Best of the Best Gen Surg - Therapeutic Effect of Oridonin against Inflammatory Bowel Disease Involves Inhibition of Intestinal Fibrosis via NF-kB and p38STAT1 Pathways - Dr. Mao

Inflammatory bowel disease affects approximately 3 million adults in the United States.

Annual medical expenses for a patient with IBD is estimated to be $15,000.

The value of work-related opportunity lost due to IBD has been reported to be up to $5.5 billion.

Intestinal fibrosis affects 30-50% of Crohn's disease patients.

Intestinal fibrosis is seen with ulcerative colitis at a rate of 5%.

The fibrosis process can lead to complications that present clinically in the form of strictures, obstruction, and fistulas.

Epithelial-mesenchymal transition (EMT) is a process that contributes to the development of fibrosis, defined by the loss of adherences, tight junctions, and cytoskeleton proteins normally found in epithelial cells.

During EMT, epithelial markers such as E-cadherin and ZO-1 (zona occludens one) are lost.

During EMT, fibroblast markers such as alpha-SMA (alpha smooth muscle actin) and fibronectin are increasingly expressed.

Oridonin is a diterpenoid derived from the plant species Rhabdosa rubiscens.

Rhabdosa rubiscens has been used for hundreds of years in eastern medicine to treat common ailments such as cough, abdominal pain, and muscle aches.

Research has demonstrated that oridonin has antioxidant, anti-tumor, and anti-inflammatory effects on various tissues through inhibition of multiple signaling pathways including NF-κB and P38.

In studies with in vitro experiments and animal models, oridonin has resulted in slower IBD disease progression and decreased levels of inflammatory cytokines and cells.

Oridonin inhibited LPS-induced fibrosis markers and restored ZO-1 expression in rat intestinal epithelial cells.

Exposure to LPS increases levels of alpha-SMA, a marker of EMT and fibrosis, but this effect was inhibited by pre-treatment with oridonin.

Exposure to LPS increases fibronectin levels, but this effect was inhibited by pre-treatment with oridonin.

Exposure to LPS decreased ZO-1 levels, and pre-treatment with oridonin was able to attenuate that effect and restore ZO-1 expression.

NF-κB is a key pro-inflammatory pathway that regulates alpha-SMA.

Oridonin inhibited the activation of NF-κB by preventing the nuclear translocation of NF-κB p65.

Oridonin inhibited the phosphorylation of IKK alpha-beta and I-κB alpha, and prevented total I-κB alpha degradation.

The P38 inhibitor SB 203,580 dose-dependently attenuated LPS-induced alpha-SMA expression.

Oridonin inhibits LPS-induced STAT1 activity, which is a downstream factor of P38.

Oridonin inhibits EMT-related fibrosis via inhibition of the NF-κB and P38/STAT1 pathways.

Oridonin is derived from China and is used in eastern medicine, having been utilized for hundreds of years for common ailments.

After breaking down the Rhabdosa rubiscens plant, researchers found that the most active compound was oridonin.