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Aloe genus plants, distributed in Old World, are widely known and have been used for centuries as topical and oral therapeutic agents due to their health, beauty, medicinal, and skin care properties. Among the well-investigated Aloe species are A. arborescens, A. barbadensis, A. ferox, and A. vera. Today, they account among the most economically important medicinal plants and are commonly used in primary health treatment, where they play a pivotal role in the treatment of various types of diseases via the modulation of biochemical and molecular pathways, besides being a rich source of valuable phytochemicals. In the present review, we summarized the recent advances in botany, phytochemical composition, ethnobotanical uses, food preservation, and the preclinical and clinical efficacy of Aloe plants. These data will be helpful to provide future directions for the industrial and medicinal use of Aloe plants.

Objective: Despite the development of several vaccines against severe acute respiratory syndrome coronavirus-2, the need for an additional prophylactic agent is evident. In recent in silico studies, isovitexin exhibited a higher binding affinity against the human angiotensin converting-enzyme 2 (hACE2) receptor than existing antiviral drugs. The research aimed to find out the point specificity of isovitexin for the hACE2 receptor and to assess its therapeutic potential, depending on the stability of the isovitexin–hACE2 complex. Materials and Methods: The pharmacokinetic profile of isovitexin was analyzed. The crystal structure of the hACE2 receptor and the ligand isovitexin were docked to form a ligand-protein complex following molecular optimization. To determine the isovitexin–hACE2 complex stability, their binding affinity, hydrogen bonding, and hydrophobic interactions were studied. Lastly, the root mean square deviation (RMSD), root mean square fluctuation, solvent accessible surface area, molecular surface area, radius of gyration (Rg), polar surface area, and principal component analysis values were found by simulating the complex with molecular dynamic (MD). Results: The predicted Lethal dose50 for isovitexin was 2.56 mol/kg, with an acceptable maximum tolerated dose and no hepatotoxicity or AMES toxicity. Interactions with the amino acid residues Thr371, Asp367, Glu406, Pro346, His345, Phe274, Tyr515, Glu375, Thr347, Glu402, and His374 of the hACE2 protein were required for the high binding affinity and specificity of isovitexin. Based on what was learned from the MD simulation, the hACE2 receptor-blocking properties of isovi¬texin were looked at. Conclusions: Isovitexin is a phytochemical with a reasonable bioactivity and safety profile for use in humans, and it can potentially be used as a hACE2-specific therapeutic to inhibit COVID-19 infection.

Recent studies on the ethnomedicinal use of Clinacanthus nutans suggest promising anti-inflammatory, anti-tumorigenic, and antiviral properties for this plant. Extraction of the leaves with polar and nonpolar solvents has yielded many C-glycosyl flavones, including schaftoside, isoorientin, orientin, isovitexin, and vitexin. Aside from studies with different extracts, there is increasing interest to understand the properties of these components, especially regarding their ability to exert anti-inflammatory effects on cells and tissues. A major focus for this review is to obtain information on the effects of C. nutans extracts and its phytochemical components on inflammatory signaling pathways in the peripheral and central nervous system. Particular emphasis is placed on their role to target the Toll-like receptor 4 (TLR4)-NF-kB pathway and pro-inflammatory cytokines, the antioxidant defense pathway involving nuclear factor erythroid-2-related factor 2 (NRF2) and heme oxygenase 1 (HO-1); and the phospholipase A2 (PLA2) pathway linking to cyclooxygenase-2 (COX-2) and production of eicosanoids. The ability to provide a better understanding of the molecular targets and mechanism of action of C. nutans extracts and their phytochemical components should encourage future studies to develop new therapeutic strategies for better use of this herb to combat inflammatory diseases.

[This corrects the article DOI: 10.3389/fimmu.2019.02650.].

