Development of Prolonged Release Microspheres of Metformin Hydrochloride Using Ion Exchange Resins

Aim To prepare the prolonged-released microspheres of mefformin hydrochloride. Methods Ion-exchange resin-drug mefformin hydrochloride complexes were prepared as core materials, and followed by coating using ethylcellulose （EC） by the emulsion solvent diffusion technique. The release rate of mefformin from the microcapsules was highly dependent on the encapsulating formulation, thus being used as an index for formulation screening. Orthogonal experiments were performed to optimize the coating formulation. Results The final chosen formulation for coating of mefformin microcapsules were as follows： （ 1 ） the ratio of EC （20cps） to EC （45cps） was 50：50; （2） the ratio of plasticizer to coating materials was 20% ;and （3） the ratio of resin-mefformin complexes to coating materials was 5 ： 1. Conclusion The prolonged release microspheres of mefformin hydrochloride were successfully prepared.

Effect of Temperature on Volumetric and Viscometric Properties of Homologous Amino Acids in Aqueous Solutions of Metformin Hydrochloride

Density（ρ）and viscosity（η）are measured for glycine,DL-α-alanine DL-α-valine,and DL-α-leucine in 0.05,0.10,0.15 and 0.20 mol·L^-1aqueous metformin hydrochloride at 308.15,313.15 and 318.15 K.The measured values are used to estimate some important parameters,such as partial molal volume Vφ,standard partial molal volume Vφ^0,transfer volume ΔVφ^0,hydration number nH,the second derivative of infinite dilution of partial molal volume with respect to temperature,viz., ^2 Vφ^0 /T^2,viscosity B-coefficient,variation of B with temperature,viz., dB/dT,free energy of activation per mole of solvent Δμ1^＊0 and solute Δμ2^0＊ of the amino acids.These parameters are interpreted in terms of solute-solute and solute-solvent interactions and structure making/breaking ability of solutes in the given solution.In addition,Vφ^0,0 ΔVφ^0,viscosity B-coefficient,ΔB and Δμ2 ^0＊ are split into group contributions（NH3^＋ COO ^-）and -CH2 of the amino acids using their linear correlation and their behavior is discussed.

Conductometric Titration of Metformin Hydrochloride: Simulation and Experimentation

In order to teach students,the importance of conductometric titrations in this work,we present a laboratory experiment to quantify the amount of metformin hydrochloride in a tablet.The quantification was carried out through the evaluation of the chloride by silver nitrate.The titration and the end point were followed by conductometric titration,as well as by potentiometric and visually by the Volhard method.In addition,the theoretical conductivities of the metformin hydrochloride solution were calculated when known volumes of titrant are added,using the limit conductivity data for each of the ions present in the literature.To simulate the conductometric titration,the calculated conductivity values were plotted based on the volume of silver nitrate added.A comparison between techniques is made in order to determine the best monitoring method,being this one conductimetry to detect the equivalence point for metformin hydrochloride with 0.99±0.03,according to relative standard deviation(%RSD).Simulated titration curves adequately describe obtained results in an experimental way.The conductometric titration is the best method for quantification since it shows less dispersion between obtained results and has the highest concordance among results.Their application is shown through the analysis and conductometric titration simulations.

Validation of Metformin Hydrochloride in Human Plasma by HPLC-Photo Diode Array （PDA） for Application of Bioequivalence Study

