets was established by STRING, GO Enrichment, and KEGG pathway enrichment analyses using the Annotation of DAVID database. Next, Cytoscape was used to build the "components-targets-pathways" networks. Additionally, a "disease-component-gene-pathways" network was constructed and verified by molecular docking methods. In addition, the active constituents ß-asarone and ß-caryophyllene were used to detect Aß₁₋₄₂-mediated SH-SY5Y cells, and mRNA expression levels of APP, Tau, and core target genes were estimated by qRT-PCR. RESULTS The results showed that the active components of ATR participate in related biological processes such as cancer, inflammation, cellular metabolism, and metabolic pathways and are closely related to the 13 predictive targets: ESR1, PPARG, AR, CASP3, JAK2, MAPK14, MAP2K1, ABL1, PTPN1, NR3C1, MET, INSR, and PRKACA. The ATR active components of ß-caryophyllene significantly reduced the mRNA expression levels of APP, TAU, ESR1, PTPN1, and JAK2. CONCLUSIONS The targets and mechanism corresponding to the active ingredients of ATR were investigated systematically, and novel ideas and directions were provided to further study the mechanism of ATR in AD.

To clarify the effects of steam distilled essential oils (SDEO) from herbs used in traditional Chinese medicine on immune functions, two potential herbs, Acorus gramineusand (AG) and Euodia ruticarpa (ER) cultivated in Taiwan, were selected to assess their immunomodulatory effects using mouse primary splenocytes and peritoneal macrophages. T helper type 1 lymphocytes (Th1) (IL-2), Th2 (IL-5), pro-inflammatory (TNF-α) and anti-inflammatory (IL-10) cytokines secreted by correspondent immune cells treated with SDEO samples were determined using enzyme-linked immunosorbent assay. The total amounts of potential phytochemicals, including total flavonoids, polyphenols and saponins, in these two selected SDEOs were measured and correlated with cytokine levels secreted by immune cells. Our results evidenced that ER SDEO is rich in total flavonoids, polyphenols and saponins. Treatments with AG and ER SDEO significantly ( p < 0.05) increased IL-5/IL-2 (Th2/Th1) cytokine secretion ratios by splenocytes, suggesting that both AG and ER SDEO have the Th2-polarization property and anti-inflammatory potential. In addition, AG and ER SDEO, particularly ER SDEO, markedly decreased TNF-α/IL-10 secretion ratios by macrophages in the absence or presence of lipopolysaccharide (LPS), exhibiting substantial effects on spontaneous and LPS-induced inflammation. Significant correlations were found between the total polyphenols, flavonoids or saponins content in the two selected SDEOs and Th1/Th2 immune balance or anti-inflammatory ability in linear, non-linear or biphasic manners, respectively. In conclusion, our results suggest that AG and ER, particularly ER, SDEO have immunomodulatory potential in shifting the Th1/Th2 balance toward Th2 polarization in splenocytes and inhibiting inflammation in macrophages in the absence or presence of LPS.

