Iranian Journal of Pharmaceutical Research最新文献

Objectives: We aimed to evaluate the impact of the tryptanthrin (TRP) compound, with antimicrobial and anti-inflammatory effects, on the excisional wound (EW) model. In an EW model in mice, we tried to explain the possible effect of TRP through vascular endothelial growth factor (VEGF) and matrix metalloproteinase-9 (MMP-9) that contribute significantly to wound healing.

Methods: A total of 90 BALB-C female mice aged 6 - 8 weeks were used in the present study. Animals were randomly divided into five groups. After creating the EW model, three different doses (1, 2.5, 5 mg/kg) of TRP compound were applied topically for 14 days, and wound closure rates were measured on days 0, 3, and 7. Vascular endothelial growth factor and MMP-9 were evaluated on days 3, 7, and 14 on wound explants and on day 14 on serum samples by enzyme-linked immunosorbent assay. Histopathological analysis was performed on wound explants.

Results: After the EW model creation, significant healing of the wound areas was observed in the groups for which TRP was applied, especially on the third day. Moreover, in groups that received the third dose of TRP, the wound closure rate was 94%. It was found that the wound areas were closed due to the increase in TRP dose. In line with wound healing, VEGF and MMP-9 levels gradually rose on the third and seventh days and decreased on the 14th day.

Conclusions: Tryptanthrin compound usage on the EW model increased wound healing and did not leave a scar after 14 days.

Background: Proteolysis-targeting chimera (PROTAC) is a bifunctional molecule comprising a ligand to recognize the targeted protein to be degraded.

Objectives: To use the advantages of the PROTAC technique, we have synthesized novel compounds to degrade inosine monophosphate dehydrogenase (IMPDH) by the proteasome system.

Methods: We describe the synthesis of new PROTACs based on a combination of mycophenolic acid (MPA) as the potent IMPDH inhibitor and pomalidomide as a ligand of E3 ubiquitin ligase via linkers formed from Cu(I)-catalyzed cycloaddition reaction.

Results: All synthesized compounds were investigated against Jurkat cells as acute T-cell leukemia and were potent apoptosis inducers at 50 nM.

Conclusion: The effect of compound 2 in 0.05 μM on IMPDH degradation can be almost prevented by competition with bortezomib as the proteasome inhibitor at 0.1 and 0.5 μM.

Background: The main therapy for head and neck cancer is radiation, and one of the toxic effects of radiation is radiation dermatitis. Aloe vera is a species of succulent plant of the genus Aloe, widely used in cosmetic and skin care products, as well as daikon (Raphanus sativus var. longipinnatus), which is high in antioxidants.

Objectives: The present study aims to evaluate the potential benefits of Aloe vera and daikon gel combination in head and neck cancer patients to prevent radiation-induced dermatitis.

Methods: A cohort study was conducted with eligible subjects, all head and neck cancer patients receiving radiation therapy selected in consecutive sampling. Samples were divided into two groups; either received Aloe vera and daikon combination gel (study group) or baby oil (control induced dermatitis (RID) were observed.

Results: A total of 44 patients were grouped into intervention (Aloe vera-daikon gel) and control (baby oil) groups. After ten radiotherapies (RT) sessions, the intervention group had a lower percentage of grade 1 RID (35% vs. 91.7%, control: 65% grade 2 RID, P < 0.001). After 20 RT sessions, 40% had no dermatitis, while all patients had RID in the control group (P = 0.061). After 30 RT sessions, the intervention group had a lower RID grade overall (gr 0: 5%, gr 1: 85%, gr 2: 10%) compared to the control group (gr 1: 33.3%, gr 2: 54.3%, gr 3: 8.3%, P = 0.002). After 35 RT sessions, the intervention group also had a lower RID grade overall (gr 0: 5%, gr 1: 65%, gr 2: 20%, gr 3: 10%) compared to the control group (gr 1: 8.3%, gr 2: 37.5%, gr 3: 45.8%, gr 4: 8.3%, P < 0.001).

Conclusions: The combination of Aloe vera and daikon gel showed promising results in reducing the severity of radiation-induced dermatitis for head and neck cancer patients.

Background: Irritant contact dermatitis is a common inflammatory skin disease characterized by skin barrier dysfunction, eczematous dermatitis, and chronic itching. This disease severely affects the quality of life. Considering that the current treatment approaches are not ideal, more extensive research is needed to develop new treatments. Mainly, a mouse model is needed to investigate the effectiveness of new drugs to treat this disease.

Objectives: This study was conducted to create a mouse model of irritant contact dermatitis.

Methods: In the current study, we used BALB/c female mice to prepare a mouse model of irritant contact dermatitis. To induce irritant contact dermatitis, we used a dinitrochlorobenzene mixture with acetone/olive oil as an irritant. After 10 days of application, the mouse skin tissue was isolated and examined in terms of histopathology.

