Modulation of the Epileptic Seizure Threshold: Implications of Biphasic Dose Responses

Calabrese, Edward J.

doi:10.1080/10408440802014261

Cited by 43 publications

(29 citation statements)

References 93 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Such hormetic dose responses have indeed been previously reported in chemically diverse proand anticonvulsant agents with different modes of action. 30,31 Another observation is that tanshinone IIA was able to exert an effect in the 6-Hz mouse seizure model at concentrations lower Figure 5. PTZ-normalized concentration−response curves for intravenous injection of vehicle-only and tanshinone IIA in 3-dpf zebrafish larvae that were subsequently exposed to 20 mM PTZ and tracked for 90 min.…”

Section: ■ Results and Discussionmentioning

confidence: 99%

Tanshinone IIA Exhibits Anticonvulsant Activity in Zebrafish and Mouse Seizure Models

Buenafe

Orellana-Paucar

Maes

et al. 2013

ACS Chem. Neurosci.

View full text Add to dashboard Cite

Danshen or Chinese red sage (Salvia miltiorrhiza, Bunge) is used by traditional Chinese medicine (TCM) practitioners to treat neurological, cardiovascular, and cerebrovascular disorders and is included in some TCM formulations to control epileptic seizures. In this study, acetonic crude extracts of danshen inhibited pentylenetetrazol (PTZ)-induced seizure activity in zebrafish larvae. Subsequent zebrafish bioassay-guided fractionation of the extract resulted in the isolation of four major tanshinones, which suppressed PTZ-induced activity to varying degrees. One of the active tanshinones, tanshinone IIA, also reduced c-fos expression in the brains of PTZ-exposed zebrafish larvae. In rodent seizure models, tanshinone IIA showed anticonvulsive activity in the mouse 6-Hz psychomotor seizure test in a biphasic manner and modified seizure thresholds in a complex manner for the mouse i.v. PTZ seizure assay. Interestingly, tanshinone IIA is used as a prescription drug in China to address cerebral ischemia in patients. Here, we provide the first in vivo evidence demonstrating that tanshinone IIA has anticonvulsant properties as well. KEYWORDS: Tanshinone IIA, Salvia miltiorrhiza, zebrafish PTZ model, mouse seizure models, pentylenetetrazol E pilepsy affects approximately 60 million people worldwide, of whom 30% suffer from pharmacoresistant seizures. The economics of maintaining a cost-effective therapeutic regimen hinge on its long-term efficacy and the probability of patients developing treatment-resistant seizures or possible side-effects ranging from sedation to Steven−Johnson syndrome.1 To address such issues, there is an ongoing hunt for new antiepileptic drugs (AEDs) with novel mechanisms of action and with minimal or no side-effects.There is a resurgence of interest in exploring plant, microbial, and marine resources used in traditional medicine for potential drug leads. According to the World Health Organization (WHO), 70−80% of the population in developing and developed countries have used, or depend on such therapies, which became the impetus for efforts in bioprospecting and drug development.2 Despite prevalent skepticism, as many as 25% of pharmaceutical drugs on the market are plant-based and were discovered through investigations on traditional or folk medicine practiced by different cultures.1,2 The rationale behind this approach in drug discovery is that small molecules isolated or derived from natural sources offer a more diverse set of structures compared with compounds synthesized through medicinal chemistry or combinatorial techniques. 2Each plant or marine extract can be treated as a library potential of hits, which can be screened using an appropriate medium-to high-throughput in vivo model such as zebrafish (Danio rerio), a freshwater teleost of the Cyprinidae family.3,4 In screening for potential hits and leads for AED development, we have previously described the use of larval zebrafish as a platform for pinpointing AED-like activity of small molecules isolated from plant sources.3,4 ...

show abstract

Section: ■ Results and Discussionmentioning

confidence: 99%

Tanshinone IIA Exhibits Anticonvulsant Activity in Zebrafish and Mouse Seizure Models

Buenafe

Orellana-Paucar

Maes

et al. 2013

ACS Chem. Neurosci.

View full text Add to dashboard Cite

show abstract

“…For example, the low dose range of a drug may stimulate a response that is desirable. This is often the case for agents such as anxiolytic (Calabrese 2008c) and antiseizure drugs (Calabrese 2008d). In the case of anxiolytic drugs doses normally increase the amount of time that a rodent will spend in lighted areas, indicating a decrease in anxiety.…”

Section: Does the Threshold Dose Response Model Have Important Limitamentioning

confidence: 97%

Hormesis: why it is important to biogerontologists

2012

Self Cite

View full text Add to dashboard Cite

This paper offers a broad assessment of the hormetic dose response and its relevance to biogerontology. The paper provides detailed background information on the historical foundations of hormesis, its quantitative features, mechanistic foundations, as well as how the hormesis concept could be further applied in the development of new therapeutic advances in the treatment of age-related diseases. The concept of hormesis has direct application to biogerontology not only affecting the quality of the aging process but also experimental attempts to extend longevity.

show abstract

“…All leading (and nonleading) toxicologic textbooks contain sections on hormesis, giving it clear standing in the field. Also not acknowledged is the fact that the concept of hormesis is central to a range of biomedical areas such as with anxiolytic drugs (Calabrese 2008b), antiseizure drugs (Calabrese 2008d), memory drugs (Calabrese 2008a), and others (Calabrese 2008c). In fact, all drugs approved by the Food and Drug Administration for Alzheimer’s disease follow the hormetic dose response (Calabrese 2008a).…”

Section: The Achievements Of Hormesis In the Last 15 Yearsmentioning

confidence: 99%

Hormesis: A Conversation with a Critic

Calabrese

2009

Environ Health Perspect

Self Cite

View full text Add to dashboard Cite

ObjectiveIn this commentary I respond to points raised in the commentary by Mushak [Ad hoc and fast forward: the science and control of hormesis growth and development. Environ Health Perspect 117:1333–1338 (2009)], which principally concerns studies by me and my colleagues concerning the frequency of hormesis in toxicology.DiscussionIn this commentary I demonstrate that Mushak’s analysis contains critical statistical errors and misunderstandings of statistical concepts that invalidate its conclusions concerning the frequency of hormesis in the toxicologic literature.ConclusionsIn his commentary Mushak offers no significant new conceptual insights, and his key technical criticisms of hormesis frequency findings are unfounded.

show abstract

Modulation of the Epileptic Seizure Threshold: Implications of Biphasic Dose Responses

Cited by 43 publications

References 93 publications

Tanshinone IIA Exhibits Anticonvulsant Activity in Zebrafish and Mouse Seizure Models

Tanshinone IIA Exhibits Anticonvulsant Activity in Zebrafish and Mouse Seizure Models

Hormesis: why it is important to biogerontologists

Hormesis: A Conversation with a Critic

Contact Info

Product

Resources

About