Archives of Biochemistry and Biophysics

2011

DOI: 10.1016/j.abb.2011.08.006

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Tanshinone II-A attenuates and stabilizes atherosclerotic plaques in Apolipoprotein-E knockout mice fed a high cholesterol diet

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Peter J. Little

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et al.

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Cited by 72 publications

(74 citation statements)

References 38 publications

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“…WISH of 7-dpf zebrafish larvae to visualize the modulation of c-fos expression: (A) larva with vehicle only pretreatment, unexposed to PTZ before fixation and staining; (B) larva with vehicle only pretreatment, exposed to PTZ for 30 min before fixation and staining; (C) larva pretreated with 80 μM tanshinone IIA for 18 h, unexposed to PTZ before fixation and staining; and (D) larva pretreated with 80 μM tanshinone IIA before PTZ exposure, fixation, and staining. than those used in preclinical cardiovascular research 32 by as much as 40-fold. This 40-fold difference can be interpreted in the following manner: off-target or alternate system effects are avoided, if low doses of the compound are used.…”

Section: ■ Results and Discussionmentioning

confidence: 99%

Tanshinone IIA Exhibits Anticonvulsant Activity in Zebrafish and Mouse Seizure Models

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Orellana-Paucar

²

,

³

et al. 2013

ACS Chem. Neurosci.

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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 ...

“…WISH of 7-dpf zebrafish larvae to visualize the modulation of c-fos expression: (A) larva with vehicle only pretreatment, unexposed to PTZ before fixation and staining; (B) larva with vehicle only pretreatment, exposed to PTZ for 30 min before fixation and staining; (C) larva pretreated with 80 μM tanshinone IIA for 18 h, unexposed to PTZ before fixation and staining; and (D) larva pretreated with 80 μM tanshinone IIA before PTZ exposure, fixation, and staining. than those used in preclinical cardiovascular research 32 by as much as 40-fold. This 40-fold difference can be interpreted in the following manner: off-target or alternate system effects are avoided, if low doses of the compound are used.…”

Section: ■ Results and Discussionmentioning

confidence: 99%

Tanshinone IIA Exhibits Anticonvulsant Activity in Zebrafish and Mouse Seizure Models

¹

,

Orellana-Paucar

²

,

³

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 ...

“…After 12 weeks, mice were euthanized and aortas were collected and subjected to Western blotting analysis. The aortic sinus cryosections were analyzed for atherosclerotic lesion size with Oil Red O staining and immunohistochemistry staining as previously described ( 13 ). The dosage of the drug used in the current study was evaluated according to a small pilot study by us ( 13 ) and reports by others ( 20 ).…”

Section: Apoementioning

confidence: 99%

“…The aortic sinus cryosections were analyzed for atherosclerotic lesion size with Oil Red O staining and immunohistochemistry staining as previously described ( 13 ). The dosage of the drug used in the current study was evaluated according to a small pilot study by us ( 13 ) and reports by others ( 20 ). All animal experimental procedures were performed in accordance with the National Institutes of Health Guide for the Care and Use of Laboratory Animals and were approved by the Institutional Ethical Committee for Animal Research at Sun Yat-sen University.…”

Section: Apoementioning

confidence: 99%

Tanshinone IIA suppresses cholesterol accumulation in human macrophages: role of heme oxygenase-1

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²

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³

et al. 2014

Journal of Lipid Research

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“…1A) have strong antiparasitic, antifungal, and antibacterial activities (17)(18)(19). These compounds belong to the group of labdane-type diterpenes (20), which also includes several other members with bioactive properties, such as tanshinones (2)(3)(4), which exhibit strong antiinflammatory activity (21) and are effective against various cardiovascular and cerebrovascular disorders (22,23), and forskolin (5), which activates adenylyl cyclase and increases the intracellular levels of cAMP (24)(25)(26) (Fig. 1A).…”

mentioning

confidence: 99%

Carnosic acid biosynthesis elucidated by a synthetic biology platform

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²

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³

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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Synthetic biology approaches achieving the reconstruction of specific plant natural product biosynthetic pathways in dedicated microbial “chassis” have provided access to important industrial compounds (e.g., artemisinin, resveratrol, vanillin). However, the potential of such production systems to facilitate elucidation of plant biosynthetic pathways has been underexplored. Here we report on the application of a modular terpene production platform in the characterization of the biosynthetic pathway leading to the potent antioxidant carnosic acid and related diterpenes in Salvia pomifera and Rosmarinus officinalis. Four cytochrome P450 enzymes are identified (CYP76AH24, CYP71BE52, CYP76AK6, and CYP76AK8), the combined activities of which account for all of the oxidation events leading to the biosynthesis of the major diterpenes produced in these plants. This approach develops yeast as an efficient tool to harness the biotechnological potential of the numerous sequencing datasets that are increasingly becoming available through transcriptomic or genomic studies.

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