ABSTRACT
Purpose: Alisma orientale (AO, Alisma orientale (Sam). Juzep) has been widely employed for the treatment of macular edema (ME) in traditional Chinese medicine due to its renowned water-relief properties. Nonetheless, the comprehensive investigation of AO in alleviating ME remained unexplored. This study aims to identify the active components of AO that target the eye and investigate its pharmacological effects and mechanisms on ME. Methods: The study commenced with UPLC-Triple-TOF/MS analysis to identify the primary constituents of AO. Zebrafish eye tissues were then analyzed after a five-day administration of AO to detect absorbed components and metabolites. Subsequently, network pharmacology, molecular docking, and molecular dynamics simulations were employed to predict the mechanisms of ME treatment via biological target pathways. In vivo experiments were conducted to corroborate the pharmacological actions and mechanisms. Results: A total of 7 compounds, consisting of 2 prototype ingredients and 5 metabolites (including isomers), were found to traverse the blood-eye barrier and localized within eye tissues. Network pharmacology results showed that AO played a role in the treatment of ME mainly by regulating the pathway network of PI3K-AKT and MAPK with TNF-α centered. Computational analyses suggested that 11-dehydro-16-oxo-24-deoxy-alisol A, a metabolite of alisol A, mitigates edema through TNF-α inhibition. Furthermore, zebrafish fundus confocal experiments and HE staining of eyes confirmed the attenuating effects of alisol A on fundus angiogenesis and ocular edema, representing the first report of AO's ME-inhibitory effects. Conclusion: In this study, computational analyses with experimental validation were used to understand the biological activity and mechanism of alisol A in the treatment of ME. The findings shed light on the bioactive constituents and pharmacological actions of AO, offering valuable insights and a theoretical foundation for its clinical application in managing ME.
Subject(s)
Alisma , Macular Edema , Network Pharmacology , Tumor Necrosis Factor-alpha , Zebrafish , Animals , Macular Edema/drug therapy , Macular Edema/metabolism , Alisma/chemistry , Tumor Necrosis Factor-alpha/antagonists & inhibitors , Tumor Necrosis Factor-alpha/metabolism , Chromatography, High Pressure Liquid , Cholestenones/pharmacology , Cholestenones/chemistry , Molecular Docking Simulation , Molecular StructureABSTRACT
Iron is a vital trace element for our bodies and its imbalance can lead to various diseases. The progression of metabolic-associated fatty liver disease (MAFLD) is often accompanied by disturbances in iron metabolism. Alisma orientale extract (AOE) has been reported to alleviate MAFLD. However, research on its specific lipid metabolism targets and its potential impact on iron metabolism during the progression of MAFLD remains limited. To establish a model of MAFLD, mice were fed either a standard diet (CON) or a high-fat diet (HFD) for 9 weeks. The mice nourished on the HFD were then randomly assigned to the HF group and the HFA group, with the HFA group receiving AOE by gavage on a daily basis for 13 weeks. Supplementation with AOE remarkably reduced overabundant lipid accumulation in the liver and restored the iron content of the liver. AOE partially but significantly reversed dysregulated lipid metabolizing genes (SCD1, PPAR γ, and CD36) and iron metabolism genes (TFR1, FPN, and HAMP) induced by HFD. Chromatin immunoprecipitation assays indicated that the reduced enrichment of FXR on the promoters of SCD1 and FPN genes induced by HFD was significantly reversed by AOE. These findings suggest that AOE may alleviate HFD-induced disturbances in liver lipid and iron metabolism through FXR-mediated gene repression.
Subject(s)
Diet, High-Fat , Iron , Lipid Metabolism , Liver , Plant Extracts , Receptors, Cytoplasmic and Nuclear , Animals , Plant Extracts/pharmacology , Liver/metabolism , Liver/drug effects , Iron/metabolism , Mice , Male , Lipid Metabolism/drug effects , Receptors, Cytoplasmic and Nuclear/metabolism , Receptors, Cytoplasmic and Nuclear/genetics , Diet, High-Fat/adverse effects , Alisma/chemistry , Mice, Inbred C57BL , Disease Models, Animal , Gene Expression Regulation/drug effects , Stearoyl-CoA Desaturase/metabolism , Stearoyl-CoA Desaturase/genetics , Non-alcoholic Fatty Liver Disease/drug therapy , Non-alcoholic Fatty Liver Disease/metabolism , Fatty Liver/drug therapy , Fatty Liver/metabolismABSTRACT
Non-alcoholic fatty liver disease (NAFLD), particularly advanced non-alcoholic steatohepatitis (NASH), leads to irreversible liver damage. This study investigated the therapeutic effects and potential mechanism of a novel extract from traditional Chinese medicine Alisma orientale (Sam.) Juzep (AE) on free fatty acid (FFA)-induced HepG2 cell model and high-fat diet (HFD) + carbon tetrachloride (CCl4)-induced mouse model of NASH. C57BL/6â¯J mice were fed a HFD for 10 weeks. Subsequently, the mice were injected with CCl4 to induce NASH and simultaneously treated with AE at daily doses of 50, 100, and 200â¯mg/kg for 4 weeks. At the end of the treatment, animals were fasted for 12â¯h and then sacrificed. Blood samples and liver tissues were collected for analysis. Lipid profiles, oxidative stress, and histopathology were examined. Additionally, a polymerase chain reaction (PCR) array was used to predict the molecular targets and potential mechanisms involved, which were further validated in vivo and in vitro. The results demonstrated that AE reversed liver damage (plasma levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), hepatocyte ballooning, hepatic steatosis, and NAS score), the accumulation of hepatic lipids (TG and TC), and oxidative stress (MDA and GSH). PCR array analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis revealed that AE protects against NASH by regulating the adipocytokine signaling pathway and influencing nuclear receptors such as PPARα. Furthermore, AE increased the expression of peroxisome proliferator-activated receptor gamma coactivator-1α (PPARGC1α) and reversed the decreased expression of PPARα in NASH mice. Moreover, in HepG2 cells, AE reduced FFA-induced lipid accumulation and oxidative stress, which was dependent on PPARα up-regulation. Overall, our findings suggest that AE may serve as a potential therapeutic approach for NASH by inhibiting lipid accumulation and reducing oxidative stress specifically through the PPARα pathway.
