Iranian Journal of Pharmaceutical Sciences

Although previous studies have demonstrated the importance of the orexin system in regulating enzymes involved in lipogenesis, its exact mechanism and the extent of this effect on different enzymes have remained unexplored. In this regard, this study is aimed at investigating the intra-duct injection of orexin receptor 1 and 2 antagonists (OX1RA and OX2RA) into the mammary glands. More specifically, the study probes the effect of this injection on glycerol 3-phosphate acyl transferase (Gpat1 and Gpat4) genes as well as the milk's triacylglycerol (TAG) level in lactating Wistar rats. Twenty four lactating Wistar rats were randomly divided into different experimental groups including the control group, the group receiving OX1RA and OX2RA intraductally (at doses of 5, 10, and 20 µg/kg of B.W.). Six hours after injection, the collection of milk samples were done using rat milking device, and TAG measurements were carried out. Moreover, using real time PCR, we measured target genes by a specific primer for each gene. One-way ANOVA with Tukey’s post hoc tests were used to analyze the results and the level of significance was considered P<0.05. The findings of the present study showed that the injection of orexin antagonists at a dose of 10 μg/kg resulted in a significant reduction in Gpat1 and Gpat4 gene expressions. In addition, the injection of antagonists with the same dose caused a significant decrease in TAG levels. Intra-ductal injection of orexin antagonists into the mammary gland decreases milk TAG levels and decreases the expression of Gpat1 and Gpat4 genes.

This study was designed to examine the effects of aqueous and hydroalcoholic extracts of oats (Avena sativa), which are rich in beta-glucan with established anti-pigmentation effects on the melanin biosynthesis rate in melanocyte cell cline, B16F10, as well as its safety effects on skin normal cells. Maceration method was used to extract the seed powder of Avena sativa and then the polysaccharide content was determined. The safety of extracts was analyzed using MTT assay on L-929 cells. The anti-melanogenic effects of the extracts were determined using the calculation of mushroom tyrosinase inhibitory effects, the B16F10 treated cells assay for evaluating the extracts tyrosinase inhibitory effects and the melanin contents, in comparison to the PBS as the negative control. Our results showed that the aqueous and hydroalcoholic extracts had no significant toxicity on L-929 normal cells. In comparison to the Kojic acid used at the EC₅₀ concentration  (3 µg/ml), both aqueous and hydroalcoholic extracts led to mushroom and intracellular tyrosinase inhibition as well as reduction in melanin content of B16F10 treated cells, concentration dependently, especially at the highest concentration, 5 mg/ml. Finally, the total polysaccharide count in water and hydroalcoholic extracts was calculated as about 2.9 and 2.8 µg, respectively, for 5 µg of dried extracts. In conclusion, this study has proven the anti-melanogenic and tyrosinase inhibitory effects of Avena sativa extracts without any toxic effects on skin normal cells in the effective concentrations. So, with reliable laboratory effectiveness, attempts to prepare suitable formulation from this herb is therefore suggested.

Avicennia marina is known as the main species of mangrove forests in Iran. The study of biological processes shows that the presence of a wide range of phytochemical compounds in this plant has made it an excellent candidate for use in therapeutic applications. The purpose of this study was to investigate the cytotoxicity and apoptosis induction of hydroalcoholic extract of A. marina on human glioblastoma and normal fibroblast cell lines. With this aim, the hydroalcoholic extract of A. marina leaves were extracted firstly and then the target cells were treated with different concentrations of the extract. Cell viability percentage of treated normal and cancer cells was assessed using MTT assay at 24, 48 and 72 h. Also, the half maximal inhibitory concentration (IC₅₀) values of hydroalcoholic extract were calculated at the times of testing for both cancer and normal cell lines. Quantitative PCR (qPCR) was used to evaluate the expression of Bcl2 and Bax apoptotic genes and dual staining (AO / EB) was used to stain the nucleus of target cells for imaging by a fluorescence microscope. The results of cytotoxicity tests showed that the hydroalcoholic extract of A. marina is able to inhibit the metabolic growth of more than half of U-87 MG cells at a concentration of 0.57 mg/ml. It was also found that hydroalcoholic extract has a higher effectiveness in inhibition of cancer cells proliferation compared to normal cells. Analysis of Bcl-2 and Bax genes expression levels in cells treated with A. marina extract showed a significant decrease in Bcl-2 anti-apoptotic gene expression levels (P <0.01) and an increase in Bax apoptotic gene expression levels (P <0.001). Eventually, the results of the dual staining study of the cell nucleus clearly depicted the morphological changes in different stages of apoptosis and confirmed the results of the qPCR and MTT assay.

