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Recently, some promising advances have been achieved in understanding the chemistry, pharmacology, and action mechanisms of constituents from genus Caulophyllum. Despite this, there is to date no systematic review of those of genus Caulophyllum. This review covers naturally occurring alkaloids and saponins and those resulting from synthetic novel t...
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... C. robustum (Asian blue cohosh) has long been traditionally used in folk medicine in China [6,7]. It is still used in the United States by midwives to aid labor [3]. ...
... It is still used in the United States by midwives to aid labor [3]. Xia et al. listed 22 phytochemicals identified in root and rhizome extracts from the Caulophyllum species; however, berberine was not included in the list [6]. Berberine is a major bioactive compound among diverse benzylisoquinoline alkaloids (BIAs) in the species in Berberidaceae [25]. ...
Caulophyllum robustum, commonly named Asian blue cohosh, is a perennial herb in the family Berberidaceae. It has traditionally been used for folk medicine in China. We isolated berberine from the leaves, stem, roots, and fruits of C. robustum, and this is the first report on berberine in this species. Transcriptome analysis was conducted for the characterization of berberine biosynthesis genes in C. robustum, in which, all the genes for berberine biosynthesis were identified. From 40,094 transcripts, using gene ontology (GO) analysis, 26,750 transcripts were assigned their functions in the categories of biological process, molecular function, and cellular component. In the analysis of genes expressed in different tissues, the numbers of genes in the categories of intrinsic component of membrane and transferase activity were up-regulated in leaves versus stem. The berberine synthesis genes in C. robustum were characterized by phylogenetic analysis with corresponding genes from other berberine-producing species. The co-existence of genes from different plant families in the deepest branch subclade implies that the differentiation of berberine synthesis genes occurred early in the evolution of berberine-producing plants. Furthermore, the copy number increment of the berberine synthesis genes was detected at the species level.
... 7.48 . Likewise,compounds 93,116,120,144,158,164,167,168,169,182,186,189,191,198,207,and 239 were tentatively deduced based on previous reports Tian et al., 2016;Xia et al., 2014). 1862, 434.1809, 356.1498, 358.1654, 328.1543, 268.133, 448.1966, 314.1751, 314.1387, 286.1438, 342.1705; h: 358.2013, 296.1645, 400.1755, 356.1856, 312.1594, 272.1281, 344.1492, 326.1751, 282.1125, 302.1387, 374.1598, 316.1543, 330.1700, 340.1543, 300.1594 ...
Ziziphus jujuba Mill is the dried ripe fruit of the Rhamnaceae family; it is widely distributed in Shandong, Henan, Liaoning, and other places in China. In folk medicine, it was used to restore vital energy, as a blood tonic, and for the treatment of spleen deficiency. To date, a complete investigation of the compounds of Z. jujuba has rarely been performed. Therefore, a reliable strategy based on UHPLC‐Q‐Exactive Orbitrap MS, combined with trace data acquisition mode (parallel reaction monitoring scanning, PRM) and multiple data processing methods, is necessary for the characterization of compounds in the Z. jujuba. Ultimately, 295 compounds, including 69 flavonoids, 60 alkaloids, 82 phenylpropanoids, 52 organic acids, and 32 other components, were identified in the Z. jujuba; of these, 270 have been reported in Z. jujuba for the first time. This study provides deep insights into the chemistry of Z. jujuba and could be useful for further studies aimed at identifying the factors contributing to the health benefits attributed to this fruit. In this study, a reliable strategy based on UHPLC‐Q‐Exactive Orbitrap MS combined parallel reaction monitoring scanning mode was established to characterize the chemistry in Z. Jujuba. Eventually, 295 compounds were identified in Z. jujuba; of these, 270 have been reported in Z. jujuba for the first time
... (21) Magnoflorine, taspine, and boldine, belonging to aporphine alkaloids, are found in Caulophyllum. (22) Typical quinolizidine alkaloids are also present in this genus. Alkaloids with piperidine-acetophenone conjugates, rare in the plant kingdom, are only found in Caulophyllum and Boehmeria. ...
