Polyphenol compound is a class of plant secondary metabolites and is the general term for polyhydroxy compounds. Their structure includes one or more sugar residues connected to hydroxyl groups, and also contains different numbers of benzene rings. Polyphenol compound can be divided into four categories according to the number of benzene rings contained and the structural elements connecting these rings: phenolic acids (gallic acid, ellagic acid, chlorogenic acid, ferulic acid, salvianolic acid, etc.), flavonoids (flavonoids, flavonols, flavanones, isoflavonoids, flavanols, anthocyanidins, etc.), stilbenes (resveratrol, piceatannol, etc.) and lignans (phyllanthin, olivil, etc.). Polyphenol compounds are widely found in natural Chinese herbal medicines, with antioxidant, antibacterial, anti-inflammatory, and anti-fibrosis activities.

Inflammatory bowel disease (IBD) is a chronic intestinal disease, which can be mainly divided into Crohn's disease (CD) and ulcerative colitis (UC). Its pathogenesis is mainly related to the damage of the intestinal mucosal barrier and the imbalance of immune homeostasis caused by a variety of factors, such as environment, heredity and intestinal flora. The pathogenesis of IBD and intestinal fibrosis is complicated. Currently, only some therapeutic drugs (such as mesalazine and dexamethasone) have potential side effects, such as steroid dependence and serious infections. Besides, it cannot fundamentally improve the symptoms of patients, and the prevention and treatment effect is limited. Studies have shown that polyphenol compounds, such as flavonoids, catechins, quinones, lignans and tannins, have potential therapeutic effects on IBD. Related studies have shown that transforming growth factor β (1 TGF-β1)/Smad, phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR), mitogen-activated protein kinase (MAPK) and other signaling pathways are involved in the occurrence and development of IBD and intestinal fibrosis. Want to know more about polyphenol compounds? Pharmasource provides the latest news on them.

Effect of polyphenol compounds on IBD and intestinal fibrosis

1. Curcumin

Curcumin is widely present in various traditional Chinese medicines and foods, such as curcuma zedoary and turmeric. It is a kind of flavonoids with pharmacological effects, such as anti-inflammatory, antioxidant and anti-fibrosis. Some scholars used different concentrations of curcumin to intervene in the rat intestinal epithelial IEC-6 cell fibrosis model induced by 10ng/mL TGF-β1, and it was found that 10μmol/L curcumin could obviously inhibit the low expression of cadherin and the high expression of α-SMA induced by TGF-β1. In addition, studies have pointed out that continuous injection of curcumin (15mg/kg, 30mg/kg and 60mg/kg) for 7 days can also down-regulate the expression of autophagy factors ATG5, beclin-1 and LC-3II in the colon tissue of colitis model mice, and up-regulate the expression of B-cell lymphoma/leukemia 2 (Bcl-2). It indicates that curcumin can inhibit autophagy, relieve intestinal inflammation in colitis model mice, and repair its damaged intestinal mucosa.

2. Baicalin

Baicalin is a kind of flavonoids extracted from the traditional Chinese medicine, scutellaria baicalensis. It has a certain inhibitory effect on tumor cells, inflammation and viruses. Studies have shown that after treating TNBS-induced colitis model rats with baicalin, PI3K/Akt antagonist and agonist, respectively, baicalin (100 mg/kg, continuous gavage for 14 days) can effectively improve TNBS-induced colitis in rats. It inhibits the apoptosis of intestinal mucosal epithelial cells, reduces the levels of IL-6, TNF-α and IL-1β in colon tissue, increases the content of IL-10, and promotes the expression of tight junction proteins ZO-1 and β-catenin. Moreover, the effect of PI3K/Akt antagonist is equivalent to that of baicalin, indicating that the effect of baicalin in alleviating colitis in rats may be achieved by inhibiting the PI3K/Akt signaling pathway. Another study showed that after continuous gavage of 150mg/kg scutellaria baicalensis extract (the main active ingredient is baicalin) for 21 days, the colon mass and length, tissue inflammation and fibrosis degree of TNBS-induced intestinal fibrosis model rats were improved, and the expressions of collagen I-III, α-SMA, CTGF, TGF-β1 and Smad3 were inhibited, suggesting that scutellaria baicalensis extract may improve intestinal fibrosis in rats by inhibiting TGF-β1/Smad signaling pathway.

3. Total Flavone of Abelmoschl manihot L medic

Total Flavone of Abelmoschl manihot L medic is commonly found in the dried corolla of abelmoschus manihot, and has strong anti-fibrosis, anti-inflammatory, anti-infective and multiple pharmacological activities. Studies have shown that in the rat intestinal epithelial IEC-6 cell fibrosis model induced by TGF-β1, 5μg/mL, 10μg/mL and 15μg/mL Total Flavone of Abelmoschl manihot L medic can dose-dependently inhibit the migration and invasion of model cells, and increase the expression of epithelial markers, such as epithelial cadherin and ZO-1, and reduce the level of mesenchymal markers, such as vimentin and N-cadherin, and reduce the occurrence of EMT, so as to inhibit intestinal fibrosis.

