فهرست مطالب

Jundishapur Journal of Natural Pharmaceutical Products
Volume:20 Issue: 1, Feb 2025

  • تاریخ انتشار: 1403/12/27
  • تعداد عناوین: 18
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  • Amer Abdollahnejad Banaderi, Maryam Rafiei Rad, Mohammadamin Edalatmanesh, Mohsen Forozanfar * Page 1
    Background

    Parkinson's disease (PD) represents a neurodegenerative condition where oxidative stress significantly contributes to its underlying pathology. Antioxidant agents may reduce neuronal degeneration.

    Objectives

    This research explores the impact of hesperidin (HES) on the hippocampus's antioxidant capacity and cholinergic function as well as its effects on memory enhancement and offer neuroprotective benefits in a rat PD model elicited by reserpine (RES).

    Methods

    Forty male Wistar rats were assigned to five experimental groups: The control group, a group receiving HES vehicle (normal saline, NS) combined with RES vehicle (VR + NS), a group treated with RES (0.2 mg/kg for 13 days, intraperitoneally) along with NS (RES + NS), a group administered HES (100 mg/kg for 14 days, orally) plus RES vehicle (HES + VR), and finally the group receiving both RES and HES. Following treatment, assessments for catalepsy and memory were performed. The enzymatic activity within the hippocampus, specifically for catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GPx), was measured employing the ELISA method. Simultaneously, the malondialdehyde (MDA) level was quantified employing the thiobarbituric acid assay, while we evaluated the activity of acetylcholinesterase (AChE) using the Ellman method in the hippocampus. Neuronal density in the hippocampal CA1 and CA3 regions was assessed using stereological techniques.

    Results

    The results indicated a significant decrease in cataleptic behavior, AChE activity, and MDA levels, along with an increase in CAT, SOD, GPx, and neuronal density in both CA1 and CA3 regions, alongside enhancements in working and avoidance memory in the RES + HES group in relation to the RES + NS group. Also, HES inhibited the RES-elicited rise in AChE levels within the hippocampus.

    Conclusions

    Hesperidin enhances the hippocampus's antioxidant function, regulates cholinergic activity, and offers neuroprotection against RES-elicited motor-cognitive impairments.

    Keywords: Reserpine, Parkinson's Disease, Hesperidin, Antioxidant Capacity
  • Mahsa Rajabi-Moghadam, Behnam Mahdavi, Azizollah Habibi, Mohammadmahdi Zangeneh, Akram Zangeneh * Page 2
    Background

    Rosa foetida is a popular plant in Iran due to its various medicinal applications.

    Objectives

    In the present study, the essential oil of R. foetida flowers was isolated to identify the chemical composition and evaluate the anti-oral cancer and antioxidant activity of the plant extract.

    Methods

    The essential oil was extracted using the hydro-distillation method. The GC-MS technique was employed to identify the essential oil composition. The anti-cancer activity of the essential oil against oral squamous cell carcinoma was evaluated using an MTT assay. The antioxidant activity of the hydroalcoholic extract of the plant was evaluated using a DPPH assay.

    Results

    The essential oil was dominated by heneicosane (27.72%), tricosane (24.30%), and nonadecane (14.75%). In the MTT assay, the essential oil exhibited dose-dependent activity against cell lines of HSC-2, HSC-3, HSC-4, and Ca9-22. The highest anticancer activity of R. foetida essential oil was observed against the Ca9-22 cell line with an IC 50 of 218 µg/mL. The extract of R. foetida was rich in phenolics, with a total phenolic content of 164 ± 0.67 mg Gallic acid equivalents (GAE)/g. The extract scavenged the free radical of DPPH with an IC 50 of 6.54 ± 0.2 µg/mL.

    Conclusions

    The obtained results revealed an acceptable anti-cancer activity against oral squamous cell lines and potent antioxidant activity for the flowers of R. foetida .

    Keywords: Antioxidant Activity, Anti-Cancer Activity, Heneicosane, Oral Squamous Cell Carcinoma, Rosa Foetida
  • Maryam Shokoohmand, Hossein Zolgharnein, Mohammadali Salarialiabadi, Mojtaba Alishahi, Reza Safari, Mohammadreza Shushizadeh, Farzaneh Sadat Motafeghi * Page 3
    Background

    Bioactive peptides, specific fragments of proteins with beneficial health effects, are increasingly recognized and utilized in drug development due to their numerous advantages. These advantages include an improved ability to penetrate biological barriers, minimal toxicity, and rapid elimination from the body.

    Objectives

    This research focused on identifying bioactive peptides obtained from the lanternfish ( Benthosema pterotum ) and their effects on the induction of apoptosis in the HT-29 cell line.

