ArticleLiterature Review

The genus Anemarrhena Bunge: A review on ethnopharmacology, phytochemistry and pharmacology

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Abstract

Ethnopharmacological relevance: Anemarrhena asphodeloides Bunge. (Asparagaceae) yields Anemarrhenae Rhizoma, which has a long history to be used as a traditional medicine to treat various ailments, like cold-induced febrile disease with arthralgia, hematochezia, tidal fever and night sweats by Yin deficiency, bone-steaming, cough, and hemoptysis. It is also used as an ingredient of healthy food, wine, tea, biological toothpaste. Its importance is demonstrated by large scale to treat kinds of diseases in eastern Asian countries. The aim of this review is to provide up-to-date information about phytochemistry, pharmacology, and toxicology of Anemarrhena asphodeloides based on scientific literatures. It will build up a new foundation for further study on mechanism and development of better therapeutic agent and healthy product from Anemarrhena asphodeloides. Material and methods: All the available information on Anemarrhena asphodeloides was collected via electronic search (using PubMed, SciFinder Scholar, CNKI, TPL (www.theplantlist.org), Google Scholar, Baidu Scholar, and Web of Science). Results: Comprehensive analysis of the literatures searched through sources available above confirmed that the ethnomedical uses of Anemarrhena asphodeloides had been recorded in China, Japan, and Korea for thousands of years. The phytochemical investigation revealed the presence of steroidal saponins, flavonoids, phenylpropanoids, alkaloids, steroids, organic acids, anthraquinones, and others. Crude extracts and pure compounds from Anemarrhena asphodeloides exhibited significant pharmacological effects on the nervous system and the blood system. They also showed valuable bioactivities, such as antitumor, anti-oxidation, anti-microbial, anti-virus, anti-inflammation, anti-osteoporosis, anti-skin aging and damage as well as other activities. Conclusions: In light of long traditional use and modern phytochemical and pharmacological studies summarized, Anemarrhena asphodeloides has demonstrated a strong potential for therapeutic and health-maintaining purposes. Both the extracts and chemical components isolated from the plant showed a wide range of biological activities. Thus more pharmacological mechanisms on main active compounds (TBII, TAIII, mangiferin and other ingredients) are necessary to be explored. In addition, as a good source of the traditional medicine, clinical studies of main therapeutic aspects (e.g. diabetes, Alzheimer׳s disease, Parkinson׳s disease, etc.), toxicity and adverse effect of Anemarrhena asphodeloides will also undoubtedly be the focus of future investigation.

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... The rhizomes of Anemarrhenae asphodeloides are also well-known as Zhimu and Yanghuzi in Chinese medicine and Chimoi and Jimo in Japanese and Korean medicine, respectively. 29 According to Chinese medicine, Anemarrhena rhizome is recognized as a traditional warm herb for yin nourishing, heat-clearing, and kidney, lung, and stomach meridian entering correlated with the curative function of treating dry cough, fevers, night sweats, menopause syndrome, and diabetes. 29,30 It contains an abundance of active constituents, such as xanthones, saponins, alkaloids, flavonoids, anthraquinones, phenylpropanoids, and organic acids 31,32 with a series of pharmacological benefits, including anti-inflammatory, antibacterial, antipyretic, antiviral, antidiabetic, and anticoagulation. ...
... 29 According to Chinese medicine, Anemarrhena rhizome is recognized as a traditional warm herb for yin nourishing, heat-clearing, and kidney, lung, and stomach meridian entering correlated with the curative function of treating dry cough, fevers, night sweats, menopause syndrome, and diabetes. 29,30 It contains an abundance of active constituents, such as xanthones, saponins, alkaloids, flavonoids, anthraquinones, phenylpropanoids, and organic acids 31,32 with a series of pharmacological benefits, including anti-inflammatory, antibacterial, antipyretic, antiviral, antidiabetic, and anticoagulation. 29,33 A recent study was conducted by Piwowar et al. 33 to evaluate the potential protective effects of the Anemarrhena rhizome ethanolic extract toward a HD in vitro model with 3-NP induced neurotoxicity in pheochromocytoma (PC-12) cells. ...
... 29,30 It contains an abundance of active constituents, such as xanthones, saponins, alkaloids, flavonoids, anthraquinones, phenylpropanoids, and organic acids 31,32 with a series of pharmacological benefits, including anti-inflammatory, antibacterial, antipyretic, antiviral, antidiabetic, and anticoagulation. 29,33 A recent study was conducted by Piwowar et al. 33 to evaluate the potential protective effects of the Anemarrhena rhizome ethanolic extract toward a HD in vitro model with 3-NP induced neurotoxicity in pheochromocytoma (PC-12) cells. Suppression of 3-NP induced cytotoxic activity and enhancement of cell proliferation were observed in Anemarrhena rhizome extract-treated cells in which cell apoptosis and morphological changes were prevented. ...
Article
Huntington’s disease (HD), a neurodegenerative disease, normally starts in the prime of adult life, followed by a gradual occurrence of characteristic psychiatric disturbances and cognitive and motor dysfunction. To the best of our knowledge, there is no treatment available to completely mitigate the progression of HD. Among various therapeutic approaches, exhaustive literature reports have confirmed the medicinal benefits of natural products in HD experimental models. Building on this information, this review presents a brief overview of the neuroprotective mechanism(s) of natural products against in vitro/in vivo models of HD. Relevant studies were identified from several scientific databases, including PubMed, ScienceDirect, Scopus, and Google Scholar. After screening through literature from 2005 to the present, a total of 14 medicinal plant species and 30 naturally isolated compounds investigated against HD based on either in vitro or in vivo models were included in the present review. Behavioral outcomes in the HD in vivo model showed that natural compounds significantly attenuated 3-nitropropionic acid (3-NP) induced memory loss and motor incoordination. The biochemical alteration has been markedly alleviated with reduced lipid eroxidation, increased endogenous enzymatic antioxidants, reduced acetylcholinesterase activity, and increased mitochondrial energy production. Interestingly, following treatment with certain natural products, 3-NP-induced damage in the striatum was ameliorated, as seen histologically. Overall, natural products afforded varying degrees of neuroprotection in preclinical studies of HD via antioxidant and anti-inflammatory properties, preservation of mitochondrial function, inhibition of apoptosis, and induction of autophagy.
... Many exogenous agents are neurotoxic and influence the condition of the central nervous system (CNS) in different ways. The overproduction of reactive oxygen antibacterial, antiviral, anti-inflammatory, antipyretic, anticoagulation, and antidiabetic [23,26,27]. The active constituents in A. asphodeloides belong to several phytochemical classes. ...
... Until now, more than 100 components have been isolated, such as: steroid saponins (total content in the rhizomes-about 6%), xanthones (2%), flavonoids, phenylpropanoids, alkaloids, anthraquinones, organic acids, and others. The summary of phytochemistry and phytopharmacology of this herb has been provided by two comprehensive reviews [23,28]. As quality and activity markers, xanthone glycosides (mangiferin, isomangiferin, neomangiferin- Figure 1) and saponins (several timosaponins with the sarsapogenin as aglycon) are mentioned. ...
... steroid saponins (total content in the rhizomes-about 6%), xanthones (2%), flavonoids, phenylpropanoids, alkaloids, anthraquinones, organic acids, and others. The summary of phytochemistry and phytopharmacology of this herb has been provided by two comprehensive reviews [23,28]. As quality and activity markers, xanthone glycosides (mangiferin, isomangiferin, neomangiferin- Figure 1) and saponins (several timosaponins with the sarsapogenin as aglycon) are mentioned. ...
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The rhizome of Anemarrhena asphodeloides Bunge, used in Traditional Chinese Medicine as a brain function-improving herb, is a promising source of neuroprotective substances. The aim of this study was to evaluate the protective action of xanthones from A. asphodeloides rhizomes on the PC12 cell line exposed to the neurotoxic agent—3-nitropropionic acid (3-NP). The xanthone-enriched fraction of the ethanolic extract of A. asphodeloides (abbreviated from now on as XF, for the Xanthone Fraction), rich in polyphenolic xanthone glycosides, in concentrations from 5 to 100 μg/mL, and 3-NP in concentrations from 2.5 to 15 mM, were examined. After 8, 16, 24, 48, and 72 h of exposure of cells to various combinations of 3-NP and XF, the MTT viability assay was performed and morphological changes were estimated by confocal fluorescence microscopy. The obtained results showed a significant increase in the number of cells surviving after treatment with XF with exposure to neurotoxic 3-NP and decreased morphological changes in PC12 cells in a dose and time dependent manner. The most effective protective action was observed when PC12 cells were pre-incubated with the XF. This effect may contribute to the traditional indications of this herb for neurological and cognitive complaints. However, a significant cytotoxicity observed at higher XF concentrations (over 10 µg/mL) and longer incubation time (48 h) requires caution in future research and thorough investigation into potential adverse effects.
... 4,8 .0 13,18 ]icosane-6,2'-oxane]-16-yl]oxyoxan-3-yl]oxy-6-(hydroxymethyl) oxane-3,4,5-triol, CAS no: 41059-79-4) is a natural steroidal saponin with multiple-pharmacological activities, and it is primary isolated from Chinese Materia Medica Anemarrhena asphodeloides Bunge (wellknown as Zhimu in Chinese) ( Figure 1) which has been used for treatment various diseases including arthralgia, hematochezia, cough, hemoptysis, and so on, in traditional Chinese medicine (Wang et al., 2014). Phytochemistry studies have identified more than 100 compounds from A. asphodeloides Bunge, and the main constitutes are steroidal saponins, flavonoids, phenylpropanoids, alkaloids, steroids, organic acids, anthraquinones, and so on (Wang et al., 2014). ...
... 13,18 ]icosane-6,2'-oxane]-16-yl]oxyoxan-3-yl]oxy-6-(hydroxymethyl) oxane-3,4,5-triol, CAS no: 41059-79-4) is a natural steroidal saponin with multiple-pharmacological activities, and it is primary isolated from Chinese Materia Medica Anemarrhena asphodeloides Bunge (wellknown as Zhimu in Chinese) ( Figure 1) which has been used for treatment various diseases including arthralgia, hematochezia, cough, hemoptysis, and so on, in traditional Chinese medicine (Wang et al., 2014). Phytochemistry studies have identified more than 100 compounds from A. asphodeloides Bunge, and the main constitutes are steroidal saponins, flavonoids, phenylpropanoids, alkaloids, steroids, organic acids, anthraquinones, and so on (Wang et al., 2014). The total saponins, which are rich in rhizome, could be extracted by hot water under reflux and purified by EtOAc, n-BuOH, and H 2 O, and the content of saponins is more than 6% (Wang et al., 2014;Yang et al., 2016;Nian et al., 2017). ...
... Phytochemistry studies have identified more than 100 compounds from A. asphodeloides Bunge, and the main constitutes are steroidal saponins, flavonoids, phenylpropanoids, alkaloids, steroids, organic acids, anthraquinones, and so on (Wang et al., 2014). The total saponins, which are rich in rhizome, could be extracted by hot water under reflux and purified by EtOAc, n-BuOH, and H 2 O, and the content of saponins is more than 6% (Wang et al., 2014;Yang et al., 2016;Nian et al., 2017). Timo AIII, Timosaponin BII (Timo BII) and sarsasapogenin are three main active saponins isolated from A. asphodeloides Bunge (Figure 1), and they have been identified as quality control and pharmacokinetic markers of diverse A. asphodeloides Bungecontained Chinese herb formulas, such as TongGuanWan, Rhizoma Anemarrhenae-Phellodendron herb pair, guizhishaoyao-zhimu herb pair, zhimu-baihe herb pair, and so on (Tang et al., 2012;Wang et al., 2014;Tang et al., 2015;Yang et al., 2018). ...
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Anemarrhena asphodeloides Bunge is a famous Chinese Materia Medica and has been used in traditional Chinese medicine for more than two thousand years. Steroidal saponins are important active components isolated from A. asphodeloides Bunge. Among which, the accumulation of numerous experimental studies involved in Timosaponin AIII (Timo AIII) draws our attention in the recent decades. In this review, we searched all the scientific literatures using the key word “timosaponin AIII” in the PubMed database update to March 2020. We comprehensively summarized the pharmacological activity, pharmacokinetics, and toxicity of Timo AIII. We found that Timo AIII presents multiple-pharmacological activities, such as anti-cancer, anti-neuronal disorders, anti-inflammation, anti-coagulant, and so on. And the anti-cancer effect of Timo AIII in various cancers, especially hepatocellular cancer and breast cancer, is supposed as its most potential activity. The anti-inflammatory activity of Timo AIII is also beneficial to many diseases. Moreover, VEGFR, X-linked inhibitor of apoptosis protein (XIAP), B-cell-specific Moloney murine leukemia virus integration site 1 (BMI1), thromboxane (Tx) A2 receptor, mTOR, NF-κB, COX-2, MMPs, acetylcholinesterase (AChE), and so on are identified as the crucial pharmacological targets of Timo AIII. Furthermore, the hepatotoxicity of Timo AIII was most concerned, and the pharmacokinetics and toxicity of Timo AIII need further studies in diverse animal models. In conclusion, Timo AIII is potent as a compound or leading compound for further drug development while still needs in-depth studies.
