Two new cycloartane triterpenoid glycosides from the rhizomes of Actaea vaginata.

Two new cycloartane triterpenoid glycosides, soulieoside V (1) and 15-deacetylbeesioside O (2), together with one known compound, beesioside J (3), were isolated from the ethanolic extract of the rhizomes of Actaea vaginata. Their structures were elucidated by spectroscopic methods and by comparison with data reported in the literature. All the compounds were tested for their cytotoxic activities against human cancer cell lines.

Cytotoxic cycloartane triterpenoid saponins from Actaea vaginata and their mechanism of action.

A further phytochemical investigation of the whole plants of Actaea vaginata afforded two new cycloartane triterpenoid saponins, (20S*,24R*)-15α,16ß-diacetoxy-20,24-epoxy-9,19-cyclolanostane-3ß,25-diol-3-O-ß-d-xylopyranoside (1) and (20S)-15ß,16ß -diacetoxy-18,20-epoxy-3ß,25-diol-24-oxo-9,19-cyclolanostan-3-O-ß-D-xylo-pyrano-syl-25-O-ß-d-glucopyranoside (2), together with four known compounds (3-6). Their structures were established on the basis of extensive analysis of NMR and HRESIMS data as well as by comparison with the reported data in the literature. All the isolates were evaluated for their cytotoxic activities against human hepatocellular carcinoma HepG2 cell line. Compounds 1 and 2 exhibited weak cytotoxicity with IC50 values of 36.10 and 27.39 µM, respectively. In addition, beesioside I (6) was found to significantly inhibit proliferation and induce apoptosis in HepG2 cells. A closer examination of underlying mechanism revealed that beesioside I could increase the levels of ROS and caspase-3 and promote phosphorylation of JNK in the JNK signaling pathway. Molecular modeling studies also shed further light on how beesioside I interacted with the key protein kinase.

Two new chemical constituents from the rhizomes of Actaea dahurica.

A new phenylpropanoid allopyranoside (1) and a new indolinone alkaloid (2) were isolated from the rhizomes of Actaea dahurica (syn. Cimicifuga dahurica). The structures of those two compounds were deduced as cimicifugaside F (1) and 3E,11E-(3-methyl-2-butenylidene acid)-2-indolinone-1-O-ß-d-glucopyranoside (2) by detailed analysis of their MS, 1D and 2D NMR data and comparison with literatures. Additionally, the isolates were evaluated for their inhibitory effects on the production of NO by LPS-stimulated RAW 264.7 macrophages.

A new cycloartane triterpene bisdesmoside from the rhizomes of Actaea vaginata.

A new cycloartane triterpene bisdesmoside, soulieoside T (1), and one known compound, oleanolic acid (2), were isolated from the ethanolic extract of the rhizomes of Actaea vaginata. Their structures were elucidated by spectroscopic methods and by comparison with data reported in the literature. Compound 1 was evaluated for cytotoxic activities against three human cancer cell lines.

Neuroprotective constituents of Actaea acuminata (Wall. ex Royle) H. Hara roots.

The methanol extract and its ethyl acetate fraction (EAF) of Actaea acuminata (Wall. ex. Royle) H. Hara roots were reported to exhibit significant antianxiety, anticonvulsant and antidepressant activities, and mild sedative activity. But the constituents responsible for these activities have not been isolated. The present study was undertaken to isolate neuroprotective compounds of A. acuminata following bioactivity-guided-fractionation. The column chromatography of EAF and its sub-fractions led to the isolation of four phenolic compounds (bergenin, gallic acid, acetyl bergenin and racemic mixture of diacetyl bergenin), which were characterized by IR and NMR spectral analysis. All the compounds exhibited significant antianxiety and antidepressant activities with respect to control. The gallic acid and bergenin did not show anticonvulsant activity, whereas acetyl bergenin and racemic mixture of diacetyl bergenin exhibited significant anticonvulsant activity. Neuropharmacological activities of A. acuminata are attributed due to polyphenolic compounds. Scientific validation of traditional claims of A. acuminata has opened up roadmap of research for the development of CNS affecting lead molecules.

Differentiation of Actaea species by NMR metabolomics analysis.

The 1H NMR spectra of crude extracts from a total of 33 Actaea samples were acquired and analyzed for their species- and plant part-specific metabolomic characteristics by identifying fingerprint resonances via visual observation as well as a chemometric approach using principal component analysis (PCA). The main study subjects were the roots/rhizomes and aerial parts of three American species, Actaea racemosa (AR), Actaea podocarpa (AP) and Actaea cordifolia (AC). AP exhibited an already visually distinct chemical profile from those of the other two species. The species-characteristic resonances were identified as analytical chemotaxonomic markers. AR and AC exhibited visually similar 1H NMR spectral profiles that required statistical analysis for differentiation. Several characteristic peaks and peak patterns were identified for each group of samples. Together with the three American Actaea species, the characteristics of the 1H NMR spectra of Asian species are also discussed. A statistical analysis method using PCA was employed to provide the metabolomic profile for visually minor but analytically significant chemotaxonomic differences. PCA scores allowed differentiation between the three American Actaea species, as well as the ability to differentiate between the various plant parts (aboveground vs. roots/rhizomes).

