The Effect of Alhagi maurorum Medik on Mitochondrial Function

Mitochondrial bioenergetics are crucial for the optimal activity of the cell and are emerging therapeutic targets for the treatment of several metabolic syndromes and cancer. Alhagi maurorum plant is traditionally used in several clinical conditions due to its potential anti-inflammatory, hepatoprotective and gastrointestinal effects. In this study changes in cell viability, reactive oxygen species (ROS) levels, mitochondrial membrane potential (MMP), oxidative phosphorylation (OXPHOS), calcium homeostasis and mitochondrial morphology in MCF-7 and MCF-10-A (control) cells after treatment with Alhagi maurorum for 24hr and its main bioactive compound hordenine for 6hr, 24hr, and 48hr are observed. Results indicate that cells treated with Alhagi maurorum have significantly reduced cell viability, ROS levels, MMP, and intracellular calcium concentrations at higher concentrations that suggest cytotoxic effects, while moderately reduced effects at 100 µg/ml, indicating possible stimulation of several other cellular processes such as cell death, antioxidant systems, and immune responses. Furthermore, Alhagi maurorum extract modulated various parameters of mitochondrial respiration too including, basal respiration, ATP production, proton leak, spare respiratory capacity, maximal respiration, and non-mitochondrial respiration. In the cells treated with hordenine, the key bioactive compound of Alhagi maurorum, results indicate that hordenine has no significant effect on MCF-7 and MCF-10-A after 24hr and 48hr of exposure, including cell viability, ROS levels, MMP, intracellular calcium concentrations and mitochondrial respiration. However, in MCF-10-A after 6hr of the treatment ROS levels are significantly reduced at concentrations 0.1 µM, 10 µM, 500 µM, and 1000 µM. Furthermore, no significant changes to mitochondrial morphology are observed at lower concentrations of Alhagi maurorum and hordenine tested in MCF-7 and MCF-10-A, though only small, rounded networks of mitochondria, increased in number in case of hordenine suggest possible occurrence of the process of fission. In conclusion, my work shows that Alhagi maurorum extract modulates mitochondrial function, and effects are concentration-dependent while one of the main bioactive compounds of hordenine phenethylamine alkaloid, has more limited effects. Characterisation of the extract through HPTLC and LC-MS analysis showed presence of more than one compound in the extract.

Name dc:type.qualificationname

Ph.D.

Level dc:type.qualificationlevel

PhD thesis

Grantor dc:publisher.institution

University of Westminster

Year dc:date.issued

2024

Author dc:creator

• Zulfiqar, Juwairiya

Advisors dc:contributor.advisor

• Booker, A.
• Bell, J.D.
• Heinrich, P.M.

Identifier

oai:westminsterresearch.westminster.ac.uk:w85z1

OAI identifier oai:identifier

oai:westminsterresearch.westminster.ac.uk:w85z1