Himatanthus bracteatus-Composed In Situ Polymerizable Hydrogel for Wound Healing.

The Himatanthus genus presents anti-inflammatory, antioxidant activities, suggesting potential wound-healing properties. This study aimed to develop and analyze the wound-healing properties of a photopolymerizable gelatin-based hydrogel (GelMA) containing an ethanolic extract of Himatanthus bracteatus in a murine model. The extract was obtained under high pressure conditions, incorporated (2%) into the GelMA (GelMA-HB), and physically characterized. The anti-inflammatory activity of the extract was assessed using a carrageenan-induced pleurisy model and the GelMA-HB scarring properties in a wound-healing assay. The extract reduced IL-1ß and TNF-α levels (48.5 ± 6.7 and 64.1 ± 4.9 pg/mL) compared to the vehicle (94.4 ± 2.3 pg/mL and 106.3 ± 5.7 pg/mL; p < 0.001). GelMA-HB depicted significantly lower swelling and increased resistance to mechanical compression compared to GelMA (p < 0.05). GelMA-HB accelerated wound closure over the time course of the experiment (p < 0.05) and promoted a significantly greater peak of myofibroblast differentiation (36.1 ± 6.6 cells) and microvascular density (23.1 ± 0.7 microvessels) on day 7 in comparison to GelMA (31.9 ± 5.3 cells and 20.2 ± 0.6 microvessels) and the control (25.8 ± 4.6 cells and 17.5 ± 0.5 microvessels) (p < 0.05). In conclusion, GelMA-HB improved wound healing in rodents, probably by modulating the inflammatory response and myofibroblastic and microvascular differentiation.

Histological Evidence of Wound Healing Improvement in Rats Treated with Oral Administration of Hydroalcoholic Extract of Vitis labrusca.

Plant extracts rich in phenolic compounds have been demonstrated to accelerate wound healing, but their use by oral route has been poorly studied. The leaves of Vitis labrusca are rich in phenolic acids and flavonoids. The goal of this study was to assess the healing properties of the oral administration of hydroalcoholic extract of V. labrusca leaves (HEVL) in a murine model. HEVL was obtained by Soxhlet and dynamic maceration, and their yield and phenolic acids and flavonoid contents were determined. For the wound healing assay, 8 mm wounds were performed on the back of 48 Wistar rats, assigned into four groups (n = 12): CTR (distilled water), HEVL100, HEVL200, and HEVL300 (HEVL at 100, 200, and 300 mg/kg, respectively). On days 7 and 14, wound closure rates were assessed, and the healing wounds were subjected to histological analysis. Soxhlet-obtained extract was selected for the wound healing assay because it provided a higher yield and phenolic acid and flavonoid contents. HEVL significantly reduced leukocytosis in the peripheral blood (p < 0.05), accelerated wound closure (p < 0.05), and improved collagenization (p < 0.05) on day 7, as well as enhanced the epidermal tissue thickness (p < 0.001) and elastic fiber deposition on day 14 (p < 0.01). Furthermore, HEVL promoted an increase in the histological grading of wound healing on both days 7 and 14 (p < 0.01). The doses of 200 and 300 mg/kg provided better results than 100 mg/Kg. Our data provide histological evidence that the oral administration of HEVL improves wound healing in rodents. Therefore, the extract can be a potential oral medicine for healing purposes.

Reduced cutaneous inflammation associated with antioxidant action after topical application of the aqueous extract of Annona muricata leaves.

