This study investigated the pharmacokinetic properties of crocin following oral administration in rats. After a single oral dose, crocin was undetected while crocetin, a metabolite of crocin, was found in plasma at low concentrations. Simultaneously, crocin was largely present in feces and intestinal contents within 24 hr.
IDENTIFICATION AND USE: Crocin is a carotenoid constituent of saffron. It is used as a laboratory reagent, antioxidant and experimental antidote in snake bites and food dye. HUMAN EXPOSURE AND TOXICITY: Volunteers received 20 mg crocin tablets or placebo for one month. General measures of health were recorded during the study such as hematological, biochemical, hormonal and urinary parameters in pre and post-treatment periods. No major adverse events were reported during the trial. Crocin tablets did not change the above parameters except that it decreased amylase, mixed white blood cells and PTT in healthy volunteers after one month. Crocus sativus extract and its major constituent, crocin, significantly inhibited the growth of human colorectal cancer cells while not affecting normal cells. ANIMAL STUDIES: The acute and sub-acute toxicity of crocin was evaluated in mice: at pharmacological doses, crocin did not exhibit marked damages to any organs. With high doses (3 g/kg, IP or orally) after 24 and 48 hr no mortality was seen by crocin in mice. Developmental study suggests that crocin or safranal can induce embryonic malformations when administered in pregnant mice. Minor skeletal malformations were the most commonly observed abnormality. Behavioral studies in male rats revealed an aphrodisiac activity of saffron aqueous extract and its constituent crocin. Crocin gave negative results in bacterial test for mutagenicity (including the Ames test) and DNA damage; it did not produce chromosome damage in mammalian cells in culture.
Viper envenomation results in inflammation at the bitten site as well as target organs. Neutrophils and other polymorphonuclear leukocytes execute inflammation resolving mechanism and will undergo apoptosis after completing the task. However, the target specific toxins induce neutrophil apoptosis at the bitten site and in circulation prior to their function, thus reducing their number. Circulating activated neutrophils are major source of inflammatory cytokines and leakage of reactive oxygen species (ROS)/other toxic intermediates resulting in aggravation of inflammatory response at the bitten/target site. Therefore, neutralization of venom induced neutrophil apoptosis reduces inflammation besides increasing the functional neutrophil population. Therefore, the present study investigates the venom induced perturbances in isolated human neutrophils and its neutralization by crocin (Crocus sativus) a potent antioxidant carotenoid. Human neutrophils on treatment with venom resulted in altered ROS generation, intracellular Ca2+ mobilization, mitochondrial membrane depolarization, cyt-c translocation, caspase activation, phosphatidylserine externalization and DNA damage. On the other hand significant protection against oxidative stress and apoptosis were evidenced in crocin pre-treated groups. In conclusion the viper venom induces neutrophil apoptosis and results in aggravation of inflammation and tissue damage. The present study demands the necessity of an auxiliary therapy in addition to antivenin therapy to treat secondary/overlooked complications of envenomation.
This study investigated the protective efficacy of crocin against hepatotoxicity induced by cyclophosphamide (CP) in Wistar rats. The experimental rats were treated with crocin orally at a dose of 10 mg/kg for 6 consecutive days after the administration of a single intraperitoneal dose of CP (150 mg/kg). The ameliorative effect of crocin on organ toxicity was studied by evaluating oxidative stress enzymes, inflammatory cytokines and histological sections. A single intraperitoneal CP injection significantly elevated endogenous reactive oxygen species and oxidation of lipids and proteins, which are the hallmarks of oxidative damage in liver and serum. In consequence, the primary defensive reduced glutathione, total thiol and antioxidant enzymes such as superoxide dismutase, catalase, glutathione-S-transferase and glutathione peroxidase, were significantly reduced. In addition, liver and serum aspartate aminotransferase and alanine aminotransferase along with acid and alkaline phosphatase were considerably increased. Oral administration of crocin significantly rejuvenated all the above altered markers to almost normal state. The protective efficacy of crocin was further supported by the histological assessment and restoration of CP-induced inflammatory cytokines and enzyme levels compared with the control drug. The results obtained suggest the protective nature of crocin against CP-induced oxidative damage/inflammation and organ toxicity.
Acrylamide (ACR) is a potent neurotoxic in human and animal models. In this study, the effect of crocin, main constituent of Crocus sativus L. (Saffron) on ACR-induced cytotoxicity was evaluated using PC12 cells as a suitable in vitro model. The exposure of PC12 cells to ACR reduced cell viability, increased DNA fragmented cells and phosphatidylserine exposure, and elevated Bax/Bcl-2 ratio. Results showed that ACR increased intracellular reactive oxygen species (ROS) in cells and ROS played an important role in ACR cytotoxicity. The pretreatment of cells with 10-50 uM crocin before ACR treatment significantly attenuated ACR cytotoxicity in a dose-dependent manner. Crocin inhibited the downregulation of Bcl-2 and the upregulation of Bax and decreased apoptosis in treated cells. Also, crocin inhibited ROS generation in cells exposed to ACR. In conclusion, our results indicated that pretreatment with crocin protected cells from ACR-induced apoptosis partly by inhibition of intracellular ROS production.