Phenylpropanoids comprise a broad spectrum of biologically active natural products. As part of our ongoing research on antiepileptic active compounds from traditional Chinese herb, Acorus calamus var. angustatus Besser, three undescribed phenylpropanoids and twenty-two known ones were isolated. All the undescribed structures were determined by a combination of 1D and 2D NMR, HRMS. In addition, γ-asaronol was identified as racemates and its absolute configuration were determined by the modified Mosher's method and ECD spectral data. Furthermore, some selected isolated compounds were evaluated for their cell viability and neuroprotective activities in H 2 O 2 -induced SH-SY5Y cells. α-Asaronol, β-asaronol, 3-(2,4,5-trimethoxyphenyl)propan-1-ol and 1,2,4-trimethoxy-5-(3-methoxypropyl)benzene exerted potential protective activity from neuronal oxidative stress in all test concentrations ranging from 0.01 to 100 μM, in which the neuroprotective activity of β-asaronol was the best., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Objective: To investigate the mechanism underlying the effects of Shichangpu (Rhizoma Acori Tatarinowii) on attention deficit hyperactivity disorder (ADHD)., Methods: A network pharmacology approach integrating ingredients of Shichangpu (Rhizoma Acori Tatarinowii) and target with ADHD, network construction, molecular function interactions and pathway analysis was used., Results: This approach successfully helped to identify 7 active ingredients of CN, interacting with 21 key targets (ADRA1A, ADRA1B, ADRA2A, ADRA2B, ADRA2C, ADRB1, ADRB2, CHRM1, CHRM2, CHRM3, PTGS1, SLC6A2, SLC6A3, SLC6A4, DRD1, DRD5, HTR2A, ADRA1D, MAOB, GRIA2, HTR1A). The molecular function interactions among candidate targets mainly consisted of four groups: G-protein coupled amine receptor activity, catecholamine binding, monoamine transmembrane transporter activity and neurotransmitter receptor activity. Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis indicated that Shichangpu (Rhizoma Acori Tatarinowii)-regulated pathways were mainly classified into signal transduction and monoamine neurotransmitters., Conclusion: Our investigation revealed that Shichangpu (Rhizoma Acori Tatarinowii) could improve the symptoms of ADHD by regulating neurotransmitter, in multiple types of compounds-target-pathway, which may be implicated in the major pathological processes of ADHD.

In recent years, the extraction fraction of volatile oil from Acorus gramineus has significant effects on anti-dementia and improving the learning and memory of animals. To date, limited studies have determined whether volatile oil from A. gramineus has the protective effect on neuronal damage. The aim of this study was to investigate the protective effects of volatile oil from A. gramineus on Alzheimer's disease (AD) mice, by means of behavior test, immunohistochemistry and western blot methods. In this study, mice were injected with Aβ 1-42 in the bilateral hippocampus to establish the AD model. On the seventh day after modeling, the mice with cognitive dysfunction were selected by the novel object recognition task. Subsequently, the volatile oil treatment groups underwent intragastric administration for per 10 g body weight 2.5 or 5 μL volatile oil from A. gramineus for 3 weeks. The control group and the AD group were given the same amount of saline. Our results showed that after treatment of volatile oil from A. gramineus, the number of Doublecortin and Nestin positive cells increased significantly, suggesting that the volatile oil from A. gramineus may induce the regeneration of hippocampal neurons in mice, and promote the growth of hippocampal neurons by upregulation of brain-derived neurotrophic factor, tyrosine protein kinase B, and neurotrophin-3 expression. These results might provide more experimental evidences for underlying mechanism about the neuroprotective effects of volatile oil from A. gramineus against AD relevant symptoms. Anat Rec, 302:2261-2270, 2019. © 2019 American Association for Anatomy., (© 2019 American Association for Anatomy.)

Based on the prescription books of herbs and medical books of all dynasties,this article makes a textual research on the name,origin,position,quality,collection,processing and concocting of Acorus tatarinowii used in the classical prescription,and clarifies the relationship between ancient and modern,so as to provide reference and basis for the development and utilization of the classical famous prescription.According to research,A. tatarinowii has many aliases and is often remembered as &quot; Chang pu&quot; when use as medicine; It has a wide distribution of resources in our country,all over the country have produced and mostly wild,its producing areas there is a trend of migration to the southeast; It is recorded in the ancient books of Chinese herbs that most of its medicinal parts are roots,and to root thin,solid quality,dense,aromatic smell,full taste,chewing less slag of high quality; It is harvested in February,May,August and December,and dried in the shade after harvesting; Its concocting methods are more than 20 species have been recorded; Before the Tang Dynasty,the basis of the medicinal A. tatarinowii was relatively chaotic,through textual research,it is concluded that A. tatarinowii should be the mainstream in all dynasties,and that its quality is superior to that of other species in the same genus.It is recommended to be used in &quot; Kaixin san&quot; and &quot; rehmannia drink&quot;.

