Vincamine as an agonist of G-protein-coupled receptor 40 effectively ameliorates diabetic peripheral neuropathy in mice.

Diabetic peripheral neuropathy (DPN) is a common complication of diabetes, which has yet no curable medication. Neuroinflammation and mitochondrial dysfunction are tightly linked to DPN pathology. G-protein-coupled receptor 40 (GPR40) is predominantly expressed in pancreatic ß-cells, but also in spinal dorsal horn and dorsal root ganglion (DRG) neurons, regulating neuropathic pain. We previously have reported that vincamine (Vin), a monoterpenoid indole alkaloid extracted from Madagascar periwinkle, is a GPR40 agonist. In this study, we evaluated the therapeutic potential of Vin in ameliorating the DPN-like pathology in diabetic mice. Both STZ-induced type 1 (T1DM) and db/db type 2 diabetic (T2DM) mice were used to establish late-stage DPN model (DPN mice), which were administered Vin (30 mg·kg-1·d-1, i.p.) for 4 weeks. We showed that Vin administration did not lower blood glucose levels, but significantly ameliorated neurological dysfunctions in DPN mice. Vin administration improved the blood flow velocities and blood perfusion areas of foot pads and sciatic nerve tissues in DPN mice. We demonstrated that Vin administration protected against sciatic nerve myelin sheath injury and ameliorated foot skin intraepidermal nerve fiber (IENF) density impairment in DPN mice. Moreover, Vin suppressed NLRP3 inflammasome activation through either ß-Arrestin2 or ß-Arrestin2/IκBα/NF-κB signaling, improved mitochondrial dysfunction through CaMKKß/AMPK/SIRT1/PGC-1α signaling and alleviated oxidative stress through Nrf2 signaling in the sciatic nerve tissues of DPN mice and LPS/ATP-treated RSC96 cells. All the above-mentioned beneficial effects of Vin were abolished by GPR40-specific knockdown in dorsal root ganglia and sciatic nerve tissues. Together, these results support that pharmacological activation of GPR40 as a promising therapeutic strategy for DPN and highlight the potential of Vin in the treatment of this disease.

Screening potential anaphylactoid components in vinpocetine injection using a high expression Mas-related G-protein-coupled receptor X2 cell membrane chromatography.

Vinpocetine injection is often used in clinical treatment of acute cardiovascular and cerebrovascular diseases. However, it was reported that vinpocetine injection caused allergic reactions in clinical use; therefore, its safety needs urgent attention. Until now, research on its sensitization is rarely reported. Here, the components contained in three vinpocetine injections were examined. It was found that besides vinpocetine, the synthetic raw material vincamine, the excipients benzyl alcohol and ethyl p-toluenesulfonate, and the impurities A, B, C, and D, which are excipients specified in the European Pharmacopoeia, were also present in them. Then the Mas-related G-protein-coupled receptor X2 (MRGPRX2)-HEK293 cell membrane chromatography was used to investigate the affinity of them with MRGPRX2 and found that vinpocetine, vincamine, and impurities A, B, C, and D bind to MRGPRX2. Afterwards, these compounds were further used to investigate the local sensitization ability in vivo. The results showed that vinpocetine, vincamine, and impurity C could induce swelling of the paw and decrease body temperature in mice, but only impurity C could cause local skin mast cell degranulation and serum histamine release increase. In vitro, the results also indicated that impurity C could increase intracellular [Ca2+ ] in MRGPRX2-HEK293 cells, whereas vinpocetine and vincamine did not. Therefore, the impurity C was the potential anaphylactoid component in vinpocetine injection, which may be one of the reasons for the occurrence of allergic reactions in the clinical use of vinpocetine injection. This work provides evidence on the sensitization of impurity C and also contributes to promoting the clinical safety of vinpocetine injection.

Disease-Modifying Effects of Vincamine Supplementation in Drosophila and Human Cell Models of Parkinson's Disease Based on DJ-1 Deficiency.

