New opportunities and perspectives on biosynthesis and bioactivities of secondary metabolites from Aloe vera.

Historically, the genus Aloe has been an indispensable part of both traditional and modern medicine. Decades of intensive research have unveiled the major bioactive secondary metabolites of this plant. Recent pandemic outbreaks have revitalized curiosity in aloe metabolites, as they have proven pharmacokinetic profiles and repurposable chemical space. However, the structural complexity of these metabolites has hindered scientific advances in the chemical synthesis of these compounds. Multi-omics research interventions have transformed aloe research by providing insights into the biosynthesis of many of these compounds, for example, aloesone, aloenin, noreugenin, aloin, saponins, and carotenoids. Here, we summarize the biological activities of major aloe secondary metabolites with a focus on their mechanism of action. We also highlight the recent advances in decoding the aloe metabolite biosynthetic pathways and enzymatic machinery linked with these pathways. Proof-of-concept studies on in vitro, whole-cell, and microbial synthesis of aloe compounds have also been briefed. Research initiatives on the structural modification of various aloe metabolites to expand their chemical space and activity are detailed. Further, the technological limitations, patent status, and prospects of aloe secondary metabolites in biomedicine have been discussed.

Aloe Vera Extract Gel-Biosynthesized Selenium Nanoparticles Enhance Disease Resistance in Lettuce by Modulating the Metabolite Profile and Bacterial Endophytes Composition.

The use of nanotechnology to suppress crop diseases has attracted significant attention in agriculture. The present study investigated the antifungal mechanism by which aloe vera extract gel-biosynthesized (AVGE) selenium nanoparticles (Se NPs) suppressed Fusarium-induced wilt disease in lettuce (Lactuca sativa). AVGE Se NPs were synthesized by utilizing sodium selenite as a Se source and AVGE as a biocompatible capping and reducing agent. Over 21 d, 2.75% of total AVGE Se NPs was dissolved into Se ions, which was more than 8-fold greater than that of bare Se NPs (0.34%). Upon exposure to soil applied AVGE Se NPs at 50 mg/kg, fresh shoot biomass was significantly increased by 61.6 and 27.8% over the infected control and bare Se NPs, respectively. As compared to the infected control, the shoot levels of citrate, isocitrate, succinate, malate, and 2-oxo-glutarate were significantly upregulated by 0.5-3-fold as affected by both Se NPs. In addition, AVGE Se NPs significantly increased the shoot level of khelmarin D, a type of coumarin, by 4.40- and 0.71-fold over infected controls and bare Se NPs, respectively. Additionally, AVGE Se NPs showed greater upregulation of jasmonic acid and downregulation of abscisic acid content relative to bare Se NPs in diseased shoots. Moreover, the diversity of bacterial endophytes was significantly increased by AVGE Se NPs, with the values of Shannon index 40.2 and 9.16% greater over the infected control and bare Se NPs. Collectively, these findings highlight the significant potential of AVGE Se NPs as an effective and biocompatible strategy for nanoenabled sustainable crop protection.

Aloe-derived nanovesicles attenuate inflammation and enhance tight junction proteins for acute colitis treatment.

Inflammatory bowel disease (IBD) is a chronic recurrent inflammatory disease of the digestive tract that causes pain and weight loss and also increases the risk of colon cancer. Inspired by the benefits of plant-derived nanovesicles and aloe, we herein report aloe-derived nanovesicles, including aloe vera-derived nanovesicles (VNVs), aloe arborescens-derived nanovesicles (ANVs), and aloe saponaria-derived nanovesicles (SNVs) and evaluate their therapeutic potential and molecular mechanisms in a dextran sulfate sodium (DSS)-induced acute experimental colitis mouse model. Aloe-derived nanovesicles not only facilitate markedly reduced DSS-induced acute colonic inflammation, but also enable the restoration of tight junction (TJ) and adherent junction (AJ) proteins to prevent gut permeability in DSS-induced acute colonic injury. These therapeutic effects are ascribed to the anti-inflammatory and anti-oxidant effects of aloe-derived nanovesicles. Therefore, aloe-derived nanovesicles are a safe treatment option for IBD.

