Chemical composition and anticonvulsant activities of herb pair of Gastrodia elata Blume-Acorus tatarinowii Schott decoction on experimentally induced seizures in mice.

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-1ß, 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.

Acorus tatarinowii Schott: A Review of Its Botany, Traditional Uses, Phytochemistry, and Pharmacology.

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.

Acorus calamus extract and its component α-asarone attenuate murine hippocampal neuronal cell death induced by l-glutamate and tunicamycin.

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.

Analysis of Environmental Contaminants in Muskrat Root, Acorus americanus Raf.: A Traditional Indigenous Medicinal Plant.

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'.

[Textual research on classical prescription of Acorus tatarinowii].

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 " Chang pu" 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 " Kaixin san" and " rehmannia drink".

[Study on preparation of volatile oil from Acorus tatarinowii self-nanoemulsion dropping pills and its protective effect on acute myocardial ischemia injury].

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 ß-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.

[Research on network pharmacology of Acori Tatarinowii Rhizoma combined with Curcumae Radix in treating epilepsy].

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.

New lignans attenuating cognitive deterioration of Aß transgenic flies discovered in Acorus tatarinowii.

Five new lignan racemates, (±)-tatarinoid D-H (1-5), and three known analogues (6-8) were isolated from the rhizomes of Acorus tatarinowii. Their structures were established by 1D, 2D-NMR, HR-MS, IR and optical spectral data. Among them, 1 and 6-8 can alleviate the cognitive deterioration of Aß transgenic flies.

[Preparation and quality evaluation of volatile oil from Acori Tatarinowii Rhizoma self-nanoemulsion].

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.

[Mechanism of Acori Tatarinowii Rhizoma-Curcumae Radix treating depression based on network pharmacology].

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.

Bioactive Asarone-Derived Phenylpropanoids from the Rhizome of Acorus tatarinowii Schott.

Eight new (1a/1b, 2a, 3a, 4a/4b, and 5a/5b) and seven known (2b, 3b, and 6-10) asarone-derived phenylpropanoids, a known asarone-derived lignan (12), and four known lignan analogues (11 and 13-15) were isolated from the rhizome of Acorus tatarinowii Schott. The structures were elucidated via comprehensive spectroscopic analyses, modified Mosher's method, and quantum chemical calculations. Compounds 1-8 were present as enantiomers, and 1-5 were successfully resolved via chiral-phase HPLC. Compounds 1a/1b were the first cases of asarone-derived phenylpropanoids with an isopropyl C-3 side-chain tethered to a benzene core from nature. Hypoglycemic, antioxidant, and AChE inhibitory activities of 1-15 were assessed by the α-glucosidase inhibitory, ORAC, DPPH radical scavenging, and AChE inhibitory assays, respectively. All compounds except 3a showed α-glucosidase inhibitory activity. Compound 3b has the highest α-glucosidase inhibitory effect with an IC50 of 80.6 µM (positive drug acarbose IC50 of 442.4 µM). In the antioxidant assays, compounds 13-15 exhibited ORAC and DPPH radical scavenging activities. The results of the AChE inhibitory assay indicated that all compounds exhibited weak AChE inhibitory activities.

In vivo evaluation of hot water extract of Acorus gramineus root against benign prostatic hyperplasia.

BACKGROUND: Acorus gramineus has been reported to exhibit various pharmacological effects including inhibition of cholesterol synthesis, enhancement of lipid metabolism, prevention of dementia and inhibition of mast cell growth. According to the Chinese compendium of materia media, it has been reported that Acorus spp. is effective for sedation, dementia prevention as well as diuretic effect. In addition, it showed more than equivalent activity compared to furosoemide, a drug known to be effective in diuretic action in animal model study. However, their effectiveness against benign prostatic hyperplasia (BPH) of Acorus gramineus has not been reported. This study was designed to evaluate the effect of Acorus gramineus root hot water extract (AG) against BPH in vivo. METHODS: Male rats, 10 weeks of age and weighing 405 g ± 10 g, were used for this study. Biomarkers were evaluated including prostate weight, prostate weight ratio, hormonal changes, 5-α reductase type II androgen receptor (AR) of the prostate gland and anti-oxidant activation factors related to BPH. These biomarkers were measured in vivo test. RESULTS: AG showed significant effect at the 250 and 500 mg/kg/day in rats. Groups treated with AG displayed significantly lower levels of prostate gland weight (0.79 g) compared to the BPH induced group (1.19 g). Also, dihydrotestosterone (DHT) level was decreased from 61.8 to 100% and androgen receptor expression level was decreased from 111 to 658%. Any hematological toxicity of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) level wasn't observed. CONCLUSION: This study indicated that AG was effective for reducing BPH symptoms. TRIAL REGISTRATION: Not applicable.

