Hepatotoxic components in Psoraleae Fructus based on high-content screening technology

doi:10.19803/j.1672-8629.20230656

Abstract

Abstract: Objective To screen the potential hepatotoxic components in Psoraleae Fructus and explore the possible mechanisms using high-content screening technology. Methods The IC₅₀ values of ten components in Psoraleae Fructus, including isobavachin, bavachinin, bavachin, isobavachalcone, 4’-O-methyl- bavachalcone, corylin, psoralen, ispsoralen, psoralidin, and bakuchiol were determined by CCK-8 cell viability assays. After treating HepG 2 cells with the same concentration of individual drug for 24 h, high-content screening was performed. The potential hepatotoxic components were revealed by evaluating the average fluorescence intensity of positive cells of four indicators, including reactive oxygen species, reduced glutathione, mitochondrial membrane potential and mitochondrial superoxide. Results CCK-8 cell viability assays showed that the IC₅₀ values of isobavachin, bavachinin, bavachin, isobavachalcone, 4’-O-methyl-bavachalcone, corylin, ispsoralen, psoralidin, and bakuchiol were 52.69, 42.72, 83.63, 42.29, 57.43, 110.80, 1 420.00, 23.58 and 25.34 μmol·L^-1, respectively. The high-content screening analysis showed that bavachinin, bavachin, isobavachalcone, psoralidin and bakuchiol could significantly increase the level of reactive oxygen species at the same concentration of 20 μmol·L^-1; Isobavachalcone, 4’-O-methyl-bavachalcone, corylin, ispsoralen, psoralidin, bakuchiol can lead to a protective increase in the level of reduced glutathione; Additionally, isobavachalcone, psoralidin and bakuchiol could prominently decrease the level of mitochondrial membrane potential and promoted the accumulation of mitochondrial superoxide. Conclusion Isobavachalcone, psoralidin and bakuchiol were the main mitotoxic components in Psoraleae Fructus, which promoted Psoraleae Fructus-induced liver injuries. The specific mechanisms of the three components remains to be investigated in the future.

Key words: Psoraleae Fructus, isobavachalcone, psoralidin, bakuchiol, hepatotoxicity, high-content screening, mitochondrial membrane potential, mitochondrial superoxide

CLC Number:

R978
R994.1

SHANG Huiying, WEI Xue, CHENG Hongbo, MA Zengchun, TU Bodan, XIAO Chengrong, LIU Xian, GAO Yue. Hepatotoxic components in Psoraleae Fructus based on high-content screening technology[J]. Chinese Journal of Pharmacovigilance, 2024, 21(1): 74-82.

