Iranian Journal of Basic Medical Sciences
Volume:28 Issue: 6, Jun 2025

Psoriasis is a long-lasting inflammatory skin condition that impacts millions globally. The occurrence of this disorder differs significantly across various areas, resulting from a complex interplay of genetic and environmental influences. In psoriasis, the pathogenesis represents a complex interaction of innate and adaptive immunity that plays a significant role in the disease manifestation process. Many genetic factors predispose to psoriasis, which is considered a polygenic disease. Several genes concerning pathways like NF-κB and PI3K/Akt that modulate the amplification of inflammatory response and keratinocyte dysregulation have been elaborated in the light of their differential expression, susceptibility loci, and polymorphisms. Such genetic insights could open a whole new avenue for precision medicine in which biomarkers and gene-targeting therapies are promising options for personalized treatment. This review emphasizes the need for complex investigations into psoriasis, from molecular mechanisms to clinical manifestations, to bridge the gap between basic research and therapeutic development by furthering the understanding of psoriasis and paving the way for innovative treatments addressing skin lesions and systemic effects.

Obesity remains a significant worldwide health concern, and further research into other strategies, including herbal weight-loss medications, is necessary. By reviewing clinical trials, this study aims to evaluate the effectiveness of herbal medicines for weight loss or obesity. A comprehensive search was conducted using multiple databases. Clinical trials evaluating the effects of herbal medicines on weight loss or obesity management were included. Relevant data, such as study design, intervention details, and outcome measures, were extracted and analyzed. The use of herbal medicines exhibited varying efficacy in promoting weight loss or managing obesity. Some herbal interventions significantly reduced body weight, body mass index (BMI), and waist circumference. Notably, these interventions led to decreases in fasting blood glucose (FBG) and homeostatic model assessment of insulin resistance (HOMA-IR), regulating insulin levels while increasing levels of catalase (CAT) and glutathione (GSH). Additionally, reductions in inflammatory markers such as high-sensitivity C-reactive protein (hs-CRP) and tumor necrosis factor-alpha (TNF-α) were observed, indicating a potential anti-inflammatory effect. Mechanisms of action included appetite regulation, fat oxidation, increased satiety, enhanced insulin sensitivity, and modulation of lipid metabolism. However, it is important to note that these herbal interventions’ efficacy and safety profiles may vary among different population groups. The findings suggest that certain herbal medicines hold promise as adjunctive therapies for weight loss and obesity management. However, comprehensive and targeted research efforts are warranted to determine these herbal interventions’ optimal use, dosages, and long-term effects in specific population subgroups.

Asthma is a complex inflammatory disease of the lungs marked by increased infiltration of leukocytes into the airways, which restricts respiratory function. Proliferator-activated receptor-γ coactivator-1 alpha (PGC-1α) has been recognized as an essential immunomodulator and has the potential as a novel anti-inflammatory target in asthma. The current study aims to investigate the functions of PGC-1α in ovalbumin (OVA)-sensitized asthmatic mice and underlying mechanisms. BALB/c mouse asthma model was induced by OVA in vivo. The therapeutic effects of PGC-1α agonist (ZLN005) on asthma were assessed by histological and biochemical analysis. In addition, we integrated real-time qPCR, western blotting, and immunofluorescence analysis to reveal the underlying mechanism. In the lung tissue of asthmatic mice, PGC-1α levels were down-regulated. Diff-Quik staining indicated that ZLN005 therapy on asthmatic mice reduced the number of inflammatory cells (eosinophilic granulocytes, neutrophils, lymphocytes, and mononuclear macrophages) in bronchoalveolar lavage fluid (BALF), ameliorated pathologic alterations in lung tissues. ZLN005 alleviated airway structure and inflammation, as well as down-regulating the serum immunoglobulin E (IgE), OVA-specific IgE, and T-helper 2 (Th2) cytokines (interleukin (IL)-4, IL-5, and IL-13) expression. Mechanistically, the results showed that ZLN005, through the NF-κB-p65 axis, prominently inhibited the activation of the NLRP3 inflammasome and reduced the levels of the NLRP3 downstream targets IL-1β and IL-18. PGC-1α agonist (ZLN005) regulated lung inflammation in asthmatic mice by inhibiting the NF-κB-p65/NLRP3 signaling pathway, supporting that ZLN005 may be a candidate for future asthma treatment.