The prevalence of psychiatric disorders namely depression, anxiety, and sleep disturbances has been increased worldwide, particularly during the COVID-19 pandemic. In this regard, the interest of recent investigations is moved toward phytomedicines and bioactive substances derived from natural sources. Although Tilia platyphyllos Scop. contains high amounts of phenolic compounds such as quercetin, kaempferol, and catechin, there is no study on the possible effects of its extract on psychological disorders. The present study was carried out to determine the antidepressant-like, anxiolytic, and sedative-hypnotic effects of the hydroethanolic extract of T. platyphyllos leaves using forced swimming test (FST), tail suspension test (TST), elevated plus maze test (EPMT), pentobarbital-induced loss of righting reflex test and open field test (OFT). Following the ethanolic extraction of T. platyphyllos leaves, the extraction yield was 14% and the total phenolic and total flavonoid contents were found to be 135.23 ± 0.14 mg gallic acid equivalent/g dry extract and 19.02 ± 0.03 mg rutin equivalent/g dry extract, respectively. Both FTS and TST revealed a significant antidepressant-like activity for the tested extract at 400 mg/kg compared to the control group. In addition, the anxiolytic activity of the extract was proven through OFT and EPMT in the same dose. Finally,
T. platyphyllos extract at 200 mg/kg and 400 mg/kg significantly increased the sleeping time when compared to the control group reflecting its potential hypnotic activity. Co-administration of T. platyphyllos extract at 400 mg/kg and flumazenil as the GABA-A receptor antagonist decreased the sleeping time but the observed effect was not statistically significant. Therefore, we cannot completely rule out the GABA-A receptor's involvement in the hypnotic activity of the extract. The biological results presented here led us to conclude that T. platyphyllos extract can be a prominent source of antidepressant, anxiolytic and hypnotic agents. Probably, the main phenolic compounds of T. platyphyllos such as quercetin, kaempferol, and catechin are involved in the observed effects. However, there is still a great need for additional investigations on the exact mechanisms.

Melanoma is the cause of most skin cancer all around the world because of its high proliferation rate, metastatic nature, and limited effective therapies. According to the rapid increment in its incidence compared to other types of skin cancers, new therapies are seemed to be essential. Natural remedies can be used to treat many diseases, including cancer, so more research is needed. The wood of Santalum album Linn, known as “white sandalwood”, is one of the herbs which is a rich source of antioxidants that can be used as a therapeutic medication in different types of cancers, especially skin cancer. This research aimed to verify the cytotoxic effects of white sandalwood on A375 and SK-MEL-3 melanoma and AGO-1522 normal human fibroblast cell lines. At first, the ethanolic extract was prepared. Then, cell viability and cytotoxic activities were evaluated. Furthermore, ROS formation, lipid peroxidation, and release of cytochrome-c were also assessed. Herb extract significantly increased the death of A375 and SK-MEL-3 melanoma cells (p < 0.001), lipid peroxidation (p < 0.01), and reactive oxygen species (p < 0.01) and cytochrome c concentration (p < 0.001). Meanwhile, the same amount was ineffective and safe on AGO-1522 normal fibroblast cells. The extract of white sandalwood has considerable cytotoxic effects on the human melanoma cell line. Further studies are required to demonstrate the therapeutic effects of white sandalwood on melanoma cancer.

