Ganoderma triterpenes slow cyst growth in polycystic kidney disease

OBJECTIVE Autosomal dominant polycystic kidney disease(ADPKD)is a common inherited disease with a high morbidity around 1/1000-1/400,characterized by progressive enlargement of fluid-fil ed cysts derived from renal tubular epithelial cells.Massive cysts gradually compress renal parenchyma destroying normal renal structures and compromising renal functions.Unfortunately,it will cause end-stage renal disease in most of the patients but without effective therapy now,who have to live on hemodialysis or kidney transplantation.Based on this present situation,it is of great significance to find early intervention to inhibit renal cyst development.The projective of this study was to investigate whether Ganoderma triterpenes(GT)can inhibit renal cyst development and study the related mechanism.METHODS and RESULTS First,we used MDCK cyst model,cultivated MDCK cells in vitro to form fluid-filled cysts surrounded by monolayer cells.GT inhibited MDCK cyst formation significantly,and inhibited cyst enlargement dose-dependently proving GT cyst inhibition in vitro.Then we used an embryonic kidney cyst model,wile-type mice kidneys were taken out on embryonic day 13.5 to form renal cysts stimulated with 8-Br-c AMP.GT inhibited embryonic kidney cyst development significantly in a dosedependent and reversible manner proving GT cyst inhibition at organ level.Furthermore,we used two ADPKD mouse models with severe cystic kidney disease phenotypes.GT dramatically inhibited renal cyst development,decreased ADPKD mouse kidney volume and the cyst index inside proving GT cyst inhibition in vivo.By Western blot,we proved GT down-regulated Ras/MAPK signal pathway without detectable effect on m TOR signal pathway both in MDCK cells and two ADPKD mouse kidneys.CONCLUSION GT retard renal cyst development both in vitro and in vivo significantly.The related mechanisms were involved in GT promoting renal tubular epithelial cell differentiation,down-regulating intracellular c AMP level and Ras/MAPK signal pathway.

Nanostructured lipid carrier based topical gel of Ganoderma Triterpenoids for frostbite treatment

The objective of this study was to prepare nanostructured lipid carrier(NLC)-based topical gel of Ganoderma Triterpenoids(GTs) and evaluate their effects on frostbite treatment. GT-NLCs was prepared by the high pressure homogenization method and then characterized by morphology and analyses of particle size, zeta potential, entrapment efficiency(EE), and drug loading(DL). The NLCs was suitably gelled for skin permeation studies in vitro and pharmacodynamic evaluation in vivo, compared with the GT emulgel. The GT-NLC remained within the colloidal range and was uniformly dispersed after suitably gelled by carbopol preparation. Transmission electron microscopy(TEM) study showed GT-NLCs was spherical in shape. The EE(%) and DL(%) could reach up to(81.84 ± 0.60)% and(2.13 ± 0.12)%, respectively. The result of X-ray diffractograms(XRD) showed that GTs were in an amorphous state in the NLC-gel. In vitro permeation studies through rat skin indicated that the amount of GTs permeated through skin of GT-NLCs after 24 h was higher than that of GT emulsion, and GT-NLCs increased the accumulative amounts of GTs in epidermis 7.76 times greater than GT emulsion. GT-NLC-gel was found to possess superior therapeutic effect for frostbite, compared with the GT emulgel. The NLC based topical gel of GTs could improve-their therapeutic effect for frostbite.