Evaluation of the Anticonvulsant Activities of Gastrodia Elata Bl.- Acorus Tatarinowii Decoction on Experimentally Induced Seizures in Mice

Epilepsy is a serious public health problem in the world. At present, the effect of drug treatment of epilepsy is are not satisfactory. Medicinal plants as pharmaceuticals and for healthcare treatments in the management of epilepsy in China for many centuries. Especially, Gastrodia elata Bl.-Acorus tatarinowii, as a classic and important herb pairs in folk medicine, has been used in folk medicine to control seizures. However, the animal experiment data of its anticonvulsant effect is limited in the literature. The objective of this study was to mainly analyze the anticonvulsant activity of Gastrodia elata-Acorus tatarinowii (GEAT) decoction in maximal electroshock (MES), pentylenetetrazole (PTZ) and trimercaptopropionic acid (3-MP) induced seizures in mice, providing scientific basis for the treatment of convulsive disorders in traditional medicine. In addition, the improvement effect were examined on seizure severity, anxiety, cognitive dysfunction, inflammation and oxidative stress in PTZ kindled mice. The results showed that GEAT decoction dose-dependently protected mice against MES, 3-MP and PTZ induced acute seizures. Meanwhile, GEAT decoction 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. Our data evidenced that the anticonvulsant properties attributed to GEAT decoction as adjunctive therapy for epileptic patients in folk medicine.

Network Pharmacology-Based Analysis on the Mechanism of Drug Pair of Astragalus Membranaceus and Acorus Tatarinowii in the Treatment of Alzheimer’s Disease

Alzheimer’s disease (AD) is a degenerative disease of central nervous system, which seriously threatens the life and health of the elderly people. It has been for long time that Traditional Chinese medicine (TCM) treatment for AD is effective. This study analyzed the potential target and molecular mechanism of the most often used drug pair of Astragalus membranaceus and Acorus tatarinowii to treat AD by network pharmacological method. Firstly, the method was performed to screen and sort out the active ingredients with good ADME properties and drug targets of Astragalus membranaceus and Acorus tatarinowii. Then, we searched for the disease targets related to AD, followed by the construction of the “active ingredients-target-disease” network. We implemented GO enrichment analysis and KEGG pathway enrichment analysis of related overlapped target proteins, and then constructed the “target-pathway” network diagram. Finally, the above overlapped target proteins are mapped to build a PPI high-position protein interoperability network, and we conducted the network topology analysis to screen out the core targets of Astragalus membranaceus-Acorus tatarinowii drug pair in the treatment of AD. According to network pharmacology, this research predicted the potential targets of the drug pair of Astragalus membranaceus and Acorus tatarinowii in the treatment of AD, and explored that Astragalus membranaceus-Acorus tatarinowii drug pair in the treatment of AD was the overall systematic regulating action of “multiple-ingredients, multiple-target and multiple-pathway”. It affords the reference for understanding the pathogenesis of AD and exploring new therapeutic methods and drug development in the future.

Protective effect of Acorus tatarinowii extract against alzheimer in 3xTg-AD mice

Purpose: To investigate the protective effect of Acorus tatarinowii extract (ATE) against Alzheimer's disease in 3xTg-AD mice. Method: The cognitive function of 3xTg-AD mice was assessed using Morris water maze test. The levels of the amyloid beta deposits and NeuN in the hippocampus were evaluated by immunohistochemical assay while brain neurotrophic derived factor (BDNF) and tyrosine kinase B (TrkB) expressions were determined by western blot analysis. Results: ATE treatment significantly ameliorated learning and memory deficits in AD mice, as shown by increased time spent in the target zone during probe tests. The escape latency in animals treated with 600 mg/kg ATE (24.8 ± 1.3 s) was significantly increased relative to ontreated 3xTg-AD mice (8.5 ± 1.0 s, p < 0.01). In addition, ATE significantly decreased Aβ deposits, increased NeuN-positive cells, and upregulated the expression of BDNF (1.9 ± 0.4, p < 0.05) and TrkB (1.9 ± 0.2, p < 0.05) in 3xTg AD mice. Conclusion: These results suggest that ATE treatment may be a useful strategy for managing memory impairment induced by several neurodegenerative diseases.

