Metformin Research Articles

Metformin's effect on male rats experiencing CMF-induced neurotoxicity.

Numerous cancers are treated with the chemotherapy drugs cyclophosphamide (CP), methotrexate (MT), and fluorouracil (FU). However, it should be noted that neurotoxicity is a possible side effect of chemotherapy. The pharmaceutical agent metformin (MTF) is used to control type 2 diabetes. The administration of MTF has been documented to exhibit a reduction in specific toxic effects associated with chemotherapy. The primary purpose of this research was to examine whether MTF could mitigate the neurotoxicity brought on by cranial magnetic field (CMF). A cohort of forty male rats was divided into four distinct groups, with ten animals in each. We classified them as either saline, MTF, CMF, or CMF+MTF. The rats in the experiment group received two doses of CMF via intraperitoneal injection and were also given MTF in their drinking water at a concentration of 2.5 mg/mL on a daily basis. Brain tissue was obtained for ELISA of Bax, Bcl-2, and caspase-3 expression, as well as to determine NMDA and AMPA receptor mRNA expression by real-time polymerase chain reaction (RT-PCR) analysis. Expression of AMPAR, NMDAR, Bax, Bcl-2, and caspase-3 was not notably different between the saline and MTF groups. In contrast, mRNA expression for AMPAR, NMDAR, Bax, and caspase-3 was notably upregulated in the CMF group, while Bcl-2 was downregulated. The co-administration of MTF and CMF did not mitigate these side effects. neurotoxicity was induced in rats by CMF treatment, but the elevation of the glutamatergic system and the elevation of apoptotic proteins were not prevented by the MTF co-treatment.

Insights into the efficient degradation of metformin - An emerging antidiabetic medicine by UV/Sulfite process

The growing utilization of metformin (MET) in diabetes treatment has resulted in its occurrence in wastewater treatment plants, where conventional techniques were proved inadequate in eliminating it. The present study evaluated the potential of UV/sulfite system in degrading MET and analyzed the influence of common factors (i.e UV intensity, dosage of reagent, the pH value of reaction solution) on the target contaminant removal. In comparison with both direct UV photolysis and merely sulfite reduction, the UV/sulfite process had a remarkable enhancement in MET removal, with 96.54% of MET (initial concentration of 15 mg/L) being degraded within 30 minutes. A strong linear relationship (R2 > 0.99) was observed between MET degradation kinetics and UV intensity. The increase of sulfite dosage and solution pH could promote MET degradation to a certain extent in the studied system. Additionally, the hydrated electron (eaq-) was found played the principle role in MET removal through scavenging reactions.

Metformin as a Potential In Vitro Anticancer Modulator of Adenosine Monophosphate Kinase: A Review.

Metformin (MET) is the commonly prescribed hypoglycemic agent used in the treatment of type 2 diabetes mellitus (DM). Pleiotropic effects of MET are emerging as a medication for other diseases including breast cancer (BC). Therefore, a literature review was conducted to investigate whether the anticancer effects of MET are mediated through adenosine monophosphate kinase (AMPK). This review assessed published data focusing on studies where BC cell lines were treated with MET to explore its potential anticancer effects via AMPK on BC cells. The published data reveals that activated AMPK induces anticancer effects primarily by suppressing cell proliferation, induction of apoptosis, and cell cycle arrest, inhibition of metastasis and invasion, alteration of tumor microenvironment, and downregulation of tumorigenesis. In addition, MET was observed to induce AMPK-mediated effects when combined with other drugs. Further studies on assessing the potential use of MET alone or in combination with other drugs would pave the way to design new treatment strategies for BC.

Surface functionalization, particle size and pharmaceutical co-contaminant dependent impact of nanoplastics on marine crustacean - Artemia salina.