Following our previous studies on the anti-obesity and cardioprotective effects of 17-beta estradiol (E2), this study was designed to determine the effects of Resisted swimming (RSW) training and E2 (alone and in combination) on cardiometabolic risk factors in an obese postmenopausal rat model. Female ovariectomized rats (OVX) were given a standard diet (SD) or a 60% high-fat diet (HFD) for 16 weeks and were divided into two groups:  SD and HFD. The rats were divided into ten groups to assess the effects of 8 weeks of E2 (1 mg/kg, IP) administration and RSW (5 days a week) on cardiometabolic risk factors. Parameters including body weight, BMI, visceral fat, blood glucose (BG), and cardiac oxidative stress were assessed 72 hr after the last swimming session. HFD increased body weight, BMI, visceral fat, and BG levels in OVX rats. Additionally, it negatively affected the lipid profile and cardiac oxidative stress, but both E2 and RSW reduced these parameters in HFD-fed OVX rats. Although RSW and E2 equally prevented these changes, swimming was more effective than estrogen in increasing HDL levels in the SD group. The combination of E2 and RSW had a more significant effect on modulating glucose, TAC, TG, and HDL indices than the individual treatments.   Overall, RSW ameliorates cardiometabolic risk factors in postmenopausal conditions caused by obesity, probably by modulating cardiac oxidative stress. It is also an effective non-pharmacological treatment for E2 substitution.

To formulate and evaluate ethosomes for the transdermal delivery of loxoprofen, a potent non-steroidal anti-inflammatory drug (NSAID). Fifteen ethosomal formulations were created via thin-film hydration and probe sonication techniques, with variations in the amounts of egg yolk lecithin, ethanol, cholesterol (CHOL), Tween 80 (TW80), and propylene glycol (PG). The formulations were assessed for their particle size (PS), zeta potential (ZP), polydispersity index (PDI), pH, and entrapment efficiency (EE). Field scanning electron microscopy (FSEM) was utilized to evaluate their morphology. The in vitro drug release and ex vivo permeability of the ethosomal formulations were evaluated against those in a hydroethanolic drug solution. The formulation labeled F14, comprising 1% loxoprofen, 1% egg yolk lecithin, 30% ethanol, 5% propylene glycol, and phosphate-buffered saline (PBS) up to 25 ml, was recognized as an optimized ethosomal formulation. These ethosomes demonstrated an average size of 164.2±19 nm, a PDI of 0.280±0.028, a ZP of +45.1±4.5 mV, and an EE of 96.8±0.43%. In vitro and ex vivo tests demonstrated that the ethosomal formulation (F14) showed superior drug release and penetration rates compared to a conventional hydroalcoholic solution. The differential scanning calorimetry (DSC) study showed that loxoprofen was completely trapped within ethosomes. On the other hand, the Fourier transform infrared (FTIR) study confirmed that the drug and the additives did not interact. The current study revealed that loxoprofen can be effectively delivered transdermally via the ethosomal system.

Insufficient breast milk supply is a common reason cited for discontinuing breastfeeding prematurely. Natural galactagogues offer promise as a solution for mothers with low milk production. This study aimed to explore puerarin’s potential effects and underlying mechanism on lactation of postpartum hypogalactia mice. Postpartum mice were randomly assigned to five groups: control group, agalactosis model group, domperidone group (3.5 mg/kg), low dose puerarin group (18 mg/kg), and high dose puerarin group (72 mg/kg). The effects of puerarin on postpartum hypogalactia mice were evaluated by lactation indicators and pathological morphology. Related hormones and prolactin receptor (PRLR)/Janus kinase 2 (JAK2)/signal transduction and activator (STAT) 5 signaling pathway were also measured. Puerarin significantly improved lactation yield and stimulated mammary gland development in postpartum hypogalactia mice. Additionally, puerarin increased the expression levels of β-casein, fatty acid synthase (FAS), and glucose transporter 1 (GLUT1). Mechanically, puerarin stimulated secretion of prolactin (PRL), estradiol (E2), and progesterone (P4) in agalactosis mice. Puerarin also substantially increased PRLR, JAK2, and STAT5a expression levels in postpartum hypogalactia mice.  This study suggested that puerarin may promote lactation by stimulating PRL secretion and activating the PRLR/JAK2/STAT5 signaling pathway.

