Vincamine activates thioredoxin reductase (TrxR). [2]
GPR40 (G-protein-coupled receptor 40): EC50 = 6.28 μM (for activation, measured by Ca2+ influx in hGPR40-CHO cells) [1]

- Cell Viability & Anti-apoptosis: Vincamine (5, 10, 20 μM) itself had no effect on INS-832/13 cell viability. However, it counteracted STZ (0.4 mM)-induced decrease in cell viability with an EC50 of 5.78 μM. Flow cytometry analysis confirmed that vincamine efficiently decreased the number of apoptotic cells induced by STZ. [1]
- Proliferation: Vincamine exhibited no effect on INS-832/13 cell proliferation. [1]
- Signaling Pathway (Anti-apoptotic): Vincamine reversed the STZ-induced reduction of p-Akt (EC50 = 3.92 μM), p-PI3K, p-GSK3β (Ser9), and p-FOXO1 (Ser256). It also decreased STZ-induced increases in Caspase 9/3 enzyme activity, cleaved Caspase 3 protein level, and Bim and p21 mRNA expression. These effects were dependent on PI3K (blocked by wortmannin), Ca2+ influx (blocked by nifedipine), and cAMP/PKA signaling (blocked by MDL-12,330A or H89). Vincamine antagonized the STZ-induced decrease of IRS2 at both mRNA and protein levels but had no effect on PI3K enzyme activity or LXRα/β. [1]
- Signaling Pathway (GSIS): Vincamine (5, 10, 20 μM) effectively promoted GSIS in INS-832/13 cells only under high glucose condition (16.8 mM), not low glucose (2.8 mM). This promotion was dependent on cAMP (blocked by MDL) and CaMKII (blocked by KN62), but not on IP3R activation or L-type VDCCs (nifedipine had no effect). The protective effect on β-cells was independent of its insulin secretion promotion, as vincamine did not stimulate insulin secretion in STZ-treated cells. [1]
- Mechanism of Target Engagement: Vincamine (20 μM) was shown to bind to GPR40 in INS-832/13 cell lysates using the Cellular Thermal Shift Assay (CETSA), where it stabilized the protein against heat denaturation compared to DMSO control. It had no effect on GK or PDE enzyme activities. The protective and GSIS-promoting effects of vincamine were blocked by the GPR40 antagonist GW1100 or by GPR40 siRNA. Overexpression of GPR40 in INS-832/13 cells mimicked the effects of vincamine, increasing cell viability, decreasing Caspase 3 activity, and enhancing insulin secretion, cAMP level, and Ca2+ influx. [1]

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Vincamine (20, 40, and 80 μM; 24 hours) protects human corneal epithelial cells (HCECs) from lipopolysaccharide (LPS) in a significant, concentration-dependent manner[1].
Vincamine (20, 40 and 80 μM; 24 hours) dramatically lowers the level of reactive oxygen species (ROS) in a dose-dependent manner in LPS-treated human corneal epithelial cells (HCECs)cells. Furthermore, following Vincamine administration, MDA levels are also markedly lowered while T-AOC and SOD levels rise in a dose-dependent manner[1].
Vincamine (20, 40 and 80 μM; 24 hours) dose-dependently restores TrxR activity in HCECs. Nevertheless, neither LPS nor Vincaminer can activate nor inhibit the intracellular activities of Trx, GR, or GPx[1].
Vincamine could activate GPR40 (EC50=6.28 µM) while DHA (a GPR40 ligand) served as a positive control (EC50=3.85 µM) in hGPR40-CHO cells[2].

