The development of drugs from natural plant sources is at growing interest due to the limitations of chemical drugs in terms of side effects and cost-effective factors of natural medicines. Among the various components contained in natural plant materials, flavonoids are of increasing interest because of their extended biological benefits. Flavonoids are classified into various types according to their structure and possess different activities depending on the structure. In this study, the flavonoids contained in Artemisia, native to Korea were examined and reviewed. HPLC chromatograms of three Artemisia species (Artemisia annua L., Artemisia iwayomogi and Artemisia argyi H.) were examined from published sources and their component analysis by MS data were summarized. The various flavonoids of Artemisia were classified into 12 types according to the main structure, and 10 flavonoids based on various activities were examined. The 10 flavonoids were identified as quercetin, kaempferol, rhamnetin, diosmetin, luteolin, methoxyflavone, catechin, apigenin, malvidin and genkwanin with extensive reported studies till date. The ten flavonoids examined have been reported to be effective in preventing and treating various diseases and exhibit activities such as anti-cancer, anti-inflammatory, antioxidant, antiviral, anti-obesity, anti-diabetic and anti-Alzheimer. The collective results from the reported studies suggest that the three types of Korean native Artemisia, contains various flavonoids with beneficial activities and may have therapeutic effects against diseases.
Cancer is the second leading cause of death worldwide and currently there are many approaches developing towards cancer treatment. Cancer treatments like chemotherapy and radiation therapy are often painful and have adverse effects. The mechanism of apoptosis is a complex process and it involves different pathways in its mechanism of action. Apoptosis can be caused by signals within the cell such as stress, or by extrinsic signals such as ligands binding to cell surface death receptors. The programmed cell death plays a important role in the several physiological and pathological processes. It plays important role in homeostasis. Flavonoids have gained importance as anticancer agents promoting cytotoxicity and apoptosis in cancer cells. Flavonoids are present in many medicinal plants which are a kind of ubiquitous natural products and essential active ingredients. They have strong biological activities with high efficiency and low toxicity, possessing good preventive and cure effects on different tumor forms. Flavonoids such as Scutellarein, Pectolinarigenin and Naringin have reported to possess significant anti-cancer effects on different cancer cell lines till date. In this review, we provide a summary about the anti-cancer effect of the three flavonoids and its mechanisms of action that can be used in future for understanding their potent anti-tumor properties.
Non-alcoholic fatty liver disease (NAFLD) is emerging as the most common liver disease in industrialized countries. Recently, natural compounds that may be beneficial for improving NAFLD have received increasing attention. Artemisia annua L. is the source of antimalarial phytomolecule, artemisinin, which has been reported to prevent obesity. However, the effect of A. annua extract on hepatic lipid metabolism remains unclear. This study was performed to determine the protective effect of Artemisia annua extract (AAE) on high-fat diet (HFD)-induced hepatic lipid accumulation, and elucidate the molecular mechanisms behind its effects in vivo and in vitro. We found that HFD-fed mice with AAE administration (50 mg/kg/day) for 8 weeks dramatically reduced hepatic lipid accumulation compared to the control mice taken with HFD alone. The body and liver weights of AAE group were significantly lower than those of HFD group, and oral administration of AAE remarkably suppressed the serum levels of triglyceride (TG), total cholesterol (TC), fasting glucose, alanine transaminase (ALT) and aspartate transaminase (AST) in HFD-fed mice. AAE significantly increased the phosphorylation of AMP-activated protein kinase (AMPK) and acetyl-CoA carboxylase (ACC) in the liver of HFD-fed mice and HepG2 hepatocytes. Moreover, AAE downregulated the hepatic expression of sterol regulatory element-binding protein-1c (SREBP-1c) and fatty acid synthase (FAS) in HFD-fed mice and high glucose-treated HepG2 cells. In addition, the inhibitory effects of AAE on the overexpression of SREBP-1c and FAS were attenuated by compound C, which is the specific AMPK inhibitor, in high glucose-treated HepG2 cells. These results indicated that AAE may represent a promising approach for the prevention and treatment of obesity-related NAFLD via the activation of AMPK and the regulation of AMPK-dependent lipogenic genes.