Annona muricata L. is used in folk medicine for treatment of diseases related to inflammatory and oxidative processes. This study investigated the effect of the aqueous extract of A. muricata leaves (AEAM) on TPA-induced ear inflammation and antioxidant capacity, both in vitro and in vivo. The in vitro antioxidant capacity of AEAM was measured by the 2,2-diphenyl-1-picrylhydrazyl (DPPH), ferric reducing/antioxidant power (FRAP) and lipoperoxidation assays. Cytotoxicity and reactive oxygen species (ROS) release were evaluated in the L929 fibroblasts. Swiss mice were submitted to TPA application and were topically treated with AEAM (0.3, 1 or 3 mg/ear). After 6 h, inflammatory and oxidative parameters were evaluated. Quercetin 3-glucoside, rutin, chlorogenic acid, catechin and gallic acid were identified in AEAM. It also presented antioxidant activity in all in vitro assays used. Incubation with AEAM did not cause cell cytotoxicity but reduced ROS release from fibroblasts. Compared with the control group, treatment with AEAM significantly reduced ear oedema and mieloperoxidase activity in inflamed ears, as well as histological parameters of inflammation. These results were associated with the reduction of total hydroperoxides and modulation of catalase, but not superoxide dismutase activity. These findings show the anti-inflammatory effect of AEAM is associated with antioxidant capacity.

In situ photocrosslinkable formulation of nanocomposites based on multi-walled carbon nanotubes and formononetin for potential application in spinal cord injury treatment.

Carbon nanotubes (CN) have been studied to treat spinal cord injuries because of its electrical properties and nanometric dimensions. This work aims to develop a photopolymerizable hydrogel containing CN functionalized with an anti-inflammatory molecule to be used in situ on spinal cord injuries. The CN functionalization step was done using the drug (formononetin). The nanocomposites were characterized by morphological analysis, FTIR, Raman Spectroscopy, thermal analysis and cytotoxicity assays (MTT and HET-CAM). The nanocomposites were incorporated into gelatin methacryloyl hydrogel and exposed to UV light for photopolymerization. The volume of the formulation and the UV exposition time were also analyzed. The CN characterization showed that formononetin acted as a functionalization agent. The functionalized CN showed safe characteristics and can be incorporated in photocrosslinkable formulation. The UV exposition time for the formulation photopolymerization was compatible with the cell viability and also occurred in the injury site.

Cytotoxic, Antitumor and Toxicological Profile of Passiflora alata Leaf Extract.

Passiflora alata or passion fruit is a native flowering plant from Amazon, geographically spread from Peru to Brazil. The plant has long been used in folks medicine for its pharmacological properties and is included in the Brazilian Pharmacopoeia since 1929. The aim of this study was to evaluate the potential cytotoxic and antitumor activities of Passiflora alata leaf extract (PaLE) in S180-tumor bearing mice. The percentage of cell proliferation inhibition (% CPI) and IC50 in relation to 4 tumor cell lines were determined in PC3, K-562, HepG2 and S180 cell lines using the MTT assay. PaLE showed a CPI > 75% and greater potency (IC50 < 30 µg/mL) against PC3 and S180 cell lines. PaLE showed antitumor activity in treatments intraperitoneally (36.75% and 44.99% at doses of 100 and 150 mg/kg/day, respectively). Toxicological changes were shown in the reduced body mass associated with reduced food consumption, increased spleen mass associated with histopathological increase in the white pulp of the spleen and increased number of total leukocytes with changes in the percentage relationship between lymphocytes and neutrophils. Our outcomes corroborate the conclusion that PaLE has antitumor activity in vitro and in vivo with low toxicity.

Decreased inflammatory response in rat bladder after intravesical administration of capsaicin-loaded liposomes.

The objective of this work was to study the reduction in the capsaicin toxicity by encapsulation in liposomes. Capsaicin was extracted from peppers and characterized with high performance liquid chromatography (HPLC). We determined the zeta potential, polydispersivity index (PdI) and vesicle size of liposomes. Wistar rats were submitted to intravesical instillation of liposomes (LIP), capsaicin (CAP) or liposomes with capsaicin (CAPLIP). After 24 hours, bladders were removed for histological analysis. Vesicle size ranged from 68 to 105 nm with PdI smaller than 0.2 and zeta potential around -30 mV. The vesicles maintained stability over the 14-day study. The histological analysis of the CAP group showed intense inflammation in almost all bladder layers, as well as ulcer formation. Conversely, the CAPLIP group showed a smooth inflammatory reaction and hyperemia. In conclusion, the liposomes effectively protected the bladder against the irritative action of capsaicin.

A systematic review of the wound-healing effects of monoterpenes and iridoid derivatives.

