Brain-derived Neurotropic factor (BDNF) mediates the protective effect of Cucurbita pepo L. on salivary glands of rats exposed to chronic stress evident by structural, biochemical and molecular study

Acute and chronic stresses affect the salivary glands, representing the source of plasma BDNF during stressful conditions. Pumpkin is a medicinal plant with an evident antioxidant, anti-inflammatory and potential antidepressant effects. Objective: To assess the structural and biochemical effects induced by exposure to chronic unpredictable mild stress (CUMS) on salivary glands of albino rats, and to evaluate the role of pumpkin extract (Pump) in ameliorating this effect. Methodology: Four groups (n=10 each) of male albino rats were included in this study: the control, CUMS, Fluoxetine-treated and Pump-treated. The corticosterone, the pro-inflammatory cytokines, tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6), and the oxidant/antioxidant profile were all assessed in the serum. The level of BDNF mRNA was measured in the salivary glands using qRT-PCR. Histopathological changes of the salivary glands were also assessed. Results: The depressive-like status was confirmed behaviorally and biochemically. Exposure to CUMS significantly up-regulated (p<0.001) the level of serum corticosterone. CUMS induced degenerative changes in the secretory and ductal elements of the salivary glands evident by increased apoptosis. Both Fluoxetine and Pumpkin significantly up-regulated (p<0.001) BDNF expression in the salivary glands and ameliorated the CUMS-induced histopathological and biochemical alterations in the salivary glands. Pumpkin significantly (p<0.001) increased the serum levels of antioxidant enzymes SOD, GPX and CAT, and reduced the serum levels of the pro-inflammatory cytokines TNF-α, IL-6. Conclusion: Pumpkin ameliorates the depressive-like status induced in rats following exposure to chronic stress through exerting a promising anti-inflammatory, antioxidant and anti-depressant-like effects. The pumpkin, subsequently, improved stress-induced structural changes in the salivary glands that might be due to up-regulation of BDNF expression in the glands

Cinnamon and ginger extracts attenuate diabetes-induced inflammatory testicular injury in rats and modulating SIRT1 expression

The current study aimed to evaluate the efficacy of simultaneous administration of Zingiber officinale (ginger) and Cinnamomum cassia (cinnamon) extracts in mitigating testicular changes associated with diabetes mellitus in rats and to investigate its molecular mode of action. After induction of diabetes using streptozotocin, 36 male rats were divided to six groups namely control, diabetic, metformin-treated, cinnamon-treated, ginger-treated and combined, each group having 6 rats. Fasting blood glucose, serum insulin, testosterone was measured. Expression of inflammatory mediators; tumor necrosis factor-alpha (TNF-α), Nuclear factor kappa B (NF-κB) and Sirtuin 1 (SIRT1) was assessed in the testicular tissue. Histopathological changes in the testis were observed and spermatogenesis and apoptosis were assessed immunohistochemically. The histological and biochemical studies of the untreated group confirmed structural changes in testes induced by diabetes. Oral administration of ginger and cinnamon increased insulin level significantly increased while the blood glucose level significantly decreased in diabetic rats, improving structural testicular changes considerably. Joint intake of ginger and cinnamon increased antihyperglycemic, antioxidant and anti-inflammatory effects markedly improving the testicular injury compared to the administration of either of them. SIRT1 expression in the testis significantly increased in ginger plus cinnamon-treated rats. These results indicate that when administrated together, ginger and cinnamon synergistically enhanced antioxidant, antiapoptotic and anti-inflammatory effects and induced antihyperglycemic effect comparable to metformin. The combination of ginger and cinnamon also upregulated SIRT1 in the testis

Decapeptide from Potato Hydrolysate Induces Myogenic Differentiation and Ameliorates High Glucose-Associated Modulations in Protein Synthesis and Mitochondrial Biogenesis in C2C12 Cells

