فهرست مطالب
Jundishapur Journal of Natural Pharmaceutical Products
Volume:20 Issue: 1, Feb 2025
- تاریخ انتشار: 1403/09/24
- تعداد عناوین: 22
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Page 2Background
Tanshinone IIA is effective in the treatment of various cardiovascular diseases. Currently, tanshinone IIA is primarily derived from the roots and rhizomes of Salvia miltiorrhiza Bunge. However, resources of S. miltiorrhiza are already facing scarcity.
ObjectivesThe aim of this study was to obtain an alternative and high-yield mutagenic strain of tanshinone IIA, thus establishing a cost-effective and non-plant-derived substitute for tanshinone IIA.
MethodsThe mutants with enhanced tanshinone IIA production were selected through protoplast mutation induced by ultraviolet radiation (UV) and sodium nitrite (NaNO 2 ). The yield of tanshinone IIA (YT) was determined using a TU-1810 ultraviolet-visible (UV/Vis) Spectrophotometer and LC-2010A high-performance liquid chromatography (HPLC). The selected mutant strains with the highest yield were subjected to continuous cultivation, and the dry weight of mycelium (DW) and the YT in the first generation were used as controls to assess passage stability. Fungal genomic DNA from the wild-type and mutant strains was extracted from axenic cultures using the modified cetyltrimethyl ammonium bromide (CTAB) method.
ResultsThe colony morphological characteristics exhibited significant differences between the wild-type TR21 and the mutant NU204. The NU204 demonstrated a significantly higher tanshinone IIA yield at 165 ± 2.52 μg/g, which was 4.67-fold greater than that of TR21 (P < 0.01), indicating a substantial enhancement in NU204 production compared to TR21. The NU204 underwent continuous cultivation for five generations, and there were no significant differences in the DW and YT among the different generations (P > 0.05). The observed genetic changes between TR21 and NU204 were induced by the protoplast mutation.
ConclusionsThe mutant NU204 is emerging as a promising novel alternative source for tanshinone IIA, offering potential practical applications in production.
Keywords: Tanshinone IIA, Endophytes, Mutation, Salvia Miltiorrhiza -
Page 3Background
Multiple sclerosis (MS) damages the myelin sheath covering nerve fibers. This condition affects 400,000 individuals in the United States and 2.5 million people globally, with a higher rate of diagnosis in women aged 20 - 40, with a ratio of 2:1. Liposomes facilitate drug dispersion, making them valuable in biomedicine. They enhance the stability of therapeutic medications, improve cellular and tissue absorption, and increase chemical bioactivity at specific locations. This technique delivers encapsulated compounds with high precision while minimizing negative consequences observed in laboratory settings.
ObjectivesThis study aims to develop an optimal nanoliposome formulation using glatiramer acetate (GA) as the active pharmaceutical ingredient by examining drug release and associated adverse effects to achieve the most effective nanoliposomal system.
MethodsThe thin layer hydration method was used to prepare nanoliposomes. A comprehensive array of analytical techniques, including FE-SEM, FTIR, XRD, HPLC, and DLS, were employed to examine the physicochemical characteristics of the product. Additionally, the biosafety of the nanoliposomes was assessed using the MTT assay on the 1321N1 human astrocytoma cell line. The release profile of GA from the carrier was studied using the dialysis diffusion method, and the stability of the nanoliposomes was also inspected.
ResultsThe size, Polydispersity Index (PDI), and zeta potential of the nanoliposomes were 91.2 ± 1.3 nm, 0.34 ± 0.03, and -27.3 ± 1.2 mV, respectively. The drug entrapment efficiency (DEE%) in nanoliposomes was approximately 70.2 ± 1.7%. The results from XRD and FTIR revealed no chemical interaction between the drug and carrier, and the nanoliposomes were safe for the cultured cell line. The nanoliposomes were stable under storage conditions and exhibited a sustained release profile.
ConclusionsNanoliposomes, as drug carriers, are known to be a potent drug delivery system due to their numerous advantages. Based on the results, GA-nanoliposomes show promise as a strategy for treating MS patients, pending further in vivo experiments and clinical trials.
