A new acylated iridoid and other chemical constituents from Valeriana jatamansi and their biological activities.

A new acylated iridoid, valejatadoid H (1), along with fourteen known compounds, were obtained from the n-BuOH extract of the roots and rhizomes of Valeriana jatamansi, and their structures were elucidated by various spectroscopic methods. Among them, compounds 8, 11 and 13 exhibited potent inhibition on NO production, with IC50 values of 4.21, 6.08 and 20.36 µM, respectively. In addition, compounds 14 and 15 showed anti-influenza virus activities, among which compound 14 exhibited significant effect with an IC50 value of 0.99 µM.

Iridoids and sesquiterpenoids from Valeriana officinalis and their bioactivities.

Twenty-six iridoids, including six undescribed ones (iridoidvols A-F) and an undescribed natural one, along with ten known sesquiterpenoids were isolated from the roots and rhizomes of Valeriana officinalis. Structurally, iridoidvol A is the first example of iridoid with sesquiterpenoid acid ester. In addition, all of the isolates were evaluated for anti-inflammatory and anti-influenza virus activities. Among them, isovaltrate isovaleroyloxyhydrin exhibited a significant inhibitory effect on NO production with an IC50 value of 19.00 µM.

Shuttle-Shape Carrier-Free Platinum-Coordinated Nanoreactors with O2 Self-Supply and ROS Augment for Enhanced Phototherapy of Hypoxic Tumor.

The synergistic nanotheranostics of reactive oxygen species (ROS) augment or phototherapy has been a promising method within synergistic oncotherapy. However, it is still hindered by sophisticated design and fabrication, lack of a multimodal synergistic effect, and hypoxia-associated poor photodynamic therapy (PDT) efficacy. Herein, a kind of porous shuttle-shape platinum (IV) methylene blue (Mb) coordination polymer nanotheranostics-loaded 10-hydroxycamptothecin (CPT) is fabricated to address the abovementioned limitations. Our nanoreactors possess spatiotemporally controlled O2 self-supply, self-sufficient singlet oxygen (1O2), and outstanding photothermal effect. Once they are taken up by tumor cells, nanoreactors as a cascade catalyst can efficiently catalyze degradation of the endogenous hydrogen peroxide (H2O2) into O2 to alleviate tumor hypoxia. The production of O2 can ensure enhanced PDT. Subsequently, under both stimuli of external red light irradiation and internal lysosomal acidity, nanoreactors can achieve the on-demand release of CPT to augment in situ mitochondrial ROS and highly efficient tumor ablation via phototherapy. Moreover, under the guidance of near-infrared (NIR) fluorescent imaging, our nanoreactors exhibit strongly synergistic potency for treatment of hypoxic tumors while reducing damages against normal tissues and organs. Collectively, shuttle-shape platinum-coordinated nanoreactors with augmented ROS capacity and enhanced phototherapy efficiency can be regarded as a novel tumor theranostic agent and further promote the research of synergistic oncotherapy.

Selective antitumor activity of drug-free TPGS nanomicelles with ROS-induced mitochondrial cell death.

D-a-tocopheryl polyethylene glycol succinate (TPGS) as a FDA-approved safe adjuvant has shown an excellent application in the targeting delivery of antitumor drugs and overcoming multidrug resistance. Beside, TPGS can result in apoptogenic activity toward many tumor types because it can induce mitochondrial dysfunction. Therefore, TPGS can serve as an antineoplastic agent. However, the current research on the selective antitumor activity of TPGS is ignored. To reveal the issue, herein we develop a mitochondria-targeting drug-free TPGS nanomicelles with the hydrodynamic diameter of about 100 nm and outstanding serum stability by weak interaction-driven self-assembly of the amphiphilic TPGS polymer. Moreover, such drug-free TPGS nanomicelles intravenously injected into tumor-bearing mice exhibit long blood circulation time, superior tumor enrichment, and inhibit the tumor growth via inducing excessive reactive oxygen species (ROS) generation within tumor cells. Further in vitro and in vivo researches jointly demonstrate that drug-free TPGS nanomicelles have more significant antitumor effect on HeLa cells compared with that of other tumor cells. On the contrary, drug-free TPGS nanomicelles display the low toxicity toward normal cells and tissues. Taken together, these new findings confirm that TPGS drug-free nanomicelles represent simple, multifunctional, safe, and efficient antineoplastic agents, which can be expected to bring new light on the development of drug-free polymers for tumor therapy.

Cardamonin Inhibits Angiogenesis by mTOR Downregulation in SKOV3 Cells.

The mammalian target of rapamycin is critical in hypoxia-triggered angiogenesis. Cardamonin inhibits proliferation of various cancer cells through suppressing the mammalian target of rapamycin. In this study, the antiangiogenic effect of cardamonin on CoCl2-mimicked hypoxic SKOV3 cells was investigated. Cardamonin exhibited an antiproliferative effect on normal and CoCl2-mimicked hypoxic SKOV3 cells. Messenger RNA expression of vascular endothelial growth factor was inhibited with cardamonin and rapamycin in SKOV3 cells under both conditions. However, cardamonin had little effect on the messenger RNA expression of hypoxia-inducible factor-α. Cardamonin inhibited the protein expression of hypoxia-inducible factor-1α, hypoxia inducible factor-2α, vascular endothelial growth factor, and the phosphorylation of mammalian target of rapamycin and ribosomal S6 kinase 1. Furthermore, angiogenesis induced by a medium of SKOV3 cells was reduced by cardamonin in a chicken embryo allantois membrane model. These findings suggest that cardamonin inhibits protein expression of hypoxia-inducible factor-α, and vascular endothelial growth factor, which was induced by CoCl2-mimicked hypoxia and this effect partially correlates with the mammalian target of rapamycin inhibition. Cardamonin might be a potential angiogenesis inhibitor for ovarian cancer therapy.