Stroke is one of the major causes of mortality worldwide. Memantine, an NMDA receptor antagonist, has protective effects on neuronal cells and is important candidate as a neuroprotective agent in cerebral ischemia. On the other hand, thyroid hormones are one of the important factors in the development of the central nervous system (CNS) and its activity and the long-term adverse effects of transient thyroid function abnormalities at birth on intellectual development has been proven. Therefore, the aim of the present study was to evaluate the effects of memantine on cerebral ischemia/reperfusion (I/R) induced injuries in transient congenital hypothyroidism (TCH). The adult male Wistar TCH rats (240±20 g) were underwent forebrain ischemia by bilateral common carotid artery occlusion for 17 min. Memantine (20 mg/kg) alone or in combination with vitamin C (200 mg/kg) were administered intraperitoneally (ip) for 7 days after cerebral ischemia. Then, histopathology, cerebral infarct size and malondialdehyde level were evaluated. Histopathological analysis showed that memantine significantly decreased leukocyte infiltration in comparison to I/R group (p<0.01). Memantine also reduced infarct size and malondialdehyde level compared with I/R group (p<0.01). Memantine and vitamin C combination group had no significant effects on leukocyte infiltration, infarct size and malondialdehyde level. Our results showed that memantine through reduction in leukocyte infiltration, lipid peroxidation and infarct size could reduce cerebral ischemia/reperfusion induced injuries in transient congenital hypothyroidism. Hence, memantine might be considered as a neuroprotective agent in hypothyroidism.

Breast cancer is the most common cancer among women and only second in terms of cancer-related death in women. Finding new approaches to treat such cancers is critically important anti-cancer peptides (ACPs) offer the possibility of efficient-cancer drugs, and therefore, the development of drug delivery systems using ACPs as a synergism factor is an attractive strategy to address the current drawbacks of cancer therapeutics. This work investigated the cytotoxicity for a series of synthesized compounds based on triazole or ciprofloxacin conjugated peptides against T-47D breast cancerous cells and possible antibacterial effects. Wang resin was used for constructing peptide sequences on a solid support using the method of solid-phase peptide synthesis (spps) with the Fmoc strategy. Cytotoxicity of the synthesized peptide compounds was evaluated by MTT assay. The antimicrobial effect of synthesized peptide compounds was evaluated by agar well diffusion and Broth microdilution method. Most of the peptide compounds showed a cytotoxic effect toward T-47D cells. The antimicrobial effect of the peptide compounds was examined by agar well diffusion test and broth microdilution method. E. coli and S. aureus strains have shown the least amount of resistance. In the end, we suggest a new design based on these compounds and modifications to gain better anti-cancer agents

Monkeypox virus is a zoonotic virus belonging to the family of Poxviridae and the genus Orthopoxvirus, which is the cause of a viral disease between humans and animals, the characteristics of which are comparable to other cases of smallpox with some differences. Recently some patients caused by the monkeypox virus (MPXV) were reported to the WHO. In recent years, the widespread and rapid spread of some epidemics highlighted the need for the rapid development of effective vaccines in scientific communities. Although conventional therapies have played an essential role in the treatment of many diseases, emerging diseases require new methods of treatment with fewer complications. It is therefore important to develop an effective vaccine for infections caused by the Monkeypox virus to prevent mortality and the safety of the community. In this research, we have used bioinformatics to design a vaccine against the F13 envelope protein Monkeypox virus.  A total epitope confined to B cells and MHC I and II alleles were structurally constructed in F13 envelope protein to stimulate immunity and antibody recognition which was used to construct a chimeric peptide vaccine. The vaccine was predicted as a stable, antigenic, and non-allergenic combination. analysis of the TRL4/vaccine docking complex and simulation indicate a sufficiently stable binding with receptor activation. The immune response simulation following hypothetical immunization indicates the potential for stimulation and production of active and memory B cells, as well as the potential for cell production of CD8 + T, CD4 + T, and the development of effective immunological responses induced by Th2 and Th1. Analysis of the in silico processes have shown that the structure of the vaccine produces high antigenicity and good cellular immunity in the host body and stimulates various immune receptors such as TLR4, MHC I and MHC II. Vaccine function was also associated with increased IgM and IgG and a set of Th1 and Th2 cytokines. But final confirmation of the effectiveness of the designed vaccine requires clinical processes.