Subject(s)
Alisma , Diet, High-Fat , Non-alcoholic Fatty Liver Disease , Plant Extracts , Signal Transduction , Animals , Humans , Male , Mice , Alisma/chemistry , Carbon Tetrachloride , Diet, High-Fat/adverse effects , Disease Models, Animal , Hep G2 Cells , Lipid Metabolism/drug effects , Liver/drug effects , Liver/metabolism , Liver/pathology , Mice, Inbred C57BL , Non-alcoholic Fatty Liver Disease/drug therapy , Non-alcoholic Fatty Liver Disease/metabolism , Non-alcoholic Fatty Liver Disease/pathology , Oxidative Stress/drug effects , Plant Extracts/pharmacology , Plant Extracts/isolation & purification , PPAR alpha/metabolism , Signal Transduction/drug effectsABSTRACT
This study developed a rapid, accurate, objective and economic method to identify and evaluate the quality of Alismatis Rhizoma (AR) commodities. Traditionally, the identification of plant species and geographical origins of AR commodities mainly relied on experienced staff. However, the subjectivity and inaccuracy of human identification negatively impacted the trade of AR. Besides, liquid chromatographic methods such as ultra-high-performance liquid chromatography (UPLC) and high-performance liquid chromatography (HPLC), the major approach for the determination of triterpenoid contents in AR was time-consuming, expensive, and highly demanded in manoeuvre specialists. In this study, the combination of near-infrared (NIR) spectroscopy and chemometrics as the method was developed and utilised to address the two common issues of identifying the quality of AR commodities. Through the discriminant analysis (DA), the raw NIR spectroscopy data on 119 batches samples from two species and four origins in China were processed to the best pre-processed data. Subsequently, orthogonal partial least squares-discriminant analysis (OPLS-DA) and random forest (RF) as the major chemometrics were used to analyse the best pre-processed data. The accuracy rates by OPLS-DA and RF were respectively 100% and 97.2% for the two species of AR, and respectively100% and 94.4% for the four origins of AR. Meanwhile, a quantitative correction model was established to rapidly and economically predict the seven triterpenoid contents of AR through combining the partial least squares (PLS) method and NIR spectroscopy, and taking the triterpenoid contents measured by UPLC as the reference value, and carry out spectral pre-processing methods and band selection. The final quantitative model correlation coefficients of the seven triterpenoid contents of AR ranged from 0.9000 to 0.9999, indicating that prediction ability of this model had good stability and applicability.
Subject(s)
Rhizome , Spectroscopy, Near-Infrared , Triterpenes , Spectroscopy, Near-Infrared/methods , Triterpenes/analysis , Discriminant Analysis , Rhizome/chemistry , Least-Squares Analysis , Alisma/chemistry , Chromatography, High Pressure Liquid/methods , Drugs, Chinese Herbal/chemistry , Drugs, Chinese Herbal/analysisABSTRACT
Four pairs of undescribed enantiomeric guaiane sesquiterpenoids, (±)-alismaenols A-D (1a/1b, 3a/3b-5a/5b), together with a pair of known ones (2a/2b) were isolated from the rhizomes of Alisma plantago-aquatica. The structures and relative configurations of the isolates were established by analysis of their 1D, 2D-NMR and HRESIMS data. Their absolute configurations were determined by comparison of their experimental CD spectra and calculated electronic circular dichroism (ECD) spectra or by single-crystal X-ray diffraction analysis. All compounds (1a/1b-5a/5b) were evaluated for their inhibitory effects on nitric oxide (NO) production in LPS-induced RAW 264.7 cells, and compound 1a exhibited stronger activity (IC50 = 12.89 µM) than indomethacin (IC50 = 14.03 µM).
