Preprint / Version 1

Comparative LC-ESIMS-Based Metabolite Profiling of Senna italica with Senna alexandrina and Evaluating Their Hepatotoxicity

Authors

  • Elaheh Zibaee Department of Traditional Pharmacy, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad 13131-99137, Iran
  • Maryam Akaberi Department of Pharmacognosy, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad 13131-99137, Iran
  • Zahra Tayarani-Najaran Targeted Drug Delivery Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad 13131-99137, Iran
  • Karel Nesměrák Department of Analytical Chemistry, Faculty of Science, Charles University, 128 43 Prague, Czech Republic
  • Martin Štícha Mass Spectrometry Laboratory, Section of Chemistry, Faculty of Science, Charles University, 128 43 Prague, Czech Republic
  • Naghmeh Shahraki Medical Toxicology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad 13131-99137, Iran
  • Behjat Javadi Department of Traditional Pharmacy, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad 13131-99137, Iran
  • Seyed Emami Department of Traditional Pharmacy, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad 13131-99137, Iran

Keywords:

Senna italica, Senna alexandrina, LC-ESIMS, LC-MS/MS, sennosides, hepatotoxicity

Abstract

Senna Mill. (Fabaceae) is an important medicinal plant distributed worldwide. Senna alexandrina (S. alexandrina), the officinal species of the genus, is one of the most well-known herbal medicines traditionally used to treat constipation and digestive diseases. Senna italica (S. italica), another species of the genus, is native to an area ranging from Africa to the Indian subcontinent, including Iran. In Iran, this plant has been used traditionally as a laxative. However, very little phytochemical information and pharmacological reports investigating its safety of use are available. In the current study, we compared LC-ESIMS metabolite profiles of the methanol extract of S. italica with that of S. alexandrina and measured the content of sennosides A and B as the biomarkers in this genus. By this, we were able to examine the feasibility of using S. italica as a laxative agent like S. alexandrina. In addition, the hepatotoxicity of both species was evaluated against HepG2 cancer cell lines using HPLC-based activity profiling to localize the hepatotoxic components and evaluate their safety of use. Interestingly, the results showed that the phytochemical profiles of the plants were similar but with some differences, particularly in their relative contents. Glycosylated flavonoids, anthraquinones, dianthrones, benzochromenones, and benzophenones constituted the main components in both species. Nevertheless, some differences, particularly in the relative amount of some compounds, were observed. According to the LC-MS results, the amounts of sennoside A in S. alexandrina and S. italica were 1.85 ± 0.095% and 1.00 ± 0.38%, respectively. Moreover, the amounts of sennoside B in S. alexandrina and S. italica were 0.41 ± 0.12 % and 0.32 ± 0.17%, respectively. Furthermore, although both extracts showed significant hepatotoxicity at concentrations of 50 and 100 µg/mL, they were almost non-toxic at lower concentrations. Taken together, according to the results, the metabolite profiles of S. italica and S. alexandrina showed many compounds in common. However, further phytochemical, pharmacological, and clinical studies are necessary to examine the efficacy and safety of S. italica as a laxative agent. Keywords: Senna italica, Senna alexandrina, LC-ESIMS, LC-MS/MS, sennosides, hepatotoxicity

Author Biographies

Elaheh Zibaee, Department of Traditional Pharmacy, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad 13131-99137, Iran

Formal analysis, Data curation, Writing – original draft, Visualization

Maryam Akaberi, Department of Pharmacognosy, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad 13131-99137, Iran

Software, Validation, Formal analysis, Data curation, Writing – review & editing

Martin Štícha, Mass Spectrometry Laboratory, Section of Chemistry, Faculty of Science, Charles University, 128 43 Prague, Czech Republic

Validation, Investigation

Naghmeh Shahraki, Medical Toxicology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad 13131-99137, Iran

Data curation

Behjat Javadi, Department of Traditional Pharmacy, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad 13131-99137, Iran

Resources, Writing – review & editing, Funding acquisition

Seyed Emami, Department of Traditional Pharmacy, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad 13131-99137, Iran

Conceptualization, Writing – review & editing, Supervision, Project administration

Downloads