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List of plants containing hydroxyanthracene derivatives permitted for use in food supplements in France ('Documentation provided to EFSA' n. 1) 

List of plants containing hydroxyanthracene derivatives permitted for use in food supplements in France ('Documentation provided to EFSA' n. 1) 

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The Panel on Food Additives and Nutrient Sources added to Food (ANS) was asked to deliver a scientific opinion on the safety of hydroxyanthracene derivatives and to provide advice on a daily intake that does not give rise to concerns about harmful effects to health. Hydroxyanthracene derivatives are a class of chemical substances naturally occurrin...

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... plants containing hydroxyanthracene derivatives, listed in Table 2, are permitted for use in food supplements, under specific conditions of use. France also accepts under mutual recognition the plants that are included in the BELFRIT list ('Documentation provided to EFSA' n. 1). ...

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Abstract Aloe vera (AV) is popular and has been commercialized as a beauty product, laxative, herbal medicine, the antimicrobial activity of AV is proven. The antiviral activity of AV however, has not been well documented except for a handful reports. Till date extraction of AV compounds is popularized using organic solvents, since the active compo...

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... The estimated exposure to hydroxyanthracene derivatives from the recommended daily doses of food supplements indicates intakes of 24.83 mg/person per day of sennoside B, 78.8 mg/person per day of rhein, 26 mg/person per day of glucofrangulin A, 24 mg/person per day of barbaloin and 51 mg/person per day of aloin A + B.; the data relating to exposure to emodin and aloe-emodin are not known and are likely to be on the same order of magnitude [6]. ...
... The European Food Safety Authority (EFSA) Food Additives and Nutrient Sources added to Food (ANS) Panel concluded that "hydroxyanthracene derivatives should be regarded as genotoxic and carcinogenic unless there are specific data to the contrary, [...] and that there is a safety concern for extracts containing hydroxyanthracene derivatives although uncertainty persists" [6]. The only study judged reliable by the ANS Panel was the one in which aloe-emodin was administered by the oral route to male (OF1) mice at doses of 500, 1000 and 2000 mg/kg bw in an in vivo rodent comet assay conducted in accordance with unspecified international recommendations [7]. ...
... The European Commission proposed placing aloe-emodin and all the extracts in which this substance is present and leaf extracts of Aloe species containing hydroxyanthracene derivatives in Part A (ban on the use in food) of Annex III of Regulation (EC) no. 1925/2006 of the European Parliament and of the Council, due to alleged genotoxic and carcinogenic effects of hydroxyanthracene derivatives identified by the EFSA [6]. ...
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Aloe ferox Mill is widely used as a traditional herbal medicine for the treatment of a broad spectrum of illnesses given its laxative, anti-inflammatory, bitter tonic, anti-oxidant, antimicrobial and anti-cancer properties. Using the in vivo alkaline comet assay in animals (OECD 489), this study investigated the potential in vivo genotoxicity of dried Aloe ferox juice at dose levels of 500, 1000, and 2000 mg/kg/day in mice. Aloe ferox showed no genotoxic activity in preparations of single cells from the colon of the treated Hsd:ICR (CD-1) male mice. No statistically significant increase in DNA migration over the negative control was observed by analysis of variance for both comet parameters, tail moment and tail intensity, apart from the positive control ethyl methanesulphonate that induced clear and statistically significant increases in DNA migration parameters over the concurrent controls. The new reported scientific evidence unequivocally demonstrates that dried Aloe ferox juice containing hydroxyanthracene derivatives does not induce DNA damage in preparations of single cells from colon in in vivo comet genotoxicity studies. This suggests that the hyperplastic changes and mucosal hyperplasia observed after long-term administration of Aloe vera non-decolourised whole leaf extract may be attributed to an epigenetic effect of the material under investigation.
... According to the authors, the selective inhibition of the JAK2/STAT3 pathway and downregulation of Mcl-1 suggests a good potential as anti-myeloma reagent. However, in a recent report of the European Food Safety Authority (EFSA), the compound (together with other hydroxyanthracene derivatives) was found to produce genotoxic effects in vitro and to increase the risk of colorectal cancer [48]. Though the genotoxic effect of emodin was only observed in vitro, Aloe extracts containing emodin were also found genotoxic in vivo. ...
