ZeXieYin Formula alleviates TMAO-induced cognitive impairment by restoring synaptic plasticity damage.

ETHNOPHARMACOLOGICAL RELEVANCE: Treating cognitive impairment is a challenging and necessary research topic. ZeXieYin Formula (ZXYF), is a traditional herbal formula documented in the book of HuangDiNeiJing. Our previous studies demonstrated the ameliorative effects of ZXYF on atherosclerosis by reducing the plasma trimethylamine oxide (TMAO) level. TMAO is a metabolite of gut microorganisms, our recent research found that the increasing level of TMAO may have adverse effects on cognitive functions. AIM OF THE STUDY: Our study mainly focused on the therapeutic effects of ZXYF on TMAO-induced cognitive impairment in mice and explored its underlying mechanism. MATERIALS AND METHODS: After the TMAO-induced cognitive impairment mice models were established, we applied behavioral tests to estimate the learning and memory ability of the ZXYF intervention mice. Liquid chromatography-mass spectrometry (LC-MS) was used to quantify the TMAO levels in plasma and the brain. The effects of ZXYF on the hippocampal synaptic structure and the neurons were observed by transmission electron microscopy (TEM) and Nissl staining. In addition, western-blotting (WB) and immunohistochemical (IHC) staining were used to detect the level of related proteins in the synaptic structure and further verify the changes in synaptic plasticity and the mTOR pathway after ZXYF administration. RESULTS: Behavioral tests showed that the learning and memory ability of mice impaired after a period of TMAO intervention and ZXYF could alleviate these changes. A series of results showed that ZXYF partly restored the damage of hippocampal synapse and neurons in TMAO-induced mice, at the same time, the expression of synapse-related proteins and mTOR pathway-related proteins were significantly regulated compared with the damage caused by TMAO. CONCLUSION: ZXYF could alleviate TMAO-induced cognitive impairment by improving synaptic function, reducing neuronal damage, regulating synapse-associated proteins, and regulating the mTOR signaling pathway.

Comparative proteomic analysis identified proteins and the phenylpropanoid biosynthesis pathway involved in the response to ABA treatment in cotton fiber development.

Abscisic acid (ABA) is a plant hormone that plays an important role in cotton fiber development. In this study, the physiological changes and proteomic profiles of cotton (Gossypium hirsutum) ovules were analyzed after 20 days of ABA or ABA inhibitor (ABAI) treatment. The results showed that compared to the control (CK), the fiber length was significantly decreased under ABA treatment and increased under ABAI treatment. Using a tandem mass tags-based quantitative technique, the proteomes of cotton ovules were comprehensively analyzed. A total of 7321 proteins were identified, of which 365 and 69 differentially accumulated proteins (DAPs) were identified in ABA versus CK and ABAI versus CK, respectively. Specifically, 345 and 20 DAPs were up- and down-regulated in the ABA group, and 65 and 4 DAPs were up- and down-regulated in the ABAI group, respectively. The DAPs in the ABA group were mainly enriched in the biosynthesis of secondary metabolites, phenylpropanoid biosynthesis and flavonoid secondary metabolism, whereas the DAPs in the ABAI group were mainly enriched in the indole alkaloid biosynthesis and phenylpropanoid biosynthesis pathways. Moreover, 9 proteins involved in phenylpropanoid biosynthesis were upregulated after ABA treatment, suggesting that this pathway might play important roles in the response to ABA, and 3 auxin-related proteins were upregulated, indicating that auxin might participate in the regulation of fiber development under ABAI treatment.