Vertigoheel improves central vestibular compensation after unilateral peripheral vestibulopathy in rats

Hatat, Bérenice; Boularand, Romain; Bringuier, Claire M.; Chanut, Nicolas; Besnard, Stéphane; Mueller, Anne; Weyer, Kathrin; Seilheimer, Bernd; Tighilet, Brahim; Chabbert, Christian

doi:10.3389/fneur.2022.969047

Cited by 6 publications

(7 citation statements)

References 62 publications

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“…The mechanisms of VH-04 effects are not well elucidated, but may involve a stimulating effect on the central nervous system activity either via vasodilatation or direct modulation of neurons. Administration of VH-04 modulated frequency components of EEG in a manner similar to that of cognition-enhancing tacrine and metanicotine as well as caffeine ( Dimpfel et al, 2019 ) and seemed to improve cognitive performance in the eight-arm radial maze task of rats sham-treated for modeling vestibular syndrome ( Hatat et al, 2022 ). These observations suggested that VH-04 may have cognition-enhancing activity.…”

Section: Discussionmentioning

confidence: 99%

Vertigoheel promotes rodent cognitive performance in multiple memory tests

Ott

Heikkinen²,

Lehtimäki³

et al. 2023

Front. Neurosci.

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IntroductionCognitive impairment associated with old age or various brain disorders may be very disabling for affected individuals, placing their carers and public health services under considerable stress. The standard-of-care drugs produce only transient improvement of cognitive impairment in older people, so the search for novel, safe and effective therapeutics that would help to reverse or delay cognitive impairment is warranted. Repurposing pharmacological therapies with well-established safety record for additional indications is a promising recent trend in drug development. Vertigoheel (VH-04), a multicomponent drug made of Ambra grisea, Anamirta cocculus L., Conium maculatum, and Petroleum rectificatum, has been successfully used for several decades in the treatment of vertigo. Here, we investigated effects of VH-04 on cognitive performance in standard behavioral tests assessing different types of memory and explored cellular and molecular underpinnings of VH-04’s biological activity.MethodsIn the majority of behavioral experiments, namely in the spontaneous and rewarded alternation tests, passive avoidance test, contextual/cued fear conditioning, and social transmission of food preference, we examined the ability of single and repeated intraperitoneal administrations of VH-04 to improve cognitive parameters of mice and rats disrupted by the application of the muscarinic antagonist scopolamine. In addition, we also assessed how VH-04 affected novel object recognition and influenced performance of aged animals in Morris water maze. Furthermore, we also studied the effects of VH-04 on primary hippocampal neurons in vitro and mRNA expression of synaptophysin in the hippocampus.ResultsAdministration of VH-04 positively influenced visual recognition memory in the novel object recognition test and alleviated the impairments in spatial working memory and olfactory memory caused by the muscarinic antagonist scopolamine in the spontaneous alternation and social transmission of food preference tests. In addition, VH-04 improved retention of the spatial orientation memory of old rats in the Morris water maze. In contrast, VH-04 did not have significant effects on scopolamine-induced impairments in tests of fear-aggravated memory or rewarded alternation. Experiments in vitro showed that VH-04 stimulated neurite growth and possibly reversed the age-dependent decrease in hippocampal synaptophysin mRNA expression, which implies that VH-04 may preserve synaptic integrity in the aging brain.DiscussionOur findings allow a cautious conclusion that in addition to its ability to alleviate manifestations of vertigo, VH-04 may be also used as a cognitive enhancer.

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Section: Discussionmentioning

confidence: 99%

Vertigoheel promotes rodent cognitive performance in multiple memory tests

Ott

Heikkinen²,

Lehtimäki³

et al. 2023

Front. Neurosci.

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“…In preclinical studies, it was shown that Vertigoheel improves central vestibular compensation ( 8 ). However, the mechanism of action in BVP and FD is so far largely unclear and should be examined in further studies.…”

Section: Discussionmentioning

confidence: 99%

“…Vertigoheel is a natural non-prescription medicinal product containing four active ingredients for the treatment of vertigo and was approved by the German regulatory authority as a treatment for vertigo of various origins. According to recent research performed with rat models, Vertigoheel enhanced central vestibular compensation after unilateral peripheral vestibulopathy ( 8 ). Vertigoheel’s mode of action is not fully understood and under evaluation.…”

Section: Introductionmentioning

confidence: 99%

Improvement of vertigo symptoms after 2 months of Vertigoheel treatment: a case series in patients with bilateral vestibulopathy and functional dizziness

Ganeva,

Tiemann,

Duller

et al. 2023

Front. Neurol.

