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.

Design and fabrication of a magnetic nanobiocomposite based on flaxseed mucilage hydrogel and silk fibroin for biomedical and in-vitro hyperthermia applications.

In this research work, a magnetic nanobiocomposite is designed and presented based on the extraction of flaxseed mucilage hydrogel, silk fibroin (SF), and Fe3O4 magnetic nanoparticles (Fe3O4 MNPs). The physiochemical features of magnetic flaxseed mucilage hydrogel/SF nanobiocomposite are evaluated by FT-IR, EDX, FE-SEM, TEM, XRD, VSM, and TG technical analyses. In addition to chemical characterization, given its natural-based composition, the in-vitro cytotoxicity and hemolysis assays are studied and the results are considerable. Following the use of highest concentration of magnetic flaxseed mucilage hydrogel/SF nanobiocomposite (1.75 mg/mL) and the cell viability percentage of two different cell lines including normal HEK293T cells (95.73%, 96.19%) and breast cancer BT549 cells (87.32%, 86.9%) in 2 and 3 days, it can be inferred that this magnetic nanobiocomposite is biocompatible with HEK293T cells and can inhibit the growth of BT549 cell lines. Besides, observing less than 5% of hemolytic effect can confirm its hemocompatibility. Furthermore, the high specific absorption rate value (107.8 W/g) at 200 kHz is generated by a determined concentration of this nanobiocomposite (1 mg/mL). According to these biological assays, this magnetic responsive cytocompatible composite can be contemplated as a high-potent substrate for further biomedical applications like magnetic hyperthermia treatment and tissue engineering.

Natural defense against multi-drug resistant Pseudomonas aeruginosa: Cassia occidentalis L. in vitro and in silico antibacterial activity.

Cassia occidentalis L. is widely used in indigenous and traditional medicine, but its impact on multi-drug resistant (MDR) bacterial infections mostly remains unknown. Therefore, this study aimed to evaluate the in vitro antibacterial efficiency of methanol and ethyl acetate extracts of C. occidentalis L. leaves (MECOL and EAECOL) against multi-drug resistant Pseudomonas aeruginosa and to identify potential antibacterial agents through computational studies targeting the LasR protein. Initially, 82 compounds were identified using GC-MS analysis, and the functional groups were determined through FT-IR analysis. Both extracts of the plant exhibited dose-dependent antibacterial activity, with MICs of 104.16 ± 36.08 µg mL-1 for MECOL and 83.33 ± 36.08 µg mL-1 for EAECOL, and an MBC of 125 µg mL-1. Among the 82 compounds, 12 potential compounds were identified based on binding scores using molecular docking with the LasR protein and MM-GBSA analysis. Furthermore, screening for ADME properties, including physicochemical features, water solubility, lipophilicity, RO5 compliance, and toxicity, identified the top three compounds: methyl dihydrojasmonate, methyl benzoate, and 4a-methyl-4,4a,5,6,7,8-hexahydro-2(3H)-naphthalenone, which also demonstrated binding affinity with the active site residues of the LpxC protein of the bacteria. Additionally, molecular dynamics (MD) simulations confirmed the binding reliability of these three phytochemicals to LasR's active pocket, comparable to the protein native inhibitory ligands (C12-HSL). The study offers scientific support for the traditional use of C. occidentalis in treating bacterial infections, highlighting the potential of the three compounds as leads for developing LasR inhibitors to combat multi-drug resistant P. aeruginosa.

Co-delivery of doxorubicin/sorafenib by DNA-decorated green ZIF-67-based nanocarriers for chemotherapy and hepatocellular carcinoma treatment.

Zeolitic imidazolate framework-67 (ZIF-67) has been decorated with natural biomaterials and DNA to develop a promising strategy and suitable and safe co-delivery platform for doxorubicin and sorafenib (DOX-SOR). FT-IR, XRD, FESEM, and TEM were used to characterize the modified MOFs. Combined Ginkgo biloba leaf extract and E. coli DNA were used as green decorations, and as environmentally-friendly methods to be developed, and DOX and SOR were attached to the porosity and on the surface of the MOFs. TEM and FESEM images demonstrated that the green MOFs were successfully synthesized for biomedical applications and showed their cubic structure. As a result of the nanocarrier-drug interactions, 59.7% and 60.2% of the drug payload were achieved with DOX and SOR, respectively. HEK-293, HT-29, and MCF-7 cells displayed excellent viability by decoration with DNA and Ginkgo biloba leaf extract at low and high concentrations (0.1 and 50 µg/mL), suggesting they could be used in biomedical applications. MTT assays demonstrated that the nanocarriers are highly biocompatible with normal cells and possess anticancer properties when applied to HT-29 and MCF-7 cells. As a result of Ginkgo biloba leaf extract and DNA modification, DOX-SOR release was prolonged and pH-sensitive (highest release at pHs 4.5 and 5.5). The internalization and delivery of the drug were also studied using a 2d fluorescence microscope, demonstrating that the drug was effectively internalized. Cell images showed NPs internalizing in MCF-7 cells, proving their efficacy as drug delivery systems.