The search for more effective and lower cost therapeutic approaches for wound healing remains a challenge for modern medicine. In the search for new therapeutic options, plants and their metabolites are a great source of novel biomolecules. Among their constituents, the monoterpenes represent 90% of essential oils, and have a variety of structures with several activities such as antimicrobial, anti-inflammatory, antioxidant and wound healing. Based on that, and also due to the lack of reviews concerning the wound-healing activity of monoterpenes, we performed this systematic review-which provides an overview of their characteristics and mechanisms of action. In this search, the terms "terpenes", "monoterpenes", "wound healing" and "wound closure techniques" were used to retrieve articles published in LILACS, PUBMED and EMBASE until May 2013. Seven papers were found concerning the potential wound healing effect of five compouds (three monoterpenes and two iridoid derivatives) in preclinical studies. Among the products used for wound care, the films were the most studied pharmaceutical form. Monoterpenes are a class of compounds of great diversity of biological activities and therapeutic potential. The data reviewed here suggest that monoterpenes, although poorly studied in this context, are promising compounds for the treatment of chronic wound conditions.

Nanomaterials-combined methacrylated gelatin hydrogels (GelMA) for cardiac tissue constructs.

Among non-communicable diseases, cardiovascular diseases are the most prevalent, accounting for approximately 17 million deaths per year. Despite conventional treatment, cardiac tissue engineering emerges as a potential alternative for the advancement and treatment of these patients, using biomaterials to replace or repair cardiac tissues. Among these materials, gelatin in its methacrylated form (GelMA) is a biodegradable and biocompatible polymer with adjustable biophysical properties. Furthermore, gelatin has the ability to replace and perform collagen-like functions for cell development in vitro. The interest in using GelMA hydrogels combined with nanomaterials is increasingly growing to promote the responsiveness to external stimuli and improve certain properties of these hydrogels by exploring the incorporation of nanomaterials into these hydrogels to serve as electrical signaling conductive elements. This review highlights the applications of electrically conductive nanomaterials associated with GelMA hydrogels for the development of structures for cardiac tissue engineering, by focusing on studies that report the combination of GelMA with nanomaterials, such as gold and carbon derivatives (carbon nanotubes and graphene), in addition to the possibility of applying these materials in 3D tissue engineering, developing new possibilities for cardiac studies.

UV-polymerizable methacrylated gelatin (GelMA)-based hydrogel containing tannic acids for wound healing.

Gelatin-based photopolymerizable methacrylate hydrogel (GelMA) is a promising biomaterial for in situ drug delivery, while aqueous extract of Punica granatum (AEPG) peel fruit rich in gallic acid and ellagic acid is used to improve wound healing. The aim of this study was to develop and analyze the healing properties of GelMA containing AEPG, gallic acid, or ellagic acid in a rodent model. GelMA hydrogels containing 5% AEPG (GelMA-PG), 1.6% gallic acid (GelMA-GA), or 2.1% ellagic acid (GelMA-EA) were produced and their mechanical properties, enzymatic degradation, and thermogravimetric profile determined. Wound closure rates, healing histological grading, and immunohistochemical counts of myofibroblasts were assessed over time. The swelling of hydrogels varied between 50 and 90%, and GelMA exhibited a higher swelling than the other groups. The GPG samples showed higher compression and Young's moduli than GelMA, GGA, and GAE. All samples degraded around 95% in 48 h. GPG and GGA significantly accelerated wound closure, improved collagenization, increased histological grading, and hastened myofibroblast differentiation in comparison to the control, GelMA, and GEA. GelMA containing AEPG (GPG) improved wound healing, and although gallic acid is the major responsible for such biological activity, a potential synergic effect played by other polyphenols present in the extract is evident.

Ent-kaurenoic acid-enriched Mikania glomerata leaves-complexed ß-cyclodextrin: Pharmaceutical development and in vivo antitumor activity in a sarcoma 180 mouse model.