Microcystis blooms and their associated microcystins pose a significant health risk to humans. Microcystis normally occurs as colonies in eutrophic water bodies, and its physiological tolerance to algaecides is dissimilar to that of unicellular forms. However, the differences of physiological response to algaecides between unicellular and colonial Microcystis have been poorly explored. The current study investigated the effects of hexane extract of Acorus calamus rhizome (HEACR) on the physiological and photosynthetic mechanisms of unicellular and colonial M. aeruginosa in the laboratory. We analyzed the cell density, reactive oxygen species (ROS) level, malonaldehyde (MDA) content, photosynthetic pigments, capsular polysaccharide (CPS), and photosystem (PS II) parameters of the two morphological forms of Microcystis. Our results show that HEACR suppresses the growth of both unicellular and colonial M. aeruginosa, increases the intracellular ROS level and cause lipid peroxidation, as well as exerting a detrimental effect on chlorophyll a (chl a) content and photosynthetic efficiency. Almost 100% inhibition was observed for unicellular and colonial M. aeruginosa after 3 d exposure to 50 and 100 mg L -1 HEACR, respectively. The ROS level increase, MDA accumulation, the chl a decrease and carotenoid increase in unicellular M. aeruginosa were all more obvious than that in colonial cells. The fall in photosynthetic efficiency of unicellular M. aeruginosa were also more significant than that of colonial cells. After 3d exposure, the maximum quantum yield of PS II photochemistry (Fv/Fm), effective quantum yield of PS II photochemistry (Fv'/Fm') and effective quantum yield of photochemical energy conversion in PS II (YII) of unicellular M. aeruginosa was almost totally inhibited by 20 mg L -1 HEACR, while the F v /F m , F v '/F m ' and YII of colonial M. aeruginosa decreased by 43%, 26% and 66% for 100 mg L -1 of HEACR, respectively. Comparing the two morphological forms of Microcystis, colonies show a greater increase in CPS level to more effectively resist the stress of HEACR and to mitigate ROS generation thereby better defending against oxidative damage. Furthermore, colonial M. aeruginosa shows better photoprotection ability than the unicellular form when exposed to HEACR. The colonies also sustain their maximum electron transport rate, increase their tolerance to strong light, and maintain a higher ability to disperse excess energy. These results demonstrated that HEACR can significantly interfere with the growth and physiological processes of both unicellular and colonial M. aeruginosa, but that colonial M. aeruginosa has a greater ability to adjust physiological tolerance to resist the stresses of HEACR., (Copyright © 2019. Published by Elsevier B.V.)

Valeriana is a common plant species used for various healing purposes in folk medicine since antiquity. This study investigates the phytochemical profile, antioxidant, cytotoxic, and insecticidal activity of Valeriana alliariifolia Adams, a species that has traditionally been used in Turkey. For the analyses we prepared four root extracts of V. alliariifolia Adams using hexane (HM1), chloroform (CM1), ethanol (EM1), and water (WM1) for maceration. Additionally, two extracts were also prepared from its roots by maceration separately with ethanol (EM2) and water (WM2). One sample was prepared as a water infusion (WI), according to the procedure used in Turkish traditional medicine. The 2,2-Diphenyl-1-picrylhydrazyl (DPPH) scavenging and 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid (ABTS) radical cation scavenging activity tests showed that ethanol extracts had the strongest antioxidant activity: EM1 (IC50 - DPPH: 17.694 µg/mL; ABTS: 23.8 µg/mL) and EM2 (IC50 - DPPH: 20 µg/mL; ABTS: 21.5 µg/mL). The hexane extract, HM1, was the most cytotoxic (IC50<10 µg/mL against HepG2 and HUVEC) and EM2 strongly cytotoxic (IC50<10 µg/mL against HepG2 and IC50: 11.96 µg/mL against HUVEC). The extracts with demonstrated cytotoxic activities were further examined to check their insecticidal activity against adult female mosquito Aedes aegypti and first instar Ae. aegypti larvae. HM1 was the most effective (90±10 %), which was consistent with its cytotoxic activity. Because of the high antioxidant, cytotoxic, and insecticidal activities, we ran phytochemical analyses of the HM1, EM1, and EM2 extracts with GC-MS (for HM1) and LC-MS/MS (for EM1 and EM2). We also analysed the composition of the essential oil obtained from V. alliariifolia roots by micro-distillation in order to compare its content with HM1, which contains volatile compounds. Phytochemical analyses revealed that the major compound in HM1 was isovaleric acid (16 %) and in the essential oil 1,8-cineole (2.9 %). EM1 and EM2 contained 5-O-caffeoylquinic acid (chlorogenic acid), verbascoside (acteoside), and 3,5-dicaffeoylquinic acid as major components. In the light of our findings and available literature, we can conclude that V. alliariifolia has a good bioactive potential that could be used for different purposes, including the development of new agents for the treatment of various diseases. The difference in the content between the essential oil and HM1 was remarkable. It suggests that the variability observed in the activity of the samples was a result of composition and that, therefore, the aim of treatment should dictate which type of preparation is to be selected. An added value of our study is that it determined verbascoside and methylquercetin rutinoside for the first time in the Valeriana extracts.