... The combination of various herbs is the main trait of traditional Chinese medicine that could improve the curative effect and treat the complications. Due to similar indications, Anemarrhena asphodeloides Bunge (Asparagaceae) and Citrus reticulata Blanco (Rutaceae) might be used in the same prescription (Wang Y et al. 2014;Liu et al. 2016). Nobiletin is a kind of polymethoxyflavonoid extracted from the leaves or stem of C. reticulata. ...
... Additionally, both anemarsaponin BII and nobiletin have been reported to possess the protective effect against epilepsy, which makes them easier to be co-administrated (Wang Y et al. 2014;Yang et al. 2018). Therefore, the investigation on the interaction between anemarsaponin BII and nobiletin is necessary for their clinical application, especially for their co-administration. ...
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Context The interaction between nobiletin and anemarsaponin BII could affect the pharmacological activity of these two drugs during their combination. Objective The co-administration of nobiletin and anemarsaponin BII was investigated to explore the interaction and the potential mechanism. Materials and methods Male Sprague-Dawley rats were only orally administrated with 50 mg/kg nobiletin as the control and another six rats were pre-treated with 100 mg/kg anemarsaponin BII for 7 d followed by the administration of nobiletin. The transport and metabolic stability of nobiletin were evaluated in vitro, and the effect of anemarsaponin BII on the activity of CYP3A4 was also assessed to explore the potential mechanism underlying the interaction. Results The increasing Cmax (2309.67 ± 68.06 μg/L vs. 1767.67 ± 68.86 μg/L), AUC (28.84 ± 1.34 mg/L × h vs. 19.57 ± 2.76 mg/L × h), prolonged t1/2 (9.80 ± 2.33 h vs. 6.24 ± 1.53 h), and decreased clearance rate (1.46 ± 0.26 vs. 2.42 ± 0.40) of nobilein was observed in rats. Anemarsaponin BII significantly enhanced the metabolic stability of nobiletin in rat liver microsomes (half-life increased from 31.56 min to 39.44 min) and suppressed the transport of nobiletin in Caco-2 cells (efflux rate decreased from 1.57 ± 0.04 to 1.30 ± 0.03). The inhibitory effect of anemarsaponin BII on CYP3A4 was also found with an IC50 value of 10.23 μM. Discussion and conclusions The interaction between anemarsaponin BII and nobiletin was induced by the inhibition of CYP3A4, which should draw special attention in their clinical co-administration.
... Anemarrhena asphodeloides was reported to possess anti-inflammatory, immune-stimulating and anti-neuroinflammatory effects (Ji et al. 2019). In paediatric use, A. asphodeloides is employed for the treatment of paediatric epilepsy, fever, coughing and allergies due to its properties of removing pathogenic heat (Park et al. 2008;Wang et al. 2014). Moreover, A. asphodeloides was reported to eliminate urinary protein, which makes it useful for the treatment of acute nephritis in children. ...
... Moreover, A. asphodeloides was reported to eliminate urinary protein, which makes it useful for the treatment of acute nephritis in children. There is a variety of compounds in A. asphodeloides, such as saponins, flavonoids, phenylpropanoids, and alkaloids, among which saponins are the main ingredients responsible for the biological function of A. asphodeloides (Wang et al. 2014;Ji et al. 2017;Xia et al. 2017). Anemarsaponin BII is one of the most active saponins isolated from A. asphodeloides that was found in high concentrations (Kim et al. 2009;Zhao et al. 2016). ...
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Context: Anemarsaponin BII is one of the most active saponins isolated from Anemarrhena asphodeloides Bunge (Asparagaceae), a commonly used Chinese traditional paediatric medicine. Objective: This study investigates the effects of anemarsaponin BII on the activity of CYP450s to provide more guidance for the clinical use of anemarsaponin BII. Materials and methods: Using various diagnostic substrates, the effects of a fixed concentration of anemarsaponin BII (100 μM) on the activity of eight main isoforms of CYP450s (CYP1A2, 2A6, 3A4, 2C8, 2C9, 2C19, 2D6 and 2E1) was first studied with pooled human liver microsomes (HLMs). Then, dose-dependent (0, 2.5, 5, 10, 25, 50 and 100 μM anemarsaponin BII) and time-dependent (0, 5, 10, 15 and 30 min) experiments were performed to obtain corresponding kinetic parameters. Results: Anemarsaponin BII showed significant inhibitory effects on the activity of CYP3A4, 2D6 and 2E1 with the IC50 values of 13.67, 16.26 and 19.72 μM. Anemarsaponin BII acted as a non-competitive inhibitor of CYP3A4 with the KI value of 6.72 μM and competitive inhibitors of CYP2D6 and 2E1 with the KI values of 8.26 and 9.82 μM, respectively. Additionally, the inhibition of CYP3A4 was revealed to be time-dependent with the KI value of 4.88 μM and the Kinact value of 0.053/min. Conclusions: The inhibitory effect of anemarsaponin BII on the activity of CYP3A4, 2D6 and 2E1 indicated the potential drug-drug interaction between anemarsaponin BII and drugs metabolized by these CYP450s. Further in vivo experiments are needed to validate the potential drug-drug interactions.
... wide and disc-shaped and diverges its surroundings. Anemarrhenae Rhizoma has been used to treat febrile diseases accompanied by high fever, thirst, dry cough, fever, and diabetes [9]. A review focused on pharmacological and biological effects of MGF on metabolic disorders showed that MGF, an Anemarrhenae Rhizoma polyphenol, alleviates obesity and fatty liver, ...
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Obesity-induced insulin resistance is the fundamental cause of metabolic syndrome. Accordingly, we evaluated the effect of mangiferin (MGF) on obesity and glucose metabolism focusing on inflammatory response and autophagy. First, an in silico study was conducted to analyze the mechanism of MGF in insulin resistance. Second, an in vivo experiment was conducted by administering MGF to C57BL/6 mice with high-fat-diet (HFD)-induced metabolic disorders. The in silico analysis revealed that MGF showed a high binding affinity with macrophage-related inflammatory cytokines and autophagy proteins. In the in vivo study, mice were divided into three groups: normal chow, HFD, and HFD + MGF 150 mg/kg. MGF administration to obese mice significantly improved the body weight, insulin-sensitive organs weights, glucose and lipid metabolism, fat accumulation in the liver, and adipocyte size compared to HFD alone. MGF significantly reduced the macrophages in adipose tissue and Kupffer cells, inhibited the gene expression ratio of tumor necrosis factor-α and F4/80 in adipose tissue, reduced the necrosis factor kappa B gene, and elevated autophagy-related gene 7 and fibroblast growth factor 21 gene expressions in the liver. Thus, MGF exerted a therapeutic effect on metabolic diseases by improving glucose and lipid metabolism through inhibition of the macrophage-mediated inflammatory responses and activation of autophagy.
... ex W.T. Ait., Dendrobium Sw., Thalictrum L., Lycoris Herb., Dipsacus L., Glycyrrhiza L., Coptis Salisb., Sedum L., Rosa L., Dioscorea L., Fritillaria L., and Swertia L. (Appendix 3). (18) Among these groups, the genera of Fritillaria, Aconitum, Iris, and Salvia are the focus of study, and the research has focused mainly on the chemical constituents, pharmacological activities, traditional therapeutic effects, and molecular phylogenetic analysis. ...
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Medicinal plants have provided numerous medicinal active ingredients for thousands of years and these ingredients have been used in Chinese medicine (CM) and traditional pharmacologies worldwide. Recently, the exploitation and utilisation of medicinal plant resources has increased significantly. The results of the studies have led to the identification of many active components, such as steroidal alkaloids, saponins, terpenoids, and glycosides, in various medicinal plants with different evolutionary levels. Moreover, research on the chemical classification, molecular phylogeny, and pharmacological activity of medicinal plants is increasing in popularity. Pharmacophylogeny is an interdisciplinary topic that studies the correlation between plant phylogeny, chemical composition, and curative effects (pharmacological activity and the traditional curative effect) of medicinal plants. In addition, it provides the basic tools to enable research and development of CM resources. This literature review, based on the genetic relationship between phytogroup and species, highlights the formation process, research content, applications, and future directions of pharmacophylogeny.
... The major biologically active compounds are steroidal saponins, including timosaponin AIII, BII, BIII, and E1, and the xanthone derivatives mangiferin and neomangiferin. [55] Recently published results have shown a broad spectrum of pharmacological activities for these two compound classes, including improvement of memory skills, anti-inflammatory, anti-tumor, and anti-diabetic effects. [56][57][58][59][60][61][62] In the mGQD formulation, 14 constituents derived from RA were assigned: three xanthone derivatives, ten steroidal saponins, and one fatty acid. ...
Article
Objective: Gegen Qinlian decoction (GQD) is a classical traditional Chinese medicine formulation which has been used for almost 2000 years. At Guang'anmen Hospital, Beijing, a modified GQD version (mGQD) with seven instead of four herbal ingredients has been applied to treat Type 2 diabetes. Quality control is a crucial prerequisite for the therapeutic application of herbal medicines. For the identification of products derived from classical GQD, the Chinese Pharmacopeia requires the analysis of only three marker compounds. Because mGQD is a more complex mixture containing seven herbs and hundreds of constituents, the pharmacopoeia method for GQD is inadequate. Materials and Methods: A more comprehensive characterization of the formula's constituents has been developed using ultra-high-performance liquid chromatography-diode array detection (UHPLC-DAD)-Q-Exactive-mass spectrometry (MS) in electrospray ionization positive and negative mode. Moreover, a new method for the fingerprint analysis of mGQD via high-performance thin-layer chromatography (HPTLC) has been established. Results: Altogether, 91 compounds have been assigned to their originating plants and 84 substances were identified either by comparison with authentic references or with data from the literature. The HPTLC method is based on the application of two different mobile phases and is able to detect both lipophilic and hydrophilic constituents of mGQD. Conclusions: The modified GQD was extensively characterized by UHPLC combined with DAD and Q-Exactive Orbitrap high-resolution MS detection, leading to the assignment and identification of compounds present in the decoction. In addition, a new method for the fingerprint analysis of the mGQD using HPTLC was established, which allows fast and simple identification of the herbal ingredients in the mixture. © 2021 World Journal of Traditional Chinese Medicine | Published by Wolters Kluwer - Medknow.
... Timosaponin AIII (TAIII) is a major steroidal saponin isolated from the root of Anemarrhena asphodeloides Bunge [9]. TAIII has multifaceted activities and is traditionally used as an anti-pyretic, antiin ammatory, anti-diabetic, and anti-coagulant agent in Chinese medicine [10]. ...
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Cell migration is a critical step in tumour invasion and metastasis. To acquire invasive properties, cancer cells use their surrounding environment through dynamic and bidirectional interactions and change their morphology and mode of migration. Thus, inhibition of morphological plasticity regulated by paracrine interactions may be a promising approach for anti-cancer therapy. In this study, we found that timosaponin AIII (TAIII), a steroidal saponin isolated from the roots of Anemarrhena asphodeloides , disrupted the morphological changes and migratory activity of breast adenocarcinoma cells promoted by paracrine interactions with mammary epithelium-derived cells. TAIII suppressed lamellipodia formation of MDA-MB-231 cells in response to exogenous stimuli from MCF10A cells, thereby inhibiting morphological changes and migration. TAIII also attenuated membrane spreading and induced contraction of HeLa cells, followed by expansion of intercellular gaps. Furthermore, we analysed the intracellular dynamics of TAIII labelled with a fluorescent dye and found that labelled TAIII was internalised in a manner dependent on dynamin. We also found that TAIII blocked internalisation of cell surface proteins including integrin b1. These results provide a novel aspect to understand how TAIII exerts pharmacological activities in suppression of cancer cell migration.
