Estrogenic and mutagenic activities of Crotalaria pallida measured by recombinant yeast assay and Ames test
TL;DR: Considering the excellent estrogenic activity performed by stigmasterol in the RYA associated with the absence of mutagenic activity when evaluated by the Ames test, stig masterol becomes a strong candidate to be used in hormone replacement therapy during menopause.
Abstract: Crotalaria pallida Ailton is a plant belonging to the Fabaceae family, popularly known as “rattle or rattlesnake” and used in traditional medicine to treat swelling of the joints and as a vermifuge. Previous pharmacological studies have also reported anti-inflammatory, antimicrobial and antifungal activities. Nevertheless, scientific information regarding this species is scarce, and there are no reports related to its possible estrogenic and mutagenic effects. Thus, the purpose of the present study was to investigate the estrogenic potential of C. pallida leaves by means of the Recombinant Yeast Assay (RYA), seeking an alternative for estrogen replacement therapy during menopause; and to reflect on the safe use of natural products to assess the mutagenic activity of the crude extract from C. pallida leaves, the dichloromethane fraction and stigmasterol by means of the Ames test. The recombinant yeast assay with the strain BY4741 of Saccharomyces cerevisiae, was performed with the ethanolic extract, dichloromethane fraction and stigmasterol isolated from the leaves of C. pallida. Mutagenic activity was evaluated by the Salmonella/microsome assay (Ames test), using the Salmonella typhimurium tester strains TA100, TA98, TA97 and TA102, with (+S9) and without (-S9) metabolization, by the preincubation method. All samples showed estrogenic activity, mainly stigmasterol. The ethanolic extract from C. pallida leaves showed mutagenic activity in the TA98 strain (-S9), whereas dichloromethane fraction and stigmasterol were found devoid of activity. Considering the excellent estrogenic activity performed by stigmasterol in the RYA associated with the absence of mutagenic activity when evaluated by the Ames test, stigmasterol becomes a strong candidate to be used in hormone replacement therapy during menopause.
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TL;DR: A comprehensive summary of more than 450 estrogenic chemicals including estrogenic endocrine disruptors is provided here to understand the complex and profound impact of estrogen action.
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55 citations
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...Stigmasterol (E) ER/Traditional medicine Boldrin et al. (2013) (R)...
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49 citations
Cites background from "Estrogenic and mutagenic activities..."
...The raw leaves are very useful for abortion since it has stigmasterol which affects estrogenic activity (Boldrin et al., 2013)....
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TL;DR: The leaves of Tridax procumbens were screened for the presence of bioactive molecules and the results showed that they had high flavonoids, alkaloids, hydroxycinnamates, tannins and phytosterols, moderate benzoic acid derivatives and lignans, and low carotenoids contents as discussed by the authors.
Abstract: The leaves of Tridax procumbens were screened for the presence of bioactive molecules. They had high flavonoids, alkaloids, hydroxycinnamates, tannins and phytosterols, moderate benzoic acid derivatives and lignans, and low carotenoids contents. Thirty nine known alkaloids (mainly akuammidine, 68.756%), twenty three known flavonoids (mainly 17.593% kaempferol and 12.538% (-)-epicatechin), five known carotenoids (mainly lutein, 62.608%), four known benzoic acid derivatives (mainly ferulic acid, 46.091%), two phytosterols (mainly stigmasterol, 80.853%) and six known lignans (mainly galgravin, 77.326%) were detected. Also detected were caffeic acid and tannic acid. The medicinal properties of the flavonoids, phytosterols, alkaloids, tannins, hydroxicinnamates, carotenoids, benzoic acid derivatives and lignans that were present in the leaves were discussed herein and proposed to be explored for their potential medicinal values. The great number of potentially active nutrients and their multifunctional properties make Tridax procumbens a perfect candidate for the production of health-promoting food and food supplements.
28 citations
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...Stigmasterol has anti-osteoarthritic, anti-hypercholestrolemic, cytotoxicity, antitumor, thyroid inhibiting, hypoglycemic, anti-mutagenic, antioxidant, anti-inflammatory, anticonvulsant and sedative [69], chemopreventive, anticancer, estrogenic [70] activities....
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References
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TL;DR: By use of combinatorial chemical and biosynthetic technology, novel natural product leads will be optimized on the basis of their biological activities to yield effective chemotherapeutic and other bioactive agents.
