Oxidative stress plays a critical role in cerebral ischemia/reperfusion (I/R)-induced blood-brain barrier (BBB) disruption. Panax notoginseng saponins (PNS) possess efficient antioxidant activity and have been used in the treatment of cerebral ischemic stroke in China. In this study, we determined the protective effects of PNS on BBB integrity and investigated the underlying mechanism in cerebral microvascular endothelial cells (bEnd.3) exposed to oxygen-glucose deprivation/reperfusion (OGD/R). MTT and LDH release assays revealed that PNS mitigated the OGD/R-induced cell injury in a dose-dependent manner. TEER and paracellular permeability assays demonstrated that PNS alleviated the OGD/R-caused disruption of BBB integrity. Fluorescence probe DCFH-DA showed that PNS suppressed ROS generation in OGD/R-treated cells. Immunofluorescence and western blot analysis indicated that PNS inhibited the degradation of tight junction proteins triggered by OGD/R. Moreover, mechanism investigations suggested that PNS increased the phosphorylation of Akt, the activity of nuclear Nrf2, and the expression of downstream antioxidant enzyme HO-1. All the effects of PNS could be reversed by co-treatment with PI3K inhibitor LY294002. Taken together, these observations suggest that PNS may act as an extrinsic regulator that activates Nrf2 antioxidant signaling depending on PI3K/Akt pathway and protects against OGD/R-induced BBB disruption in vitro.

Purpose: Maytansine (DM1) is a potent anticancer drug and limited in clinical application due to its poor water solubility and toxic side effects. Zein is widely used in nano drug delivery systems due to its good biocompatibility. In this study, we prepared DM1-loaded zein nanoparticles (ZNPs) to achieve tumor targeting and reduce toxic side effects of DM1. Methods: ZNPs were prepared by phase separation and Box-Behnken design was used to optimize the formulation. Then, confocal fluorescence microscope and flow cytometry were used to determine cellular uptake of ZNPs. A549 cells were cultured in vitro to study cytotoxicity and used to establish tumor xenografts in nude mice. Biodistribution and antitumor activity of ZNPs were performed in vivo experiments. In addition, we also performed histological and immunohistochemical examinations on tumors and viscera. Results: The optimal prescription was obtained by using 120 μL zein added to 2 mL water under stirring in 300 rpm. The encapsulation efficiency and drug loading were 82.97 ± 0.80% and 3.32 ± 0.03%, respectively. We found that DM1-loaded ZNPs have a strong inhibitory effect on A549 cells, which stemmed from the ability of ZNPs to enhance cellular uptake. Furthermore, we demonstrated that DM1-loaded ZNPs exhibits a better antitumor efficacy than DM1, which tumor inhibition rate were 97.3% and 92.7%, respectively. The biodistribution revealed that ZNPs could targeted to tumor. Finally, we confirmed by histological that DM1-loaded ZNPs are nontoxic. Conclusion: DM1-loaded ZNPs have considerable antitumor activity. Thus, DM1-loaded ZNPs are a promising treatment of non-small cell lung cancer.

Notoginsenoside (NG)-R1 is one of the main bioactive compounds from Panax notoginseng (PN) root, which is well known in the prescription for mediating the micro-circulatory hemostasis in human. In this article, we mainly discuss NG-R1 in metabolism and the biological activities, including cardiovascular protection, neuro-protection, anti-diabetes, liver protection, gastrointestinal protection, lung protection, bone metabolism regulation, renal protection, and anti-cancer. The metabolites produced by deglycosylation of NG-R1 exhibit higher permeability and bioavailability. It has been extensively verified that NG-R1 may ameliorate ischemia-reperfusion (IR)-induced injury in cardiovascular and neuronal systems mainly by upregulating the activity of estrogen receptor α-dependent phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) and nuclear factor erythroid-2-related factor 2 (NRF2) pathways and downregulating nuclear factor-κB (NF-κB) and mitogen-activated protein kinase (MAPK) pathways. However, no specific targets for NG-R1 have been identified. Expectedly, NG-R1 has been used as a main bioactive compound in many Traditional Chinese Medicines clinically, such as Xuesaitong, Naodesheng, XueShuanTong, ShenMai, and QSYQ. These suggest that NG-R1 exhibits a significant potency in drug development.

Traditional chemotherapy is one of the main methods of cancer treatment, which is largely limited by severe side effects and frequent development of multi-drug resistance by cancer cells. Antimicrobial peptides (AMPs) with high efficiency and low toxicity, as one of the most promising new drugs to replace chemoradiotherapy, have become a current research hotspot, attracting the attention of worldwide researchers. AMPs are natural-source small peptides from the innate immune system, and certain AMPs can selectively kill a broad spectrum of cancer cells while exhibiting less damage to normal cells. Although it involves intracellular mechanisms, AMPs exert their anti-cancer effects mainly through membrane destruction effect; thus, AMPs also hold unique advantages in fighting drug-resistant cancer cells. However, the poor stability and hemolytic toxicity of peptides limit their clinical application. Fortunately, functionalized nanoparticles have many possibilities in overcoming the shortcomings of AMPs, which provides a huge prospect for better application of AMPs. In this paper, we briefly introduce the characteristics and different sources of AMPs, review and summarize the mechanisms of action and the research status of AMPs used as an anticancer therapy, and finally focus on the further use of AMPs nano agents in the anti-cancer direction.