Hypericum Perforatum Research Articles

Characterization of NR1J1 Paralog Responses of Marine Mussels: Insights from Toxins and Natural Activators.

The pregnane X receptor (PXR) is a nuclear hormone receptor that plays a pivotal role in regulating gene expression in response to various ligands, particularly xenobiotics. In this context, the aim of this study was to shed light on the ligand affinity and functions of four NR1J1 paralogs identified in the marine mussel Mytilus galloprovincialis, employing a dual-luciferase reporter assay. To achieve this, the activation patterns of these paralogs in response to various toxins, including freshwater cyanotoxins (Anatoxin-a, Cylindrospermopsin, and Microcystin-LR, -RR, and -YR) and marine algal toxins (Nodularin, Saxitoxin, and Tetrodotoxin), alongside natural compounds (Saint John's Wort, Ursolic Acid, and 8-Methoxypsoralene) and microalgal extracts (Tetraselmis, Isochrysis, LEGE 95046, and LEGE 91351 extracts), were studied. The investigation revealed nuanced differences in paralog response patterns, highlighting the remarkable sensitivity of MgaNR1J1γ and MgaNR1J1δ paralogs to several toxins. In conclusion, this study sheds light on the intricate mechanisms of xenobiotic metabolism and detoxification, particularly focusing on the role of marine mussel NR1J1 in responding to a diverse array of compounds. Furthermore, comparative analysis with human PXR revealed potential species-specific adaptations in detoxification mechanisms, suggesting evolutionary implications. These findings deepen our understanding of PXR-mediated metabolism mechanisms, offering insights into environmental monitoring and evolutionary biology research.

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.

Determination of Antimicrobial, Anticarcinogenic Activity of Bioactive Components of Hypericum Perforatum L. Plant

Hypericum perforatum L. (St John's wort), although primarily utilized in traditional medicine, is also frequently employed in modern therapy. Within the scope of the study, H. perforatum was collected from Kahramanmaraş region and dried. Extracts derived from above-ground parts were analyzed to determine their levels of total phenolic and flavonoid compounds, as well as their antioxidant, anticancer and antimicrobial properties. Following the GC-MS analysis of the extracts, a total of 18 distinct fatty acids were identified. The main fatty acid components were identified as behenic (37.90 %), linoleic (21.22 %), gamma-linolenic (15.87 %), oleic (9.45 %) and palmitic acid (7.64 %). The plant extracts were found to have a total phenolic content of 60.22 mg GAE g-1 and a flavonoid content of 7.68 µg QE g-1, as determined through analysis. Additionally, FRAP and IC50 values were determined as 26.96 µg AAE g-1 and 0.44 µg mL-1, respectively. The antimicrobial activities of H. perforatum extracts were investigated among a total of 11 microorganisms, including 9 bacteria and 2 yeasts. It has been observed that extracts possess significant antimicrobial activity against all tested microorganisms. H. perforatum extracts were observed to have dose-dependent inhibition of all organisms. It was observed that H. perforatum extracts killed cancer cells at concentrations of 0.1 mg mL-1 and above on H1299, MCF-7 and HUVEC cancer cell lines.

In silico prediction of polyketide biosynthetic gene clusters in the genomes of Hypericum-borne endophytic fungi

