A reanalysis and integration of transcriptomics and proteomics datasets unveil novel drug targets for Mekong schistosomiasis.

Schistosomiasis, caused by Schistosoma trematodes, is a significant global health concern, particularly affecting millions in Africa and Southeast Asia. Despite efforts to combat it, the rise of praziquantel (PZQ) resistance underscores the need for new treatment options. Protein kinases (PKs) are vital in cellular signaling and offer potential as drug targets. This study focused on focal adhesion kinase (FAK) as a candidate for anti-schistosomal therapy. Transcriptomic and proteomic analyses of adult S. mekongi worms identified FAK as a promising target due to its upregulation and essential role in cellular processes. Molecular docking simulations assessed the binding energy of FAK inhibitors to Schistosoma FAK versus human FAK. FAK inhibitor 14 and PF-03814735 exhibited strong binding to Schistosoma FAK with minimal binding for human FAK. In vitro assays confirmed significant anti-parasitic activity against S. mekongi, S. mansoni, and S. japonicum, comparable to PZQ, with low toxicity in human cells, indicating potential safety. These findings highlight FAK as a promising target for novel anti-schistosomal therapies. However, further research, including in vivo studies, is necessary to validate efficacy and safety before clinical use. This study offers a hopeful strategy to combat schistosomiasis and reduce its global impact.

Physicochemical properties and fatty acid profile of oil extracted from black soldier fly larvae (Hermetia illucens).

Background and Aim: Hermetia illucens, a black soldier fly, is widely recognized for sustainable recycling of organic waste. Black soldier fly larvae (BSFLs) can consume various types of biowastes and convert them into nutrient-rich biomass, including proteins, lipids, chitin, and minerals. This study investigated the best extraction method by comparing the fatty acid profiles, percentage yield, and antioxidant properties of BSFL oil extracted using different extraction methods. Materials and Methods: The physicochemical properties, fatty acid profile, and free radical scavenging ability of BSFL oil were analyzed using six extraction methods. Results: Ultrasonic extraction with hexane resulted in the highest yields compared with different extraction methods. Lauric acid (28%-37%) was the most abundant fatty acid in all extracts, followed by palmitic acid, myristic acid, oleic acid, and linoleic acid. Compared with other methods, aqueous extraction showed the highest lauric acid composition and free radical scavenging activities. In addition, high-temperature aqueous extraction resulted in higher oil yield and free radical scavenging activities than low-temperature extraction. Conclusion: High-temperature aqueous extraction is the best extraction method because it is rich in lauric acid, has antioxidant ability, and can be further developed to produce novel sustainable biomaterials for humans and animals.

Effect of the oil from the fatty tissues of Crocodylus siamensis on gut microbiome diversity and metabolism in mice.

Dietary fat can alter host metabolism and gut microbial composition. Crocodile oil (CO) was extracted from the fatty tissues of Crocodylus siamensis. CO, rich in monounsaturated- and polyunsaturated fatty acids, has been reported to reduce inflammation, counter toxification, and improve energy metabolism. The aim of this study was to investigate the effect of CO on gut microbiota (GM) in laboratory mice as well as the accompanying metabolic changes in the animals. Forty-five C57BL/6 male mice were randomly divided into five groups and orally administrated either sterile water (control [C]); 1 or 3% (v/w) CO (CO-low [CO-L] and CO-high [CO-H], respectively); or 1 or 3% (v/w) palm oil (PO-low and PO-high, respectively) for 11 weeks. Body weight gain, food intake, energy intake, blood glucose levels, and blood lipid profiles were determined. Samples from colon tissue were collected and the 16S rRNA genes were pyrosequenced to clarify GM analyses. The results showed that there were no differences in body weight and blood glucose levels. Food intake by the mice in the CO-L and CO-H groups was statistically significantly less when compared to that by the animals in the C group. However, neither CO treatment had a statistically significant effect on calorie intake when compared to the controls. The CO-H exhibited a significant increase in serum total cholesterol and low-density lipoprotein but showed a downward trend in triglyceride levels compared to the control. The GM analyses revealed that both CO treatments have no significant influence on bacterial diversity and relative abundance at the phylum level, whereas increases of Choa1 and abundance-based coverage estimator indexes, distinct ß-diversity, and Proteobacteria abundance were observed in the PO-high group compared with the C group. Furthermore, the abundance of Azospirillum thiophilum and Romboutsia ilealis was significantly higher in the CO-L and CO-H groups which could be associated with energy metabolic activity. Thus, CO may be an alternative fat source for preserving host metabolism and gut flora.

Targeted proteomic analysis reveals that crocodile oil from Crocodylus siamensis may enhance hepatic energy metabolism in rats.

