UPLC-Q-TOF-MS/MS combined with machine learning methods for screening quality indicators of Hypericum perforatum L.

Hypericum perforatum L. (HPL), also known as St. John's wort, is one of the extensively researched domestically and internationally as a medicinal plant. In this study, non-targeted metabolomics combined with machine learning methods were used to identify reasonable quality indicators for the holistic quality control of HPL. First, the high-resolution MS data from different samples of HPL were collected, and visualized the chemical compounds through the MS molecular network. A total of 122 compounds were identified. Then, the orthogonal partial least squares-discriminant analysis (OPLS-DA) model was established for comparing the differences in metabolite expression between flower, leaf, and branches. A total of 46 differential metabolites were screened out. Subsequently, analyzing the pharmacological activities of these differential metabolites based on protein-protein interaction (PPI) network. A total of 25 compounds associated with 473 gene targets were retrieved. Among them, 13 highly active compounds were selected as potential quality markers, and five compounds were ultimately selected as quality control markers for HPL. Finally, three different classifiers (support vector machine (SVM), random forest (RF), and K-nearest neighbor (KNN)) were used to validate whether the selected quality control markers are qualified. When the feature count is set to 122 and 46, the RF model demonstrates optimal performance. As the number of variables decreases, the performance of the RF model degrades. The KNN model and the SVM model also exhibit a decrease in performance but still manage to satisfy the intended requirements. The strategy can be applied to the quality control of HPL and can provide a reference for the quality control of other herbal medicines.

Predicting the Potential Distribution of Hypericum perforatum under Climate Change Scenarios Using a Maximum Entropy Model.

H. perforatum, as one of the Traditional Chinese Medicinal materials, possesses a variety of pharmacological activities and high medicinal value. However, in recent years, the wild resources of H. perforatum have been severely depleted due to global climate change and human activities, and artificial cultivation faces problems such as unstable yield and active ingredient content. This poses a serious obstacle to the development and utilization of its resources. Therefore, this experiment took H. perforatum as the research object and used 894 distribution records of H. perforatum and 36 climatic environmental factors, using the MaxEnt model and GIS technology to explore the main climatic factors affecting the distribution of H. perforatum. Additionally, by utilizing the principles of ecological niche theory, the potential suitable distribution regions of H. perforatum across past, present, and future timelines were predicted, which can ascertain the dynamics of its spatial distribution patterns and the trend of centroid migration. The results indicate that the main environmental factors affecting the geographical distribution of H. perforatum are solar radiation in April (Srad4), solar radiation in September (Srad9), mean temperature of driest quarter (Bio9), solar radiation in November (Srad11), annual mean temperature (Bio1), and annual precipitation (Bio12). Under future climate scenarios, there is a remarkable trend of expansion in the suitable distribution areas of H. perforatum. The centroid migration indicates a trend of migration towards the northwest direction and high-altitude areas. These results can provide a scientific basis for formulating conservation and sustainable use management strategies for H. perforatum resources.

Hyperguanyes A and B, two new PPAPs from the branches and leaves of Hypericum perforatum L. with anti-cholinesterase activities.

Two new polycyclic polyprenylated acylphloroglucinols, hyperguanyes A and B (1-2) together with eight known compounds (3-10), were isolated from Hypericum perforatum L. Their structures were determined by using comprehensive spectroscopic techniques and quantum chemical calculation. The in vitro anti-cholinesterase activity of all compounds were studied. Among them, compounds 1-4, 8 and 9 exhibited anti-AchE and anti-BchE effects with IC50 ranging from 0.34 ± 0.04 to 15.68 ± 0.54 µM.

Dermal Delivery of Hypericum perforatum (L.)Loaded Nanogel: Formulation to Preclinical Psoriasis Assessment.

