SuanZaoRen decoction alleviates neuronal loss, synaptic damage and ferroptosis of AD via activating DJ-1/Nrf2 signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: SuanZaoRen Decoction (SZRD), a famous herbal prescription, and has been widely proven to have positive therapeutic effects on insomnia, depression and Alzheimer's disease (AD). However, the anti-AD molecular mechanism of SZRD remains to be further investigated. AIM OF THE STUDY: To elucidate the molecular mechanism of SZRD's improvement in AD's neuronal loss, synaptic damage and ferroptosis by regulating DJ-1/Nrf2 signaling pathway. MATERIALS AND METHODS: LC-MS/MS was used to detect the active ingredients from SZRD. APP/PS1 mice was treated with SZRD and a ferroptosis inhibitor (Liproxstatin-1), respectively. Upon the completion of behavioral tests, Nissl staining, FJB staining, Golgi staining, immunofluorescence, immunohistochemistry, and transmission electron microscopy were preformed to evaluate the effects of SZRD on neuronal loss, synaptic damage, Aß deposition. Iron staining, transmission electron microscopy, and iron assay kit was performed to estimate the effects of SZRD on ferroptosis. SOD kit, MDA kit, GSH kit, and GSH/GSSG kit were utilized to measure the oxidative stress levels in the hippocampus. The protein expression of TfR1, FTH1, FTL, FPN1, DJ-1, Nrf2, GPX4, SLC7A11, and ACSL4 were detected by Western blot. RESULTS: A total of 16 active ingredients were identified from SZRD extract. SZRD SZRD significantly alleviated learning and memory impairment in APP/PS1 mice. SZRD improved the hippocampal neuronal loss and degenerated neurons in APP/PS1 mice via inhibiting the Aß deposit. SZRD mitigated the hippocampal synaptic damage in APP/PS1 mice. SZRD inhibited iron accumulation, and alleviated the oxidative stress level in the hippocampus of APP/PS1 mice. Meanwhile, SZRD could up-regulate the protein expression level of FPN1, DJ-1, Nrf2, GPX4 and SLC7A11 in the hippocampus, and inhibit TfR1, FTH1, FTL, and ACSL4 protein expression. CONCLUSION: SZRD alleviated neuronal loss, synaptic damage and ferroptosis in AD via activating DJ-1/Nrf2 signaling pathway.

Quercetin and Allicin Can Alleviate the Hepatotoxicity of Lead (Pb) through the PI3K Signaling Pathway.

Lead (Pb) is a common toxic heavy metal pollutant in the environment that seriously endangers the health of animals. The liver is a key target organ affected by Pb toxicity. Plant extracts allicin and quercetin have a strong antioxidant capacity that can promote the excretion of heavy metals by improving the body's antioxidant defense and chelating heavy metal ions. To explore the preventive and therapeutic effects of allicin and quercetin on Pb poisoning in chickens, 96 chickens were randomly divided into eight groups: control, Pb, allicin, quercetin, allicin + quercetin, Pb + allicin, Pb + quercetin, and Pb + allicin + quercetin groups. The chickens were given feed containing the above treatments for 90 days. The results indicated that Pb can affect the growth and development of the liver, damage the circulatory system, destroy the structure of mitochondria and nuclei in liver cells, cause an imbalance in the oxidation system, inhibit PI3K protein, and activate the mitochondrial apoptotic pathway. Allicin and quercetin, alone or in combination, can improve the antioxidant capacity of the liver and alleviate liver tissue damage caused by Pb. In summary, allicin and quercetin could alleviate oxidative damage and apoptosis in the Pb-poisoned chicken liver through the PI3K signaling pathway, with stronger effects achieved by their combination.