Objective:Triple-negative breast cancer (TNBC) is the most metastatic type of breast cancer. Cynaropicrin, a sesquiterpene lactone, shows potential anticancer effects. This study evaluated cynaropicrin's impact on metastasis and angiogenesis in TNBC cells.Materials and Methods:MDA-MB-231 and MDA-MB-468 cell lines were exposed to incrementing concentrations of cynaropicrin. The proliferation of the cell lines was assayed using the MTT method. A wound scratch technique was chosen to appraise the migratory properties of cells following cynaropicrin treatment. The transcript levels of epithelial-mesenchymal transition (EMT) and pro-angiogenic factors were quantified via quantitative polymerase chain reaction. The western blotting technique estimated the amount of E-cadherin, N-cadherin, Fibronectin, Vimentin, and VEGFA.Results:The proliferation of MDA-MB-231 and MDA-MB-468 cells was significantly lowered due to cynaropicrin in a concentration-associated way. Results of the wound healing method uncovered that cynaropicrin could mitigate the migration of breast-derived MDA-MB-231 and MDA-MB-468 cells. Cynaropicrin also upregulated E-cadherin and hindered the protein expression of N-cadherin, Vimentin, Fibronectin 1, and VEGFA in breast-derived MDA-MB-468 and MDA-MB-231 cells.Conclusion:The present findings indicated the anti-metastatic capacity of cynaropicrin against TNBC by a mechanism that implicated the inhibition of the EMT and pro-angiogenic factor VEGFA. These outcomes suggest cynaropicrin as an anti-metastatic and anti-angiogenic sesquiterpene lactone against TNBC.

Objective:The first-line drugs used for treating leishmaniasis are highly costly and aggressive. Extracts from Lonchocarpus cultratus have trypanocidal activity and possess several compounds with biological activities. This study sought to observe the in vitro anti-Leishmania amazonensis action of extracts from seeds of L. cultratus. Furthermore, the immunomodulatory and antioxidant characteristics of the extracts were determined. Materials and Methods:Sequential extraction with hexane, dichloromethane, and methanol was performed to obtain extracts from L. cultratus seeds, which were characterized via 1H NMR. Promastigotes, intracellular amastigotes, and murine macrophages were treated with increasing concentrations of the extracts, and the inhibition rates were determined by scanning electron microscopy (SEM) analysis of the extracellular forms of the extracts. The immunomodulatory activity of the extract was determined against stimulated RAW macrophages. Results: Isocordoin and lonchocarpine were identified in dichloromethane and hexane extracts. Dichloromethane (LDS), hexane (LHS), and methanolic (LMS) extracts inhibited promastigote cell growth (IC50 values of 5.18±1.18, 5.25±1.47, and 33.89±1.62 μg/ml, respectively) and decreased the number of amastigotes in the macrophages (IC50 values of 1.41±0.31, 6.33±1.42, and 5.87±1.37 μg/ml, respectively). Hexane and methanolic extracts showed low toxicity in macrophages, resulting in a high selectivity index against promastigotes and amastigotes. In addition, the three extracts immunomodulated macrophages, reducing nitric oxide (NO) secretion. Conclusion:The results revealed that the activities of the L. cultratus extracts included leishmanicidal effects, low cytotoxicity to macrophages, and immunosuppression in vitro.

Objective:Second-generation antipsychotics can lead to metabolic problems. This study investigated whether an herbal compound with green tea, Persian borage, and purslane extracts could help in antipsychotic-induced weight management in schizophrenia patients.Materials and Methods: This triple-blind, placebo-controlled study at Hijazi Psychiatry Hospital in Mashhad, Iran, involved 73 schizophrenia patients. Participants received either an herbal compound or a placebo, alongside their antipsychotic medication. The primary outcome was changes in body mass index (BMI), with secondary outcomes including waist-to-hip ratio (WHR), fasting blood sugar (FBS), HbA1c, lipid profile, blood pressure, appetite, quality of life, and psychotic symptom severity.Results:The herbal compound significantly reduced BMI (p<0.001), WHR (p<0.001), HbA1c (p=0.042), low-density lipoprotein (LDL) concentration (p=0.009), and systolic blood pressure (p=0.015) compared to the placebo. No significant differences were observed in FBS or lipid profile (except LDL) between the two groups. The intervention group had significantly lower appetite levels than the placebo group at weeks four and eight (p=0.001). There was no significant difference between the two groups in the Positive and Negative Syndrome Scale (PANSS) score at any time. Participants reported no serious adverse effects.Conclusion:Adding herbal compound to antipsychotics significantly lowered BMI, WHR, HbA1c, LDL levels, systolic blood pressure, and appetite in schizophrenia patients.