BACKGROUND: Nanophytosomes represent an effective choice for topical drug delivery systems thanks to their small size, general non-toxicity, ease of functionalization and high surface to volume ratio. The goal of the current study was to investigate the potential benefits of using Hypericum perforatum extract nanogel as a means of improving skin penetration and prolonging skin deposition in dermatitis similar to psoriasis. METHOD: Nanophytosomes (NPs) were developed, optimised and thoroughly characterised. The optimised NPs were then placed in a Carbopol gel base matrix and tested ex-vivo (skin penetration and dermatokinetic) and in-vivo (antipsoriatic activity in an Imiquimod-induced psoriatic rat model). RESULTS: The optimised NPs had a spherical form and entrapment efficiency of 69.68% with a nanosized and zeta potential of 168nm and -10.37mV, respectively. XRD spectra and transmission electron microscopy tests confirmed the plant botanical encapsulation in the NPs. Following 60 days of storage at 40 ± 2°C/75 ± 5% RH, the optimised formula remained relatively stable. As compared to extract gel, nano-gel showed a much-improved ex vivo permeability profile and considerable drug deposition in the viable epidermal-dermal layers. When developed nano-gel was applied topically to a rat model of psoriasis, it demonstrated distinct in vivo anti-psoriatic efficacy in terms of drug activity and reduction of epidermal thickness in comparison to other formulations and the control. ELISA and histopathologic studies also demonstrated that nano-organogel had improved skin integrity and downregulated inflammatory markers (IL-17, IL-6, IFN-γ and MCP-1). CONCLUSION: Findings suggest that a developed plant botanicals-based nanogel has a potential for the treatment of psoriasis-like dermatitis with better skin retention and effectiveness.

Biologically active sodium pentaborate pentahydrate and Hypericum perforatum oil loaded polyvinyl alcohol: chitosan membranes.

In this study, sodium pentaborate pentahydrate (NaB) and Hypericum perforatum (HP) oil were incorporated into polyvinyl alcohol (PVA) and chitosan (CH) polymer blend to obtain membranes by solution casting method. In order to see the synergistic effects of NaB and HP oil on the biological and physical properties of the membranes NaB and HP oil were incorporated into membrane matrix in different ratios. Fourier-transform infrared spectroscopy (FTIR) results showed that no significant bond formation between the bioactive components and the PVA:CH matrix. According to mechanical test results, Young's Modulus and elongation at break decreased from 426 MPa to 346 MPa and 52.23 % to 15.11 % for neat PVA:CH membranes and NaB and HP oil incorporated PVA:CH (PVA:CH@35NaB:HP) membranes, respectively. Antimicrobial activity tests have shown the membranes were over 99 % effective against Escherichia coli, Staphylococcus aureus, and Candida albicans, underlining their potential for infection control. Cytocompatibility assay performed with Human Dermal Fibroblast (HDFa) cells highlight the biocompatibility of the membranes, revealing 74.84 % cell viability after 72 h. The properties of NaB and HP oil doped PVA:CH based membranes obtained from these experiments reveal the promise of a versatile membrane for applications in wound healing, tissue engineering and other biomedical fields.

The potential role of Hypericum perforatum in wound healing: A literature review on the phytochemicals, pharmacological approaches, and mechanistic perspectives.

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.

Four New Polyprenylated Acylphloroglucinols from Hypericum perforatum L.

Hyperforatums A-D (1-4), four new polyprenylated acylphloroglucinols, together with 13 known compounds were isolated and identified from the aerial parts of Hypericum perforatum L. (St. John's wort). Their structures were confirmed with a comprehensive analysis comprising spectroscopic methods, including 1D and 2D NMR, HRESIMS, and electronic circular dichroism (ECD) calculations. Hyperforatum A featured an unusual chromene-1,4-dione bicyclic system, and hyperforatums B and C were two rare monocyclic PPAPs with five-membered furanone cores. Compound 1 exhibited a moderate inhibition effect on NO production in BV-2 microglial cells stimulated by LPS.

Fluorescence-Guided Laparoscopy after Oral Hypericin Administration for Staging of Locally Advanced Gastric Cancer-A Pilot Study.

(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.

Hyperatins A-D, highly oxidized polycyclic polyprenylated acylphloroglucinols from Hypericum perforatum L. with hypoglycemic potential in liver cells.