Fermented Aloe arborescens Miller Leaf Extract Suppresses Acute Alcoholic Liver Injury via Antioxidant and Anti-Inflammatory Effects in C57BL/6J Mice.

This study confirmed the change in functional composition and alcohol-induced acute liver injury in Aloe arborescens after fermentation. An acute liver injury was induced by administration of ethanol (3 g/kg/day) to C57BL/6J mice for 5 days. A fermented A. arborescens Miller leaf (FAAL) extract was orally administered 30 minutes before ethanol treatment. After fermentation, the emodin content was approximately 13 times higher than that of the raw material. FAAL extract significantly attenuated ethanol-induced aspartate aminotransferase, alanine aminotransferase, and triglyceride increases in serum and liver tissue. Histological analysis revealed that FAAL extract inhibits inflammatory cell infiltration and fat accumulation in liver tissues. The cytochrome P450 2E1, superoxide dismutase, and glutathione (GSH), which involved in alcohol-induced oxidative stress, were effectively regulated by FAAL extract in serum and liver tissues, except for GSH. FAAL also maintained the antioxidant defense system by upregulating heme oxygenase 1 and nuclear factor erythroid 2-related factor 2 protein expression. In addition, FAAL extract inhibited the decrease in alcohol dehydrogenase and aldehyde dehydrogenase activity, which promoted alcohol metabolism and prevented the activation of inflammatory response. Our results suggest that FAAL could be used as a potential therapeutic agent for ethanol-induced acute liver injury.

Aloe polymeric acemannan inhibits the cytokine storm in mouse pneumonia models by modulating macrophage metabolism.

The cytokine storm is highly associated with inflammatory-type disease severity and patients' survival. Plant polysaccharides, the main natural phytomedicine source, have a great potential to be an effective drug to treat cytokine storm. Herein we found that a polymeric acemannan (ABPA1) isolated from Aloe Vera Barbadensis extract C (AVBEC) exerted prominent inhibitory effects on inflammation-induced cytokine storm. The results displayed that ABPA1 effectively suppressed LPS-induced proinflammatory cytokines release in vitro. Moreover, ABPA1 treatment alleviated the cytokine storm and tissue damage in LPS- and IAV-induced mouse pneumonia models, and altered the phenotypic balance of macrophages in lung tissues. Functionally, ABPA1 enhanced macrophage M2 polarization and phagocytosis in RAW264.7 cells and inhibited LPS-induced M1 polarization. Mechanistically, ABPA1 enhanced mitochondrial metabolism and OXPHOS through activated PI3K/Akt/GSK-3ß signalling pathway. Overall, our findings suggest that ABPA1 may modulate macrophage activation and mitochondrial metabolism by targeting PI3K/Akt/GSK-3ß signalling pathway, thereby alleviating cytokine storm and inflammation.

Effects of Aloe vera extract on growth, viability, ultrastructure and expression of mRNA for antioxidant enzymes in bovine secondary follicles cultured in vitro.

This study aimed to investigate the effects of Aloe vera extract on follicular growth, viability, ultrastructure, and mRNA levels for superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase 1 (GPX1) and peroxiredoxin 6 (PRDX6) in bovine secondary follicles cultured in vitro. To this end, secondary follicles were mechanically isolated from the ovarian cortex and cultured at 38.5 °C, with 5% CO2 in air, for 18 days in TCM-199+ alone or supplemented with 2.5%, 5.0%, 10.0% and 20.0% Aloe vera extract. Follicular growth, morphology and antrum formation were evaluated every 6 days, while ultrastructure was evaluated at the end of culture. Analysis of viability was performed by calcein-AM and ethidium homodimer-1, while mRNA levels for SOD, CAT, GPX1 and PRDX6 were evaluated by real-time PCR at the end of culture. The results show that follicles cultured with 2.5% Aloe vera had increased the rate of antrum formation, while 2.5% and 5.0% Aloe vera improved follicular viability rate. Follicles cultured with 2.5% and 10.0% Aloe vera increased the levels of mRNA for SOD and GPX1 respectively, but the levels of CAT were reduced in follicles cultured with 2.5%, 5.0%, 10.0% and 20.0%. Additionally, follicles cultured with 2.5% of Aloe vera had their ultrastructure well preserved, while those cultured with 5.0%, 10.0% and 20.0% exhibited increased oocyte vacuolization and damaged organelles. In conclusion, 2.5% Aloe vera increases antrum formation, viability and expression of mRNA for SOD in cultured secondary follicles, but higher concentrations of Aloe vera have negative effects on follicular ultrastructure.

