Safranal

Safranal exerts a neuroprotective effect on Parkinson's disease with suppression of NLRP3 inflammation activation.[Pubmed:38683404]

Mol Biol Rep. 2024 Apr 29;51(1):593.

BACKGROUND: Parkinson's disease (PD) is a common central nervous system neurodegenerative disease. Neuroinflammation is one of the significant neuropathological hallmarks. As a traditional Chinese medicine, Safranal exerts anti-inflammatory effects in various diseases, however, whether it plays a similar effect on PD is still unclear. The study was to investigate the effects and mechanism of Safranal on PD. METHODS: The PD mouse model was established by 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine MPTP firstly. Next, the degree of muscle stiffness, neuromuscular function, motor retardation and motor coordination ability were examined by observing and testing mouse movement behavior. Immunofluorescence staining was used to observe the expression of tyrosine hydroxylase (TH). The dopamine (DA) content of the striatum was detected by High-performance liquid chromatography (HPLC). The expression of TH and NLRP3 inflammasome-related markers NLRP3, IL-1beta, and Capase-1 were detected by Real-time Polymerase Chain Reaction (qRT-PCR) and western blotting (WB) respectively. RESULTS: Through behavioral testing, Parkinson's mouse showed a higher muscle stiffness and neuromuscular tension, a more motor retardation and activity disorders, together with a worse motor coordination compared with sham group. Simultaneously, DA content and TH expression in the striatum were decreased. However, after using Safranal treatment, the above pathological symptoms of Parkinson's mouse all improved compared with Safranal untreated group, the DA content and TH expression were also increased to varying degrees. Surprisingly, it observed a suppression of NLRP3 inflammation in the striatum of Parkinson's mouse. CONCLUSIONS: Safranal played a neuroprotective effect on the Parkinson's disease and its mechanism was related to the inhibition of NLRP3 inflammasome activation.

Effects of Crocus sativus and its constituent, safranal, and pioglitazone, on systemic inflammation and oxidative stress induced by paraquat aerosol in rats.[Pubmed:38629099]

Iran J Basic Med Sci. 2024;27(5):640-646.

OBJECTIVES: The effects of Crocus sativus, Safranal, and pioglitazone on aerosolized paraquat (PQ)-induced systemic changes were examined. MATERIALS AND METHODS: Control (Ctrl) and PQ groups of rats were exposed to saline or PQ (27 and 54 mg/m3, PQ-L and PQ-H) aerosols eight times on alternate days. Nine PQ-H groups were treated with dexamethasone (0.03 mg/kg/day, Dexa), two doses of C. sativus extract (20 and 80 mg/kg/day, CS-L and CS-H), Safranal (0.8 and 3.2 mg/kg/day, Saf-L and Saf-H), pioglitazone (5 and 10 mg/kg/day, Pio-L and Pio-H), and the combination of low dose of the pioglitazone and extract or Safranal (Pio + CS and Pio + Saf) after the end of PQ exposure. RESULTS: Interferon-gamma (INF-gamma), interleukin 10 (IL-10), superoxide dismutase (SOD), catalase (CAT), and thiol serum levels were reduced, but tumor necrosis factor (TNF-alpha), malondialdehyde (MDA), and total and differential WBC were increased in both PQ groups (P<0.05 to P<0.001). All measured variables were improved in all treated groups (P<0.05 to P<0.001). The effects of high dose of C. sativus and Safranal on measured parameters were higher than dexamethasone (P<0.05 to P<0.001). The effects of Pio + CS and Pio + Saf treatment on most variables were significantly higher than three agents alone (P<0.05 to P<0.001). CONCLUSION: C. sativus and Safranal improved inhaled PQ-induced systemic inflammation and oxidative stress similar to those of dexamethasone and showed synergic effects with pioglitazone suggesting the possible PPARgamma receptor-mediated effects of the plant and its constituent.

