Zinc and iron complexes of oleanolic acid, (OA) attenuate allergic airway inflammation in rats

Oleanolic acid (OA) is a hydroxyl pentacyclic triterpene acid (HTAs) used in various ailments. Inflammatory diseases may be profoundly influenced by iron (Fe) and zinc (Zn) status. We studied the anti-asthmatic effects of two metal complexes (Fe and Zn) of OA in the ovalbumin (OVA)-induced rat model. Delayed type hypersensitivity (DTH) was measured. Total and differential leucocyte count was done in blood as well as bronchoalveolar lavage fluid (BALF). The mRNA expression levels of pro-inflammatory cytokines were measured in lung tissue by reverse transcription polymerase chain reaction. The levels of cyclooxygenase-2 (COX-2), immunoglobulin E (IgE) and 5-lipoxygenase (5-LOX) were estimated by enzyme linked immunosorbent assay. Splenocyte proliferation was performed through BrdU uptake method and nitric oxide levels were measured by colorimetric assay kit. The acute toxicity study was also done for the complexes. The asthmatic group developed allergic airway inflammation shown by increased DTH and inflammatory markers in blood and BALF. OA + Fe and OA + Zn displayed significant decrease in DTH, NO, expression of IL-4, 5, 13, 17, toll-like receptor-2, nuclear factor-kappa B and tumor necrosis factor-α; serum IgE, COX-2, and 5-LOX. The metal complexes also attenuated OVA-stimulated splenocyte proliferation. While no hepatotoxic or nephrotoxic potential was shown by OA + Fe and OA + Zn. Our findings indicate that both OA + Fe and OA + Zn possess significant anti-asthmatic effect which may be ascribed to its immunomodulatory and anti-inflammatory features.