... This section contains one phenylethanoid, namely oleacein, two simple phenylpropanoids, and two condensed phenylpropanoids, also known as lignans ( Figure 4). (EFSA), the compound (together with other hydroxyanthracene derivatives) was found to produce genotoxic effects in vitro and to increase the risk of colorectal cancer [48]. Though the genotoxic effect of emodin was only observed in vitro, Aloe extracts containing emodin were also found genotoxic in vivo. ...
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A literature search on plant natural products with antimyeloma activity until the end of 2020 resulted in 92 compounds with effects on at least one human myeloma cell line. Compounds were divided in different compound classes and both their structure–activity-relationships as well as eventual correlations with the pathways described for Multiple Myeloma were discussed. Each of the major compound classes in this review (alkaloids, phenolics, terpenes) revealed interesting candidates, such as dioncophyllines, a group of naphtylisoquinoline alkaloids, which showed pronounced and selective induction of apoptosis when substituted in position 7 of the isoquinoline moiety. Interestingly, out of the phenolic compound class, two of the most noteworthy constituents belong to the relatively small subclass of xanthones, rendering this group a good starting point for possible further drug development. The class of terpenoids also provides noteworthy constituents, such as the highly oxygenated diterpenoid oridonin, which exhibited antiproliferative effects equal to those of bortezomib on RPMI8226 cells. Moreover, triterpenoids containing a lactone ring and/or quinone-like substructures, e.g., bruceantin, whitaferin A, withanolide F, celastrol, and pristimerin, displayed remarkable activity, with the latter two compounds acting as inhibitors of both NF-κB and proteasome chymotrypsin-like activity.
... AQs have been routinely used for decades as natural dyes or drugs [5]; for more than 30 years, many studies have attempted to determine their genotoxic potential, which is currently debated [5,143]. Recently, the EFSA (European Food and Safety Authority) provided a scientific opinion on the possible harmful effects on health of long-term use of AQs present in dietary products, generally used as laxatives [144]. The main concern was the possible association of AQs consumption with colon cancer. ...
... However, a safe daily intake for AQ products was not defined for the general population. The EFSA report states that "AQs should be considered genotoxic and carcinogenic unless there are sufficient evidence on the contrary" [144]. A recent meta-analysis tried to quantify the risk of colon cancer associated with AQ consumption considering both active compounds (emodin, aloe-emodin, physhion, chrysophanol, rhein, danthron, senna glycosides) and herbal laxative preparations. ...
... One reason may be the mistaken belief that "natural means safe," which prompts the use of these products above the recommended dose, underestimating the risk for health. On the contrary, "natural" laxatives bring many risks and, not without reason, their use for more than 2 weeks requires medical supervision [144]. ...
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The marine ecosystem, populated by a myriad of animals, plants, and microorganisms, is an inexhaustible reservoir of pharmacologically active molecules. Among the multiple secondary metabolites produced by marine sources, there are anthraquinones and their derivatives. Besides being mainly known to be produced by terrestrial species, even marine organisms and the uncountable kingdom of marine microorganisms biosynthesize anthraquinones. Anthraquinones possess many different biological activities, including a remarkable antitumor activity. However, due to their peculiar chemical structures, anthraquinones are often associated with toxicological issues, even relevant, such as genotoxicity and mutagenicity. The aim of this review is to critically describe the anticancer potential of anthraquinones derived from marine sources and their genotoxic and mutagenic potential. Marine-derived anthraquinones show a promising anticancer potential, although clinical studies are missing. Additionally, an in-depth investigation of their toxicological profile is needed before advocating anthraquinones as a therapeutic armamentarium in the oncological area.
... Leaves are the most used part of the plant, with bioactive acetylated glucomannan and anthraquinone glycosides being obtained from the Aloe gel, while the latex contains too high an anthraquinoids content (aloin A and B); an excessive consumption of these compounds presented in aloe juice can have toxic effects, and therefore, its consumption must be limited [10]. Recently, some studies have reported the antioxidant properties [11,12] or carotenoids content, composition of phenolic compounds, and fatty acid profile of Aloe vera flowers [13,14]. ...