Hyperatins A-D (1-4), four previously undescribed polycyclic polyprenylated acylphloroglucinols, were isolated from Hypericum perforatum L. (St. John's wort). Compound 1 possessed a unique octahydroindeno[1,7a-b]oxirene ring system with a rare 2,7-dioxabicyclo[2.2.1]heptane fragment. Compounds 2-4 had an uncommon decahydrospiro[furan-3,7'-indeno[7,1-bc]furan] ring system. Their structures were established by spectroscopic analyses and X-ray crystallography. Plausible biosynthetic pathways of 1-4 were also proposed. Compounds 1 and 2 exerted promising hypoglycemic activity by inhibiting glycogen synthase kinase 3 expression in liver cells.

Hypericum perforatum: a comprehensive review on pharmacognosy, preclinical studies, putative molecular mechanism, and clinical studies in neurodegenerative diseases.

The herb Hypericum perforatum, also referred to as St. John's wort, has drawn a lot of interest because of its potential therapeutic benefits in treating neurodegenerative illnesses. Due to the absence of effective therapies, illnesses like Alzheimer's and Parkinson's disease pose an increasing worldwide health concern. Because of its wide variety of phytochemicals, especially hyperforin, and hypericin, Hypericum perforatum is well known for its neuroprotective properties. These substances have proven to be able to affect different cellular processes linked to neurodegeneration. They can act as anti-inflammatory, antioxidant, and neurotransmitter system regulators, which may help halt neurodegenerative illnesses' progression. The use of Hypericum perforatum extracts and its contents has shown encouraging results in research on animal models of neurodegenerative disorders. These advantages include higher nerve cell survival, lowered oxidative stress, and higher cognitive performance. Underscoring its versatile potential to combat neurodegeneration, Hypericum perforatum has neuroprotective mechanisms that modulate neuroinflammation and prevent apoptotic pathways. In conclusion, Hypericum perforatum shows tremendous promise as a potential treatment for neurological illnesses due to its wide variety of phytochemicals. To completely comprehend its specific mechanisms of action and turn these discoveries into efficient clinical therapies, additional research is needed. Investigating Hypericum perforatum's function in neurodegenerative disorders may present new opportunities for the advancement of ground-breaking therapeutic strategies.

Methyl cellulose/okra mucilage composite films, functionalized with Hypericum perforatum oil and gentamicin, as a potential wound dressing.

There is a growing demand for the development of functional wound dressings enriched with bioactive natural compounds to improve the quality of life of the population by accelerating the healing process of chronic wounds. In this regard, a functional composite film of okra mucilage (OM) and methylcellulose (MC) incorporated with Hypericum perforatum oil (Hp) and gentamicin (G) was prepared and characterized as a wound dressing. Increasing Hp resulted in improved film properties with a more porous structure, higher WVTR, and lower surface hydrophobicity. Furthermore, incorporating Hp into OM:MC films led to increased elongation at the break while reducing the tensile strength of the films. The highest values of total antioxidant capacity (1.09-1.16 mM trolox equivalent) and total phenolic content (13.76-16.94 µg GA equivalent mL-1) were measured in the composite films containing the highest Hp concentration (1.5 %). In addition, OM:MC/HpG composite films exhibited significant antibacterial activity against both E. coli and S. aureus and prevented the transmission of these bacteria through the films. Hp incorporation reduced the cytotoxic effects of OM:MC films on BJ cells and increased the wound closure rate in vitro. In conclusion, the developed OM:MC/HpG composite film can be a promising candidate as a novel wound dressing with its superior properties.

In vitro assessment of Momordica charantia/Hypericum perforatum oils loaded PCL/Collagen fibers: Novel scaffold for tissue engineering.

