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Protection against the negative effects of solar radiation involves using cosmetics with a UV filter, but visible radiation can also have negative effects. We use dietary supplements and take medications; unfortunately, many of them contain substances that degrade under the influence of visible light, which transform into chemical compounds harmful to health. Manufacturers often include information on the prohibition of exposure to sunlight on the packaging, but consumers often do not read the product leaflet. The solution to this problem may be the addition of silver particles to preparations. In the presented article, we proposed the use of silver nanoparticles to reduce the photobleaching and photoreaction of fluorophore, while increasing the fluorescence intensity. For our research, we used a compound that is particularly sensitive to radiation: hypericin. [ABSTRACT FROM AUTHOR]

(1) Background: The SARS-CoV-2 papain-like protease (PLpro) remains an underexplored antiviral target so far. The reduced efficacy of approved treatments against novel variants highlights the importance of developing new agents. This review aims to provide a comprehensive understanding of phytochemicals as inhibitors of PLpro, identify gaps, and propose novel insights for future reference. (2) Methods: A thorough literature search was conducted using Google Scholar, ScienceDirect, and PubMed. Out of 150 articles reviewed, 57 met inclusion criteria, focusing on SARS-CoV-2 PLpro inhibitors, excluding studies on other coronaviruses or solely herbal extracts. Data were presented class-wise, and phytochemicals were grouped into virtual, weak, modest, and potential inhibitors. (3) Results: Approximately 100 phytochemicals are reported in the literature as PLpro inhibitors. We classified them as virtual inhibitors (70), weak inhibitors (13), modest inhibitors (11), and potential inhibitors (6). Flavonoids, terpenoids, and their glycosides predominated. Notably, six phytochemicals, including schaftoside, tanshinones, hypericin, and methyl 3,4-dihydroxybenzoate, emerged as potent PLpro inhibitors with favorable selectivity indices and disease-mitigation potential; (4) Conclusions: PLpro stands as a promising therapeutic target against SARS-CoV-2. The phytochemicals reported in the literature possess valuable drug potential; however, certain experimental and clinical gaps need to be filled to meet the therapeutic needs. [ABSTRACT FROM AUTHOR]

Conventional topical psoriasis treatments suffer from limited delivery to affected areas and skin irritation due to high local drug concentration. This study aims to prepare hypericin (HYP) loaded nanostructured lipid carriers (NLCs) and their application in psoriasis treatment through intradermal administration using hollow microneedles assisted by photodynamic therapy. The colloidal characteristics of NLCs, entrapment efficiency and morphology were evaluated. An ex-vivo skin distribution study was conducted along with testing the in vivo antipsoriatic activity in mice with the imiquimod-induced psoriasis model. The particle size and zeta potential of HYP-NLCs were 167.70 nm and −18.1, respectively. The ex-vivo skin distribution study demonstrated the superior distribution of HYP-NLCs to a depth of 1480 µm within the skin layers relative to only 750 µm for free HYP. In vivo studies revealed that the levels of NF-KB, IL 6, MMP1, GSH, and catalase in the group treated with HYP-NLCs in the presence of light were comparable to the negative control. The histopathological inspection of dissected skin samples reflected the superiority of HYP-NLCs over HYP ointment. This could be ascribed to the effect of nanoencapsulation on improving HYP properties besides the ability of hollow microneedles to ensure effective HYP delivery to the affected psoriatic area. [ABSTRACT FROM AUTHOR]

Photodynamic therapy is a noninvasive treatment in which specific photosensitizers and light are used to produce high amounts of reactive oxygen species (ROS), which can be employed for targeted tissue destruction in cancer treatment or antimicrobial therapy. However, it remains unknown whether lower amounts of ROS produced by mild photodynamic therapy increase lifespan and stress resistance at the organism level. Here, we introduce a novel photodynamic treatment (PDTr) that uses 20 μM hypericin, a photosensitizer that originates from Hypericum perforatum , and orange light (590 nm, 5.4 W/m2, 1 min) to induce intracellular ROS formation (ROS), thereby resulting in lifespan extension and improved stress resistance in C. elegans. The PDTr-induced increase in longevity was abrogated by N -acetyl cysteine, suggesting the hormetic response was driven by prooxidative mechanisms. PDTr activated the translocation of SKN-1/NRF-2 and DAF-16/FOXO, leading to elevated expression of downstream oxidative stress-responsive genes, including ctl-1 , gst-4, and sod-3. In summary, our findings suggest a novel PDTr method that extends the lifespan of C. elegans under both normal and oxidative stress conditions through the activation of SKN-1 and DAF-16 via the involvement of many antioxidant genes. [Display omitted] • A Photodynamic reaction with hypericin and orange light generates ROS in C. elegans. • Mild PDTr increases the lifespan and resistance to oxidative stress in C. elegans. • PDTr-induced oxidative stress resistance depends on NRF2, FOXO, AMPK, and p38 MAPK. • PDTr induces NRF2 and FOXO nuclear translocation and ctl-1 , gst-4 , and sod-3 expression. [ABSTRACT FROM AUTHOR]

SARS-CoV-2 is a highly pathogenic virus responsible for the COVID-19 disease. It belongs to the Coronaviridae family, characterized by a phospholipid envelope, which is crucial for viral entry and replication in host cells. Hypericin, a lipophilic, naturally occurring photosensitizer, was reported to effectively inactivate enveloped viruses, including SARS-CoV-2, upon light irradiation. In addition to its photodynamic activity, Hyp was found to exert an antiviral action also in the dark. This study explores the mechanical properties of heat-inactivated SARS-CoV-2 viral particles using Atomic Force Microscopy (AFM). Results reveal a flexible structure under external stress, potentially contributing to the virus pathogenicity. Although the fixation protocol causes damage to some particles, correlation with fluorescence demonstrates colocalization of partially degraded virions with their genome. The impact of hypericin on the mechanical properties of the virus was assessed and found particularly relevant in dark conditions. These preliminary results suggest that hypericin can affect the mechanical properties of the viral envelope, an effect that warrants further investigation in the context of antiviral therapies. [ABSTRACT FROM AUTHOR]

In this study, a novel drug delivery system (MSN-PEG-Hypericin) was successfully fabricated using tetraethyl orthosilicate and 3-aminopropyltriethoxysilane as raw materials, and the PEGylation of the prepared aminated mesoporous silica and grafting of hypericin onto the carrier were further conducted to obtain MSN-PEG-Hypericin. The successful preparation of MSN-PEG-Hypericin was characterized by several physical-chemical techniques. Furthermore, the MSN-PEG-Hypericin system increased the ability of hypericin to generate reactive oxygen species (ROS) in vitro. The cytotoxicity assay and hemolysis analysis showed that MSN-PEG-Hypericin had good biocompatibility. For antibacterial studies, the irradiation time and incubation time of photodynamic therapy (PDT) for S. aureus and E. coli were respectively 8 min and 8 h, and the concentrations of hypericin were 2.5 and 5 μg/mL. The result of triphenyl tetrazolium chloride assay indicated that MSN-PEG-Hypericin had stronger photodynamic antibacterial activity than free hypericin, and S. aureus was more sensitive to PDT than E. coli, which was related to their cell structural differences. The antibacterial mechanism study indicated that the generated ROS could destroy the bacterial structures and cause bacterial death due to the leakage of the contents. The MSN-PEG-Hypericin system prepared in this study had potential application prospects in the antibacterial field. [ABSTRACT FROM AUTHOR]