Keywords: Drug Delivery, Nanoliposomes, Multiple Sclerosis, Glatiramer Acetate -
Page 4
Antimicrobial resistance poses a significant global health challenge, necessitating the search for novel therapeutic approaches. Streptococcus mutans , a key etiological agent in dental caries, requires innovative strategies due to its biofilm-forming ability and resistance to conventional antibiotics. Natural plant-derived compounds have garnered attention as potential antimicrobial agents with a low risk of resistance development. In this study, we investigated the synergistic antibacterial effect of a hydroalcoholic Mentha extract combined with alum against Streptococcus mutans (PTCC 16836). The well diffusion assay demonstrated that alum exhibited a larger inhibition zone diameter (12.04 ± 2.02 mm) compared to the hydroalcoholic Mentha extract (10.33 ± 1.53 mm). However, the minimum inhibitory concentration (MIC) values for the hydroalcoholic Mentha extract (8.20 ± 5.57 mg/mL) and alum (0.35 ± 0.20 mg/mL) were comparable. The minimum bactericidal concentration (MBC) for the hydroalcoholic Mentha extract was 10 mg/mL, while the MBC for alum was 0.625 ± 0.006 mg/mL. The combination of these substances demonstrated a synergistic effect, indicating enhanced antibacterial activity against Streptococcus mutans .The study's findings suggest potential applications in dentistry, offering a natural and effective adjunctive treatment for dental caries management. The underlying mechanisms of this synergistic effect warrant further exploration. To translate these promising findings into clinical applications, further in vivo investigations and rigorously designed clinical trials are necessary to establish the safety and efficacy of this combination therapy. The natural origin of these substances may provide an environmentally sustainable and cost-effective approach in the fight against antimicrobial resistance.
Keywords: Alum, Antibacterial Activity, Dental Caries, Menthaextract -
Page 5Background
Hypercholesterolemia is a critical risk factor for cardiovascular diseases. Although there is no cure for it, controlling lifestyle factors such as diet and exercise is essential. One potential approach for treating hypercholesterolemia is developing novel delivery platforms incorporating probiotics. Probiotics have been shown to significantly reduce lipid profiles due to their antioxidant properties.
ObjectivesIn this study, the researchers investigated the effects of oral supplementation with the lyophilized probiotic extract (LPE) of Lactobacillus casei on reducing lipid profiles in hyperlipidemic rats fed a fatty diet and fructose.
MethodsThis study involved 40 adult male Wistar rats, randomly divided into five groups: A negative control, a sham, and three treatment groups (T1, T2, and T3). The rats in the treatment groups received doses of 60, 120, and 240 mg/mL of LPE, respectively. Hyperlipidemia was induced in all groups by administering a mixture of 0.5% cholesterol, 30% tallow, and 20% fructose. The LPE supplementation was given orally once a day for two weeks. After the treatment period, blood samples were taken from all the rats 15 days later.
ResultsThe results indicated that hyperlipidemia led to a significant increase in total blood cholesterol levels, including TG, LDL, and ALP (P < 0.001). Lyophilized probiotic extract supplementation significantly decreased total blood cholesterol levels (P < 0.05).
ConclusionsThe study demonstrated that LPE can reduce lipid levels and have a hypolipidemic effect in hyperlipidemic rats. Additionally, histopathology showed that a 540 mg/kg dose of LPE had an effective liver-protective effect.
Keywords: Probiotic, Hyperlipidemia, LPE, Lactobacillus Casei, Rat -
Page 6Background
Thymus extracts have become attractive targets for screening bioactive compounds with potential applications in pharmaceuticals, food, and cosmetics industries.
ObjectivesThis is the first report assessing the anticholinesterase and antioxidant activities, along with total phenolic and flavonoid contents (TPC and TFC), of hydroethanolic extracts from six populations of Thymus caramanicus Jalas at vegetative and flowering stages, collected from different regions in Kerman province, Iran.
MethodsThe anticholinesterase and antioxidant activity, as well as TPC and TFC of T. caramanicus hydroethanolic extracts, were evaluated using Ellman, DPPH, Folin-Ciocalteu, and aluminum chloride assays, respectively.
ResultsAll extracts inhibited both acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) enzymes, with most showing a stronger effect on AChE. The extract T2-F exhibited the highest anti-AChE (IC 50 : 28.74 ± 0.21 µg/mL) and anti-BuChE (IC 50 : 65.49 ± 0.81 µg/mL) activities. The DPPH results indicated overall suitable antioxidant activity, with T4-F showing the highest antioxidant capacity (IC 50 : 16.22 ± 0.07 µg/mL), though about 4.2 times lower than ascorbic acid. The TPC (76.60 ± 0.98 - 211.73 ± 2.13 mg GAE/g extract) and TFC (19.15 ± 0.09 - 53.90 ± 0.13 mg QE/g extract) analyses revealed that T6-V and T5-F are rich sources of polyphenolic and flavonoid compounds. Pearson’s correlation analysis showed no direct correlation between TPC and TFC with their anticholinesterase and antioxidant activities.
