With the worldwide prevalence of diabetes and considering the complicated microenvironment of diabetic wounds, the design and development of innovative multifunctional wound dressing materials are much wanted for the treatment of hard-to-heal wounds in diabetic patients. In the present study, anti-inflammatory ingredients loaded with nanofibrous wound dressing materials were manufactured by a promising blend-electrospinning strategy, and their capability for treating the diabetic wound was also systematically explored. A polymer blend consisting of Chitosan (CS) and polyvinyl alcohol (PVA) was electrospun into CS-PVA nanofibrous mats as control groups. In the meanwhile, a bioactive ingredient of Chinese medicine Pulsatilla, anemoside B4(ANE), with different contents were loaded into the electrospinning solution to construct CS-PVA-ANE nanofibrous mats. The developed CS-PVA-ANE wound dressing materials exhibited multifunctional properties including prominent water absorption, biomimetic elastic mechanical properties, and sustained ANE releasing behavior, as well as outstanding hemostatic properties. The in vitro studies showed that the CS-PVA-ANE nanofiber mats could significantly suppress lipopolysaccharide (LPS)-stimulated differentiation of pro-inflammatory (M1) macrophage subsets, and notably reduce the reactive oxygen species (ROS) generation, as well as obviously decrease inflammatory cytokine release. The in vivo animal studies showed that the CS-PVA-ANE nanofiber mats promoted the healing of diabetic wounds by significantly enhancing wound closure rates, accelerating excellent angiogenesis, promoting re-epithelization and collagen matrix deposition throughout all stages of wound healing. The present study demonstrated that CS-PVA-ANE nanofiber mats could effectively shorten the wound-healing time by inhibiting inflammatory activity, which makes them promising candidates for the treatment of hard-to-heal wounds caused by diabetes.

Atherosclerosis, a chronic inflammatory disease, is a major contributor to cardiovascular diseases. Ursolic acid (UA) is a phytonutrient with widely biological effects including anti-oxidative, anti-inflammatory, and so on. At present, the effect of UA on atherosclerosis and the mechanism of action are still obscure. This study focused on investigating the effects of UA on atherosclerosis both in vivo and in vitro. We first selected LOX-1 as our target, which was reckoned as a new promising receptor for treating atherosclerosis. The evaluation in vitro suggested that UA significantly decreased endothelial LOX-1 expression induced by LPS both in mRNA and protein levels. Pre-treatment of UA also inhibited TLR4/MyD88 signaling activated by LPS. Moreover, UA reduced ROS production and suppressed the activation of NF-κB stimulated by LPS. Particularly, the evaluation in vivo further verified the conclusion obtained in vitro. In ApoE^−/− mice fed with an atherogenic diet, both UA (100 mg/kg/day) and simvastatin significantly attenuated atherosclerotic plaque formation and shrunk necrotic core areas. The enhanced expression of LOX-1 in atherosclerotic aorta was also dramatically decreased by administration of UA. Taken together, these results suggested that UA, with anti-atherosclerotic activity through inhibition of LOX-1 mediated by ROS/NF-κB signaling pathways, may become a valuable vascular protective candidate for the treatment of atherosclerosis.

Aims: Vulnerable plaque disruption in advanced atherosclerosis leads to acute thrombus and subsequent myocardial infarction and severely threatens human health. Necroptosis of macrophage involved in the necrotic core is one key factor for plaque vulnerability. Dihydrotanshinone I (DHT) is a natural diterpenoid isolated from Danshen demonstrating effective anti-inflammatory property. It is accepted that inflammation plays a crucial role in the process of atherogenesis. However, whether DHT prevents atherosclerosis is poorly understood. Here, we investigated the effect of DHT on vulnerable plaque in an apolipoprotein E-deficient (ApoE^−/−) mice model of atherosclerosis and the underlying protective mechanisms. Results: In the in vitro experiment, first LPS/ZVAD (LPS, lipopolysaccharide; ZVAD, ZVAD-FMK, a cell-permeable pan-caspase inhibitor) stimulated necroptosis of macrophage in a receptor-interacting protein 3 (RIP3)-dependent pathway, which was regulated by Toll-like receptor 4 (TLR4) dimerization. Further study illustrated that activated RIP3 evoked endoplasmic reticulum stress as well as reactive oxygen species generation. Both DHT and RIP3 silence reversed the above phenomena. In the in vivo experiment, aorta and serum samples were collected to determine features of plaque stability, including plaque size, necrotic core area, as well as collagen content in fibrous cap and the expression of related protein molecules. Both DHT and RIP3 inhibitor GSK872 significantly enhanced plaque stability in ApoE^−/− mice by reducing oxidative stress, shrinking necrotic core area, increasing collagen content, and decreasing RIP3 expression. Innovation and Conclusion: Our study showed that DHT may stabilize vulnerable plaque by suppressing RIP3-mediated necroptosis of macrophage, which indicates its potential application as a lead compound for cardiovascular treatments, especially for advanced atherosclerosis. Antioxid. Redox Signal. 34, 351–363.

We report here the discovery of an acidic polysaccharide, namely IAPS-2, from the root of Ilex asprella, with anti-tumor activity via a repolarizing tumor associated macrophages (TAMs) phenotype. We obtained IAPS-2 polysaccharide from this herb based on acidity and found that IAPS-2 expressed the activity of promoting the secretion of anti-tumor cytokines in macrophages. Furthermore, we evaluated its anti-tumor effect on TAM cells, through the activation of nuclear factor-κB (NF-κB) and signal transducer and activator of transcription (STAT) signaling. In particular, in the tumor murine model, IAPS-2 demonstrated that it could significantly inhibit the growth of tumors via modulating the function of TAMs and increase the animal survival rate. In summary, IAPS-2, with a clearly illustrated chemical composition, potent anti-tumor activity, and a solid mechanism of action, may be developed into a valuable therapeutic tool for cancer immunotherapy.

We herein report a food-derived polysaccharide (EJP) with the effect of relieving myocardial ischemia reperfusion injury (MIRI). This novel polysaccharide was isolated from the leaf of Eriobotrya japonica, and we first found its myocardium protective effects in vitro. Then, we firstly characterized EJP with a series of analytical technologies and further tested its effect on myocardial ischemia reperfusion injury (MIRI) with the illustration of the potential mechanisms in vivo. Interestingly, in the murine model of MIRI, administration of EJP effectively improved post-I/R heart contraction and limited the infarct size. Moreover, EJP significantly attenuated IR-induced oxidative damage and inflammatory reaction, as evidenced by decreasing MDA, IL-6, and TNF-α contents and increasing SOD activity and GSH-Px expression. In addition, we proved that EJP not only had no nephrotoxicity but also demonstrated a protective effect on the kidneys through HE staining and biochemical analysis. In sum, EJP, with a significant protective effect against myocardial I/R injury by showing anti-inflammatory and anti-oxidative activities, may become a meaningful drug candidate for the treatment of myocardial I/R injury.