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The flowering plant genus Alisma, which belongs to the family Alismataceae, comprises 11 species, including Alisma orientale, Alisma canaliculatum, and Alisma plantago-aquatica. Alismatis rhizome (Ze xie in Chinese, Takusha in Japanese, and Taeksa in Korean, AR), the tubers of medicinal plants from Alisma species, have long been used to treat infla...
Contexts in source publication
Context 1
... AB23A suppressed HepG2 cell growth by inducing G1 arrest and increasing the percentage of apoptotic cells without affecting LO2 normal cells [29]. In addition to in vitro models, AB23A significantly reduced tumor volume and weight by inducing apoptosis in BALB/c mice inoculated with SK-HEP-1 [30] (Table 1). ...Context 2
... pharmacological effects of AR and its triterpenes in suppressing tumor proliferation and metastasis in various human cancer cells have gained attention because of their potential as anticancer therapies. This review indicates that AR and its triterpene can inhibit the proliferation of various cancers by inducing cell cycle arrest, apoptosis, and autophagy, as suggested in Table 1 and Figure 2. Most studies regarding the cytotoxic effects of AR and its triterpene have shown that the inhibition of cell viability, on which the growth of cancer depends, is a useful target for the suppression of cell proliferation. ...Context 3
... pharmacological effects of AR and its triterpenes in suppressing tumor proliferation and metastasis in various human cancer cells have gained attention because of their potential as anticancer therapies. This review indicates that AR and its triterpene can inhibit the proliferation of various cancers by inducing cell cycle arrest, apoptosis, and autophagy, as suggested in Table 1 and Figure 2. Most studies regarding the cytotoxic effects of AR and its triterpene have shown that the inhibition of cell viability, on which the growth of cancer depends, is a useful target for the suppression of cell proliferation. ...Similar publications
Background:
Salvianolic acid B (Sal B) is a representative component of phenolic acids derived from the dried root and rhizome of Salvia miltiorrhiza Bge. (Labiatae), which promotes angiogenesis in myocardial infarction and diabetic cardiomyopathy. However, whether Sal B has a neuroprotective function in ischemic stroke by promoting angiogenesis i...
Citations
... Protostane triterpenes constitute the main medicinal components of A. orientale, which include alisol B 23-acetate (AB23A), alisol C 23-acetate (AC23A), alisol A 24-acetate (AA24A), alisol C, and others (Zhao et al. 2013). Protostane triterpenes derived from A. orientale are associated with protection against diseases such as hyperlipidemia, hypertension, human immunodeficiency virus 1 (HIV1) (Yang et al. 2023;Li et al. 2019b, a;Shao et al. 2018;Wang et al. 2019), and cancer (Jang et al. 2021;Xia et al. 2019). In plants, terpenes are synthesized by MVA and 2-C-methyl-D-erythritol-4-phosphate (MEP) pathways and triterpenes are mainly synthesized by the MVA pathway. ...
Protostane triterpenes are medicinally important components found in members of the Alismataceae botanical family, notably Alisma orientale. Methyl jasmonate (MeJA) is known to regulate protostane triterpene biosynthesis in A. orientale, but the microRNA (miRNA) mechanism underlying MeJA response to promote triterpene biosynthesis remains unknown. In this study, we conducted miRNA sequencing analysis after MeJA induction in A. orientale to uncover the role of miRNAs in protostane triterpene biosynthesis. We identified 222 known miRNAs and 379 novel miRNAs, including 16 differentially expressed miRNAs (DEMs) between control and MeJA-treated leaf samples. Based on the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and Gene Ontology (GO) enrichment analysis, four DEMs and eight miRNA target genes were significantly enriched in the triterpene biosynthesis pathway. Integrated analysis of the transcriptome and miRNAome revealed a negative expression pattern between miRNAs and their target genes. We then constructed a regulatory network of miRNA-target gene relationships involved in the triterpene biosynthesis pathway. We found miRNAs may be involved in the response of A. orientale to exogenous MeJA by regulating the expression of key biosynthesis enzymes, leading to increased accumulation of medically important protostane triterpenes.
