To evaluate the effect of endothelin receptor agonist IRL-1620 alone and in combination with donepezil in modulating neurodegeneration elicited by amyloid-ß in rats.

BACKGROUND: The development of efficient therapies for Alzheimer''s disease is essential since it is a serious public health problem. This investigation sought to ascertain any potential synergistic benefits of treating Alzheimer's disease with IRL-1620 monotherapy in addition to Donepezil. Additionally, the effect of IRL-1620 was evaluated using different doses (5 µg/kg,7 µg/kg, and 9 µg/kg). The study further assessed neurobehavioral, biochemical, molecular, and histopathological parameters to evaluate the efficacy of both IRL1620 by its own and in association with Donepezil. Fifty-eight adult male Wistar rats were allocated to eight experimental groups. A dose-ranging study of IRL-1620 was conducted using different doses administered via intravenous injection. Alzheimer's disease was induced by Aß administration, and treatment arms included disease Control (Sham), Donepezil monotherapy, and combination treatment with IRL-1620 5 µg/kg (Dose selected from the dose-ranging study). The treatment using IRL-1620 (9 µg/kg) intravenously and Donepezil (1 mg/kg orally) both on its own and in addition substantially enhanced memory in comparison with the control group (p < 0.05). Dose of IRL-1620 (9 µg/kg) intravenously, escape latency decreased and the time spent in the target quadrant was considerably increased, and they further benefited from combination therapy. Moreover, IRL-1620 (9 µg/kg) intravenously and combination treatment reduced lipid peroxidation and acetylcholinesterase levels while increasing antioxidant enzyme levels. Immunohistochemistry and molecular analysis revealed enhanced expression of neurotrophic factors with combination treatment. The combination of IRL-1620 and Donepezil showed significant improvements in memory and neurobehavioral parameters (p < 0.05). Alzheimer's disease in male Wistar rats. These results indicate to the probable therapeutic advantages of IRL-1620 and Donepezil in the management of Alzheimer's disease. The combination treatment exhibited enhanced effects compared to monotherapy, highlighting its potential promising therapeutic approach. Additional research is required to understand the mechanisms behind these synergistic benefits and to establish the ideal dosage and duration of therapy for therapeutic applications.

Evaluation of the effect of probiotic as add-on therapy with conventional therapy and alone in malaria induced mice.

OBJECTIVE: Chloroquine is used as a conventional drug therapy for the treatment of malaria. The existence of resistance to chloroquine shown among various species of Plasmodium leads to the search for more efficacious therapy to treat malaria. Probiotic (Lactobacillus casei) has been tried as an add-on therapy with chloroquine. Probiotics are ingested microorganisms associated with a beneficial effect on humans and other species. The study was done to check the efficacy of L. casei as an add-on therapy along with conventional drug therapy (chloroquine) to treat malaria. RESULTS: Probiotic in combination with chloroquine showed complete suppression in parasitemia rate. Representation of parasitemia rate was done using mean ± SD. p < 0.05 is considered as statistically significant. The results showed a reduction in parasitemia with probiotic treatment, which was further confirmed through histological observation of two major organs, the liver and spleen. Interestingly, further suppression of parasitemia and hemosiderosis was observed when probiotic was given along with chloroquine.