The extract obtained from Mikania glomerata leaves rich in ent-kaurenoic acid (ERKA) shows cytotoxic activity in vitro, but its hydrophobic nature and thermosensitivity are issues to be solved prior to in vivo antitumor studies. The purpose of this study was to investigate the antitumor activity of inclusion complexes formed between ERKA and ß-cyclodextrin (ERKA:ß-CD) in rodents. ERKA:ß-CD complexes obtained by malaxation (MX) and co-evaporation (CE) methods were firstly characterized regarding their physical properties, encapsulation efficiency, and cytotoxicity againts L929 cells. The antitumor activity study was then performed in mice with sarcoma 180 treated with saline, 5-fluouracil (5FU) and ERKA:ß-CD at 30, 100 and 300 µg/kg. The weight, volume, percentage of inhibition growth, gross and pathological features and positivity for TUNEL, ki67, NFκB and NRF2 in the tumors were assessed. Serum lactate-dehydrogenase activity (LDH), white blood cells count (WBC) and both gross and pathological features of the liver, kidneys and spleen were also evaluated. The formation of the inclusion complexes was confirmed by thermal analysis and FTIR, and they were non-toxic for L929 cells. The MX provided a better complexation efficiency. ERKA:ß-CD300 promoted significant tumor growth inhibition, and attenuated the tumor mitotic activity and necrosis content, comparable to 5-fluorouracil. ERKA:ß-CD300 also increased TUNEL-detected cell death, reduced Ki67 and NF-kB immunoexpression, and partially inhibited the serum LDH activity. No side effect was observed in ERKA:ß-CD300-treated animals. The ERKA:ß-CD inclusion complexes at 300 µg/kg displays antitumour activity in mice with low systemic toxicity, likely due to inhibition on the NF-kB signaling pathway and LDH activity.

Antitumor Profile of Combined Matricaria recutita Flower Extract and 5-Fluorouracil Chemotherapy in Sarcoma 180 In Vivo Model.

Medicinal plants have been commonly associated with chemotherapeutic treatments, as an approach to reduce the toxicological risks of classical anticancer drugs. The objective of this study was to evaluate the effects of combining the antineoplastic drug 5-fluorouracil (5-FU) with Matricaria recutita flowers extract (MRFE) to treat mice transplanted with sarcoma 180. Tumor inhibition, body and visceral mass variation, biochemical, hematological, and histopathological parameters were evaluated. The isolated 5-FU, 5-FU+MRFE 100 mg/kg/day, and 5-FU+MRFE 200 mg/kg/day reduced tumor growth; however, 5-FU+MRFE 200 mg/kg/day showed a more significant tumor reduction when compared to 5-FU alone. These results corroborated with the analysis of the tumor histopathological and immunodetection of the Ki67 antigen. In the toxicological analysis of the association 5-FU+MRFE 200 mg/kg/day, an intense loss of body mass was observed, possibly as a result of diarrhea. In addition, spleen atrophy, with a reduction in white pulp, leukopenia and thrombocytopenia, was observed in the 5-FU groups alone and associated with MRFE 200 mg/kg/day; however, there was no statistical difference between these groups. Therefore, the MRFE 200 mg/kg/day did not interfere in myelosuppressive action of 5-FU. In hematological analysis, body and visceral mass variation and biochemical parameters related to renal (urea and creatinine) and cardiac (CK-MB) function, no alteration was observed. In biochemical parameters related to liver function enzymes, there was a reduction in aspartate transaminase (AST) values in the 5-FU groups alone and associated with MRFE 200 mg/kg/day; however, there was no statistical difference between these groups. Therefore, the MRFE 200 mg/kg/day does not appear to influence enzyme reduction. The results of this study suggest that the association between the 5-FU+MRFE 200 can positively interfere with the antitumor activity, promoting the antineoplastic-induced reduction in body mass, while minimizing the toxicity of chemotherapy.

Liposomal formulations of oxybutynin and resiniferatoxin for the treatment of urinary diseases: improvement of drug tolerance upon intravesical.

