Suppress the cell growth of cancer stem-like cells (NTERA-2) using Sox2-Oct4 decoy oligodeoxynucleotide-encapsulated niosomes-zinc hybrid nanocarriers under X-irradiation.

Sox2 and Oct4 dysregulations could significantly increase in the cancer stem cell (CSC) population in some cancer cells and resistance to common treatments. In this study, the synergistic effects of Sox2-Oct4 decoy oligodeoxynucleotides-encapsulated Niosomes-zinc hybrid nanocarriers along with X-irradiation conditions as a combinational therapy tool were investigated in the treatment of cancer-like stem cells (NTERA-2). The NTERA-2 cell line known as a cancer-like stem cell line was used in this investigation. Sox2-Oct4 decoy oligodeoxynucleotides were designed based on the sequence of the Sox2 promoter and synthesized. Physicochemical characteristics of ODNs-encapsulated niosomes-zinc hybrid nanocarriers (NISM@BSA-DEC-Zn) investigated with FT-IR, DLS, FESEM, and ODNs release kinetic estimation assays. Further investigations such as hemolysis, uptake, cell viability, apoptosis, cell cycle, and scratch repair tests were performed. All the above assays were completed with and without X-ray exposure conditions (fractionated 2Gy). Physicochemical characteristics results showed that the Niosomes-Zn nanocarriers were successfully synthesized. NISM@BSA-DEC-Zn was efficiently taken up by NTERA-2 cells and significantly inhibited cell growth, increased apoptosis, and reduced cell migration in both conditions (with and without X-ray exposure). Furthermore, NISM@BSA-DEC-Zn treatment resulted in G1 and G2/M cell cycle arrest without and with X-irradiation, respectively. The prepared nanocarrier system can be a promising tool for drug delivery in cancer treatment. Decoy ODN strategy along with zinc nanoparticles could increase the sensitivity of cancer cells toward irradiation, which has the potential for combinational cancer therapies.

Photothermal and radiotherapy with alginate-coated gold nanoparticles for breast cancer treatment.

Radiation therapy and phototherapy are commonly used cancer treatments that offer advantages such as a low risk of adverse effects and the ability to target cancer cells while sparing healthy tissue. A promising strategy for cancer treatment involves using nanoparticles (NPs) in combination with radiation and photothermal therapy to target cancer cells and improve treatment efficacy. The synthesis of gold NPs (AuNPs) for use in biomedical applications has traditionally involved toxic reducing agents. Here we harnessed dopamine (DA)-conjugated alginate (Alg) for the facile and green synthesis of Au NPs (Au@Alg-DA NPs). Alg-DA conjugate reduced Au ions, simultaneously stabilized the resulting AuNPs, and prevented aggregation, resulting in particles with a narrow size distribution and improved stability. Injectable Au@Alg-DA NPs significantly promoted ROS generation in 4T1 breast cancer cells when exposed to X-rays. In addition, their administration raised the temperature under a light excitation of 808 nm, thus helping to destroy cancer cells more effectively. Importantly, no substantial cytotoxicity was detected in our Au@Alg-DA NPs. Taken together, our work provides a promising route to obtain an injectable combined radio enhancer and photothermally active nanosystem for further potential clinic translation.

The role of gender differences in the outcome of juvenile social isolation: Emphasis on changes in behavioral, biochemical and expression of nitric oxide synthase genes alteration.

Social isolation can cause serious problem in performance of individuals in community. As gender differences may cause variation results in the severity of depressive behavior and response of patients to therapy, the impact of gender and the interaction of the level of endocrine secretion in depression were investigated in this study. Wistar rats of both sexes were subjected to post-weaning social isolation (PWSI) conditions and, together with the control group, experienced several behavioral tests including open-field Test (OFT), elevated plus maze (EPM), force swimming test (FST), splash test and novel object recognition test (NOR). Hippocampal tissue was isolated to measure biochemical factors such as nitric oxide level, FRAP amount, MDA level. In addition, real-time-PCR test was used to quantify the genes expression level of inducible nitric oxide synthase (iNOS) and neuronal nitric oxide synthase (nNOS). On the other hand, sexual hormone levels in blood were measured. Both cognitive and behavioral f unctions were declined as the result of PWSI induction in male and diestrus female rats. The consequent surge of estradiol during estrous phase seems to suppress the accumulation of reactive oxygen species (ROS), and modulate iNOS and nNOS expression. In conclusion, while the pattern of PWSI in surge cellular antioxidants, raising cellular ROS level is gender-specific, this alleviation was in relation with the drop of estradiol and unrelated with testosterone level.

