Actaticas A-G, Cycloartane Triterpenes From Actaea asiatica With Their Antiproliferative Activity.
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ABSTRACT:
SUBMITTER: Hu M
PROVIDER: S-EPMC8358065 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description: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 N?-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-?-d-xylopyranosyl-acta-(16S,23R,24R)-16,23;16,24-binoxoside (1) and 3-O-?-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 N?-methylserotonin.
| S-EPMC4808447 | biostudies-literature
Project description:The cycloartane triterpene content in the roots/rhizomes (RR) and aerial parts (PX) of Actaea racemosa (AR), A. podocarpa (AP), and A. cordifolia (AC) have been investigated by quantitative 1H NMR (qHNMR). Thereby, it was demonstrated that qHNMR represents a powerful methodology for the analysis of crude plant extracts as it does not rely on the rarely available identical reference triterpenes. Specifically, the presence of the characteristic C-19 cyclopropane (exo/endo) hydrogen signals made it possible to quantify the less common/not ubiquitously present group of cycloartane triterpenes, directly in extracts. As an example, ARPX and ARRR were shown to contain, 3.8-20.8% ± 8.2% and 7.2-19.3% ± 4.0% of cycloartane triterpenes, respectively. The cycloartane concentration in ACPX and ACRR was 7.5-8.7% ± 0.8% and 13.9-28.5% ± 7.3%, respectively, based on the weight of the extract. AP was shown to contain notably lower amounts of the cycloartane triterpenes as compared to AR and AC in the roots/rhizomes. The content for APPX and APRR was only 2.1-3.3% ± 0.7% and 1.1-4.0% ± 1.5%, respectively. In addition, an example is presented for the identification of specific cycloartanes as marker compounds for AR within crude extracts based on the same qHNMR spectra and 2D NMR methods.
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Project description:Two new triterpenes cycloartane-type, named 24-methylencycloartan-12-oxo-3β,22α-diol and trichiliol, were isolated from the leaves of Trichilia casaretti C. DC. together with three known triterpenes—24-methylencycloart-3β,22-diol, 22,25-dihydrocycloart-23(E)-en-3β-ol, and 22(R)-hydroxycycloart-24-en-3-ol. These compounds were characterized on the basis of their spectral data, mainly 1D (¹H and 13C) and 2D NMR (¹H-¹H-COSY, ¹H-¹H-NOESY, HMQC, HSQC, and HMBC), and mass spectra (EI-MS and HR-ESI-MS), also involving comparison with data from the literature.
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Project description:The genus Actaea (including Cimicifuga) has been the source of ?200 cycloartane triterpenes. While they are major bioactive constituents of complementary and alternative medicines, their structural similarity is a major dereplication problem. Moreover, their trivial names seldom indicate the actual structure. This project develops two new tools for Actaea triterpenes that enable rapid dereplication of more than 170 known triterpenes and facilitates elucidation of new compounds. A predictive computational model based on classification binary trees (CBTs) allows in silico determination of the aglycone type. This tool utilizes the Me (1)H NMR chemical shifts and has potential to be applicable to other natural products. Actaea triterpene dereplication is supported by a new systematic naming scheme. A combination of CBTs, (1)H NMR deconvolution, characteristic (1)H NMR signals, and quantitative (1)H NMR (qHNMR) led to the unambiguous identification of minor constituents in residually complex triterpene samples. Utilizing a 1.7 mm cryo-microprobe at 700 MHz, qHNMR enabled characterization of residual complexity at the 10-20 ?g level in a 1-5 mg sample. The identification of five co-occurring minor constituents, belonging to four different triterpene skeleton types, in a repeatedly purified natural product emphasizes the critical need for the evaluation of residual complexity of reference materials, especially when used for biological assessment.
