Vinpocetine Research Articles

Vinpocetine attenuates 5-fluorouracil-induced intestinal injury: role of the Keap1/Nrf2/HO-1, NF-κB/TLR4/SOCS3 and RIPK1/RIPK3/MLKL signals

Objectives 5-Fluorouracil (5-FU) is a chemotherapy drug commonly prescribed in cancer management. Unfortunately, intestinal mucositis restricts 5-FU clinical use. Vinpocetine (VNP) is a synthetic alkaloid that is derived from vincamine. Our study was conducted to elucidate the intestinal protective effects of VNP on 5-FU intestinal injury in rats and explore the underlying mechanisms. Materials and methods 5-FU was injected i.p. for five days, while VNP was given P.O (5 and 10 mg/kg). Results VNP effectively mitigates oxidative stress by a significant increase in GSH and SOD and decreasing MDA content mediated by Nrf2, HO-1 upregulation, and significant Keap1 downregulation. VNP mitigated inflammatory perturbations by decreasing MPO, TNF-α, IL-1β, and IL-6 facilitated by downregulating NF-κB and TLR4 and upregulating SOCS3 levels. In addition, the RIPK1, RIPK3, MLKL, and caspase-8 expression levels were significantly decreased, evidenced improvement of intestinal necroptosis by VNP. Conclusion Hence, VNP potently prevents intestinal injury induced by 5-FU by modulating Keap1/Nrf2/HO-1, NF-κB/TLR4/SOCS3, and RIPK1/RIPK3/MLKL signals.

Vinpocetine Ameliorates Neuronal Injury After Cold-Induced Traumatic Brain Injury in Mice.

Traumatic brain injury (TBI), also known as intracranial injury, is a common condition with the highest incidence rate among neurodegenerative disorders and poses a significant public health burden. Various methods are used in the treatment of TBI, but the effects of cold-induced traumatic brain injury have not been thoroughly studied. In this context, vinpocetine (VPN), derived from Vinca minor, exhibits notable anti-inflammatory and antioxidant properties. VPN is known for its neuroprotective role and is generally utilized for treating various neurodegenerative disorders. However, the function of VPN after cold-induced TBI needs to be studied in more detail. This study aims to investigate the neuroprotective effects of VPN at varying doses (5mg/kg or 10mg/kg) after cold-induced TBI. C57BL/6 mice were sacrificed 2 or 28days after cold-induced TBI. Results indicate that VPN administration significantly reduces brain infarct volume, brain swelling, blood-brain barrier disruption, and DNA fragmentation in a dose-dependent manner. Additionally, VPN enhances neuronal survival in the ipsilesional cortex. In the long term, VPN treatment (5mg/kg/day or 10mg/kg/day, initiated 48h post-TBI) improved locomotor activity, cell proliferation, neurogenesis, and decreased whole brain atrophy, specifically motor cortex atrophy. We performed liquid chromatography-tandem mass spectrometry (LC-MS/MS) to elucidate the underlying mechanisms to profile proteins and signaling pathways influenced by prolonged VPN treatment post-TBI. Notably, we found that 192 different proteins were significantly altered by VPN treatment, which is a matter of further investigation for the development of therapeutic targets. Our study has shown that VPN may have a neuroprotective role in cold-induced TBI.

The protective effect of vinpocetine against Estradiol-benzoate induced cervical hyperkeratosis in female rats via modulation of SIRT1/Nrf2, and NLRP3 inflammasome

The current study was assigned to determine the putative preventive role of vinpocetine (VIN) in cervical hyperkeratosis (CHK) in female rats. Estradiol Benzoate (EB) was utilized in a dose f (60 μg/100 g, i.m) three times/week for 4 weeks to induce cervical hyperkeratosis. VIN was administered alone in a dose of (10 mg/kg/day, orally) for 4 weeks and in the presence of EB. Levels of malondialdehyde (MDA), total nitrites (NOx), reduced glutathione (GSH), interleukin-18 (IL-18), IL-1β, tumor necrosis factor-alpha (TNF-α) were measured in cervical tissue. The expression of NLRP3/GSDMD/Caspase-1, and SIRT1/Nrf2 was determined using ELISA. Cervical histopathological examination was also done. EB significantly raised MDA, NOx, TNF-α, IL-18, IL-1β, and GSDMD and up-regulated NLRP3/Caspase-1 proteins. However, GSH, SIRT1, and Nrf2 levels were reduced in cervical tissue. VIN significantly alleviates all biochemical and histopathological abnormalities. VIN considerably mitigates EB-induced cervical hyperkeratosis via NLRP3-induced pyroptosis and SIRT1/Nrf2 signaling pathway.

