Current Pharmaceutical Biotechnology - Volume 21, Issue 11, 2020

Curcumin, isolated from the rhizome of Curcuma longa, is one of the most extensively studied phytochemicals. This natural compound has a variety of pharmacological effects including antioxidant, anti-inflammatory, anti-tumor, cardio-protective, hepato-protective and anti-diabetic. Wnt signaling pathway, one of the potential targets of curcumin through upregulation and/or downregulation, plays a significant role in many diseases, even in embryogenesis and development of various organs and systems. In order to exert an anti-tumor activity in the organism, curcumin seems to inhibit the Wnt pathway. The downstream mediators of Wnt signaling pathway such as c-Myc and cyclin D1 are also modified by curcumin. This review demonstrates how curcumin influences the Wnt signaling pathway and is beneficial for the treatment of neurological disorders (Alzheimer’s and Parkinson’s diseases), cancers (melanoma, lung cancer, breast cancer, colon cancer, endothelial carcinoma, gastric carcinoma and hepatocellular carcinoma) and other diseases, such as diabetes mellitus or bone disorders.

Graphene Derivatives (GDs) have captured the interest and imagination of pharmaceutical scientists. This review exclusively provides pharmacokinetics and pharmacodynamics information with a particular focus on biopharmaceuticals. GDs can be used as multipurpose pharmaceutical delivery systems due to their ultra-high surface area, flexibility, and fast mobility of charge carriers. Improved effects, targeted delivery to tissues, controlled release profiles, visualization of biodistribution and clearance, and overcoming drug resistance are examples of the benefits of GDs. This review focuses on the application of GDs for the delivery of biopharmaceuticals. Also, the pharmacokinetic properties and the advantage of using GDs in pharmaceutics will be reviewed to achieve a comprehensive understanding about the GDs in pharmaceutical sciences.

Background: Cancer is the leading cause of death worldwide and the current mode of cancer treatment causes side effects on normal cells and are still the key challenges in its’ treatment. However, natural products or active compounds of medicinal plants have shown to be safe, affordable, and effective in diseases cure. Methods: In this context, scientific studies evidence the health-promoting effects of natural products, which work through its anti-oxidant, anti-inflammatory, and anti-cancer activity. Thymoquinone (TM), a predominant active compound of Nigella sativa, has confirmed anti-neoplastic activity through its ability to regulate various genetic pathways. In addition, thymoquinone has established anti-cancerous effects through killing of various cancerous cells,and inhibiting the initiation, migration, invasion, and progression of the cancer. The anti-cancer effects of TM are chiefly mediated via regulating various cell signaling pathways such as VEGF, bcl2/bax ratio, p53, NF-kB, and oncogenes. Results: The anti-cancer drugs have limitations in efficacy and also causes adverse side effects on normal cells. The combination of anti-cancer drugs and thymoquinone improves the efficacy of drugs which is evident by decrease resistance to drugs and regulation of various cell signaling pathways. Moreover, combination of anti-cancer drugs as well as thymoquinone shows synergistic effect on killing of cancer cells and cells viability. Thus, TM, in combination with anti-cancer drugs, can be a good strategy in the management of various types of cancer. Conclusion: In this review article, we deliver an outline of thymoquinone role in cancer inhibition and prevention of cancer-based on in vivo and in vitro studies. Further studies on thymoquinone based on clinical trials are highly required to explore the benefits of thymoquinone in cancer management.

Background: Probiotics can be used for the treatment of viral gastroenteritis. Objective: This systematic review is to evaluate the evidence regarding the effect of probiotics on human cases of viral gastroenteritis. Methods: The objective of this review is to evaluate the effectiveness of probiotics against placebo or standard treatment for viral gastroenteritis. A comprehensive search of Cochrane Library, EMBASE, MEDLINE via PubMed and Ovid databases, and unpublished studies (till 27 January 2018) was conducted followed by a process of study selection and critical appraisal by two independent reviewers. Randomized controlled trials assessing probiotic administration in human subjects infected with any species of gastroenteritis viruses were considered for inclusion. Only studies with a confirmed viral cause of infection were included. This study was developed using the JBI methodology for systematic reviews, which is in accordance with the PRISMA guideline. Meta-analysis was conducted where feasible. Data were pooled using the inverse variance method with random effects models and expressed as Mean Differences (MDs) with 95% Confidence Intervals (CIs). Heterogeneity was assessed by Cochran Q statistic and quantified by the I2 statistic. We included 17 RCTs, containing 3,082 patients. Results: Probiotics can improve symptoms of viral gastroenteritis, including the duration of diarrhea (mean difference 0.7 days, 95% CI 0.31 to 1.09 days, n = 740, ten trials) and duration of hospitalization (mean difference 0.76 days, 95% CI 0.61 to 0.92 days, n = 329, four trials). Conclusion: The results of this review show that the administration of probiotics in patients with viral gastroenteritis should be considered.