A sensitive and specific high performance liquid chromatography （HPLC） method was developed and validated for the simultaneous determination of metformin hydrochloride （HCI） in human plasma. The HPLC method consists of isocratic eluation with a mixture of 60% buffer （10 mM sodium dihyrogenphosphate-10 mM sodium dodecyl sulphate） and 40% acetonitrile with final pH 7.0 with flow rate of 1.0 mL/min on a Kromasil~ Akzo Nobel RP-18 （4.6 mm ID ~ 250 mm, 5 ~tm） column at an ambient temperature. Photo diode array detection was performed in program mode at 234 rim. The analyte and diazepam as internal standard （IS） were extracted from plasma using 10% trichloroacetic acid. The assay was linear over the therapeutic concentration range of 20-2,500 ng/mL for metformin HCI with correlation coefficient of r = 0.9999. Limit of quantitation was 20 ng/mL. The results obtained for intraJinter day accuracy and precision complied very well with the generally accepted criteria for bio-analytical assay. The method was applied to bioequivalence （BE） study of metformin HCI in healthy Indonesian volunteers after treatment with 750 mg XR metformin HCI. This BE study shows that the two formulations are equivalent so that they were therapeutically interchangeable for each other.

Preparation and <i>in Vitro</i>Drug Release Evaluation of Once-Daily Metformin Hydrochloride Sustained-Release Tablets

The objective of this study was to develop once-daily metformin hydrochloride sustained-release tablets (MHSRT) and evaluate their in vitro release behavior. MHSRT were prepared by the film coating method. The in vitro drug release rate of MHSRT and the commercial tablets Fortamet? made in the United States of America in water was fitted with zero order kinetic equation, and Ritger-Peppas kinetic equation in 0.1 M HCl and pH 6.8-phosphate buffer, respectively. The similarity factor f2 values of MHSRT in three different dissolution medium were 82, 80 and 74, respectively in comparison with imported Fortamet?, which were all greater than 50. The results of storage-stability showed that MHSRT were stable for at least 6 months under stress condition (40℃ ± 2℃, RH 75% ± 5%). Therefore, in this study, MHSRT were successfully prepared using optimized formulation technologies that meet mass produce. The in vitro release behavior of MHSRT was almost similar to that of imported Fortamet?.

<i>In-Vitro</i>Antiproliferative Analysis of Metformin Hydrochloride on Androgen-Sensitive, LNCAP and Androgen-Insensitive, PC-3 Human Prostate Cancer Cell Lines

Prostate cancer is one of the diseases worldwide that causes cancer-related deaths in men. Metformin is an antidiabetic drug that has been in use for over two decades for the treatment of Type II Diabetes mellitus (DM2). The purpose of this study was to evaluate the anti-proliferative property of metformin hydrochloride on androgen-sensitive, LNCAP and androgen-insensitive, PC-3 human prostate cancer cell lines at different concentrations (μM and mM) using 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) assay. Metformin hydrochloride displayed a stronger cytotoxicity on the androgen-insensitive PC-3 than on the androgen-sensitive human prostate cancer cell lines. For both cell lines, the antiproliferative activity of metformin hydrochloride was best displayed at 0.1 mM concentration with average cell death percentage of 60% after 120-hour exposure.

Development and Validation of a Method for Simultaneous Determination of Metformin Hydrochloride and Sitagliptin Phosphate in a Formulation by RP-HPLC

Present study was aimed to develop and validate a reverse-phase high-performance liquid chromatography method for simultaneous determination of sitagliptin phosphate and metformin hy-drochloride in a marketed formulation. The drug separation was performed on Hibar-240, Li-chrosphere-100 C18 ODS (250 × 4.6 mm, 5 μm) column, at a flow rate of 1 mL/min. The mobile phase used was a mixture of methanol: potassium di-hydrogen phosphate buffer at a ratio of 70:30 v/v. The detection was carried out at a wavelength of 266 nm. The retention times of sitagliptin phosphate and metformin hydrochloride were found as 6.1 and 4.9 min respectively. Linear calibration curves with good correlation coefficients were obtained over the concentration ranges of 10 - 50 μg/mL for sitagliptin and 20 - 100 μg/mL for metformin. The limit of detection was 0.016 and 0.14 μg/mL and the limit of quantification was 0.048 and 0.42 μg/mL for sitagliptin phosphate and metformin hydrochloride respectively. Validation of the method demonstrated system selectivity, specificity, linearity, accuracy and precision. The developed method was found useful in the simultaneous analysis of sitagliptin phosphate and metformin hydrochloride in formulation.