BackgroundThe search for new bioactive natural compounds with anticancer activity is still of great importance. Even though their potential for diagnostics and treatment of cancer has already been proved, the availability is still limited. Hypericin, a naphthodianthrone isolated essentially from plant source Hypericum perforatum L. along with other related anthraquinones and bisanthraquinones belongs to this group of compounds. Although it has been proven that hypericin is synthesized by the polyketide pathway in plants, none of the candidate genes coding for key enzymes has been experimentally validated yet. Despite the rare occurrence of anthraquinones in plants, their presence in microorganisms, including endophytic fungi, is quite common. Unlike plants, several biosynthetic genes grouped into clusters (BGCs) in fungal endophytes have already been characterized.ResultsThe aim of this work was to predict, identify and characterize the anthraquinone BGCs in de novo assembled and functionally annotated genomes of selected endophytic fungal isolates (Fusarium oxysporum, Plectosphaerella cucumerina, Scedosporium apiospermum, Diaporthe eres, Canariomyces subthermophilus) obtained from different tissues of Hypericum spp. The number of predicted type I polyketide synthase (PKS) BGCs in the studied genomes varied. The non-reducing type I PKS lacking thioesterase domain and adjacent discrete gene encoding protein with product release function were identified only in the genomes of C. subthermophilus and D. eres. A candidate bisanthraquinone BGC was predicted in C. subthermophilus genome and comprised genes coding the enzymes that catalyze formation of the basic anthraquinone skeleton (PKS, metallo-beta-lactamase, decarboxylase, anthrone oxygenase), putative dimerization enzyme (cytochrome P450 monooxygenase), other tailoring enzymes (oxidoreductase, dehydrogenase/reductase), and non-catalytic proteins (fungal transcription factor, transporter protein).ConclusionsThe results provide an insight into genetic background of anthraquinone biosynthesis in Hypericum-borne endophytes. The predicted bisanthraquinone gene cluster represents a basis for functional validation of the candidate biosynthetic genes in a simple eukaryotic system as a prospective biotechnological alternative for production of hypericin and related bioactive anthraquinones.

Hypericin Alleviates Chronic Kidney Disease-induced Left Ventricular Hypertrophy by Regulation of FGF23-FGFR4 Signaling Pathway.

Chronic kidney disease (CKD) is a significant global health threat that imposes a substantial burden on both individuals and societies. CKD frequently correlates with cardiovascular events, particularly left ventricular hypertrophy (LVH), which contributes to the high mortality rate associated with CKD. Fibroblast growth factor 23 (FGF23), a hormone primarily involved in regulating calcium and phosphorus metabolism, has been identified as a major risk factor for LVH in CKD patients. Elevated serum FGF23 levels are known to induce LVH and myocardial fibrosis by activating the fibroblast growth factor receptor 4 (FGFR4) signal pathway. Therefore, targeting FGFR4 and its downstream signaling pathways holds potential as a treatment strategy for cardiac dysfunction in CKD. In our current study, we have discovered that Hypericin, a key component derived from Hypericum perforatum , has the ability to alleviate CKD-related LVH by targeting the FGFR4/phospholipase C gamma 1 (PLCγ1) signaling pathway. Through in vitro experiments using rat cardiac myocyte H9c2 cells, we observed that Hypericin effectively inhibits FGF23-induced hypertrophy and fibrosis by suppressing the FGFR4/PLCγ1/calcineurin/nuclear factor of activated T-cell (NFAT3) signaling pathway. In addition, our in vivo studies using mice on a high-phosphate diet and rat models of 5/6 nephrectomy demonstrated that Hypericin has therapeutic effects against CKD-induced LVH by modulating the FGFR4/PLCγ1/calcineurin/NFAT3 signaling pathway. In conclusion, our research highlights the potential of Hypericin as a candidate for the treatment of CKD-induced cardiomyopathy. By suppressing the FGFR4/PLCγ1 signaling pathway, Hypericin shows promise in attenuating LVH and myocardial fibrosis associated with CKD.

