Hypericum Perforatum Callus Extract-Loaded Composite Hydrogel with Diverse Bioactivities for Enhanced Wound Healing and Fibrosis Prevention.

Plant Callus are a valuable source of pluripotent stem cells and bioactive phytochemicals. Meanwhile, the Hypericum perforatum callus extract (HPCE) is particularly rich in compounds such as hyperforin, hypericin, quercetin, and other phenolic and flavonoid derivatives. These phytochemicals exhibit strong antibacterial, antioxidant, anti-inflammatory, and anti-fibrotic properties, making them promising for wound healing. One of the most critical challenges following wound healing is the formation of fibrosis, which can compromise the complex structural integrity of skin. To address this issue, a poly(vinyl alcohol)/chitosan/alginate (PCA) wound dressing loaded with HPCE is developed. This hydrogel dressing features a porous structure with suitable mechanical properties and a high swelling capacity, potentially enhancing its effectiveness in promoting tissue regeneration and wound healing. In vitro studies have confirmed its biocompatibility, cell proliferation, and cell adhesion properties. Additionally, the dressing has demonstrated the ability to inhibit the proliferation of certain antibiotic-resistant bacteria. The in vivo studies revealed the anti-inflammatory properties, promotion of angiogenesis, facilitation of re-epithelialization, and stimulation of collagen deposition of the dressing under investigation. Moreover, the immunohistochemistry analysis of the two key markers, p16 and p53, has shown that the application of the dressing helps prevent fibrosis after wound healing.

Hypericum perforatum L. (St. John's Wort) in broilers diet improve growth performance, intestinal microflora and immunity.

Hypericum perforatum L. (St. John's Wort) extract (HPE), powdered H. perforatum (PHP), and selenium (Se) on growth, intestinal flora, and immunity of broiler chicks were investigated. In total, 504 one-day-old broiler chicks were randomly allocated into 6 dietary treatments, which were then denoted as negative control (NC) group (basal diet), containing organic Se 0.2% in the starter and grower period as positive control (PC), containing 1% PHP in the starter and grower period, and HPE I, HPE II, and HPE III groups containing respectively, 1.5, 3.0, and 4.5 mL / kg HPE in the starter and grower period. The results on performance showed that a significant (P < 0.05) higher body weight of chickens in the HPE III group was observed when compared with that of the NC and PHP groups. Although average daily weight gain and feed intake are significant in the HPE III group, the difference in terms of total feed conversion rate was insignificant (P > 0.05). The liver weights in PC and HPE III were lower compared to HPE I (P < 0.05). The difference in total lactic acid bacteria count (TLABC) between the NC group and all HPE groups was found to be significant (P ˂ 0.05), in addition to TLABC was higher in the HPE III group than other groups (P = 0.001). The highest serum antibody titers to the Newcastle disease vaccine were determined in the HPE III group on the 24th, 35th, and 42nd days of age. IL-1B and IL-6 were found to be insignificant between the groups in chickens (P ˃ 0.05). TNF-α in the HPE III group was greatly increased than the other groups and significant compared to the NC and HPE I groups (P = 0.018). In conclusion, 4.5 mL / kg HPE, which has a low production cost and is easy to extract and without causing environmental problems, varied significantly in their impact on growth performance, intestinal microflora, and immunity of growing broilers.

Chemical Composition and Biological Activity of Hypericum Species-H. hirsutum, H. barbatum, H. rochelii.