Bacillus subtilis stimulates plant growth and production of bioactive components in saffron.[Pubmed:38598323]

Nat Prod Res. 2024 Apr 10:1-6.

The effects of B. subtilis on the morphology and physiology of saffron were investigated using two types of soils. Three different bacterial suspensions were applied at 14-day intervals to treat saffron. Morphological attributes were recorded, and the amounts of alpha-crocin and Safranal in the stigma extracts were quantified. The longest stigma, petal, and leaf were observed in the treated groups with 10(5) and 10(8) cfu/ml. The highest weight of stigma per corm belonged to the treated groups with 10(2) cfu/ml in unsterile soil and 10(5) and 10(8) cfu/ml in sterile soil. Treatment with 10(2) and 10(8) cfu/ml caused a significant increase in Safranal production in sterile and unsterile peat/perlite. While treatment with 10(5) and 10(8) cfu/ml in sterile peat/perlite and exposure to 10(2) cfu/ml in unsterile peat/perlite soil resulted in an increase in alpha-crocin. The data showed that B. subtlis triggers the morphological and physiological processes in saffron.

Therapeutic effects of saffron (Crocus sativus L) on female reproductive system disorders: A systematic review.[Pubmed:38558480]

Phytother Res. 2024 Apr 1.

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.

Improvement of inhaled paraquat induced lung and systemic inflammation, oxidative stress and memory changes by safranal.[Pubmed:38484848]

Toxicon. 2024 Apr;241:107687.

The effects of Safranal and pioglitazone alone and their combination on inhaled paraquat (PQ)-induced systemic oxidative stress and inflammation as well as behavioral changes were examined in rats. In this study, animals were exposed to saline (Ctrl) or PQ (PQ groups) aerosols. PQ exposed animals were treated with dexamethasone, 0.8 and 3.2 mg/kg/day Safranal (Saf-L and Saf-H), 5 mg/kg/day pioglitazone (Pio), and Saf-L + Pio for 16 days during PQ exposure period. PQ group showed increased numbers of total and differential WBCs in blood and bronchoalveolar lavage fluid (BALF), increased malondialdehyde (MDA), in the serum BALF and brain reduced thiol, catalase (CAT), and superoxide dismutase (SOD) levels compared to the control group (for all, p < 0.001). The escape latency and traveled distance were enhanced, but the time spent in the target quadrant in the probe day and the latency to enter the dark room 3, 24, 48, and 72 h after receiving an electrical shock, (in the shuttle box test) were decreased in the PQ group (p < 0.05 to P < 0.001). In all treated groups, all measure values were improved compared to PQ group (p < 0.05 to p < 0.001). In combination treated group of Saf-L + Pio, most measured values were more improved than the Saf-L and Pio groups (p < 0.05 to p < 0.001). Saf and Pio improved PQ-induced changes similar to dexamethasone but the effects produced by combination treatments of Saf-L + Pio were more prominent than Pio and Saf-L alone, suggesting a potentiating effect for the combination of the two agents.

The CB1 cannabinoid receptors involvement in anti-epileptic effect of safranal on penicillin-induced epileptiform activity in rats.[Pubmed:38464610]

Vet Res Forum. 2024;15(1):35-41.

Neuroprotective effects for natural products are supported by several studies. In this regard, Safranal, a constitute of saffron, has the potential to exert beneficial effects in neuro-logical disorders such as Parkinson's disease, epilepsy, stroke, multiple sclerosis and Alzheimer's disease. Here, we investigated the effect of Safranal on penicillin-induced epileptiform activity. Also, the effects of intracerebroventricular (ICV) microinjection of AM251 as a CB1-cannabinoid receptors antagonist to clarify the possible mechanism of Safranal were evaluated. Epileptiform activity was induced by intra-cortical administration of penicillin (300 IU, 1.50 muL) in urethane-anesthetized rats. Electrocorticographic recordings were used to analyze the frequency and amplitude of spike waves. Intraperitoneal injections of Safranal at doses of 1.00 and 4.00 mg kg(-1) significantly reduced both the number and amplitude of spike waves. The ICV microinjection of AM251 (0.50 mug 2.00 muL(-1)) significantly increased the frequency and amplitude of spike waves. In addition, the anti-epileptic effect induced by administration of Safranal at a dose of 4.00 mg kg(-1) was partially prevented by ICV microinjection of 0.50 mug 2.00 muL(-1) of AM251. The results showed anti-epileptiform activities for Safranal. Central CB1 cannabinergic receptors might be involved in the anti-epileptiform activity of Safranal.

