hypericum and Neoplasms

Progress in chronobiology thus far has been built on botanical field investigation records, experiments on the development of biological clocks, open questions, established rules, and molecular mechanisms. In this review, three clock-related diseases, namely cancer, Alzheimer's disease (AD), and depression, are discussed. Evidence-based mechanisms of action of active compounds, namely epigallocatechin-3-gallate (EGCG), curcumin, and melatonin, from three medicinal plants, Camellia sinensis K., Curcuma longa L., and Hypericum perforatum L., respectively, as potential therapies against cancer, AD, and depression, respectively, have been explained. Feedback loops of basic inputs and application outputs of various studies will lead to the development of chronobiology for applications in time-keeping, disease prevention, and control, and future agricultural practices.

Topics: Agriculture; Alzheimer Disease; Biological Clocks; Camellia sinensis; Curcuma; Depression; Humans; Hypericum; Neoplasms; Plants, Medicinal

Cancer is one of the leading causes of death worldwide (approximately 8.2 million cases/year) and, over the next two decades, a 70% increase in new cancer cases is expected. Through analysis of the available drugs between the years of 1930 and 2014, it was found that 48% were either natural products or their derivatives. This proportion increased to 66% when semi-synthetic products were included. The family Clusiaceae Juss. (Malpighiales) includes approximately 1000 species distributed throughout all tropical and temperate regions. The phytochemical profile of this family includes many chemicals with interesting pharmacological activities, including anticancer activities. This study includes an overview of the in vitro and in vivo anticancer activity of secondary metabolites from Garcinia and Hypericum and the mechanisms involved in this activity. Hypericum no longer belong to Clusiaceae family, but was considered in the past by taxonomists, due to similarities with this family. Research in the area has shown that several compounds belonging to different chemical classes exhibit activity in several tumor cell lines in different experimental models. This review shows the significant antineoplasic activity of these compounds, in particular of these two genera and validates the importance of natural products in the search for anticancer drugs.

Topics: Animals; Antineoplastic Agents, Phytogenic; Garcinia; Humans; Hypericum; Neoplasms; Plant Extracts

Topics: Animals; Anti-Infective Agents; Antidepressive Agents; Antineoplastic Agents, Phytogenic; Antioxidants; Bacterial Infections; Humans; Hypericum; Mycoses; Neoplasms; Plant Extracts

During the last couple of years great advances in vibrational spectroscopy including near-infrared (NIR), mid-infrared (MIR), attenuated total reflection (ATR) and imaging and also mapping techniques could be achieved. On the other hand spectral treatment features have improved dramatically allowing filtering out relevant information from spectral data much more efficiently and providing new insights into the biochemical composition. These advances offer new possible quality control strategies in phytomics and enable to get deeper insights into biochemical background in terms of medicinal relevant questions. It is the aim of the present article pointing out the technical and methodological advancements in the NIR and MIR field and to demonstrate the individual methods efficiency by discussing distinct selected applications.

Topics: Humans; Hypericum; Neoplasms; Plant Extracts; Quality Control; Spectrophotometry, Infrared; Spectroscopy, Near-Infrared; Vibration

Because 30 to 70% of tumour patients use complementary and alternative medicines; herb-drug combinations are particularly frequent in this population. Some of these combinations can critically alter exposure of anti-neoplastic and palliative treatment.. This review summarises pharmacokinetic drug interactions caused by the herbal products most frequently used by tumour patients (garlic, ginkgo, ginseng, echinacea and St John's wort [SJW]).. Herb-drug interactions, in general, and some interactions in particular (e.g., transporters, Phase II metabolism enzymes) are still poorly investigated and are difficult to evaluate because mixtures are administered with variable and often unspecified amounts of ingredients. Current evidence suggests that garlic and ginkgo can be safely co-administered, whereas CYP2C9 substrates (e.g., warfarin) should be monitored closely when ginseng therapy is started. Echinacea can induce drug metabolism mediated by CYP3A, but most likely relevant when administered with substances with a narrow therapeutic index or low oral bioavailability. The most relevant herbal perpetrator drug is SJW, which has substantial impact on CYP3A4- and CYP2C9-mediated metabolism and P-glycoprotein-mediated transport. This may lower exposure of co-administered drugs by up to 70%. Such an interaction is expected to occur with most of the tyrosine kinase inhibitors, but current evidence is limited.