Potential Use of Common Administration of Emulsion for Parenteral Nutrition and Vinpocetine: Compatibility Study and Prospect.

Vinpocetine (VP) is distributed after oral and intravenous administration, and its uptake in the thalamus, basal ganglia, and visual cortex. Due to poor bioavailability (~7%) and marked first-pass effect (~75%), including a short half-life (2-3 h), oral administration of VP is limited. It requires frequent administration of the drug to obtain a therapeutic effect. Attempts to overcome these difficulties include the use of new drug delivery systems and/or alternative routes of drug administration. One possibility is the common administration of lipid emulsion and drug using the same catheter. However, this procedure is not recommended due to potential interaction and lack of safety data. For this purpose, we checked the compatibility of VP solutions with eight commercially available parenteral nutrition admixtures, i.e., Lipoflex special, Omegaflex special, Lipoflex peri, Omegaflex peri, Kabiven, SmofKabiven, Kabiven Peripheral, and Olimel Peri N4E. Coadministration is only possible if the stability of the drug and the lipid emulsion is confirmed. The available data are scarce and only concern the incompatibility of VP with ibuprofen. Compatibility tests were carried out in simulated administration through a Y-site connector using clinical flow rates. The stability of the drug and lipid emulsion was assessed by visual inspection and measurement of pH, osmolality, particle size as mean droplet diameter (MDD) and percentage of lipids residing in globules larger than 5 µm (PFAT5), zeta potential, polydispersity index, and lipid-free parenteral nutrition admixture(PNA) turbidity. The results of the compatibility of VP with eight commercial PN admixtures showed that all lipid emulsions show different signs of destabilization. In the studied samples, particles larger than 1000 nm, a significant increase in MDD, zeta potential, and loss of homogeneity visible as an increase in the polydispersity index were observed. Most of the samples had PFAT5 above the USP limit (0.05%). Taking into account the obtained data, VP should not be administered with the studied lipid emulsions for parenteral nutrition.

Vinpocetine attenuates methotrexate-induced hippocampal intoxication via Keap-1/Nrf2, NF-κB/AP-1, and apoptotic pathways in rats

Methotrexate (MTX) is an anti-folate chemotherapeutic commonly used to treat cancer and autoimmune diseases. Despite its widespread clinical use, MTX has been linked to serious neurotoxicity side effects. Vinpocetine (VNP) has been widely used clinically to treat many neurological conditions. This study was conducted to study the potential neuroprotective effects of VNP against MTX hippocampal intoxication in rats. Thirty-two rats were randomly allocated into 4 groups: (I) control (Vehicle); (II) VNP-treated group (20 mg/kg/day, p.o); (III) MTX-control (20 mg/kg/once, i.p.) group; and (IV) the VNP + MTX group. VNP was administered orally for 10 days, during which MTX was given intraperitoneally once at the end of day 5. Our data indicated that VNP administration significantly improved MTX-induced neuronal cell death, odema, vacuolation and degeneration. VNP attenuated oxidative injury mediated by significant upregulation of the Nrf2, HO-1, and GCLC genes, while the Keap-1 mRNA expression downregulated. Moreover, VNP suppressed cytokines release mediated by increasing IκB expression level while it caused a marked downregulation in NF-κB and AP-1 (C-FOS and C-JUN) levels. Additionally, VNP attenuated apoptosis by reducing hippocampal Bax levels while increasing Bcl2 levels in MTX-intoxicated rats. In conclusion, our results suggested that VNP significantly attenuated MTX hippocampal intoxication by regulating Keap-1/Nrf2, NF-κB/AP-1, and apoptosis signaling in these effects.

First report on the electrooxidation of vinpocetine using a modification free sensing platform: application to pharmaceutical formulations.

