Analysis of Peganum harmala, Melia azedarach and Morus alba extracts against six lethal human cancer cells and oxidative stress along with chemical characterization through advance Fourier Transform and Nuclear Magnetic Resonance spectroscopic methods towards green chemotherapeutic agents

Huma Mehreen Sadaf; Yamin Bibi; Muhammad Arshad; Abdul Razzaq; Shakil Ahmad; Marcello Iriti; Abdul Qayyum

doi:10.1016/j.jsps.2021.04.016

Analysis of Peganum harmala, Melia azedarach and Morus alba extracts against six lethal human cancer cells and oxidative stress along with chemical characterization through advance Fourier Transform and Nuclear Magnetic Resonance spectroscopic methods towards green chemotherapeutic agents

Saudi Pharm J. 2021 Jun;29(6):552-565. doi: 10.1016/j.jsps.2021.04.016. Epub 2021 Apr 23.

Authors

Huma Mehreen Sadaf¹, Yamin Bibi¹, Muhammad Arshad¹, Abdul Razzaq², Shakil Ahmad³, Marcello Iriti⁴, Abdul Qayyum⁵

Affiliations

¹ Department of Botany, Pir Mehr Ali Shah-Arid Agriculture University Rawalpindi, 46300, Pakistan.
² Department of Agronomy, Pir Mehr Ali Shah-Arid Agriculture University Rawalpindi, 46300, Pakistan.
³ Central Library, Prince Sultan University, Riyadh, Saudi Arabia.
⁴ Department of Agricultural and Environmental Sciences, Milan State University, via G. Celoria 2, 20133 Milan, Italy.
⁵ Department of Agronomy, The University of Haripur, 22620, Pakistan.

Abstract

Traditional medicines implicate consumption of plant crude extracts, which may consist of extensive phytochemical diversity. Overall, the most biologically active extract of Peganum harmala (seeds) exhibited significant cytotoxic activity on Artemia salina with LC₅₀ value of 61.547 µg/mL, while P. harmala (roots) [LC₅₀ = 124.229 µg/mL] and M. azedarach (fruits) [LC₅₀ = 147.813 µg/mL] showed moderate cytotoxic potential. P. harmala (seeds) extract also showed the maximum antitumor potential with 52.278 µg/mL LC₅₀. Branches of P. harmala and Morus alba were not active in both bioassays. These outcomes were further reinforced by the levels of phenolics and flavonoids checked against gallic acid and quercetin equivalents, respectively, by standard curves. Current study aims to isolate, structurally characterize and analyze the bioactive compound from plant extracts by using chromatographic and spectrophotometric techniques. Bioactivity guided isolation of extracts led to the isolation of PH-HM-16 from ethyl acetate fraction P. harmala seeds. Chemical structure of PH-HM-16 was elucidated by ESI-MS, ¹H NMR, ¹³C NMR, HSQC and IR spectrum. The results demonstrated significant positive anticancer activities against six human cancer cell lines assessed through MTT cancer cell growth inhibition assay. PH-HM-16 was most effective against prostate cancer cell lines [IC₅₀ = 17.63 µg/mL] followed by breast cancer cell line MCF7 [IC₅₀ value of 41.81 µg/mL]. IC₅₀ value of PH-HM-16 against human myeloid leukemia cell line HL-60 and human colorectal tumor cells HCT-116 was observed as 68.77 µg/mL and 71.54 µg/mL respectively. The IC 50 value of PH-HM-16 compound was not significant against human gastric cancer SGC-7901 (111.89 µg/mL) and human lung adenocarcinoma epithelial cell line A549 (176.04 µg/mL). Isolated bioactive metabolite PH-HM-16 possesses significant antitumor potential so this could be the first step to develop an effective anticancer agent. Hence, this compound represents a promising potential to be chemically standardized or developed into pharmaceuticals for the chemoprevention and/or the treatment of certain types of cancer, especially as adjuvant phytotherapeutics in conventional chemotherapy.

Keywords: Anticancer; Flavonoids; Melia azedarach; Phenolics; Phytochemicals.