Uncovering the Protective Mechanism of the Volatile Oil of Acorus tatarinowii against Acute Myocardial Ischemia Injury Using Network Pharmacology and Experimental Validation

Acorus tatarinowii is a traditional aromatic resuscitation drug that can be clinically used to prevent cardiovascular diseases. The volatile oil of Acorus tatarinowii (VOA) possesses important medicinal properties, including protection against acute myocardial ischemia (MI) injury. However, the pharmacodynamic material basis and molecular mechanisms underlying this protective effect remain unclear. Using network pharmacology and animal experiments, we studied the mechanisms and pathways implicated in the activity of VOA against acute MI injury. First, VOA was extracted from three batches of Acorus tatarinowii using steam distillation, and then, its chemical composition was determined by GC-MS. Next, the components-targets and protein-protein interaction networks were constructed using systematic network pharmacology. Gene Ontology (GO) function and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were also conducted in order to predict the possible pharmacodynamic mechanisms. Furthermore, animal experiments including ELISAs, histological examinations, and Western blots were performed in order to validate the pharmacological effects of VOA. In total, 33 chemical components were identified in VOA, and ß-asarone was found to be the most abundant component. Based on network pharmacology analysis, the therapeutic effects of VOA against myocardial ischemia might be mediated by signaling pathways involving COX-2, PPAR-α, VEGF, and cAMP. Overall, the obtained results indicate that VOA alleviates the pathological manifestations of isoproterenol-hydrochloride-induced myocardial ischemia in rats, including the decreased SOD (superoxide dismutase) content and increased LDH (lactic dehydrogenase) content. Moreover, the anti-MI effect of VOA might be attributed to the downregulation of the COX-2 protein that inhibits apoptosis, the upregulation of the PPAR-α protein that regulates energy metabolism, and the activation of VEGF and cAMP signaling pathways.

Exploring the biosynthetic pathway of lignin in Acorus tatarinowii Schott using de novo leaf and rhizome transcriptome analysis

Acorus tatarinowii Schott is a well-known Chinese traditional herb. Lignin is the major biologically active ingredient and exerts a broad range of pharmacological effects: it is an antitumor, antioxidant, and bacteriostatic agent, and protects the cardiovascular system.In this study, the transcriptomes of the leaf and rhizome tissues of A. tatarinowii Schott were obtained using the BGISEQ-500 platform. 141,777 unigenes were successfully assembled, of which 76,714 were annotated in public databases. Further analysis of the lignin biosynthesis pathway revealed a total of 107 unigenes encoding eight key enzymes, which were involved in the lignin biosynthetic pathway. Furthermore, the expression of the key genes involved in lignin synthesis in different tissues was identified by quantitative real-time PCR. Analysis of the differentially expressed genes showed that most of the upregulated unigenes were enriched in rhizome tissues. In addition, 2,426 unigenes were annotated to the transcriptome factor (TF) family. Moreover, 16 TFs regulating the same key enzyme (peroxidase) were involved in the lignin synthesis pathway. The alignment of peroxidase amino acid sequences and the analysis of the structural characteristics revealed that the key peroxidase enzyme had well-conserved sequences, spatial structures, and active sites. This study is the first to provide comprehensive genetic information on A. tatarinowii Schott at the transcriptional level, and will facilitate our understanding of the lignin biosynthesis pathway.

A New Brominated Norsesquiterpene Glycoside From the Rhizomes of Acorus tatarinowii Schott

A new brominated norsesquiterpene glycoside, acoruside (1), has been isolated from the rhizomes of Acorus tatarinowii Schott, together with 8 known compounds (2-9). Their structures were elucidated mainly based on 1-dimensional (1D) and 2D nuclear magnetic resonance spectra. The absolute configuration of compound 1 was determined by comparing its experimental and calculated electronic circular dichroism spectra. The in vitro tests indicated that at 10 µM, compounds 2, 3, and 4 aggravated serum deprivation injuries of PC12 cells, compound 2 aggravated rotenone-induced injuries of PC12 cells, and compounds 3 and 4 aggravated the oxygen-glucose deprivation-induced injuries of PC12 cells.