This study presents the first insights into vinpocetine (VIN) behavior, a nootropic compound, on a glassy carbon electrode (GCE). Cyclic voltammetry (CV) revealed an irreversible oxidation peak at +1.0 V (vs. Ag/AgCl), with pH dependency indicating proton involvement in the electrochemical reaction. Density functional theory (DFT) optimized VIN's molecular geometry, while Fukui functions and dual descriptors elucidated its reactivity for a more straightforward exploration of the complete electrooxidation mechanism. Differential pulse voltammetry (DPV) demonstrated VIN sensing capabilities within a concentration range of 0.20 to 12.8 mg L-1, with a theoretical limit of detection (LOD) at 0.07 mg L-1, using optimized conditions of supporting electrolyte. The method showed selectivity in the presence of excipients and interfering species commonly found in pharmaceutical formulations. Recovery tests yielded 95.5% (n = 3), and quantification in pharmaceutical formulations showed no significant differences compared to the reference method based on HPLC DAD. This novel electroanalytical method holds promise for VIN nootropic sensing and routine pharmaceutical analysis.

Development and optimization of in-situ gel containing chitosan nanoparticles for possible nose-to-brain delivery of vinpocetine

Vinpocetine (VIN), a derivative of vincamine found in the vinca plant, widens blood vessels in the brain and has been shown to improve cognitive function, memory, and cerebrovascular disorders. Nevertheless, the clinical utility of VIN is constrained by factors such as low oral bioavailability owing to the first-pass metabolism that often demands frequent dosing of 3–4 tablets/day. In this regard, the present work aimed to develop VIN-loaded chitosan nanoparticles (VIN-CH-NPs) to surmount these limitations and in view to enhance delivery to the brain of VIN by minimizing systemic exposure. The chitosan (CH) nanoparticles (NP) were developed by ionotropic gelation technique employing tripolyphosphate (TPP) as a cross-linking agent. Employing Design of Experiments (DoE), the effect of CH and TPP concentrations and stirring speed were systematically optimized using Box Behnken design (BBD). The optimized batch of nanoparticles displayed a particle size, zeta potential, entrapment efficiency, and drug loading of 130.6 ± 8.38 nm, +40.81 ± 0.11 mV, 97.56 ± 0.04 %, and 61 ± 0.89 %, respectively. Fourier Transform Infrared Spectroscopy indicated the chemical integrity of the drug ruling out the interaction between the VIN and excipients used. DSC and PXRD data indicated that reduction of the crystallinity of VIN in the chitosan matrix. These VIN-CH-NPs manifested good stability, exhibiting an almost spherical morphology. To mitigate rapid mucociliary clearance upon intranasal administration, the optimized VIN-CH-NPs were incorporated into thermosensitive in situ gel (VIN-CHN-ISG). It was observed that the in-situ gel loaded with nanoparticles was opalescent with a pH level of 5.3 ± 0.38. It was also noted that the gelation temperature was 32 ± 0.89 °C, and the gelation time was approximately 15 s. The drug delivery to the brain through the nasal application of optimized VIN-NPs in situ gel was assessed in rats. The results indicated significant nasal application of the in-situ gel nearly doubled the Cmax (P < 0.05) and AUC0-t (P < 0.05) in the brain compared to oral administration. Nasal administration improved drug delivery to the brain by reducing systemic exposure to VIN. A histopathological study of the nasal mucosa revealed no irritation or toxicity, making it safe for nasal administration. These findings suggest that the developed NPs in-situ gel effectively targeted vinpocetine to the brain through the nasal pathway, providing a potential therapeutic strategy for managing Alzheimer's disease.

Mannose-anchored solid lipid nanoparticles loaded with atorvastatin calcium and vinpocetine as targeted therapy for breast cancer

