Absorption, Distribution and Excretion
This study investigated the pharmacokinetic characteristics of crocin in rats after oral administration. Following a single oral dose, crocin was not detected, while its metabolite, crocin acid, was present in low concentrations in plasma. Simultaneously, crocin was abundant in feces and intestinal contents within 24 hours. After six consecutive days of oral administration, crocin remained undetectable in plasma, while the concentration of crocin acid in plasma was comparable to that after a single oral dose. Furthermore, the absorption characteristics of crocin were assessed in situ using an intestinal perfusion method. During circulation, crocin was not detected, while low concentrations of crocin acid were detected in plasma. The concentration of crocin in the perfusion fluid gradually decreased across different intestinal segments, with the greatest loss of drug in the colon. These results indicate that: (1) crocin is not absorbed after oral administration, whether as a single dose or repeated doses; (2) after oral administration, crocin is mainly excreted through the intestines; (3) repeated oral administration of crocin does not lead to an increase in plasma crocin acid concentration; and (4) the intestine is an important site for crocin hydrolysis.

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Metabolism/Metabolites
This study investigated the pharmacokinetic characteristics of crocin in rats after oral administration. Crocin was not detected after a single oral administration, while the crocin metabolite crocin acid showed low concentrations in plasma. Simultaneously, crocin was abundant in feces and intestinal contents within 24 hours.

Toxicity Summary
Identification and Uses: Crocin is a carotenoid component of saffron. It is used as a laboratory reagent, antioxidant, experimental antidote for snake bites, and food coloring. Human Exposure and Toxicity: Volunteers received 20 mg crocin tablets or a placebo for one month. General health indicators, such as hematological, biochemical, hormonal, and urinary parameters, were recorded in subjects before and after treatment during the study. No major adverse events were reported during the trial. Crocin tablets did not affect the above parameters, but after one month, amylase, mixed leukocytes, and partial thromboplastin time (PTT) decreased in healthy volunteers. Saffron extract and its main component, crocin, significantly inhibited the growth of human colorectal cancer cells without affecting normal cells. Animal Studies: Acute and subacute toxicity of crocin was evaluated in mice: At pharmacological doses, crocin did not cause significant damage to any organs. No mice died 24 and 48 hours after administration of high doses (3 g/kg, intraperitoneal or oral). Developmental studies have shown that administration of crocin or crocinaldehyde to pregnant mice can induce embryonic malformations. Mild skeletal malformations are the most common abnormalities. Behavioral studies in male rats have shown that saffron aqueous extract and its component crocin have aphrodisiac effects. Crocin was negative in bacterial mutagenicity tests (including the Ames test) and DNA damage tests; in cultured mammalian cells, crocin did not cause chromosomal damage.

