Metabolomics significantly impacts drug discovery and precise disease management. This study meticulously assesses the metabolite profiles of cells treated with Crocin, Dexamethasone, and mesenchymal stem cells (MSCs) under oxidative stress induced by 2-chloroethyl ethyl sulfide (CEES). Gas chromatography/mass spectrometry (GC/MS) analysis unequivocally identified substantial changes in 37 metabolites across the treated groups. Notably, pronounced alterations were observed in pathways associated with aminoacyl-tRNA biosynthesis and the metabolism of aspartate, serine, proline, and glutamate. These findings demonstrate the potent capacity of the analyzed treatments to effectively reduce inflammation, mitigate reactive oxygen species production, and enhance cell survival rates. SIGNIFICANCE.

UNASSIGNED: Mobile devices are sources of electromagnetic fields (EMFs) that cause increasing concern among scientists about human health, especially with the long-term use of mobile phones. With regard to this issue, the potential adverse health effects, particularly on brain function have raised public concern. There is considerable evidence that natural compounds have neuro-protective effects due to their antioxidant and anti-inflammatory properties. Growing evidence suggests that crocin as a natural bioactive compound can be considered a potential therapeutic agent against various neurologic disorders. Therefore, the present study investigated the effects of crocin on the cerebellum after exposure to EMF.
UNASSIGNED: Twenty-four Male Balb/c mice were divided into control group, EMF group (2100 MHZ), EMF +Crocin group (2100 MHZ+50 mg/kg), and crocin group (50 mg/kg). The animals in the EMF and EMF+Crocin groups were exposed continuously for 30 days to an EMF 120 min/day. After 30 days, cerebellar cortex was evaluated by histomorphometric and immunohistochemical methods.
UNASSIGNED: The results showed that 30 days of exposure to EMF had no significant effect on Purkinje cell size. However, EMF reduced significantly the diameter of astrocytes and increased Glial fibrillary acidic protein (GFAP) expression compared to the controls (p<0.05). Our findings also indicated that crocin treatment could improve the diameter of astrocytes and normalize GFAP expression (p<0.05).
UNASSIGNED: This study concluded that 2100-MHz EMF caused adverse effects on the cerebellum through astrocyte damage and crocin could partially reverse the EMF-related adverse effects.

Orally administered crocin rapidly and efficiently rescues depressive-like behaviors in depression models; however, crocin levels in the circulatory and central nervous systems are rather low. The underlying mechanism responsible for the inconsistency between pharmacokinetics and pharmacodynamics is unknown. To identify the active metabolites and clarify the underlying mechanisms, the pharmacokinetics and metabolic effects of the gut flora and hepatic and intestinal microsomes on crocin were examined, and the pharmacodynamics of crocin and its major metabolite, crocetin, were also evaluated in both normal and pseudo germ-free mice subjected to chronic social defeat stress. The results showed that oral administration of 300 mg/kg crocin significantly improved the depression-like behaviors of chronic social defeat stress mice, although the levels of crocin in the circulatory system were rather low (Cmax = 43.5 ± 8.6 μg/L; AUC = 151 ± 20.8 μg·h/L). However, the primary metabolite of crocetin was much more abundant in vivo (Cmax = 4662.5 ± 586.1 μg/L; AUC = 33,451.9 ± 3323.6 μg·h/L). Orally administered crocin was primarily metabolized into crocetin by the gut flora instead of hepatic or intestinal microsomal enzymes, and less than 10% of crocin was transformed into crocetin in the liver or intestinal microsomes. Inhibition of the gut flora dramatically reduced the production of and in vivo exposure to crocetin, and the rapid antidepressant effect of crocin disappeared. Moreover, crocetin showed rapid antidepressant effects similar to those of crocin, and the effects were independent of the gut flora. In conclusion, the metabolic transformation of crocin to crocetin primarily contributes to the rapid antidepressant effects of crocin and is dependent on the gut flora.

