In vitro genotoxicity assessment of non-photoactivated hypericin (original) (raw)
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Genotoxicity and antigenotoxicity evaluation of non-photoactivated hypericin
Phytotherapy Research, 2010
The potential genotoxicity and antigenotoxicity of non-photoactivated hypericin was investigated in fi ve experimental models. Hypericin was non-mutagenic in the Ames assay, with and without metabolic activation. It did not exert a protective effect against mutagenicity induced by 9-aminoacridine. In a yeast (Saccharomyces cerevisiae) assay, hypericin did not increase the frequency of mitotic crossovers or total aberrants at the ade 2 locus, the number of convertants at the trp5 locus, or the number of revertants at the ilv1 locus. In combined application with 4-nitroquinoline-1-oxide, it signifi cantly enhanced the number of revertants at the ilv1 locus at the highest concentration used. Hypericin was not mutagenic in the alga Chlamydomonas reinhardtii. However, in combined application with methyl methane sulfonate, toxicity and mutagenicity were slightly reduced. In a chromosome aberration assay using three mammalian cell lines, hypericin did not alter the frequency of structural chromosome aberrations, and in the DPPH radical scavenging assay, it did not exert any antioxidant effects.
The mutagenic, antimutagenic and antioxidant properties of Hypericum lydium
Pharmaceutical Biology, 2016
Context: There is a growing market demand for Hypericum sp., a pharmacologically active plant that has been traditionally used to treat various ailments. However, there have been limited studies on the extract or essential oil of Hypericum lydium Boiss (Hypericaceae). Objective: This study investigates for the first time the antioxidant, mutagenic and antimutagenic activity of an ethanol extract of H. lydium. Material and methods: Ethanol extract from aerial parts of H. lydium harvested from Turkey were tested for this mutagenic and antimutagenic activities (2.0-0.002 mg/plate) using Ames Salmonella/microsome test system. 4-Nitro-o-phenylenediamine (4-NPD) (3 lg/plate) for the Salmonella typhimurium TA98 and sodium azide (NaN 3) (8 lg/plate) for the S. typhimurium TA100 were used as positive controls. The antioxidant activity, total antioxidant activity and phenolic constituent of the extract (2.0-0.002 mg/mL) was determined by the inhibition of 2,2-diphenyl-1-picrylhydrazyl radical (DPPH), b-carotene-linoleic acid model and by means of Folin-Ciocalteu reagent, respectively. Results: The extract showed no sign of mutagenicity at the tested concentrations (0.002-2.0 mg/mL), and showed concentration-dependent antimutagenic activity against NaN 3 and 4-NPD ranging from 26.8 to 81.5%. The extract was found to be an efficient scavenger of DPPH (IC 50 0.165 ± 0.23 mg/mL) and to inhibit b-carotene-linoleic acid bleaching (IC 50 0.39 ± 0.11 mg/mL). Discussion and conclusion: These findings indicate ethanol extract of H. lydium to be a safe and effective agent that may be incorporated into new strategies for the prevention of cancer and mutagenesis.
Photodynamic therapy (PDT) has been catagorized as a new therapeutic approach for cancer. PDT includes the combination of a photosensitizer compound, which is taken up and retained by tumor cells, and visible light of an appropriate wavelength matching the absorption spectrum of the compound. Hypericin is a plant-derived compound and is a powerful natural photosensitizer. The focus of our interest was to promote the production of hypericin from Egyptian Hypericum sinaicum culture in vitro by using biotechnological applications, employ hypericin-PDT for the treatment of bladder cancer in vivo and to suggest the possible mechanisms underlying this action. Eighty adult albino rats were assigned into eight groups. The 1 st group served as negative control. The 2 nd group received N-butyl-N-(4 hydroxybutyle)-nitrosamine (BBN); 0.1 g in 100 ml of drinking water for a period of 8 weeks for induction of bladder cancer and served as positive control. The 3 rd , 4 rd and 5 th groups received intraperitonealy (i.p) 5, 7.5 and 10 mg/kg hypercin-PDT respectively. The 6 th , 7 th and 8 th were bladder cancer bearing groups treated i.p with 5, 7.5 and 10 mg/kg hypercin-PDT respectively. Histopathological investigation of bladder specimens in all groups was carried out. Treatment with hypericin-PDT could restore the structural organization of bladder and maintain the architectural integrity of bladder cells. The outcomes of this investigation offer a convincing evidence for the importance of biotechnological approaches in improving the production of natural compounds. Also, this study provides spotlight on hypericin-PDT as an appropriate therapeutic modality for bladder cancer. The mechanisms behind this effect seem to depend on promoting apoptotic pathway, targeting tumor vasculature and activating immune response.
