Crocus Sativus (Saffron): An Immunoregulatory Factor in the Autoimmune and Non-autoimmune Diseases.

It has been reported that patients with arthritis, osteoarthritis, atherosclerosis, coronary artery disease, brain ischemia, diabetes, and inflammatory bowel disease (IBD) suffer from pro-inflammatory and oxidant related responses. Therefore, anti-inflammatory and anti-oxidant therapies are used to improve the quality of life of the patients. Saffron is a herbal drug that has immunomodulatory and antioxidant properties. Hence, Saffron and its components have been proposed as therapeutic agents for the treatment of the diseases. Therefore, this review article was designed to collect recent information regarding the effects of saffron and its components on the amelioration of the inflammatory symptoms in the autoimmune and non-autoimmune diseases and anti-cancerous effects from 1999 up to now via searching the Pubmed, Google Scholar, and Scopus databases. Due to fact that several investigations have reviewed the roles played by Saffron on autoimmune and non-autoimmune diseases such as multiple sclerosis, mood disorders, and Alzheimer's disease, this review article focuses on other diseases to keep the novelty of the present review for readers.

Crocin alleviates coronary atherosclerosis via inhibiting lipid synthesis and inducing M2 macrophage polarization.

Atherosclerosis is a chronic inflammatory disease arising from an imbalance in lipid levels and the accumulation of cholesterol-laden macrophages in the artery wall. Crocin is an active ingredient of Crocus sativus L. This study established a rat coronary atherosclerosis model induced by vitamin D3 (VD3), to explore the effect of Crocin on lipid metabolism, macrophage polarization and the activity of inflammatory proteins. The results revealed that Crocin decreased blood lipid levels by decreasing the levels of endothelin (ET), total cholesterol (TC), triglyceridelow (TG) and low-density lipoprotein cholesterol (LDL-c), elevating the level of high-density lipoprotein cholesterin (HDL-c). Crocin also inhibited lipogenesis by suppressing the expression of lipogenesis-related proteins and elevating lipid catabolism-related proteins. Moreover, Crocin effectively alleviated inflammation by suppressing the expression of pro-inflammatory cytokines and increasing levels of anti-inflammatory cytokines. We further found that Crocin promoted macrophage polarization to the M2 phenotype by reducing M1 markers (CD40+ and CD11c+) and elevating M2 markers (CD68+ and CD206+). Finally, Crocin strongly inhibited the expression of NF-κB p65 and its translocation into the nucleus. Crocin partially counteracted nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) p65 expression and the nuclei accumulation caused by NF-κB p65 overexpression. Taken together, our research indicated that Crocin inhibited lipogenesis and alleviated the inflammation in a VD3-induced rat coronary atherosclerosis model by promoting M2 macrophage polarization and maybe by inhibiting NF-κB p65 nuclear translocation. This study implicates Crocin as a potential therapeutic strategy for coronary atherosclerosis.

Crocin modulates IL-4/IL-13 signaling and ameliorates experimentally induced allergic airway asthma in a murine model.

Allergic asthma is a chronic respiratory disease with a prevalent T helper (Th2)-mediated immune reaction. Crocin, the major bioactive constituent of saffron, has been reported in multiple studies to have numerous pharmacological activities, including prominent anti-oxidant activities. In the current study, the anti-asthmatic potential of crocin was evaluated. Adult male Swiss Albino mice were administered 10mg of ovalbumin (OVA) mixed with 1mg of aluminum hydroxide intraperitoneally on days 0 and 7 and were administered crocin (25mg/kg) orally daily for 16days. Asthma progression was associated with significant increase in the lung/body weight index, inflammatory cell counts in bronchoalveolar lavage fluid (BALF), lung total protein content, and serious index of lung permeability, indicating pulmonary edema with accumulation of serous fluids within the lungs. Serum lactate dehydrogenase (LDH) activity and lung malondialdehyde (MDA) content were significantly increased, while lung superoxide dismutase (SOD) activity, reduced glutathione (GSH) levels, and serum and lung catalase activities were significantly decreased. These changes reflect significant pulmonary inflammation with concomitant disturbance of oxidant/antioxidant homeostasis. Moreover, tumor necrosis factor (TNF)-α, interleukin (IL)-4, and IL-13 contents in the lung were also significantly high after OVA sensitization. Crocin treatment significantly alleviated the OVA-induced allergic asthma-associated alterations in inflammatory and oxidative stress biomarkers. Crocin enhanced anti-oxidant defenses, reduced the incidence of oxidative stress, and restored pro-inflammatory cytokines to normal levels. Histopathological analysis showed significant lung improvement in crocin-treated mice. In conclusion, crocin showed a significant protective effect against allergic asthma progression, which was associated with down-regulation of inflammatory cytokine expression and restoration of oxidant/antioxidant homeostasis.

Crocetin ester improves myocardial ischemia via Rho/ROCK/NF-κB pathway.

Crocetin ester (CE) is the active ingredient of Crocus sativus L. stigmas and Gardenia jasminoides Ellis fruit. The main purpose of the present study was to investigate the protective effect of CE on isoproterenol (ISO)-induced acute myocardial ischemia (AMI) through Rho/ROCK/NF-κB pathway and explore its underlying mechanism. Administration of CE (25 and 50mg/kg) could significantly reduce the serum contents of pro-inflammatory cytokines including tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1ß) and interleukin-6 (IL-6). In addition, pretreatment with CE attenuated the contents of creatine kinase (CK), malondialdehyde (MDA) and the activities of lactate dehydrogenase (LDH), superoxide dismutase (SOD) in serum. Treatment with CE also improved the histopathological alteration and decreased the ST elevation. Furthermore, CE could ameliorate the cardiac expressions of Cu, Zn-superoxide dismutase (SOD1), MDA5, Rho, ROCK, p-IκB and p-NF-κBp65 in ISO-induced rats. It was assumed that CE might be a new therapeutic candidate for the treatment of AMI possibly through the inhibition of Rho/ROCK/NF-κB pathway.

Production and characterization of monoclonal antibody against Saffron pollen profilin, Cro s 2.

BACKGROUND: Allergy to Saffron (Crocus sativus) pollen has been described in people involved in processing of saffron flower stamens. Profilins have been identified as a pan-allergen in different plant pollens and foods. This molecule is an actin-binding protein with a molecular weight of 12-16 kDa found in eukaryotic species. OBJECTIVE: The aim of this study was to generate monoclonal antibody against Cro s 2 in order to characterize this major allergen of saffron pollen. METHODS: BALB/c mice were immunized to obtain adequate humoral response. Splenocytes were prepared from the immunized animals, mixed with the P3-X63-Ag8.653 myeloma cells and fused by means of PEG 1500. After two weeks of culturing in HAT-containing media, the supernatant from those wells growing hybridomas were screened by ELISA using plates coated with Cro s 2. Cells from positive wells were cloned at least 3 times by limiting dilution. Specificity and cross-reactivity of the mAbs were determined by Western blot analysis and sandwich ELISA. RESULTS: Two stable hybridoma clones secreting mAbs against Cro s 2 were obtained and expanded. The anti-Cro s 2 mAbs were also found to cross-react with other plant profilins. Isotype of this mAb was identified as micro heavy chain and k light chain. CONCLUSION: The anti-Cro s 2 mAb could be a useful tool for characterization and standardization of many pollen and fruit-derived profilins.