... The rhizome of Anemarrhena asphodeloides (family Liliaceae) has been commonly used in China for years to treat febrile diseases, fever, and diabetes (Y. Wang et al., 2014). It mainly contains steroidal saponins such as timosaponin AI, AIII, and BII (Kite, Porter, & Simmonds, 2007), whose aglycone is compound (6). ...
Article
Natural products and their derivatives are known to be useful for treating numerous diseases since ancient times. Because of their high therapeutic potentials, the use of different medicinal plants is possible to treat varied inflammation-mediated chronic diseases. Among natural products, phytosteroids have emerged as promising compounds mostly because they have diverse pharmacological activities. Currently, available medications exert numerous systemic toxicities, including hypertension, immune suppression, osteoporosis, and metabolic abnormalities. Thus, further research on phytosteroids to subside these complications is of significant importance. In this study, the information on phytosteroids, their types, and actions against inflammation , and allergic complications was collected by a systematic survey of literature on several scientific search engines. The literature review suggested that phytosteroids exhibit antiinflammatory action via different modes through transrepression or selective COX-2 enzymes. Also, in silico ADMET analysis was carried out on available phytosteroids to uncover their pharmacokinetic properties. Our analysis has shown that eight compounds: withaferin A, stigmasterol, β-sitosterol, guggulsterone, diosgenin, sarsasapogenin, physalin A, and dioscin, Àisolated from medicinal plants show similar pharmacokinetic properties as compared to dexamethasone, commercially available glucocorticoid. These phytosteroids could be useful for the treatment of inflammatory diseases, such as rheumatoid arthritis, inflammatory bowel diseases, multiple sclerosis, asthma, and cardiovascular diseases. Thus, systematic research is Abbreviations: (PI3K)
... Nevertheless, studies on pure constituents that equip these plants with antistress properties are in scarcity. Most of the studies have reported attributes of antistress properties in terms of flavonoids (Zheng et al. 2013;Zhao et al. 2008;Das et al. 2015;Gupta et al. 2012 andTiwari et al. 2014), triterpenoids or saponins (Selvi et al. 2012;Wang et al. 2014;Alok et al. 2013;Shin et al. 2014;Wanasuntronwong et al. 2012;Khan et al. 2016;Kazmi et al. 2013) and alkaloids (Xie et al. 2011;Tiwari et al. 2014). Examples of constituents that have potential antistress-related activity were presented in Figure 2. Most plants have been used in monotherapy, while only a handful of studies have probed into multiple ethnomedicinal therapies (mixing two or more plants) to treat stressrelated and depression disorders. ...
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Asian countries are reckoned for their vast plant-rich regions with a long history of traditional medicine that spans approximately 6,500 years. Asian people inherit knowledge from their ancestors about the use of the surrounding plants to treat many infirmities and diseases, including stress-related disorders such as anxiety and depression. As such, this review provides an ethnopharmacological and phytochemical overview of Asian plants with high antistress potential. This review serves as a baseline for the discovery of new and potent antidepressants. Articles from 2007 to 2020 were reviewed extensively using Google Scholar and Scopus search engines based on the following keywords: ‘antidepressant AND Asia AND plants’, ‘anxiolytic AND Asia AND plants’, as well as ‘antistress AND Asia AND plants’. In total, 71 Asian plants were documented. Most of the plants were reported from India (36%) and followed by China (31%). Other countries, including Japan, Bangladesh, Thailand, Pakistan, Korea, Taiwan and Algeria, have published several reports regarding local plants with antidepression potential. As a result, 15 pure compounds isolated from these plants displayed antidepressive potential.
... Studies have shown that Anemarrhena saponins have a variety of pharmacological activities, including effects on the symptoms of dementia, improvements in learning and memory, remission of depression, vascular protection, anticoagulant and antithrombotic activities, regulation of glucose and lipid metabolism, and antitumor activities [1][2][3][4][5][6][7]. At present, more than 40 Anemarrhena saponins have been reported and widely exist in Anemarrhena asphodeloides Bge [8]. As the saponin with the highest content in Anemarrhena asphodeloides Bge., timosaponin BII has been a focus of research in recent years; its structure is (25S)-26-O-β-D-glucopyranosyl-22-hydroxy-5β-furostane-3β,26-diol-3-O-β-D-glucopyranosyl-(1→2)-β-D-galactopyranoside [9]. ...
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Timosaponin BII is one of the most abundant Anemarrhena saponins and is in a phase II clinical trial for the treatment of dementia. However, the pharmacological activity of timosaponin BII does not match its low bioavailability. In this study, we aimed to determine the effects of gut microbiota on timosaponin BII metabolism. We found that intestinal flora had a strong metabolic effect on timosaponin BII by HPLC-MS/MS. At the same time, seven potential metabolites (M1-M7) produced by rat intestinal flora were identified using HPLC/MS-Q-TOF. Among them, three structures identified are reported in gut microbiota for the first time. A comparison of rat liver homogenate and a rat liver microsome incubation system revealed that the metabolic behavior of timosaponin BII was unique to the gut microbiota system. Finally, a quantitative method for the three representative metabolites was established by HPLC-MS/MS, and the temporal relationship among the metabolites was initially clarified. In summary, it is suggested that the metabolic characteristics of gut microbiota may be an important indicator of the pharmacological activity of timosaponin BII, which can be applied to guide its application and clinical use in the future.
... Kaurene, atractyloside, carboxyatractyloside, and 4 -desulphate-atractyloside are known poisonous glycosides causing liver injury, found in medicinal plants such as Xanthium strumarium and Callilepis laureola [20][21][22][23][24]. Besides, cycasin from cycad plants was early recognized to cause experimental hepatic injuries such as toxic hepatitis and cirrhosis in nonhuman primates [25,26]. Saponin compounds and their derivatives have been linked to toxic hepatitis and were identified in various MP species consisting of Albizia julibrissin, Dumasia truncata, Anemarrhena asphodeloides, Melia azedarach, Tripterygium wilfordii [22][23][24][25][26][27][28][29][30][31][32][33][34][35]. In this context, monodesmosyl saponin 3-O-α-l-rhamnopyranosyl-(1→3)-β-d-glucuronopyranosyl-28-O-β-d-glucopyranosyl oleanolic acid from Dumasia truncata showed the most remarkable toxicity toward liver cells [29]. ...
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The risk of liver injury associated with the use of herbal medicinal products (HMPs) is well known among physicians caring for patients under a HMP therapy, as documented in case reports or case series and evidenced by using the Roussel Uclaf Causality Assessment Method (RUCAM) to verify a causal relationship. In many cases, however, the quality of HMPs has rarely been considered regarding potential culprits such as contaminants and toxins possibly incriminated as causes for the liver injury. This review aims to comprehensively assemble details of tentative hepatotoxic contaminants and toxins found in HMPs. Based on the origin, harmful agents may be divided according two main sources, namely the phyto-hepatotoxin and the nonphyto-hepatotoxin groups. More specifically, phyto-hepatotoxins are phytochemicals or their metabolites naturally produced by plants or internally in response to plant stress conditions. In contrast, nonphyto-hepatotoxic elements may include contaminants or adulterants occurring during collection, processing and production, are the result of accumulation of toxic heavy metals by the plant itself due to soil pollutions, or represent mycotoxins, herbicidal and pesticidal residues. The phyto-hepatotoxins detected in HMPs are classified into eight major groups consisting of volatile compounds, phytotoxic proteins, glycosides, terpenoid lactones, terpenoids, alkaloids, anthraquinones, and phenolic acids. Nonphyto-hepatotoxins including metals, mycotoxins, and pesticidal and herbicidal residues and tentative mechanisms of toxicity are discussed. In conclusion, although a variety of potential toxic substances may enter the human body through HMP use, the ability of these toxins to trigger human liver injury remains largely unclear.
... Anemarrhena asphodeloides is one of the most commonly used component herbs in TCM products currently approved for diabetes treatment in China [14,15]. A. asphodeloides extract (AAE) and its main components have shown anti-diabetic effects [16]. However, the main components of AAE, comprising mostly flavonoids and saponins, have low oral bioavailability in the body [17,18]. ...
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Anemarrhena asphodeloides is an herb widely used to treat symptoms associated with diabetes in traditional Chinese medicine. However, its key components and metabolites have low bioavailability and poor host absorption. To clarify the anti-diabetic mechanism of A. asphodeloides extract (AAE), we examined the anti-diabetic effects of AAE in rats with diabetes induced by a high-fat diet and streptozotocin. Faeces levels of the main components and metabolites of AAE were significantly higher than levels in plasma, which indicated that gut microbiota might play important roles in its anti-diabetic effect. Microbiological studies showed that unabsorbed components increased the diversity of the gut microbiota, enriched potentially beneficial bacteria, and suppressed potentially harmful bacteria. In vitro studies showed that AAE promoted the proliferation of Blautia coccoides, a bacterium with positive implication for diabetes, in a dose-dependent manner. AAE also promoted pancreatic cell regeneration and restored the function of pancreatic islet cells via peroxiredoxin 4 overexpression. Overall, these results suggest that AAE alleviates diabetes via modulating gut microbiota and protein expression.
... It is recognized after sarsaparilla (Smilax sp.), a climbing plant presented in subtropical areas. It is commonly named a natural Chinese Material Medica (Zhimu in Chinese), and is widely applied in China to treat and manage several ailments, including febrile diseases, fever, and DM [127][128][129]. Liu et al. demonstrated that SAR administration could significantly reduce renal index, urinary protein secretion, and serum UA levels [130]. ...
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Diabetic nephropathy (DN), a sterile inflammatory disease, is a serious complication common to diabetes mellitus. Recent evidence indicates that pyroptosis, a new term for pro-inflammatory cell death featured by gasdermin D (GSDMD)-stimulated plasma membrane pore generation, cell expansion and rapid lysis with the extensive secretion of pro-inflammatory factors, including interleukin-1β (IL-1β) and -18 (IL-18) may be involved in DN. Caspase-1-induced canonical and caspase-4/5/11-induced non-canonical inflammasome-signaling pathways are mainly believed to participate in pyroptosis-mediated cell death. Further research has uncovered that activation of the caspase-3/8 signaling pathway may also activate pyroptosis. Accumulating evidence has shown that NLRP3 inflammasome activation plays a critical role in promoting DN pathogenesis. In addition, current studies have suggested that pyroptosis-induced cell death promoted several diabetic complications that include DN. Our present study briefs the cellular mechanisms of pyroptosis-related signaling pathways and their impact on the promotion of DN. In this review, several investigational compounds suppressing pyroptosis-mediated cell death are explored as promising therapeutics in DN.
... Based on a network pharmacology study, QWBD was found to exert antisepsis actions by regulating protein phosphorylation, the cell response to cytokine stimulation, cell proliferation, the inflammatory response, the transmembrane receptor protein tyrosine kinase signaling pathway, and cytokine-mediated signaling pathways [201]. Although the phytochemistry of the component herbs Dihuang [202], Xijiao [203], Huanglian [204], Zhizi [121,205], Jiegeng [206], Huangqin [207], Zhimu [208], Chishao [209], Xuanshen [210], Lianqiao [211], Danzhuye [212], Gancao [213], Danpi [214], and Shigao (CaSO 4 ·2H 2 O) have been widely reported, chemical composition studies of QWBD are limited. A total of 21 compounds from 11 component herbs were detected in QWBD and characterized, among which 15 analytical markers were selected for the quality evaluation of QWBD: baicalin (content level, 563.1-852.8 ...
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Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection; the pathophysiology of sepsis is complex. The incidence of sepsis is steadily increasing, with worldwide mortality ranging between 30% and 50%. Current treatment approaches mainly rely on the timely and appropriate administration of antimicrobials and supportive therapies, but the search for pharmacotherapies modulating the host response has been unsuccessful. Chinese herbal medicines, i.e., Chinese patent medicines, Chinese herbal prescriptions, and single Chinese herbs, play an important role in the treatment of sepsis through multicomponent, multipathway, and multitargeting abilities and have been officially recommended for the management of COVID-19. Chinese herbal medicines have therapeutic actions promising for the treatment of sepsis; basic scientific research on these medicines is increasing. However, the material bases of most Chinese herbal medicines and their underlying mechanisms of action have not yet been fully elucidated. This review summarizes the current studies of Chinese herbal medicines used for the treatment of sepsis in terms of clinical efficacy and safety, pharmacological activity, phytochemistry, bioactive constituents, mechanisms of action, and pharmacokinetics, to provide an important foundation for clarifying the pathogenesis of sepsis and developing novel antisepsis drugs based on Chinese herbal medicines.