Biological and Cosmetical Importance of Fermented Raw Materials: An Overview.

The cosmetics industry is currently looking for innovative ingredients with higher bioactivity and bioavailability for the masses of natural and organic cosmetics. Bioferments are innovative ingredients extracted from natural raw materials by carrying out a fermentation process with appropriate strains of microorganisms. The review was conducted using the SciFinder database with the keywords "fermented plant", "cosmetics", and "fermentation". Mainly bioferments are made from plant-based raw materials. The review covers a wide range of fermented raw materials, from waste materials (whey with beet pulp) to plant oils (F-Shiunko, F-Artemisia, F-Glycyrrhiza). The spectrum of applications for bioferments is broad and includes properties such as skin whitening, antioxidant properties (blackberry, soybean, goji berry), anti-aging (red ginseng, black ginseng, Citrus unshiu peel), hydrating, and anti-allergic (aloe vera, skimmed milk). Fermentation increases the biochemical and physiological activity of the substrate by converting high-molecular compounds into low-molecular structures, making fermented raw materials more compatible compared to unfermented raw materials.

Novel Bio-Functional Aloe vera Beverages Fermented by Probiotic Enterococcus faecium and Lactobacillus lactis.

Aloe vera has been medicinally used for centuries. Its bioactive compounds have been shown to be very effective in the treatment of numerous diseases. In this work, a novel functional beverage was developed and characterized to combine the health benefits of probiotic bacteria with the Aloe vera plant itself. Two Aloe vera juices were obtained by fermentation either by a novel isolated Enterococcus faecium or a commercial Lactococcus lactis. The extraction of Aloe vera biocompounds for further fermentation was optimized. Extraction with water plus cellulase enhanced the carbohydrates and phenolic compounds in the obtained extracts. The biotransformation of the bioactive compounds from the extracts during fermentation was assessed. Both probiotic bacteria were able to grow on the Aloe vera extract. Lactic acid and short-chain fatty acids (SCFA) together with fourteen individual phenolic compounds were quantified in the produced Aloe vera juice, mainly epicatechin, aloin, ellagic acid, and hesperidin. The amount of total phenolic compounds was maintained through fermentation. The antioxidant activity was significantly increased in the produced juice by the ABTS method. The novel produced Aloe vera juice showed great potential as a functional beverage containing probiotics, prebiotics, SCFA, and phenolic compounds in its final composition.

Aloe derived nanovesicle as a functional carrier for indocyanine green encapsulation and phototherapy.

BACKGROUND: Cancer is one of the devastating diseases in the world. The development of nanocarrier provides a promising perspective for improving cancer therapeutic efficacy. However, the issues with potential toxicity, quantity production, and excessive costs limit their further applications in clinical practice. RESULTS: Herein, we proposed a nanocarrier obtained from aloe with stability and leak-proofness. We isolated nanovesicles from the gel and rind of aloe (gADNVs and rADNVs) with higher quality and yield by controlling the final centrifugation time within 20 min, and modulating the viscosity at 2.98 mPa S and 1.57 mPa S respectively. The gADNVs showed great structure and storage stability, antioxidant and antidetergent capacity. They could be efficiently taken up by melanoma cells, and with no toxicity in vitro or in vivo. Indocyanine green (ICG) loaded in gADNVs (ICG/gADNVs) showed great stability in both heating system and in serum, and its retention rate exceeded 90% after 30 days stored in gADNVs. ICG/gADNVs stored 30 days could still effectively damage melanoma cells and inhibit melanoma growth, outperforming free ICG and ICG liposomes. Interestingly, gADNVs showed prominent penetrability to mice skin which might be beneficial to noninvasive transdermal administration. CONCLUSIONS: Our research was designed to simplify the preparation of drug carrier, and reduce production cost, which provided an alternative for the development of economic and safe drug delivery system.