    Methods

    Lanternfish collected from the Makran coast were hydrolyzed using Alcalase (HA) and Flavourzyme (HF) enzymes. The protein hydrolysates were then purified by fast protein liquid chromatography (FPLC), resulting in BPHA and BPHF. Cells were treated with protein hydrolysates under 3 kDa at different concentrations and cisplatin for 48 hours. Cell proliferation was assessed using the MTT assay and flow cytometry analysis.

    Results

    Hydrolyzed proteins HA and HF exhibited high protein levels, with 80.26% and 79.45%, respectively. Additionally, based on the MTT assay results, the IC 50 values of the bioactive peptides digested with HA and HF in HT-29 cells were 313.7 μg/mL and 392.8 μg/mL, respectively. These results indicated significant apoptosis in cancer cells, with effects comparable to those of cisplatin (P < 0.01).

    Conclusions

    The potential of the bioactive peptide assessed in this investigation was demonstrated by its ability to inhibit the proliferation of HT-29 human colon cancer cells. This finding underscores its promise as a prospective candidate for colon cancer treatment.

    Keywords: Fish Protein Hydrolysates, Benthosema Pterotum, Colorectal Adenocarcinoma, Flowcytometry
  • Seyede Fatemeh Mesbahi, Amirali Moghadam Sadegh, Esmaeil Mousavi Asl, Neda Sadrizadeh Irani, Hatam Boostani * Page 4
    Background

    Anxiety and depression are significant factors that can increase the likelihood of concurrent substance use in patients undergoing treatment.

    Objectives

    This study aims to address the gap in knowledge regarding the treatment of anxiety and depression resulting from substance withdrawal by evaluating the effectiveness of ginseng on depression and anxiety symptoms in patients at addiction treatment clinics in Ahvaz.

    Methods

    This research is categorized as applied research and falls under experimental designs for data collection. It was a randomized clinical trial with a pre-test and post-test design involving two groups. The statistical population included all patients visiting addiction treatment clinics in Ahvaz during 2023 - 2024. A total of 68 participants meeting the inclusion and exclusion criteria were randomly assigned to two groups: One receiving ginseng and the other a placebo (34 participants each). One group received 100 mg capsules of ginseng, while the other received a placebo for four weeks. All participants were assessed at the beginning of the study and after the intervention using the Hamilton Depression Rating Scale (HDRS) and the Hamilton Anxiety Rating Scale (HARS). Data analysis was conducted using descriptive statistics and analysis of covariance, utilizing SPSS-26 software.

    Results

    The study involved 68 individuals aged 28 to 59 years, with a mean age of 43.22 ± 8.89. The mean ± standard deviation of depression and anxiety in the pre-test of the intervention group was 29.85 ± 6.19 and 25.00 ± 6.06, respectively, and in the placebo group was 27.79 ± 7.21 and 23.91 ± 4.82, respectively. The mean ± standard deviation of depression and anxiety in the post-test of the intervention group was 15.44 ± 11.37 and 12.26 ± 10.40, respectively, and in the placebo group was 11.91 ± 10.83 and 13.32 ± 10.10, respectively. The results indicate no significant difference between post-test and pre-test scores in the intervention group compared to the placebo group (P > 0.05).

    Conclusions

    The results indicate that there was no significant difference in post-test means compared to pre-test means in the intervention group relative to the placebo group. However, further randomized trials with larger sample sizes are necessary for confirmation. Findings should be interpreted with caution.

    Keywords: Randomized Controlled Trial, Depression, Anxiety, Ginseng, Effectiveness
  • Arezoo Ravanan, Nosrat Mahmoodi, Bahman Sharifzadeh, Atefeh Ghavidast, Maryam Mohammadbeigi, Fahime Majlesi * Page 5
    Background

    One of the major advances in the application of nanoparticles is the recognition of steric stabilization, which can enhance particle stability in biological environments and provide opportunities for the development of drug delivery systems (DDSs) aimed at achieving drug targeting and controlled drug release. Nanocrystalline silver particles (AgNPs) have significant applications in biomolecular recognition, antimicrobial treatment, catalysis, and sensor manufacturing. Nanoparticles are utilized in various medical applications, including image quality enhancement, medicine, tissue engineering, and magnetic resonance imaging (MRI) of targeted tissues and cell types. Nanocrystalline silver particles, in particular, significantly contribute to a wide range of industrial and medical applications.

    Objectives

    In this study, the green synthesis of one-pot reaction AgNPs with omeprazole (OMP) and omeprazole sulfide (OMPS) was investigated for their antibacterial properties.

    Methods

    The synthesis of OMP and OMPS drugs was completed on AgNPs, and the resulting nanoparticles were characterized using transmission electron microscopy (TEM), diffuse reflectance spectroscopy (DRS), Fourier transform infrared spectroscopy (FT-IR), and X-ray diffraction (XRD).

