Pharmacodynamics, Pharmacokinetics, and Kidney Distribution of Raw and Wine-Steamed Ligustri Lucidi Fructus Extracts in Diabetic Nephropathy Rats

The purpose of this study was to investigate differences in the pharmacodynamic, pharmacokinetic, and kidney distribution between Ligustri Lucidi Fructus (LLF) and wine-steamed Ligustri Lucidi Fructus (WLL) extracts in diabetic nephropathy (DN) rats. The DN rats were induced by high-fat-sugar diet (HFSD)/streptozotocin (STZ) regimen. For pharmacodynamics, the DN rats were treated with LLF and WLL extracts to assess the anti-diabetic nephropathy effects. For pharmacokinetics and kidney distribution, the concentrations of drugs (hydroxytyrosol, salidroside, nuezhenidic acid, oleoside-11-methyl ester, specnuezhenide, 1‴-O-β-d-glucosylformoside, G13, and oleonuezhenide) were determined. Regarding the pharmacodynamics, LLF and WLL extracts decreased the levels of blood glucose, serum creatinine (SCr), blood urea nitrogen (BUN), and 24-h urinary protein (24-h Upro) in DN rats. Furthermore, LLF and WLL extracts increased the level of high-density lipoprotein cholesterol (HDL-C); decreased the levels of total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C); and reduced levels of pro-inflammatory cytokines (IL-1β, TNF-α, and IL-6) in DN rats. The anti-diabetic nephropathy effect of the WLL extract was better than that of the LLF extract. Regarding the pharmacokinetic and kidney tissue distribution, there were obvious differences in the eight ingredients between LLF and WLL extracts in DN rats. LLF and WLL extracts had protective effects on DN rats, while the WLL extract was better than the LLF extract regarding anti-diabetic nephropathy effects. The pharmacokinetic parameters and kidney distribution showed that wine-steaming could affect the absorption and distribution of the eight ingredients. The results provided a reasonable basis for the study of the clinical application and processing mechanism of LLF.