Sarcopenia is characterized as an age-related loss of muscle mass that results in negative health consequences such as decreased strength, insulin resistance, slowed metabolism, increased body fat mass, and a substantially diminished quality of life. Additionally, conditions such as high blood sugar are known to further exacerbate muscle degeneration. Skeletal muscle development and regeneration following injury or disease are based on myoblast differentiation. Bioactive peptides are biologically active peptides found in foods that could have pharmacological functions. The aim of this paper was to investigate the effect of decapeptide DI-10 from the potato alcalase hydrolysate on myoblast differentiation, muscle protein synthesis, and mitochondrial biogenesis in vitro. The treatment of C2C12 myoblasts with DI-10 (10 µg/mL) did not induce cell death. DI-10 treatment in C2C12 myoblast cells accelerates the phosphorylation of promyogenic kinases such as ERK, Akt and mTOR proteins in a dose-dependent manner. DI-10 improves myotubes differentiation and upregulates the expression of myosin heavy chain (MyHC) protein in myoblast cells under differentiation medium with high glucose. DI-10 effectively increased the phosphorylation of promyogenic kinases Akt, mTOR, and mitochondrial-related transcription factors AMPK and PGC1α expression under hyperglycemic conditions. Further, decapeptide DI-10 decreased the expression of Murf1 and MAFbx proteins, which are involved in protein degradation and muscle atrophy. Our reports support that decapeptide DI-10 could be potentially used as a therapeutic candidate for preventing muscle degeneration in sarcopenia

Antimicrobial and In Vitro Cytotoxic Efficacy of Biogenic Silver Nanoparticles (Ag-NPs) Fabricated by Callus Extract of Solanum incanum L.

The in vitro callus induction of Solanum incanum L. was executed on MS medium supplemented with different concentrations of auxin and cytokinin utilizing petioles and explants of leaves. The highest significant fresh weights from petioles and leaf explants were 4.68 and 5.13 g/jar for the medium supplemented with1.0 mg L−1 BA and 1.0 mg L−1 2,4-D. The callus extract of the leaves was used for the green synthesis of silver nanoparticles (Ag-NPs). Analytical methods used for Ag-NPs characterization were UV-vis spectroscopy, Fourier Transform Infrared spectroscopy (FT-IR), X-ray diffraction (XRD), and Transmission Electron Microscopy (TEM). Spherical, crystallographic Ag-NPs with sizes ranging from 15 to 60nm were successfully formed. The FT-IR spectra exhibited the role of the metabolites involved in callus extract in reducing and capping Ag-NPs. The biological activities of Ag-NPs were dose-dependent. The MIC value for Staphylococcus aureus, Bacillus subtilis, and Escherichia coli was 12.5 µg mL−1, while it was 6.25 µg mL−1 for Klebsiella pneumoniae, Pseudomonas aeruginosa, and Candida albicans. The highest inhibition of phytopathogenic fungi Alternaria alternata, Fusarium oxysporum, Aspergillus niger, and Pythium ultimum was 76.3 ± 3.7, 88.9 ± 4.1, 67.8 ± 2.1, and 76.4 ± 1.0%, respectively at 200 µg mL−1. Moreover, green synthesized Ag-NPs showed cytotoxic efficacy against cancerous cell lines HepG2, MCF-7 and normal Vero cell line with IC50 values of 21.76 ± 0.56, 50.19 ± 1.71, and 129.9 ± 0.94 µg mL−1, respectively

The Efficacy of Silver Nitrate (AgNO₃) as a Coating Agent to Protect Paper against High Deteriorating Microbes

This study focuses on the efficacy of silver nitrate (AgNO3) as a coating agent used to preserve papers against microbial deterioration. To this end, the in vitro cytotoxicity of AgNO3 was assessed against two normal cell lines, WI-38 and HFB-4, to detect a safe dose that can be used as a coating agent, which was 80 µg mL−1. Bacillus subtilis B3 and Penicillium chrysogenum F9 were selected as high deteriorating microbes, previously isolated from a historical manuscript dating back to 1677 A.-D. The microbial growth inhibition, color change, mechanical properties, and cellulosic fibers of untreated/treated papers were evaluated. The data showed the efficacy of AgNO3 to inhibit the growth of B. subtilis with a percentage of 100% after 7 days, while it inhibits the growth of P. chrysogenum with a percentage of 85.9 ± 1.1% after 21 days. The color and mechanical properties of treated paper in the presence/absence of microbial inoculation were slightly changed, although they changed greatly due to microbial growth in the absence of AgNO3. The EDX analysis confirmed the successful adsorption of Ag-ion on papers, with a weight percentage of 1.9%. The cellulosic fibers of untreated paper in the presence of microbial growth were highly deteriorated as compared with treated and standard filter paper (shown by FT-IR and SEM)

