Background and Aim: Consumption of fatty acids (FA) can alter hepatic energy metabolism and mitochondrial function in the liver. Crocodile oil (CO) is rich in mono-and polyunsaturated FAs, which have natural anti-inflammatory and healing properties. In rat livers, we investigated the effect of CO on mitochondrial function for energy homeostasis. Materials and Methods: Twenty-one male Sprague-Dawley rats were divided into three groups at random. Group 1 rats were given sterile water (RO), Group 2 rats were given CO (3% v/w), and Group 3 rats were given palm oil (PO) (3% v/w). For 7 weeks, rats were given sterile water, CO, and PO orally. The researchers looked at body weight, food intake, liver weight, energy intake, blood lipid profiles, and mitochondria-targeted metabolites in the liver. The liver's histopathology, mitochondrial architecture, and hydrolase domain containing 3 (HDHD3) protein expression in liver mitochondria were studied. Results: Body weight, liver weight, liver index, dietary energy intake, and serum lipid profiles were all unaffected by CO treatment. The CO group consumed significantly less food than the RO group. The CO group also had significantly higher levels of oxaloacetate and malate than the PO group. CO treatment significantly ameliorated hepatic steatosis, as evidenced by a greater decrease in the total surface area of lipid particles than PO treatment. CO administration preserved mitochondrial morphology in the liver by upregulating the energetic maintenance protein HDHD3. Furthermore, chemical-protein interactions revealed that HDHD3 was linked to the energy homeostatic pathway. Conclusion: CO may benefit liver function by preserving hepatic mitochondrial architecture and increasing energy metabolic activity.

Type 1 Diabetes mellitus (T1DM) is associated with abnormal liver function, but the exact mechanism is unclear. Cordycepin improves hepatic metabolic pathways leading to recovery from liver damage. We investigated the effects of cordycepin in streptozotocin-induced T1DM mice via the expression of liver proteins. Twenty-four mice were divided into four equal groups: normal (N), normal mice treated with cordycepin (N+COR), diabetic mice (DM), and diabetic mice treated with cordycepin (DM+COR). Mice in each treatment group were intraperitoneally injection of cordycepin at dose 24 mg/kg for 14 consecutive days. Body weight, blood glucose, and the tricarboxylic acid cycle intermediates were measured. Liver tissue protein profiling was performed using shotgun proteomics, while protein function and protein-protein interaction were predicted using PANTHER and STITCH v.5.0 software, respectively. No significant difference was observed in fasting blood glucose levels between DM and DM+COR for all time intervals. However, a significant decrease in final body weight, food intake, and water intake in DM+COR was found. Hepatic oxaloacetate and citrate levels were significantly increased in DM+COR compared to DM. Furthermore, 11 and 36 proteins were only expressed by the N+COR and DM+COR groups, respectively. Three unique proteins in DM+COR, namely, Nfat3, Flcn, and Psma3 were correlated with the production of ATP, AMPK signaling pathway, and ubiquitin proteasome system (UPS), respectively. Interestingly, a protein detected in N+COR and DM+COR (Gli3) was linked with the insulin signaling pathway. In conclusion, cordycepin might help in preventing hepatic metabolism by regulating the expression of energy-related protein and UPS to maintain cell survival. Further work on predicting the performance of metabolic mechanisms regarding the therapeutic applications of cordycepin will be performed in future.