Topics: Antineoplastic Agents; ATP Binding Cassette Transporter, Subfamily B, Member 1; Clinical Trials as Topic; Complementary Therapies; Cytochrome P-450 Enzyme System; Echinacea; Garlic; Ginkgo biloba; Herb-Drug Interactions; Humans; Hypericum; Neoplasms; Panax; Phytotherapy; Plant Preparations

The use of complementary and alternative medicines (CAM) by cancer patients is increasing. Concomitant use of CAM and anticancer drugs could lead to serious safety issues in patients. CAM have the potential to cause pharmacokinetic interactions with anticancer drugs, leading to either increased or decreased plasma levels of anticancer drugs. This could result in unexpected toxicities or a reduced efficacy. Significant pharmacokinetic interactions have already been shown between St. John's Wort (SJW) and the anticancer drugs imatinib and irinotecan. Most pharmacokinetic CAM-drug interactions, involve drug metabolizing cytochrome P450 (CYP) enzymes, in particular CYP3A4. The effect of CAM on CYP3A4 activity and expression can be assessed in vitro. However, no data have been reported yet regarding the relevance of these in vitro data for the prediction of CAM-anticancer drug interactions in clinical practice. To address this issue, a literature research was performed to evaluate the relevance of in vitro data to predict clinical effects of CAM frequently used by cancer patients: SJW, milk thistle, garlic and Panax ginseng (P. ginseng). Furthermore, in clinical studies the sensitive CYP3A4 substrate probe midazolam is often used to determine pharmacokinetic interactions. Results of these clinical studies with midazolam are used to predict pharmacokinetic interactions with other drugs metabolized by CYP3A4. Therefore, this review also explored whether clinical trials with midazolam are useful to predict clinical pharmacokinetic CAM-anticancer drug interactions. In vitro data of SJW have shown CYP3A4 inhibition after short-term exposure and induction after long-term exposure. In clinical studies using midazolam or anticancer drugs (irinotecan and imatinib) as known CYP3A4 substrates in combination with SJW, decreased plasma levels of these drugs were observed, which was expected as a consequence of CYP3A4 induction. For garlic, no effect on CYP3A4 has been shown in vitro and also in clinical studies garlic did not affect the pharmacokinetics of both midazolam and docetaxel. Milk thistle and P. ginseng predominantly showed CYP3A4 inhibition in vitro. However, in clinical studies these CAM did not cause significant pharmacokinetic interactions with midazolam, irinotecan, docetaxel and imatinib. Most likely, factors as poor pharmaceutical availability, solubility and bioavailability contribute to the lack of significant clinical interactions. In conclusion, in vit

Topics: Cytochrome P-450 CYP3A; Enzyme Activation; Garlic; Herb-Drug Interactions; Humans; Hypericum; Neoplasms; Panax; Phytotherapy; Plant Preparations; Silybum marianum

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.

Topics: Anthracenes; Anti-Infective Agents; Antidepressive Agents; Cell Survival; Humans; Hypericum; Neoplasms; Perylene; Photochemotherapy; Photosensitizing Agents

Cancer patients on chemotherapy treatment often seek herbal therapies and this may alter the clearance of anticancer drugs.. Many anticancer drugs are metabolized by CYPs and are substrates of P-glycoprotein, breast cancer resistance protein and multi-drug resistance proteins. CYPs and drug transporters are subject to inhibition and/or induction by the herbal medicines used by cancer patients and the metabolism and pharmacokinetics of anticancer agents may be altered by herbal products. There are increased reports on the interaction of herbal medicines with anticancer agents. A clinical study in cancer patients reported that treatment of St John's wort at 900 mg/day orally for 18 days decreased the plasma levels of the active metabolite of irinotecan, SN-38, by 42%. In healthy subjects, treatment with St John's wort for 2 weeks significantly decreased the systemic exposure of imatinib by 32%. Induction and/or inhibition of CYPs and transporters is considered an important mechanism for these interactions.. Potential interactions of herbal medicines with anticancer agents have become a safety concern in cancer chemotherapy.. Further studies are warranted to investigate the efficacy and safety profiles of herbal medicines commonly used by cancer patients.

