Journal of Food and Drug Analysis最新文献

Diabetes is associated with an increased risk of muscle wasting/atrophy, which adversely affects quality of life. We hypothesized that long term supplementation of fish oil may have protective effects against sarcopenia or muscle atrophy in streptozotocin (STZ) and high-fat (HF) diet-induced diabetic rat model. Wistar rats at age of 7 weeks were injected with saline or STZ to induce hyperglycemia. After one week, they were fed on a normal control diet or HF diet with/without supplementation of fish oil for 18 weeks. Feeding diabetic rats with a fish oil-enriched diet alleviated body weight loss and the impaired glucose tolerance using OGTT test. Although fish oil did not improve the decreased muscle mass, the muscle atrophy induced by diabetes was attenuated by fish oil in gastrocnemius, soleus, tibialis anterior, and extensor digitorum longus muscles. Fish oil supplementation reversed the decreased expression of phospho (p)-AKT, pmTOR, and p-p70s6k, which are molecules related to protein synthesis. Besides, protein degradation-related signaling pathways were inhibited by fish oil, such as increasing p-FoxO1 and decreasing Atrogin-1 and MURF1 protein expression. Fish oil down-regulated the expression of autophagy-related molecules including ATG5, p62, and LC3B II/I ratio, which may result in less muscle atrophy. Inflammation-related signaling regulators including TNF-α, NF-κB, AGEs, and RAGE were suppressed by fish oil supplementation as well. Moreover, the down-regulated p-AMPKα, SIRT1, and PGC-1 in diabetic rats were counteracted by fish oil, which may improve mitochondrial function and further block FoxO action. These data suggest that long-term fish oil supplementation exerts protective effects against diabetes-induced muscle atrophy, which may in turn ameliorate insulin resistance and impaired glucose tolerance.

Ji-Ming-Shan (JMS) is a traditional prescription use for patients with rheumatism, tendons swelling, athlete's foot, diuresis and even gout. This study developed a rapid and sensitive method for the analysis of JMS chemical components in the Traditional Chinese medicine (TCM) prescription and in the serum samples of rats which were administered with the herbal extract. Two mass spectrometric approaches were used namely Ultra-performance liquid chromatography-quadrupole time-of-flight-mass spectrometry (UPLC-Q-TOF-MS) method for the major metabolites of the JMS extract while Ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) was employed for the detection of the JMS metabolites in the sera of rats. It was revealed that the major components in the JMS extract were identified to be narirutin and hesperidin. It was confirmed that 17 compounds were determined in JMS prescription extract and 16 metabolites resulting from the biotransformation of narirutin and hesperidin were identified in the serum samples. In silico analyses also revealed that the metabolite hersperidin-7-glucoside exhibited the best binding ability with respect to the Cyclooxygenase-2 (COX-2) enzyme target. This study showcased the possible biochemical mechanism involved in the therapeutic efficiency of JMS components and their biotransformation products.

Statins induce nitric oxide (NO) bioavailability by activating endothelial nitric oxide synthase via kinase- and calcium-dependent pathways in endothelial cells (ECs). However, their effect on the metabolism of L-arginine, the precursor for NO biosynthesis, and regulatory mechanism have not yet been investigated. In this study, we investigated the role of the autophagy-urea cycle-L-arginine pathway in simvastatin-mediated NO bioavailability in ECs. Griess's assay was used to determine the NO bioavailability. Protein expression was assessed using Western blot analysis. Further, immunocytochemistry was performed to observe autophagosome formation, while conventional assay kits were used to quantify the levels of different intermediate substrates of the urea cycle. In ECs, treatment with simvastatin induced the activation of autophagy flux, as evidenced by the increased levels of microtubule-associated protein 1A/1B-light chain 3 II and autophagolysosome formation and decreased levels of p62. Inhibition of autophagy by ATG7 small interfering RNA (siRNA), chloroquine and bafilomycin A1 abolished simvastatin-induced NO bioavailability, EC proliferation, migration, and tube formation. Additionally, simvastatin increased the intermediate substrates levels of the urea cycle, including glutamate, acetyl-CoA, urea, and L-arginine, all of which were abrogated by chloroquine or bafilomycin A1. Genetic knockdown of argininosuccinate lyase using siRNA abrogated simvastatin-induced increase in NO bioavailability and EC-related functions. Moreover, inhibition of AMP-activated protein kinase (AMPK) and transient receptor potential vanilloid 1 (TRPV1) prevented simvastatin-induced activation of the autophagy-urea cycle pathway and NO production. Our findings suggest that simvastatin activates the autophagy-urea cycle pathway via TRPV1-AMPK signaling, which increases L-arginine bioavailability and ultimately promotes NO production in ECs.

