Search Results (6)

Cortex Lycii Radicis, a medicinal plant, has been reported to inhibit epithelial–mesenchymal transition (EMT) and exhibit anti-lung cancer properties. Our previous study identified its major compound, Kukoamine B (KuB), as an inhibitor of membrane PD-1/PD-L1 interaction, thereby restoring T-cell function. However, the effect of KuB on EMT and the underlying mechanism thereof remain unknown. Herein, we show that PD-L1 overexpression enhances the proliferation, migration, and EMT of LUAD cells, upregulating N-cadherin and Vimentin, while downregulating E-cadherin. Mechanistically, PD-L1 directly binds phosphorylated p65 (p-p65) and facilitates p65 nuclear translocation, an interaction confirmed by molecular simulations. We found that KuB disrupts the PD-L1/p65 complex, impedes p65 nuclear translocation, and suppresses EMT, proliferation, and migration in LUAD cells. These inhibitory effects were reversed by PD-L1 overexpression. We therefore conclude that KuB suppresses EMT in LUAD by targeting intracellular PD-L1, blocking PD-L1–p65 interaction and nuclear translocation of p65. Full article

Skin is the first line of defence between the human body and the outside world, and it is constantly exposed to external injuries and wounds for a variety of reasons. Collagen is a structural protein of the extracellular matrix and an important component of the dermis. As a wound dressing, collagen not only provides nutrients to wounds but also enhances the immune response in the pre-healing phase, making it an excellent biomaterial for healing. In this study, we used electrospinning and freeze-drying technology to prepare a Bovine Achilles Tendon Collagen (BATC) electrospun composite membrane and a BATC freeze-dried composite membrane using BATC as a substrate supplemented with 16.7% Polyethylene oxide (PEO) and 0.2% Kukoamine B (KuB). The physicochemical properties and biocompatibility of the BATC composite membrane were verified via scanning electron microscopy, Fourier-transform infrared spectroscopy, and DSC analysis and by measuring the DPPH radical-scavenging capacity, water absorption, water retention, in vitro drug release, and extract cytotoxicity. The BATC composite membrane was found to have a significant effect on skin wound healing, especially in the middle stage of healing, in a mouse full-thickness skin injury model. The BATC/PEO/KuB electrospun composite membrane (EBPK) had the best capacity for promoting wound healing and can be used as a wound dressing for in-depth research and development, and KuB, a monomer component with a clear structure and mechanism of action, can be used as a candidate component of composite dressings. Full article

The unsaturated aldehyde trans-2-nonenal is known to be generated by lipid peroxidation at the surface of the skin in an aging-related manner and has harmful effects on keratinocytes in the skin. In this study, the protective effect of a Lycii Radicis Cortex (LRC) extract against trans-2-nonenal-induced cell damage on human keratinocyte cell lines (HaCaT) was investigated. Notably, treatment with the LRC extract resulted in an increase in cell survival, while trans-2-nonenal decreased the viability of HaCaT cells. For identification of interaction between the LRC extract and trans-2-nonenal, this mixture was incubated in simulated physiological conditions, showing a strong decrease in the amount of trans-2-nonenal by the LRC extract. Subsequent LC-ESI-MS analysis revealed that kukoamine B (KB) formed Schiff base-derived pyridinium adducts with trans-2-nonenal. Thus, these results suggest that KB could be a potential agent that may protect HaCaT cells by forming new products with trans-2-nonenal. Full article

Osteoporosis is an abnormal bone remodeling condition characterized by decreased bone density, which leads to high risks of fracture. Previous study has demonstrated that Lycii Radicis Cortex (LRC) extract inhibits bone loss in ovariectomized (OVX) mice by enhancing osteoblast differentiation. A bioactive compound, kukoamine B (KB), was identified from fractionation of an LRC extract as a candidate component responsible for an anti-osteoporotic effect. This study investigated the anti-osteoporotic effects of KB using in vitro and in vivo osteoporosis models. KB treatment significantly increased the osteoblastic differentiation and mineralized nodule formation of osteoblastic MC3T3-E1 cells, while it significantly decreased the osteoclast differentiation of primary-cultured monocytes derived from mouse bone marrow. The effects of KB on osteoblastic and osteoclastic differentiations under more physiological conditions were also examined. In the co-culture of MC3T3-E1 cells and monocytes, KB promoted osteoblast differentiation but did not affect osteoclast differentiation. In vivo experiments revealed that KB significantly inhibited OVX-induced bone mineral density loss and restored the impaired bone structural properties in osteoporosis model mice. These results suggest that KB may be a potential therapeutic candidate for the treatment of osteoporosis. Full article

The fruits, leaves and root barks of L. barbarum plant are widely used as functional foods and as ingredients in traditional Chinese prescriptions and patent medicines. They are considered to have different pharmacological activities and health benefits because of their diverse constituents. Here, the chemical constituents of the extracts from fruits, leaves and root barks of L. barbarum were compared by ultra-high performance liquid chromatography coupled with high resolution mass spectrometry (UPLC-HR-MS). A total of 131 compounds were identified and seven of them were quantified. Among them, 98, 28 and 35 constituents were detected in fruits, leaves and root barks respectively. Dicaffeoylspermidine/spermine derivatives were the most detected compounds (74/131); among them, dicaffeoylspermine isomers and propionyl-dicaffeoylspermidine were found in root barks in very large amounts (e.g., kukoamine B = 10.90 mg/g dry powder); dicaffeoyl-spermidine isomers were detected in fruits/leaves in a high amount, and many of their glycosylated derivatives were mainly detected in fruits. In addition, six saponins from L. barbarum fruits were reported for the first time, and 5,6-dihydrosolasonine was reported for the first time in plants. The activity assays showed that the root bark extract possessed the strongest antioxidative activity and cytotoxicity, which was presumed due to the large amount of dicaffeoylspermine/spermidines in root barks. Fourteen potential bioactive components from fruits were identified by a target cell-based screening method. These results will help to understand the different biological activities of these three parts of L. barbarum plant and will benefit the discovery of new functional components. Full article

In this study, two natural phenolic polyamines, kukoamine A and B, were comparatively investigated for their antioxidant and cytoprotective effects in Fenton-damaged bone marrow-derived mesenchymal stem cells (bmMSCs). When compared with kukoamine B, kukoamine A consistently demonstrated higher IC₅₀ values in PTIO•-scavenging (pH 7.4), Cu²⁺-reducing, DPPH•-scavenging, •O₂⁻-scavenging, and •OH-scavenging assays. However, in the PTIO•-scavenging assay, the IC₅₀ values of each kukoamine varied with pH value. In the Fe²⁺-chelating assay, kukoamine B presented greater UV-Vis absorption and darker color than kukoamine A. In the HPLC–ESI–MS/MS analysis, kukoamine A with DPPH• produced radical-adduct-formation (RAF) peaks (m/z 922 and 713). The 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyl (MTT) assay suggested that both kukoamines concentration-dependently increased the viabilities of Fenton-damaged bmMSCs at 56.5–188.4 μM. However, kukoamine A showed lower viability percentages than kukoamine B. In conclusion, the two isomers kukoamine A and B can protect bmMSCs from Fenton-induced damage, possibly through direct or indirect antioxidant pathways, including electron-transfer, proton-transfer, hydrogen atom transfer, RAF, and Fe²⁺-chelating. Since kukoamine B possesses higher potentials than kukoamine A in these pathways, kukoamine B is thus superior to kukoamine A in terms of cytoprotection. These differences can ultimately be attributed to positional isomeric effects. Full article