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References

[1] LIU XQ, ZHAO BL, QIAN F, et al.Research on the historical evolution of the processing of psoralea[J]. Chinese Journal of Ethnomedicine and Ethnopharmacy(中国民族民间医药), 2022, 31(19): 29-36.
[2] ZHANG JQ, QU XL, YIN J.Research progress on liver injury caused by psoralen[J]. Shandong Journal of Traditional Chinese Medicine(山东中医杂志), 2022, 41(5): 576-582.
[3] REN YL, SONG XMT, TAN L, et al.A review of the pharmacological properties of psoralen[J]. Front Pharmacol, 2020, 11: 571535.
[4] CHEN LL, CHEN SG, SUN P, et al.Psoralea corylifolia L.: a comprehensive review of its botany, traditional uses, phytochemistry, pharmacology, toxicology, quality control and pharmacokinetics[J]. Chin Med, 2023, 18(1): 4.
[5] KATAREY D, VERMA S.Drug-induced liver injury[J]. Clin Med(Lond), 2016, 16(Suppl 6): s104-s109.
[6] WANG YF, WU B, YANG J, et al.A rapid method for the analysis of ten compounds in psoraleacorylifolia,L.by UPLC[J]. Chromatographia, 2009, 70(1-2): 199-204.
[7] TAN GG, YANG TH, MIAO HY, et al.Characterization of compounds in psoralea corylifolia using high-performance liquid chromatography diode array detection, time-of-flight mass spectrometry and quadrupole ion trap mass spectrometry[J]. J Chromatogr Sci, 2015, 53(9): 1455-1462.
[8] CHOI YH, YON GH, HONG KS, et al.In vitro BACE-1 inhibitory phenolic components from the seeds of psoralea corylifolia[J]. Planta Med, 2008, 74(11): 1405-1408.
[9] CHEN XX.Preliminary study on resource utilization of psoralen residue[D]. Zhengzhou: Henan University, 2016.
[10] LIN YL, KUO YH.Two new benzofuranderivatives, corylifonol and isocorylifonol from the seeds of Psoralea corylifolia[J]. Heterocycles, 1992, 34(8): 1555-1564.
[11] QIAO CF, HAN QB, MO SF, et al.Psoralenosideand isopsoralenoside, two new benzofuran glycosides from psoralea corylifolia[J]. Chemical & Pharmaceutical Bulletin, 2006, 54(4): 714-716.
[12] WANG J, ZHOU ZX, YANG L, et al.Establishment of UPLC fingerprint and determination of 12 Main components of psoralea[J]. Chinese Herbal Medicine(中草药), 2021, 52(2): 552-557.
[13] LI XY, WANG J, CHEN SK, et al. Progress in the application of high content screening technology in the study of the mechanism of action and material basis of traditional Chinese medicine[J]. Pharmacology and Clinics of Chinese Materia Medica(中药药理与临床),(2023-04-27)[2023-10-17]https://kns.cnki.net/kcms/detail/51.1188.R.20230427.0856.002.html.
[14] MA Z, ZHAO JR, DONG RR, et al.Study on the hepatotoxicity of polygonum multiflorum extract and its main components based on high content analysis technology[J]. Chinese Herbal Medicine(中草药), 2016, 47(22): 4021-4029.
[15] YU X, MA Z, WANG M.Screening and evaluation of hepatotoxicity of various traditional Chinese medicine components based on high content cell image analysis system[J]. Chinese Patent Drug(中成药), 2021, 43(4): 1046-1052.
[16] XIAO Z.Study on the methodology of screening high-content hepatotoxicity and its application in traditional Chinese medicine injection[D]. Beijing: Beijing University of Traditional Chinese Medicine(北京中医药大学), 2017.
[17] DENG Y, NGO DTM, HOLIEN JK, et al.Mitochondrial dynamin-related protein drp1: a new player in cardio-oncology[J]. Curr Oncol Rep, 2022, 24(12): 1751-1763.
[18] XIN ZL, WU X, JI T, et al.Bakuchiol: a newly discovered warrior against organ damage[J]. Pharmacol Res, 2019, 141: 208-213.
[19] OUYANG LQ, FAN ZQ, HE Y, et al.4-hydroxylonchocarpin and corylifol A: the potential hepatotoxic components of psoralea corylifolia L[J]. Toxicol Lett, 2023, 385: 31-41.
[20] GAO C, LIU C, WEI YY, et al.The acute oral toxicity test of ethanol extract of salt-processed psoraleae fructus and its acute hepatotoxicity and nephrotoxicity risk assessment[J]. J Ethnopharmacol, 2023, 309: 116334.
[21] WANG S, WANG M, WANG M, et al.Bavachinin induces oxidative damage in HepaRG cells through p38/JNK MAPK pathways[J]. Toxins(Basel), 2018, 10(4): 154.
[22] YU RL, YU YL, SU SJ, et al.Psoralen induces liver injuries through endoplasmic reticulum stress signaling in female mice[J]. Drug Chem Toxicol, 2022, 45(4): 1818-1824.
[23] LI LD, WANG DF, WU GY.Research progress on target sites for reactive oxygen species production in mitochondria[J]. Life Sciences(生命科学研究), 2015, 19(6): 530-535.
[24] CARINCI M, VEZZANI B, PATERGNANI S, et al.Different roles of mitochondria in cell death and inflammation: focusing on mitochondrial quality control in ischemic stroke and reperfusion[J]. Biomedicines, 2021, 9(2): 169.
[25] FU Q, HUANG X, SHU B, et al.Inhibition of mitochondrial respiratory chain is involved in triptolide-induced liver injury[J]. Fitoterapia, 2011, 82(8): 1241-1248.
[26] National Medical Products Administration. National medical products administration has drawn attention to the drug risks of Xianling Gubao oral preparation[EB/OL].(2016-12-08)[2023-10-17]. https://www.nmpa.gov.cn/directory/web/nmpa/xxgk/yjjsh/ypblfytb/20161208170501622. html.
[27] XIANG L, SHAO Y, CHEN YP.Mitochondrial dysfunction and mitochondrion-targeted therapeutics in liver diseases[J]. J Drug Target, 2021, 29(10): 1080-1093.
[28] GUO ZJ, LI P, WANG CG, et al.Five constituents contributed to the psoraleae fructus-induced hepatotoxicity via mitochondrial dysfunction and apoptosis[J]. Front Pharmacol, 2021, 12: 682823.
[29] YANG CQ, LIAN WY, LIN Y, et al.In vitro toxicity screening and mechanism exploration of alkaloid components in Zuojin Wan based on HK-2 cells[J]. Chinese Pharmacological Bulletin(中国药理学通报), 2022, 38(1): 110-118.
[30] LAN J, WEN HR, HUANG ZY, et al.Study on the cytotoxicity of anthraquinone monomers in polygonum multiflorum to HK-2 cells[J]. Chinese Journal of Pharmacovigilance(中国药物警戒), 2023, 20(6): 616-622.
[31] ZHAO L, YU YL, LI L, et al.Isobavachalcone disrupts mitochondrial respiration and induces cytotoxicity through ROS accumulation and Akt suppression[J]. Toxicon, 2022(216): 28-36.
[32] WANG Y, XU G, WANG ZL, et al.Psoralidin, a major component of psoraleae fructus, induces inflammasome activation and idiosyncratic liver injury[J]. Int Immunopharmacol, 2021, 92: 107352.
[33] LIU TT, XU G, LI YR, et al.Discovery of bakuchiol as an AIM2 inflammasome activator and cause of hepatotoxicity[J]. J Ethnopharmacol, 2022, 298: 115593.