St. John's Wort, commonly known as Hypericum perforatum L., is a flowering plant in the Clusiaceae family that traditionally been employed for treating anxiety, depression, wounds, burns, sunburn, irritation, and stomach ailments. This review provides a synopsis of H. perforatum L. phytoconstituents and their biological effects, highlighting its beneficial therapeutic properties for dermatological indications, as well as its antioxidant, antimicrobial, anti‐inflammatory, and anti‐angiogenic activity in various applications including wound healing and skin conditions such as eczema, sun burn and minor burns also spastic paralysis, stiff neck and mood disorders as anti‐depressant and nerve pains such as neuralgia. The data were collected from several databases as Web of Science PubMed, ScienceDirect, Scopus and Google Scholar using the terms: "H. perforatum L.", "H. perforatum L. /phytochemistry," and "H. perforatum extracts/wound healing" collected from 1994 to 2023. The findings suggest H. perforatum L. acts through various mechanisms and plays a role in each phase of the wound healing process, including re‐epithelialization, angiogenesis, wound contraction, and connective tissue regeneration. H. perforatum L. enhances collagen deposition, decreases inflammation, inhibits fibroblast migration, and promotes epithelialization by increasing the number of fibroblasts with polygonal shape and the number of collagen fibers within fibroblasts. H. Perforatum L. extracts modulate the immune response and reduce inflammation were found to accelerate the wound healing process via inhibition of inflammatory mediators' production like interleukin‐6, tumor necrosis factor‐α, cyclooxygenase‐2 gene expression, and inducible nitric oxide synthase. Thus, H. perforatum L. represents a potential remedy for a wide range of dermatological problems, owing to its constituents with beneficial therapeutic properties. H. perforatum L. could be utilized in the development of novel wound healing therapies. [ABSTRACT FROM AUTHOR]

Determination of the hypericin–photodynamic (HY–PDT) effect on the secretion of cytokines secreted by the skin cells, may be the basis for using the immunomodulatory effect of photodynamic action in the treatment of inflammatory skin diseases. The study aimed to evaluate the cytotoxic and immunomodulatory effects of hypericin (HY) in photodynamic therapy (PDT) performed in vitro on cultures of selected skin cell lines. The study used two human cell lines, primary dermal fibroblast (HDFa) and primary epidermal keratinocytes (HEKa). The MTT test was used to define the metabolic activity of treated cells. Cell supernatants subjected to sublethal PDT were assessed to determine the interleukins: IL-2, IL-8, IL-10, IL-11, IL-19, IL-22, and metalloproteinase 1 (MMP-1). The results confirm the destructive effect of HY–PDT and the immunomodulatory effects of sublethal doses on the selected skin cells, depending on the concentration of HY and the light doses. No statistically significant differences were noted in IL-2 and IL-10 concentration after HY–PDT for HEKa and HDFa lines. After using HY–PDT, the concentration of IL-8, MMP-1, IL-22, and IL-11 significantly decreased in the HEKa line. Moreover, the concentration of IL-19 and MMP-1 significantly decreased in the HDFa line. The concentration of IL-11 in the HDFa line after using only the HY, without the light, increased but decreased after HY–PDT. Our experiment confirmed that HY–PDT has not only a cytotoxic effect but, used in sublethal doses, also presents immunomodulatory properties. These may be an advantage of HY–PDT when used in the treatment of persistent skin inflammation, connected with the release of pro-inflammatory cytokines resistant to conventional treatment methods. [ABSTRACT FROM AUTHOR]

Photodynamic Therapy (PDT) is an emerging method to treat colorectal cancers (CRC). Hypericin (HYP) is an effective mediator of PDT and the ABCG2 inhibitor, Febuxostat (FBX) could augment PDT. HT29 and HEK293 cells showed light dependant cytotoxic response to PDT in both 2D and 3D cell models. FBX co-treatment was not found to improve PDT cytotoxicity. Next, ABCG2 protein expression was observed in HT29 but not in HEK293 cells. However, ABCG2 gene expression analysis did not support protein expression results as ABCG2 gene expression results were found to be higher in HEK293 cells. Although HYP treatment was found to significantly reduce ABCG2 gene expression levels in both cell lines, FBX treatment partially restored ABCG2 gene expression. Our findings indicate that FBX co-treatment may not be suitable for augmenting HYP-mediated PDT in CRC but could potentially be useful for other applications. [ABSTRACT FROM AUTHOR]

Hypericum perforatum (HP) contains valuable and beneficial bioactive compounds that have been used to treat or prevent several illnesses. Encapsulation technology offers protection of the active compounds and facilitates to expose of the biologically active compounds in a controlled mechanism. Microcapsulation of the hydroalcoholic gum arabic and maltodextrin have hot been used as wall materials in the encapsulation of HP extract. Therefore, the optimum microencapsulation parameters of Hypericum perforatum (HP) hydroalcoholic extract were determined using response surface methodology (RSM) for the evaluation of HP extract. Three levels of three independent variables were screened using the one-way ANOVA. Five responses were monitored, including total phenolic content (TPC), 2,2-Diphenyl-1-picrylhydrazyl (DPPH), carr index (CI), hausner ratio (HR), and solubility. Optimum drying conditions for Hypericum perforatum microcapsules (HPMs) were determined: 180 °C for inlet air temperature, 1.04/1 for ratio of maltodextrin to gum arabic (w/w), and 1.98/1 for coating to core material ratio (w/w). TPC, antioxidant activity, CI, HR, and solubility values were specified as 316.531 (mg/g GAE), 81.912%, 6.074, 1.066, and 35.017%, respectively, under the optimized conditions. The major compounds of Hypericum perforatum (hypericin and pseudohypericin) extract were determined as 4.19 μg/g microcapsule and 15.09 μg/g microcapsule, respectively. Scanning electron microscope (SEM) analysis revealed that the mean particle diameter of the HPMs was 20.36 µm. Based on these results, microencapsulation of HPMs by spray drying is a viable technique which protects the bioactive compounds of HP leaves, facilitating its application in the pharmaceutical, cosmetic, and food industries. [ABSTRACT FROM AUTHOR]