It was previously reported that crocin, a water-soluble carotenoid isolated from the Crocus sativus L. (saffron), has protective effects on cardiac cells and may neutralize and even prevent the formation of excess number of free radicals; however, functional mechanisms of crocin activity have been poorly understood. In the present research, we aimed to study the functional mechanism of crocin in the heart exposed to oxidative stress. Accordingly, oxidative stress was modeled in vitro on human umbilical vein endothelial cells (HUVECs) and in vivo in mice using cellular stressors. The beneficial effects of crocin were investigated at cellular and molecular levels in HUVECs and mice hearts. Results indicated that oral administration of crocin could have protective effects on HUVECs. In addition, it protects cardiac cells and significantly inhibits inflammation via modulating molecular signaling pathways TLR4/PTEN/AKT/mTOR/NF-κB and microRNA (miR-21). Here we show that crocin not only acts as a direct free radical scavenger but also modifies the gene expression profiles of HUVECs and protects mice hearts with anti-inflammatory action under oxidative stress.

Gardenia jasminoides Ellis (Zhi-zi), which belongs to the Rubiaceae family, has been used mainly with its fry fruit for thousands of years, and it is an herb with the homology of medicine and food. In traditional Chinese medicine (TCM) theory, Zhi-zi can be used for \"Quench Xiaoke\", meaning for therapying diabetes in modern medicine. Based on numerous pharmacological studies, Gardenia jasminoides Ellis (Zhi-zi), and its ingredients, mainly including iridoid glycosides and carotenoids (crocins), possess potent antioxidant and anti-inflammatory properties, and can promote insulin secretion and sensitization, stimulate GLP-1 pathway activity, and protect islet β cells and the macro- and microvascular systems. These properties are the primary reasons why Zhi-zi and its ingredients are effective in reducing glucose levels, treating diabetes, and preventing its complications. This review aims to summarize the current situation and the advances of the studies on the mechanisms of Zhi-zi in improving diabetes and its complications, and it is expected to provide useful and systematic references for future research and clinical application of Zhi-zi and its active ingredients in the therapy of diabetes and complications.

Crocins are bioactive natural products that rarely exist in plants. High costs and resource shortage severely limit its development and application. Synthetic biology studies on crocins are of considerable global interest. However, the lack of high-efficiency genetic tools and complex cascade biocatalytic systems have substantially hindered progress in crocin biosynthesis-related research. Based on mutagenesis, a high-efficiency GjCCD4a mutant (N212m) was constructed with a catalytic efficiency that was 25.08-fold higher than that of the wild-type. Solubilized GjCCD4a was expressed via fusion with an MBP tag. Moreover, N212m and ten other genes were introduced into Escherichia coli for the de novo biosynthesis of five crocins. The engineered E57 strain produced crocins III and V with a total yield of 11.50 mg/L, and the E579 strain produced crocins I-V with a total output of 8.43 mg/L at shake-flask level. This study identified a marvelous genetic element (N212m) for crocin biosynthesis and achieved its de novo biosynthesis in E. coli using glucose. This study provides a reference for the large-scale production of five crocins using E. coli cell factories.

BACKGROUND: Parkinson\'s disease (PD), the second most prevalent neurological disorder in the elderly, manifests with distinctive movement disorders, including bradykinesia, resting tremor, and stiffness. With a progressive course, current treatment strategies primarily target symptomatic relief. Crocin is a chemical compound isolated from the dry stigma of Crocus sativus, and has demonstrated neuroprotective properties.
OBJECTIVE: This study explores the impact of crocin on movement disorders and neuronal oxidative DNA damage in PD patients.
METHODS: Conducted as a randomized, blinded, and controlled trial, this research focused on patients aged 30 to 80 with idiopathic PD. Using the second and third parts of the movement disorder society-unified PD rating scale (MDS-UPDRS), aspects of daily life activity and movement disorders were assessed before and after an 8-week intervention. Patients in the crocin groups received capsules containing 30 mg of crocin twice daily. Additionally, the 8-hydroxy-2-deoxydiguanosine (8-OHdG) to urinary creatinine ratio (8-OHdG/uCr) was measured to evaluate neuronal oxidative DNA damage.
RESULTS: Out of the initially evaluated 164 patients, 30 were randomly assigned to each group, with 53 subjects completing the study. Within-group analysis revealed a significant improvement in the second and third parts of MDS-UPDRS after 8 weeks of crocin intervention (P < 0.05). However, the 8-OHdG/uCr did not show significant changes. The well-tolerated daily dose of 60 mg of crocin demonstrated minimal side effects.
CONCLUSIONS: This study establishes the efficacy of crocin in enhancing daily life activities and mitigating movement disorders, suggesting its potential as a supplementary intervention alongside conventional PD medications.