BackgroundThis study was aimed to design mannose-conjugated solid lipid nanoparticles (MSLNs) for the targeted delivery of Atorvastatin Calcium (ATS) and Vinpocetine (VIN) to augment its therapeutic efficacy against breast cancer. SLNs were prepared by hot emulsification ultra-probe sonication method and conjugated with mannose. In vitro cell line, in vivo pharmacokinetic and in vivo tumor regression studies were performed for MSLNs.ResultsMSLNs had an average particle size of 435.4 ± 3 nm with polydispersity index 0.298 ± 0.03 and a zeta potential of − 28.2 ± 1 emv. Entrapment efficiency was found to be 69.17 ± 0.92%, 71.18 ± 0.68% for ATS and VIN, respectively. The IC50 value of MSLNs was 1.46 µg/ml, which is efficient to control the growth of MDA MB231 cells as compared to the individual drugs and combinatorial SLNs. The combination index was found to be 0.7. MSLNs inhibited cell growth via necrosis by promoting to apoptosis through arresting SubG1 phase. The relative bioavailability of ATS and VIN loaded in MSLNs was 1.47 and 5.70, respectively, as compared to the marketed formulation. Maximal tumor volume reduction and higher survival rate was found for the MSLNs group (76.03%, P = 0.0001) as compared to the control group (P = 0.0364), individual drugs SLNs group.ConclusionThe results revealed that the MSLNs formulation augmented activity against breast cancer by inhibiting the cell growth. This promising drug delivery reduces the doses for both the drugs and attains minimal dose-associated side effects with synergism by reaching the specific target site, furthermore improving the therapeutic efficacy.

Attenuated effects of topical vinpocetine in an imiquimod-induced mouse model of psoriasis

Psoriasis is an uncontrolled, long-lasting inflammatory dermatosis distinguished by thickened, erythematous, and flaky skin lesions. Massive amounts of inflammatory cytokines are produced when immune system imbalances are driven by genetic and environmental triggers. Vinpocetine (VNP), a man-made analogue of the compound vincamine found in the dwarf periwinkle herb, has robust anti-inflammatory, immunomodulatory, and anti-oxidative effects; alleviates the epidermal penetration of immune cells, such as eosinophils and neutrophils; and abolishes the generation of pro-inflammatory molecules. ObjectiveThis study was aimed at exploring the effects of long-term topical VNP, both alone and co-administered with clobetasol propionate, in an imiquimod-induced mouse model of psoriasiform dermatitis. MethodsThe study protocol consisted of 48 Swiss albino mice, randomly divided into six groups of eight mice each. In group I, petroleum jelly was administered daily for 8 days. In group II, imiquimod was administered topically at 62.5 mg daily for 8 days. In groups III, VI, V, and VI, 0.05% clobetasol propionate, 1% VNP, 3% VNP, and 3% VNP plus 0.05% clobetasol were administered topically for an additional 8 days after the induction, thus resulting in a total trial length of 16 days. ResultsTopical VNP at various doses alleviated the severity of imiquimod-induced psoriatic lesions—including erythema, silvery-white scaling, and thickening—and reversed the histopathological abnormalities. Moreover, imiquimod-exposed animals treated with VNP showed markedly diminished concentrations of inflammatory biomarkers, including tumour necrosis factor-α, interleukin (IL)-8, IL-17A, IL-23, IL-37, nuclear factor-kappa B (NF-κB), and transforming growth factor-β1. ConclusionThis research provides new evidence that VNP, alone and in combination with clobetasol, may serve as a potential adjuvant for long-term management of autoimmune and autoinflammatory skin diseases, particularly psoriasis, by attenuating psoriatic lesion severity, suppressing cytokine generation, and limiting NF-κB-mediated inflammation.

Vinpocetine mitigates methotrexate-induced duodenal intoxication by modulating NF-κB, JAK1/STAT-3, and RIPK1/RIPK3/MLKL signals

Objectives Methotrexate (MTX) is an antimetabolite agent widely used to manage a variety of tumors and autoimmune diseases. Nonetheless, MTX-induced intestinal intoxication is a serious adverse effect limiting its clinical utility. Inflammation and oxidative stress are possible mechanisms for MTX-induced intestinal toxicity. Vinpocetine (VNP) is a derivative of the alkaloid vincamine with potent anti-inflammatory and antioxidant effects. The current study investigated the protective intestinal impact of VNP in attenuating MTX-induced intestinal intoxication in rats. Materials and Methods VNP was administered orally in a dose of 20 mg/kg, while MTX was injected intraperitoneal in a dose of 20 mg/kg. Results VNP administration attenuated drastic histological changes induced by MTX and preserved both normal villus and crypt histology. VNP significantly attenuated oxidative injury by upregulating intestinal Nrf2 and HO-1 expression. VNP attenuated inflammation by reducing MPO, NO2 −, TNF-α, and IL-1β levels mediated by downregulating NF-κB, NDAPH-oxidase, IRF3, p-JAK-1, and p-STAT-3 expressions. Moreover, VNP potently counteracted intestinal necroptosis by effectively downregulating RIPK1, RIPK3, MLKL, and caspase-8 proteins. Conclusion Therefore, VNP may represent a promising approach that can attenuate intestinal toxicity in patients receiving MTX.