Microglia are the brain's immune cells and play an important role in regulating the microenvironment in the central nervous system. Activated microglia are capable of acquiring the pro-inflammatory (M1) phenotype and anti-inflammatory (M2) phenotype. Overactivation of microglia is neurotoxic and may lead to neuroinflammatory brain disorders. Neuroinflammation in the brain plays a crucial role part in the pathophysiology of many psychiatric and neurological diseases. The inhibition of M1 microglia and promotion of M2 microglia was demonstrated to treat and prevent these diseases through reduced neuroinflammation. Isovitexin (IVX) has anti-inflammatory properties and passes through the blood-brain barrier; however, the molecular mechanism that modulates IVX-mediated microglial polarization remains unclear. In BV-2 cells and mouse primary microglia, IVX suppressed the expression of M1 microglial markers, enhanced the expression of M2 microglial markers, and enhanced the release of interleukin 10 (IL-10). IVX promoted the expression of peroxisome proliferator-activated receptor-γ (PPARγ) and PPARγ coactivator-1α (PGC-1α) in LPS-induced microglial activation. The inhibition of PPARγ and PGC-1α attenuated the regulatory effect of IVX in LPS-induced microglial polarization. IVX increased the expression of p-CaMKKβ, p-AMPK, and PGC-1α in BV-2 cells. Inhibition of CaMKKβ with STO-609 or knockdown of CaMKKβ with CaMKKβ siRNA attenuated IVX-mediated M2 microglial polarization in LPS-treated cells. In LPS-treated mice, the inhibition of CaMKKβ and PGC-1α attenuated the IVX-mediated prevention of sickness behavior and enhanction of IVX-mediated M2 microglial polarization. IVX promoted M2 microglial polarization which exerted anti-inflammatory effects on LPS-induced neuroinflammation via the activation of the CaMKKβ/AMPK-PGC-1α signaling axis.

Tinctures are medicinal plant extracts obtained by extraction with a hydroalcoholic solution (70%) by percolation (PER). This process takes about 26 h to prepare, in addition to using a large amount of solvent. In our research, passion fruit leaf tinctures were obtained using extract with the same pressurized hydroalcoholic solution as in an intermittent process. The objective was to demonstrate that this emerging technology can be economical and profitable. An optimization using Central Composite Rotatable Design (CCRD) was performed to evaluate the influence of process variables on the yields and compositions of the extracts. The temperature (T) was the factor that most influenced the responses. Extraction with pressurized liquid (PLE) provided total yields and total phenolic and flavonoid contents in greater amounts than PER. The optimized conditions of the process variables studied in the CCRD for the highest content of total phenolics (43.2 mg GAE/g) and flavonoids (58.8 mg QE/g) were at 100 °C with a rinse volume of 120% of the divided extractor volume in four cycles of the intermittent process. When adjusting the PLE in an intermittent process, and according to the one-dimensional mass transfer by the continuous diffusion of the Fick model, the effective diffusion coefficient (1.28 × 10−12 m2/s) was not affected by T. The kinetic curve of PLE extraction indicates that the adjusted intermittent process occurred in the period of the constant extraction rate when compared to the kinetics of the semi-continuous process. The yielded extracts were rich in isovitexin, and the highest levels were identified in the extracts obtained via PLE, indicating that this intermittent process can bring a product to market with the same quality but with a much shorter production time and the use of fewer solvents. Antioxidant activity, determined by DPPH, FRAP and ORAC, was also higher in extracts obtained via PLE.

Vitexin and isovitexin are natural flavone C-glucosides that have numerous benefits for human health. However, their low oral bioavailability and poor gastrointestinal absorption dramatically restrict their potential medicinal uses. To overcome this challenge, chitosan-coated alginate microcapsules were prepared for intragastrical administration to rabbits. An LC-MS/MS method was developed and validated for the simultaneous determination of vitexin and isovitexin in the plasma of treated rabbits, using salicylic acid as the internal standard. Raw rabbit plasma samples were deproteinized using acetonitrile as a precipitation agent. Chromatographic separation was performed on a reversed-phase C18 column (100 mm × 4.6 mm, 3.5 µm), with an isocratic mobile solvent system comprising methanol and 0.1% acetic acid (40:60) as the mobile phase. All the analytes and the internal standard were ionized on a triple quadrupole mass spectrometer and electrospray ionization, operating in negative mode and multiple reaction monitoring. The analytical approach developed underwent validation in terms of system suitability, specificity, selectivity, LLOQ of 2 ng/mL, linearity (2.0–200 ng/mL, R2 > 0.99), accuracy (the intra- and inter-day from 94 to 110% with the relative standard deviations no more than 8.7%, precision with the recoveries from 97% to 102%, matrix effect (90–100%), carry-over, dilution integrity (2 times), and stability at room and frozen temperature for up to 1 month, and all the parameters met FDA and EMA requirements for bioanalytical methods. The validated procedure was applied to measure the absorption of vitexin and isovitexin from encapsulated extracts in a pilot pharmacokinetic study on rabbit plasma. Compared to the raw traditional extracts, the microcapsules enhanced the bioavailability of vi-texin and isovitexin regarding Cmax and AUC values.