Objective:To evaluate whether Panax notoginseng flower extract (PNF) can alleviate depression-like behavior caused by chronic unpredictable mild stress (CUMS) in mice and to explore its relations to neuroinflammation.Materials and Methods:C57BL/6J mice were subjected to CUMS for 7 weeks to induce depressive-like behaviors. Then PNF 1.7 or 3.4 g/kg was administered via intragastric gavage once a day for 4 consecutive weeks. After behavioral assessment, the systemic inflammation and neuroinflammation were investigated by detecting inflammatory factors in serum and brain with enzyme-linked immunosorbent assay (ELISA). The serum levels of adrenocorticotropic hormone (ACTH) and glucocorticoids (GC) were also determined. The activation of microglia and astrocyte was investigated by immunohistochemistry. The chemical components in PNF were analyzed with Ultra-high performance liquid chromatography/MS (UPLC/MS). Results:PNF 1.7 and 3.4 g/kg treatment alleviated depressive behavior in CUMS mice in various behavioral studies. In both serum and brain, PNF treatment significantly counteracted the CUMS-induced enhancement of typical pro-inflammatory factors, Tumor Necrosis Factor alpha (TNF-α), Interleukin-1β (IL-1β), and IL-6 and counteracted the CUMS-induced decrease of anti-inflammatory factorIL-10. Treatment with PNF also attenuated the CUMS-induced serum ACTH and GC elevation. Immunohistochemical analysis revealed that PNF treatment significantly reduced the number of ionized calcium-binding adapter molecule 1 (Iba-1) and glial fibrillary acidic protein (GFAP) positive cells in the brains of CUMS mice, indicating an inhibition of microglial and astrocytic activation. UPLC/MS study suggest that ginsenoside Rh1 is the main ginsenoside in the extract.Conclusion:PNF ameliorates CUMS-induced depression-like behaviors in mice, which may be mainly related to reducing neuroinflammation in the brain.

Objective:Multiple sclerosis (MS) is a debilitating disorder related to damage to the central nervous system (CNS). MS incidence in about 2.3 million people worldwide. Royal jelly (RJ) is a white material with many medicinal properties. Omega-3 (ω−3) is a natural substance that its beneficial effects were demonstrated in several studies performed on MS patients.Materials and Methods: 60 patients referring to the MS Society of Iran were randomly divided into two groups (1:1 ratio) receiving 1-gram RJ and 1-gram ω-3 capsule 1 gr capsules of RJ and 1 gr ω−3 daily in addition to receiving their daily treatment. Then, their information was recorded. Blood samples of all subjects were collected to evaluate the level of IL-4, INF-Y, TGF-B, and TNF-α with Enzyme-linked immunosorbent assay (ELISA) method twice; first, before the intervention and then, received supplements for one month. The duration of treatment was one month, and the patients returned to the center. Results:The results indicated that RJ, similar to ω−3, could improve the cytokines levels in MS patients. RJ significantly improved TNF-α (p<0.05), and ω−3 significantly decreased TGF-β levels (p<0.05). Both decreased IFN-γ and increased IL-4, but it was more in the group receiving RJ.Conclusion:According to the findings, it is hoped that using RJ and ω−3 could be helpful in MS patients.