Despite a significant amount of research on micronanoplastics (MNPs), there is still a gap in our understanding of their function as transporters of other environmental pollutants (known as the Trojan horse effect) and the combined effects of ingestion, bioaccumulation, and toxicity to organisms. This study examined the individual effects of polystyrene nanoplastics (PSNPs) with various surface functionalizations (plain (PS), carboxylated (PS-COOH), and aminated (PS-NH2)), particle sizes (100 nm and 500 nm), and a pharmaceutical co-contaminant (metformin hydrochloride (MH), an anti-diabetic drug) on the marine crustacean - Artemia salina. The study specifically aimed to determine if MH alters the detrimental effects of PSNPs on A. salina. The potential toxicity of these emerging pollutants was assessed by examining mortality, hatching rate, morphological changes, and biochemical changes. Smaller nanoparticles had a more significant impact than larger ones, and PS-NH2 was more harmful than PS and PS-COOH. Exposure to the nanoparticle complex with MH resulted in a decrease in hatching rate, an increase in mortality, developmental abnormalities, an increase in reactive oxygen species, catalase, and lipid peroxidase, and a decrease in total protein and superoxide dismutase, indicating a synergistic effect. There were no significant differences between the complex and the individual nanoparticles. However, accumulating these particles in organisms could contaminate the food chain. These results highlight the potential environmental risks associated with the simultaneous exposure of aquatic species to plastics, particularly smaller PS, aminated PS, and pharmaceutical complex PS.

The inhibition of YAP Signaling Prevents Chronic Biliary Fibrosis in the Abcb4-/- Model by Modulation of Hepatic Stellate Cell and Bile Duct Epithelium Cell Pathophysiology.

Primary sclerosing cholangitis (PSC) represents a chronic liver disease characterized by poor prognosis and lacking causal treatment options. Yes-associated protein (YAP) functions as a critical mediator of fibrogenesis; however, its therapeutic potential in chronic biliary diseases such as PSC remains unestablished. The objective of this study is to elucidate the possible significance of YAP inhibition in biliary fibrosis by examining the pathophysiology of hepatic stellate cells (HSC) and biliary epithelial cells (BEC). Human liver tissue samples from PSC patients were analyzed to assess the expression of YAP/connective tissue growth factor (CTGF) relative to non-fibrotic control samples. The pathophysiological relevance of YAP/CTGF in HSC and BEC was investigated in primary human HSC (phHSC), LX-2, H69, and TFK-1 cell lines through siRNA or pharmacological inhibition utilizing verteporfin (VP) and metformin (MF). The Abcb4-/- mouse model was employed to evaluate the protective effects of pharmacological YAP inhibition. Hanging droplet and 3D matrigel culture techniques were utilized to investigate YAP expression and activation status of phHSC under various physical conditions. YAP/CTGF upregulation was observed in PSC patients. Silencing YAP/CTGF led to inhibition of phHSC activation and reduced contractility of LX-2 cells, as well as suppression of epithelial-mesenchymal transition (EMT) in H69 cells and proliferation of TFK-1 cells. Pharmacological inhibition of YAP mitigated chronic liver fibrosis in vivo and diminished ductular reaction and EMT. YAP expression in phHSC was effectively modulated by altering extracellular stiffness, highlighting YAP's role as a mechanotransducer. In conclusion, YAP regulates the activation of HSC and EMT in BEC, thereby functioning as a checkpoint of fibrogenesis in chronic cholestasis. Both VP and MF demonstrate effectiveness as YAP inhibitors, capable of inhibiting biliary fibrosis. These findings suggest that VP and MF warrant further investigation as potential therapeutic options for the treatment of PSC.

Green and High Throughput Assay Using 96-Microwell Base to Determine Metformin Hydrochloride in the Tablet Dosage Form.

Metformin (MET) is an oral antidiabetic drug widely used as the primary treatment for type 2 diabetes mellitus (T2DM). While various spectrophotometric assays exist for determining MET in pharmaceutical formulations, they often have limited throughput for quality control purposes. This study describes the validation of a 96-microwell plate spectrophotometer method using charge-transfer complexes (CTCs) with chloranilic acid (CLA) and 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ) for the quality control and detected of MET. This reaction was carried out in 96-microwell plates, and the absorbance of the colored complexes of CLA and DDQ were measured at 530 nm and 460 nm, respectively, using an absorbance microplate reader. This study aims to identify and quantify the use of a 96-microwell plate spectrophotometer analytical technique for assessing complicated formulations. The method was successfully used for the quantification of MET in the tablet dosage form. The results showed good correlation coefficients (0.996 and 0.997) with CLA and DDQ, respectively. The present method showed high precision with RSD % not exceeding 2.17%. The accuracy of the method was obtained by recovery percentage, with percentage values less than ±5%. The Analytical Greenness Metric (AGREE) was used to evaluate greenness of the assays. The result show that the microwell assay method is greenness and suitable for handling large samples on a daily used with high throughput analysis. The use of the 96-microwell-plate method is superior to the existing method in terms of simplicity of the procedure, the low economic cost, and its consumption of low amounts of reagents and organic ethanol solvent, making it an environmentally friendly method. Therefore, these advantages make them suitable and rapid alternatives method to current methods for routine metformin analysis in quality control laboratories.

