Randomized, Double-Blind, Placebo-Controlled Clinical Trial of Concurrent Use of Crocin During Chemoradiation for Esophageal Squamous Cell Carcinoma.

Crocin is the major active carotenoid of saffron (Crocus sativus L.). Its pluripotent effects have led to a growing body of literature investigating its antitumor properties as well as its diverse potentials for mood stabilization, normal tissue protection, and inflammation reduction; However, there is a gap in clinical trials testing this substance in cancer patients. In this randomized, double-blind, placebo-controlled clinical trial, patients with newly diagnosed esophageal squamous cell carcinoma were randomly assigned to either 30 mg/day of crocin or placebo, prescribed during the neoadjuvant chemo-radiotherapy. The primary endpoints were pathological response and toxicity, and secondary endpoints were depression and anxiety levels and survival analysis.

Nutritional Support of Crocin on Neurobehavioral Disabilities Induced by Cisplatin-Based Chemotherapy in Rats.

Cisplatin, a chemotherapy drug containing platinum, is considered a neurotoxic agent. On the other hand, crocin, the primary component of saffron, possesses neuroprotective and antioxidant properties. In this study, 28 healthy adult male Wistar rats weighing 200-250 g were used (6-7 weeks old). Rats were divided into a control group (Ctr), a crocin group (Cro), a cisplatin group (Cis), and a crocin with cisplatin group (Cro + Cis). Rotarod, open field, and shuttle box tests were performed to assess balance, explorative behavior, and avoidance memory. After behavioral testing, the hippocampus was extracted to analyze oxidative stress parameters such as GPx (glutathione peroxidase), SOD (superoxide dismutase), CAT (catalase), and MDA (malondialdehyde) activity. Shuttle box, rotarod, and open field results showed that crocin can substantially mitigate the deleterious effects of cisplatin on avoidance memory, explorative behavior, motor coordination, and balance. Crocin was also able to effectively avoid the negative effects of cisplatin on MDA, GPx, and CAT during the assessment of oxidative indicators, while the beneficial effect of crocin on cisplatin was not statistically significant in terms of SOD level. In conclusion, since free radicals produced by cisplatin are a contributing factor to memory loss and movement disorders, crocin, owing to its antioxidant properties, improved passive avoidance learning as well as motor activity.

Complete microbial synthesis of crocetin and crocins from glycerol in Escherichia coli.

BACKGROUND: Crocin, a glycosylated apocarotenoid pigment predominantly found in saffron, has garnered significant interest in the field of biotechnology for its bioactive properties. Traditional production of crocins and their aglycone, crocetin, typically involves extraction from crocin-producing plants. This study aimed to develop an alternative biosynthetic method for these compounds by engineering the metabolic pathways of zeaxanthin, crocetin, and crocin in Escherichia coli strains. RESULTS: Employing a series of genetic modifications and the strategic overexpression of key enzymes, we successfully established a complete microbial pathway for synthesizing crocetin and four glycosylated derivatives of crocetin, utilizing glycerol as the primary carbon source. The overexpression of zeaxanthin cleavage dioxygenase and a novel variant of crocetin dialdehyde dehydrogenase resulted in a notable yield of crocetin (34.77 ± 1.03 mg/L). Further optimization involved the overexpression of new types of crocetin and crocin-2 glycosyltransferases, facilitating the production of crocin-1 (6.29 ± 0.19 mg/L), crocin-2 (5.29 ± 0.24 mg/L), crocin-3 (1.48 ± 0.10 mg/L), and crocin-4 (2.72 ± 0.13 mg/L). CONCLUSIONS: This investigation introduces a pioneering and integrated microbial synthesis method for generating crocin and its derivatives, employing glycerol as a sustainable carbon feedstock. The substantial yields achieved highlight the commercial potential of microbial-derived crocins as an eco-friendly alternative to plant extraction methods. The development of these microbial processes not only broadens the scope for crocin production but also suggests significant implications for the exploitation of bioengineered compounds in pharmaceutical and food industries.