4. Isoliquiritigenin

Isoliquiritigenin is a flavonoid compound with outstanding biological activity extracted from the roots of natural plant licorices. It has such important functions as anti-inflammatory and anti-oxidative stress. The results showed that after continuous intragastric administration of 30mg/kg isoliquiritigenin for 10 days, the body weight, diarrhea, stool bleeding and other symptoms of colitis model mice were alleviated, and the DAI score was significantly reduced. In addition, isoliquiritin can also reduce the expression of IL-6 and TNF-α in the colon tissue of model mice, inhibit the phosphorylation of ERK1/2, p38 MAPK and the activation of nuclear factor κB, thereby exerting an anti-colitis effect.

5. Chlorogenic acid

Chlorogenic acid is a phenolic acid compound extracted from the dried buds or flowers of honeysuckle. It is also commonly found in other Chinese herbal medicines, such as honeysuckle, hawthorn, and Eucommia ulmoides. It has antibacterial, anti-oxidant biological activities and regulates sugar metabolism and improves lipid metabolism. Studies have shown that after the intervention of sulfasalazine (100 mg/kg) and chlorogenic acid (30, 60, 120 mg/kg), the pathological changes, such as colonic mucosal injury and inflammatory cell infiltration, in model mice have been significantly improved. The levels of inflammatory factors (IL-1β, IL-6 and TNF-α) in serum and colon tissue were significantly reduced, and the effects of high-dose chlorogenic acid and sulfasalazine were more obvious. In addition, some scholars have found that after the intervention of 200 mg/kg chlorogenic acid, the body weight of the colitis model mice is reduced, the colon shortens, the DAI score increases and other adverse symptoms are significantly improved. The phosphorylation of ERK1/2 and JNK1/2 in colon tissues, as well as the expression of TNF-α and COX-2 are inhibited. The expression of Bcl-2 is up-regulated and the severity of colitis is reduced. These results indicate that the effects of chlorogenic acid in reducing colitis inflammation, inhibiting cell apoptosis, and alleviating intestinal mucosal damage may be achieved through the MAPK/ERK/JNK signaling pathway.

6. Resveratrol

Resveratrol is a natural polyphenolic substance extracted from the rhizomes of Polygonum cuspidatum. It is also the main active ingredient of the traditional Chinese medicine polygonum cuspidatum. It has such functions as antioxidant and anti-inflammatory. Studies have shown that radiation can cause intestinal oxidative stress damage and cause intestinal inflammation. Continuous gavage of resveratrol can significantly improve the intestinal damage induced by radiation in rats. After intervention, resveratrol can significantly inhibit the expression of PI3K, Akt and mTOR, decrease the content of malondialdehyde, increase the levels of glutathione and catalase, and significantly inhibit the high expression of inflammatory factors TNF-α and IL-1β, so as to exert the effect of anti-inflammatory and reduce intestinal inflammation. It can be seen that resveratrol can alleviate radiation-induced intestinal inflammation by inhibiting PI3K/Akt/mTOR signaling pathway, and it is a promising radiotherapy adjuvant.

Polyphenol compounds are commonly found in natural Chinese herbal medicines, and have the effects of anti-inflammatory, anti-oxidant, anti-fibrosis, and other biological activities. Their medicinal and food homogenous effects have become one of the research hotspots. The medicinal value of polyphenol compounds has been increasingly recognized by scholars, but there is still a lack of clinical research on the therapeutic effect of polyphenols on IBD and intestinal fibrosis. In the future, based on the characteristics of multi-target and multi-pathway, further studies on polyphenols active ingredients and their pharmacological mechanisms should be carried out, and gradually applied to the prevention and treatment of IBD and intestinal fibrosis, so as to lay a foundation for the development of safer and more effective new drugs.

References:        

[1] Li Wanying, Zhao Jian, Chen Haokun, Zeng Zhen, Li Hewei, Song Jiale. Research Progress on the Mechanism of Polyphenol Compounds in the Treatment of Inflammatory Bowel Disease and Intestinal Fibrosis [J]. China Pharmacy, 2021, 32 (16): 2044-2048.

About the author: Xiao Nisha, food science and technology worker and Master of Food Science, currently works in a large Chinese drug R&D company and engages in the development and research of nutritious food. 

About the Author

Xiao Nisha, a food science and technology worker working in a large R&D company of drugs in China, engages in the R&D of nutritious food and functional food.