St. John's wort (Hypericum perforatum, Hypericaceae) is the most well-known species in the genus Hypericum, which comprises several hundred species. This study investigates the biological and phytochemical potential of the under-researched Hypericum species, H. hirsutum, H. barbatum, and H. rochelii. A high level of similarity between the chemical profiles of H. hirsutum and H. barbatum and the official source of the herbal drug (H. perforatum) was shown, but a higher content of quercetin and rutin was also found in all three evaluated species (116-230 µg/g dry herb). The highest amount of phenolics (195 mg GAE/g) was recorded in H. hirsutum extract, while the highest amount of flavonoids (47 mg QE/g) was recorded in H. barbatum extract. The evaluated species were excellent scavengers of DPPH, OH, and NO radicals, as well as strong ferric ion reducers in the FRAP test. Prominent monoamine oxidase A and α-glucosidase inhibition was observed, compared to modest inhibition of monoamine oxidase B, α-amylase, and acetylcholinesterase. High activity against Gram-positive MRSA S. aureus was demonstrated for the tested species, with MIC/MBC values recorded at 12.5 µg/mL. Antifungal activity against Candida strains was not observed. The obtained results emphasize the need for further investigation of species of the genus Hypericum to discover potentially new sources of biologically active compounds.

Identification of molecular targets of Hypericum perforatum in blood for major depressive disorder: a machine-learning pharmacological study.

BACKGROUND: Major depressive disorder (MDD) is one of the most common psychiatric disorders worldwide. Hypericum perforatum (HP) is a traditional herb that has been shown to have antidepressant effects, but its mechanism is unclear. This study aims to identify the molecular targets of HP for the treatment of MDD. METHODS: We performed differential analysis and weighted gene co-expression network analysis (WGCNA) with blood mRNA expression cohort of MDD and healthy control to identify DEGs and significant module genes (gene list 1). Three databases, CTD, DisGeNET, and GeneCards, were used to retrieve MDD-related gene intersections to obtain MDD-predicted targets (gene list 2). The validated targets were retrieved from the TCMSP database (gene list 3). Based on these three gene lists, 13 key pathways were identified. The PPI network was constructed by extracting the intersection of genes and HP-validated targets on all key pathways. Key therapeutic targets were obtained using MCODE and machine learning (LASSO, SVM-RFE). Clinical diagnostic assessments (Nomogram, Correlation, Intergroup expression), and gene set enrichment analysis (GSEA) were performed for the key targets. In addition, immune cell analysis was performed on the blood mRNA expression cohort of MDD to explore the association between the key targets and immune cells. Finally, molecular docking prediction was performed for the targets of HP active ingredients on MDD. RESULTS: Differential expression analysis and WGCNA module analysis yielded 933 potential targets for MDD. Three disease databases were intersected with 982 MDD-predicted targets. The TCMSP retrieved 275 valid targets for HP. Separate enrichment analysis intersected 13 key pathways. Five key targets (AKT1, MAPK1, MYC, EGF, HSP90AA1) were finally screened based on all enriched genes and HP valid targets. Combined with the signaling pathway and immune cell analysis suggested the effect of peripheral immunity on MDD and the important role of neutrophils in immune inflammation. Finally, the binding of HP active ingredients (quercetin, kaempferol, and luteolin) and all 5 key targets were predicted based on molecular docking. CONCLUSIONS: The active constituents of Hypericum perforatum can act on MDD and key targets and pathways of this action were identified.

A novel normonoterpene glycoside and a new benzophenone derivative from Hypericum cerastioides and their in vitro cytotoxic activities.

Phytochemical investigations on the aerial parts of Hypericum cerastioides led to the isolation and identification of a novel normonoterpene (1) and a previously undescribed benzophenone glycoside (3) along with eleven known secondary metabolites (2, 4-13). Their structures were deduced based on extensive 1D and 2D NMR analyses as well as HRESIMS. Compound 1 is a rare type of normonoterpene derivative with eight carbon atoms. The chemotaxonomic significance of the isolates was also discussed. Compounds were evaluated for their in vitro cytotoxic activities against SW480, A375, DU145 and MCF7 cancer cell lines using doxorubicin as a reference drug. Compounds 1 and 7 demonstrated weak cytotoxicity.

Biological activities of Hypericum spectabile extract optimized using artificial neural network combined with genetic algorithm application.

