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 defined by the loss of adherences, tight junctions, and cytoskeleton proteins that are normally found in epithelial cells, with loss of epithelial markers such as E-cadherin and ZO-1.

During EMT, cells gain extracellular matrix and fibroblast morphology as well as migratory capacity, with increased expression of fibroblast markers such as α-SMA and fibronectin.

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, thought to be due to 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 increases in α-SMA, a marker of EMT and fibrosis.

Oridonin inhibited LPS-induced increases in fibronectin, another marker of EMT and fibrosis.

Pre-treatment with oridonin attenuated LPS-induced decreases in ZO-1 levels and restored ZO-1 expression.

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

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

Oridonin inhibited the phosphorylation of IKK-α/β and I-κB-α, and prevented total I-κB-α degradation.

The P38 inhibitor SB 203580 dose-dependently attenuated LPS-induced α-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 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.