Hypericin is one of the most important phenanthoperylene quinones extracted mainly from plants of the genus Hypericum belonging to the sections Euhypericum and Campylosporus of Keller's classification. Widespread attention to the antiviral and anti-tumor properties of hypericin has spurred investigations of the chemical synthesis and biosynthesis of this unique compound. However, the synthetic strategies are challenging for organic and biological chemists. In this review, specific significant advances in total synthesis, semi-synthesis, and biosynthesis in the past decades are summarized.
Antineoplastic Agents, Phytogenic ; Antiviral Agents ; Humans ; Hypericum ; chemistry ; metabolism ; Perylene ; analogs & derivatives ; chemical synthesis ; metabolism ; Plant Extracts ; biosynthesis ; chemical synthesis

OBJECTIVETo develop a high-performance liquid chromatography (HPLC) method for simultaneous determination of hypocrellin A, hypocrellin B, and hypocrellin C.

METHODThe separation was carried out on a Kromasil C18 (4.6 mm x 250 mm, 5 micrm) colum eluted with in mobile phases of water containing 0.5% glacial acetic acid and acetonitrile. The column temperature was 35 degrees C, and the flow rate was 1.0 mL x min(-1). The detection wavelength was set at 265 nm.

RESULTThe three compounds were well separated. Calibration curves of hypocrellin A, hypocrellin B, and hypocrellin C showed good linear relationship RSD > 2.0%. The average recoveries of the hypocrellin A, hypocrellin B, and hypocrellin C were 101.8%, 102.3%, 100.0%, respectively.

CONCLUSIONThe developed method is simple, accurate, and repeatable, and can be readily used as valid tool for the quality control of Hypocrella bambusae.

Chromatography, High Pressure Liquid ; methods ; Drugs, Chinese Herbal ; analysis ; Hypocreales ; chemistry ; Perylene ; analogs & derivatives ; analysis ; Quinones ; analysis

Hypericin, a red-colored naphtodianthrone, is a natural product synthesized in the medicinal plant Hypericum perforatum, commonly known as St. John's wort. Hypericin has attracted a growing attention of the pharmaceutical industry because of its potential application to various therapies, including the treatment of depression and remarkable antiviral and photodynamic activities, hyp-1 gene encodes for phenolic coupling protein which catalyzes in vitro direct and specific conversion of emodin to hypericin which, however, has not formed common opinion so far. Six pairs of primers specific to hyp-1 gene were synthesized. The rapid cloning of hyp-1 gene was performed based on step-by-step extension of a short region of the gene through a series of PCR reactions. All cloned sequences were confirmed by DNA sequencing. A vector named pET32ahyp containing hyp-1 gene was constructed and was transformed into E. coli to induce heterologous expression. SDS-PAGE and Western blot results showed the recombinant Hyp-1 protein was expressed successfully in E. coli. The soluble fraction was used to test the function of the recombinant Hyp-1. Hypericin was detected by LC-MS/MS with emodin as a substrate under in vitro conditions. The above results corroborated the Hyp-1 function, a confusing question, which lay a material foundation for the synthesis of hypericin by synthetic biotechnology.
Antidepressive Agents ; isolation & purification ; metabolism ; Antiviral Agents ; isolation & purification ; metabolism ; Chemistry Techniques, Synthetic ; Emodin ; metabolism ; Escherichia coli ; metabolism ; Gene Expression Regulation, Plant ; Genes, Plant ; Genetic Vectors ; Hypericum ; chemistry ; Peptide Synthases ; genetics ; isolation & purification ; metabolism ; Perylene ; analogs & derivatives ; isolation & purification ; metabolism ; Plant Proteins ; genetics ; isolation & purification ; metabolism ; Plants, Medicinal ; chemistry ; Recombinant Proteins ; genetics ; metabolism ; Transformation, Genetic

AIM: To study the metabolites of a halotolerant fungus Alternaria sp. M6. METHODS: The metabolites were isolated and purified by various chromatographic techniques. Their structures were determined on the basis of physical properties and spectroscopic data. RESULTS: Nine compounds were isolated and identified as 8β-chloro-3, 6aα, 7β, 9β, 10-pentahydroxy-9, 8, 7, 6a-tetrahydroperylen-4(6aH)-one (1), alterperylenol (2), dihydroalterperylenol (3), adenine (4), adenosine (5), deoxyadenosine (6), guanosine (7), tryptophan (8), and hexadecanoic acid (9). CONCLUSION Compound 1 is a new perylenequinone.
Alternaria ; chemistry ; metabolism ; Biological Products ; chemistry ; isolation & purification ; Molecular Structure ; Perylene ; analogs & derivatives ; chemistry ; isolation & purification ; Quinones ; chemistry ; isolation & purification ; Salt Tolerance