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Vincamine protected human corneal epithelial cells (HCECs) from lipopolysaccharide (LPS)-induced reduction in cell viability. In cells treated with 10 µg/mL LPS for 24h, viability dropped to about 52.2%. Co-treatment with Vincamine (20, 40, and 80 µM) exerted a significant, concentration-dependent protective effect, increasing cell viability. [2]
Vincamine significantly reduced intracellular reactive oxygen species (ROS) levels elevated by LPS treatment in a dose-dependent manner. The ROS levels in the 40 and 80 µM Vincamine groups were significantly lower than in the LPS-only group. [2]
Vincamine attenuated LPS-induced oxidative stress in HCECs. It significantly decreased the elevated levels of malondialdehyde (MDA), a marker of lipid peroxidation, and increased the levels of total antioxidant capacity (T-AOC) and superoxide dismutase (SOD) in a dose-dependent manner. [2]
Vincamine exerted anti-inflammatory effects by significantly reducing the mRNA expression levels of pro-inflammatory cytokines (IL-6, IL-8, IL-1β, TNF-α, TGF-β) that were increased by LPS treatment in HCECs, in a dose-dependent manner. [2]
Vincamine specifically activated the intracellular activity of thioredoxin reductase (TrxR) in LPS-treated HCECs in a dose-dependent manner. However, it did not significantly affect the activities of related redox proteins thioredoxin (Trx), glutathione reductase (GR), or glutathione peroxidase (GPx). Western blot analysis indicated that the expression levels of TrxR, Trx, GR, and GPx were not altered by either LPS or Vincamine, suggesting activation occurred at the functional level, not through protein expression changes. [2]

- HFD/STZ Male Mice: Daily i.p. injection of vincamine (15 or 30 mg/kg/day) for 6 weeks effectively lowered fasting blood glucose and HbA1c levels, improved oral glucose tolerance (OGTT), and elevated glucose-induced plasma insulin concentration. It increased the area and number of pancreatic islets and β-cells, and improved islet integrity. Vincamine administration increased phosphorylation levels of PI3K, Akt, GSK3β, and FOXO1, elevated IRS2 protein level, and decreased Caspase 3 enzymatic activity and cleaved Caspase 3 levels in pancreatic islets. [1]
- db/db Male Mice: Daily i.p. injection of vincamine (15 or 30 mg/kg/day) for 5 weeks effectively lowered fasting blood glucose and HbA1c levels, improved OGTT, and elevated glucose-induced plasma insulin concentration. It increased the area of insulin-positive islets and improved islet integrity. Similar to the HFD/STZ model, vincamine modulated the IRS2/PI3K/Akt signaling pathway in the pancreas, increasing p-PI3K, p-Akt, p-GSK3β, p-FOXO1, and IRS2, while decreasing Caspase 3 activity and cleaved Caspase 3. [1]
- db/db Female Mice (Insulin Sensitivity): Daily i.p. injection of vincamine (30 mg/kg/day) for 6 weeks improved glucose tolerance (OGTT) but had no effect on insulin tolerance (ITT), indicating no improvement in insulin sensitivity. This was confirmed ex vivo in mouse primary hepatocytes, where vincamine did not affect insulin signaling cascades (p-IR, p-Akt) unlike the insulin sensitizer rosiglitazone. [1]

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Vincamine (intraperitoneal injection; 15 and 30 mg/kg/day; 6 weeks) improves glucose tolerance in type 2 diabetic model mice. It successfully reduces glycated hemoglobin and fasting blood glucose levels. In addition, it improves glucose-induced plasma insulin concentration and oral glucose tolerance without affecting basal insulin secretion in vivo[2].

- GK Activity Assay: Glucokinase (GK) activity was detected by initiating a reaction with 10 mM ATP in an assay solution (25 mM HEPES, 25 mM KCl, 2 mM MgCl2, 1 mM ATP, 1 mM DTT, 1 mM NAD, 0.1% w/v BSA, 5 units/mL glucose-6-phosphate dehydrogenase (G6PDH), 5 mM glucose, and 18.7 mg/mL hLGK2, pH 7.1) to produce NADH. The absorbance was measured at 340 nm. The assay tested the effect of vincamine (10, 20 μM) on GK activity. [1]
- PDE Activity Assay: Phosphodiesterase (PDE) activity was assessed using a commercial PDE Activity Assay Kit. The assay tested the effect of vincamine (5, 10, 20 μM) on PDE activity, with IBMX (500 μM) as a positive control. [1]
- GPR40 Activity Assay (FLIPR): Activation of GPR40 was measured as a change in Ca2+ flux in hGPR40-CHO cells. Cells were pre-incubated with Fluo-4 AM (2 μM) for 40-50 minutes. Vincamine or DHA (positive control) at various concentrations were added automatically, and fluorescence signals (494/525 nm) were monitored constantly for 60-120 seconds with 1.6-second intervals using a fluorescence imaging plate reader. The EC50 for vincamine was calculated to be 6.28 μM. [1]

