The most common cause of anovulatory infertility is polycystic ovarian syndrome (PCOS), which is closely associated with obesity and metabolic syndrome. Artificial sweetener, notably saccharin sodium (SS), has been utilized in management of obesity in PCOS. However, accumulating evidence points towards SS deleterious effects on ovarian physiology, potentially through activation of ovarian sweet and bitter taste receptors, culminating in a phenotype reminiscent of PCOS. This research embarked on exploration of SS influence on ovarian functions within a PCOS paradigm. Rats were categorized into six groups: Control, Letrozole-model, two SS groups at 2 dose levels, and two groups receiving 2 doses of SS with Letrozole. The study underscored SS capability to potentiate PCOS-related anomalies. Elevated cystic profile with outer thin granulosa cells, were discernible. This owed to increased apoptotic markers as cleaved CASP-3, mirrored by high BAX and low BCL-2, with enhanced p38-MAPK/ERK pathway. This manifestation was accompanied by activation of taste receptors and disruption of steroidogenic factors; StAR, CYP11A1, and 17β-HSD. Thus, SS showed an escalation in testosterone, progesterone, estrogen, and LH/FSH ratio, insinuating a perturbation in endocrine regulation. It is found that there is an impact of taste receptor downstream signaling on ovarian steroidogenesis and apoptosis instigating pathophysiological milieu of PCOS.

Recently, numerous studies have confirmed the importance of chitosan nanoparticles (CNP) as a viable drug delivery carrier for increasing the efficacy of anticancer drugs in cancer treatment. It is a macromolecule and natural biopolymer compound, more stable and safer in use than metal nanoparticles. Bee venom (BV), a form of defense venom, has been shown to have anti-tumor, neuroprotective, anti-inflammatory, analgesic, and anti-infectivity properties. Moreover, the regulation of cell death has been linked to reactive oxygen species (ROS)-mediated cell apoptosis, which induces mitochondrial damage and ER stress through oxidative stress events. Therefore, this study aimed to illustrate the ROS-mediated effect on the cancer cells treatment with CNP-loaded BV (CNP-BV) and explained the adverse effects of ROS generation on Mitochondria and ER. We have found that the targeted CNP-BV were high in cytotoxicity against MCF-7 (IC 437.2 μg/mL) and HepG2 (IC 109.5 μg/mL) through the induction of massive generation of ROS, which in turn results in activating the mitochondrial cascade and ER stress. These results highlighted the role of ROS generation in inducing apoptosis in cancer cells.

Recently, numerous studies have confirmed the importance of chitosan nanoparticles (CNP) as a viable drug delivery carrier for increasing the efficacy of anticancer drugs in cancer treatment. It is a macromolecule and natural biopolymer compound, more stable and safer in use than metal nanoparticles. Bee venom (BV), a form of defense venom, has been shown to have anti-tumor, neuroprotective, anti-inflammatory, analgesic, and anti-infectivity properties. Moreover, the regulation of cell death has been linked to reactive oxygen species (ROS)-mediated cell apoptosis, which induces mitochondrial damage and ER stress through oxidative stress events. Therefore, this study aimed to illustrate the ROS-mediated effect on the cancer cells treatment with CNP-loaded BV (CNP-BV) and explained the adverse effects of ROS generation on Mitochondria and ER. We have found that the targeted CNP-BV were high in cytotoxicity against MCF-7 (IC 437.2 μg/mL) and HepG2 (IC 109.5 μg/mL) through the induction of massive generation of ROS, which in turn results in activating the mitochondrial cascade and ER stress. These results highlighted the role of ROS generation in inducing apoptosis in cancer cells.