Investigation of the use of cobalt and nickel based nanoalloys as cement mortar additives

The usage potential of chemical and green synthesized cobalt (Co) and nickel (Ni) nanoalloys (CoNiNAs) as mortar additives at different ratios was evaluated. The CoCl2 and NiCl2 metallic salt solutions were mixed in volume ratios of 1-1, 1-2, and 2-1 and reduced with NaBH4 and St. John's Wort aqueous extract, respectively. The obtained Co-Ni based complex nanoalloys were analyzed by Ultraviolet-Visible Spectroscopy (UV-Vis), X-Ray Diffraction Analysis (XRD), Field Emission Scanning Electron Microscopy (FE-SEM), Fourier Transform Infrared Spectroscopy (FT-IR), and Dynamic Light Scattering Particle Size Analyzer (DLS). The effect of CoNiNAs was investigated based on the amount used in mortar, flexural and compressive strengths of mortar, setting time retarder properties, and carbonation depth measurements of mortars and nanoalloy form based on whether they were solid (chemical synthesise) or liquid (green synthesise). The results revealed that the chemical synthesized CoNiNAs were amorphous metal-metal-oxide complexes with small spherical particles and a low dispersity index, whereas the green synthesized complexes had a more crystalline structure and smaller sizes. The mortar properties were affected by Co and Ni synthesis ratios and addition amounts. The incorporation of CoNiNAs led to an increase in the setting times of mortar. Furthermore, the ‘CN’ 2% sample exhibited the highest compression (49.10±1.19 MPa) and flexural (8.19±0.20 MPa) strengths. In addition, the ‘CN2’ 1% sample exhibited the lowest carbonation depth (2.95±0.35 mm) compared to other samples. Overall, mortars with CoNiNAs additives may be used in high temperature environments, and long shipment times require remote locations due to setting time retarder effect without losing necessary physical properties.

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

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. 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). 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). 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.

Regulation of carbohydrate metabolism and insulin secretion in diabetic rats following treatment with Hypericum perforatum L. hairy root aqueous methanol extract

Hairy root (HR) cultures of Hypericum perforatum L. have shown promise in controlling hyperglycemia, regulating blood lipid and enzyme profiles, and improving metabolic function in vivo. These benefits are mainly attributed to the phenolic acids, flavonoids, and xanthones present in HR extracts. However, the specific mechanism underlying these effects remains unclear. This study was performed to elucidate the biochemical and molecular mechanisms driving HR the antihyperglycemic and antidiabetic effects of HR extracts. HR extract (200 mg/kg body weight) was administered daily for 14 days to healthy rats and rats with streptozotocin-induced diabetes, with glibenclamide serving as a positive control. The phenolic composition of the HR extracts was confirmed through high-performance liquid chromatography/diode array detection/electrospray ionization mass spectrometry (HPLC/DAD/ESI-MSn ) analysis. The results showed that HR extract treatment increased the plasma insulin level and pancreatic poly (adenosine diphosphate-ribose) polymerase (PARP) activity in diabetic rats, thus normalizing blood glucose levels. Additionally, it reduced the activity of gluconeogenic enzymes, increased the activity of glycolytic enzymes, and normalized the glycogen content in the liver. HR extract-treated rats also exhibited increased hepatic adenosine monophosphate-activated protein kinase (AMPK) mRNA expression and a decreased protein kinase Cε (PKCε) concentration. In conclusion, HR extract demonstrated insulinotropic effects and effectively regulated hepatic carbohydrate metabolism in diabetic rats by modulating AMPK expression and the PKCε concentration. These findings suggest the potential use of HR extract as an herbal medicine for diabetes treatment and a source of antidiabetic drug development.

Tissue Regeneration and Remodeling in Rat Models after Application of Hypericum perforatum L. Extract-Loaded Bigels.

The wound-healing effect of St. John's Wort (SJW) is mainly attributed to hyperforin (HP), but its low stability restricts its topical administration. This study investigates how "free" HP-rich SJW extract (incorporated into a bigel; B/SJW) and extract "protected" by nanostructured lipid carriers (also included in a biphasic semisolid; B/NLC-SJW) affect tissue regeneration in a rat skin excision wound model. Wound diameter, histological changes, and tissue gene expression levels of fibronectin (Fn), matrix metalloproteinase 8 (MMP8), and tumor necrosis factor-alpha (TNF-α) were employed to quantify the healing progress. A significant wound size reduction was achieved after applying both extract-containing semisolids, but after a 21-day application period, the smallest wound size was observed in the B/NLC-SJW-treated animals. However, the inflammatory response was affected more favorably by the bigel containing the "free" SJW extract, as evidenced by histological studies. Moreover, after the application of B/SJW, the expression of Fn, MMP8, and TNF-α was significantly higher than in the positive control. In conclusion, both bigel formulations exhibited beneficial effects on wound healing in rat skin, but B/SJW affected skin restoration processes in a comprehensive and more efficient way.