Folate-Targeted Curcumin-Loaded Niosomes for Site-Specific Delivery in Breast Cancer Treatment: In Silico and In Vitro Study.

As the most common cancer in women, efforts have been made to develop novel nanomedicine-based therapeutics for breast cancer. In the present study, the in silico curcumin (Cur) properties were investigated, and we found some important drawbacks of Cur. To enhance cancer therapeutics of Cur, three different nonionic surfactants (span 20, 60, and 80) were used to prepare various Cur-loaded niosomes (Nio-Cur). Then, fabricated Nio-Cur were decorated with folic acid (FA) and polyethylene glycol (PEG) for breast cancer suppression. For PEG-FA@Nio-Cur, the gene expression levels of Bax and p53 were higher compared to free drug and Nio-Cur. With PEG-FA-decorated Nio-Cur, levels of Bcl2 were lower than the free drug and Nio-Cur. When MCF7 and 4T1 cell uptake tests of PEG-FA@Nio-Cur and Nio-Cur were investigated, the results showed that the PEG-FA-modified niosomes exhibited the most preponderant endocytosis. In vitro experiments demonstrate that PEG-FA@Nio-Cur is a promising strategy for the delivery of Cur in breast cancer therapy. Breast cancer cells absorbed the prepared nanoformulations and exhibited sustained drug release characteristics.

A Computational Approach Identified Andrographolide as a Potential Drug for Suppressing COVID-19-Induced Cytokine Storm.

BACKGROUND: The newly identified betacoronavirus SARS-CoV-2 is the causative pathogen of the coronavirus disease of 2019 (COVID-19) that killed more than 3.5 million people till now. The cytokine storm induced in severe COVID-19 patients causes hyper-inflammation, is the primary reason for respiratory and multi-organ failure and fatality. This work uses a rational computational strategy to identify the existing drug molecules to target host pathways to reduce the cytokine storm. RESULTS: We used a "host response signature network" consist of 36 genes induced by SARS-CoV-2 infection and associated with cytokine storm. In order to attenuate the cytokine storm, potential drug molecules were searched against "host response signature network". Our study identified that drug molecule andrographolide, naturally present in a medicinal plant Andrographis paniculata, has the potential to bind with crucial proteins to block the TNF-induced NFkB1 signaling pathway responsible for cytokine storm in COVID-19 patients. The molecular docking method showed the binding of andrographolide with TNF and covalent binding with NFkB1 proteins of the TNF signaling pathway. CONCLUSION: We used a rational computational approach to repurpose existing drugs targeting host immunomodulating pathways. Our study suggests that andrographolide could bind with TNF and NFkB1 proteins, block TNF-induced cytokine storm in COVID-19 patients, and warrant further experimental validation.

Evaluation of vegetables and fish oils for the attenuation of diabetes complications.

The present study was accomplished to examine and compare the effect of specific antioxidant-rich oils on hyperglycemia, dyslipidemia, renal function markers and oxidative renal damage in diabetic rats for four weeks. Papaya (P), olive (O), fenugreek (Fe), bitter gourd (B) and fish (Fi) oils were used for this purpose. Streptozotocin (STZ) was injected intraperitoneally in a single dose to induce diabetes. All oils were given orally at a dose of 3g/kg for four weeks in respective group after induction of diabetes. After treatment with oils, blood was collected, and their kidneys were stored. The level of fasting blood glucose (FBG), glycated hemoglobin (HbA1c), total cholesterol (TC), triglycerides (TG), low-density lipoprotein-cholesterol (LDL-C) and very low-density lipoprotein-cholesterol (VLDL-C) increased while amylase and high-density lipoprotein cholesterol (HDL-C) level decreased in the diabetic rats. These changes were augmented by fenugreek, bitter gourd and olive oils treatment. Diabetic rats showed elevated renal function markers in serum, including, serum creatinine (Scr), blood urea nitrogen (BUN) and alkaline phosphatase (ALP), which were restrained significantly by fenugreek and bitter gourd oil treatment. Moreover, fenugreek and bitter gourd oils treatment significantly modulated the level of thiobarbituric reactive substances (TBARS), malonaldehyde (MDA) and catalase (CAT) in the kidney of diabetic rats. The histopathological examination also showed the protective effect of these oils. The study suggests that vegetable oils are effective in reducing hyperglycemia, dyslipidemia and renal damage related to the side effects of diabetes. Thus they may have therapeutic value for preventing diabetes side effects and may be included in oil diet treatment synergically. Thus, our data suggest that oils as potent antidiabetic agent and beneficial in the control of diabetes-related abnormalities such as hyperglycemia, dyslipidemia and renal damage of STZ induced rat model of type 2 diabetes. Our study also supports the suggestion that synergistic possibilities exist concerning the use of these oils in the treatment of diabetes mellitus.

