Crocin

Nat Prod Commun. 2015 Feb;10(2):249-52.

Ovarian cancer HO-8910 cell apoptosis induced by crocin in vitro.[Pubmed: 25920253]

The effect and mechanism of ovarian cancer HO-8910 cell apoptosis induced by Crocin.
METHODS AND RESULTS:
MTT assay was performed to detect the inhibitory action of Crocin on the proliferation of HO-8910 cells. Flow cytometry was used to test the cell cycle distribution and apoptosis rate of ovarian cancer HO-8910 cells. Western blot analysis was utilized to measure the levels of apoptotic proteins such as p53, Fas/APO-1, and Caspase-3. MTT analysis revealed that Crocin significantly inhibited the growth of HO-8910 cells. Additionally, flow cytometry illustrated that Crocin raised the proportion of HO-8910 cells in the G0/G1 phase and increased their apoptosis rate. Furthermore, Western blot analysis revealed that Crocin up-regulated the expression of p53, Fas/APO-1, and Caspase-3.
CONCLUSIONS:
The results of this study showed that Crocin can significantly inhibit the growth of HO-8910 cells and arrest them in the G0/G1 phase. Crocin can also promote ovarian cancer HO-8910 cell apoptosis, most likely by increasing p53 and Fas/APO-1 expression, and then activating the apoptotic pathway regulated by Caspase-3.

Invest Ophthalmol Vis Sci. 2006 Jul;47(7):3156-63.

Protective effect of crocin against blue light- and white light-mediated photoreceptor cell death in bovine and primate retinal primary cell culture.[Pubmed: 16799063 ]

The present study was performed to investigate the effect of Crocin on blue light- and white light-induced rod and cone death in primary retinal cell cultures.
METHODS AND RESULTS:
Primary retinal cell cultures were prepared from primate and bovine retinas. Fifteen-day-old cultures were exposed to blue actinic light or to white fluorescent light for 24 hours. Cultures were treated by the addition of different concentrations of Crocin for 24 hours before light exposure or for 8 hours after light exposure. Cultures kept in the dark were used as controls. Green nucleic acid stain assay was used to evaluate cell death. Rods and cones were immunolabeled with specific antibodies and counted. TUNEL labeling was used to detect fragmented DNA in fixed cells after light exposure. Primary retinal cell cultures contained a mixture of retinal cells enriched in photoreceptors, bipolar cells, and Müller cells. Twenty-four-hour exposure to blue and white light induced death in 70% to 80% of the photoreceptors in bovine and primate retinal cell cultures. Crocin protected the photoreceptors against blue light- or white light-mediated damage in a concentration-dependent manner with an EC50 of approximately 30 microM. TUNEL assays confirmed that Crocin protected photoreceptors from light damage.
CONCLUSIONS:
These results show that blue and white light selectively induce rod and cone cell death in an in vitro model. Crocin protects retinal photoreceptors against light-induced cell death.

Immunopharmacol Immunotoxicol. 2015 Jun;37(3):236-43.

Anti-asthma potential of crocin and its effect on MAPK signaling pathway in a murine model of allergic airway disease.[Pubmed: 25753844]

Crocin, a diterpenoid glucoside, has multitudinous activities such as anti-inflammation, anti-allergy, anti-oxidation and relaxing smooth muscles. In this study, the potential of Crocin as an anti-asthma agent was investigated in a murine model.
METHODS AND RESULTS:
BALB/c mice were sensitized and challenged by ovalbumin (OVA) to induce allergic airway inflammation, with Crocin administered one hour before every OVA challenge. Airway hyper-reactivity was evaluated by lung function analysis systems. Leukocyte counts in bronchoalveolar lavage fluid (BALF) were measured by a hemocytometer and Diff-Quick-stained smears. Lung tissues were stained with hematoxylin-eosin, Congo red and methylene blue for histopathological inspection. Inflammatory mediators in serum, BALF and lung were measured by ELISA or RT-PCR. Effects of Crocin on MAPK signaling pathways were investigated by western blot analysis. Crocin significantly suppressed airway inflammation and hyper-reactivity, reduced levels of BALF interleukin (IL-4), IL-5, IL-13 and tryptase, lung eosinophil peroxidase and serum OVA-specific IgE, and inhibited the expression of lung eotaxin, p-ERK, p-JNK and p-p38 in the OVA-challenged mice.
CONCLUSIONS:
These results demonstrated that the suppression of Crocin on airway inflammation and hyper-reactivity in a murine model, thus Crocin might have a great potential to be a candidate for the treatment of asthma.