    Results

    Briefly, the size of OMP nanoparticles is less than 40 nm, and the length of OMPS nanoparticles is less than 60 nm. Omeprazole@AgNPs (Ag@OMP) and omeprazol sulfide@AgNPs (Ag@OMPS) can repel bacteria. In the UV-Visible (UV-Vis) spectrum, it has been observed that pure OMPS appear with a λmax at 400 nm, corresponding to the n→π* transition of the S-OMPS molecule, while the Ag@OMPS arrangement appears with a λmax at 300 nm.

    Conclusions

    The green synthesis of AgNPs with OMP and OMPS has been investigated for their antibacterial properties. The nanoparticles were characterized using various techniques. The results indicate that the size of OMP nanoparticles is less than 40 nm, while the length of OMPS nanoparticles is less than 60 nm. Omeprazole@AgNPs and Ag@OMPS have demonstrated antibacterial properties, with the UV-Vis spectrum showing distinct peaks for the different arrangements. Overall, the study demonstrates the potential of utilizing AgNPs in combination with OMP and OMPS for enhanced antibacterial activities.

    Keywords: Green Synthesis, Nanocrystalline Silver Particles, Omeprazole, Omeprazole Sulfide, Antibacterial Properties, Characterization Techniques, Drug-Delivery Systems
  • Omolbanin Shahraki, Maryam Sadat Nabavinia, Abdolmotaleb Tiba, Sara Daneshmand * Page 6
    Background

    The application of cutting-edge nanotechnologies is enhancing the delivery of herbal-based treatments. Nanocarriers, characterized by their unique features, can overcome certain limitations of traditional drug delivery systems, thus serving as effective drug delivery vehicles. Concurrently, the antibacterial properties of piperine have been documented in numerous studies.

    Methods

    Nanostructured lipid carriers (NLCs) containing piperine (NLC-Pip) were synthesized using hot homogenization and ultrasound techniques. Their antibacterial activity against Staphylococcus aureus biofilm was evaluated. In formulating NLC-Pip, various percentages of lipids and surfactants were employed. Additionally, the size, Polydispersity Index (PDI), and zeta potential of each formulation were measured using dynamic light scattering (DLS).

    Results

    The optimal formulation was identified with a particle size of 187 nm, a PDI of 0.241, and a zeta potential of -23.1 mV. The encapsulation efficiency was approximately 99%. In antibacterial assays, the minimum inhibitory concentration (MIC) for NLC-Pip was 40 μg/mL, while the minimum bactericidal concentration (MBC) was 80 μg/mL. NLC-Pip demonstrated superior antibacterial activity against S. aureus biofilm compared to both free piperine and piperine-free NLC.

    Conclusions

    The developed NLC-Pip formulation represents a promising vehicle for the development of a drug delivery system aimed at combating S. aureus biofilm.

    Keywords: Nanostructured Lipid Carriers, Piperine, Lavender, Antibacterial, Staphylococcus Aureus
  • Amirmohammad Bagheri, Mehdi Ranjbar * Page 7
    Background

    Recently, introducing new drug delivery approaches to maintain drug concentrations at reasonable levels for longer periods is widely emerging in pharmaceutical science. In this respect, multilamellar nanomaterials such as layered double hydroxide (LDH) nanocomposites are considered favorable topics due to their high specific surface areas and abundant interlayer spaces for drug loading, as well as appropriate properties, including ease of synthesis, high thermodynamic stability, and controlled drug delivery.

    Objectives

    In the current study, we aimed to prepare a honey-incorporated Cu/Al-LDH (Ho@Cu/Al-LDH) nanocomposite as a platform for controlled drug delivery using ibuprofen (Ibu) as a model pharmaceutical agent. Additionally, the dye removal potential of this nanocomposite was also assessed.

    Methods

    Cu/Al-LDH nanocomposite was prepared using honey as an anionic ligand by hydrothermal precipitation. The product was collected and dried after several washing steps. Subsequently, the prepared nanocomposite was evaluated through physicochemical properties, dye removal potential, total antioxidant capacity, and entrapment efficiency as well as drug release properties.

    Results

    The Ho@Cu/Al-LDH nanocomposite exhibited good physicochemical properties with an average particle size of 123.7 nm and a PDI of 0.37, as well as relative uniformity and suitable morphology. The nanocomposite also presented good antioxidant properties [ferric reducing antioxidant power (FRAP) value of 298.42 ± 0.93 μM Fe(II)/g], high entrapment efficiency (EE) during the evaluation, and a pH-dependent controlled release profile (42.3 ± 0.243% at pH 7.4 and 0.481 ± 32.1% at pH 9.5), which was in good agreement with the Korsmeyer-Peppas model.