Fabrication of a Biocompatible Nanoantimicrobial Suture for Rapid Wound Healing after Surgery.

Suture-associated infections on surgical sites are known to be related to the surface characteristics of the sutures. The present study aimed to fabricate a novel functional suture for surgical procedures and characterize its antioxidative, antimicrobial, and in vitro wound healing properties. St John's wort, Hypericum perforatum, extract (eHp), and biogenic silver nanoparticles (AgNPs) have been combined and used for coating the silk sutures. Antioxidant, antimicrobial capacity, and in vitro wound healing potential of the coated sutures have been examined. The morphological and microanalytical examination of the coated sutures was also performed by scanning electron microscopy (SEM) and energy-dispersive X-ray spectroscopy (EDS). According to the antioxidant activity tests, free radical scavenging and β-carotene linoleic acid tests revealed that the antioxidative potential of H. perforatum extract-AgNP combination (eHp-AgNP) at 10 mg/mL concentration was higher than those of positive controls, ascorbic acid and α-tocopherol. Coating the sutures with eHp-AgNP resulted in a remarkable inhibition activity of the sutures against Staphylococcus aureus, which is a pathogenic member of human microbiota. When compared with the control groups, it was investigated that coating the sutures with eHp-AgNP stimulated the cell migration of the fibroblasts to heal the artificial wound. Due to their beneficial effects, the eHp-AgNP-coated silk sutures might be a potential antibacterial and wound healing accelerator for surgical approaches.

Assessment of Undergraduate Nursing Students' Understanding of Herbal Medicines and Herb-Drug Interactions in Riyadh, Saudi Arabia.

BACKGROUND The use of herbal medicines (HMs) is increasing, which raises concerns of herb-drug interactions (HDIs). This questionnaire-based study aimed to evaluate knowledge of HMs and HDIs in 147 undergraduate nursing students in Riyadh, Saudi Arabia, between March 2022 to June 2022. MATERIAL AND METHODS An online cross-sectional study was conducted among 147 nursing undergraduates at King Saud University, Riyadh, Saudi Arabia from March 2022 to June 2022, using a self-administered 24-item questionnaire. The convenience sampling method was used to evaluate the knowledge of HMs and interactions of anticoagulants, anti-inflammatory drugs, antibiotics, and antiplatelet drugs with herbs like ginkgo biloba, St. John's wort, garlic, ginger, green tea, and chamomile tea. RESULTS The findings of this study reported that 74.8% of the undergraduates used HMs. With regard to HDIs, 20.4% of nursing undergraduates identified the interaction between gingko biloba and drugs like ibuprofen and warfarin, while 13.6% identified interactions between drugs like warfarin with green tea, ginger, and chamomile tea. Regarding general knowledge, 59% of the students (n=84) reported good knowledge of HMs. Previous history of HM use significantly affected the mean HM knowledge score (t=4.635; P=0.0001). CONCLUSIONS To summarize, Saudi nursing students showed a lack of understanding and knowledge of HDIs. Ability to identify specific HDIs, like ginkgo biloba interactions with warfarin and ibuprofen, and warfarin interactions with green tea and ginger, was limited. There is a need to introduce HM and HDI courses in the academic curriculum.