Therapeutic potential of saffron in brain disorders: From bench to bedside.[Pubmed:38446350]

Phytother Res. 2024 Mar 6.

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.

An overview of pharmacological effects of Crocus sativous and its constituents.[Pubmed:38419885]

Iran J Basic Med Sci. 2024;27(4):391-417.

Crocus sativus L. was used for the treatment of a wide range of disorders in traditional medicine. Due to the extensive protective and treatment properties of C. sativus and its constituents in various diseases, the purpose of this review is to collect a summary of its effects, on experimental studies, both in vitro and in vivo. Databases such as PubMed, Science Direct, and Scopus were explored until January 2023 by employing suitable keywords. Several investigations have indicated that the therapeutic properties of C. sativus may be due to its anti-oxidant and anti-inflammatory effects on the nervous, cardiovascular, immune, and respiratory systems. Further research has shown that its petals also have anticonvulsant properties. Pharmacological studies have shown that crocetin and Safranal have anti-oxidant properties and through inhibiting the release of free radicals lead to the prevention of disorders such as tumor cell proliferation, atherosclerosis, hepatotoxicity, bladder toxicity, and ethanol induced hippocampal disorders. Numerous studies have been performed on the effect of C. sativus and its constituents in laboratory animal models under in vitro and in vivo conditions on various disorders. This is necessary but not enough and more clinical trials are needed to investigate unknown aspects of the therapeutic properties of C. sativus and its main constituents in different disorders.

Iron oxide nanoparticles coated with Glucose and conjugated with Safranal (Fe(3)O(4)@Glu-Safranal NPs) inducing apoptosis in liver cancer cell line (HepG2).[Pubmed:38360669]

BMC Chem. 2024 Feb 15;18(1):33.

Magnetic nanoparticles can be considered a reliable tool for targeted drug delivery to cancer tissues. Based on this, in this study, the anticancer effect of iron oxide nanoparticles coated with glucose and conjugated with Safranal (Fe(3)O(4)@Glu-Safranal NPs) on a liver cancer cell line (HepG2) was investigated. Physicochemical properties of nanoparticles were characterized using FT-IR, XRD, VSM, EDS-mapping, SEM and TEM imaging, zeta potential, and DLS analyses. MTT test was used to investigate the inhibitory effect of nanoparticles on cancer and normal cell lines. Also, the reactive oxygen species (ROS) level, the population of apoptotic cells, and cell cycle analysis were evaluated in control and nanoparticle-treated cells. The synthesized particles were spherical, in a size range of 17-49 nm, without impurities, with a surface charge of - 13 mV and hydrodynamic size of 129 nm, and with magnetic saturation of 22.5 emu/g. The 50% inhibitory concentration (IC(50)) of Safranal, Fe(3)O(4), Fe(3)O(4)@Glu-Safranal and Cisplatin drug on liver cancer cells were 474, 1546, 305 and 135 microg/mL, respectively. While, the IC(50) of Fe(3)O(4)@Glu-Safranal for normal cell line was 680 microg/mL. Treating liver cancer cells with nanoparticles significantly increased the population of apoptotic cells from 2.5% to 34.7%. Furthermore, the population of the cells arrested at the G2/M phase increased in nanoparticle-treated cells. Due to the biocompatibility of the constituent compounds of these nanoparticles, their magnetic properties, and their inhibitory effects on cancer cells, Fe(3)O(4)@Glu-Safranal NPs can be further considered as a promising anticancer compound.

