Zhichen Pu

Acute lung injury (ALI) can lead to severe respiratory system damage, characterized by extensive inflammation and lung tissue injury. Ophiopogonin D (OD), from Ophiopogon japonicus, has pharmacological effects such as anti-inflammatory and anti-oxidant, hypoglycemic, anti-aging, and immune regulation properties. This study attempts to identify the protective mechanism of OD against ALI by the inhibition of ferroptosis of macrophages. The tissue-specific expression of USP25 in patients with COVID-19 was evaluated using single-cell data from the China National GeneBank and the GSE147507 dataset from Gene Expression Omnibus (GEO). C57BL/6 mice, Murine bone marrow derived macrophages (BMDM) or RAW264.7 cells were induced by Lipopolysaccharide (LPS). OD prevented ALI, and reduced inflammation levels and oxidative stress in mice models. OD significantly decreased the number of monocyte/macrophages (CD11b [ ]Ly6G-cells) in the peritoneal cavity after ALI induction. OD-mitigated inflammation and oxidative stress of macrophages in the ALI model. OD-reduced ferroptosis of macrophages in a model of ALI through the inhibition of ROS-induced mitochondrial damage. USP25 is significantly expressed in macrophages in patients with COVID-19 using single-cell analysis. OD-suppressed Rac1/NOX1-derived ROS to reduce the mitochondrial damage of macrophages in a model of ALI by the induction of USP25 activity. OD-identified USP25 at 907-VAL and 975-ARG in an ALI model to suppress USP25 Ubiquitination. OD from Ophiopogon japonicus induces USP25 activity to reduce ferroptosis of macrophages in ALI by binding the Rac1 and Nox1 complex. Therefore, it can be concluded that OD may be a potential therapeutic drug for the treatment of ALI.

Diabetes is a common occurring disease that seriously endangers human health. The prevalence rate of diabetes among adults aged ≥18 years in China is as high as 11.6%, with 114 million patients; In...

Background: According to the Chinese Pharmacopoeia, the fruit of Schisandra chinensis (Turcz.) Baill. (SC) is an important traditional Chinese medicine that can be used to treat diarrhea. Despite the increasing research on the anti-inflammatory and anti-oxidant aspects of SC, the studies on the anti-ulcerative colitis of Schisandrin (SCH), the main constituent of SC, are relatively few. Methods: The mice used in the study were randomly distributed into 6 groups: control, model, 5-ASA, and SCH (20, 40, 80 mg/kg/d). The mice in the model group were administered 3% (w/v) dextran sulfate sodium (DSS) through drinking water for 7 days, and the various parameters of disease activity index (DAI) such as body weight loss, stool consistency, and gross blood were measured. ELISA was used to detect inflammatory factors, and bioinformatics combined with transcriptome analysis was done to screen and verify relevant targets. 16S rDNA high-throughput sequencing was used to analyze the composition of the gut microbiota(GM), while mass spectrometry was done to analyze the changes in the content of bile acids (BAs) in the intestine. Results: Mice treated with SCH experienced significant weight gain, effectively alleviating the severity of colitis, and decreasing the levels of inflammatory factors such as TNF-α, IL-1β, IL-18, IL-6, and other related proteins (NLRP3, Caspase-1, SGK1) in UC mice. Furthermore, the analysis of GM and BAs in mice revealed that SCH increased the relative abundance of Lactobacilli spp, reduced the relative abundance of Bacteroides, and promoted the conversion of primary BAs to secondary BAs. These effects contributed to a significant improvement in the DSS-induced GM imbalance and the maintenance of intestinal homeostasis. Conclusion: It seems that there is a close relationship between the SCH mechanism and the regulation of SGK1/NLRP3 pathway and the restoration of GM balance. Therefore, it can be concluded that SCH could be a potential drug for the treatment of UC.

Schisandra chinensis, as a Chinese functional food, is rich in unsaturated fatty acids, minerals, vitamins, and proteins. Hence, this study was intended to elucidate the effects and biological mechanism of Schisandrin A from Schisandra chinensis in DN. C57BL/6 mice were fed with a high‐fat diet and then injected with streptozotocin (STZ). Human renal glomerular endothelial cells were stimulated with 20 mmol/L d‐glucose for DN model. Schisandrin A presented acute kidney injury in mice of DN. Schisandrin A reduced oxidative stress and inflammation in model of DN. Schisandrin A reduced high glucose‐induced ferroptosis and reactive oxygen species (ROS‐)‐mediated pyroptosis by mitochondrial damage in model of DN. Schisandrin A directly targeted AdipoR1 protein and reduced LPS+ATP‐induced AdipoR1 ubiquitination in vitro model. Schisandrin A activated AdipoR1/AMPK signaling pathway and suppressed TXNIP/NLRP3 signaling pathway in vivo and in vitro model of DN. Conclusively, our study revealed that Schisandrin A from Schisandra chinensis attenuates ferroptosis and NLRP3 inflammasome‐mediated pyroptosis in DN by AdipoR1/AMPK‐ROS/mitochondrial damage. Schisandrin A is a possible therapeutic option for DN or other diabetes.

