Evaluation of Tanshinone IIA Developmental Toxicity in Zebrafish Embryos

Wang, Tao; Wang, Chengxi; Wu, Qiong; Zheng, Kangdi; Chen, Jiaojiao; Lan, Yutao; Qin, Yao; Mei, Wenjie; Wang, Baoguo

doi:10.3390/molecules22040660

Cited by 39 publications

(22 citation statements)

References 30 publications

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“…Although tan IIA had a positive effect at the doses used here, we and other groups found that tan IIA increased the cytotoxicity of cortical neurons and SH-SY5Y cells at higher doses [22,25,57]. Furthermore, tan IIA exhibited severe cardiotoxicity, development malformation, and growth inhibition at high concentrations in a zebrafish embryo model [58]. These studies demonstrate that tan IIA has cytotoxic effects at higher doses and point to the potential risk of clinical application of increased doses.…”

Section: Discussioncontrasting

confidence: 39%

Tanshinone IIA attenuates neuroinflammation via inhibiting RAGE/NF-κB signaling pathway in vivo and in vitro

Ding

Lin

Liu

et al. 2020

J Neuroinflammation

114

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Background Glial activation and neuroinflammation play a crucial role in the pathogenesis and development of Alzheimer’s disease (AD). The receptor for advanced glycation end products (RAGE)-mediated signaling pathway is related to amyloid beta (Aβ)-induced neuroinflammation. This study aimed to investigate the neuroprotective effects of tanshinone IIA (tan IIA), a natural product isolated from traditional Chinese herbal Salvia miltiorrhiza Bunge, against Aβ-induced neuroinflammation, cognitive impairment, and neurotoxicity as well as the underlying mechanisms in vivo and in vitro. Methods Open-field test, Y-maze test, and Morris water maze test were conducted to assess the cognitive function in APP/PS1 mice. Immunohistochemistry, immunofluorescence, thioflavin S (Th-S) staining, enzyme-linked immunosorbent assay (ELISA), real-time quantitative reverse-transcription polymerase chain reaction (qRT-PCR), and western blotting were performed to explore Aβ deposition, synaptic and neuronal loss, microglial and astrocytic activation, RAGE-dependent signaling, and the production of pro-inflammatory cytokines in APP/PS1 mice and cultured BV2 and U87 cells. Results Tan IIA treatment prevented spatial learning and memory deficits in APP/PS1 mice. Additionally, tan IIA attenuated Aβ accumulation, synapse-associated proteins (Syn and PSD-95) and neuronal loss, as well as peri-plaque microgliosis and astrocytosis in the cortex and hippocampus of APP/PS1 mice. Furthermore, tan IIA significantly suppressed RAGE/nuclear factor-κB (NF-κB) signaling pathway and the production of pro-inflammatory cytokines (TNF-α, IL-6, and IL-1β) in APP/PS1 mice and cultured BV2 and U87 cells. Conclusions Taken together, the present results indicated that tan IIA improves cognitive decline and neuroinflammation partly via inhibiting RAGE/NF-κB signaling pathway in vivo and in vitro. Thus, tan IIA might be a promising therapeutic drug for halting and preventing AD progression.

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Section: Discussioncontrasting

confidence: 39%

Tanshinone IIA attenuates neuroinflammation via inhibiting RAGE/NF-κB signaling pathway in vivo and in vitro

Ding

Lin

Liu

et al. 2020

J Neuroinflammation

114

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“…Teratogenic effects such as scoliosis, malformation of the tail, and pericardium oedema of dechorionated embryos were manifested at a concentration of about 1 μ M. Normal embryos were less sensitive to Tan-IIA, but with the increasing concentration, severe abnormalities of heart and pericardium were observed. Moreover, after treatment with Tan-IIA ≥ 6 μ M, the time it took for the embryos to mature into fish was longer than that for the control [43].…”

Section: Resultsmentioning

confidence: 99%

Toxicity Assessment of Herbal Medicine Using Zebrafish Embryos: A Systematic Review

