Linlin Fang

Oxypeucedanin hydrate is a bioactive coumarin component from Angelica dahurica (A.dahurica), which has two enantiomers possessing distinct pharmacological activities. In the present research, Oxypeucedanin hydrate and seven analogs including Byakangelicin, Byakangelicol, Praeruptorin A, Oxypeucedanin, Decursin, Nodakenin and Marmesin were enantioseparated on the cellulose tris-(3,5-dichlorophenylcarbamate) (CDCPC)-based chiral stationary phase (CSP) in the normal phase mode. The influences of polar modifier type, the acid additives type, the flow rate, the proportion of organic modifiers were systematically evaluated. As a result, seven enantiomers were completely separated and partial chiral separation for Oxypeucedanin was found on CDCPC. To gain further mechanistic understanding of enantioselective recognition, molecular docking simulations were systematically performed to investigate the intermolecular interactions between CDCPC and eight analytes. In conclusion, the chiral separation of coumarin compounds on CDCPC was governed by a synergistic interplay of multiple interactions, including hydrogen bonding, hydrophobic interactions, and steric influences. Finally, the modified QuEChERS method was developed to extract and purify samples. Combined with the optimized method, the chiral content of Oxypeucedanin hydrate enantiomers was determined in A.dahurica.

N-hexane is a widely used aliphatic hydrocarbon solvent that can cause central–peripheral neuropathy. Compared to peripheral nerve tissue, spinal nerve tissue is more vulnerable and typically non-regenerable. However, no effective treatments are currently available. Stem cells are attractive therapeutic cells because of their extensive self-renewal and pluripotent differentiation abilities. Accordingly, numerous studies are focused on their restorative potential. In the present study, we investigated the effects and mechanisms of stem cell therapy on spinal nerves damaged by 2,5-HD (a proximate toxic metabolite of n-hexane). Our results showed that spinal axonopathy induced by 2,5-HD was alleviated by bone mesenchymal stem cell (BMSC) transplantation. Further, by examining the expression of molecules associated with axonal outgrowth, NGF signaling was found to be involved in the regeneration of spinal axons. Moreover, intervention experiments showed that PTEN was also an essential component of BMSC therapy. Conclusively, our data suggested that BMSC transplantation can alleviate spinal injury induced by 2,5-HD through AKT/mTOR/CREB by NGF-dependent and -independent pathways.

The Dahuoluo pill (DHLP) is a classic Chinese patent medicine used to treat rheumatoid arthritis and other conditions. However, there has been no research on the chemical components of DHLP and the mechanisms by which it ameliorates rheumatoid arthritis. Hence, we analysed the chemical components of DHLP and the DHLP components absorbed in blood by using ultraperformance liquid chromatography-Q-exactive-orbitrap-mass spectrometry. We then used network pharmacology to predict the underlying mechanisms by which DHLP ameliorates rheumatoid arthritis. We identified 153 chemical compounds from DHLP, together with 27 prototype components absorbed in blood. We selected 48 of these compounds as potential active ingredients to explore the mechanism. These compounds are related to 88 significant pathways, which are linked to 18 core targets. This study preliminarily reveals the potential mechanisms by which DHLP ameliorates rheumatoid arthritis and provides a basis for further evaluation of the drug’s efficacy.

As a typical and broad-spectrum benzimidazole, mebendazole (MBZ) has long been used in human and veterinary medicine to treat parasitic infestations, and is widely employed in the aquaculture of Japanese pufferfish (Takifugu rubripes). However, there have been no studies examining the pharmacokinetic characteristics of MBZ in Japanese pufferfish. Furthermore, the presence of MBZ and its metabolites in animal-derived raw food represents a notable safety concern. Here, we investigated the metabolism of MBZ using a UPLC-Q-TOF system. Additionally, we evaluated the pharmacokinetics of MBZ and two metabolites, 2-amino-5(6)-benzoylbenzimidazole (MBZ-NH₂) and 5-hydroxymebendazole (MBZ-OH), in Japanese pufferfish following intramuscular injection of 20 mg/kg MBZ. We detected three metabolites of MBZ (M1–M3), among which, 2-amino-5(6)-(a-hydroxybenzyl) benzimidazole (M3) was detected in an aquatic animal for the first time. The plasma dispositions of MBZ, MBZ-NH₂, and MBZ-OH were characterized by low plasma clearance, medium distribution volume, and long terminal half-life. Moreover, these compounds were widely distributed in the muscle, from which they were rapidly cleared. The pharmacokinetics and metabolism of mebendazole in Japanese pufferfish are described for the first time in this study. Our findings provide a basis for the rational application of MBZ in Japanese pufferfish farming and contribute to our understanding of the metabolism of MBZ in cultured fish.

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.

In this work, we utilized adsorbed BSA and multiwalled carbon nanoparticles (BSA/MWCNTs) as a stationary phase in open tubular (OT) capillary for separation of chiral drugs. (3‐Aminopropyl)triethoxysilane was used to assist fabrication of BSA/MWCNTs‐coated OT column by covalent bonding. Incorporation of MWCNTs nanomaterials into a polymer matrix could increase the phase ratio and take advantage of the easy preparation of an open tubular CEC column. SEM was carried out to characterize the BSA/MWCNTs OT columns. The electrochromatographic performance of the OT columns was evaluated by separation of ketoprofen, ibuprofen, uniconazole, and hesperidin. The effects of MWCNTs concentration, background solution pH and concentration, and applied voltage on separation were investigated. Chiral separations of ketoprofen, ibuprofen, uniconazole, and hesperidin were achieved using the BSA/MWCNTs‐coated OT column with resolutions of 24.20, 12.81, 1.50, and 1.85, respectively. Their optimas were found in the 30 mM phosphate buffers at pH 5.0, 6.5, 7.0, and 6.5, respectively. In addition, the columns demonstrated good repeatability and stability with the run‐to‐run, day‐to‐day, and batch‐to‐batch RSDs of migration times less than 3.5%.

The use of plant-based beverages to interfere with the onset of diabetes may be a promising approach towards type 2 diabetes mellitus (T2DM). The present study investigated the antidiabetic effects of the oral consumption of white tea and G. pentaphyllum (Jiaogulan), especially their combination on HFD/STZ-induced T2DM in C57BL/6 mice. White tea and Jiaogulan administration could mitigate glycolipid metabolic disorders in the diabetic mice by different degrees. White tea administration markedly reduced the blood glucose and ameliorated the glucose intolerance compared to the T2DM mice. Moreover, white tea consumption could protect the islet β-cells against oxidative and inflammatory damage, related to the Nrf-2 signaling pathway. Jiaogulan prominently attenuated liver lipid accumulation by downregulation of SREBP levels. However, interestingly, when white tea was used in combination with Jiaogulan, these effects were enhanced to a certain extent. In particular, the combination significantly suppressed the hepatic G6Pase expressions by activating the AMPK pathway, thus inhibiting gluconeogenesis and improving insulin resistance. On the other hand, the combined formula could regulate the PPAR expressions and ameliorate the hepatic inflammation, further activating the IRS/PI3K/AKT pathway and exerting the antidiabetic potential. Therefore, it was speculated that the antidiabetic effect of this combination may be associated with the AMPK/PI3K pathways. Our findings might provide insight into the combined use of white tea with Jiaogulan tea as a potential functional beverage or food for preventing T2DM.