The use of liposomes for drug release has demonstrated to be a promising therapeutic platform for biomedical applications. In this study, intravesical administration of OXI (1.5 mM) and RTX (100 nM) was used to compare histological changes caused in Wistar female rats by the drugs both unloaded and loaded in liposomes. After instillation of formulations by intravesical catheter, bladders were removed and histological analysis carried out at pre-determined time intervals over a period of 60 days. Urinalysis was performed to verify the presence of infection and of liposomes. Results showed that RTX caused a higher bladder damage, with inflammatory reaction that reached all bladder layers. After 60 days, RTX-treated group showed urothelial alterations, collagen replacement by fibrosis and also abdominal adherence, but not the OXI-treated group. At the end of the assay, the liposomal-treated groups showed a minimal inflammatory reaction and significantly increased bladder size. Moreover, urinalysis confirmed the presence of liposomes in rat urine. RTX promoted higher bladder damage than OXI. Intravesical administration of liposomal OXI or RTX formulations minimized inflammatory reaction, with an extended drug effect on bladders. After a single intravesical administration, liposomes were found in rat urine samples after 60 days.

Gastroprotective action of the ethanol extract of Leonurus sibiricus L. (Lamiaceae) in mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Leonurus sibiricus L. (Lamiaceae) is a medicinal plant known in Brazil as "rubim" or "erva de macaé". It is used for various purposes, including stomach disorders. AIM OF THE STUDY: To evaluate the effect of the ethanol extract of the aerial parts of L. sibiricus (EELs) in models of gastric damage in mice. MATERIAL AND METHODS: The effect of EELs (50, 100 and 300 mg/kg, p.o., 1 h before induction) was tested on acidified ethanol (ACEt)-induced gastric ulcers. Additionally, we tested the effect of EELs (by intraduodenal administration) in the pylorus ligation (PL) model. RESULTS: Pretreatment with EELs, at 300 mg/kg, but not 50 and 100 mg/kg, reduced the relative area of gastric ulcers induced by ACEt (p < 0.01) and lipoperoxidation (p < 0.001), and increased the sulfhydryl content (p < 0.01) in the stomach in comparison with the vehicle group. Pretreatment with N-ethylmaleimide (a blocker of non-protein sulfhydryl groups, 10 mg/kg, i.p.) or glibenclamide (a KATP channel blocker, 10 mg/kg, i.p.) inhibited the gastroprotective response caused by EELs (300 mg/kg; p < 0.001), but there were no alterations due to pretreatments with inhibitors of the synthesis of prostaglandins (indomethacin, 10 mg/kg), nitric oxide (L-NAME, 70 mg/kg) or hydrogen sulfide (DL-propargylglycine, 10 mg/kg). Treatment with EELs (300 mg/kg) reduced mucus production (p < 0.001) and the volume of gastric secretion (p < 0.001) after PL without affecting gastric acidity or pH. CONCLUSIONS: These results provide evidence that EELs exerts gastroprotective action in mice, with the participation of oxidative stress and mediation of NP-SH, KATP channels and mucus production.

Photoprotection and skin irritation effect of hydrogels containing hydroalcoholic extract of red propolis: A natural pathway against skin cancer.

The use of natural products in sunscreen formulations as a prophylactic measure against skin cancer is receiving special attention attributed to the photoprotective and antioxidant properties of their chemical components. In this work, we describe the development of topical hydrogel formulations containing hydroalcoholic extract of red propolis (HERP), and the evaluation of the dermal sensitizing effect of the developed products. Sunscreen formulations composed of HERP in different concentrations (1.5, 2.5 or 3.5% w/w) alone or in combination with a chemical (octyl methoxycinnamate) and/or physical (titanium dioxide) filters were developed using poloxamer 407 as gel basis. The preliminary and accelerated stability tests, texture analysis and spreadability tests were performed. All formulations revealed to be stable in preliminary stability assessment. The formulations containing HERP 1.5 and 2.5% alone or associated with the filters showed intense modifications during accelerated stability test, which were confirmed by rheological analyses. The incorporation of HERP and filters in the poloxamer hydrogel decreased the toughness of product (p < 0.05) and the formulation containing HERP alone presented the lowest adhesivity (p < 0.001). The incorporation of HERP in the hydrogel decreased the poloxamer transition temperature, showing different rheological behavior with the increase of HERP concentration. The developed formulations were stable, exhibited non-Newtonian and pseudoplastic behavior, showing in vivo skin compatibility and no skin irritancy.