(1) Background: Laparoscopic staging is essential in gastric cancer (GC) to rule out peritoneal metastasis (PM). Hypericin, a plant-derived fluorescent compound, has been suggested to improve laparoscopic visualization of PM from GC. This prospective, single-arm, open-label clinical trial aimed to assess the feasibility and safety of oral hypericin administration as well as the suitability of fluorescence-guided laparoscopy (FGL) for improving the sensitivity and specificity of staging in GC patients (EudraCT-Number: 2015-005277-21; clinicaltrials.gov identifier: NCT-02840331). (2) Methods: GC patients received Laif® 900, an approved hypericin-containing phytopharmaceutical, once orally two to four hours before white light and ultraviolet light laparoscopy. The peritoneal cancer index was evaluated, biopsies taken and hypericin concentrations in serum and peritoneal tissue were determined by mass spectrometry. (3) Results: Between 2017 and 2021, out of 63 patients screened for eligibility, 50 patients were enrolled and treated per protocol. The study intervention was shown to be feasible and safe in all patients. Standard laparoscopy revealed suspicious lesions in 27 patients (54%), among whom 16 (59%) were diagnosed with PM. FGL identified suspicious areas in 25 patients (50%), among whom PM was confirmed in 13 cases (52%). Although hypericin concentrations in serum reached up to 5.64 ng/mL, no hypericin was detectable in peritoneal tissue biopsies. (4) Conclusions: FGL in patients with GC was shown to be feasible but futile in this study. Sufficient levels of hypericin should be ensured in target tissue prior to reassessing FGL with hypericin. [ABSTRACT FROM AUTHOR]

St. John's Wort preparations are used for the treatment of mild to moderate depression. They are usually well tolerated but can cause adverse reactions including liver toxicity in rare cases. To date, the mechanism(s) underlying the hepatotoxicity of St. John's Wort extracts are poorly investigated. We studied the hepatocellular toxicity of hypericin and hyperforin as the two main ingredients of St. John's Wort extracts in HepG2 and HepaRG cells and compared the effects to citalopram (a synthetic serotonin uptake inhibitor) with a special focus on mitochondrial toxicity and oxidative stress. In HepG2 cells, hypericin was membrane-toxic at 100 µM and depleted ATP at 20 µM. In HepaRG cells, ATP depletion started at 5 µM. In comparison, hyperforin and citalopram were not toxic up to 100 µM. In HepG2 cells, hypericin decreased maximal respiration starting at 2 µM and mitochondrial ATP formation starting at 10 µM but did not affect glycolytic ATP production. Hypericin inhibited the activity of complex I, II and IV of the electron transfer system and caused mitochondrial superoxide accumulation in cells. The protein expression of mitochondrial superoxide dismutase 2 (SOD2) and thioredoxin 2 (TRX2) and total and reduced glutathione decreased in cells exposed to hypericin. Finally, hypericin diminished the mitochondrial DNA copy number and caused cell necrosis but not apoptosis. In conclusion, hypericin, but not hyperforin or citalopram, is a mitochondrial toxicant at low micromolar concentrations. This mechanism may contribute to the hepatotoxicity occasionally observed in susceptible patients treated with St. John's Wort preparations. [Display omitted] • Exposure to hypericin induces cytotoxicity in hepatic HepG2 and HepaRG cells. • Hypericin decreases mitochondrial ATP production in HepG2 cells. • Hypericin inhibited the activity of complex I, II and IV of the ETS in HepG2 cells. • Hypericin induces mitochondrial oxidative stress in HepG2 cells. • Hypericin diminishes the mitochondrial DNA copy number and causes cell necrosis. [ABSTRACT FROM AUTHOR]

Hypericin, a polycyclic naphthodianthrone and active plant pigment with the molecular formula C30H16O8, is a crucial phytochemical extracted from the dark-colored glands present on the aerial parts of the genus Hypericum. It is biosynthesized through the polyketide pathway by plant-specific type III polyketide synthases (PKSs). In addition to hypericin, the genus Hypericum is rich in various classes of phytochemicals. Alongside other bioactive compounds like hyperforin and flavonoids, hypericin exhibits antidepressant activity. Recently, hypericin has gained increased importance in the research due to its unique properties. Its photodynamic nature makes it an effective natural photosensitizer, extending its use in investigating skin disorders. Moreover, hypericin demonstrates antiviral and antitumoral properties. Despite its effectiveness in treating cancers and neurological disorders, hypericin production faces challenges due to its site-specific nature. Conventional methods struggle to meet the growing demand for hypericin. Biotechnological approaches, including plant tissue culture and bioreactor-based large-scale production, offer promising solutions to address this demand. This review focuses on various plant tissue culture techniques, such as cell and organ culture, and elucidates their biosynthetic pathways. It also discusses hypericin production using elicitation strategies involving biotic and abiotic components, as well as genetic engineering approaches to enhance hypericin yields. Bioreactor-scale production presents significant potential for sustainable hypericin production. Further advancements in understanding and engineering biosynthetic pathways hold promise for unlocking new avenues in hypericin production. [ABSTRACT FROM AUTHOR]

[Objective]To establish a method for the simultaneous determination of hyperin, quercetin and farrerol in Rhododendron dauricum by HPLC, and to discuss the effects of Rhododendron dauricum extract and its three main components on the relaxation of rat tracheal smooth muscle and the mechanism. [Method] The contents of hypericin, quercetin and farrerol in Rhododendron dauricum were determined by HPLC and the methodology was investigated. Rat tracheal rings were obtained by in vivo air tube perfusion method, and fixed in a Mack’s bath. The tracheal rings were pre-incubated with chlorphenamine, indometacin, glibenclamide, L-nitroarginine methyl ester (L-NAME), nifedipine and propranolol. After the tension of the tracheal ring stabilized, 60 mmol/ L KCl solution was added to shrink the tracheal ring. The relaxation experiment of tracheal ring by Rhododendron dauricum was conducted to observe the changes of tracheal smooth muscle tension in rats. [Result] The investigation results of the HPLC determination method for three main components in Rhododendron dauricum showed that the linear relationship between the three components was good in the range of 2-80 μg / mL. The average recovery rates were 100. 3% (RSD = 2. 63%) of hypericin, 102. 7% (RSD= 2. 89%) of quercetin and 102. 1% (RSD= 2. 36%) of farrerol. The diastolic effects of the extract and the three main components of Rhododendron dauricum in the incubated tissue of indometacin, glibenclamide and propranolol were not significantly different from those in the unincubated group. The diastolic effects of Rhododendron dauricum and hypericin in the tissues incubated with chlorphenamine, L-NAME and nifedipine were significantly different from those in the unincubated tissues. This phenomenon may be achieved through inhibition of histamine H1 receptors, nitric oxide synthase pathways, and calcium channel mediated calcium influx. [Conclusion] The established method is simple, accurate, and can quickly determine the content of hypericin, quercetin and farrerol in Rhododendron dauricum, providing an effective analytical means for quality evaluation and control. In addition, these three components are related to the effect of diastolic trachea of Rhododendron dauricum L., and can be used as a theoretical basis for the development of bronchodilators. [ABSTRACT FROM AUTHOR]

Protection against the negative effects of solar radiation involves using cosmetics with a UV filter, but visible radiation can also have negative effects. We use dietary supplements and take medications; unfortunately, many of them contain substances that degrade under the influence of visible light, which transform into chemical compounds harmful to health. Manufacturers often include information on the prohibition of exposure to sunlight on the packaging, but consumers often do not read the product leaflet. The solution to this problem may be the addition of silver particles to preparations. In the presented article, we proposed the use of silver nanoparticles to reduce the photobleaching and photoreaction of fluorophore, while increasing the fluorescence intensity. For our research, we used a compound that is particularly sensitive to radiation: hypericin.