Parkinson's disease (PD) is an incurable neurodegenerative disorder caused by the selective loss of dopaminergic neurons in the substantia nigra pars compacta. Current therapies are only symptomatic and are not able to stop or delay its progression. In order to search for new and more effective therapies, our group carried out a high-throughput screening assay, identifying several candidate compounds that are able to improve locomotor ability in DJ-1ß mutant flies (a Drosophila model of familial PD) and reduce oxidative stress (OS)-induced lethality in DJ-1-deficient SH-SY5Y human cells. One of them was vincamine (VIN), a natural alkaloid obtained from the leaves of Vinca minor. Our results showed that VIN is able to suppress PD-related phenotypes in both Drosophila and human cell PD models. Specifically, VIN reduced OS levels in PD model flies. Besides, VIN diminished OS-induced lethality by decreasing apoptosis, increased mitochondrial viability, and reduced OS levels in DJ-1-deficient human cells. In addition, our results show that VIN might be exerting its beneficial role, at least partially, by the inhibition of voltage-gated sodium channels. Therefore, we propose that these channels might be a promising target in the search for new compounds to treat PD and that VIN represents a potential therapeutic treatment for the disease.

ALK and ERBB2 Protein Inhibition is Involved in the Prevention of Lung Cancer Development by Vincamine.

BACKGROUND: According to the WHO report of 2022, 2.21 million new cases and 1.80 million deaths were reported for lung cancer in the year 2020. Therefore, there is an urgent need to explore novel, safe, and effective therapeutic interventions for lung cancer. OBJECTIVE: To find the potential targets of vincamine using a network pharmacology approach and docking studies and to evaluate the anti-cancer effect of vincamine on A549 cell line. METHODS: Hence, in the present study, we explored the anti-cancer potential of vincamine by using network pharmacology, molecular docking, and in vitro approaches. Network pharmacology demonstrated that the most common targets of vincamine are G-protein coupled receptors, cytosolic proteins, and enzymes. Among these targets, two targets, ALK and ERBB2 protein, were common between vincamine and non-small cell lung cancer. RESULTS: We discovered a link between these two targets and their companion proteins, as well as cancer-related pathways. In addition, a docking investigation between the ligand for vincamine and two targeted genes revealed a strong affinity toward these targeted proteins. Further, the in vitro study demonstrated that vincamine treatment for 72 h led to dosedependent (0-500 µM) cytotoxicity on the A549 lung cancer cell line with an IC50 value of 291.7 µΜ. The wound-healing assay showed that vincamine treatment (150 and 300 µM) significantly inhibited cell migration and invasion. Interestingly, acridine orange/ethidium bromide dual staining demonstrated that vincamine treatment induces apoptosis in A549 cells. Additionally, the dichloro-dihydro-fluorescein diacetate (DCFH-DA) assay showed an increased level of reactive oxygen species (ROS) after the vincamine treatment, indicating ROS-mediated apoptosis in A549 cells. CONCLUSION: Altogether, based on our findings, we hypothesize that vincamine-induced apoptosis of lung cancer cells via ALK and ERBB2 protein modulation may be an attractive futuristic strategy for managing lung cancer in combination with chemotherapeutic agents to obtain synergistic effects with reduced side effects.

Vincamine, an active constituent of Vinca rosea ameliorates experimentally induced acute lung injury in Swiss albino mice through modulation of Nrf-2/NF-κB signaling cascade.