... Pharmacological studies show that Zhimu also has anti-thrombosis, ameliorating Alzheimer's disease, anti-tumor, anti-inflammatory, anti-depression and other effects [16,17] . Through analyzing the relevant literature on the treatment of precocious puberty of Chinese medicine in the past 40 years, it is found that among the precocious puberty of Chinese medicine, Zhimu is used most frequently [18] . ...
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Background Precocious puberty is a common endocrine disorder in children,and its pathogenic factor is early initiation of hypothalamic-pituitary-gonadal (HPG) axis. Sarsasapogenin is the main component of traditional Chinese medicine Zhimu, which has anti-fertility effect. There is already evidence that anti-fertility drugs may be resistant to precocity by regulating the HPG axis. Therefore, we speculated that sarsasapogenin might also has the effect. In order to test this hypothesis, this study determined the effect and mechanism of sarsasapogenin on precocious puberty by establishing a danazol-induced precocious puberty model. Methods Female Sprague-Dawley rats were divided into normal(N)group, model (M) group, leuprolide (L) group and sarsasapogenin (Sar) group. Rats at 5 days of age were given a single subcutaneous injection of 300 microgram of danazol dissolved in 25 microliter vehicle of ethylene glycol-ethanol (1:1, v/v), to establish the precocious puberty model. After 10 days of modeling, drug intervention was started. Vaginal opening was started at the age of 20 days, and then vaginal cell smears were examined. The development of uterus and ovary was observed by hematoxylin and eosin (HE) staining. The levels of Serum luteinizing hormone (LH), follicle-stimulating hormone (FSH) and estradiol (E2) were determined by radioimmunoassay. The expressions of hypothalamic gonadotropin releasing hormone (GnRH), Kiss-1, G protein-coupled receptor 54 (GPR54) and pituitary gonadotropin releasing hormone receptor (GnRH-R) were detected by RT-PCR. Results The day of vaginal opening was significantly advanced in the M than that in the N group. Compared with the M group, the Sar and L groups could significantly delay the opening time of vaginal (P < 0.001,P < 0.05,respectively). The Sar group could significantly decrease uterine and ovarian coefficients, and reduce uterine wall thickness (P < 0.05, respectively). In terms of serum hormones (LH, FSH, E2), the M group was significantly higher than the N group (P < 0.001,respectively). Moreover, the Sar group can significantly down-regulate the levels of serum hormones (P < 0.001, P < 0.01, P < 0.01,respectively). Also, the expression of GnRH, GnRH-R, Kiss-1 mRNA were significantly decreased in the Sar group compared with that in the M group (P < 0.01, P < 0.05, P < 0.001, respectively). Conclusions The results showed that sarsasapogenin had the effect of treating precocious puberty, and its mechanism might be to down-regulate the expression of GnRH and GnRH-R mRNA through the Kiss-/GPR54 system, thus delaying the initiation of HPG axis.
... Li et al. (1998) found that Mangiferin has been an active constituent of Tsu-kan-gan, which has been used for inhibiting in vivo and in vitro bone resorption. As a flavonoid, Mangiferin is also extracted from the Anemarrhena Asphodeloides Bunge and found to have anti-osteoporosis properties (Wang et al., 2014). Ang et al. (2011) found that Mangiferin was able to attenuate osteoclastogenesis and bone resorption by activating the nuclear factor-k-gene binding (NF-κB) and extracellular regulated protein kinase (ERK) pathway. ...
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Mangiferin is a xanthone glucoside extracted from multiple plants, which has been shown to inhibit bone resorption and alleviate osteoporosis. However, the effect of purified Mangiferin on osteoporosis and its specific mechanisms is unknown. This study aimed to explore whether Mangiferin can promote osteogenic differentiation and alleviate osteoporosis in ovariectomized (OVX) mice and explore the potential mechanisms. Different concentrations and durations of Mangiferin were applied to MC3T3-E1 cells. The optimal concentration and duration of Mangiferin were determined by evaluating the cell viability via cell count kit-8 (CCK-8). The gene and protein expressions of AXL, ERK5, and osteogenic differentiation markers, including BMP2, Collagen1, OPN, Osterix, and Runx2, were detected using western blotting, qRT-PCR, immunofluorescence, and flow cytometry. Mangiferin was administered to OVX mice, and the severity of osteoporosis was evaluated by H and E staining, immunohistochemistry (IHC), microscopic computed-tomography (micro-CT) scanning, western blotting, and immunofluorescence of bone tissue. We found that Mangiferin promoted osteogenic differentiation in a dose-dependent manner at concentrations less than 30 μM. The 30 μM Mangiferin significantly upregulated the expression of AXL, ERK5, and osteogenic differentiation, including the ALP activity, percentage of alizarin red, and the levels of osteogenic differentiation markers. However, these expression levels decreased when AXL was knocked down in MC3T3-E1 cells and it could not be rescued by Mangiferin. Mangiferin relieved osteoporosis in OVX mice without causing severe organ damage. This study concluded that Mangiferin promoted osteogenic differentiation of MC3T3-E1 cells and alleviated osteoporosis in OVX mice. The potential mechanism was via the AXL/ERK5 pathway.
... Anemarrhena asphodeloides Bunge is a herbal medicine used for a long time to treat high fever and diseases such as diabetes [20]. In addition, the anti-cancer activity of Anemarrhena asphodeloides, through cell cycle arrest and apoptosis, has been reported in colon, pancreatic, gastric, and liver cancers [21][22][23][24]. ...
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Timosaponin A3 (TA3), extracted from the rhizome of Anemarrhena asphodeloides Bunge, has been reported to affect various diseases, such as cancer, Alzheimer’s disease, and allergies. However, the underlying molecular mechanisms and impacts are largely unknown. In the present study, we hypothesized that TA3 induces apoptosis through the inhibition of c-Myc expression via CNOT2 or MID1IP1 in HCT116. An MTT assay and colony formation assay were used to measure cell viability and proliferation. The protein expression of apoptotic markers and oncogenes was measured using immunoblotting and immunofluorescence assays. The interaction between MID1IP1 and c-Myc was confirmed by performing an immunoprecipitation assay. TA3 markedly inhibited colon cancer cell proliferation. Consistently, TA3 regulated the apoptotic proteins pro-PARP and caspase 3. TA3 inhibited the half-life of c-Myc and suppressed its expression in response to serum stimulation. In addition, TA3 enhanced the apoptotic effects of doxorubicin and 5-FU in colon cancer cells. Altogether, our results reveal a mechanism by which TA3 induces apoptosis through inhibiting c-Myc expression via CNOT2 or MID1IP1 in HCT116, which may help in the development of new therapies for colon cancer based on TA3 in the future.
... Steroidal saponins are a group of remarkable active components of Anemarrhena asphodeloides Bunge. with bioactivities such as anti-inflammation [9] and tumor suppression [10]. In our study, the prototype of steroidal saponins timosaponin BIII (P14) and timosaponin AIII (P18) were identified after BHGZD gavage. ...
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Background Baihu-Guizhi decoction (BHGZD) is a well-documented traditional Chinese Medicine (TCM) prescription that has been extensively applied to treating rheumatoid arthritis. Despite of its beneficial outcomes, the chemical constituents of BHGZD have not been fully portrayed and the in vivo absorption, distribution, metabolism, and excretion (ADME) patterns of absorbed components have never been described. Methods Characterization of absorbed components and in vivo biotransformation profiling of these feature compounds were based on the ultra-fast liquid chromatography-quadrupole-time-of-flight tandem mass spectrometry (UFLC-Q-TOF-MS/MS). Furthermore, the ultra-high-performance liquid chromatography tandem ion trap quadrupole mass spectrometry (UHPLC-Q-TRAP-MS/MS) system were performed to investigate the pharmacokinetics of active ingredients from BHGZD. Results In this study, we have identified and tentatively characterized 18 feature absorbed prototype and 15 metabolites of BHGZD in rat serum and the in vivo transformation pathways of these absorbed constituents were proposed. Besides, we have established novel quantitative methodology of five crucial components of BHGZD and have monitored the pharmacokinetic behaviors of these constituents spontaneously in rat serum after BHGZD gavage. After rats received two ways of BHGZD gavage, the pharmacokinetic behaviors of each compound exhibited relatively similar behaviors, as evidenced by similar curve track as well as relatively close time to reach maximum concentration (Tmax) and half washout time (T1/2). Whereas the maximum plasma concentration (Cmax) and area under the plasma concentration–time curve (AUC) values of five analytes with multiple dosage were a bit higher than single dosage. Conclusion This study added knowledge into the material basis and bio-transformation patterns of BHGZD in vivo, which would be of great value for exploring pharmacological effects and mechanism of BHGZD.
... Timosaponin A-III (TM A-III), abundantly found in Anemarrhena asphodeloides rhizomes has antidepressant, antipyretic, anticancer, and antidiabetic property. [61][62][63][64][65] Im et al [66] have evaluated the photo protective effect of TM A-III on UV B irradiated HaCaT cells. TM A-III was isolated by method described by Kim et al. [67] Cell viability assay was performed on nontumorigenic HaCaT cells (1×10 4 ) upon UV B exposure (20 mJ/cm 2 ) with and without TM A-III. ...
... In vivo experiments showed that poria cocos and its derivatives had anti-cancer, anti-in ammation, anti-oxidation, anti-virus and other bene cial biological activities, and anemarrhena had anti-cancer, anti-nervous disorder, anti-in ammation, anti-coagulation and other pharmacological activities [28,29]. Clinical trials had shown that salvia miltiorrhiza could improve redox homeostasis, inhibit cell apoptosis and inhibit in ammatory response [37]. In the previous experiment, we found that TCM prescriptions not only had an impact on the phenotype of obese mice, but also had a certain impact on the intestinal tract of mice, so we started our study from this point. ...
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Background: Obesity, in particular with the excessive visceral fat distribution which accompanied by several alterations at hormonal, inflammatory and endothelial level, was great to the detriment to human health. Although there were many treatments for obesity, most of them fail to had a radical effect or were accompanied with several side effects. Traditional Chinese medicine (TCM) for regulating the intestinal flora, lipids, and inflammation were considered to be effective. Based on previous research, Artemisia capillaris, Astragalus propinquus, Phellodendron amurense, Salvia miltiorrhiza, Poria cocos, and Anemarrhena asphodeloides were eventually selected to form an innovative herbal formula. Methods: The anti-inflammatory and lipid-lowering effects of the TCM were evaluated in an obese mouse models fed with a high-fat diet, and the effects of the TCM on the intestinal flora were further investigated. Results: The weights and insulin resistant of mice, as well as the inflammation, decreased after treatment. At the same time, the lipid metabolism increased after the mice were gavage with the TCM formula for 2 weeks. The intestinal motility of mice in the drug administration group was enhanced, and the intestinal flora was partially restored. Conclusion: In summary, our innovative Chinese herbal formula could significantly reduce the weight of obese mice, reduce the intestinal inflammation, improve intestinal motility, and improve the lipid metabolism in mice. Furthermore, the innovative formular could effectively prevent relevant metastasis diseases induced by obesity in mice.
... Anemarrhena asphodeloides, known as the only perennial plant belonging to the Anemarrhena genus of the monocotyledonous Liliaceae family, is one of the most popular medicinal herb in China. The dried rhizome of A. asphodeloides is a traditional Chineses herbal medicine, called 'Zhimu', and often used for the treatment of febrile diseases, fever, cough, and diabetes [2]. In addition, the herbal extracts of A. asphodeloides are acknowledged as a potential drug candidate for regulating mood due to its beneficial effects on central nervous system [3]. ...
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Anemarrhena asphodeloides is an immensely popular medicinal herb in China, which contains an abundant of mangiferin. As an important bioactive xanthone C-glycoside, mangiferin possesses a variety of pharmacological activities and is derived from the cyclization reaction of a benzophenone C-glycoside (maclurin). Biosynthetically, C-glycosyltransferases are critical for the formation of benzophenone C-glycosides. However, the benzophenone C-glycosyltransferases from Anemarrhena asphodeloides have not been discovered. Herein, a promiscuous C-glycosyltransferase (AaCGT) was identified from Anemarrhena asphodeloides. It was able to catalyze efficiently mono-C-glycosylation of benzophenone, together with di-C-glycosylation of dihydrochalcone. It also exhibited the weak O-glycosylation or potent S-glycosylation capacities toward 12 other types of flavonoid scaffolds and a simple aromatic compound with –SH group. Homology modeling and mutagenesis experiments revealed that the glycosylation reaction of AaCGT was initiated by the conserved residue H23 as the catalytic base. Three critical residues H356, W359 and D380 were involved in the recognition of sugar donor through hydrogen-bonding interactions. In particular, the double mutant of F94W/L378M led to an unexpected enzymatic conversion of mono-C- to di-C-glycosylation. This study highlights the important value of AaCGT as a potential biocatalyst for efficiently synthesizing high-value C-glycosides.