[A new spirocyclic cycloartane triterpenoid from Souliea vaginata].

The 70% ethanol extract of the whole plant of Souliea vaginata was purified by multi-chromatographic methods including macroporous resin,silica gel,Sephadex LH-20,and C18-reversed-phase column chromatography. A new spirocyclic cycloartane triterpenoid was isolated and identified as( 16 R*,20 R*,23 S*,24 R*,25 S*)-16,23: 23,26-diepoxy-15α,24,25-trihydroxy-9,19-cycloart-3ß-O-ß-D-xylopyranoside( 1),and named as soulieoside S. Its planar structure and relative configuration were determined by spectroscopic techniques including 2 D NMR and HRESI-MS. As one of the main components of S. vaginata,compound 1 was evaluated for its anti-inflammatory activity by a lipopolysaccharide( LPS)-stimulated NO production model in RAW264. 7 macrophages,but it didn't show NO production inhibitory effect.

Authentication of black cohosh (Actaea racemosa) dietary supplements based on chemometric evaluation of hydroxycinnamic acid esters and hydroxycinnamic acid amides.

Ester and amide derivatives of hydroxycinnamic acids are found in black cohosh (Actaea racemosa) and other Actaea plants. These two compound groups were evaluated for authentication of black cohosh dietary supplements. The hydroxycinnamic acid esters (HCAE) were profiled by ultra-performance liquid chromatography-photodiode array detection (UPLC-PDA). The hydroxycinnamic acid amides (HCAA) were acquired simultaneously by mass spectrometry-multiple reaction monitoring (UPLC-MRM) mode. In contrast with the traditional HCAE method using 8 compounds, profiles of HCAA using only 4 feruloyl dopamine-O-hexosides was more convenient for peak by peak comparison. Partial least square discriminant analysis (PLS-DA) was applied to both HCAE and HCAA datasets. Authenticated plant samples of five Actaea species were randomly divided into training and test sets to build and validate the two PLS-DA models. Both models provided reasonable estimates for the classification of A. racemosa and other Actaea plant samples. However, HCAA model performs better in sensitivity, specificity, and accuracy. Assessment of supplement samples provided quite different results for the solid and liquid dietary supplement samples, indicating the dosage form could affect the composition of marker compounds. Graphical abstract.

Cytotoxic 9,19-cycloartane Triterpenoids from the Roots of Actaea dahurica.

Eight undescribed 9,19-cycloartane type triterpenoid glycosides (cimdalglnoside A-H) and ten known analogues were obtained from the phytochemical research on the roots of Actaea dahurica (syn. Cimicifuga dahurica). All compounds were characterised by spectroscopic experiments, and chemical method. All the compounds isolated were assayed for cytotoxicity to five human cancer cell lines. Cimdalglnoside G showed promising cytotoxicities against Hela, and MCF-7 cell lines with IC50 values at 7.7 and 12.2 µM.

Cytotoxic 9,19-cycloartane type triterpenoid glycosides from the roots of Actaea dahurica.

Ten undescribed 9,19-cycloartane type triterpenoid glycosides (cimdahxynoside A-J) and five known analogues were obtained from the phytochemical research on the roots of Actaea dahurica (syn. Cimicifuga dahurica). All compounds were characterised by spectroscopic experiments, chemical method and X-ray Single-crystal diffraction analysis. Cimdahxynoside A represented the first X-ray crystallography of 9,19-cycloartane type triterpenoid diglycoside. The cytotoxicity of all compounds were tested against five human cancer cell lines. Cimdahxynoside F showed significant cytotoxicity, with IC50 values between 6.6 and 9.9 µM.

Cycloartane triterpenoids from Actaea vaginata with anti-inflammatory effects in LPS-stimulated RAW264.7 macrophages.

Five undescribed cycloartane triterpenoids, including two cycloartane trinor-triterpenoids, were isolated from a 70% ethanol extract of the whole plant of Actaea vaginata (Ranunculaceae), together with thirteen known cycloartane triterpenoids. Their structures were determined by spectroscopic techniques and quantum chemical calculations for intramolecular noncovalent interactions with reduced density gradient method. All compounds were evaluated for their anti-inflammatory effects by a lipopolysaccharide (LPS)-stimulated nitric oxide (NO) production model in RAW264.7 macrophage cells, and some showed potent inhibitory effects with IC50 values ranging from 5.0 to 24.4 µM. Further mechanism studies showed that one compound dose-dependently suppressed LPS-induced NO production and pro-inflammatory cytokines secretion, and decreased the expression of iNOS, through inhibiting NF-κB activation.