| S-EPMC3392135 | biostudies-literature
Project description:The interpretation of NMR spectroscopic information for structure elucidation involves decoding of complex resonance patterns that contain valuable molecular information (? and J), which is not readily accessible otherwise. We introduce a new concept of 2D-NMR barcoding that uses clusters of fingerprint signals and their spatial relationships in the ?-? coordinate space to facilitate the chemical identification of complex mixtures. Similar to widely used general barcoding technology, the structural information of individual compounds is encoded as a specifics pattern of their C,H correlation signals. Software-based recognition of these patterns enables the structural identification of the compounds and their discrimination in mixtures. Using the triterpenes from various Actaea (syn. Cimicifuga) species as a test case, heteronuclear multiple-bond correlation (HMBC) barcodes were generated on the basis of their structural subtypes from a statistical investigation of their ?H and ?C data in the literature. These reference barcodes allowed in silico identification of known triterpenes in enriched fractions obtained from an extract of A. racemosa (black cohosh). After dereplication, a differential analysis of heteronuclear single-quantum correlation (HSQC) spectra even allowed for the discovery of a new triterpene. The 2D barcoding concept has potential application in a natural product discovery project, allowing for the rapid dereplication of known compounds and as a tool in the search for structural novelty within compound classes with established barcodes.
| S-EPMC4004191 | biostudies-literature
Project description:Centella asiatica (also known as Centella asiatica (L.) Urb. or Gotu kola) is a traditional Chinese medicine with extensive medicinal value, which is commonly used in Southeast Asian countries. This study aimed to summarize the effects of C. asiatica and its main components on neurological diseases, endocrine diseases, skin diseases, cardiovascular diseases, gastrointestinal diseases, immune diseases, and gynecological diseases, as well as potential molecular mechanisms, to study the pathological mechanism of these diseases based on the changes at the molecular level. The results showed that C. asiatica and its triterpenoids had extensive beneficial effects on neurological and skin diseases, which were confirmed through clinical studies. They exhibited anti-inflammatory, anti-oxidative stress, anti-apoptotic effects, and improvement in mitochondrial function. However, further clinical studies are urgently required due to the low level of evidence and lack of patients.
| S-EPMC7498642 | biostudies-literature
Project description:This study clarifies the chemical constituents and botanical origin of Tetragonula sapiens Cockerell bee propolis collected from Southeast Sulawesi, Indonesia. Propolis samples and resin of Mangifera indica were extracted with 99% ethanol to obtain an ethanol extract of propolis (EEP) and an ethanol extract of M. indica resin (EEM). Column chromatography, thin-layer chromatography (TLC), and high-performance liquid chromatography (HPLC) were developed and used for the separation and isolation of compounds from the ether-soluble fraction. The structure of the compounds was determined by nuclear magnetic resonance (NMR) spectroscopic analysis, and their molecular weight analyzed by gas chromatography?mass spectrometry (GC?MS). The HPLC chromatogram of the EEP was then compared with the HPLC chromatogram of EEM to investigate the botanical origin of propolis. Five compounds were isolated from the EEP, and their structures were determined as mangiferolic acid, cycloartenol, ambonic acid, mangiferonic acid, and ambolic acid, which are cycloartane-type triterpenes. The characteristic peak of the HPLC chromatograms of EEP and EEM showed a similar pattern, which is that the main components of propolis were also found in M. indica resin. These results suggested that the propolis from Southeast Sulawesi was rich in cycloartane-type triterpenes, and the plant source of the propolis could be Mangifera indica (mango).
| S-EPMC6473588 | biostudies-literature
Project description:Background:Diabetic neuropathy (DN), a common complication of diabetes mellitus, results from hyperglycemia, poor microcirculation and attendant nerve damage. Currently available treatments relieve symptoms, but do not modify the neurodegeneration underlying DN. Centella asiatica (CA) triterpenes improved microcirculation in earlier clinical studies, and showed neurotropic effects in preclinical models suggesting a potential disease modifying effect in DN. This 52-week, randomized, double-blind, placebo-controlled trial examined the effects of CAST, a standardized CA extract containing triterpenes, on neuropathy symptoms in Type II diabetic subjects. Patients and Methods:The study enrolled patients with a history of Type II diabetes, with evidence of symptomatic symmetrical DN with total symptom score (TSS) ?4, and stable HbA1c level <8. The primary outcome measure was TSS, which assessed intensity and frequency of parasthesia, numbness, pain and burning symptoms self-reported by patients. Secondary measures were nerve conduction, neurological impairment score, and quantitative sensory testing. Results:Comparing CAST (n=21) and Placebo (n=22) groups, significant reductions from baseline for TSS (p<0.01) and paresthesia (p<0.01) were seen only in CAST treated groups. Numbness increased from baseline only in the Placebo group (p<0.05) and was significantly higher than for the CAST group (p<0.001). Burning sensation was reduced in both groups (p<0.01). Plasma triterpene levels in patients treated with CAST mirrored neurotropic concentrations in vitro. Conclusions:CAST is a potential oral treatment for diabetic neuropathy, as it is well tolerated and effective in reducing the severity of DN symptoms in patients with Type II diabetes.
