Comparative Evaluation of Hepatoprotective Activities of Geniposide, Crocins and Crocetin by CCl4-Induced liver Injury in Mice

Iridoid glycosides (mainly geniposide) and crocetin derivatives (crocins) are the two major active constituents in Gardenia jasminoides Ellis. In the present study, geniposide, crocins, crocin-1 and crocetin were separated from gardenia chromatographically. Then, mice were orally administrated with geniposide (400 mg/kg b.w.), crocins (400 mg/kg b.w.), crocin-1 (400 mg/kg b.w.) and crocetin (140 mg/kg b.w.) once daily for 7 days with CCl4. Hepatoprotective properties were evaluated by biochemical parameters: Administration of geniposide, crocins, crocin-1and crocetin significantly lowered serum alanine transaminase (ALT), aspartate transaminase (AST) and alkaline phosphatase (ALP) levels in CCl4-treated mice. The reduced glutathione (GSH) levels and antioxidant enzymes (SOD and CAT) activities were also increased by geniposide, crocins, crocin-1 and crocetin. Histopathological examination of livers showed that these components reduced deformability, irregular arrangement and rupture of hepatocyte in CCl4-treated mice. These biochemical results and liver histopathological assessment demonstrated that geniposide, crocetin derivatives and crocetin show comparative beneficial effects on CCl4-induced liver damage via induction of antioxidant defense. Therefore, contents of geniposide and crocetin derivatives should be both considered for hepatoprotective efficacy of Gardenia jasminoides Ellis.

Effect of crocin-1 on learning, memory, and expression of SIRT1 in hippocampus of rats under acute hypoxia / 中草药

Objective: To investigate the effect of crocin-1 on behavior of learning and memory in rats under acute hypoxia and on the expression of silent information regulator l (SIRT1) in hippocampus of rats. Methods: SD rats were randomly divided into five groups: control, hypoxia model, low-, mid-, and high-dose (25, 50, and 100 mg/kg) crocin-1 groups. The SD rats in crocin-1 groups were im administered once daily for 3 d and then were stimulated for 72 h under hypoxia. Morris water maze was used to investigate the learning and memory behaviors. Immunohistochemical staining and Western blotting were used to detect the SIRT1 expression. Results: The escape latency in crocin-1 groups was shorter than that in hypoxia model group, while the frequency of bestriding platform was increased (P < 0.05). Immunohistochemical staining and Western blotting both showed that the expression level of SIRT1 was higher in crocin-1 groups than that in hypoxia model group (P < 0.05), and the expression levels in mid- and high-dose groups were obviously higher. Conclusion: Crocin-1 could increase the expression of SIRT1 in hippocampus of rats, which maybe one of the important mechanisms for crocin-1 improving learning and memory function of SD rats under acute hypoxia.

Pharmacokinetics of crocin-1 after oral administration in rats / 中国药学杂志

OBJECTIVE: To elucidate the intestinal absorption and pharmacokinetic characteristics of crocin-1, a major active constituent of the stigmas of saffron (Crocus sativus L) in rats after oral administration. METHODS: Extracted plasma samples were eluted by the mobile phase composed of methanol-2% acetate acid (pH 2) (48: 52 for crocin-1 and 74: 36 for crocetin) on Agilent Zorbax SB-C18 column monitored at 420 nm. RESULTS: An accurate, precise and selective analysis method was developed to determine crocein in rat plasma with the quantitation limit of 10 ng · mL-1. No crocin-1 was detected in both original and β-glucuronidase treated plasma samples. However, appreciable crocetin, the aglycon form of crocin-1, was observed in the original plasma. The concentration of crocetin did not increase obviously after hydrolization by β-glucuronidase. The average concentration-time data after oral administration of 1 mg · kg-1 crocin-1 showed that crocin-1 was rapidly absorbed as erocein and remained above 50 ng · mL-1 for about 10 h. The first peak appeared at 20 min and the second peak at 6 h. The area under curve (AUC), mean residence time (MRT) during 0 - 24 h and elimination half-life (t1/2k) were calculated as (1.16 ± 0.22) μg · h · mL-1, (5.4 ± 0.7) and (3.0 ± 0.6) h, respectively. CONCLUSION: Crocin-1 is absorbed as its hydrolyzation metabolite and shows relatively good pharmacokinetic characteristics. Crocetin may be thereby related to the pharmacological activities of crocin-1 in vivo. Copyright 2012 by the Chinese Pharmaceutical Association.

Effect of Tibetan medicine Zuotai on in vivo pharmacokinetics of crocin-1 in rats / 中草药

Objective To study the effect of Tibetan medicine Zuotai on in vivo pharmacokinetics of crocin-1 in rats.Methods After im injection of crocin-1 (5 mg/kg) in control (continuously ig normal saline for 7 d) and expermental (continuously ig Zuotai suspension for 7 d or 21 d) rats,The plasma concentration of crocin-1 was determined by RP-HPLC,and plasma concentration-time data were analyzed by DAS 2.0 software to get the related pharmacokinetic parameters of crocin-1.Results After continuously ig administration of Zuotai [10 mg/(kg?d)] for 7 d and 12 d in experimental rats,the pharmacokinetic parameters of crocin-1 changed significantly.The AUC,Cmax,and MRT were significantly greater in experimental rats than those in control rats,and the CL and Vd were significantly lower than those in control rats,and the AUC of crocin-1 was greater in the 21 d administration group than that in the 7 d administration group.Conclusion The result demonstrates that Tibetan medicine significantly affects the pharmacokinetics of crocin-1 in rats.After administration of Zuotai in rats,the absorption degree of crocin-1 is significantly increased and the clearance rate is significantly decreased.