Dipeptide IF and Exercise Training Attenuate Hypertension in SHR Rats by Inhibiting Fibrosis and Hypertrophy and Activating AMPKα1, SIRT1, and PGC1α

Bioactive peptides are physiologically active peptides produced from proteins by gastrointestinal digestion, fermentation, or hydrolysis by proteolytic enzymes. Bioactive peptides are resorbed in their whole form and have a preventive effect against various disease conditions, including hypertension, dyslipidemia, inflammation, and oxidative stress. In recent years, there has been a growing body of evidence showing that physiologically active peptides may have a function in sports nutrition. The present study aimed to evaluate the synergistic effect of dipeptide (IF) from alcalase potato protein hydrolysates and exercise training in hypertensive (SHR) rats. Animals were divided into five groups. Bioactive peptide IF and swimming exercise training normalized the blood pressure and decreased the heart weight. Cardiac, hepatic, and renal functional markers also normalized in SHR rats. The combined administration of IF peptide and exercise offer better protection in SHR rats by downregulating proteins associated with myocardial fibrosis, hypertrophy, and inflammation. Remarkably, peptide treatment alongside exercise activates the PI3K/AKT cell survival pathway in the myocardial tissue of SHR animals. Further, the mitochondrial biogenesis pathway (AMPKα1, SIRT1, and PGC1α) was synergistically activated by the combinatorial treatment of IF and exercise. Exercise training along with IF administration could be a possible approach to alleviating hypertension

Uxi (Endopleura uchi (Huber) Cuatrec) bark extract mitigates HFD-induced adiposity in rats via targeting oxidative stress, and lipogenic genes expression

Here, we compared the modulatory effects of different dose levels of Uxi (Endopleura uchi aqueous bark extract, EUAE) vs simvastatin (SIM) on hyperlipidemia, metabolic stress, and liver dysfunction in HFD-induced obese rats. HFD significantly increased BMI, lee index, body adipose index, atherogenic indices, cellular toxicity markers, blood glucose level, adipokines, pro-inflammatory mediators, lipid peroxidation and promoted lipid accumulation and HMGCR and ACC. Furthermore, it significantly decreased antioxidants, ghrelin, and AG/UAG ratio as well as hepatic glycogen content, while these changes were mitigated by either SIM or EUAE treatment. The expression of FASN & SREBP1c genes were elevated in the HFD group, with downregulation of PPARα expression. These alterations were ameliorated by SIM or EUAE treatment. The beneficial effects of EUAE may be attributed to its phenolic compounds and their derivatives. This study supports the hypothesis that Uxi may have antihyperlipidemic, antioxidant, hepatoprotective, and anti-inflammatory properties in rat model of obesity

Origanum majorana L. Extract Attenuated Benign Prostatic Hyperplasia in Rat Model: Effect on Oxidative Stress, Apoptosis, and Proliferation

Benign prostatic hyperplasia (BPH) is a widespread androgenic illness influencing elderly men. It is distinguished by prostatic epithelial and stromal muscle cell proliferation. Inflammation, oxidative stress, and apoptosis have all been interrelated to the development of BPH. Marjoram (Origanum majorana L.) is a herb with reported antiproliferative, proapoptotic, and antioxidative properties, which have not yet been studied in relation to BPH. Consequently, in this work, an ethanolic extract of O. majorana was prepared in two doses (250 and 500 mg/kg/day) to be injected into castrated rats after induction of a testosterone-BPH model. Testosterone propionate (TP) was subcutaneously injected (0.5 mg/kg/day) for one week after castration to induce BPH. Forty adult Wistar male rats were randomly allocated into five groups: control, BPH model, high and low O. majorana doses (250, 500 mg/kg/day), and finasteride (FN) (0.8 mg/kg/day) as a positive control. Treatment was continued with drugs/normal saline for 28 days. Rat’s body and prostate were weighed, prostate index (PI) and % of prostate growth inhibition were calculated, serum dihydrotestosterone (DHT), prostatic content of superoxide dismutase (SOD), catalase (CAT), total antioxidant capacity (TAC), and malondialdehyde (MDA), DN damage, histopathological changes, immune expression of proliferating cell nuclear antigen (PCNA), caspase-3, α-SMA, and TGF-β1 were assessed. In addition, molecular quantitative PCR and ELISA analyses were performed to identify the expression of mRNAs and related proteins of both caspase-3 and TGF-β1 in prostate tissue from O. majorana-treated and untreated groups. Rats with BPH had significantly higher prostate weights and PI, higher DHT, DNA damage (8-hydroxyguanine, 8-OH-dG), and MDA levels with prominent PCNA, α-SMA, and TGF-β expression, but lower SOD, CAT, and TAC activity and caspase-3 expression. O. majorana (250 and 500 mg/kg/day)-treated groups revealed a decrease in prostate weights and PI, lower levels of DHT, suppressed oxidative stress, reduced tissue proliferation and fibrosis, and restored antioxidant and proapoptotic activity. Additionally, quantitative PCR and ELISA analysis showed that treatment with O. majorana significantly upregulated the expression of caspase-3 and downregulated the expression of TGF-β in prostate tissues of BPH rats. The data were confirmed by the immunohistological reactivity of these targeted markers in the prostate tissues. These effects were more significant with O. majorana 500 mg/mL/rat. In conclusion, the current study indicates the efficient use of O. majorana in the treatment of testosterone-induced BPH through its antiproliferative, proapoptotic, and antioxidative mechanisms