Drug Chem Toxicol. 2014 Oct;37(4):378-83.

Protective effect of crocin on diazinon induced vascular toxicity in subchronic exposure in rat aorta ex-vivo.[Pubmed: 24392635]

Diazinon (DZN) is a widely used organophosphate insecticide. Although mechanism of DZN cardiovascular toxicity is primarily mediated through inhibition of acetylcholinesterase, however, DZN causes remarkable atropine-insensitive hypotension in rats. It has been proved that oxidative stress is an important mechanism of DZN toxicity especially in chronic exposure. Crocin, an active ingredient of saffron, has been found to antagonize the hypotensive effects of DZN in rats, but do not reverse acetylcholinesterase inhibition. In this study the effects of DZN on contractile and relaxant responses in rat aorta as well as ex-vivo antioxidant actions of Crocin have been investigated.
METHODS AND RESULTS:
Rats were divided into 7 groups: corn oil (control), DZN (15 mg/kg/day, gavage), Crocin (12.5, 25 and 50 mg/kg/day, i.p.) plus DZN, vitamin E (200 IU/kg, i.p., three days a week) plus DZN and Crocin (50 mg/kg/day, i.p.) groups. Treatments were continued for 4 weeks. Contractile and relaxant responses were evaluated on the isolated aorta. Our results showed that DZN not only decreased the contractile responses to KCl and Phenylephrine (PE) (p < 0.001), but also attenuated the relaxant response to acetylcholine (ACh) (p < 0.01). Crocin and vitamin E attenuated lipid peroxidation, improved the reduction of contractile responses by KCl and PE and restored the decrease in ACh relaxation in rat aorta.
CONCLUSIONS:
DZN induced vascular toxicity which may be due to oxidative stress and not to a cholinergic mechanism. Crocin improved toxic effects of DZN via reducing lipid peroxidation and restoring altered contractile and relaxant responses in rat aorta.

Life Sci . 2019 Oct 15;235:116794.

Crocin attenuates lung inflammation and pulmonary vascular dysfunction in a rat model of bleomycin-induced pulmonary fibrosis[Pubmed: 31465731]

Abstract Amongst the various forms of lung injury; pulmonary fibrosis remains the most intricate form with limited therapeutic options to both the patient and the physicians. Bleomycin (BLM) is a chemotherapeutic agent used for the treatment of various carcinomas; however, its therapeutic value is significantly limited by its associated pulmonary fibrosis. The current study highlights the prominent antioxidant, anti-inflammatory and anti-fibrotic effect of Crocin against BLM-induced pulmonary fibrosis. Intratracheal BLM instillation induced significant biochemical, structural, functional and vascular pulmonary injury. BLM instillation increased oxidant load with quenching of antioxidant defenses together with increase inflammatory and fibrotic cytokines expression. Crocin significantly attenuated BLM-induced lung injury and its effect was comparable to the standard anti-fibrotic; halofuginone. The observed anti-inflammatory and anti-fibrotic and antioxidant impacts are thought to be embroiled in the therapeutic impacts of Crocin. Down-regulation of TLR4, IL-10 expression is the major pathway involved in the observed anti-inflammatory effects and finally, down-regulation of tissue expression of TNF-α and TGF-β1 is the major pathways implicated in the observed anti-fibrotic activities and modulation of Nrf2 and HO-1 pathways is the main mechanism involved in the observed antioxidant effects. Keywords: Bleomycin; Crocin; HO-1; Halofuginone; NrF2; TGF-β1.

Chem Biol Interact. 2015 Mar 5;229:26-35.

Gastroprotective effect of crocin in ethanol-induced gastric injury in rats.[Pubmed: 25637687]