Sleep impacts the well-being and quality of life of millions. Given conventional pharmacotherapy’s limitations and side effects, the quest for adequate and proper sleep promotion is imperative. This study aims to identify a suitable and effective compound for sleep by examining qualified herbal compounds in the PubChem database using in silico methods. Ultimately, the extracted compound (ginkgetin, a bioactive flavonoid from Ginkgo biloba) through molecular docking by considering the GABA A receptors will be evaluated through the in vivo method in an animal model to serve as proof for the findings from the molecular docking process. Utilizing a comprehensive approach, this research employed molecular docking to screen 2299 phytochemicals for their affinity towards the GABAA receptor, focusing on the GABA, benzodiazepine, and steroid-binding sites. Ginkgetin emerged as a top candidate due to its high binding affinity. Subsequent in vivo electrophysiological assessments in rats treated with G. biloba extract containing ginkgetin evaluated alterations in sleep architecture, REM, and NREM sleep phases. Molecular docking identified ginkgetin as possessing the highest binding affinity among the screened phytochemicals. In vivo studies corroborated these findings, demonstrating that rats treated with Ginkgo biloba extract significantly enhanced REM and NREM sleep compared to controls. Ginkgetin, derived from G. biloba, shows promising potential as a novel therapeutic agent for sleep disorders, supported by its strong affinity to key receptor sites and its efficacy in modulating sleep architecture in vivo. These findings contribute to the expanding evidence base for the therapeutic use of G. biloba in sleep promotion and underscore the need for further research to elucidate the mechanisms and clinical applicability of ginkgetin in sleep disorder treatment.

Hydatid cysts are typically treated with albendazole. Nevertheless, this drug has side effects and limited bioavailability. In this study, we aimed to explore a nanoemulsion of black seed oil to enhance the therapeutic efficacy of albendazole in mice with hydatid cysts.  The size of the prepared nanoemulsions was characterized using a Zetasizer analyzer. Additionally, the stability of the nanoemulsions was assessed after 45 days. MTT assay was used to compare the cytotoxicity of free albendazole, nanoemulsion containing albendazole, and nanoemulsion without albendazole. Furthermore, infected mice were treated with these preparations, euthanized, and subjected to autopsy examination. Cysts obtained from mice were examined for histopathological features.  ALB-NE (albendazole-loaded nanoemulsion) DLS results were obtained from black seed oil. Freshly prepared ALB-NE showed (d50 = 170 nm), PDI: 0.323, ALB-NE after 45 days storage at 25 ºC were (d50 = 92.4 nm), and ALB-NE after 45 days storage at 45 ºC revealed (d50 = 118 nm). The cytotoxicity of albendazole was reduced when loaded into the nanoemulsion. Moreover, the group treated with nanoemulsion containing albendazole showed a significant decrease in size and number of cysts compared to those receiving free albendazole or nanoemulsion without the drug. Additionally, after 60 days, the nanoemulsion containing albendazole showed 100% survival, while the survival rate was 50% for free albendazole, 75% for nanoemulsion without albendazole, and 37.5% for PBS.  The nanoemulsion containing albendazole can be a promising treatment for hydatid cysts.

Knee osteoarthritis (KOA) is a persistent degenerative disease affecting the joints, significantly reducing the quality of life for individuals afflicted. This study explores the therapeutic effects of total  saponin Achranthes (TSA) on KOA rats and its underlying mechanism.  Forty-eight rats were randomly assigned to six experimental groups: a blank control group, a model group, a sham-operated group, and a TSA treatment group (low, medium, and high dose), with eight rats in each group. The rats were treated continuously for four weeks. The degree of joint swelling was quantified, and the Lequesne MG score was evaluated. Network pharmacology approaches were employed to pinpoint potential TSA targets and related pathways for managing KOA. Additionally, histopathological examinations were conducted on the knee cartilage of the rats. Serum levels of TNF-α and IL-1β were assessed through the ELISA assay.  The network pharmacology results indicate that TSA may effectively treat KOA through the MAPK and PI3K/Akt signaling pathways. Moreover, TSA significantly decreased the serum concentrations of pro-inflammatory cytokines such as TNF-α and IL-1β, and  TSA down-regulated the P38 MAPK, PI3K/Akt, and NF-κB pathways, whereas the KOA model showed up-regulation. The treatment also significantly reduced MMP-9, MMP-13, and ADAMTS-5 protein levels. TSA can potentially ameliorate inflammation, safeguard knee cartilage tissue, and alleviate symptoms of KOA by inhibiting the MAPK/Akt/NF-κB signaling pathway.

