ABSTRACT
CY-1-4 is a tryptanthrin derivative exhibiting antitumor activity. The solubility of CY-1-4 was poor and the corresponding mechanism needs further study. To solve this problem, we prepared nanoparticles encapsulated with CY-1-4 (CY-1-4 NPs) by nanoprecipitation method using poly(caprolactone) (PCL) and poly(ethylene glycol)-co-poly(ε-caprolactone) (PEG-PCL) as carriers to improve solubility. We then explored whether CY-1-4 NPs induced B16-F10 cytotoxicity via ferroptosis by determining the effect of CY-1-4 NPs on reactive oxygen (ROS) levels, repairing efficacy of lipid reactive oxygen inhibitor ferrostatin-1 and iron chelator deferoxamine (DFO), and potentiation of protoporphyrin (PPIX) induced B16-F10 cell death. The results showed that nanoparticlated strategy significantly improved solubility of CY-1-4. With the particle size about 116 nm, encapsulating efficacy was about 83% and the drug loading capacity was about 4.80%. Ferroptosis mechanistic studies indicated that CY-1-4 NPs could improve the ROS level in B16-F10 cells, whereas ferrostatin-1 and DFO could partly inhibited the cytotoxicity and PPIX could potentiated the cytotoxicity of CY-1-4 NPs in B16-F10 cells. These results showed that ferroptosis was one of the cell death mechanisms induced by tryptanthrin derivative CY-1-4 nanoparticle.
ABSTRACT
Diabetic cognitive dysfunction (DCD) is a common chronic complication of diabetes mellitus with sophisticated path-ogenesis which has not yet been fully elucidated. In this review paper, the mechanisms of metabolic abnormalities, insulin re-sistance,endoplasmic reticulum stress,neuronal calcium dysho-meostasis, in ammation, blood brain barrier impairment, and mitochondrial injury associated with DCD are reviewed. In addi-tion,the prevention and treatment of DCD by traditional Chinese medicines (TCMs) and the effective compounds are comprehen-sively summarized, in order to provide an updated overview on the DCD pathogenesis,as well as the scientific evidence under-pinning the use of TCM interventions for the treatment and pre-vention of DCD.
ABSTRACT
The aim of this study is to investigate the protective effects of Panax notoginseng saponins (PNS) against 6-hydroxydopamine (6-OHDA)-induced apoptosis in SH-SY5Y cells and the possible underlying mechanisms. Cell viability was examined by MTT assay. The levels of lactate dehydrogenase (LDH), reactive oxygen species (ROS), malondialdehyde (MDA) and the activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px) were measured using the respective assay kits. Apoptosis was measured by TUNEL kit, JC-1 and ROS was measured by staining with fluorescent dyes. The activation of caspase-3 was measured with the caspase-3 assay kit. The expression of nuclear protein Nrf2 and HO-1 were determined by Western blot. PNS had significant protective effects against 6-OHDA-induced apoptosis in SH-SY5Y cells in a time- and dose-dependent manner. PNS could attenuate 6-OHDA-induced suppression of SOD, GAT, GSH-Px (PPP<0.01). Moreover, PNS pretreatment increased the expression of the nuclear Nrf2 and up-regulate HO-1. The protective effects of PNS could be inhibited by HO-1 inhibitor SnPP. In conclusion, PNS has significant protective effects against 6-OHDAinduced apoptosis in SH-SY5Y cells. The possible mechanisms of PNS are due to PNS-mediated activation of Nrf2, up-regulation of HO-1 and inhibition of oxidative stress.