Background: Vancomycin is the first-line antibiotic used for the treatment of staphylococcal infections. Because of its narrow therapeutic window and the pharmacokinetics variability, vancomycin trough serum concentration should be monitored. However, due to the increased cases of staphylococcus’ commensal species infections and the case of vancomycin resistance, the minimal inhibitory concentration should be considered on antimicrobial therapy. Objective: This article aimed to show the importance of the minimal inhibitory concentration to infants on vancomycin therapy as regular criteria. Materials and Methods: Three infants in the use of vancomycin, hospitalized in the same maternity hospital, and that had at least one blood culture performed during the intensive-care-unit hospitalization were included in the study. Vancomycin serum concentrations were determined by particleenhanced- turbidimetric inhibition-immunoassay. The vancomycin minimal inhibitory concentration data were interpreted by following the Clinical and Laboratory Standards Institute (CLSI) and the European Committee on Antimicrobial Susceptibility Testing (EUCAST). The trough serum concentration range of 10 to 20 mg.L-1 was considered therapeutic. Results: All three patients had at least one infection by S. epidermidis, being one patient exhibit vancomycin- resistant S. epidermidis infection. All patients had stoppages in the vancomycin treatment, and the minimal inhibitory concentration was performed for only one patient. Conclusion: The data obtained from these patients also showed the need to perform therapeutic monitoring by using minimal inhibitory concentration values, because, although the serum concentrations were within the reference range, they are insufficient to guarantee patient therapeutic success.

Background: The folkloric profile of Delonix regia demonstrates that it can be used in the management of diabetes. Objective: The present study was conducted to evaluate the safety profile of the aerial part extracts of Delonix regia and their antidiabetic potential along with improvement in oxidative stress. Materials and Methods: Phytochemical screening, total phenolic, and flavonoid contents along with in-vitro antioxidant and alpha-amylase inhibitory activities were determined. HPLC analysis, acute toxicity, glucose tolerance, in-vivo antidiabetic effect along with the influence on biochemical, oxidative stress parameters, and comet assay of the active extract were performed and assessed. Results: Total phenolic (831.6±0.002 mg/g GAE) and flavonoid (361.4±0.002 mg/g QE) contents were found to be higher in the methanolic extract. Inhibitory concentration IC50 indicated better results for the methanolic extract in DPPH (47.6μg/mL) and alpha-amylase inhibitory (14.61μg/mL) assays. HPLC analysis of the methanolic extract confirmed the presence of quercetin, gallic acid, caffeic acid, cinnamic acid, ferulic acid, and p-coumaric acid. Acute oral toxicity exhibited no mortality and morbidity during the 24h period. The methanolic extract showed better tolerance to glucose. Streptozotocin- nicotinamide (55-110 mg/kg) induced hyperglycemia declined along with improvement in hematological, biochemical parameters and oxidative stress markers (SOD, CAT, H202) in a dose-dependent manner. The maximum effect was recorded at 500mg/kg dose. Comet assay was performed for genotoxic studies and it was observed that the methanolic extract of Delonix regia showed the maximum genoprotective effect at 100μg/mL. Conclusion: The findings suggest that the methanolic aerial part extract of Delonix regia exhibited hypoglycemic, antioxidant, and hypolipidemic activities. The antidiabetic effect was comparable to glibenclamide suggesting its therapeutic use as a natural anti-diabetic remedy.