Carcass grade primarily depends on marbling of intramuscular fat, which is associated with the texture and tenderness of beef. Accordingly, various economical molecular tests for high intramuscular fat in beef have been attempted. Especially, Hanwoo (Korean Cattle) intramuscular fat has higher levels of monounsaturated fatty acids than that in the beef of other cattle. Intramuscular fats are associated with levels of lipid metabolic genes in the liver transcriptome. Therefore, hepatic triglyceride synthesis can considerably increase intramuscular fat. To investigate the relationship between hepatic lipogenesis and carcass grade, we analyzed 52 Hanwoo liver samples from domestic farms, and evaluated lipid levels and transcript levels of glucose and lipid metabolism-related genes according to carcass grade. Oil-Red-O staining revealed fatty livers in high carcass grades. Moreover, we found significantly higher levels of mRNA for lipogenesis, glycolysis, and triglyceride synthesis genes in high carcass grade livers. Importantly, progesterone receptor membrane component 1 (Pgrmc1) levels were significantly lower in high carcass grade livers. As Pgrmc1 suppression is correlated with induction of de novo lipogenesis (DNL) and glycolysis genes, it has a diagnostic impact for high carcass grades. These results could be used for genetic improvements in carcass grades of cattle. More importantly, as Pgrmc1 can be detected in blood peripheral nucleated cells, it also has value for rapid blood diagnosis.
Radioisotope ADME (RI-ADME) studies are enabling visualization of the biodistribution in molecular imaging. We applied RI-ADME to investigate the tumor targeting capacity and biodistribution of trastuzumab-monomethyl auristatin F (LCB14-0110) in JIMT-1 xenograft mice and healthy marmoset. The LCB14-0110 was labelled with 125I. 125I-LCB14-0110 was intravenously administered to the animals. The gamma-count and single-photon emission computed tomography/computed tomography (SPECT/CT) was conducted for biodistributioon and bioimaging of the biopharmaceutics. Tumor uptake in xenograft mice was highest at three-day after 125I-LCB14-0110 administration in both the biodistribution and SPECT/CT bioimaging. Alternatively, blood and organ tissues showed gradual decrease in radioactivity over time. In marmosets, radioactivity in all organ tissues rapidly reduced and no specific targeting of organs was observed in the biodistribution study and SPECT/CT imaging. Hence, 125ILCB14- 0110 demonstrated effective tumor targeting capacity and accumulated in JIMT-1 cell-bearing mice. However, accumulation did not occur in the organs of xenograft mice. Additionally, marmosets showed rapidly decrease in radioactivity throughout the entire body without accumulation in the normal organs. We also confirmed that the drug distribution was similar in normal organs between the two experimental animal species except spleen. Therefore, 125I is expected to be a useful tool in the study of RI-ADME in biopharmaceuticals through minimal antibody modification.
Limb amputation is a salvage surgical procedure relatively common in small animals and other species. Wild animals after forelimb amputation have many difficulties in returning to normal life because forelimbs of arboreal quadrupeds are used to carry most of their weight and hold feed. This study investigated forelimb amputation and its outcomes in two raccoon dogs. Two male raccoon dogs presented for radio-ulnar fractures. Shoulder disarticulation amputation was applied to protect the thoracic cavity and reduce surgical time. After the operation, they could run comparatively faster with three legs. As they had good body condition and regular appetite during the hospitalization period, they were released to the area from which they were captured. Six months after the release, one of the raccoon dogs represented for hair loss by mites. It showed satisfactory function of the existing three limbs. Thus, amputation of forelimb could be considered as a treatment in raccoon dogs with severe limb status.
Canine inflammatory mammary carcinoma (CIMC) similar to human inflammatory breast cancer is a very aggressive, metastatic type of cancer. Previous studies have introduced a new type of tumor angiogenesis called vasculogenic mimicry that may play an important role in the progression of inflammatory mammary cancer. The purpose of this study is to investigate the development process of vessels by neoplastic cells in CIMC. Patient dog, 14-year old Shit-Tzu female, had a hard and somewhat movable dark-reddish mammary tumor, sized 6.2 cm in diameter. Bloody dark turbid exudate was released from the tumor. In addition to histological examination, immunohistochemistry for pancytokeratin, VCAM-1, MECA- 32, TWIST-1, and Ki-67 was respectively performed using the ABC method. Histologically, the inflammatory mammary carcinoma was characterized by tubular solid tumor emboli within the lymphatic vessels surrounded by desmoplastic fibrous connective tissue. Some of the neoplastic cells were transforming into elongate or spindle shapes and forming small vessel-like structures in the solid tumor mass. The neoplastic cells were immunoreactive for VCAM-1 and MECA-32, but showed low immunoreactivity for Ki-67. Immunoreactive neoplastic cells for VCAM-1 and MECA-32 suggested the possibility that the neoplastic cells transform into endothelial cells of vessels by epithelial-mesenchymal transition, further supported by serial morphological changes identified by histological investigation and immunohistochemistry for TWIST-1. The high capacity of the neoplastic cells forming the vasculatures in CIMC explains the high ratio of metastasis to other regions, even though Ki-67 index was not so high.