SARS-CoV-2 is a highly pathogenic virus responsible for the COVID-19 disease. It belongs to the Coronaviridae family, characterized by a phospholipid envelope, which is crucial for viral entry and replication in host cells. Hypericin, a lipophilic, naturally occurring photosensitizer, was reported to effectively inactivate enveloped viruses, including SARS-CoV-2, upon light irradiation. In addition to its photodynamic activity, Hyp was found to exert an antiviral action also in the dark. This study explores the mechanical properties of heat-inactivated SARS-CoV-2 viral particles using Atomic Force Microscopy (AFM). Results reveal a flexible structure under external stress, potentially contributing to the virus pathogenicity. Although the fixation protocol causes damage to some particles, correlation with fluorescence demonstrates colocalization of partially degraded virions with their genome. The impact of hypericin on the mechanical properties of the virus was assessed and found particularly relevant in dark conditions. These preliminary results suggest that hypericin can affect the mechanical properties of the viral envelope, an effect that warrants further investigation in the context of antiviral therapies.

Cannabis sativa is a well-known plant for its psychoactive effects; however, its many derivatives, such as Cannabidiol (CBD), contain several therapeutic applications. Tetrahydrocannabinol (THC) is the main cannabis derivative responsible for psychoactive properties, while CBD is non-psychotropic. For this reason, CBD has been more exploited in the last decade. CBD has been connected to multiple anticancer properties, and when combined with photodynamic therapy (PDT), it is possible to eradicate tumors more effectively. In this study, CBD was utilized to treat MCF-7 breast cancer cells, followed by in vitro PDT combination therapy. Conventional breast cancer treatment modalities such as chemotherapy, radiotherapy, etc. have been reported for inducing a number of undesirable side effects, recurrence of the disease, and low quality of life. In this study, cells were exposed to varying concentrations of CBD (i.e., 1.25, 2.5, 5, 10, and 20 μg/mL) and incubated 12 and 24 h after treatment. The optimal doses were then used in combination therapy. Morphology and biochemical assays, including lactate dehydrogenase (LDH) for membrane integrity, adenosine triphosphate (ATP) for viability, and trypan blue exclusion assay for viability, were used to examine cellular responses after treatments. The optimal concentration was then utilized in Hypericin-Gold nanoparticles mediated PDT combination. The results revealed that, in a dose-dependent manner, conventional morphological characteristics of cell death, such as vacuolization, blebbing, and floating were observed in treated cells. The biochemical responses demonstrated an increase in LDH, a decrease in ATP, and a reduction in viability. This study demonstrated that CBD induces cell death in MCF-7 breast cancer cells cultured in vitro. The immunofluorescence results of combination therapy indicated that cell death occurred via apoptosis. In conclusion, this study proposes that the CBD and PDT combination therapy is effective in killing MCF-7 breast cancer cells in vitro by induction of apoptosis. [ABSTRACT FROM AUTHOR]

In 2020, there were 377,713 new oral and lip cancer diagnoses and 177,757 deaths. Oral cancer is a malignancy of the head and neck region, and 90% of cases are squamous cell carcinomas (OSCCs). One of the alternative methods of treating pre-cancerous lesions and oral cancer is photodynamic therapy (PDT). In addition to the cytotoxic effect, an important mechanism of PDT action is the immunomodulatory effect. This study used the OSCC (SCC-25) cell line and the healthy gingival fibroblast (HGF-1) line. A compound of natural origin—hypericin (HY)—was used as the photosensitizer (PS). The HY concentrations of 0–1 µM were used. After two hours of incubation with PS, the cells were irradiated with light doses of 0–20 J/cm2. The MTT test determined sublethal doses of PDT. Cell supernatants subjected to sublethal PDT were assessed for interleukin 6 (IL-6), soluble IL-6 receptor alpha (sIL-6Ralfa), sIL-6Rbeta, IL-8, IL-10, IL-11 IL-20, IL-32, and Pentraxin-3 using the Bio-Plex ProTM Assay. The phototoxic effect was observed starting with a light dose of 5 J/cm2 and amplified with increasing HY concentration and a light dose. HY-PDT affected the SCC-25 cell secretion of sIL-6Rbeta, IL-20, and Pentraxin-3. HY alone increased IL-8 secretion. In the case of HGF-1, the effect of HY-PDT on the secretion of IL-8 and IL-32 was found. [ABSTRACT FROM AUTHOR]

β-actin belongs to cytoskeletal structures that change dynamically in cells according to various stimuli. Human skin can be considered as an organ that is very frequently exposed to various stress factors, of which light plays an important role. The present study focuses on adult human fibroblasts exposed to two types of light stress. Orange light with a wavelength of 590 nm was used here to stimulate the photosensitizer localized in the cells as a residual dose of photodynamic therapy (PDT). On the other hand, near-infrared light with a wavelength of 808 nm was considered for photobiomodulation (PBM), which is often used in healing processes. Confocal fluorescence microscopy was used to observe changes in intercellular communication, mitochondrial structures, and cytoskeletal dynamics defined by the remodulation of β-actin of fibroblasts. The number of β-actin bundles forming spherical structures was detected after light exposure. These structures as β-actin oligomers were confirmed with super-resolution microscopy. While PDT led to the disintegration of actin oligomers, PBM increased their number. The interaction of β-actin with mitochondria was observed. The combination of PDT and PBM treatments is important to minimize the side effects of cancer treatment with PDT on healthy cells, as shown by the cell metabolism assay in this work. In this work, β-actin is presented as an important parameter that changes and is involved in the response of cells to PDT and PBM. [ABSTRACT FROM AUTHOR]

Time‐resolved phosphorescence detection was employed to determine the lifetime of singlet oxygen in live cells. Using hypericin as a photosensitizer, singlet oxygen was generated in U87MG glioblastoma cells. The phosphorescence of singlet oxygen was detected in aqueous cell suspensions following pulsed laser excitation. Our goal was to eliminate or reduce the problems associated with lifetime measurements in water‐based cell suspensions. The apparatus enabled simultaneous singlet oxygen phosphorescence and transient absorption measurements, reducing uncertainty in lifetime estimation. The changes in singlet oxygen lifetime were observed during early and late apoptosis induced by photodynamic action. Our findings show that the effective lifetime of singlet oxygen in the intracellular space of the studied glioblastoma cells is 0.4 μs and increases to 1.5 μs as apoptosis progresses. Another group of hypericin, presumably located in the membrane blebs and the plasma membrane of apoptotic cells, generates singlet oxygen with a lifetime of 1.9 μs. [ABSTRACT FROM AUTHOR]