Hypocrellin A has gained much attention in recent years due to its light-induced antitumor, antifungal and antiviral activities. Here we report that hypocrellin A exerts immunomodulatory effects on MHC-restricted presentation of antigen. Hypocrellin A inhibited class II-MHC restricted presentation of exogenous antigen, but not class I MHC-restricted presentation of exogenous antigen, in dendritic cells. Hypocrellin A also inhibited the cytosolic pathway of endogenous antigen presentation. However, hypocrellin A did not inhibit the expression of class I and class II MHC molecules on dendritic cells (DCs), the phagocytic activity of DCs, or the H-2K(b)-restricted presentation of a synthetic peptide, SIINFEKL. These results show that hypocrellin A differentially modulates the MHC-restricted antigen presentation pathways.
Antigen Presentation ; Cytosol ; Dendritic Cells ; Perylene ; Quinones

OBJECTIVEBy examining the colony growth rate, colony texture, substrate mycelium color and separation method of 40 anamorph strains of Shiraia bambusicola to investigate the relationship between these indexes and content of hypocrellin A.

METHODIn UV-spectrophotometry and microscopic observation were applied in the experiments. The results were analyzed by the clustering and variance analysis.

RESULTSPSS clustering analysis showed that the colony characters of S. bambusicola anamorph strains had significant differences with hypocrellin A content.

CONCLUSIONIn the tested conditions, substrate mycelium color of S. bambusicola anamophs has the most distinct correlation with the yield of hypocrellin A.

Ascomycota ; growth & development ; isolation & purification ; metabolism ; Cluster Analysis ; Mycelium ; growth & development ; isolation & purification ; metabolism ; Perylene ; analogs & derivatives ; metabolism ; Pigmentation ; Quinones ; metabolism ; Spectrophotometry, Ultraviolet

OBJECTIVETo provide anatomical evidences for the morphological and histological identification of 20 medicinal species in Hypericum.

METHODMorphological and anatomical study on the organs of 20 medicinal species in Hypericum using tissue clearing, paraffin sectioning and thin sectioning.

RESULTAccording to their anatomical characteristics, the secretory structures can be divided into nodules, secretory cavities (canals) and tiny secretory tubes of 20 medicinal species in Hypericum. Hypericin was produced and stored in the nodules, while the volatile oil was produced and stored in the secretory cavities (canals) and tiny secretory tubes. The types differed markedly from each other in location, diameter and distributional density of leaf, and the anatomical structures differed from each other of stem, calyx, petal, anther and fruit among the 20 species in Hypericum.

CONCLUSIONThe secretory structures may be as anatomical evidences for the morphological and histological identification of 20 medicinal species in Hypericum.

Flowers ; anatomy & histology ; chemistry ; Fruit ; anatomy & histology ; chemistry ; Hypericum ; anatomy & histology ; chemistry ; classification ; Oils, Volatile ; analysis ; Perylene ; analogs & derivatives ; analysis ; Plant Leaves ; anatomy & histology ; chemistry ; Plant Stems ; anatomy & histology ; chemistry ; Plants, Medicinal ; anatomy & histology ; chemistry ; classification ; Species Specificity

OBJECTIVETo establish the quality control method of the extract enriched hypericins and flavonoids (HFEE) prepared from Hypericum perforatum by means of HPLC fingerprint analysis, and to evaluate the validity, stability of within-day and between-day of the preparing process of HFEE as well as the influence of antioxidant and the herbal source to the quality of HFEE.

METHODHPLC-UV-MS was employed to the qualitative and quantitative analyses of HFEE.

RESULTTen peaks on the HPLC fingerprint of HFEE were indicated, and eight compounds of them had been identified. With respect of the preparing process of HFEE, the validity and stability were significantly observed. There was almost no effect observed on the quality of HFEE whether or not adding the antioxidant during the process. However, different parts of the plant collected as the materials could significantly affect the quality of HFEE.

