No abstract

Ligustri Lucidi Fructus is a dried and mature fruit of Ligustrum lucidum Ait., which has the effects of nourishing liver and kidney. Herein, an accurate and sensitive method was established for the separation and identification of the absorbed constituents and metabolites of Ligustri Lucidi Fructus in rat plasma based on ultra‐high‐performance liquid chromatography‐Q‐Exactive Orbitrap tandem mass spectrometry. A total of 73 prototype constituents and 148 metabolites were identified or characterized in administered plasma, and the possible metabolic pathways of constituents mainly involved hydroxylation, sulfation, demethylation, and glucuronidation. Besides, the network pharmacology was further investigated to illuminate its potential mechanism of treatment for liver injury by the biological targets regulating related pathways. Network pharmacological analysis showed that target components through 399 targets regulate 220 pathways. The docking results showed that 36 key target components were closely related to liver injury. Overall, the study clearly presented the metabolic processes of Ligustri Lucidi Fructus and gave a comprehensive metabolic profile of Ligustri Lucidi Fructus in vivo first. Combining with network pharmacology and molecular docking discovered potential drug targets and disclose the biological processes of Ligustri Lucidi Fructus, which will be a viable step toward uncovering the secret mask of study for traditional Chinese medicine.

Ligustri Lucidi Fructus (LLF), the dry and ripe fruit of Ligustrum lucidum W. T. Aiton (Oleaceae), is a traditional Chinese medicine for nourishing the liver and kidney in clinics for thousands of years. Wine-steamed Ligustri Lucidi Fructus (WLL) can alleviate coolness and smoothness of LLF and enhance the function of nourishing the liver and kidney, so ancient and modern medicine usually used it in clinics. First of all, we prepared the extracts of different polar fractions of WLL to explore the effective fractions and potential mechanisms of WLL in the treatment of diabetic nephropathy (DN). Then, HPLC method was used to determine the contents of 12 active components in WLL and its different polar components. Finally, the potential relationship between 12 active components and physicochemical parameters of DN rats was explored. The pharmacological experiments showed that WLL, ethyl acetate (EtOAc), and n-butanol (n-BuOH) extracts not only significantly alleviated the clinical symptoms and kidney damage of DN rats but also had obvious anti-inflammatory and antioxidant effects. In addition, the results of HPLC analysis showed that the 12 active components of WLL mainly existed in the extracts of EtOAc and n-BuOH. The Pearson correlation analysis showed 12 active components and physicochemical parameters had different degrees of correlation. In conclusion, we proved that the extracts of EtOAc and n-BuOH were the effective fractions of WLL in treating DN in rats, and they could regulate the levels of inflammatory cytokines and decrease oxidation stress, which provides a basis for further research on the mechanism of WLL in treating DN and provides a pharmacological and chemical foundation for the development of new anti-DN drugs.

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.