Mechanism of the alleviation of colonic mucosal injury and inflammatory response in rats with ulcerative colitis by asperuloside
- VernacularTitle:车叶草苷减轻溃疡性结肠炎大鼠结肠黏膜损伤及炎症反应的机制
- Author:
Xia ZHANG
1
,
2
;
Xiufen LI
2
;
Hanqing ZHAO
3
;
Huiyu JIA
4
;
Liping DONG
5
Author Information
1. Graduate School of Hebei North University，Hebei Zhangjiakou 075051，China
2. Dept. of Geriatric Medicine，the Second Hospital Affiliated to Hebei North University，Hebei Zhangjiakou 075100，China
3. Dept. of Traditional Chinese Medicine，the Second Hospital Affiliated of Hebei North University，Hebei Zhangjiakou 075100，China
4. Dept. of Laboratory，the Second Hospital Affiliated of Hebei North University，Hebei Zhangjiakou 075100，China
5. Dept. of Geriatric Medicine，the First Hospital Affiliated of Hebei North University，Hebei Zhangjiakou 075061，China
- Publication Type:Journal Article
- Keywords:
asperuloside;
ulcerative colitis;
colonic pathological injury;
inflammatory response;
STING/TBK1/IRF3 signaling
- From:
China Pharmacy
2024;35(22):2756-2762
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE To explore the effects and potential mechanism of asperuloside （ASP） on colonic pathological injury and inflammatory response in rats with ulcerative colitis （UC） based on the stimulator of interferon genes （STING）/TANK binding kinase 1 （TBK1）/interferon regulatory factor 3 （IRF3） signaling pathway. METHODS A UC rat model was established by intrarectal injection of trinitrobenzenesulfonic acid and ethanol. The successfully modeled rats were allocated to model group， low- dose ASP group （17.5 mg/kg）， high-dose ASP group （35 mg/kg）， and high-dose ASP+STING activator ADU-S100 group （35 mg/kg ASP+20 mg/kg ADU-S100）， with 16 rats in each group. Another 16 healthy rats were selected as control group， by intrarectally injecting with normal saline. The rats in each group were given the corresponding drug solutions or normal saline by gavage or/and intraperitoneal injection once a day for 14 consecutive days. Twenty-four hours after the last administration， the disease activity index （DAI） and colonic mucosal damage index （CMDI） were employed to assess the severity of UC and colonic mucosal damage in each group. Colonic tissue pathological changes were observed， and histopathological scores were recorded. Apoptosis in colonic tissue， levels of inflammatory cytokines [tumor necrosis factor-α （TNF-α）， interferon-β （IFN-β）， interleukin-4 （IL-4）， IL-10]， and expressions of pathway-related proteins [STING， TBK1， IRF3， nuclear factor-κB p65 （NF-κB p65）] were detected. RESULTS Compared with the control group， the model group showed severe destruction of colonic mucosa and glandular structure， mucosal epithelial erosion， crypt loss， marked inflammatory cell infiltration； it also demonstrated significant increase in DAI score， CMDI score， colonic histopathological score， apoptosis rate， the levels of TNF-α and IFN-β， and protein expression of STING and phosphorylation levels of TBK1， IRF3 and NF-κB p65， while the levels of IL-4 and IL-10 were significantly decreased （P＜0.05）. Compared with the model group， the low- and high-dose ASP groups showed relatively intact colonic mucosal structure， orderly glandular arrangement， reduced congestion and edema， and markedly reduced inflammatory cell infiltration and ulcers； all quantitative indicators were significantly improved， with the high-dose group showing more pronounced improvements than the low-dose group （P＜0.05）. Compared with the high-dose ASP group， the above indicators of rats in the high-dose ASP+STING activator group were significantly reversed （P＜0.05）. CONCLUSIONS ASP may alleviate colonic pathological injury and inflammatory response in UC rats by inhibiting the STING/TBK1/IRF3 signaling pathway.