Photoactivated hypericin is not genotoxic
General physiology and biophysics, 2016
The study was designed to test the potential photogenotoxicity of hypericin (HYP) at three different levels: primary DNA damages, gene mutations and chromosome aberrations. Primary genetic changes were detected using the comet assay. The potential mutagenic activity of HYP was assessed using the Ames/Salmonella typhimurium assay. Finally, the ability of photoactivated HYP to induce chromosome aberrations was evaluated by the in vitro mammalian chromosome aberration test and compared to that of non-photoactivated HYP. The results have shown that photoactivated HYP can only induce primary DNA damages (single-strand DNA breaks), acting in a dose-response manner. This activity depended both on HYP concentrations and an intensity of the light energy needed for its photoactivation. However, mutagenic effect of photoactivated HYP evaluated in the Ames assay using three bacterial strains S. typhimurium (TA97, TA98 and TA100) was not confirmed. Moreover, photoactivated HYP in the range of concentrations (0.005-0.01 µg/ml) was not found to be clastogenic against HepG2 cells. Our findings from both the Ames assay and the chromosome aberrations test provide evidence that photoactivated HYP is not genotoxic, which might be of great importance mainly in terms of its use in the photodynamic therapy.
Hypericins as Potential Leads for New Therapeutics
International Journal of Molecular Sciences, 2010
70 years have passed since the first isolation of the naphthodianthrones hypericin and pseudohypericin from Hypericum perforatum L. Today, they continue to be one of the most promising group of polyphenols, as they fascinate with their physical, chemical and important biological properties which derive from their unique chemical structure. Hypericins and their derivatives have been extensively studied mainly for their antitumor, antiviral and antidepressant properties. Notably, hypericin is one of the most potent naturally occurring photodynamic agents. It is able to generate the superoxide anion and a high quantum yield of singlet oxygen that are considered to be primarily responsible for its biological effects. The prooxidant photodynamic properties of hypericin have been exploited for the photodynamic therapy of cancer (PDT), as hypericin, in combination with light, very effectively induces apoptosis and/or necrosis of cancer cells. The mechanism by which these activities are expressed continues to be a main topic of discussion, but according to scientific data, different modes of action (generation of ROS & singlet oxygen species, antiangiogenesis, immune responces) and multiple molecular pathways (intrinsic/extrinsic apoptotic pathway, ERK inhibition) possibly interrelating are implicated. The aim of this review is to analyse the most recent advances (from 2005 and thereof) in the chemistry and biological activities (in vitro and in vivo) of the pure naphthodianthrones, hypericin and pseudohypericin from H. perforatum. Extracts from H. perforatum were not considered, nor pharmakokinetic or clinical data. Computerised literature searches were performed using the Medline (PubMed), ChemSciFinder and Scirus Library databases. No language restrictions were imposed.
The Multifaceted Photocytotoxic Profile of Hypericin
Molecular Pharmaceutics, 2009
Photodynamic therapy (PDT) is an established anticancer treatment employing a phototoxin (photosensitizer), visible light and oxygen. The latter is photochemically converted into reactive oxygen species, which are highly toxic to the cells. Hypericin, a natural pigment of hypericum plants, is prominent among photosensitizers. The unique perylenequinone structure of hypericin is responsible for its intriguing multifaceted photochemical cytotoxicity. The diverse photodynamic action of hypericin targets a range of subcellular organelles most importantly the mitochondria and the endoplasmic reticulum (ER)-Golgi complex. Hypericin exerts its phototoxicity through intricate mechanisms, implicating key proteins, vital enzymes, organelle membranes and changes in cellular homeostasis. This, depending on drug and light administration conditions, leads to cell death, which occurs mainly by the induction of apoptosis and/or necrosis. Cell photosensitization with hypericin is also associated with the stimulation of macroautophagy, which may promote cell demise when the apoptotic machinery is defective. Herein, we aim to integrate the most important findings with regard to hypericin photocytotoxicity, into a unified scenario, detailing its potential in cancer photomedicine.
