Asiatic Acid

Bacterial infection caused by intracellular pathogens such as Shigella flexneri is a rapidly increasing global health concern that requires urgent and necessary action. The dearth of licensed vaccines against shigellosis and the decline in susceptibility to conventional antibiotics has encouraged the development of new antibiotic principles and drugs. The treatment options are decreasing faster than the discovery rate of new antibacterial agents. Combinatorial approach of antibiotics with non-antibiotic adjuvants is a promising aspect to treat resistant bacterial infections. Asiatic acid, a membrane-disrupting triterpenoid with wide antimicrobial and immunomodulatory properties, can potentiate antibiotics, but the exact mechanisms remain broadly unexplored. Therefore, in this study, we screened the interaction of asiatic acid with several antibiotics. The results showed synergistic interactions of asiatic acid with antibiotics against susceptible and multidrug-resistant S. flexneri clinical isolates. Particularly important was the interaction of asiatic acid with the quinolone antibiotics ciprofloxacin and nalidixic acid. A detailed study showed that combined treatment of asiatic acid with ciprofloxacin inhibited S. flexneri biofilm formation and resistance development. An increase in membrane disruption and depolarization upon co-treatment was evident by surface electron and confocal microscopy. In addition, asiatic acid and ciprofloxacin synergism was identified to inhibit efflux activity and intracellular bacterial viability. However, asiatic acid showed no synergistic toxicity with ciprofloxacin towards mammalian cells. The antibacterial activity was further verified in a S. flexneri infected mice model. Therapeutic benefits were evident with reduced bacterial burden, recovery from intestinal tissue damage and increase in mice survivability. The results showed that this combination can target the bacterial membrane, efflux pump proteins and biofilm formation, thereby preventing resistance development. The combination treatment offers a proof of concept in targeting essential bacterial activities and might be developed into a novel and efficient treatment alternative against S. flexneri.

Centella asiatica (L.) Urb., a traditional medicinal plant widely distributed in Southeast Asia, has been demonstrated to possess significant neuroprotective effect. However, the pharmacological and molecular mechanisms of C. asiatica (CA) in treating neurological diseases remain to be further explored. This review synthesizes evidence on CA's pharmacokinetics, antioxidant/anti-inflammatory mechanisms, and therapeutic potential in various neurological disorders.

Evidence shows CA can mitigate oxidative stress, inflammation, mitochondrial dysfunction, and neuronal apoptosis-key mechanisms underlying these conditions. In epilepsy models, asiatic acid suppresses glutamate release, improves synaptic and mitochondrial function, and reduces neuronal damage. In neurodegenerative diseases, CA extracts enhance memory and cognitive functions by activating antioxidant response pathways and protecting hippocampal mitochondria from oxidative stress. CA extracts also display anticonvulsant effects without major toxicity. Against Bisphenol A-induced neurotoxicity, CA alleviates oxidative stress and inflammation while restoring mitochondrial function. For radiation-induced brain injury, CA improves cognition and memory via antioxidant pathways and anti-inflammatory effects. In cerebral ischemia-reperfusion injury, asiaticoside reduces oxidative stress and neuroinflammation through NOD2/MAPK/NF-κB pathway modulation and microglial regulation. Recent research suggests that CA also plays a significant role in alleviating symptoms of anxiety and depression. The plant's active components have been found to regulate neurotransmitter activity, reduce oxidative stress, and modulate the hypothalamic-pituitary-adrenal (HPA) axis.

CA demonstrates broad neuroprotective potential, offering multi-target benefits with relatively low toxicity. These findings support its development as a novel therapeutic agent for neurological disorders. Further clinical research is warranted to confirm safety, optimize dosing, and translate preclinical results into effective human treatments.