Acori Tatarinowii Rhizoma (ATR, the dried rhizome of Acorus tatarinowii Schott.) is a traditional Chinese medicine widely used to treat brain diseases, e.g. depression, forgetfulness, anxiety and epilepsy. Several lines of evidence support that ATR has neuronal beneficial functions in animal models, but its action mechanism in cellular level is unknown. Here, we identified α-asarone and β-asarone could be the major active ingredients of ATR, which, when applied onto cultured rat astrocytes, significantly stimulated the expression and secretion of neurotrophic factors, i.e. nerve growth factor (NGF), brain derived neurotrophic factor (BDNF) and glial derived neurotrophic factor (GDNF), in dose-dependent manners. These results suggested that the neuronal action of ATR, triggered by asarone, might be mediated by an increase of expression of neurotrophic factors in astrocytes, which therefore could support the clinical usage of ATR. In addition, application of PKA inhibitor, H89, in cultured astrocytes partially blocked the asarone-induced neurotrophic factor expression, suggesting the involvement of PKA signaling. The results proposed that α-asarone and β-asarone from ATR could serve as potential candidates for drug development in neurodegenerative diseases., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Objective: To investigate the effects of Acorus tatarinowii Schott and its active component 5- hydroxymethyl furfural (HMF) on learning and memory and ERK/CREB signal in hippocampus of rats with exercise-induced fatigue., Methods: SD rats were randomly divided into normal group (A), exercise group (B), exercise + HMF low, middle and high dose treatment group (C, D, E), exercise + acorus tatarinowii Schott low, middle and high dose treatment group (F, G, H), with ten rats in each group. The rats in group C, D and E were treated with HMF at the doses of 0.10, 1.00 and 3.00 mg. kg -1 by ig. The rats in group F, G and H were treated with the extracts of Acorus tatarinowii Schott at the doses of 0.12, 1.20 and 4.80 g. kg -1 by ig. Learning and memory of rats were tested by the method of water maze experiment, and the expression levels of p-ERK1/2 and p-CREB protein in hippocampus of rats were tested by the method of Western blot in the end of the experiment., Results: The escape latencies of E and H groups were lower than those of groups B, C, D, F and G; and the numbers of plateau crossing were more than those of groups B, C, D, F and G and the expression levels of p-ERK1/2, p-CREB protein were higher than those of groups B, C, D, F and G , respectively(P ＜ 0.01). There was no significant difference in the above indexes among groups A, E and H(P＞0.05) except that the expression levels of p-ERK2 protein in group E were lower than those in group A and H (P＜0.05)., Conclusion: Acorus tatarinowii and its active component- HMF can improve the learning and memory of rats with exercise-induced fatigue, and the mechanism is related to the up-regulation of ERK / CREB signal in hippocampus of rats with exercise-induced fatigue.

