Background: Patchouli alcohol (PA) is a tricyclic sesquiterpene extracted fromPogostemonis Herba, which is a traditional Chinese medicine used for therapy of inflammatory diseases. Recent studies have shown that PA has various pharmacological activities, including anti-bacterial and anti-viral effects.Methods: In this study, the anti-influenza virus (IAV) activities and mechanisms were investigated both in vitro and in vivo. The inhibitory effects of PA against IAV in vitro were evaluated by plaque assay and immunofluorescence assay. The neuraminidase inhibition assay, hemagglutination inhibition (HI) assay, and western blot assay were used to explore the anti-viral mechanisms. The anti-IAV activities in vivo were determined by mice pneumonia model and HE staining.Results: The results showed that PA significantly inhibited different IAV strains multiplication in vitro, and may block IAV infection through inactivating virus particles directly and interfering with some early stages after virus adsorption. Cellular PI3K/Akt and ERK/MAPK signaling pathways may be involved in the anti-IAV actions of PA. Intranasal administration of PA markedly improved mice survival and attenuated pneumonia symptoms in IAV infected mice, comparable to the effects of Oseltamivir.Conclusions: Therefore, Patchouli alcohol has the potential to be developed into a novel anti-IAV agent in the future.
Hepatocellular carcinoma (HCC) patients suffer from severe pain due to the serious systemic side effects and low efficiency of chemotherapeutic drugs, and it is important to develop novel drug delivery systems to circumvent these issues. In this study, a series of galactose-based glycopolymers, poly(N-(prop-2-enoyl)-β-D-galactopyranosylamine)-b-poly(N-isopropyl acrylamide) (pGal(OH)-b-pNIPAA), were prepared through a sequential reversible addition-fragmentation chain transfer (RAFT) polymerization and tetrabutylammonium hydroxide (TBAOH)-mediated removal of acetyl groups. Hydrophilic doxorubicin hydrochloride was introduced to undergo collaborative assembly with poly(N-(prop-2-enoyl)-β-D-peracetylated galactosamine)-b-poly(N-isopropyl acrylamide) (pGal(Ac)-b-pNIPAA) via TBAOH treatment. pGal-b-pNIPAA/doxorubicin (DOX) delivery nanoparticles (GND NPs) formed by collaborative assembly were fully characterized by NMR, TEM and FT-IR, indicating the well-controlled formation of particles with uniform size and high efficiency in terms of drug loading and encapsulation compared with conventional adsorption methods. Meanwhile, the GND NPs were observed to be rapidly disintegrated under acidic conditions and resulted in an increased release of DOX. Cellular experiments showed that pGal-b-pNIPAA/DOX is apparently an asialoglycoprotein receptor (ASGPR)-mediated target of HCC, resulting in enhanced cellular uptake to HepG2 cells and anti-tumor efficacy in vitro. Furthermore, GND NPs III exerted more sustainable and effective anti-tumor effects compared to free DOX on a transgenic zebrafish TO(KrasG12V) model in vivo. These results indicated that the biocompatible nanomaterials developed by collaborative assembly with galactosyl diblock glycopolymers and DOX may serve as a promising candidates for targeting therapy of HCC.