Does crocin create new hope for the treatment of oral problems? A focus on periodontitis.

According to the World Health Organization (WHO) reports, oral health has an indispensable role in the maintenance of human public health. However, oral problems, especially periodontitis, are known as bad players in this issue. Periodontitis, as the most prevalent oral disease, is a type of chronic illness mediated by bacterial pathogens and immune system reactions, which is linked with the destruction of tooth-protecting tissues, such as alveolar bone and periodontal ligament. Periodontitis has a high prevalence (over 40% in the United States) and can be associated with other systemic ailments, for instance, arthritis, osteoporosis, metabolic syndrome, cancer, respiratory diseases, chronic kidney disease, and Alzheimer's disease. The common treatments for periodontitis are classified into invasive (surgical) and noninvasive (antibiotic therapy, scaling, and root planning) methods; however, these therapies have not reflected enough effectiveness for related patients. New documents inform the beneficial effects of plant-based compounds in healing various disorders, like periodontitis. In conjunction with this subject, it has been revealed that crocin, as an active component of saffron, regulates the balance between osteoclasts and osteoblasts and has a stroking role in the accumulation of the most common collagen in teeth and bone (type 1 collagen). Besides, this carotenoid compound possesses anti-inflammatory and anti-oxidative effects, which can be associated with the therapeutic processes of crocin in this oral disease. Hence, this narrative review study was performed to reflect the reparative/regenerative aspects of crocin agonist periodontitis.

Interaction of aerobic exercise and crocin improves memory, learning and hypocampic tau and neurotrophins gene expression in rats treated with trimethytin as a model of Alzheimer's disease.

INTRODUCTION: Alzheimer's disease (AD) is characterized by progressive cognitive decline and a reduction in hippocampal neurotrophins, in which trimethytin (TMT) infusion causes tangles and neuronal dysfunction, creating an AD-like model in rats. Previous studies have demonstrated that crocin, which has anti-inflammatory properties, can enhance learning, memory acquisition, and cognitive behavior. This study aimed to assess the combined impact of aerobic exercise and crocin on memory, learning, and hippocampal Tau and neurotrophins gene expression in AD-like model rats. METHODS: Forty male Sprague Dawley rats were randomly divided into five groups: (1) healthy control, (2) Alzheimer's control, (3) endurance training, (4) crocin consumption, and (5) endurance training + crocin. Alzheimer's induction was achieved in groups 2-5 through intraperitoneal injection of 8 mg/kg TMT. Rats in groups 3 and 5 engaged in treadmill running three sessions per week, 15-30 min per session, at a speed of 15-20 m/min for eight weeks, and groups 4 and 5 received daily crocin supplementation of 25 mg/kg. RESULTS: Alzheimer's induction with TMT showed significant reduction in memory, learning, NGF, BDNF, and TrkB gene expression, and increase in tau gene expression (all p < 0.05). Notably, endurance training and crocin consumption separately significantly increased memory, learning, NGF, BDNF, and TrkB gene expression while significantly decreasing tau gene expression (all p < 0.05). Importantly, combined endurance training with crocin yielded the most profound effects on memory (p = 0.001), NGF (p = 0.002), BDNF (p = 0.001), and TrkB (p = 0.003) gene expression (p < 0.005), as well as a reduction in tau gene expression (p = 0.001). CONCLUSION: These findings underscore the possible impact of endurance training, particularly when coupled with crocin, on enhancing memory, learning, and neurotrophin gene expression and reducing tau gene expression in Alzheimer's rats. These results highlight the possibility of synergistic interventions for improved therapeutic outcomes.

"Combination treatments of imatinib with astaxanthin and crocin efficiently ameliorate antioxidant status, inflammation and cell death progression in imatinib-resistant chronic myeloid leukemia cells".

