Si-Ni-San promotes liver regeneration by maintaining hepatic oxidative equilibrium and glucose/lipid metabolism homeostasis.

ETHNOPHARMACOLOGICAL RELEVANCE: The efficacy of clinical treatments for various liver diseases is intricately tied to the liver's regenerative capacity. Insufficient or failed liver regeneration is a direct cause of mortality following fulminant hepatic failure and extensive hepatectomy. Si-Ni-San (SNS), a renowned traditional Chinese medicine prescription for harmonizing liver and spleen functions, has shown clinical efficacy in the alleviation of liver injury for thousands of years. However, the precise molecular pharmacological mechanisms underlying its effects remain unclear. AIMS OF THE STUDY: This study aimed to investigate the effects of SNS on liver regeneration and elucidate the underlying mechanisms. MATERIALS AND METHODS: A mouse model of 70% partial hepatectomy (PHx) was used to analyze the effects of SNS on liver regeneration. Aquaporin-9 knockout mice (AQP9-/-) were used to demonstrate that SNS-mediated enhancement of liver regeneration was AQP9-targeted. A tandem dimer-Tomato-tagged AQP9 transgenic mouse line (AQP9-RFP) was utilized to determine the expression pattern of AQP9 protein in hepatocytes. Immunoblotting, quantitative real-time PCR, staining techniques, and biochemical assays were used to further explore the underlying mechanisms of SNS. RESULTS: SNS treatment significantly enhanced liver regeneration and increased AQP9 protein expression in hepatocytes of wild-type mice (AQP9+/+) post 70% PHx, but had no significant effects on AQP9-/- mice. Following 70% PHx, SNS helped maintain hepatic oxidative equilibrium by increasing the levels of reactive oxygen species scavengers glutathione and superoxide dismutase and reducing the levels of oxidative stress molecules H2O2 and malondialdehyde in liver tissues, thereby preserving this crucial process for hepatocyte proliferation. Simultaneously, SNS augmented glycerol uptake by hepatocytes, stimulated gluconeogenesis, and maintained glucose/lipid metabolism homeostasis, ensuring the energy supply required for liver regeneration. CONCLUSIONS: This study provides the first evidence that SNS maintains liver oxidative equilibrium and glucose/lipid metabolism homeostasis by upregulating AQP9 expression in hepatocytes, thereby promoting liver regeneration. These findings offer novel insights into the molecular pharmacological mechanisms of SNS in promoting liver regeneration and provide guidance for its clinical application and optimization in liver disease treatment.

Mycophenolic Acid Exposure Optimization Based on Vitamin D Status in Children with Systemic Lupus Erythematosus: A Single-Center Retrospective Study.

INTRODUCTION: Systemic lupus erythematosus (SLE) can affect bone metabolism and homeostasis of serum electrolytes that are associated with abnormal levels of vitamin D. Mycophenolate mofetil (MMF) is a commonly used immunosuppressant with the active metabolite mycophenolic acid (MPA). The area under the plasma concentration-time curve (AUC) of MPA is often monitored during the treatment to assess the exposure levels. This study aims to explore the association between exposure levels of MPA and 25-hydroxyvitamin D [25(OH)D] levels in children with SLE. METHODS: Repeated measured data of children with SLE who were treated with MMF and under therapeutic drug monitoring (TDM) were retrospectively collected from the electronic medical records. MPA exposure levels were reflected by the area under the concentration-time curve over 24 h (AUC0-24h). Univariate and multivariate linear regression models were employed to analyze factors associated with 25(OH)D levels. Hierarchical linear models were developed to analyze the intra- and inter-individual effects of AUC0-24h on the variance of 25(OH)D levels. RESULTS: Data from 184 children with SLE (142 female and 42 male) with 518 follow-ups were collected. The median age was 14 years (range 3-18 years) at TDM. Children with normal 25(OH)D levels had significantly higher AUC0-24h than children with low 25(OH)D levels (98.71 vs. 84.05 mg·h/L, P = 0.004). Intra- and inter-individual effects of AUC0-24h on 25(OH)D levels were similar ([Formula: see text] = 0.034 vs. [Formula: see text] = 0.037) but only the intra-individual effect was significant (P = 0.001) in hierarchical models. Other associated factors include age, sex, season at measurement, glucocorticoid daily dose, and external vitamin D3 supplements. CONCLUSION: 25(OH)D levels are associated with MPA exposure levels, and may serve as a potential indicator to optimize the exposure level of MPA during treatment. AUC0-24h of 98.71 mg·h/L or AUC0-12h of 49.36 mg·h/L could be the targeted exposure level for children with SLE.

Glycoglycerolipids from Stellera chamaejasme.

Two new glycoglycerolipids (1 and 2), along with three known compounds (3-5) were isolated from Stellera chamaejasme. The structure of the new compounds was elucidated by chemical and spectroscopic data analysis. The cytotoxic activity of 1-3 was evaluated and showed no activity against the assayed human cancer cell lines.