Separation of crude methanol extract of Plantago major root: identification of phytochemicals and assessment of biological activities.

Plantago major root extracts were used for analysis by Gas Chromatography-Mass Spectrometry (GC-MS). The anticancer and antibacterial functions of extracts were also investigated. The dichloromethane extract of P. major had the highest inhibitory effect against Salmonella paratyphi (18.00 ± 1.4 mm) at 100 mg/mL concentration. The lowest MIC was also achieved for S. paratyphi treated with dichloromethane extract of P. major (1.5 mg/mL). The minimum MBC (2 mg/mL) was observed for dichloromethane extract of P. major root against S. paratyphi. IC50 values of dichloromethane extracts of P. major root (184.84 µg/mL) against HCT116 were lower than the ethyl acetate and butanol extracts (212.41 µg/mL and 223.93 µg/mL) at 72h. The butanol extract exhibited the most IC50 value on HEK293 (748.19 µg/mL). The biological properties of P. major extracts may be assigned to the presence of numerous compounds detected in GC/MS analysis including n-Hexadecanoic acid, Linolenic acid, Palmitic acid, methyl ester, Stearic acid.

Antiproliferative assay of suma or Brazilian ginseng (Hebanthe eriantha) methanolic extract on HCT116 and 4T1 cancer cell lines, in vitro toxicity on Artemia salina larvae, and antibacterial activity.

Hebanthe eriantha is a medicinal plant used in folk medicine and a subject of commercial interest. The cytotoxicity effects from H. eriantha root extracts on cancerous and normal cells were assessed by the MTT method, and in vitro toxicity was evaluated on Artemia salina. The inhibition of the proliferation of bacteria and MIC values were examined by the disc diffusion and the broth microdilution method, respectively. Human colon cancer HCT116 and mouse breast tumour model 4T1 cells treated with methanolic extract showed a significant decrease in viability of cells with IC50: 272.6 and 88.5 µg/mL at 72h, respectively. The methanolic extract of H. eriantha showed moderate toxicity against A. salina (LC50: 589.4 µg/mL). In antimicrobial activity, the methanolic extract showed the highest inhibitory function against S. aureus and P. vulgaris (17.5 and 16 mm) with MICs of 500 µg/mL. The results confirmed the potential of plant roots as cytotoxic agents.

Synthesis of Pt nanoparticles with gelatin-assisted green route to improve sensitization of cancer cells to X-Ray irradiation.

This study aimed to develop a novel radiosensitizer consisting of platinum nanoparticles (Pt NPs) as a high-atomic-number element in order to maximize the generation of ROS under ionizing radiation at the tumor site. Pt NPs were produced via a green and facile method in the presence of gelatin (Gel) as both reducing and stabilizing agent. After determining the physical structure and chemical composition of Pt@Gel NPs by STEM, FeSEM, EDS, DLS, XRD and FTIR, in vitro cytotoxicity on human umbilical vein endothelial cells (HUVEC) and breast cancer cell line (4T1) was evaluated by MTT assay. Finally, ROS generation assay, calcein AM/PI staining assay and clonogenic test were performed on 4T1 cells under X-Ray irradiation to evaluate the radioenhancment efficiency of Pt@Gel. The prepared NPs exhibited spherical and uniform shapes and narrowly distributed sizes in addition to an acceptable radiosensitization capability. The nanosystem provided higher levels of intracellular ROS in malignant cells and enhanced cancer cell death rate under X-Ray irradiation. Overall, the findings suggested that Pt@Gel could be a safe and effective alternative to existing radiosensitizers and potentially be employed for the treatment of breast cancer.

In vitro elicitation and detection of apigenin, catalpol and gallic acid in hairy root culture of Plantago major L. and assessment of cytotoxicity and anti-bacterial activity of its methanolic extract.

