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Background: Rheumatoid arthritis (RA) is a chronic autoimmune disorder characterized by severe pain, inflammation, and joint deformity. Currently, it affects 1% of the population, with a projection to exceed 23 million cases by 2030. Despite significant advancements, non-steroidal anti-inflammatory drugs (NSAIDs), the first line of treatment, are associated with a range of adverse effects. Consequently, plant-based derivatives are being utilized as an effective alternative. This study evaluates the anti-inflammatory and safety profile of Colchicum luteum hydroethanolic extract (CLHE) in comparison to NSAIDs, with a focus on COX-2 and TNFα inhibition. Methods: CLHE potential was evaluated by phytochemical screening and in vitro bioactivity assays. Toxicity profile was conducted in Human Colon Epithelial Cells (HCEC) and Balb/c mice. Anti-inflammatory potential was explored in a collagen-induced arthritic (CIA) mice model. Bioactive compounds were identified computationally from GCMS data and subjected to docking and simulation studies against COX2 and TNFα. Results: CLHE demonstrated significant antioxidant (IC-50 = 6.78 µg/mL) and anti-inflammatory (IC-50 = 97.39 µg/mL) activity. It maintained 50% cell viability at 78.5 μg/µL in HCEC cells and exhibited no toxicity at a dose of 5000 mg/kg in mice. In the CIA model, CLHE significantly reduced paw swelling, arthritic scoring, C-reactive protein levels, and spleen indices, outperforming ibuprofen. Expression analysis confirmed the downregulation of COX-2, TNFα, and MMP-9. Histopathological analysis indicated the superior efficacy of CLHE compared to ibuprofen in reducing inflammation, synovial hyperplasia, and bone erosion. Computational studies identified compound-15 (CL15), (4-(4,7-dimethoxy-1,3-benzodioxol-5-yl)-2-oxo pyrrolidine-3-carboxylic acid), a non-toxic compound with strong binding affinities to COX-2 (−12.9 KJ/mol), and TNF-α (−5.8 KJ/mol). Conclusions: The findings suggest the potential of Colchicum luteum as a safer, anti-inflammatory, and multi-targeted alternative to NSAIDs for RA treatment. Full article

Bioassay-guided isolation from Camellia sinensis (Theaceae) and Colchicum luteum (Liliaceae) utilizing an in vitro model of protease assay revealed colchicine (1) and caffeine (2) from chloroform fractions, respectively. Their structures were validated using spectral techniques. The purified compounds were further optimized with Gaussian software utilizing the B3LYP functional and 6-31G(d,p) basis set. The result files were utilized to determine several global reactivity characteristics to explain the diverse behavior of the compounds. Colchicine (1) showed a higher inhibition of protease activity (63.7 ± 0.5 %age with IC₅₀ = 0.83 ± 0.07 mM), compared with caffeine (2) (39.2 ± 1.3 %age). In order to determine the type of inhibition, compound 1 was further studied, and, based on Lineweaver–Burk/Dixon plots and their secondary replots, it was depicted that compound 1 was a non-competitive inhibitor of this enzyme, with a Ki value of 0.690 ± 0.09 mM. To elucidate the theoretical features of protease inhibition, molecular docking studies were performed against serine protease (PDB #1S0Q), which demonstrated that compound 1 had a strong interaction with the different amino acid residues located on the active site of this understudied enzyme, with a high docking score of 16.2 kcal/mol. Full article

Colchicum luteum L. is an economically important and endangered medicinal plant of the Kashmir Himalaya. The corm extract is used for the treatment of rheumatism, gout, Behcet’s syndrome, and Alzheimer disease. It is also used extensively in plant breeding programs for the doubling of chromosomes. The present study was carried out for two years (2017–2019) to study the genetic diversity of C. luteum, an economically important and endangered medicinal plant of Kashmir Himalaya. The mapping of genetic diversity of C. luteum was estimated using Mahalanobis D² analysis in the Aharbal (Kulgam), Dhara (Theed), and Baera Baal Hills (Harwan) of Kashmir Valley. The results showed the presence of 5 clusters for 30 populations. There were 17 populations in cluster-1, 1 in cluster-2, 2 in cluster-3, 3 in cluster-4, and 7 in cluster-5. The majority of the population was a group in cluster-1 followed by cluster-5. The maximum intracluster distance (D² values) was observed in cluster-5 (46.55588) followed by cluster-3 (41.61871), and the maximum inter-cluster distance (D² values) was observed in cluster-3 (46.55588) followed by cluster-5 (41.61871). Our study revealed that plant species possessed sufficient genetic diversity among the populations. Cluster-5 showed superiority in plant⁻¹ respect of the maximum mean plant height (28.46 cm), leaf area (47.0 cm²), number of seeds plant⁻¹ (26.85), corm length (5.15 cm), corm width (3.17 cm), fresh weight of corm plant (6.87 g), and dry weight of corm plant (4.81 g) as compared to other clusters. Out of five clusters, cluster-5 is a promising one for better yield and yield attributing traits. The present study revealed that plant species possessed sufficient genetic diversity among the populations as 30 populations were arranged into 5 clusters. Therefore, cluster-5, consisting of seven populations from the undisturbed area of Harwan, and consequently the populations from the same cluster can be multiplied for initiating a conservation and breeding program and can serve as a tool for the scientific community to evolve better contemporary varieties of C. luteum with profitable characters such as more yield of corms, etc. This will assist farmers, particularly the marginal farmers, to alleviate their income. Full article