Derivative Spectrophotometric and Isocratic High Performance Liquid Chromatographic Methods for Simultaneous Determination of Repaglinide and Metformin Hydrochloride in Pharmaceutical Preparations

In this study, a derivative spectrophotometric method and one HPLC method were developed and validated for analysis of anti-diabetic drugs, repaglinide (RPG) and metformine hydrochloride (MTF) in tablets. The spectrophotometric methods were based on zero-crossing first-derivative and fourth-derivative spectrophotometric method for simultaneous analysis of RPG (308 nm) and MTF (267 nm), respectively. Linear relationship between the absorbance at λmax and the drug concentration was found to be in the ranges of 5.0 - 50.0 μg·mL-1 for both RPG and MTF. The quantification limits for RPG and MTF were found to be 0.568 and 1.156 μg·mL-1, respectively. The detection limits were 0.170 and 0.347 μg·mL-1 for RPG and MTF, respectively. The second method is a rapid stability-indicating isocratic HPLC method developed for the determination of RPG and MTF. A linear response was observed within the concentration range of 5.0 - 50.0 μg·mL-1 for both RPG and MTF. The quantification limits for RPG and MTF were found to be 1.821 and 1.653 μg·mL-1, respectively. The detection limits were 0.601 and 0.545 μg·mL-1 for RPG and MTF, respectively. The proposed methods were successfully applied to the tablet analysis with good accuracy and precision.

Hypidone hydrochloride(YL-0919)ameliorates functional deficits after traumatic brain injury in mice by activating the sigma-1 receptor for antioxidation

Traumatic brain injury involves complex pathophysiological mechanisms,among which oxidative stress significantly contributes to the occurrence of secondary injury.In this study,we evaluated hypidone hydrochloride(YL-0919),a self-developed antidepressant with selective sigma-1 receptor agonist properties,and its associated mechanisms and targets in traumatic brain injury.Behavioral experiments to assess functional deficits were followed by assessment of neuronal damage through histological analyses and examination of blood-brain barrier permeability and brain edema.Next,we investigated the antioxidative effects of YL-0919 by assessing the levels of traditional markers of oxidative stress in vivo in mice and in vitro in HT22 cells.Finally,the targeted action of YL-0919 was verified by employing a sigma-1 receptor antagonist(BD-1047).Our findings demonstrated that YL-0919 markedly improved deficits in motor function and spatial cognition on day 3 post traumatic brain injury,while also decreasing neuronal mortality and reversing blood-brain barrier disruption and brain edema.Furthermore,YL-0919 effectively combated oxidative stress both in vivo and in vitro.The protective effects of YL-0919 were partially inhibited by BD-1047.These results indicated that YL-0919 relieved impairments in motor and spatial cognition by restraining oxidative stress,a neuroprotective effect that was partially reversed by the sigma-1 receptor antagonist BD-1047.YL-0919 may have potential as a new treatment for traumatic brain injury.

Design and optimization of a greener sinomenine hydrochloride preparation process considering variations among different batches of the medicinal herb

The current methods used to industrially produce sinomenine hydrochloride involve several issues,including high solvent toxicity,long process flow,and low atomic utilization efficiency,and the greenness scores of the processes are below 65 points.To solve these problems,a new process using anisole as the extractant was proposed.Anisole exhibits high selectivity for sinomenine and can be connected to the subsequent water-washing steps.After alkalization of the medicinal material,heating extraction,water washing,and acidification crystallization were carried out.The process was modeled and optimized.The design space was constructed.The recommended operating ranges for the critical process parameters were 3.0–4.0 h for alkalization time,60.0–80.0℃ for extraction temperature,2.0–3.0(volume ratio)for washing solution amount,and 2.0–2.4 mol·L^(-1) for hydrochloric acid concentration.The new process shows good robustness because different batches of medicinal materials did not greatly impact crystal purity or sinomenine transfer rate.The sinomenine transfer rate was about 20%higher than that of industrial processes.The greenness score increased to 90 points since the novel process proposed in this research solves the problems of long process flow,high solvent toxicity,and poor atomic economy,better aligning with the concept of green chemistry.

