Ceiba pentandra ethyl acetate extract improves doxorubicin antitumor outcomes against chemically induced liver cancer in rat model: a study supported by UHPLC-Q-TOF-MS/MS identification of the bioactive phytomolecules

Mohamed A A Orabi; Mohamed E Abouelela; Faten M M Darwish; Mohamed S A Abdelkader; Bakheet E M Elsadek; Ahmed Abdullah Al Awadh; Mohammed Merae Alshahrani; Abdulaziz Hassan Alhasaniah; Nayef Aldabaan; Reda A Abdelhamid

doi:10.3389/fphar.2024.1337910

Ceiba pentandra ethyl acetate extract improves doxorubicin antitumor outcomes against chemically induced liver cancer in rat model: a study supported by UHPLC-Q-TOF-MS/MS identification of the bioactive phytomolecules

Front Pharmacol. 2024 Feb 2:15:1337910. doi: 10.3389/fphar.2024.1337910. eCollection 2024.

Affiliations

¹ Department of Pharmacognosy, College of Pharmacy, Najran University, Najran, Saudi Arabia.
² Department of Pharmacognosy, Faculty of Pharmacy (Boys), Al-Azhar University, Cairo, Egypt.
³ Department of Pharmacognosy, Faculty of Pharmacy, Assiut University, Assiut, Egypt.
⁴ Department of Pharmacognosy, Faculty of Pharmacy, Sohag University, Sohag, Egypt.
⁵ Department of Biochemistry and Molecular Biology, Faculty of Pharmacy, Al-Azhar University, Assiut, Egypt.
⁶ Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, Najran University, Najran, Saudi Arabia.
⁷ Department of Pharmacology, College of Pharmacy, Najran University, Najran, Saudi Arabia.
⁸ Department of Pharmacognosy, Faculty of Pharmacy, Al-Azhar University, Assiut, Egypt.

Abstract

Hepatocellular carcinoma (HCC) is a prevalent cancer worldwide. Late-stage detection, ineffective treatments, and tumor recurrence contribute to the low survival rate of the HCC. Conventional chemotherapeutic drugs, like doxorubicin (DOX), are associated with severe side effects, limited effectiveness, and tumor resistance. To improve therapeutic outcomes and minimize these drawbacks, combination therapy with natural drugs is being researched. Herein, we assessed the antitumor efficacy of Ceiba pentandra ethyl acetate extract alone and in combination with DOX against diethylnitrosamine (DENA)-induced HCC in rats. Our in vivo study significantly revealed improvement in the liver-function biochemical markers (ALT, AST, GGT, and ALP), the tumor marker (AFP-L3), and the histopathological features of the treated groups. A UHPLC-Q-TOF-MS/MS analysis of the Ceiba pentandra ethyl acetate extract enabled the identification of fifty phytomolecules. Among these are the dietary flavonoids known to have anticancer, anti-inflammatory, and antioxidant qualities: protocatechuic acid, procyanidin B2, epicatechin, rutin, quercitrin, quercetin, kaempferol, naringenin, and apigenin. Our findings highlight C. pentandra as an affordable source of phytochemicals with possible chemosensitizing effects, which could be an intriguing candidate for the development of liver cancer therapy, particularly in combination with chemotherapeutic drugs.

Keywords: AFP-l3; Ceiba pentandra; UHPLC-Q-ToF-MS/MS; antitumor; dietary flavonoids; doxorubicin; hepatocellular carcinoma; in vivo.

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This research was funded by Deanship of Scientific research, Najran University, Saudi Arabia, under the National Research Priority funding Program (Grant number. NU/NRP/MRC/12/1).