Dongyao Han

The liver, as the largest metabolic and detoxification organ in mammals, metabolizes approximately 80–90% of drugs. However, drug-induced liver injury (DILI) is common and driven by factors such as individual variability, differences in liver metabolism, and improper drug use. Mesenchymal stem cells (MSCs), with their self-renewal and multipotent differentiation capabilities, offer therapeutic potential, but face challenges such as limited proliferation and increased apoptosis during in vitro expansion. Although MSCs exhibit low immunogenicity, they are often cleared by the host immune system, which limits their survival and engraftment. Glutathione peroxidase 3 (GPX3) is a key antioxidant enzyme that reduces reactive oxygen species (ROS), protecting cells from oxidative damage. CD47, also known as integrin-associated protein (IAP), helps cells evade immune clearance by binding to signal regulatory protein alpha (SIRPα) on the immune cells. Here, we used an acetaminophen (APAP)-induced DILI mouse model to evaluate the therapeutic efficacy of intravenously infused MSCs overexpressing GPX3 and CD47. Compared to unmodified MSCs, modified MSCs showed improved survival, reduced liver inflammation, and alleviated oxidative damage, offering enhanced protection against APAP-induced DILI.

We aimed to study the effects of an ethyl acetate fraction of Physalis alkekengi (PAE) on d-galactose (d-gal)-induced senescence and the underlying mechanism. Firstly, analysis of the phytochemical composition revealed total flavonoids, total phenolics, total saponins, rutin, and luteolin contents of 71.72 ± 2.99 mg rutin equivalents/g, 40.19 ± 0.47 mg gallic acid equivalents/g, 128.13 ± 1.04 mg oleanolic acid equivalents/g, 1.67 ± 0.07 mg/g and 1.61 ± 0.01 mg/g, respectively. The mice were treated with d-gal for six weeks, and from the fifth week, the mice were administered with PAE by gavage once a day for five weeks. We found significant d-gal-induced ageing-related changes, such as learning and memory impairment in novel object recognition and Y-maze, fatigue in weight-loaded forced swimming, reduced thymus coefficient, and histopathological injury of the liver, spleen, and hippocampus. The PAE effectively protected from such changes. Further evaluation showed that PAE decreased the senescence-associated β-galactosidase of the liver, spleen, and hippocampus, as well as the oxidative stress of the liver, plasma, and brain. The abundance of flavonoids, phenols, and saponins in PAE may have contributed to the above results. Overall, this study showed the potential application of PAE for the prevention or treatment of ageing-associated disorders.