- Cell Viability (MTT Assay): INS-832/13 cells were seeded in 96-well plates. After overnight culture, cells were treated with test compounds and STZ (0.4 mM) for 24 h. Then, 0.5 mg/mL MTT was added for 4 h to form formazan crystals. The crystals were dissolved in DMSO, and absorbance was determined at 570 nm. [1]
- Proliferation Assay (CyQUANT): INS-832/13 cells were treated with liraglutide (0.32 nM) or vincamine (5, 10, 20 μM) for 24 h. Proliferation was detected using a CyQUANT Cell Proliferation Assay Kit, measuring fluorescence at 480/520 nm. [1]
- Apoptosis Assay (Flow Cytometry): INS-832/13 cells were plated in 12-well plates and treated with compounds. Cells were collected and stained using an FITC Annexin V Apoptosis Detection Kit I. The number of apoptotic cells was quantified by flow cytometry, with 10,000 events per sample. [1]
- p-Akt (Ser473) AlphaLISA Assay: INS-832/13 cells were grown in 96-well plates and incubated with compounds for 24 h. Cell lysates were collected to examine p-Akt (Ser473) content using AlphaLISA SureFire Ultra p-Akt (Ser473) Assay Kits. [1]
- Quantitative Real-Time PCR (qRT-PCR): INS-832/13 cells were plated in 6-well plates and incubated with compounds for 24 h. Total mRNA was isolated, and first-strand cDNA was synthesized. mRNA expression of Irs2, p21, and Bim was detected using qRT-PCR with SYBR Premix Ex Taq. Primer sequences are listed in the article. [1]
- Caspase 3/9 Activity Assay: INS-832/13 cells were cultured in white opaque 96-well plates and treated with compounds. The activity of Caspase 3 or Caspase 9 was detected using Apo-ONE Homogeneous Caspase-3/7 Assay and Caspase-Glo 9 Assay kits. [1]
- Intracellular cAMP Assay: INS-832/13 cells were treated with FSK (10 μM) or vincamine (5, 10, 20 μM) for 1 h. The concentration of intracellular cAMP was tested using a cAMP-Glo assay kit, which has a reciprocal relationship between cAMP concentration and light output. [1]
- Fluorescence Imaging Plate Reader (FLIPR) Assay for Ca2+: INS-832/13 cells were pre-incubated with Fluo-4 AM (2 μM) for 40-50 minutes. Cytosolic Ca2+ was measured by constantly monitoring fluorescence signals (494/525 nm) after the automatic addition of test compounds. The detection lasted for 60-120 seconds with 1.6-second intervals. [1]
- Glucose-Stimulated Insulin Secretion (GSIS) Assay: INS-832/13 cells were maintained for 2 h in Krebs-Ringer bicarbonate buffer (115 mM NaCl, 5 mM KCl, 24 mM NaHCO3, 2.5 mM CaCl2, 1 mM MgCl2, 10 mM HEPES, pH 7.2) with 0.2% BSA, then further incubated for 2 h with 2.8 mM or 16.8 mM glucose containing indicated compounds. Insulin content in the supernatant was measured with an AlphaLISA insulin kit. [1]
- Cellular Thermal Shift Assay (CETSA): INS-832/13 cell lysates were treated with DMSO or vincamine (20 μM) or TAK-875 (20 μM). The lysates were then heated at a series of gradient temperatures. Heated samples were centrifuged to collect soluble proteins, which were analyzed by Western blot to detect the remaining target protein (GPR40). [1]
- siRNA Transfection: INS-832/13 cells were transfected using Lipofectamine RNAiMAX with non-targeting siRNA or GPR40 siRNA (100 pM). Knockdown efficiency was verified by qRT-PCR and Western blot. [1]
- Plasmid Transfection (Overexpression): A GPR40-overexpression plasmid was constructed and transfected into INS-832/13 cells using Lipofectamine 3000. An empty vector was used as a negative control. Overexpression efficiency was verified by Western blot. [1]