Abstract: Nature has been a source of medicinal agents for thousands of years, and an impressive number of modern drugs have been isolated from natural sources, many based on their use in traditional medicine. In the past century, however, an increasing role has been played by microorganisms in the production of antibiotics and other drugs for the treatment of some serious diseases. Advances in the description of the human genome, as well as the genomes of pathogenic microbes and parasites, is permitting the determination of the structures of many proteins associated with disease processes. With the development of new molecular targets based on these proteins, there is an increasing demand for novel molecular diversity for screening. Natural products will play a crucial role in meeting this demand through the continued investigation of world's biodiversity, much of which remains unexplored. With less than 1% of the microbial world currently known, advances in procedures for microbial cultivation and the extraction of nucleic acids from environmental samples from soil and marine habitats, will provide access to a vast untapped reservoir of genetic and metabolic diversity. The same holds true for nucleic acids isolated from symbiotic and endophytic microbes associated with terrestrial and marine macroorganisms. By use of combinatorial chemical and biosynthetic technology, novel natural product leads will be optimized on the basis of their biological activities to yield effective chemotherapeutic and other bioactive agents. The investigation of these resources requires multi-disciplinary, national, and international collaboration in the discovery and development process.
452 citations
"Estrogenic and mutagenic activities..." refers background in this paper
...Their absorption spectra (220–400 nm) allowed us to observe the presence of flavonoids, mainly derivatives of apigenin and luteolin (flavones) (λ = 254 nm) and phenolic acids and derivatives (λ = 254 nm) [17]....
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TL;DR: A formal method of deciding which points are on the initial linear part of the curve is described, and a statistical method is proposed for analyzing these points, which provides a very satisfactory, robust method for the standard analysis of Salmonella data.
Abstract: A number of recent papers have suggested basing the statistical analysis of Salmonella (Ames) mutagenicity test results on a mathematical model of the complete dose-response curve. For most mutagens at low doses the curve increases linearly; then, as the dose increases, the curve may flatten and finally turn downwards due primarily to effects of toxicity. The exact mechanism underlying this shape is, however, not well understood and is likely to vary for different chemicals. A different approach is to assume that the initial part of the curve is linear and to base the statistical analysis solely on this region, reasoning that it contains most of the interpretable information about the mutagenesis dose response. In this paper a formal method of deciding which points are on the initial linear part of the curve is described, and a statistical method is proposed for analyzing these points. Computer simulations are used to examine the properties of the procedure and comparisons are made with a previously proposed mathematical model of the whole curve. It is concluded that the method suggested here provides a very satisfactory, robust method for the standard analysis of Salmonella data.
396 citations
TL;DR: In this paper, plant sterols and stanols, which are structurally related to cholesterol, decrease the incorporation of dietary and biliary cholesterol into micelles, which leads to decreased serum LDL cholesterol concentrations.
Abstract: High serum LDL cholesterol concentration is a major risk factor for cardiovascular complications. This risk can be lowered by diet. In this respect foods containing plant sterol or stanol esters can be useful for mildly- and hypercholesteraemic subjects. Plant sterols and stanols, which are structurally related to cholesterol, decrease the incorporation of dietary and biliary cholesterol into micelles. This lowers cholesterol absorption. Furthermore, these components increase ABC-transporter expression, which may also contribute to the decreased cholesterol absorption. Consequently, cholesterol synthesis and LDL receptor activity increase, which ultimately leads to decreased serum LDL cholesterol concentrations. Animal studies have further shown that these dietary components may also lower atherosclerotic lesion development. Plant sterols and stanols also lower plasma lipid-standardized concentrations of the hydrocarbon carotenoids, but not those of the oxygenated cartenoids and tocopherols. Also, vitamin A and D concentrations are not affected. Although absorption of plant sterols and stanols (0.02-3.5%) is low compared to cholesterol (35-70%), small amounts are found in the circulation and may influence other physiological functions. However, there is no consistent evidence that plant sterols or stanols can change the risk of colon or prostate cancer, or immune status. In conclusion, plant sterols and stanols effectively reduce serum LDL cholesterol and atherosclerotic risk. In addition potential effects of plant sterols and stanols on other metabolic processes remain to be elucidated.