ConclusionsThe hydroethanolic extracts of T. caramanicus demonstrated significant anticholinesterase and antioxidant activities, making them promising candidates for further studies aimed at developing therapeutic compounds with dual anticholinesterase and antioxidant properties, potentially for treating Alzheimer's disease (AD).
Keywords: Thyme, Thymus Caramanicusjalasanticholinesterase Activity, Antioxidant Activity, Alzheimer's Disease (AD) -
Page 7
Dendritic cell-based cancer immunotherapy is considered an innovative and promising approach aimed at enhancing the host's immune response to combat tumors. Additionally, IPI-549 has been identified as a first-line therapeutic option for breast cancer treatment. The objective of this research was to develop and formulate a novel therapeutic supplement by combining dendritic cells with IPI-549 (Eganelisib) for breast cancer treatment. The concurrent administration of dendritic cells and IPI-549 (DC-IPI) was utilized to treat mice and elicit immunological responses triggered by vaccination. Tumor regression and overall survival rates were evaluated across five distinct experimental groups. The administration of tumor cell lysate alongside DC-IPI resulted in a significant reduction in tumor growth and a two- to three-fold increase in the survival duration of treated mice. DC-IPI, whether decorated with mannan or not, elicited stronger responses in terms of delayed-type hypersensitivity, lymphocyte proliferation, and CD107a expression. Moreover, our findings demonstrated a reduction in IL-4 production in the supernatants of splenocyte cultures. A significant reduction in BRCA1 mRNA levels was also observed following treatment with DC-IPI. In conclusion, our results suggest that the DC-IPI antigen delivery system exhibited substantial anti-tumor efficacy in a breast cancer mouse model, representing a potential advancement in immunotherapy for human breast cancer.
Keywords: Breast Cancer, Dendritic Cells, IPI-549, BRCA-1 Gene, BALB, C Mice -
Page 8Background
Cervical cancer is the fourth most common cancer among women. In recent years, significant progress has been made in its treatment. Quercetin, a polyphenolic compound found in flavonoid-containing plants, is of interest due to its potential therapeutic effects. miR-21 plays a crucial role in cervical tumor metastasis by activating pathways related to invasion and migration, while miR-34a-5p is essential in regulating epithelial-to-mesenchymal transition and preventing increased cell proliferation and migration. The findings of this study could provide insight into the role of quercetin in cancer cells.
ObjectivesThis study aims to investigate the effect of quercetin on the expression levels of miR-21 and miR-34a-5p in HeLa and Ca Ski cervical cancer cell lines.
MethodsIn this study, HeLa and Ca Ski cells were treated with quercetin. Cell viability and apoptosis were evaluated using the MTT assay and flow cytometry over a 48-hour period. Additionally, the effects of quercetin on the expression levels of miR-21 and miR-34a-5p were analyzed using qRT-PCR.
ResultsThe study demonstrated that quercetin inhibited the viability of HeLa and Ca Ski cells and induced apoptosis in these cells. Quercetin suppressed cell viability with an IC 50 of 102.9 μM for HeLa and 304.1 μM for Ca Ski cells after 48 hours. Quercetin down-regulated miR-21 in HeLa and Ca Ski cell lines by 2.5 ± 0.1 (P = 0.045) and 2.0 ± 0.2 (P = 0.016) fold, respectively. Additionally, miR-34a-5p increased by 3.3 ± 0.7 (P = 0.010) and 2.4 ± 0.8 (P = 0.047) fold after exposure to quercetin in HeLa and Ca Ski cell lines, respectively.
ConclusionsOur study showed that quercetin has an anti-cervical cancer effect and can be used alongside standard therapies as a promising agent with fewer side effects in cervical cancer treatment.
Keywords: Quercetin, Mir-21, Mir-34A-5P, Hela, Ca Ski -
Page 9Background
Sesame oil (SO) is one of the edible oils beneficial to health. The use of SO due to its high content of antioxidants and unsaturated fatty acids has many applications in the production of functional foods and pharmaceuticals. In recent years, many efforts have been made to use nanotechnology, including encapsulation technology, to protect functional foods from destructive environmental factors and thereby extend the shelf life of foods.
ObjectivesThis study aimed to prepare and investigate the Physicochemical characteristics of SO-nanoemulsion coated with maltodextrin/acacia gum powder by spray drying method.
MethodsSesame Oil-nanoemulsion (SO-NE) was prepared and encapsulated using maltodextrin and acacia gum. The coated nanoemulsion was spray dried, and its Physicochemical properties including Encapsulation Efficiency, Particle Size, Thermal Analysis, and zeta potential were investigated. The size and morphology of produced nanoparticles were investigated by FESEM imaging.
