[A new neolignan glycoside from Acori Tatarinowii Rhizoma].

The main chemical constituents from Acori Tatarinowii Rhizoma were isolated and purified using the macroporous resin,microporous resin(MCI) and octadecylsilyl silica gel(ODS) column chromatography, as well as semi-preparative high performance liquid chromatography. Their chemical structures were elucidated by spectroscopic analyses including mass spectrometry(MS),nuclear magnetic resonance(NMR), ultraviolet(UV), infrared(IR) and circular dichoism(CD) combined with literature data.A total of 11 compounds were isolated and identified, including 4 lignan glycosides, 2 benzyl alcohol glycosides, 4 flavonoid glycosides, and 1 α-tetralone glycoside:(7S,8R)-dihydrodehydrodiconiferyl alcohol 9-O-ß-D-glucopyranosyl-9'-O-ß-D-glucopyranosyl-(1 → 6)-ß-D-glucopyranoside(1),(7S, 8R)-dihydrodehydrodiconiferyl alcohol 9-O-ß-D-glucopyranoside(2),(7S, 8R)-dihydrodehydrodiconiferyl alcohol di-9, 9'-O-ß-D-glucopyranoside(3),(+)-lyoniresinol 3α-O-ß-D-glucopyranoside(4), benzyl alcohol O-ß-D-glucopyranosyl-(1→6)-ß-D-glucopyranoside(5), benzyl alcohol O-ß-D-xylopyranosyl-(1→6)-ß-D-glucopyranoside(6), 3'-O-methylepicatechin 7-O-ß-D-glucopyranoside(7), 3'-O-methylcatechin 7-O-ß-D-glucopyranoside(8), apigenin 6-C-ß-D-glucopyranosyl-7-O-ß-D-glucopyranoside(9), isoscoparin 7-O-ß-D-glucopyranoside(10), and(4R)-8-hydroxy-α-tetralone-4-O-ß-D-glucopyranoside(11). Compound 1 is a new neolignan glycoside, and compounds 2-5 and 7-11 are isolated from genus Acorus for the first time.

Network pharmacology and experimental validation reveal the mechanisms of sniffing essential oil of Acori Tatarinowii rhizoma in treating olfactory dysfunction.

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.

Safety assessment of Acori Tatarinowii Rhizoma: acute and subacute oral toxicity.

Introduction: Acori Tatarinowii Rhizoma (ATR) is a well-known traditional Chinese medicine that is used for treating neuropathic diseases. However, there is little information about the safety of ATR. Methods: The present study evaluated the acute and subacute oral toxicity of a water extract of ATR in Institute of Cancer Research (ICR) mice. In acute trials, a single administration of extract at a dose 5,000 mg/kg body weight led to no clinical signs of toxicity or mortality, indicating that the lethal dose (LD50) exceeded 5,000 mg/kg. A subacute toxicity test was done using daily doses of 1,250, 2,500, and 5,000 mg/kg of the ATR extract for 28 days, which did not show any adverse clinical symptoms or mortality. However, the male renal organ index and urea level in mice given 5,000 mg/kg was obviously abnormal, which was consistent with pathological results and suggested that this dose might cause kidney injury. Results: Doses of ATR lower than 2,500 mg/kg could be regarded as safe, although the potential cumulative effects of long-term use of high doses of ATR need to be considered. Discussion: The study highlights the function of ATR in reducing blood lipids and provides a new idea for its widespread clinical use in the future.

Acori Tatarinowii Rhizoma prevents the fluoxetine-induced multiple-drug resistance of Escherichia coli against antibiotics.