UNASSIGNED: Crocin is a water-soluble carotenoid compound present in saffron (Crocus sativus L.), known for its wide range of pharmacological activities, including cardioprotective, hepatoprotective, anti-tumorigenic, anti-atherosclerosis, and anti-inflammatory effects.
UNASSIGNED: The instability of crocin, its low miscibility with oils, and poor bioavailability pose challenges for its pharmaceutical applications. This study aimed to design and prepare a crocin-phospholipid complex (CPC) and assess its physicochemical properties.
UNASSIGNED: The study investigated the formation of the complex and its binding affinity through molecular docking. Molecular dynamics (MD) simulations were conducted to find the optimal molar ratio of crocin to phospholipid for the complex\'s preparation. The CPC was produced using the solvent evaporation method. Techniques such as X-ray diffraction (XRD), Fourier-transform infrared spectroscopy (FTIR), field-emission scanning electron microscopy (FE-SEM), nuclear magnetic resonance (NMR), and solubility studies were utilized to characterize and confirm the formation of CPC. Additionally, the in vitro antioxidant activity of crocin and CPC was evaluated.
UNASSIGNED: Molecular dynamic simulations explored molar ratios of 1: 1, 1: 1.5, and 1: 2 for crocin to phospholipid. The ratio of 1: 2 was found to be the most stable, exhibiting the highest probability of hydrogen bond formation. Molecular docking, FTIR, and NMR studies indicated hydrogen bond interactions between crocin and phospholipid, confirming CPC\'s formation. XRD and FE-SEM analyses showed a decrease in crocin\'s crystallinity within the phospholipid complex. Furthermore, the solubility of crocin in n-octanol was enhanced post-complexation, indicating an increase in crocin\'s lipophilic nature.
UNASSIGNED: Phospholipid complexation emerges as a promising technique for enhancing the physicochemical characteristics of crocin.

Crocin is a carotenoid compound in saffron with anti-cancer properties. However, its therapeutic application is limited by its low absorption, bioavailability, and stability, which can be overcome through nanocarrier delivery systems. This study used surface-modified Nano-crystalline cellulose (NCC) to deliver crocin to cancer cells. NCC modified with CTAB were loaded with crocin and then conjugated with folic acid (NCF-CR-NPs). The synthesized nanoparticles (NPs) were characterized using FTIR, XRD, DLS, and FESEM. The crystallinity index of NCC was 66.64%, higher than microcrystalline cellulose (61.4%). The crocin loading and encapsulation efficiency in NCF-CR-NPs were evaluated. Toxicity testing by MTT assay showed that NCF-CR-NPs had higher toxicity against various cancer cell lines, including colon cancer HT-29 cells (IC50 ~ 11.6 μg/ml), compared to free crocin. Fluorescent staining, flow cytometry, and molecular analysis confirmed that NCF-CR-NPs induced apoptosis in HT-29 cells by increasing p53 and caspase 8 expression. The antioxidant capacity of NCF-CR-NPs was also evaluated using ABTS and DPPH radical scavenging assays. NCF-CR-NPs exhibited high free radical scavenging ability, with an IC50 of ~ 46.5 μg/ml for ABTS. In conclusion, this study demonstrates the potential of NCF-CR-NPs to deliver crocin to cancer cells effectively. The NPs exhibited enhanced anti-cancer and antioxidant activities compared to free crocin, making them a promising nanocarrier system for crocin-based cancer therapy.

Crocus sativus L. is a perennial crop for its valuable active compounds. Plant-associated microbes impact on the quality and efficacy of medicinal herbs by promoting bioactive components accumulation. However, how microbes influence the accumulation of bioactive components in saffron have not been well studied. Here, the microbiome in C. sativus derived from 3 core production areas were deciphered by 16S rDNA sequencing and the relationship between endophytes and bioactive ingredients were further investigated. The main results are as follows: (1) Both Comamonadaceae and Burkholderiaceae were positively correlated with the content of bioactive components in the stigmas. (2) The synthesis of crocin was positively correlated with Xanthomonadaceae, negatively correlated with Lachnospiraceae and Prevotellaceae. Therefore, further investigation is required to determine whether Xanthomonadaceae plays an unknown function in the synthesis of crocin. These findings provide guidelines for disentangling the function of endophytes in the production of bioactive ingredients and thus for microbe-mediated breeding.