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In this paper, a series of glycyrrhetic acid derivatives 3a–3f were synthesized via the esterification reaction. The cytotoxicity of these compounds against five tumor cells (SGC-7901, BEL-7402, A549, HeLa and B16) and normal LO2 cells was investigated using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) method. The results showed that compound 3a exhibited high antiproliferative activity against HeLa cells (IC50 = 11.4 ± 0.2 μM). The anticancer activity was studied through apoptosis, cloning, and scratching; the levels of the intracellular ROS, GSH, and Ca2+; and the change in the mitochondrial membrane potential, cell cycle arrest and RNA sequencing. Furthermore, the effects of compound 3a on gene expression levels and metabolic pathways in HeLa cells were investigated via transcriptomics. The experimental results showed that this compound can block the cell cycle in the S phase and inhibit cell migration by downregulating Focal adhesion kinase (FAK) expression. Moreover, the compound can reduce the intracellular glutathione (GSH) content, increase the Ca2+ level and the intracellular ROS content, and induce a decrease in the mitochondrial membrane potential, further leading to cell death. In addition, it was also found that the mechanism of compounds inducing apoptosis was related to the regulation of the expression of mitochondria-related proteins B-cell lymphoma-2 (Bcl-2), Bcl-2-Associated X (Bax), and the activation of the caspase proteins. Taken together, this work provides a help for the development of glycyrrhetinic acid compounds as potential anticancer molecules. [ABSTRACT FROM AUTHOR]

Three benzoxanthone derivatives were synthesized through a new photochemical strategy. The in vitro cytotoxic activity of these compounds was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, and their partition coefficients (logP) were measured by shake flask method. The pKa values of the compounds were detected by potentionmetric titration. The interaction of the compounds with calf thymus DNA (CT-DNA) was investigated by electronic absorption, luminescence spectra and viscosity. A molecular docking analysis was performed. The antitumor efficacy of the compounds was evaluated by cell apoptosis, cell cycle arrest, intracellular Ca2+ concentrations and reactive oxygen species (ROS) levels. The mitochondrial membrane potential was assayed using JC-1 (5,5′,6,6′-tetrachloro-1,1,3′,3′-tetraethyl-imidacarbocyanine iodide) as the fluorescence probe. The expression of Bcl-2 family protein, caspase 3 and poly ADP-ribose polymerase (PARP) was explored by western blot. The results showed that the compounds induced apoptosis through a ROS-mediated mitochondrial dysfunction pathway. This work provides an efficient approach to synthesize benzoxanthone derivatives, and is helpful for understanding the apoptotic mechanism. [ABSTRACT FROM AUTHOR]

Fucoxanthin, a special xanthophyll derived from marine algae, has increasingly attracted attention due to its diverse biological functions. However, reports on its ocular benefits are still limited. In this work, the ameliorative effect of fucoxanthin on visible light and lipid peroxidation-induced phagocytosis disruption in retinal pigment epithelium (RPE) cells was investigated in vitro. Marked oxidative stress, inflammation, and phagocytosis disruption were evident in differentiated RPE cells following their exposure to visible light under a docosahexaenoic acid (DHA)-rich environment. Following pretreatment with fucoxanthin, however, the activated nuclear factor erythroid-derived-2-like 2 (Nrf2) signaling pathway was observed and, furthermore, when the fucoxanthin -pretreated RPE cells were irradiated with visible light, intracellular reactive oxygen species (ROS), malondialdehyde (MDA) levels and inflammation were obviously suppressed, while phagocytosis was significantly improved. However, following the addition of Nrf2 inhibitor ML385, the fucoxanthin exhibited no ameliorative effects on the oxidative stress, inflammation, and phagocytosis disruption in the RPE cells, thus indicating that the ameliorative effect of fucoxanthin on the phagocytosis of RPE cells is closely related to the Nrf2 signaling pathway. In conclusion, these results suggest that fucoxanthin supplementation might be beneficial to the prevention of visible light-induced retinal injury. [ABSTRACT FROM AUTHOR]