Hundreds of adventitious root lines from Hypericum perforatum L. were examined for their hypericin content in order to establish a system for studying the production of hypericin in adventitious root lines. The effects of the medium consistency (solid and liquid) and the effects of three different auxins (Indole-3-butyric acid (IBA), Indole-3-acetic acid (IAA), and 1-Naphthaleneacetic acid (NAA)) on the induction of adventitious roots in leaf explants were studied. In a half-strength MS liquid medium with 2 mg/L IBA concentration, adventitious roots developed from H. perforatum leaves, whereas NAA and IAA caused callus-like and low branch roots. HPLC-UV was used to profile hypericin content variations in 100 H. perforatum adventitious root lines. Hierarchical component analysis (HCA) was used for selecting elite lines. After cluster analysis and selecting high-performance lines in terms of hypericin, five elite lines were chosen and the amount of hypericin production, as well as the phenol and flavonoid content, was analysed. [ABSTRACT FROM AUTHOR]

The aim of this study was to explore the potential of hypericin, a naturally occurring photosensi-tizer, for photodynamic therapy (PDT) in skin cancer, investigating its phototoxic effects and mechanisms of action in cancer cells compared to normal skin keratinocytes, squamous cell cancer (SCC-25) cells and melanoma (MUG-Mel2) cells. Hypericin was applied at concentrations ranging from 0.1–40 μM to HaCaT, SCC-25, and MUG-Mel2 cells. After 24 h of incubation, the cells were exposed to orange light at 3.6 J/cm2 or 7.2 J/cm2. Phototoxicity was assessed using MTT and SRB tests. Cellular uptake was measured by flow cytometry. Apoptosis-positive cells were estimated through TUNEL for apoptotic bodies' visualization. Hypericin exhibited a higher phototoxic reaction in cancer cells compared to normal keratinocytes after irradiation. Cancer cells demonstrated increased and selective uptake of hypericin. Apoptosis was observed in SCC-25 and MUG-Mel2 cells following PDT. Our findings suggest that hypericin-based PDT is a promising and less invasive approach for treating skin cancer. The higher phototoxic reaction, selective uptake by cancer cells, and observed proapoptotic properties support the promising role of hypericin-based PDT in skin cancer treatment. [ABSTRACT FROM AUTHOR]

In this study, we analyzed the composition of essential oils obtained through hydrodistillation from the leaves and flowers of Hypericum perforatum L., a wild plant species found in Şile, İstanbul, located in the northwest of Turkey. We employed gas chromatography-mass spectrometry (GC-MS) to identify the constituents. Additionally, we investigated the antioxidant capacity and total phenolic composition of the plant using DPPH (2,2-diphenyl-1-picryl-hydrazyl), CUPRAC (CUPric Reducing Antioxidant Capacity), and Folin-Ciocalteu methods. Furthermore, we determined the total amount of hypericin present in the plant. The analysis of essential oils from the leaves revealed the identification of fifty-nine compounds, with 2-methyloctane (34.93%), cyclotetradecane (9.12%), limonene (7.24%), 3-methylnonane (5.58%), α-pinene (5.55%), n-tetradecanol (3.15%), 2-methyldecane (3.03%), nonane (3.0%), and spathulenol (2.07%) as the primary constituents. On the other hand, the essential oil from the flowers contained fifty-seven compounds, with 2-methyloctane (52.81%), α-pinene (4.65%), cyclotetradecane (4.04%), n-tetradecanol (2.99%), D-verbenone (2.28%), 2-methyl-2-octanol (2.17%), and caryophyllene oxide (2.0%) as the major components. When evaluating the antioxidant capacity of H. perforatum L. extracts, our results indicated that both leaves and flowers exhibited significant antioxidant capacity in DPPH assays. However, the Cu2+ ion reduction capacity was comparatively low in the CUPRAC method. The highest hypericin contents of leaves and flowers were determined in extraction with 60% ethanol/water for 120 minutes at 50°C as 0.122 g/g % and with 80% ethanol/water for 120 minutes at 50°C as 0.360 g/g %. [ABSTRACT FROM AUTHOR]

Hypericin can be derived from St. John's wort, which is widely spread around the world. As a natural product, it has been put into clinical practice such as wound healing and depression for a long time. In this article, we review the pharmacology, pharmacokinetics, and safety of hypericin, aiming to introduce the research advances and provide a full evaluation of it. Turns out hypericin, as a natural photosensitizer, exhibits an excellent capacity for anticancer, neuroprotection, and elimination of microorganisms, especially when activated by light, potent anticancer and antimicrobial effects are obtained after photodynamic therapy. The mechanisms of its therapeutic effects involve the induction of cell death, inhibition of cell cycle progression, inhibition of the reuptake of amines, and inhibition of virus replication. The pharmacokinetics properties indicate that hypericin has poor water solubility and bioavailability. The distribution and excretion are fast, and it is metabolized in bile. The toxicity of hypericin is rarely reported and the conventional use of it rarely causes adverse effects except for photosensitization. Therefore, we may conclude that hypericin can be used safely and effectively against a variety of diseases. We hope to provide researchers with detailed guidance and enlighten the development of it. [ABSTRACT FROM AUTHOR]

Tumors provide a significant barrier to individual well-being and the overall health of the worldwide community. The unregulated proliferation and capacity for metastasis of these cells significantly contribute to global morbidity and death. The achievement of successful therapy necessitates using accurate medication delivery techniques, hence highlighting the need for developing novel methodologies. Conventional drug delivery methods often need help with variability in release rates, suboptimal cellular absorption, and inherent instability. The study introduces the Hollow Microneedles for Nanocapsule Delivery System (HM-NCDS) as a potentially practical and viable approach. The HM-NCDS technique utilizes microscopic needles to precisely administer drug-loaded lipid nanocapsules, thereby eliminating the limitations associated with current methodologies. The characteristics of the system include microneedles of about 201.5 µm, nanocapsules exhibiting an average drug loading capacity of 47.98%, regulated drug release rates with an average of 2.88 µg/hour, and effective cellular absorption with an average of 68.53%. The results indicate the potential for enhanced, focused, and uniform medication administration, presenting novel opportunities for tackling the worldwide impact of cancer, upgrading individual health results, and augmenting overall population welfare. [ABSTRACT FROM AUTHOR]

Breast cancer (BC) is the most common malignancy among women worldwide. In recent years, significant progress has been made in BC therapy. However, serious side effects resulting from the use of standard chemotherapeutic drugs, as well as the phenomenon of multidrug resistance (MDR), limit the effectiveness of approved therapies. Advanced research in the BC area is necessary to create more effective and safer forms of therapy to improve the outlook for individuals diagnosed with this aggressive neoplasm. For decades, plants and natural products with anticancer properties have been successfully utilized in treating various medical conditions. Anthraquinone derivatives are tricyclic secondary metabolites of natural origin that have been identified in plants, lichens, and fungi. They represent a few botanical families, e.g., Rhamnaceae, Rubiaceae, Fabaceae, Polygonaceae, and others. The review comprehensively covers and analyzes the most recent advances in the anticancer activity of 1,8-dihydroanthraquinone derivatives (emodin, aloe-emodin, hypericin, chrysophanol, rhein, and physcion) applied both individually, or in combination with other chemotherapeutic agents, in in vitro and in vivo BC models. The application of nanoparticles for in vitro and in vivo evidence in the context of 1,8-dihydroanthraquinone derivatives was also described. [ABSTRACT FROM AUTHOR]

