crocin and Osteoarthritis

Osteoarthritis (OA) is known to be the most prevalent form of joint disease. We conducted this clinical trial to investigate the effects of KrocinaTM, a natural product containing crocin, on the gene expression of unique transcription factors of various T cell subsets in patients with OA. We collected 40 peripheral blood samples of OA patients receiving Krocina™ and equal number of those who took a placebo (IRCT2015021910507N2, NCT03375814). RNA extraction was performed from the cultured peripheral blood mononuclear cells of the OA patients who received Krocina™ and placebo and SYBR Green Real-time PCR technique was applied to assess the relative gene expression of T-bet, GATA3, ROR-γt, and FOXP3 as the unique transcription factors of various T cell subsets. The relative gene expression of T-bet and ROR-γt insignificantly decreased in the Krocina™ receiving group as compared to the placebo group. In addition, the relative gene expressions of GATA-3 and FOXP3 after the treatment with KrocinaTM showed a significant and insignificant increase, respectively. Moreover, an insignificant decrease was observed in the gene expression of GATA-3 and FOXP3 in the placebo group. A significant and insignificant decrease in the gene expression of T-bet and ROR- γt was detected in the OA patients who received a placebo. GATA-3 is known as a unique transcription factor for the differentiation of T-cells to the Th2 subset. The significant increase in the gene expression of GATA-3 in the patients with OA treated with crocin may suggest the beneficial effect of crocin on shifting towards the Th2 subset and enhancing an anti-inflammatory condition.

Topics: Carotenoids; Forkhead Transcription Factors; GATA3 Transcription Factor; Gene Expression; Humans; Leukocytes, Mononuclear; Nuclear Receptor Subfamily 1, Group F, Member 3; Osteoarthritis; T-Box Domain Proteins

Osteoarthritis (OA) is the most common form of arthritis associated with gradual joint destruction. The current treatment aims to alleviate pain and inflammation and improve the quality of life. Crocin is an active ingredient in saffron, with anti-inflammatory properties. MicroRNAs are small, non-coding RNAs that regulate gene expression. We aimed to evaluate the effect of crocin on the gene expression of microRNA-146a, microRNA-155, microRNA-223, and microRNA-21 in OA patients and compare it with a placebo. This study was approved and registered in the Iranian Registry of Clinical Trials (2015021910507N2) and ClinicalTrials.gov identifier: NCT03375814. Forty OA patients were randomly divided into two equal groups, receiving either crocin or placebo. Peripheral blood samples were collected before and four months after the intervention. The pain was assessed using the visual analog scale, and laboratory tests included C-reactive protein and erythrocyte sedimentation rate. The expression levels of microRNA-146a, microRNA-155, microRNA-223, and microRNA-21 genes were evaluated by SYBR Green real-time PCR. The results showed that the gene expression levels of microRNA-21 and microRNA-155 in patients receiving crocin were significantly decreased and increased, respectively. No significant changes were observed in microRNA-146a and microRNA-223 gene expression levels. In conclusion, crocin's anti-inflammatory role might be partly attributed to its effects on the gene expression of microRNA-21 and microRNA-155.

Topics: Anti-Inflammatory Agents; Carotenoids; Gene Expression; Humans; MicroRNAs; Osteoarthritis; Quality of Life

Osteoarthritis (OA) is the major cause of joint pain and disability. This research was planned to examine the effects of Krocina™, aherbal medicine made of crocin, an ingredient of saffron, in patients with OA. Forty patients suffering from OA were enrolled in our study and randomly divided into two groups, receiving Krocina™ and placebo, and the clinical trial continued for four months.Peripheral blood was taken from all patients and the percentage ofvarious subsets of T cells in addition to the levels of forkhead box protein P3 (FOXP3) and interleukin (IL)-17 were measured by flow cytometry technique. The visualan alog scale (VAS) index analysis decreased significantly in both groups (krocinaTM and placebo) (p<0.05). Assessment of the C-reactive protein (CRP) level in serum showed a significant decrease in the krocinaTM group (p<0.05). Moreover, we found a meaningful increase in the percentage of regulatory T cells (Tregs)cellin samples gathered from Krocina™ group (P=0.02) patients. The mean percentages of T helper (Th) 17 cellsinthe Krocina™ group and CD8+ T cellsin the placebo group patients were also meaningfully reduced (p<0.05). The geometric mean fluorescence intensity (GMFI) for IL-17 showed a significant decrease and increase in Krocina™ and placebo groups, respectively (p<0.05). No noticeable difference was observed in the percentages of Th cells and GMFI-FOXP3 in either group. Treg/Th17 ratio was shifted towards Tregscell in Krocina™ group at the end of the intervention. It is concluded that Krocina™ has immunoregulatory effects on patients with OA, ameliorating the disease.