BACKGROUND: Imatinib resistance remains a major obstacle in the treatment of chronic myelogenous leukemia (CML). Crocin (CRC) and astaxanthin (ATX) are phytochemicals with anti-cancer properties. AIMS: This study aimed to explore the effects of combination treatment of Imatinib with CRC and ATX on Imatinib-resistant K562 (IR-K562) cells. METHODS AND RESULTS: After the establishment of IR-K562 cells, growth inhibitory activity was determined by the MTT assay. To test the regeneration potential, a colony formation assay was performed. Cell cycle analyses were examined by flow cytometry. Cell injury was evaluated by lactate dehydrogenase (LDH) leakage. Real-time PCR was applied to assess the expression of IL6, TNF-α, STAT3, BAD, CASP3, TP53, and Bcl-2 genes. Caspase-3 activity was determined by a colorimetric assay. Antioxidant activity was measured using a diphenylpicrylhydrazyl (DPPH) assay. After 48 h of treatment, ATX (IC50 = 30µM) and CRC (IC50 = 190µM) significantly inhibited cell proliferation and colony formation ability, induced G1 cell cycle arrest and cell injury, upregulated the expression of apoptosis-associated genes, and downregulated the expression of anti-apoptotic and inflammatory genes. The combination of IM with ATX and/or CRC synergistically reduced cell viability (combination index [CI] < 1). CONCLUSION: Our data suggest that IM shows better therapeutic efficacy at lower doses when combined with ATX and/or CRC.

The effect of crocin-selenium nanoparticles on the cognition and oxidative stress markers of multiple sclerosis patients: a randomized triple-blinded placebo-controlled clinical trial.

The prevalence of cognitive impairment in multiple sclerosis (MS) patients is estimated to be approximately 40-60%. There is an increasing body of evidence regarding the impact of both selenium and crocin as antioxidant agents on cognitive function. In the present study, for the first time, we investigated the effect of crocin-selenium nanoparticles (Cor@SeNs) on cognitive function and oxidative stress markers in MS patients. A triple-blind randomized clinical trial was conducted among 60 MS patients. The participants were randomly divided in a 1:1 ratio to either the Cor@SeNs or placebo group, employing block randomization. During the course of 12 weeks, the participants received Cor@SeNs capsules, containing 5.74 mg crocin and 55 mcg Selenium, or placebo capsules. Cognition assessed using the Persian version of the Brief International Cognitive Assessment for MS (BICAMS) battery. Serum levels of total antioxidant capacity (TAC), glutathione reductase (GR) activity and malondialdehyde (MDA) determined by colorimetric kits. Data analysis was performed in SPSS, version 26. P < 0.05 was considered as the significant range. The mean ± SD of TAC change was 0.03 ± 0.07 mM vs. - 0.03 ± 0.09 mM in intervention and placebo groups, respectively (Time × group effect P: 0.01; effect size: 0.10). The time effect of intervention on the California Verbal Learning Test second edition (CVLT-II) (P < 0.01; effect size: 0.29), CVLT-II-delay (P < 0.01; effect size: 0.29), and the Symbol Digit Modalities Test (SDMT) (P < 0.01; effect size: 0.18) was increasing and significant. In addition, the time effect of intervention on GR activity was significant and decreasing in both groups (P < 0.01; effect size: 0.20). Our results suggested a significant effect of the Cor@SeNs intervention in improving TAC. We also observed a significant improvement in cognitive function in both groups during our study. However, although not statistically significant, a higher amount of change in cognitive function and serum antioxidant markers was noted in the Cor@SeNs group compared to the placebo group. This is the first study on this nano product with low dose of selenium and crocin. More investigations with longer duration and varied doses are suggested.

Therapeutic effects of saffron (Crocus sativus L) on female reproductive system disorders: A systematic review.