Topics: Animals; Antineoplastic Agents; Biological Transport; Clinical Trials as Topic; Cytochrome P-450 Enzyme System; Herb-Drug Interactions; Humans; Hypericum; Neoplasms; Plant Extracts

To critically evaluate and synthesize intervention research related to hot flashes in the context of cancer and to identify implications and future directions for policy, research, and practice.. Published, peer-reviewed articles and textbooks; editorials; and computerized databases.. Although a variety of pharmacologic and nonpharmacologic treatments are available, they may not be appropriate or effective for all individuals.. The large and diverse evidence base and current national attention on hot flash treatment highlight the importance of the symptom to healthcare professionals, including oncology nurses.. Using existing research to understand, assess, and manage hot flashes in the context of cancer can prevent patient discomfort and improve the delivery of evidence-based care.

Topics: Antidepressive Agents; Antineoplastic Agents; Belladonna Alkaloids; Cimicifuga; Combined Modality Therapy; Complementary Therapies; Drug Combinations; Drug Interactions; Ergotamines; Female; Glycine max; Hot Flashes; Humans; Hypericum; Male; Methysergide; Neoplasms; Neurotransmitter Agents; Phenobarbital; Progestins; Selective Serotonin Reuptake Inhibitors; Treatment Outcome; Vitamin E

Topics: Alcoholism; Antidepressive Agents; Depression; Drug Interactions; Humans; Hypericum; Neoplasms; Phytotherapy; Somatoform Disorders; Wound Healing

Topics: Depressive Disorder; Humans; Hypericum; Neoplasms; Phytotherapy; Plant Extracts

Photodynamic therapy (PDT) has been described as a promising new modality for the treatment of cancer. PDT involves the combination of a photosensitizing agent (photosensitizer), which is preferentially taken up and retained by tumor cells, and visible light of a wavelength matching the absorption spectrum of the drug. Each of these factors is harmless by itself, but when combined they ultimately produce, in the presence of oxygen, cytotoxic products that cause irreversible cellular damage and tumor destruction. Hypericin, a powerful naturally occurring photosensitizer, is found in Hypericum perforatum plants, commonly known as St. John's wort. In recent years increased interest in hypericin as a potential clinical anticancer agent has arisen since several studies established its powerful in vivo and in vitro antineoplastic activity upon irradiation. Investigations of the molecular mechanisms underlying hypericin photocytotoxicity in cancer cells have revealed that this photosensitizer can induce both apoptosis and necrosis in a concentration and light dose-dependent fashion. Moreover, PDT with hypericin results in the activation of multiple pathways that can either promote or counteract the cell death program. This review focuses on the more recent advances in the use of hypericin as a photodynamic agent and discusses the current knowledge on the signaling pathways underlying its photocytotoxic action.

Topics: Anthracenes; Antineoplastic Agents; Apoptosis; Cytochrome c Group; HeLa Cells; Humans; Hypericum; Microscopy, Fluorescence; Models, Biological; Molecular Structure; Neoplasms; Perylene; Photochemotherapy; Photosensitizing Agents; Proto-Oncogene Proteins c-bcl-2; Signal Transduction