The chemical constituents and action targets of Acori Tatarinowii Rhizoma and Curcumae Radix were screened by network pharmacological method,and the mechanism of the combination of Acori Tatarinowii Rhizoma and Curcumae Radix in the treatment of epilepsy was analyzed. All chemical constituents of Acori Tatarinowii Rhizoma and Curcumae Radix were retrieved by TCMSP,and their action targets were screened. Component target PPI network was constructed. Epilepsy-related genes were retrieved from PharmGkb database,and PPI networks of disease targets were drawn by Cytoscape software. Cytoscape software was used to merge the network,screen the core network,and further analyze the gene GO function and KEGG pathway enrichment,which was verified by experimental research. One hundred and five chemical constituents of Acori Tatarinowii Rhizoma and 222 chemical constituents of Curcumae Radix were retrieved. Nineteen compounds were selected as candidate compounds according to OB and DL values. Among them,4 chemical constituents of Acori Tatarinowii Rhizoma and 15 chemical constituents of Curcumae Radix were found. A total of 88 target proteins were retrieved by retrieving TCMSP data,and PPI network was constructed. Through PharmGkb database,29 epilepsy-related genes were retrieved and disease target network was established. Cytoscape software and plug-ins were used for network merging and core network screening,and 69 genes were screened out. Through GO function analysis and KEGG pathway analysis,the mechanism of anti-epilepsy is related to prolactin signaling pathway,HTLV-Ⅰ infection signaling pathway,MAPK signaling pathway and herpes simplex infection signaling pathway. Further experimental verification showed that the serum prolactin level in epileptic rats was significantly increased. The neurons in hippocampal CA1 area degenerated,necrotized and lost 24 hours after epileptic seizure,and some neuron interstitial edema occurred. The possible mechanism of compatibility of Acori Tatarinowii Rhizoma and Curcumae Radix is related to serum prolactin level,MAPK signaling pathway,HTLV-Ⅰ infection and herpes simplex infection. The analysis may be related to viral encephalitis caused by HTLV-Ⅰ virus and herpes simplex infection,which damages nerve cells and causes seizures.

Resveratrol and its methyl ethers, which belong to a class of natural polyphenol stilbenes, play important roles as biologically active compounds in plant defense as well as in human health. Although the biosynthetic pathway of resveratrol has been fully elucidated, the characterization of resveratrol-specific O-methyltransferases remains elusive. In this study, we used RNA-seq analysis to identify a putative aromatic O-methyltransferase gene, AcOMT1, in Acorus calamus. Recombinant AcOMT1 expressed in Escherichia coli showed high 4'-O-methylation activity toward resveratrol and its derivative, isorhapontigenin. We purified a reaction product enzymatically formed from resveratrol by AcOMT1 and confirmed it as 4'-O-methylresveratrol (deoxyrhapontigenin). Resveratrol and isorhapontigenin were the most preferred substrates with apparent K m values of 1.8 μM and 4.2 μM, respectively. Recombinant AcOMT1 exhibited reduced activity toward other resveratrol derivatives, piceatannol, oxyresveratrol, and pinostilbene. In contrast, recombinant AcOMT1 exhibited no activity toward pterostilbene or pinosylvin. These results indicate that AcOMT1 showed high 4'-O-methylation activity toward stilbenes with non-methylated phloroglucinol rings., (Copyright © 2018 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.)

In this study, solid dispersion technology was used to develop volatile oil from Acorus tatarinowii self-nanoemulsion dropping pills(VOA-SNEDDS-DP) and its protective effect on acute myocardial ischemia injury was evaluated. Taking exterior quality, weight variation and the resolving time as comprehendsive evaluation indexes, the preparation process and formulation of the dropping pills were optimized by orthogonal design, and the dissolution rate in vitro of the optimized VOA-SNEDDS-DP was investigated. The rat model of acute myocardial ischemia was induced by intraperitoneal injection of isoproterenol hydrochloride and the serum levels of superoxide dismutase(SOD), malondialdehyde(MDA), creatine kinase(CK) and pathological changes of myocardial tissue were determined to evaluate therapeutic effect of the dropping pills on acute myocardial ischemia. The results showed that the optimal formulation and preparation process of VOA-SNEDDS-DP were as follows: PEG6000-PEG8000 was 1∶1, proportion of VOA-SNEDDS and matrix was l∶2.5, the temperature of drug fluids was 75 ℃, drop rate was 35 drops/min, drop distance was 5 cm, the condensing agent temperature was 2-10 ℃. The content of β-asarone in the dropping pills was 42.46 mg·g~(-1). The accumulated dissolution rate of the dropping pills reached 93.85% in 10 min. The results of pharmacodynamic experiments showed that VOA-SNEDDS-DP could significantly increase the SOD content(P<0.05), reduce the levels of MDA and CK(P<0.05) in serum, and effectively improve the pathological morphology of myocardial tissue. These results revealed that the preparation of VOA-SNEDDS-DP by solid dispersion technology was stable and feasible, and VOA-SNEDDS-DP had protective effect on acute myocardial ischemia injury.