    Conclusions

    However, the incorporation of natural compounds into LDHs is no longer restricted. In particular, the present study introduces a promising approach to reduce dose-related adverse effects and address health concerns by developing organic-inorganic nanocomposites for controlled drug delivery. In addition, this nanocomposite can also be used as an effective and low-cost recyclable adsorbent.

    Keywords: Nanomaterials, Layered Double Hydroxide (LDH) Nanocomposites, Intercalation Compounds, Antioxidant Properties, Controlled Drug Delivery
  • Habib Malekpour, Ali Abazarikia, Laleh Mahmoudi, Roja Qobadighadikolaei, Amir Farrokhian, Veria Naseri, Mohammad Abbasinazari * Page 8
    Background

    Given the limited evidence on the efficacy of α-pinene, a herbal terpenoid, in the management of ulcerative colitis (UC), this clinical trial aims to investigate the effects of α-pinene compared to a placebo.

    Methods

    Eligible UC patients were randomized to receive either α-pinene or a placebo, alongside their routine pharmacologic regimen, for two months. Quality of life (QoL) and disease severity were assessed using the Simple Clinical Colitis Activity Index Questionnaire (SCCAIQ) and the Crohn’s and UC Questionnaire-8 (CUCQ-8), respectively. Additionally, erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) levels were measured as inflammatory markers.

    Results

    The QoL was significantly improved in the α-pinene group compared to the placebo group (P = 0.02). Several items of the CUCQ-8 also showed better outcomes in the α-pinene group. However, there were no significant differences in ESR and CRP levels between the two groups (P = 0.64 and P = 0.78, respectively).

    Conclusions

    α-pinene may be considered as a dietary supplement to enhance QoL and alleviate several symptoms in patients with UC.

    Keywords: Ulcerative Colitis, Α-Pinene, Quality Of Life, Randomized Clinical Trial, Inflammatory Markers, ESR, CRP
  • Atefeh Bahmei, Mohammad Yaghoubzad-Maleki, Gholamhossein Tamaddon * Page 9
    Background

    B-acute lymphoblastic leukemia (B-ALL) presents significant global public health challenges.

    Objectives

    This study aimed to evaluate the effect of vitamin C alone and in combination with vincristine or parthenolide, focusing on changes in miR-17-5p, miR-125b-5p, and miR-181b-5p in a B-ALL cell model (NALM6 cell line).

    Methods

    In this experimental study, cell viability was determined through the MTT assay and propidium iodide (PI) staining. Flow cytometry was applied to evaluate apoptosis. The expression of miRNAs was assessed using real-time polymerase chain reaction (RT-PCR). Molecular docking was utilized to validate that miR-17-5p, miR-181b-5p, and miR-125b-5p were modulated by vitamin C, parthenolide, and vincristine treatment.

    Results

    Propidium iodide staining revealed that vitamin C (0.5 mM) reduced cell viability by nearly 50%. Flow cytometry analysis further demonstrated that combining vitamin C (0.5 mM) with either vincristine (0.8 nM) or parthenolide (1.925 µM) increased apoptosis compared to untreated controls. The combination treatments induced apoptosis in 79.22% of cells treated with vitamin C and vincristine, and 82.52% of cells treated with vitamin C and parthenolide, respectively. Real-time PCR analysis showed a decrease in the expression of all three miRNAs. Notably, the combination therapies further decreased their expression, suggesting potential involvement in the observed enhanced apoptosis. Further, molecular docking validated the modulation of these microRNAs (miRNAs) by vitamin C and its combinatory conditions.

    Conclusions

    These findings suggest that vitamin C may improve the effectiveness of vincristine or parthenolide in inducing apoptosis in NALM6 leukemia cells. The modulation of miR-17-5p, miR-125b-5p, and miR-181b-5p expression likely plays a role in the synergistic effect. Overall, this evidence supports the potential application of vitamin C as an adjunct therapy for B-ALL.

    Keywords: B-ALL, Micrornas, Apoptosis, Vitamin C, NALM6, Herbal Compounds
  • Elaheh Basirat, Fariba Mahmoudi, Homayoun Khazali * Page 10
    Background

    Formononetin is a phytoestrogen that exhibits antioxidant, analgesic, anxiolytic, and anti-inflammatory properties. However, there is limited information about the central molecular mechanisms mediating the analgesic effects of formononetin.

    Objectives

    The present study aimed to assess the impacts of formononetin on hypothalamic mRNA levels of hypocretin ( HCRT ), corticotropin-releasing hormone ( CRH ), and melanin-concentrating hormone ( MCH ).

    Methods

    Twenty male Wistar rats weighing 200 ± 10 g were divided into four groups (n = 5). Groups 1 and 2 were the control and the pain model groups, respectively, which received saline. Groups 3, 4, and 5 were the pain model rats that received 20 and 40 µg of formononetin and 20 µg of diclofenac via the third cerebral ventricle, respectively. To induce pain, formalin (50 µL of 5%) was injected into the plantar surface of the hind paw subcutaneously. Behavioral tests were performed. Hypothalamic samples were removed, and gene expression was measured using the real-time polymerase chain reaction (RT-PCR) method.