Hypericum roeperianum is a medicinal spice traditionally used in West Africa to treat female sterility, fungal infections, and cancer. It has previously been reported that H. roeperianum exhibits cytotoxic potential by reducing the viability of cancer cells involving multidrug-resistant phenotypes, but its underlying molecular mechanism remains unknown.. The mechanistic involvement of H. roeperianum methanolic crude extract (HRC) in attenuating breast cancer progression by exploring the effects on mitochondrial apoptosis and epithelial-mesenchymal transition (EMT) was investigated.. In the present study, we examined the anticancer properties of HRC through MTT assay, colony formation, wound healing assay, spheroid formation, DNA fragmentation and flow cytometry for cell cycle arrest, apoptosis (Annexin V/PI staining) and mitochondrial membrane potential (MMP) (JC-1) detection. In addition, western blot analysis of various proteins and quantitative real time PCR of various genes involved in apoptosis, EMT and the PI3K/Akt/mToR signal transduction pathway were performed.. This study revealed that HRC treatment significantly decreased breast cancer cell viability, colony forming efficiency and reduced the ability of cell migration and spheroid formation. HRC also induced apoptosis in MDA-MB-231 and MCF-7 via promoting G0/G1 cell cycle arrest, disruption of mitochondrial membrane potential and induction of DNA damage. The crude extract induced apoptosis by activating the intrinsic pathway with a stronger effect that relies on the combined potency of associated molecular markers including Bax, Bad, Bcl-2, cytochrome C, caspase-9, and cleaved-PARP. It was also found that HRC regulates the PI3K/Akt/mToR pathway. In addition, HRC inhibited EMT by expressional alteration of Vimentin and E-cadherin, as well as the regulatory transcription factors such as Snail and Slug. The in vitro findings reflected similar mechanistic approach in 4T1 cell induced syngeneic mice model, indicating the reduction of tumor volume along with the significant expressional alteration of EMT and apoptotic markers.. Taken together the findings concluded that H. roeperianum is a potential source of cytotoxic phytochemicals that exhibit abortifacient effect on breast cancer, both in vitro and in vivo, thus could further be utilized in breast cancer therapy.

Topics: Animals; Antineoplastic Agents; Apoptosis; Cell Line, Tumor; Cell Proliferation; Complex Mixtures; Down-Regulation; Epithelial-Mesenchymal Transition; Female; Hypericum; Mice; Neoplasms; Phosphatidylinositol 3-Kinases; Plant Bark; Proto-Oncogene Proteins c-akt; Signal Transduction; TOR Serine-Threonine Kinases

Hypericum bellum Li is rich in xanthones with various bioactivities, especially in anti-breast cancer. While the scarcity of mass spectral data of xanthones in Global Natural Products Social Molecular Networking (GNPS) libraries have challenged the rapid recognition of xanthones with similar structures.. This study is aimed to enhance the molecular networking (MN)-based dereplication and visualisation ability of potential anti-breast cancer xanthones from H. bellum to overcome the scarcity of xanthones mass spectral data in GNPS libraries. Separating and purifying the MN-screening bioactive xanthones to verify the practicality and accuracy of this rapid recognition strategy.. A combined strategy of "seed" mass spectra-based MN, in silico annotation tools, substructure identification tools, reverse molecular docking, ADMET screening, molecular dynamics (MDs) simulation experiments, and an MN-oriented separation procedure was first introduced to facilitate the rapid recognition and targeted isolation of potential anti-breast cancer xanthones in H. bellum.. A total of 41 xanthones could only be tentatively identified. Among them, eight xanthones were screened to have potential anti-breast cancer activities, and six xanthones that were initially reported in H. bellum were obtained and verified to have good binding abilities with their paired targets.. This is a successful case study that validated the application of "seed" mass spectral data could overcome the drawbacks of GNPS libraries with limited mass spectra and enhance the accuracy and visualisation of natural products (NPs) dereplication, and this rapid recognition and targeted isolation strategy can be also applicable for other types of NPs.

Topics: Biological Products; Hypericum; Molecular Docking Simulation; Neoplasms; Tandem Mass Spectrometry; Xanthones