Comparative Study of Different Acorus Species in Potentiating Neuronal Differentiation in Cultured PC12 Cells.

Acori Tatarinowii Rhizoma (ATR), the rhizome of Acorus tatarinowii Schott, is a common traditional Chinese medicine being used clinically for mental disorder. However, other Acorus species herbs are all having the same Chinese name 'Chang Pu', making the confusion in herbal market. Acori Graminei Rhizoma (AGR) and Acori Calami Rhizoma (ACR) are common adulterants of ATR. Here, we aim to provide a comparative analysis between ATR, AGR, and ACR in potentiating neuronal differentiation. Volatile oil, derived from Acorus species, was applied onto cultured PC12 cells, and various parameters were determined: (i) transcriptional activation of neurofilament promoters was determined by the promoter-driven luciferase activity assay; (ii) the neurite outgrowth of PC12 cells was captured and measured; and (iii) the neurofilament expression and its underlying mechanism were analyzed by western blotting. The co-treatment of ATR, AGR, or ACR volatile oil with low concentration of nerve growth factor (NGF) could potentiate the NGF-induced neuronal differentiation in cultured PC12 cells. In addition, application of protein kinase A inhibitor H89 in cultures blocked the induction of neurofilament. Among these three Acorus species, ATR volatile oil showed the highest NGF-induced induction in neurite outgrowth and neurofilament expression, as compared with that of AGR and ACR. Copyright © 2017 John Wiley & Sons, Ltd.

A Novel Tropoloisoquinoline Alkaloid, Neotatarine, from Acorus calamus L.

A novel tropoloisoquinoline alkaloid, neotatarine (1), was isolated from the 95% ethanol extract of the rhizome parts of Acorus calamus L. The chemical structure was unambiguously elucidated by spectroscopic and single-crystal X-ray diffraction analysis. Neotatarine (1) exhibited significantly inhibitory activity against Aß25 - 35 induced PC12 cell death with 2, 4 and 8 µm comparing with the assay control (P < 0.01).

New Acorane-Type Sesquiterpene from Acorus calamus L.

A new sesquiterpene, named neo-acorane A (1), and two known ones, acoric acid (2) and calamusin D (3), were isolated from a 95% ethanol extract of the rhizome parts of Acorus calamus L. Their structures were elucidated by spectroscopic methods, and the absolute configurations were determined by single-crystal X-ray diffraction analysis. Compounds 1 and 2 are nonisoprenoid sesquiterpenoids, likely biosynthesized from an acorane-type sesquiterpene by oxidative fission of the six- or five-membered ring. Moreover, compounds 1 (10 µM), 2 (5 µM and 10 µM) and 3 (10 µM) showed cell proliferation activity on the SK-N-BE (2) cell line.

Effect of Acorus calamus L. Polysaccharide on CD274 and CD326 Expression by Lewis Lung Carcinoma Cells in Mice.

Tumor cells can maintain their growth via immunosuppression and escape from host antitumor immunity by controlling the PD-1/PD-L1 system. Expression of PD-L1 (CD274) is an inhibitory signal for T cells, while the increase in CD326 expression in the tumor tissue correlates with metastasis development. The experimental preparation on the basis of α(1,2)-L-rhamno-α(1,4)-D-galactopyranosyluronan from Acorus calamus L. produces an antitumor effect: it reduces tumor node size and the number and area of metastases after transplantation of Lewis lung carcinoma. Using flow cytometry, we demonstrated a decrease in the population of tumor cells expressing surface CD274 (PD-L1) and CD326 antigens after 20-day course of α(1,2)-L-rhamno-α(1,4)-D-galactopyranosyluronan.

[A new sesquiterpene from Acorus calamus (â ¡)].