The liver is a key organ governing body energy metabolism. Dietary fats influence energy metabolism and mitochondrial functioning. Crocodile oil (CO) is rich in mono- and polyunsaturated fatty acids that contain natural anti-inflammatory and healing properties. Our study examined how CO affects the expressions of liver proteins involved in energy metabolism in rats. Twenty-one male Sprague Dawley rats were divided into three groups and underwent oral gavage with 3 ml/kg of sterile water (N group), CO (CO group), or palm oil (PO group) for 7 weeks. Body weight, energy intake, liver weight, liver indexes, blood lipid profiles, and liver-energy intermediates were measured. The liver proteome was analyzed using shotgun proteomics, and the functions and network interactions of several candidate proteins were predicted using the STITCH v.5.0 software. Body weights, energy intake, liver contents, and lipid profiles did not differ between the groups. However, hepatic oxaloacetate and malate levels were significantly higher in the CO group than in the PO group. Targeted proteomics reveals that 22 out of 1,790 unique proteins in the CO group were involved in energy-generating pathways, including the tricarboxylic acid cycle and oxidative phosphorylation (OXPHOS), and were correlated with the AMP-activated protein kinase signaling pathway. Cluster analysis of 59 differentially expressed proteins showed that OXPHOS-associated proteins were upregulated in the CO group and that three glycolytic metabolism-related proteins were downregulated in the CO group. CO may enhance hepatic energy metabolism by regulating the expressions of energy expenditure-related proteins.

Antioxidant Activity of Crocodile Oil (Crocodylus siamensis) on Cognitive Function in Rats.

Crocodile oil (CO) is rich in monounsaturated fatty acids and polyunsaturated fatty acids. The antioxidant activity and cognitive effect of monounsaturated fatty acids and polyunsaturated fatty acids have been largely reported. This work aimed to investigate the effect of CO on antioxidant activity and cognitive function in rats. Twenty-one rats were divided into three treatment groups: (1) sterile water (NS), (2) 1 mL/kg of CO (NC1), and (3) 3 mL/kg of CO (NC3). Rats underwent oral gavage once daily for 8 weeks. CO treatment decreased the triglycerides level significantly compared with that in the NS group. CO had a free radical scavenging ability greater than that of olive oil but had no effect on levels of antioxidant markers in the brain. Expression of unique proteins in the CO-treatment group were correlated with the detoxification of hydrogen peroxide. Rats in the NC1 group had better memory function than rats in the NC3 group. Expression of unique proteins in the NC1 group was correlated with memory function. However, CO did not cause a decline in cognitive function in rats. CO can be an alternative dietary oil because it has a hypolipidemia effect and antioxidant activity. In addition, CO did not cause a negative effect on cognitive function.

Effects of Crocodile Oil (Crocodylus siamensis) on Liver Enzymes: Cytochrome P450 and Glutathione S-Transferase Activities in High-fat DietFed Rats.

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.

The first study on the effect of crocodile oil from Crocodylus siamensis on hepatic mitochondrial function for energy homeostasis in rats.

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.

Serum proteomic analysis reveals the differential dose effects of crocodile oil from Crocodylus siamensis on energy metabolism in rats.

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.

Metabolic impacts of cordycepin on hepatic proteomic expression in streptozotocin-induced type 1 diabetic mice.

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.

The effect of cordycepin on brain oxidative stress and protein expression in streptozotocin-induced diabetic mice.

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.

A study of the aphrodisiac properties of Cordyceps militaris in streptozotocin-induced diabetic male rats.

BACKGROUND AND AIM: Cordyceps militaris (CM) is a fungus that has been used to enhance aphrodisiac activity in men, but to date, no studies have focused on its antidiabetic properties. This study aimed to investigate the effects of CM on reproductive performance of streptozotocin (STZ)-induced diabetic male rats. MATERIALS AND METHODS: Six-week-old Wistar rats were randomly divided into four groups: control Group 1 consisting of healthy rats; Group 2, healthy rats treated with CM (100 mg/kg); Group 3, diabetic untreated rats; and Group 4, diabetic rats treated with CM (100 mg/kg). Rats were orally administered with vehicle or CM for 21 days. The body weight, blood glucose level, food intake, epididymal sperm parameter, sexual behavior, serum testosterone level, and antioxidant parameters were determined. RESULTS: The results indicated that CM treatment in STZ-induced diabetic rats significantly improved the epididymal sperm parameter and serum testosterone level and, in turn, their copulatory behavior. CM treatment in diabetic rats significantly ameliorated malondialdehyde level and significantly improved the glutathione and catalase levels. CONCLUSION: These results provide new information on the pharmacological properties of CM in ameliorating testicular damage due to oxidative stress and improving sexual performance in diabetic male rats.