Anti-Alzheimer Activity of Combinations of Cocoa with Vinpocetine or Other Nutraceuticals in Rat Model: Modulation of Wnt3/β-Catenin/GSK-3β/Nrf2/HO-1 and PERK/CHOP/Bcl-2 Pathways.

Alzheimer's disease (AD) is a devastating illness with limited therapeutic interventions. The aim of this study is to investigate the pathophysiological mechanisms underlying AD and explore the potential neuroprotective effects of cocoa, either alone or in combination with other nutraceuticals, in an animal model of aluminum-induced AD. Rats were divided into nine groups: control, aluminum chloride (AlCl3) alone, AlCl3 with cocoa alone, AlCl3 with vinpocetine (VIN), AlCl3 with epigallocatechin-3-gallate (EGCG), AlCl3 with coenzyme Q10 (CoQ10), AlCl3 with wheatgrass (WG), AlCl3 with vitamin (Vit) B complex, and AlCl3 with a combination of Vit C, Vit E, and selenium (Se). The animals were treated for five weeks, and we assessed behavioral, histopathological, and biochemical changes, focusing on oxidative stress, inflammation, Wnt/GSK-3β/β-catenin signaling, ER stress, autophagy, and apoptosis. AlCl3 administration induced oxidative stress, as evidenced by elevated levels of malondialdehyde (MDA) and downregulation of cellular antioxidants (Nrf2, HO-1, SOD, and TAC). AlCl3 also upregulated inflammatory biomarkers (TNF-α and IL-1β) and GSK-3β, leading to increased tau phosphorylation, decreased brain-derived neurotrophic factor (BDNF) expression, and downregulation of the Wnt/β-catenin pathway. Furthermore, AlCl3 intensified C/EBP, p-PERK, GRP-78, and CHOP, indicating sustained ER stress, and decreased Beclin-1 and anti-apoptotic B-cell lymphoma 2 (Bcl-2) expressions. These alterations contributed to the observed behavioral and histological changes in the AlCl3-induced AD model. Administration of cocoa, either alone or in combination with other nutraceuticals, particularly VIN or EGCG, demonstrated remarkable amelioration of all assessed parameters. The combination of cocoa with nutraceuticals attenuated the AD-mediated deterioration by modulating interrelated pathophysiological pathways, including inflammation, antioxidant responses, GSK-3β-Wnt/β-catenin signaling, ER stress, and apoptosis. These findings provide insights into the intricate pathogenesis of AD and highlight the neuroprotective effects of nutraceuticals through multiple signaling pathways.

Vinpocetine prevents rotenone-induced Parkinson disease motor and non-motor symptoms through attenuation of oxidative stress, neuroinflammation and α-synuclein expressions in rats

Parkinson’s disease (PD) is a progressive neurodegenerative disease characterized by motor and non-motor symptoms. Epidemiological reports showed a significant association between environmental toxicants-induced gut dysbiosis and PD. Neuroinflammation, mitochondrial dysfunction and decreased cerebral blood flow are hallmarks of PD. This study sought to evaluate the protective ability of vinpocetine (VIN), a neuroprotectant, on rotenone (ROT) (mitochondrial complex I inhibitor) induced PD in rats. Sixty male Sprague Dawley rats were randomly divided into six groups (n = 10) and treated orally as follows; group 1: vehicle (10 ml/kg); group 2: rotenone (10 mg/kg) + vehicle; group 3–5: vinpocetine (5, 10 or 20 mg/kg) + rotenone (10 mg/kg), respectively, or group 6: vinpocetine 20 mg/kg before behavioural assay for motor symptoms (fore-limb hanging test and open field test) and non-motor symptoms (working memory and learning capabilities in Y-maze/Morris water maze tasks, anxiety in hole board test and gut motility with intestinal transit time). Following treatment for 28 days, biochemical assays and immunostaining was performed. We examined the effect of vinpocetine on rotenone-induced oxidative stress and inflammatory markers. The pretreatment of rats with vinpocetine reversed rotenone-induced locomotor deficit, motor incoordination, cognition deficits and gut dysfunction. In addition, rotenone-induced a significant increase in the level of interleukin-6 and tumor necrotic factor-α, oxidative stress markers, cholinergic signalling, gut dysfunction and haematologic dysfunctions which were attenuated by vinpocetine administration. Immunostainings showed that rotenone-induced dopamine neuron loss, microglia reactivity, astrocytes activation, toll-like receptor 4 (TLR4) and α-synuclein (SNCA) expressions which were attenuated by vinpocetine administration. Findings from this study revealed a neuroprotective effect of vinpocetine on rotenone-induced PD through anti-neuroinflammatory and antioxidant mechanisms.

