# A Review on Bioactive Compounds and Pharmacological Activities of _Citrus unshiu_
## 4 Pharmacological Activities of Satsuma Mandarin
### Anti-Obesity and Anti-Diabetic Activities  
In experimental models, _C. unshiu_ bioactives demonstrated an anti-obesity effect via various mechanisms. Oral administration of \(\beta\)CX from _C. unshiu_ significantly reduced body weight, serum lipid levels, and adipocyte hypertrophy in experimental obese mice via upregulating and/or downregulating of genes involved in chemotaxis, cell proliferation, steroid metabolism, wound response, immune system development, lipid transport, fatty acid biosynthesis, muscle contraction, and DNA replication initiation [51]. The bioconversion of _C. unshiu_ extracts with cytolase treatment promoted aglycoside forms (hesperetin and naringenin) and enhanced the anti-adipogenic activity in 3T3-L1 adipocyte cells through suppressing adipogenic transcription factors and inducing lipolytic activity [68]. Combined treatment with _C. unshiu_ extracts (hesperidin) and _Crataegus pinnatifida_ leaf effectively inhibited adipocyte differentiation in 3T3-L1 cells through downregulating the adipogenesis-related gene expression. The treatment also decreased the body weight, serum lipid levels, and visceral fat mass in Sprague-Dawley rats fed with a high-fat diet. These effects were mediated by multiple mechanisms, including activation of \(\beta\)-oxidation genes and downregulation of lipogenic and adipogenic genes [69]. Treatment with _C. unshiu_ ethanolic extract and hesperidin induced the mRNA expression of uncoupling protein 3 (UCP3) in differentiated C2C12 myocytes. _C. unshiu_ treatment also reduced the body fat contents and average fat cell size in skeletal muscle of obese mice fed with a high-fat diet by upregulating the mRNA expression of UCP3 [70]. Oral administration of celluclast extract from _C. unshiu_ (narrutin) effectively reduced the body weight, white adipose tissue/liver weights, serum lipid levels, and hepatic lipid accumulation in high-fat-diet-induced obese mice through upregulating and/or downregulating of multiple genes/enzymes involved in lipogenesis, adipogenesis, and \(\beta\)-oxidation [71]. Treatment with Jeju roasted _C. unshiu_ peel extracts resulted in the reduction of lipid accumulation during 3T3-L1 adipocyte differentiation. In obese mice fed with a high-fat diet, the treatment improved enzymes involved in lipid metabolism and decreased gene expression involved in lipid/energy metabolism [72]. In a few experimental rat models, _C. unshiu_ also demonstrated anti-diabetic effects. Treatment with _C. unshiu_ resulted in the reduction of hyperglycemia-induced oxidative stress in streptozotocin-induced diabetic rats liver. This was mediated by decreasing serum liver enzyme levels and improving antioxidant enzyme levels [73]. Goto-Kakizaki rats \begin{table}
\begin{tabular}{c c c c c c c} \hline \hline \multirow{2}{*}{**Cancers**} & \multirow{2}{*}{**Model Type**} & \multirow{2}{*}{**Bioactive Compounds**} & \multicolumn{2}{c}{**Extraction Techniques**} & \multicolumn{2}{c}{**Anticancer**} & \multicolumn{2}{c}{**Target**} \\  & & & & **and Application in Treatment** & **Activity/ Mechanisms** & **Genes/Signaling Pathways** & **Ref.** \\ \hline \multirow{10}{*}{Cervical} & \multirow{6}{*}{HeLa human CC cells} & \multirow{6}{*}{Hesperidin, heperetin} & CC cells were treated with chloroform extracts of _C. unshiu_ at different concentrations (0, 2, 4, 8, 16, 31, 63, 125, 250, and 500 \(\mu\)g/mL) for 72 h. The & Anti-proliferative, anti-migration, inhibition of colony formation, apoptosis, induction of cell cycle arrest & \multirow{6}{*}{Antigniti-migration, Bad, Fas \(\uparrow\); Akt, PI3K, p21, p53, ERK1/2, cyclin B1/D1, Bcl-2, Induction of cell cycle arrest} & \multirow{6}{*}{[67]} \\  & & & & & \\ \cline{1-1}  & & & & & \\ \cline{1-1}  & & & & & \\ \cline{1-1}  & & & & & \\ \cline{1-1}  & & & & & \\ \hline \hline \end{tabular} (i) Decrease; (\(\uparrow\)) increase; NA = not available.  
\end{table} 
Table 3: _Cont._demonstrated reduced blood glucose levels and improved glucose tolerance after 10 weeks feeding of _C. unshiu_[74]. The administration of _C.