Subject(s)
Alisma , Nitric Oxide , Phytochemicals , Rhizome , Sesquiterpenes, Guaiane , Rhizome/chemistry , Mice , RAW 264.7 Cells , Molecular Structure , Nitric Oxide/metabolism , Animals , Alisma/chemistry , Phytochemicals/pharmacology , Phytochemicals/isolation & purification , Sesquiterpenes, Guaiane/isolation & purification , Sesquiterpenes, Guaiane/pharmacology , Sesquiterpenes, Guaiane/chemistry , China , Stereoisomerism , Anti-Inflammatory Agents/pharmacology , Anti-Inflammatory Agents/isolation & purification , Anti-Inflammatory Agents/chemistryABSTRACT
BACKGROUND: Acute pancreatitis (AP) is an inflammatory disorder of the exocrine pancreas, especially hyperlipidemia acute pancreatitis (HLAP) is the third leading cause of acute pancreatitis which is more severe with a greater incidence of persistent multiorgan failure. HLAP inflicts injury upon the organelles within the acinar cell, particularly mitochondria, the endolysosomal-autophagy system, and is accompanied by senescence-associated secretory phenotype (SASP). RAD, only two consists of Rhizoma Alismatis and Atractylodes macrocephala Rhizoma, which is best known for its ability to anti-inflammatory and lipid-lowering. Nevertheless, the mechanism by which RAD alleviates HLAP remains obscure, necessitating further investigation. PURPOSE: The study aimed to assess the effects of the RAD on HLAP and to elucidate the underlying mechanism in vivo and in vitro, offering a potential medicine for clinical treatment for HLAP. STUDY DESIGN AND METHODS: C57BL/6 mice with hyperlipidemia acute pancreatitis were induced by HFD and CER, then administrated with RAD. AR42J were stimulated by cerulein or conditioned medium and then cultured with RAD. Serums were analyzed to evaluate potential pancreas and liver damage. Furthermore, tissue samples were obtained for histological, and protein investigations by H&E, Oil red staining, and Western blot. In addition, western blot and immunofluorescent staining were utilized to estimate the effect of RAD on mitochondrial function, autophagy flux, and SASP. RESULTS: In vivo, RAD considerably alleviated systemic inflammation while attenuating TC, TG, AMY, LPS, inflammatory cytokines, histopathology changes, oxidative damage, mitochondrial fission, and autophagy markers in HLAP mice. Impaired autophagy flux and mitochondrial dysfunction resulted in a significant enhancement of NLRP3 and IL-1ß in the pancreas. RAD could reverse these changes. In vitro, RAD significantly restored mitochondrial membrane potential and oxidative phosphorylation levels. RAD decreased Beclin-1 and LC3-II expression and increased LAMP-1 and Parkin-Pink expression, which showed that RAD significantly ameliorated HLAP-induced damage to the mitochondria function by suppressing mitochondrial oxidative damage and enhancing autophagy flux and mitophagy to remove the damaged mitochondria. In addition, we found that RAD could up-regulate the expression of BAX, and Bad and down-regulate the expression of p16, and p21, indicating that RAD could promote damaged cell apoptosis and alleviate SASP. CONCLUSIONS: This study revealed that RAD ameliorates mitochondrial function to alleviate SASP through enhancing autophagy flux, mitophagy, and apoptosis which provided a molecular basis for the advancement and development of protection strategies against HLAP.
Subject(s)
Apoptosis , Autophagy , Hyperlipidemias , Mice, Inbred C57BL , Mitochondria , Pancreatitis , Animals , Pancreatitis/drug therapy , Autophagy/drug effects , Apoptosis/drug effects , Hyperlipidemias/drug therapy , Mitochondria/drug effects , Mitochondria/metabolism , Mice , Male , Atractylodes/chemistry , Drugs, Chinese Herbal/pharmacology , Pancreas/drug effects , Pancreas/pathology , Rhizome/chemistry , Disease Models, Animal , Alisma/chemistryABSTRACT
BACKGROUND: The occurrence of hyperlipidemia is significantly influenced by lipid synthesis, which is regulated by sterol regulatory element binding proteins (SREBPs), thus the development of drugs that inhibit lipid synthesis has become a popular treatment strategy for hyperlipidemia. Alisol B (ALB), a triterpenoid compound extracted from Alisma, has been reported to ameliorate no-nalcoholic steatohepatitis (NASH) and slow obesity. However, the effect of ALB on hyperlipidemia and mechanism are unclear. PURPOSE: To examine the therapeutic impact of ALB on hyperlipidemia whether it inhibits SREBPs to reduce lipid synthesis. STUDY DESIGN: HepG2, HL7702 cells, and C57BL/6J mice were used to explore the effect of ALB on hyperlipidemia and the molecular mechanism in vivo and in vitro. METHODS: Hyperlipidemia models were established using western diet (WD)-fed mice in vivo and oleic acid (OA)-induced hepatocytes in vitro. Western blot, real-time PCR and other biological methods verified that ALB regulated AMPK/mTOR/SREBPs to inhibit lipid synthesis. Cellular thermal shift assay (CETSA), molecular dynamics (MD), and ultrafiltration-LC/MS analysis were used to evaluate the binding of ALB to voltage-dependent anion channel protein-1 (VDAC1). RESULTS: ALB decreased TC, TG, LDL-c, and increased HDL-c in blood, thereby ameliorating liver damage. Gene set enrichment analysis (GSEA) indicated that ALB inhibited the biosynthesis of cholesterol and fatty acids. Consistently, ALB inhibited the protein expression of n-SREBPs and downstream genes. Mechanistically, the impact of ALB on SREBPs was dependent on the regulation of AMPK/mTOR, thereby impeding the transportation of SREBPs from endoplasmic reticulum (ER) to golgi apparatus (GA). Further investigations indicated that the activation of AMPK by ALB was independent on classical upstream CAMKK2 and LKB1. Instead, ALB resulted in a decrease in ATP levels and an increase in the ratios of ADP/ATP and AMP/ATP. CETSA, MD, and ultrafiltration-LC/MS analysis indicated that ALB interacted with VDAC1. Molecular docking revealed that ALB directly bound to VDAC1 by forming hydrogen bonds at the amino acid sites S196 and H184 in the ATP-binding region. Importantly, the thermal stabilization of ALB on VDAC1 was compromised when VDAC1 was mutated at S196 and H184, suggesting that these amino acids played a crucial role in the interaction. CONCLUSION: Our findings reveal that VDAC1 serves as the target of ALB, leading to the inhibition of lipid synthesis, presents potential target and candidate drugs for hyperlipidemia.