Acute lung injury (ALI) or acute respiratory distress syndrome (ARDS) is one of the leading pulmonary inflammatory disorders causing significant morbidity and mortality. Vincamine is a novel phytochemical with promising anti-inflammatory properties. In the current work, the protective effect of vincamine was studied in vitro (Raw 264.7 macrophages) and in vivo against lipopolysaccharide (LPS) induced ALI in Swiss albino mice. Vincamine significantly reduced nitrite and TNF-α release from the LPS stimulated macrophages and increased the levels of IL-10, indicating potent anti-inflammatory effects. It was observed that vincamine at the dose of 40 mg/kg, significantly reduced LPS induced inflammatory cell count in blood and in bronchoalveolar lavage (BAL) fluid. Further, vincamine exerted potent suppression of inflammation by reducing the expression of proinflammatory cytokines, while significantly increased (p < 0.001) the expression of anti-inflammatory cytokine (IL-10 and IL-22). Interestingly, histological changes were reversed in vincamine treated groups in a dose-dependent manner. Immunohistochemical analysis revealed significantly enhanced expression of NF-κB, TNF-α and COX-2 while reduced expression of Nrf-2 in disease control group, which were significantly (p < 0.001) ameliorated by vincamine. We, to the best of our knowledge, report for the first time that vincamine possesses protective potential against LPS induced inflammation and oxidative stress, possibly by inhibiting the NF-κB cascade, while positively regulating the Nrf-2 pathway. These findings are of potential relevance for COVID-19 management concerning the fact that lung injury and ARDS are its critical features.

Efficacy of Vincamine treatment in a rat model of anterior ischemic optic neuropathy.

Non-arteritic anterior ischemic optic neuropathy (NAION) is characterized by the progressive and irreversible death of retinal ganglion cells (RGCs) which is caused by the insufficient blood supply to the optic nerve (ON) head. At present, hormone therapy is used to reduce optic edema, followed by nerve nutrition therapy to protect the ON. However, no surgical or medical therapy has proven to be beneficial consistently in treating NAION. Vincamine is an alkaloid extracted from the Apocynaceae Vinca plant. Vincamine and its derivatives acting as cerebral vasodilators can easily cross the blood-brain barrier, improve the metabolism of ischemic tissue and protect the neuron. In this study, we aimed to investigate the potential neuroprotection of Vincamine in the photodynamic induced rat model of NAION (rAION), to evaluate its effects and possible mechanisms. We found that Vincamine can rescue RGC death and reduce the number of apoptotic cells. The protection of Vincamine might play through the PI3K/Akt/eNOS signaling pathway. Therefore, Vincamine can be an effective therapy method for NAION.

Alpneumines A-H, new anti-melanogenic indole alkaloids from Alstonia pneumatophora.

Eight new indole alkaloids, alpneumines A-H (1-8) were isolated from the Malaysian Alstonia pneumatophora (Apocynaceae) and their structures were determined by MS and 2D NMR spectroscopic methods. Alpneumines E and G (5 and 7), vincamine, and apovincamine showed anti-melanogenesis in B16 mouse melanoma cells.

WITHDRAWN: Interventions for normal tension glaucoma.

BACKGROUND: Normal tension glaucoma is a clinical condition in which the optic nerve is pathologically excavated and the visual field is disturbed. Nevertheless it has been assumed that intraocular pressure plays a role in the progression of visual field defects in this disease, but other, mainly vascular factors, have been discussed as well. OBJECTIVES: The objective of this review is to assess the effects of medical and surgical treatments for normal tension glaucoma. SEARCH STRATEGY: Trials were identified from the Cochrane Central Register of Controlled Trials (CENTRAL) (which contains the Cochrane Eyes and Vision Group trials register), MEDLINE, EMBASE and BIOSIS Previews. Bibliographies of identified trials were searched to find additional trials. In addition, investigators and pharmaceutical companies were contacted. Date of last search: January 2001. SELECTION CRITERIA: This review includes randomised controlled trials in which medical or surgical interventions were compared to no treatment, placebo or other treatment in people with normal tension glaucoma. DATA COLLECTION AND ANALYSIS: Data were extracted by two reviewers and results were compared for differences. Discrepancies were resolved by discussion. The heterogeneity of interventions, follow-up periods and outcomes did not allow for statistical combinations of the study results. MAIN RESULTS: According to the selection criteria on visual field loss, eight studies were included in this review. Only three studies focussed on patient relevant outcomes. In one trial a beneficial effect of lowering intraocular pressure was found, but only if data were corrected for cataract development. In two small studies a beneficial effect on visual field loss of brovincamine, a calcium antagonist was reported. AUTHORS' CONCLUSIONS: In one study the effect of intraocular pressure lowering on visual field outcome was only significant when data were corrected for cataract development. The results for calcium antagonists are promising, but larger trials have to be performed. Studies that focussed on reduction of intraocular pressure or haemodynamic variables are not necessarily relevant for the outcome in people with normal tension glaucoma.