Phytochemical and In-Vivo Anti-Arthritic Significance of Aloe thraskii Baker in Combined Therapy with Methotrexate in Adjuvant-Induced Arthritis in Rats.

Unlike other widely known Aloe species used for treatment of rheumatoid arthritis, this species suffers from a lack of sufficient studies on its biological and chemical characters. This is what drove us to perform this work to evaluate the in vivo anti-arthritic potential of its leaf ethanolic extract. The in vivo anti-arthritic activity of the leaf ethanolic extract at 100 and 200 mg/kg/day b.wt. was evaluated alone and in combination with methotrexate (MTX) using complete Freund's adjuvant. Serum levels of rheumatoid factor, anti-cyclic citrullinated peptide (anti-CCP), cytokines pro-inflammatory marker, inflammatory mediator serum levels, and oxidative stress mediators were analyzed, in addition to liver function. Orientin, isoorientin, ß-sitosterol, its palmitate and its glucoside were isolated. The combined therapy of MTX and the leaf ethanolic extract (especially at 200 mg/kg b.wt.) group showed better activity compared to MTX alone. Moreover, the combined therapy provided additional benefits in lowering the liver toxicity by comparison to MTX alone. We concluded that a synergetic combination of the leaf ethanolic extract and MTX is beneficial in the management of rheumatoid arthritis with fewer side effects on liver function, as well as the possibility of the leaf extract to stand alone as an effective natural anti-arthritic agent.

Analysis of the Composition of Lyophilisates Obtained from Aloe arborescens Gel of Leaves of Different Ages from Controlled Crops.

The aim of the study is to evaluate the composition of lyophilisates obtained from Aloe arborescens leaf gel at the age of one to four years. The leaves were obtained from controlled crops, which allowed to exclude environmental factors as variables. It was confirmed that the lyophilisates obtained from different years of Aloe arborescens leaf gel varied in chromatographic analyses in terms of aloin A and aloenin A content (high-performance liquid chromatography with diode-array detection HPLC-DAD, high-performance liquid chromatography with tandem mass spectrometric detection HPLC-MS/MS). Similarly, while testing the phenolic acids and the sum of polyphenols content, differences in their levels in leaf gel lyophilisates from plants of individual years were observed (spectrophotometric method UV-VIS). The lyophilisate composition analysis showed that the one-year-old leaves were characterized by the highest content of aloin A and aloenin A. While the content of polyphenols, including phenolic acids, was higher in the leaves of older plants. The antioxidant potential of the tested lyophilisates was assessed simultaneously. Regardless of the research model used (CUPRAC, DPPH, ABTS), an antioxidant effect was noted for Aloe arborescens leaves.

Ameliorative effect of Aloe gel against L-T4-induced hyperthyroidism via suppression of thyrotropin receptors, inflammation and oxidative stress.

