ABSTRACT
Objective: To study the effects of RehmanniaeRadix (RR), AnemarrhenaeRhizoma (AR) and PhellodendriChinensisCortex(PCC) on adrenal function in mice with drug-induced yin deficiency syndrome. Methods:A total of 72 male ICR mice were randomly divided into normal control group, hydrocortisone model group, RRtreatment group, ARtreatment group, PCC treatment group, and RR-AR-PCC compatibility treatment group, with12 mice in each group. The mice were given 25 mg/(kg∙d) hydrocortisone by intragastric administration once a day for 5 consecutive days to replicate the drug-induced yin deficiency syndrome model, and then administrated9g/(kg∙d) RR, 6.0g/(kg∙d) AR, 5.0g/(kg∙d)PCC, 6.7g/(kg∙d) RR-AR-PCC compatibility of water decoction liquid for 5 d. The adrenal cortex was examined by transmission electron microscopy; Serum corticosterone were measured by ELISA; The expressions of Star, Cyp11a1, Cyp21a1, Cyp11b1, Ldlr, Scarb1, Hmgcr, Acat1, Lipe, Abca1, Abcg1, Nr1h3 genes were detected by real-time quantitative PCR. The expressions of LDLR, SRB1, LIPE, ACAT1, CYP11A1, StAR, LXRα protein were detected by Western blotting. Results: Compared with the normalcontrol group, the body weight and serum corticosterone levels of the mice were significantly decreased after 5 d of administration of 25 mg/(kg∙d) hydrocortisone (P<0.05). Adrenal gland zona fasciculate cells appeared fat droplet fusion andmitochondrial atrophy. Hydrocortisone significantly inhibited the expression of Star, Cyp21a1, Cyp11b1, Ldlr, Scarb1 and Acat1 genes expression in adrenocortical hormone synthesis (P<0.05), and inhibited the expression of StAR, LDLR, SBR1 and LXRα proteins (P<0.05), and promoted the Abcg1 gene expression (P<0.05). Compared with the model group, no obvious lipid droplet fusion was observed in the adrenal gland zona fasciculate cells after each drug treatment; RR, AR and PCC significantly inhibit corticosterone secretion after treatment alone (P<0.05); The combination of RR, AR and PCC significantly increased the expression of Star, Cyp11a1, Cyp21a1, Lipe, Abca1, Nr1h3 genes (P<0.05), and enhanced the expression of CYP11A1, StAR, LDLR, SBR1 and LXRα proteins (P<0.05). Conclusion: RR, AR and PCCcombinationcan improve the damaged adrenal function more thantheir alone by regulating cholesterol homeostasis and restoring partially inhibited corticosteroid synthase.
ABSTRACT
Abstract Niemann-Pick disease type C (NP-C) is a rare autosomal-recessive neurovisceral lysosomal storage disease. We report on a juvenile onset, now 25-year-old female patient with typical neurologic symptoms, including vertical gaze palsy, of NP-C. The diagnosis was supported by a positive filipin test ("variant biochemical phenotype" of cholesterol accumulation) in cultured fibroblasts, high numbers of "Niemann-Pick cells" in the bone marrow, and 1 positive out of 3 NP-C biomarkers tested, but NP-C was not definitely confirmed genetically. She showed only 1 known NPC1 variant (3 bp deletion in exon 18; p.N916del); this allele, however, being distinctly overexpressed at the messenger RNA level as compared to the wild-type allele, as a not as yet clarified (copathogenic?) phenomenon. The patient's mother, also carrying the p.N916del allele but without overexpression, has a chronic inflammatory disease of the central nervous system classified as multiple sclerosis. However, her severe clinical phenotype includes some signs also consistent with NP-C. The laboratory diagnosis of NP-C can be challenging in detecting novel disease constellations.