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Human corneal epithelial cells (HCECs) were cultured in DMEM supplemented with glutamine, fetal bovine serum, and antibiotics. For viability assays, HCECs were seeded into 96-well plates and treated with various concentrations of LPS (0.5, 1, 5, 10, 20, 50, 100 µg/mL) or Vincamine (20, 40, 80 µM) for 6 or 24h. Cell viability was assessed using a Cell Counting Kit-8 (CCK-8) by measuring the absorbance at 450 nm and 630 nm. [2]
For oxidative stress and inflammation studies, HCECs were seeded into 6-well plates. After attachment, cells were pre-treated with different concentrations of Vincamine (20, 40, 80 µM) for 1 hour, then co-treated with 10 µg/mL LPS for 24h. Control groups included untreated cells and cells treated with LPS only. [2]
Intracellular ROS levels were measured using a ROS assay kit based on the oxidation of DCFH-DA to fluorescent DCF. Cells were incubated with DCFH-DA, washed, and fluorescence was measured. [2]
Levels of oxidative stress markers (MDA, T-AOC, SOD) were measured in cell lysate supernatants using commercial assay kits following the manufacturer's instructions. Protein concentration was determined using a Bradford protein assay. [2]
For gene expression analysis, total RNA was extracted from cells using an RNA isolation kit. cDNA was synthesized, and quantitative real-time PCR was performed using SYBR Green and specific primers for IL-6, IL-8, IL-1β, TNF-α, TGF-β, with β-actin as the reference gene. [2]
For enzyme activity assays, cell lysates were prepared. TrxR activity was determined using an insulin reduction assay. Briefly, cell lysate was incubated with insulin, Trx, EDTA, and NADPH. The reaction was quenched, and the amount of free thiols generated from insulin reduction was measured by DTNB reduction at 412 nm. Trx activity was measured similarly but using TrxR in the reaction mixture. GPx activity was determined by monitoring NADPH consumption at 340 nm in a reaction mixture containing cell lysate, GR, GSH, NADPH, and H₂O₂. GR activity was determined by measuring the decrease in absorbance at 340 nm due to NADPH consumption in a reaction mixture containing cell lysate, GSSG, and NADPH. [2]
For protein expression analysis, cells were lysed, proteins were separated by SDS-PAGE, transferred to PVDF membranes, and probed with antibodies against TrxR, Trx, GR, GPx, and GAPDH (loading control). Proteins were visualized using an ECL detection system, and band intensity was quantified using ImageJ software. [2]

Animal Protocol - Animals: HFD/STZ-induced type 2 diabetic male mice, db/db male mice, and db/db female mice were used. Animals were housed at 20–25°C with 50% relative humidity, a 12:12 light/darkness cycle, and water and food ad libitum. [1]
- HFD/STZ Model Induction: After a 4-week high-fat diet (58% fat), 6-week-old male mice were intraperitoneally (i.p.) injected with a single dose of 100 mg/kg STZ. Diabetic model mice were screened by detecting 6-h fasting blood glucose after 3 days. [1]
- Administration in HFD/STZ and db/db Male Mice: Vehicle (physiological saline) and vincamine hydrochloride (15 or 30 mg/kg) were administered daily by intraperitoneal (i.p.) injection for 5-6 weeks. [1]
- In Vivo Glucose Tolerance Test (OGTT): At the fourth week, an oral glucose tolerance test (1.0 g/kg glucose) was carried out after overnight fasting. Blood samples from tail veins were collected to determine glucose and insulin levels. [1]
- In Vivo Insulin Tolerance Test (ITT): At the fifth week, an i.p. insulin tolerance test (1.5 U/kg) on db/db female mice was carried out after 6-h fasting. [1]
- Ex Vivo Primary Hepatocyte Study: Mouse primary hepatocytes were isolated. The effect of vincamine on insulin signaling cascades (p-IR and p-Akt) was examined, with rosiglitazone as a positive control. [1]