Carbon-doped CuFe_(2)O_(4) with C-O-M channels for enhanced Fenton-like degradation of tetracycline hydrochloride: From construction to mechanism

Carbon-doped copper ferrite(C–CuFe_(2)O_(4))was synthesized by a simple two-step hydrothermal method,which showed enhanced tetracycline hydrochloride(TCH)removal efficiency as compared to the pure CuFe_(2)O_(4) in Fenton-like reaction.A removal efficiency of 94%was achieved with 0.2 g L^(-1) catalyst and 20 mmol L^(-1) H_(2)O_(2) within 90 min.We demonstrated that 5%C–CuFe_(2)O_(4) catalyst in the presence of H_(2)O_(2) was significantly efficient for TCH degradation under the near-neutral pH(5–9)without buffer.Multiple techniques,including SEM,TEM,XRD,FTIR,Raman,XPS M€ossbauer and so on,were conducted to investigate the structures,morphologies and electronic properties of as-prepared samples.The introduction of carbon can effectively accelerate electron transfer by cooperating with Cu and Fe to activate H_(2)O_(2) to generate·OH and·O_(2)^(-).Particularly,theoretical calculations display that the p,p,d orbital hybridization of C,O,Cu and Fe can form C–O–Cu and C–O–Fe bonds,and the electrons on carbon can transfer to metal Cu and Fe along the C–O–Fe and C–O–Cu channels,thus forming electron-rich reactive centers around Fe and Cu.This work provides lightful reference for the modification of spinel ferrites in Fenton-like application.

Benzydamine hydrochloride ameliorates ethanol-induced inflammation in RAW 264.7 macrophages by stabilizing redox homeostasis

Objective:To evaluate the protective effect of benzydamine hydrochloride against ethanol-induced oxidative stress and inflammation in RAW 264.7 macrophages.Methods:RAW 264.7 macrophages were treated with ethanol(100 mM)and benzydamine hydrochloride(7.5μM).The imflammatory status was confirmed by measuring pro-(TNF-αand IL-6)and anti-inflammatory(IL-10)cytokines through ELISA and RT-PCR assays.Reactive oxygen species generation and mitochondrial membrane potential were investigated to study the protective role of benzydamine hydrochloride against ethanol-induced oxidative stress.Apoptosis detection was also investigated using flow cytometry and acridine orange/ethidium bromide staining.Results:Benzydamine hydrochloride significantly decreased the secretion of TNF-αand IL-6,as well as the generation of reactive oxygen species inside the cells,thereby stabilizing the mitochondrial membrane potential and reducing DNA fragmentation.The ethanol-induced cellular necrosis was also reversed by the administration of benzydamine hydrochloride.Conclusions:Benzydamine hydrochloride ameliorates ethanol-induced cell apoptosis and inflammation in RAW macrophages.

Method Verification and Validation of Hydralazine Hydrochloride: Spectrophotometric Analysis in Pure and Pharmaceutical Formulations

The new method proposed is based on the formation of hydralazine-Bromophenol blue ion pair simply and without further extraction or heating. The ion pair was prepared in the presence of pH 3 citrate buffer forming a yellow-colored chromogen. A new maximum UV-visible band formed at 416 nm. The color was stable for more than 10 hours and obeyed Beer’s Law over the concentration range of 10 - 50 µg/mL. The calculated molar absorptivity and Sandell’s sensitivity were 1.01 × 104 L∙mol−1∙cm−1 and 0.0514 µg/mL, respectively. The elements of method validation stipulated by The International Conference on Harmonization [Q2 (R1)] were applied for hydralazine hydrochloride assay in pure and pharmaceutical tablet formulation. The average recoveries of the pure solution and the pharmaceutical formulation were 98.94% and 99.50%, respectively. The results were statistically compared by F-test, which indicates that the method can be precise and repeatable for both pure and pharmaceutical solutions. The method was found to be accurate, reproducible, and cost-effective, and validated for the assay of hydralazine in terms of the routine quality control.

