The overlapping between asthmatic subtypes, including both CD4+ T helper (TH)2 and TH17 cells, is found in the natural course of allergic asthma, especially in exacerbations and severe and insensitive forms to steroids, which are in need of new molecular therapies. In the TH2-subset mediated asthma, fenofibrate displays therapeutic promises, besides evidenced therapeutic effects on TH17-mediated colitis and myocarditis. Therefore, the effects of fenofibrate versus dexamethasone on IL-23/IL-17 axis in ovalbumin (OVA)/lipopolysaccharide (LPS)-induced airway inflammation and bronchial asthma in rats were explored. The OVA/LPS sensitization and challenge were performed for 28 days in male Wistar rats. After sensitization, fenofibrate (100 mg/kg/day) or dexamethasone (2.5 mg/kg/day) was orally administered from the day 15 to 28. Either fenofibrate or dexamethasone attenuated the severity of OVA/LPS-induced airway inflammation and bronchial asthma through significant ameliorations in the total serum immunoglobulin (Ig)E assay; the total and differential leukocytic counts in the bronchoalveolar lavage (BAL) fluid; the lung inflammatory cytokines such as interleukin (IL)-4, IL-13, IL-17, and IL-23, transforming growth factor (TGF)-β, and tumor necrosis factor(TNF)-α levels; and the lung IL-17 and IL-23 expressions. In addition to the reduction in the inflammatory and fibrotic histopathological scores, fenofibrate significantly ameliorated the BAL neutrophilic count and the lung IL-17 and IL-23 expressions in comparison to dexamethasone. The suppression of IL-23/IL-17 axis could be considered a molecular therapeutic target for fenofibrate in OVA/LPS-induced airway inflammation and bronchial asthma. Combined therapeutic regimens of fenofibrate and steroids should be furtherly investigated in severe and resistant asthma.

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Targeting peroxisome proliferator-activated receptor-gamma (PPAR-γ) is an approved strategy in facing insulin resistance (IR) for diabetes mellitus (DM) type 2. The PPAR-γ modulators display improvements in the insulin-sensitizing and adverse effects of the traditional thiazolidinediones. Nitazoxanide (NTZ) is proposed as a PPAR-γ receptor ligand with agonistic post-transcriptional effects. Currently, NTZ antidiabetic activities versus pioglitazone (PIO) in a high-fat diet/streptozotocin rat model of type 2 diabetes was explored. Diabetic adult male Wistar rats were treated orally with either PIO (2.7 mg·kg·day) or NTZ (200 mg·kg·day) for 14, 21, and 28 days. Body masses, fasting blood glucose, IR, lipid profiles, and liver and kidney functions of rats were assayed. Hepatic glucose metabolism and PPAR-γ protein expression levels as well as hepatic, pancreatic, muscular, and renal histopathology were evaluated. Significant time-dependent euglycemic and insulin-sensitizing effects with preservation of liver and kidney functions were offered by NTZ. Higher hepatic levels of glucose-6-phosphatase and glucose-6-phosphate dehydrogenase enzymes and PPAR-γ protein expressions were acquired by NTZ and PIO, respectively. NTZ could be considered an oral therapeutic strategy for DM type 2. Further systematic NTZ/PPAR-γ receptor subtype molecular activations are recommended. Simultaneous use of NTZ with other approved antidiabetics should be explored.

Therapeutically, metformin and α-LA could be administered in chronic colitis. The combination of currently used pharmaceutics with natural and synthetic potent antioxidant compounds will become a therapeutic strategy of choice for UC to improve the quality of life if sufficient clinical trials are available.