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Project description:Alzheimer's disease (AD) is a neurodegenerative disease and the most cause of dementia in elderly adults. Acetylcholinesterase (AChE) is an important beneficial target for AD to control cholinergic signaling deficit. Centella asiatica (CA) has proven to be rich with active ingredients for memory enhancement. In the present study, the chemical profiling of three accession extracts of CA namely SECA-K017, SECA-K018, and, SECA-K019 were performed using high-performance liquid chromatography (HPLC). Four biomarker triterpene compounds were detected in all CA accessions. Quantitative analysis reveals that madecassoside was the highest triterpene in all the CA accessions. The biomarker compounds and the ethanolic extracts of three accessions were investigated for their acetylcholinesterase (AChE) inhibitory activity using Ellman's spectrophotometer method. The inhibitory activity of the triterpenes and accession extracts was compared with the standard AChE inhibitor eserine. The results from the in vitro study showed that the triterpene compounds exhibited an AChE inhibitory activity with the half-maximal inhibitory concentration (IC50) values between 15.05 ± 0.05 and 59.13 ± 0.18 µg/mL. Asiatic acid was found to possess strong AChE inhibitory activity followed by madecassic acid. Among the CA accession extracts, SECA-K017 and SECA-K018 demonstrated a moderate AChE inhibitory activity with an IC50 value of 481.5 ± 0.13 and 763.5 ± 0.16 µg/mL, respectively from the in silico docking studies, it is observed that asiatic acid and madecassic acid showed very good interactions with the active sites and fulfilled docking parameters against AChE. The present study suggested that asiatic acid and madecassic acid in the CA accessions could be responsible for the AChE inhibitory action and could be used as markers to guide further studies on CA as potential natural products for the treatment of AD.
| S-EPMC7436049 | biostudies-literature
Project description:Centella asiatica (CA) is a culinary vegetable and well-known functional food that is widely used as a medicinal herb and dietary supplement. CA is rich in pentacyclic triterpenes (TTs), including asiaticoside (AS), madecassoside (MS) and the related aglycones asiatic acid (AA), madecassic acid (MA). Traditionally, TTs have been associated with the bioactivity and health promoting effect of CA. Recently, mono-caffeoylquinic acids (MonoCQAs) and di-caffeoylquinic acids (DiCQAs) have been found to contribute to the bioactivity of CA as well. This work reports an analytical strategy based on liquid chromatography coupled to multiple reaction monitoring mass spectrometry (LC-MRM-MS) for the simultaneous rapid and accurate quantification of 12 bioactive compounds in CA, namely AS, MS, AA, MA, 5-CQA, 4-CQA, 3-CQA, 1,3-DiCQA, 3,4-DiCQA, 1,5-DiCQA, 3,5-DiCQA, 4,5-DiCQA. Method selectivity, accuracy, precision, repeatability, robustness, linearity range, limit of detection (LOD), and limit of quantitation (LOQ) were validated. The validated LC-MRM-MS method has been successfully applied to quantify the 12 bioactive compounds in CA aqueous extracts and two related formulations: a standardized CA product (CAP) used in a phase I clinical trial and formulated CA rodent diets used in preclinical studies. The validated method allows us to support the standardization of CA products used for clinical trials and conduct routine LC-MRM-MS analyses of formulated preclinical diets to confirm correct levels of CA phytochemical markers.
| S-EPMC10544816 | biostudies-literature