A new quaiane-tgpe sesquiterpene was isolated from the 95% ethanol extract of the rhizomes of Acorus calamus by silica gel and sephadex LH-20 column chromatographic methods. Structure and absolute configuration of the sesquiterpene were elucidated by spectroscopic data and X-ray crystallographic analysis, and named as 1R,5R,7S-guaiane-4R,10R-diol-6-one.

Cytotoxic Lignans and Sesquiterpenoids from the Rhizomes of Acorus tatarinowii.

Five new compounds, including a rare phenyldihydronaphthalene lignanamide (1), an unusual hybrid-norlignan derivative (2), a rare cycloheptenone oxide derivative (3), one new acorane-type sesquiterpenoid (4), and one new guaiane-type sesquiterpenoid (5), together with seven known compounds (6-12), have been isolated from the rhizomes of Acorus tatarinowii. The structures of compounds 1-5 were determined by means of extensive spectroscopic methods. To the best of our knowledge, this is first report of a phenyldihydronaphthalene lignanamide and hybrid-norlignan and cycloheptenone oxide derivatives from the genus Acorus. In addition, compound 5 represents the first guaiane-type sesquiterpenoid with an epoxy group located between C-6 and C-9 from natural sources. Compounds 1-12 were evaluated for their in vitro cytotoxicity against five tumor cell lines. Among them, 2, 3, 5, and 10 exhibited moderate cytotoxicity with IC50 values of 2.11-9.23 µM.

Acorus calamus Linn.: phytoconstituents and bactericidal property.

Acorus calamus Linn. of the family Araceae (Acoraceae), commonly known as Sweet Flag and Vacha. The rhizome of this plant has medicinal properties against bugs, moths, lice and emetic stomach in dyspepsia. Chemical composition of the hydro-distilled essential oil obtained from the rhizomes of A. calamus was analyzed by gas chromatography equipped with flame ionization detector and gas chromatography coupled with mass spectrometry. The essential oil of A. calamus and its major compound ß-asarone were tested against five Gram-positive, eight Gram-negative bacteria, and three fungi by the tube-dilution method at a concentration rang of 5.0-0.009 mg/mL. Forty constituents were identified which comprised 98.3 % of the total oil. The major compound ß-asarone (80.6 %) was identified and confirm by NMR ((1)H- & (13)C-) in rhizome oil of A. calamus. The organism Micrococcus luteus was found to be more susceptible to the oil with minimum bactericidal concentration (MBC) value of 0.032 ± 0.004 mg/mL, followed by Aspergillus fumigatus, Aspergillus niger and Micrococcus flavus with MBC values of 0.104 ± 0.016, 0.117 ± 0.017 and 0.143 ± 0.013 mg/mL, respectively. The compound ß-asarone was susceptible to the microorganism A. niger with MBC value 0.416 ± 0.065 mg/mL. The present study revealed that tetraploid variety of A. calamus is growing in this region with substantial amount of ß-asarone. The oil showed bactericidal property against tested bacteria and fungi. The ß-asarone exhibited poorer bactericidal activity against test microorganisms.

Effects of Water-Soluble Polysaccharides with Different Chemical Structure, Isolated from Acorus calamus L. and Trifolium pratense L., on Nitric Oxide Production: A Screening Study.

Screening study of the effects of sweet flag (Acorus calamus L.) rhizome and clover (Trifolium pratense L.) aerial part on the production of NO by mouse macrophages was carried out. The polysaccharides were separated by ion exchange chromatography into fractions differing by monomeric composition and ramification type and were used in concentrations of 20, 40, and 100 µg/ml. Four fractions of Acorus calamus L. (PSF-101, PSF-102, PSF-103, and PSF-105), used in different concentrations, moderately stimulated nitrite production by macrophages. Three of five Trifolium pratense L. polysaccharides (PS62-3, PS62-4, and PS62-5) exhibited a significant specific effect on NO production. Rhamnogalactouronans from clover PS63-3 in all concentrations and from PS62-5 in a concentration of 100 µg/ml exhibited the highest activity, comparable to the NO-stimulatory activity of the reference LPS, while polysaccharide PS62-3 in a concentration of 40 µg/ml exhibited even higher activity.