ResultsThe mean particle size determined by the DLS technique and FESEM was 166.5 and 96.5 nm, respectively, with a spherical shape. The zeta potential of the coated SO-nanoemulsion was -48.1 mV, showing suitable stability. Comparison of thermograms of the coated nanoemulsion containing SO and without it did not show any change in the thermal behavior of the ingredients. According to the GC-MS analysis, the encapsulation efficiency was found to be 92.93 ± 4.61%.
ConclusionsIt can be concluded that due to the high efficiency of encapsulation processes and spray drying technique in maintaining the Physicochemical Stability of SO, the method used in this research can be applied in the food and pharmaceutical industry.
Keywords: Encapsulation, Shelf Life, Sesame Oil, Functional Food -
Page 10Background
Cyclophosphamide (CP) can induce severe hepatotoxicity in certain patients by generating oxidative molecules and increasing reactive oxygen species (ROS). There are limited reports on the antioxidant and anti-inflammatory properties of sildenafil.
ObjectivesThis study aimed to evaluate the effect of sildenafil on CP-induced hepatotoxicity.
MethodsAnimals were randomly divided into five groups (n = 6): Group 1 (control) received water distillate by gavage. Group 2 received CP (200 mg/kg) intraperitoneally to induce hepatotoxicity. Group 3 was orally administered sildenafil (75 mg/kg) along with CP (200 mg/kg), while Group IV received vitamin E (500 mg/kg) and CP (200 mg/kg). Group V was administered 75 mg/kg of sildenafil, 200 mg/kg of CP, and 500 mg/kg of vitamin E. At the end of the experiment, blood samples were collected from the animals' hearts to measure serum levels of liver enzymes, including aspartate transaminase (AST) and alanine aminotransferase (ALT), as well as oxidative stress markers malondialdehyde (MDA), nitric oxide (NO), and ferric reducing antioxidant power (FRAP). Liver tissue was also collected for assessment of antioxidant enzyme activity, including catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GPx), along with histological examination.
ResultsThe CP-treated group exhibited significant increases in AST, ALT, MDA, and NO levels, while CAT, SOD, GPx, and FRAP levels were markedly lower in the CP group compared to the saline group (P ≤ 0.01). Administration of sildenafil, alone and in combination with vitamin E, significantly reduced levels of AST, ALT, MDA, and NO. Meanwhile, antioxidant enzyme activity was markedly enhanced following sildenafil and vitamin E intake (P ≤ 0.01). Additionally, histological analysis confirmed sildenafil's hepatoprotective properties.
ConclusionsThis study demonstrated that sildenafil, both alone and in combination with vitamin E, was effective in reducing CP-induced liver toxicity through antioxidant mechanisms. Therefore, these findings suggest that sildenafil, especially when combined with vitamin E, may serve as a complementary therapy to mitigate the hepatotoxic effects of CP.
Keywords: Sildenafil, Cyclophosphamide, Hepatotoxicity, Rat, Vitamin E -
Page 11Background
Herbal medicines have recently been incorporated into the treatment algorithm for functional dyspepsia (FD). Persian-FACT, a traditional herbal medicine compound, has been used for centuries in Persian medicine to alleviate dyspeptic symptoms. This compound includes anise, fennel, ajwain, and cumin seeds.
ObjectivesTo investigate the efficacy of Persian-FACT as a therapeutic agent for FD.
MethodsWe conducted an add-on, single-center, double-arm, parallel-group, double-blind, randomized controlled clinical trial at the Imam-Reza Clinic, affiliated with Shiraz University of Medical Sciences in Shiraz, Iran, in 2022. Adults aged 18 to 65 years with a confirmed diagnosis of FD, as referred by a gastroenterologist, were included in the study. After block randomization, participants received sachets containing either Persian-FACT or a placebo (oat) to be taken twice daily for two weeks. The severity of dyspepsia, postprandial distress syndrome (PDS), and epigastric pain syndrome (EPS) (PPI) was assessed using the Gastrointestinal Symptom Rating Scale and the Rome IV questionnaire every week.
ResultsThirty-two patients in the Persian-FACT group and twenty-three in the placebo group completed all visits. According to the results of the GEE analysis, the severity of dyspepsia symptoms in the Persian-FACT group was significantly lower than in the placebo group after the intervention (P-value = 0.019). Patients with EPS showed significant improvement from the first week, and those with PDS showed significant improvement after two weeks in the Persian-FACT group compared to the placebo group (P-value = 0.001 vs. P-value = 0.028). Additionally, constipation, gastroesophageal reflux, postprandial fullness, and bloating were significantly reduced with Persian-FACT.
ConclusionsPersian-FACT appears to be effective in improving dyspepsia symptoms.
