Ultrasound-assisted deep eutectic solvents extraction of glabridin and isoliquiritigenin from Glycyrrhiza glabra: Optimization, extraction mechanism and in vitro bioactivities.

Licorice (Glycyrrhiza glabra) is extensively used owing to the superior pharmacological effects. However, its maximum application potential has not been fully exploited due to the limitation of currently available extraction solvent and methods. In this study, an eco-friendly deep eutectic solvent (NADESs) based ultrasound-assisted extraction (DES-UAE) method was applied to prepare licorice extracts. The DES-UAE using choline chloride and lactic acid as solvent was optimized and modeled by using response surface methodology to maximize the extraction yields of glabridin (GLA) and isoliquiritigenin (ISL). The optimized extracts possessed higher contents of GLA and ISL than available extraction methods, and the enriched products showed superior pharmacological activities in vitro. Furthermore, scanning electron microscopy (SEM) and molecular dynamic simulation analyses were performed to deeply investigate the interaction between solvent and targeted compounds. This study not only provides an eco-friendly method for high-efficient extraction of GLA and ISL from licorice but also illustrates the mechanism of the increased extraction efficacy, which may contribute to the application of licorice and deep insight into extraction mechanism using DES.

Study on the Effective Material Basis and Mechanism of Traditional Chinese Medicine Prescription (QJC) Against Stress Diarrhea in Mice.

Stress diarrhea is a major challenge for weaned piglets and restricts pig production efficiency and incurs massive economic losses. A traditional Chinese medicine prescription (QJC) composed of Astragalus propinquus Schischkin (HQ), Zingiber officinale Roscoe (SJ), and Plantago asiatica L. (CQC) has been developed by our laboratory and shows marked anti-stress diarrhea effect. However, the active compounds, potential targets, and mechanism of this effect remain unclear and warrant further investigation. In our study, we verified the bioactive compounds of QJC and relevant mechanisms underlying the anti-stress diarrhea effect through network pharmacology and in vivo experimental studies. After establishing a successful stress-induced diarrhea model, histomorphology of intestinal mucosa was studied, and Quantitative real-time PCR (RT-qPCR) probe was used for the phosphoinositide 3-kinase (PI3K)-Akt signaling pathway to verify the therapeutic effect of QJC on diarrhea. First, using the network pharmacology approach, we identified 35 active components and 130 Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways in QJC. From among these, we speculated that quercetin, luteolin, kaempferol, scutellarein, and stigmasterol were the main bioactive compounds and assumed that the anti-diarrhea effect of QJC was related to the PI3K-Akt signaling pathway. The RT-qPCR indicated that QJC and its bioactive components increased the expression levels of PI3K and Akt, inhibited the expression of phosphatase and tensin homolog (PTEN), and activated the PI3K-Akt signaling pathway to relieve stress-induced diarrhea. Furthermore, we found that QJC alleviated the pathological condition of small intestine tissue and improved the integrity of the intestinal barrier. Taken together, our study showed that the traditional Chinese medicine QJC, quercetin, luteolin, kaempferol, scutellarein, and stigmasterol alleviated the pathological condition of small intestine tissue and relieved stress-induced diarrhea by increasing the expression levels of PI3K and Akt and inhibiting the expression levels of PTEN.

Engineering Cu2-xS-conjugated upconverting nanocomposites for NIR-II light-induced enhanced chemodynamic/photothermal therapy of cancer.

The integration of chemodynamic therapy (CDT) and photothermal therapy (PTT) has played a huge role in improved anticancer treatments. Here, a novel multifunctional nanoplatform based on Cu2-xS conjugated NaYF4:Yb/Er@NaYF4:Yb upconversion nanoparticles (UCNPs) was proposed and designed. In the UCNPs-Cu2-xS nanocomposites, UCNPs with excellent luminescent properties and a high X-ray attenuation coefficient can serve as an upconversion luminescence (UCL) and computer tomography (CT) imaging contrast agent; meanwhile, Cu(II) in the Cu2-xS nanodots enables the nanocomposites to have a magnetic resonance imaging (MRI) ability owing to the presence of unpaired electrons. Moreover, the Cu2-xS nanodots with a strong absorbance in the NIR II biowindow not only could be employed as a stable photothermal agent under NIR laser irradiation, but also could be used as a photothermal-enhanced Fenton nanocatalyst to respond to over-expressed H2O2 in the tumor microenvironment (TME) and generate toxic hydroxyl radicals (˙OH) to effectively kill cancer cells. Furthermore, the UCNPs-Cu2-xS nanocomposites possess negligible cytotoxicity and a high photothermal conversion efficiency (43.8%) in the NIR-II biowindow (1064 nm), indicating that they possess great potential for the UCL/CT/MR multi-modal imaging guided synergistic enhanced CDT/PTT of cancer.

Inhibition of invadopodia formation by diosgenin in tumor cells.