A Review on Method Development and Validation of RP-HPLC Method for Simultaneous Estimation of Teneligliptin, Metformin Hydrochloride and Pioglitazone Hydrochloride in Pharmaceutical Dosage Form

A Review on Method Development and Validation of RP-HPLC Method for Simultaneous Estimation of Teneligliptin, Metformin Hydrochloride and Pioglitazone Hydrochloride in Pharmaceutical Dosage Form

Tratamento de diabetes mellitus tipo 2 em um sagui-de-orelha-preta (Callithrix penicillata)

ABSTRACT: Type-2 diabetes mellitus (T2DM) is characterized by defects in insulin secretion and combined peripheral resistance to the hormone. Several non-human primates (NHP) species develop T2DM, mainly captive animals with reduced physical activity and incorrect feeding. This case report describes the T2DM treatment of a black-eared marmoset (Callithrix penicillata) by diet reformulation and metformin oral administration. An adult female was diagnosed with T2DM after hyperglycemia and high serum fructosamine associated with glycosuria and obesity. Metformin hydrochloride (125mg/animal, orally, q24h) associated with feeding intervention was started. After 26 days, a significant reduction in weight, glycemia, and serum fructosamine could be observed, showing satisfactory results for the adopted therapy. Metformin is considered a safe drug for T2DM treatment due to its low hypoglycemia risk. The new diet consisted of sweet potato, squash, and varied fruits offered twice daily. In addition, thawed-mice newborns, egg whites, and small portions of pelleted primate food. In the present report, metformin use, associated with a low glycemic index diet, was effective in treating this particular marmoset and may present a potential for T2DM treatment in other NHPs.

Optimizing Metformin HCl manufacturing: A Six Sigma approach to assess process capability

A process capability analysis uses indices such as process capability, process capability index, process performance index, and process performance to evaluate the output of an in-control process in relation to stated restrictions. In the instance of Metformin HCl tablets, the goal of a Six Sigma study is to enhance the method for creating perfect pills while ensuring maximum customer satisfaction. Process capability is critical for meeting industry standards, reducing variation, and ensuring product quality before commercialization, consequently streamlining and cost-effectively streamlining the inspection process. The control and capacities of antidiabetic pills are described in this study, with a focus on data collection and process capability analysis utilizing statistical tools such as MINITAB 21.2. The results show that the process capabilities for several tests-hardness, thickness, disintegration, dissolution, and friability exceed the 3.64 threshold. Finally, based on this analysis, the current process capability is rated appropriate, showing its capability to fulfill industry standards effectively.

The role and mechanism of AMPK in pulmonary hypertension.

Pulmonary hypertension (PH) is a chronic progressive disease with high mortality. There has been more and more research focusing on the role of AMPK in PH. AMPK consists of three subunits-α, β, and γ. The crosstalk among these subunits ultimately leads to a delicate balance to affect PH, which results in conflicting conclusions about the role of AMPK in PH. It is still unclear how these subunits interfere with each other and achieve balance to improve or deteriorate PH. Several signaling pathways are related to AMPK in the treatment of PH, including AMPK/eNOS/NO pathway, Nox4/mTORC2/AMPK pathway, AMPK/BMP/Smad pathway, and SIRT3-AMPK pathway. Among these pathways, the role and mechanism of AMPK/eNOS/NO and Nox4/mTORC2/AMPK pathways are clearer than others, while the SIRT3-AMPK pathway remains still unclear in the treatment of PH. There are drugs targeting AMPK to improve PH, such as metformin (MET), MET combination, and rhodiola extract. In addition, several novel factors target AMPK for improving PH, such as ADAMTS8, TUFM, and Salt-inducible kinases. However, more researches are needed to explore the specific AMPK signaling pathways involved in these novel factors in the future. In conclusion, AMPK plays an important role in PH.

Metformin inhibits high glucose-induced apoptosis of renal podocyte through regulating miR-34a/SIRT1 axis.