Oat containing rich β-glucan, polyphenols, flavonoids, saponins, alkaloids, and other substances shows good biological activities. Therefore, the present study aimed to uncover the possible mechanism and therapeutic effect of Avenanthramide C in lessening inflammatory responses in pediatric pneumonia. Pediatric pneumonia was induced by liposaccharide (LPS) for vivo model and vitro model. Macrophage was performed to determine the mechanism and effects of Avenanthramide C in pediatric pneumonia. NLRP3 activity participated in the effects of Avenanthramide C in pediatric pneumonia. Avenanthramide C induced p-PI3K and p-Akt expressions and reduced ubiquitination of PI3K expression in pediatric pneumonia. On the other hand, Avenanthramide C integrated serine at 821 sites of the PI3K protein function. Avenanthramide C reduced ROS (reactive oxygen species)-induced mitochondrial damage by PI3K/AKT function in a model of pediatric pneumonia. Avenanthramide C protects pyroptosis in a model of pediatric pneumonia by PI3K/AKT/Nrf2/ROS signaling. Taken together, our results demonstrated that Avenanthramide C protects pyroptosis through dependent ROS-induced mitochondrial damage by PI3K ubiquitination and phosphorylation in a model of pediatric pneumonia, suggesting its potential use for the treatment of pediatric pneumonia and other inflammatory diseases.

Ulcerative colitis (UC) is a chronic inflammatory disease with increasing incidence and prevalence in many countries. The purpose of this study is to explore the function of Schisandrin B and its underlying molecular mechanisms in colitis.

Digoxin (DIG) is a positive inotropic drug with a narrow therapeutic window that is used in the clinic for heart failure. The active efflux transporter of DIG, P-glycoprotein (P-gp), mediates DIG absorption and excretion in rats and humans. Up to date, several studies have shown that the ginger and Poria extracts in Zhenwu Tang (ZWT) affect P-gp transport activity. This study aimed to explore the effects of ZWT on the tissue distribution and pharmacokinetics of DIG in rats. The deionized water or ZWT (18.75g/kg) was orally administered to male SpragueDawley rats once a day for 14 days as a pretreatment. On day 15, 1 hour after receiving deionized water or ZWT, the rats were given the solution of DIG at 0.045mg/kg dose, and the collection of blood samples was carried out from the fundus vein or excised tissues at various time points. HPLC-MS/MS was used for the determination of the DIG concentrations in the plasma and the tissues under investigation. The pharmacokinetic interactions between DIG and ZWT after oral coadministration in rats revealed significant reductions in DIG C_max and AUC_0-∞, as well as significant increases in T_1/2 and MRT_0-∞. When coadministered with ZWT, the DIG concentration in four of the investigated tissues statistically decreased at different time points except for the stomach. This study found that combining DIG with ZWT reduced not only DIG plasma exposure but also DIG accumulation in tissues (heart, liver, lungs, and kidneys). The findings of our study could help to improve the drug's validity and safety in clinical applications and provide a pharmacological basis for the combined use of DIG and ZWT.

Overexpression lentivirus platform was established of OATP1B1 (organic anion transporting polypeptides 1B1) wild‑type and mutant type genetic polymorphism in vitro, and using this platform we investigated and compared the uptake of tamoxifen and its metabolites by mutating the 388 and the 521 bases. The overexpression lentivirus cell platforms were successfully constructed, including OATP1B1*1a-HEK293T and OATP1B1*1b-HEK293T and OATP1B1*5-HEK293T cell model, the infection efficiency is not less than 80%. It shows a high level of gene expression at the mRNA and protein level. The tamoxifen and endoxifen can be taken up into the cells through organic anion transporter polypeptide 1B1, and OATP1B1521T>C inhibits the function of the transport protein, resulting in the content of drug in cell lysis liquid in OATP1B1*5-HEK293T group is lower than in OATP1B1*1a-HEK293T group (tamoxifen or endoxifen), with statistical significance. The content of the drug in cell lysis liquid in OATP1B1*1b-HEK293T group and the OATP1B1*1a-HEK293T group, similar with no statistical significance. These results suggest that tamoxifen and endoxifen can be transported by OATP1B1. However, OATP1B1 521T>C can inhibit the effects of OATP1B1 on tamoxifen and endoxifen in the cells.