Developing Small Molecule Therapeutics for Inducing Abnormal Cell Apoptosis and Mitigating Chromosomal Aberrations

Background and Objectives: Allicin which is the principal bioactive organosulfur compound of Allium sativum, has witnessed a transition from ethnopharmacological use to modern-day precision medicine. For 5,000 years it has been used as a medicine for inflammatory and reproductive diseases, yet there remains an enormous translational gap between mechanistic evidence from laboratories and use in the clinic. This study assessed the effectiveness of MEnera, an FDA-registered Allicin-based Small-Molecule Therapeutic, in decreasing genomic instability and chromosomal abnormalities. Develop a link between the molecular genoprotective properties of Allicin in wild garlic and the clinical therapeutic effects in reproductive and cancer diseases. Mechanism of Action: Allicin's primary bioactive mechanisms were clinically proven to be an apoptosis-inducing mechanism and a DNA-stabilising mechanism. Allicin induces mitochondrial depolarization and caspase activation that contribute to programmed cell death in malignant and hyperplastic tissues. In particular, the compound opens the mitochondrial permeability transition pore (mPTP) resulting in an apoptosis rate of 50% in malignant cell lines. At the same time, the compound is genoprotective in healthy tissues by activating the NRF2 cellular defense pathway. This mechanism stimulates the movement of NRF2 into the nucleus, leading to a tripling of DNA repair enzymes and antioxidant genes important for keeping up the normal quality of oocyte and protecting from oxidative damage. Methods: The MEnera trial was a controlled clinical trial, stratified by age, with 80 female participants with reproductive disorders, such as Polycystic Ovary Syndrome (PCOS), endometriosis, menorrhagia, and others. To detect large effect sizes with a power of 80% and assurance level of p=0.05, the trial has used a sample size of n=80. The 40 participants were divided into two groups, A (21-40 years) and B (41-65 years) and C group was given placebo (n=40). Over a 90-day period, the treatment groups received stabilized Allicin-based small-molecule therapy (150 mg) twice daily. The study’s primary ends included menstrual regularity, the biomarker (8- OHdG) in follicular fluid and genomic stability, as assessed by micronuclei in PBMCs. Results: Based on the age at which they were treated, the trial had a good outcome. In Group A, pregnancy was achieved in 15% of the cases which was associated with 40% lowering of oxidative stress markers in follicular fluid. On the other hand, Group B had a pregnancy rate of 5% indicating that Allicin is not effective in combating severe chromosomal abnormality due to age. However, both treatment groups had an overall reduction of 80%, and menorrhagia showed an overall reduction of 85%. The placebo group experienced an enhancement of fewer than 10%. Confirmation given by the statistics showed that treated subjects were 4.2 times (95% CI: 2.8–6.1) less risky as compared to controls (p