MODULATION OF MITOCHONDRIAL MEDIATED APOPTOSIS BY SOLVENT FRACTIONS OF THE FRUIT EXTRACTS OF SARCOCEPHALUS LATIFOLIUS (SMITH) BRUCE

Background and aims: The mitochondrial membrane permeability transition (mPT) pore is a critical event exploited in situations where apoptosis is dysregulated. Bioactive agents of plant origin induce mitochondrial-mediated apoptosis via the opening of the mitochondrial outer membrane permeabilization (MOMP). The fruit of Sarcocephalus latifolius is used in folklore medicine for the treatment of tumors and cancer. However, this claim has not been scientifically substantiated. Methods: In this study, we investigated the inductive effect of the crude methanol extract (CMESL) and a chloroform sub fraction (sCFSL) of Sarcocephalus latifolius fruits on mPT, in vivo. Thirty-five male wistar rats (90 ± 10 g) were acclimatized, divided into seven groups, and treated with 1% DMSO (control) and 25, 50, and 100 mg/kgbw of each of the fractions for thirty days. Rats were sacrificed and liver mitochondria were isolated by differential centrifugation. The MOMP, DNA fragmentation, p53, Bax and BCl-2 protein expressions, Cytochrome c release, and caspase – 3 and -9 activities were assayed in liver tissue by standard methods. CMESL and sCFSL induced mPT pore. Results: The sCFSL induced MOMP maximally at 100 mg/kgbw, inhibited LPO (78%), enhanced mitochondrial ATPase activity (27.96± 0.04 µmole/mg Protein/min) than CMESL (17.58± 0.03 µmole/mg Protein/min) at the same dose. Similarly, sCFSL caused DNA fragmentation; (77.33%), enhanced caspases -3 and -9 activation; increased p53 and Bax expression levels, increased Cytochrome c release, and downregulated BCl-2 protein expression, compared to CMESL. Conclusion: These findings showed that sCFSL contains bioactive agents that can induce mitochondrial-mediated apoptosis, and therefore a potential target to be explored in the management of tumors and cancer. Peer Review History: Received 12 July 2024; Reviewed 19 September 2024; Accepted 24 October; Available online 15 November 2024 Academic Editor: Dr. Iman Muhammad Higazy, National Research Center, Egypt, [email protected] Average Peer review marks at initial stage: 6.5/10 Average Peer review marks at publication stage: 7.5/10 Reviewers: Dr. Sangeetha Arullappan, Universiti Tunku Abdul Rahman, Malaysia, [email protected] Dr. Nazim Hussain, North East Frontier Technical University, Arunachal pradesh, India, [email protected]