a Department of Pharmaceutical Biology, Institute of Pharmacy and Biochemistry, Johannes Gutenberg University, Staudinger Weg 5, Mainz, Germany
b Institut für Biotechnologie und Wirkstoff Forschung GGmbH, Erwin-Schrödinger-Straße 56, Kaiserslautern, Germany
c Department of Pharmacognosy, University of Khartoum, Khartoum, Sudan
b Institut für Biotechnologie und Wirkstoff Forschung GGmbH, Erwin-Schrödinger-Straße 56, Kaiserslautern, Germany
c Department of Pharmacognosy, University of Khartoum, Khartoum, Sudan
Abstract
Background Ziziphus spina-christi (L.) Desf. (Christ's Thorn Jujube) is a wild tree today found in Jordan, Israel, Egypt, and some parts of Africa, which was already in use as a medicinal plant in Ancient Egypt. In ancient Egyptian prescriptions, it was used in remedies against swellings, pain, and heat, and thus should have anti-inflammatory effects. Nowadays, Z. spina-christi, is used in Egypt (by Bedouins, and Nubians), the Arabian Peninsula, Jordan, Iraq, and Morocco against a wide range of illnesses, most of them associated with inflammation. Pharmacological research undertaken to date suggests that it possesses anti-inflammatory, hypoglycemic, hypotensive and anti-microbial effects. The transcription factor NF-κB (nuclear factor kappa-light-chain-enhancer of activated B cells) is critical in inflammation, proliferation and involved in various types of cancer. Identification of new anti-inflammatory compounds might be an effective strategy to target inflammatory disorders and cancer. Therefore, extracts from Z. spina-christi are investigated in terms of their anti-inflammatory effects. We evaluate ancient Egyptian prescriptions to identify new anti-inflammatory compounds from Z. spina-christi. Furthermore, we determine the active ingredients in crude extracts for their inhibitory activity toward NF-κB pathway. Materials and methods To determine the active ingredients of Z. spina-christi, we fractionated the extracts for bioassays and identified the active compounds. Epigallocatechin, gallocatechin, spinosin, 6''' feruloylspinosin and 6''' sinapoylspinosin and crude extracts of seed, leaf, root or stem were analyzed for their effect on NF-κB DNA binding by electromobility shift assay (EMSA) and nuclear translocation of NF-κB-p65 by Western blot analysis. The binding mode of the compounds to NF-κB pathway proteins was compared with the known inhibitor, MG-132, by in silico molecular docking calculations. Log10IC50 values of gallocatechin and epigallocatechin as two main compounds of the plant were correlated to the microarray-based mRNA expression of 79 inflammation-related genes in cell lines of the National Cancer Institute (NCI, USA) as determined. The expression of 17 genes significantly correlated to the log10IC50 values for gallocatechin or epigallocatechin. Results Nuclear p65 protein level decreased upon treatment with each extract and compound. Root and seed extracts inhibited NF-κB-DNA binding as shown by EMSA. The compounds showed comparable binding energies and similar docking poses as MG-132 on the target proteins. Conclusion Z. spina-christi might possess anti-inflammatory activity as assumed by ancient Egyptian prescriptions. Five compounds contributed to this bioactivity, i.e. epigallocatechin, gallocatechin, spinosin, 6''' feruloylspinosin and 6''' sinapoylspinosin as shown in vitro and in silico. © 2016 Elsevier GmbH. All rights reserved.
Author keywords
Ancient Egyptian medicinal papyri; Ethnopharmacology; Inflammation; Microarray; Molecular docking; Rhamnaceae
ISSN: 09447113 CODEN: PYTOESource Type: Journal Original language: English
DOI: 10.1016/j.phymed.2016.01.004Document Type: Article
Publisher: Elsevier GmbH
Pommerening, T.; Department of Egyptology, Institute of Ancient Studies, Johannes Gutenberg University, Hegelstraße 59, Germany; email:tpommere@uni-mainz.de
© Copyright 2016 Elsevier B.V., All rights reserved.
© Copyright 2016 Elsevier B.V., All rights reserved.