Assessment of the content of biologically active substances in Hypericum perforatum along an altitude gradient

An assessment of the content of flavonoids in the herb St. John’s wort, selected in natural phytocoenosis along an altitudinal gradient, is presented. We used generally accepted methods described in the relevant manuals when conducting research. The material for the study was air-dried samples of the aerial parts of St. John’s wort (Hypericum perforatum) collected at different altitudes. The features of the accumulation of flavonoids (leucoanthocyanins, catechins, flavonols) and the amount of anthracene derivatives in the herb St. John’s wort (Hypericum perforatum) in the phase of mass flowering along an altitudinal gradient were studied. It has been shown that an increased level of anthracene derivatives (in terms of hypericin) is observed at altitudes of 615 - 716 m above sea level. The amount of anthracene derivatives (in terms of hypericin) significantly decreases along the altitudinal gradient. The content of catechins in samples taken along the altitudinal gradient varies within 0.17 - 0.36 mg%. It has been established that plants selected at different altitudes from 615 to 2025 m above sea level are characterized by other content of flavonoids. The samples in the altitude range 615 - 716 m above sea level have the maximum content. The plants selected in the vicinity of the village had the best characteristics for the accumulation of the mass fraction of flavonols. Makhchesk, Irafsky district of the Republic of North Ossetia - Alania, in coenopopulations of a cereal-forb meadow at 1340 m above sea level. Thickets of Hypericum perforatum are found on slopes of southern and southeastern exposure.

Optimization of Hypericum Perforatum Microencapsulation Process by Spray Drying Method

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

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.

IDENTIFICATION AND QUANTIFICATION OF FLAVONOIDS IN MEDICINAL PLANTS GROWING IN THE REPUBLIC OF UZBEKISTAN

Introduction. In recent years, the popularity of herbal medicine has been increasing. One of the most numerous classes of biologically active substances of plant origin are flavonoids, which have a wide range of biological activities: anticarcinogenic, antioxidant, antimicrobial, neuroprotective, immunomodulatory, hepatoprotective effects, and also capable of stimulating the damaged body tissues regeneration processes. The relevant area of the research is the search for medicinal plants with a high content of flavonoids for the development of herbal remedies with wound-healing activity. This problem can be solved through the use of plant raw materials from the Republic of Uzbekistan, which have a high content and a wide range of biologically active substances, thanks to the sharply continental climate of the country with consistently hot summers and increased levels of ultraviolet radiation. The purpose of the research is to select medicinal plant raw materials as a source of flavonoids for the development of wound healing agents. Material and methods. The object of the study was medicinal plant raw materials harvested on the territory of the Republic of Uzbekistan: oregano herb, sage leaves, St. John's wort herb, sandy everlasting flowers, bur beggar-ticks herb. Identification and quantification of flavonoids in the studied samples of medicinal plants was carried out using thin-layer chromatography, absorption spectrophotometry in the visible region using reaction with aluminum chloride and high-performance liquid chromatography-mass spectrometry. Results. It has been established that the content of flavonoids in the herb of oregano, leaves of medicinal sage, St. John's wort herb, flowers of sandy everlasting, harvested in the Republic of Uzbekistan, is significantly higher than in medicinal plant materials harvested in the territory of the Republic of Belarus and the Russian Federation. Using the method of thin-layer chromatography and high-performance liquid chromatography-mass spectrometry, kaempferol-3-β-D-glucopyranoside was identified in the extract of sandy everlasting flowers, and isoquercitrin was identified in the extract of St. John's wort herb. Conclusions. As a result of the research, sandy everlasting and St. John's wort, growing on the territory of the Republic of Uzbekistan, were selected as the sources of flavonoids (glycoside kaempferol and isoquercitrin) with regenerating properties for the development of wound healing agents.

St. John's wort extract with a high hyperforin content does not induce P-glycoprotein activity at the human blood-brain barrier.