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BackgroundDizziness is a common leading symptom in bilateral vestibulopathy (BVP) and functional dizziness (FD), with significant negative effects on functional ability and quality of life. Vertigoheel is a widely used non-prescription drug for the treatment of vertigo. In order to generate systematic data for Vertigoheel in BVP and FD, we conducted a non-interventional study assessing vertigo symptoms.MethodsThis study was conducted as an open-label, prospective, monocentric, non-interventional case series (ClinicalTrials.gov identifier NCT05897853). Patients with BVP and FD received Vertigoheel according to market approval for an observational period of 2 months. Change from baseline after 2 months was assessed for the following endpoints: Dizziness Handicap Inventory (DHI) as the primary endpoint, quality of life (QoL) by EQ-5D-5L, and body sway by static posturography. Patients with FD were additionally assessed for depression and anxiety by PHQ-9 and GAD-7 questionnaires. Patients with BVP were assessed for vestibular function by video head impulse testing and caloric testing. Adverse events and other safety-related observations were evaluated.ResultsOf 41 patients with FD and 13 with BVP, two with FD and none with BVP dropped out before the follow-up visit. Both patient groups showed significantly improved disability caused by dizziness after 2 months: In BVP, the DHI decreased on average by 13.2 points from 45.4 to 32.2 (p < 0.001). In FD, the DHI decreased on average by 12.0 points from 46.5 to 34.5 (p < 0.001). In patients with FD, significant improvements were also observed for the secondary endpoints QoL, anxiety, and depression. No significant change was observed for posturography readouts. In patients with BVP, there were no statistically significant improvements for the secondary endpoints QoL, posturography, or vestibular function within the observation period. The study found no evidence of a safety risk.ConclusionThe study provides evidence for Vertigoheel’s clinical safety and limited evidence – because of the non-interventional design – for its effectiveness in BVP and FD that are considered disease entities with high medical need for new treatment options. The results may serve as the basis for randomized placebo-controlled trials.

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“…Simultaneous or sequential bilateral administration of arsanilate makes it possible to reproduce bilateral vestibular areflexia reproducing those encountered in humans following massive administration of aminoglycosides or after heavy chemotherapy. Under these conditions, the animals also exhibit cognitive deficits of memory loss and spatial navigation [ 20 , 21 , 22 ] characteristic of those observed in patients with double vestibular areflexia [ 23 ].…”

Section: Animal Models Of Peripheral Vestibulopathiesmentioning

confidence: 99%

What Predictability for Animal Models of Peripheral Vestibular Disorders?

et al. 2022

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The different clinical entities grouped under the term peripheral vestibulopathies (PVs) or peripheral vestibular disorders (PVDs) are distinguished mainly based on their symptoms/clinical expression. Today, there are very few commonly accepted functional and biological biomarkers that can confirm or refute whether a vestibular disorder belongs to a precise classification. Consequently, there is currently a severe lack of reliable and commonly accepted clinical endpoints, either to precisely follow the course of the vertigo syndrome of vestibular origin or to assess the benefits of therapeutic approaches, whether they are pharmacological or re-educational. Animal models of PV are a good means to identify biomarkers that could subsequently be exploited in human clinical practice. The question of their predictability is therefore crucial. Ten years ago, we had already raised this question. We revisit this concept today in order to take into account the animal models of peripheral vestibular pathology that have emerged over the last decade, and the new technological approaches available for the behavioral assessment of vestibular syndrome in animals and its progression over time. The questions we address in this review are the following: are animal models of PV predictive of the different types and stages of vestibular pathologies, and if so, to what extent? Are the benefits of the pharmacological or reeducational therapeutic approaches achieved on these different models of PV (in particular the effects of attenuation of the acute vertigo, or acceleration of central compensation) predictive of those expected in the vertiginous patient, and if so, to what extent?

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Vertigoheel improves central vestibular compensation after unilateral peripheral vestibulopathy in rats

Cited by 6 publications

References 62 publications

Vertigoheel promotes rodent cognitive performance in multiple memory tests

Vertigoheel promotes rodent cognitive performance in multiple memory tests

Improvement of vertigo symptoms after 2 months of Vertigoheel treatment: a case series in patients with bilateral vestibulopathy and functional dizziness

What Predictability for Animal Models of Peripheral Vestibular Disorders?

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