Exploring the efficacy of(R)-PFI-2 hydrochloride in mitigating noise-induced hearing loss by targeting NLRP3 inflammasome and NF-κB pathway to reduce inner ear inflammation

Noise-induced hearing loss(NIHL)is primarily driven by inflammatory processes within the cochlea,where noise exposure triggers the activation of the NOD-like receptor protein 3(NLRP3)inflammasome,leading to an inflammatory cascade.The interaction between increased NLRP3 expression and NF-κB activity can further amplify cochlear inflammation.Our findings reveal that(R)-PFI-2 hydrochloride,a selective inhibitor of the SETD7 enzyme,effectively inhibits the activation of the cochlear NF-κB pathway,suppresses the release of proinflammatory factors,and prevents inflammasome assembly.This intervention disrupts the perpetuating cycle of inflammation,thereby alleviating damage to cochlear hair cells attributed to acoustic trauma.Consequently,(R)-PFI-2 hydrochloride emerges as a promising pharmacological candidate for NIHL,targeting and moderating the excessive immune and inflammatory responses implicated in the pathology of hearing loss.

Clinical effect of acupuncture at ghost points combined with fluoxetine hydrochloride on mild-to-moderate depression

BACKGROUND Depression is a common,chronic,and recurrent mood disorder that has become a worldwide health hazard.Fluoxetine hydrochloride,a common treatment method,can inhibit 5-hydroxytryptamine(5-HT)recycling in the presynaptic membrane;however,the efficacy of a single drug is inadequate.At present,mildto-moderate depression can be treated with acupuncture of ghost caves,but the clinical curative effect of combined therapy with fluoxetine hydrochloride has not been sufficiently reported.AIM To evaluate the clinical effect of acupuncture at ghost points combined with fluoxetine hydrochloride in the treatment of mild-to-moderate depression.METHODS This retrospective study included 160 patients with mild-to-moderate depression who were admitted to Shanghai Hospital of Integrated Traditional Chinese and Western Medicine,Affiliated to Shanghai University of Traditional Chinese Medicine,between January 2022 and June 2023.Patients were separated into a single-agent group(fluoxetine hydrochloride treatment,n=80)and a coalition group(fluoxetine hydrochloride treatment combined with acupuncture at ghost points,n=80).Pre-treatment symptoms were recorded,and the clinical curative effect and adverse reactions[Asberg Antidepressant Side Effects Scale(SERS)]were assessed.Depression before and after treatment[Hamilton Depression Scale(HAMD)-24],neurotransmitter levels[5-HT,norepinephrine(NE),dopamine(DA)],oxidative stress indicators[superoxide dismutase(SOD),malondialdehyde(MDA)],and sleep quality[Pittsburgh Sleep Quality Index(PSQI)]were compared.RESULTS The total efficacy rate was 97.50%in the coalition group and 86.25%in the single-agent group(P<0.05).After 2,4,6,and 8 wk of treatment,the HAMD,self-rating depression scale,and SERS scores of the coalition and single-agent groups decreased compared with pre-treatment,and the decrease was more significant in the coalition group(P<0.05).After 8 wk of treatment,the levels of NE,DA,5-HT,and SOD in the coalition and single-agent groups increased,while the levels of MDA decreased;the increases and decrease in the coalition group were more significant(P<0.05).The PSQI scores of the coalition and single-agent groups decreased,and the decrease was more significant in the coalition group(P<0.05).CONCLUSION Acupuncture at ghost points combined with paroxetine tablets can safely improve depressive symptoms and sleep disorders,regulate neurotransmitter levels,and reduce stress responses in patients with mild-to-moderate depression.