BACKGROUND: In treating depression, the residual anti-depressant in gut interacts with the microbiome, leading to the appearance of multiple drug resistant (MDR) mutants, which poses a challenge for the treatment of infectious complications. Strategy is needed to combat this issue. Acori Tatarinowii Rhizoma (ATR, rhizome of Acorus tatarinowii Schott, Araceae), a traditional Chinese medicine, has been widely used for treatment of neurological disorders and gastrointestinal digestive disease in China. Here, ATR was demonstrated an excellent MDR-preventing effect in fluoxetine-induced Escherichia coli (E. coli). AIM OF THE STUDY: This study aimed to reveal the effective role of ATR and its signaling cascades involved in preventing fluoxetine-induced MDR. MATERIALS AND METHODS: The water extract of ATR was co-applied with sub-minimum inhibitory concentration (100 mg/l) of fluoxetine in E. coli to evaluate its anti-MDR potential. Formation of reactive oxygen species (ROS) and expression of MDR-related genes in bacteria were measured by dichloro-dihydro-fluorescein diacetate assay and real-time PCR, respectively. Two fluorescent dyes, 1-N-phenylnapthylamine and 3,3'-dipropylthiadicarbocyanine were used to analyze the outer membrane permeability and inner membrane depolarization of E. coli. The accumulation of fluoxetine in the treated E. coli was determined via HPLC. The active fraction of ATR was identified. RESULTS: The water extract of ATR significantly decreased the number of MDR mutants induced by fluoxetine and had half effective concentrations (EC50) of 55.5 µg/ml and 16.8 µg/ml for chloramphenicol and tetracycline, respectively. ATR robustly reversed the fluoxetine-induced superoxide response and membrane damage in E. coli. In addition, the inclusion of ATR significantly reduced the accumulation of fluoxetine in E. coli. After further fractionation, the polysaccharide of ATR was demonstrated as the fraction with the most significant anti-MDR activity. CONCLUSIONS: This is the first report to investigate the MDR-preventing effect of ATR. The results of this study proposed ATR as an excellent herbal product to prevent MDR issues, as induced by fluoxetine, with the potential to reduce the side effects during the drug therapy of depression.

Network pharmacology analysis on Panacis Quinquefolii Radix- Acori Tatarinowii Rhizoma for diabetes encephalopathy and experimental verification of its anti-inflammatory mechanism / 国际中医中药杂志

Objective:To predict the mechanism of Panacis Quinquefolii Radix- Acori Tatarinowii Rhizoma (PQ-AT) in the treatment of diabetes encephalopathy (DE) using network pharmacology combined with molecular docking; To conduct experimental verification.Methods:The active components and targets of PQ and AT were screened by TCMSP database. The GeneCards and Disgenet were used to collect DE related target genes. String database and Cytoscape software were used to structure PPI network and perform visualization analysis. The common targets were imported into Metascape platform for GO annotation and KEGG enrichment analysis. Molecular docking was used to verify the binding ability of active components to core targets. Rats were randomly divided into a blank group, a model group, and a low-dose group of PQ-AT (1.08 g/kg), a high-dose group of PQ-AT (2.16 g/kg), and a metformin group (0.18 g/kg) using a random number table. To establish the rat model of diabetes encephalopathy, intraperitoneal injection of streptozotocin was used in addition to the blank group. After a 12-week drug intervention, TNF-α and Cyclooxygenase-2 (PTGS2) protein expression in the cerebral cortex of rats was detected using Western blot.Results:A total of 26 active components in PQ-AT and 107 related targets of DE were obtained, mainly including TNF, JUN, and PTSG2, which were mainly concentrated in TNF signaling pathway, cancer and other signal pathways. Molecular docking showed that the main active components of PQ-AT had relatively stable binding activity with TNF-α and PTGS2. Western blot results shows that compared with the model group, the expressions of PTGS2 and TNF-α significantly decreased in each administration group ( P<0.05 or P<0.01). Conclusion:PQ-AT can act on TNF, CASP3, JUN, STAT3, PTGS2 and other core targets to regulate signal pathways such as TNF, and inhibit inflammatory reaction to achieve the effect of treating DE.

Acori Tatarinowii Rhizoma: A comprehensive review of its chemical composition, pharmacology, pharmacokinetics and toxicity.