Melanoma is one of the most aggressive and deadly skin cancers. Despite advances, effective melanoma treatment is challenging, often requiring a shift from individual therapies to combination approaches. This study explores whether combining dacarbazine (DTIC) and temozolomide (TMZ) with the siRNA approach holds promise for melanoma treatment. To determine the IC50 values of DTIC and TMZ, the A375 cell line was treated with different drug concentrations for 24–72 hr. The best exposure time of BRAF siRNA transfection was performed. Subsequently, cell viability (using the MTT assay), apoptosis (by flow cytometry), and gene expression levels of B-Raf proto-oncogene, serine/threonine kinase (BRAF), caspase 3 (CASP3), and phosphoinositide-3-kinase regulatory subunit 3 (PIK3R3) genes (by quantitative real-time PCR) were assessed in the treated groups (i.e., control, negative controls, DTIC alone, TMZalone, DTIC+ TMZ, BRAF(V600E)siRNA alone, siRNA+ DTIC, siRNA+ TMZ, and siRNA+ DTIC+ TMZ groups).  Cell viability significantly decreased in the chemotherapy-only and siRNA+drug groups, although no difference was observed between them. The apoptosis percentage in all treated groups indicated a significant difference compared to the control group. The expression of the BRAF gene notably decreased in the BRAF (V600E) siRNA +drug groups compared to the chemotherapy groups. Despite overexpression of CASP3 in the chemotherapy-treated groups, the most effective enhancement was noted in the siRNA+DTIC+TMZ group (P<0.0001). The mean expression of the PIK3R3 gene in siRNA+chemotherapy groups revealed a notable reduction.  These findings suggest that the siRNA-transfected treatment groups have the potential to provide therapeutic effects comparable to those of chemotherapy.

Arsenic is classified as a toxic metal that is naturally found in the Earth’s crust, and long-term exposure to it can result in chronic human disorders like cancer and diabetes. Azelaic acid (AZA), a natural dicarboxylic acid, has been reported to have anti-oxidant and anti-inflammatory effects; hence, it may protect against the metabolic toxicity of arsenic. This study aimed to investigate whether AZA could ameliorate sodium arsenite (SA) toxicity toward rat islets of Langerhans.  Pancreatic Islets of Langerhans isolated from adult male Wistar rats were divided into four groups of 10: control, SA, AZA, and SA plus AZA. Twenty-four hours after incubation, cell viability, cell death pathways, reactive oxygen species (ROS), inflammatory factor gene expression, and insulin secretion were evaluated.  SA dose-dependently decreased cell viability, increased apoptosis, ROS generation, expression of inflammatory mediators (NF-κB, IL-1β, and TNF-α), and insulin secretion. AZA was able to ameliorate all these changes significantly.  Our results indicate that SA can potentially disrupt cellular homeostasis and function in the islets of Langerhans and can increase the risk of metabolic diseases such as diabetes. On the other hand, AZA protected islets of Langerhans against the toxic effects of SA, seemingly due to its anti-apoptotic, anti-inflammatory, and anti-oxidant properties, indicating that AZA may have the potential to run intracellular mechanisms beneficial for coping with the metabolic toxicity of arsenic.

This study was planned to elucidate the mechanism of the protective effect of adropin in an experimental rat model of Parkinson’s Disease (PD).  Three-month-old male Wistar rats were randomly divided into four groups: i) Control, ii) Sham, iii) PD, and iv) PD+Adropin. The performance tests were performed seven days after the 6-Hydroxydopamine hydrochloride (6-OHDA) injection into the striatum. The immunoreactivities for tyrosine hydroxylase (TH), G protein-coupled receptor 19 (GPR19), and vascular endothelial growth factor receptor 2 (VEGFR2) were detected by immunohistochemistry (IHC) in the substantia nigra (SN). Dopamine levels were measured by mass spectrometry. Glycogen synthase kinase 3β (GSK‑3β) and p‑GSK‑3β (Ser9) protein levels were evaluated by western blot analysis.  Our study demonstrated that motor performances were significantly improved by adropin treatment. Central adropin injection prevented the loss of nigral dopaminergic neurons and induced VEGFR2 expression but not GPR19 compared to the PD group. The ratio of p-GSK3β/GSK3β did not differ between groups. However, the level of dopamine in SN was increased with adropin injection in the PD+Adropin group.  Our findings reveal that adropin administration has a protective effect on nigral dopaminergic neurons and acts through the VEGFR2 signaling pathway.