Since ancient times, several people in the Mediterranean region have employed Hypericum triquetrifolium Turra in traditional medicine. However, only the composition of its essential oils has received extensive research.. This study investigated the cytogenetic and cytotoxic effects of H. triquetrifolium methanolic leaf extract on four different cancer cell lines.. Methanolic extract of H. triquetrifolium leaves was prepared. Albino male mice were grouped into five: group 1 (blank control) received water;group II (CYP) received cyclophosphoamide; groups III, IV, and V were administered 50, 100, and 200 mg/kg of H. triquetrifolium extracts. On the 11th day, the animals were sacrificed and bone marrowwascollected. The metaphase index (MI) of the bone marrow cells was determined to evaluate the cytogenetic effect of the extract. The cytotoxic activity of the extract was tested on four cancer cell lines (HepG2, PC3, MDA, and A594), while WRL-68 normal cells were employed as control.. The index of bone marrow cells in cyclophosphamide (CYP)-treated albino male mice shows a significant difference (P ≤ 0.05) between concentration inhibition 50 % IC50 of cancer cell line compered to WRL-68 normal cells, on MDA and WRL-68 cells (IC50 =185.7, 200.7), HepG2 and WRL-68 (IC50 104.9, 564.6), A549 and WRL-68 (IC50 115, 192), PC3 and WRL-68 (IC50 160.7, 298.7). The results showed that the extracts was able to increase metaphase index compared to cyclophasoamide-treated mice, which caused a drop in the percentage of metaphase index.. The current study was showed that significant anti - proliferation activity of Hypericum triquetrifolium methanolic extract against MDA-MB-231 cell line is an epithelial, human breast cancer cell line,WRL-68, HepG2 and lung cancer cell lines (A594).

Topics: Animals; Antineoplastic Agents; Cell Line; Humans; Hypericum; Methanol; Mice; Neoplasms; Plant Extracts

Chronic inflammation has an important role in the development of cancers. Hypericum sampsonii, known as "Yuanbao Cao", is mainly distributed in the southwest of China. As a folk medicinal plant, "Yuanbao Cao" is traditionally used for treatment of various inflammation-related diseases including swelling, burns, arthritis, and dermatitis, etc. The plant is a promising anticancer herb. However, there is no research on the antitumor potential of this plant from the view of cancer-related inflammation strategy.. To explore the H. sampsonii in relation to cancer-related chemical constituents with anti-inflammatory and cytotoxic activity in cancer-related inflammation.. The chemical constituents of H. sampsonii were isolated by repeated chromatography techniques, and their structures were identified mainly by spectroscopic methods and compared to published data. The chemical profile of the herb was analyzed using HPLC. The cytotoxicities of compounds against five cancer cell lines: human melanoma cell (A375), human breast cancer cell (MDA-MB-231), human gastric cancer cell (SGC-7901), human colon cancer cell (SiHa), and human bone marrow neuroblastoma cell (SHSY-5Y), were tested using MTT assay; their anti-inflammatory activities were evaluated by inhibition on NO production in LPS-stimulated RAW 264.7, THP-1 and BV-2 microglial cells.. Twenty-five compounds, including four phenols (1-4), two anthraquinonoids (5 and 6), six xanthones (7-12), one benzophenone (13), one phloroglucinol (14), nine flavonoids (15-23), one sterol (24) and one alkaloid (25), were isolated from the EtOH extract of H. sampsonii. Of them, compounds 3, 4, 6, 7, 10-14, 17, 19, 22 and 23 were reported in H. sampsonii for the first time. HPLC analysis showed that flavonoids were the main constituents in the herb. MTT assay revealed that compounds 1, 2, 5-14, 15, 17, 18, 20, 21, 22 and 25 had selective cytotoxic activities (IC. Compounds 3, 4, 6, 7, 10-14, 17, 19, 22 and 23 were isolated for the first time from H. sampsonii. Compound 5, 6, 13 and 14 displayed high cytotoxic activities against the tested cancer cell lines. Compounds (1-2, 5-23) showed anti-inflammatory activities, of them, compounds 5, 6, 13, 14 and 15 exhibited the high activity. From the view of cancer-related inflammation point, not only the compounds with high cytotoxicity, but those compounds with anti-inflammatory activities, especially the flavonoids, contribute to the antitumor potential of H. sampsonii. The results and viewpoint of present study provide a different insight to better understand the antitumor potential of H. sampsonii, and may also promote the reasonable usage of this folk medical herb.