The effect of Crocus sativus on several disorders has been discussed or even confirmed, but the efficacy of this herb on the female reproductive system has not been well presented. In this regard, this systematic review comprehensively discussed the efficacy of C. sativus and its main phytochemical compounds on the female reproductive system and its disorders for the first time. In this systematic review, scientific databases, including PubMed, Web of Sciences, Google Scholar, Scopus, and Scientific Information Database, were explored profoundly. In vivo, in vitro, and human studies published until the end of July 2023, which had investigated the pharmacological properties of C. sativus, crocin, crocetin, safranal, or picrocrocin on the female reproductive system, were selected. A total of 50 studies conducted on the effect of C. sativus on the female reproductive system were acquired. These studies confirmed the efficacy of C. sativus or its main phytochemical ingredients in several aspects of the female reproductive system, including regulation of sex hormones, folliculogenesis, ovulation, and protection of the ovary and uterus against several oxidative stress. Several retrieved studies indicated that this herb also can alleviate the symptoms of patients suffering from dysmenorrhea, premenstrual syndrome, menopause, polycystic ovary disease (PCOD), and sexual dysfunction. Furthermore, it is a promising candidate for future studies or even trials regarding ovarian and cervical cancers. This review concluded that C. sativus can improve the symptoms of several female reproductive system disorders, which is particularly due to the presence of phytochemical ingredients, such as crocin, crocetin, and safranal.

Therapeutic potential of saffron in brain disorders: From bench to bedside.

Saffron is a spice derived from the flower of Crocus sativus L., which has been used for centuries as a coloring and flavoring agent, as well as a source of medicinal compounds. Saffron contains various bioactive constituents, such as crocin, crocetin, safranal, picrocrocin, and kaempferol, that have shown potential benefits for human health. Among them, crocin is the most abundant and characteristic constituent of saffron, responsible for its bright red color and antioxidant properties. One of the most promising applications of saffron and its constituents is in the prevention and treatment of neurological disorders, such as depression, anxiety, Alzheimer's disease, Parkinson's disease, and other brain disorders. Saffron and its constituents have been reported to exert neuroprotective effects through various mechanisms, such as modulating neurotransmitters, enhancing neurogenesis, reducing neuroinflammation, regulating oxidative stress, activating the Nrf2 signaling pathway, and modulating epigenetic factors. Several clinical and preclinical studies have demonstrated the efficacy and safety of saffron and its constituents in improving cognitive function, mood, and other neurological outcomes. In this review, we summarize the current evidence on the therapeutic potential of saffron and its constituents in neurological disorders, from bench to bedside. We also discuss the challenges and future directions for the development of saffron-based therapies for brain health.

Ameliorative effect of crocin on post-thaw quality, fertility-associated gene expression and fertilization potential of buffalo (Bubalus bubalis) bull sperm.

Buffalo bull sperm suffer more cryoinjuries due to lipid peroxidation of high structural polyunsaturated fatty acid contents than cattle sperm. Consequently, the post-thaw fertilization potential of buffalo bull sperm is compromised. Crocin is a carotenoid known for its antioxidant potential through scavenging reactive oxygen species. Objectives of the current study were to investigate the effect of crocin addition in the semen extender on post-thaw quality, fertility-associated gene expression and fertilization potential of buffalo bull sperm. Semen samples (n = 32) from four Nili-Ravi buffalo bulls were extended with tris-citric acid extender containing different concentrations of crocin (0 mM; control, 0.5, 1, 1.5 and 2 mM). The extended semen was packed in 0.5 mL French straws (25 × 106 sperm/straw) and cryopreserved in liquid nitrogen. Computer-assisted semen analysis, hypo-osmotic swelling test, normal apical ridge assay, Rhodamine 123, acridine orange, propidium iodide staining, and thiobarbituric acid reactive substances assay were performed to assess sperm motility parameters, plasma membrane integrity, acrosome integrity, mitochondrial membrane potential, DNA integrity, viability, and lipid peroxidation, respectively. Expression levels of sperm acrosome-associated SPACA3, DNA condensation-related PRM1, anti-apoptotic BCL2, pro-apoptotic BAX, and oxidative stress-associated ROMO1 genes were evaluated through qPCR. The fertility of semen doses containing the most potent concentration of crocin (based on optimum post-thaw semen quality) was compared with control during the breeding season. Buffaloes (n = 400; 200/group) were inseminated 24 h after the onset of oestrus and transrectally palpated for pregnancy at least 60 days post-insemination. Results revealed that 0.5 and 1 mM crocin improved sperm post-thaw total motility, plasma membrane integrity, acrosome integrity, mitochondrial membrane potential and viability, and 1 and 1.5 mM crocin enhanced catalase activity and reduced lipid peroxidation compared to control (p < .05). Moreover, 1 mM crocin improved sperm post-thaw progressive motility, kinematics, and DNA integrity, and 1.5 mM crocin enhanced plasma membrane integrity than control (p < .05). Expression levels of SPACA3, PRM1 and BCL2 genes were higher (p < .05) with 1 mM crocin compared to other groups. In contrast, no difference (p > .05) was noticed in expressions of BAX and ROMO1 genes among all groups. The fertility rate of semen doses containing the most potent concentration (1 mM) of crocin was higher (p = .0465) compared to control (56 ± 0.03% vs. 46 ± 0.04%, respectively). In conclusion, 1 mM crocin in the semen extender improves post-thaw quality, fertility-associated gene expression and fertilization potential of buffalo bull sperm.