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Interactions
Viper bites lead to inflammation at the bite site and target organs. Neutrophils and other polymorphonuclear leukocytes perform inflammatory resolution mechanisms and undergo apoptosis after completing their tasks. However, target-specific toxins induce apoptosis in neutrophils at the bite site and in the circulatory system before they can function, thereby reducing their numbers. Activated neutrophils in circulation are a major source of inflammatory cytokines and reactive oxygen species (ROS)/other toxic intermediates, leading to an exacerbation of the inflammatory response at the bite/target site. Therefore, neutralizing venom-induced neutrophil apoptosis can not only reduce inflammation but also increase the number of functional neutrophils. This study investigated the interference of venom on isolated human neutrophils and its neutralization by the potent antioxidant carotenoid, crocus sativus. Venom treatment of human neutrophils led to altered reactive oxygen species (ROS) production, intracellular calcium ion (Ca2+) mobilization, mitochondrial membrane depolarization, cytochrome C translocation, caspase activation, phosphatidylserine outflow, and DNA damage. Conversely, the crocus sativus pretreatment group showed significant protection against oxidative stress and apoptosis. In conclusion, viper venom can induce neutrophil apoptosis and exacerbate inflammation and tissue damage. This study emphasizes the need for adjuvant therapy, in addition to antivenom treatment, to address secondary/neglected complications of poisoning. This study also investigated the protective effect of crocus sativus against cyclophosphamide (CP)-induced hepatotoxicity in Wistar rats. Experimental rats were administered a single intraperitoneal injection of cyclophosphamide (CP) (150 mg/kg) followed by oral administration of crocin (10 mg/kg) for 6 consecutive days. This study investigated the ameliorative effect of crocin on organ toxicity by evaluating oxidative stress kinases, inflammatory cytokines, and histological sections. A single intraperitoneal injection of cyclophosphamide (CP) significantly increased the levels of endogenous reactive oxygen species (ROS) and lipid and protein oxidation in the liver and serum, which are hallmarks of oxidative damage. Consequently, the levels of major defense mechanisms—reduced glutathione, total thiols, and antioxidant enzymes such as superoxide dismutase, catalase, glutathione S-transferase, and glutathione peroxidase—were significantly decreased. Furthermore, the levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), and acid and alkaline phosphatases in the liver and serum were significantly elevated. Oral administration of crocin significantly restored all of the above abnormal indicators to near-normal levels. Compared with the control drug, histological assessment and the recovery of CP-induced inflammatory cytokine and enzyme levels further confirmed the protective effect of crocin. The results indicate that crocin has a protective effect against acrylamide (CP)-induced oxidative damage/inflammation and organ toxicity. Acrylamide (ACR) exhibits potent neurotoxicity in both humans and animal models. This study used PC12 cells as a suitable in vitro model to evaluate the effect of crocin (the main component of saffron) on ACR-induced cytotoxicity. ACR treatment of PC12 cells resulted in decreased cell viability, increased DNA fragmentation, increased phosphatidylserine exposure, and an elevated Bax/Bcl-2 ratio. These results suggest that ACR increases intracellular reactive oxygen species (ROS) levels, which play a crucial role in ACR cytotoxicity. Pretreatment of cells with 10–50 μM crocin before ACR treatment significantly reduced ACR cytotoxicity in a dose-dependent manner. Crocin inhibited the downregulation of Bcl-2 and the upregulation of Bax, and reduced apoptosis in treated cells. Furthermore, crocin also inhibited the generation of reactive oxygen species (ROS) in cells exposed to ACR. In summary, our results indicate that crocin pretreatment partially protects cells from ACR-induced apoptosis by inhibiting intracellular ROS production. Saffron (Crocus sativus L.) has been shown to interact with the opioid system. Therefore, we evaluated the effects of aqueous and ethanolic extracts of saffron stigmas and their components on morphine withdrawal syndrome in mice. Morphine dependence was induced in mice by subcutaneous injection of morphine for 3 days. On day 4, morphine was injected intraperitoneally 0.5 hours before the injection of extracts, crocin, crocinaldehyde, clonidine (0.3 mg/kg), or saline. Two hours after the last morphine injection, naloxone (5 mg/kg) was injected intraperitoneally, and the number of jumps within 30 minutes was used as the severity of withdrawal syndrome. Clonidine, saffron aqueous extract, and ethanolic extract all reduced jumping activity. Crocinaldehyde was injected subcutaneously 30 minutes before and 1 and 2 hours after morphine injection. Crocinaldehyde exacerbated some withdrawal syndrome symptoms. In open field studies, the aqueous extract of saffron reduced activity levels in animals at all doses (80, 160, and 320 mg/kg), while the ethanol extract also reduced activity levels at a dose of 800 mg/kg. However, crocin and the ethanol extract at a dose of 400 mg/kg had no effect on activity levels in these studies. It is concluded that the extracts and crocin may interact with the opioid system, thereby alleviating withdrawal symptoms. For more complete data on interactions with crocin (13 items in total), please visit the HSDB records page.

[1]. Crocin attenuates lung inflammation and pulmonary vascular dysfunction in a rat model of bleomycin-induced pulmonary fibrosis. Life Sci. 2019 Aug 26:116794.