... They have been used to treat diseases such as diuresis, oliguria, diabetes, hyperlipidemia, hepatitis and obesity (Liu et al., 2013;Jang et al., 2015). The potential of these two plants' tubers in cancer treatment had been also explored in one recent research (Jang and Lee, 2021). Furthermore, the extracts of A. canaliculatum have been used to treat gastric cancer (Kwon et al., 2021). ...
Alisma L. is a medicinally important genus of aquatic and wetland plants consisting of c. 10 recognized species. However, largely due to polyploidy and limited taxon and gene sampling, the phylogenomic relationships of Alisma remain challenging. In this study, we sequenced 34 accessions of Alismataceae, including eight of the ten species of Alisma, one species of Echinodorus and one species of Luronium, to perform comparative analyses of plastid genomes and phylogenetic analyses. Comparative analysis of plastid genomes revealed high sequence similarity among species within the genus. Our study analyzed structural changes and variations in the plastomes of Alisma, including IR expansion or contraction, and gene duplication or loss. Phylogenetic results suggest that Alisma is monophyletic, and constitutes four groups: (1) A. lanceolatum and A. canaliculatum; (2) the North American clade of A. subcordatum and A. triviale; (3) A. wahlenbergii and A. gramineum; and (4) A. plantago-aquatica from Eurasia and northern Africa with the eastern Asian A. orientale nested within it. Hence the results challenge the recognition of A. orientale as a distinct species and raise the possibility of treating it as a synonym of the widespread A. plantago-aquatica. The well-known Alismatis Rhizoma (Zexie) in Chinese medicine was likely derived from the morphologically variable Alisma plantago-aquatica throughout its long history of cultivation in Asia. The plastome phylogenetic results also support the tetraploid A. lanceolatum as the likely maternal parent of the hexaploid eastern Asian A. canaliculatum.
... In addition, these triterpenoids might mediate beneficial effects by blocking the PI3K/Akt/mTOR signaling pathway. [18][19][20] In this investigation, we utilized UPLC-Triple-TOF/MS to isolate and identify the constituents and metabolites of AO extract that could enter the eye. This approach was complemented with network pharmacology, molecular docking, molecular dynamics simulation, and experimental validation, to elucidate the AO's potential targets and mechanisms of ameliorating ME. ...
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.
... The binding of VeGF to its receptor VeGFr activates the Pi3K/aKT signaling pathway, which, in turn, regulates endothelial cell formation of blood vessels (38). results of previous studies demonstrated that triterpene saponins markedly inhibit the Pi3K/aKT signaling pathway (39,40). notably, results of the present study demonstrated that treatment with VeGF-165 activated the Pi3K/aKT signaling pathway and HuVec migration and tube formation were significantly increased. ...
Anemone flaccida Fr. Schmidt, a Traditional Chinese Medicine, has been used in the treatment of rheumatoid arthritis (RA) for numerous years. However, the specific mechanisms remain to be elucidated. Thus, the present study aimed to investigate the main chemical constituents and potential mechanisms of Anemone flaccida Fr. Schmidt. The ethanol extract obtained from Anemone flaccida Fr. Schmidt (EAF) was analyzed using mass spectrometry to determine the main components and the therapeutic effects of EAF on RA were verified using a collagen‑induced arthritis (CIA) rat model. Results of the present study demonstrated that synovial hyperplasia and pannus of the model rats were significantly improved following EAF treatment. Moreover, the protein expression levels of VEGF and CD31‑labeled neovascularization were significantly reduced in the synovium of CIA rats following treatment with EAF, compared with those of the untreated model group. Subsequently, in vitro experiments were carried out to verify the impact of EAF on synovial proliferation and angiogenesis. Results of the western blot analysis revealed that EAF inhibited the PI3K signaling pathway in endothelial cells, which is associated with anti‑angiogenesis. In conclusion, results of the present study demonstrated the therapeutic effects of Anemone flaccida Fr. Schmidt on RA and preliminarily revealed the mechanisms of this drug in the treatment of RA.