Untreated hyperthyroidism may develop serious complications. This attempt was made to investigate the potential of Aloe vera gel in regulating experimentally induced hyperthyroidism in rats. Female Wistar rats were made hyperthyroid with L-thyroxine (L-T4) at 0.5 mg/kg/day, i.p. for 14 days and the effects of Aloe vera methanolic fraction (AVMF) (50 or 500 mg/kg/day, p.o.,) and a conventional antithyroid drug propylthiouracil (PTU) (10 mg/kg, i.p.) for 30 days were studied in those hyperthyroid rats. At the end, alterations in serum thyroid hormones and thyroid stimulating hormone (TSH); hepatic 5'mono-deiodinase-1(5'D1) activity, oxidative stress markers and antioxidants; serum inflammatory cytokines and the expression of thyrotropin receptor in thyroid gland were evaluated in all experimental animals. Hyperthyroid condition was confirmed by an increase in thyroid hormone levels and hepatic 5'D-1 activity with a decrease in TSH. However, either AVMF or PTU treatment in hyperthyroid rats decreased the levels of thyroid hormones and 5'D1 activity. AVMF administration in T4-induced rats also decreased the oxidative stress markers such as thiobarbituric acid reactive substances and lipid hydroperoxides and increased the antioxidant levels in liver tissues. Levels of liver marker enzymes, cytokines and different lipids were decreased in T4-induced AVMF treated rats. Further, a down regulation in the TSHR expression in thyroid was observed in AVMF or PTU treated groups. All these thyroid inhibiting effects were supported by an improvement in thyroid histology in hyperthyroid rats. It appears, about 15 compounds, as evidenced by LC-MS/MS study, mostly phenolics are involved in this anti-thyroid effects of the test compound.

Chitosan-glucan complex hollow fibers reinforced collagen wound dressing embedded with aloe vera. Part I: Preparation and characterization.

Collagen (CO)/chitosan-glucan complex (CSGC) hollow fibers encapsulated aloe vera (AV) dressing scaffold (CO/CSGC@AV) were fabricated for the first time by the freeze-dried process. Extraction process, morphology, mechanical properties, pore size, porosity, swelling ability, and degradation behavior of composites scaffold were investigated. CSGC hollow fibers were extracted from mycelium of Schizophyllum commune CSGC hollow fiber exhibited inner diameter of (600 ±â€¯250 nm) and outer fiber diameter of (2.5 ±â€¯0.5 µm). The results of swelling and hydrolytic degradation studies demonstrated that the physicochemical of CO/CSGC@AV was significantly enhanced by CSGC in a concentration-dependent manner. The mechanical property of the CO/CSGC@AV was improved after encapsulated AV into CSGC hollow fibers compared with native CO. The pore size and porosity of the CO/CSGC@AV were slightly decreased in the presence of AV. All these results suggested that the new dressing scaffold has a potential for clinical skin regeneration, particularly for infected chronic wounds and ulcers.

Enhanced photocatalysis and anticancer activity of green hydrothermal synthesized Ag@TiO2 nanoparticles.

Titanium dioxide (TiO2) nanoparticles (NPs) have been doped with varying amounts (0.005, 0.010 and 0.015 M) of silver nanoparticles (Ag NPs) using hydrothermal method. Further, in this work, a green approach was followed for the formation of Ag@TiO2 NPs using Aloe vera gel as a capping and reducing agent. The structural property confirmed the presence of anatase phase TiO2. Increased peak intensity was observed while increasing the Ag concentration. Further, the morphological and optical properties have been studied, which confirmed the effective photocatalytic behavior of the prepared Ag@TiO2 NPs. The photocatalytic performance of Ag@TiO2 has been considered for the degradation of picric acid in the visible light region. The concentration at 0.010 M of the prepared Ag@TiO2 has achieved higher photocatalytic performance within 50 min, which could be attributed to its morphological behavior. Similarly, anticancer activity against lung cancer cell lines (A549) was also determined. The Ag@TiO2 NPs generated a large quantity of reactive oxygen species (ROS), resulting in complete cancer cell growth suppression after their systemic in vitro administration. Ag@TiO2 NPs was adsorbed visible light that leads to an enhanced anticancer sensitivity by killing and inhibiting cancer cell reproduction through cell viability assay test. It was clear that 0.015 M of Ag@TiO2 NPs were highly effective against human lung cancer cell lines and showed increased production of ROS in cancer cell lines due to the medicinal behavior of the Aloe vera gel.

Synthesis of titanium oxide nanoparticles using Aloe barbadensis mill and evaluation of its antibiofilm potential against Pseudomonas aeruginosa PAO1.

