ABSTRACT
In an attempt to search for new natural products-based antifungal agents, fifty-three nootkatone derivatives were designed, synthesized, and evaluated for their antifungal activity against Phytophthora parasitica var nicotianae, Fusarium oxysporum, Fusarium graminearum and Phomopsis sp. by the mycelium growth rate method. Nootkatone derivatives N17 exhibited good inhibitory activity against Phomopsis. sp. with EC50 values of 2.02â µM. The control effect of N17 against Phomopsis. sp. on kiwifruit showed that N17 exhibited a good curative effect in reducing kiwifruit rot at the concentration of 202â µM(100×EC50 ), with the curative effect of 41.11 %, which was better than commercial control of pyrimethanil at the concentration of 13437â µM(100×EC50 ) with the curative effect of 38.65 %. Phomopsis. sp. mycelium treated with N17 showed irregular surface collapse and shrinkage, and the cell membrane crinkled irregularly, vacuoles expanded significantly, mitochondria contracted, and organelles partially swollen by the SEM and TEM detected. Preliminary pharmacological experiments show that N17 exerted antifungal effects by altering release of cellular contents, and altering cell membrane permeability and integrity. The cytotoxicity test demonstrated that N17 showed almost no toxicity to K562 cells. The presented results implied that N17 may be as a potential antifungal agents for developing more efficient fungicides to control Phomopsis sp.
Subject(s)
Antifungal Agents , Drug Design , Fusarium , Microbial Sensitivity Tests , Oximes , Antifungal Agents/pharmacology , Antifungal Agents/chemical synthesis , Antifungal Agents/chemistry , Fusarium/drug effects , Oximes/chemistry , Oximes/pharmacology , Oximes/chemical synthesis , Structure-Activity Relationship , Hydrazones/pharmacology , Hydrazones/chemistry , Hydrazones/chemical synthesis , Phytophthora/drug effects , Molecular Structure , Polycyclic Sesquiterpenes/pharmacology , Polycyclic Sesquiterpenes/chemistry , Polycyclic Sesquiterpenes/chemical synthesis , Dose-Response Relationship, Drug , Ascomycota/drug effectsABSTRACT
BACKGROUND/AIMS: The paper aimed to investigate the effects of Stigmasterol on inflammatory factors, antioxidant capacity, and apoptotic signaling pathways in brain tissue of rats with cerebral ischemia/reperfusion (I/R) injury. METHODS: The neurological deficits of the rats were analyzed and HE staining was performed. The cerebral infarct volume was calculated by means of TTC staining, and neuronal apoptosis was detected by TUNEL staining. At the same time, the contents of glutathione peroxidase, glutathione, superoxide dismutase (SOD), nitric oxide, and malondialdehyde in brain tissue were measured. The expression of the relevant protein was detected by means of Western blotting. RESULTS: The results showed that the neurological deficit score and infarct area of the I/R rats in the soy sterol treatment group were significantly lower than those in the I/R group. Moreover, the levels of carbon monoxide and malondialdehyde in the soysterol group were significantly lower than those in the I/R group, and the expressions of cyclooxygenase-2 (Cox-2) and NF-κB (p65) in the soysterol group were also significantly lower than those in the I/R group. The expression of Nrf2 (nucleus) and heme oxygenase-1 (HO-1) increased significantly, and the activities of antioxidant enzymes and SOD were increased. In addition, the stigmasterol treatment can inhibit apoptosis, down-regulate Bax and cleaved caspase-3 expression, and up-regulate Bcl-Xl expression. CONCLUSION: Stigmasterol protects the brain from brain I/R damage by reducing oxidative stress and inflammation.