Beneficial effects of Ilex paraguariensis in the prevention of obesity-associated metabolic disorders in mice.

Obesity is a chronic condition involving inflammation and oxidative stress that commonly predisposes affected individuals to develop metabolic disorders. We hypothesize that Ilex paraguariensis (IP) can modulate oxidative stress and inflammation underpinning metabolic disorders caused by obesity. C57BL/6 mice were fed a high-fat diet (HFD group) for 12 weeks. Concomitantly, some mice were treated with roasted IP (15 mg/ml - HFD + IP) or dimethyl fumarate (DMF) as a positive control (2 mg/ml - HFD + DMF). The control group received standard chow and water ad libitum. Histological analyses of fat tissue and liver, and quantification of mediators related to oxidative stress (Kelch-like ECH-associated protein 1/NF-E2-related factor 2, NADP(H) quinone oxidoreductase-1 [NQO1], heme oxygenase 1 [HO1], and superoxide dismutase) as well as metabolic profile blood biomarkers (glucose, leptin, resistin, high-density lipoproteins [HDLs], and triglycerides) were performed. Metabolic disorders were prevented in mice treated with IP, as evidenced by the observation that glucose, HDL, and resistin levels were similar to those assessed in the control group. Morphological analyses showed that both IP and DMF treatments prevented hepatic steatosis and adipocyte hypertrophy in visceral adipose tissue. Finally, although the antioxidant response stimulated by IP was quite limited, significant effects were found on NQO1 and HO1 expression. In conclusion, IP has promising preventative effects on the development of metabolic disorders caused by obesity.

Eucalyptol promotes lung repair in mice following cigarette smoke-induced emphysema.

BACKGROUND: Eucalyptol is a monoterpenoid oil present in many plants, principally the Eucalyptus species, and has been reported to have anti-inflammatory and antioxidative effects. HYPOTHESIS/PURPOSE: Since the potential effect of eucalyptol on mouse lung repair has not yet been studied, and considering that chronic obstructive pulmonary disease (COPD) is the fourth leading cause of death worldwide, the aim of this study was to investigate eucalyptol treatment in emphysematous mice. STUDY DESIGN: Male mice (C57BL/6) were divided into the following groups: control (sham-exposed), cigarette smoke (CS) (mice exposed to 12 cigarettes a day for 60 days), CS + 1 mg/ml (CS mice treated with 1 mg/ml eucalyptol for 60 days), and CS + 10 mg/ml (CS mice treated with 10 mg/ml eucalyptol for 60 days). Mice in the CS and control groups received vehicle for 60 days. Eucalyptol (or the vehicle) was administered via inhalation (15 min/daily). Mice were sacrificed 24 h after the completion of the 120-day experimental procedure. METHODS: Histology and additional lung morphometric analyses, including analysis of mean linear intercept (Lm) and volume density of alveolar septa (Vv[alveolar septa]) were performed. Biochemical analyses were also performed using colorimetric assays for myeloperoxidase (MPO), malondialdehyde (MDA), and superoxide dismutase (SOD) activity, in addition to using ELISA kits for the determination of inflammatory marker levels (tumor necrosis factor alpha [TNF-α], interleukin-1 beta [IL-1ß], interleukin 6 [IL-6], keratinocyte chemoattractant [KC], and tumor growth factor beta 1 [TGF-ß1]). Finally, we investigated protein levels by western blotting (nuclear factor (erythroid-derived 2)-like 2 [Nrf2], nuclear factor kappa B [NF-κB], matrix metalloproteinase 12 [MMP-12], tissue inhibitor of matrix metalloproteinase 1 [TIMP-1], neutrophil elastase [NE], and elastin). RESULTS: Eucalyptol promoted lung repair at the higher dose (10 mg/ml), with de novo formation of alveoli, when compared to the CS group. This result was confirmed with Lm and Vv[alveolar septa] morphometric analyses. Moreover, collagen deposit around the peribronchiolar area was reduced with eucalyptol treatment when compared to the CS group. Eucalyptol also reduced all inflammatory (MPO, TNF-α, IL-1ß, IL-6, KC, and TGF-ß1) and redox marker levels (MDA) when compared to the CS group (at least p < 0.05). In general, 10 mg/ml eucalyptol was more effective than 1 mg/ml and, at both doses, we observed an upregulation of SOD activity when compared to the CS group (p < 0.001). Eucalyptol upregulated elastin and TIMP-1 levels, and reduced neutrophil elastase (NE) levels, when compared to the CS group. CONCLUSION: In summary, eucalyptol promoted lung repair in emphysematous mice and represents a potential therapeutic phytomedicine in the treatment of COPD.

Nifedipine in semi-solid formulations for topical use in peripheral vascular disease: preparation, characterization, and permeation assay.

Nifedipine (NFD) has been used for the treatment of cutaneous lesions caused by peripheral vascular disease and diabetic ulcers. NFD was formulated at 8% in three semi-solid formulations: Polaxamer 407 Lecithin Organogel (PLO), PLO plus Transcutol(®), and an oil-in-water (o/w) emulsion. In vitro release and permeation tests were carried out using a synthetic (cellulose acetate) or natural membrane (pig ear skin), respectively, mounted in a Franz-type diffusion cell at 37°C in a constant water bath. As a receptor solution, isotonic phosphate buffer at pH 7.4 was used. All samples were analyzed by high-performance liquid chromatography by employing a previously validated method. The drug flow values were 6.126 ± 0.288, 4.030 ± 0.081, and 6.660 ± 0.254 µg/cm(2)/h for PLO, PLO plus Transcutol(®), and o/w emulsion, respectively. The three formulations did not show significant differences in drug flow, considering p > 0.05. Furthermore, their penetration profiles in both the epidermis and dermis were statistically different. Thus, the incorporation of NFD in PLO, PLO plus Transcutol(®), and o/w emulsion changed the drug thermodynamic activity, as expected. In addition, Transcutol(®) increased the solubility of NFD in the formulation and promoted its penetration in both the epidermis and dermis.