280 citations
01 Jan 2003
TL;DR: There is no consistent evidence that plant sterols or stanols can change the risk of colon or prostate cancer, or immune status, and potential effects of plant sterol or stanol esters on other metabolic processes remain to be elucidated.
Abstract: High serum LDL cholesterol concentration is a major risk factor for cardiovascular complications. This risk can be lowered by diet. In this respect foods containing plant sterol or stanol esters can be useful for mildly- and hypercholesteraemic subjects. Plant sterols and stanols, which are structurally related to cholesterol, decrease the incorporation of dietary and biliary cholesterol into micelles. This lowers cholesterol absorption. Furthermore, these components increase ABC-transporter expression, which may also contribute to the decreased cholesterol absorption. Consequently, cholesterol synthesis and LDL receptor activity increase, which ultimately leads to decreased serum LDL cholesterol concentrations. Animal studies have further shown that these dietary components may also lower atherosclerotic lesion development. Plant sterols and stanols also lower plasma lipid-standardized concentrations of the hydrocarbon carotenoids, but not those of the oxygenated cartenoids and tocopherols. Also, vitamin A and D concentrations are not affected. Although absorption of plant sterols and stanols (0.02-3.5%) is low compared to cholesterol (35-70%), small amounts are found in the circulation and may influence other physiological functions. However, there is no consistent evidence that plant sterols or stanols can change the risk of colon or prostate cancer, or immune status. In conclusion, plant sterols and stanols effectively reduce serum LDL cholesterol and atherosclerotic risk. In addition potential effects of plant sterols and stanols on other metabolic processes remain to be elucidated. © 2003 Elsevier Inc. All rights reserved.
275 citations
TL;DR: It is stressed that species differences and mechanistic data have to be taken into account and that new mechanism- and toxicokinetic-based methods and models are required for cancer risk extrapolation from high dose experimental animal data to low dose carcinogenic risks for man.
Abstract: The present review focuses on the mechanisms of mutagenic action and the carcinogenic risk of two categories of botanical ingredients, namely the flavonoids with quercetin as an important bioactive representative, and the alkenylbenzenes, namely safrole, methyleugenol and estragole. For quercetin a metabolic pathway for activation to DNA-reactive species may include enzymatic and/or chemical oxidation of quercetin to quercetin ortho-quinone, followed by isomerisation of the ortho-quinone to quinone methides. These quinone methides are suggested to be the active alkylating DNA-reactive intermediates. Recent results have demonstrated the formation of quercetin DNA adducts in exposed cells in vitro. The question that remains to be answered is why these genotoxic characteristics of quercetin are not reflected by carcinogenicity. This might in part be related to the transient nature of quercetin quinone methide adducts, and suggests that stability and/or repair of DNA adducts may need increased attention in in vitro genotoxicity studies. Thus, in vitro mutagenicity studies should put more emphasis on the transient nature of the DNA adducts responsible for the mutagenicity in vitro, since this transient nature of the formed DNA adducts may play an essential role in whether the genotoxicity observed in vitro will have any impact in vivo. For alkenylbenzenes the ultimate electrophilic and carcinogenic metabolites are the carbocations formed upon degradation of their 1'-sulfooxy derivatives, so bioactivation of the alkenylbenzenes to their ultimate carcinogens requires the involvement of cytochromes P450 and sulfotransferases. Identification of the cytochrome P450 isoenzymes involved in bioactivation of the alkenylbenzenes identifies the groups within the population possibly at increased risk, due to life style factors or genetic polymorphisms leading to rapid metaboliser phenotypes. Furthermore, toxicokinetics for conversion of the alkenylbenzenes to their carcinogenic metabolites and kinetics for repair of the DNA adducts formed provide other important aspects that have to be taken into account in the high to low dose risk extrapolation in the risk assessment on alkenylbenzenes. Altogether the present review stresses that species differences and mechanistic data have to be taken into account and that new mechanism- and toxicokinetic-based methods and models are required for cancer risk extrapolation from high dose experimental animal data to low dose carcinogenic risks for man.
260 citations
"Estrogenic and mutagenic activities..." refers background in this paper
...[35] have described essential features in the flavonoid structure for the mutagenic activity to be present, such as: a free hydroxyl at the 3 position of the ring C, double bond between the 2 and 3 positions and the keto group at the 4 position....
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