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.

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.

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.

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.

Hypericum perforatum L. attenuates depression by regulating Akkermansia muciniphila, tryptophan metabolism and NFκB-NLRP2-Caspase1-IL1ß pathway.

BACKGROUND: Gut microbiota dysbiosis significantly contributes to progression of depression. Hypericum perforatum L. (HPL) is traditionally used in Europe for treating depression. However, its mechanism remains largely underexplored. PURPOSE: This study aims to investigate the pivotal gut microbiota species and microbial signaling metabolites associated with the antidepressant effects of HPL. METHODS: Fecal microbiota transplantation was used to assess whether HPL mitigates depression through alterations in gut microbiota. Microbiota and metabolic profiling of control, chronic restraint stress (CRS)-induced depression, and HPL-treated CRS mice were examined using 16S rRNA gene sequencing and metabolomics analysis. The influence of gut microbiota on HPL's antidepressant effects was assessed by metabolite and bacterial intervention experiments. RESULTS: HPL significantly alleviated depression symptoms in a manner dependent on gut microbiota and restored gut microbial composition by enriching Akkermansia muciniphila (AKK). Metabolomic analysis indicated that HPL regulated tryptophan metabolism, reducing kynurenine (KYN) levels derived from microbiota and increasing 5-hydroxytryptophan (5-HTP) levels. Notably, supplementation with KYN activated the NFκB-NLRP2-Caspase1-IL1ß pathway and increased proinflammatory IL1ß in the hippocampus of mice with depression. Interestingly, mono-colonization with AKK notably increased 5-hydroxytryptamine (5-HT) and decreased KYN levels, ameliorating depression symptoms through modulation of the NFκB-NLRP2-Caspase1-IL1ß pathway. CONCLUSIONS: The promising therapeutic role of HPL in treating depression is primarily attributed to its regulation of the NFκB-NLRP2-Caspase1-IL1ß pathway, specifically by targeting AKK and tryptophan metabolites.

Hypericum perforatum-derived exosomes-like nanovesicles for adipose tissue photodynamic therapy.

BACKGROUND: Recent investigations underscore the capacity of photodynamic therapy (PDT) to induce adipocyte apoptosis, thereby mitigating obesity. Nonetheless, extant synthetic photosensitizers manifest limitations that hinder their clinical viability. PURPOSE: In the current study, we used Hypericum perforatum-derived exosomes-like nanovesicles (HPExos) as a novel photosensitizer, and investigated its PDT effects in adipose tissue during obesity. METHOD: HPExos-were administered to high fat diet mice via intraperitoneal injection, followed by targeted irradiation with specialized LED lights. Mass spectrometric analysis was analyzed in adipose tissues. CCK8 assay and Oil Red O staining were used to investigate lipid accumulation in 3T3-L1 cells to clarify adipocyte differentiation. The expression levels of related markers associated with adipogenesis and lipogenesis were assessed by RT-PCR. Apoptosis analysis was performed by TUNEL staining of and western blotting. RESULTS: HPExos combined with PDT accumulated in visceral white adipose tissues results in a reduced body weight and improved insulin sensitivity. HPExos combined with PDT induced apoptosis by driving high levels of ROS. In addition, HPExos combined with PDT significantly downregulated the expression of transcription factors, PPARγ, C/EBPα, and SREBP and lipogenesis protein FABP4 both in vitro and in vivo, associated with a decreased FFA levels. CONCLUSION: These findings suggest that HPExos could act as an effective photosensitizer in regulating glucose hemostasis by inhibiting adipocyte differentiation and lipogenesis, offering a promising approach for obesity treatment.

New polycyclic polyprenylated acylphloroglucinols with antidepressant activities from Hypericum perforatum L.

Six new polycyclic polyprenylated acylphloroglucinols (PPAPs), hyperidiones A-F (1-6), were obtained from Hypericum perforatum L. Their structures were characterized via extensive spectroscopic analyses, the circular dichroism data of the in situ formed [Mo2(OCOCH3)4] complexes, the nuclear magnetic resonance calculation with DP4 + probability analysis, and the calculated electronic circular dichroism (ECD) spectra. Compounds 1-6 are bicyclic polyprenylated acylphloroglucinols with a major bicyclo[3.3.1]nonane-2,4,9-trione skeleton. Notably, compound 1 is a rare PPAP with a hydroperoxy group, and a plausible biosynthetic pathway for 1 was proposed. Compounds 4 and 6 exhibited significant neuroprotective effects under 10 µM against corticosterone (CORT)-injured SH-SY5Y cells. Furthermore, compound 4 demonstrated a noteworthy antidepressant effect at the dose of 5 mg/kg in the tail suspension test (TST) of mice, which was equivalent to 5 mg/kg of fluoxetine. And it potentially exerted an antidepressant effect through the hypothalamic-pituitary-adrenal (HPA) axis.

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.

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.

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. METHODS: 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 168 nm 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.

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.

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.

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.

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.

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.

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.