Abstract
Many studies have shown that Orthosiphon stamineus extract (OE) has antioxidant activity, and we previously reported that OE protects the intestine against injury from a high-fat diet. However, the molecular mechanism underlying this protective effect of OE was unclear. Here, OE was separated according to polarity and molecular weight, and the antioxidant activity of each component was compared. The components with the highest antioxidant activity were analyzed by HPLC, which confirmed that rosmarinic acid (RA) was the main effective constituent in OE. OE and RA were then tested in a mouse high-fat diet-induced intestinal injury model. The antioxidant indices and morphological characteristics of the mouse jejunum were measured, and activation of the nuclear factor E2-related factor 2 (Nrf2) pathway and apoptosis of jejunal epithelial cells were analyzed. Of all the constituents in OE, RA contributed the most. Both RA and OE activated the Nrf2 pathway and increased downstream antioxidant enzyme activity. RA and OE protected the mouse intestine against high-fat diet-induced oxidative stress by preventing intestinal epithelial cell apoptosis via both extracellular and intracellular pathways. Thus, RA, the main effective constituent in OE, inhibits intestinal epithelial apoptosis by regulating the Nrf2 pathway in mice.
Highlights
Owing to rapid economic development, dietary habits in China and other eastern countries are similar to the “Western diet,” including excess energy from fat
These results indicate that Rosmarinic acid (RA) is the main contributor to the antioxidant activity of Orthosiphon stamineus extract (OE)
The high-fat diet caused an increase in body weight during the 8-week feeding trial (normal diet (NC), 26.34 ± 0.46 g; high-fat diet (FC), 33.64 ± 0.34 g; or high-fat diet with OE, 33.09 ± 0.36 g or RA, 33.89 ± 0.40 g), but OE and RA did not alter body weight compared with the mice in FC group (S3, P > 0.05)
Summary
Owing to rapid economic development, dietary habits in China and other eastern countries are similar to the “Western diet,” including excess energy from fat. A high-fat diet causes oxidative stress in the intestines [1]. Is the main phenolic constituent in the alcohol (methanol)-water extract [4], and RA has been reported to have an anti-apoptotic effect in oxidative stress-induced apoptosis [5]. There are no reports confirming that RA is the predominant effective compound in the antioxidant activity of OE. Pathway is regarded as the major mechanism protecting against oxidative stress because it modulates the expression of hundreds of genes, including those encoding antioxidant enzymes and their relative responses [8]. We hypothesized that OE might protect the intestinal epithelium against apoptosis via the Nrf pathway. OE regulates intestinal cell apoptosis and to assess the influence of OE on the Nrf pathway and investigate the underlying mechanism
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