The aim of the present study was to evaluate the effects of catalpol administration on atherosclerosis. Atherogenesis was induced by a high-cholesterol chow in male New Zealand White rabbits that were randomly assigned to receive atorvastatin (5 mg/kg/day), catalpol (5 mg/kg/day), or vehicle by oral gavage for 12 weeks. The rabbits were sacrificed after 12 weeks, and the thoracic aorta and serum were collected for further pathological and molecular biological analysis. Catalpol administration resulted in significantly attenuated atherosclerotic lesions. Total cholesterol, triglycerides, and low-density lipoprotein cholesterol were remarkably reduced, and high-density lipid cholesterol was elevated in the catalpol-treated group. Catalpol reduced the levels of tumor necrosis factor-α, interleukin-6, monocyte chemoattractant protein-1, soluble vascular cell adhesion molecule-1, and soluble intercellular adhesion molecule-1 in the serum, as well as vascular cell adhesion molecule-1, monocyte chemoattractant protein-1, tumor necrosis factor-α protein, inducible nitric oxide synthase, matrix metalloproteinases-9, and nuclear factor-κB protein65 in the aortic arch. In addition, catalpol treatment reduced the lipid peroxidation levels, while elevating antioxidant capacity. Catolpol pretreatment inhibited the nuclear translocation and DNA binding activity of nuclear factor-κB protein in oxygenized low-density lipoprotein-stimulated EA.hy926 cells. Furthermore, catolpol pretreatment activated nuclear factor erythroid 2-related factor 2 and upregulated the expression of its downstream antioxidant enzyme heme oxygenase. In summary, catalpol attenuated atherosclerotic lesions by the inhibition of inflammatory cytokines and oxidative stress status in a rabbit atherosclerotic model and enhanced the antioxidant capacity in oxygenized low-density lipoprotein-stimulated EA.hy926 cells. These results suggest that catalpol may be used to prevent and attenuate atherosclerosis.

Abstract:Objectives: The aim of this study was to investigate the proliferative and protective effects of striatisporolide A (SA) obtained from the rhizomes of Athyrium multidentatum (Doell.) Ching on human umbilical vein endothelial cells (HUVECs). Methods: Cell viability was measured by the MTT method. Cell apoptosis was determined by flow cytometry. Intracellular ROS was measured by the 2,7-dichlorodihydrofluorescein diacetate (DCFH-DA) fluorescent probe. Results: The viability rate in cells treated with 100 µM SA alone was increased to 128.72% ± 0.19% and showed a significant difference compared with the control group (p < 0.05). Meanwhile, SA augmented the cell viabilities in H 2 O 2 -treated HUVECs, and the cell viability was enhanced to 56.94% ± 0.13% (p < 0.01) when pre-incubated with 50 µM SA. The cell apoptosis rates were reduced to 2.17% ± 0.20% (p < 0.05) and 3.1% ± 0.34% (p < 0.01), respectively, after treatment with SA alone or SA/H 2 O 2 . SA inhibited the overproduction of reactive oxygen species (ROS) in HUVECs induced by H 2 O 2 and the fluorescent intensity was abated to 9.47 ± 0.61 after pre-incubated with 100 µM SA. Conclusions: The biological activities of SA were explored for the first time. Our results stated that SA exhibited significant cytoproliferative and minor cytoprotective effects on HUVECs. We presume that the mechanisms of the proliferation and protection actions of SA involve interference with the generation of ROS and the cell apoptosis. These findings provide a new perspective on the biological potential of butenolides.

Tumor-associated macrophages (TAMs) widely exist in the solid tumors, which participate in the entire course of tumor development and execute momentous impacts. Therefore, manipulating TAMs has been identified as an expecting strategy with immense potential for cancer therapy. Herein, a nanodrug delivery system was leveraged for simultaneously targeting tumor cells and M2-type TAMs for efficient colon cancer therapy. The broad-spectrum anticancer chemotherapeutic drug doxorubicin (DOX) was hitchhiked in a mannose-modified bovine serum albumin (MAN-BSA) carrier. The DOX@MAN-BSA nanodrug delivery system was verified to possess feasible physical performances for unhindered systemic circulation and active targeting on colon tumors. DOX@MAN-BSA nanoparticles could be preferentially swallowed by colon tumor cells and M2 TAMs through mannose receptor-mediated endocytosis. Further in vivo antitumor therapy in CT26 colon tumor-bearing mice has achieved remarkable suppression efficacy with satisfactory biosafety. Leveraging the nanodrug delivery system for simultaneously targeting tumor cells and M2 TAMs has contributed a feasible strategy to collaboratively repress the malignant tumor cells and the collusive M2 TAMs for efficient cancer therapy.

Liver regeneration post severe liver injury is crucial for the recovery of hepatic structure and function. The energy sensor AMP‑activated protein kinase (AMPK) has a crucial role in the regulation of nutrition metabolism in addition to other energy‑intensive physiological and pathophysiological processes. Cellular proliferation requires intensive energy and nutrition support, therefore the present study investigated whether AMPK is involved in liver regeneration post carbon tetrachloride (CCl4)‑induced acute hepatic injury. The experimental data indicated that phosphorylation level of AMPK increased 48 h post‑CCl4 exposure, which was accompanied with upregulation of proliferating cell nuclear antigen (PCNA) and recovery of alanine aminotransferase (ALT) level. Pretreatment with the AMPK inhibitor compound C had no obvious effects on ALT elevation in plasma and histological abnormalities in liver 24 h post CCl4 exposure. However, treatment with compound C 24 h post CCl4 exposure significantly suppressed CCl4‑induced AMPK phosphorylation, PCNA expression and ALT recovery. These data suggest that endogenous AMPK was primarily activated at the regeneration stage in mice with CCl4‑induced acute liver injury and may function as a positive regulator in liver regeneration.

No abstract