Acori Tatarinowii Rhizoma (ATR, Shi Chang Pu in Chinese), a natural product with multiple targets in various diseases. This review provides the comprehensive summary of the chemical composition, pharmacological effects, pharmacokinetics parameters and toxicity of ATR. The results indicated that ATR possesses a wide spectrum of chemical composition, including volatile oil, terpenoids, organic acids, flavonoids, amino acids, lignin, carbohydrates and so on. Accumulating evidence from various studies has shown that ATR exerts a wide range of pharmacological properties, including protecting nerve cells, alleviating learning and memory impairment, anti-ischemic, anti-myocardial ischemia, anti-arrhythmic, anti-tumor, anti-bacterial, and anti-oxidant activities. Currently, ATR is widely used in the central nervous system, cardiovascular system, gastrointestinal digestive system, respiratory system in China, and for the treatment of epilepsy, depression, amnesia, consciousness, anxiety, insomnia, aphasia, tinnitus, cancers, dementia, stroke, skin diseases, and other complex diseases. Pharmacokinetic studies indicated that ß-asarone, α-asarone, cis-methylisoeugenol, and asarylaldehyde, the active components of ATR, were absorbed slowly after oral administration of ATR. Moreover, toxicity studies have suggested that ATR has no carcinogenic, teratogenic and mutagenic toxicity. Nevertheless, long term or high-dose toxicity testing in animals to explore the acute and chronic toxicity of acori Tatarinowii Rhizoma is still lacking. In view of good pharmacological activities, ATR is expected to be a potential drug candidate for the treatment of Alzheimer's disease, depression, or ulcerative colitis. However, further studies are needed to elucidate its chemical composition, pharmacological effects, molecular mechanisms and targets, improve its oral bioavailability, and clarify its potential toxicity.

Polygoni Multiflori Radix Praeparata and Acori Tatarinowii Rhizoma ameliorate scopolamine-induced cognitive impairment by regulating the cholinergic and synaptic associated proteins.

ETHNOPHARMACOLOGICAL RELEVANCE: The combination of Polygoni Multiflori Radix Praeparata (PMRP) and Acori Tatarinowii Rhizoma (ATR) is often used in traditional Chinese medicine to prevent and treat Alzheimer's disease (AD). However, it is not clear whether the effects and mechanisms of the decoction prepared by traditional decocting method (PA) is different from that prepared by modern decocting method (P + A). AIM OF THE STUDY: The present study aimed to investigate the differences in the protective effects of PA and P + A on scopolamine induced cognitive impairment, and to explore its potential mechanism. MATERIALS AND METHODS: To assess the protective effect of PA and P + A on cognitive dysfunction, the mice were orally administrated with PA (1.56, 6.24 g kg-1•day-1) and P + A (1.56, 6.24 g kg-1•day-1) for 26 days before co-treatment with scopolamine (4 mg kg-1•day-1, i.p.). The learning and memory abilities of mice were examined by Morris water maze test, and the expressions of proteins related to cholinergic system and synaptic function were detected by the methods of ELISA, real-time PCR and Western blotting. Then, molecular docking technique was used to verify the effect of active compounds in plasma after PA administration on Acetylcholinesterase (AChE) protein. Finally, the Ellman method was used to evaluate the effects of different concentrations of PA, P + A (1 µg/mL-100 mg/mL) and the compounds (1-100 µM) on AChE activity in vitro. RESULTS: On one hand, in the scopolamine-induced cognitive impairment mouse model, both of PA and P + A could improve the cognitive impairment, while the effect of PA on cognitive amelioration was better than that of P + A. Moreover, PA regulated the cholinergic and synaptic functions by enhancing the concentration of acetylcholine (ACh), the mRNA levels of CHT1, Syn, GAP-43 and PSD-95, and the related proteins (CHT1, VACHT, Syn, GAP-43 and PSD-95), and significantly inhibiting the expression of AChE protein. Meanwhile, P + A only up-regulated the mRNA levels of GAP-43 and PSD-95, increased the expressions of CHT1, VACHT, Syn, GAP-43 and PSD-95 proteins, and inhibited the expression of AChE protein. On the other hand, the in vitro study showed that some compounds including emodin-8-o-ß-d-Glucopyranoside, THSG and α-Asarone inhibited AChE protein activity with the IC50 values 3.65 µM, 5.42 µM and 9.43 µM, respectively. CONCLUSIONS: These findings demonstrate that both of PA and P + A can ameliorate the cognitive deficits by enhancing cholinergic and synaptic related proteins, while PA has the stronger improvement effect on the cholinergic function, which may be attributed to the compounds including THSG, emodin, emodin-8-O-ß-D-glucopyranoside and α-asarone. The present study indicated that PA has more therapeutic potential in the treatment of neurodegenerative diseases such as AD. The results provide the experimental basis for the clinical use of PA.

