Actaea racemosa L. (syn. Cimicifuga racemosa (L.) Nutt., black cohosh) rhizomes contain triterpene glycosides (TTGs) that serve as principal quality markers in the European Pharmacopoeia (Ph. Eur.) monograph. However, discrepancies between chromatographic profiles of the plant material and the herbal reference standard (HRS) dry extract complicate quality assessment. This study elucidated the chemical origin of these discrepancies and evaluated whether the extract-based HRS can represent the analytical fingerprint of the plant material. Thirteen TTGs were identified and characterized within the official Ph. Eur. HPLC-ELSD method using centrifugal partition chromatography, semi-preparative UPLC, HRMS, GC-MS and NMR spectroscopy, employing reference standards and isolated compounds. Three malonylated TTGs (8a, 9a, 10a) were detected in wild and cultivated rhizomes but were absent from the A. racemosa dry extract HRS and other dry extracts. Quantitative analysis revealed that cultivated plants contained an insufficient amount of TTGs; however, after extraction, both the amount and the profile aligned with the Ph. Eur. requirements. This behavior is explained by the degradation and rearrangement pathways of the TTGs. Overall, these findings clarify the origin of chemical variability between plant and extract fingerprints and support the inclusion of malonylated TTGs in the quantitative determination of A. racemosa triterpene glycosides in the Ph. Eur.

Actaea cimicifuga L. (syn. Cimicifuga foetida L.) is an important medicinal plant widely used in China. In this study, the complete chloroplast genome of A. cimicifuga was characterized and assembled. The complete chloroplast genome is 159,761 bp in length and exhibits a typical tetrad structure, consisting of a large single-copy region (88,805 bp) and a small-single copy region (17,838 bp), separated by two inverted repeat regions of 26,559 bp each. A total of 129 unique genes were annotated, including 84 protein-coding genes, 8 rRNA genes, and 37 tRNA genes. Fourteen genes containing introns were identified in the chloroplast genome of A. cimicifuga. Among these, two genes (ycf3 and clpP) contain two introns, whereas the remaining genes contain a single intron. Phylogenetic analysis based on maximum likelihood using 20 complete chloroplast genomes showed that A. cimicifuga is closely related to other species within the Actaea genus. The chloroplast genome of A. cimicifuga provides valuable genetic information.

Most Germans consider herbal medicinal products (HMPs) to be an important supplement to conventional medicine. Despite existing clinical evidence for safety and efficacy, they are still not sufficiently integrated into drug therapy of gynaecological complaints in everyday practice. By analysing patient-reported outcomes (PROs), this gap in medical care can be closed. Real-world data was extracted from the pharmaco-epidemiological database PhytoVIS. We analysed a sample (n = 1658) containing PROs from women who utilised HMPs to treat their gynaecological complaints applying descriptive and non-parametric bivariate statistical tests. Perceived effectiveness and tolerability of HMPs was rated as very good. For the treatment of menstrual complaints, Vitex agnus-castus L. was primarily used, and Actaea racemosa L. for menopausal complaints. Various herbal drugs were applied for uncomplicated urinary tract infections (uUTIs), but mainly Arctostaphylos uva-ursi (L.) Spreng. Regarding the pharmaceutical form, herbal teas were preferred for the treatment of uUTIs or by very young or elderly women. All other pharmaceutical forms were favoured for menstrual and menopausal complaints or middle-aged women. The pharmaceutical form did not impact the perceived therapeutic effectiveness. Our results provide valuable insights into patient preferences and show options for their integration into existing treatment strategies. By identifying the most popular and efficacious plants for certain gynaecological ailments, we support healthcare providers to better address the growing demand for complementary treatment options. This knowledge helps in tailoring healthcare to meet patient needs and to ensure the safety and efficacy of HMPs.