Liang X, Xu C, Cao X, Wang W. Cancer Manag Res. 2019;11:8923-8936. We, the Editors and Publisher of Cancer Management and Research, have retracted the following article. Since publication, concerns have been raised about the integrity of the data in the article. This includes the duplication of images from Figure 2 with images from another article. Specifically, The western blot image for Figure 2J, DNMT1, has been duplicated with the image for Figure 3h, CD44, from Liang X, Xu C, Wang W, Li X, The DNMT1/miR-34a Axis Is Involved in the Stemness of Human Osteosarcoma Cells and Derived Stem-Like Cells. Stem Cells Int. 2019;2019:7028901. https://doi.org/10.1155/2019/7028901. When approached for an explanation, the authors did not respond to our queries, nor did they provide original data for their study. As the findings could not be verified the Editor and Publisher made the decision to retract the article and the authors were notified of this. We have been informed in our decision-making by our editorial policies and COPE guidelines. The retracted article will remain online to maintain the scholarly record, but it will be digitally watermarked on each page as 'Retracted'.

Qiu Y, Cao X, Liu L, et al. Cancer Manag Res. 2020;12:5759‒5771. The Editor and Publisher of Cancer Management and Research wish to retract the published article. Concerns were raised regarding the alleged duplication of cell migration and invasion images throughout the article. Specifically, Figure 1B, panel 0h HCSLC, appears to have been duplicated with the image from Figure 2C, panel 0h 0.0 µM ISOV. Figure 3B, panel 24h Ad-shMnSOD, appears to have been duplicated with the image from Figure 5G, panel 24h Mock. Figure 4G, panel 24h Ad-GFP+/Ad-MnSOD-/ISOV (10µM)-, appears to have been duplicated with the image from Figure 4G, panel 24h Ad-GFP+/Ad-MnSOD-/ISOV (10µM)+. Figure 1B, panel 24h HCSLC, appears to have been duplicated with an image from Figure 5c, panel 24h Isovitexin (0µg/mL) Ad-GFP from Liu et al, 2021 (https://doi.org/10.1155/2021/9972057). The authors responded to our initial queries but were unable to provide a satisfactory explanation for the alleged image duplication, nor were they able to provide adequate original data for their study. The decision was made to retract the article and the authors agreed with this decision. Our decision-making was informed by our policy on publishing ethics and integrity and the COPE guidelines on retraction. The retracted article will remain online to maintain the scholarly record, but it will be digitally watermarked on each page as \"Retracted\". This retraction relates to this paper

Young barley plants are a good source of bioactive compounds. This paper presents the effects of gaseous O3 (trioxygen or ozone) on the biosynthesis of compounds, determining the antioxidant potential of young barley plants. The total content of polyphenols was determined along with their profile, as well as total antioxidant potential and vitamin C content. The highest contents of these compounds were identified in young barley plants exposed to gaseous O3. The main bioactive compound, representing polyphenols, determined in the examined raw materials was saponarin (isovitexin 7-O-glucoside). The induction of increased biosynthesis of these molecules was directly linked to the modification of the activity of selected enzymes. The increased polyphenol content resulted from the modified activities of polyphenol oxidase (PPO) and phenylalanine ammonia lyase (PAL). On the other hand, the oxidative effect of ozone on barley plants was reduced, owing to the modified activities of catalases (CAT), glutathione peroxidases (SOD) and guaiacol peroxidase (GPOX). Analysis of the results showed that by applying gaseous O3 at a dose of 50 ppm for 10 min, the contents of bioactive compounds can be maximised in a residue-free way by activating oxidative stress defence mechanisms.