C/EBPβ converts bovine fibroblasts to adipocytes without hormone cocktail induction

Background: Adipogenesis and fibrogenesis can be considered as a competitive process in muscle, which may affect the intramuscular fat deposition. The CCAAT/enhancer-binding protein beta (C/EBPβ) plays an important role in adipogenesis, which is well-characterized in mice, but little known in bovine so far. Results: In this study, real-time qPCR revealed that the level of C/EBPβ was increased during the developmental stages of bovine and adipogenesis process of preadipocytes. Overexpression of C/EBPβ promoted bovine fibroblast proliferation through mitotic clonal expansion (MCE), a necessary process for initiating adipogenesis, by significantly downregulating levels of p21 and p27 (p < 0.01). Also, the PPARγ expression was inhibited during the MCE stage (p < 0.01). 31.28% of transfected fibroblasts adopted lipid-laden adipocyte morphology after 8 d. Real-time qPCR showed that C/EBPβ activated the transcription of early stage adipogenesis markers C/EBPα and PPARγ. Expression of ACCα, FASN, FABP4 and LPL was also significantly upregulated, while the expression of LEPR was weakened. Conclusions: It was concluded C/EBPβ can convert bovine fibroblasts into adipocytes without hormone induction by initiating the MCE process and promoting adipogenic genes expression, which may provide new insights into the potential functions of C/EBPβ in regulating intramuscular fat deposition in beef cattle.How to cite: Cheng G, Raza SHA, Khan R, et al. C/EBPβ converts bovine fibroblasts to adipocytes without hormone cocktail induction. Electron J Biotechnol 2021;52. https://doi.org/10.1016/j.ejbt.2021.04.00

A Novel Sprague-Dawley Rat Model Presents Improved NASH/NAFLD Symptoms with PEG Coated Vitexin Liposomes

Chronic liver disease (CLD) is a global threat to the human population, with manifestations resulting from alcohol-related liver disease (ALD) and non-alcohol fatty liver disease (NAFLD). NAFLD, if not treated, may progress to non-alcoholic steatohepatitis (NASH). Furthermore, inflammation leads to liver fibrosis, cirrhosis, and hepatocellular carcinoma. Vitexin, a natural flavonoid, has been recently reported for inhibiting NAFLD. It is a lipogenesis inhibitor and activates lipolysis and fatty acid oxidation. In addition, owing to its antioxidant properties, it appeared as a hepatoprotective candidate. However, it exhibits low bioavailability and low efficacy due to its hydrophobic nature. A novel rat model for liver cirrhosis was developed by CCL4/Urethane co-administration. Vitexin encapsulated liposomes were synthesized by the &lsquo;thin-film hydration&rsquo; method. Polyethylene glycol (PEG) was coated on liposomes to enhance stability and stealth effect. The diseased rats were then treated with vitexin and PEGylated vitexin liposomes, administered intravenously and orally. Results ascertained the liposomal encapsulation of vitexin and subsequent PEG coating to be a substantial strategy for treating liver cirrhosis through oral drug delivery