RESUMEN
The natural alkaloid evodiamine enhances cholesterol efflux from cultured THP-1-derived macrophages, but whether it has any impact on blood lipids in vivo remains unknown. In this study, the effect of evodiamine on hyperlipidemia induced by a high-fat diet (HFD) was investigated in mice. Intragastric administrations of evodiamine (10 and 20 mg/kg) for 8 weeks resulted in a significant improvement of metabolic lipid profiles by reducing the plasma levels of triglycerides (TG), total cholesterol (TC), and low-density lipoprotein cholesterol (LDL-C). Evodiamine also significantly decreased hepatic lipid accumulation and hepatic total bile acids (TBA). Mechanistically, evodiamine increased ATP-binding cassette transporter G1 (ABCG1) mRNA and protein expression and up-regulated peroxisome proliferator-activated receptor gamma (PPARγ) expression in the liver. Taken together, the natural product evodiamine lowers blood lipids in HFD-fed mice likely through promoting the PPARγ-ABCG1 signaling pathway.
Asunto(s)
Transportador de Casetes de Unión a ATP, Subfamilia G, Miembro 1/metabolismo , Dieta Alta en Grasa , Lípidos/sangre , PPAR gamma/metabolismo , Quinazolinas/farmacología , Animales , Ácidos y Sales Biliares/metabolismo , Peso Corporal/efectos de los fármacos , Hígado/efectos de los fármacos , Hígado/metabolismo , Ratones , Extractos Vegetales/farmacologíaRESUMEN
Widely used in three-dimensional (3D) modeling, reverse engineering and other fields, point cloud registration aims to find the translation and rotation matrix between two point clouds obtained from different perspectives, and thus correctly match the two point clouds. As the most common point cloud registration method, ICP algorithm, however, requires a good initial value, not too large transformation between the two point clouds, and also not too much occlusion; Otherwise, the iteration would fall into a local minimum. To solve this problem, this paper proposes an ICP registration algorithm based on the local features of point clouds. With this algorithm, a robust and efficient 3D local feature descriptor (density, curvature and normal angle, DCA) is firstly designed by combining the density, curvature, and normal information of the point clouds, then based on the feature description, the correspondence between the point clouds and also the initial registration result are found, and finally, the aforementioned result is used as the initial value of ICP to achieve fine tuning of the registration result. The experimental results on public data sets show that the improved ICP algorithm boosts good registration accuracy and robustness, and a fast running speed as well.
RESUMEN
Natural piperine from black pepper is known to function as hypocholesterolemic agent, but how it lowers the blood cholesterol remains unclear. In this study, we found that intragastric administrations of piperine (25 mg/kg/day) for 8 weeks significantly reduced the plasma triglyceride (TG), total cholesterol (TC), and low-density lipoprotein cholesterol (LDL-C) in high-fat diet (HFD)-fed mice. H&E staining indicated that piperine significantly decreased hepatic lipid accumulation compared with the control group. The Oil Red O staining further showed that piperine attenuated lipid deposition in liver HepG2 cells in a concentration-dependent manner. Mechanistically, piperine treatment caused a significant upregulation of hepatic scavenger receptor B1 (SR-B1) in the liver and transporter protein of ATP binding cassette SGM8 (ABCG8) in the small intestine. Taken together, our findings demonstrate the role of natural piperine in improving lipid metabolic profile that is involved in the reverse cholesterol transport (RCT)-mediated mechanism through upregulation of SR-B1 in the liver and ABCG8 in the small intestine.
Asunto(s)
Transportador de Casete de Unión a ATP, Subfamilia G, Miembro 8/metabolismo , Alcaloides/farmacología , Anticolesterolemiantes/farmacología , Benzodioxoles/farmacología , Lipoproteínas/metabolismo , Metaboloma , Piperidinas/farmacología , Alcamidas Poliinsaturadas/farmacología , Receptores Depuradores de Clase B/metabolismo , Animales , Transporte Biológico , Dieta Alta en Grasa , Células Hep G2 , Humanos , Intestino Delgado/metabolismo , Lípidos/sangre , Hígado/metabolismo , Masculino , Ratones , Ratones Endogámicos ICR , Regulación hacia ArribaRESUMEN
Treatment of chronic pain remains an unmet medical need. The neuronal voltage-gated potassium Kv7/KCNQ/M channel has been implicated as a therapeutic target for chronic pain. However, whether pharmacological activation of the Kv7 channel can alleviate pain remains elusive. In this study, we show that selective activation of native M-currents by a novel channel opener SCR2682 reduces repetitive firings of dorsal root ganglia (DRG) sensory neurons. Intraperitoneal administration of SCR2682 relieves mechanical allodynia and thermal hyperalgesia in rat models of pain induced by complete Freund's adjuvant (CFA) or spared nerve injury (SNI) in a dose-dependent manner without affecting locomotor activity. The antinociceptive efficacy of SCR2682 can be reversed by the channel-specific blocker XE991. Furthermore, SCR2682 increases Kv7.2/KCNQ2 mRNA and protein expression in DRG neurons from rats in the SNI model of neuropathic pain. Taken together, pharmacological activation of neuronal Kv7 channels by opener SCR2682 can alleviate pain in rats, thus possessing therapeutic potential for chronic pain or hyperexcitability-related neurologic disorders. SIGNIFICANCE STATEMENT: A novel voltage-gated potassium Kv7 channel opener SCR2682 inhibits action potential firings in dorsal root ganglia sensory neurons and exhibits efficacy in antinociception, thus possessing a developmental potential for treatment of chronic pain or epilepsy.