The research on tissue engineering applications has been progressing to manufacture ideal tissue scaffold biomaterials. In this study, a double-layered electrospun biofiber scaffold biomaterial including Polycaprolactone (PCL)/Collagen (COL) fibrous inner layer and PCL/ Momordica charantia (MC) and Hypericum perforatum (HP) oils fibrous outer layer was developed to manufacture a functional, novel tissue scaffold with the advantageous mechanical and biological properties. The main approach was to combine the natural perspective using medicinal oils with an engineering point of view to fabricate a potential functional scaffold for tissue engineering. Medicinal plants MC and HP are rich in functional oils and incorporation of them in a tissue scaffold will unveil their potential to augment both new tissue formation and wound healing. In this study, a novel double-layered scaffold prototype was fabricated using electrospinning technique with two PCL fiber layers, first is composed of collagen, and second is composed of oils extracted from medicinal plants. Initially, the composition of plant oils was analyzed. Thereafter the biofiber scaffold layers were fabricated and were evaluated in terms of morphology, physicochemistry, thermal and mechanical features, wettability, in vitro bio-degradability. Double-layered scaffold prototype was further analyzed in terms of in vitro biocompatibility and antibacterial effect. The medicinal oils blend provided antioxidant and antibacterial properties to the novel PCL/Oils layer. The results signify that inner PCL/COL layer exhibited advanced biodegradability of 8.5% compared to PCL and enhanced wettability with 11.7° contact angle. Strength of scaffold prototype was 5.98 N/mm2 thanks to the elastic PCL fibrous matrix. The double-layered functional biofiber scaffold enabled 92% viability after 72 h contact with fibroblast cells and furthermore provided feasible attachment sites for the cells. The functional scaffold prototype's noteworthy mechanical, chemical, and biological features enable it to be suggested as a different novel biomaterial with the potential to be utilized in tissue engineering applications.

Apolar Extracts of St. John's Wort Alleviate the Effects of ß-Amyloid Toxicity in Early Alzheimer's Disease.

Hypericum perforatum (St. John's wort) has been described to be beneficial for the treatment of Alzheimer's disease (AD). Different extractions have demonstrated efficiency in mice and humans, esp. extracts with a low hypericin and hyperforin content to reduce side effects such as phototoxicity. In order to systematically elucidate the therapeutic effects of H. perforatum extracts with different polarities, APP-transgenic mice were treated with a total ethanol extract (TE), a polar extract obtained from TE, and an apolar supercritical CO2 (scCO2) extract. The scCO2 extract was formulated with silicon dioxide (SiO2) for better oral application. APP-transgenic mice were treated with several extracts (total, polar, apolar) at different concentrations. We established an early treatment paradigm from the age of 40 days until the age of 80 days, starting before the onset of cerebral ß-amyloid (Aß) deposition at 45 days of age. Their effects on intracerebral soluble and insoluble Aß were analyzed using biochemical analyses. Our study confirms that the scCO2H. perforatum formulation shows better biological activity against Aß-related pathological effects than the TE or polar extracts. Clinically, the treatment resulted in a dose-dependent improvement in food intake with augmentation of the body weight, and, biochemically, it resulted in a significant reduction in both soluble and insoluble Aß (-27% and -25%, respectively). We therefore recommend apolar H. perforatum extracts for the early oral treatment of patients with mild cognitive impairment or early AD.

Chemical profiling of botanical extracts obtained in NADES systems using centrifugal partition chromatography combined with 13 C NMR dereplication-Hypericum perforatum as a case study.

INTRODUCTION: Natural deep eutectic solvents (NADES) have emerged as interesting extractants to develop botanical ingredients. They are nontoxic and biodegradable, nonflammable, easy to prepare, and able to solubilize a wide range of molecules. However, NADES extracts remain difficult to analyze because the metabolites of interest stay highly diluted in the nonvolatile viscous NADES matrix. OBJECTIVE: This study presents a robust analytical workflow for the chemical profiling of NADES extracts. It is applied to Hypericum perforatum aerial parts extracted with the neutral mixture fructose/glycerol/water (3/1/1, w/w/w), and compared to the chemical profiling of a classical dry methanol extract. METHODS: Exploiting polarity differences between metabolites, the H. perforatum NADES extract was partitioned in a liquid-liquid solvent system to trap the hydrophilic NADES constituents in the lower phase. The upper phase, containing a diversity of secondary metabolites from H. perforatum, was fractionated by centrifugal partition chromatography. All fractions were chemically investigated using a 13 C NMR dereplication method which involves hierarchical clustering analysis of the whole NMR dataset, a natural metabolite database for metabolite identification, and 2D NMR analyses for validation. Liquid chromatography-mass spectrometry (LC-MS) analyses were also performed to complete the identification process. RESULTS: A range of 21 metabolites were unambiguously identified, including glycosylated flavonols, lactones, catechins, phenolic acids, lipids, and simple sugars, and 15 additional minor extract constituents were annotated by LC-MS based on exact mass measurements. CONCLUSION: The proposed identification process is rapid and nondestructive and provides good prospects to deeply characterize botanical extracts obtained in nonvolatile and viscous NADES systems.

