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

Xingjiang Hu; Meihua Lin; Wei Zhu; Yunliang Zheng; Qiao Zhang; Guolan Wu; Yunqing Qiu

doi:10.1055/a-1107-3058

Planta Medica, Table of Contents

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

¹Research Center of Clinical Pharmacy, First Affiliated Hospital, Zhejiang University, Hangzhou, China

²Zhejiang Provincial Key Laboratory for Drug Evaluation and Clinical Research, First Affiliated Hospital, Zhejiang University, Hangzhou, China

,

Meihua Lin

¹Research Center of Clinical Pharmacy, First Affiliated Hospital, Zhejiang University, Hangzhou, China

²Zhejiang Provincial Key Laboratory for Drug Evaluation and Clinical Research, First Affiliated Hospital, Zhejiang University, Hangzhou, China

,

Wei Zhu

³Department of Biomedical Engineering, Zhejiang University, Hangzhou, China

,

Yunliang Zheng

¹Research Center of Clinical Pharmacy, First Affiliated Hospital, Zhejiang University, Hangzhou, China

²Zhejiang Provincial Key Laboratory for Drug Evaluation and Clinical Research, First Affiliated Hospital, Zhejiang University, Hangzhou, China

,

Qiao Zhang

¹Research Center of Clinical Pharmacy, First Affiliated Hospital, Zhejiang University, Hangzhou, China

²Zhejiang Provincial Key Laboratory for Drug Evaluation and Clinical Research, First Affiliated Hospital, Zhejiang University, Hangzhou, China

,

Guolan Wu

¹Research Center of Clinical Pharmacy, First Affiliated Hospital, Zhejiang University, Hangzhou, China

²Zhejiang Provincial Key Laboratory for Drug Evaluation and Clinical Research, First Affiliated Hospital, Zhejiang University, Hangzhou, China

,

Yunqing Qiu

¹Research Center of Clinical Pharmacy, First Affiliated Hospital, Zhejiang University, Hangzhou, China

²Zhejiang Provincial Key Laboratory for Drug Evaluation and Clinical Research, First Affiliated Hospital, Zhejiang University, Hangzhou, China