New Cytotoxic Cycloartane Triterpenes from the Aerial Parts of Actaea heracleifolia (syn. Cimicifuga heracleifolia).

One new 15,16-seco-cycloartane triterpene (1: ), three new cycloartane triterpene glycosides (2: -4: ), and five known compounds (5: -9: ) were isolated from the aerial parts of Actaea heracleifolia. The chemical structures of these compounds were determined on the basis of NMR analysis, HRTOF-ESIMS data, and other spectroscopic methods. Selected compounds were evaluated for their cytotoxicity against human tumor cell lines (HL-60, SMMC-7721, A549, MCF-7, and SW480) in vitro. Compounds 3: and 4: showed weak activity against the HL-60, A-549, and MCF-7 cell lines with IC50 values ranging from 21.34 to 36.98 µM.

[Research progress on cycloartane triterpenoids of Actaea].

The genus Actaea plants are widely distributed in China, and the cycloartane triterpenoids are the characteristic constituents of this genus. They are divided into types of cimigenol, hydroshengmanol, shengmanol, cimiacerogenin, acteol, 16, 23-diketo, foetidonol, dahurinol, etc. Cycloartane triterpenoids show many biological activities, such as cytotoxicity, anti-osteoporosis, antiviral, anti-inflammatory, anti-nucleoside transport, neuroprotective, anti-oxidant, antibacterial activities. The present paper reviewed the distribution of the plant resources of Actaea, chemical structures and biological activities of cycloartane triterpenoids, aiming to provide a reference for the further research in the future.

Quantification of the total amount of black cohosh cycloartanoids by integration of one specific 1H NMR signal.

Quantitative analysis is an important field in the quality control of medicinal plants, aiming to determine the amount of pharmacologically active constituents in complex matrices. Often biological effects of herbal drugs are not restricted to single compounds, but are rather caused by a number of often biogenetically related plant metabolites. Depending on the complexity of the analyzed plant extract, conflicts between accuracy, such as total content assays using photometric or colorimetric methods, and comprehensiveness, e.g. quantification of one or a few lead compounds can occur. In this study, we present a qHNMR approach determining the total amount of cycloartanoids in black cohosh (Actaea racemosa) rhizomes. Perdeuterated methanol containing 1,2,4,5-tetrachloro-3-nitrobenzene as an internal standard was used for extraction. Amounts of cycloartanoids were then measured by integrating 1H NMR signals of all cycloartenoids' H-19 exo protons. Due to their unusually low chemical shifts, these signals are well separated from all remaining signals in crude extracts. Thus, accurate (recovery rates of 99.5-102.5%) and precise (relative standard deviations below 2.5%) quantification of cycloartanoids was accomplished. To the best of our knowledge, this is the first example of a quantification of the total amount of a pharmacologically relevant compound class by integration of one 1H NMR signal characteristic for all members of this particular compound class. Additionally, we propose a new term and unit for the evaluation of medicinal plants and herbal medicinal products: the "specific partial amount of substance" of pharmacologically active constituents, indicated in mmol/g.

Hyperspectral Imaging and Support Vector Machine: A Powerful Combination to Differentiate Black Cohosh (Actaea racemosa) from Other Cohosh Species.

Actaea racemosa (black cohosh) has a history of traditional use in the treatment of general gynecological problems. However, the plant is known to be vulnerable to adulteration with other cohosh species. This study evaluated the use of shortwave infrared hyperspectral imaging (SWIR-HSI) in tandem with chemometric data analysis as a fast alternative method for the discrimination of four cohosh species (Actaea racemosa, Actaea podocarpa, Actaea pachypoda, Actaea cimicifuga) and 36 commercial products labelled as black cohosh. The raw material and commercial products were analyzed using SWIR-HSI and ultra-high-performance liquid chromatography coupled to mass spectrometry (UHPLC-MS) followed by chemometric modeling. From SWIR-HSI data (920 - 2514 nm), the range containing the discriminating information of the four species was identified as 1204 - 1480 nm using Matlab software. After reduction of the data set range, partial least squares discriminant analysis (PLS-DA) and support vector machine discriminant analysis (SVM-DA) models with coefficients of determination (R2 ) of ≥ 0.8 were created. The novel SVM-DA model showed better predictions and was used to predict the commercial product content. Seven out of 36 commercial products were recognized by the SVM-DA model as being true black cohosh while 29 products indicated adulteration. Analysis of the UHPLC-MS data demonstrated that six commercial products could be authentic black cohosh. This was confirmed using the fragmentation patterns of three black cohosh markers (cimiracemoside C; 12-ß,21-dihydroxycimigenol-3-O-L-arabinoside; and 24-O-acetylhydroshengmanol-3-O-ß-D-xylopyranoside). SWIR-HSI in conjunction with chemometric tools (SVM-DA) could identify 80% adulteration of commercial products labelled as black cohosh.