Protective effect of crocin on peroxidation-induced oxidative stress and apoptosis in IPEC-J2 cells.

The antioxidant properties of crocin are attracting interest, yet the underlying mechanisms by which crocin mitigates oxidative stress-induced intestinal damage have not been determined. This study aimed to elucidate the effects of crocin on oxidative stress, apoptosis, and intestinal epithelial injury in intestinal epithelial cells (IPEC-J2). Using an H2O2-induced oxidative stress model in IPEC-J2 cells, crocin was added to assess its effects. Cell viability and apoptosis were evaluated using methyl thiazolyl tetrazolium assays and flow cytometry. Additionally, oxidative stress markers, such as superoxide dismutase (SOD), catalase (CAT), reactive oxygen species (ROS), and malondialdehyde (MDA), were quantified. We investigated, in which cell oxidation and apoptosis were measured at the gene and protein levels and employed transcriptome analysis to probe the mechanism of action and validate relevant pathways. The results showed that crocin ameliorates H2O2-induced oxidative stress by reducing ROS and MDA levels and by countering the reductions in CAT, total antioxidant capacity, and SOD. Crocin also attenuates the upregulation of key targets in the Nrf2 pathway. Furthermore, it effectively mitigated IPEC-J2 cell apoptosis caused by oxidative stress, as evidenced by changes in cell cycle factor expression, apoptosis rate, mitochondrial membrane potential, and apoptosis pathway activity. In addition, crocin preserves the integrity of the intestinal barrier by protecting tight junction proteins against oxidative stress. Transcriptome sequencing analysis suggested that the mitochondrial pathway may be a crucial mechanism through which crocin exerts its protective effects. In summary, crocin decreases oxidative stress molecule formation, inhibits Nrf2 pathway activity, prevents apoptosis-induced damage, enhances oxidative stress resistance in IPEC-J2 cells, and maintains redox balance in the pig intestine.

Investigation of crocin's protective effect on cyclophosphamide-induced hypothalamic-pituitary-gonadal axis defects in adult female rats.

Cyclophosphamide is a drug used in chemotherapy. However, it has side effects, including changes in reproductive system functioning. Some herbal compounds can reduce the harmful effects of cyclophosphamide. This study aims to investigate the protective role of crocin against changes caused by Cyclophosphamide in ovarian tissue through changes in the expression of genes involved in the hypothalamic-pituitary-gonadal axis. This experimental study was performed on 24 adult female Wistar rats. Mice were divided into four groups (normal saline, 30 mg/kg cyclophosphamide, 100 mg/kg crocin and 30 mg/kg cyclophosphamide, and 200 mg/kg crocin and 30 mg/kg cyclophosphamide). At the end of the treatment period, the hypothalamus and ovaries were also removed to evaluate ob-Rb, ob-Ra, and NPY genes expression using real-time PCR and histological changes in the ovaries. Data were analyzed by SPSS statistical software. The expression of genes, number of follicles, and follicle diameter significantly decreased in the cyclophosphamide-treated groups compared with the control group. In the crocin and cyclophosphamide-treated groups, drug-induced reproductive complications were mitigated. The current findings indicate that by increasing the expression of genes ob-Rb, ob-Ra, and NPY, crocin could modulate the harmful effects of cyclophosphamide.