The aim of this study was to establish the hairy root (HR) culture of Plantago major to evaluate the accumulation of apigenin, catalpol and gallic acid after elicitation and investigate the biological activity of its methanolic extraction. The highest transformation frequency was obtained by Agrobacterium rhizogenes strain A4, 0.5 mg/L 6-Benzylaminopurine in pre-cultivation medium, 150 µM acetosyringone in co-cultivation medium (1/2 MS), and immersion method for inoculation of leaf explants. The production of apigenin, catalpol and gallic acid compounds were significantly affected by treatment of 1.18 mM AgNO3 at 24 h which yielded 4.30, 8.24 and 2.89-fold increase, respectively. The assessment of anti-bacterial activity showed that the methanolic extracts of the HRs elicited with 1.18 mM AgNO3 were significantly active against Proteus vulgaris (PTCC 1182) (MIC = 25 mg/mL and MBC = 25 mg/mL). Furthermore, the MTT assay revealed that the methanolic extracts of the HRs were cytotoxic on the SW-480 cell (IC50=337.56 ± 1.82 µg/mL).

Combinational therapy with Myc decoy oligodeoxynucleotides encapsulated in nanocarrier and X-irradiation on breast cancer cells.

The Myc gene is the essential oncogene in triple-negative breast cancer (TNBC). This study investigates the synergistic effects of combining Myc decoy oligodeoxynucleotides-encapsulated niosomes-selenium hybrid nanocarriers with X-irradiation exposure on the MDA-MB-468 cell line. Decoy and scramble ODNs for Myc transcription factor were designed and synthesized based on promoter sequences of the Bcl2 gene. The nanocarriers were synthesized by loading Myc ODNs and selenium into chitosan (Chi-Se-DEC), which was then encapsulated in niosome-nanocarriers (NISM@Chi-Se-DEC). FT-IR, DLS, FESEM, and hemolysis tests were applied to confirm its characterization and physicochemical properties. Moreover, cellular uptake, cellular toxicity, apoptosis, cell cycle, and scratch repair assays were performed to evaluate its anticancer effects on cancer cells. All anticancer assessments were repeated under X-ray irradiation conditions (fractionated 2Gy). Physicochemical characteristics of niosomes containing SeNPs and ODNs showed that it is synthesized appropriately. It revealed that the anticancer effect of NISM@Chi-Se-DEC can be significantly improved in combination with X-ray irradiation treatment. It can be concluded that NISM@Chi-Se-DEC nanocarriers have the potential as a therapeutic agent for cancer treatment, particularly in combination with radiation therapy and in-vivo experiments are necessary to confirm the efficacy of this nano-drug.

Targeted anti-tumor synergistic effects of Myc decoy oligodeoxynucleotides-loaded selenium nanostructure combined with chemoradiotherapy on LNCaP prostate cancer cells.

In the present study, we investigated the synergistic effects of targeted methotrexate-selenium nanostructure containing Myc decoy oligodeoxynucleotides along with X-irradiation exposure as a combination therapy on LNCaP prostate cancer cells. Myc decoy ODNs were designed based on the promoter of Bcl-2 gene and analyzed by molecular docking and molecular dynamics assays. ODNs were loaded on the synthesized Se@BSA@Chi-MTX nanostructure. The physicochemical characteristics of nanostructures were determined by FTIR, DLS, UV-vis, TEM, EDX, in vitro release, and hemolysis tests. Subsequently, the cytotoxicity properties of them with and without X-irradiation were investigated by uptake, MTT, cell cycle, apoptosis, and scratch assays on the LNCaP cell line. The results of DLS and TEM showed negative charge (-9 mV) and nanometer size (40 nm) for Se@BSA@Chi-DEC-MTX NPs, respectively. The results of FTIR, UV-vis, and EDX showed the proper interaction of different parts and the correct synthesis of nanoparticles. The results of hemolysis showed the hemocompatibility of this nanoparticle in concentrations less than 6 mg/mL. The ODNs release from the nanostructures showed a pH-dependent manner, and the release rate was 15% higher in acidic pH. The targeted Se@BSA@Chi-labeled ODN-MTX NPs were efficiently taken up by LNCaP cells by targeting the prostate-specific membrane antigen (PSMA). The significant synergistic effects of nanostructure (containing MTX drug) treatment along with X-irradiation showed cell growth inhibition, apoptosis induction (~57%), cell cycle arrest (G2/M phase), and migration inhibition (up to 90%) compared to the control. The results suggested that the Se@BSA@Chi-DEC-MTX NPs can potentially suppress the cell growth of LNCaP cells. This nanostructure system can be a promising approach for targeted drug delivery and chemoradiotherapy in prostate cancer treatment.