Fibroblast growth factor 9 (FGF9) is a member of FGF family, and abnormal expression of FGF9 can promote tumorigenesis. Cordycepin, a major bioactive component in fungus Cordyceps sinensis, could suppress various tumors. We have shown that cordycepin could inhibit FGF9-induced testicular tumor growth in vitro and in vivo with MA-10 mouse Leydig tumor cells. In the present study, the mechanisms related to apoptosis and autophagy were determined. Results show that cordycepin significantly suppressed cell viability and colony formation with correlatedly morphological change related to cell death in FGF9-treated MA-10 cells. Flow cytometry and western blotting results further demonstrate that cordycepin induced apoptosis through the cleavage of caspase-8, -9, -3 and PARP in FGF9-treated MA-10 cells. However, the expressions of LC3-II, beclin-1 and p62 were not stimulated by cordycepin with the presence of FGF9, suggesting cordycepin would activate apoptosis, but not autophagy, in FGF9-treated MA-10 cells. Moreover, inhibition of ERK signal pathway and autophagy would enhance cordycepin-induced cell death effects in FGF9-treated MA-10 cells, referring that ERK signaling was regulated under cordycepin and FGF9 treatments. In NOD-SCID mouse allograft model inoculated with MA-10 cells, cordycepin significantly suppressed tumor growth with the presence of FGF9, and the cleavage of caspase-3 could be observed in tumor tissue, implying cordycepin induced caspase cascade to suppress tumor growth. Moreover, cordycepin plus U0126, ERK inhibitor, further significantly suppressed tumor growth with the presence of FGF9 as compared to the FGF9 only group, confirming the involvement of ERK signaling in this event. In conclusion, cordycepin induced caspase and ERK pathways to promote MA-10 cell apoptosis, but not autophagy, with the presence of FGF9.

Induction of antioxidant proteins and phase 2 detoxifying enzymes that neutralize reactive electrophiles are important mechanisms for protection against carcinogenesis. Normal cells provide multifaceted pathways to tightly control NF-E2-related factor 2 (NRF2)-mediated gene expression in response to an assault by a range of endogenous and exogenous oncogenic molecules. Transient activation of NRF2 by its activators is able to induce ARE-mediated cytoprotective proteins which are essential for protection against various toxic and oxidative damages, and NRF2 activators thereby have efficacy in cancer chemoprevention. Because NRF2 has a cytoprotective function, it can protect normal cells from carcinogens like an angel, but when the protective effect acts on cancer cells, it will give rise to invincible cancer cells and play a devilish role in tumor progression. Indeed, aberrant activation of NRF2 has been found in a variety of cancers that create a favorable environment for the proliferation and survival of cancer cells and leads to drug resistance, ultimately leading to the poor clinical prognosis of patients. Therefore, pharmacological inhibition of NRF2 signaling has emerged as a promising approach for cancer therapy. This review aims to compile the regulatory mechanisms of NRF2 and its double-edged role in cancer. In addition, we also summarize the research progress of NRF2 modulators, especially phytochemicals, in chemoprevention and cancer therapy.