Crocus sativus L. has been shown to interact with the opioid system. Thus, the effects of aqueous and ethanolic extracts of stigma and its constituents were evaluated on morphine-withdrawal syndrome in mice. Dependence was induced using subcutaneous (s.c.) injections of morphine for 3 days. On day 4, morphine was injected 0.5 hr prior the intraperitoneal (i.p.) injections of the extracts, crocin, safranal, clonidine (0.3 mg/kg) or normal saline. Naloxone was injected (5 mg/kg i.p.) 2 hr after the final dose of morphine and the number of episodes of jumping during 30 min was considered as the intensity of the withdrawal syndrome. Clonidine, the aqueous and ethanolic extracts of saffron reduced the jumping activity. Safranal was injected (s.c.) 30 min prior and 1 and 2 hr after the injection of morphine. It potentiated some signs of withdrawal syndrome. The aqueous extract decreased the movement in all of the doses (80, 160, 320 mg/kg) and the ethanolic extract decreased it in the dose of 800 mg/kg in open field test. But crocin and the dose of 400 mg/kg ethanolic extract showed no effect on activity in this test. It is concluded that the extracts and crocin may have interaction with the opioid system to reduce withdrawal syndrome.
This study investigated the pharmacokinetic properties of crocin following oral administration in rats. After a single oral dose, crocin was undetected while crocetin, a metabolite of crocin, was found in plasma at low concentrations. Simultaneously, crocin was largely present in feces and intestinal contents within 24 hr. After repeated oral doses for 6 days, crocin remained undetected in plasma and plasma crocetin concentrations were comparable to the corresponding data obtained after the single oral dose. Furthermore, the absorption characteristics of crocin were evaluated in situ using an intestinal recirculation perfusion method. During recirculation, crocin was undetected and low concentrations of crocetin were detected in plasma. The concentrations of crocin in the perfusate were reduced through different intestinal segments, and the quantities of drug lost were greater throughout the colon. These results indicate that (1) orally administered crocin is not absorbed either after a single dose or repeated doses, (2) crocin is excreted largely through the intestinal tract following oral administration, (3) plasma crocetin concentrations do not tend to accumulate with repeated oral doses of crocin, and (4) the intestinal tract serves as an important site for crocin hydrolysis.
UGT75L6 and UGT94E5 mediate sequential glucosylation of crocetin to crocin inGardenia jasminoides
摘要：
Crocin is an apocarotenoid glycosyl ester accumulating in fruits of Gardenia jasminoides and used as a food coloring and nutraceutical. For the first time, the two glucosyltransferases UGT75L6 and UGT94E5 that sequentially mediate the final glucosylation steps in crocin biosynthesis in G. jasminoides have been identified and functionally characterized. UGT75L6 preferentially glucosylates the carboxyl group of crocetin yielding crocetin glucosyl esters, while UGT94E5 glucosylates the 6′ hydroxyl group of the glucose moiety of crocetin glucosyl esters. The expression pattern of neither UGT75L6 nor UGT94E5 correlated with the pattern of crocin accumulation in G. jasminoides.
Biocompatible natural sugar-based surfactant assisted oxidation of citric acid by MnO<sub>4</sub><sup>−</sup> in absence and presence of SDS
作者：Zaheer Khan、Shaeel Ahmad Al-Thabaiti、Maqsood Ahmad Malik
DOI：10.1039/c6ra04242b
日期：——
Crocin, a natural carotenoid with antioxidant properties, was used in the present investigation as a surfactant in the citric acid–MnO4− redox system for the first time.
[EN] METHOD FOR THE PURIFICATION OF CROCETIN<br/>[FR] PROCEDE DE PURIFICATION DE LA CROCETINE
申请人：RIKEN VITAMIN CO
公开号：WO2004078695A1
公开（公告）日：2004-09-16
The present invention provides an easily operated, industrially advantageous method for the production of crocetin. In more detail, the present invention relates to a method for the purification of crocetin, which comprises treating crocetin obtained by hydrolysis of crocin, which exists in a plant extract, with lower alcohol or a mixed solvent containing 50% by volume or more of lower alcohol and removing a soluble component in the solvent. The present invention also relates to a method for the purification of crocetin, which comprises dissolving crocetin obtained by hydrolysis of crocin, which exists in a plant extract, into an aprotic solvent which can crystallize crocetin and crystallizing crocetin from the solvent. The present invention makes it possible to efficiently prepare a desired purified crocetin of high purity. The purified crocetin is useful as a pharmaceutical composition, cosmetic product or skin cosmetics and can be used as an additive in food and health food.
The present invention relates to a composition derived from the hydrolysate of plant containing crocin or the derivatives thereof. The composition includes a significant amount of crocetin monoester. The present invention also provides a method to hydrolyze crocin existing in a plant extract, and further relates to the use.