St. John's wort (SJW) extract, a herbal medicine with antidepressant effects, is a potent inducer of intestinal and/or hepatic cytochrome P450 (CYP) enzymes and P-glycoprotein (P-gp), which can cause clinically relevant drug interactions. It is currently not known whether SJW can also induce P-gp activity at the human blood-brain barrier (BBB), which may potentially lead to decreased brain exposure and efficacy of certain central nervous system (CNS)-targeted P-gp substrate drugs. In this study, we used a combination of positron emission tomography (PET) imaging and cocktail phenotyping to gain a comprehensive picture on the effect of SJW on central and peripheral P-gp and CYP activities. Before and after treatment of healthy volunteers (n = 10) with SJW extract with a high hyperforin content (3-6%) for 12-19 days (1800 mg/day), the activity of P-gp at the BBB was assessed by means of PET imaging with the P-gp substrate [11C]metoclopramide and the activity of peripheral P-gp and CYPs was assessed by administering a low-dose phenotyping cocktail (caffeine, omeprazole, dextromethorphan, and midazolam or fexofenadine). SJW significantly increased peripheral P-gp, CYP3A, and CYP2C19 activity. Conversely, no significant changes in the peripheral metabolism, brain distribution, and P-gp-mediated efflux of [11C]metoclopramide across the BBB were observed following the treatment with SJW extract. Our data suggest that SJW does not lead to significant P-gp induction at the human BBB despite its ability to induce peripheral P-gp and CYPs. Simultaneous intake of SJW with CNS-targeted P-gp substrate drugs is not expected to lead to P-gp-mediated drug interactions at the BBB.

Acute Toxicity and Hepatoprotective Influence of Hypericum perforatum Against Thioactamid-Induced Liver Fibrosis in Rats

Background: Hypericum perforatum (MEHP) is a broadly used therapeutic plant exhibiting numerous bioactivities. The present study evaluates acute toxicity and hepatoprotective effects of MEHP against thioacetamide (TAA)-induced liver injury in rats. Methods: The toxicity trial included a single oral administration of 2000 and 5000 mg/kg to rats. In the hepatoprotective experiment, 30 adult rats were arbitrarily clustered into 5 groups: Normal (A) and TAA control rats (B) treated with daily distilled water; reference rats received 3 oral doses/week of 50 mg/kg silymarin; D and E, rats received daily doses of 250 and 500 mg/kg MEHP, respectively. In addition, group B-E received 3 injections of 200 mg/kg TAA in a week for 60 days. Results: The results have shown a lack of any toxic signs in rats following oral administration of up to 5000 mg/kg. The hepatoprotective evaluations revealed a noticeably lower hepatic injury in MEHP-treated rats shown by reduced liver index and hepatocyte proliferation. Histopathological evaluation (H&E and Masson trichrome stains) showed a significant inhibitory potential of MEHP on the incidence rate of hepatic lesions represented by decreased liver necrosis and lower fibrous connective tissue proliferation initiated by TAA in rats. MEHP treatment meaningfully decreased proliferating cell nuclear antigen and α-SMA (myofibroblasts) in liver parenchymal tissues as well as improved redox (up-regulated SOD, CAT, GPx, and down-regulated MDA) and inflammatory state (decreased serum TNF-α and IL-6 cytokines) compared to fibrosis control rats. In addition, MEHP treatment caused significant restoration of serum liver biomarkers (enzymes and proteins) against TAA-induced hepatotoxicity. Conclusion: The present hepatoprotectives of MEHP could be attributed to its chemical contents (hypericin, hyperforin, quercitrin, and p-coumaric acid) that may validate it as a therapeutic additive for liver fibrosis after some pharmacological evaluations.