Study on network pharmacology of Polygalae Radix- Acori Tatarinowii Rhizoma medicinal pair for depression and Alzheimer disease with the same treatment / 国际中医中药杂志

Objective:To explore the molecular mechanism of Polygalae Radix - Acori Tatarinowii Rhizoma medicinal pair for depression and Alzheimer disease (AD) with the same treatment through network pharmacology. Methods:Effective components of Polygalae Radix - Acori Tatarinowii Rhizoma medicinal pair were retrieved from TCMSP, TCMID and ETCM databases. The disease targets of depression and AD were retrieved from GeneCards, TTD and CTD databases. Targets of action of drugs on active components were predicted through SwissTargetPrediction, and then the intersection targets of medicinal pair and the diseases were taken. Cytoscape 3.6.1 was used to construct the interaction network of Polygalae Radix - Acori Tatarinowii Rhizoma medicinal pair on "component-common target-disease". The enrichment analysis of GO function and KEGG pathway was carried out with the help of Metascape platform, and molecular docking verification was carried out. Results:Through searching the databases and literature, 78 compounds in Polygalae Radix - Acori Tatarinowii Rhizoma medicinal pair were obtained, corresponding to 41 targets of different diseases with the same treatment. The GO function was mainly concentrated in response to lipopolysaccharide and cellular response to nitrogen compound. The KEGG pathway was mainly concentrated in lipid and atherosclerosis, calcium signaling pathway, serotonergic synapse, insulin resistance and so on. The core targets were PTGS2, ESR2, etc. Molecular docking showed that most of the core components could form stable conformation with the core targets. Conclusions:Polygalae Radix - Acori Tatarinowii Rhizoma medicinal pair has the characteristics of multi-component, multi-target and multi-pathway in the same treatment of depression and AD. Through their core components of senegenin, 1-carbobutoxy-β-carboline, 6-hydroxy-1,2,3,7-tetramethoxyxanthone, kaempferol and etc., the pair can act on PTGS2 and other targets, regulate lipid and atherosclerosis, calcium signaling pathway, serotonergic synapse, insulin resistance and so on, and play a therapeutic role in depression and Alzheimer's disease with the same treatment.

[Data mining-based analysis of formulation rules for prescriptions containing herbal pair Acori Tatarinowii Rhizoma-Polygalae Radix].