Topics: Anti-Inflammatory Agents; Carotenoids; Double-Blind Method; Female; Forkhead Transcription Factors; Humans; Immunologic Factors; Interleukin-17; Iran; Male; Middle Aged; Osteoarthritis; Pain Measurement; Phytotherapy; T-Lymphocytes

Osteoarthritis is the most prevalent form of arthritis, affecting a large part of population. It has been reported that muscle weakness and inflammation contribute to osteoarthritis development and progression. Oxidative stress plays important roles in muscle dysfunction and inflammation induction. Crocin, a component of saffron, has excellent antioxidative property. However, it is unclear if crocin can be a potential medicine for osteoarthritis therapy. Osteoarthritis in rats was induced by meniscectomy (MNX) surgery. Then, rats were given with 30 mg/kg of crocin daily for 10 days after osteoarthritis induction. The parameters were determined 7 days after crocin administration. MNX surgery induced osteoarthritis in rats. Crocin treatment significantly decreased osteoarthritis-associated joint pain, decreased muscular interleukin-6 (IL-6) level, and increased citrate synthase (CS) activity, as well as myosin heavy chain (MHC) IIα expression. In addition, crocin reduced muscular lipid peroxidation (LPO) and Nrf2 expression and increased glutathione production and glutathione peroxidase activity. Finally, crocin inhibited the activity of JNK, but not ERK, to repress NF-κB activation and inflammation induction. Crocin attenuates osteoarthritis symptoms through alleviating oxidative stress and inflammation, suggesting that crocin is a potential medicine for osteoarthritis therapy.

Topics: Animals; Arthralgia; Carotenoids; Inflammation; Muscle Weakness; Muscles; Osteoarthritis; Oxidative Stress; Rats

Interleukin-1β-mediated production of matrix metalloproteinases (MMPs) plays a pivotal role in the process of osteoarthritis. Crocin, a pharmacologically active component of Crocus sativus L. (saffron), has been used in Chinese traditional medicine. In this study, we aimed to investigate the effects of crocin on MMP-1, MMP-3 and MMP-13 expression in rabbit chondrocytes induced by interleukin-1β (IL-1β) and in an experimental rabbit model induced by anterior cruciate ligament transection.. Chondrocytes isolated from the articular cartilage of 4-week-old rabbits were cultured and passaged. Confluent chondrocytes were treated with various concentrations of crocin in the presence or absence of IL-1β (10 ng/ml) for 24 h. Quantitative real-time polymerase chain reaction, enzyme-linked immunosorbent assay, and Western blotting were used to investigate the expression of inducible MMP-1, MMP-3 and MMP-13. In addition, the in-vivo effects of crocin were assessed by morphological and histological analysis.. IL-1β markedly upregulated the expression of MMP-1, -3 and -13 in chondrocytes, and this activation was inhibited by co-incubation with crocin in a dose-dependent manner, in contrast with the control group. Moreover, crocin inhibited IL-1β-induced activation of the nuclear factor kappa B pathway through suppressing degradation of inhibitory-kappa-B-α. In-vivo investigations showed that crocin ameliorated cartilage degeneration and that expression of the MMP-1, -3 and -13 genes in cartilage was significantly inhibited by crocin.. Taken together, our findings suggest that the anti-inflammatory activity of crocin may be of potential value in the prevention and treatment of osteoarthritis.

Topics: Animals; Carotenoids; Cartilage, Articular; Cell Survival; Cells, Cultured; Chondrocytes; Female; Interleukin-1beta; Matrix Metalloproteinases; NF-kappa B; Osteoarthritis; Rabbits