Previous studies have reported SIRT1 was inversely modulated by miR-34a, However, mechanism of metformin (MFN)'srenal podocyte protection under high glucose (HG)conditions and the connection between miR-34a and SIRT1 expression in diabetic nephropathy (DN)remain unclear. We aimed to further elucidate the role of miR-34a in HG-treated podocytes in DN. A conditionally immortalized human podocyte cell line was cultivated in d-glucose (30 mM). Microarray and RT-qPCRrevealed that miR-34a was downregulated in HG-treatedpodocytes. Additionally, miR-34a levels increased in MFN-treated HG-induced podocytes. CCK-8assay, colony formation assay,flow cytometry,and Western blotdetection showed that HG treatment reduced cell viability and promoted via HG treatment, and MFN treatment reversed this phenotypic change. MiR-34a upregulation caused restored cell viability and suppressed cell apoptosis in HG-treated podocytes, and miR-34a downregulation led to damaged cell survival and induced apoptosis in MFN-administered and HG-treated podocytes. The dual luciferase reporter assay showed that SIRT1 3'-UTR was a direct miR-34a target. Further studies demonstrated an elevation in SIRT1 levels in HG-exposed podocytes, whereas MFN treatment decreased SIRT1 levels. In addition, miR-34a upregulation led to reduced SIRT1 expression, whereas miR-34a inhibition increased SIRT1 levels in cells. MFN-induced miR-34a suppresses podocyte apoptosis under HG conditions by acting on SIRT1. This study proposes a promising approach to interpret the mechanisms of action of the MFN-miR-34a axis involved in DN.

Network Toxicology Prediction and Molecular Docking-based Strategy to Explore the Potential Toxicity Mechanism of Metformin Chlorination Byproducts in Drinking Water.

Metformin (MET), a worldwide used drug for treating type 2 diabetes but not metabolized by humans, has been found with the largest amount in the aquatic environment. Two MET chlorination byproducts, including Y and C, were transformed into drinking water during chlorination. However, the potential toxicity of the byproducts in hepatotoxicity and reproduction toxicity remains unclear. The TOPKAT database predicted the toxicological properties of metformin disinfection by-products. The targets of metformin disinfection by-products were mainly obtained from the PharmMapper database, and then the targets of hepatotoxicity and reproductive toxicity were screened from GeneCards. The overlapping targets of toxic component targets and the hepatotoxicity or reproduction toxicity targets were regarded as the key targets. Then, the STRING database analyzed the key target to construct a protein-protein interaction network (PPI) and GO, and KEGG analysis was performed by the DAVID platform. Meanwhile, the PPI network and compound- target network were constructed by Cytoscape 3.9.1. Finally, Discovery Studio 2019 software was used for molecular docking verification of the two toxic compounds and the core genes. Y and C exhibited hepatotoxicity, carcinogenicity, and mutagenicity evaluated by TOPKAT. There were 22 potential targets relating to compound Y and hepatotoxicity and reproduction toxicity and 14 potential targets relating to compound C and hepatotoxicity and reproduction toxicity. PPI network analysis showed that SRC, MAPK14, F2, PTPN1, IL2, MMP3, HRAS, and RARA might be the key targets; the KEGG analysis indicated that compounds Y and C caused hepatotoxicity through Hepatitis B, Pathways in cancer, Chemical carcinogenesis-reactive oxygen species, Epstein-Barr virus infection; compound Y and C caused reproduction toxicity through GnRH signaling pathway, Endocrine resistance, Prostate cancer, Progesterone-mediated oocyte maturation. Molecular docking results showed that 2 compounds could fit in the binding pocket of the 7 hub genes. This study preliminarily revealed the potential toxicity and possible toxicity mechanism of metformin disinfection by-products and provided a new idea for follow-up research.

Novel pH-sensitive gum ghatti-cl-poly(acrylic acid) composite hydrogel based on graphene oxide for metformin hydrochloride and sodium diclofenac combined drug-delivery systems

The results showed that the mixtures of synthetic hydrogels might be utilised as potential agents for controlled drug delivery vehicles.