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Male and female db/db mice (BKS.Cg-Dock^7m+/+Lepr^db/J) and HFD/STZ-induced type 2 diabetic model mice
15 and 30 mg/kg/day
Intraperitoneal injection; 15 and 30 mg/kg/day; 6 weeks

Absorption, Distribution and Excretion
In a crossover study, researchers investigated the pharmacokinetics and bioavailability of vinblastine hydrochloride in six healthy volunteers after oral administration of two different dosage forms. All subjects received 60 mg of vinblastine hydrochloride orally. …The pharmacokinetics of this drug generally conformed to a one-compartment model. The mean time to peak concentration (Tmax) was 1.4 ± 0.5 h for tablets and 1 ± 0.6 h for solution; the peak plasma concentration (Cmax) was 155 ± 82 μg·L⁻¹ for tablets and 133 ± 104 μg·L⁻¹ for solution. The area under the curve (AUC) was 443 ± 156 μg·L⁻¹ for tablets and 315 ± 178 μg·L⁻¹ for solution. Treatment with the solution for 1 hour was also performed.
Biopharmaceutics and pharmacokinetic evaluations of vinblastine hydrochloride were conducted. To perform biopharmaceutical characterization of the drug, the apparent lipid-water partition coefficient (APC), pKa, protein (bovine) binding, and erythrocyte (human) uptake were determined. Vinpocetine had an APC of 2.05, a pKa of 6.17, and exhibited 64% binding to plasma proteins and approximately 6% binding to erythrocytes. Since gerbils were used as a model in the pharmacodynamic studies, the pharmacokinetic distribution of the drug in this species was determined and compared with parameters reported in other species. The terminal half-life was approximately 1 hour, the apparent volume of distribution was 2.9 L/kg, and the total clearance was approximately 33.3 mL/min/kg. These parameters are comparable to those in other species, including humans. Brain tissue concentrations were approximately five times higher than plasma concentrations. In gerbils, the therapeutic steady-state concentration of vinpocetine was estimated to be 0.02 μg/mL. In rats, the pharmacokinetic parameters of vinblastine were determined after oral administration of 20 mg/kg body weight of vinblastine and intravenous injection of 10 mg/kg body weight of vinblastine hydrochloride. Following oral administration, the bioavailability was 58%, and the concentration-time curve conformed to a two-compartment open model. The observed parameters were as follows: elimination half-life of 1.71 h, time to peak concentration (t_max) of 1.27 h, peak concentration (C_max) of 0.87 μg/mL, total clearance of 0.818 L/h (higher than plasma perfusion, indicating that vinblastine is also rapidly metabolized in organs other than the liver), and volume of distribution of 2.018 L. Unmetabolized vinblastine was excreted in very low amounts, accounting for only 3% to 11% in urine and only 2% to 5% in bile. Vincamine exhibits high absorption concentrations in different organs, with concentration ratios of: lung/plasma 21, brain/plasma 14.6, kidney/plasma 14.3, liver/plasma 8.9, and heart/plasma 7.6. However, the clearance rate of Vincamine from these organs is significantly faster than that from plasma. Following intravenous injection, the observed pharmacokinetic parameters were: elimination half-life 1.68 h, Cmax 5.46 μg/ml, total clearance 0.866 L/h, and volume of distribution 2.104 L. There were no significant differences in elimination half-life, volume of distribution, and total clearance between oral and intravenous administration. The pharmacokinetics of Vincamine in dogs also conformed to a two-compartment open model. After intravenous administration of 10, 20, and 40 mg doses, both the half-life and clearance were dose-dependent. Following oral administration of 20 mg Vincamine hydrochloride, the bioavailability ranged from 23% to 58%. Vincamine was detectable in urine depending on the urine pH, with a maximum concentration of 9.5%. For more complete data on the absorption, distribution, and excretion of vinblastine (6 types), please visit the HSDB record page. Metabolism/Metabolites This study investigated the metabolism of vinblastine hydrochloride in rats after oral administration. Vinblastine is almost completely metabolized, with only a small amount of the original drug excreted in the urine. Metabolites detected in blood, urine, and tissues were purified in various solvent systems by preparative thin-layer chromatography and column chromatography, and analyzed by mass spectrometry. The major metabolites in urine were found to be vinblastine conjugates (sulfate and glucuronide). Two novel metabolites were detected in all analyzed biological fluids and samples: these compounds are more polar than vinblastine, their structures were characterized by mass spectrometry, infrared spectroscopy, and ultraviolet spectroscopy, and were confirmed by synthesis in our laboratory. [Vigano V et al.; Farmaco] Vinblastine metabolism is very extensive, with only a small amount of unmetabolized compounds detected in urine. Radiolabeled studies of vinblastine metabolism in rats after oral administration of 10 mg/kg body weight revealed the metabolic pathway of vinblastine. On one hand, it is hydrolyzed by plasma esterases into unstable vinblastine. The latter is rapidly decarboxylated and oxidized to ependymine. On the other hand, vinblastine is hydroxylated to produce the major metabolite 6-β-hydroxyvinblastine, which accounts for 40% of the total radioactivity in urine and bile, followed by 6-α-hydroxyvinblastine (8%) and 6-ketovinblastine (approximately 10% of the administered dose), the latter being an oxidative metabolite of the first two metabolites. 6-ketovinblastine is excreted via a conjugation reaction. The same metabolite (hydroxy-ketone) was also detected in the urine of rabbits, dogs, and humans. Within 72 hours, 40% of the total radioactive material was excreted in urine and 23% in feces.