The diets of Indigenous people rely on food and medicinal plants harvested directly from the land and there is increasing concern from Indigenous knowledge holders over changes to the appearance and flavor of wild harvested food and medicinal plants. We collected samples of muskrat root, considered an important medicinal plant, at 11 traditional collection locations to quantify contaminants of concern. There were no spatial or temporal trends apparent and the risk via consumption was found to be very low. This study provides a "base" measure to which future samples may be compared, especially as development and other anthropogenic pressures increase. This study is also an example of how western science and Indigenous knowledge, can be merged for the benefit of both knowledge systems in what is known to Indigenous groups as etuaptmumk or 'two-eyed seeing'.

Background: Some traditional Oriental herbal medicines, such as Acorus tatarinowii and Acorus gramineus, produce beneficial effects for cognition enhancement. An active compound in rhizomes and the bark of these plants is α-asarone., Purpose: This study investigated the effects of α-asarone on the proliferation and differentiation of neural progenitor cells (NPCs) in a primary culture and a murine model of ischemic stroke., Methods: NPCs were isolated from mouse fetal cerebral cortices on embryonic day 15, and all experiments were performed using passage 3 NPCs. We utilized a cell counting kit-8 assay, flow cytometry, western blot, and immunohistochemical analysis to assess proliferation and differentiation of NPCs and employed α-asarone in NPC transplanted ischemic stroke mice to evaluate stroke-related functional recovery using behavioral and immunohistochemical analysis., Result: Treatment with 1 µM, 3 µM, or 10 μM α-asarone induced significant NPC proliferation compared to vehicle treatment. Induced NPCs expressed the neuronal marker neuronal nuclei (NeuN) or the astrocyte marker S100 calcium-binding protein B (S100β). Both immunohistochemistry and flow cytometry revealed that treatment with α-asarone increased the number of NeuN-immunoreactive cells and decreased the number of S100β-immunoreactive cells. Treatment with α-asarone also increased the expression of β-catenin, cyclin D1, and phosphorylated extracellular signal-regulated kinase (ERK) compared to vehicle treatment. In a murine model of ischemic stroke, treatment with α-asarone and transplanted NPCs alleviated stroke-related functional impairments. The corner and rotarod test results revealed that treatment with α-asarone in the NPC transplanted group had greater-than-additive effects on sensorimotor function and motor balance. Moreover, α-asarone treatment promoted the differentiation of transplanted NPCs into NeuN-, glial fibrillary acidic protein (GFAP)-, platelet-derived growth factor-α (PDGFR-α)-, and 2', 3'-cyclic nucleotide 3'-phosphodiesterase (CNPase)-immunoreactive cells., Conclusion: α-asarone may promote NPC proliferation and differentiation into neuron-lineage cells by activating β-catenin, cyclin D1, and ERK. Moreover, α-asarone treatment facilitated neurofunctional recovery after NPC transplantation in a murine model of ischemic stroke. Therefore, α-asarone is a potential adjunct treatment to NPC therapy for functional restoration after brain injuries such as ischemic stroke., (Copyright © 2018 Elsevier GmbH. All rights reserved.)