Introduction: The plant, Astilboides tabularis (Hemsl.) Engler, is used in Chinese and Korean medicine to regulate blood sugar levels; however, little is known about its precise effects. Materials and Methods: In this study, we aimed to measure the composition as well as the antioxidant, and anti-proliferative capacities of A. tabularis. Various extracts were generated using different organic solvents, and in vitro antioxidant activities were evaluated using DPPH free radical-scavenging and reducing power assays. The extracts were also evaluated based on their ability to inhibit lipopolysaccharide (LPS)-induced Nitric Oxide (NO) production in RAW 264.7 cells. Results: Research shows that the A. tabularis ethyl acetate (EtOAc) extract showed significant antioxidant activity. Additionally, this extract could inhibit the LPS-induced expression of inflammatory mediators and pro-inflammatory cytokines in RAW 264.7 cells, including inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), and interleukin-1 beta (IL-1ß). Notably, the A. tabularis EtOAc extract also displayed potent cytotoxic effects against MCF-7 and HeLa cancer cell lines, as determined by MTT assays. Lastly, total phenol and flavonoid content was measured for all extracts, and four flavonoid compounds-catechin, kaempferol, quercitrin, and isoquercetin were isolated from the EtOAc extract. Their structures were confirmed using mass spectrometry and nuclear magnetic resonance, and these isolated compounds were found to display potent DPPH free radical-scavenging activity. Conclusion: Thus, our data suggest that phenolic compounds in A. tabularis extracts promote antioxidant activity, and furthermore, these extracts show numerous features that indicate potential for therapeutic development.

Background: PCL has a long history as an industrialized biomaterial for preparing microspheres, but its hydrophobic property and slow degradation rate often cause drug degeneration, quite slow drug release rate and undesirable tri-phasic release profile. Materials and Methods: In this study, we used the blending material of PLGA-PEG-PLGA and PCL to prepare microspheres. The microspheres degradation and drug release behaviors were evaluated through their molecular weight reduction rate, mass loss rate, morphology erosion and drug release profile. The hydrophilic PLGA-PEG-PLGA is expected to improve the degradation and drug release behaviors of PCL microspheres. Results: Microspheres in blending materials exhibited faster erosion rates than pure PCL microspheres, forming holes much quickly on the particle’s surface for the drug to diffuse out. A higher proportion of PLGA-PEG-PLGA caused faster degradation and erosion rates. The blending microspheres showed much faster drug release rates than pure PCL microspheres. Conclusion: With blending of 25wt% PLGA-PEG-PLGA, the release rate of microspheres speeded up significantly, while, with a further increase of PLGA-PEG-PLGA proportion (50%, 75%, 100%), it accelerated a little. The microspheres with PCL/PLGA-PEG-PLGA of 1/1 exhibited a linear-like drug release profile. The results could be a guideline for preparing microspheres based on blending materials to obtain a desirable release.

Objective: The folate-modified graphene oxide (GO-FA), which had good stability and biocompatibility on rat glioma cells was successfully prepared. Methods: The formation and composition of GO-FA were confirmed by Scanning Electron Microscope (SEM), Transmission Electron Microscope (TEM), Fourier Transform Infrared Spectrum (FT-IR), Raman spectra and X-ray Photoelectron Spectroscopy (XPS spectra). The cell experiment suggested good biocompatibility of GO-FA on rat glioma cells. Results: The experiment of GO-FA loading with Temozolomide (TMZ) showed that the maximum drug loading of GO-FA was 8.05 ± 0.20 mg/mg, with the drug loading rate of 89.52 ± 0.19 %. When TMZ was released from the folate-modified graphene oxide loading with temozolomide (GO-FATMZ), its release behavior in vitro showed strong pH dependence and sustained release property. The growth of rat glioma cells can be effectively inhibited by GO-FA-TMZ, with the cell inhibition rate as high as 91.72 ± 0.13 % at the concentration of 600 μg/mL and time of 72 h. Conclusion: According to the above experimental results, this composite carrier has potential applications in drug delivery and cancer therapy.

Background: Chlorogenic Acid (CA) has diverse, recognized health effects. Objective: This study aimed to explore the effects of CA on fat reduction and the underlying mechanism of these effects. Materials and Methods: First, we established a Monosodium Glutamate (MSG)-induced obesity mouse model and subjected the mice to 4 weeks of CA gavage. Then, we established an oleic acidinduced model of human fatty liver in HepG2 cells, and administered a CA intervention to the cells for 48 h. Finally, we used Oil red O staining, biochemical detection kits, RT-PCR and Western blot analysis to evaluate the effects of CA on fat reduction and on related pathways. Results: The CA treatment could reduce fat accumulation in the liver and reduce blood lipid levels. In addition, CA decreased the mRNA and protein levels of peroxisome proliferator-activated receptor gamma, coactivator 1 α (PGC-1α) and Uncoupling Protein 1 (UCP1) in the MSG-induced obesity mouse model and the oleic acid-induced HepG2 cells. Conclusion: Based on the above results, we deduced that CA could reduce body weight and fat deposition in vitro and in vivo and that the mechanism may be related to the PGC-1α/UCP-1 pathway. CA can be developed as a drug to lower blood lipids and to treat obesity.