Results: The introduced protocol created an irritant contact dermatitis model clinically and histopathologically.

Conclusions: In the present study, we introduced a new protocol using a mixture of dinitrochlorobenzene and acetone/olive oil to create an irritant contact dermatitis model. Mouse models have been extensively used to discover the complex mechanisms of irritant contact dermatitis and provide a preclinical platform before conducting clinical interventional research on humans to evaluate a new therapeutic approach. However, one should always look for models that cause the least pain and suffering in the animal and simultaneously are simple and reliable for the desired studies. Thus, our protocol is a new approach that can be effective and painless in creating a model of irritant contact dermatitis.

Background: Recent studies on Leishmaniasis treatment have confirmed the antiparasitic effects of flavonols and organic antimony pentavalent [(Sb(V)] complexes.

Objectives: This study aimed to identify new Sb(V) complexes by combining the benefits of antimonials and flavonols as well as by optimizing their properties.

Methods: Kaempferol and quercetin peracetate were prepared using acetic anhydride in pyridine. By performing regioselective synthesis, 7-O-paramethylbenzyl as an electron-donating group and 7-O-paranitrobenzyl as an electron-withdrawing group were added to quercetin, and, then, the synthesis of Sb(V) kaempferol and quercetin derivative complexes were performed using SbCl₅ solution in glacial acetic acid. The structures were confirmed by UV, ESI mass, IR, 1H-, and ¹³C-NMR spectral data, and the Stoichiometry of the ligand-metal complex by the mole ratio method. Computational molecular modeling was conducted using the Gaussian program.

Results: The structures were confirmed based on the results from UV, nuclear magnetic resonance (NMR), and electrospray ionization (ESI) mass analyses (3-12). Among the produced compounds, 11 and 12 as newly described, and other compounds as pre-defined compounds were identified. According to the results from biological test, kaempferol triacetate with more lipophilicity showed the highest anti-promastigote activity with an IC₅₀ value of 14.93 ± 2.21 µM. As for anti-amastigote activity, despite the differences, all antimony complexes showed anti-amastigote effects in vitro with IC₅₀ values of 0.52 to 14.50 µM.

Conclusions: All flavonol Sb(V) complexes showed higher activity compared to meglumine antimonate in anti-amastigote effect. Inside the host macrophages, by breaking down the complex into antimony and quercetin or kaempferol analogs, the observed antiparasitic effects may have been related to both Sb(V)/Sb(III) conversion and flavonoid antileishmanial activities.

Background: Hepatic ischemia/reperfusion injury is a major problem that can exacerbate complications, particularly in liver transplantations.

Objectives: This study aimed to investigate the cellular mechanisms of ischemia/reperfusion injury and hepatoprotection by curcumin.

Methods: Wistar albino rats were divided into four groups as Control, Sham, I/R, and Cur+I/R. Hepatic ischemia/reperfusion was induced in I/R and Cur+I/R animals, the latter of which was also given 50 mg/kg/day of curcumin for 14 days. Liver aminotransferases and the transcription regulators of inflammation (RelA, IκB, PPAR-α, PPAR-γ, CREB1) were examined along with the histological examination.

Results: Hepatic ischemia/reperfusion was found to disrupt hepatic microstructure and downregulate PPAR-α, PPAR-γ, and CREB1 transcripts. Curcumin supplementation in hepatic ischemia/reperfusion recovered the structural organization and promoted the hepatocyte regeneration while increasing expressions of PPARs and CREB1. RelA and IκB were found unaltered, possibly due to the crosstalk between targeted transcripts by ischemia/reperfusion and curcumin.

Conclusions: In sum, PPAR-α/γ and CREB1 were involved in hepatic ischemia/reperfusion and, moreover, were detected to be stimulated by curcumin. PPAR and CREB pathways were found to provide a route to hepatoprotection for curcumin supplementation as evidenced by the microstructural improvement.

Background: Cell culture has a crucial role in many applications in biotechnology. The production of vaccines, recombinant proteins, tissue engineering, and stem cell therapy all need cell culture. Most of these activities needed adherent cells to move, which should be trypsinized several times until received on a large scale. Although trypsin is manufactured from the bovine or porcine pancreas, the problem of contamination by unwanted animal proteins, unwanted immune reactions, or contamination to pathogen reagents is the main problem.

Objectives: This study investigated microbial proteases as a safe alternative for trypsin replacement in cell culture experiments for the detachment of adherent cells.

Methods: The bacteria were isolated from the leather industry effluent based on their protease enzymes. After sequencing their 16S ribosomal deoxyribonucleic acid, their protease enzymes were purified, and their enzyme activities were assayed. The alteration of enzymatic activities using different substrates and the effect of substrate concentrations on enzyme activities were determined. The purified proteases were evaluated for cell detachment in the L929 fibroblast cells compared to trypsin. The separated cells were cultured again, and cell proliferation was determined by the MTT assay.