... The maturity stage I provided the flowers with the highest TPC value (130.24 ± 6.07 mg of GAE/100 g f.w.), and the maturity stage III showed the lowest value (79.95 ± 7.10 mg GAE/100 g f.w.). Debnath et al. [10] described much lower TPC in Aloe barbadensis flower extracts, 17.52 mg GAE/100 g d.w. on flower ethanol extracts than the present research work. These authors used dried flowers, which could lead to a loss in bioactive compounds depending on the drying method used. ...
... Lucini et al. [74], obtained a TPC in whole leaf of 1206 ± 60 mg GAE/100 g f.w. and 217 ± 9 mg GAE/100 g f.w. in inner parenchyma, while The maturity stage I provided the flowers with the highest TPC value (130.24 ± 6.07 mg of GAE/100 g f.w.), and the maturity stage III showed the lowest value (79.95 ± 7.10 mg GAE/100 g f.w.). Debnath et al. [10] described much lower TPC in Aloe barbadensis flower extracts, 17.52 mg GAE/100 g d.w. on flower ethanol extracts than the present research work. These authors used dried flowers, which could lead to a loss in bioactive compounds depending on the drying method used. ...
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Flowers of Aloe vera are a byproduct providing a valuable source of bioactive compounds with different functions for health benefits. The characterization in amino acids, organic acids, sugars, trigonelline, volatiles compounds, fatty acids, total phenolic, carotenoids, vitamin C content, and antioxidant capacity of Aloe flowers (Aloe barbadensis Miller) has been studied at three maturity stages (I: immature; II: mature; III: mature, with flowers buds opened). Immature flowers presented the highest content in phenyl alanine, tyrosine, citric acid, trigonelline, carotenoids, retinol activity equivalent, vitamin C, and total phenolic and antioxidant capacity. As the flower develops, the content of these compounds decreases. Aloe vera flowers presented an important content in fatty acids, and the principal concentration was identified in polyunsaturated unsaturated fatty acids (PUFAs) as α-linolenic acid, and linoleic acid, with a ratio close to one. The main saturated fatty acid was palmitic acid, followed by stearic acid. Maturity stage III showed the lowest fatty acid content. The bioactive compounds found in Aloe vera flowers have potential applications in the cosmetic, pharmaceutical, nutraceutical, and food industries. Depending on the compound of interest, it could be worthwhile harvesting flowers at maturity stage I, thereby reducing the energy consumption of flowers from the plant and thus favoring plant development. This is an example of a circular economy for Aloe vera producers, generating economic and business opportunities and thus providing environmental and social benefits.
... Although some anthraquinones can be toxic to humans, rhein and derivatives seem to have little to no toxicity, even at mg levels, when added to food [29]. A review published by the European Food Safety Authority (EFSA, 2018) states that after evaluating in vitro and in vivo studies on hydroxyanthracene derivatives, rhein and sennoside B showed no genotoxic effects at 78.8 mg-and 24. ...
... A review published by the European Food Safety Authority (EFSA, 2018) states that after evaluating in vitro and in vivo studies on hydroxyanthracene derivatives, rhein and sennoside B showed no genotoxic effects at 78.8 mg-and 24. 84 mg-/adult/day, respectively [29]. Baqui et al. 2009 showed that the anthraquinone scaffold (1-amino-4-anilino-9,10-dioxo-9,10-dihydroanthracene-2-sulfonate) showed preferential cytotoxicity for cancerous compared to non-cancerous cells [30]. ...
