Paeonol exhibits a wide range of pharmacological activities, such as anti-inflammatory, antidiabetic as well as pain-relieving activities. However, its intrinsic properties, such as low water solubility, poor stability and low oral bioavailability, restrict its clinical application. The current study aimed to optimize paeonol-loaded ethosomal formulation and characterize it in terms of encapsulation efficiency (EE), vesicle size (VS), zeta potential (ZP) and polydispersity index (PDI), in addition to differential scanning calorimetry (DSC), X-ray diffraction (XRD) and Fourier-transform infrared spectroscopy (FT-IR) studies. Here, paeonol-loaded ethosomes were prepared by the injection method and optimized by the single-factor test and central composite design-response surface methodology. The optimized paeonol-loaded ethosomes had an EE of 84.33 ± 1.34%, VS of 120.2 ± 1.3 nm, negative charge of −16.8 ± 0.36 mV, and PDI of 0.131 ± 0.006. Ethosomes showed a spherical morphology under the transmission electron microscope (TEM). DSC, XRD and FT-IR results indicated that paeonol was successfully incorporated into the ethosomes. In-vitro transdermal absorption and skin retention of paeonol from paeonol-loaded ethosomes were 138.58 ± 9.60 µg/cm² and 52.60 ± 7.90 µg/cm², respectively. With reasonable skin tolerance, ethosomes could be a promising vehicle for transdermal delivery of paeonol.

Aim: Aralia taibaiensis is a natural medicinal and food plant that is rich in triterpenoid saponins with hypoglycaemic, antioxidant, hepatoprotective, anti-gastric ulcer and anti-inflammatory effects. This study has significance in terms of the antioxidant, anti-aging and organ protective effects of Aralia taibaiensis total saponins (TSAT) in D-galactose-induced aging rats. Methods: The saponin composition of TSAT was determined and quantified by high performance liquid chromatography (HPLC). We consolidated the antioxidant and enzyme inhibitory activities of TSAT in vitro and assessed the effects of TSAT on daily mobility, body weight, behaviour, organ indices, oxidation-related indices and pathological changes in aging rats. Results: In vitro experiments showed that TSAT had a scavenging effect on 1,1-diphenyl-2-picrylhydrazyl (DPPH), 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS), tyrosinase, hydroxyl radicals (HO•) and superoxide radicals (•O^2-) and was closely related to the dose of TSAT. In vivo experiments showed that after 8 weeks of continuous gavage administration, the rats gradually recovered their body weight, daily activity ability, learning and memory ability and organ index and effectively improved D-gal-induced organ injury. Specifically, TSAT significantly increased the levels of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px) and total antioxidant capacity (T-AOC) and significantly decreased malondialdehyde (MDA) levels in the serum, brain, heart, lung, spleen and kidney of aging rats compared to the model group. In addition, TSAT significantly inhibited the D-gal-induced upregulation of hepatic alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels. The histopathological results showed that TSAT reversed D-gal-induced damage to the brain, heart, lung, kidney, liver and spleen to varying degrees. Conclusion: TSAT is a high-quality natural product with antioxidant and anti-aging properties that can alleviate D-gal-induced aging damage in rats.

Phloretin is a natural dihydrochalcone flavonoid that is mainly distributed in apple, pear and other juicy fruit peels or root peels. Phloretin exhibits several pharmacological properties, such as antidiabetic, antioxidant, anti-inflammatory, and antitumor activities. However, the poor water solubility of phloretin limits its application in the treatment of numerous diseases. To date, the underlying mechanisms of phloretin absorption have not been investigated. In this study, the pharmacokinetics of phloretin orally administered to Sprague-Dawley (SD) rats were examined, and the absorption mechanisms of phloretin were investigated in a Caco-2 cell monolayer and single-pass intestinal perfusion in SD rat. The effects measured by basic parameters, such as compound concentration, time, temperature, paracellular pathway, in different intestinal segments were analyzed, and various inhibitors, such as the P-glycoprotein (P-gp) inhibitor verapamil, the multidrug resistance protein 2 (MRP2) inhibitor indomethacin, the breast cancer resistance protein (BCRP) inhibitor reserpine, and the closely related regulator EDTA, were evaluated to determine their effects on the absorption of phloretin. The pharmacokinetics of phloretin was studied by oral and intravenous injection in rats. The bioavailability was 8.676 %.The SPIP experiments showed that P-gp, MRP2, BCRP protein inhibitor and closely related regulator, could significantly increase the apparent permeability coefficient (Papp) of phloretin. Monolayer transport experiments in Caco-2 cells showed that P-gp, MRP2 protein inhibitor and closely related regulator EDTA, significantly increased the Papp value of phloretin. In conclusion, phloretin is a substrate of P-gp and MRP2, and its modes of transport include active transport, efflux protein transport and cell bypass.

Hepatic fibrosis is a pathophysiological process, which causes excessive extracellular matrix (ECM) deposition resulting from persistent liver damage. Myofibroblasts are the core cells that produce ECM. It is known that epithelial-mesenchymal transition (EMT) is not a simple transition of cells from the epithelial to mesenchymal state. Instead, it is a process, in which epithelial cells temporarily lose cell polarity, transform into interstitial cell-like morphology, and acquire migration ability. Hepatocytes, hepatic stellate cells, and bile duct cells are the types of intrahepatic cells found in the liver. They can be transformed into myofibroblasts via EMT and play important roles in the development of hepatic fibrosis through a maze of regulations involving various pathways. The aim of the present study is to explore the relationship between the relevant regulatory factors and the EMT signaling pathways in the various intrahepatic cells.