Topics: Animals; Anti-Inflammatory Agents; Antineoplastic Agents, Phytogenic; Cell Proliferation; Dose-Response Relationship, Drug; Humans; Hypericum; Inflammation Mediators; Inhibitory Concentration 50; Macrophages; Mice; Microglia; Neoplasms; Phytochemicals; Plant Extracts; RAW 264.7 Cells; THP-1 Cells

Mosquito control with naturally derived herbal insecticides has gained much momentum, with the increased insecticide resistance of vectors and the multiple infectious diseases spread by them. Yet, recent studies also suggest that mosquitoes could probably transmit some cancerous cells or cancer-causing viruses from one individual to another between their blood meals. The current research thus focused on the screening and characterization of novel plants with both mosquitocidal and anticancerous properties. Accordingly, different solvent extracts of Hypericum japonicum, a key plant in Chinese medicine, were screened for its larvicidal efficacy using the fourth instar larvae of Aedes aegypti (major vector of Dengue and chikungunya). Methanolic extracts of the plant showed effective larvicidal property with LC

Topics: Aedes; Animals; Antineoplastic Agents, Phytogenic; Cell Line, Tumor; Chikungunya virus; Dengue Virus; Drug Screening Assays, Antitumor; Female; Gas Chromatography-Mass Spectrometry; Hypericum; Insecticides; Larva; Methanol; Mosquito Control; Mosquito Vectors; Neoplasms; Plant Extracts

Cancer is an unnatural type of tissue growth in which the cells exhibit unrestrained division, leading to a progressive increase in the number of dividing cells. It is now the second largest cause of death in the world. The present study concerned antioxidant, anticancer and anticholinesterase activities and protocatechuic, catechin, caffeic acid, syringic acid, p-coumaric acid and o-coumaric concentrations in methanol extracts of flowers, fruits and seeds of Hypericum amblysepalum.. Antioxidant properties including free radical scavenging activity and reducing power, and amounts of total phenolic compounds were evaluated using different tests. Protocatechuic, catechin, caffeic acid, syringic acid, p-coumaric acid and o-coumaric concentrations in extracts were determined by HPLC. Cytotoxic effects were determined using the MTT test with human cervix cancer (HeLa) and rat kidney epithelium cell (NRK-52E) lines. Acetyl and butyrylcholinesterase inhibitory activities were measured by by Ellman method.. Total phenolic content of H. amblysepalum seeds was found to be higher than in fruit and flower extracts. DPPH free radical scavenging activity of the obtained extracts gave satisfactory results versus butylated hydroxyanisole and butylated hydroxytoluene as controls. Reducing power activity was linearly proportional to the studied concentration range: 10-500 μg/ mL LC50 values for H. amblysepalum seeds were 11.7 and 2.86 respectively for HeLa and NRK-52E cell lines. Butyryl-cholinesterase inhibitory activity was 76.9±0.41 for seed extract and higher than with other extracts.. The present results suggested that H. amblysepalum could be a potential candidate anti-cancer drug for the treatment of human cervical cancer, and good source of natural antioxidants.

Topics: Acetylcholinesterase; Animals; Antineoplastic Agents; Antioxidants; Biphenyl Compounds; Butyrylcholinesterase; Cell Proliferation; Cells, Cultured; Cholinesterase Inhibitors; Chromatography, High Pressure Liquid; Flowers; Free Radical Scavengers; Fruit; HeLa Cells; Humans; Hypericum; Neoplasms; Picrates; Plant Extracts; Rats; Seeds