A new cycloartane triterpenoid glycoside from Souliea vaginata.

One new cycloartane triterpenoid glycoside, soulieoside Q (1), together with four known compounds (2-5) were isolated from the ethanolic extract of the rhizomes of Souliea vaginata Maxim. The structure of the new compound was determined by extensive spectroscopic analysis including 1D and 2D NMR and HRESIMS, as well as chemical methods. Compound 1 was evaluated for its cytotoxic activities against HepG2 and A549 cancer cell lines.

Neuropharmacological investigations on Actaea acuminata Wall. ex Royle roots.

Actaea acuminata Wall. ex Royle, synonym of Actaea spicata var. acuminata (Wall. ex Royle) H.Hara, commonly called the Himalayan Baneberry ( Ranunculaceae) has been investigated for various pharmacological activities, based on its traditional claims. Properly identified A. acuminata roots were defatted by extracting with petroleum ether. The marc was then extracted in a Soxhlet apparatus with methanol. Various pharmacological activities such as antianxiety (Elevated plus maze, Hole board and Light/Dark tests), anticonvulsant (Maximum electroshock test), antidepressant (Despair swim test), sedative (Actophotometer), antistress (Cold swim test), analgesic (Tail immersion test) and anti-inflammatory (Carrageenin-induced paw edema model) were evaluated after administration of 50, 100 or 200 mg/kg, p.o., doses of methanol extract. The methanol extract exhibited significant antianxiety, anticonvulsant, antidepressant and antistress activities, and mild sedative activity at a dose of 200 mg/kg. It was found to be devoid of analgesic and anti-inflammatory activities. Preliminary phytochemical screening of methanol extract showed the presence of alkaloids and polyphenols. Thus, CNS activities of the plant may be attributed to these groups of phytoconstituents.

A new cycloartane triterpene glycoside from Souliea vaginata.

A new cycloartane-type triterpene glycoside, namely soulieoside M (1), and one known compound, beesioside I (2), were isolated from the ethanolic extract of the rhizomes of Souliea vaginata. Their structures were determined spectroscopically and compared with previously reported spectral data. Compounds 1 and 2 were evaluated for their cytotoxic activities against three human cancer cell lines.

Cycloartane Triterpenes from the Aerial Parts of Actaea racemosa.

Investigating the phytochemical equivalence of the aerial parts of Actaea racemosa (syn. Cimicifuga racemosa) relative to the widely used roots/rhizomes, this study provides a perspective for the potential use of renewable ("green") plant parts as a source of black cohosh botanical preparations. In addition to the characterization of Nω-methylserotonin as one representative marker of the Actaea alkaloids, nine cycloartane triterpenes were isolated and characterized, including the two new triterpene glycosides (1S,15R)-1,15,25-trihydroxy-3-O-ß-d-xylopyranosyl-acta-(16S,23R,24R)-16,23;16,24-binoxoside (1) and 3-O-α-l-arabinopyranosyl-(1S,24R)-1,24,25-trihydroxy-15-oxo-acta-(16R,23R)-16,23-monoxoside (2). Their structures were elucidated by spectroscopic data interpretation. The relative configuration of 1 was deduced by (1)H iterative full-spin analysis (HiFSA), making it the first example of the complete analysis of the complex (1)H NMR spectrum of a triterpene glycoside. In addition to the new compounds 1 and 2, the aerial plant parts were shown to contain the previously known binoxosides 3, 4, 6, and 7, the monoxoside 8, and the binoxols 5 and 9. Overall, the metabolome of the aerial plant parts consists of a variety of Actaea triterpenes, similar to those found in roots/rhizomes, a tendency toward C-1 and C-7 hydroxylation of the cycloartanol skeleton, a greater abundance of aglycones, and the presence of comparable amounts of Nω-methylserotonin.

Comparison of phenolic content and antioxidant activity of Actaea racemosa L. and Actaea cordifolia DC.

Actaea racemosa L. is used as a component of drugs or dietary supplements to alleviate the menopause symptoms. Its biological activity is associated with the presence of phenolic compounds. In our work, the analysis of isoflavones and phenolic acids - caffeic acid (CA), ferulic acid and isoferulic acid (iFA) - both free and bonded in two species of Actaea, was conducted using HPLC-PAD technique. Moreover, the antioxidant effect of extracts from different parts of the investigated plants was determined on the basis of DPPH assay. Significant variation of CA and iFA content was observed. The highest content of CA was found in A. racemosa, while Actaea cordifolia contained the highest amount of iFA. Isoflavones were not found in the investigated plants. The antioxidant activity assay showed the high free radical-scavenging ability of the extracts obtained from different parts of the plant.