Fluoxetine (Flx), the first-line antidepressant drug, has been reported to cause organ toxicity. This study examines the chronic toxicity of Flx on brain, kidney, and reproductive functions in male rats and its amelioration by baicalin. Albino Wistar rats were treated with Flx dose of 10 mg/kg bodyweight. Ameliorative effect of baicalin against toxicity was studied at a dose of 50 and 100 mg/kg bodyweight along with baicalin control (100 mg/kg) daily for 28 days. Serum levels of testosterone, acetylcholinesterase (AChE), total protein, albumin, γ-glutamyltransferase (GGT), creatinine, blood urea nitrogen (BUN) and uric acid were analyzed. The antioxidant profile of brain, kidney, and testicular tissues was evaluated by assessing enzymatic and non-enzymatic markers, including SOD, CAT, GST, GSH, MDA, and advanced oxidative protein products (AOPP). Histopathological examination of tissue sections was conducted, and the gene expression of MnSOD, transferrin, and BDNF were analyzed. Flx treatment showed the diminished serum levels of testosterone, AChE, total protein, and albumin while GGT, creatinine, BUN and uric acid increased. In brain, kidney and testis homogenates decline in SOD, CAT, GST, and GSH with increase in MDA, and AOPP was observed. Expression profiling showed downregulation of MnSOD and Transferrin genes while BDNF gene was upregulated in Flx treated rats. Baicalin supplementation produced marked restoration of biochemical and molecular parameters which was supported by histopathological study. Overall, baicalin neutralizes the free radical induced toxicity through restoration of tissue antioxidant defenses, highlighting its therapeutic potential in counteracting fluoxetine-induced toxicity in male rats.
Extracorporeal membrane oxygenation (ECMO) is a rescue therapy for severe COVID-19-associated respiratory failure, yet its molecular impact on critically ill patients remains insufficiently characterized. In this retrospective study of 52 ICU patients, clinical, proteomic and metabolomic data were associated to identify ECMO-associated biochemical signatures between ECMO and non-ECMO in discharged patients, deceased patients, and all patients regardless of outcome. Clinical data showed that ECMO recipients exhibited greater physiological derangements, including higher leukocyte and neutrophil counts and prolonged IMV and ICU stays. Proteomic analysis revealed ECMO-associated perturbations in cytokine signaling, myeloid activation, and antigen-presentation pathways. Among survivors, ECMO was linked to reduced HLA class II expression and elevated CSF3, suggesting dampened antigen presentation with concurrent granulopoeitic stimulation. In non-survivors, ECMO was associated with increased inflammatory-metabolic mediators such as FASN and PTGIS, consistent with mitochondrial dysfunction, lipid turnover, and endothelial stress. Metabolomics revealed a coherent ECMO-associated metabolic phenotype across comparison. Key discriminating metabolites include sphingomyelin, lysophosphatidic acid, tocotrienol- and steroid-derivates, collectively indicating redox imbalance, membrane remodeling, pro-inflammatory lipid signaling, and steroid-metabolic dysregulation. Conversely, depletion of cysteinylglycine pointed to impaired glutathione-dependent antioxidant defense. Together, these multi-omics alterations define a consistent ECMO-associated molecular signature across study comparisons characterized by oxidative stress, lipidomic reprogramming, immune modulation, and structural membrane injury. These findings provide a molecular framework for understanding ECMO-related physiological stress and may provide a basis for prospective validation in larger cohorts of critically ill COVID-19 patients.
Alzheimer’s disease (AD) is a chronic neurodegenerative disorder characterized by progressive impairment of memory, language, and cognitive function. The present study investigated the chemical composition and therapeutic potential of the aqueous methanol extract obtained from the aerial parts (leaves and flowers) of Salvia verticillata L. in aluminum chloride (AlCl3)-induced AD in rat model using donepezil-HCl as a reference drug. Ultra-high-performance liquid chromatography coupled with high-resolution mass spectrometry (UHPLC/HRMS) analysis led to the identification of 74 compounds in the extract. Notably, salvianic acid C was isolated for the first time from S. verticillata, and its structure was confirmed using nuclear magnetic resonance (NMR) spectroscopy. Quantitative HPLC-PDA analysis revealed a high rosmarinic acid content (7.21
Moringa oleifera leaves have a long history of nutritional and ethnomedicinal use, including traditional applications related to glycemic disorders, but the specific bioactive constituents that may contribute to these effects remain poorly defined. We isolated Mo–D3, an anion-exchange protein fraction from M. oleifera leaves selected by reactivity with an anti-insulin antibody, and evaluated its metabolic effects in male C57BL/6 mice (n = 6/group). In glucose-challenged mice, Mo–D3 reduced glycemia at 30 and 60 min and decreased the 0–180-min area under the glucose curve at doses of 5–500 mg/kg; 5 mg/kg was the lowest effective dose and was used thereafter. Mo–D3 increased hepatic and skeletal-muscle glycogen and acutely reduced total cholesterol while increasing high-density lipoprotein cholesterol. In dexamethasone-treated mice, Mo–D3 partially restored the glucose disappearance rate constant and reversed the increases in intestinal maltase and sucrase activities. Five-day Mo–D3 treatment also approximately doubled skeletal-muscle Akt messenger RNA and increased pancreatic Ins1 messenger RNA by more than tenfold. Collectively, these findings support a multimodal metabolic effect involving improved glucose disposal, tissue glycogen storage, recovery of insulin responsiveness, and coordinated intestinal and transcriptional responses.
Polycystic ovary syndrome (PCOS) is a prevalent endocrine-metabolic disorder affecting women of reproductive age, characterized by reproductive dysfunction and enlarged ovaries with numerous small cysts. Despite its substantial health impact, developing safe and effective treatments remains a significant challenging. This study evaluated the therapeutic efficacy of the Ayurvedic polyherbal formulation “Dhatrayadi Yoga” in a rat model of PCOS induced by estradiol valerate (EV). An initial acute toxicity assessment of the polyherbal preparation (2000 mg/kg) confirmed its safety. Rats were divided into five groups (n = 6): Group I (negative control) received saline; Groups II–V were given EV (4 mg/kg) on days 1 and 14 to induce PCOS. Groups III and IV were treated with the polyherbal formulation (100 mg/kg or 50 mg/kg, respectively), and Group V received clomiphene citrate (1 mg/kg) for 60 days. Daily vaginal smears were sampled to monitor the estrous cycle. Body weight was measured weekly, and at the end-of-study, blood samples assessed hematological and hormonal profiles (LH, FSH, estrogen, progesterone, and testosterone). Ovarian morphology was further evaluated by histopathological examination. EV administration produced marked reproductive endocrine disturbance, hormonal imbalances, and estrous cycle disruption. In contrast, Dhatryadi Yoga significantly reduced estrogen and testosterone levels, restored normal estradiol and progesterone concentrations, and improved ovarian histopathology, with a marked decrease in cyst formation. These results indicate a strong correlation between Dhatryadi Yoga and the relief of PCOS symptoms. Although specific internal chemical triggers were not measured, the observed improvements likely stem from the combined effect of the herbal ingredients. These findings warrant more detailed research to understand the formulation’s effect at molecular level.