Aims: Alzheimer's disease (AD) and type 2 diabetes (T2D) are two of the most common diseases in elderly population and they have a high rate of comorbidity. Study has revealed that T2D is a major risk factor of AD, and thus exploring therapeutic approaches that can target both diseases has drawn much interest in recent years. In this study, we tried to explore drugs that could be potentially used to prevent or treat both AD and T2D via a drug repositioning approach. Methods: We first searched the known drugs that may be effective to T2D treatment based on the network distance between the T2D‐associated genes and drugs deposited in the DrugBank database. Then, via molecular docking, we further screened these drugs by examining their interaction with islet amyloid polypeptide (IAPP) and Aβ42 peptide, the key components involved in the pathogenesis of T2D or AD. Finally, the binding between the selected drug candidates and the target proteins was verified by molecular dynamics (MD) simulation; and the potential function of the drug candidates and the corresponding targets were analyzed. Results: From multiple resources, 734 T2D‐associated genes were collected, and a list of 1109 drug candidates for T2D was obtained. We found that hypericin had the lowest binding energy and the most stable interaction with either IAPP or Aβ42 peptide. In addition, we also found that the target genes regulated by hypericin were differentially expressed in the tissues related to the two diseases. Conclusion: Our results show that hypericin may be able to bind with IAPP and Aβ42 stably and prevent their accumulation, and thus could be a promising drug candidate for treating the comorbidity of AD and T2D. [ABSTRACT FROM AUTHOR]

Background: Hypericin (HYP) is a natural compound widely used as a food supplement. The encapsulation of HYP into nanosystems, such as nanostructured lipid carriers (NLC), is a promising strategy for delivering this lipophilic molecule and protecting it from degradation. Objective: This study aims to develop and validate an analytical method to quantify the encapsulation efficiency of HYP in NLC. Method: A reverse-phase high-performance liquid chromatography (HPLC) method was developed and validated according to the International Conference on Harmonization (ICH) guide Q2 (R1). NLC was prepared through the ultrasonication method, and HYP encapsulation efficiency was evaluated using the validated method. Results: Separation was achieved using an isocratic mobile phase composed of acetonitrile, methanol, and ammonium acetate buffer (10 mM, pH 5.0) (54:36:10, v/v/v) and a reverse stationary phase. The specificity, linearity, precision, accuracy, and robustness of the method were assessed and confirmed during the validation. Furthermore, the validated method was able to determine the encapsulation efficiency of HYP in NLC. Conclusions: The HPLC method was validated, and the results indicated the ability of NLC to deliver HYP compounds for further application as a food supplement. Highlights: HYP is used as a food supplement and for photodynamic therapy (PDT). The developed method was specific, linear, precise, accurate, and robust. NLCs showed a high ability to encapsulate HYP. [ABSTRACT FROM AUTHOR]

Background: Staphylococcus is a genus of Gram-positive bacteria, known to cause food poisoning and gastrointestinal illness in humans. Additionally, the emergence of methicillin-resistant S. aureus (MRSA) strains has caused a major health care burden worldwide. Cronobacter is a group of Gram-negative bacteria that can survive in extreme dry conditions. Cronobacter sakazakii is known to contaminate powdered infant formula and cause life-threatening infections in neonates. Vibrio is a genus of humanpathogenic Gram-negative bacteria that can cause foodborne illness by consuming undercooked or raw seafood. Vibrio parahaemolyticus can cause serious gastrointestinal disease in humans. Thus, rapid identification of Staphylococcus spp., Cronobacter spp., and Vibrio spp. is crucial for the source tracking of contaminated food, as well as to measure the transmission dynamics of these bacterial pathogens causing foodborne diseases and outbreaks. Objective: This single-laboratory performance evaluation study used the VITEK MS system to evaluate the potential of MALDI-TOF MS technology for rapid identification of S. aureus-like, C. sakazakii-like, and V. parahaemolyticus-like isolates of public health importance. Method: A total of 226 isolates recovered from various food, environmental surveillance samples, and other sources were identified by bioMerieux VITEK 2 and VITEK MS systems as Staphylococcus spp., Cronobacter spp., and Vibrio spp. Five American Type Culture Collection (ATCC) reference Gram-positive and Gram-negative bacterial isolates were also tested to complete the study. In addition, for some Staphylococcus spp. isolates, whole genome sequencing (WGS) and DNA sequencing of 16S rRNA partial region were also performed for species identification. Results: The VITEK MS system was able to provide species identification to all 96 isolates of Staphylococcus spp. and to all 29 isolates of Vibrio spp. examined with a high confidence value (99.9%). Similarly, species identification was observed for the majority of spots (245 of 303) for the 101 Cronobacter spp. isolates (82.0%) with a high confidence value (99.9%), and genus level identification was noticed for the rest of the Cronobacter spp. isolates (18.0%; 58 of the 303 spots) analyzed. Species identification data generated by VITEK 2 system were comparable to data obtained by the VITEK MS system. Conclusions: The VITEK MS system is a reliable high-throughput platform that can rapidly identify Staphylococcus, Vibrio, and Cronobacter to the genus level, as well as S. aureus, C. sakazakii, V. parahaemolyticus, and other closely related foodborne isolates and bacterial isolates from additional sources, in most cases. Highlights: The VITEK MS system can be used in the rapid genus and species identification of human-pathogenic Staphylococcus spp., Cronobacter spp., and Vibrio spp. isolates. [ABSTRACT FROM AUTHOR]

Determination of the hypericin–photodynamic (HY–PDT) effect on the secretion of cytokines secreted by the skin cells, may be the basis for using the immunomodulatory effect of photodynamic action in the treatment of inflammatory skin diseases. The study aimed to evaluate the cytotoxic and immunomodulatory effects of hypericin (HY) in photodynamic therapy (PDT) performed in vitro on cultures of selected skin cell lines. The study used two human cell lines, primary dermal fibroblast (HDFa) and primary epidermal keratinocytes (HEKa). The MTT test was used to define the metabolic activity of treated cells. Cell supernatants subjected to sublethal PDT were assessed to determine the interleukins: IL-2, IL-8, IL-10, IL-11, IL-19, IL-22, and metalloproteinase 1 (MMP-1). The results confirm the destructive effect of HY–PDT and the immunomodulatory effects of sublethal doses on the selected skin cells, depending on the concentration of HY and the light doses. No statistically significant differences were noted in IL-2 and IL-10 concentration after HY–PDT for HEKa and HDFa lines. After using HY–PDT, the concentration of IL-8, MMP-1, IL-22, and IL-11 significantly decreased in the HEKa line. Moreover, the concentration of IL-19 and MMP-1 significantly decreased in the HDFa line. The concentration of IL-11 in the HDFa line after using only the HY, without the light, increased but decreased after HY–PDT. Our experiment confirmed that HY–PDT has not only a cytotoxic effect but, used in sublethal doses, also presents immunomodulatory properties. These may be an advantage of HY–PDT when used in the treatment of persistent skin inflammation, connected with the release of pro-inflammatory cytokines resistant to conventional treatment methods.