... The Caulophyllum extracts and compounds showed the antibacterial activity, anti-infl ammatory and analgesic effects, antioxidant effects, antiacetylcholinesterase activity, effect on atherosclerosis and myocardial ischemia, antitumor activity, cytochrome p450 inhibition, topoisomerase inhibition, and effect on wound healing. (22) The genus Nandina is used in heat-clearing and detoxification (TRI 405, β 100), cough suppression (TRI 605, β 100), bronchitis (TRI 405, β 100), and pertussis (TRI 845, β 100). Nandina extract and compounds showed the antibacterial, antitumor and anti-inflammatory effects. ...
Ranunculales, comprising of 7 families that are rich in medicinal species frequently utilized by traditional medicine and ethnomedicine, represents a treasure chest of biodiversity and chemodiversity. The phylogenetically related species often have similar chemical profile, which makes them often possess similar therapeutic spectrum. This has been validated by both ethnomedicinal experiences and pharmacological investigations. This paper summarizes molecular phylogeny, chemical constituents, and therapeutic applications of Ranunculales, i.e., a pharmacophylogeny study of this representative medicinal order. The phytochemistry/metabolome, ethnomedicine and bioactivity/pharmacology data are incorporated within the phylogenetic framework of Ranunculales. The most studied compounds of this order include benzylisoquinoline alkaloid, flavonoid, terpenoid, saponin and lignan, etc. Bisbenzylisoquinoline alkaloids are especially abundant in Berberidaceae and Menispermaceae. The most frequent ethnomedicinal uses are arthritis, heat-clearing and detoxification, carbuncle-abscess and sore-toxin. The most studied bioactivities are anticancer/cytotoxic, antimicrobial, and anti-inflammatory activities, etc. The pharmacophylogeny analysis, integrated with both traditional and modern medicinal uses, agrees with the molecular phylogeny based on chloroplast and nuclear DNA sequences, in which Ranunculales is divided into Ranunculaceae, Berberidaceae, Menispermaceae, Lardizabalaceae, Circaeasteraceae, Papaveraceae, and Eupteleaceae families. Chemical constituents and therapeutic efficacy of each taxonomic group are reviewed and the underlying connection between phylogeny, chemodiversity and clinical uses is revealed, which facilitate the conservation and sustainable utilization of Ranunculales pharmaceutical resources, as well as developing novel plant-based pharmacotherapy.
... Modern pharmacological studies have demonstrated that alkaloids and triterpenoidsaponins are responsible for its major biological function as an anti-inflammatory [3]. As part of our effort to search for novel triterpene from C. robustum Maxim, we report here the isolation and structure determination of the three new terpenoids: (1) 23-hydroxy-3,19-dioxo-olean-12-en-28-oic-acid; ...
... The structures of the new compounds (1)(2)(3) were elucidated on the basis of extensive NMR spectroscopic analysis, including a series of 2D-NMR experiments ( Figure 2) (HSQC, HMBC), and mass spectrometry data. The known compounds (4)(5)(6)(7)(8)(9)(10) were identified by comparison of their experimental spectral data with literature data [4][5][6][7][8][9][10]. ...
... The structures of the new compounds (1)(2)(3) were elucidated on the basis of extensive NMR spectroscopic analysis, including a series of 2D-NMR experiments ( Figure 2) (HSQC, HMBC), and mass spectrometry data. The known compounds (4)(5)(6)(7)(8)(9)(10) were identified by comparison of their experimental spectral data with literature data [4][5][6][7][8][9][10]. . ...
Caulophyllum robustum Maxim is widely distributed in China and used as a traditional herbal medicine to induce childbirth, ease the pain of labor, rectify delayed or irregular menstruation, alleviate heavy bleeding and pain during menstruation, and treat external injuries and irregular menses. According to our detailed chemical investigation, three new triterpene derivatives (1⁻3), together with seven known compounds, were isolated from the root and rhizome of C. robustum Maxim. Their structures were elucidated by 1D- and 2D-NMR spectroscopic analysis and physio-chemical methods. They were identified as (1) 23-hydroxy-3,19-dioxo-olean-12-en-28-oic-acid; (2) 23-hydroxy-3,11-dioxo-olean-12-en-28-oic acid; and (3) 16α,23-dihydroxy-3-oxo-olean-12-en-28-oic acid. Compounds (1⁻10) inhibited the LPS-activated NO production in RAW264.7 cells. Furthermore, the anti-inflammatory characteristics of these compounds were confirmed on the basis of decreases in iNOS and NF-κB protein expression in RAW264.7 cells.