Subject(s)
AMP-Activated Protein Kinases , Cholestenones , Hyperlipidemias , TOR Serine-Threonine Kinases , Voltage-Dependent Anion Channel 1 , Animals , Humans , Male , Mice , Alisma/chemistry , AMP-Activated Protein Kinases/metabolism , Cholestenones/pharmacology , Hep G2 Cells , Hepatocytes/drug effects , Hepatocytes/metabolism , Hyperlipidemias/drug therapy , Mice, Inbred C57BL , Molecular Docking Simulation , Signal Transduction/drug effects , TOR Serine-Threonine Kinases/metabolism , Voltage-Dependent Anion Channel 1/metabolismABSTRACT
Two undescribed protostane triterpenoids, 11-deoxy-13(17),15-dehydro-alisol B 23-acetate (2) and alisol S (3), together with 21 known ones (1, 4-23), were isolated from the dried rhizome of Alisma plantago-aquatica. Of these compounds, 13(17),15-Dehydro-alisol B 23-acetate (1) and 11-deoxy-13(17),15-dehydro-alisol B 23-acetate (2) are two protostane triterpenoids containing conjugated double bonds in the five-membered ring D that are rarely found from nature resource, while alisol S (3) is a protostane triterpenoid with undescribed tetrahydrofuran moiety linked via C20 -O-C24 at the side chain. Additionally, compoundâ 18 is a new natural product, and cycloartenol triterpenoid 23 is a non protostane triterpenoid firstly isolated from genus Alisma. Their structures were elucidated by extensive spectral analysis of the UV, IR, MS, 1D and 2D NMR, and comparison of the experimental and calculated CD curves.
Subject(s)
Alisma , Triterpenes , Alisma/chemistry , Rhizome/chemistry , Triterpenes/chemistry , Plant Extracts/chemistry , Magnetic Resonance SpectroscopyABSTRACT
Ovule morphology, megasporogenesis, and megagametogenesis processes were examined in Hydrocleys nymphoides, Alisma plantago-aquatica, and Sagittaria montevidensis. Each of these species belongs to a different clade within the Alismataceae family. It is worth mentioning that the genus Hydrocleys previously belonged to the Limnocharitaceae family but is now classified within the Alismataceae. Flowers in different developmental stages were processed following classical histological methods for their observation with bright-field microscope. The three species present an anatropous and bitegmic mature ovule. This is tenuinucellate in A. plantago-aquatica and S. montevidensis and pseudo-crassinucellate in H. nymphoides. Although all three species have the same type of megasporogenesis, they differ in the megagametogenesis and in the total number of nuclei and cells that form the mature gametophyte. H. nymphoides has a female gametophyte composed of four cells and four nuclei, while A. plantago-aquatica and S. montevidensis have a female gametophyte of five cells and six nuclei. The results are discussed according to the phylogenetic position of each of the species. Moreover, new types of megagametophyte development are described: Hydrocleys and Sagittaria types. The reduction of the female gametophyte with respect to the Polygonum type is found in families belonging to the ANA grade and in other aquatic families within the order Alismatales. We infer that the reduction in the number of cells and nuclei in the female gametophyte is characteristic of species that inhabit aquatic environments. Future studies in aquatic species belonging to other families would be necessary to confirm this hypothesis.