Safranal acts as a neurorestorative agent in rats with cerebral ischemic stroke via upregulating SIRT1.[Pubmed:38234630]

Exp Ther Med. 2023 Dec 19;27(2):71.

Safranal is an active ingredient of saffron (Crocus sativus L.). Its neuroprotective role in ischemic stroke (IS) through reducing oxidative stress damage has been widely reported. However, the neurorestorative mechanisms of Safranal are still in the preliminary stage of exploration. the present study is aimed to discuss the effects of Safranal on the recovery of neural function after IS. A middle cerebral artery occlusion/reperfusion (MCAO/R) rat model and an oxygen-glucose deprivation/reoxygenation (OGD/R) model in rat brain microvascular endothelial cells (RBMEC) were established to explore the effects of Safranal on IS in vivo and in vitro. It was found that Safranal dramatically reduced infarct size and Nissl's body loss in rats subjected to MCAO/R. Safranal also promoted neuron survival, stimulated neurogenesis, induced angiogenesis and increased SIRT1 expression in vivo and in vitro. Silencing of SIRT1 reversed the above effects of Safranal on OGD/R-induced RBMEC. The present study indicated that Safranal was a promising compound to exert neurorestorative effect in IS via upregulating SIRT1 expression. These results offer insight into developing new mechanisms in the recovery of neural function after Safranal treatment of IS.

Proteomic and molecular analyses to understand the promotive effect of safranal on soybean growth under salt stress.[Pubmed:38218428]

J Proteomics. 2024 Mar 15;294:105072.

Safranal is a free radical scavenger and useful as an antioxidant molecule; however, its promotive role in soybean is not explored. Salt stress decreased soybean growth and Safranal improved it even if under salt stress. To study the positive mechanism of Safranal on soybean growth, a proteomic approach was used. According to functional categorization, oppositely changed proteins were further confirmed using biochemical techniques. Actin and calcium-dependent protein kinase decreased in soybean root and hypocotyl, respectively, under salt stress and increased with Safranal application. Xyloglucan endotransglucosylase/ hydrolase increased in soybean root under salt stress but decreased with Safranal application. Peroxidase increased under salt stress and further enhanced by Safranal application in soybean root. Actin, RuvB-like helicase, and protein kinase domain-containing protein were upregulated under salt stress and further enhanced by Safranal application under salt stress. Dynamin GTPase was downregulated under salt stress but recovered with Safranal application under salt stress. Glutathione peroxidase and PfkB domain-containing protein were upregulated by Safranal application under salt stress in soybean root. These results suggest that Safranal improves soybean growth through the regulation of cell wall and nuclear proteins along with reactive‑oxygen species scavenging system. Furthermore, it might promote salt-stress tolerance through the regulation of membrane proteins involved in endocytosis and post-Golgi trafficking. SIGNIFICANCE: To study the positive mechanism of Safranal on soybean growth, a proteomic approach was used. According to functional categorization, oppositely changed proteins were further confirmed using biochemical techniques. Actin and calcium-dependent protein kinase decreased in soybean root and hypocotyl, respectively, under salt stress and increased with Safranal application. Xyloglucan endotransglucosylase/ hydrolase increased in soybean root under salt stress but decreased with Safranal application. Peroxidase increased under salt stress and further enhanced by Safranal application in soybean root. Actin, RuvB-like helicase, and protein kinase domain-containing protein were upregulated under salt stress and further enhanced by Safranal application under salt stress. Dynamin GTPase was downregulated under salt stress but recovered with Safranal application under salt stress. Glutathione peroxidase and PfkB domain-containing protein were upregulated by Safranal application under salt stress in soybean root. These results suggest that Safranal improves soybean growth through the regulation of cell wall and nuclear proteins along with reactive‑oxygen species scavenging system. Furthermore, it might promote salt-stress tolerance through the regulation of membrane proteins involved in endocytosis and post-Golgi trafficking.