Hypericum perforatum L. protects against renal function decline in ovariectomy rat model by regulating expressions of NOS3 and AKT1 in AGE-RAGE pathway.

BACKGROUND: Hypericum perforatum L. (HPL) is a potential traditional Chinese medicine. It could promotes menopausal 'kidney-yin deficiency syndrome' that characterized by renal function decline. However, its potential pharmacological effect and mechanism remains unknown. OBJECTIVE: The aim of this study was to investigate whether HPL can improve menopausal renal function decline and to explore its mechanism of action. METHODS: The mainly ingredients of HPL were identified using UPLC-Q-TOF-MS/MS approach, and the potential therapeutic targets of HPL for renal function decline were chose via network pharmacology technique. The key therapeutic metabolites were selected through non-targeted metabolomic and chemometric methods. Then, the network were constructed and the key targets and metabolites were screened. At last, the validation experiments and mechanism exploring were adopted by using Immunofluorescence, enzyme-linked immunosorbent assay (ELISA), real-time PCR (RT-PCR), and western blotting assays. RESULTS: mainly ingredients of HPL were identified and determined 17 compounds and 29 targets were chose as mainly active compounds and potential therapeutic targets. Based on OVX induced renal decline rat model, after chemometric analysis, 59 endo-metabolites were selected as key therapeutic metabolites, and AGE-RAGE signal pathway in diabetes complications was enriched as the key pathway. By constructing a "disease-component-target" network, Hyperoside, Quercetrin, and quinic were selected as the key therapeutic compounds, and the AKT1 and NOS3 were selected as the key therapeutic targets. The results of ELISA, RT-PCR and western blot experiments indicated that HPL could rescue the abnormal expressions both of AKT1 and NOS3, as well as their related metabolites distortion. CONCLUSION: Our findings indicated that HPL regulated expression of AKT1 and NOS3 through modulating AGE-RAGE signaling pathway in OVX stimulated rats` renal dysfunction, implicating the potential values of HPL in menopause syndromes therapy.

Fabrication of wound dressings: Herbal extract-loaded nanoliposomes embedded in fungal chitosan/polycaprolactone electrospun nanofibers for tissue regeneration.

Wound healing is a complex process and one of the major therapeutic and economic subjects in the pharmaceutical area. In recent years, the fabrication of nano-sized wound dressing models has attracted great attention for tissue regeneration. Plant extracts loaded nanoparticles are environmentally friendly and non-toxic and the release of the bioactive substance will be controlled to the wound area. This study aims to fabricate wound dressing models that contain bioactive components for tissue regeneration. Fungal chitosan/polycaprolactone nanofiber was fabricated by electrospinning and it has been characterized. Plant extracts loaded nanoliposomes were prepared, characterized, and embedded in nanofiber structures. The effectiveness of wound dressing models for tissue regeneration was evaluated by in vitro and in vivo studies. It was observed that all wound dressing models positively affect the cell viability of human dermal fibroblast cells. It was determined that plant extracts loaded nanoparticles embedded in nanofibers increased in cell viability than nanoparticles that were non-embedded in nanofiber structures. Histological analysis showed that plant extract-loaded nanoliposomes embedded in chitosan/PCL nanofibers were used for tissue regeneration. The most effective nanofibers were determined as Wd-ClNL nanofibers. RESEARCH HIGHLIGHTS: Hypericum perforatum L. and Cistus laurifolius L. were prepared by modified ultrasonic extraction method. Fungal chitosan/polycaprolactone nanofiber was fabricated by electrospinning and it has been characterized. Plant extract-loaded nanoliposomes were prepared, and characterized. They were embedded in chitosan/polycaprolactone nanofiber. Effects of the wound dressing model were analyzed by in vitro and in vivo assays for tissue regeneration.

Antibacterial activity of Hypericum perforatum L. (St. John's wort) extracts against Gram-positive bacteria and characterisation of its secondary metabolites.