Antidiabetic, antihyperlipidemic and antioxidant effect of Vincamine, in streptozotocin-induced diabetic rats.

Diabetes mellitus is the most common endocrine disorder characterized by hyperglycemia resulting from defects in insulin secretion or insulin action. The present study was designed to investigate the antidiabetic effects of vincamine, one of the monoterpenoid indole alkaloid, in streptozotocin-induced diabetic rat model. Diabetes was induced in rats by an intraperitoneal injection of streptozotocin (40 mg/kg bw). Vincamine 20 and 30 mg/kg.bw were administrated orally as a single dose per day to the diabetic rats for 30 days. The vehicle control group received 0.5% dimethyl sulfoxide for the same duration. After 30 days of treatment, fasting blood glucose, glycosylated haemoglobin, total cholesterol, triglyceride, low-density lipoprotein cholesterol and very low-density lipoprotein cholesterol levels were significantly increased, whereas, body weight, plasma insulin, high-density lipoprotein cholesterol, antioxidant enzymes and reduced glutathione were markedly decreased in diabetic rats. Treatment with vincamine significantly restored these parameters to the normal level. The protective effect of vincamine was compared with glibenclamide, a well-known hypoglycemic drug. Our results clearly suggest that vincamine exhibit hypoglycemic, hypolipidemic and antioxidant activity. The anti-diabetic effect of vincamine was comparable to the protective effect of glibenclamide, suggesting its potential as a natural anti-diabetic compound with therapeutic benefits.

'Cerebroactive' drugs. Clinical pharmacology and therapeutic role in cerebrovascular disorders.

While their importance in the market-place is steadily increasing in developed (mainly continental Europe) and even in developing countries, compounds included in the broad category of 'cerebroactive' drugs hardly rate a mention in reference pharmacology and therapeutics textbooks. It is an undeniable fact, however, that the principal users or targets of this drug class, mainly elderly people, represent an increasingly worrying problem, with their often puzzling cohort of ill-definable and even less predictable neurological and mental symptoms. The combination of the above factors cannot but produce a rather confused situation, in which the pressure to treat and the adherence to scientifically rigorous assessment are likely to prevail alternately, on a purely casual basis. This review aims to provide sound methodological guidelines for assessment of 'cerebroactive' drugs in a not always easily accessible literature. It covers firstly the general problems of stroke, dementia and 'common symptoms' of the elderly, and then looks in detail at those compounds which have to date attracted most attention (ergot derivatives, cinnarizine, flunarizine, vincamine, eburnamonine, naftidrofuryl, oxpentifylline, piracetam and citicoline), as well as those which are currently considered investigational (choline and lecithin). The pharmacology and available clinical studies of each drug are examined. No therapeutic indication can be derived from the available evidence, as the few positive results do not go beyond random improvement of symptoms. More fundamentally, the lines of research which need to be pursued most intensively relate to better preliminary definition of diagnostic and prognostic criteria and, with the establishment of adequate testing tools for the assessment of behaviour and neuropsychological performance, those basal conditions which are modified 'naturally' or by drugs.

The pharmacotherapy of focal cortical ischaemia in the mouse.