Hypericin is widely utilized for its precise antidepressant properties, but its exact antidepressant mechanism remains unclear. Gap junctions, which were predominantly expressed in astrocytes in the central nervous system, are concerned with the pathogenesis of depression. However, the role of hypericin in gap junctional dysfunction in depression has rarely been investigated. Here, we found that gap junctions were ultra-structurally broadened in the chronic unpredictable stress (CUS) rat model of depression, while hypericin repaired the dysfunction of gap junctions. Suppression of gap junctions by bilateral injection of carbenoxolone (CBX) in the prefrontal cortex of rats significantly inhibited the restoration of gap junctional dysfunction in depression by hypericin. Meanwhile, hypericin failed to show antidepressant benefits. Furthermore, in corticosterone (CORT)-stimulated primary astrocytes derived from neonatal rats, hypericin dramatically reversed the phosphorylation of connexin 43 (Cx43), normalizing the expression of Cx43 and thereby ameliorating gap junctional dysfunction. Comparatively, CBX inhibited the remission of hypericin on gap junctional intercellular communication function. Gap junctional function might be a novel therapeutic target for hypericin in the treatment of depression and provide potential novel insights into the antidepressant mechanism of other herbal ingredients.

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Objective. MAPK3 activates several nuclear transcription factors, including c-Jun and c-fos, by phosphorylating its downstream cytoplasmic protein, thereby contributing to cell proliferation and survival. Different carcinomas' initiation, progression, cancer cell metastasis, and drug resistance have been associated with MAPK3 overexpression. Given the need for new and potent MAPK3 inhibitors, this study aimed to explore the potential of anthraquinones (AQs) as organic compounds capable of inhibiting MAPK3. Methods. Using AutoDock 4.0 software, the binding affinity of 21 AQs to the receptor's active site was evaluated. AQs were ranked based on their ΔGbinding values to the receptor's active site, with the highest rankings receiving the most favorable scores. The Discovery Studio Visualizer tool was used to demonstrate the interaction modes between the highest-ranked AQs and the MAPK3 catalytic site. Furthermore, a 100-nanosecond molecular dynamics (MD) computer simulation was performed to assess the stability of the docked pose of the most potent enzyme inhibitor identified in this study. Results. The binding affinity of emodin-8-glucoside, aloe-emodin 8-glucoside, pulmatin, rhodoptilometrin, and hypericin to the receptor's ATP binding cleft was noteworthy, as the ΔGbinding values were < − 10 kcal/mol. In addition, emodin-8-glucoside, aloe-emodin 8-glucoside, and pulmatin were found to have inhibition constant values at the picomolar concentration. According to our computer simulation results, the docked pose of emodin-8-glucoside within the active site of MAPK3 achieved a stable state after 70 ns. In other words, the root mean square deviation (RMSD) graph indicated stability within the 70–100 ns timeframe. Conclusion. Inhibition of MAPK3 by emodin-8-glucoside, aloe-emodin 8-glucoside, pulmatin, rhodoptilometrin, and hypericin may have therapeutic potential in cancer treatment. [ABSTRACT FROM AUTHOR]

• We provide first detailed phenolic profiles of six Turkish Hypericum L. species. • Results indicate a significant chemodiversirty among the investigated populations. • Results also indicate little chemotaxonomic significance for tested phenolics. • Such data are essential in clarifying evolutionary relationships within the genus Hypericum. • Such data are also crucial in identifying the heterogeneous germplasms. Hypericum species have been of great interest to mankind for centuries and Türkiye is a global intersection for these species. In the present study, 20 wild populations of six under-exploited species of Turkish Hypericum from four sections (Hypericaceae; H. orientale, H. bupleuroides, H. venustum, H. hirsutum, H. linarioides and H. androsaemum) were analyzed qualitatively and quantitatively for the presence of 16 phenolic compounds by detailed high-performance liquid chromatography (HPLC) analyses for the first time. Except for quercetin, which was not accumulated by H. bupleuroides, H. venustum and H. linarioides , and hyperoside which was only accumulated by H. bupleuroides and H. venustum , all phenolics were detected at different levels depending on species and their populations. In order to differentiate the samples according to their geographical origin and botanical section, as well as to elucidate the function of the phenolics as chemotaxonomic markers in taxonomy of the Hypericum genus, two multivariate approaches namely, hierarchical cluster analysis (HCA) and principal component analysis (PCA) were performed. The results indicate a significant inter and intra species chemovariability, which has little chemosystemic significance for the taxa studied and makes a poor contribution to the chemotaxonomic understanding of the Turkish Hypericum species. The presented data could be possibly beneficial in clarifying evolutionary relationships within the botanical sections of the genus Hypericum and offer interesting proposals for further studies in the chemotaxonomy and pharmacognosy of this genus. [ABSTRACT FROM AUTHOR]

The factors affecting purification of concentrated extracts obtained from the aerial parts of two Hypericum species (H. scabrum L. and H. perforatum L.) using 80% EtOH were studied. A five-fold treatment with extraction naphtha followed by six-fold extraction with EtOAc was shown to provide a dry extract with a hypericin content of at least 0.29%. The recommended conditions for obtaining a spray-dried extract of Hypericum were coolant temperature at the inlet, 160 – 180°C; at the outlet, 80 – 90°C; solution delivery rate, 5 L/h; air pressure supplied to the nozzle, 0.15 MPa; and solution concentration, 15%. A unified technology for production of Hypericum dry extract substance from the aerial parts of H. scabrum and H. perforatum was developed and could produce a finished product that met the requirements of foreign pharmacopoeias. [ABSTRACT FROM AUTHOR]

Wnt/β‐catenin signaling pathway plays a role in cancer development, organogenesis, and embryogenesis. The abnormal activation promotes cancer stem cell renewal, proliferation, and differentiation. In the present study, molecular docking simulation and ADMET studies were carried out on selected bioactive compounds in search of β‐catenin protein inhibitors for drug discovery against cancer. Blind docking simulation was performed using PyRx software on Autodock Vina. β‐catenin protein (PDB ID: 1jdh) and 313 bioactive compounds (from PubChem database) with selected standard anticancer drugs were used for molecular docking. The ADMET properties of the best‐performing compounds were calculated using SwissADME and pkCMS web servers. The results obtained from the molecular docking study showed that glycyrrhizic acid, solanine, polyphyllin I, crocin, hypericin, tubeimoside‐1, diosmin, and rutin had the best binding interactions with β‐catenin protein based on their binding affinities. Glycyrrhizic acid and solanine had the same and lowest binding energy of −8.5 kcal/mol. This was followed by polyphyllin I with −8.4 kcal/mol, and crocin, hypericin, and tubeimoside‐1 which all had a binding energy of 8.1 kcal/mol. Other top‐performing compounds include diosmin and rutin with binding energy of −8.0 kcal/mol. The ADMET study revealed that the following compounds glycyrrhizic acid, solanine, polyphyllin I, crocin, hypericin, tubeimoside‐1, diosmin, rutin, and baicalin all violated Lipinski's rule of 5 which implies poor oral bioavailability. However, based on the binding energy score, it was suggested that these pharmacologically active compounds are potential molecules to be tested against cancer. [ABSTRACT FROM AUTHOR]