Correlation between coenzyme Q10 content and the nutrient sensors in AKI induced by Hemiscorpius lepturus envenomation.

Introduction: Acute kidney injury (AKI) may have a negative effect on mitochondrial hemostasis and bioenergetics as well as coenzyme Q10 (CoQ10) content. PGC-1α, AMPK, sirtuin 1 (Sirt1), and Sirt3, as the key metabolic regulators under nutritional stress, stimulate energy production via mitochondrial biogenesis during AKI. However, no report is available on the relationship between CoQ10 level and nutrient sensors in the pathophysiology of AKI caused by Hemiscorpius lepturus scorpion envenomation. Methods: Three doses of venoms (1, 5, and 10 mg/kg) were administered by subcutaneous (SC) injection to male albino mice. The animals were sacrificed 1 day or 7 days after administration of venom and their kidneys were collected to analyze gene expression involved in AKI, nutrient sensors, and apoptosis signaling activation by real-time polymerase chain reaction (PCR) and the measurement of CoQ10 level using the High-performance liquid chromatography (HPLC) method. Results: The data indicated a significant decrease in CoQ10 level after the administration of venom in 5 and 10 mg/kg. In addition, 1 day after the treatment, a significant over-expression of Sirt1 (5 and 10 mg/kg) was observed compared with normal mice. Overexpression of Sirt3 occurred 1 day and 7 days after treatment only at the dose of 5.0 mg/kg of venom. Furthermore, over-expression of AMPK as an important mitochondrial energetic sensor happened 1 day and 7 days after the injection of venom (5 mg/kg) (P < 0.01). The significant increase in the gene expression of caspase-9 and 3 after the injection of venom (5 and 10 mg/kg) confirmed the role of cell death signaling. Conclusion: The venom-induced energy-sensing pathways have a key role in gene expression of PGC-1α, AMPK, Sirt3, and CoQ10 content after venom-induced AKI.

The impacts of vorinostat on NADPH oxidase and mitochondrial biogenesis gene expression in the heart of mice model of depression.

The comorbidity of depression and high risk of cardiovascular diseases (CVD) have been reported as major health problems. Our previous study confirmed that fluoxetine (FLX) therapy had a significant influence on brain function but not on the heart in depression. In the present study, suberoyanilide hydroxamic acid (SAHA) was proposed as another therapeutic candidate for treatment of depression comorbid CVD in maternal separation model, following behavioral analyses and gene expression level in the heart. Our data demonstrated that SAHA significantly attenuates the NOX-4 gene expression level in treated mice with SAHA and FLX without significant change in NOX-2 expression level. SAHA decreased the gene expression level of peroxisome proliferator-activated receptor-gamma coactivator (PGC-1α) and nuclear respiratory factors (Nrf2) in heart tissues of maternally separated mice. It supposed that non-effectiveness of FLX on mitochondrial biogenesis and NOX gene expression level in the heart of depressed patient can be related to recurrence of depression. It revealed that SAHA not only reversed the depressive-like behavior similar to our previous data but also recovered the heart mitochondrial function via effect on NOX-2, NOX-4, and mitochondrial biogenesis genes' (PGC-1α, Nrf-2, and peroxisome proliferator-activated receptor-α (PPAR-α)) expression levels. We suggest performing more studies to confirm SAHA as a therapeutic candidate in depression comorbid CVD.

Biogenic and facile synthesis of selenium nanoparticles using Vaccinium arctostaphylos L. fruit extract and anticancer activity against in vitro model of breast cancer.