Analysis of the Efficacy of Atomoxetine Hydrochloride Combined with Psycho-Behavioral Modification Therapy in the Treatment of ADHD in Children

Objective: To evaluate the therapeutic efficacy of atomoxetine hydrochloride (ATX) combined with psychological-behavioral modification therapy for attention-deficit/hyperactivity disorder (ADHD) in children. Methods: A total of 60 cases of ADHD children admitted to our hospital between November 2021 and November 2022 were selected and randomly grouped into Group I and Group II. There were 30 cases in Group I who were treated with ATX combined with psychological-behavioral modification therapy. There were 30 cases in Group II who were treated with ATX monotherapy, and the therapeutic effects were compared. Results: Before treatment, there was no difference in the behavioral problem scores and cognitive function indexes of the two groups (P>0.05). After treatment, the behavioral problem scores of Group I were lower than those of Group II, and the cognitive function indicators of Group I were lower than those of Group II (P < 0.05). The adverse reaction rate of Group I was lower than that of Group II, and the total effective rate was higher than that of Group II (P < 0.05). Conclusion: ATX combined with psychological-behavioral modification therapy improved the behavioral problems of ADHD children, enhanced their cognitive function, and reduced the adverse reactions to drug treatment.

Clinical Study on the Treatment of Senile Alzheimer’s Dementia with Sodium Oligomannate Combined with Memantine Hydrochloride

Objective:To analyze the clinical effects of sodium oligomannate combined with memantine hydrochloride in the treatment of senile Alzheimer’s dementia.Methods:Sixty-eight cases of Alzheimer’s dementia treated at the Second People’s Hospital of Fujian University of Traditional Chinese Medicine from March 2020 to March 2022 were selected as the study subjects.The patients were divided into two groups based on different treatment methods:the control group(treated with memantine hydrochloride,34 cases)and the treatment group(treated with sodium oligomannate+memantine hydrochloride,34 cases).Cognitive function,activities of daily living,neurotransmitters,serum intestinal flora metabolic markers,inflammatory factors,neurotrophic factors,and adverse reactions were compared between the two groups.Results:The treatment group showed better cognitive function,quality of life scores,and levels of relevant metabolic markers in the body compared to the control group,with statistically significant differences(P<0.05).The incidence of adverse reactions between the two groups(treatment group:2%;control group:4%)was not statistically significant(χ^(2)=0.731,P=0.393).Conclusion:Sodium oligomannate combined with memantine hydrochloride has better efficacy than the control group for treating senile Alzheimer’s dementia.It significantly improves and restores cognitive function and daily living abilities,benefits neurotransmitter secretion and internal regulation,upregulates the expression of neurotrophic factors,and has fewer adverse reactions,making it a treatment worthy of further clinical promotion and application.

Metformin and pancreatic neuroendocrine tumors:A systematic review and meta-analysis