⁴State 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 Affiliations

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

Full Text

References

References
1 Boubertakh B, Liu XG, Cheng XL, Li P. A spotlight on chemical constituents and pharmacological activities of Nigella glandulifera Freyn et Sint seeds. J Chem 2013; 2013: 820183
2 Chinese Pharmacopoeia Commission. Pharmacopoeia of the Peopleʼs Republic of China, 2015 Edition. Beijing: China Medical Science Press; 2015: 345
3 Ramadan MF. Nutritional value, functional properties and nutraceutical applications of black cumin (Nigella sativa L.): an overview. Int J of Food Sci Technol 2007; 42: 1208-1218
4 Randhawa MA, Alghamdi MS. Anticancer activity of Nigella sativa (black seed) – a review. Am J Chin Med 2011; 39: 1075-1091
5 Fico G, Panizzi L, Flamini G, Braca A, Morelli I, Tome F, Cioni PL. Biological screening of Nigella damascena for antimicrobial and molluscicidal activities. Phytother Res 2004; 18: 468-470
6 Alamgir ANM. Therapeutic Use of medicinal Plants and their Extracts: Volume 1: Pharmacognosy. In: Rainsfor KD. ed. Progress in Drug Research 73. Berlin: Springer International Publishing AG; 2017: 200
7 Tian Z, Liu YM, Chen SB, Yang JS, Xiao PG, Wang L, Wu E. Cytotoxicity of two triterpenoids from Nigella glandulifera . Molecules 2006; 11: 693-699
8 Zhao J, Xu F, Huang H, Gu Z, Wang L, Tan W, He J, Chen Y, Li C. Evaluation on anti-inflammatory, analgesic, antitumor, and antioxidant potential of total saponins from Nigella glandulifera seeds. Evid Based Complement Alternat Med 2013; 2013: 827230
9 Li J, Wu DD, Zhang JX, Wang J, Ma JJ, Dong WG. Mitochondrial pathway mediated by reactive oxygen species involvement in α-hederin-induced apoptosis in hepatocellular carcinoma cells. World J Gastroenterol 2018; 24: 1901-1910
10 Sun DD, Shen WX, Zhang F, Fan HS, Xu CL, Li L, Tan JN, Miao YJ, Zhang HB, Yang Y, Cheng HB. α-Hederin inhibits interleukin 6-induced epithelial-to-mesenchymal transition associated with disruption of JAK2/STAT3 signaling in colon cancer cells. Biomed Pharmacother 2018; 101: 107-114
11 Zhan YJ, Wang K, Li Q, Zou YD, Chen BN, Gong Q, Ho HTI, Yin T, Zhang FY, Lu YH, Wu WJ, Zhang YL. The novel autophagy inhibitor alpha-hederin promoted paclitaxel cytotoxicity by increasing reactive oxygen species accumulation in non-small cell lung cancer cells. Int J Mol Sci 2018; 19: E3221
12 Wang HY, Wu B, Wang HT. Alpha-hederin induces the apoptosis of oral cancer SCC-25 cells by regulating PI3K/Akt/mTOR signaling pathway. Electron J Biotechn 2019; 38: 27-31
13 Sun J, Feng Y, Wang Y, Ji Q, Cai G, Shi L, Wang YY, Huang Y, Zhang J, Li Q. α-hederin induces autophagic cell death in colorectal cancer cells through reactive oxygen species dependent AMPK/mTOR signaling pathway activation. Int J Onco 2019; 54: 1601-1612
14 Sun LL, Luan M, Zhu W, Gao S, Zhang QL, Xu CJ, Lu XH, Xu XD, Tian JK, Zhang L. Study on antitubercular constituents from the seeds of Nigella glandulifera . Chem Pharm Bull 2013; 61: 873-876
15 Zhao M, Da-Wa ZM, Guo DL, Fang DM, Chen XZ, Xu HX, Gu YC, Xia B, Chen L, Ding LS, Zhou Y. Cytotoxic triterpenoid saponins from Clematis tangutica . Phytochemistry 2016; 130: 228-237
16 Feller G, Kugel A, Moonshine D, Chalifa-Caspi V, Scholz M, Prufer D, Rabinski T, Muller KJ, Ofir R. African descents are more sensitive than European descents to the antitumor compounds α-hederin and kalopanaxsaponin I. Planta Med 2010; 76: 1847-1851
17 Pasi S, Aligiannis N, Pratsinis H, Skaltsounis AL, Chinou IB. Biologically active triterpenoids from Cephalaria ambrosioides . Planta Med 2009; 75: 163-167
18 Porsche FM, Molitor D, Beyer M, Charton S, Andre C, Kollar A. Antifungal activity of saponins from the fruit pericarp of Sapindus mukorossi against Venturia inaequalis and Botrytis cinerea . Plant Dis 2018; 105: 991-1000
19 Yu M, Liu JX, Li L, Xu HY, Xing YY, Zhao YL, Yu ZG. Pharmacokinetic parameters of three active ingredients hederacoside C, hederacoside D, and α-hederin in Hedera helix in rats. J Sep Sci 2016; 39: 3292-3301
20 Li K, Tang Y, Fawcett JP, Gu J, Zhong D. Characterization of the pharmacokinetics of dioscin in rat. Steroids 2005; 70: 525-530
21 Hu XJ, Xu XB, Gong MH, Zheng YL, Wu GL, Shentu JZ, Zhang L. Development and validation of liquid chromatography-tandem mass spectrometry method for quantification of a potential anticancer triterpene saponin from seeds of Nigella glandulifera in rat plasma: application to a pharmacokinetic study. J Chromatogr B 2014; 967: 156-161
22 Yu K, Chen F, Li C. Absorption, disposition, and pharmacokinetics of saponins from Chinese medicinal herbs: what do we know and what do we need to know more?. Curr Drug Metab 2012; 13: 577-598
23 Lin MH, Lv D, Zheng YL, Zhang Q, Wu LH. Downregulation of CPT2 promotes tumorigenesis and chemoresistance to cisplatin in hepatocellular carcinoma. Onco Targets Ther 2018; 11: 3101-3110

Supplementary Material

Supporting Information