Hydrophilic Scaffolds Containing Extracts of Stryphnodendron adstringens and Abarema cochliacarpa for Wound Healing: In Vivo Proofs of Concept.

The present work aimed to evaluate the healing effect of hydrophilic polymeric resorbable biomembrane scaffolds containing plant extracts obtained from two different species, both popularly known as Stryphnodendron adstringens or Barbatimão. The hydrogel-based scaffolds were characterized and submitted to biological tests using Wistar rats to evaluate their healing capacity. The wound retraction index and the evaluation of the inflammatory process and tissue collagenization were recorded. The extracts showed antioxidant activity with IC50 between 10 and 20 µg/mL (DPPH assay) and 4-6 mmol Trolox/g (FRAP assay). The extract of Stryphnodendron adstringens (SA) presented gallocatechin, epigallocatechin, and O-methylpigalocatechin, while the extract of Abarema cochliacarpa (AC) presented catechin, dimers of procyanidins, di-O-hydroxide, O-deoxyhexosi-hexoside, and epicatechin. The membranes containing SA extract (GELSA) were more rigid, with a more intense color, but less thick, with a more compact structure and few pores. The membranes containing AC extract (GELAC) presented a mechanical profile like the gelatin membrane (GEL), with greater permeability to water vapor. The GELAC and GELSA membranes showed similar thermal degradation profiles. The wounds treated with the membranes containing the extracts obtained high levels of retraction of the wounds with values around 60% and 80% in three and seven days, respectively. These data indicate that the compounds of both species have promising biological activities in the repair process, showing that the extracts accelerated the healing process due to the lower intensity of the inflammatory reaction and the presence of compounds such as catechin and epigallocatechin.

Africanized Bee Venom (Apis mellifera Linnaeus): Neuroprotective Effects in a Parkinson's Disease Mouse Model Induced by 6-hydroxydopamine.

This study evaluated the neuroprotective effects of the Africanized bee venom (BV) and its mechanisms of action after 6-hydroxydopamine-(6-OHDA)-induced lesion in a mice model. Prior to BV treatment, mice received intrastriatal microinjections of 6-OHDA (no induced dopaminergic neuronal death) or ascorbate saline (as a control). BV was administered subcutaneously at different dosages (0.01, 0.05 or 0.1 mg·Kg-1) once every two days over a period of 3 weeks. The open field test was carried out, together with the immunohistochemical and histopathological analysis. The chemical composition of BV was also assessed, identifying the highest concentrations of apamin, phospholipase A2 and melittin. In the behavioral evaluation, the BV (0.1 mg·Kg-1) counteracted the 6-OHDA-induced decrease in crossings and rearing. 6-OHDA caused loss of dopaminergic cell bodies in the substantia nigra pars compacta and fibers in striatum (STR). Mice that received 0.01 mg·Kg-1 showed significant increase in the mean survival of dopaminergic cell bodies. Increased astrocytic infiltration occurred in the STR of 6-OHDA injected mice, differently from those of the groups treated with BV. The results suggested that Africanized BV has neuroprotective activity in an animal model of Parkinson's disease.

Biosynthesis of Silver Nanoparticles Mediated by Entomopathogenic Fungi: Antimicrobial Resistance, Nanopesticides, and Toxicity.

Silver nanoparticles are widely used in the biomedical and agri-food fields due to their versatility. The use of biological methods for the synthesis of silver nanoparticles has increased considerably due to their feasibility and high biocompatibility. In general, microorganisms have been widely explored for the production of silver nanoparticles for several applications. The objective of this work was to evaluate the use of entomopathogenic fungi for the biological synthesis of silver nanoparticles, in comparison to the use of other filamentous fungi, and the possibility of using these nanoparticles as antimicrobial agents and for the control of insect pests. In addition, the in vitro methods commonly used to assess the toxicity of these materials are discussed. Several species of filamentous fungi are known to have the ability to form silver nanoparticles, but few studies have been conducted on the potential of entomopathogenic fungi to produce these materials. The investigation of the toxicity of silver nanoparticles is usually carried out in vitro through cytotoxicity/genotoxicity analyses, using well-established methodologies, such as MTT and comet assays, respectively. The use of silver nanoparticles obtained through entomopathogenic fungi against insects is mainly focused on mosquitoes that transmit diseases to humans, with satisfactory results regarding mortality estimates. Entomopathogenic fungi can be employed in the synthesis of silver nanoparticles for potential use in insect control, but there is a need to expand studies on toxicity so to enable their use also in insect control in agriculture.