The measurement of cortical omega 3 (peripheral-type benzodiazepine binding) site densities provides an accurate index for the detection and quantification of ischaemic brain lesions following middle cerebral artery occlusion (MCAO) in mice. Here, we have used this marker to assess the neuroprotective activity of potential anti-ischaemic drugs belonging to several chemical classes. In untreated mice, the mean infarcted volume measured 96 h after unilateral coagulation of the middle cerebral artery was 27.9 +/- 4.3 mm3 (17.5% of the hemisphere volume) and omega 3 site densities (measured by incubation with 3H-PK 11195) were increased by 107.3 +/- 4.8% (cortical homogenates) or by 81% (coronal brain sections). The administration of the anti-ischaemic agent SL 82.0715 (10 mg/kg i.p.), 5 min, 6 h and 18 h after the occlusion and then twice daily until sacrifice evoked a decrease of similar magnitude (ca. 60-70%) in the volume of the infarction and in the proliferation of omega 3 sites. The constant tissue sparing effect of SL 82.0715 allowed the examination of the window of therapeutic opportunity. A significant diminution of cortical omega 3 sites was still noted when the first administration was delayed until 3 h post-occlusion. Moreover, the protective effect of SL 82.0715 was enhanced by repeated treatment for the first 36 h but not thereafter. Based on the histological, autoradiographic and homogenate binding results obtained with SL 82.0715, we studied the protective effects of several competitive and non-competitive NMDA receptor antagonists. When administered according to the above-described standard protocol, these drugs reduced omega 3 site levels in cortical homogenates from MCAO mice in a dose-dependent manner. The dose preventing by 50% the increase in omega 3 site levels (in mg/kg i.p.) and the maximal inhibition were respectively: MK-801 (0.2, 93%); TCP (1.6, 66%); kynurenate (260, 58%); ifenprodil (7.0, 58%); SL 82.0715 (1.1, 72%); CGS 19755 (46% at 10 mg/kg); dextromethorphan (46% at 30 mg/kg). In contrast, agents acting preferentially upon sigma (sigma) opiate receptors ((+)-3PPP, 1-10 mg/kg i.p. and haloperidol, 0.3-3 mg/kg i.p.) did not provide a significant protection. In general, calcium channel blockers (nimodipine, flunarizine, verapamil, perhexiline, diltiazem) were devoid of a clear neuroprotective potential when administered at non-toxic doses after the coagulation of the middle cerebral artery. Diltiazem (3 and 10 mg/kg i.p.) provided a significant protection when the first administration was performed 10 min prior to the occlusion. Limited protection was observed with adenosine A1 receptor agonists (N6-cyclohexyladenosine and 2-chloro-adenosine).(ABSTRACT TRUNCATED AT 400 WORDS)

Vinpocetine: nootropic effects on scopolamine-induced and hypoxia-induced retrieval deficits of a step-through passive avoidance response in rats.

Vinpocetine, vincamine, aniracetam, and Hydergine, compounds with purported cognition activating activity, were evaluated for their ability to prevent scopolamine-induced and hypoxia-induced impairment of passive avoidance retention (24 hr) in rats. Vinpocetine (peak effect dose [PED]= 200 mg/kg PO), aniracetam (PED = 100 mg/kg PO), vincamine (PED = 30 mg/kg PO), and Hydergine (PED = 1 mg/kg PO) prevented memory disruption by scopolamine. Vinpocetine (PED = 3 mg/kg PO) and aniracetam (PED = 30 mg/kg PO) were also effective in preventing disruption of passive avoidance retention impaired by 7% oxygen hypoxia. In contrast, Hydergine (0.05 to 3 mg/kg PO) and vincamine (0.3 to 100 mg/kg PO) were not effective against hypoxia-induced impairment. Hydergine at doses greater than 10 mg/kg PO markedly impaired motor function. In both tests the protection was dose-related for all test substances in an inverted U-shaped manner. Mecamylamine (1, 3, 10 mg/kg SC), (-)-nicotine (0.1 to 0.4 mg/kg SC), apovincaminic acid (1-400 mg/kg PO) and pemoline (1-100 mg/kg PO) did not protect against memory impairment induced by either procedure. These data support the view that vinpocetine, a compound chemically distinct from the pyrrolidinones, has a cognitive activating ability as defined in models of both scopolamine-induced and hypoxia-induced memory impairment in rats.