The diversity of floral traits in angiosperms has evolved over time as an adaptive response to reproductive demands. Investigating floral characteristics and pollination systems helps elucidate the evolutionary drivers behind morphological variation in flowers. In this study, we examined A. erythrocarpa to systematically document its floral morphology, stigma receptivity, pollen-ovule ratio, breeding system, and pollinator behavior. Results showed that the sepals abscised completely at the early flowering stage, while stigmas became receptive even during the bud phase. The pollen-ovule ratio was 1773.58 ± 689.75, indicating a facultatively xenogamous breeding system. Bagging experiments further confirmed that the species is self-compatible but does not exhibit apomixis or wind pollination. Field observations identified Agromyzidae sp. and E. balteatus as the primary pollinators, which visited flowers at high frequency after sepal abscission but before anther dehiscence. Compared with its congener A. asiatica, which exhibits delayed sepal abscission and relies mainly on selfing, A. erythrocarpa demonstrates distinct floral morphological adaptations linked to its specialized pollination strategy. These two species thus represent divergent reproductive adaptation patterns within the genus. Therefore, the visiting behavior of fly insects and the early shedding of sepals promotes cross-pollination of A. erythrocarpa.

Despite the global prevalence of herbal medicine use and the common perception of their safety, substantial evidence indicates a significant potential for clinically relevant herb-drug interactions that may affect the pharmacokinetics and pharmacodynamics of co-administered pharmaceuticals. This critical issue poses a considerable threat to patient safety and the effectiveness of conventional treatments, primarily through modulation of the cytochrome P450 (CYP450) enzyme system, a key metabolic pathway for many drugs. This research aims to elucidate how herbal remedies affect CYP450 enzyme activity, thereby influencing drug pharmacokinetics. Our methodology involves a comprehensive critical evaluation of existing scientific data from in silico, in vitro, and in vivo studies, clinical trials, and meta-analyses to identify specific herbal medicines with significant effects on CYP450. The investigation outlines their mechanisms of action, distinguishing between enzyme induction, which can diminish drug efficacy, and inhibition, which may lead to increased drug concentrations and toxicity. It was highlighted that certain medicinal plants and their bioactive compounds may act as inducers or inhibitors across major isoforms, including CYP1A2, CYP2C9, CYP2D6, and CYP3A4. Comprehensive data were compiled for ten plant species with the most extensive scientific information regarding their effects on CYP450, namely St John's wort (Hypericum perforatum L.), Echinacea (Echinacea purpurea (L.) Moench), Ginkgo (Ginkgo biloba L.), Danshen (Salvia miltiorrhiza Bunge), Garlic (Allium sativum L.), Ginger (Zingiber officinale Roscoe), Milk thistle (Silybum marianum L. Gaertn.), Black cohosh (Actaea racemosa L.), Ginseng (Panax ginseng C.A. Mey), and Liquorice (Glycyrrhiza glabra L.). Ultimately, this study underscores the vital role of the CYP450 system in mediating these interactions and advocates for increased awareness among healthcare professionals and patients. Looking ahead, conducting robust, standardised clinical trials, developing predictive interaction models, and performing comprehensive analyses of herbal constituents are crucial to ensuring safe and effective pharmacotherapy involving herbal medicines.

Triterpenoids with diverse structural features have shown considerable potential as pharmaceutical precursors for anti-inflammatory therapies. Beesioside O (BO), a representative triterpenoid (cycloartane triterpene saponin), has previously been reported to exhibit notable anti-HIV and anticancer activities. However, its anti-inflammatory mechanisms have not been fully elucidated. In this study, we investigated the anti-inflammatory activity and underlying molecular mechanisms of BO in LPS-induced RAW264.7 macrophages. In addition, NP AI Engine predictions, molecular docking, density functional theory (DFT) calculations, and molecular dynamics simulations were conducted to characterize the anti-inflammatory properties of BO further. The experimental results indicated that BO inhibited the mRNA expression levels of iNOS and COX-2. Moreover, it can regulate the phosphorylation of ERK at 3 h. Potential signaling pathways and targets were subsequently analyzed. The structural and electronic properties of BO were calculated using the B3LYP/6-311+G (d,p) basis set. The BO-ERK2 kinase complex was also constructed for simulation. Furthermore, a BO derivative was prepared through hydrolysis followed by acylation, and its anti-inflammatory activity was evaluated. Overall, this study provides deeper insight into the anti-inflammatory effects of BO and supports its potential for further development as an anti-inflammatory agent.