Article
Background: Modulation of the arachidonic acid (AA) cascade via 5-lipoxygenase (5-LOX) and cyclooxygenase-2 (COX-2) represent the two major pathways for treatments of inflammation and pain. The design and development of inhibitors targeting both 5-LOX and COX-2 has gained increasing popularity. As evidenced, 5-LOX and COX-2 dual targeted inhibitors have recently emerged as the front runners of anti-inflammatory drugs with improved efficacy and reduced side effects. Natural products represent a rich resource for the discovery of dual targeted 5-LOX and COX-2 inhibitors. By combining affinity ultrafiltration and high-performance liquid chromatography-mass spectrometry (AUF-LC-MS), an efficient method was developed to identify spirostanol glycosides and furostanol glycosides as the 5-LOX/COX-2 dual inhibitors from saponins extract of Anemarrhenae Rhizoma (SEAR). Methods: A highly efficient method by combining affinity ultrafiltration and high-performance liquid chromatography-mass spectrometry (AUF-LC-MS) was first developed to screen and characterize the 5-LOX/COX-2 dual targeted inhibitors from SEAR. The structures of compounds in the ultrafiltrate were characterized by high resolution Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR-MS). In addition, in vitro 5-LOX/COX-2 inhibition assays and their dual expression in vivo were performed to confirm the inhibitory activities of the compounds screened by AUF-LC-MS. Molecular docking studies with the corresponding binding energy were obtained which fit nicely to both 5-LOX and COX-2 protein cavities and in agreement with our affinity studies. Results: A total of 5 compounds, timosaponin A-II, timosaponin A-III, timosaponin B-II, timosaponin B-III and anemarrhenasaponin I, were identified as potential 5-LOX/COX-2 dual targeted inhibitors with specific binding values > 1.5 and IC50 ≤ 6.07 μM. Conclusion: The present work demonstrated that spirostanol glycoside and furostanol glycoside were identified as two novel classes of dual inhibitors of 5-LOX/COX-2 enzymes by employing a highly efficient screening method of AUF-LC-MS. These natural products represent a novel class of anti-inflammatory agents with the potential of improved efficacy and reduced side effects.
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Oxidative stress (OS) refers to the physiological imbalance between oxidative and antioxidative processes leading to increased oxidation, which then results in the inflammatory infiltration of neutrophils, increased protease secretion, and the production of a large number of oxidative intermediates. Oxidative stress is considered an important factor in the pathogenesis of cardiovascular disease (CVD). At present, active components of Chinese herbal medicines (CHMs) have been widely used for the treatment of CVD, including coronary heart disease and hypertension. Since the discovery of artemisinin for the treatment of malaria by Nobel laureate Youyou Tu, the therapeutic effects of active components of CHM on various diseases have been widely investigated by the medical community. It has been found that various active CHM components can regulate oxidative stress and the circulatory system, including ginsenoside, astragaloside, and resveratrol. This paper reviews advances in the use of active CHM components that modulate oxidative stress, suggesting potential drugs for the treatment of various CVDs.
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A novel and simple method was established for the extraction and determination of seven compounds in Anemarrhena asphodeloides Bge. using silica gel‐based vortex‐homogenized matrix solid‐phase dispersion and ultra high performance liquid chromatography quadrupole‐time of‐flight mass spectrometer. The conditions for the extraction were optimized. Silica gel was served as the dispersant, 50% methanol‐water was selected as an elution solvent and the grinding time was 3 min. Compared with the traditional ultrasonic‐assisted extraction, the developed method was rapid and efficient. In order to screen potential antioxidants, extract dealing with the optimized method was applied to a polyamide chromatography column and a D‐101 macroporous resin column. Fr.2.2 showed the highest antioxidant activities with the most content of flavonoid. A total of 25 peaks were identified from the active fraction. A 2,2’‐diphenyl‐1‐picrylhydrazyl ultra high performance liquid chromatography coupled with mass spectrometry approach was adopted for the rapid and exact screening and identification of antioxidant compounds. It indicated that flavonoids exhibited potential antioxidant activities. The antioxidant activities of 9 monomeric compounds in vivo were tested. Structure‐activity relationships were discussed. Five flavonoids with the concentration of 500 μg·mL−1 would reduce the oxidative stress of PC12 cells which were induced with 2,2′‐azobis[2‐methylpropionamidine] dihydrochloride. This article is protected by copyright. All rights reserved
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The present study aims to investigate the effects and mechanisms of sarsasapogenin resistance to precocious puberty. Female Sprague Dawley rats were divided into a normal (N) group, model (M) group, leuprolide (L) group, and sarsasapogenin (Sar) group. Rats at 5 days of age were given a single subcutaneous injection of 300 micrograms of danazol to establish the precocious puberty model. After 10 days of modeling, drug intervention was started. The development of the uterus and ovary was observed by hematoxylin and eosin (HE) staining. The levels of the serum luteinizing hormone (LH), follicle-stimulating hormone (FSH), and estradiol (E2) were determined by radioimmunoassay. Also, the expressions of the hypothalamic gonadotropin releasing hormone (GnRH), Kiss-1, G protein-coupled receptor 54 (GPR54), and pituitary gonadotropin releasing hormone receptor (GnRH-R) were detected by RT-PCR. The results showed that compared with the model group, sarsasapogenin could significantly delay the opening time of vaginal, decreased uterine and ovarian coefficients, and reduced uterine wall thickness. Moreover, it can significantly downregulate the levels of serum hormones and reduce the expression of GnRH, GnRH-R, and kiss-1. In summary, our results indicate that sarsasapogenin can regulate the HPG axis through the kiss-1/GPR54 system for therapeutic precocious puberty.
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Background Timosaponin A-III is one of the most promising active saponins from Anemarrhena asphodeloides Bge. As an oral chemotherapeutic agent, there is an urgent need to clarify its biopharmaceutics and pharmacokinetics to improve its development potential. Objective This research explores the bioavailability of timosaponin A-III and clarifies its absorption and metabolism mechanisms by a sensitive and specific HPLC-MS/MS method. Methods Pharmacokinetics and bioavailability studies of timosaponin A-III were performed in Sprague-Dawley rats by oral (20 g/kg) and intravenous administration (2 mg/kg). Control group was given the same volume of normal saline. The absorption of timosaponin A-III was investigated in a rat intestinal perfusion model in situ and a Caco-2 cell transport model in vitro. The metabolic rate of timosaponin A-III was determined in a rat liver microsome incubation system. Results After the oral administration, timosaponin A-III reached Cmax of 120.90 ± 24.97 ng/mL at 8 h, and the t1/2 was 9.94 h. The absolute oral bioavailability of timosaponin A-III is 9.18%. The permeability coefficients of timosaponin A-III in four intestinal segments ranged from 4.98 to 5.42 cm/s, indicating a difficult absorption. A strikingly high transport of timosaponin A-III was found, PappBA 3.27 ± 0.64 × 10−6 cm/s, which was abolished by a P-gp inhibitor. Rat liver microsome incubation studies showed that timosaponin A-III could hardly be metabolized, with a t1/2 of over 12 h. In addition, the solubility test showed a low solubility in PBS solution, 30.58 μg/mL. Conclusion Timosaponin A-III exhibited low oral bioavailability by oral and intravenous admiConclusion: nistration, which was probably caused by its low permeability and solubility. This study may provide a reference for the rational clinical use and further study on the pharmacology or toxicology of timosaponin A-III.
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Zhibai Dihuang Wan (ZDW) is an eight-herbal formula of traditional Chinese medicine. Clinically, it regulated immune activity and was used to treat diabetes and renal disease. In this study, we aimed to explore the nephroprotective effect of ZDW in an aristolochic acid- (AA-) intoxicated zebrafish model. We used a green fluorescent kidney transgenic zebrafish to evaluate the nephroprotective effects of ZDW by recording subtle changes in the kidney. Our results demonstrated that ZDW treatment can attenuate AA-induced kidney malformations (60% for AA-treated, 47% for pretreatment with ZDW, and 17% for cotreatment ZDW with AA, n = 50). Furthermore, we found that the expression levels of tnfα and mpo were decreased either in pretreatment or cotreatment groups. In conclusion, our findings revealed that AA-induced nephrotoxicities can be attenuated by ZDW. Therefore, we believe that zebrafish represent an efficient model for screening AA-protective Chinese medicine.
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The molecular mechanism underlying the anticancer effects of Anemarrhena asphodeloides (A. asphodeloides) on colon cancer is unknown. This is the first study evaluating the anticancer effect of A. asphodeloides extract (AA-Ex) in serum-starved colorectal cancer cells. Changes in cell proliferation and morphology in serum-starved MC38 and HCT116 colorectal cancer cells were investigated using MTS assay. Cell cycle and apoptosis were investigated using flow cytometry, and cell cycle regulator expression was determined using qRT-PCR. Apoptosis regulator protein levels and mitogen-activated protein kinase (MAPK) phosphorylation were assessed using western blotting. AA-Ex sensitively suppressed proliferation of serum-starved colorectal cancer cells, with MC38 and HCT116 cells showing greater changes in proliferation after treatment with AA-Ex under serum starvation than HaCaT and RAW 264.7 cells. AA-Ex inhibited cell cycle progression in serum-starved MC38 and HCT116 cells and increased the expression of cell cycle inhibitors (p53, p21, and p27). Furthermore, AA-Ex induced apoptosis in serum-starved MC38 and HCT116 cells. Consistently, AA-Ex suppressed the expression of the anti-apoptotic molecule Bcl-2 and upregulated pro-apoptotic molecules (cytochrome c, cleaved caspase-9, cleaved caspase-3, and cleaved-PARP) in serum-starved cells. AA-Ex treatment under serum starvation decreased AKT and ERK1/2 phosphorylation in the cell survival signaling pathway but increased p38 and JNK phosphorylation. Furthermore, AA-Ex treatment with serum starvation increased the levels of the transcription factors of the p38 and JNK pathway. Serum starvation sensitizes colorectal cancer cells to the anticancer effect of A. asphodeloidesvia p38/JNK-induced cell cycle arrest and apoptosis. Hence, AA-Ex possesses therapeutic potential for colon cancer treatment.
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Durability deterioration of cementitious concrete and reinforced concrete (RC) is critical to durability, safety, and sustainability of infrastructures, especially for offshore concrete structures under marine environment. In this paper, the effects of marine environment on the deterioration mechanism, performance, and durability of concrete materials and structures are systematically reviewed. For the deterioration mechanism, the effect of various chemicals in seawater and different marine exposure zones on the cementitious concrete and reinforced concrete is firstly analyzed and compared. At material level, this paper discusses the characterizations of cementitious concrete, including compressive strength, chloride diffusion, carbonation depth, and pore structure. On the other hand, the performance of cementitious concrete with the addition of supplementary cementitious materials was also compared when exposed to marine environment. At structure level, the durability of RC structures, including beams and slabs and other elements with corrosion protection under marine environment is evaluated. This paper also assesses some cases studies of RC structures after many years of exposure to marine environment. Furthermore, prospectives are proposed for practical applications on concrete under marine environment. The conclusions are of great benefit to the researchers and engineers in the concrete-related industry who aim to develop durable and sustainable concrete infrastructures under marine environment.
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Ethnopharmacological relevance Flavonoids are the main components of the traditional Chinese medicine Anemarrhenae Rhizoma (dried rhizome of Anemarrhena asphodeloides Bge.), which has been reported to possess activity against inflammation and tumor. Aim of study Regulation of the arachidonic acid (AA) cascade through cyclooxygenase (COX) and lipoxygenase (LOX) represent the two major pathways to treat inflammatory of benign prostatic hyperplasia (BPH). In this study, Anemarrhenae Rhizoma flavonoids and its main compounds (mangiferin, neomangiferin and isomangiferin) were investigated for effects on AA metabolism. Methods Ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) was used to monitor AA metabolites in BPH rats and in PC-3 cells. COX-2 and 5-LOX protein and mRNA levels were measured by Western blot and qPCR, respectively, along with histopathological assessment of prostate tissues. Results Treatment with flavonoids significantly ameliorated BPH-associated prostate inflammation and inhibited the expression of COX-2 and 5-LOX at the protein and mRNA levels. Quantitative metabolomic analysis of blood plasma showed flavonoids treatment decreased AA levels and its metabolites associated with the COX and LOX pathways. Further exploration of the flavonoid compounds mangiferin, neomangiferin and isomangiferin showed they inhibited AA metabolism to varying degrees in PC-3 cell cultures. Conclusion Anemarrhenae Rhizoma flavonoids act to inhibit BPH-related inflammation in vivo and in vitro by targeting AA metabolism and interfering with COX and LOX pathways. The identification of mangiferin, neomangiferin and isomangiferin as anti-inflammatory components suggests flavonoids interventions represent a promising therapeutic approach for BPH.
