Abstract
The Zingiber zerumbet rhizomes are traditionally used to treat fever, and the in vitro inhibitory effect of ethyl acetate extract from Zingiber zerumbet rhizomes (EAEZZR) against DENV2 NS2B/NS3 (two non-structural proteins, NS2 and NS3 of dengue virus type 2) has been reported earlier. This study was carried out to establish an acute toxicity profile and evaluate the anti-fever (anti-pyretic) activities of EAEZZR in yeast-induced fever in rats. The major compound of EAEZZR, zerumbone, was isolated using chromatographic methods including column chromatography (CC) and preparative thin-layer chromatography (PTLC). Additionally, the structure of zerumbone was elucidated using nuclear magnetic resonance (NMR), liquid chromatography mass spectrometer-ion trap-time of flight (LCMS-IT-TOF), infrared (IR), and ultraviolet (UV) spectroscopy. The toxicity of EAEZZR was evaluated using Organization for Economic Cooperation and Development Test Guideline 425 (OECD tg-425) with minor modifications at concentrations EAEZZR of 2000 mg/kg, 3000 mg/kg, and 5000 mg/kg. Anti-fever effect was determined by yeast-induced fever (pyrexia) in rats. The acute toxicity study showed that EAEZZR is safe at the highest 5000 mg/kg body weight dose in Sprague Dawley rats. Rats treated with EAEZZR at doses of 125, 250, and 500 mg/kg exhibited a significant reduction in rectal temperature (TR) in the first 1 h. EAEZZR at the lower dose of 125 mg/kg showed substantial potency against yeast-induced fever for up to 2 h compared to 0 h in controls. A significant reduction of TR was observed in rats treated with standard drug aspirin in the third through fourth hours. Based on the present findings, ethyl acetate extract of Zingiber zerumbet rhizomes could be considered safe up to the dose of 5000 mg/kg, and the identification of active ingredients of Zingiber zerumbet rhizomes may allow their use in the treatment of fever with dengue virus infection.
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Data availability
The supporting materials can be obtained upon request via email to the corresponding author.
Abbreviations
- ASA:
-
Aspirin
- CO2 :
-
Carbon dioxide
- HPLC:
-
High-performance liquid chromatography
- IR:
-
Infrared
- LCMS:
-
Liquid chromatography mass spectrometry
- MeOH:
-
Methanol
- NMR:
-
Nuclear magnetic resonance
- NSAIDs:
-
Non-steroidal anti-inflammatory drugs
- PGE2 :
-
Prostaglandin E2
- SD:
-
Standard deviation
- EAEZZR:
-
Ethyl acetate extract of Zingiber zerumbet
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Acknowledgements
The authors thank Mr. Teo Eng Leong, Mr. Rafly Syamsir, and Mr. Din Mohd Noor for the identification of sample material and the sample preparation for this study. The authors also acknowledge Assoc. Prof. Dr. Jamaludin Mohamad for his kind advice and guidance in toxicity and anti-pyretic studies.
Funding
This work was supported by the Ministry of Education Malaysia (TRGS/1/2014/UM/01/2/2), Universiti Sains Islam Malaysia (PPP/UCG-0116/FPQS/30/14316), and Universiti Malaya (PG101-2016A).
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HMS and KA participated in research design and interpretation data. HMS, SYL, SLC, and AA conducted the experimental works, performed the statistical analysis, and drafted the manuscript. HH, NT, NF, HAW, MAO, SYL, and KA participated in edited and revised the manuscript. All authors read and approved the final manuscript.
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The ethical standards for animal care in this study was approved by Faculty of Medicine Institutional Animal Care and Use Committee, Universiti Malaya with the reference number 2017–180309/IBS/R/AAB.
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Mohd Salleh, H., Ablat, A., Chong, SL. et al. The protective effects of Zingiber zerumbet rhizome against fevers in rats. Sci Nat 111, 20 (2024). https://doi.org/10.1007/s00114-024-01907-7
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DOI: https://doi.org/10.1007/s00114-024-01907-7