Acute toxicity, 28-day repeated-dose toxicity and toxicokinetic study of timosaponin BII in rats

Ni, Lin; Liu, Baofeng; Zhang, Jie; Long, Yongpeng; Dong, Guoming; Jin, Hongtao; B, Ma

doi:10.1016/j.yrtph.2017.09.021

Cited by 11 publications

(8 citation statements)

References 42 publications

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“…Body weight is the most intuitive index to reflect health and is used in many research studies [6]. To evaluate the preliminary toxicity of PH toward mice, body weight was monitored every three days until the 16th day.…”

Section: Resultsmentioning

confidence: 99%

Evaluation of the Liver Toxicity of Pterocephalus hookeri Extract via Triggering Necrosis

Wang

Dong

Zhang

et al. 2019

Toxins

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Pterocephalus hookeri (C. B. Clarke) Höeck, recorded in the Chinese Pharmacopoeia (2015 version) as a Tibetan medicine for the treatment of various diseases, especially rheumatoid arthritis, was believed to possess a slight toxicity. However, hardly any research has been carried out about it. The present study aimed to evaluate the toxicity in vivo and in vitro. Toxicity was observed by the evaluation of mice weight loss and histopathological changes in the liver. Then, the comparison research between ethyl acetate extract (EAE) and n-butanol extract (BUE) suggested that liver toxicity was mainly induced by BUE. The mechanical study suggested that BUE-induced liver toxicity was closely associated with necrosis detected by MTT and propidium iodide (PI) staining, via releasing lactate dehydrogenase (LDH), reducing the fluidity, and increasing the permeability of the cell membrane. Western blot analysis confirmed that the necrosis occurred molecularly by the up-regulation of receptor-interacting protein kinase 1 (RIP1) and receptor-interacting protein kinase 3 (RIP3), as well as the activation of the nuclear factor-kappa-gene binding (NF-κB) signaling pathway in vivo and in vitro. This finding indicated that the liver toxicity induced by BUE from P. hookeri was mainly caused by necrosis, which provides an important theoretical support for further evaluation of the safety of this folk medicine.

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Section: Resultsmentioning

confidence: 99%

Evaluation of the Liver Toxicity of Pterocephalus hookeri Extract via Triggering Necrosis

Wang

Dong

Zhang

et al. 2019

Toxins

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“…In vitro studies showed that ethyl acetate extract of Anemarrhenae Rhizoma promoted the proliferation of Blautia coccoides , a bacterium with positive implication for diabetes, in a dose-dependent manner 401 . Timosaponin A3 reverses multi-drug resistance via the downregulation of MDR1, MRP1, and P-gp expression levels 400 , 401 , 402 , 403 .…”

Section: Tcms For the Treatment Of Covid-19 Infectionsmentioning

confidence: 99%

“…Given that Remdesivir is a substrate of P-gp, the compounds that affect P-gp activity might affect the efflux of Remdesivir. For example, herbal medicines and their bioactive ingredients including Alismatis Rhizoma (alisol B 23-acetate and alisol F 24-acetate) 118 , Bupleuri Radix (saikosaponins a/c/d) 160 , Citri Reticulatae Pericarpium (hesperidin) 259 , Descurainiae semen lepidii semen (quercetin) 318 , Magnoliae Officinalis Cortex (honokiol) 343 , 344 , Rhei Radix et Rhizoma 352 , 356 , Fritillariae Thunbergii Bulbus (peimisine, imperialine) 396 , Anemarrhenae Rhizoma (timosaponin A3) 400 , 401 , 402 , 403 , Arctii Fructus exerts inhibitory effects on P-gp, which may suppress Remdesivir's absorption or elimination 405 . On the contrary, many herbs such as Aurantii Fructus Immaturus (ethanol extract), Astragali Radix (astragaloside IV, calycosin and formononetin), and Menthae Haplocalycis Herba (menthol) can increase the activity or expression of P-gp 251 , 366 , 411 .…”

Section: Potential Hdi Between Anti-covid-19 Drugs and The Tcm Recipesmentioning

confidence: 99%

Potential herb–drug interactions between anti-COVID-19 drugs and traditional Chinese medicine

Ye¹,

Fan²,

Zhao³

et al. 2023

Acta Pharmaceutica Sinica B

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“…As one of the important parts of medical practice, traditional Chinese herbs serve as a natural chemical library which produce synergistic effects via principle active ingredients, and it is a good strategy to screen potential substances in these herbs for treating PF. Among this chemical library, Anemarrhena asphodeloides Bunge [Asparagaceae] has been extensively used to treat several diseases in clinical practices for centuries in China, Korea and Japan (Lin et al, 2017). Steroidal saponins are the main active components of Anemarrhena asphodeloides Bunge [Asparagaceae], among which timosaponin BII (TS BII) shows outstanding anti‐diabetic and cardioprotective effects (Tian et al, 2019; Xing et al, 2020); however, the role of TS BII in lung fibrosis has not been explored yet.…”

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Timosaponin BII inhibits TGF‐β mediated epithelial‐mesenchymal transition through Smad‐dependent pathway during pulmonary fibrosis

Ding

Shen

et al. 2023

Phytotherapy Research

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Pulmonary fibrosis (PF) is a progressive and fatal interstitial lung disease with limited therapeutic options at present, and epithelial-mesenchymal transition (EMT) is recognized as a major cause of lung fibrosis. Our previous work has confirmed that total extract of Anemarrhena asphodeloides Bunge [Asparagaceae] exerted the effect of anti-PF. As a main constituent of Anemarrhena asphodeloides Bunge [Asparagaceae], the effect of timosaponin BII (TS BII) on drug-induced EMT process in PF animals and alveolar epithelial cells remains unknown. In this study, we evaluated the effect of TS BII on bleomycin (BLM)-induced PF. The results showed that TS BII could restore the structure of lung architecture and MMP-9/TIMP-1 balance in fibrotic rat lung and inhibit collagen deposition. Moreover, we found that TS BII could reverse the abnormal expression of TGF-β1 and EMT-related marker proteins including E-cadherin, vimentin, and α-SMA. Besides, aberrant TGF-β1 expression and phosphorylation of Smad2 and Smad3 in BLM-induced animal model and TGF-β1-induced cell model were downregulated by TS BII treatment, indicating that EMT in fibrosis was suppressed by inhibition of TGF-β/Smad pathway both in vivo and in vitro. In summary, our study suggested that TS BII could be a promising candidate for PF treatment.

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Acute toxicity, 28-day repeated-dose toxicity and toxicokinetic study of timosaponin BII in rats

Cited by 11 publications

References 42 publications

Evaluation of the Liver Toxicity of Pterocephalus hookeri Extract via Triggering Necrosis

Evaluation of the Liver Toxicity of Pterocephalus hookeri Extract via Triggering Necrosis

Potential herb–drug interactions between anti-COVID-19 drugs and traditional Chinese medicine

Timosaponin BII inhibits TGF‐β mediated epithelial‐mesenchymal transition through Smad‐dependent pathway during pulmonary fibrosis

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