Optimizing extraction conditions can help maximize the efficiency and yield of the extraction process while minimizing negative impacts on the environment and human health. For the purpose of the current study, an artificial neural network (ANN) combined with a genetic algorithm (GA) was utilized for that the extraction conditions of Hypericum spectabile were optimized. In this particular investigation, the main objective was to get the highest possible levels of total antioxidant status (TAS) for the extracts that were obtained. In addition to this, conditions of the extract that exhibited the maximum activity have been determined and the biological activity of the extract that was obtained under these conditions was analyzed. TAS values were obtained from extracts obtained using extraction temperatures of 30-60 °C, extraction times of 4-10 h, and extract concentrations of 0.25-2 mg/mL. The best model selected from the established ANN models had a mean absolute percentage error (MAPE) value of 0.643%, a mean squared error (MSE) value of 0.004, and a correlation coefficient (R) value of 0.996, respectively. The genetic algorithm proposed optimal extraction conditions of an extraction temperature of 59.391 °C, an extraction time of 8.841 h, and an extraction concentration of 1.951 mg/mL. It was concluded that the integration of ANN-GA can successfully be used to optimize extraction parameters of Hypericum spectabile. The total antioxidant value of the extract obtained under optimum conditions was determined as 9.306 ± 0.080 mmol/L, total oxidant value as 13.065 ± 0.112 µmol/L, oxidative stress index as 0.140 ± 0.001. Total phenolic content (TPC) was 109.34 ± 1.29 mg/g, total flavonoid content (TFC) was measured as 148.34 ± 1.48 mg/g. Anti-AChE value was determined as 30.68 ± 0.77 µg/mL, anti-BChE value was determined as 41.30 ± 0.48 µg/mL. It was also observed that the extract exhibited strong antiproliferative activities depending on the increase in concentration. As a result of LC-MS/MS analysis of the extract produced under optimum conditions in terms of phenolic content. The presence of fumaric, gallic, protocatechuic, 4-hydroxybenzoic, caffeic, 2-hydoxycinamic acids, quercetin and kaempferol was detected. As a result, it was determined that the H. spectabile extract produced under optimum conditions had significant effects in terms of biological activity.

Hypericum sampsonii ameliorates radiodermatitis by inhibiting NLRP3 inflammasome activation.

BACKGROUND: Radiodermatitis (RD) is an inflammatory lesion of skin mucosa caused by radiation, which causes itching and pain in patients' skin. Hypericum sampsonii has an anti-inflammatory effect. This study aims to explore the potential effect and mechanism of H. sampsonii on RD. MATERIALS AND METHODS: The RD model was established using X-ray irradiation of mice and the pain response of mice under different treatment methods. Serum levels of IL-1ß, IL-6, and TNF-α were measured by ELSA. The RD cell model was constructed by RAW264.7 cell, H. sampsonii intervention was conducted, and the changes of the NLRP3 inflammasome in the cells were detected by qRT-PCR. The cells were stimulated with LPS and the protein changes of TLR4/NF-κB were investigated by Western Blotting. RESULTS: H. sampsonii can better improve the skin status of RD mice, relieve pain, and reduce the secretion of serum inflammatory factors IL-1ß, IL-6, and TNF-α. H. sampsonii significantly down-regulated the expression of NLRP3, Caspase-1, pro IL-1ß, and IL-1ß. Lps-induced activation of the TLR4/NF-κB pathway promotes the expression of NLRP3 and pro-IL-1ß, and H. sampsonii can inhibit this promotion. CONCLUSION: H. sampsonii may inhibit NLRP3 inflammatory vesicle activation via interfering with TLR4/NF-κB signaling to reduce the inflammatory response in macrophages and thus play a role in the treatment of RD.

Enhancment of zebrafish (Danio rerio) immune and antioxidant systems using medicinal plant extracts encapsulated in alginate-chitosan nanocapsules with slow sustained release.

