The Methanolic Extract of Shirazi Thyme (Zataria Multiflora) and Its Combination with Arsenic Trioxide (Ato) Changes the Expression of Onco-Mirnas and Ts-Mirnas in Acute Promyelocytic Leukemia Cell Line (Nb4)

Mahsa Asghari.1 Ali Afgar.2 Hajar Mardani Valandani.1 Amir Mohammad Zahedi.1,3 Alireza Farsinejad.1,3 Mohsen Ehsan.1 Roohollah Mirzaee Khalilabadi.1

.1Department of Hematology and Medical Laboratory Science, Faculty of Allied Medicine, Kerman University of Medical Sciences, Kerman, Iran

.2Research Center for Hydatid Disease in Iran, School of Medicine, Kerman University of Medical Sciences, Kerman, Iran

.3Cell Therapy and Regenerative Medicine Comprehensive Center, Kerman University of Medical Sciences, Kerman, Iran

Correspondence: Roohollah Mirzaee Khalilabadi. Associate Professor, Department of Hematology and Medical Laboratory Sciences, Faculty of Allied Medicine, Kerman University of Medical Sciences, Kerman, Iran.

Received: November 20, 2024 Published: February 20, 2025

Citation: Roohollah MK, The Methanolic Extract of Shirazi Thyme (Zataria Multiflora) and Its Combination with Arsenic Trioxide (Ato) Changes the Expression of Onco-Mirnas and Ts-Mirnas in Acute Promyelocytic Leukemia Cell Line (Nb4). AOJ Emerg and Int Med. 2026;1(4):85–97.

Copyright: ©2025 Roohollah MK. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and build upon your work non-commercially.

Abstract

Acute promyelocytic leukemia (APL) is responsible for 10–15% of new AML cases. ATO is often used for recurrence after ATRA treatment but may cause complications. MicroRNAs (miRNAs) are crucial in various cancers. Zataria Multiflora (Shirazi thyme) is a medicinal plant that promotes apoptosis. This study investigates the effects of thyme's methanol extract and its combination with ATO on onco-MiRs and TS-MiRs in the NB4 cell line. Cell viability and metabolic activity of NB4 cells were assessed via trypan blue dye exclusion test and MTT assay. Cell apoptosis rate was evaluated using flow cytometry, and changes in the expression of miRNAs 19a-3p, 23a-5p, 181b-5p, 3156-5p, and 4498 were analyzed through real-time PCR. Finally, docking was performed using MVD and HDOCK software. Combining ATO 0.25 µM with 20 µg/ml of Shirazi thyme extract significantly reduced cell viability, metabolic activity, and gene expression (except 181b-5p), while increasing apoptosis rates compared to individual treatments. These findings indicate that Zataria Multiflora can act as a synergistic adjuvant with ATO and, in some cases, produce superior effects compared to high doses of ATO alone. Docking results confirmed thymol and carvacrol as the potential compounds in the apoptotic effect of ZME.

Keywords: Zataria Multiflora, arsenic trioxide, microRNA, acute promyelocytic leukemia

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