This study aimed to determine the secondary metabolite profiles and antibacterial activity of H. perforatum L extracts against Gram-positive clinical isolates. The plant materials (Sample A and Sample B) were macerated with n-hexane, ethyl acetate and methanol (MeOH). The antibacterial activitiy of plant extracts and routinely used antibiotics were tested against Gram-positive bacteria. The secondary metabolite profiles of Sample A were determined by LC-Q-TOF-MS. The MIC values for n-hexane and ethyl acetate extracts of Sample A were lower than the susceptibility breakpoints of most broad-spectrum antibiotics (e.g. vancomycin, teicoplanin and linezolid) in a certain proportion of Gram-positive bacteria. The n-hexane extract of Sample A showed good antibacterial activity with MICs lower than the susceptibility breakpoint of teicoplanin in 58% of coagulase-negative staphylococci. The n-hexane and ethyl acetate extracts of Sample A had rich phloroglucinol constituents. The n-hexane and ethyl acetate extracts of Sample A could be alternative antibacterial agents against Gram-positive bacteria.

Two new constituents from the endophyte of Alternaria alternata and its anti-neuroinflammatory activity guided by molecular docking.

Two new compounds, 3-hydroxy-1-(3-hydroxy-5-methoxyphenyl)-2-methyl propan-1-one (1) and 1,2,6-trihydroxy-8-methoxy-2,3,3a,9b-tetrahydrocyclopenta[c] isochromen-5(1H)-one (2), along with nine known compounds 3-11, involving pyranones, phenylpropenoids and alkaloids, were obtained from Alternaria alternata, an endophyte isolated from Hypericum perforatum L. The structures were elucidated by extensive spectroscopic analyses, including 1D NMR, 2D NMR, HRESIMS, IR, UV spectroscopy. The absolute configuration was established via spectroscopy techniques and X-ray crystallisation method. Furthermore, guided by molecular docking, compounds 1 and 3 exhibited promising anti-neuroinflammatory activity in LPS-induced BV-2 microglial cells, with IC50 values of 0.9 ± 0.3 µM and 3.0 ± 0.4 µM respectively. Moreover, they effectively attenuated the LPS-induced elevation of NO, TNF-α, IL-6, and IL-1ß production in BV-2 microglial cells. These findings diversify the metabolite of A. alternata and highlight their potential as leading compounds against neuroinflammatory-related diseases.

Hyperipersions A-C, three new acylphloroglucinols from the branches and leaves of Hypericum perforatum L. with antiangiogenic activities.

Three new acylphloroglucinols were isolated from the branches and leaves of Hypericum perforatum L., named as hyperipersions A-C (1-3), together with three known compounds which were identified as elegaphenone (4), 2,6-dihydroxy-3,4-dimethylbenzoic acid methyl ester (5) and 2,3-methylenedioxyxanthone (6), respectively. The structures of isolated compounds were determined by UV, IR, HR-ESI-MS, NMR analysis. Their antiangiogenic activities were studied against HUVECs. The IC50 value of compound 3 was 2.39 ± 0.21 µM against HUVECs, which was stronger than vatalanib, and other compounds had moderate antiangiogenic activity.

Cytotoxic and anti-metastatic effects of Hypericum perforatum olive oil extract in colorectal cancer cells and human bone marrow derived stem cells.

This study is aimed to investigate the effects of Hypericum perforatum olive oil extract on the cytotoxic and metastatic properties of human colorectal cancer cells and human bone marrow-derived mesenchymal stem cells. In addition, ALDH3A1 and Vimentin expressions were evaluated by qRT-PCR and western blot analysis. Total phenolic and flavonoid contents and antioxidant activity of methanol extracts prepared with oil enrichment were measured using spectrophotometry-based methods. The cytotoxic effects of the extracts on SW-480 and bone marrow-derived mesenchymal stem cells were evaluated by MTT assay, resulting in IC50 values of 4.8 mg/ml and 4.9 mg/ml, respectively. It was determined that cell migration and colony formation were significantly reduced at the IC50 values determined for SW-480 and human bone marrow-derived mesenchymal stem cells.