Curcumin inhibits the formation of atherosclerosis in ApoE-/- mice by suppressing cytomegalovirus activity in endothelial cells.

BACKGROUND: Curcumin (Cur) is a hydrophobic polyphenol compound derived from the rhizome of the herb Curcuma longa. Cur has a wide spectrum of biological and pharmacological activities. It has been shown that human cytomegalovirus (HCMV) infection was an important risk factor for atherosclerosis (AS) and Cur exhibited an outstanding anti-HCMV effect. However, anti-AS effects of Cur remain unclear when HCMV infected endothelial cells. AIMS: This study will investigate the anti-AS activities and mechanism of Cur,when HCMV infected in vivo and in vitro. MATERIALS AND METHODS: Cur (0.5, 1, and 2 µM) was used to explore the anti-AS activities and mechanism after HCMV infected endothelial cells in vitro. ApoE-/- mice were fed a high fat and cholesterol diet (HD) and given 4000,000 copies/mouse MCMV infection by intraperitoneal and treated with ganciclovir (5 mg/kg/d), Cur (25, 15 mg/kg/d) for 10 weeks in vivo. KEY FINDINGS: As our results showed that Cur inhibited CMV replication and proliferation, reduced the intracellular ROS overproduction, decreased the release of inflammatory cytokines, down-regulated the level of HMGB1-TLRS-NF-κB signaling pathway-related proteins in vitro experiments. Cur reduced the serum levels of LDL-C, TC and TG, significantly decreased the formation of atherosclerotic plaque in the aorta, reduced the lipid deposition in liver and inflammatory damage in heart, lung and kidney in vivo experiments. SIGNIFICANCE: This study showed that Cur prevent AS progression by inhibiting CMV activity and CMV-induced HMGB1-TLRS-NF-κB signaling pathway.

Vitamin D supplementation rescues simvastatin induced myopathy in mice via improving mitochondrial cristae shape.

Statin induced myopathy (SIM) is a main deleterious effect leading to the poor treatment compliance, while the preventive or therapeutic treatments are absent. Mounting evidences demonstrated that vitamin D plays a vital role in muscle as a direct modulator. The deficiency of vitamin D was considered as a cause of muscle dysfunction, whereas the supplementation resulted in a remission. However, there is no causal proof that vitamin D supplementation rescues SIM. Here, using the mice model of simvastatin-induced myopathy, we investigated the role of vitamin D supplementation and the mechanisms associated with mitochondria. Results indicated that simvastatin administration (80 mg/kg) impaired skeletal muscle with the increased serum creatine kinase (CK) level and the declined grip strength, which were alleviated by vitamin D supplementation. Moreover, vitamin D supplementation rescued the energy metabolism dysfunction in simvastatin-treated mice gastrocnemius by reducing the abnormal aggregation of muscular glycogen and lactic acid. Mitochondrial homeostasis plays a key role in the process of energy metabolism. Thus, the mitochondrial dysfunction is a mortal damage for the highly energy-requiring tissue. In our study, the mitochondrial cristae observed under transmission electron microscope (TEM) were lytic in simvastatin-treated gastrocnemius. Interestingly, vitamin D supplementation improved the mitochondrial cristae shape by regulating the expression of mitofusin-1/2 (MFN1/2), optic atrophy 1 (OPA1) and dynamin-related protein 1 (Drp1). As expected, the mitochondrial dysfunction and oxidative stress was mitigated by vitamin D supplementation. In conclusion, these findings suggested that moderate vitamin D supplementation rescued simvastatin induced myopathy via improving the mitochondrial cristae shape and function.

Anti-nociceptive and anti-inflammatory potentials of Akebia saponin D.

Akebia saponin D, which is originates from Dipsacus asper Wall, has been used as a tonic, an analgesic and anti-inflammatory agent for the therapy of low back pain, rheumatic arthritis, traumatic hematoma, habitual abortion and bone fractures in traditional Chinese medicine. However, the anti-nociceptive and anti-inflammatory activity and mechanism of Akebia saponin D has been rarely reported. The aim of this study was to investigate the anti-nociceptive and anti-inflammatory activity of Akebia saponin D and to assess its possible mechanism. The anti-nociceptive effect was measured by formalin test, hot plate, and acetic acid-induced writhing in mice while the anti-inflammatory effect was measured by carrageenan induced paw edema test, xylene-induced ear swelling and acetic acid-induced vascular permeability in mice and rats. Furthermore, anti-inflammatory effect was also measured in vitro using LPS-induced RAW 264.7 cells. Our results demonstrated that Akebia saponin D dose-dependently decreased the licking time in the formalin test, delayed the reaction time of mice to the hot plate, and inhibited acetic acid-induced writhing. Treatment of Akebia saponin D attenuated the carrageenan induced paw edema in rats, inhibited the mouse ear swelling, and decreased Evans blue concentration in acetic acid induced vascular permeability test, revealing its strong anti-inflammatory effect. Akebia saponin D significantly decreased NO production and iNOS expression. Our results indicate that Akebia saponin D has anti-nociceptive and anti-inflammatory effects. It will provide experimental evidences for the use of Akebia saponin D and can be used to develop a therapeutic drug against pain and inflammation related diseases.

Akebia saponin D alleviates hepatic steatosis through BNip3 induced mitophagy.

Akebia Saponin D (ASD) is the most abundant constituent of the rhizome of Dipsacus asper Wall. The prior studies have shown that ASD alleviates hepatic steatosis targeted at the modulation of autophagy and exerts hepatoprotective effects through mitochondria. However, it is still unclear which signal transduction pathway that ASD increase autophagy and protect the mitochondria. The purpose of this paper was to explore the mechanisms through which ASD alleviates hepatic steatosis. ASD significantly reduced lipid accumulation in BRL cells. Furthermore, ASD significantly increased the mitophagy acting as increase the colocalization between mitochondria and punctate EGFP-LC3. ASD treatment increased the expression of BNip3, phospho-AMPK, prevented oleic acid (OA) induced LC3-II and phospho-mTOR expression. These effects were similar to the effects cotreatment with rapamycin. ASD treatment could not attenuate the expression of BNip3 blocked by chloroquine (CQ) or siRNA-mediated knockdown of BNip3. These results suggest that Akebia saponin D alleviates hepatic steatosis targeted at BNip3 mediated mitophagy. Activation of BNip3 via ASD may offer a new strategy for treating NAFLD.