... Historically, C. robustum is a traditional Chinese herb used in the treatment of RA [10]. It is acrid and bitter in taste and warm in nature. ...
... C. robustum consists of more than 60 constituents, including sterols, triterpenes, glycosides, and alkaloids. Triterpene saponins are believed to be the major bioactive compounds contributing to the anti-inflammatory effects on RA [10]. Triterpene saponins constitute an important class of potential pharmacological agents possessing a range of different physiological activities including anticancer, 10 Evidence-Based Complementary and Alternative Medicine anticoagulation, anti-inflammation, antibacterial, analgesic, and comparative immune-modulation activity [23]. ...
Caulophyllum robustum
Maxim(C. robustum)has commonly been used as traditional Chinese medicine for the treatment of rheumatic pain and rheumatoid arthritis (RA) in China. This paper first investigated the anti-inflammation effect ofC. robustumextraction (CRME) on RAW264.7 cells stimulated by lipopolysaccharide (LPS) and gene expression levels of inflammatory factors. Moreover, we first evaluated the anti-RA effects of CRME using collagen-induced arthritis (CIA) in DBA/1J mice, and the incidence, clinical score, and joint histopathology were evaluated. The levels of IL-1, IL-6, TNF-α, and PGE2 inflammatory factors in sera of mice were detected by enzyme-linked immunosorbent assay. The expression of NF-κB p65 in the joint was tested by immune histochemical technique. The results showed that, compared with the model group, CRME significantly improved symptoms of the arthritis index, limb swelling, and histological findings by decreasing synovial membrane damage, the extent of inflammatory cell infiltration, and the expansion of capillaries in CIA mice. The results also showed that CRME can reduce the levels of IL-1, IL-6, TNF-α, and PGE2 and inhibit the expression of NF-κB p65. All these results indicated the anti-inflammatory efficacy of CRME as a novel botanical extraction for the treatment of RA.
... Its roots and rhizomes are the main medicinal parts [8]. Caulophyllum thalictroides, a related plant in the same genus, is also widely used to relieve pain, induce childbirth, and rectify delayed or irregular menstruation in America [9]. Further, C. thalictroides extract and its main components can suppress the levels of COX-2, iNOS, TNF-α, IL-1β, and IL-6 [10,11]. ...
Caulophyllum robustum Maxim (CRM) is a Chinese folk medicine with significant effect on treatment of rheumatoid arthritis (RA). This study was designed to explore the spectrum-effect relationships between high-performance liquid chromatography (HPLC) fingerprints and the anti-inflammatory effects of CRM. Seventeen common peaks were detected by fingerprint similarity evaluation software. Among them, 15 peaks were identified by Liquid Chromatography-Mass Spectrometry (LC-MS). Pharmacodynamics experiments were conducted in collagen-induced arthritis (CIA) mice to obtain the anti-inflammatory effects of different batches of CRM with four pro-inflammation cytokines (TNF-α, IL-β, IL-6, and IL-17) as indicators. These cytokines were suppressed at different levels according to the different batches of CRM treatment. The spectrum-effect relationships between chemical fingerprints and the pro-inflammation effects of CRM were established by multiple linear regression (MLR) and gray relational analysis (GRA). The spectrum-effect relationships revealed that the alkaloids (N-methylcytisine, magnoflorine), saponins (leiyemudanoside C, leiyemudanoside D, leiyemudanoside G, leiyemudanoside B, cauloside H, leonticin D, cauloside G, cauloside D, cauloside B, cauloside C, and cauloside A), sapogenins (oleanolic acid), β-sitosterols, and unknown compounds (X3, X17) together showed anti-inflammatory efficacy. The results also showed that the correlation between saponins and inflammatory factors was significantly closer than that of alkaloids, and saponins linked with less sugar may have higher inhibition effect on pro-inflammatory cytokines in CIA mice. This work provided a general model of the combination of HPLC and anti-inflammatory effects to study the spectrum-effect relationships of CRM, which can be used to discover the active substance and to control the quality of this treatment.