Subject(s)
Sagittaria , Sagittaria/cytology , Ovule/cytology , Alisma/chemistry , Alisma/cytology , Alismataceae/cytologyABSTRACT
INTRODUCTION: The Chinese traditional herbs Cortex Moutan, Poria cocos, and Alisma orientale are considered to have potential to ameliorate periodontitis, although the possible underlying mechanisms remain mostly unknown. Due to the complex formulation of Chinese herbs, it is important to understand the mechanisms of pharmacologic effects of traditional herbs for better application in modern medical treatment. METHODS: Network pharmacology was applied to explore the mechanism of Cortex Moutan, Poria cocos, and Alisma orientale. First we analysed their chemical ingredients using the Traditional Chinese Medicine Systems Pharmacology database and identified 20 active ingredients. Then we analysed the target genes of these 20 active ingredients as well as genes associated with periodontitis and found 74 co-target genes. We further analysed the protein-protein interaction network of these 74 co-target genes using the STRING database and enriched the pathways using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. RESULTS: The top 10 core targets elicited were vascular endothelial growth factor A (VEGFA), interlukin-6 (IL-6), tumour necrosis factor (TNF), matrix metalloproteinase-2 (MMP2), matrix metalloproteinase-9 (MMP9), AKT serine/threonine kinase 1 (AKT1), prostaglandin-endoperoxide synthase 2 (PTGS2), kinase insert domain receptor (KDR), fibroblast growth factor 2 (FGF2), and serpin family E member 1 (SERPINE1). Using these a network of "herbs-ingredients-targetgenes-KEGG pathways." was constructed. CONCLUSIONS: The target and bioprocess network suggested that the pharmacologic effects of Cortex Moutan, Poria cocos, and Alisma orientale may be mainly dependent on their anti-inflammatory potential. Further work is required to eucidate their detailed mechanisms of activity.
Subject(s)
Alisma , Periodontitis , Wolfiporia , Humans , Matrix Metalloproteinase 2 , Alisma/chemistry , Vascular Endothelial Growth Factor AABSTRACT
Since the ethanol extract of Alisma orientale Juzepzuk (EEAO) suppresses lung inflammation by suppressing Nuclear Factor-kappa B (NF-κB) and activating Nuclear Factor Erythroid 2-related Factor 2 (Nrf2), we set out to identify chemicals constituting EEAO that suppress lung inflammation. Here, we provide evidence that among the five most abundant chemical constituents identified by Ultra Performance Liquid Chromatography (UPLC) and Nuclear Magnetic Resonance (NMR), alismol is one of the candidate constituents that suppresses lung inflammation in a lipopolysaccharide (LPS)-induced acute lung injury (ALI) mouse model and protects mice from ALI-like symptoms. Alismol did not induce cytotoxicity or reactive oxygen species (ROS). When administered to the lung of LPS-induced ALI mice (n = 5/group), alismol decreased the level of neutrophils and of the pro-inflammatory molecules, including Tumor Necrosis Factor-alpha (TNF-α), Interleukin-1 beta (IL-1ß), Interleukin-6 (IL-6), Monocyte Chemoattractant Protein-1 (MCP-1), Interferon-gamma (IFN-γ), and Cyclooxygenase-2 (COX-2), suggesting an anti-inflammatory activity of alismol. Consistent with these findings, alismol ameliorated the key features of the inflamed lung of ALI, such as high cellularity due to infiltrated inflammatory cells, the development of hyaline membrane structure, and capillary destruction. Unlike EEAO, alismol did not suppress NF-κB activity but rather activated Nrf2. Consequently, alismol induced the expression of prototypic genes regulated by Nrf2, including Heme Oxygenase-1 (HO-1), NAD(P)H: quinine oxidoreductase-1 (NQO-1), and glutamyl cysteine ligase catalytic units (GCLC). Alismol activating Nrf2 appears to be associated with a decrease in the ubiquitination of Nrf2, a key suppressive mechanism for Nrf2 activity. Together, our results suggest that alismol is a chemical constituent of EEAO that contributes at least in part to suppressing some of the key features of ALI by activating Nrf2.
Subject(s)
Acute Lung Injury , Alisma , Pneumonia , Animals , Mice , Acute Lung Injury/metabolism , Heme Oxygenase-1/genetics , Heme Oxygenase-1/metabolism , Interleukin-6/metabolism , Lipopolysaccharides/toxicity , NF-E2-Related Factor 2/genetics , NF-E2-Related Factor 2/metabolism , NF-kappa B/metabolism , Pneumonia/metabolismABSTRACT
Titanium dioxide nanoparticles (nTiO2) and phosphorus (P) are widely present in sewages. To verify the hypothesis and the associated mechanisms that root-to-shoot translocation of nTiO2 can enhance plant P uptake thus P removal during sewage treatment, two wetland plants (Pistia stratiotes and Alisma plantago-aquatica) with different lateral root structures were used to examine the effect of nTiO2 (89.7% anatase and 10.3% rutile) on plant growth and P uptake in a hydroponic system. Inductively coupled plasma-optical emission spectroscopy and transmission electron microscopy-energy dispersive spectroscopy showed that P. stratiotes with well-developed lateral roots translocated 1.4-16 fold higher nTiO2 than A. plantago-aquatica with poorly developed roots, indicating P. stratiotes is efficient in nTiO2 uptake. In addition, nTiO2 root-to-shoot translocation in P. stratiotes increased with increasing nTiO2 concentration, while the opposite occurred in A. plantago-aquatica. Corresponding to the stronger nTiO2 translocation in P. stratiotes, its P uptake efficiency (Imax) and P accumulation were greater than that in A. plantago-aquatica, with Imax being increased by 35.8% and -16.4% and shoot P concentrations being increased by 16.2-64.6% and 11.4%, respectively. The strong positive correlation between Ti and P concentrations in plant tissues (r = 0.72-0.89, P < 0.01) indicated that nTiO2 translocation enhanced P uptake. Moreover, nTiO2-enhanced P uptake promoted plant growth and photosynthetic pigment synthesis. Therefore, wetland plants with well-developed lateral roots like P. stratiotes have potential to be used in P removal from nTiO2-enriched sewages.