Hypericin (Hy), a naturally occurring photosensitizer (PS), is extracted from Hypericum perforatum plants, commonly known as St. John's wort. The discovery of the in vitro and in vivo photodynamic activities of hypericin as a photosensitizer generated great interest, mainly to induce a very potent antitumoral effect. However, this compound belongs to the family of naphthodianthrones which are known to be poorly soluble in physiological solutions and produce non-fluorescent aggregates (A. Wirz et al., Pharmazie, 2002, 57, 543; A. Kubin et al., Pharmazie, 2008, 63, 263). These phenomena can reduce its efficiency as a photosensitizer for the clinical application. In the present contribution, we have prepared, characterized, and studied the photochemical properties of Hy-loaded lipid nanocapsule (LNC) formulations. The amount of singlet oxygen ((1)O2) generated was measured by the use of p-nitroso-dimethylaniline (RNO) as a selective scavenger under visible light irradiation. Our results showed that Hy-loaded LNCs suppressed aggregation of Hy in aqueous media, increased its apparent solubility, and enhanced the production of singlet oxygen in comparison with free drug. Indeed, encapsulation of Hy in LNCs led to an increase of (1)O2 quantum yield to 0.29-0.44, as compared to 0.02 reported for free Hy in water. Additionally, we studied the photodynamic activity of Hy-loaded LNCs on human cervical carcinoma (HeLa) and Human Embryonic Kidney (HEK) cells. The cell viability decreased radically to 10-20% at 1 μM, reflecting Hy-loaded LNC25 phototoxicity.

Topics: Anthracenes; Cell Line; Cell Survival; Drug Carriers; HeLa Cells; Humans; Hypericum; Light; Lipids; Microscopy, Video; Nanocapsules; Neoplasms; Particle Size; Perylene; Photochemotherapy; Photosensitizing Agents; Singlet Oxygen; Spectrophotometry, Ultraviolet

Topics: Animals; Antineoplastic Agents; Beverages; Dietary Supplements; Herb-Drug Interactions; Humans; Hypericum; Neoplasms; Self Medication; Vitamins

Topics: Antidepressive Agents; Antineoplastic Agents; Antineoplastic Agents, Phytogenic; Camptothecin; Cytochrome P-450 CYP3A; Cytochrome P-450 Enzyme System; Enzyme Induction; Enzyme Inhibitors; Humans; Hypericum; Irinotecan; Mixed Function Oxygenases; Neoplasms

Hyperforin is a plant derived antibiotic from St. John's wort. Here we describe a novel activity of hyperforin, namely its ability to inhibit the growth of tumour cells by induction of apoptosis. Hyperforin inhibited the growth of various human and rat tumour cell lines in vivo, with IC(50) values between 3-15 microM. Treatment of tumour cells with hyperforin resulted in a dose-dependent generation of apoptotic oligonucleosomes, typical DNA-laddering and apoptosis-specific morphological changes. In MT-450 mammary carcinoma cells hyperforin increased the activity of caspase-9 and caspase-3, and hyperforin-mediated apoptosis was blocked by the broad-range caspase inhibitor zVAD.fmk. When added to MT-450 cells, hyperforin, but not paclitaxel, induced a rapid loss of the mitochondrial transmembrane potential Deltapsi(m), and subsequent morphological changes such as homogenization and vacuolization of mitochondria. Monitoring of Deltapsi(m) revealed that the hyperforin-mediated mitochondrial permeability transition can not be prevented by zVAD.fmk. This indicates that mitochondrial permeabilization is a cause rather than a consequence of caspase activation. Moreover, hyperforin was capable of releasing cytochrome c from isolated mitochondria. These findings suggest that hyperforin activates a mitochondria-mediated apoptosis pathway. In vivo, hyperforin inhibited the growth of autologous MT-450 breast carcinoma in immunocompetent Wistar rats to a similar extent as the cytotoxic drug paclitaxel, without any signs of acute toxicity. Owing to the combination of significant antitumour activity, low toxicity in vivo and natural abundance of the compound, hyperforin holds the promise of being an interesting novel antineoplastic agent that deserves further laboratory and in vivo exploration.

Topics: Animals; Antineoplastic Agents; Apoptosis; Bridged Bicyclo Compounds; Caspases; Cell Division; Cytochrome c Group; Dose-Response Relationship, Drug; Enzyme Activation; Female; Humans; Hypericum; Intracellular Membranes; Microscopy, Electron; Mitochondria; Neoplasms; Phloroglucinol; Rats; Staurosporine; Terpenes; Time Factors; Tumor Cells, Cultured

Topics: Beverages; Drugs, Chinese Herbal; Humans; Hypericum; Neoplasms; Phytotherapy; Plant Extracts