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Antioxidants (Basel). 2019 Sep 19;8(9). pii: E415. doi: 10.3390/antiox8090415.

Chemical Profiling of Polyphenolics in Eucalyptus globulus and Evaluation of Its Hepato-Renal Protective Potential Against Cyclophosphamide Induced Toxicity in Mice.

Author information

1
Medicinal Chemistry Department, Theodor Bilharz Research Institute, Kornaish El Nile, Warrak El-Hadar, Imbaba (P.O. 30), Giza 12411, Egypt. m.ghareeb@tbri.gov.eg.
2
Institute of Pharmacy and Molecular Biotechnology, Heidelberg University, 44883-2462 Heidelberg, Germany. sobeh@uni-heidelberg.de.
3
AgroBioSciences Research Division, Mohammed VI Polytechnic University, Lot 660-Hay MoulayRachid, 43150 Ben-Guerir, Morocco. sobeh@uni-heidelberg.de.
4
Pharmacology Department, Theodor Bilharz Research Institute, Kornaish El Nile, Warrak El-Hadar, Imbaba (P.O. 30), Giza 12411, Egypt. w.elmadawy@tbri.gov.eg.
5
Department of Pharmacognosy, Faculty of Pharmacy (Girls), Al-Azhar University, Cairo 11311, Egypt. halash1977@hotmail.com.
6
Pathology Department, Theodor Bilharz Research Institute, Kornaish El Nile, Warrak El-Hadar, Imbaba (P.O. 30), Giza 12411, Egypt. Seif200731@gmail.com.
7
Pharmacology Department, Theodor Bilharz Research Institute, Kornaish El Nile, Warrak El-Hadar, Imbaba (P.O. 30), Giza 12411, Egypt. s.botros@tbri.gov.eg.
8
Institute of Pharmacy and Molecular Biotechnology, Heidelberg University, 44883-2462 Heidelberg, Germany. wink@uni-heidelberg.de.

Abstract

Cyclophosphamide (CP) is a potent anti-neoplastic and immunosuppressive agent; however, it causes multi-organ toxicity. We elucidated the protective activities of Eucalyptus globulus (EG) leaf extract against CP-induced hepato-renal toxicity. Mice were treated with EG for 15 days plus CP on day 12 and 13 of the experiment. Using HPLC-DAD-ESI-MS/MS, 26 secondary metabolites were identified in EG leaf extract. Out of them, 4 polyphenolic compounds were isolated: (1) 4-(O-β-d-xylopyranosyloxy)-3,5-di-hydroxy-benzoic acid, (2) 4-(O-α-l-rhamnopyranosyloxy)-3,5-di-hydroxy-benzoic acid, (3) gallic acid, and (4) methyl gallate. Effects of EG extract on biochemical parameters, gene expression, and immune-histopathological changes were assessed in comparison to mesna positive control. Results showed that EG improved CP-increased serum ALT, AST, creatinine, and blood urea nitrogen levels. The hepatic and renal tissue levels of MDA, nitric oxide, protein carbonyl, TNF-α, IL-6, and immunohistochemical expression of nuclear factor kappa-B (NF-kB) and caspase-3 were reduced. Also, hepatic and renal GSH contents, and nuclear factor E2-related factor 2 (NRf2)/ hemoxygenase-1 (HO-1) signaling levels were increased. Histopathological findings supported our findings where hepatic and renal architecture were almost restored. Results revealed the protective effects of EG against CP-induced hepato-renal toxicity. These effects may be related to EG antioxidant, anti-inflammatory, and anti-apoptotic properties coupled with activation of Nrf2/HO-1 signaling.

KEYWORDS:

Eucalyptus globulus; Nrf2/HO-1 signaling; anti-inflammatory; antioxidant; cyclophosphamide; hepatotoxicity; nephrotoxicity; polyphenolics

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