Biogenic synthesis of selenium nanoparticles (SeNPs) using plant extracts has emerged as a promising alternative approach to traditional chemical synthesis. The current study aims to introduce a safe, low-cost, and green synthesis of SeNPs using fresh fruit extract of Vaccinium arctostaphylos L. The biogenic synthesis of SeNPs was confirmed by different analyses including ultraviolet-visible spectrophotometry, Fourier transform infrared, and energy-dispersive X-ray. Also, the crystalline nature, size, and morphology of the obtained SeNPs were characterized by X-ray diffraction, dynamic light scattering, field emission scanning electron microscopy, and transmission electron microscopy techniques. The SeNPs were successfully synthesized with fruit extract of V. arctostaphylos L. in a regular spherical form and narrow size distribution with suitable zeta-potential values and exhibited appropriate biocompatibility. It revealed that the synthesized SeNPs can significantly inhibit the growth of 4T1 breast cancer cells with an IC50 of ∼84.19 ± 25.96 µg/ml after 72 h treatment. Overall, it can be concluded that the green synthesized SeNPs can be attractive, nontoxic, and eco-friendly candidates for drug delivery or medicinal applications.

Clavulanic Acid: A Novel Potential Agent in Prevention and Treatment of Scopolamine-Induced Alzheimer's Disease.

Background and Aim: Alzheimer's disease (AD) is the most common form of dementia in the elderly. It is characterized as a multifaced disorder with a greater genetic contribution. The contribution of many genes such as BDNF, Sirtuin 6, and Seladin 1 has been reported in the pathogenesis of AD. Current therapies include acetylcholinesterase inhibitors and N-methyl-d-aspartate receptor antagonists, which are only temporarily beneficial. Therefore, it seems that more studies should be conducted to determine the exact mechanisms of drugs to deal with the diseases' multifactorial features that we face. Methods: In this study, 42 adult rats were randomly divided into 7 groups and received drugs intraperitoneally and orally according to the protocol as follows: scopolamine group, clavulanic acid group, memantine group, scopolamine + memantine group, clavulanic acid pre- and post-treatment, and normal saline group. The Morris water maze method was performed to evaluate the spatial memory of animals, and the terminal deoxynucleotidyl transferase dUTP nick end labeling assay and real-time polymerase chain reaction were performed to study neuronal cell apoptosis and gene expression, respectively. Results: Significant differences were observed in the spatial memory of rats that received clavulanic acid prophylactically compared to the Alzheimer's model on the day of the test. Moreover, the results obtained during the training showed that both memantine and clavulanic acid improved spatial memory by increasing the time of rats present in the platform position and by reducing the swimming time in the scopolamine-induced Alzheimer's group. Besides, rats that received clavulanic acid and memantine had a greater percentage of healthy cells in comparison with the scopolamine-induced Alzheimer's group; however, the results were more significant for clavulanic acid. Furthermore, the expressions of BDNF, Seladin 1, and Sirtuin 6 as neuroprotective target genes were modified after clavulanic acid and memantine administrations; similarly, the results obtained from clavulanic acid were more significant. Conclusion: The results show that the administration of clavulanic acid before and after the use of scopolamine can reduce the percentage of apoptotic cells in the hippocampus and also improve the parameters related to learning and spatial memory; however, its effect in the prophylactic state was stronger. The results obtained from memantine revealed that it has neuroprotective potency against AD; however, clavulanic acid had a greater effect. Also, with increased expression of the neuroprotective genes, clavulanic acid could be considered as an option in the upcoming preclinical and clinical research about Alzheimer's disease.

HPLC-DAD-ESI/MSn analysis of phenolic components of Scutellaria araxensis, S. bornmuelleri and S. orientalis.

Scutellaria araxensis, S. bornmuelleri and S. orientalis are traditional herbs widely used by native Iranians for the treatment various ailments. In the current study, we used HPLC-DAD-ESI/MSn to investigate the presence of phenolic compounds of root and shoot methanolic extracts. The flavonoid composition were identified based on mass of pseudomolecular [M - H]- ions and fragmentation spectra and comparisons with literature data. A total of 26, 25, 17, 23, 19 and 26 flavonoids were identified from roots and shoots of S. araxensis, S. bornmuelleri and S. orientalis, respectively. The obtained phenolic profiles revealed the presence of the major flavonoid components of Scutellaria genus including baicalein, wogonin, scutellarein and their glycosides, as well as chrysin, tricin, skullcapflavon II, pinocembrin and phenylethanoid glycosides such as acteoside and verbascoside. This study, in addition to reveal the potency of chromatographic profiling for identification of Scutellaria flavonoids, introduces this species as a potential source of bioactive metabolites.