St. John's wort extract Ze 117 alters the membrane fluidity of C6 glioma cells by influencing cellular cholesterol metabolism

Chronic stress is associated with major depressive disorder (MDD). Increased glucocorticoid levels caused by uncontrolled release through the hypothalamic‒pituitary‒adrenal (HPA) axis can cause changes in the lipid content of the cellular plasma membrane. These changes are suspected to be involved in the development of depressive disorders. St. John's wort extract (SJW) Ze 117 has long been used as an alternative to synthetic antidepressants. Part of its effect may be due to an effect on the cellular lipid composition and thus on the properties of plasma membranes and receptor systems embedded therein. In this study, we investigated the effect of Ze 117 on that of dexamethasone and simvastatin. Dexamethasone increases the fluidity of C6 cell plasma membranes. This effect is counteracted by administration of Ze 117. Here we demonstrate that this is not due to a change in C16:1/16:0 and C18:1/18:0 ratios in C6 cell fatty acids. On the other hand, Ze 117 increased the cellular cholesterol content by 42.5%, whereas dexamethasone reduced cholesterol levels similarly to simvastatin. Lowering cholesterol levels by dexamethasone or simvastatin resulted in decreased β-arrestin 2 recruitment to the 5-HT1a receptor. This effect was counterbalanced by Ze 117, whereas the SJW extract had little effect on β-arrestin 2 recruitment in non-stressed cells. Taken together, in C6 cells, Ze 117 induces changes in membrane fluidity through its effect on cellular cholesterol metabolism rather than by affecting fatty acid saturation. This effect is reflected in an altered signal transduction of the 5-HT1a receptor under Ze 117 administration. The current in vitro results support the hypothesis that Ze 117 addresses relevant parts of the cellular lipid metabolism, possibly explaining some of the antidepressant actions of Ze 117.

Imperforate St. John's-Wort (Hypericum maculatum subsp. obtusiusculum): A New Overlooked Nonnative Forb for Eastern North America

Imperforate St. John's-Wort (Hypericum maculatum subsp. obtusiusculum): A New Overlooked Nonnative Forb for Eastern North America

Exploring the Biochemical Profiles of Medicinal Plants Cultivated Under Stressful Environmental Conditions

The therapeutic potential of medicinal plants, attributed to diverse bioactive chemicals, is impacted by dynamic metabolic changes under environmental stressors such as salt, drought, and heavy metal exposure. This study aimed to elucidate the biochemical alterations in stressed medicinal plants and their implications for therapeutic qualities. Two groups of plants were compared: one cultivated in optimal conditions, serving as a control, and the other exposed to stressors mimicking real-world scenarios. Biochemical parameters, including total phenolic content, flavonoids, antioxidant activity, and specific secondary metabolites, were assessed using established analytical methods. In a case study involving Aloe vera under elevated soil salinity, a significant decrease in total phenolic content and antioxidant activity was observed. Surprisingly, aloin, an anti-inflammatory bioactive compound, exhibited notable upregulation. Stress-induced biochemical variations in medicinal plants differed significantly from those in ideal conditions, demonstrating adaptive responses, including modulation of secondary metabolite synthesis. While certain stresses led to an overall decrease in secondary metabolites, specific instances showed an overexpression of beneficial chemicals. Exploring drought stress in Lavandula angustifolia (lavender), Vitis vinifera, and Artemisia tridentata, revealed a marked reduction in flavonoids and specific secondary metabolites. The study aimed to establish connections between metabolic alterations and stress-adaptive reactions. The findings contribute to understanding how environmental stress influences the therapeutic efficacy of medicinal plants and shed light on the molecular pathways governing stress-induced changes. In the investigation of heavy metal exposure, Hypericum perforatum, and Coriandrum sativum subjected to cadmium-contaminated soil exhibited an overall decline in secondary metabolites, including reduced hypericin content. Contrarily, hyperforin, linked to antidepressant properties, experienced a significant increase. These results have implications for pharmaceutical applications, sustainable farming practices, and the conservation of medicinal plant biodiversity amidst changing environmental dynamics. The study underscores the intricate relationship between environmental stressors and the biochemical makeup of medicinal plants, emphasizing their resilience and capacity to produce valuable bioactive molecules in challenging conditions. The comparative biochemical analysis of stressed medicinal plants involves assessing various parameters to comprehend how stress influences plant metabolism and bioactive compound production.