Any defects in bile formation, secretion, or flow may give rise to cholestasis, liver fibrosis, cirrhosis, and hepatocellular carcinoma. As the pathogenesis of hepatic disorders is multifactorial, targeting parallel pathways potentially increases the outcome of therapy. Hypericum perforatum has been famed for its anti-depressive effects. However, according to traditional Persian medicine, it helps with jaundice and acts as a choleretic medication. Here, we will discuss the underlying molecular mechanisms of Hypericum for its use in hepatobiliary disorders. Differentially expressed genes retrieved from microarray data analysis upon treatment with safe doses of Hypericum extract and intersection with the genes involved in cholestasis are identified. Target genes are located mainly at the endomembrane system with integrin-binding ability. Activation of α5β1 integrins, as osmo-sensors in the liver, activates a non-receptor tyrosine kinase, c-SRC, which leads to the insertion of bile acid transporters into the canalicular membrane to trigger choleresis. Hypericum upregulates CDK6 that controls cell proliferation, compensating for the bile acid damage to hepatocytes. It induces ICAM1 to stimulate liver regeneration and regulates nischarin, a hepatoprotective receptor. The extract targets the expression of conserved oligomeric Golgi (COG) and facilitates the movement of bile acids toward the canalicular membrane via Golgi-derived vesicles. In addition, Hypericum induces SCP2, an intracellular cholesterol transporter, to maintain cholesterol homeostasis. We have also provided a comprehensive view of the target genes affected by Hypericum's main metabolites, such as hypericin, hyperforin, quercitrin, isoquercitrin, quercetin, kaempferol, rutin, and p-coumaric acid to enlighten a new scope in the management of chronic liver disorders. Altogether, standard trials using Hypericum as a neo-adjuvant or second-line therapy in ursodeoxycholic-acid-non-responder patients define the future trajectories of cholestasis treatment with this product. [ABSTRACT FROM AUTHOR]

Nanoparticles (NPs) are one of the most preferred materials in drug release systems. Photodynamic therapy (PDT) acts by activating natural components with light to form radicals and causing death due to intracellular toxicity. Hypericin (HY) which was derived from Hypericum perforatum was used as a photosensitizer and anticancer agent. It is already known that cytotoxicity, antiproliferative and antitumor effects of HY-mediated PDT. However, HY is clustered in an aqueous environment which decreases its efficiency. Therefore, it was preferred to be used with NP-based carriers. In this study, HY-loaded chitosan NPs (HY-CH-NPs) were prepared for in vitro assessment. It was aimed to increase the cytotoxic effect of HY by prolonging the duration and uptake of HY action in the A549 lung cancer cells after PDT irradiation (6 J/cm2) with fluorescent lamps. HY-CH-NPs were characterized to examine their size and surface change with dynamic light scattering (DLS) and scanning electron microscopy (SEM), and it was achieved that the particles were below 400 nm diameter. All HY-CH-NPs showed a peak at around 1260 cm−1 according to FTIR spectrum. With the FITC staining, the penetration of NPs into the cell was demonstrated. And the drug (HY) loading efficiency was found as 3%. The cell viability decreased to 56% in the HY-CH-NP group after 48 h incubation in MTT assay. The amount of ROS in the HY-CH-NP 600 nM group was formed 1.6 times higher in the DCFDA analysis, and the total cell death was 40% in the AO/PI staining. It was observed that nanoparticles were able to cross the cell membrane barrier, and as a result of it, apoptosis and secondary necrosis were induced in the cancer cell. Lactate dehydrogenase release was also the highest in the 600 nM HY-CH-NP group, indicating increased necrotic cell death. [ABSTRACT FROM AUTHOR]

Commonly used to treat mood disorders, St. John's Wort (Hypericum perforatum) is a popular herb in the natural health products industry. The potency of its active ingredients can be determined using a number of different analytical methods, but it is more widely determined using high performance liquid chromatography (HPLC). While monographs in the United States Pharmacopeia (USP) can often be relied upon for suitable analytical methods, the method proposed for determining hypericin content in St. John's Wort products is inefficient in carrying out this purpose. This paper presents a modified new HPLC method for determining the hypericin content that can also be used for St. John's Worts capsules and tablets by making use of purified hypericin as a chemical standard instead of oxybenzone, applying a wavelength of 588 nm during analysis and utilizing a binary instead of ternary mobile phase gradient. The resulting method and sample chromatograms provide better resolved, more easily identifiable peaks, shorter run time, and increased sustainability compared to the original USP method. This proposed method was developed using the more refined ultra-high performance liquid chromatography (UHPLC) and serves as a more accurate and reliable method for determining hypericin content in St. John's Wort. [ABSTRACT FROM AUTHOR]

Hypericin, one of the major antidepressant constituents of St. John's wort, was shown to exert antidepressant effects by affecting cerebral CYP enzymes, serotonin homeostasis, and neuroinflammatory signaling pathways. However, its exact mechanisms are unknown. Previous clinical studies reported that the mRNA modification N6-methyladenosine (m6A) interferes with the neurobiological mechanism in depressed patients, and it was also found that the antidepressant efficacy of tricyclic antidepressants (TCAs) is related to m6A modifications. Therefore, we hypothesize that the antidepressant effect of hypericin may relate to the m6A modification of epitranscriptomic regulation. We constructed a UCMS mouse depression model and found that hypericin ameliorated depressive-like behavior in UCMS mice. Molecular pharmacology experiments showed that hypericin treatment upregulated the expression of m6A-modifying enzymes METTL3 and WTAP in the hippocampi of UCMS mice. Next, we performed MeRIP-seq and RNA-seq to study m6A modifications and changes in mRNA expression on a genome-wide scale. The genome-wide m6A assay and MeRIP-qPCR results revealed that the m6A modifications of Akt3, Ntrk2, Braf, and Kidins220 mRNA were significantly altered in the hippocampi of UCMS mice after stress stimulation and were reversed by hypericin treatment. Transcriptome assays and qPCR results showed that the Camk4 and Arhgdig genes might be related to the antidepressant efficacy of hypericin. Further gene enrichment results showed that the differential genes were mainly involved in neurotrophic factor signaling pathways. In conclusion, our results show that hypericin upregulates m6A methyltransferase METTL3 and WTAP in the hippocampi of UCMS mice and stabilizes m6A modifications to exert antidepressant effects via the neurotrophin signaling pathway. This suggests that METTL3 and WTAP-mediated changes in m6A modifications may be a potential mechanism for the pathogenesis of depression and the efficacy of antidepressants, and that the neurotrophin signaling pathway plays a key role in this process. [ABSTRACT FROM AUTHOR]