Objective:The aim of the current study was to determine the therapeutic effects of combination therapy with propolis extract and rat bone marrow mesenchymal stem cells (MSCs) in streptozotocin (STZ)-induced diabetic rats.Materials and methods:Firstly, characterization of MSCs was performed and MTT assay was done to determine the optimum concentration of propolis for incubation with MSCs. Rats were divided into 8 groups: Control, diabetic , diabetic+propolis, diabetic+metformin, diabetic+MSCs, diabetic+MSCs+ propolis, diabetic+ MSCs pre-incubated with propolis. MSCs were transplanted via the tail vein on the 7th and 21st days of the study. Renal function tests and histopathologic examination were performed for all groups.Results:Serum glucose concentration in all propolis and MSCs treatment groups was significantly lower than that of the STZ group on the 21st and 42nd days of the study. On the 42nd day, the concentration of serum albumin in the STZ group was significantly lower than the control. Serum albumin concentration in all diabetic groups treated with propolis and MSCs was significantly higher than the diabetic animals. On the 42nd day, the concentrations of creatinine and urea in the STZ group were significantly higher than all the treatment and control groups. The renal index and histopathological parameters improved in all treatment groups compared with the STZ group.Conclusion: Our findings demonstrated, MSCs, propolis, and their combination demonstrate positive effects on renal function, kidney index, and histopathology in all treated animals compared with the STZ diabetic rats. These beneficial effects are comparable to those of metformin.

Objective:The chronic metabolic disease diabetes mellitus (DM) dramatically increases the risk of mental illness and cognitive decline. Allium saralicum M. Fritsch (ASRMF) has demonstrated antioxidant, anti-inflammatory, and neuroprotective properties. This study aimed to investigate the effects of ASRMF on memory impairment, Insulin-like growth factor 1(IGF-1) expression, and inflammation in a streptozotocin (STZ)-induced model of cognitive dysfunction.Materials and Methods:Male Wistar rats were randomly divided into five groups (n = 7): Control, Sham, STZ, ASRMF extract, and STZ+ASRMF. Memory impairment and hypoglycemia were induced following a single intraperitoneal injection of STZ (60 mg/kg). Twenty-eight days later, animals in the treated groups received oral administration of ASRMF extract (250 mg/kg) daily for 15 consecutive days. Hyperglycemia confirmation occurred through blood glucose measurements on days 3 and 28 post-inductions, and at the end of the experiment in all groups. Spatial learning and memory performance was evaluated using the Morris water maze (MWM). Brain tissue was fixed in formalin and analyzed via immunohistochemical staining to assess IGF-1 and NF-κB levels.Results:Our results demonstrated that ASRMF extract treatment significantly improved memory performance, which correlated with increased IGF-1 expression and reduced NF-κB in the hippocampus and blood glucose levels. These findings suggest that ASRMF exerts a neuroprotective effect in the diabetic rat model, likely through its anti-inflammatory properties. Conclusion:This study underscores the therapeutic potential of ASRMF in alleviating cognitive impairment associated with diabetes mellitus. However, further investigations are warranted to elucidate the precise mechanisms underlying its neuroprotective effects.

Objective:This study investigated the hepatoprotective effects of Cotoneaster nummularius manna extract (CNE) against phenylhydrazine (PHZ)-induced hyperbilirubinemia and oxidative stress in a neonatal rat model.Materials and Methods:Fifty neonatal Wistar rats (2 weeks old) were divided into five groups (n=10): a control group, a PHZ-only group, and three PHZ-treated groups receiving CNE (1, 2.5, and 5 mg/kg, orally, thrice daily for 10 days). PHZ was used to induce hemolysis and hyperbilirubinemia. Markers of liver function, oxidative stress, and antioxidant capacity were analyzed, alongside β-glucuronidase activity.Results:CNE significantly mitigated PHZ-induced hyperbilirubinemia by reducing serum bilirubin levels and dose-dependently decreasing oxidative stress markers, including reactive oxygene species ROS, malondialdehyde (MDA), and protein carbonylation. It also restored glutathione (GSH) levels and total antioxidant capacity. The highest CNE dose (5 mg/kg) demonstrated the most pronounced effects. Furthermore, CNE inhibited β-glucuronidase activity, contributing to its hepatoprotective action. Hierarchical clustering and heatmap analyses corroborated the dose-dependent antioxidant and hepatoprotective properties of CNE.Conclusion:These findings highlight the hepatoprotective potential of C. nummularius extract in reducing oxidative stress and hyperbilirubinemia. CNE dose-dependent effects, particularly at 5 mg/kg, suggest its promise as a therapeutic agent for neonatal liver dysfunction and oxidative damage. Further clinical studies are warranted to explore its potential applications in managing liver disorders.