Plumbagin, a plant derived natural agent inhibits the growth of pancreatic cancer cells in in vitro and in vivo via targeting EGFR, Stat3 and NF-κB signaling pathways.

Pancreatic cancer (PC) is the most aggressive malignant disease, ranks as the fourth most leading cause of cancer-related death among men and women in the United States. We present here that plumbagin (PL), a quinoid constituent isolated from the roots of the medicinal plant Plumbago zeylanica L, inhibits the growth of PC cells both in vitro and in vivo model systems. PL treatment induces apoptosis and inhibits cell viability of PC cells (PANC1, BxPC3 and ASPC1). In addition, i.p. administration of PL (2 mg/kg body weight, 5 days a week) in severe combined immunodeficiency (SCID) mice beginning 3 days after ectopic implantation of PANC1 cells resulted in a significant (P < 0.01) inhibition of both tumor weight and volume. PL treatment inhibited (1) constitutive expression of epidermal growth factor receptor (EGFR), pStat3Tyr705 and pStat3Ser727, (2) DNA binding of Stat3 and (3) physical interaction of EGFR with Stat3, in both cultured PANC1 cells and their xenograft tumors. PL treatment also inhibited phosphorylation and DNA-binding activity of NF-κB in both cultured PC cells (PANC1 and ASPC1) and in PANC1 cells xenograft tumors. Downstream target genes (cyclin D1, MMP9 and Survivin) of Stat3 and NF-κB were similarly inhibited. These results suggest that PL may be used as a novel therapeutic agent against human PC. Published 2012 Wiley-Liss, Inc. This article is a US Government work, and, as such, is in the public domain in the United States of America.

Plumbagin (5-hydroxy-2-methyl-1,4-naphthoquinone), isolated from Plumbago zeylanica, inhibits ultraviolet radiation-induced development of squamous cell carcinomas.

Plumbagin (PL) (5-hydroxy-2-methyl-1,4-napthoquinone), a medicinal plant-derived naphthoquinone, was isolated from the roots of the Plumbago zeylanica L. (also known as Chitrak). The roots of P. zeylanica L. have been used in Indian medicine for >2500 years as an anti-atherogenic, cardiotonic, hepatoprotective and neuroprotective agent. We present here that topical application of non-toxic doses (100-500 nmol) of PL to skin elicits dose-dependent inhibition of ultraviolet radiation (UVR)-induced development of squamous cell carcinomas (SCC). In this experiment, FVB/N mice were exposed to UVR (2 kJ/m(2)) three times weekly from a bank of six Kodacel-filtered FS40 sunlamps (∼ 60% UVB and 40% UVA). Carcinoma incidence in mice treated with vehicle, 100, 200 or 500 nmol PL, at 44 weeks post-UVR, were 86, 80 (P = 0.67), 53 (P = 0.12) and 7% (P = 0.0075), respectively. Both vehicle and PL-treated mice gained weight and did not exhibit any signs of toxicity during the entire period of the experiment. Molecular mechanisms associated with inhibition of UVR-induced development of SCC involved induction of apoptosis and inhibition of cell proliferation. Specific findings are that PL treatment (i) inhibited UVR-induced DNA binding of activating protein-1, nuclear factor-kappaB, Stat3 transcription factors and Stat3-regulated molecules (cdc25A and Survivin); (ii) inhibited protein levels of pERK1/2, PI3K85, pAKTSer473, Bcl(2), BclxL, proliferating cell nuclear antigen and cell cycle inhibitory proteins p27 and p21 and (iii) increased UVR-induced Fas-associated death domain expression, poly (ADP-ribose) polymerase protein cleavage and Bax/Bcl(2) ratio. Taken together, our findings suggest that PL may be a novel agent for the prevention of skin cancer.

The spectrum of colovesical fistula and diagnostic paradigm.

BACKGROUND: Our experience with colovesical fistula (CVF) over a 12-year period was reviewed to clarify its clinical presentation and diagnostic confirmation. METHODS: Twelve patients with CVF were identified. Presenting symptoms, etiologic factors, diagnostic investigations, and subsequent treatment were reviewed. RESULTS: Underlying etiologies were diverticular disease (75%), colon cancer (16%), and bladder cancer (8%). Pneumaturia (77%) was the most common presentation, followed by urinary tract infections, dysuria and frequency (45%), fecaluria (36%), hematuria (22%), and orchitis (10%). The ability of various preoperative investigations to identify a CVF were: computed tomography (CT) (90%), barium enema (BE) (20%), and cystography (11%), whereas cystoscopy, intravenous pyelogram (IVP), and colonoscopy were nondiagnostic. All patients underwent single- or multiple-staged repair of the fistula. CONCLUSIONS: In patients with a suspected CVF, we recommend CT followed by a colonoscopy as a first-line investigation to rule out malignancy as a cause of CVF. Other modalities should only be used if the diagnosis is in doubt or additional information is needed to plan operative management.