Chaihu-Longgu-Muli decoction improves sleep disorders by restoring orexin-A function in CKD mice.

Introduction: Chaihu-Longgu-Muli decoction (CLMD) is a well-used ancient formula originally recorded in the "Treatise on Febrile Diseases" written by the founding theorist of Traditional Chinese Medicine, Doctor Zhang Zhongjing. While it has been used extensively as a therapeutic treatment for neuropsychiatric disorders, such as insomnia, anxiety and dementia, its mechanisms remain unclear. Methods: In order to analyze the therapeutic mechanism of CLMD in chronic renal failure and insomnia, An adenine diet-induced chronic kidney disease (CKD) model was established in mice, Furthermore, we analyzed the impact of CLMD on sleep behavior and cognitive function in CKD mice, as well as the production of insomnia related regulatory proteins and inflammatory factors. Results: CLMD significantly improved circadian rhythm and sleep disturbance in CKD mice. The insomnia related regulatory proteins, Orexin, Orexin R1, and Orexin R2 in the hypothalamus of CKD mice decreased significantly, while Orexin and its receptors increased remarkably after CLMD intervention. Following administration of CLMD, reduced neuron loss and improved learning as well as memory ability were observed in CKD mice. And CLMD intervention effectively improved the chronic inflflammatory state of CKD mice. Discussion: Our results showed that CLMD could improve sleep and cognitive levels in CKD mice. The mechanism may be related to the up-regulation of Orexin-A and increased phosphorylation level of CaMKK2/AMPK, which further inhibits NF-κB downstream signaling pathways, thereby improving the disordered inflammatory state in the central and peripheral system. However, More research is required to confirm the clinical significance of the study.

Shenqi Yanshen Formula (SQYSF) protects against chronic kidney disease by modulating gut microbiota.

In this study, we make an elucidation toward both the therapeutic effect and the mechanism of Shenqi Yanshen Formula (SQYSF) to chronic kidney disease (CKD). CKD mouse model was established and achieved in a way of adenine (200 mg/kg) perfusion. Six weeks later, those mice in the model group were fed with SQYSF (3.60 g/kg/day) every day (the captopril group was given 12.5 mg/kg/day by gavage every day, and control group and the model group were both given the gavage of equal volumes of normal saline); 4 weeks after the administration, we had our detection to physiological indicators of mice, performed ELISA assay to detect inflammatory factor expressions, then assay of 16S sequencing was used to reveal the difference of intestinal flora. Our results showed that after SQYSF treatment, both the expressions of serum creatinine (Scr) and blood urea nitrogen (BUN) came with a significant decline, indicating the outstanding performances of SQYSF in alleviating impairment in renal function and elevating mice's physiological function. SQYSF significantly reduced the degree of renal fibrosis in CKD mice, and remarkably down-regulated the expressions of toll-like receptor 5 (TLR5), nuclear factor-kappaB (NF-κb), p65, tumor necrosis factor (TNF)-α, interleukin (IL)-1ß and IL-6. Additionally, SQYSF has more than ability in significantly changing the composition in mice's intestinal flora, but also in greatly increasing the abundance of Succinivibrionaceae and Aeromonadales in the mouse intestine. This study clarified the therapeutic effect of SQYSF on CKD and regulation of inflammatory factors and intestinal flora, and provided new ideas for treatment on CKD.

[Inhibitory effect of polydatin on expression of toll-like receptor 4 in ischemia-reperfusion injured NRK-52E cells].

Polydatin is a monocrystaline compound isolated from Polygonum cuspidatum Sieb. et Zucc. (Polygonaceae) with biological properties, such as anti-inflammation, anti-oxidative and nephroprotective effects. Increasing number of studies have demonstrated the protective effect of polydatin on renal ischemia reperfusion injury. However, the possible mechanisms of this protection are not fully elucidated. This study aimed to investigate the effect of polydatin on ischemia-reperfusion induced expression of toll-like receptor4 (TLR4) in rat renal tubular epithelia cells (NRK-52E), and analyze the mechanism of polydatin on TLR4 signal pathway. The cultured NRK-52E cells were incubated in three gas incubators for a period of 6 h at hypoxia and 24h at reoxygenation to simulate the ischemia-reperfusion injury in vitro. TLR4 mRNA level was analyzed by real-time-PCR, and the protein expression of TLR4 and NF-κB by Western blotting, while TNF-α and IL-1ß proteins expressions were detected by ELISA. Polydatin downregulated I/R induced mRNA and protein expressions of TLR4, and decreased the protein expression of NF-κB, TNF-α and IL-1ß. The TLR4 blocker partially antagonized the effect of I/R on NF-κB signaling, and such inhibitory effect was markedly enhanced by polydatin. In the present study, polydatin protects NRK-52E cells from I/R injury possibly by relieving the inflammatory response through regulation of TLR4/NF-κB signaling pathway.