Jayasinghe

Jayawardena

2019

Evidence-Based Complementary and Alternative Medicine

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Herbal remedies have been practiced by humans over centuries and therefore possess time-proven safety. However, it is imperative to evaluate the toxic effects of herbal medicine to confirm their safety, particularly when developing therapeutic leads. Use of laboratory animals such as rats, mice, and rabbits was considered as gold standard in herbal toxicity assessments. However, in the last few decades, the ethical consideration of using higher vertebrates for toxicity testing has become more contentious. Thus, possible alternative models entailing lower vertebrates such as zebrafish were introduced. The zebrafish embryotoxicity model is at the forefront of toxicology assessment due to the transparent nature of embryos, low cost, short cycle, higher fecundity, and genetic redundancy to the humans. Recently, its application has been extended to herbal toxicology. The present review intends to provide a comprehensive assembly of studies that applied the zebrafish embryo model for the assessment of herbal toxicity. A systematic literature survey was carried out in popular scientific databases. The literature search identified a total of 1014 articles in PubMed = 12, Scopus SciVerse® = 623, and Google Scholar = 1000. After screening, 25 articles were included in this review, and they were categorized into three groups in which the zebrafish embryotoxicity assay has been applied to investigate the toxicity of (1) polyherbal formulae/medical prescription (2 full texts), (2) crude extracts (12 full texts), and (3) phytocompounds/isolated constituents (11 full texts). These studies have investigated the toxicity of 6 polyherbal formulae, 16 crude extracts, and more than 30 phytocompounds/isolated constituents using the zebrafish embryotoxicity model. Moreover, this model has explicated the teratogenic effects and specific organ toxicities such as the kidney, heart, and liver. Furthermore, in some studies, the molecular mechanisms underlying the toxicity of herbal medicine have been elucidated. This comprehensive collection of scientific data solidifies the zebrafish embryo model as an effective model system for studying toxicological effects of a broad spectrum of herbal remedies. Henceforth, it provides a novel insight into the toxicity assessment of herbal medicine.

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“…Studies demonstrated that treatment with a high dose of tan IIA alone increased the cytotoxicity of cortical neurons and SH-SY5Y cells, suggesting that tan IIA has a positive effect on cell viability at low dose [30,39,40]. Furthermore, tan IIA exhibited severe growth inhibition, development malformation, and cardiotoxicity at high concentrations in a zebrafish embryo model, pointing to the potential risk of clinical application of increased doses [41]. These researches showed that tan IIA has cytotoxic effects at higher doses itself.…”

Section: Discussionmentioning

confidence: 99%

Tanshinone IIA reduces palmitate‐induced apoptosis via inhibition of endoplasmic reticulum stress in HepG2 liver cells

Wang

Hu²,

Chen

et al. 2019

Fundamemntal Clinical Pharma

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Research has indicated that stress on the endoplasmic reticulum (ER) of a cell affects the pathogenesis of metabolic disorders such as obesity, type 2 diabetes mellitus, and non‐alcoholic fatty liver disease (NAFLD). Palmitate, a saturated fatty acid, is known to induce toxicity and cell death in various types of cells. Tanshinone IIA (Tan IIA), one of the effective components of the traditional Chinese medicine Danshen, was reported to exhibit a variety of biochemical activities, including amelioration of ER stress‐mediated apoptosis in renal preservation. To address the hypothesis that tan IIA attenuates apoptosis and triglycerides (TG) accumulation via reducing ER stress, we studied the effect of tan IIA on experimentally induced ER stress using palmitate in HepG2 cells. Palmitate led to cytotoxicity, TG accumulation, and apoptosis in HepG2 cells and also strongly induced ER stress indicated by increased GRP78, phosphorylation of eIF2α, ATF6, and CHOP. Pretreatment with tan IIA (10 μm) significantly increased cell viability, decreased apoptotic cell death, and reduced the activity of caspase‐3. Meanwhile, tan IIA significantly decreased palmitate‐induced TG accumulation. Moreover, tan IIA significantly suppressed the phosphorylation of eIF2α, and inhibited GRP78, ATF6, and CHOP expression. In conclusion, tan IIA protects the HepG2 cells exposed to palmitate partially by inhibiting excessive ER stress, ER stress‐induced apoptosis, and hepatic steatosis. Therefore, tan IIA has therapeutic potential in the treatment of NAFLD.

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Evaluation of Tanshinone IIA Developmental Toxicity in Zebrafish Embryos

Cited by 39 publications

References 30 publications

Tanshinone IIA attenuates neuroinflammation via inhibiting RAGE/NF-κB signaling pathway in vivo and in vitro

Tanshinone IIA attenuates neuroinflammation via inhibiting RAGE/NF-κB signaling pathway in vivo and in vitro

Toxicity Assessment of Herbal Medicine Using Zebrafish Embryos: A Systematic Review

Tanshinone IIA reduces palmitate‐induced apoptosis via inhibition of endoplasmic reticulum stress in HepG2 liver cells

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