Cymbopogon winterianus Essential Oil Attenuates Bleomycin-Induced Pulmonary Fibrosis in a Murine Model.

The essential oil of Cymbopogon winterianus (EOCW) is a natural product with antioxidant, anti-inflammatory, and antifibrotic properties. We studied the effect of EOCW in the progression of histological changes of pulmonary fibrosis (PF) in a rodent model. The oil was obtained by hydrodistillation and characterized using gas chromatography-mass spectrometry. Intratracheal instillation of bleomycin was performed in 30 rats to induce PF, while Sham animals were subjected to instillation of saline solution. The treatment was performed using daily oral administration of distilled water, EOCW at 50, 100, and 200 mg/kg, and deflazacort (DFC). After 28 days, hemogram and bronchoalveolar lavage fluid (BALF), tissue levels of malondialdehyde (MDA), superoxide dismutase (SOD), and catalase (CAT) were assayed. Histological grading of PF, immunohistochemical expression of α-smooth muscle actin (α-SMA), and transforming growth factor-ß (TGF-ß) were also analyzed. The EOCW major compounds were found to be citronellal, geraniol, and citronellol. EOCW significantly reduced inflammation in BALF, reduced MDA levels, and increased SOD activity. EOCW attenuated histological grading of PF and reduced immunohistochemical expression of α-SMA and TGF-ß in a dose-dependent way, likely due to the reduction of oxidative stress, inflammation, and TGF-ß-induced myofibroblast differentiation.

Rutin-Functionalized Multi-Walled Carbon Nanotubes: Molecular Docking, Physicochemistry and Cytotoxicity in Fibroblasts.

Multi-Walled Carbon Nanotubes (MWCNT) have been functionalized with rutin through three steps (i. reaction step; ii. purification step; iii. drying step) and their physicochemical properties investigated with respect to morphological structure, thermal analysis, Fourier Transform Infrared Spectroscopy (FTIR), and cytotoxicity. The molecular docking suggested the rutin-functionalized MWCNT occurred by hydrogen bonds, which was confirmed by FTIR assays, corroborating the results obtained by thermal analyses. A tubular shape, arranged in a three-dimensional structure, could be observed. Mild cytotoxicity observed in 3T3 fibroblasts suggested a dose-effect relationship after exposure. These findings suggest the formation of aggregates of filamentous structures on the cells favoring the cell penetration.

Anti-Tumor Efficiency of Perillylalcohol/ß-Cyclodextrin Inclusion Complexes in a Sarcoma S180-Induced Mice Model.

The low solubility and high volatility of perillyl alcohol (POH) compromise its bioavailability and potential use as chemotherapeutic drug. In this work, we have evaluated the anticancer activity of POH complexed with ß-cyclodextrin (ß-CD) using three complexation approaches. Molecular docking suggests the hydrogen-bond between POH and ß-cyclodextrin in molar proportion was 1:1. Thermal analysis and Fourier-transform infrared spectroscopy (FTIR) confirmed that the POH was enclosed in the ß-CD cavity. Also, there was a significant reduction of particle size thereof, indicating a modification of the ß-cyclodextrin crystals. The complexes were tested against human L929 fibroblasts after 24 h of incubation showing no signs of cytotoxicity. Concerning the histopathological results, the treatment with POH/ß-CD at a dose of 50 mg/kg promoted approximately 60% inhibition of tumor growth in a sarcoma S180-induced mice model and the reduction of nuclear immunoexpression of the Ki67 antigen compared to the control group. Obtained data suggest a significant reduction of cycling cells and tumor proliferation. Our results confirm that complexation of POH/ß-CD not only solves the problem related to the volatility of the monoterpene but also increases its efficiency as an antitumor agent.