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Sesquiterpene lactones isolated from Carpesium abrotanoides L. by LC–MS combined with HSCCC inhibit liver cancer through suppression of the JAK2/STAT3 signaling pathway

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Abstract

Carpesium abrotanoides L. is rich in sesquiterpene lactones, the experiments of anti-tumor activity in vitro showed that total sesquiterpene lactone extracts exhibited the most cytotoxicity activities against HepG-2 cells (IC50 = 4.2 μg/mL). In order to isolated the active compounds quickly, the strategy of HPLC-ESI-Q-TOF-MS/MS combined with high-speed counter-current chromatography (HSCCC) was implemented. Three sesquiterpene lactone compounds, 2α,5α-dihydroxy-11αH-eudesma-4(15)-en-12,8β-olide (1), telekin (2), oxoeudesm-11(13)-eno-12,8α-lactone (3) were obtained. Their structures were elucidated by detailed analysis of 1D, 2D NMR and HRMS data. In addition, compounds 1–3 were evaluated for their cytotoxic activities against HepG-2 cell line with IC50 value of 9.83, 2.95, and 4.15 μM, respectively. Moreover, all compounds not only can reduce the expression of JAK2 and STAT3 mRNA but also inhibit the p-JAK2 and p-STAT3 protein expression levels in a dose‐dependent manner in the HepG-2 cells. In conclusion, three sesquiterpene lactone compounds inhibited the proliferation of HepG-2 cells via suppressing the JAK2/STAT3 signaling pathway.

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Funding

This work has been supported by Key project at central government level for the ability establishment of sustainable use for valuable Chinese medicine resources (2060302), and Natural Science Foundation of Hunan province (2019JJ50351).

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Authors and Affiliations

  1. Research Institute of Chinese Medicine, Hunan academy of Chinese Medicine, Changsha, China

    Bingbing Shen, Dan Wan, Yuan Cai & Shuihan Zhang

  2. School of Pharmacy, Hunan university of Chinese Medicine, Changsha, China

    Yupei Yang & Huanghe Yu

  3. Hunan Times Sunshine Pharmaceutical Co., Ltd., Yongzhou, China

    Xionglong Wang, Daifeng Tang & Chunyu Tang

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  1. Bingbing Shen
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  2. Yupei Yang
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  3. Dan Wan
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  4. Huanghe Yu
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  5. Yuan Cai
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  7. Daifeng Tang
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  9. Shuihan Zhang
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Correspondence to Shuihan Zhang.

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Shen, B., Yang, Y., Wan, D. et al. Sesquiterpene lactones isolated from Carpesium abrotanoides L. by LC–MS combined with HSCCC inhibit liver cancer through suppression of the JAK2/STAT3 signaling pathway. Med Chem Res 31, 436–445 (2022). https://doi.org/10.1007/s00044-021-02838-y

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