High-frequency adventitious shoot organogenesis from in vitro stem explants of Scutellaria araxensis Grossh.

The present study introduced an in vitro shoot organogenesis protocol for the medicinal plant Scutellaria araxensis (Lamiaceae). Stem, leaf, and petiole explants were cultured in half-strength Murashige and Skoog (MS) medium containing different concentrations of 6-benzylaminopurine (BAP) alone or in combination with thidiazuron (TDZ), indole-3-butyric acid (IBA), or α-naphthalene acetic acid. Callus formation occurred from stem and petiole explants in most cultures; however, in leaf explants, it was observed only in cultures containing 0.5 mg/l BAP supplemented with TDZ at all concentrations. The highest frequency of indirect shoot induction (100 and 90%) with an average of 20.33 and 12 shoots per explant was observed in stem-derived calli cultured on half-strength MS medium containing 2.0 mg/l BAP plus 0.5 and 1.5 mg/l TDZ, respectively. The best direct shoot organogenesis (40%) was observed in stem explants cultured on half-strength MS medium containing 0.5 mg/l BAP and 0.5 mg/l IBA with a mean of 18 shoots per stem explant. The regenerated micro-shoots were elongated on a medium fortified with 0.5 mg/l gibberellic acid and then successfully rooted in half-strength MS medium supplemented with 0.5 mg/l IBA. The obtained plantlets were acclimatized in a growth chamber with a survival rate of 100%. This study is the first report of a simple and efficient in vitro shoot organogenesis and regeneration protocol for S. araxensis by using stem explants, which could be useful for the conservation, genetic manipulation, and exploitation of biological molecules of this valuable genetic source.

Bovine serum albumin-mediated synthesis and quorum sensing inhibitory properties of Ag-Ag2S nanoparticles.

Aim: Quorum sensing (QS) is a density-dependent chemical process of cell-to-cell communication in which certain signals are activated, leading to the coordination of pathogenic behaviors and the regulation of virulence in bacteria. Inhibition of QS can prevent biofilm formation and reduce virulence behaviors of bacteria. Herein, bovine serum albumin (BSA)-coated silver nanoparticles (NPs) (Ag-Ag2S@BSA NPs) were synthesized and studied as an anti-QS agent. Materials & methods: Ag-Ag2S NPs prepared through a BSA-mediated biomineralization process under ambient aqueous conditions and their physicochemical properties were characterized. The anti-QS activity of the resulting BSA-coated NPs (Ag-Ag2S@BSA NPs) was investigated for the first time. Results & conclusion: The result confirmed the potential of Ag-Ag2S@BSA NPs as novel and useful therapeutic tools for antibacterial purposes.

The overuse of antibiotics has caused the development of drug-resistant strains of bacteria. Nowadays, drug resistance is one of the main challenges in the treatment and prevention of microbial diseases. In general, many bacterial species communicate with each other through a population-dependent mechanism called quorum sensing to control their physiological activities. Therefore, inhibiting the quorum sensing mechanism is an attractive alternative to antibiotics and also reduces the risk of drug resistance, and this can be achieved by nanoparticles (NPs). Among these nanostructures, Ag NPs have received particular attention due to their antimicrobial, antibiofilm, anticancer and antioxidant properties. Herein, we report a method that applies a BSA-guided green and one-pot approach for achieving Ag­Ag₂S NPs as potential antibacterial agents.

Scutellaria orientalis subsp. Bornmuelleri: phytochemical composition and biological activities.