NMR Study of Water-Soluble Carotenoid Crocin: Formation of Mixed Micelles, Interaction with Lipid Membrane and Antioxidant Activity.

Crocin is a unique water-soluble carotenoid found in crocus and gardenia flowers. Crocin has been shown to have a variety of pharmacological activities, such as antioxidant, anti-cancer, memory improvement, antidepressant, anti-ischemia, blood pressure lowering and aphrodisiac, gene protection and detoxification activities. Due to their amphiphilicity, crocin molecules form concentration-dependent self-associates (micelles) in a water solution. In the present study, using various NMR techniques (T2 relaxation and selective gradient NOESY), we have demonstrated that crocin forms mixed micelles with water-soluble drug delivery system glycyrrhizin and linoleic acid molecules. Note, that the spin-spin T2 relaxation time and NOESY spectroscopy are very sensitive to intermolecular interactions and molecular diffusion mobility. The second purpose of this work was the elucidation of the interaction of crocin with a model lipid membrane using NMR techniques and a molecular dynamics simulation and its effects on lipid oxidation. It was shown that the crocin molecule is located near the surface of the lipid bilayer and effectively protects lipids from oxidation by peroxyl radicals. The role of glycyrrhizin and vitamin C in metal-induced lipid oxidation was also elucidated. The results of this study may be useful for expanding the field of application of crocin in medicine and in the food industry.

Immunocytochemical Analysis of Crocin against Oxidative Stress in Trigeminal Sensory Neurons Innervating the Cornea.

Corneal diseases are a major cause of vision loss, often associated with aging, trauma and disease. Damage to corneal sensory innervation leads to discomfort and pain. Environmental stressors, such as short-wavelength light, can induce oxidative stress that alters mitochondrial function and affects cell and tissue homeostasis, including corneal innervation. Cellular antioxidant mechanisms may attenuate oxidative stress. This study investigates crocin, a derivative of saffron, as a potential antioxidant therapy. In vitro rat trigeminal sensory ganglion neurons were exposed to both sodium azide and blue light overexposure as a model of oxidative damage. Crocin was used as a neuroprotective agent. Mitochondrial and cytoskeletal markers were studied by immunofluorescence analysis to determine oxidative damage and neuroprotection. In vivo corneal innervation degeneration was evaluated in cornea whole mount preparations using Sholl analyses. Blue light exposure induces oxidative stress that affects trigeminal neuron mitochondria and alters sensory axon dynamics in vitro, and it also affects corneal sensory innervation in an in vivo model. Our results show that crocin was effective in preserving mitochondrial function and protecting corneal sensory neurons from oxidative stress. Crocin appears to be a promising candidate for the neuroprotection of corneal innervation.

Nanocrocin Protective Effects on Paraquat-Induced Oxidative Stress in the MRC-5 Cell Line.

Paraquat (PQ) herbicide poisoning is a severe medical problem in developing countries without suitable therapy. This study aimed to investigate the effects of crocin (CCN) and nano crocin (NCCN) on PQ -induced toxicity in the MRC-5 cell line. The results showed that the particle size of NCCN was 140.3 ± 18.0 nm, and the zeta potential of the optimal crocin-loaded niosomes was 23.4 ± 2.8 mV. The NCCN was more effective than CCN in the inhibition of PQ-induced toxicity. Treatment of the MRC-5 cells leads to a decrease in ROS and an increase in SOD, CAT, GPX, and TAC levels in PQ-CCN and PQ-NCCN groups compared with the PQ group. These changes tended to be positively associated with the NCCN compared to CCN. Overall, NCCN was more effective than crocin in treating PQ-induced toxicity in vitro and deserved further preclinical consideration.