Keywords: Ajwain, Anise, Cumin, Fennel, Herbal Compounds, Traditional Medicine, Persian Medicine -
Page 12Background
This study synthesized alginate-chitosan nanoparticles (ALG/CS NPs) as nanocarriers for the hydrophobic drug levothyroxine and investigated their nanoparticle size.
ObjectivesAlginate-chitosan nanoparticles were prepared through ionotropic gelation of the chitosan core followed by complexation with alginate.
MethodsThe nanoparticles were characterized for particle morphology, size, and polydispersity index using transmission electron microscopy (TEM) and photon correlation spectroscopy.
ResultsAlginate-chitosan nanoparticles were found in a nanoscale spherical shape with an average particle size of 90 - 110 nm. Results indicated that the release mechanism depends on dissolution in the initial hours. For levothyroxine release from ALG/CS NPs, the Higuchi model fits better than the other models. The drug release kinetics were investigated, and the release kinetics data were best fitted with the Higuchi model.
ConclusionsLevothyroxine was released mainly in the first 20 hours at an average rate of up to 78% at pH 7.4.
Keywords: Levothyroxine, Nanocarriers, Chitosan, Alginate, Nanoparticle, Drug Delivery -
Page 13Background
Limitations in drug penetration are overcome by nanotechnology, particularly liposomes, which enhance targeted administration of ocular medications. Liposomes can augment the therapeutic effects of curcumin, a natural compound with positive impacts on the retina. Treatments for eye diseases can also benefit from the antibacterial properties of ozonated oil liposomes.
ObjectivesThis study aims to develop and evaluate ozonated liposomes loaded with curcumin for ocular drug delivery applications, specifically targeting diabetic retinopathy (DR).
MethodsLiposomal nanoparticles were prepared using thin-film hydration, incorporating phospholipids, lecithin, cholesterol, ozonated oil, and curcumin. We assessed physicochemical properties including particle size, zeta potential, encapsulation efficiency (EE), and morphology. Drug release profiles and stability studies were also conducted.
ResultsThe optimized liposomes showed a particle size of 84.77 nm, a zeta potential of -16.8 mV, and an EE of 94.73%. The formulation exhibited sustained curcumin release over 24 hours, reaching 82.09% cumulative release. Stability studies indicated minimal changes in key parameters over three months at room temperature.
ConclusionsThe developed ozonated liposomal formulation demonstrates promising characteristics for curcumin delivery, potentially enhancing its therapeutic efficacy in ocular applications, particularly for DR.
Keywords: Curcumin, Liposomes, Ozonated Oil, Ocular Drug Delivery, Diabetic Retinopathy -
Page 14Background
Ulcerative colitis (UC) is a chronic inflammatory disease of the large intestine that cannot be cured, but its symptoms can be managed.
ObjectivesThis study aimed to evaluate the protective effects of hydroalcoholic and aqueous extracts of Ulmus minor leaves on UC induced by acetic acid in rats.
MethodsRats were randomly divided into seven groups of five, and 3% acetic acid was used to induce colitis. To assess the protective effect of Ulmus minor leaves, macroscopic, microscopic, and histological evaluations were performed on the different study groups.
ResultsMacroscopic examinations of both the hydroalcoholic and aqueous extract groups showed that the aqueous extract at a dose of 200 mg/kg provided the best protective effect on colon tissue. Rats treated with hydroalcoholic extracts at doses of 100 mg/kg and 200 mg/kg, as well as those treated with aqueous extract at 100 mg/kg, also showed favorable outcomes compared to the control group, with a significant difference (P < 0.05). Furthermore, among the groups treated with hydroalcoholic and aqueous extracts, the aqueous extract at 200 mg/kg demonstrated the most protective effects based on microscopic and histological evaluations of the colon.
ConclusionsThe extracts of Ulmus minor leaves demonstrated anti-inflammatory properties in an animal model of colitis. Further studies are required to evaluate their potential therapeutic benefits in patients with UC.
Keywords: Acetic Acid, Colitis, Rat, Inflammation, Ulmus Minorleaves -
Page 15Background
There has been significant interest in using Cotoneaster for treating jaundice or elevated bilirubin levels in newborns, and it has, in many cases, replaced phototherapy in herbal medicine. However, using these compounds to treat hyperbilirubinemia can lead to complications in neonates, potentially resulting in morbidity and even death.
ObjectivesThis study examined the side effects of Cotoneaster consumption in jaundiced neonates admitted to the Children’s Medical Center between 2021 and 2022.
MethodsWe conducted a cross-sectional study involving healthy neonates who consumed Cotoneaster following treatment for neonatal jaundice and subsequently experienced complications. The data were recorded using pre-prepared questionnaire forms.