Titanium dioxide nanoparticles (TiO2-NPs) were synthesized using the aqueous leaf extract of Aloe barbadensis as a reducing and fabricating agent. The biosynthesis of the TiO2-NPs was initially confirmed by UV-vis spectroscopy. Based on the HRTEM and FESEM analysis, the biosynthesized NPs were found to be polydispersed and predominantly spherical in shape, with an average size of ~20 nm. A sharp and strong characteristic peaks of titanium (Ti) and oxygen (O) observed in the EDS pattern confirmed the synthesis of the TiO2-NPs. The FTIR spectroscopy suggested the presence of terpenoids, flavonoids and proteins which might be responsible for the biosynthesis and fabrication of the TiO2-NPs. The crystalline nature of the synthesized TiO2-NPs constituting of a mixture of brookite, anatase, and rutile phases was indicated by the XRD pattern. The spectral window around 180-1000 cm-1 covered the high-frequency Raman spectra of the TiO2-NPs. The Raman vibrational spectrum showed four Eg modes centered at 197.84, 399.24, 514.50, and 641.58 cm-1 representing the anatase phase of TiO2-NPs. The strongest and broadened peak of anatase was observed at the frequency of 641.58 cm-1. The metabolic activity of P. aeruginosa exposed to the MIC of TiO2-NPs was measured based on the reduction of tetrazolium salt by the dehydrogenase enzyme, produced by the metabolically active bacterial cells. The reduction in TTC was evident from the appearance of a red colored formazan in the solution. A noticeable suppression in the cell viability by 30.76 ±â€¯3.96% of P. aeruginosa in the biofilm mode was found in presence of TiO2-NPs. Furthermore, the Minimum Inhibitory Concentration (MIC) of TiO2-NPs exhibited profound antibiofilm activity against P. aeruginosa by effectively preventing the adherence of the planktonic cells to the substratum. Thus, these NPs may be employed in controlling bacterial infections associated with biofilm.

Secondary metabolites from the resins of Aloe vera and Commiphora mukul mitigate lipid peroxidation.

Oxidative stress is often considered detrimental for cellular processes and damaging for the lipid bi-layer. Counteracting such stresses with the aid of nature-based chemical constituents can be an ideal therapeutic approach. The current study aimed to investigate the chemical constituents of resins derived from the well-known Aloe vera and less known Commiphora mukul trees and their effect in mitigating the lipid peroxidation (LPO) process. The bio-guided isolation of bio-active fractions from both resins afforded 20 chemical constituents (17 from A. vera and 3 from C. mukul). These compounds belonged to anthraquinones, anthraquinone glycosides, quinones, coumarins, polypodane-type terpenoids and benzene derivatives. Major chemical constituents of the resins of A. vera and C. mukul were from the classes of quinones and terpenoids. Feroxidin (4, from A. vera) showed slightly higher inhibition (IC50 = 201.7 ± 0.9 µmol L-1) than myrrhanone C (18, from C. mukul: IC50 = 210.7 ± 0.0 µmol L-1) and methyl 3-(4-hydroxyphenyl) propionate from A. vera (13, IC50 = 232.9 ± 0.2 µmol L-1) compared to the other compounds. Structure-activity relationship showed that the existence of hydroxyl, methoxy and ether groups might play a major role in countering oxidative stress. To the best of our knowledge, anti-LPO activities of compounds 1-4, 14, 18 and 20 are reported for the first time. Such chemical constituents with high anti-lipid peroxidation activity could be helpful in synthesizing candidate drugs.

Evaluation of the Treatment Effect of Aloe vera Fermentation in Burn Injury Healing Using a Rat Model.