Article
Ethnopharmacological relevance The rhizomes of Anemarrhena asphodeloides Bunge., belonging to the family Liliaceae, are named ‘Zhi-mu’ according to traditional Chinese medicine theory. It is a medicinal plant that has long been used as a tonic agent in various ethnomedicinal systems in East Asia, especially in China, and also for treating arthralgia, hematochezia, tidal fever, night sweats, cough, dry mouth and tongue, hemoptysis, etc. The arm of the review The review aims to provide a systematic overview of botany, ethnopharmacology, phytochemistry, pharmacology, toxicology and quality control of Anemarrhena asphodeloides and to explore the future therapeutic potential and scientific potential of this plant. Materials and methods A comprehensive literature search was performed on Anemarrhena asphodeloides using scientific databases including Web of Science, PubMed, Google Scholar, CNKI, Elsevier, SpringerLink, ACS publications, ancient books, Doctoral and master's Theses. Collected data from different sources was comprehensively summarised for botany, ethnopharmacology, phytochemistry, pharmacology, toxicology and quality control of Anemarrhena asphodeloides. Results A comprehensive analysis of the literature as mentioned above confirmed that the ethnomedical uses of Anemarrhena asphodeloides had a history of thousands of years in eastern Asian countries. Two hundred sixty-nine compounds have been identified from Anemarrhena asphodeloides, including steroidal saponins, flavonoids, phenylpropanoids, alkaloids, steroids, organic acids, polysaccharides, benzophenones and other ingredients. Studies have shown that the extracts and compounds from Anemarrhena asphodeloides have extensive pharmacological activities, such as nervous system activity, antitumour, anti-inflammatory, antidiabetic, antiosteoporotic, antiallergic, antiplatelet aggregation, antimicrobial, antiviral, anti-ageing, hair growth promoting, preventing cell damage, etc. Evaluating the quality and toxicity of Anemarrhena asphodeloides is essential to confirm its safe use in humans. Conclusion Anemarrhena asphodeloides is widely used in traditional medicine and have diverse chemical constituents with obvious biological activities. Nevertheless, more studies should be carried out in animals and humans to evaluate the cellular and molecular mechanisms involved in its biological activity and confirm its safe use.
Article
Neomangiferin (NMF) is an extremely special xanthone that could be simultaneously attributed to C-glycoside and O-glycoside with a variety of biological activities, such as anti-inflammatory, antitumor, antipyretic, and so on. So far as we know, the metabolism profiling has been insufficient until now. Herein, Drug Metabolite Cluster Centers (DMCCs)-based Strategy has been developed to profile the NMF metabolites in vivo and in vitro. Firstly, the DMCCs was proposed depending on literature-related and preliminary analysis results. Secondly, the specific metabolic rule was implemented to screen the metabolites of candidate DMCCs from the acquired Ultra High Performance Liquid Chromatography Quadrupole Exactive Orbitrap Mass Spectrometry (UHPLC-Q-Exactive Orbitrap MS) data by extracted ion chromatography (EIC) method. Thirdly, candidate metabolites were accurately and tentatively identified according to the pyrolysis law of mass spectrometry, literature reports, comparison of reference substances, and especially the diagnostic product ions (DPIs) deduced preliminarily. Finally, network pharmacology was adopted to elucidate the anti-inflammatory action mechanism of NMF on the basis of DMCCs. As a result, 3 critical metabolites including NMF, Mangiferin (MF) and Norathyriol (NA) were proposed as DMCCs, and a total of 61 NMF metabolites (NMF included) were finally screened and characterized coupled with 3 different biological sample preparation methods including solid phase extraction (SPE), acetonitrile precipitation and methanol precipitation. Among them, 32 metabolites were discovered in rat urine, 30 in rat plasma, 12 in rat liver, 9 metabolites in liver microsomes and 8 in rat faeces, respectively. Our results also illustrated that NMF primarily underwent deglucosylation, glucuronidation, methylation, sulfation, dihydroxylation and their composite reactions in vivo and in vitro. Additionally, network pharmacology analysis based on DMCCs revealed 85 common targets of disease-metabolites, and the key targets were TNF, EGFR, ESR1, PTGS2, HIF1A, IL-2, PRKCA and PRKCB. They exerted anti-inflammatory effects mainly through the pathways of inflammatory response, calcium-dependent protein kinase C activity, nitrogen metabolism, pathways in cancer and so on. In general, our study constructed a novel strategy to comprehensive elucidate the biotransformation pathways of NMF in vivo and in vitro, and provided vital reference for further understanding its anti-inflammatory action mechanism. Moreover, the established strategy could be generalized to the metabolism and action mechanism study of other natural products.
Article
Certain herbs used in traditional Chinese medicine may produce a growth-enhancing effect by promoting the secretion of growth hormone (GH) by the pituitary gland or mimicking the function of GH. In this study, we aimed to identify herbs that could serve as GH alternatives. A reporter gene assay for GH was developed, and 100 different herbal extracts were assayed. We found that Rhizoma Anemarrhenae (RA) water extracts exhibited transactivation activities that stimulate the activation of signal transducer and activator of transcription 5 (STAT5). The growth-promoting effect of RA in NB2–11 cells was inhibited by co-treatment with GH receptor (GHR)-Fc fusion protein. Unlike GH, RA extracts did not enhance the growth of B16F10 melanoma cells. The activation of the Janus kinase 2-STAT5 signaling pathway was confirmed in both NB2–11 cells and WI-38 human normal lung fibroblasts; the activation was inhibited by co-treatment with GHR-Fc fusion protein. Docking analysis of the active ingredients of RA, including mangiferin, neomangiferin, isomangiferin, anemarsaponin E, 7-O-methylmangiferin, officinalisinin I, timosaponin BII, timosaponin AI, and timosaponin AIII, using SWISSDOCK indicated a direct interaction of these compounds with GHR. The growth-promoting effects and activation of STAT5 were also confirmed. Moreover, we found that RA extract significantly increased the height of the tibial growth plate and stimulated the production of insulin-like growth factor 1 in the serum, liver, and muscle tissues. Our findings provide evidence that herbal extracts, particularly, RA extracts, can promote growth by mimicking GH bioactivity.
Article
Background : Compound drug Zhizi Jinhua Pills (ZZJHP) is composed of 8 herbal medicines (HMs), and it is necessary to control the HMs to ensure its holistic quality. Purpose : To establish a quality monitoring method for ZZJHP from precise control of multiple active ingredients to contour control of fingerprint, to calculate the contribution of HMs and predict the quality of compound drugs. Methods : In this study, HPLC method was established for content determination of 11 analytes and fingerprint assessment. In vivo and in vitro studies of antioxidant activity were performed, Orthogonal Partial Least Squares analysis was applied for spectrum-effect correlation between antioxidant activity and HPLC fingerprint. The compound synthesizing fingerprint (CSF) of ZZJHP was fitted with 8 HMs, and the contribution of the single herb to prescription was evaluated by Sub-quantified profiling method. Results : The content of 11 analytes and fingerprints of ZZJHP were measured simultaneously, 32 batches of samples were divided into 6 grades. In vivo and in vitro researches suggested significant antioxidant activity capacity of ZZJHP. Then, spectrum-effect relationship study showed that 24 of the 30 fingerprint peaks had antioxidant activity. By prescription and decomposition profiling, the qualitative and quantitative contributions of the 8 herbs were revealed in turn. The negative solution experiment proved that CSF could accurately predict the quality of composite drugs. Conclusion : The intelligent prediction strategy could intervene at the source to realize rapid screening of HMs and prediction of the quality of preparations, which could provide guidance for the use of HMs and improve the quality of composite drugs.
Article
Ethnopharmacological relevance Suanzaoren Decoction (SZRD) is a traditional and classic prescription for the treatment of insomnia, with a history of more than 1,000 years. It replenishes blood components, calms the nerves, reduces fever and irritability. It is commonly used in the clinical treatment of chronic fatigue syndrome, cardiac neurosis, and menopausal syndromes. Modern pharmacological studies have shown that it improves cognitive impairment; however, its mechanism of action remains unclear. Aim of the study This study preliminarily investigated the potential bioactive components and mechanism of SZRD in improving cognitive impairment by exploring network pharmacology, molecular docking, and conducting in vivo experiments. Materials and methods The components of various Chinese herbs in SZRD and their disease-related targets were identified through network pharmacology and literature. Gene ontology (GO) function enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses of intersection targets were performed using the relevant database. Next, the “Components-Targets-Pathways” (C-T-P) and “Protein-Protein interaction” networks were constructed using the enrichment analysis results to further identify potential pathways, bioactive components, and hub genes. At the same time, molecular docking was used to further distinguish the key bioactive components and genes of SZRD responsible for improving cognitive impairment. Finally, the potential mechanism of action was further analysed and verified using in vivo experiments. Results A total of 117 potential active components and 138 intersection targets were identified by network pharmacology screening. The key bioactive components, including calycosin, 5-Prenylbutein, licochalcone G, glypallichalcone, and ZINC189892, were identified by analysing the networks and molecular docking results. Hub genes included ACHE, CYP19A1, EGFR, ESR1, and ESR2. The oestrogen signalling pathway was the most important in the enrichment analysis. In vivo experiments further proved that SZRD could improve cognitive impairment by affecting the oestrogen signalling pathway and the expression of ACHE and CYP19A1. Conclusions Network pharmacology and in vivo experiments demonstrate that SZRD improves cognitive impairment caused by sleep disturbance through estrogen receptor pathway, which provides a basis for its clinical application.
Article
A new polysaccharide (AABP-2B) was obtained from Anemarrhena asphodeloides Bunge after purification by gradient alcohol precipitation and DEAE-52 cellulose column chromatography. AABP-2B was confirmed to be a homogeneous polysaccharide with a molecular weight of 5800 Da and was composed of mannose and glucose at a molar ratio of 7.2 : 2.8. Structural analysis demonstrated that the backbone of AABP-2B was mainly composed of 4)-β-D-Manp-(1, 4,6)-β-D-Glcp-(1 and 3,6)-β-D-Manp-(1. The hypoglycaemic effect of AABP-2B was evaluated by its inhibition of α-glucosidase activities and insulin resistance in a HepG2 cell model. The results showed that AABP-2B displayed α-glucosidase inhibitory activities and could significantly improve glucose consumption by activating the IRS-1/PI3K/Akt signalling pathway in insulin-resistant HepG2 cells. Hence, AABP-2B may have potential as a functional food or medicine for diabetes therapy.
Article
The COVID-19 disease has currently overwhelmed all other health issues throughout the world. There can be many repercussions on existing public health issues, especially tuberculosis (TB), which is endemic in many low and middle-income countries (LMICs). In most of the LMICs, the health services are poorly equipped, the resources being diverted to control the pandemic of COVID-19, which can lead to grave consequences for LMICs. COVID-19 and TB are known to affect the respiratory system, so their symptoms are very similar, and at times can be perplexing for diagnosis. Moreover, lack of proper treatment and vaccine for COVID-19 can further increase the mounting pressure. Synthetic drugs, such as hydroxychloroquine, are currently being used, but the side effects are a cause of concern. Hence, the efficacy of repositioned drugs is still under evaluation. The situation is further worsened by the possible development of drug-resistant mutants. What we need in current times is potential novel anti-viral drugs that are highly productive and economic in control and management of viral infections in LMICs. The only option which we can look upon is the natural products which are also known as bioactive compounds and their phytochemicals like flavonoids, alkaloids and peptides that have anti-viral secondary metabolites which have shown promising results on COVID-19. This review systematically emphasizes the urgency for treatment options, which can be both safe and effective, especially for TB patients from LMICs.