The medicinal plant, Scutellaria orientalis, is used for the treatment of several diseases in North-western of Iran. The purpose of this study was to investigate the phytochemical content, cytotoxicity assay against SW-480 and HCT-116 cells and anti-haemolytic activities using HPLC-PDA, GC/MS, MTT and spectrophotometry methods, respectively. Phytochemical screening revealed the presence of different terpenoids and flavonoids such as baicalin, tricin and wogonin and also some of the other medicinally active compounds such as conhydrine and cannabidiol. MTT results revealed that HCT-116 cells were more sensitive to examined extracts compared with SW-480 cells. Methanol extract had the most anti-proliferative activity against HCT-116 and SW-480 cells at 48 h with IC50 values of 614.5 and 592.3 µg/mL, respectively. Also, all samples had no significant haemolytic effect on human erythrocytes. Our results revealed that S. orientalis root extract has a promising anticancer activity, indicating the presence of major anti-cancer agents on human colon cell lines.

Fractional analysis of dichloromethane extract of Scutellaria araxensis Grossh root and shoot by HPLC-PDA-ESI-MSn.

Scutellaria araxensis is a well-known ethnobotanical herb for the treatment of various diseases in Iranian traditional medicine. In this study, dichloromethanolic fraction of partitioned methanol root and shoot extract was analysed by silica gel column chromatography, thin layer chromatography and high-performance liquid chromatography combined with photodiode-array detector, and coupled to electrospray ionization with Q-Exactive Orbitrap mass spectrometry (HPLC-PDA-ESI-MSn) in positive ion mode. Metabolites were tentatively characterized by comparing their mass spectrometry spectra with those of bibliographic data. A total of 11 flavonoids were identified from different fractions. Results showed that root and shoot produced very similar flavone patterns characterized by the presence of baicalein, tricin, tenaxin I, tenaxin II, skullcapflavon II, chrysin, wogonin and isorhamnetin. Norwogonin and apigenin-7-glucoside were identified only from shoot. Remarkably, Tenaxin I, II, tricin, apigenin-7-glucoside and norwogonin were tentatively profiled as new compounds for the first time from S. araxensis formula.

Neuroprotective Effect of Apigenin on Depressive-Like Behavior: Mechanistic Approach.

Apigenin, as a natural flavonoid present in several plants is characterized with potential anticancer, antioxidant, and anti-inflammatory properties. Recent studies proposed that apigenin affects depression disorder through unknown mechanistic pathways. The effects of apigenin's anti-depressive properties on streptozocin-mediated depression have been investigated through the evaluation of behavioral tests, oxidative stress, cellular energy homeostasis and inflammatory responses. The results demonstrated anti-depressive properties of apigenin in behavioral test including forced swimming and splash tests and oxidative stress biomarkers such as reduced glutathione, lipid peroxidation, total antioxidant power and coenzyme Q10 levels. Apigenin, also, demonstrated its regulatory potency in cellular energy homeostasis and immune system gene expression through inhibiting Nlrp3 and Tlr4 overexpression. Furthermore, failure in energy production as the key factor in various psychiatric disorders was reversed by apigenin modulating effect on AMPK gene expression. Overall, 20 mg/kg of apigenin was recognized as the dose suitable for minimizing the undesirable adverse effects in the STZ-mediated depression model proposed in this study. Our data suggested that apigenin could be able to adjust behavioral dysfunction, biochemical biomarkers and recovered cellular antioxidant level in depressed animals. The surprising results were achieved by raise in COQ10 level, which could regulate the overexpression of the AMPK gene in stressful conditions. The regulatory effect of apigenin in inflammatory signaling pathways such as Nlrp3, and Tlr4 gene expression was studied at the surface part of the hippocampus.

Prodrug Polymeric Nanoconjugates Encapsulating Gold Nanoparticles for Enhanced X-Ray Radiation Therapy in Breast Cancer.

An optimal radiosensitizer with improved tumor retention has an important effect on tumor radiation therapy. Herein, gold nanoparticles (Au NPs) and drug-containing, mPEG-conjugated CUR (mPEG-CUR), self-assembled NPs (mPEG-CUR@Au) are developed and evaluated as a drug carrier and radiosensitizer in a breast cancer mice model. As a result, cancer therapy efficacy is improved significantly by applying all-in-one NPs to achieve synchronous chemoradiotherapy, as evidenced by studies evaluating cell viability, proliferation, and ROS production. In vivo anticancer experiments show that the mPEG-CUR@Au system improves the radiation sensitivity of 4T1 mammary carcinoma and completely abrogates breast cancer.