By the in-depth excavation of prescriptions containing herbal pair Acori Tatarinowii Rhizoma-Polygalae Radix in the Dictionary of Traditional Chinese Medicine Prescriptions, this study analyzed their formulation rules, so as to provide reference for their clinical application and new drug development. First, the prescriptions containing Acori Tatarinowii Rhizoma-Polygalae Radix were collected from the Dictionary of Traditional Chinese Medicine Prescriptions, and their indications, herbal compatibility, and dosage forms were analyzed statistically using the Traditional Chinese Medicine Inheritance Support System(TCMISS). Meanwhile, the formulation rules and common dosage forms for the top four indications(amnesia, palpitation, mania, and epilepsy) sorted by frequency were analyzed with Apriori algorithm. A total of 507 prescriptions containing Acori Tatarinowii Rhizoma-Polygalae Radix were screened out, involving 15 indications(frequency>10) like amnesia, palpitation, mania, and epilepsy. There were 30 commonly used Chinese herbs(frequency≥60), with the Qi-tonifying herbs(Ginseng Radix et Rhizoma and Glycyrrhizae Radix et Rhizome), mind-tranquilizing herbs(Poria and Poria cum Radix Pini), and Yin-nourishing herbs(Angelicae Sinensis Radix and Ophiopogonis Radix) being the core ones. The commonly used dosage forms were honey pill, paste pill, decoction, and powder. These have indicated that the herbal pair Acori Tatarinowii Rhizoma-Polygalae Radix is often combined with Qi-tonifying, Yin-nourishing, and mind-tranquilizing herbs for the treatment of "heart or brain diseases" caused by phlegm production due to spleen deficiency, Qi and blood deficiency, and phlegm-turbidity blocking orifice. In the treatment of amnesia, supplementing essence and replenishing marrow are considered on the basis of tonifying Qi, nourishing Yin, and tranquilizing mind. In the treatment of palpitation and mania, tranquilizing mind is emphasized. In the treatment of epilepsy, the emphasis is placed on resolving phlegm, extinguishing wind, and stopping convulsion.

Data mining-based analysis of formulation rules for prescriptions containing herbal pair Acori Tatarinowii Rhizoma-Polygalae Radix / 中国中药杂志

By the in-depth excavation of prescriptions containing herbal pair Acori Tatarinowii Rhizoma-Polygalae Radix in the Dictionary of Traditional Chinese Medicine Prescriptions, this study analyzed their formulation rules, so as to provide reference for their clinical application and new drug development. First, the prescriptions containing Acori Tatarinowii Rhizoma-Polygalae Radix were collected from the Dictionary of Traditional Chinese Medicine Prescriptions, and their indications, herbal compatibility, and dosage forms were analyzed statistically using the Traditional Chinese Medicine Inheritance Support System(TCMISS). Meanwhile, the formulation rules and common dosage forms for the top four indications(amnesia, palpitation, mania, and epilepsy) sorted by frequency were analyzed with Apriori algorithm. A total of 507 prescriptions containing Acori Tatarinowii Rhizoma-Polygalae Radix were screened out, involving 15 indications(frequency>10) like amnesia, palpitation, mania, and epilepsy. There were 30 commonly used Chinese herbs(frequency≥60), with the Qi-tonifying herbs(Ginseng Radix et Rhizoma and Glycyrrhizae Radix et Rhizome), mind-tranquilizing herbs(Poria and Poria cum Radix Pini), and Yin-nourishing herbs(Angelicae Sinensis Radix and Ophiopogonis Radix) being the core ones. The commonly used dosage forms were honey pill, paste pill, decoction, and powder. These have indicated that the herbal pair Acori Tatarinowii Rhizoma-Polygalae Radix is often combined with Qi-tonifying, Yin-nourishing, and mind-tranquilizing herbs for the treatment of "heart or brain diseases" caused by phlegm production due to spleen deficiency, Qi and blood deficiency, and phlegm-turbidity blocking orifice. In the treatment of amnesia, supplementing essence and replenishing marrow are considered on the basis of tonifying Qi, nourishing Yin, and tranquilizing mind. In the treatment of palpitation and mania, tranquilizing mind is emphasized. In the treatment of epilepsy, the emphasis is placed on resolving phlegm, extinguishing wind, and stopping convulsion.