Interventions for normal tension glaucoma.

BACKGROUND: Normal tension glaucoma is a clinical condition in which the optic nerve is pathologically excavated and the visual field is disturbed. Nevertheless it has been assumed that intraocular pressure plays a role in the progression of visual field defects in this disease, but other, mainly vascular factors, have been discussed as well. OBJECTIVES: The objective of this review is to assess the effects of medical and surgical treatments for normal tension glaucoma. SEARCH STRATEGY: Trials were identified from the Cochrane Central Register of Controlled Trials (CENTRAL) (which contains the Cochrane Eyes and Vision Group trials register), MEDLINE, EMBASE and BIOSIS Previews. Bibliographies of identified trials were searched to find additional trials. In addition, investigators and pharmaceutical companies were contacted. Date of last search: January 2001. SELECTION CRITERIA: This review includes randomised controlled trials in which medical or surgical interventions were compared to no treatment, placebo or other treatment in people with normal tension glaucoma. Two reviewers independently assessed the full text copies of the possibly relevant trials. Trial quality was assessed according to the methods set out in Section 6 of the Cochrane Reviewers' Handbook (Clarke 2000). DATA COLLECTION AND ANALYSIS: Data were extracted by two reviewers and results were compared for differences. Discrepancies were resolved by discussion. The heterogeneity of interventions, follow-up periods and outcomes did not allow for statistical combinations of the study results. MAIN RESULTS: According to the selection criteria on visual field loss, eight studies were included in this review. Only three studies focussed on patient relevant outcomes. In one trial a beneficial effect of lowering intraocular pressure was found, but only if data were corrected for cataract development. In two small studies a beneficial effect on visual field loss of brovincamine, a calcium antagonist was reported. REVIEWER'S CONCLUSIONS: In one study the effect of intraocular pressure lowering on visual field outcome was only significant when data were corrected for cataract development. The results for calcium antagonists are promising, but larger trials have to be performed. Studies that focussed on reduction of intraocular pressure or haemodynamic variables are not necessarily relevant for the outcome in people with normal tension glaucoma.

Effects induced by vincamine teprosilate on chronic cerebrovascular disease: preliminary results.

A group of 90 patients suffering from chronic cerebrovascular disease (CCVD) were selected on the basis of definite clinical criteria and pretests indicating a well-preserved general level of the higher functions. The purpose was to perform a clinical and neuropsychological assessment of CCVD sufferers during treatment with vincamine teprosilate (Teproside) for 90 days. Each selected patient was submitted to neurological examination and neuropsychological testing before treatment, after 45 days and at the termination of treatment. Neuropsychological examination included the reaction-time task, memory tests, verbal fluency test, trail making test, PM 38, MACL and STAI depression scales. Preliminary results are discussed and compared with previous data reported in the literature.

Cerebral antioedematous effect of Teproside and of some vincamine derivatives.

Alkyltin compounds are known to produce in the rat a selective oedema of the CNS, especially of the white matter. Vincamine and vincamine derivatives, among which Teproside is the most potent, are able to prevent the occurrence of such an oedematous reaction whereas xanthine derivatives and papaverine fail to prevent this oedema. It is suggested that there may be a potentiation of the effect of vincamine by the xanthine part of the Teproside chemical structure.

Evaluation of the effect of vincamine teprosilate on behavioural performances of patients affected with chronic cerebrovascular disease.