... Alismatis rhizoma (Ze Xie in Chinese, Takusha in Japanese, and Taeksa in Korean) (Jang and Lee, 2021), derived from the dried tubers of Alisma plantago-aquatica L. of the Alismataceae family, has been recorded by Zhongjing Zhang of the Eastern Han dynasty in "Jin Gui Yao Lue" (Synopsis of Prescriptions of the Golden Chamber) (Song, 2009) and Li Shizhen of the Ming Dynasty in "Compendium of Materia Medica" (Li and Luo, 2003). Its traditional efficacy mainly includes diuretic and hypolipidemic therapy. ...
Alismatis rhizoma is a traditional Chinese medicine. Studies have demonstrated that Alismatis rhizoma also has therapeutic effects on metabolic syndrome. However, the pharmacodynamic material basis and mechanism are still unclear. First, UHPLC/Q-Orbitrap MS was used to detect the chemical components of the Alismatis rhizoma extract, and 31 triterpenoids and 2 sesquiterpenes were preliminarily identified. Then, to investigate the mechanism of the Alismatis rhizoma extract on metabolic syndrome, a mouse model of metabolic syndrome induced by high-fructose drinks was established. The results of serum biochemical analysis showed that the levels of TG, TC, LDL-C, and UA after the Alismatis rhizoma extract treatment were markedly decreased. ¹H-NMR was used to conduct non-targeted metabolomics studies. A total of 20 differential metabolites were associated with high-fructose–induced metabolic syndrome, which were mainly correlated with 11 metabolic pathways. Moreover, UHPLC/Q-Orbitrap MS lipidomics analysis found that a total of 53 differential lipids were screened out. The results showed that Alismatis rhizoma extract mainly reduces the synthesis of glycerophospholipid and ceramide and improves the secretion of bile acid. This study shows that the Alismatis rhizoma extract can treat metabolic syndrome mainly by inhibiting energy metabolism, amino acid metabolism, and regulating bile acid to reduce phospholipid content.
... It exerts anti-apoptotic effects in this cell system [98] and also reduces apoptosis of neurons, via up-regulation of the expression of phosphorylated PI3K and AKT [99]. The blockade of thee PI3K/Akt/mTOR signaling pathway is important to the mechanism of action of AR and specifically to Ali-A 24-acetate, not only providing a protection against neuronal damages but also essential to the anticancer action of the extract and the product, as discussed thereafter [100]. ...
More than 100 protostane triterpenoids have been isolated from the dried rhizomes of Alisma species, designated Alismatis rhizoma (AR), commonly used in Asian traditional medicine to treat inflammatory and vascular diseases. The main products are the alisols, with the lead compounds alisol-A/-B and their acetate derivatives being the most abundant products in the plant and the best-known bioactive products. The pharmacological effects of Ali-A, Ali-A 24-acetate, Ali-B, Ali-B 23-acetate, and derivatives have been analyzed to provide an overview of the medicinal properties, signaling pathways, and molecular targets at the origin of those activities. Diverse protein targets have been proposed for these natural products, including the farnesoid X receptor, soluble epoxide hydrolase, and other enzymes (AMPK, HCE-2) and functional proteins (YAP, LXR) at the origin of the anti-atherosclerosis, anti-inflammatory, antioxidant, anti-fibrotic, and anti-proliferative activities. Activities were classified in two groups. The lipid-lowering and anti-atherosclerosis effects benefit from robust in vitro and in vivo data (group 1). The anticancer effects of alisols have been largely reported, but, essentially, studies using tumor cell lines and solid in vivo data are lacking (group 2). The survey shed light on the pharmacological properties of alisol triterpenoids frequently found in traditional phytomedicines.
... It has become very clear that, considering their very large plethora of biologic effects, triterpenic acids presumably act on multiple pathways; indeed, there are many reviews published in the past 10 years regarding their mechanism of action responsible for various activities, such as anticancer [15][16][17][18][19][20][21][22], immunomodulatory [23,24], antidiabetic [25][26][27][28][29][30], anti-inflammatory [31], cardioprotective [32], antiurolithic [33], antiviral [34], and wound healing [35,36]. This review aims to summarize the most recent (last five years) discoveries on triterpenic acids' mechanisms of action in order to provide scientists with exhaustive knowledge, which in turn might propel and diversify future studies. ...