Detailed studies of foraging behavior are needed for scientific management of the endangered rusty-patched bumblebee (Bombus affinis) in the disjunct and ecologically differentiated habitats it presently occupies. Current knowledge gaps hinder recovery planning but are challenging to redress through direct observation of rare interactions in the field.

Black cohosh (Actaea racemosa L) has been utilized for centuries by Native Americans as a traditional herbal medicine. The rhizome and root extract from black cohosh (BCE) is one of the most popular herbal dietary supplements worldwide. Due to its claimed estrogen-like effects, contemporary uses of black cohosh products are primarily for alleviating menopausal and perimenopausal symptoms. However, recent studies indicate that BCE is not only ineffective for menopausal therapy, but also induces genotoxicity through an aneugenic mode of action (MoA). Adverse effects induced by BCE have been reported in humans, with many case studies documenting outcomes ranging from mild reactions to acute liver damage and even death. Consequently, concerns about the safety of BCE have emerged. There are more than 100 chemical constituents in black cohosh products, including triterpene glycosides (>40 chemicals), polyphenols (>20 chemicals), and nitrogenous compounds (>70 chemicals). Therefore, commercially available BCE products can differ markedly in composition, leading to the potential for variable bioactivities among these complex commercial products. This review presents the latest information on the toxicological effects of BCE from both in vivo and in vitro experiments and summarizes the adverse effects of BCE in human clinical trials.

For the first time, hydroethanolic extracts from Actaea cimicifuga and Actaea erythrocarpa were analyzed using LC-HRMS, HPLC, and spectrometry in this study. Extracts from the above-ground parts of Actaea species exhibited higher concentrations of saponins (up to 248 mg/g of DE), coumarins (up to 162 mg/g of DE), flavonols (up to 32 mg/g of DE), and catechins (up to 11 mg/g of DE) compared to extracts from the underground parts. The concentrations of phenolic acids (up to 112 mg/g of DE) and tannins (up to 202 mg/g of DE) in the underground parts were comparable to or even higher than those in the above-ground parts of the two analyzed species. The concentration of the main metabolites detected was higher in the extract of A. erythrocarpa than that of A. cimicifuga. The metabolite profile of the extracts from both species showed 66 compounds, including chromones, coumarins, phenolic and nitrogenous compounds, fatty acids, and triterpenes. The HPLC analysis of the four extracts revealed that the concentration of caffeic acid (0.74 mg/g of the dry extract [DE]) was the highest in the extract from the underground part of A. erythrocarpa, whereas the extract from the above-ground part of this species showed the highest levels of ferulic (1.16 mg/g of DE) and isoferulic acids (1.49 mg/g of DE) and of hyperoside (13.05 mg/g of DE). The study of biological activity showed that A. erythrocarpa is most promising for further research, with the highest antioxidant activity found in the underground parts of this species (IC50 = 79.7 μg/mL) compared to the above-ground parts (IC50 = 85.8 μg/mL). In addition, the extract from the above-ground part of A. erythrocarpa was found to exhibit the greatest cytotoxic activity among the studied specimens against 3T3-L1, HepG2, and MDA-MB-231 cells.

Black cohosh is a popular herbal medication derived from a plant of the buttercup family indigenous to North America (Actaea racemosa, syn Cimicifuga racemosa), which is claimed to have estrogen-like effects and is used primarily for relief of symptoms of menopause. In recent years, products labeled as black cohosh has been implicated in many instances of clinically apparent, acute liver injury, some cases of which have been severe and led to emergency liver transplantation or death.

One-class modeling is a supervised multivariate botanical identification method based on principal component analysis (PCA) that constructs a model based only on the characteristics of the reference samples and uses the Q statistic as a combined metric. Test samples are judged to be similar (authentic) if their combined metric falls within the model limits or different (adulterated or contaminated) if the metric falls outside the model limits. This review initially considers three major factors affecting identification: the number of variables (univariate versus multivariate), the number of classes (one-class versus multi-class), and the type of analysis (quantitative versus qualitative). Multivariate analysis is commonly used for identification, providing a broader coverage of the identity specifications of the samples. With a combined metric, multivariate methods are analogous to univariate methods. One-class modeling and multi-class modeling employ different approaches for identification with one-class modeling being more flexible. While most methods to date have had a quantitative basis, qualitative methods are possible. This review focuses on multivariate, one-class modeling based on PCA. Examples are presented for the application of one-class modeling to identification of American ginseng (Panax quinquefolius), Echinacea purpurea, Black Cohosh (Actaea racemosa), and Maca (Lepidium meyenii). These examples demonstrate the utility and flexibility of one-class modeling.