Crocin Attenuates NLRP3 Inflammasome Activation by Inhibiting Mitochondrial Reactive Oxygen Species and Ameliorates Monosodium Urate-Induced Mouse Peritonitis.

Crocin is a hydrophilic carotenoid pigment found in the stigma of Crocus sativus or the fruit of Gardenia jasminoides. In this study, we investigated the effects of Crocin on the activation of the nucleotide-binding oligomerization domain, leucine-rich repeat, and pyrin domain containing 3 (NLRP3) inflammasome in J774A.1 murine macrophage cells and monosodium urate (MSU)-induced peritonitis. Crocin significantly inhibited Nigericin-, adenosine triphosphate (ATP)-, MSU-induced interleukin (IL)-1ß secretion, and caspase-1 cleavage without affecting pro-IL-1ß and pro-caspase-1. Crocin also suppressed gasdermin-D cleavage and lactate dehydrogenase release and enhanced cell viability, indicating that Crocin reduces pyroptosis. Similar effects were observed in primary mouse macrophages. However, Crocin did not affect poly(dA:dT)-induced absent in melanoma 2 (AIM2) and muramyl dipeptide-induced NLRP1 inflammasomes. Crocin decreased Nigericin-induced oligimerization and the speck formation of apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC). Crocin also dramatically alleviated the ATP-induced production of mitochondrial reactive oxygen species (mtROS). Finally, Crocin ameliorated the MSU-induced production of IL-1ß and IL-18 and the recruitment of neutrophils during peritoneal inflammation. These results suggest that Crocin suppresses NLRP3 inflammasome activation by blocking mtROS production and ameliorates MSU-induced mouse peritonitis. Thus, Crocin may have therapeutic potential in various NLRP3 inflammasome-related inflammatory diseases.

Network pharmacology-based prediction and experimental verification of the involvement of the PI3K/Akt pathway in the anti-thyroid cancer activity of crocin.

Crocin, a unique water-soluble carotenoid extracted from saffron, is known to exert anticancer activity against various cancer types, including thyroid cancer (TC). However, the detailed mechanism underlying the anticancer effect of crocin in TC needs further exploration. Targets of crocin and targets associated with TC were acquired from public databases. Gene Ontology (GO) and KEGG pathway enrichment analyses were performed using DAVID. Cell viability and proliferation were assessed using MMT and EdU incorporation assays, respectively. Apoptosis was assessed using TUNEL and caspase-3 activity assays. The effect of crocin on phosphatidylinositol-3-kinase (PI3K)/protein kinase B (Akt) was explored by western blot analysis. A total of 20 overlapping targets were identified as candidate targets of crocin against TC. GO analysis showed that these overlapping genes were significantly enriched in the positive regulation of cell proliferation. KEGG results showed that the PI3K/Akt pathway was involved in the effect of crocin against TC. Crocin treatment inhibited cell proliferation and promoted apoptosis in TC cells. Moreover, we found that crocin inhibited the PI3K/Akt pathway in TC cells. 740Y-P treatment reversed the effects of crocin on TC cells. In conclusion, crocin suppressed proliferation and elicited apoptosis in TC cells via inactivation of the PI3K/Akt pathway.

Effect of crocin of Crocus sativus L. on serum inflammatory markers (IL-6 and TNF-α) in chronic obstructive pulmonary disease patients: a randomised, double-blind, placebo-controlled trial.