This study aimed to screen 10 medicinal plant extracts on zebrafish (Danio rerio), evaluating their impact on the complement system, immunoglobulin M (IgM) levels, lysozyme, and peroxidase activity, while also enhancing their efficacy through the gradual release using alginate-chitosan nanocapsules. The prepared methanolic extracts were combined with fish feed. The fish were divided into 12 groups, including 10 treatment groups, a positive and a negative control group. Results showed varying impacts of the extracts on the immune and antioxidant systems, with Cinnamon (Cinnamon cassia) and Hypericum (Hypericum perforatum) extracts demonstrating the most significant effects. Subsequently, Cinnamon and Hypericum extract were encapsulated in alginate-chitosan nanocapsules to assess their impact on zebrafish immune parameters, separately and synergistically. Gradual release of the extracts from the nanocapsules was observed, with slower release at pH 2 compared to pH 7. Overall, Cinnamon and Hypericum extracts exhibited substantial immune system enhancement, and their encapsulation in nanocapsules improved their effects on zebrafish immune parameters. These findings suggest using these encapsulated extracts to enhance immune responses in aquatic organisms.

Phytochemical and Toxicological Analyses of Herbal Mixtures Containing Hypericum perforatum and Melissa officinalis.

Objectives: This study aimed to formulate a novel herbal mixture of Hypericum perforatum (H) and Melissa officinalis (M) and evaluate its toxicity, microbial load, and phytochemical content. Materials and Methods: Total flavonoids were measured using the AlCl3/NaNO2 complex formation method and colorimetric assay. The quercetin content of the herbal mixture was determined by reverse-phase high-performance liquid chromatography. The in vitro and in vivo safety of the herbal formulations were analyzed using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and acute oral toxicity analysis in the rat model, respectively. Results: The formulated extract (HM), compared with the standard rutin extract, had a total flavonoid content of 15.29 ± 0.64 mg rutin per mL sample. Reverse-phase high-performance liquid chromatography revealed a quercetin content of 0.187 mg/mL. Microbial tests for Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, and Salmonella spp. were negative. Colony counts for total aerobic microbial and yeast and mold counts were 10 in each case. The MTT assay (with up to about 5% v/v HM extract) using the NIH/3T3 cell line revealed no cell toxicity in the range of concentrations tested. Acute oral toxicity was tested in the Wistar rat model, and the LD50 was 695.2 ± 7.5 mg/kg. The dry weight of the HM extract was 38.1 mg/mL. Conclusion: Preliminary results proved the safety of the HM herbal mixture, with its toxicity and microbial load within the limits of accepted guidelines allowable for use in clinical trials.

Rapid discovery of natural antioxidants in Hypericum japonicum: Dual roles of the liquid phase mobile phase as extraction and separation solvent.

Hypericum japonicum is a traditional folk medicine with various bioactivities such as hepatoprotective, antioxidant, and anti-tumorous. The antioxidant effect of H. japonicum is one of the most prominent effects due to its responsibility for many of its activities. To clarify active natural substance, the antioxidant properties of H. japonicum were preliminarily assessed by ferric reducing-antioxidant power (FRAP), 2,2-azino-bis-3-ethylbenzothiazoline-6-sulphonic acid (ABTS) and Oxygen radical absorbance capacity (ORAC), as well as superoxide dismutase (SOD). Then, a straightforward and effective method named online liquid extraction-high performance liquid chromatography combined with ABTS antioxidant assay and mass spectrometry (OLE-HPLC-ABTS/Q-TOF-MS) was developed to swiftly and directly discover the antioxidants in H. japonicum. Using mobile phase as extraction and separation reagent, coupled with online activity analysis and compounds identification by high-resolution MS, the online system enables rapid screening of natural antioxidant bioactives from complex mixture. By using it, a total of 9 compounds including flavonoids and phenolic acids characterized by retention time, precise mass, and fragmentation ions in MS/MS spectra showed antioxidant action. Finally, the antioxidant and SOD activity of main found active compounds were validated by in vitro experiment assay and molecular docking. In summary, these results suggested that H. japonicum could be considered as a potential source of natural antioxidants, and the online integrated system might become a promising candidate for the natural antioxidants discovery in the future.