    Results

    Formalin-induced pain caused a significant increase in the mRNA levels of HCRT, CRH, and MCH compared to the control. Administration of 20 and 40 µg of formononetin significantly decreased the mRNA levels of HCRT , CRH , and MCH in comparison to the formalin group.

    Conclusions

    Downregulation of hypothalamic CRH and blocking the effects of neuropeptide orexin and MCH signaling pathways upstream of CRH neurons may mediate the antinociceptive effects of formononetin.

    Keywords: Formononetin, Corticotropin-Releasing Hormone, Hypocretin, Melanin-Concentrating Hormone, Pain
  • Maryam Behrouzi, Fatemeh Borazjani, Sima Jafarirad, Mehrnoosh Zakerkish, Krista Casazza, Kambiz Ahmadi Angali * Page 11
    Background

    Limited access to conventional treatments for type 2 diabetes mellitus (T2DM) necessitated alternative therapies. Curcumin and Amla, both medicinal plants, exhibited therapeutic properties. Their combination might have yielded synergistic effects, enhancing antioxidant defense, reducing inflammation, and improving glycemic control and lipid profiles more effectively than either agent alone. This approach aimed to develop an intervention for managing T2DM..

    Objectives

    This study evaluated the combined effects of curcumin and Amla on lipid profiles, glycemic status, inflammation, antioxidant levels, and liver enzymes in patients with T2DM.

    Methods

    This double-blind, randomized controlled trial involved 50 patients with T2DM from the Ahvaz Jundishapur University of Medical Sciences clinic. Participants, aged 25 to 65 years with a BMI of 25 to 34.9, were assigned to receive either two 500 mg capsules of curcumin plus Amla (n = 25) or a placebo (n = 25) daily for 12 weeks.

    Results

    Outcomes assessed changes in glycemic status, Hemoglobin A1c (HbA1c), inflammation, liver enzymes, oxidative stress, lipid profile, blood pressure, body measurements, quality of life, physical activity, and dietary intake.

    Conclusions

    To ensure rigorous control, adherence was monitored through daily contact and three 24-hour food recalls at baseline and at the end of the trial. Only individuals with stable medication regimens for at least three months were included, with regular check-ins confirming no new medications affecting glycemic control or lipid profiles. Random assignment to the intervention or control group minimized bias, with the control group receiving placebo treatment for accurate comparison..

    Keywords: T2DM, Curcumin, Amla, Protocol Study, Clinical Trial
  • Mohammadmehdi Gravandi, Hanieh Alidoust, Maedeh Tahvilian, Elnaz Moradi, Mohammad Hashemnia, Leila Behbood, Maryam Naseri, Mohammadhosein Farzaei * Page 12
    Background

    Inflammatory bowel disease (IBD) encompasses chronic gastrointestinal conditions such as Crohn's disease and ulcerative colitis (UC). Despite their differing pathophysiologies, these conditions are influenced by common factors, including genetics, environmental influences, and gut microbiota. Recent studies suggest that oxidative stress significantly contributes to intestinal inflammation. Additionally, medicinal plants are recognized for their efficacy in treating various illnesses, forming the basis of many modern medications.

    Objectives

    This study investigated the potential of rutin, a natural compound, by synthesizing it into nanoparticles. These rutin nanoparticles were designed to enhance drug solubility and intestinal absorption, thereby improving therapeutic efficacy and shelf life.

    Methods

    Thirty adult rats were divided into six groups for this experiment. Excluding the control group, all were treated with 2 mL of 4% acetic acid (AA) followed by sulfasalazine. Subsequently, three different dosages of rutin nanoparticles (100, 150, and 200 mg/kg) were administered. The evaluation included tests for glutathione (GSH), nitric oxide (NO), superoxide dismutase (SOD), and tumor necrosis factor-alpha (TNF-α), as well as macroscopic and microscopic analyses.

    Results

    Intracolonic administration of AA resulted in severe acute inflammation in the colonic tissue, which was improved by rutin nanoparticles in both microscopic and macroscopic aspects. Additionally, rutin nanoparticles modified TNF-α and oxidative stress-related markers, including GSH, NO, and SOD levels.

    Conclusions

    Our results indicate that rutin nanoparticles exhibit significant therapeutic effects in treating UC. These findings suggest the potential of natural products and their nanoparticle formulations in treating inflammatory diseases.

