# A Review on Bioactive Compounds and Pharmacological Activities of _Citrus unshiu_
## 4 Pharmacological Activities of Satsuma Mandarin
### Gastroprotective Activity  
The bioactives of _C. unshiiu_ have been shown in experimental models to have strong gastroprotective activities. In a mouse model of ulcerative colitis, the therapeutic effects of _C. unshiiu_ water extracts (hesperidin and narirutin) were investigated. The dried peel (300 g) was extracted with water at 100 \({}^{\circ}\)C for 2 h using a hot water extractor. The extracts were then evaporated at 50 \({}^{\circ}\)C, freeze-dried, and stored at \(-\)80 \({}^{\circ}\)C. The experiment was performed on male Balb/_c_ mice induced by acute colitis. Ulcerative colitis mice were randomized into control, distilled water-treated, 100 mg/kg sulfasalazine-treated, and 100/200 mg/kg _C. unshiiu_ peel water extract-treated groups. Compared to other groups, the sulfasalazine and _C. unshiiu_ peel water extract-treated groups showed a significant reduction in weight gain, colon length, and inflammatory cell infiltration/inflammatory lesions. These effects were mediated by the decrease in oxidative stress biomarkers (ROS; malondialdehydedehyde, MDA; NADPH oxidase 2, NOX2), inflammatory cytokines (interleukin IL-6/IL-18; cyclooxygenase-2, COX-2; inducible nitric oxide synthase, iNOS), and apoptotic-related proteins (Bax, caspase-3),as well as the inhibition of phosphatidylinositol 3-kinase/threonine kinase (PI3K/Akt) and mitogen-activated protein kinase/nuclear factor kappa B (MAPK/NF-\(\kappa\)B) signaling pathways [80]. The bioconversion of _C. unshiu_ peel containing naringenin and hesperetin was evaluated in Caco-2 epithelial cells and murine with dextran sodium sulfate-induced colitis. _C. unshiu_ peel was extracted with 70% ethanol at room temperature for 24 h. Caco-2 cells were treated with _C. unshiu_ extracts at a dose of 50 \(\upmu\)g/mL. Female C57 BL/6 mice were orally administered _C. unshiu_ extracts at a dose of 500 mg/kg for two weeks and then treated with 3% dextran sodium sulfate for one week. _C. unshiu_ extracts reduced gut inflammation, improved the intestinal permeability of Caco-2 cells by increasing the mRNA levels of occludin, and inhibited the activation of canonical NF-\(\kappa\)B through decreasing the expression of IkappaB kinase (I\(\kappa\)B) and protein 50 (p50). The administration of _C. unshiu_ to mice demonstrated anti-inflammatory effects by decreasing the frequency of T-helper 17 (Th17) cells in the large intestine [81]. An experiment assessed the efficacy of pectin extracted from _C. unshiu_ using male C57 BL/KsJ-\(db\)/\(db\) and \(db\)/m mice by regulating the gut microbiota and its metabolites. Mice were first given access to food and water for one week and then assigned to \(db\)/m mice as the control group, type 2 diabetes model group, metformin-positive group (100 mg/kg), pectin from basic/acid water group (200 mg/kg), and commercial pectin group (200 mg/kg). Mice were orally administered pectin for four weeks. Pectin administration not only decreased the fasting blood glucose/glycated serum protein and serum lipid profiles, but also modulated the gut microbiota composition in mice by increasing the relative abundance of specific microbiota (_Lactobacillus_, _Ligilactobacillus_, _Limosiactobacillus_) and promoting the production of metabolite short-chain fatty acids (SCFAs) [82]. An experimental mouse model was used to study the effects of dietary fiber extracted from _C. unshiu_ on intestinal microecology and SCFAs contents. Mice were first injected with d D-galactose solution (200 mg/kg/d) for 42 days and then orally administered soluble dietary fiber (low/high doses 100/200 mg/kg/d) for 28 days. The treatment with soluble dietary fiber reduced MDA, and increased SOD and glutathione peroxidase activity (GSH-Px) in the liver/serum of D-galactose-stimulated oxidative stress mice. Mice receiving high doses of soluble dietary fiber exhibited high microbial richness and butyric acid concentration, while those receiving low doses demonstrated high levels of valeric acid, acetic acid, and butyric acid.