Effects of Hypericum attenuatum Choisy extract on the immunologic function and intestinal microflora of broilers under oxidative stress.

This study investigated the impact of Hypericum attenuatum Choisy extract (HYG) on immunological function and the cecum microflora in broilers. A total of 240 one-day-old AA broilers were randomly divided into 5 groups with 6 replicates of 8 broilers each: 1) the CN group, in which broilers were injected with saline and fed a basal diet; 2) the PC group, in which broilers were injected with lipolyaccharide (LPS) and fed a basal diet; 3) the HYG1 group, in which broilers were injected with LPS and fed a 400 mg/kg HYG-supplemented diet; 4) the HYG2 group, in which broilers were injected with LPS and fed a 800 mg/kg HYG-supplemented diet; 5) the HYG3 group, in which broilers were injected with LPS and fed a 1,200 mg/kg HYG-supplemented diet. Broilers were injected with 1 mg/kg LPS or the same amount saline 12 hours before sampling on d 21 and 42. The results revealed that dietary 400 mg/kg HYG supplementation alleviated spleen index and thymus index abnormalities, balanced the disturbance of serum immunoglobulin (Ig)M and IgA levels, and regulated the cytokine balance in the serum, liver, spleen and jejunum tissues included induced by LPS. Dietary supplementation with 400 mg/kg HYG also downregulated the relative expression of the inhibitor of kappa B kinase alpha (IKKα) and interleukin (IL)-6 mRNAs in the liver and upregulated the relative expression of the inhibitor kappa B alpha (IκBα) and IL-10 mRNAs in the spleen. Dietary HYG improved the cecal microflora balance at 42 d by increasing the relative abundance of beneficial bacteria, such as Alistipes and Phascolarctobacterium, while reducing the relative abundance of harmful bacteria, such as Helicobacter and Colidextribacter. Spearman correlation analysis revealed a negative correlation between activation of the NF-κB inhibitory pathway in the liver and the presence of Phascolarctobacterium, Erysipelatoclostridium, Subdoligranulum and Parabacteroides. Conclusions: The incorporation of 400 mg/kg HYG into the diet was optimal in improving broiler immunological function.

Anti-Inflammatory Effect of Xanthones from Hypericum beanii on Macrophage RAW 264.7 Cells through Reduced NO Production and TNF-α, IL-1ß, IL-6, and COX-2 Expression.

Hypericum beanii N. Robson, a perennial upright herb, predominantly inhabits temperate regions. This species has been utilized for the treatment of various inflammation-related diseases. One new xanthone 3,7-dihydroxy-1,6-dimethoxyxanthone (1) and twenty-three known xanthones (2-24) were isolated from the aerial parts of H. beanii. The structure of the new compound was determined based on high-resolution electrospray ionization mass spectroscopy (HR-ESIMS), nuclear magnetic resonance (NMR), Infrared Spectroscopy (IR), ultraviolet spectrophotometry (UV) spectroscopic data. The anti-inflammatory effects of all the isolates were assessed by measuring the inhibitory effect on nitric oxide (NO) production in LPS-stimulated RAW 264.7 macrophages. Compounds 3,4-dihydroxy-2-methoxyxanthone (15), 1,3,5,6-tetrahydroxyxanthone (19), and 1,3,6,7-tetrahydroxyxanthone (22) exhibited significant anti-inflammatory effects at a concentration of 10 µM with higher potency compared to the positive control quercetin. Furthermore, compounds 15, 19, and 22 reduced inducible NO synthase (iNOS), tumor necrosis factor alpha (TNF-α), interleukin-1ß (IL-1ß), IL-6, and cyclooxygenase 2 (COX-2) mRNA expression in the LPS-stimulated RAW 264.7 macrophages, suggesting that these compounds may mitigate the synthesis of the aforementioned molecules at the transcriptional level, provisionally confirming their anti-inflammatory efficacy.