[2]. Crocin exerts anti-tumor effect in colon cancer cells via repressing the JAK pathway. Eur J Histochem. 2023 Sep 12;67(3):3697.

Therapeutic Uses
Crocin, a carotenoid component of saffron, has been shown to possess various pharmacological activities, including antioxidant, anticancer, memory-improving, antidepressant, brain, kidney, heart, and skeletal muscle protection, anti-ischemic, blood pressure-lowering, aphrodisiac, gene-protective, and detoxifying effects. Crocin can also inhibit morphine withdrawal syndrome and restore morphine-induced positional preference in mice. Snakebites are a serious medical and socioeconomic problem affecting healthy populations and agricultural and livestock workers worldwide. In India, Russell viper bites are common, leading to high morbidity and mortality rates. Its venom components trigger multifactorial stress responses and alter physiological states by damaging blood cells and vital organs. This study confirms the antivenom properties of crocus sativus, a potent antioxidant that counteracts viper venom-induced oxidative stress. In vivo experimental results clearly demonstrate that venom-induced oxidative damage manifests as elevated levels of oxidative stress markers and antioxidant enzymes/molecules, as well as increased levels of pro-inflammatory cytokines, including IL-1β, TNF-α, and IL-6. Furthermore, venom also leads to a decrease in hemoglobin, hematocrit, mean corpuscular volume, and platelet count in experimental animals. Crocin can alleviate venom-induced oxidative stress, hematological changes, and pro-inflammatory cytokine levels. Currently, antivenom injection is an effective treatment for systemic toxicity, but it cannot prevent the rapid spread of oxidative damage and the infiltration of pro-inflammatory mediators. These pathological changes persist even after antivenom injection. Therefore, long-term adjunctive therapy is needed to manage secondary complications and neglected complications of snakebites.
Exploratory Treatment: Due to effective antivenom therapy, the mortality rate from snakebites has significantly decreased. Intravenously infused antivenom can neutralize free toxins and targeted-bound toxins, but it cannot neutralize the inflammation and oxidative stress caused by venom because the antigen-antibody complex itself has a pro-inflammatory effect. Therefore, adjunctive therapy is needed to manage secondary/neglected poisoning complications. Blood samples collected from healthy donors were treated with viper venom (100 μg/mL) for 2 hours. The effects of venom-induced inflammation, oxidative damage, and crocin pretreatment were determined by measuring serum levels of cytoplasmic, lysosomal, and oxidative stress markers, as well as pro-inflammatory mediators such as tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6, and cyclooxygenase (COX)-2. Results showed significantly elevated levels of stress markers, cytoplasmic, lysosomal, and extracellular matrix degrading enzymes, as well as pro-inflammatory mediators TNF-α, IL-1β, IL-6, and COX-2, indicating exacerbated cellular damage, but oxidative damage and inflammation were significantly reduced in the crocin pretreatment group. Conclusion: The data clearly demonstrate that venom-induced oxidative stress and inflammation are also causes of oxidative bursts and cell death in the circulatory system, which may be exacerbated even after antivenom treatment. Therefore, this study, in addition to antivenom treatment, also calls for adjuvant therapies to address the often-overlooked issues in snakebite treatment.
Experimental Treatment/This Study/Using a rat model, this study investigated the long-term effects of crocin (a glycosylated carotenoid extracted from saffron stigmas) on colon cancer. BD-IX rats were divided into four groups: G1 and G2 (cancer groups) were used to study the effects of crocin on colon cancer progression; G3 and G4 (toxicity groups) were used to study the effects of this therapy on metabolic processes and parenchymal tissues. DHD/K12-PROb cells were subcutaneously injected into the thoracic cavity of animals in groups G1 and G2. From 1 to 13 weeks post-inoculation, animals in groups G2 and G4 received weekly injections of crocin (400 mg/kg body weight, subcutaneous injection). Animals in groups G1 and G3 received no treatment. In addition, this study also conducted in vitro experiments using animal and human colon adenocarcinoma cell lines (DHD/K12-PROb and HT-29) to detect the cytotoxicity of crocin. Female rats treated with crocin showed prolonged lifespan and slowed tumor growth, but no significant anti-tumor effect was observed in male rats. Acute tubular necrosis was observed in kidney samples from all animals treated with crocin, but serum biochemical analysis showed only mild signs of nephrotoxicity. In vitro experiments demonstrated that crocin had significant cytotoxic effects on human and animal adenocarcinoma cells (HT-29 and DHD/K12-PROb cells, with median lethal doses of 0.4 mM and 1.0 mM, respectively). The treated cells showed a significant reduction in cytoplasm and the appearance of large vacuolated areas. In conclusion, long-term treatment with crocin selectively improves the survival rate of female rats with colon cancer without significant toxic side effects. The effect of crocin may be related to its strong cytotoxicity against cultured tumor cells.
Exploring the Therapeutic Effects of Saffron (Crocus sativus L.) Saffron has traditionally been used to treat insomnia and other neurological disorders. Crocin and crocinic acid are two carotenoid pigments and the main components responsible for various pharmacological activities of saffron. This study investigated the sleep-promoting activities of crocin and crocinic acid in mice by monitoring their motor activity and electroencephalograms after administration. After lights out at 8:00 PM, intraperitoneal injections of crocin (30 and 100 mg/kg) increased the total non-rapid eye movement (non-REM) sleep time by 60% and 170%, respectively, over a four-hour period from 8:00 PM to midnight. Injection of crocinic acid (100 mg/kg) also increased the total non-REM sleep time by 50%. These compounds did not alter the amount of rapid eye movement (REM) sleep after sleep induction, nor did they show any adverse effects such as rebound insomnia.