ResultsThe most common complications following Cotoneaster derivatives were exaggerated hyperbilirubinemia, dehydration, and poor feeding.
ConclusionsGiven the sensitivity of neonates, the treatment of jaundice in babies should be approached with caution and supported by extensive studies. The use of herbal medicines in neonates remains questionable due to associated complications.
Keywords: Cotoneaster, Neonate, Jaundice, Complications, Herbal Drugs -
Page 17Background
Pseudomonas aeruginosa is an opportunistic pathogen with a high mortality rate, particularly among immunocompromised patients. The increase in antibiotic resistance in P. aeruginosa isolates from clinical samples has prompted researchers to seek alternative ways to reduce the pathogenicity of this microorganism. Targeting quorum sensing (QS) presents a promising approach for limiting infections caused by this bacterium.
ObjectivesThis study aimed to evaluate mechanisms for reducing QS and controlling bacterial growth using various medicinal plants.
MethodsIn this study, the anti-QS effects of seven plant extracts—thyme ( Thymus vulgaris ), chamomile ( Matricaria chamomilla ), sumac ( Rhus coriaria ), ginger ( Zingiber officinale ), lemon balm ( Melissa officinalis ), rosehip ( Echinacea angustifolia ), and marshmallow ( Althaea officinalis )—were investigated against P. aeruginosa . A total of 180 P. aeruginosa clinical isolates were examined. High-performance liquid chromatography (HPLC) was then used to detect phenolic compounds and flavonoids in the seven extracts. The presence of quorum-sensing genes ( lasR , rhlR , and rhlI ) was also evaluated. In addition, pyocyanin quantification, swarming motility assays, and biofilm formation assays were conducted with the herbal extracts.
ResultsThe HPLC analysis results were determined based on relative times and peak areas, revealing specific peaks at different points. Molecular methods confirmed the presence of QS genes, including LasI (54%), lasR (34%), rhlR (12%), and rhlI (4%), which were used in anti-QS screening. Expression of the LasI gene decreased in P. aeruginosa strains treated with herbal extracts compared to untreated strains. Notably, Thymus vulgaris extract demonstrated the strongest inhibition, reducing violacein production by 70.5%, suppressing pyocyanin by 94%, and inhibiting swarming motility and biofilm formation by 80.3%.
ConclusionsThis study demonstrated that herbal extracts influence virulence factors and gene expression, particularly targeting the las gene, in P. aeruginosa isolates. We recommend further research on the extraction and identification of active ingredients, which may hold potential as therapeutic agents.
Keywords: Pseudomonas Aeruginosa, Quorum Sensing, Chromobacterium Violaceum, HPLC, Medicinal Plant -
Page 18Background
The increasing prevalence of antibiotic-resistant Staphylococcus epidermidis strains underscores the urgent need for alternative therapeutic approaches. Probiotics, known for their ability to competitively exclude pathogens and modulate host immune responses, present promising potential in combating S. epidermidis infections.
ObjectivesThis study aimed to evaluate the effectiveness of probiotics in inhibiting the growth of S. epidermidis .
MethodsStaphylococcus epidermidis was isolated from urine samples of hospitalized patients in Isfahan, Iran. Probiotics were isolated from yogurt and milk. The antibacterial activity of these probiotics was assessed using agar well diffusion and broth microdilution methods. Time-kill assays and acid tolerance tests were also conducted. Anti-biofilm effects were evaluated, and the potential inhibitory mechanisms were explored through chemical analysis using high-performance liquid chromatography (HPLC). Cytotoxicity was assessed via 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays.
ResultsTwo probiotic strains, Streptococcus lutetiensis OR496927.1 and Lactiplantibacillus plantarum OR496928, were successfully isolated from dairy products. Both strains exhibited cytotoxic effects on S. epidermidis isolates, with S. lutetiensis demonstrating significant activity at 1/2 minimum inhibitory concentration (MIC) and L. plantarum at 1/4 MIC. L. plantarum thrived at pH 3, while S. lutetiensis exhibited growth at both pH 3 and 4. Both probiotics showed anti-biofilm activity, though L. plantarum demonstrated stronger effects overall. The strains produced lactic, formic, and acetic acids, which were key factors in their inhibitory effects. Toxicity was observed at a concentration of 50% after 24 hours, while cell viability remained unaffected at lower concentrations.
ConclusionsThe findings highlight the potential of probiotics to address antibiotic-resistant S. epidermidis infections. Further research is necessary to explore their therapeutic applications and optimize treatment strategies.