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Entamoeba histolytica infects 50 million people worldwide and causes 55 thousand fatalities every year. Current anti-amebic drugs (e.g. paromomycin) work either at the level of the intestinal lumen (where trophozoites proliferate via cell divisions) or on the invasive trophozoites that have penetrated the gut or colonized internal organs (e.g. metronidazole). Some of these drugs are highly toxic to patients, have generated trophozoite resistance, or caused mutations and cancer in laboratory animals. Thus, alternative anti-amebic compounds need to be identified to minimize the side effects (on patients) or resistance (by amebas) to current treatments. The literature suggests that anthraquinones (chemicals found in medicinal plants) have antibacterial, antiparasitic, anti-inflammatory and antioxidant properties. Here we provide experimental evidence that Chinese rhubarb (Rheum palmatum) leaves' extract (rich in the anthraquinone rhein) inhibits E. histolytica trophozoite growth in vitro. In addition, from a set of ten isolated/synthetic anthraquinones (which we suspected to have anti-amebic properties), four analogs (rhein; AHHDAC = 1-amino-4-hydroxy-9, 10-dioxo-9, 10-dihydro-anthracene-2-carboxylic acid; unisol blue AS; and sennoside B) efficiently inhibited amebic growth at EIC50 concentrations comparable to metronidazole. The mechanism of action of these compounds still needs to be determined, although anthraquinones might enhance the production of toxic oxygen metabolites as it has been suggested for various protists (e.g. Leishmania, Plasmodium, Trypanosoma). Our research is the first to explore anti-amebic effects of Chinese rhubarb leaves' extract and isolated/synthetic anthraquinones on pathogenic Entamoeba.
... From a purely technological standpoint, in fact, current scientific knowledge does not even allow researchers to describe the pharmacodynamic and kinetic properties of a mixture of compounds in terms of the sum of the properties of its individual components. This would, anyway, represent a conceptual approximation of the actual subject matter [53,54], as such an approach would fail to consider any of the supramolecular phenomena, synergisms and antagonisms, that occur in the context of a mixture of compounds. Importantly, these phenomena are nowadays known to potentially alter the pharmacodynamic and kinetic profiles of the individual components in a mixture, thus generating profiles that are different to those that are observed when the same compounds are studied as isolated [55,56]. ...
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Abdominal pain is a frequent symptom of irritable bowel syndrome (IBS) and inflammatory bowel diseases (IBDs). Although the knowledge of these pathologies is progressing, new therapeutic strategies continue to be investigated. In the present study, the effect of a system of molecules of natural origin (a medical device according to EU Directive 93/42/EC, engineered starting from Boswellia serrata resins, Aloe vera polysaccharides and Matricaria chamomilla and Melissa officinalis polyphenols) was evaluated against the intestinal damage and visceral pain development in DNBS-induced colitis model in rats. The system (250 and 500 mg kg−1) was orally administered once daily, starting three days before the injection of 2,4-dinitrobenzenesulfonic acid (DNBS) and for 14 days thereafter. The viscero-motor response (VMR) to colon-rectal balloon distension (CRD) was used as measure of visceral sensitivity. The product significantly reduced the VMR of DNBS-treated animals. Its effect on pain threshold was better than dexamethasone and mesalazine, and not lower than amitriptyline and otilonium bromide. At microscopic and macroscopic level, the tested system was more effective in protecting the intestinal mucosa than dexamethasone and mesalazine, promoting the healing of tissue lesions. Therefore, we suggest that the described system of molecules of natural origin may represent a therapeutic option to manage painful bowel diseases.
... These compounds are highly valorised in the pharmaceutical industry, allowed in dietary supplements, and used in small quantities as a bittering agent in alcoholic beverages. However, because of their laxative properties, levels of aloin A and B in Aloe leaf preparations intended for oral consumption were limited by the International Aloe Science Council to 10 ppm (10 mg/kg) or less [56]. These levels can be controlled and limited by adding purification steps in the manufacturing process. ...