Results: The results showed that the isolated bacteria were Bacillus pumilus, Stenotrophomonas sp., Klebsiella aerogenes, Stenotrophomonas maltophilia, and Bacillus licheniformis. Among the isolated bacteria, the highest and the lowest protease activity belonged to Stenotrophomonas sp. and K. aerogenes, with 60.34 and 11.09 U/mL protease activity, respectively. All the isolated microbial proteases successfully affected L929 fibroblast cells' surface proteins and detached the cells. A significant induction in cell proliferation was observed in the cells treated with K. aerogenes protease and B. pumilus protease, respectively (P < 0.05).

Conclusions: The obtained results suggested that microbial proteases can be used as safe and efficient alternatives to trypsin in cell culture in biopharmaceutical applications.

In this study, molecularly imprinted Mn-doped ZnS quantum dots were used as nanosensors to determine diazepam and its metabolites. Mn-doped ZnS quantum dots (QDs) capped with L-cysteine were prepared using a sodium thiosulfate precursor and characterized by various methods. Methacrylic acid was used as a precursor for the synthesis of MIP Mn-doped ZnS QDs and then used to measure diazepam in various samples. The linear dynamic range, coefficient of determination, and detection limit were found to be 0.3 - 250 µmol/L, 0.989 and 8.78 × 10^-2 µmol/L, respectively. The interference studies showed that the prepared nanosensor was selective for diazepam and its metabolites.

Background: Silkworm products were first used by physicians more than 8500 years ago, in the early Neolithic period. In Persian medicine, silkworm extract has several uses for treating and preventing neurological, cardiac, and liver diseases. Mature silkworms (Bombyx mori) and their pupae contain a variety of growth factors and proteins that can be used in many repair processes, including nerve regeneration.

Objectives: The study aimed to evaluate the effects of mature silkworm (Bombyx mori), and silkworm pupae extract on Schwann cell proliferation and axon growth.

Methods: Silkworm (Bombyx mori) and silkworm pupae extracts were prepared. Then, the concentration and type of amino acids and proteins in the extracts were evaluated by Bradford assay, sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), and liquid chromatograph-mass spectrometer (LC-MS/MS). Also, the regenerative potential of extracts for improving Schwann cell proliferation and axon growth was examined by 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl tetrazolium bromide (MTT) assay, electron microscopy, and NeuroFilament-200 (NF-200) immunostaining.

Results: According to the results of the Bradford test, the total protein content of pupae extract was almost twice that of mature worm extract. Also, SDS-PAGE analysis revealed numerous proteins and growth factors, such as bombyrin and laminin, in extracts that are involved in the repair of the nervous system. In accordance with Bradford's results, the evaluation of extracts using LC-MS/MS revealed that the number of amino acids in pupae extract was higher than in mature silkworm extract. It was found that the proliferation of Schwann cells at a concentration of 0.25 mg/mL in both extracts was higher than the concentrations of 0.01 and 0.05 mg/mL. When using both extracts on dorsal root ganglion (DRGs), an increase in length and number was observed in axons.

Conclusions: The findings of this study demonstrated that extracts obtained from silkworms, especially pupae, can play an effective role in Schwann cell proliferation and axonal growth, which can be strong evidence for nerve regeneration, and, consequently, repairing peripheral nerve damage.

Background: As a chronic joint condition, osteoarthritis (OA) is a common problem among older people. Pain, aching, stiffness, swelling, decreased flexibility, reduced function, and disability are the symptoms of arthritis.

Objectives: In this study, we tested the extracts of Ziziphus jujuba (ZJE) and Boswellia serrata (BSE) to reduce OA symptoms as an alternative treatment.

Methods: NMRI mice were administered an intra-articular injection of monosodium iodoacetate (MIA; 1 mg/10 mL) in the left knee joint cavity for the induction of OA. Hydroalcoholic extracts of ZJE (250 and 500 mg/kg), BSE (100 and 200 mg/kg), and combined ZJE and BSE were orally administered daily for 21 days. Following behavioral tests, plasma samples were collected to detect inflammatory factors. To screen for general toxicity, acute oral toxicity was evaluated.

Results: Oral administration of all the hydroalcoholic extracts significantly increased the locomotor activity, pixel values of the foot-print area, paw withdrawal threshold, the latency of the withdrawal response to heat stimulation, and decreased the difference between pixel values of hind limbs compared to the vehicle group. Also, the elevated levels of IL-1β, IL-6, and TNF-α were reduced. As tested in this study, ZJE and BSE were practically nontoxic and had a high degree of safety.

Conclusions: This study demonstrated that the oral administration of ZJE and BSE slows the progression of OA through anti-nociceptive and anti-inflammatory properties. Oral co-administration of ZJE and BSE extracts can be used as herbal medicine to inhibit OA progression.