ABSTRACT
The effect of Qizhi Jiangtang vapsule (QJC) on degree of dermal ulcer cicatrization in 2 type diabetic rats was studied. Except the rats for blank group, other male Wistar rats were used to establish type 2 diabetic model by feeding with high sugar and high fat diet for four weeks and intraperitonally injecting with 30 mg•kg⁻¹ streptozotocin (STZ). After that, the rats were divided into balanced groups according to blood sugar, and received corresponding drugs for treatment for 8 weeks. At the end of week 8, 2 cm diameter circular incision was done on the back of rats. After that, the rats were administered continuously for10 days. Area of ulcer surface was detected every two days. After the last administration, wound granulation tissues were cut down to conduct pathological examination and detect the expression of VEGF, PI3K, p-ERK protein in wound tissues. The results showed that compared with the model group, after application of Qizhi Jiangtang capsule (2.24 g•kg⁻¹), the wound was significantly reduced on day 6 and day 10 of wound formation; inflammation reaction on ulcer surface was significantly reduce; Qizhi Jiangtang capsule can increase VEGF expression in the wound tissues of diabetic rats, and inhibit ERK phosphorylation. It can be concluded that Qizhi Jiangtang capsule can promote skin ulcer healing for diabetes rats, and its mechanism may be related to regulating the expression of VEGA and p-ERK proteins.
ABSTRACT
To observe the hypoglycemic effect of Qizhi Jiangtang capsule in rats with type 2 diabetes, and investigate the preliminary mechanism of its hypoglycemic effect, type 2 diabetes rat models were established by high glucose and high fat combined with small dose of streptozotocin (STZ). After continuous administration for 6 weeks, blood glucose, and glycosylated serum protein (GSP) levels were detected in all of the animals; immunohistochemistry assay was used to detect the number of islet β cells; Western blot assay was used to detect the protein expression levels of insulin receptor (InsR), phosphoinositide-3 kinases (PI3K), glucose transporter-2 (GLUT2) and phosphorylated Jun N-terminal kinases (p-JNK)in hepatic tissues. The results showed that Qizhi Jiangtang capsule could reduce the blood sugar and GSP levels in serum in animals with type 2 diabetes mellitus, increase the level of insulin in serum and number of islet β cells, increase the protein expression levels of InsR, PI3K and GLUT2, and reduce the level of p-JNK protein expression. In conclusion, Qizhi Jiangtang capsule has relatively stable hypoglycemic effect, and the mechanism may be associated with increasing the number of islet β cells and level of insulin in serum, up-regulating the protein expression levels of InsR, PI3K and GLUT2, down-regulating the level of p-JNK protein expression in hepatic tissues, and reducing the level of insulin in hepatic tissues.
ABSTRACT
This study is to report the study of protective effects of myricitrin against oxidative stress-induced apoptosis of vascular endothelial cells and the investigation of the possible mechanisms of action of myricitrin. The model of H2O2-induced apoptosis of vascular endothelial cells was used to determine the protective effects of myricitrin. The levels of LDH, MDA and the activities of SOD, NO were measured using the respective kits. The H2O2-induced apoptosis of vascular endothelial cells was detected using MTT reduction, TUNEL assay, JC-1 and ROS staining. The activation of Caspase-3 was also measured by fluorometry. The expression of apoptosis-related proteins was determined with Western blotting assay. Myricitrin had significant protective effects against H2O2-induced apoptosis of vascular endothelial cells in a time- and dose-dependent manner. The results show that myricitrin could attenuate H2O2-induced decrease in the activities of SOD (P < 0.01). Myricitrin could decrease the levels of LDH, MDA and increase cell viability and the mitochondrial membrane potential (P < 0.01). Myricitrin had protective effects in a dose-dependent manner between 32 micromol x L(-1) to 64 micromol x L(-1). Myricitrin pretreatment could attenuate H2O2-induced increase of p-ERK. Moreover, myricitrin pretreatment could up-regulate the expression of the anti-apoptotic protein Bcl-2, down-regulate the expression of the pro-apoptotic protein Bax, and decrease the expression of Caspase-3, 9. In conclusion, myricitrin had significant protective effects against H2O2-induced apoptosis of vascular endothelial cells. Myricitrin can enhance the activities of anti-oxidative enzymes and decrease the production of free radicals. The possible mechanisms of action of myricitrin are due to myricitrin-mediated inhibition of phosphorylation of the apoptosis signaling pathways-related kinase ERK, up-regulation of the expression of the anti-apoptotic protein, and down-regulation of the expression of the pro-apoptotic protein.