Fucoxanthin, a special xanthophyll derived from marine algae, has increasingly attracted attention due to its diverse biological functions. However, reports on its ocular benefits are still limited. In this work, the ameliorative effect of fucoxanthin on visible light and lipid peroxidation-induced phagocytosis disruption in retinal pigment epithelium (RPE) cells was investigated in vitro. Marked oxidative stress, inflammation, and phagocytosis disruption were evident in differentiated RPE cells following their exposure to visible light under a docosahexaenoic acid (DHA)-rich environment. Following pretreatment with fucoxanthin, however, the activated nuclear factor erythroid-derived-2-like 2 (Nrf2) signaling pathway was observed and, furthermore, when the fucoxanthin -pretreated RPE cells were irradiated with visible light, intracellular reactive oxygen species (ROS), malondialdehyde (MDA) levels and inflammation were obviously suppressed, while phagocytosis was significantly improved. However, following the addition of Nrf2 inhibitor ML385, the fucoxanthin exhibited no ameliorative effects on the oxidative stress, inflammation, and phagocytosis disruption in the RPE cells, thus indicating that the ameliorative effect of fucoxanthin on the phagocytosis of RPE cells is closely related to the Nrf2 signaling pathway. In conclusion, these results suggest that fucoxanthin supplementation might be beneficial to the prevention of visible light-induced retinal injury.

The situation of drug resistance has become more complicated due to the scarcity of plant resistance genes, and overcoming this challenge is imperative. Isatis indigotica has been used for the treatment of wounds, viral infections, and inflammation for centuries. Antimicrobial peptides (AMPs) are found in all classes of life ranging from prokaryotes to eukaryotes. To identify AMPs, I. indigotica was explored using a novel, sensitive, and high-throughput Bacillus subtilis screening system. We found that IiR515 and IiR915 exhibited significant antimicrobial activities against a variety of bacterial (Xanthomonas oryzae, Ralstonia solanacearum, Clavibacter michiganensis, and C. fangii) and fungal (Phytophthora capsici and Botrytis cinerea) pathogens. Scanning electron microscope and cytometric analysis revealed the possible mechanism of these peptides, which was to target and disrupt the bacterial cell membrane. This model was also supported by membrane fluidity and electrical potential analyses. Hemolytic activity assays revealed that these peptides may act as a potential source for clinical medicine development. In conclusion, the plant-derived novel AMPs IiR515 and IiR915 are effective biocontrol agents and can be used as raw materials in the drug discovery field., Competing Interests: The authors declare no conflict of interest.

The Maize Wip1 gene encodes a wound-induced Bowman-Birk inhibitor (BBI) protein which is a type of serine protease inhibitor, and its expression is induced by wounding or infection, conferring resistance against pathogens and pests. In this study, the maize Wip1 promoter was isolated and its function was analyzed. Different truncated Wip1 promoters were fused upstream of the GUS reporter gene and transformed into Arabidopsis, tobacco and rice plants. We found that (1) several truncated maize Wip1 promoters led to strong GUS activities in both transgenic Arabidopsis and tobacco leaves, whereas low GUS activity was detected in transgenic rice leaves; (2) the Wip1 promoter was not wound-induced in transgenic tobacco leaves, but was induced by wounding in transgenic rice leaves; (3) the truncated Wip1 promoter had different activity in different organs of transgenic tobacco plants; (4) the transgenic plant leaves containing different truncated Wip1 promoters had low GUS transcripts, even though high GUS protein level and GUS activities were observed; (5) there was one transcription start site of Wip1 gene in maize and two transcription start sites of GUS in Wip1::GUS transgenic lines; (6) the adjacent 35S promoter which is present in the transformation vectors enhanced the activity of the truncated Wip1 promoters in transgenic tobacco leaves, but did not influence the disability of truncated Wip1231 promoter to respond to wounding signals. We speculate that an ACAAAA hexamer, several CAA trimers and several elements similar to ACAATTAC octamer in the 5'-untranslated region might contribute to the strong GUS activity in Wip1231 transgenic lines, meanwhile, compared to the 5'-untranslated region from Wip1231 transgenic lines, the additional upstream open reading frames (uORFs) in the 5'-untranslated region from Wip1737 transgenic lines might contribute to the lower level of GUS transcript and GUS activity.