Towards a better understanding of the therapeutic potential of Rhizoma Alismatis: A phytochemical and pharmacological review

Rhizoma Alismatis(RA),the dried rhizome of Alisma orientalis(Sam.)Juzep,isa widely used traditional herbal medicine popularly known as″Ze Xie″in Chinese.RA is an important crude herb component of several famous Chinese preparations including Zexie decoction,Liu Wei Di Huang pills,Wu Ling power and so on.It has been used to treat various ailments such as dysuria,edema,nephropathy,hypertension,hyperlipidemia and diabetes,etc.A wide range of chemical compounds mainly triterpenes,diterpenes and sesquiterpenes have been isolated from RA,among which the protostane-type triterpenes termed alisols attract the most attention owing to their unique chemical structure and various biological activity.The extract and active compounds of RAhave been demonstrated to possess a wide spectrum of pharmacological effects which support its clinical use,e.g.diuretic,hypoglycemic,hypolipidemic,hepatoprotective,preventing bone loss,anti-inflammatory andantivirus activities.In our previous studies,we have investigatedthe anti-proliferative activities of terpenoids isolated from RA and their structure-activity relationships.Alisol B 23-acetate was demonstrated to induce G1 phase cell cycle arrest and apoptosis,and inhibit migration and invasion of ovarian cancer cells.The present paper reviews the up-to-date information concerning the ethnopharmacology,phytochemistry,pharmacology and toxicology of RA.This information will be helpful for a better understanding of therapeutic potential of RA as wel as the further explorations.

Comprehensive metabolic profiling of Alismatis Rhizoma triterpenes in rats based on characteristic ions and a triterpene database

Alismatis Rhizoma(AR)is widely used in Chinese medicine,and its major bioactive components,triterpenes,reportedly possess various pharmacological activities.Therefore,it is very important to study the metabolism of triterpenes in vivo.However,the metabolism of AR triterpene extract has not been comprehensively elucidated due to its complex chemical components and metabolic pathways.In this study,an ultra-performance liquid chromatography quadrupole time-of-flight mass spectrometry method,which was based on the characteristic ions from an established database of known triterpenes,was used to analyze the major metabolites in rats following the oral administration of Alismatis Rhizoma extracts(ARE).As a result,a total of 233 constituents,with 85 prototype compounds and 148 metabolites,were identified for the first time.Hydrogenation,oxidation,sulfate and glucuronidation conjugation were the major metabolic pathways for triterpenes in AR.In addition,the mutual in vivo transformation of known ARE triterpenes was discovered and confirmed for the first time.Those results provide comprehensive insights into the metabolism of AR in vivo,which will be useful for future studies on its pharmacodynamics and pharmacokinetics.Moreover,this established strategy may be useful in metabolic studies of similar compounds.

Comparison of the effects and mechanisms of Alismatis Rhizoma with and without salt processing in ameliorating edema due to kidney Yin deficiency based on UPLC-Q-TOF-MS and transcriptomics

Salt-processed Alismatis Rhizoma(SAR)is extensively used in clinical practice and exhibits a more robust urination-promoting effect than Alismatis Rhizoma(AR).This study employed ultra-performance liquid chromatography–quadrupole-time-of-flight mass spectrometry(UPLC-Q-TOF-MS)and pattern analysis to compare the terpenoids between AR and SAR.Additionally,this study compared the effects of AR and SAR on the gene expression in the kidneys of the rat model of edema(syndrome of kidney Yin deficiency)by transcriptomics to decipher the mechanism of salt processing.Materials and methods:AR and SAR were extracted by ultrasonication,and data were collected by UPLC-Q-TOF-MS in the positive ionmode.Transcriptome sequencing was employed to determine the gene expression levels of the ratmodel treated with AR and SAR,and the differentially expressed genes(DEGs)were obtained.Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment was performed for the DEGs.The protein-protein interaction(PPI)network was built,on the basis of which the core targets were screened out.Finally,real-time quantitative polymerase chain reaction(RT-PCR)was conducted to verify the core targets.Results:A total of 63 terpenoids were detected in AR and SAR,and salt processing had a significant effect on the content of terpenoids.AR and SAR mainly participated in the regulation of inflammation and immune responses,and SAR regulated more DEGs than AR.Additionally,SAR exerted more extensive regulatory effects on the targets than AR.Conclusion:Salt processing mainly changes the content of chemical compounds in AR,which may indirectly optimize the proportion of the main compounds to enhance the therapeutic effect while reducing the toxicity.AR and SAR mainly ameliorate the edema due to kidney Yin deficiency by reducing inflammation and improving immunity.Finally,SAR regulates more genes and signaling pathways and exerts more extensive regulatory effects than AR.

Correlation analysis between the chemical contents and bioactivity for the quality control of Alismatis Rhizoma

In order to clarify regions of production and to discriminate processing methods, quantitative and qualitative analyses for saccharides and terpenes in 35 batches of Alismatis Rhizoma were performed.Methodologies included HPLC–PDA, HPLC–VWD and UHPLC–MSn, combined with principal component analysis(PCA) and partial least squares regression techniques(PLSR). The inhibitory effects of triterpenes and Alismatis Rhizoma extracts on lipase activity were evaluated in vitro. PLSR analysis revealed significant positive correlations(R2= 0.5795) between the contents of triterpenes 10, 14, 15, 18 and 22 and the inhibitory effects of Alismatis Rhizoma. The present study establishes an effective method for simultaneous determination of multiple components, and identifies key bioactive triterpenes. These results can be used for systematic and novel analytical strategies for the quality control of Alismatis Rhizoma production.

Hypolipidemic effects of Alismatis Rhizoma decoction on the lipid profile in hyperlipidemia rats by RNA-sequencing

As a disorder of lipid metabolism,hyperlipidemia(HLP)is characterized by elevated levels of lipids in the blood circulation.It is consistently related to the development of cardiovascular events and diseases associated with metabolic syndrome.Alismatis Rhizoma decoction(ARD),a well-known traditional Chinese medicine prescription,has long been used for treating vertigo,which is a symptom experienced by HLP patients.In this study,we aimed to investigate the hyperlipidemic activity and the potential molecular mechanisms of ARD in HLP rats at the transcriptional level.RNA sequencing and transcriptome analysis were performed collaboratively,including analysis of differentially expressed genes(DEGs),GO functions,and KEGG pathway analysis.The results showed that 1981 DEGs(1370 upregulated and 611 downregulated)were identified in the HFD group compared with the CON group.Moreover,474 DEGs(350 upregulated and 124 downregulated)were detected in the ARD group compared with the HFD group.Furthermore,GO analysis revealed that DEGs were mainly involved in the following functions:developmental process,response to an external stimulus,ion transport,alcohol binding,and plasma membrane part.Pathway analysis suggested that these DEGs were significantly enriched in bile secretion,malaria,cell adhesion molecules,retinol metabolism,the sphingolipid signaling pathway,chemical carcinogenesis,and the T cell receptor signaling pathway.In conclusion,our study demonstrated that ARD alleviated the lipid metabolism disorder caused by HLP through multiple mechanisms,which provided vital scientific evidence for further pharmacological studies of ARD.