Formohyperins G-L, polycyclic prenylated benzoylphloroglucinols from the flowers of Hypericum formosanum.

Phytochemical study on the flowers of Hypericum formosanum Maxim. (Hypericaceae) led to the isolation of formohyperins G-L (1-6), whose structures were assigned by detailed spectroscopic analysis. Formohyperins G-L (1-6) are new benzoylphloroglucinols substituted by a C10 unit, a prenyl group, and a methyl group. Formohyperins G-J (1-4) possess a 6/6/6-tricyclic structure, while formohyperins K (5) and L (6) have a unique 6/6/5/4-tetracyclic structure consisting of cyclohexadienone, dihydropyrane, cyclopentane, and cyclobutane rings. The absolute configurations of 1-6 were deduced by analysis of the ECD spectra. Formohyperins G-J (1-4) and L (6) were found to show potent inhibitory activities against IL-1ß release from LPS-treated murine microglial cells with EC50 values of 5.0, 10.9, 6.3, 10.8, and 13.7 µM, respectively, without cytotoxicity. 6-O-Methylformohyperins G (1a) and I (3a) also exhibited the inhibitory activities with EC50 values of 4.7 and 2.7 µM, respectively, although they were cytotoxic against microglial cells.

Single-cell RNA sequencing facilitates the elucidation of the complete biosynthesis of the antidepressant hyperforin in St. John's wort.

Hyperforin is the compound responsible for the effectiveness of St. John's wort (Hypericum perforatum) as an antidepressant, but its complete biosynthetic pathway remains unknown. Gene discovery based on co-expression analysis of bulk RNA-sequencing data or genome mining failed to discover the missing steps in hyperforin biosynthesis. In this study, we sequenced the 1.54-Gb tetraploid H. perforatum genome assembled into 32 chromosomes with the scaffold N50 value of 42.44 Mb. By single-cell RNA sequencing, we identified a type of cell, "Hyper cells", wherein hyperforin biosynthesis de novo takes place in both the leaves and flowers. Through pathway reconstitution in yeast and tobacco, we identified and characterized four transmembrane prenyltransferases (HpPT1-4) that are localized at the plastid envelope and complete the hyperforin biosynthetic pathway. The hyperforin polycyclic scaffold is created by a reaction cascade involving an irregular isoprenoid coupling and a tandem cyclization. Our findings reveal how and where hyperforin is biosynthesized, enabling synthetic-biology reconstitution of the complete pathway. Thus, this study not only deepens our comprehension of specialized metabolism at the cellular level but also provides strategic guidance for elucidation of the biosynthetic pathways of other specializied metabolites in plants.

Phytochemical Analysis, Biological Activities, and Docking of Phenolics from Shoot Cultures of Hypericum perforatum L. Transformed by Agrobacterium rhizogenes.

Hypericum perforatum transformed shoot lines (TSL) regenerated from corresponding hairy roots and non-transformed shoots (NTS) were comparatively evaluated for their phenolic compound contents and in vitro inhibitory capacity against target enzymes (monoamine oxidase-A, cholinesterases, tyrosinase, α-amylase, α-glucosidase, lipase, and cholesterol esterase). Molecular docking was conducted to assess the contribution of dominant phenolic compounds to the enzyme-inhibitory properties of TSL samples. The TSL extracts represent a rich source of chlorogenic acid, epicatechin and procyanidins, quercetin aglycone and glycosides, anthocyanins, naphthodianthrones, acyl-phloroglucinols, and xanthones. Concerning in vitro bioactivity assays, TSL displayed significantly higher acetylcholinesterase, tyrosinase, α-amylase, pancreatic lipase, and cholesterol esterase inhibitory properties compared to NTS, implying their neuroprotective, antidiabetic, and antiobesity potential. The docking data revealed that pseudohypericin, hyperforin, cadensin G, epicatechin, and chlorogenic acid are superior inhibitors of selected enzymes, exhibiting the lowest binding energy of ligand-receptor complexes. Present data indicate that H. perforatum transformed shoots might be recognized as an excellent biotechnological system for producing phenolic compounds with multiple health benefits.

