# A Review on Bioactive Compounds and Pharmacological Activities of _Citrus unshiu_
## 6 Limitations and Future Perspectives  
The utilization of _C. unshiu_ bioactives in clinical studies was not assessed, despite the fact that they demonstrated a broad spectrum of therapeutic activities when examined in vitro and in vivo. The majority of in vivo studies were carried out on mouse models; however, some were carried out on guinea pigs. The bioactives of _C. unshiu_ have been shown in a limited number of studies to have non-toxic effects. The pharmacological actions of _C. unshiu_ bioactives were not determined by any tests that showed their bioavailability. The effective dose for attaining the best therapy effect was unclear, despite the fact that each experiment assessing the bioactives of _C. unshiu_ demonstrated therapeutic efficiency.  
More experiments are still needed in order to clarify the mechanisms of action of _C. unshiu_ bioactives and investigate their therapeutic potential. Additional investigations on the possible toxicity at various doses are required to ascertain the applicability of _C. unshiu_ bioactives. Further experiments are required to ascertain the best dosage and mode of administration for _C. unshiu_ extracts. Clinical studies are required to evaluate the therapeutic activities of _C. unshiu_ bioactives. Preclinical animal investigations are needed to ascertain the therapeutic potential of _C. unshiu_ bioactives before being translated to clinical practice.  
**Funding:** This review received no financial support.  
**Data Availability Statement:** Not applicable.  
**Conflicts of Interest:** The author declares no conflicts of interest.  
**Abbreviations**  
8-oxodG 8-oxo-7-8-dihydro-2'-deoxyguanosine  
Abca1  ATP-binding cassette subfamily A member 1  
ABTS+  Diammonium salt  
ACC  Acetyl-CoA carboxylase JAK Janus kinase  
JNK c-jun NH2-terminal kinase  
Kng Kininogen  
LDH Lactate dehydrogenase  
LPS Lipopolysaccharideacharide  
MAFbx Muscle atrophy F-box  
MAPK Mitrogen-activated protein kinase  
MCM Mini-chromosome maintenance  
MCP-1 Monocyte chemoattractant protein-1  
MDA Malondialdehydedehyde  
MDC Macrophage-derived chemokine  
ME Malic enzyme  
MKK Mitogen-activated protein kinase kinase  
MMP Metalloproteinase  
MSC Melanoma skin cancer  
mTORC1 Mammalian target of rapamycin complex 1  
MuRF1 Muscle RING finger 1  
Myh \(\beta\)-myosin heavy chain  
NF-kB Nuclear factor kappa B  
NO Nitric oxide  
NOX2 NADPH oxidase 2  
ORAC Oxygen radical absorbance capacity  
p21 Protein 21  
p38 Protein 38  
p50 Protein 50  
p53 Protein 53  
PaC Pancreatic cancer  
PAP Phosphatidate phosphohydrolase  
PARP Poly(ADP-ribose) Polymerase  
PCNA Proliferating cell nuclear antigen  
PGE\({}_{2}\) Prostaglandin 2  
PI3K Phosphatidylinositol 3-kinase  
PKC Protein kinase C  
PPAR\(\alpha\) Peroxisome proliferatorator-activated receptor gamma  
PPAR\(\gamma\) Peroxisome proliferatorator-activated receptor alpha  
FRAP Ferric-reducing antioxidant power  
RCC Renal cell carcinoma  
ROS Reactive oxygen species  
SA-\(\beta\)-gal \(\beta\)-galactosidase  
Scd1 Stearoyl-CoA desaturase  
SCD-1 Stearoyl-CoA desaturase-1  
SCFAs Short chain fatty acids  
Sepinc1 Serpin family C member 1  
SOD Superoxide dismutase  
SPT Serine palmitosyltransferase  
SREBP1c Sterol regulatory element-binding protein-1c  
STAT1 Signal transducer and activator of transcription 1  
TARC Thymus and activation-regulated chemokine  
TEAC Trolox equivalent antioxidant capacity  
Th T-helper type  
Th17 T-helper 17  
TIMP Tissue inhibitor of matrix metalloproteinases  
TNF-\(\alpha\) Tumor necrosis factor-alpha  
Tnnc1 Troponin C 1