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This work aimed to characterize compositional and bioactive features of Aloe vera leaf (fillet, mucilage, and rind) and flower. The edible fillet was analysed for its nutritional value, and all samples were studied for phenolic composition and antioxidant, anti-inflammatory, antimicrobial, tyrosinase inhibition, and cytotoxic activities. Dietary fibre (mainly mannan) and available carbohydrates (mainly free glucose and fructose) were abundant macronutrients in fillet, which also contained high amounts of malic acid (5.75 g/100 g dw) and α-tocopherol (4.8 mg/100 g dw). The leaf samples presented similar phenolic profiles, with predominance of chromones and anthrones, and the highest contents were found in mucilage (131 mg/g) and rind (105 mg/g) extracts, which also revealed interesting antioxidant properties. On the other hand, the flower extract was rich in apigenin glycoside derivatives (4.48 mg/g), effective against Pseudomonas aeruginosa (MIC = 0.025 mg/mL and MBC = 0.05 mg/mL) and capable of inhibiting the tyrosinase activity (IC50 = 4.85 mg/mL). The fillet, rind, and flower extracts also showed a powerful antifungal activity against Aspergillus flavus, A. niger, Penicillium funiculosum, and Candida albicans, higher than that of ketoconazole. Thus, the studied Aloe vera samples displayed high potential to be exploited by the food or cosmetic industries, among others.
... 40 The European Food Safety Authority (EFSA) published a safety assessment of hydroxyanthracene derivatives, including anthrones from aloe vera, used in food supplements in 2018, and based on limited data collected and reviewed, the EFSA Panel on Food Additives and Nutrition Sources Added to Food concluded no safe intake levels can be established. 42 While insufficient data are available to assess the carcinogenicity of non-decolorized aloe vera leaf juice in humans, IARC has classified nondecolorized aloe vera whole leaf extract as a possible human carcinogen. 36 In the United States, aloe vera in food and supplement products is either derived from inner leaf or decolorized leaf preparations in which anthrones are largely removed. ...
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The goal of this bulletin is to provide timely information and/or updates on issues of adulteration and mislabeling of aloe vera leaf juice ingredients that purport to meet the quality standard established by the International Aloe Science Council (IASC), an international trade association of aloe vera leaf juice ingredient producers and product manufacturers based in the United States and founded in 1980, applicable for use in dietary supplement, personal care, and cosmetic products. The bulletin may serve as guidance for quality control personnel, the international herbal products industry, and the extended natural products community in general. It is also intended to present a summary of the scientific data and methods on the occurrence of species substitution and adulteration, the market situation, and economic and safety consequences for the consumer and the industry.
... Due to Al ingestion caused a preferential activation of receptor sites on the cells which favoured the synthesis of cholesterol in these organs by up-regulating hydroxymethylglutaryl coenzyme A reductase (a rate-limiting enzyme in cholesterol synthesis pathway) since virtually all cells can synthesize cholesterol or Al changes the integrity of the cell membrane thereby causing a constipation of cholesterol in the organs by modifi cation of the composition, structure and stability of the cell membranes. The liver has been shown to be one of the target organs of Al toxicity-induced injury, liver damage is likely to cause some membrane lipids to be released into circulation; metabolism with oxidative stress and lipid peroxidation and reactive oxygen species as hydroxyl and superoxide radicals in liver alter the lipid level in serum (Kolomiytseva, 2011;Ugbaja et al., 2015;Younes et al., 2018). ...
Article
Objective: The objective of this study was to characterize properties of aqueous Sennae fructus extracts prepared by spray-drying at varying process conditions. Significance: From an industrial point of view it is essential to develop a formulation which has a constant quality over the whole period of its specified shelf-life. Method: Sennae fructus extracts were spray-dried with different atomizing gas pressures, pump feed rates, and inlet temperatures. The extracts were analysed for their physical properties and stored at accelerated conditions. Sennoside degradation was monitored by HPLC analysis. Results: An increase of the atomizing gas pressure had the most pronounced influence on the decrease of moisture content and particle size. An increase of the inlet temperature led to a decrease of moisture content and particle density, as well as an increase of smooth particle amount. An increase of the pump feed rate increased moisture content and resulted in stable hollow spheres. The different conditions also led to smooth or wrinkled particle surfaces, and to golfball, doughnut, and shard particle shapes. The chemical stability of the sennosides differed from each other after storage. Stability-reducing factors were the moisture content of the samples and their hygroscopicities, as well as different particle morphologies. These factors were influenced by the inlet temperature of the spray-drying process. High inlet temperatures led to a positive influence on dryness and particle morphology and therefore on the stability of the sennosides. Conclusion: Variation of the process conditions affected the resulting particle properties and their storage stability of Sennae fructus extract.