Exploring the potential to enhance drug distribution in the brain subregion via intranasal delivery of nanoemulsion in combination with borneol as a guider

The number of people with Alzheimer's disease (AD) is increasing annually, with the nidus mainly concentrated in the cortex and hippocampus. Despite of numerous efforts, effective treatment of AD is still facing great challenges due to the blood brain barrier (BBB) and limited drug distribution in the AD nidus sites. Thus, in this study, using vinpocetine (VIN) as a model drug, the objective is to explore the feasibility of tackling the above bottleneck via intranasal drug delivery in combination with a brain guider, borneol (BOR), using nanoemulsion (NE) as the carrier. First of all, the NE were prepared and characterized. In vivo behavior of the NE after intranasal administration was investigated. Influence of BOR dose, BOR administration route on drug brain targeting behavior was evaluated, and the influence of BOR addition on drug brain subregion distribution was probed. It was demonstrated that all the NE had comparable size and similar retention behavior after intranasal delivery. Compared to intravenous injection, improved brain targeting effect was observed by intranasal route, and drug targeting index (DTI) of the VINNE group was 154.1%, with the nose-to-brain direct transport percentage (DTP) 35.1%. Especially, remarkably enhanced brain distribution was achieved after BOR addition in the NE, with the extent depending on BOR dose. VIN brain concentration was the highest in the VIN-1-BOR-NE group at BOR dose of 1 mg/kg, with the DTI reaching 596.1% and the DTP increased to 83.1%. BOR could exert better nose to brain delivery when administrated together with the drug via intranasal route. Notably, BOR can remarkably enhance drug distribution in both hippocampus and cortex, the nidus areas of AD. In conclusion, in combination with intranasal delivery and the intrinsic brain guiding effect of BOR, drug distribution not only in the brain but also in the cortex and hippocampus can be enhanced significantly, providing the perquisite for improved therapeutic efficacy of AD.

Surface-tailoring of emulsomes for boosting brain delivery of vinpocetine via intranasal route: in vitro optimization and in vivo pharmacokinetic assessment

Vinpocetine (VNP), a semisynthetic active pharmaceutical ingredient, is used for oral management of cerebrovascular diseases because of its ability to enhance the blood flow to the brain. However, despite that, the therapeutic application of VNP is restricted due to its reduced bioavailability and diminished brain levels that could be attributed to its low aqueous solubility, short half-life, and presystemic metabolism exposure. Accordingly, the goal of this work was to explore the ability of surface-tailored intranasal emulsomes to boost brain delivery of the drug. A 3221 factorial design was implemented to explore the impact of phospholipid (PL) to solid lipid weight ratio, PL to cholesterol molar ratio, and type of solid lipid on vesicle size, zeta potential, drug entrapment, and release efficiency of the new developed VNP emulsomes. Tailoring of the optimized emulsomal surface formulation was performed using either cationization or PEGylation approaches to boost blood–brain barrier penetration. The pharmacokinetic assessment in rats showed significantly improved bioavailability of VNP emulsomal formulations compared to the oral market product. Additionally, surface-tailored emulsomes exhibited significantly higher brain levels compared to the optimized emulsomes. Based on these findings, the proposed surface-tailored emulsomes could be considered as a promising platform for achieving high brain levels of VNP following intranasal administration.