In this study, silver nanoparticles were synthesized (AgNPs) using aqueous rhizome extract of Acorus calamus (ACRE) and evaluated their in vitro anticancer activity and in vivo toxicity in a Wistar rat model. The synthesized AgNPs showed good catalytic activity against different organic pollutant dyes. In vitro cytotoxic effects of AgNPs were assessed in Hep2, COLO 205 and SH-SY5Y cells using MTT assay. Further, the apoptotic changes induced by AgNPs in more susceptible Hep2 cells were observed through AO/EB, DCFH-DA, Rhodamine 123, PI/DAPI staining, oxidative stress markers and Western blotting. In vivo toxicity study revealed substantial alterations in the levels of serum biochemical markers including AST, ALT, LDH and inflammatory markers such as TNF-α and IL-6 on day 29 when rats treated with AgNPs as compared to control, however, these levels were restored to normal at the end of washout period on day 89. No remarkable changes were observed in liver oxidative stress enzymes. ICP-OES analysis indicated bio-distribution of silver in spleen (5.67 μg/g) and liver (4.98 μg/g) in rats treated with 10 mg/kg b.w of AgNPs on day 29 and elimination of silver from all organs was observed at the end of washout period on day 89. Histopathological analysis revealed no significant changes in kidney, spleen, lungs, heart, testis and brain with 5 and 10 mg/kg b.w of AgNP. However, 10 mg/kg b.w of AgNPs showed moderate degree of cell swelling and vacuolar degeneration in liver and these alterations were reverted back to normal at the end of washout period. Findings from this study signify green synthesized AgNPs at low concentrations might be useful in many ways with ecofriendly nature., (Copyright © 2018 Elsevier B.V. All rights reserved.)

In order to increase the solubility of volatile oil from Acori Tatarinowii Rhizoma, this study was to prepare self-nanoemulsion of volatile oil from Acori Tatarinowii Rhizoma . The prescriptions were preliminarily screened by miscibility studies, excipient compatibility tests, and pseudo-ternary phase diagrams, and then the optimal formulation was obtained by using the Box-Behnken response surface method, with particle size and drug-loading rate as the indicators. The self-nanoemulsion prepared by optimal prescription was characterized and evaluated for in vitro dissolution. The results showed that the optimal prescription for this volatile oil self-nanoemulsion was as follows: 41.7% volatile oil, 46.8% Tween-80, and 11.5% PEG-400. The prepared self-nanoemulsion was clear and transparent, with drug-loading of (192.77±1.64) mg·g⁻¹, particle diameter of (53.20±0.94) nm, polydispersity index of 0.230± 0.013, and Zeta potential of (-12.2±0.7) mV. The in vitro dissolution of self-nanoemulsion was higher than that of volatile oil. In this research, volatile oil served as the oil phase in self-nanoemulsion, so the prescription was simpler and the drug loading rate was higher. The prepared self-nanoemulsion complied with the relevant quality requirements, providing a reference for the preparation of volatile oil formulations., Competing Interests: The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose., (Copyright© by the Chinese Pharmaceutical Association.)

To screen the target for the treatment of depression of Acori Tatarinowii Rhizoma and Curcumae Radix using the pharmacological method of network pharmacology, in order to define the mechanism of antidepressant effect. Pharmacological data (TCMSP) of forall of chemical constituents of Acori Tatarinowii Rhizoma and Curcumae Radix through traditional Chinese medicine system (TCMSP) was retrieved to screen the target sites, and construct the component target PPI network. PharmGkb database was retrieved for the genes associated with depression, and the disease target was mapped using the Cytoscape software. The Cytoscape software was used to merge the network and filter the core network, and further analyze the gene GO function and the KEGG pathway enrichment. There were 62 nodes and 87 connections on the target PPI network. The PPI network had 1 289 nodes and 17 714 connections. After the network merged, the component-target-disease network had 1 337 nodes and 17 801 connections. Through screening the core network, there were 63 nodes and 935 connections, which represented the complex interaction between the components and the target. Gene GO functional analysis suggested that biological processes, molecular functions and cell components were involved. Gene KEGG pathway enrichment analysis showed associations with misfolded protein, secretory hormone secretion, and apoptosis of hippocampal neurons. The possible mechanism for treating depression is the adjustment of wrong folding protein, sex hormone secretion and apoptosis of hippocampal neurons., Competing Interests: The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose., (Copyright© by the Chinese Pharmaceutical Association.)