JPBA: Paiyu San reduces colitis in mice by regulating the intestinal flora and restoring the intestinal barrier function

Background: Intestinal barrier dysfunction and intestinal flora imbalance with excessive inflammation areOne of the reasons for the occurrence and acceleration of ulcerative colitis (UC)
.
Chinese medicine theory, UC invasive colon caused by the cold dampness appendicitis , often accompanied by hot and humid, blood stagnation and intestinalvascularischemia, its therapeutic application to heat, dampness, yang of the law
.
The traditional Chinese medicine prescription Paiyu San comes from"The Synopsis of the Golden Chamber", which is mainly composed of Citrus aurantium, Radix Paeoniae Alba and Platycodon grandiflorum.
Studies have found that it has an anti-colitis effect, but itis unclear whetheritspreventiveeffect of UC is related to the intestinal flora
.

Objective: To explore the effect of Paiyusan extract on UC, to understand the mechanism of PNS in the treatment of UC , to provide a theoretical basis for its modern clinical application, and to reveal its related mechanism with intestinal flora
.

Method: Firstly, the main active components in PNS extract (PNS) were identified by ultra performance liquid chromatography quadrupole tandem time -of- flight mass spectrometry ( UPLC-Q-TOF-MS ) , and dextran sulfate was used.
Sodium (DSS) induced UC mice (control group, DSS group-2.
5% DSS aqueous solution, PNS low and high dose groups-PNS 0.
36 g/kg/day and 1.
44 g/kg/day, sulfasalazine group-SASP 0.
42 g/kg/day), to explore the relevant mechanisms of PNS in the treatment of UC from the aspects of intestinal flora, intestinal barrier and TLR4/NF-κB signaling pathway .

Results: 125 compounds were identified from PNS, including 42 flavonoids, 29 triterpenoids, 21 monoterpenoids, 11 polyphenols, 6 citrins, and alkaloids 5, 4 coumarin compounds and 7 other compounds
.

In vivo experimental results show that PNS treatment can reduce the weight loss and disease activity index of mice with DSS-induced colitis, prevent colon shortening, and reduce colonic histological inflammation , and PNS treatment has a dose-dependent protection against DSS-induced colitis Role
.

Tight junction protein (TJP) isthe main component tomaintain the intestinal barrier function
.
After modeling, the expression levels of claudin-1, occludin and ZO-1 proteins in colon tissue were significantly lower than those in the control group.
High-dose PNS can significantly increase the expression levels of claudin-1, occludin and ZO-1 proteins.
These results indicate that PNS It can regulate the expression of these genes and effectively alleviate the intestinal barrier damage induced by DSS in mice
.

Compared with the DSS group, PNS treatment can significantly reverse the decrease in the diversity of intestinal flora , inhibit the overgrowth of conditional pathogenic bacteria such as Oscillospiraceae and Helicobacter, while the intestinal flora of probiotics such as Romboutsia, Lactobacillus, Bifidobacterium and Akkermansia increases
.
In addition, PNS inhibits the intestinal TLR4/NF-κB signaling pathway by down-regulating TLR4, MyD88, p-NF-κB p65 and p-IκBα protein expression, and significantly improves colonic inflammation
.

Conclusion: PNS can effectively improve the DSS-induced colitis by regulating the intestinal flora , restoring the intestinal barrier function, weakening the TLR4/NF-κB signaling pathway , which may provide a new explanation for the anti-UC mechanism of PNS, and also for the regulation of traditional Chinese medicine.
The intestinal microbiota plays a therapeutic role and provides an important reference
.

Literature source:

Wang K, Guo J, Chang X, et al.
Painong-San extract alleviates dextran sulfate sodium-induced colitis in mice by modulating gut microbiota, restoring intestinal barrier function and attenuating TLR4/NF-κB signaling cascades [published online ahead of print, 2021 Dec 10].
J Pharm Biomed Anal.
2021;209:114529.
doi:10.
1016/j.
jpba.
2021.
114529