... The cytotoxicity of taspine expressed as IC 50 was 1.69 µM [177]. Moreover, it has been reported that taspine has the ability to suppress tumor-induced angiogenesis in non-small cell lung cancer and human umbilical vein endothelial cells by modulation the phosphatidylinositol-3 kinase and mitogen activated protein kinase signaling pathways [178]. Similarly, one of the main furochinoline alkaloids kokusaginine (Fig. 4) from Rutaceae family, possesses AChE inhibitory activity (IC 50 46 µM) and has been reported to exhibit cytotoxic activity toward some leukemia, breast, colon, glioblastoma and hepatocarcinoma cell lines (IC 50 from 44.56 to 119.88 µM). ...
Background:
Acetylcholinesterase (AChE) is involved in the termination of impulse transmission by rapid hydrolysis of the neurotransmitter acetylcholine in numerous cholinergic pathways in the central and peripheral nervous systems. The enzyme inactivation leads to acetylcholine accumulation, hyperstimulation of nicotinic and muscarinic receptors, and disrupted neurotransmission. Hence, acetylcholinesterase inhibitors, interacting with the enzyme as their primary target, are applied as relevant drugs for different neurodegenerative diseases (such as Alzheimer's and Parkinson's) as well as toxins. At the same time, there are increasing evidence that in non-neuronal context, AChE is involved in the regulation of cell proliferation, differentiation, apoptosis and cell-cell interaction. An irregular expression of AChE has been found in different types of tumors, suggesting the involvement of AChE in the regulation of tumor development. Having all this in mind, there is a possibility that some AChE inhibitors could be used as anti-cancer agents.
Objective:
This contribution will discuss a broad range of possible application of different AChE inhibitors as drugs, from well-known anti-Alzheimer's disease drugs to their use in cancer treatment in future. Emphasis will be put on various known AChE inhibitors classes, whose application as drugs could be controversy, as well as on newly investigated natural products, which can also modulate AChE activity.
Conclusion:
It is not clear is a patient treated for neurodegenerative condition prone to increased risk for some types of cancer and vice versa. This is necessary to keep in mind during rational drug design process for all therapies, which are based on AChE as a target molecule.
Caulophyllum robustum Maxim (CRM) is a well-known traditional Chinese medicine (TCM) mainly present in the northeast, northwest and southwest regions of China, which is belong to the family Berberidaceae. The roots and rhizomes of CRM have been used as a famous TCM for the treatment of rheumatoid arthritis (RA). The selective, sensitive and accurate high-performance liquid chromatography-electrospray ionization tandem mass spectrometry (HPLC-ESI-MS/MS) method for the determination and pharmacokinetic study cauloside H, leonticin D, cauloside G, cauloside D, cauloside C and magnoflorine in rat plasma was developed and validated in this paper. Chromatographic separation was achieved by using a Waters ACQUITY UPLC HSS T3 (100 mm × 2.1 mm, 1.7 μm) with gradient elution using a mobile phase consisting of acetonitrile and 0.1 % formic acid in water at a flow rate of 0.4 mL/min. The detection was performed in multiple reaction monitoring (MRM) mode and electrospray ionization (ESI) in positive and negative modes. The linearity, precision, accuracy, extraction recovery, matrix effects and stability were assessed to validate the current high-performance liquid chromatography/mass spectrometry (HPLC-MS) assay. Good linearity was achieved for each analyte with a correlation coefficient (r2) > 0.99). All the precision (RSD) data were less than 12.20 %, the accuracies ranged from -12.39 % to 10.55 %, the recovery rates from the rat plasma ranged from 85.48%-98.69 %, and the matrix effects ranged from 80.96 % to 91.35 %. The validated approach was successfully applied to study the pharmacokinetic characteristics of saponins and alkaloids in plasma after administering CRME to rats, and this assay provides a platform for studying the active components of multicomponent traditional Chinese medicines and provides useful information for further clinical studies.