Article
The crude polysaccharide was extracted from A. asphodeloides rhizomes and further purified to produce two fractions F1 (50.0%) and F2 (19.6%). The chemical constitutions of the polysaccharides were neutral sugars (51.4%–89.7%), uronic acids (1.0%–30.2%) and sulfate esters (3.4%–8.1%), with various ratios of monosaccharides including rhamnose (1.4%–6.1%), arabinose (7.1%–21.2%), xylose (0.2%–4.8%), mannose (39.9%–79.0%), glucose (6.0%–11.1%) and galactose (2.6%–22.0%). The molecular properties of the polysaccharides were investigated by the HPSEC-UV-MALLS-RI system, revealing the Mw 130.0 × 10³–576.5 × 10³ g/moL, Rg 87.6–382.6 nm and SVg 0.3–54.3 cm³/g. The polysaccharides stimulated RAW264.7 cells to produce considerable amounts of NO and up-regulate the expression of TNF-α, IL-1 and COX-2 genes. Polysaccharides exhibited the growth inhibitory effects on cancer cells lines of AGS, MKN-28 and MKN-45, in which F2 fraction exhibited prominent bioactivities. The AGS cells treated with F2 experienced condensed cytoplasm, shrinkage of nucleus and chromatin marginalization with the highest number of cells at early-stage apoptosis reaching 54.6%. The inhibitory effect of F2 polysaccharide on AGS cells was through MAPKs and STAT3 signaling pathways. The backbone of the F2 was mainly linked by (1 → 4)-linked mannopyranosyl and (1 → 3)-linked galactopyranosyl. Taken together, the polysaccharide from A. asphodeloides rhizomes could be utilized as medicinal, pharmacological and functional food ingredients.
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Osteoporosis (OP) is a highly prevalent orthopedic condition in postmenopausal women and the elderly. Currently, OP treatments mainly include bisphosphonates, receptor activator of nuclear factor kappa-B ligand (RANKL) antibody therapy, selective estrogen receptor modulators, teriparatide (PTH1-34), and menopausal hormone therapy. However, increasing evidence has indicated these treatments may exert serious side effects. In recent years, Traditional Chinese Medicine (TCM) has become popular for treating orthopedic disorders. Erxian Decoction (EXD) is widely used for the clinical treatment of OP, but its underlying molecular mechanisms are unclear thanks to its multiple components and multiple target features. In this research, we designed a network pharmacology method, which used a novel node importance calculation model to identify critical response networks (CRNs) and effective proteins. Based on these proteins, a target coverage contribution (TCC) model was designed to infer a core active component group (CACG). This approach decoded the mechanisms underpinning EXD’s role in OP therapy. Our data indicated that the drug response network mediated by the CACG effectively retained information of the component-target (C-T) network of pathogenic genes. Functional pathway enrichment analysis showed that EXD exerted therapeutic effects toward OP by targeting PI3K-Akt signaling (hsa04151), calcium signaling (hsa04020), apoptosis (hsa04210), estrogen signaling (hsa04915), and osteoclast differentiation (hsa04380) via JNK, AKT, and ERK. Our method furnishes a feasible methodological strategy for formula optimization and mechanism analysis and also supplies a reference scheme for the secondary development of the TCM formula.
Article
Three compounds were identified from the ethanolic extract of Anemarrhena asphodeloides Bunge (A. asphodeloides) plant using silica gel chromatography. Their structures were confirmed by NMR and MS data analysis. The inhibitory activities against the MCF7 cancer cell line were evaluated and study the caspase 3 activation activity. Compound 3 exhibited good inhibitory activity and caspase 3 activation activity on the MCF7 cell line.
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Defective autophagy occurred in osteoblasts under stress induced by high glucose and played an essential role in the development of diabetic osteoporosis. Timosaponin BII, a steroidal saponin isolated from the rhizomes of Anemarrhena asphodeloides Bunge, possessed anti-osteoporosis properties. In this study, we investigated the efficacy and mechanism of timosaponin BII on diabetic osteoporosis both in vitro and in vivo. Timosaponin BII attenuated the deterioration in the microarchitecture of the tibias in diabetic rats. Furthermore, treatment with timosaponin BII dose-dependently reduced hyperglycemia-induced cell apoptosis in primary osteoblasts from rat calvaria. High glucose-exposed osteoblasts exhibited increased mitochondrial superoxide level, decreased mitochondrial membrane potential and impaired autophagic flux, which was attenuated by timosaponin BII, as evidenced by the upregulation of autophagosome numbers, LC3B puncta formation and Beclin1 expression. The antiapoptotic and antioxidative effect of timosaponin BII were repressed by the autophagy inhibitor 3-methyladenine and enhanced by the autophagy inducer rapamycin. Further studies showed that timosaponin BII suppressed the phosphorylation of mTOR and S6K, as well as the downstream factors NFκB and IκB, consequently activating autophagy and decreasing apoptosis. Of note, coincubation of timosaponin BII with MHY1485, a pharmacological activator of mTOR, diminished the protein expression of Bcl2 induced by timosaponin BII, which was in parallel with decreased autophagy and increased phosphorylation of NFκB and IκB. Overexpression of NFκB reduced timosaponin BII-evoked autophagy and promoted apoptosis. The in vivo results showed that oral administration of timosaponin BII downregulated the phosphorylation of mTOR and NFκB and upregulated Beclin1 expression in the proximal tibias of diabetic rats. These results suggested that timosaponin BII attenuated high glucose-induced oxidative stress and apoptosis through activating autophagy by inhibiting mTOR/NFκB signalling in osteoblasts.
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Rhizoma Anemarrhenae is a well-known herbal medicine with saponins as its commonly regarded major bioactive components. It is essential to classify the properties of saponins which are associated with their toxicity and efficacy. In this study, 25 compounds were identified by HPLC-Q-TOF/MS in the extract of Rhizoma Anemarrhenae and 8 saponins were detected in rat plasma by HPLC-MS/MS after oral administration of this extract. These were neomangiferin, mangiferin, timosaponin E1, timosaponin E, timosaponin B-II, timosaponin B-III, timosaponin A-III and timosaponin A-I. A sensitive and accurate HPLC-MS/MS method was developed and successfully applied to a pharmacokinetic study of the abovementioned eight saponins after oral administration of the Rhizoma Anemarrhenae extract to rats. The method validation, including specificity, linearity, precision, accuracy, recovery, matrix effect and robustness, met the requirements of the intended use. The pharmacokinetic parameter, Tmax value, ranged from 2 to 8 h for these eight saponins whereas their elimination half-life (t1/2) ranged from 4.06 to 9.77 h, indicating slow excretion. The plasma concentrations of these eight saponins were all very low, indicating a relatively low oral bioavailability. All these results provide support for further clinical studies.
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Pressurized water extraction (PWE) of the polysaccharides from Anemarrhena asphodeloides rhizomes was optimized by the response surface method (RSM). The high yield of 34.82 ± 0.38% was gained under the optimal conditions of material to liquid ratio 42 mL/g, pressure 6.4 MPa, extraction temperature 51 °C, and extraction time 15.3 min. An Anemarrhena asphodeloides rhizome polysaccharide (AARP) was obtained after purifying by D4006 macroporous resin and Sephadex G-100 column. High-performance liquid chromatography (HPLC) analysis showed that AARP with the molecular weight of 5100 Da consisted of four monosaccharides including mannose, glucose, galactose, and arabinose. 1D and 2D NMR analyses confirmed that the backbone of AARP was comprised of →4)-β-D-Manp-(1→, →4)-β-D-Glcp-(1→, β-L-Araf-(1→, →2)-β-D-Manp-(1→, and →3)-α-D-Galp-(1→ residues. In addition, AARP exhibited the property of inhibiting the pasting and in vitro digestion of wheat starch. These findings laid the foundations for AARP as an additive in regulating starch foods.
Article
Although ultraviolet detector or mass spectrometer could be coupled with two-dimensional liquid chromatography (2DLC) to analyze complex constituents, full detection and identification of the compounds are difficult. Suffering from biased UV detection and insufficient MS data interpretation, a number of minor compounds are neglected though they are separated. In this study, we report a global chemical profiling strategy using comprehensive 2DLC coupled with dual-MS platforms, including Orbitrap-MS and QqQ-MS. It was exemplified by an 11-herb Chinese medicine formula Xiaoer-Feire-Kechuan (XFK). Firstly, constituents in XFK were separated on a CSH C18 × Phenyl-Hexyl 2DLC system with a practical peak capacity of 990.5 and an orthogonality of 90.3%. Secondly, untargeted mass spectral data was collected using dd-MS² scan on an Orbitrap-MS. In total 542 peaks were detected, which was 4 times of that detected by 2DLC/UV (131 peaks). A total of 108 compounds were tentatively identified. Thirdly, targeted mass spectral data was collected for 8 characteristic substructures using neutral loss and precursor ion (NL/PRE) scan on a QqQ-MS. Extracted ion chromatogram was used to recognize minor constituents. An additional of 151 compounds were detected. Our study indicated that comprehensive 2DLC coupled with dd-MS² and NL/PRE-MS is a powerful technique for the global profiling of multi-component systems.
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In order to produce an effective and multi-targeted clinical drug that could prevent progressive neurodegeneration, a series of diosgenin carbamate derivatives were designed, synthesized and tested for their anti-inflammatory, antioxidant and anti-Aβ activities. The results demonstrated that compound M15 was the most promising derivative against inflammatory (NO inhibition 22.7 ± 2.2%,10 μM) and cellular damage induced by H2O2 (SH-SY5Y cell protection = 75.3 ± 3.4%, 10 μM) or Aβ (astrocytes protection = 70.2 ± 6.5%, 10 μM). Molecular docking studies revealed the strong binding affinity of M15 to the active site of nNOS, Aβ42 and pro-inflammatory proteins. Western blot demonstrated that M15 decreased IL-1β, IL-6 and TNF-α level, which may contribute to its anti-inflammatory effects. In addition, M15 maintained mitochondrial function as well as cell viability through reducing H2O2-induced ROS production. The results indicated that oral administration of M15 attenuated memory deficits and played a neuroprotective effect on subcutaneous (s.c.) D-gal aging mice. In summary, M15 could be considered as a potential multifunctional neuroprotective agent due to the effects of anti-inflammatory, antioxidant and anti-Aβ activities.
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EtOAc soluble part of MeOH extract of Anemarrhena asphodeloides rhizome was evaluated for the cytotoxicity against the five kinds of human tumor cell lines (A-549, SK-OV-3, SK-MEL-2, XF498 and HCT15) in vitro. Bioassay-guided fractionation of EtOAc soluble part led to the isolation of active compound which was identified as timosaponin A-III showed potent cytotoxic activity, but its genin, sarsasapogenin, did not show cell growth inhibition.
Article
Aim: To observe the effects of sarsasapogenin (SAR) on osteoblasts and osteoclasts cultured in vitro. Methods: Colonal murine calvarial osteoblast-like cell line MC3T3-E1 cells were cultured in vitro. MTT,p-nitropheneye phosphate and tinctorial method of alizarin Bordeaux were used to investigate the effects of SAR on the proliferation, ALP expression, and mineralization tuberculation of MC3T3-E1 cells. Mature osteoclasts were isolated from the long bone of one-day rat. Meanwhile, marrow cells of mouse bone were cultured with induction of 1,25(OH)2 VitD3. During the culturing of osteoclasts or marrow cells, SAR of different concentrations was added into the medium. The number of osteoclasts was recognized as tartrate resistant acid phosphatase (TRAP) (+) multinucleate cells and the resorption lacuna on bone slice were examined with toluidine blue staining. Results: Comparing with the control group, SAR (0.01, 0.1, 1μg/mL) significanthy increased the proliferation of MC3T3-E1 cells (P <0.05, P <0.01). There was no significant difference in the expression of ALP in early proliferating MC3T3-E1 cells exposed to SAR of 0.01,0.1, 1 μg/mL, but in the differentiation phase MC3T3-E1 cells, SAR improved ALP activity very significantly if compared with the control group, of which SAR of 1 μg/mL had the most promotion effect(P<0.01). In addition, compared to the control group, there were, to various extents, increased in the number of mineral nodes in MC3T3-E1 cells after 15day incubation with SAR of different conentrations. Furthermore, no obvious effects of 0.01-1 μg/mL SAR on mature osteoclast were observed. But typical osteoclasts were formed when marrow cells were cultured with the induction of 1,25(OH)2D 3 in medium for 7 days while little or no osteoclasts were induced from marrow cells in the presence of SAR. Conclusion: The results suggest that SAR can effectively promote the proliferation, differentiation and mineralization of osteoblasts cultured in vitro. Besides, SAR can inhibit the generation of osteoclasts from marrow cells.