Different factors, such as inflammation, oxidative stress, extracellular matrix degradation and apoptosis, affect the pathophysiology of chronic obstructive pulmonary disease (COPD), as a progressive disease characterised by permanent airflow limitation. Herbal supplements with anti-inflammatory and antioxidant properties can help treat certain chronic diseases. The current study aimed at investigating the preventive effects of crocin supplementation on the serum concentrations of IL-6, TNF-α, exercise capacity and pulmonary function tests (PFT) in patients with COPD. The present prospective randomised clinical trial equally divided fifty-seven patients with COPD into a placebo and an intervention group, who respectively received a placebo and crocin (15 mg twice day for 12 weeks) as a supplement. ELISA was used to measure serum levels of IL-6 and TNF-α, also PFT and exercise capacity based on 6-min walking distance test (6MWD), which was performed at the beginning and end of the study. Crocin improved the results of PFT (P < 0·05) and 6-MWD (P < 0·001) and exerted preventive effects by increasing the serum levels of IL-6 in patients with COPD compared with those in the placebo group (P < 0·05). Intervention with crocin significantly lowered serum levels of TNF-α at the end of the study (P < 0·01). The present findings suggest crocin supplementation improves exercise capacity and PFT in patients with COPD by reducing serum levels of inflammatory factors.

Genomic and Transcriptomic Analyses Illuminates Unique Traits of Elusive Night Flowering Jasmine Parijat (Nyctanthes arbor-tristis).

The night-flowering Jasmine, Nyctanthes arbor-tristis also known as Parijat, is a perennial woody shrub belonging to the family of Oleaceae. It is popular for its fragrant flowers that bloom in the night and is a potent source of secondary metabolites. However, knowledge about its genome and the expression of genes regulating flowering or secondary metabolite accumulation is lacking. In this study, we generated whole genome sequencing data to assemble the first de novo assembly of Parijat and use it for comparative genomics and demographic history reconstruction. The temporal dynamics of effective population size (Ne ) experienced a positive influence of colder climates suggesting the switch to night flowering may have provided an evolutionary advantage. We employed multi-tissue transcriptome sequencing of floral stages/parts to obtain insights into the transcriptional regulation of nocturnal flower development and the production of volatiles/metabolites. Tissue-specific transcripts for mature flowers revealed key players in circadian regulation and flower development, including the auxin pathway and cell wall modifying genes. Furthermore, we identified tissue-specific transcripts responsible for producing numerous secondary metabolites, mainly terpenoids and carotenoids. The diversity and specificity of Terpene Synthase (TPS) and CCDs (Carotenoid Cleavage Deoxygenases) mediate the bio-synthesis of specialised metabolites in Parijat. Our study establishes Parijat as a novel non-model species to understand the molecular mechanisms of nocturnal blooming and secondary metabolite production.

Transcriptome and metabolome analysis revealed the changes of Geniposide and Crocin content in Gardenia jasminoides fruit.

BACKGROUND: Gardenia jasminoides Ellis is a perennial evergreen shrub of G. jasminoides of Rubiaceae. Geniposide and Crocin are important components in the fruit of G. jasminoides. In addition to being used as medicinal materials, they are also widely used in food, medicine, cosmetics, and other fields. They have high medicinal value, economic value, and ornamental value. However, at present, the utilization rate of G. jasminoides resources is low, mainly focused on germplasm cultivation, primary processing, and clinical pharmacology, and there are few studies on the quality of Gardenia fruit. METHODS AND RESULTS: Based on transcriptome sequencing and metabolic group analysis, the morphological and structural changes of Gardenia fruit with young fruit, middle fruit, and ripe fruit were analyzed, and the formation mechanism and content changes of Geniposide and Crocin in Gardenia fruit were studied. The content of Geniposide decreased with the development of fruit, so did the expression of the main structural gene GES, G10H, and IS in its synthesis pathway, while the content of Crocin increased with the development of fruit, and the expression of the main structural gene CCD, ALDH, and UGT in its synthesis pathway also increased. The relationship between the morphological structure of G. jasminoides and the accumulation of Geniposide and Crocin was summarized. CONCLUSIONS: This study not only provides a theoretical basis for the mining and utilization of Geniposide and Crocin, but also provides a theoretical basis for genetic background for the identification and cloning of bioactive substances in gardenia fruit in future. At the same time, it provides support for increasing the dual-use value of G. jasminoides and breeding excellent germplasm resources.