Citrus unshiu Peel Attenuates Dextran Sulfate Sodium-Induced Ulcerative Colitis in Mice due to Modulation of the PI3K/Akt Signaling Pathway and MAPK and NF-κB

Abstract

Aim. Citrus unshiu peel has been used to treat various diseases in traditional East Asian medicine including Korea, and many studies have been reported regarding inflammatory diseases including ulcerative colitis (UC). However, the underlying mechanism by which Citrus unshiu peel modulates inflammation in UC remains unclear. Therefore, this study aimed to evaluate the therapeutic effect and underlying mechanism of Citrus unshiu peel water extract (CUP) for UC. Methods. The experiment for UC was conducted with 8-week-old male Balb/c mice. After 1 week of adaptation, acute colitis was induced in all groups except the normal group by 5% DSS dissolved in drinking water for 1 week. Balb/c mice were divided into 5 groups (n = 8/group): control group (Control), distilled water-treated group (DSS), 100 mg/kg sulfasalazine-treated group (SASP), 100 mg/kg CUP-treated group (CUPL), and 200 mg/kg CUP-treated group (CUPH). The efficacy of CUP on UC was evaluated by biochemical analyses such as ROS and MPO in serum and MDA in tissues, and expression of proteins related to inflammation and apoptosis was evaluated through Western blot. Results. As a result of confirming the macroscopic changes and H&E staining in colon tissues to confirm the preventive and therapeutic effects of CU, decrease in colon length and inflammatory lesions were inhibited in the CUP-treated group compared to the DSS group. In addition, as a result of serum ROS and tissue MDA analysis and oxidative stress-related protein analysis, it was significantly decreased in the CUP-administered group compared to the control group. In addition, treatment with CUP not only inactivated MAPK, p-IκBα, and NF-κBp65 by blocking the PI3K/Akt pathway but also significantly reduced the expression of inflammatory cytokines. Conclusion. These results show that CUP not only suppresses oxidative stress in UC but also regulates inflammation-related proteins and apoptotic proteins by regulating the PI3K/Akt signaling pathway, suggesting that it has the potential as a material for developing new natural therapeutic agents for UC.

Biometabolites of Citrus unshiu Peel Enhance Intestinal Permeability and Alter Gut Commensal Bacteria

“…Recent studies have reported that CUP downregulates the expression of pro-inflammatory cytokines by repressing the NF-κB signaling pathway in a macrophage cell line [ 63 , 64 ]. In addition, it is already known that water extracts of CUP decrease phospho-IκB in murine colon tissues [ 21 ]. Consistently, our data showed that the bioconversion of the CUP downregulated p50 and phospho-IκB, followed by the recovery of tight junction proteins, whereas the ethanol extracts of the CUP did not mediate this mechanism.…”

“…For example, the ethanol derivative of CUP ameliorated oxidative stress by suppressing nicotinamide adenine dinucleotide phosphate (NADPH) oxidase 2 expression (NOX2) in a chemotherapy-induced neuropathic pain animal model [ 15 ] and decreasing the expression levels of pro-inflammatory cytokines, such as interleukin (IL)-6, interferon (IFN)-γ, and tumor necrosis factor-alpha (TNFα), in a type 2 diabetes and systemic inflammation mouse model [ 18 , 20 ]. Moreover, water extracts of CUP have been reported to attenuate dextran sulfate sodium-induced colitis by regulating the phosphoinositide 3-kinase (PI3K)/Akt signaling pathway [ 21 ]. This prompted us to explore other pharmaceutically active products in CUP.…”

Mechanism of Jiawei Zhengqi Powder in the Treatment of Ulcerative Colitis Based on Network Pharmacology and Molecular Docking

“…The JWZQS-H group (23.4 g/kg) had twice the concentration as the JWZQS-M group, and the JWZQS-L group (5.85 g/kg) had 0.5 times the concentration as the JWZQS-M group. The SASP (Shanghai Xinyi Co. LTD.) group 100 mg/kg SASP suspension by gavage [ 19 ]. Gavage was used to administer the corresponding volume of distilled water to the NT group.…”

Study of the Effect and Underlying Mechanism of Enzyme-Treated Garlic Extract on a Lipopolysaccharide-Induced Acute Colitis Model

“…염증성 장질환은 크게 궤양성 대장염(Ulcerative colitis)과 크론병(Crohn's Disease)으로 나뉘며 위장관 전체 및 장점막에서 염증의 완화와 악화가 반복되어 대장암의 발병률 을 상승시키는 특징을 가지고 있다 5 . 나타나는 증 상으로는 복통, 설사, 혈변 및 고름 등이 있으며, 이러한 증상들이 반복적으로 일어나 환자의 신체 적 및 정신적 건강에 심각한 영향을 미친다 6 . 지금 까지 염증성 장질환의 치료는 항염증제, 면역억제 제, steroid 및 corticosteroid 등의 약물을 사용하였 지만 약 20~40%의 환자들은 치료에 실패하거나 장기간 복용으로 인하여 부작용이 발생하게 된다 7,8 .…”