Subject(s)
Alisma , Araceae , Nanoparticles , Phosphorus , Wetlands , Alisma/chemistryABSTRACT
A new sesquiterpene (1) and a new norsesquiterpene (2) belonging guaiane-type skeleton together with six known compounds (3-8) were isolated from the rhizomes of Alisma plantago-aquatica. Their structures were determined by HR-ESI-MS, 1D and 2D NMR spectroscopic methods. Absolute configurations of new compounds were established by experimental and TD-DFT computational ECD spectra. Compounds 1-8 exhibited xanthine oxidase inhibitory activity with their IC50 values in range of 9.4-66.7â µM. The sesquiterpenoids 1-5 displayed the inhibitory activity and hence they could be potential xanthine oxidase inhibitors from A. plantago-aquatica.
Subject(s)
Alisma , Sesquiterpenes , Molecular Structure , Alisma/chemistry , Xanthine Oxidase , Sesquiterpenes/pharmacology , Sesquiterpenes/chemistryABSTRACT
Alisma L. is a genus of aquatic and wetland plants belonging to family Alismataceae. At present, it is thought to contain ten species. Variation in ploidy level is known in the genus, with diploids, tetraploids and hexaploids recorded. Previous molecular phylogenetic studies of Alisma have generated a robust backbone that reveals important aspects of the evolutionary history of this cosmopolitan genus, yet questions remain unresolved about the formation of the polyploid taxa and the taxonomy of one particularly challenging, widely distributed species complex. Here we directly sequenced, or cloned and sequenced, nuclear DNA (nrITS and phyA) and chloroplast DNA (matK, ndhF, psbA-trnH and rbcL) of multiple samples of six putative species and two varieties, and conducted molecular phylogenetic analyses. Alisma canaliculatum and its two varieties known in East Asia and A. rariflorum endemic to Japan possess closely related but heterogeneous genomes, strongly indicating that the two species were generated from two diploid progenitors, and are possibly siblings of one another. This evolutionary event may have occurred in Japan. Alisma canaliculatum var. canaliculatum is segregated into two types, each of which are geographically slightly differentiated in Japan. We reconstructed a single phylogeny based on the multi-locus data using Homologizer and then applied species delimitation analysis (STACEY). This allowed us to discern A. orientale as apparently endemic to the Southeast Asian Massif and distinct from the widespread A. plantago-aquatica. The former species was most likely formed through parapatric speciation at the southern edge of the distribution of the latter.
Subject(s)
Alisma , Alismataceae , Phylogeny , Alisma/genetics , Alismataceae/genetics , DNA, Plant/genetics , Sequence Analysis, DNA , Polyploidy , Evolution, MolecularABSTRACT
ETHNOPHARMACOLOGICAL RELEVANCE: The combination of Alisma and Atractylodes (AA), a classical traditional Chinese herbal decoction, may protect against cerebral ischaemia/reperfusion injury (CIRI). However, the underlying mechanism has not been characterized. Intriguingly, exosomal microRNAs (miRNAs) have been recognized as vital factors in the pharmacology of Chinese herbal decoctions. AIM OF THE STUDY: The aim of the present study was to assess whether the neuroprotective effect of AA was dependent on the efficient transfer of miRNAs via exosomes in the brain. MATERIALS AND METHODS: Bilateral common carotid artery ligation (BCAL) was used to induce transient global cerebral ischaemia/reperfusion (GCI/R) in C57BL/6 mice treated with/without AA. Neurological deficits were assessed with the modified neurological severity score (mNSS) and Morris water maze (MWM) test. Western blot (WB) analysis was used to detect the expression of sirtuin 1 (SIRT1) in the cerebral cortex. The inflammatory state was quantitatively evaluated by measuring the expression of phospho-Nuclear factor kappa B (p-NF-κB), Interleukin-1ß (IL-1ß) and tumor necrosis factor-α (TNF-α) using WB analysis and glial fibrillary acidic protein (GFAP) immunohistochemical staining. The protein expression of zonula occluden-1 (ZO-1), occludin, caudin-5 and CD31 was examined by immunohistochemical staining to determine bloodâbrain barrier (BBB) permeability. Exosomes were extracted from the brain interstitial space by ultracentrifugation and identified by transmission electron microscopy (TEM), WB analysis and nanoparticle tracking analysis (NTA). The origin of exosomes was clarified by measuring the specific mRNAs within exosomes via Real Time Quantitative PCR (RTâqPCR). Differential miRNAs in exosomes were identified using microarray screening and were validated by RTâqPCR. Exosomes were labelled with fluorescent dye (PKH26) and incubated with bEnd.3 cells, the supernatant was collected, IL-1ß/TNF-α expression was measured using enzyme-linked immunosorbent assay (ELISA), total RNA was extracted, and miR-200a-3p/141-3p expression was examined by RTâqPCR. In addition, the levels of miR-200a-3p/141-3p in oxygen glucose deprivation/reoxygenation (OGD/R)-induced bEnd.3 cells were quantified. The direct interaction between miR-200a-3p/141-3p and the SIRT1 3' untranslated region (3'UTR) was measured by determining SIRT1 expression in bEnd.3 