Diosgenin is a type of steroid extracted from the rhizome of Dioscorea plants. In traditional Chinese medicine, Dioscorea has the effect of 'eliminating phlegm, promoting digestion, relaxing tendons, promoting blood circulation and inhibiting malaria'. Recent studies have confirmed that diosgenin exhibits a number of pharmacological effects, including antitumor activities. Through its antitumor effect, diosgenin is able to block tumor progression and increase the survival rate of patients with cancer; ultimately improving their quality of life. However, the mechanism underlying its pharmacological action remains unclear. Once tumor cells reach a metastatic phase, it can be fatal. Increased migration and invasiveness are the hallmarks of metastatic tumor cells. Invadopodia formation is key to maintaining the high migration and invasive ability of tumor cells. Invadopodia are a type of membrane structure process rich in filamentous-actin and are common in highly invasive tumor cells. In addition to actin, numerous actin regulators, including cortical actin-binding protein (Cortactin), accumulate in invadopodia. Cortactin is a microfilament actin-binding protein with special repetitive domains that are directly involved in the formation of the cortical microfilament actin cell skeleton. Cortactin is also one of the main substrates of intracellular Src-type tyrosine protein kinases and represents a highly conserved family of intracellular cortical signaling proteins. In recent years, great progress has been made in understanding the role of Cortactin and its molecular mechanism in cell motility. However, the diosgenin-Cortactin-invadopodia mechanism is still under investigation. Therefore, the present review focused on the current research on the regulation of invadopodia by diosgenin via Cortactin.

Targeting of the Sonic Hedgehog pathway by atractylenolides promotes chondrogenic differentiation of mesenchymal stem cells.

Molecules that enhance chondrogenic differentiation in mesenchymal stem cells (MSCs) were identified and isolated using an in vitro Gli reporter gene assay in MSCs incorporating a Sonic Hedgehog (Shh) target. Atractylenolide III, which promoted Gli1-mediated transcriptional activity, was isolated from an ethyl acetate extract of the Rhizoma, Atractylodis macrocephalae. After dehydration, atractylenolide III was transformed to atractylenolide I. Both atractylenolides were confirmed by MS, UV, IR, 1H- and 13C-NMR spectra. Atractylenolide III (which contains -OH at the 8-position) and atractylenolide I (which lacks -OH at the 8-position) were found to effectively promote the activity of the Gli promoter. While the hydroxyl group of atractylenolide III was not essential for the effect of atractylenolide, its effect was dependent on Shh signaling. Phenotypic cellular analysis indicated that atractylenolides induced MSCs to differentiate into chondrocytes, as shown by increased expression of specific chondrogenic markers including collagen II, aggrecan and the cartilage related transcription factor, Sox9. Atractylenolides significantly increased the expression of Shh and its target gene Gli-1, indicating that Shh signaling was activated by atractylenolides. Moreover, inhibition of Shh signaling reduced the effect of atractylenolides on the chondrogenic phenotype. The discovery that atractylenolides induce chondrocytes from MSCs is promising for bony disease therapy.

Concordance between antioxidant activities in vitro and chemical components of Radix Astragali (Huangqi).

Five Radix Astragali (RA) extracts were prepared and their antioxidant activities were measured in vitro using ABTS [2, 2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid diammonium salt)], DPPH · (1,1-diphenyl-2-picrylhydrazyl radical), reducing power, •O2⁻ and •OH assays. Their chemical contents were then determined, including total phenolics, total flavonoids, total saponins and total sugars. The 1/IC50 values of the various antioxidant assays were used to evaluate the level of antioxidant activity of the RA extracts (plot showing 1/IC50 values vs. chemical contents), and the average R values (correlation coefficients) of total phenolics and total flavonoids were 0.762 and 0.638. In contrast, the average R values of the total saponins and total sugars were -0.0386 and -0.132, respectively. This large difference clearly demonstrates that the antioxidant effects of RA in vitro might be generally considered to be a result of the presence of phenolic compounds (including flavonoids) but not astragalosides and polysaccharides.

Evaluation of antioxidant activity of isoferulic acid in vitro.

Isoferulic acid (3-hydroxy-4-methoxycinnamic acid, IFA), the isomer of ferulic acid (4-hydroxy-3-methoxycinnamic acid), is a rare phenolic acid occurring in Rhizoma Cimicifugae. Unlike ferulic acid, which has been well investigated, the antioxidant activity of IFA has not been measured. In this study, IFA was systematically evaluated for its in vitro antioxidant activity for the first time. IC50 values were calculated of 7.30 +/- 0.57, 4.58 +/- 0.17, 1.08 +/- 0.01, 8.84 +/- 0.43, 7.69 +/- 0.39, 1.57 +/- 0.2, 13.33 +/- 0.49 microg/mL, respectively, for lipid peroxidation, DPPH (1,1-diphenyl-2-picrylhydrazyl radical) and ABTS (3-ethylbenzthiazoline-6-sulfonic acid diammonium salt) radical scavenging, reducing power on Fe3+ and CU2+ ions, and hydroxyl and superoxide anion radical scavenging. Comparison with the IC50 values with those of the positive controls, Trolox and butylated hydroxyanisole (BHA), it can be concluded that isoferulic acid is an effective natural antioxidant in both lipid and aqueous media.

Genes and regulatory networks involved in persistence of Mycobacterium tuberculosis.

The causative agent of tuberculosis, Mycobacterium tuberculosis, is one of the most successful of human pathogens. It can evade the host immune response and establish a persistent infection or enter a dormant state within the host which can be reactivated if the host becomes immuno-compromised. Both of these features are major obstacles to tuberculosis eradication. Dormancy and reactivation of M. tuberculosis are tightly coordinated dynamic processes involving numerous genes and their products. Molecular mechanisms underlying M. tuberculosis persistence may provide an opportunity for the discovery of effective drug targets for tuberculosis control. Here, we review the genes required for M. tuberculosis persistence and propose a regulatory network for the action of these genes using text mining. This should provide fresh insights into the persistence mechanisms of M. tuberculosis and suggest candidates for new drug targets and immune intervention.