Burn injury is a growing medical problem associated with public health, and few effective agents are available for treatment of this disease. In the present study, a burn injury rat model was developed and the accelerated effect of Aloe vera fermentation on burn injury healing was evaluated. Our results indicated that Aloe vera fermentation could markedly reduce the DPPH (56.12%), O2·- (93.5%), ·OH (76.12%), Fe2+ chelation (82%), and oxygen-reduction activity (0.28 µg/ml) and significantly inhibited the growth of pathogens S. typhimurium ATCC 13311 (inhibition zone diameter: 14 mm), S. enteritidis ATCC13076 (IZD: 13 mm), S. flexneri ATCC 12022 (IZD: 18 mm), E. coli 44102 (IZD: 10 mm), L. monocytogenes ATCC 19111 (IZD: 18 mm), S. dysenteriae 301 (IZD: 20 mm), S. aureus COWAN1 (IZD: 19 mm), and P. acnes ATCC 11827 (IZD: 25 mm) in vitro. The in vivo results indicated that Aloe vera fermentation produced more eosinophils and fibroblasts and less vessel proliferation compared with the model group on the 14th day, which had greatly accelerated burn injury healing via shedding of the scab and promoting hair growth. ELISA results indicated that Aloe vera fermentation had significantly reduced the production of proinflammatory factors TNF-α and IL-1ß (p < 0.05) and greatly enhanced the yield of anti-inflammatory factor IL-4 in animal serum (p < 0.05). In addition, the high-throughput sequencing results indicated that Aloe vera fermentation obviously increased the percentage of Firmicutes (65.86% vs. 49.76%), while reducing the number of Bacteroidetes (27.60% vs. 45.15%) compared with the M group at the phylum level. At the genus level, Aloe vera fermentation increased the probiotic bacteria Lactobacillus (3.13% vs. 2.09%) and reduced the pathogens Prevotella (10.60% vs.18.24%) and Blautia (2.91% vs. 16.41%) compared with the M group. Therefore, we concluded that the use of Aloe vera fermentation significantly accelerates burn injury healing via reduction of the severity of inflammation and through modification of gut microbiota.

Improved Multicellular Response, Biomimetic Mineralization, Angiogenesis, and Reduced Foreign Body Response of Modified Polydioxanone Scaffolds for Skeletal Tissue Regeneration.

The potential of electrospun polydioxanone (PDX) mats as scaffolds for skeletal tissue regeneration was significantly enhanced through improvement of the cell-mediated biomimetic mineralization and multicellular response. This was achieved by blending PDX ( i) with poly(hydroxybutyrate- co-valerate) (PHBV) in the presence of hydroxyapatite (HA) and ( ii) with aloe vera (AV) extract containing a mixture of acemannan/glucomannan. In an exhaustive study, the behavior of the most relevant cell lines involved in the skeletal tissue healing cascade, i.e. fibroblasts, macrophages, endothelial cells and preosteoblasts, on the scaffolds was investigated. The scaffolds were shown to be nontoxic, to exhibit insignificant inflammatory responses in macrophages, and to be degradable by macrophage-secreted enzymes. As a result of different phase separation in PDX/PHBV/HA and PDX/AV blend mats, cells interacted differentially. Presumably due to varying tension states of cell-matrix interactions, thinner microtubules and significantly more cell adhesion sites and filopodia were formed on PDX/AV compared to PDX/PHBV/HA. While PDX/PHBV/HA supported micrometer-sized spherical particles, nanosized rod-like HA was observed to nucleate and grow on PDX/AV fibers, allowing the mineralized PDX/AV scaffold to retain its porosity over a longer time for cellular infiltration. Finally, PDX/AV exhibited better in vivo biocompatibility compared to PDX/PHBV/HA, as indicated by the reduced fibrous capsule thickness and enhanced blood vessel formation. Overall, PDX/AV blend mats showed a significantly enhanced potential for skeletal tissue regeneration compared to the already promising PDX/PHBV/HA blends.

Differential surface contact killing of pristine and low EPS Pseudomonas aeruginosa with Aloe vera capped hematite (α-Fe2O3) nanoparticles.