Network Pharmacology Integrated Molecular Docking and Dynamics to Elucidate Saffron Compounds Targeting Human COX-2 Protein.[Pubmed:38138161]

Medicina (Kaunas). 2023 Nov 22;59(12):2058.

Background and Objectives: Cyclooxygenase-2 (COX-2) is mostly linked to inflammation and has been validated as a molecular target for treating inflammatory diseases. The present study aimed to identify novel compounds that could inhibit COX-2, which is associated with various diseases including inflammation, and in such a scenario, plant-derived biomolecules have been considered as attractive candidates. Materials and Methods: In the present study, physiochemical properties and toxicity of natural compounds/drugs were determined by SWISSADME and ProTox-II. In the present study, the molecular docking binding features of saffron derivatives (crocetin, picrocrocin, quercetin, Safranal, crocin, rutin, and dimethylcrocetin) against human COX-2 protein were assessed. Moreover, protein-protein interactions, topographic properties, gene enrichment analysis and molecular dynamics simulation were also determined. Results: The present study revealed that picrocrocin showed the highest binding affinity of -8.1 kcal/mol when docked against the COX-2 protein. PROCHECK analysis revealed that 90.3% of the protein residues were found in the most favored region. Compartmentalized Protein-Protein Interaction identified 90 interactions with an average interaction score of 0.62, and the highest localization score of 0.99 found in secretory pathways. The Computed Atlas of Surface Topography of Proteins was used to identify binding pockets and important residues that could serve as drug targets. Use of WEBnmalpha revealed protein dynamics by using normal mode analysis. Ligand and Receptor Dynamics used the Molecular Generalized Born Surface Area approach to determine the binding free energy of the protein. Gene enrichment analysis revealed that ovarian steroidogenesis, was the most significant enrichment pathway. Molecular dynamic simulations were executed for the best docked (COX-2-picrocrocin) complex, and the results displayed conformational alterations with more pronounced surface residue fluctuations in COX-2 with loss of the intra-protein hydrogen bonding network. The direct interaction of picrocrocin with various crucial amino-acid residues like GLN(203), TYR(385), HIS(386 and 388), ASN(382), and TRP(387) causes modifications in these residues, which ultimately attenuates the activity of COX-2 protein. Conclusions: The present study revealed that picrocrocin was the most effective biomolecule and could be repurposed via computational approaches. However, various in vivo and in vitro observations are still needed.

A Combined Gas and Liquid Chromatographic Approach for Quality Evaluation of Saffron-Based Food Supplements.[Pubmed:38002129]

Foods. 2023 Nov 9;12(22):4071.

Considering the interest in the bioactive properties of saffron (Crocus sativus L.), as well as its limited production and high price, saffron-based food supplements (SFS) are highly susceptible to adulteration. However, their complex composition and the wide variety of potential fraudulent practices make the comprehensive assessment of SFS quality a challenging task that has been scarcely addressed. To that aim, a new multianalytical strategy based on gas chromatography coupled to mass spectrometry (GC-MS) and liquid chromatography with diode array detection coupled to mass spectrometry (HPLC-DAD-MS) was developed and validated in order to detect different frauds affecting SFS. Dried saffron stigmas and a commercial standardized saffron extract (affron((R))) were selected as reference samples (RS) to obtain an authenticity profile, which was further used to evaluate the quality of 17 SFS. Up to 17 crocins and crocetins, 5 kaempferol glycosides, picrocrocin (determined for the first time by GC-MS), Safranal, furanone and isophorone-related compounds were determined in RS. Safranal and crocins were identified in all SFS except for one sample. However, discrepancies with the content declared were detected in 65% of the cases. Moreover, this multianalytical methodology also allowed identifying undeclared additives and the non-declared addition of vegetable sources other than saffron.