Antiepileptic Pharmacological Mechanism of Acori Tatarinowii Rhizoma： A Review / 中国实验方剂学杂志

Epilepsy is a recurrent neurological disease with synchronous abnormal high discharge of neurons in the brain. The pathogenesis of this disease is extremely complex， which is closely related to neurotransmitter regulation， oxidative stress response， inflammatory factors， neuroglial cell， and abnormal gene expression. Western medicine mainly uses phenobarbital， phenytoin sodium， carbamazepine， and other drugs， but long-term use also produces certain toxic and side effects. Traditional Chinese medicine （TCM） believes that the pathogenesis of epilepsy is related to wind， fire， phlegm， and blood stasis， which leads to dysfunction of viscera， disorder of Qi movement， and finally uncontrolled spirit. In recent years， TCM has achieved certain curative effects on the treatment of epilepsy. As a high-frequency antiepileptic drug， Acori Tatarinowii Rhizoma has the effects of opening orifices and eliminating phlegm， awakening spirit and benefiting intelligence， and removing dampness and opening stomach， which has been widely used in clinic. In this paper， the pathogenesis of epilepsy and the pharmacological mechanism of Acori Tatarinowii Rhizoma extract and chemical components in the treatment of epilepsy were expounded by referring to relevant pharmacological studies and animal experiments. It was found that Acori Tatarinowii Rhizoma played a role in regulating the neurotransmitter level， antioxidant stress response， scavenging oxygen free radicals， regulating the expression of c-fos gene， reducing the level of inflammatory mediators， resisting neuronal apoptosis， and regulating the neuroglial cells and the permeability of blood-brain barrier. This paper summarizes the positive effects of Acori Tatarinowii Rhizoma on the treatment of epilepsy， and provides a scientific basis for the popularization and application of Acori Tatarinowii Rhizoma in the prevention and treatment of epilepsy.

Antiepileptic Pharmacological Mechanism of Acori Tatarinowii Rhizoma： A Review / 中国实验方剂学杂志

Epilepsy is a recurrent neurological disease with synchronous abnormal high discharge of neurons in the brain. The pathogenesis of this disease is extremely complex， which is closely related to neurotransmitter regulation， oxidative stress response， inflammatory factors， neuroglial cell， and abnormal gene expression. Western medicine mainly uses phenobarbital， phenytoin sodium， carbamazepine， and other drugs， but long-term use also produces certain toxic and side effects. Traditional Chinese medicine （TCM） believes that the pathogenesis of epilepsy is related to wind， fire， phlegm， and blood stasis， which leads to dysfunction of viscera， disorder of Qi movement， and finally uncontrolled spirit. In recent years， TCM has achieved certain curative effects on the treatment of epilepsy. As a high-frequency antiepileptic drug， Acori Tatarinowii Rhizoma has the effects of opening orifices and eliminating phlegm， awakening spirit and benefiting intelligence， and removing dampness and opening stomach， which has been widely used in clinic. In this paper， the pathogenesis of epilepsy and the pharmacological mechanism of Acori Tatarinowii Rhizoma extract and chemical components in the treatment of epilepsy were expounded by referring to relevant pharmacological studies and animal experiments. It was found that Acori Tatarinowii Rhizoma played a role in regulating the neurotransmitter level， antioxidant stress response， scavenging oxygen free radicals， regulating the expression of c-fos gene， reducing the level of inflammatory mediators， resisting neuronal apoptosis， and regulating the neuroglial cells and the permeability of blood-brain barrier. This paper summarizes the positive effects of Acori Tatarinowii Rhizoma on the treatment of epilepsy， and provides a scientific basis for the popularization and application of Acori Tatarinowii Rhizoma in the prevention and treatment of epilepsy.

Combination of Polygoni Multiflori Radix Praeparata and Acori Tatarinowii Rhizoma Alleviates Learning and Memory Impairment in Scopolamine-Treated Mice by Regulating Synaptic-Related Proteins.