Epigallocatechin gallate (EGCG) exhibits various biological effects, including antiviral, anti-inflammatory, cardioprotective, and lipid-regulating properties. This study aims to investigate the therapeutic effects and mechanisms of EGCG in spinal cord injury (SCI). TThe bioinformatic databases were used to screen therapeutic target genes for drugs against SCI. Component-Target-Disease networks were constructed with Cytoscape software, and inter-target interactions were analyzed using the String database. Additionally, KEGG pathway enrichment analyses were conducted on the identified target genes. SCI was evaluated by detecting inflammation-related factors, H&E staining, and immunohistochemistry. Furthermore, ROS and JC1 staining were performed on HT22 cells subjected to various treatments. Molecular mechanisms were investigated using western blot and qRT-PCR analyses.  Forty-four overlapping genes were identified as potential targets, with HMOX1, GPX-4, and HIF-1A emerging as central hub genes. Key pathways associated with these targets included Ferroptosis and HIF-1 signaling. In vivo studies demonstrated that EGCG effectively promotes motor function recovery and reduces the expression of proteins and genes such as IL-1β, IL-6, HIF-1α, and 4HNE. In vitro experiments showed that EGCG decreases ROS and intracellular lipid ROS levels in HT22 cells while increasing GPX-4 and HMOX1 expression to inhibit ferroptosis and HIF-1 signaling pathways.  Our findings reveal a significant new mechanism by which EGCG can reduce SCI through the inhibition of ferroptosis, facilitated by the activation of HMOX1 expression and the down-regulation of the HIF-1 signaling pathway. This suggests its potential as a therapeutic option for this condition.

Psoriasis is a chronic skin disease that usually manifests as white and silver spots on the skin. Because of its anti-inflammatory properties, we investigated the effects of ivermectin (IVM) on imiquimod (IMQ)-induced psoriasis in rats. Fifteen rats were assigned to 3 different groups (n=5 per group): the control group received normal water and food; the psoriasis group, in which psoriasis was induced by topical application of IMQ (1 mg per rat), and treatment group where rats were treated daily with topical IVM-gel (1%) from day 3 to 7. The Psoriasis Area Severity Index (PASI) Score for the entire treatment period was used to assess erythema, silver scale, and skin thickness on the dorsal region of rats, and the spleen-to-body weight index on day 7 was examined. Moreover, histological assessment of skin tissues was performed using fluorescence immunostaining and hematoxylin-eosin (H&E) staining.  The severity of lesions in the ivermectin group was reduced compared to the IMQ group, with a significant decrease in the average PASI scores. The results of fluorescence immunostaining showed that topical administration of IVM-gel reduced inflammation by decreasing Toll-like receptor 4 (TLR4) levels and p65 nuclear factor kappa-B (NF-κB). Furthermore, findings from H&E staining revealed that IVM-gel decreased dermal fibrosis, epidermal thickness, and infiltration of inflammatory cells caused by IMQ.  Based on the obtained results, it can be concluded that IVM-gel can effectively reduce psoriasis lesions due to its therapeutic properties, such as anti-inflammatory effects via targeting TLR4/p65 NF-κB.

This research examined the protective function of salidroside (SAL) against angiotensin II (Ang II)-infused myocardial fibrosis and its associated mechanism. The C57BL/6 male murine models (n=24) received either saline solution or Ang II (1500 ng/kg/day) subcutaneously and an oral dosage of SAL (50 mg/kg/day) once daily for 28 days. Newborn Sprague-Dawley (SD) rats were used to isolate atrial fibroblasts. The fibrotic region was raised by Ang II infusion, while SAL treatment inhibited it. Collagen I and III expression was raised by Ang II induction, but SAL therapy reduced their expression. SAL therapy also decreased the expression of other fibroblast differentiation-related markers induced by Ang II infusion. It elevated SIRT1, Nrf2, and HO-1 levels in atrial fibroblasts. Additionally, SAL significantly inhibited atrial fibroblasts, whereas EX527, an inhibitor of SIRT1, noticeably increased the migration ability. Furthermore, SAL suppressed intracellular ROS production and oxidative stress in Ang II-infused atrial fibroblasts.  SAL protects against myocardial fibrosis infused by Ang II by activating the SIRT1-Nrf2 pathway.