Background: Dietary fat composition is a potential major factor affecting energy metabolism. Crocodile oil (CO) is rich in mono- and poly-unsaturated fatty acids exhibiting anti-inflammatory and healing properties. Aim: This study investigated different levels of CO consumption on alterations and expression of proteins involved in energy metabolism in rats. Methods: Twenty-one male Sprague-Dawley rats were divided into three groups and administered sterile water (N) or different doses of CO (1% or 3% [v/w] CO) orally once daily for 8 weeks. Body weight gain, food intake, energy intake, blood lipid profiles, and serum energy-related metabolites were determined. The serum proteome was analyzed using shotgun proteomics, and the functions of several candidate proteins were classified using PANTHER software. Results: There were no significant differences in body weight or energy intake were observed between groups. However, both CO-treated groups showed significantly decreased serum triglyceride (TG) levels (p<0.05). Moreover, post-treatment serum TG levels in the 1% CO group were significantly lower than pre-treatment compared with other groups. The serum oxaloacetate level was also significantly higher in both CO groups than in the N group. The proteomic analysis classified 4,525 serum proteins and revealed more unique proteins involved in cellular metabolic activity in both CO-treated groups than in the N group. Self-organizing tree algorithm clustering of 295 shared differentially expressed proteins in both CO-treatment groups showed that upregulated hyper-expressed protein clusters in both CO groups were associated with catalytic activity and molecular activity on the same levels. Conclusion: CO simultaneously enhances energy metabolism and improves lipid profiles.

Diabetes mellitus (DM) is characterized by metabolic disorders and psychological deficits, including cognitive decline. Here, we investigated the effect of cordycepin on oxidative stress and protein expression in the brains of diabetic mice. Twenty-four mice were divided into four groups, one comprising untreated healthy mice (N); one comprising healthy mice treated with cordycepin (24 mg/kg body weight) (N+Cor); one comprising untreated DM mice; and one comprising DM mice treated with cordycepin (24 mg/kg body weight) (DM+Cor). After 14 days of treatment, cognitive behavior was assessed using the novel object recognition (NOR) test. The brain levels of oxidative stress markers (glutathione, catalase, and superoxide dismutase) were examined using the respective detection kits.Protein expression in brain tissues was assessed by liquid chromatography with tandem mass spectrometry (LC-MS/MS); the functions of the identified proteins were annotated by PANTHER, while major protein-protein interactions were assessed using STITCH. We found that cordycepin treatment significantly decreased body weight and food and water intake in the DM+Cor group compared with that in the DM group; however, no differences in blood glucose levels were found between the two groups. Cordycepin treatment significantly reversed cognitive decline in diabetic mice in the NOR test and ameliorated antioxidant defenses. Additionally, we identified ULK1 isoform 2, a protein associated with cognitive function via the activated AMPK and autophagic pathways, as being uniquely expressed in the DM+Cor group. Our findings provide novel insights into the cellular mechanisms underlying how cordycepin improves cognitive decline in diabetic mice.

Crocodile oil is a highly effective treatment for ailments ranging from skin conditions to cancer. However, the effects of the oil on liver detoxification pathways are not well studied. This study aimed to investigate the effects of crocodile oil on the detoxification enzyme activities and the mRNA expressions of cytochrome P450 1A2 (CYP1A2), cytochrome P450 2E1 (CYP2E1), and glutathione S-transferase (GST) in rats. The rats were divided into four groups (n = 7/group): rats received a standard diet (C), a high-fat diet or HFD (H), and HFD with 1 ml (HCO1) and 3 ml (HCO3) of the oil per kg body weight. Interestingly, the oil yields from this study presented alpha-linolenic acid (0.96%) at similar levels compared with fish oil. The results revealed that HFD significantly increased the activity and relative gene expression of CYP1A2 in the H group ( P < 0.05 ), whereas 3% crocodile oil normalized the enzyme activities compared to the C group. This suggested inhibiting the HFD-induced expression of CYP1A2 mediated by the omega-3 fatty acids found in the oil. Also, crocodile oil supplementation did not reduce the activities of GST. However, the relative gene expression of GSTA1 was significantly decreased ( P < 0.05 ) in the HCO1 and HCO3 groups compared to the H group, which might be attributed to the lower lipid peroxidation that occurred in the liver tissues. Therefore, it could be suggested that using crocodile oil could help in liver detoxification through the CYP1A2 even when offered with a HFD.