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Biological Half-Life
The pharmacokinetic parameters in rats after intravenous injection of vinblastine hydrochloride were: elimination half-life of 1.68 hours.
After oral administration of 20 mg/kg vinblastine (base), the pharmacokinetic parameters in rats were: elimination half-life of 1.71 hours…
After oral administration of 4 mg/kg body weight vinblastine hydrochloride, the elimination half-life in dogs was 4.5 hours (longer than in rats), with a total clearance of 0.52 L/hour. The elimination half-life of vinblastine hydrochloride solution ranged from 0.57 to 1.07 hours (169 mg vinblastine hydrochloride solution and 33.81 mg vinblastine hydrochloride controlled-release tablets).
Biopharmaceutics and pharmacokinetic evaluations of vinblastine hydrochloride were performed. …The terminal half-life is approximately 1 hour…

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Vincamine has an oral elimination half-life of approximately 2 hours and is primarily metabolized in the liver and excreted by the kidneys. The compound exhibits approximately 64% binding to human plasma proteins and 6% binding to erythrocytes. Vincamine can penetrate the blood-brain barrier, with detectable levels of unbound drug in both rat hippocampus and blood, demonstrating rapid exchange and equilibration between the peripheral compartment and the central nervous system. In rat studies, protein-unbound vincamine levels in both blood and brain decline rapidly, indicating rapid distribution between the central and peripheral compartments. As a substrate of P-glycoprotein (P-gp), vincamine's brain distribution is influenced by P-gp efflux: co-administration with the P-gp inhibitor cyclosporine significantly increases unbound vincamine levels in both blood and brain. Sublingual administration promotes buccal absorption of vincamine, although gastrointestinal absorption of drug dissolved in saliva still occurs. In silico predictions indicate positive Caco-2 permeability (78.27%) and blood-brain barrier penetration (72.50%), with no violations of Lipinski's rule of five. Vincamine is metabolized by multiple cytochrome P450 enzymes, including CYP3A4, CYP1A2, CYP2D6, and CYP2E1.