    Keywords: Rutin, Ulcerative Colitis, Acetic Acid, Chitosan, Nanoparticles, Rat
  • Yudith Escobar-Zuñiga, Francisco Delgado-Vargas, José Angel López-Valenzuela, Jesús Ricardo Parra-Unda, José Geovanni Romero-Quintana, Guadalupe Loarca-Piña, Margarita Del Socorro Dávila-Paredes, Karen Virginia Pineda-Hidalto, Gabriela López-Angulo * Page 13
    Background

    Treatments for type 2 diabetes mellitus (DM2) are not universally effective, underscoring the need for new therapeutic alternatives. Extracts of Echeveria subrigida have demonstrated potent in vitro activities, such as antioxidant and α-glucosidase inhibitory effects, as well as in vivo activities, including hypoglycemic, antihyperglycemic, immunomodulatory, and adaptogenic effects.

    Objectives

    The present study aimed to investigate the antidiabetic mechanisms of ethanolic (EEEs) and methanolic (MEEs) extracts of E. subrigida , standardized for isorhamnetin-3-O-glucoside (I3G), in streptozotocin (STZ)-induced diabetic rats.

    Methods

    The E. subrigida extracts, EEEs and MEEs, were obtained by maceration and standardized for the content of I3G. The antidiabetic effect was evaluated using STZ-induced diabetic rats, which were randomly allocated to experimental groups (n = 6). Isorhamnetin (ISO) and metformin (MET) treatments served as positive controls. Parameters were measured at least in triplicate, and means were compared using the Fisher test (P < 0.05). The following evaluations were conducted: Levels of monocyte chemoattractant protein-1 (MCP-1), leptin, and inflammatory-related cytokines in serum; expression of proteins in the phosphatidylinositol 3-kinase (PI3K) and adenosine monophosphate-activated protein kinase (AMPK) pathways; transcriptional expression of peroxisome proliferator-activated receptor alpha (PPARα) and sterol regulatory element-binding protein 1c (SREBP-1c) in liver tissue; and histology of the liver and pancreas.

    Results

    All treatments, except ISO, demonstrated antidiabetic effects, with glucose levels in MET (183.75 ± 61.89 mg/dL) and MEEs (168.00 ± 48.10 mg/dL) rats comparable to healthy control (HC) rats (109.25 ± 6.11 mg/dL). Leptin levels decreased in diabetic control (DC) rats (0.17 ± 0.07 ng/mL), while levels in the EEEs (0.65 ± 0.06 ng/mL) and MEEs (0.77 ± 0.09 ng/mL) groups were similar to those of the HC group (0.71 ± 0.19 ng/mL). The levels (pg/mL) of cytokines (IL-10, IL-6, IFN-γ, and IL-4) were elevated in DC rats (72.26 ± 12.91, 36.72 ± 2.91, 4.56 ± 0.63, and 16.34 ± 2.06, respectively), but were effectively reduced in rats treated with EEEs (29.64 ± 2.86, 9.85 ± 2.92, 1.11 ± 0.24, and 6.71 ± 1.15, respectively) and MEEs (26.65 ± 5.31, 7.30 ± 1.89, 1.25 ± 0.28, and 5.55 ± 0.43, respectively). Liver histology showed nearly normal structures, although pancreatic histology revealed hypertrophied Langerhans islets across all DM2 groups. The Akt activation and inactivation of AS160 by phosphorylation were detected in the livers of EEEs and MEEs rats without AMPK activation. Additionally, these groups expressed the SREBP-1c mRNA.

    Conclusions

    The EEEs and MEEs exhibited antidiabetic activity via the PI3K/Akt pathway, suggesting E. subrigida as a potential preventive or therapeutic agent for type 2 diabetes.

    Keywords: Diabetes, Antidiabetic Mechanism, PI3K, Akt Pathway, Crassulaceae, Leptin, Cytokines
  • Elham Ranjbar, Laya Sadat Khorsandi, Mehdi Goudarzi * Page 14
    Background

    D-Galactose (D-Gal) is naturally produced in the body and significantly impacts the aging process and the pathogenesis of some diseases.

    Objectives

    This study aimed to investigate the protective impact of oleuropein (OLE) against D-Gal-induced heart aging in rat models.

    Methods

    Forty Wistar male adult rats were categorized into five groups. The primary group was given distilled water, and the second group was given D-Gal at 100 mg/kg intraperitoneally. The rats in groups 3 to 5 were orally administered D-Gal (100 mg/kg) once a day. These groups were simultaneously subjected to dosages of OLE (20, 40, and 80 mg/kg, respectively) via the oral route. All treatments were administered once a day for eight consecutive weeks. Approximately 24 hours after the final treatment, the rats were euthanized, and serum and heart specimens were collected. The levels of protein carbonyl (PC), malondialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase (GPx), and the expression of proliferator-activated receptor-gamma coactivator (PGC-1α) and sirtuin 1 (SIRT1) genes in heart tissue were determined. Heart tissue was preserved in 10% formalin for hematoxylin and eosin (H&E) and histological examination.