CONCLUSIONThe method established in the present study is convenient, reliable, and could be used for the quality control of the extract of H. perforatum and for the monitor and control of the preparing process of the extract.

Chromatography, High Pressure Liquid ; methods ; Drugs, Chinese Herbal ; chemistry ; isolation & purification ; Flavonoids ; chemistry ; isolation & purification ; Hypericum ; chemistry ; Perylene ; analogs & derivatives ; chemistry ; isolation & purification ; Plant Components, Aerial ; chemistry ; Plants, Medicinal ; chemistry ; Quality Control ; Quercetin ; chemistry ; isolation & purification ; Rutin ; chemistry ; isolation & purification ; Technology, Pharmaceutical

OBJECTIVETo explore the possible mechanism of apoptosis induced by photodynamic therapy (PDT) in human pancreatic cancer cells Capan-1 with 2-butylamino-2-demethoxy-hypocrellin B (BAHB) as photosensitizer.

METHODSThe localization of BAHB in Capan-1 cells was studied, apoptosis was determined by DNA gel electrophoresis after PDT. The mitochondria membrane potential (DYm) and cytochrome C release were observed by laser scan confocal microscopy and Western blotting.

RESULTSThe low concentration photosensitizer was mainly localized in mitochondria and also in lysosomes when the concentration is high. DNA ladder analysis showed characteristic of apoptosis. The mitochondria membrane potential (DYm) showed a loss of 30% around, after 6 hours by PDT under laser scan confocal microscopy, which is caused by a sudden increase in the permeability of mitochondria membrane accompanied with apoptosis. In Western blotting, cytochrome C release was observed from the mitochondria into the cytoplasm during BAHB-induced apoptosis.

CONCLUSIONThe research suggests that BAHB-induced apoptosis is related to photosensitization of mitochondria.

Apoptosis ; drug effects ; Dose-Response Relationship, Drug ; Humans ; Membrane Potentials ; drug effects ; Mitochondria ; drug effects ; physiology ; Pancreatic Neoplasms ; drug therapy ; pathology ; Perylene ; administration & dosage ; analogs & derivatives ; pharmacology ; Photochemotherapy ; Photosensitizing Agents ; administration & dosage ; pharmacology ; Quinones ; administration & dosage ; pharmacology ; Tumor Cells, Cultured

Nitric oxide has emerged as a key signaling molecule in plants recently. The role of nitric oxide in elicitor-induced defense responses of plants has been extensively investigated. In this work, sodium nitroprusside was utilized as the donor of nitric oxide to investigate the effects of exogenous nitric oxide on hypericin production and cell growth of suspension cell cultures of Hypericum perforatum L.. Compared with the untreated Hypericum perforatum L. suspension cells, external application of 0.5 and 15.0 mmol/L sodium nitroprusside induced 1.4 and 0.5-fold dry cell weight, and 0.9 and 2.1-fold hypericin content respectively. The results showed that low concentration of sodium nitroprusside promoted the growth of Hypericum perforatum L. suspension cells, while high concentration of sodium nitroprusside enhanced hypericin biosynthesis in Hypericum perforatum L. suspension cells. The maximum hypericin production was achieved by adding 0.5 mmol/L and 15.0 mmol/L sodium nitroprusside to the culture at day 0 and day 14 respectively, increasing the total hypericin yield by nearly 3.2-fold. The effects of sodium nitroprusside on hypericin content and growth of Hypericum perforatum L. suspension cells were abolished by nitric oxide specific scavenger 2-4-carboxyphenyl-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide, which indicated that the effects of the application of sodium nitroprusside were caused by nitric oxide released from sodium nitroprusside rather than sodium nitroprusside itself. The results also showed that 15.0 mmol/L sodium nitroprusside stimulated the activities of phenylalanine ammonia-lyase (PAL), one of the key enzymes of phenylpropanoid pathway, in suspension cells of Hypericum perforatum L., which suggested that the synthetic pathway of hypericin might be activated by NO through triggering the defense responses of Hypericum perforatum L. suspension cells.
Cells, Cultured ; Hypericum ; cytology ; drug effects ; metabolism ; Nitric Oxide ; metabolism ; Nitroprusside ; pharmacology ; Perylene ; analogs & derivatives ; metabolism ; Phenylalanine Ammonia-Lyase ; metabolism ; Plant Growth Regulators ; biosynthesis