With a view to determining the efficacy of Teproside versus placebo in patients affected with cerebrovascular disease, 30 subjects, selected at the Montescano Medical Rehabilitation Centre, were randomly divided into two groups of 15 subjects each. After a two-week wash-out period, the first group was treated with placebo and the second with vincamine teprosilate (Teproside) at 120 mg daily, both for a period of 90 days. The assessment of each patient took place in two stages, one at the beginning and one at the end of treatment. It was performed according to both clinical criteria (including an interview with the patient and his family) and neuro-psychological criteria (memory tests, perceptive-spatial and logical functions tests). The data obtained showed a significant improvement of the behavioural performance, the mnemonic ability and the perceptive-motor activity in the Teproside group treated.

The effects of vincamine on experimental cerebral infarction in Mongolian gerbils: a pilot study.

Unilateral ligation of the common carotid artery was performed in 134 gerbils. Study I was comprised of 60 controls and 60 animals receiving I.P. vincamine 1 mg/kg q4h. In a small second study 14 animals received vincamine I.P. 40 mg/kg q12h. In all groups ligation of the carotid artery was performed 6 days after starting dosing. The animals were observed for a further 6 days after carotid artery ligation. Whereas vincamine had no effect on the percent of animals in each group dying after carotid ligation, the extent of stroke lesion, measured histometrically, was significantly reduced (P less than 0.05) in the vincamine treated animals.

[Controlled clinical study of the effects of Anasclerol in hospitalized patients with cerebrovascular disorders]. / Studio clinico controllato sugli effetti dell'Anasclerol in pazienti cerebro-vasculopatici ospedalizzati.

A double-blind clinical trial of vincamine hydrochloride and a known dihydrogenated ergotoxine derivative, administered i.m. for 10 days, was conducted on 2 groups of 10 hospitalised cerebrovascular patients. Hemiplegia was evaluated prior to treatment and on its 5th and 10th day, by a scoring system. Statistical assessment of the results and the clinical observations showed that vincamine hydrochloride can be usefully employed in the treatment of acute cerebrovascular accidents on account of its marked effectiveness and rapid action--these being attributable to its cerebral vasoregulatory and metabolic mechanism, and to increased availability due to salification of the basic molecule--, coupled with its excellent local and general tolerability.

[Neuropsychologic evaluation of the action of oxovinca in the syndrome of diffuse deterioration of vascular origin (author's transl)]. / Valoración neuropsicológica de la acción de oxovinca en el sindrome de deterioro difuso de origen vascular.

A controlled double-blind study of the effects of oxovinca in the syndrome of diffuse deterioration of vascular origin has been carried out. The measurement and follow-up the degree of deterioration has been done by application of a new scale. The subjects of the study were divided into an experimental sample (formed by 33 patients) and a placebo sample (formed by 6 patients), all with the syndrome of diffuse deterioration of vascular origin, and a control sample formed by 10 normal individuals of comparable age. After three consecutive courses of the drug given within a two-month period to the experimental and placebo groups, and comparing the results with those of the control sample, the statistical analysis of the data demonstrates that, given the temporal limitations of the trial, a partial reversibility of the signs and symptoms of the syndrome of diffuse deterioration is possible and correlates with the therapeutic action of oxovinca.

[Effects of Ginkgo biloba extract on a cerebral ischemia model in gerbils]. / Effets de l'extrait de Ginkgo biloba sur un modèle d'ischémie cérébrale chez la gerbille.

Certain anatomical characteristics peculiar to the gerbil make it the animal model best adapted to experimental pathology studies of acute ischaemia. In this animal species, devoid of any substitute vertebro-basilar vascular tissue, unilateral ligature of the carotid artery produces a cerebral ischaemia with neurological signs (well quantifiable), metabolic perturbations (especially mitochondrial) and cerebral oedema development closely resembling the symptoms revealed by physiopathology in human clinical studies. Using this model and under the experimental conditions described, clear-cut, highly significant results were obtained with Ginkgo biloba, whether by oral or intravenous administration. These results were normalization of mitochondrial respiration, diminution of cerebral oedema, correction of the accompanying ionic perturbations, and practically total functional restoration revealed by a normal neurological index in the gerbils treated with Ginkgo biloba extract.