Keywords: Lactiplantibacillus Plantarum, Staphylococcus Epidermidis, Probiotic, Streptococcus Lutetiensis -
Page 19Background
Shikonin, a compound extracted from Lithospermum erythrorhizon , has demonstrated therapeutic effects on cancer; however, its effects on oral cancer remain unclear.
ObjectivesThis study aimed to explore the therapeutic value of shikonin for the treatment of oral cancer.
MethodsMTT, colony formation, and Transwell assays were employed to evaluate the inhibitory effects of shikonin on the proliferation and migration abilities of human oral cancer cell lines (SCC-4 and SAS). Apoptosis and cell viability were assessed using the TdT-mediated deoxyuridine triphosphate-biotin nick end-labeling (TUNEL) assay. To investigate the potential anticancer mechanisms of shikonin, RNA sequencing, quantitative PCR, and western blotting were performed to analyze changes in the expression levels of oral cancer cell-related genes and proteins (matrix metalloproteinases-2 (MMP-2), matrix metalloproteinases-9 (MMP-9), VEGF-A, VEGF-C, Beclin-1, autophagy-related genes (ATG5), and light chain-3 (LC-3)). Additionally, animal xenograft experiments were conducted to examine the in vivo antitumor effects of shikonin.
ResultsThe findings revealed that the external application of shikonin specifically targeted oral cancer cells without affecting normal cells and led to a dose-dependent inhibition of their growth. Even at non-lethal doses, shikonin effectively suppressed the production of metalloproteinases, thereby inhibiting cancer cell migration and wound healing. Furthermore, shikonin treatment reduced levels of tumor progression factors, such as vascular endothelial growth factor (VEGF)-A and VEGF-C, which are released during the early stages of cancer cell angiogenesis and lymphangiogenesis. Meanwhile, higher doses of shikonin induced cell autophagy and activated proteins such as ATG-5, LC-3B, and Beclin-1. At lethal doses, shikonin further decreased mitochondrial membrane potential, released calcium ions, and triggered apoptotic pathways. However, the administration of a calcium ion chelator (BAPTA-AM) inhibited shikonin-induced apoptosis.
ConclusionsThese results demonstrate that shikonin induces autophagy and activates apoptotic pathways in oral cancer cells. Shikonin treatment significantly inhibited oral cancer growth and induced apoptosis in a rat model. In conclusion, shikonin effectively inhibited oral cancer cell growth, metastasis, and the expression of tumor progression-related proteins. Given the ease of drug delivery to the affected area in oral cancer, shikonin holds substantial potential for future applications that may improve patient recovery and enhance cure rates.
Keywords: Shikonin, Oral Cancer, Cell Apoptosis, Autophagy, Metastasis, Healing -
Page 20Background
The Artemisia genus is well-known for its medicinal properties, particularly in Iranian traditional medicine. Artemisia biennis , a species within this genus, is widely distributed across Iranian rangelands.
ObjectivesThis study aimed to evaluate the cytotoxic activity and chemical composition of essential oils (EO) isolated from the aerial parts of A. biennis in Iran at different growth stages.
MethodsThe aerial parts of A. biennis from northeast Iran were collected during June (early vegetative stage), July (pre-flowering stage), August (full-flowering stage), and October (late vegetative stage). The essential oils (EOs) of the A. biennis species were extracted by hydro-distillation using a Clevenger-type apparatus and analyzed using gas chromatography–mass spectrometry (GC/MS). The cytotoxic activity of the EOs against normal fibroblasts, MCF-7, and HT-29 cell lines was evaluated using the MTT assay.
ResultsData from GC/MS analysis revealed that (Z)-nerolidol (22.62 - 54.4%), (E)-β-farnesene (6.89-16.38%), and (Z)-tonghaosu (12.33 - 18.61%) were the most abundant chemical constituents. The essential oil (EO) of A. biennis was characterized by a high content of oxygenated sesquiterpenes, with (Z)-nerolidol being the main constituent identified. Based on the MTT assay, the EO of the plant species collected in June exhibited the most potent cytotoxicity against MCF-7 (IC 50 = 2.84 ± 0.15 µg/mL) and HT-29 cell lines (IC 50 = 2.41 ± 0.2 µg/mL).
ConclusionsThe growth stage of A. biennis affects EO yields, the composition of extracted secondary metabolites, and cytotoxic activity. A. biennis EOs can be considered potential sources of cytotoxic phytochemicals.
Keywords: Artemisia Biennis, Growth Stages, Nerolidol, Tonghaosu, Farnesene, Cytotoxic Activity -
Page 21Background
Medicinal plants like Guiera senegalensis J. F. Gmel. (GS) have gained attention for their potential neuroprotective effects due to their rich composition of bioactive compounds, including flavonoids and polyphenolic acids. While previous studies have highlighted the antioxidant, anti-inflammatory, and neuroplasticity-enhancing properties of GS extract, its efficacy in mitigating dementia-related pathology remains to be fully understood.