Breast cancer remains a leading cause of malignancy-related mortality among women, with rising global incidence. While surgical intervention is effective for early-stage breast cancer, drug therapy is indispensable, particularly for triple-negative breast cancer, where treatment options are still limited. Actaea vaginata, a traditional Chinese medicinal herb, has been historically applied for inflammatory conditions, including pharyngitis and stomatitis. However, its antitumor potential remains under-reported. In this study, a cycloartane triterpene saponin, beesioside O (BO), was isolated from this plant. Its antitumor activity was evaluated in vitro. Its potential therapeutic mechanisms were elucidated through network pharmacology. BO exhibited substantial potency in inhibiting breast cancer cells. Network pharmacology analysis uncovered 179 potential pharmacological targets of BO, which were predominantly concentrated in pathways, such as pathways in cancer, the PI3K-Akt signaling pathway, and chemical carcinogenesis receptor activation. Molecular docking analysis indicated that STAT3 exhibited minimal binding energy with BO. Additionally, molecular dynamics simulations verified the conformational stability of the BO-STAT3 complex. Western blot analysis demonstrated that STAT3 was downregulated following administration. These results imply that BO may exhibit a multi-target, synergistic therapeutic effect against breast cancer, with STAT3 recognized as a pivotal target. This study demonstrates the potential of BO for development as a chemotherapeutic agent for breast cancer treatment. It lays the groundwork for further exploration of BO's bioactivity and provides valuable insights into its molecular mechanisms in breast cancer therapy.

Botanical dietary supplements are widely used, but issues of authenticity, consistency, safety, and efficacy that complicate their poorly understood mechanism of action have prompted questions and concerns in the popular and scientific literature. Black cohosh (Actaea racemosa L., syn. Cimicifuga racemosa, Nutt., Ranunculaceae) is a multicomponent botanical therapeutic used as a popular remedy for menopause and dysmenorrhea and explored as a treatment in breast and prostate cancer. However, its use and safety are controversial. A. racemosa tissues contain the bioactive serotonin analog N-methylserotonin, which is thought to contribute to the serotonergic activities of black cohosh-containing preparations. A. racemosa has several TDC-like genes hypothesized to encode tryptophan decarboxylases (TDCs) converting L-tryptophan to tryptamine, a direct serotonin precursor in plants. Expression of black cohosh TDC1, TDC2, and TDC3 in Saccharomyces cerevisiae resulted in the production of tryptamine. TDC1 and TDC3 had approximately fourfold higher activity than TDC2, which was attributable to a variable Cys/Ser active site residue identified by site-directed mutagenesis. Co-expression in yeast of the high-activity black cohosh TDCs with the next enzyme in serotonin biosynthesis, tryptamine 5-hydroxylase (T5H), from rice (Oryza sativa) resulted in the production of serotonin, whereas co-expression with low-activity TDCs did not, suggesting that TDC activity is a rate-limiting step in serotonin biosynthesis. Two T5H-like sequences were identified in A. racemose, but their co-expression with the high-activity TDCs in yeast did not result in serotonin production. TDC expression was detected in several black cohosh tissues, and phytochemical analysis using LC-MS revealed several new tryptamines, including tryptamine and serotonin, along with N-methylserotonin and, interestingly, N-N-dimethyl-5-hydroxytryptamine (bufotenine), which may contribute to hepatotoxicity. Incubation of A. racemosa leaves with tryptamine and N-methyltryptamine resulted in increased concentrations of serotonin and N-methylserotonin, respectively, suggesting that methylation of tryptamine precedes hydroxylation in the biosynthesis of N-methylserotonin. This work indicates a significantly greater variety of serotonin derivatives in A. racemosa than previously reported. Moreover, the activities of the TDCs underscore their key role in the production of serotonergic compounds in A. racemosa. Finally, it is proposed that tryptamine is first methylated and then hydroxylated to form the black cohosh signature compound N-methylserotonin.