BACKGROUND Most patients with advanced pancreatic neuroendocrine tumors(pNETs)die due to tumor progression.Therefore,identifying new therapies with low toxicity and good tolerability to use concomitantly with the established pNET treatment is relevant.In this perspective,metformin is emerging as a molecule of interest.Retrospective studies have described metformin,a widely used agent for the treatment of patients with type 2 diabetes mellitus(T2DM),to be effective in modulating different tumor-related events,including cancer incidence,recurrence and survival by inhibiting mTOR phosphorylation.This systematic review evaluates the role of T2DM and metformin in the insurgence and post-treatment outcomes in patients with pNET.AIM To systematically analyze and summarize evidence related to the diagnostic and prognostic value of T2DM and metformin for predicting the insurgence and posttreatment outcomes of pNET.METHODS A systematic review of the published literature was undertaken,focusing on the role of T2DM and metformin in insurgence and prognosis of pNET,measured through outcomes of tumor-free survival(TFS),overall survival and progression free survival.RESULTS A total of 13 studies(5674 patients)were included in this review.Analysis of 809 pNET cases from five retrospective studies(low study heterogeneity with I^(2)=0%)confirms the correlation between T2DM and insurgence of pNET(OR=2.13,95%CI=1.56-4.55;P<0.001).The pooled data from 1174 pNET patients showed the correlation between T2DM and post-treatment TFS in pNET patients(hazard ratio=1.84,95%CI=0.78-2.90;P<0.001).The study heterogeneity was intermediate,with I^(2)=51%.A few studies limited the possibility of performing pooled analysis in the setting of metformin;therefore,results were heterogeneous,with no statistical relevance to the use of this drug in the diagnosis and prognosis of pNET.CONCLUSION T2DM represents a risk factor for the insurgence of pNET and is a significant predictor of poor post-treatment TFS of pNET patients.Unfortunately,a few studies with heterogeneous results limited the possibility of exploring the effect of metformin in the diagnosis and prognosis of pNET.

Promising use of metformin in treating neurological disorders:biomarker-guided therapies

Neurological disorders are a diverse group of conditions that affect the nervous system and include neurodegenerative diseases(Alzheimer’s disease,multiple sclerosis,Parkinson’s disease,Huntington’s disease),cerebrovascular conditions(stroke),and neurodevelopmental disorders(autism spectrum disorder).Although they affect millions of individuals around the world,only a limited number of effective treatment options are available today.Since most neurological disorders express mitochondria-related metabolic perturbations,metformin,a biguanide type II antidiabetic drug,has attracted a lot of attention to be repurposed to treat neurological disorders by correcting their perturbed energy metabolism.However,controversial research emerges regarding the beneficial/detrimental effects of metformin on these neurological disorders.Given that most neurological disorders have complex etiology in their pathophysiology and are influenced by various risk factors such as aging,lifestyle,genetics,and environment,it is important to identify perturbed molecular functions that can be targeted by metformin in these neurological disorders.These molecules can then be used as biomarkers to stratify subpopulations of patients who show distinct molecular/pathological properties and can respond to metformin treatment,ultimately developing targeted therapy.In this review,we will discuss mitochondria-related metabolic perturbations and impaired molecular pathways in these neurological disorders and how these can be used as biomarkers to guide metformin-responsive treatment for the targeted therapy to treat neurological disorders.

Metformin alleviates spinal cord injury by inhibiting nerve cell ferroptosis through upregulation of heme oxygenase-1 expression

Previous studies have reported upregulation of heme oxygenase-1 in different central nervous system injury models.Heme oxygenase-1 plays a critical anti-inflammatory role and is essential for regulating cellular redox homeostasis.Metformin is a classic drug used to treat type 2 diabetes that can inhibit ferroptosis.Previous studies have shown that,when used to treat cardiovascular and digestive system diseases,metformin can also upregulate heme oxygenase-1 expression.Therefore,we hypothesized that heme oxygenase-1 plays a significant role in mediating the beneficial effects of metformin on neuronal ferroptosis after spinal cord injury.To test this,we first performed a bioinformatics analysis based on the GEO database and found that heme oxygenase-1 was upregulated in the lesion of rats with spinal cord injury.Next,we confirmed this finding in a rat model of T9 spinal cord compression injury that exhibited spinal cord nerve cell ferroptosis.Continuous intraperitoneal injection of metformin for 14 days was found to both upregulate heme oxygenase-1 expression and reduce neuronal ferroptosis in rats with spinal cord injury.Subsequently,we used a lentivirus vector to knock down heme oxygenase-1 expression in the spinal cord,and found that this significantly reduced the effect of metformin on ferroptosis after spinal cord injury.Taken together,these findings suggest that metformin inhibits neuronal ferroptosis after spinal cord injury,and that this effect is partially dependent on upregulation of heme oxygenase-1.