ObjectivesThis study aimed to investigate the neuroprotective effects of hydroethanolic GS extract against scopolamine (Sco)-induced dementia in Wistar rats, focusing on its impact on cholinergic function, oxidative stress, neuroinflammation, neurodegeneration, and memory impairment.
MethodsFresh leaves were processed for extraction using standard methods. Antioxidant activity was evaluated using FRAP and DPPH assays. Adult male Wistar rats were used for behavioral tests (Y-maze, NOR, MWM) and biochemical analyses, including ELISA for cholinergic activity, oxidative stress markers (Aβ1-42, phosphorylated Tau), pro-inflammatory cytokines (IL-1β, TNF-α, IL-6, IFN-γ), GFAP, BDNF, and IL-10. Brain tissues underwent histopathological examination. Data were analyzed using GraphPad Prism software.
ResultsThe study assessed the antioxidant potential of GS extract and found that it significantly scavenged DPPH radicals (70.29%) and reduced Fe 3+ (49.69%). Behavioral tests showed that GS extract (100 - 400 mg/kg) improved spatial memory and learning in Sco-treated rats. Y-maze results indicated increased spontaneous alternation with GS extract (P < 0.01). NOR and MWM tests showed improved memory and learning, with GS extract-treated rats spending more time in the target quadrant. Biochemical analysis revealed that GS extract increased acetylcholine (ACh), Superoxide Dismutase (SOD), Catalase (CAT), Glutathione (GSH), IL-10, and BDNF levels, while decreasing acetylcholinesterase (AChE), malondialdehyde (MDA), nitrite, Aβ1-42, phosphorylated Tau, IL-1β, TNF-α, IL-6, IFN-γ, and GFAP levels in the hippocampus. Histological analysis confirmed restored hippocampal tissue architecture in AD rats treated with GS extract.
ConclusionsOur findings suggest that GS modulates cholinergic, antioxidant, anti-inflammatory, and neuroplasticity pathways, exerting beneficial effects on cognitive functions and biochemical markers associated with Alzheimer's disease (AD) pathology. These results indicate the potential of GS as a neuroprotective agent for the treatment of AD.
Keywords: Guiera Senegalensis (GS), Alzheimer's Disease (AD), Neuroprotective, Cholinesterase Inhibitors, Antioxidants, Anti-Inflammatory -
Page 22Background
Preeclampsia is one of the most serious complications of pregnancy, leading to various maternal and fetal complications.
ObjectivesThis study aimed to determine the effect of oral esomeprazole in the treatment of preeclampsia in pregnant mothers.
MethodsIn this double-blind clinical trial, we compared oral esomeprazole with a placebo. The study population included 120 pregnant women with preeclampsia (60 in the esomeprazole 40 mg group and 60 in the placebo group) who were referred to Ba'ath Hospital in Sanandaj in 2023. Patient care and follow-up were conducted from the time of diagnosis of preeclampsia and inclusion in the study groups until delivery and the final condition of the baby. The outcomes investigated included prolongation of pregnancy and maternal, fetal, and neonatal outcomes.
ResultsThe average delivery time in the esomeprazole group was 37.3 ± 1.2 weeks, compared to 37.5 ± 1.7 weeks in the placebo group, with no statistically significant difference (P = 0.75). The frequency of maternal outcomes, such as eclampsia, pulmonary edema, hemolysis, placental abruption, renal failure, hepatic hematoma, ascites, thromboembolism, and maternal death, was not statistically different between the esomeprazole and placebo groups, and no severe complications were observed in either group. Similarly, fetal outcomes, including intrauterine growth restriction (IUGR) and changes in fetal heart rate patterns, did not significantly differ between groups, with no instances of fetal or neonatal death observed. Additionally, neonatal outcomes, such as Apgar scores below 7, NICU admissions, mechanical ventilation, and other severe neonatal complications, were not significantly different between the two groups (P > 0.05). Although the esomeprazole group showed a lower frequency of adverse maternal, fetal, and neonatal outcomes compared to the placebo group, these differences were not statistically significant.
ConclusionsThe frequency of adverse maternal, fetal, and neonatal outcomes was lower in the esomeprazole group than in the placebo group for most variables, but the differences were not statistically significant. Therefore, it cannot be concluded with certainty that esomeprazole is ineffective in preventing or controlling preeclampsia.
Keywords: Preeclampsia, Esomeprazole, Maternal Outcome, Fetal Outcome, Neonatal Outcome