Polygoni Multiflori Radix Praeparata (ZhiHeShouWu, PMRP) and Acori Tatarinowii Rhizoma (ShiChangPu, ATR) and their traditional combination (PA) are frequently used in traditional Chinese medicine to prevent and treat Alzheimer disease (AD) based on the theory that PMRP tonifies the kidney and ATR dissipates phlegm. However, the components of PA and their mechanisms of action are not known. The present study analyzed the active components of PA, and investigated the protective effect of PA against cognitive impairment induced by scopolamine in mice along with the underlying mechanism.The aqueous extract of PA was analyzed by high-performance liquid chromatography-mass spectrometry (HPLC-MS) and gas chromatography (GC)-MS in order to identify the major components. To evaluate the protective effect of PA against cognitive dysfunction, mice were orally administered PA, PMRP, or ATR for 30 days before treatment with scopolamine. Learning and memory were assessed in mice with the Morris water maze test; neurotransmitter levels in the hippocampus were analyzed by HPLC-MS; and the expression of synapse-related proteins in the hippocampus was detected by western blotting and immunohistochemistry. Eight active compounds in PA and rat plasma were identified by HPLC-MS and GC-MS. Plasma concentrations of 2,3,5,4'-tetrahydroxystilbene-2-O-ß-d-glucoside, emodin, α-asarone, and asarylaldehyde were increased following PA administration; meanwhile, gallic acid, emodin-8-O-ß-d-glucopyranoside, ß-asarone, and cis-methyl isoeugenol concentrations were similar in rats treated with PA, PMRP, and ATR. In scopolamine-treated mice, PA increased the concentrations of neurotransmitters in the hippocampus, activated the brain-derived neurotrophic factor (BDNF)/extracellular signal-regulated kinase (ERK)/cAMP response element binding protein (CREB) signaling pathway, and increased the expression of p90 ribosomal S6 kinase (p90RSK) and postsynaptic density (PSD)95 proteins. Thus, PA alleviates cognitive deficits by enhancing synaptic-related proteins, suggesting that it has therapeutic potential for the treatment of aging-related diseases such as AD.

GC-MS analysis of extraction kinetics of volatile oil from Acori Tatarinowii Rhizoma by steam distillation / 中草药

Objective: The experiment was designed to reveal the extraction, distribution and influencing factors of volatile components in the extraction process of volatile oil from Acori Tatarinowii Rhizoma (ATR). Methods: Volatile oil of ATR was extracted by steam distillation and the extract was collected every 30 min to separate the aromatic water and volatile oil. Results: A total of 56 volatile compounds were determined, of which β-asarone, methyleugenol, cis-methylisoeugenol and γ-asarone were the main characteristic constituents. There were 41 kinds of components distributed only in water, four components only in oil and 11 kinds in both oil and water. Correlation analysis showed that the specific components in water were positively correlated with the dissolution/diffusion of the main components in water, but negatively correlated with the main components in volatile oil. The water solubility of the unique components in water was the highest. The results of radar and PCA showed that the water solubility and boiling point of the specific components in water were very high, the vapor pressure of the common components of oil and water was the highest, and the polar surface areas of the special components in oil were high. Conclusion: Affected by the physical and chemical properties of volatile component, some components specifically distributed in water increased the content of main components in the aromatic water, may resulting in volatile oil extraction process easy to "emulsification", in turn, leading to an important reason for the declining quality of volatile oil.

[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.

Asarones from Acori Tatarinowii Rhizoma stimulate expression and secretion of neurotrophic factors in cultured astrocytes.

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 ß-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 ß-asarone from ATR could serve as potential candidates for drug development in neurodegenerative diseases.

Research on network pharmacology of Acori Tatarinowii Rhizoma combined with Curcumae Radix in treating epilepsy / 中国中药杂志

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.