Biogenic hematite (α-Fe2O3) nanoparticles (NPs) of average size <10 nm were synthesized using green approach with Aloe vera extract (ALE). The aim of the study was to assess the protective effect of extracellular polymeric substances (EPS) against antibacterial and antibiofilm activities of ALE-α-Fe2O3NPs in normal EPS producers (pristine) and experimentally modified (low-EPS) Pseudomonas aeruginosa (P. aeruginosa) cells and the mechanism of cell killing. Formation of ALE-α-Fe2O3NPs has been validated by X-ray diffraction (XRD), transmission electron microscopy (TEM), scanning electron microscopy (SEM) and Fourier-transformed infrared spectroscopy (FTIR) analysis. The FTIR data suggested the possible role OH group bearing organic compounds of ALE in metal reduction and nucleation of NPs. Gas Chromatography-Mass spectroscopy (GC-MS) analysis revealed the presence of oxime-methoxy-phenyl, ethanone 1-phenyl, hexadecanoic acid, cyclohexanol 2,6-dimethyl, tetracontane, stigmast-5-en-3-ol, cyclohexanol 2,6-dimethyl, and cyclohexasiloxane dodecamethyl on the surface of ALE-α-Fe2O3NPs. Cell viability assay and SEM imaging revealed significantly greater bacteriostatic and/or bactericidal effect of ALE-α-Fe2O3NPs in low EPS cells compared to pristine cells or bare-α-Fe2O3NPs. This is attributed to thinner protective layer of EPS around the low EPS cells, and higher dispersibility and stability of ALE-α-Fe2O3NPs. Absorption of ALE-α-Fe2O3NPs and bare-α-Fe2O3NPs on EPS surface and within EPS matrix was ascertained by atomic absorption spectroscopy (AAS). The results suggest differential internalization of ALE-α-Fe2O3NPs and bare-α-Fe2O3NPs in P. aeruginosa cells. The flow cytometry (FCM) results exhibited increased intracellular granularity in low EPS (18.94%) as compared with pristine (10.94%) cells, which signifies the greater internalization of ALE-α-Fe2O3NPs. Moreover, the proportionate increase in intracellular ROS generation in low EPS (20.47%) via-a-vis pristine (7.56%) cells was observed. Overall, the results elucidate that ALE-α-Fe2O3NPs-bacterial interaction leads to attachment of NPs to EPS surface, migration within the EPS matrix and penetration into cell, which eventually results in growth inhibition due to intracellular ROS activity. Owing to significant antibacterial and antibiofilm activities, ALE-α-Fe2O3NPs may serve as a good candidate for clinical management of extended spectrum beta lactamases (ESBL) positive P. aeruginosa.

Analysis of Aloe vera cytotoxicity and genotoxicity associated with endodontic medication and laser photobiomodulation.

This study aims to evaluate, in vitro, the effect of Aloe vera associated with endodontic medication, with or without laser photobiomodulation (FTL) irradiation in FP6 human pulp fibroblasts. The materials were divided into eight groups: CTR - control; CL - FTL alone; AA - Aloe vera with distilled water; AL - Aloe vera with distilled water and FTL; HA - calcium hydroxide P.A. with distilled water; HL - calcium hydroxide P.A. with distilled water and FTL; HAA - calcium hydroxide P.A. with Aloe vera and distilled water; HAL - calcium hydroxide P.A. with Aloe vera, distilled water, and FTL. The cytotoxicity was evaluated by MTT assay at 24, 48, and 72h and the genotoxicity by micronucleus test assay. This study was performed in triplicate. Data obtained in both tests were statistically analyzed by ANOVA and Tukey's tests (p≤0.05). Group AA presented high genotoxicity and low cytotoxicity. After 24, 48, and 72h, the group HAA significantly reduced the cell viability. Interaction with FTL showed slightly increase cell viability after 24 and 48h in groups CL and HL (p<0.001), despite the high genotoxicity in group CL and low genotoxicity in group HL. Group AL showed higher cell survival rate at 72h (p<0.05) and high genotoxicity (p<0.001). It was concluded that Aloe vera allowed higher cell viability in human pulp fibroblasts in the presence of calcium hydroxide or with FTL separately, but genotoxicity increased in these associations.