Article
Aim: To investigate the effects of all-trans-retinoic acid (ATRA) on the expression of α-smooth muscle actin(α-SMA), Collagen-I and heat shock protein 47 (HSP47) in the TGF-β1-stimulated human lung fibroblasts (HFL-I). Methods: Firstly, cell proliferation of HFL-I was detected by MTT after the cells were treated with different concentrations of TGF-β1 and ATRA respectively for 3 days. HFL-I cells in vitro were divided into six experimental groups; the control group; 5 μg·L-1 TGF-β1 group; 10 μmol·L-1 ATRA group; 5 μg·L-1 TGF-β1 + 0.1 μmol·L-1 ATRA group; 5 μg·L-1 TGF-β1 + 1 μmol·L -1 ATRA group; 5 μg·L-1 TGF-β1 + 10 μmol·L-1 ATRA group. Expressions of α-SMA, Collagen-I, HSP47 were determined through RT-PCR and Western blot. Results: Different concentrations of TGF-β1 and ATRA could respectively promote cell proliferation of HFL-I in a concentration-dependent manner. Furthermore, in a concentration-dependent manner, ATRA reduced the mRNA and protein expressions of α-SMA, Collagen-I and HSP47 which obviously increased in the TGF-β1-stimulated HFL-I cells. Conclusions: ATRA can inhibit TGF-β1-stimulated differentiation and proliferation of HFL-I cells. The mechanism may be related to the down-regulation of the expression of Collagen-I and HSP47.
Article
Objective: To investigate the neuroprotective effects of a sapogenin from Rhizoma Anemarrhenae (ZMR) on nigrostriatal dopaminergic neurons in chronic 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP)-lesioned mouse model. Methods: C57BL/6 mice were divided into control group, model group, low-dose ZMR group and high-dose ZMR group. Chronic MPTP-lesioned mouse models were established by subcutaneous injection of MPTP and intraperitoneal injection of probenecid in model group, low-dose ZMR group and high-dose ZMR group. One week after model establishment, ZMR 10 mg·kg-1 d-1 and ZMR 26 mg·kg -1 · d-1 were administered to low-dose ZMR group and high-dose ZMR group, respectively, by oral gavage once daily for 60 days. Locomotor ability was tested by rotarod performance test, nigral tyrosine hydroxylase(TH) was examined by immunohistochemical staining, and striatal glial cell-derived neurotrophic factor (GDNF) and brain-derived neurotrophic factor (BDNF) were determined by ELISA. Results: Compared with model group, the locomotor abilities in low-dose ZMR group and high-dose ZMR group increased by 20.6% and 23.8%, respectively (P < 0.05), numbers of nigral TH immunoreactive cells increased by 104.1% and 228.8%, respectively (P<0.05), striatal GDNF levels increased by 99.0% and 125.5%, respectively (P<0.01), and striatal BDNF levels increased by 76.8% and 80.2%, respectively (P<0.01). Conclusion: ZMR can increase levels of striatal BDNF and GDNF, number of nigral TH immunoreactive cells and locomotor ability in chronic MPTP-lesioned mouse model, which implies ZMR has protective effects on nigral dopaminergic neurons in chronic MPTP-lesioned mouse model.
Article
AIM: To observe the effects of ZMS and ZMR(isomer of ZMS), two active components of Zhimu on learning and memory ability and muscarinic subtype M 1 receptor density in aged rats. METHODS: 24 month-old SD rats were randomly divided into aged control group, ZMS and ZMR treatment group. Young rats were used as normal control group. The learning and memory ability was detected by Y-maze method. The muscarinic subtype M1 receptor density in the brain was detected by 3H-QNB binding tests. RESULTS: It was found that daily oral administration of ZMS and ZMR for 40 d significantly enhanced the learning and memory ability and the muscarinic subtype M 1 receptor density in the brain of the aged rats. CONCLUSION: These results suggested that ZMS and ZMR probably have potential preventive and curative action for the progressive deterioration of the cholinergic system in Alzheimers disease (AD).
Article
Objective: To investigate the alkaloids of Anemarrhena asphodeloides. Method: The compounds were isolated and purified by Sephadex LH - 20, Rp-18 and silica gel column chromatography. Their chemical structures were elucidated on the basis of physicochemical properties and spectral data (IR, FAB-MS, 1H-NMR, and 13C-NMR). Result: Six compounds were isolated and identified as: aurantiamide acetate (1), cyclo (Tyr-Leu) (2), N-p-coumaroyltyramine (3), N-trans-feruloyltyramine (4), N-cis-feruloyltyramine (5), and nicotinic acid (6), respectively. Conclusion: For the first time, compounds 1-5 were separated from Liliacae plant, and compounds 1-6 were obtained from this plant.
Article
A homoisoflavanone, 7,4'-dihydroxyhomoisoflavanone (1) and a flavanone, (2S)-7,4'-dihydroxy-5- methoxyflavanone (2), were isolated from the rhizomes of Anemarrhena asphodeloides, together with 4,4'- dihydroxychalcon (3), 2'-O-methylphlorethin (4), 1,3-bis-di-p-hydroxyphenyl-4-penten-1-one (5), and 2,4'- dihydroxy-4-methoxybenzophenone (6) on the basis of spectroscopic and physicochemical analyses including 1Dand 2D- NMR techniques as well as by comparison of their data with the published values. Compounds 1 - 4 were isolated for the first time from this plant source. Among isolates, compound 2 exhibited moderate inhibitory effect on the differentiation of pre-adipocyte 3T3-L1 cells.
Article
A pyridyl alkaloid, 3-pyridylcarbinol (1) and benzoic acid derivatives, 4-hydroxy benzoic acid (2), 4- hydroxyactophenone (3), vanilic acid (4), and benzoic acid (5) were isolated from the rhizomes of Anemarrhena asphodeloides on the basis of spectroscopic and physicochemical analyses including 1D- and 2D- NMR techniques as well as by comparison of their data with the published values. Compounds 1 - 5 were isolated for the first time from this plant source.
Article
AIM: To investigate the neuroprotective effects and possible mechanisms of saponins from Anemarrhena asphodeloides Bge. (SAaB) on neuronal damage induced by amyloid β-protein fragments 25-35 (Aβ25-35). METHODS: Cultured mouse peritoneal macrophages were stimulated with Aβ 25-35 (20 μ·L-1) for 0.5, 1, 2 and 6 h or preincubated with SAaB (10, 30 and 100 μmol·L-1) for 10 min or mitogen-activated protein kinase (MAPK) specific inhibitors (p38 MAPK inhibitor SB 203580 and MEK specific inhibitor PD98059) for 30 min prior to the addition of Aβ25-35(20 μmol·L-1). After stimulation with Aβ25-35 for the indicated times, total cellular extracts were prepared for Western blotting of extracellular signal-regulated kinase (ERK) and p38 MAPK. After stimulation with Aβ25-35 for 48 h, the supernatants of cultured macrophages were collected for quantification of tumor necrosis factor-α (TNF-α) and nitric oxide (NO) and protein expression of inducible nitric oxide synthase (iNOS) in macrophages was determined by immunocytochemical staining. To determine whether SAaB has protective effect against neuronal apoptosis mediated by Aβ 25-35-induced macrophages activation, macrophages were stimulated with Aβ25-35 in the presence or absence of SAaB (10, 30 and 100 μmol·L-1) for 48 h and then the cell-free supernatant of Aβ25-35-stimulated macrophages was transferred to the culture of cerebellar granule neurons for 72 h. Neuronal apoptosis was quantitated by scoring the percentage of cells with apoptotic nuclear morphology after Hoechst 33258 staining. RESULTS: Aβ25-35 (20 μmol·L -1) significantly induced increase in phospho-ERK1/2 and phospho-p38 MAPK protein expression without affecting total protein levels and in the production of TNF-α and NO in cultured macrophages. Aβ 25-35-induced increase of TNF-α production in macrophages involved activation of ERK1/2 signal pathway. Importantly, TNF-α and NO generated by cultured macrophages after Aβ25-35 stimulation may be responsible for the majority of the neuronal apoptosis. SAaB (30 and 100 μmol·L-1) significantly suppressed Aβ25-35- induced increase in phospho-ERK1/2 and phospho-p38 MAPK protein. In addition, SAaB (10, 30 and 100 μmol·L-1) also decreased the level of TNF-α and NO in supernatants of cultured macrophage and inhibited Aβ25-35-induced increase in iNOS protein expression of macrophages. Neuronal apoptosis mediated by Aβ25-35-induced macrophage activation was also significantly attenuated by treatment with SAaB (10, 30 and 100 μmol·L-1). CONCLUSION: SAaB protects neurons against the neuronal cell death induced by Aβ25-35. The beneficial effects of SAaB may be related to the reduction of TNF-α and NO from activated macrophage induced by Aβ25-35.
Article
Aim: To investigate the inhibitory effect and the possible signaling mechanism of Sapoin from Anemarrhena asphdeloids Bge (SAaB) on the release of inflammatory mediators induced by amyloid β-protein fragments 25-35(Aβ25-35) in cultured macrophages. Methods: Cultured mouse peritoneal macrophages were preincubated with SAaB (10, 30 and 100 μmol·L-1) or specific kinase inhibitors including SMT, PD98059, SB20358 and LY294002 (20 μmol·L-1 Aβ25-35), then stimulated with Aβ25-35 (20 μmol·L-1). After stimulation with Aβ25-35 for the indicated time, total cellular extracts were prepared for Western blot analysis of Akt/PKB. The supernatants of macrophages were collected and analyzed for tumor necrosis factor-α (TNF-α) and nitric oxide (NO) generation. Results: Aβ25-35 significantly induced increase in phospho-Akt/PKB protein expression without affecting total protein levels and the production of TNF-a and NO in cultured macrophages. iNOS inhibitor SMT notablely reduced Aβ25-35-induced increase of NO generation. PD98059 and LY294002 could distinctly inhibit the production of TNF-α and the expression of phospho-Akt/PKB. SAaB (100 μmol·L-1) significantly suppressed Aβ25-35-induced increase in phospho-Akt/PKB protein level. In addition, SAaB(10,30 and 100 μmol·L-1) also decreased TNF-α and NO generation in supernatants of cultured macrophages in a concentration-dependent manner. Conclusion: SAaB can significantly inhibit the over-release of inflammatory mediators induced by Aβ25-35 in cultured macrophages, a process when the down regulation of Akt/PKB signal transduction pathway took part in.
Article
OBJECTIVE: To observe the effect of Saponins from Anemarrhena asphodeloides Bge (SAaB) on the activity of acetylcholinesterase (AchE) in cortices of rats. METHODS: The dysmnesia model of acquired learning induced by scopolamine was used. The activity of AchE in cortices of model animal was determined. Serum containing SAaB was prepared by serum pharmacological method. Brain cortices homogenate was treated with the serum and the SAaB solution respectively, and the influence of SAaB on AchE activity was determined by AchE test kit. RESULTS: SAaB antagonized the increase of AchE induced by scopolamine (P < 0.01). The serum containing SAaB was shown to inhibit AchE (P < 0.01) in vitro while there was no SAaB effect on AchE (P > 0.01). CONCLUSION: SAaB can inhibit the activity of AchE after the absorption and transformation in vivo.
Article
This study was designed to investigate the anti-inflammatory effects of mangiferin isolated from the rhizome of Anemarrhena asphodeloides, a natural polyphenol, on lipopolysaccharide (LPS)-treated RAW 264.7 macrophages. Mangiferin dose-dependently inhibited LPS-induced nitric oxide (NO) and prostaglandin E2 (PGE2) productions in RAW 264.7 macrophages and peritoneal macrophages isolated from C57BL/ 6 mice. Consistent with these data, mangiferin suppressed the LPS-induced expressions of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) at the protein and mRNA levels in a concentration-dependent manner, as determined by Western blotting and RT-PCR, respectively. In addition, the release of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6), and the mRNA expression levels of these cytokines were reduced by mangiferin in a dose-dependent manner. Moreover, mangiferin effectively inhibited the transcriptional activation of nuclear factor-kappa B (NF-κB). These results suggest that the anti-inflammatory properties of mangiferin are caused by iNOS, COX-2, TNF-α, and IL-6 down-regulation due to NF-κB inhibition in RAW 264.7 macrophages.
Article
Neurodegenerative diseases such as Alzheimer's disease, stroke, and Parkinson's disease, are caused by neuronal cell death. Apoptosis, oxidative stress,