Effect of Acori Tatarinowii Rhizoma on Intestinal Absorption of Ginsenosides in Dingzhi Xiaowan / 中国实验方剂学杂志

Objective: To explore the effect of Acori Tatarinowii Rhizoma on intestinal absorption of ginsenosides in Dingzhi Xiaowan,and reveal the mechanism of Acori Tatarinowii Rhizoma acting as " adjuvant drug" in this formula. Method: The contents of ginsenoside Rg1,Re and Rb1 were measured by UPLC-MS/MS and the absorption of three ginsenosides in different intestine segments was investigated by rat single pass intestinal perfusion in situ,including absorption rate constant(Ka) and apparent permeability coefficient(Papp).Everted intestinal sac model was used to investigate the absorption dosage of three ginsenosides affected by volatile oil from Acori Tatarinowii Rhizoma and verapamil[Ver,a P-glycoprotein(P-gp) inhibitor]. Result:Papp values of three ginsenosides were ≤ 0.191×10-3 cm·min-1 in Dingzhi Xiaowan when lack of Acori Tatarinowii Rhizoma.Compared with lack of Acori Tatarinowii Rhizoma in Dingzhi Xiaowan group,the Ka and Papp values of lack of volatile oil from Acori Tatarinowii Rhizoma in Dingzhi Xiaowan group slightly increased without significant difference in the four intestinal segments,but when the prescription had Acori Tatarinowii Rhizoma,the Ka increased by 3.97-8.35 fold and the Papp increased by 3.99-8.49 fold.The results of everted intestinal sac test showed that volatile oil of Acori Tatarinowii Rhizoma could significantly promote the intestinal absorption of ginsenoside Rg1,Re and Rb1,but there was no dose-dependent. Conclusion:Volatile oil of Acori Tatarinowii Rhizoma can promote the intestinal absorption of three ginsenosides in Dingzhi Xiaowan,and the mechanism may be related to the inhibiting function on P-gp.

Screening of anti-depressant active ingredients in Acori Tatarinowii Rhizoma based on molecular docking technique / 中草药

Objective: To screen the anti-depressant active ingredients in Acori Tatarinowii Rhizoma by molecular docking technique. Methods: All the chemical constituents of Acori Tatarinowii Rhizoma were obtained by Traditional Chinese Medicine Pharmacology Database (TCMSP). Combined with oral bioavailability, 65 candidate compounds were obtained. The studied anti-depressant targets included monoamine oxidase A, dopamine transporter, serotonin transporter, and histamine H1 receptor. AutoDock Vina was used to explore the affinity and binding modes of the candidate compounds with the above targets. Results: There were 18 compounds from Acori Tatarinowii Rhizoma that could bind to the above four targets. Among them, four compounds could bind to four targets, three compounds could bind to two targets, and the other 11 compounds could interact with one target. Conclusion: Molecular docking technology can be used to investigate the molecular mechanism of Acori Tatarinowii Rhizoma and determine the active ingredients, which provides an alternative method for the discovery of novel anti-depressants and lead compounds from Chinese herbal medicines.

Preparation and quality evaluation of Acori Tatarinowii Rhizoma-volatile oil microemulsion / 中草药

Objective: Taking the volatile oil of Acori Tatarinowii Rhizoma with the effect of anti-senile dementia as model drug to prepare Acori Tatarinowii Rhizoma-volatile oil microemulsion (AO-ME). Methods: The composition of microemulsion was preliminarily determined according to the solubility of volatile oil from Acori Tatarinowii Rhizoma in various solvents. By drawing pseudo-ternary phase diagram, the optimal microemulsion formulation was selected according to the size of particles and microemulsion region, stability of preparations and drug loading. Results: The optimal microemulsion formulation was that volatile oil of Acori Tatarinowii Rhizoma-Cremophor EL-glycerol-water was 6.25:20.83:10.42:62.5. The average particle size of AO-ME was (30.5 ± 0.2) nm with a polydispersity index of 0.150 ± 0.002. The viscosity value of AO-ME was (2.80 ± 0.21) mPa∙s. In vitro transdermal rate of AO-ME was (1 288.76 ± 16.20) μg/(cm2∙h), measured in β-asarone. Compared with ordinary emulsion, the transdermal rate of AO-ME was increased 14 times. The ciliary toxicity test of toad showed that the preparation had no significant toxicity. Conclusion: The preparation of AO-ME was prepared with stable physicochemical properties, good transdermal properties, and low toxicity to nasal mucosa cilia.