The present study investigated the gastroprotective effect of Crocin in ethanol-induced gastric injury in rats.
METHODS AND RESULTS:
Rats were allocated into a normal group, an ulcer group, a Crocin-treated group, an ulcer group pretreated with Crocin, and an ulcer group pretreated with omeprazole as a reference anti-ulcer drug. Rats were sacrificed 3h after ethanol administration. Prophylactic administration of Crocin (50mg/kg/day, i.p.) for 3 consecutive days before the administration of 70% ethanol (10 ml/kg, orally) resulted in significant gastroprotection compared to ethanol-ulcerated rats as manifested by significant reduction in the gastric ulcer index. Crocin pretreatment increased ethanol-lowered levels of gastric juice mucin and mucosal prostaglandin E2 (PGE2) and interleukin-6 (IL-6). Moreover, Crocin significantly decreased ethanol-elevated tumor necrosis factor-alpha (TNF-α) level, myeloperoxidase activity and heat shock protein 70 mRNA and protein levels. It also restored ethanol-altered mucosal levels of glutathione, malondialdehyde and superoxide dismutase activity. Furthermore, Crocin-pretreatment alleviated ethanol-induced mucosal apoptosis as revealed by significant down-regulation of cytochrome c and caspase-3 mRNA expression, significant decrease in caspase-3 activity and mitigated DNA fragmentation as indicated by significant decrements in comet parameters. The protective efficacy of Crocin was further supported by histological assessment. No significant difference was observed between Crocin and omeprazole (20mg/kg orally 1h before ethanol administration) regarding their mucin-secretagogue and antioxidant effects, as well as their effects on TNF-α, IL-6 and cytochrome c. On the other hand, omeprazole was superior in enhancing PGE2 level and in alleviating neutrophil infiltration, caspase-3 activation and DNA fragmentation.
CONCLUSIONS:
Conclusively, Crocin protects rat gastric mucosa against ethanol-induced injury via anti-inflammatory, anti-oxidative, anti-apoptotic and mucin-secretagogue mechanisms that are probably mediated by enhanced PGE2 release.

Gen Physiol Biophys. 2015 May 22.

Effect of crocin on oxidative stress in recovery from single bout of swimming exercise in rats.[Pubmed: 26001290]

Physical exercise could cause muscle and tissue damage due to increase in the formation of free oxygen radicals during exercise. The aim of the present study was to investigate the effect of Crocin on parameters associated with oxidative stress in recovery from acute swimming exercise in rats.
METHODS AND RESULTS:
Rats were divided into eight groups; Normal Control (NC: untreated and did not swim), Crocin Control (CC: received Crocin and did not swim), Exercise-1 (Exe-1: untreated and swam), Exercise-24 (Exe-24: untreated and swam), Exercise-48 (Exe-48: untreated and swam), Exercise+Crocin-1 (Exe-Cro-1: received Crocin and swam), Exercise+Crocin-24 (Exe-Cro-24: received Crocin and swam), Exercise+Crocin-48 (Exe-Cro-48: received Crocin and swam). AST, ALP, LDH, CK, XO enzymes levels increased after swimming in untreated and Crocin-treated groups, but there was a less increase in Crocin-treated groups. The highest MDA levels in serum were determined in Exe-1 compared with all other groups. There was significant difference between control and exercise groups in MDA level (p = 0.033). In contrast, there was significant difference between control and exercise groups in GSH level (p < 0.001). In addition, Crocin given to swimming rats significantly increased GSH levels (p < 0.05) and decreased MDA levels when compared with untreated exercise groups.
CONCLUSIONS:
In conclusion, Crocin is able to protect liver and skeletal muscle tissue against exercise-induced oxidative damage by preventing reactive oxygen species (ROS) production.

Eur J Pharmacol. 2006 Aug 14;543(1-3):116-22.

Mechanism of hypolipidemic effect of crocin in rats: crocin inhibits pancreatic lipase.[Pubmed: 16828739 ]

The hypolipidemic mechanism of Crocin, an active ingredient in Gardenia jasminoides Ellis and Crocus sativus L, was examined in rats.
METHODS AND RESULTS:
In diet-induced hyperlipidemic rats, a 10-day treatment with Crocin significantly reduced serum triglyceride, total cholesterol, low density lipoprotein (LDL) cholesterol and very low density lipoprotein (VLDL) cholesterol level in the daily dose range of 25 to 100 mg/kg. Results of the modified fat-loading method indicated that Crocin inhibited the absorption of fat and cholesterol and this inhibition is closely related to the hydrolysis of fat. In addition, the modified fat-balance method demonstrated that Crocin increased the fecal excretion of fat and cholesterol in rats, but had no influence on the elimination of bile acids. The results of the in situ loop method and enzyme assay indicated that Crocin could not directly block the absorption of cholesterol from rat jejunum but could selectively inhibit the activity of pancreatic lipase as a competitive inhibitor.
CONCLUSIONS:
These findings suggest that Crocin yielded its hypolipidemic effect by inhibiting pancreatic lipase, leading to the malabsorption of fat and cholesterol.