Triterpenic acids are phytocompounds with a widespread range of biological activities that have been the subject of numerous in vitro and in vivo studies. However, their underlying mechanisms of action in various pathologies are not completely elucidated. The current review aims to summarize the most recent literature, published in the last five years, regarding the mechanism of action of three triterpenic acids (asiatic acid, oleanolic acid, and ursolic acid), corelated with different biological activities such as anticancer, anti-inflammatory, antidiabetic, cardioprotective, neuroprotective, hepatoprotective, and antimicrobial. All three discussed compounds share several mechanisms of action, such as the targeted modulation of the PI3K/AKT, Nrf2, NF-kB, EMT, and JAK/STAT3 signaling pathways, while other mechanisms that proved to only be specific for a part of the triterpenic acids discussed, such as the modulation of Notch, Hippo, and MALAT1/miR-206/PTGS1 signaling pathway, were highlighted as well. This paper stands as the first part in our literature study on the topic, which will be followed by a second part focusing on other triterpenic acids of therapeutic value.
... Cancer is a serious public health issue, with increasing rates of occurrence and mortality [1]. It is ranked by the WHO as one of the major causes of death worldwide, and was responsible for 10 million deaths in 2020 [2][3][4][5][6][7]. ...
... In past decades, immense advances in cancer research were achieved, especially in the provision of targeted prevention and treatments, which improved the quality of life and survival time remarkably. Nevertheless, cancer treatment remains a tremendous challenge due to its severe adverse effects, chemotherapy resistance or tumor progression and metastasis, and therefore worse prognoses [1,2,9,12]. Thus, there is an increased demand for new anticancer candidates to face these health concerns and reduce the cancer burden worldwide [5,6]. ...
... Herbal medicines can potentiate the activity and diminish the adverse effects and organ toxicities of chemotherapy. Moreover, medicinal plants themselves and natural product-derived compounds can target cancer cells effectively and selectively, without affecting normal cells [1,15]. This might be correlated to their diverse chemotypes and pharmacological effects [14]. ...
This study presents a comparison between two mistletoe plants—P. acacia and P. curviflorus—regarding their total phenolic contents and antioxidant and anticancer activities. P. curviflorus exhibited a higher total phenolics content (340.62 ± 19.46 mg GAE/g extract), and demonstrated higher DPPH free radical scavenging activity (IC50 = 48.28 ± 3.41µg/mL), stronger reducing power (1.43 ± 0.54 mMol Fe+2/g) for ferric ions, and a greater total antioxidant capacity (41.89 ± 3.15 mg GAE/g) compared to P. acacia. The cytotoxic effects of P. acacia and P. curviflorus methanol extracts were examined on lung (A549), prostate (PC-3), ovarian (A2780) and breast (MDA-MB-231) cancer cells. The highest anticancer potential for the two extracts was observed on PC-3 prostate cancer cells, where P. curviflorus exhibited more pronounced antiproliferative activity (IC50 = 25.83 μg/mL) than P. acacia (IC50 = 34.12 μg/mL). In addition, both of the tested extracts arrested the cell cycle at the Pre-G1 and G1 phases, and induced apoptosis. However, P. curviflorus extract possessed the highest apoptotic effect, mediated by the upregulation of p53, Bax, and caspase-3, 8 and 9, and the downregulation of Bcl-2 expression. In the pursuit to link the chemical diversity of P. curviflorus with the exhibited bioactivities, its metabolomic profiling was achieved by the LC-ESI-TOF-MS/MS technique. This permitted the tentative identification of several phenolics—chiefly flavonoid derivatives, beside some triterpenes and sterols—in the P. curviflorus extract. Furthermore, all of the metabolites in P. curviflorus and P. acacia were inspected for their binding modes towards both CDK-2 and EGFR proteins using molecular docking studies in an attempt to understand the superiority of P. curviflorus over P. acacia regarding their antiproliferative effect on PC-3 cancer cells. Docking studies supported our experimental results; with all of this taken together, P. curviflorus could be regarded as a potential prospect for the development of chemotherapeutics for prostate cancer.