    Results

    The findings showed that D-Gal significantly decreased GPx, catalase (CAT), and SOD, glutathione (GSH) levels, as well as SIRT1 and PGC1 expression within the heart tissue (P < 0.05). Additionally, D-Gal significantly increased PC and MDA levels and serum cardiac markers [creatine kinase-MB (CK-MB), lactate dehydrogenase (LDH), aspartate aminotransferase (AST), and cardiac troponin I (cTnI)] (P < 0.05). The protective effect of OLE was confirmed by histological examination.

    Conclusions

    The study demonstrated that OLE dose-dependently reduced heart lesions caused by D-Gal. The findings suggest that the protective effect of OLE is through the reduction of oxidative damage.

    Keywords: Oleuropein, D-Galactose, Oxidative Stress, Heart Tissue
  • Nguyen Thi Linh Tuyen, Cao Tan Duy, Nguyen Thi Tuong Vy, Le Thi Ngoc Quyen, Do Chau Minh Vinh Tho, Do Quang Duong * Page 15
    Background

    Herbal-based sunscreens are gaining popularity due to their ability to protect against ultraviolet (UV) rays and offer additional benefits such as moisturizing and anti-aging effects derived from bioactive compounds.

    Objectives

    The present study aimed to investigate cause-effect relationships, optimize, and assess the quality of a herbal sunscreen formulated from Polypodium leucotomos , almond oil, Camellia sinensis , and Lycopersicum esculentum .

    Methods

    A total of 19 sunscreen formulations were designed using BCPharSoft software and the D-optimal model. Independent variables included P. leucotomos leaves extract (X 1 ), almond oil (X 2 ), and a mixture of stearic acid and cetyl alcohol in a 1:1 ratio (X 3 ). These variables were selected to enhance sun protection factor (SPF) and spreadability.

    Results

    The optimized herbal sunscreen formulation consisted of 20% P. leucotomos leaves extract, 8% almond oil, and 5% stearic acid-cetyl alcohol mixture. The formulation achieved an SPF of 47.32 ± 0.66 and a spreadability of 28.17 ± 1.00 cm 2 , meeting established quality standards.

    Conclusions

    This study contributes to advancements in natural cosmetics, meeting the growing demand for eco-friendly products and supporting the expansion of Vietnam's sunscreen market.

    Keywords: Almond Oil, Camellia Sinensis, Lycopersicum Esculentum, Polypodium Leucotomos, Spreadability, Sun Protection Factor
  • Ali Vakili*, Shahein Momenabadi, Ahmadreza Bandegi, Abbasali Vafaei, Abedin Vakili Page 16
    Background

    Cerebral ischemia activates harmful biochemical pathways that result in blood-brain barrier (BBB) breakdown and neuronal damage. Natural compounds such as chrysin and gallic acid (GA), known for their antioxidant and anti-inflammatory properties, may protect the BBB and reduce neuronal injury.

    Objectives

    This study aimed to examine the effects of combining chrysin and GA on hippocampal neuronal damage, cognitive function, BBB integrity, and claudin-5 expression in a mouse model of cerebral ischemia.

    Methods

    Cerebral ischemia was induced through bilateral common carotid artery occlusion (BCCAO) for 30 minutes, followed by 48 hours of reperfusion. Chrysin (30 mg/kg, intraperitoneally), GA (50 mg/kg, intraperitoneally), and their combination were administered at the start of reperfusion and subsequently at 30 minutes and 1 hour. Hippocampal neuronal damage, spatial memory, Evans blue (EB) leakage, and claudin-5 expression were evaluated 48 hours after reperfusion.

    Results

    Administration of chrysin, GA, and their combination significantly enhanced neuronal survival in the CA1, CA3, and dentate gyrus (DG) regions (P < 0.001). The combination diminished neurological deficit scores (1.5 ± 0.22 vs. control 3.5 ± 0.56, P < 0.05) and escape latency time (12.8 ± 4.5 vs. control 40 ± 4.82 seconds, P < 0.01). Likewise, these interventions significantly reduced EB leakage (3.46 ± 0.62 vs. control 11.28 ± 0.98 μg/g of brain tissue) and upregulated claudin-5 expression (38% ± 1.29 vs. control 10.75% ± 1.65, P < 0.001).

    Conclusions

    This study demonstrated that the combined treatment of chrysin and GA synergistically promoted hippocampal neuron survival, improved neurological function, and maintained BBB integrity by upregulating claudin-5 expression. We suggest that this therapeutic approach may offer potential benefits for stroke patients, though further experimental and clinical investigation is required to confirm its efficacy.