Objective:This randomized, double-blind trial evaluated trans sodium crocetinate (TSC)—a crocetin-derived antioxidant and crocetin with potential cardioprotective effects—on reperfusion injury in 90 ST-elevation myocardial infarction (STEMI) patients after primary percutaneous coronary intervention (PPCI). Materials and Methods: Patients received either TSC (0.5 mg/kg injection pre-PPCI + 7.5 mg crocetin tablets for 3 days) or placebo. The primary outcome was ≥ 70% ST-segment resolution 1-hr post-PPCI. Secondary outcomes included corrected thrombolysis in myocardial infarction frame count (CTIMIFC), arrhythmia rates, and echocardiographic parameters (left ventricular ejection fraction (LVEF) and LV size). Results:ST-segment resolution occurrence was significantly higher in the TSC group versus placebo (p=0.018). There was no difference in CTIMIFC between the two groups. Echocardiographic parameters were similar between the TSC and placebo groups. Although not statistically significant, the frequency of supraventricular and ventricular arrhythmias was lower in the TSC group. Adverse drug effects were comparable between the two groups.Conclusion: TSC (0.5 mg/kg injection pre-PPCI + 7.5 mg crocetin tablets for 3 days) administration improved myocardial reperfusion, as evidenced by enhanced ST-segment resolution, suggesting reduced reperfusion injury in STEMI patients post-PPCI. While no benefits were observed in CTIMIFC or cardiac remodeling, the safety profile and primary outcome results support further investigation. Larger trials are needed to confirm efficacy and assess long-term clinical impacts.

Objective:The present study aimed to assess the effect of training along with administration of Tribulus terrestris (T) on the antioxidant system and telomere functional markers in the liver tissue of rats exposed to stanozolol.Materials and Methods: Forty- nine male rats, with average age and weight of 8-10 weeks and 180-220 g respectively, were randomly divided into 7 groups of seven rats: 1) Sh: Sham, 2) S: stanozolol, 3) S+T50: stanozolol+ 50 mg/kg T. terrestris, 4) S+T100: stanozolol+ 100 mg/kg T. terrestris, 5) S+RT: stanozolol + resistance training, 6) S+RT+T50: stanozolol + resistance training + 50 mg/kg T. terrestris, and 7) S+RT+T100: stanozolol + resistance training + 100 mg/kg T. terrestris. Rats in the S groups received 5 mg/kg stanozolol intraperitoneally (25 mg/kg/wk). Groups 5 (R+T), 6 (S+RT+T50), and 7 (S+RT+T100) performed resistance trainings three sessions per week with an intensity of 30-100 percent of body weight for eight weeks. Also, groups 3 (S+T50), 4 (S+T100), 6 (S+RT+T50) and 7 (S+RT+T100) received daily ethanolic extract of T with doses of 50 and 100 mg/kg intraperitoneally. Results:In the S+RT, S+T50, S+T100, S+RT+T50, and S+RT+T100 groups, malondialdehyde (MDA) levels were significantly lower and gene expression of phosphoinositide 3-kinases (PI3K), protein kinase B (Akt), and telomerase reverse transcriptase (TERT) levels were higher than the S group. Also, phosphatase and tensin homolog (PTEN) and TERT gene expression levels in the S+T100 group were significantly higher than the S+T50 group.Conclusion: Training and T have a positive effect on the transcription pathway of antioxidants and telomere protection.