... Therefore, the activation of AKT/GSK3β pathway exerts protective effects on NVU by reducing in ammation and apoptosis. Some triterpene components isolated from Alismatis Rhizoma (AR) have been widely con rmed for their anti-in ammation activities [10] . Alisol A is one of the triterpenes isolated from AR extract, which has been shown to exhibit various physiological effects [11] , including downregulating expression of TNF-α, IL-1β, IL-6 [12] . ...
Background
Neurovascular unit (NVU) dysfunction is a major process in the pathophysiological process of cerebral ischemia-reperfusion (CI/R). Our previous studies have confirmed that the main active ingredient of Alisma orientale exhibits protective effect on CI/R injury. Therefore, this study is designed to verify whether Alisol A, one of the main active components of Alisma, attenuates CI/R-induced NVU dysfunction through activation of AKT/GSK3β pathway.
Methods
C57BL/6J mice were used to establish the animal model of global cerebral ischemia- reperfusion (GCI/R) and treated with Alisol A and GSK690693 (an AKT inhibitor). We carried out modified neurological severity score (mNSS) and morris water maze (MWM) to test learning and memory abilities. Nissl staining and CD31, GFAP, Iba1, NeuN immunostaining were performed to determine morphological and quantitative changes in neuronal and endothelial cells, as well as overactivation of astrocytes and microglia. Ultrastructure changes of NVU were observed by transmission electron microscope (TEM). Expression of IL-6, IL-1β, BAX, Bcl-2 and AKT/GSK3βwere detected by enzyme-linked immunosorbent assay (ELISA) and western blot. The alterations in neuronal/glial metabolism were measured using magnetic resonance spectroscopy (MRS).
Results
The data showed that Alisol A treatment significantly improved neurological deficits and memory loss caused by GCI/R in C57BL/6J mice. Furthermore, Alisol A administration effectively suppressed the disruption of neurons and endothelial cells, activation of astrocytes and microglia, cell apoptosis and release of inflammatory factors in GCI/R-induced C57BL/6J mice, which were reversed by GSK690693.
Conclusions
Alisol A significantly alleviated NVU damage caused by GCI/R via activation of AKT/GSK3β, suggesting that Alisol A maybe a promising medicine for the treatment of GCI/R.
... Rhizoma alisamatis (Ze xie in Chinese, Takusha in Japanese, and Taeksa in Korean, AR) is one of a widely used medicinal and dietary plants in some East Asian countries (Jang and Lee, 2021). Alisol B 23-acetate (AB23A) was isolated from the rhizome of Rhizoma alisamatis as a natural triterpenoid and has been proven to show outstanding bioactivity, comprising anti-hyperlipidemia, hepatoprotective, and anti-inflammatory (Meng et al., 2015;Wang et al., 2019). ...
Alisol B 23-Acetate (AB23A) is a naturally occurring triterpenoid, which can be indicated in the rhizome of medicinal and dietary plants from Alisma species. Previous studies have demonstrated that AB23A could inhibit intestinal permeability by regulating tight junction (TJ)-related proteins. Even so, the AB23A protective mechanism against intestinal barrier dysfunction remains poorly understood. This investigation seeks to evaluate the AB23A protective effects on intestinal barrier dysfunction and determine the mechanisms for restoring intestinal barrier dysfunction in LPS-stimulated Caco-2 monolayers. According to our findings, AB23A attenuated the inflammation by reducing pro-inflammatory cytokines production like IL-6, TNF-α, IL-1β, and prevented the paracellular permeability by inhibiting the disruption of TJ in LPS-induced Caco-2 monolayers after treated with LPS. AB23A also inhibited LPS-induced TLR4, NOX1 overexpression and subsequent ROS generation in Caco-2 monolayers. Transfected with NOX1-specific shRNA diminished the up-regulating AB23A effect on ZO-1 and occludin expression. Moreover, transfected with shRNA of TLR4 not only enhanced ZO-1 and occludin expression but attenuated NOX1 expression and ROS generation. Therefore, AB23A ameliorates LPS-induced intestinal barrier dysfunction by inhibiting TLR4-NOX1/ROS signaling pathway in Caco-2 monolayers, suggesting that AB23A may have positive impact on maintaining the intestinal barrier’s integrity.