Vinpocetine and coenzyme Q10 combination alleviates cognitive impairment caused by ionizing radiation by improving mitophagy

ObjectiveThis research was designed to ascertain the effect and mechanism of vinpocetine (VIN) and coenzyme Q10 (CoQ10) combination on cognitive impairment induced by ionizing radiation (IR). MethodsCognitive impairment in mice was induced by 9-Gy IR, and they were intraperitoneally injected with VIN, CoQ10, or VIN + CoQ10. Then novel object recognition and Morris water maze tests were used to detect cognitive function. The number of hippocampal neurons and BrdU+Dcx+ cells was observed by Nissl and immunofluorescence staining. Mitochondrial respiratory complex I, adenosine triphosphate (ATP), and mitochondrial membrane potential (MMP) were evaluated, as well as oxidative stress injury. Mitophagy in hippocampal neurons was evaluated by observing the ultrastructure of hippocampal neurons and assessing the expression of mitophagy-related proteins. ResultsIR reduced novel object discrimination index, the time for platform crossing, and the time spent in platform quadrant, in addition to neuron loss, downregulated levels of mitochondrial respiratory complex I, ATP, and MMP, aggravated oxidative stress injury, increased expression of LC3 II/I, Beclin1, PINK1, and parkin, and decreased P62 expression. VIN or CoQ10 treatment mitigated cognitive dysfunction, neurons loss, mitochondrial damage, and oxidative stress injury, and enhanced mitophagy in hippocampal neurons. VIN and CoQ10 combination further protected against IR-induced cognitive dysfunction than VIN or CoQ10 alone. ConclusionVIN combined with CoQ10 improved neuron damage, promoted mitophagy, and ameliorated cognitive impairment in IR mice.

Evaluating the neuroprotective activities of vinpocetine, punicalagin, niacin and vitamin E against behavioural and motor disabilities of manganese-induced Parkinson's disease in Sprague Dawley rats

The current study investigated the neuroprotective activity of some drugs and nutriceuticals with antioxidant and anti-inflammatory potential on the pathogenesis of Parkinson’s disease (PD). Rats were categorized into seven groups: Rats received tween80 daily for 5 weeks as a control group, MnCl2 (10 mg/kg, i.p) either alone (group II) or in combination with vinpocetine (VIN) (20 mg/kg) (group III), punicalagin (PUN) (30 mg/kg) (group IV), niacin (85 mg/kg) (group V), vitamin E (Vit E) (100 mg/kg) (group VI) or their combination (group VII). Motor activities was examined using open-field and catalepsy. Striatal monamines, acetylcholinesterase, excitatory/inhibitory neurotransmitters, redox status, pro-oxidant content, brain inflammatory, apoptotic and antioxidant biomarkers levels were assessed. Besides, histopathological investigations of different brain regions were determined. Groups (IV –GVII) showed improved motor functions of PD rats. Applied drugs significantly increased the brain levels of monoamines with the strongest effect to PUN. Meanwhile, they significantly decreased levels of acetylcholinesterase with a strongest effect to PUN. Moreover, they exhibited significant neuronal protection and anti-inflammatory abilities through significant reduction of the brain levels of COX2, TNF-α and Il-1β with a strongest effect to the PUN. Interestingly; groups (IV – GVII) showed restored glutamate/GABA balance and exhibited a pronounced decrease in caspase-3 content and GSK-3β protein expression levels. In addition, they significantly increased Bcl2 mRNA expression levels with a strongest effect for PUN. All these findings were further confirmed by the histopathological examinations. As a conclusion, we propose VIN and PUN to mitigate the progression of PD via their antioxidant, anti-inflammatory, anti-apoptotic, neurotrophic and neurogenic activities.

Vinpocetine is the forthcoming adjuvant agent in the management of COVID-19.

Vinpocetine (VPN) is an alkaloid derivative of vincamine inhibits phosphodiesterase type 1 that increase cyclic guanosine monophosphate and cyclic adenosine monophosphate. VPN have anti-inflammatory and antioxidant effects with suppression release of pro-inflammatory cytokines. Moreover, VPN mitigates oxidative stress (OS) and inflammatory reactions through inhibition of mitogen-activated protein kinase (MAPK) signaling pathway. Therefore, VPN may decrease hyper-inflammation-induced acute lung injury in COVID-19 through modulation of NF-κB pathway. Taken together, VPN has pulmonary and extra-pulmonary protective effects against COVID-19 through mitigation of OS and hyperinflammation. In conclusion, VPN has noteworthy anti-inflammatory and anti-oxidant effects through inhibition of NF-κB/MAPK signaling pathway so, it may reduce SARS-CoV-2-induced hyper inflammatory and OS.