Vincamine is classified as an acute toxicity Category 4 substance, harmful if swallowed (H302), and prolonged exposure through inhalation may cause serious damage to health. In animal studies, the LD50 of this compound is 1000 mg/kg. Vincamine exhibits reproductive toxicity risk (predicted probability 95.56%), with rat studies indicating that long-term exposure can damage the reproductive system; mitochondrial toxicity and respiratory toxicity are also predicted positive (95.00% and 85.56%, respectively). Regarding cardiovascular effects, vincamine may cause arrhythmias, particularly QT interval prolongation and torsade de pointes; it is contraindicated in patients with hypokalemia, hyperkalemia, or existing QT prolongation. Cardiac toxicity may be related to hERG potassium channel inhibition (predicted probability 68.01%). Hepatotoxicity risk is predicted positive (53.18%). The predicted probability for Ames mutagenesis is 58.00%, with a micronucleus test positive prediction of 61.00%, indicating potential genotoxicity risk. The Canadian WHMIS classification identifies this substance as hazardous, with rat studies suggesting that ingestion of less than 150 grams may be fatal. Common adverse effects include gastrointestinal symptoms (nausea, vomiting, diarrhea, elevated liver enzymes), headache, and fatigue. As vincamine was withdrawn from the market in 1987 due to drug safety concerns, it is intended for research use only. Contraindications include: known hypersensitivity to vincamine, intracranial tumors or conditions associated with increased intracranial pressure, acute stage of cerebrovascular accident, severe electrolyte disturbances (hypokalemia or hyperkalemia), QT interval prolongation, pregnancy, and lactation.

[1]. Vincamine as a GPR40 agonist improves glucose homeostasis in type 2 diabetic mice. J Endocrinol. 2019 Feb 1;240(2):195-214.

[2]. Vincamine prevents lipopolysaccharide induced inflammation and oxidative stress via thioredoxin reductase activation in human corneal epithelial cells. Am J Transl Res . 2018 Jul 15;10(7):2195-2204. eCollection 2018.

- Background: Vincamine is clinically used for the treatment of cardio-cerebrovascular diseases and as a dietary supplement with nootropic function. This is the first report on vincamine targeting GPR40 and its potential in the treatment of T2DM. [1]
- Mechanism of Action in T2DM: Vincamine functions as a GPR40 agonist. It protects against STZ-induced β-cell apoptosis by regulating the GPR40/cAMP/Ca2+/IRS2/PI3K/Akt signaling pathway. It promotes glucose-stimulated insulin secretion (GSIS) via the GPR40/cAMP/Ca2+/CaMKII signaling pathway. Vincamine has no effect on insulin sensitivity. [1]