Chitosan/Hyaluronate Complex-Coated Electrospun Poly(3-hydroxybutyrate) Materials Containing Extracts from Melissa officinalis and/or Hypericum perforatum with Various Biological Activities: Antioxidant, Antibacterial and In Vitro Anticancer Effects.

The present study aimed to fabricate innovative fibrous materials with various biological activities from poly(3-hydroxybutyrate), sodium hyaluronate (HA), chitosan (Ch), Melissa officinalis (MO), Hypericum perforatum (HP) extract, or a combination of both extracts. Electrospinning or electrospinning followed by dip coating and the subsequent formation of a polyelectrolyte complex were the methods used to prepare these materials. Scanning electron microscopy (SEM), transmission electron microscopy (TEM), thermogravimetric analysis (TGA), and attenuated total reflection-Fourier transform infrared spectroscopy (ATR-FTIR) were applied for investigating the morphology of materials, their thermal characteristics, and their surface chemical composition. The composition and design of the mats had an influence on the in vitro release behavior of the main bioactive compounds present in the MO and HP extracts incorporated in the materials. It was found that as-created materials comprising a combination of both extracts and a Ch/HA complex exerted higher antioxidant activity than that of (non-)coated MO-containing mats and Ch/HA-coated mats containing HP. The novel materials manifested antibacterial efficacy towards the pathogenic bacteria S. aureus and E. coli, as evidenced by the performed microbiological screening. Furthermore, the mats possessed a great growth inhibitory effect on HeLa cancer cells but had a less pronounced effect on the growth of normal mouse BALB/3T3 fibroblasts. The loading of both extracts in the mats and the formation of coating led to the enhancement of the in vitro anticancer and antibacterial activities of the materials. Thus, the novel materials have potential for use in local cancer therapy as well as for use as wound dressings.

Anti-Biofilm Action of Cineole and Hypericum perforatum to Combat Pneumonia-Causing Drug-Resistant P. aeruginosa.

Hospital-acquired antibiotic-resistant pneumonia is one of the major causes of mortality around the world that pose a catastrophic threat. Pseudomonas aeruginosa is one of the most significant opportunistic pathogens responsible for hospital-acquired pneumonia and gained resistance to the majority of conventional antibiotics. There is an urgent need for antibiotic alternatives to control drug-resistant pneumonia and other related respiratory infections. In the present study, we explored the antibacterial potential of cineole in combination with homeopathic medicines against biofilm-forming drug-resistant P. aeruginosa. Out of 26 selected and screened homeopathic medicines, Hypericum Perforatum (HyPer) was found to eradicate biofilm-forming drug-resistant P. aeruginosa most effectively when used in combination with cineole. Interestingly, the synergistic action of HyPer and cineole was also found to be similarly effective against planktonic cells of P. aeruginosa. Further, the potential synergistic killing mechanisms of cineole and HyPer were determined by analyzing zeta membrane potential, outer membrane permeability, and DNA release from P. aeruginosa cells upon treatment with cineole and HyPer. Additionally, molecular docking analysis revealed strong binding affinities of hypericin (an active ingredient of HyPer) with the PqsA (a quorum sensing protein) of P. aeruginosa. Overall, our findings revealed the potential synergistic action of cineole and HyPer against biofilm-forming drug-resistant P. aeruginosa. Cineole and HyPer could be used in combination with other bronchodilators as inhalers to control the biofilm-forming drug-resistant P. aeruginosa.