C44H64O24

976.9646

976.378

42553-65-1

5281233

Pink to red solid powder

1.5±0.1 g/cm3

1169.0±65.0 °C at 760 mmHg

186° (effervescence)

337.8±27.8 °C

0.0±0.6 mmHg at 25°C

1.650

-0.83

14

24

20

68

1730

20

C/C(=C\C=C\C=C(\C=C\C=C(\C(=O)O[C@@H]1O[C@@H]([C@H]([C@@H]([C@H]1O)O)O)CO[C@@H]2O[C@@H]([C@H]([C@@H]([C@H]2O)O)O)CO)/C)/C)/C=C/C=C(/C(=O)O[C@@H]3O[C@@H]([C@H]([C@@H]([C@H]3O)O)O)CO[C@@H]4O[C@@H]([C@H]([C@@H]([C@H]4O)O)O)CO)\C

SEBIKDIMAPSUBY-RTJKDTQDSA-N

InChI=1S/C44H64O24/c1-19(11-7-13-21(3)39(59)67-43-37(57)33(53)29(49)25(65-43)17-61-41-35(55)31(51)27(47)23(15-45)63-41)9-5-6-10-20(2)12-8-14-22(4)40(60)68-44-38(58)34(54)30(50)26(66-44)18-62-42-36(56)32(52)28(48)24(16-46)64-42/h5-14,23-38,41-58H,15-18H2,1-4H3/b6-5+,11-7+,12-8+,19-9+,20-10+,21-13+,22-14+/t23-,24-,25-,26-,27-,28-,29-,30-,31+,32+,33+,34+,35-,36-,37-,38-,41-,42-,43+,44+/m1/s1

bis[(2S,3R,4S,5S,6R)-3,4,5-trihydroxy-6-[[(2R,3R,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxymethyl]oxan-2-yl] (2E,4E,6E,8E,10E,12E,14E)-2,6,11,15-tetramethylhexadeca-2,4,6,8,10,12,14-heptaenedioate

Crocin

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Note: This product requires protection from light (avoid light exposure) during transportation and storage.

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

DMSO : ~125 mg/mL (~127.95 mM)

Solubility in Formulation 1: ≥ 2.08 mg/mL (2.13 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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Solubility in Formulation 2: ≥ 2.08 mg/mL (2.13 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.

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 (Please use freshly prepared in vivo formulations for optimal results.)