Turkish Journal of Botany
The genus Hypericum L. belongs to the family Guttiferae and includes about 450 species (Robson, 2003). Hypericum species have been used as medicinal plants for centuries and have an important place among medicinal plants. The economic importance of the genus Hypericum resides largely in a wide range of medicinal effects exhibited by Hypericum perforatum L. such as anti-inflammatory, antiviral, antimicrobial, antifungal, cytotoxic, and antidepressant activity (Pilepić et al., 2010). Hypericum species contain a number of biologically active compounds such as hypericin, pseudohypericin, hyperforin, adhyperforin, xanthones, flavonoids, biflavonoids, tannins, and phenolic acids (Greeson et al., 2001). Among them, hypericins (hypericin and pseudohypericin) belong to a group of compounds known as naphthodianthrones (Hölzl & Petersen, 2003). Hypericin and pseudohypericin, naturally occurring red pigments, have been very intensively studied (Kitanov, 2001). Hypericins have antidepressive, antimicrobial, antiviral, antitumor, and anti-inflammatory properties (Karioti & Bilia, 2010). H. perforatum is the most important and commercially recognised representative species among Hypericum species (Karioti & Bilia, 2010). H. perforatum was among the top 10 best-selling herbal dietary supplements sold in the food, drug, and mass market channel in the United States for 2008, with sales of about $8.2 million (Cavaliere et al., 2009). Anti-depressant applications of H. perforatum medicinal products (e.g., Psychotonin ® , Neuroplant ® , and Hyperforat ®) have become increasingly popular in Europe, particularly in Germany (Gioti et al., 2005). Hypericum adenotrichum Spach is a perennial, herbaceous medicinal plant that grows in Turkey. This plant has great potential value as a pharmaceutical because it contains hypericin, pseudohypericin, chlorogenic acid, hyperoside, quercetin, quercitrin, rutin, amentoflavone, apigenin-7-O-glucoside, and kaempferol (Çırak et al., 2009). Additionally, it has been shown that H. adenotrichum has a potent p53-independent antineoplastic property (Özmen et al., 2009). H. adenotrichum can be used for studies related to the genus Hypericum in view of the above information. The production, consumption, and international trade in medicinal plants and phytomedicine (herbal medicine) have grown and are expected to grow further in the future. To satisfy growing market demands, surveys are being conducted to unearth new plant sources of herbal remedies and medicines and at the same time develop new strategies for better yield and quality (Gokhale & Bansal, 2010). Plant tissue culture has an important role in the production
Content of hypericins from plants and in vitro shoots of Hypericum undulatum Schousb. ex Willd
Natural Product Research, 2012
This study reports the first quantification study of pseudohypericin (PsHyp) and hypericin (Hyp) in Hypericum undulatum Schousb. ex Willd in vitro cultures developed by a Portuguese company. Both compounds were quantified by high-performance liquid chromatography and their levels were compared with those in commercial samples of Hypericum perforatum. PsHyp was found to be the major naphthodianthrone of H. undulatum, with an average ratio of 3.73:1 compared to Hyp. Significant statistical differences were found between the content of Hyp and PsHyp in H. undulatum regenerated shoots compared to in vivo samples. The mean concentration of total Hyps varied from 178.41 to 358.93 µg g−1 dry extract in H. undulatum regenerated shoots, which is on average two to three times less than naphthodianthrone levels found in H. undulatum in vivo and H. perforatum commercial samples. However, none of the analysed samples presented the levels of Hyps required by the European and United States Pharmacopoeias.
Advances in Zoology and Botany, 2015
Hypericum triquetrifolium Turra. is a valuable medicinal plant owing to source of many bioactive compounds. Hypericin is one of the significant components among these compounds. The aim of this study was to develope an efficient method allowing to improve hypericin production from calli and cell suspension cultures of Hypericum triquetrifolium Turra. Callus formation was obtained from axenic leaf explants grown in Murashige and Skoog (MS) salts supplemented with 1 mg l-1 6-benzyl adenine (BA) and 2 mg l-1 α-naphtaleneacetic acid (NAA) and 1 mg l-1 (BA) + 0.4 mg l-1 2,4-dichlorophenoxyacetic acid (2,4-D). Growth medium of cell suspension culture was the same with callus medium but devoid of agar. The increase of biomass in cell suspension culture was obtained between 6.31-6.28 fold compared to the first day of culture, on the 20 th day. We assayed hypericin content in methanolic extracts of calli and cell suspension cultures of H. triquetrifolium Turra. Hypericin contents of the samples were measured at 589 nm by a UV-VIS spectrophotometer. Analysis of hypericin contents showed that levels found in callus were 0.0527 and 0.0485 mg g-1 , while in cell suspension cultures these rates were 0.0018 and 0.0016 mg g-1 , suggesting that the accumulation of this compound in cell suspension needs further modifications.