The water-soluble alkaloid from Sophora moorcroftiana enhances Tregs populations and ameliorate ulcerative colitis in mice.

Abstract

Ulcerative colitis (UC) is a chronic inflammatory disease that damages colonic and rectal mucosa, and pharmacotherapy is the primary measure. However, the UC drug presents several notable problems, including low therapeutic efficacy, side effects, and high cost. Sophora moorcroftiana (S. moorcroftiana) is a plant native to the Tibetan Plateau. It is recorded that the aqueous extract of the seeds is used for treating digestive tract diseases, and the main alkaloids possess anti-inflammatory properties. Therefore, it is suggested that the water-soluble alkaloid (E2) from S. moorcroftiana may be a potential therapeutic agent against UC. The main alkaloids of the extract (E2, E2-a, and E2-b) were detected and identified by liquid chromatography-mass spectrometry (LC-MS). UC mice were induced with dextran sulfate sodium (DSS), followed by treatment with extract from S. moorcroftiana seeds. Disease activity index (DAI) scores and H&E staining were used to determine which extract has a therapeutic effect. The proportion of Tregs/Th17 cells was detected by flow cytometry, the levels of IL-6, TNF-α, IL-1β, and IL-28B in colon tissue were measured by ELISA, and the expression of p-STAT3, p-p65, p-IκBα, and p-p38 was detected with western blot. The main alkaloids of the extract were identified; there are 7 distinct alkaloids in E2, with E2-a and E2-b each containing 4, and piperine is present only in E2. Compared with the DSS group, mice treated with E2-b or E2 exhibited less severe damage, based on the milder DAI scores, longer colon length, and less pathological injury. In contrast, E2-a failed to alleviate the progression of UC. Further research revealed that both E2-b and E2 reduced the population of IL-17 Acells, while E2 upregulated the population of Tregs. In addition, all extracts induced a low level of IL-6, and E2 decreased the level of IL-1β. Moreover, the protein expression of p-STAT3 was significantly inhibited by E2. In the extracts of S. moorcroftiana seeds, the water-soluble alkaloid (E2) exhibits the best therapeutic efficacy in UC mice, suggesting that the compounds present in the extract is a potential therapeutic agent in UC.