cells transfected with the miR-200a-3p/141-3p mimic/inhibitor. RESULTS: Severe neurological deficits and memory loss caused by GCI/R in mice was markedly ameliorated by AA treatment, particularly in the AA medium-dose group. Moreover, AA-treated GCI/R-induced mice showed significant increases in SIRT1, ZO-1, occludin, caudin-5, and CD31 expression levels and decreases in p-NF-κB, IL-1ß, TNF-α, and GFAP expression levels compared with those in untreated GCI/R-induced mice. Furthermore, we found that miR-200a-3p/141-3p was enriched in astrocyte-derived exosomes from GCI/R-induced mice and could be inhibited by treatment with a medium dose of AA. The exosomes mediated the transfer of miR-200a-3p/141-3p into bEnd.3 cells, promoted IL-1ß and TNF-α release and downregulated the expression of SIRT1. No significant changes in the levels of miR-200a-3p/141-3p were observed in OGD/R-induced bEnd.3 cells. The miR-200a-3p/141-3p mimic/inhibitor decreased/increased SIRT1 expression in bEnd.3 cells, respectively. CONCLUSION: Our findings demonstrated that AA attenuated inflammation-mediated CIRI by inhibiting astrocyte-derived exosomal miR-200a-3p/141-3p by targeting the SIRT1 gene, which provided further evidence and identified a novel regulatory mechanism for the neuroprotective effects of AA.
Subject(s)
Alisma , Atractylodes , Brain Ischemia , MicroRNAs , Reperfusion Injury , Mice , Animals , Sirtuin 1/genetics , Alisma/genetics , Alisma/metabolism , NF-kappa B , Tumor Necrosis Factor-alpha/pharmacology , Endothelial Cells/metabolism , Astrocytes/metabolism , Occludin , Mice, Inbred C57BL , MicroRNAs/metabolism , Brain Ischemia/metabolism , Reperfusion Injury/metabolism , ApoptosisABSTRACT
The treatment of cardiovascular diseases and obesity, two diseases posing a major risk to human health, has been plagued by the scarcity of potent and effective medication with fewer side effects. To address this problem, numerous efforts, and some progress, have been made. Among possible treatments are some medicinal herbs; particularly promising is Alisma orientale (AO). In the last decade, an increasing amount of research has shown that AO has some desirable therapeutic effects on cardiovascular diseases and obesity. Because of its efficacy, natural origin, and minimal adverse effects, AO has aroused great attention. Based on this, this review provides an overview of the latest progress from the last decade regarding the pharmacological and therapeutic effects, molecular mechanisms, and related effective constituents of AO in the treatment of cardiovascular diseases and obesity. Results from the research currently available reveal that active constituents of AO, such as alisol B 23-acetate, alisol A 24-acetace, and alisol A, have been proven to be effective for treating cardiovascular diseases by modulating the lipid metabolism of macrophages, improving the biological behavior of vascular smooth muscle cells (VSMCs), and enhancing anti-inflammatory effects. Moreover, the active constituents of AO can also intervene in obesity by modulating abnormal glucose and lipid metabolism and fat decomposition of the body by activating the AMPK- and PPAR-related signaling pathways. In summation, based upon our research of available literature, this review reveals that AO and its active constituents have a great potential to be used as drugs for treating cardiovascular diseases and ameliorating obesity.
Subject(s)
Alisma , Cardiovascular Diseases , Humans , Plant Extracts/pharmacology , Plant Extracts/therapeutic use , Cardiovascular Diseases/drug therapyABSTRACT
CONTEXT: Previously, we found Alisma orientalis beverage (AOB), a classic traditional Chinese medicine (TCM) formulation, had the potential effect of treating atherosclerosis (AS). The underlying mechanism was still unclear. OBJECTIVE: As an extention of our previous work, to investigate the underlying mechanism of action of AOB in the treatment for AS. MATERIALS AND METHODS: Network pharmacology was conducted using SwissTargetPrediction, GeneCards, DrugBank, Metascape, etc., to construct component-target-pathway networks. In vivo, AS models were induced by a high-fat diet (HFD) for 8 consecutive weeks in APOE-/- mice. After the administration of AOB (3.8 g/kg, i.g.) for 8 weeks, we assessed the aortic plaque, four indicators of blood lipids, and expression of the PI3K/AKT/SREBP-1 pathway in liver. RESULTS: Network pharmacology showed that PI3K/AKT/SREBP-1 played a role in AOB's treatment for AS (PI3K: degree = 18; AKT: degree = 17). Moreover, we found that the arterial plaque area and four indicators of blood lipids were all significantly reversed by AOB treatment in APOE-/- mice fed with HFD (plaque area reduced by about 37.75%). In addition, phosphorylated expression of PI3K/AKT and expression of SREBP-1 were obviously increased in APOE-/- mice fed with HFD, which were all improved by AOB (PI3K: 51.6%; AKT: 23.6%; SREBP-1: 40.0%). CONCLUSIONS: AOB had therapeutic effects for AS by improving blood lipids and inhibition of the PI3K/AKT/SERBP-1 pathway in the liver. This study provides new ideas for the treatment of AS, as well as new evidence for the clinical application of AOB.