    Keywords: Chrysin, Gallic Acid, Combination, Brain Ischemia, Claudin-5, BBB, Mice
  • Marziyeh Saghebjoo, Seyed Masoud Seyed Moosavi, Elham Ghasemi, Mehdi Hedayati * Page 17
    Background

    Evidence suggests that exercise training and dill extract can influence obesity and related metabolic conditions, such as type 2 diabetes.

    Objectives

    This study aimed to investigate the effects of endurance training (ET) and dill seed extract (DSE) on insulin sensitivity and nicotinamide N-methyltransferase (NNMT) levels in the liver and adipose tissue of obese rats.

    Methods

    Forty male Wistar rats were divided into a high-fat diet [HFD (n = 32)] group and a standard diet [normal control (NC ) n = 8] group. After inducing obesity in the HFD group over 8 weeks, the rats were further divided into four groups: Obese control (OC), DSE, ET, and ET+DSE. Endurance training was performed at 70 - 80% VO₂max, and DSE was administered at a dose of 300 mg/kg body weight (five and three times per week, respectively) for 10 weeks. Plasma and tissue samples were collected after the intervention. The NNMT levels were measured using ELISA, and insulin sensitivity was assessed using the QUICKI Index. Data were analyzed using repeated measures analysis of variance, one-way analysis of variance (ANOVA), Tukey's post hoc test, Kruskal-Wallis test, and Mann-Whitney U test, with a significance level of P < 0.05.

    Results

    After 10 weeks of intervention, blood glucose levels were significantly lower in the DSE (10.63%, P = 0.001), ET (15.89%, P = 0.001), ET + DSE (22.09%, P = 0.001), and NC (25.30%, P = 0.001) groups compared to the OC group. Similarly, insulin levels were significantly reduced in the DSE (57.30%, P = 0.01), ET (48.07%, P = 0.02), ET+DSE (63.88%, P = 0.002), and NC (59.00%, P = 0.007) groups compared to the OC group. The QUICKI Index was significantly higher in the DSE (11.87%, P = 0.003), ET (10.66%, P = 0.01), ET + DSE (16.82%, P = 0.001), and NC (15.18%, P = 0.001) groups compared to the OC group. However, no significant differences were observed in NNMT levels in the liver and adipose tissue or in liver triglyceride (TG) levels between the groups (P ≥ 0.05).

    Conclusions

    Endurance training and DSE improved insulin sensitivity in obese rats but did not affect NNMT levels in the liver and adipose tissue. This lack of effect on NNMT levels may be due to the HFD's inability to influence this enzyme.

    Keywords: Endurance Training, Herbal Medicine, High-Fat Diet, Insulin Sensitivity, Nicotinamide N-Methyltransferase
  • Neda Sistanikarampour, Ardeshir Arzi, Annahita Rezaie, Niloofar Ghanaddezfouli * Page 18
    Background

    Peptic ulcer is a mucosal lesion in the stomach or duodenum. The formation of ulcers and resistance to them depend on the balance between aggressive factors such as acid, pepsin, and leukotrienes, and mucosal defense factors, particularly blood flow, nitric oxide, and prostaglandins. In ulcers caused by alcohol, stress, or infection, oxygen reactions, particularly the production of hydroxyl free radicals, are responsible for gastric ulcer formation. Therefore, many studies focus on finding compounds that act as antioxidants. Bee Pollen is a natural substance noted in traditional medicine for its various effects and possesses antioxidant properties due to its flavonoid content.

    Objectives

    This study investigates the effect of hydroalcoholic extract of Bee Pollen in preventing ethanol-induced gastric ulcers.

    Methods

    This study utilized 42 male Wistar rats, each weighing between 200 and 250 g. The hydroalcoholic extract of Bee Pollen was prepared through maceration. Animals were randomly divided into 7 groups of 6. The experimental groups were administered varying doses of the hydroalcoholic extract of Bee Pollen (200, 400, and 800 mg/kg). The positive control group was administered ranitidine (50 mg/kg), while the negative control group received normal saline (5 mL/kg) one hour prior to the administration of 96% ethanol (5 mL/kg). One group received normal saline (5 mL/kg), and another group received the extract (800 mg/kg) alone. After one hour, the stomachs of the animals were removed, and factors such as the number of ulcers, length of ulcers, and malondialdehyde (MDA) levels were assessed. The stomachs were also examined macroscopically and microscopically.

    Results

    The hydroalcoholic extract of Bee Pollen significantly reduced the number and length of ulcers as well as MDA levels in a dose-dependent manner. The optimal dose for preventing gastric ulcers was found to be 800 mg/kg.

    Conclusions

    According to the findings of this research, the hydroalcoholic extract of Bee Pollen may be effective in preventing ethanol-induced gastric ulcers in rats.

    Keywords: Bee Pollen, Ranitidine, Ethanol, Gastric Ulcer, Rat