Vincamine activates thioredoxin reductase (TrxR). [2]

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]

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].

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]

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…

[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.

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; 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.)