Subject(s)
Alisma , Atherosclerosis , Plaque, Atherosclerotic , Animals , Mice , Proto-Oncogene Proteins c-akt/metabolism , Phosphatidylinositol 3-Kinases/metabolism , Alisma/metabolism , Sterol Regulatory Element Binding Protein 1/metabolism , Sterol Regulatory Element Binding Protein 1/pharmacology , Signal Transduction , Diet, High-Fat/adverse effects , Atherosclerosis/drug therapy , Plaque, Atherosclerotic/drug therapy , Lipids , Apolipoproteins E/genetics , Apolipoproteins E/pharmacology , Apolipoproteins E/therapeutic use , Mice, Inbred C57BLABSTRACT
Background: Over the years, Alisma Shugan Decoction (ASD), because of its potent anti-inflammation activity, has been used in traditional Chinese medicine (TCM) for treatment of many inflammation-associated disorders including those of the heart, blood vessel and brain. Methods: Herein, we examined the probable therapeutic effect of ASD in carbon tetrachloride (CCl4)-induced liver injury and fibrosis mice models. Results: Our results demonstrate that ASD dose-dependently reduced the fibrosis-related increased collagen deposition secondary to liver tissue exposure to CCl4. Data from our biochemical analyses showed significantly less liver damage biomarkers including ALT, AST and hydroxyproline in the ASD-treated samples, suggesting hepato-protective effect of ASD. Furthermore, we demonstrated that treatment with ASD significantly reversed CCl4-induced elevation of TNF-α, IL-6, IL-1ß and MP-1. Interestingly, NF-κB signalling, a principal regulator of inflammation was markedly suppressed by ASD treatment. In addition, treatment with ASD deregulated stress signalling pathways by suppressing the expression of markers of unfolded protein response, such as ATF6, IRE and GRP78. Conclusion: In conclusion, the present study provides preclinical evidence for the use of ASD as an efficacious therapeutic option in cases of chemical-induced liver damage and/or fibrosis. Further large-cohort validation of these findings is warranted.
Subject(s)
Alisma , Carbon Tetrachloride , Humans , Rats , Mice , Animals , Carbon Tetrachloride/adverse effects , Carbon Tetrachloride/metabolism , Rats, Sprague-Dawley , Liver Cirrhosis/chemically induced , Liver Cirrhosis/drug therapy , Liver/pathology , Fibrosis , Inflammation/metabolism , Endoplasmic Reticulum StressABSTRACT
Targeted high-throughput screening of inhibitors from natural products is an effective approach in the treatment of cancer progression. RhoA protein is essential for many signaling pathways. It is closely related to the occurrence and development of tumor. So far, there are only a few reports on the screening of small molecule inhibitors of RhoA protein from natural products. In this study, an online UHPLC-PDA-MS2-RhoA-FLD screening system was established for the first time to identify RhoA inhibitors from medicinal Alisma. Using this online system by adding fluorescent probes protopine [LZ1] to proteins, 17 active components were identified from Alisma, including 14 terpenoids. Their binding abilities were evaluated by Surface Plasmon Resonance experiments. The activities of representative compounds were tested and showed anti-proliferative effect in cancer cells. Mechanistic studies showed that these compounds were able to downregulate the cellular expressions of RhoA associated proteins. This study provides potential lead compounds as small molecule inhibitors of RhoA protein for cancer therapy. This reported method can be used for targeted screening of small molecule inhibitors against tumors, and provides an approach for screening tumor inhibitors from natural products.
Subject(s)
Alisma , Biological Products , rhoA GTP-Binding Protein/metabolism , Online SystemsABSTRACT
Field observations of flowering Alisma plantago-aquatica plants were carried out in Moscow region (Russia). The A. plantago-aquatica flower remains anthetic for a single light day, from 9:00 a.m. to 8:00 p.m. White petals showed a contrast bicolored pattern in UV light, and the pattern probably serves as a nectar clue for pollinators. Flowers were visited by insects in daytime from 11:00 a.m. to 3:00 p.m. Coleopterans (Coccinellidae), dipterans (Drosophilidae, Hybotidae, Muscidae, Sepsidae, and Syrphidae), and hymenopterans (Apidae) were observed as flower visitors. Hoverflies (Syrphidae) and bees (Apidae) were the most frequent visitors. Large amounts of A. plantago-aquatica pollen grains were found on their bodies, and a major role in pollination was consequently assumed for the insects. Based on the original findings and literature data on A. plantago-aquatica reproductive biology in Belgium, Slovakia, and the Czech Republic, hoverflies were identified as the most stable and efficient pollinators of A. plantago-aquatica in various parts of the species range. Bees (Apidae) were recognized as A. plantago-aquatica pollinators for the first time in this work. A flower isolation experiment confirmed that A. plantago-aquatica is a self-compatible plant, but requires insects for the most efficient cross-pollination.