Comparative Study of Metformin Hydrochloride Tablets in Argentina

Comparative Study of Metformin Hydrochloride Tablets in Argentina

Dissolution Test of Patent and Generic Drugs of Metformin Hydrochloride

Dissolution Test of Patent and Generic Drugs of Metformin Hydrochloride

A Novel Validated High Performance Thin Layer Chromatographic Method for the Simultaneous Quantification of Metformin Hydrochloride and Empagliflozin in Fixed-Dose Combination

A Novel Validated High Performance Thin Layer Chromatographic Method for the Simultaneous Quantification of Metformin Hydrochloride and Empagliflozin in Fixed-Dose Combination

In Vitro Drug-Drug Interaction of Metformin HCl with Omeprazole and Lansoprazole

In Vitro Drug-Drug Interaction of Metformin HCl with Omeprazole and Lansoprazole

Indirect Spectrophotometric Determination of Metformin Via Decolorization Eriochrome Black-T

The research included the description of a simple indirect spectrophotometric method for the determination of Metformin, which depended on the oxidation of Metformin with an amount of N- bromosuccinimide in the presence of acetic acid and the excess amount of it oxidized the dye Eriochrome black-T, and the absorption was measured at 520 nm, and the molar absorption coefficient was 4 × 104 L / mol. cm, indicating the sensitivity of the method. And compliance with Beer's law for concentrations ranged from (2-16) micrograms. ML-1, the method was characterized by good accuracy and compatibility, with a recoverability of 100.155%. While the relative standard deviation was less than 1.0.The method was applied to pharmaceutical preparations of Metformin hydrochloride.

Comparison between the effect of Empagliflozin and Pioglitazone added to metformin in patients with type 2 diabetes and nonalcoholic fatty liver disease

Background/aimsNon-alcoholic fatty liver disease (NAFLD), defined as the accumulation of >5% fat in the liver, is the most frequently co-exist disease with diabetics up to 70%. Current study was conducted to compare efficacy of combination therapy of empagliflozin (EMPA) or pioglitazone (PGZ) with metformin (MET) in patients with T2DM and NAFLD. MethodsIn this open label, prospective clinical trial, sixty patients were randomly assigned to receive EMPA 10 mg/day or PGZ 30 mg/day in combination Metformin (at least 1500 mg) for six months. NAFLD grade and liver stiffness were defined and measured at the beginning and after 6 months. As the secondary outcomes, anthropometric characteristics, lipid profile, plasma glucose test, and liver enzymes test were measured at the baseline and endpoint. ResultsThe results showed that both combination therapy with EMPA+ MET or PGZ+MET significantly reversed fibrosis stage of NAFLD (P<0.05). Significant reduction in lipid profile test, and liver enzymes test were seen in both groups (P<0.05). However, the greater reduction in waist circumference was observed in EMPA groups compared to PGZ (-4.4 ± 2.39 vs -2.05±1.28, p<0.001), meanwhile weight and BMI decreased significantly only in the patients receiving EMPA (-5.78 ± 3.6 kg vs 0.93 ± 0.33 kg and -2.01± 3.19 kg/m2 vs 0.33 ± 0.12 kg/m2, respectively, P<0.001). Conclusioncombination of EMPA or PGZ with metformin equally improved liver fibrosis stage and stiffness in T2DM patients with NAFLD. The improvements of laboratory tests were observed in the both groups, while, regarding weight reduction, only the regimen containing EMPA was effective.

Spectrophotometric Multi-Component Quantitation of Rosiglitazone, Glibenclamide and Metformin HCl in Pharmaceutical Dosages Form by using Cramer’s Matrix

Objective: This article illustrates the development of a simple, precise and accurate spectrophotometric analysis method for the determination of Rosiglitazone, Glibenclamide and Metformin hydrochloride in their pharmaceutical preparations by using Cramer's matrix. Method: The absorbance of the sample solution was measured at 315.6nm and 229.2nm for the estimation of rosiglitazone and glibenclamide, respectively and at 237.0nm for estimation of metformin hydrochloride by Shimadzu double beam UV-visible spectrophotometer. Results: The result of the analysis for method was tested and validated for various parameters according to ICH guidelines and found satisfactory. The method was successfully applied for the determination of these drugs in their tablet dosage forms. Conclusion: Simultaneous estimation of active ingredients in multicomponent pharmaceutical products normally requires the use of chromatographic separation techniques, like thin layer chromatography, high performance thin layer chromatography, high performance liquid chromatography or gas chromatography etc., followed by their quantitation. But this article illustrates direct spectroscopic estimation of multicomponent formulation by using Cramer's matrix.