Actaea racemosa 6c homeopathic tablets

BACKGROUND: Botanical reference materials (BRMs) generally account for the species, cultivar, and year and location of harvest that result in variability in the chemical composition that may lead to statistically significant differences using chemometric methods. OBJECTIVE: To compare the chemical composition of five species of Actaea root BRMs, four herbal sources of A. racemosa root BRMs, and A. racemosa BRMS, and commercial roots and supplements using chemometric methods and selected pre-processing approaches. METHOD: Samples were analyzed by flow injection mass spectrometry (FIMS), principal component analysis (PCA), and factorial multivariate analysis of variance (mANOVA). RESULTS: Statistically significant (P = 0.05) compositional differences were found between three genera (Actaea, Panax, and Ginkgo), five species of Actaea (A. racemosa, A. cimicifuga, A. dahurica, A. pachypoda, and A. rubra) root BRMs, four herbal sources of A. racemosa root BRMs, and A. racemosa BRMS and commercial roots and supplements. The variability of 6% of the BRM variables was found to be quantitatively conserved and reduced the compositional differences between the four sources of root BRMs. Compositional overlap of A. racemosa and other Actaea BRMs was influenced by variation in technical repeats, pre-processing methods, selection of variables, and selection of confidence limits. Sensitivity ranged from 94 to 97% and specificity ranged from 21 to 89% for the pre-processing protocols tested. CONCLUSIONS: Environmental, genetic, and chemometric factors can influence discrimination between species and authentic botanical reference materials. HIGHLIGHTS: Frequency distribution plots derived from soft independent modeling of class analogy provide excellent means for understanding the impact of experimental factors.

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Background: Given the cytotoxicity of chemotherapy drugs used in cancer treatment, there is a need to develop alternative agents to protect female fertility. This study investigated the effect of Actaea racemosa (A. racemosa) extract on mice ovarian cells and the damage caused by doxorubicin (DOX) to the mice ovaries. Methods: We evaluated the effects of A. racemosa extract on mice ovaries (n=42) after DOX treatment. The mice were pre-treated with saline solution (controls) or with 0.5 or 5 mg/kg A. Racemosa extract. Afterward, during a period of 10 days, they were treated daily with one of the six protocols: (i) saline solution (control), (ii) 10 mg/kg DOX, (iii) 0.5 mg/kg A. racemosa extract, (iv) both DOX and 5 mg/kg A. racemosa extract, (v) A. racemosa extract (5 mg/kg), and (vi) both DOX and 0.5 mg/kg A. racemosa extract. At the end of these treatments, the ovaries were fixed for histopathological examinations. Ovarian follicular morphology, stromal cell density, collagen fibers, and TNF-α expression were evaluated. Some ovaries were fixed for transmission electron microscopy or stored at -80oC to study the mRNA expression for Caspase-3 and TNF-α. Results: The Mice treated with A. racemosa extract had reduced follicular degeneration and cell death after exposure to DOX. Ovaries of mice treated with 0.5 mg/kg A. racemosa extract had granulosa cells and oocytes with preserved ultrastructure, decreased immunostaining for TNF-α, and reduced Caspase-3 mRNA. Conclusion: The A. racemosa extract supported follicular survival and protected the ovarian follicles and stromal cells against DOX-induced cytotoxicity.

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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.

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Abstract Main conclusion Hydroxy(phenyl)pyruvic acid reductase from Actaea racemosa catalyzes dual reactions in reducing 4-hydroxyphenylpyruvic acid as well as β-hydroxypyruvic acid. It thus qualifies to be part of fukinolic and cimicifugic acid biosynthesis and also photorespiration. Abstract The accumulation of fukinolic acid and cimicifugic acids is mainly restricted to Actaea racemosa (Ranunculaceae) and other species of the genus Actaea / Cimicifuga . Cimicifugic and fukinolic acids are composed of a hydroxycinnamic acid part esterified with a benzyltartaric acid moiety. The biosynthesis of the latter is unclear. We isolated cDNA encoding a hydroxy(phenyl)pyruvic acid reductase (GenBank OR393286) from suspension-cultured material of A. racemosa (ArH(P)PR) and expressed it in E. coli for protein production. The heterologously synthesized enzyme had a mass of 36.51 kDa and catalyzed the NAD(P)H-dependent reduction of 4-hydroxyphenylpyruvic acid to 4-hydroxyphenyllactic acid or β-hydroxypyruvic acid to glyceric acid, respectively. The optimal temperature was at 38 °C and the pH optimum at pH 7.5. NADPH is the preferred cosubstrate (K m 23 ± 4 µM). Several substrates are accepted by ArH(P)PR with β-hydroxypyruvic acid (K m 0.26 ± 0.12 mM) followed by 4-hydroxyphenylpyruvic acid (K m 1.13 ± 0.12 mM) as the best ones. Thus, ArH(P)PR has properties of β-hydroxypyruvic acid reductase (involved in photorespiration) as well as hydroxyphenylpyruvic acid reductase (possibly involved in benzyltartaric acid formation).

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