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Planta Med 2020; 86(05): 356-363
DOI: 10.1055/a-1107-3058
Pharmacokinetic Investigations
Original Papers
Georg Thieme Verlag KG Stuttgart · New York

Potential Cytotoxicity, Pharmacokinetics, and Excretion Properties of Sapindoside B from the Seeds of Nigella sativa var. hispidula

Xingjiang Hu
1   Research Center of Clinical Pharmacy, First Affiliated Hospital, Zhejiang University, Hangzhou, China
2   Zhejiang Provincial Key Laboratory for Drug Evaluation and Clinical Research, First Affiliated Hospital, Zhejiang University, Hangzhou, China
,
Meihua Lin
1   Research Center of Clinical Pharmacy, First Affiliated Hospital, Zhejiang University, Hangzhou, China
2   Zhejiang Provincial Key Laboratory for Drug Evaluation and Clinical Research, First Affiliated Hospital, Zhejiang University, Hangzhou, China
,
Wei Zhu
3   Department of Biomedical Engineering, Zhejiang University, Hangzhou, China
,
Yunliang Zheng
1   Research Center of Clinical Pharmacy, First Affiliated Hospital, Zhejiang University, Hangzhou, China
2   Zhejiang Provincial Key Laboratory for Drug Evaluation and Clinical Research, First Affiliated Hospital, Zhejiang University, Hangzhou, China
,
Qiao Zhang
1   Research Center of Clinical Pharmacy, First Affiliated Hospital, Zhejiang University, Hangzhou, China
2   Zhejiang Provincial Key Laboratory for Drug Evaluation and Clinical Research, First Affiliated Hospital, Zhejiang University, Hangzhou, China
,
Guolan Wu
1   Research Center of Clinical Pharmacy, First Affiliated Hospital, Zhejiang University, Hangzhou, China
2   Zhejiang Provincial Key Laboratory for Drug Evaluation and Clinical Research, First Affiliated Hospital, Zhejiang University, Hangzhou, China
,
Yunqing Qiu
1   Research Center of Clinical Pharmacy, First Affiliated Hospital, Zhejiang University, Hangzhou, China
2   Zhejiang Provincial Key Laboratory for Drug Evaluation and Clinical Research, First Affiliated Hospital, Zhejiang University, Hangzhou, China
4   State Key Laboratory for Diagnosis and Treatment of Infectious Disease, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, First Affiliated Hospital, Zhejiang University, Hangzhou, China
› Author AffiliationsSupported by: Zhejiang Provincial Natural Science Foundation of China LY16H280002
Supported by: Key Technologies R&D Program of 13th Five-year Plan of China 2018ZX09301025002
Further Information

Publication History

received 29 July 2019
revised 06 January 2020

accepted 23 January 2020

Publication Date:
13 February 2020 (online)

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Abstract

The seeds of Nigella sativa var. hispidula are widely used in food preparation by the Uighur people in western China. Recently, series of oleanane triterpenoid saponins were extracted from the seeds of Nigella sativa var. hispidula, especially α-hederin as representative that exhibited strong antitumor activity. Compared to α-hederin, sapindoside B has just 1 more terminal xylopyranose in the 3-O position and displays similar effects against various human cancer cell lines with cisplatin. Considering this potential cytotoxic activity, a reliable LC-MS/MS method was developed to quantify sapindoside B in rat plasma, urine, and feces. Chromatographic separation was conducted on an Agilent Zorbax SB-Aq (3.0 × 150 mm, 3.5 µm) column via an isocratic elution procedure with acetonitrile and water containing 0.1% formic acid. Mass spectrometric detection was coupled with an electrospray ionization source in the MRM mode. The linear range of calibration curves was 15 ~ 3000 ng/mL in plasma/urine and 30 ~ 3000 ng/g in feces. The intra-day and inter-day precision was less than 11.1%, and accuracy ranged from 92.2% to 108.7%. The proposed method was validated and shown to be reliable, precise, and accurate and was successfully applied to its pharmacokinetics and excretion studies. Sapindoside B exhibited dosage-dependent pharmacokinetics in the range of 2.5 mg/kg to 12.5 mg/kg, and only about 2% of intravenous dose of sapindoside B was excreted by the feces and urine in its unchanged form over 48 h. These results provide further data support for evaluating the druggability of sapindoside B.

Key words

cytotoxicity - excretion - Nigella sativa var. hispidula - pharmacokinetics - anunculaceae - sapindoside B

Supporting Information

    MRM chromatograms of sapindoside B and IS obtained from rat urine and feces samples are available as Supporting information (Fig. 1S and 2S). Chemical structures of α-hederin and sapindoside B (Fig. 3S).

  • Supporting Information
 

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