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Vincamine is a periwinic alkaloid belonging to the alkaloid ester, organic heteropentane compound, methyl ester, and hemiacetal classes. It possesses antihypertensive, vasodilatory, and metabolic effects. Its function is similar to that of ibuprofen. Vincamine is a monoterpenoid indole alkaloid extracted from the leaves of Vinca minor and exhibits vasodilatory activity. Studies have shown that Vincamine can increase local cerebral blood flow. Vincamine has been reported to exist in Vinca difformis, Vinca major, and other organisms with relevant data. It is the main alkaloid of Vinca minor L., a plant in the Apocynaceae family. It has been used to treat vasodilation and hypotension, particularly in cerebrovascular diseases. Mechanism of Action: ...Perfusion of Vincamine for 5 minutes at concentrations of 1, 10, and 100 μM did not affect synaptic activation of pyramidal neurons induced by Schaffer commissural system stimulation. The effects of vinblastine on pyramidal neuron excitability were investigated by studying its influence on the inversely induced field potential and the input-output relationship of Schaffer commissure fiber input. At a concentration of 100 μM vinblastine, no effect on either parameter was observed. Vinblastine…attenuates posttetanic enhancement (PTP) and long-term enhancement (LTP) induced by repetitive stimulation of the Schaffer commissure fiber system. At a concentration of 100 μM vinblastine, PTP was significantly reduced, and LTP was almost completely inhibited. In Mongolian gerbils, intravenous injection of 30 mg vinblastine for 20 minutes increased cerebral blood flow by approximately 10%, and increased local cerebral blood flow by approximately 15% in areas of insufficient cerebral blood supply, confirming the function and therapeutic use of vinblastine as a vasodilator, particularly at the central nervous system level. While the mechanism of this vasodilatory effect is not fully elucidated, it appears to be partly attributed to its norepinephrine-like depletion effect, similar to reserpine. Therefore, its sedative effect is similar to that of reserpine. Vincamine is an indole alkaloid found in periwinkle (Vinca minor L.). It is used clinically to treat cerebral sclerosis and postoperative conditions of the central nervous system. Vincamine acts as an oxygen carrier in living cells and has been proposed for the treatment of sickle cell anemia. It has selective vasomotor effects on microvascular circulation, especially cerebral microvascular circulation, and can increase cerebral blood flow as a peripheral vasodilator. It can also be used as a nootropic to counteract the effects of aging. Vincamine enhances brain metabolism by affecting ATP production and the efficient use of glucose and oxygen, while also enhancing protection against ischemia and hypoxia. It may enhance dopaminergic, serotonergic and noradrenergic functions through its antioxidant capacity (comparable to vitamin E). [2] In this study, Vincamine had a protective effect against LPS-induced HCEC inflammation and oxidative stress, which may be achieved by activating the TrxR pathway. This suggests its potential application value in protecting corneal epithelial cells from LPS-induced keratitis. [2]

C21H26N2O3

354.4427

354.194

C, 71.16; H, 7.39; N, 7.90; O, 13.54

1617-90-9

42971-09-5 (Vinpocetine); 4880-92-6 (Apovincamine); 4429-63-4 (Tabersonine); 4880-88-0 (CH846; CH-846; CH 846; Vinburnine; Eburnal; Eburnamonine); 19877-89-5 (Vincanol; Vincanolum); 68779-67-9 (Vindeburnol)

15376

Yellow crystals from acetone or methanol

1.4±0.1 g/cm3

508.9±50.0 °C at 760 mmHg

232ºC (dec.)

261.6±30.1 °C

0.0±1.4 mmHg at 25°C

1.682

3.1

1

4

3

26

598

3

O([H])[C@]1(C(=O)OC([H])([H])[H])C([H])([H])[C@]2(C([H])([H])C([H])([H])[H])C([H])([H])C([H])([H])C([H])([H])N3C([H])([H])C([H])([H])C4C5=C([H])C([H])=C([H])C([H])=C5N1C=4[C@@]32[H]

RXPRRQLKFXBCSJ-GIVPXCGWSA-N

InChI=1S/C21H26N2O3/c1-3-20-10-6-11-22-12-9-15-14-7-4-5-8-16(14)23(17(15)18(20)22)21(25,13-20)19(24)26-2/h4-5,7-8,18,25H,3,6,9-13H2,1-2H3/t18-,20+,21+/m1/s1

methyl (15S,17S,19S)-15-ethyl-17-hydroxy-1,11-diazapentacyclo[9.6.2.02,7.08,18.015,19]nonadeca-2,4,6,8(18)-tetraene-17-carboxylate

Vincamine; Vinca Minor extract; 1617-90-9; Pervincamine; Arteriovinca; Angiopac; periwinkle extract; Angiopac; Devincan; Equipur; Minorin; Novicet; Oxybral; Perval; Sostenil; Tripervan

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

DMSO: 3~25 mg/mL (8.5~70.5 mM)

Solubility in Formulation 1: ≥ 2.5 mg/mL (7.05 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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Solubility in Formulation 2: ≥ 2.5 mg/mL (7.05 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

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 (Please use freshly prepared in vivo formulations for optimal results.)