Eriobotrya japonica Water Extract Characterization: An Inducer of Interferon-Gamma Production Mainly by the JAK-STAT Pathway.
Eriobotrya japonica (Thunb.) Lindl. (Loquat) (EJ) has been used as a medicinal plant to treat chronic bronchitis, coughs, phlegm, high fever and gastro-enteric disorders. Since the traditional use of EJ is related to modulating inflammation processes, our earlier studies on EJ leaves were performed on the water extract to investigate specific cytokines' modulation. These earlier studies, however, have shown that EJ leaf water extract (WE) and the water phase (WP) induce cytokines' production in in vitro and in vivo models. Therefore, the aim of this study was to specify the group(s) of compounds in EJ leaves that have this immunomodulatory activity and their mechanism of action. WE was obtained from boiling the leaves followed by butanol extraction, yielding a butanol-water phase (WP). WP was then subjected to methanol:acetone fractionation, yielding upper (MAU) and lower (MAL) phases. For further fractionation, MAU was subjected to column chromatography followed by elution with ethanol:water (EW), methanol:ethanol (ME) and, lastly, acetone:water (AW), respectively, to reveal three sub-fractions; MAU-EW, MAU-ME and MAU-AW. MAU-AW significantly increased IFN-γ production from unstimulated and stimulated mouse spleen cells, as well as CD3+ T cells and natural killer cells. Furthermore, the fold increase of IFN-γ production by MAU-AW was concentration dependent, higher than the parent extract or any of the other sub-fractions, and such an IFN-γ increase was reversed by two JAK-STAT inhibitors. In addition, MALDI-TOF-MS analysis of the extracts and sub-fractions showed compounds with molecular weights of >500 Daltons. The MAU-AW sub-fraction contained more polar compounds, such as flavonol and caffeic glycosides. In conclusion, these polar compounds in the EJ extract are responsible for inducing IFN-γ production. Further chemical elucidation is warranted to lead to a specific IFN-γ inducer and an immunomodulator in polarizing immune cells and balancing immune responses in certain diseases.
Department of Pharmacology and Biomedical Sciences, Faculty of Pharmacy and Medical Sciences, University of Petra, Amman 11196, Jordan. k.matalka@aum.edu.jo.|Petra University Pharmaceutical Center (PUPC), University of Petra, Amman 11196, Jordan. k.matalka@aum.edu.jo.
Khalid Z
KZ
Matalka
Department of Pharmacology and Biomedical Sciences, Faculty of Pharmacy and Medical Sciences, University of Petra, Amman 11196, Jordan. nido892@yahoo.com.
Nada A
NA
Abdulridha
Department of Pharmacology and Biomedical Sciences, Faculty of Pharmacy and Medical Sciences, University of Petra, Amman 11196, Jordan. mujtabambadr@gmail.com.|Petra University Pharmaceutical Center (PUPC), University of Petra, Amman 11196, Jordan. mujtabambadr@gmail.com.
Mujtaba M
MM
Badr
Department of Pharmaceutical Medicinal Chemistry and Pharmacognosy, Faculty of Pharmacy and Medical Sciences, University of Petra, Amman 11196, Jordan. kmansoor@uop.edu.jo.
Kenza
K
Mansoor
Department of Pharmacology and Biomedical Sciences, Faculty of Pharmacy and Medical Sciences, University of Petra, Amman 11196, Jordan. nqinna@uop.edu.jo.|Petra University Pharmaceutical Center (PUPC), University of Petra, Amman 11196, Jordan. nqinna@uop.edu.jo.
Nidal A
NA
Qinna
Eusano GmbH &amp; Co., Tussenhausen 86874, Germany. fqadan@googlemail.com.
Fadi
F
Qadan
D000818:Animals; D002845:Chromatography; D031983:Eriobotrya / Q000737:chemistry*; D005419:Flavonoids / Q000008:administration & dosage / Q000737:chemistry / Q000302:isolation & purification; D006027:Glycosides / Q000008:administration & dosage / Q000737:chemistry / Q000302:isolation & purification; D007155:Immunologic Factors / Q000008:administration & dosage* / Q000737:chemistry; D007371:Interferon-gamma / Q000096:biosynthesis; D053612:Janus Kinases / Q000096:biosynthesis; D007694:Killer Cells, Natural / Q000187:drug effects* / Q000276:immunology; D051379:Mice; D010936:Plant Extracts / Q000008:administration & dosage* / Q000737:chemistry; D018515:Plant Leaves / Q000737:chemistry; D050791:STAT Transcription Factors / Q000096:biosynthesis; D015398:Signal Transduction / Q000187:drug effects; D013154:Spleen / Q000187:drug effects / Q000276:immunology; D014867:Water / Q000737:chemistry
D005419:Flavonoids; D006027:Glycosides; D007155:Immunologic Factors; D010936:Plant Extracts; D050791:STAT Transcription Factors; D014867:Water; D007371:Interferon-gamma; D053612:Janus Kinases; C041477:3-hydroxyflavone
Eriobotrya japonica; IFN-γ; IL-12; JAK-STAT; MALDI-TOF; MCA fibrosarcoma; immunomodulator