Objective: Renal fibrosis is a common pathway leading to the progression of chronic kidney disease. Activated fibroblasts contribute remarkably to the development of renal fibrosis. Although apigenin has been demonstrated to play a protective role from fibrotic diseases, its pharmacological effect on renal fibroblast activation remains largely unknown. Materials and Methods: Here, we examined the functional role of apigenin in the activation of renal fibroblasts response to transforming growth factor (TGF)-β1 and its potential mechanisms. Cultured renal fibroblasts (NRK-49F) were exposed to apigenin (1, 5, 10 and 20 μM), followed by the stimulation of TGF-β1 (2 ng/mL) for 24 h. The markers of fibroblast activation were determined. In order to confirm the anti-fibrosis effect of apigenin, the expression of fibrosis-associated genes in renal fibroblasts was assessed. As a consequence, apigenin alleviated fibroblast proliferation and fibroblastmyofibroblast differentiation induced by TGF-β1. Results: Notably, apigenin significantly inhibited the fibrosis-associated genes expression in renal fibroblasts. Moreover, apigenin treatment significantly increased the phosphorylation of AMP-activated protein kinase (AMPK). Apigenin treatment also obviously reduced TGF-β1 induced phosphorylation of ERK1/2 but not Smad2/3, p38 and JNK MAPK in renal fibroblasts. Conclusion: In a summary, these results indicate that apigenin inhibits renal fibroblast proliferation, differentiation and function by AMPK activation and reduced ERK1/2 phosphorylation, suggesting it could be an attractive therapeutic potential for the treatment of renal fibrosis.

Background: Semaphorin 3F (SEMA3F) plays a substantial role in carcinogenesis, because of its role in inducing angiogenesis, and creating a microenvironment for the developing tumor. Objective: The purpose of this work was to assess the impact of cisplatin, depending on the concentration and exposure time on the expression pattern of SEMA3F in an endometrial cancer cell line. Materials and Methods: Cultures of the Ishikawa endometrial cancer cells were incubated with cisplatin with the following concentrations: 2.5μM; 5μM; and 10μM and for the following periods of time: 12; 24; and 48 hours. Cells not incubated with the drug constituted the control in the experiment. To determine the effect of cisplatin on the expression of SEMA3F, the real-time quantitative reverse transcription reaction (RtqPCR; mRNA) was used, as well as the ELISA assay (protein). The statistical analysis was done with the admission of p<0.05. Results: The silencing of SEMA3F expression on the transcriptome and proteome levels in a culture unexposed to the effects of cisplatin in comparison to endometrial cancer cells under the influence of cisplatin (p<0.05) were noted. Along with an increase in the concentration of the drug used, the number of copies of the gene transcript, during the shortest incubation period had a gradual increase. Only for the highest concentration of the drug, substantial statistical differences in the expression of the SEMA3F protein between 24 and 48 hour incubation periods (p<0.05) were determined. Conclusion: Using cisplatin in an endometrial cancer cell culture results in an increased expression of SEMA3F, which advantageously affects the normalization of the neoplastic angiogenic process and lowers the proliferation of the cells making up the mass of the tumor.

Background: Herein, we report the biosynthesis procedure to prepare silver nanoparticles as reduction and capping agents with the aqueous plant extract of Perovskia abrotanoides. Methods: The therapeutic application of silver nanoparticles entirely depends on the size and shape of the nanoparticles therefore, their control during the synthesis procedure is so important. The effects of synthesis factors, for example, silver ion concentration, the mass of plant extract, reaction time and extraction temperature, on the size of silver particles were considered and optimized. Several analytical methods were used for the characterization of silver NPs including FT-IR and UV–Vis spectrophotometer, XRD and SEM. Results: The results showed that the mean size of the silver particles was about 51 nm. Moreover, the antibacterial properties of biosynthesized silver NPs were investigated by the minimum inhibitory concentration, minimum bactericidal concentration, and Well-diffusion tests. The minimum inhibitory concentration/ minimum bactericidal concentration values of silver NPs and aqueous plant extract versus Gram-positive bacteria (Staphylococcus aureus and Bacillus cereus) and Gram-negative bacteria (E. coli) were 3.03/0.00, 1.20/0.01, 3.06/0.00, 0.98/1.04, 1.00/0.05 and 1.30/0.03 (mg/mL), respectively. Conclusion: The antimicrobial activity study displayed that the synthesized silver nanoparticles by plant extract have better antimicrobial properties compared to aqueous plant extract of Perovskia abrotanoides.