Effects of crocin on the enhancement of in vitro neurogenesis: Involvement of Notch and CREB/BDNF signaling pathways.

Objectives: Adult neurogenesis, the process of generating new neurons, continues throughout life. Unfortunately, this process is insufficient in pathological conditions and needs to be promoted. Crocin, the active component of saffron, affects neurogenesis in vivo and in vitro. We aimed to investigate the enhancing effects of crocin on the neurogenesis of adipose-derived mesenchymal stem cells in the presence of retinoic acid, as well as the molecular pathways involved. Materials and Methods: Differentiation capacities and stemness potential of harvested ADSCs were evaluated by differentiating into osteocytes and adipocytes, and expression of mesenchymal CD markers by flow cytometry. The optimum dose of crocin was assessed with an MTT assay. Crocin, retinoic acid, CREB/BDNF, and Notch inhibitors and their combination were added to the culture medium. Jag1, Hes1, Notch, and BDNF gene expression were analyzed by RT-PCR on days 7, 14, and 21, while CREB, DCX, SOX2, and NeuN expression were analyzed by immunofluorescence. Results: Expression of mesenchymal CD markers as well as adipogenic and osteogenic differentiation confirmed the origin and properties of ADSCs. The optimal dose of crocin was 1 mM. Crocin significantly (P<0.05) increased, while inhibitors (DATP&Naphthol) significantly (P<0.05) decreased Jag1, Hes1, Notch, and BDNF expression. Immunofluorescent assessments showed that expression of DCX, BDNF, NeuN, and Sox2 proteins increased significantly (P<0.05) after crocin administration and decreased significantly (P<0.05) after inhibitor administration. Conclusion: Crocin can be used as an enhancer for neural differentiation of MSCs in vitro in the presence of retinoic acid. The mechanism is proposed through Notch and CREB/BDNF signaling pathways.

Exosome odyssey to original line in dental regeneration.

BACKGROUND: Exosomes are bilayer lipid membrane nanoparticles that can contain DNA, mRNA, proteins, etc. Exosomes can be considered safe because they are produced endogenously. Today, utilizing exosomes as a cell-free procedure is considered to be approved in regenerative medicine. They are being used in dental regenerative medicine as well. In this review, we briefly describe exosomes, their characteristics, routes of isolation, and ways of administration. In addition, some therapeutic aspects of these extracellular vesicles, especially in dental degenerative lesions, are also discussed. Based on previous studies, exosome therapy is beneficial in dental regeneration. Exosomes can induce dental pulp regeneration and periodontal regeneration. For instance, they can promote angiogenesis and neurogenesis, or stimulate bone regeneration in the periodontal ligaments and alveolar bone, among many other therapeutic aspects. CONCLUSION: It seems that exosomes will play a significant role in future medicine. Although exosomes are approved as beneficial for therapeutic purposes, it seems there is still a long way to go before they are applied to human treatments. However, perhaps one day it will come to reality.

The Effects of Crocin on Bone and Cartilage Diseases.

Crocin, the main biologically active carotenoid of saffron, generally is derived from the dried trifid stigma of Crocus sativus L. Many studies have demonstrated that crocin has several therapeutic effects on biological systems through its anti-oxidant and anti-inflammatory properties. The wide range of crocin activities is believed to be because of its ability to anchor to many proteins, triggering some cellular pathways responsible for cell proliferation and differentiation. It also has therapeutic potentials in arthritis, osteoarthritis, rheumatoid arthritis, and articular pain probably due to its anti-inflammatory properties. Anti-apoptotic effects, as well as osteoclast inhibition effects of crocin, have suggested it as a natural substance to treat osteoporosis and degenerative disease of bone and cartilage. Different mechanisms underlying crocin effects on bone and cartilage repair have been investigated, but remain to be fully elucidated. The present review aims to undertake current knowledge on the effects of crocin on bone and cartilage degenerative diseases with an emphasis on its proliferative and differentiative properties in mesenchymal stem cells.

Protective effect of crocin on electromagnetic field-induced testicular damage and heat shock protein A2 expression in male BALB/c mice.

OBJECTIVES: Exposure to electromagnetic fields (EMF) emitted from mobile phones may cause a deleterious effect on human health and may affect the male reproductive system. Crocin, a carotenoid isolated from Crocus Sativus L. (Saffron), is a phar¬macologically active component of saffron. So, this study was conducted to investigate the protective effect of crocin on the male reproductive system of 60 day old mice after EMF exposure. MATERIALS AND METHODS: Twenty-four male BALB/c mice were randomly divided into 4 groups: 1. Em group (2100 MHZ); 2. Cr group (50 mg/kg); 3. Em+Cr group (2100 MHZ+50 mg/kg), and 4. Control group. Sperm parameters (count, and abnormal percent), testis weight index, testis volume, seminiferous tubule diam¬eter, germinal epithelium thickness, LH, FSH and testosterone serum level, testicular Heat shock protein A2 (HspA2) immunoreactivity, and apoptosis were evaluated. RESULTS: HspA2 immunoreactivity, apoptosis in the germinal epithelium and abnormal sperm were increased in Em group compared with the control group (P<0.05). Sperm count, LH, and testosterone serum level were decreased in the Em group compared with the control group (P<0.05). These parameters were improved in the Em+Cr group compared with Em group significantly (P<0.05). CONCLUSION: our findings revealed that EMF exposure leads to harmful impressions on the male reproductive system, while crocin can attenuate EMF-induced destructive effects.