Essential Oil of Acorus tatarinowii Schott Ameliorates Aβ-Induced Toxicity in Caenorhabditis elegans through an Autophagy Pathway

Background. Acorus tatarinowii Schott [Shi Chang Pu in Chinese (SCP)] is a traditional Chinese medicine frequently used in the clinical treatment of dementia, amnesia, epilepsy, and other mental disorders. Previous studies have shown the potential efficacy of SCP against Alzheimer’s disease (AD). Nevertheless, the active constituents and the modes of action of SCP in AD treatment have not been fully elucidated. Purpose. The aim of this study was to investigate the protective effects of SCP on abnormal proteins and clarify its molecular mechanisms in the treatment of AD by using a Caenorhabditis elegans (C. elegans) model. Methods. This study experimentally assessed the effect of SCP-Oil in CL4176 strains expressing human Aβ in muscle cells and CL2355 strains expressing human Aβ in pan-neurons. Western blotting, qRT-PCR, and fluorescence detection were performed to determine the oxidative stress and signaling pathways affected by SCP-Oil in nematodes. Results. SCP-Oil could significantly reduce the deposition of misfolded Aβ and polyQ proteins and improved serotonin sensitivity and olfactory learning skill in worms. The analysis of pharmacological action mechanism of SCP-Oil showed that its maintaining protein homeostasis is dependent on the autophagy pathway regulated partly by hsf-1 and sir-2.1 genes. Conclusion. Our results provide new insights to develop treatment strategy for AD by targeting autophagy, and SCP-Oil could be an alternative drug for anti-AD.

Acorus tatarinowii Schott extract reduces cerebral edema caused by ischemia–reperfusion injury in rats: involvement in regulation of astrocytic NKCC1/AQP4 and JNK/iNOS-mediated signaling

Background This study aimed to evaluate the effects of the Acorus tatarinowii Schott [Shi Chang Pu (SCP)] extract administered at the start of 2 h of middle cerebral artery occlusion (MCAo), followed by 3 d of reperfusion, and to determine mechanisms involved in anti-edema effects in the penumbra of the cerebral cortex. Method Rats were intraperitoneally administered the SCP extract at a dose of 0.25 g/kg (SCP-0.25 g), 0.5 g/kg (SCP-0.5 g), or 1 g/kg (SCP-1 g) at the start of MCAo. Result SCP-0.5 g and SCP-1 g treatments effectively reduced the cerebral infarct size, ameliorated cerebral edema, reduced blood–brain barrier permeability, and restored neurological function. SCP-0.5 g and SCP-1 g treatments markedly downregulated the levels of glial fibrillary acidic protein, Na+-K+-2Cl− cotransporter type 1 (NKCC1), aquaporin 4 (AQP4), phospho-c-Jun N-terminal kinase (p-JNK)/JNK, inducible nitric oxide synthase (iNOS), 3-nitrotyrosine, intercellular adhesion molecule-1 (ICAM-1), matrix metalloproteinase-9 (MMP-9), vascular endothelial growth factor-A (VEGF-A), and zonula occluden-1 (ZO-1) and upregulated ZO-3 expression in the penumbra of the cerebral cortex 3 d after reperfusion. Conclusions SCP-0.5 g and SCP-1 g treatments exert neuroprotective effects against cerebral infarction and cerebral edema partially by mitigating astrocytic swelling and blood–brain barrier disruption. Moreover, the anti-cerebral edema effects of SCP extract treatments are possibly associated with the downregulation of astrocytic NKCC1/AQP4 and JNK/iNOS-mediated ICAM-1/MMP-9 signaling in the penumbra of the cerebral cortex 3 d after reperfusion.