Polyprenylated acylphloroglucinols from Hypericum sampsonii with cytotoxicity against pancreatic carcinomas.

Chemical investigation on the 80% EtOH extract of the air dried aerial parts of Hypericum sampsonii resulted in the isolation of two new polycyclic polyprenylated derivatives, hypersampines A and B (1 and 2). The structures of the new compounds were elucidated by spectroscopic data (NMR, IR, and UV) and high resolution mass analysis. The two isolated polyprenylated acylphloroglucinols were tested in vitro for cytotoxic activities against 6 pancreatic cell lines. As a result, compounds 1 and 2 possessed modest cytotoxic activities against all the tested tumor cell lines with IC50 values less than 40 µM.

[Two new glycosides from Hypericum elatoides].

The column chromatography with silica gel, reversed-phase C_(18), and Sephadex LH-20 was employed to separate the methanol extract of the aerial parts of Hypericum elatoides. The compounds were identified by the comprehensive analysis of IR, NMR, and MS data as methyl 8-O-ß-D-glucopyranosyl-(Z)-5-octenoate(1), methyl 3-O-ß-D-glucopyranosyl-4-methylhexanoate(2), byzantionoside B(3), 9-epi-blumenol C glucoside(4), corchoionoside C(5),(6S,9R)-roseoside(6), cis-p-coumaric acid 4-O-ß-D-glucopyranoside(7), trans-p-coumaric acid 4-O-ß-D-glucopyranoside(8), methyl 3-(4-hydroxyphenyl)propanoate(9),(E)-chlorogenic acid methyl ester(10), quercetin-3-O-ß-D-glucopyranoside(11), ß-sitosterol(12), stigmasterol(13), stigmast-4-en-3-one(14), ß-amyrin(15), daucosterol(16), sitoindoside Ⅰ(17), oleic acid(18), methyl α-linolenate(19), trilinolein(20), and cassipourol(21). Among them, compounds 1 and 2 were identified as new glycosides and named hyperelatosides G and H. Compounds 3-5, 7-9, 17, and 20-21 were isolated from the genus Hypericum for the first time. The remaining compounds were isolated from H. elatoides for the first time. The results of biological assays revealed that compound 11 exhibited significant anti-neuroinflammatory activity, and compounds 1, 3, and 19 displayed certain neuroprotective effects.

Higher thermal plasticity in flowering phenology increases flowering output.

Ongoing climate change poses an increasing threat to biodiversity. To avoid decline or extinction, species need to either adjust or adapt to new environmental conditions or track their climatic niches across space. In sessile organisms such as plants, phenotypic plasticity can help maintain fitness in variable and even novel environmental conditions and is therefore likely to play an important role in allowing them to survive climate change, particularly in the short term. Understanding a species' response to rising temperature is crucial for planning well-targeted and cost-effective conservation measures. We sampled seeds of three Hypericum species (H. maculatum, H. montanum, and H. perforatum), from a total of 23 populations originating from different parts of their native distribution areas in Europe. We grew them under four different temperature regimes in a greenhouse to simulate current and predicted future climatic conditions in the distribution areas. We measured flowering start, flower count, and subsequent seed weight, allowing us to study variations in the thermal plasticity of flowering phenology and its relation to fitness. Our results show that individuals flowered earlier with increasing temperature, while the degree of phenological plasticity varied among species. More specifically, the plasticity of H. maculatum varied depending on population origin, with individuals from the leading range edge being less plastic. Importantly, we show a positive relationship between higher plasticity and increased flower production, indicating adaptive phenological plasticity. The observed connection between plasticity and fitness supports the idea that plasticity may be adaptive. This study underlines the need for information on plasticity for predicting species' potential to thrive under global change and the need for studies on whether higher phenotypic plasticity is currently being selected as natural populations experience a rapidly changing climate.