Les Ranunculales sont un ordre d’angiospermes d’environ 4500 espèces, incluant des plantes communes comme les boutons d’or et les coquelicots. Leurs fleurs sont très diversifiées et ont piqué l’intérêt des botanistes depuis des décennies. Les sept familles de l’ordre sont faciles à reconnaître sur le terrain, mais paradoxalement, certaines familles n’ont pas de synapomorphies et ont des états ancestraux peu clairs, comme les Ranunculaceae (~ 2500 espèces). Cette diversité florale peut être liée à la pollinisation et des innovations ont pu être guidées par cette interaction. De plus, les plantes de ce groupe produisent une grande variété de composés secondaires, certains dont les propriétés sont connues depuis fort longtemps (comme la morphine et le curare). Ces substances pourraient jouer un rôle dans la défense contre les herbivores. Les caractères floraux et chimiques sont donc de bons candidats pour produire des hypothèses adaptatives. Ici nous utilisons des méthodes analytiques modernes pour comprendre les patrons d’évolution expliquant la distribution actuelle de la diversité et l’évolution des fleurs et des toxines de Ranunculales. Un nouveau cadre phylogénétique synthétique a été produit avec des séquences publiées de 144 espèces. Seize caractères floraux et la présence de certains composés métaboliques ont été reconstruits sur cet arbre avec la méthode de parcimonie et la méthode de « Reversible Jump Monte Carlo Markov Chains ». Un nouveau scénario d’évolution florale a été produit, où les Ranunculales avaient une fleur ancestrale trimère avec trois cycles de tépales et où les ancêtres des familles ont évolué en perdant ou en différenciant des cycles du périanthe. Les patrons d’évolution des toxines montrent de la variabilité, certaines apparaissant et disparaissant aléatoirement (comme les saponines), d’autres étant des synapomorphies bien soutenues de certains clades (comme les diterpènes de type aconitine pour la tribu des Delphinieae). Ces résultats offrent une meilleure compréhension de l’histoire naturelle des Ranunculales. En outre, cet ordre est le groupe-frère de toutes les autres eudicotylédones, et a donc une position clef pour comprendre l’évolution précoce de ce clade. Ces résultats vont fournir une compréhension plus profonde des changements floraux et phytochimiques qui ont eu lieu à la base des eudicotylédones, qui contiennent 70% des angiospermes actuelles.
Malonyl-triterpene saponins (MTSs) attract scientific attentions due to their structural diversities and valuable bioactivities. However, its thermal instability brings a huge amount of challenges for isolation and purification of this class of compounds. To our best knowledge, there has been no report on isolation and analysis of MTSs from genus Caulophyllum. In this study, a strategy combining data acquisition using an energy-resolved technique and the narrow widow extracted ion chromatograms as data mining method, was developed for discovery and identification of MTSs in C. robustum hair roots by ultra high liquid chromatography coupled to electrospray ionization Fourier transform mass spectrometry. The method was performed at an independent MS full scan using our bottom-up energies by in-source collision induced dissociations with 0, 25, 50 and 100 eV in both positive and negative modes. Precursor ion as well as fragment ion information was simultaneously collected from four energy-resolved MS spectra in a single run of 18 min. The fragmentation pathways of intact deprotonated, protonated and sodium ions of MTSs were proposed for the structural elucidation of Caulophyllum MTSs. A flowchart involving a stepwise procedure based on key fragments from ESI(-) /ESI(+) -FT-MS((1, 1)) to MS((1, 4)) spectra was constructed for the identification of structural elements in the MTSs. As a result, a total of twenty-three MTSs were discovered and tentatively identified, which had not been reported from Caulophyllum species before. All of these were potentially new compounds. This study provides an excellent example for discovery and identification of MTSs in herb medicines.