Phosphodiesterase inhibitor, Vinpocetine, guards against doxorubicin induced cardiotoxicity via modulation of HIF/VEGF and cGMP/cAMP/SIRT signaling pathways.

50 male Wistar albino rats were subjected to DOX toxicity via administration of single i.p. Dose (15mg/kg) on the 4th day with or without co-administration of VIN (10, 20, 30mg/kg/day) orally for 5days. Our data revealed that VIN succeeded in protecting the heart against DOX induced damage as manifested by significant decrease of cardiac enzymes, hypoxia inducible factor alpha (HIF-1α), vascular endothelial growth factor-A (VEGF-A), tissue malondialdehyde (MDA), tumor necrosis factor alpha (TNF-α) and caspase3 levels. Furthermore, VIN given group showed marked improvement of the histopathological changes of cardiac injury, total antioxidant capacity (TAC), elevation of reduced glutathione (GSH), cyclic guanosine monophosphate (cGMP), cyclic adenosine monophosphate (cAMP) and sirtuin-1 (SIRT-1). We concluded that VIN could ameliorate DOX induced cardiac damage and this effect may be attributed to modulation of HIF/VEGF signaling pathway, up-regulation of cGMP/cAMP/SIRT pathway, inhibition of phosphodiesterase enzyme, besides its anti-apoptotic, anti-inflammatory, and anti-oxidant properties.

Vinpocetine (A comprehensive profile).

Vinpocetine (VIN) is a herbal supplement extracted from the periwinkle plant. It is a multi-action agent, which is used to treat various neurological disorders such as Alzheimer's and Parkinson's disease. Vinpocetine has also anti-inflammatory, analgesic, antioxidant property and treats various thinking and memory problems. Currently, vinpocetine is also available in the market as a dietary supplement to enhance cognition and memory. This profile explains the physicochemical properties, methods of preparation, content of related impurities and different spectroscopical behavior of vinpocetine. It also discusses the reported methods of analysis of the drug, which include Compendial Methods, Electrochemical Methods, Spectrophotometric Methods and Chromatographic Methods of analysis. Furthermore, this profile explains the stability of the drug subjected to stress conditions of acid, alkaline and photolytic degradation. In addition, the clinical applications of the drug, its uses, side effects, dosing information, pharmacokinetics and mechanism of action are also discussed.

Development, optimization, and in vitro evaluation of atorvastatin calcium and vinpocetine codelivery by solid lipid nanoparticles for cancer therapy

BackgroundThe main objective of the present study was to formulate, optimize and characterize solid lipid nanoparticles (SLNs) loaded with Atorvastatin Calcium (ATS) and Vinpocetine (VIN) as a potential drug delivery system to improve its solubility and assess its anti-tumor activity on cell lines. The SLNs were formulated by emulsification with high speed homogenization followed by probe sonication. Central composite design was selected for optimization. Drug: lipid ratio, surfactant: co-surfactant ratio and homogenization speed were considered critical process parameters (CPP) to study the effects on critical quality attributes (CQA) of SLNs i.e. particle size, percent entrapment efficiency (% EE) and percent drug loading (% DL).ResultsThe optimized (F3) SLNs formulations were characterized by transmission electron microscopy (TEM), X- ray diffraction (X-RD), in vitro drug release by dialysis bag method and stability studies. In vitro cell line studies were performed on HepG2, MCF 7 and melanoma B16 F10 cell line. The optimized F3 formulation showed a particle size of 323 ± 6 nm, poly dispersity index (PDI) 0.333 ± 0.02, Zeta potential (ZP) − 30.4 ± 0.66 emv with % EE 64.69 ± 1.1; 65.98 ± 0.91 of ATS and VIN respectively. In vitro release (F3) of ATS and VIN in PBS pH 7.4 was found to be 89.45% and 91.86%, respectively, up to 24 h.ConclusionsIn vitro cell line study demonstrated that SLNs enhanced the anti-cancer activity of ATS, VIN on all the stated cell lines when compared with free drugs. Combination index (CI) for HEPG2 was 0.8, which signified synergistic effect. The results exhibited that SLNs is effective, stable and had enhanced activity against HepG2, MCF 7 and melanoma B16 F10 cell lines.