Osteoarthritis (OA) is a degenerative joint disease characterized by a progressive articular cartilage degradation manifested with significant functional impairment in consort with signs and symptoms of inflammation, stiffness, and loss of mobility. Current OA management is inadequate due to the lack of nominal therapies proven to be effective in hampering disease progression where symptomatic therapy focused intervention masks the primary etiology leading to irreversible structural damage. In this study, we describe the effect of UP1306, a composition containing a proprietary blend of two standardized extracts from the heartwood of Acacia catechu and the root bark of Morus alba, in maintaining joint structural integrity and alleviating OA associated symptoms in monosodium-iodoacetate (MIA)-induced rat OA disease model. Data from pain sensitivity, histopathology, and glycosaminoglycan (GAG) level were analyzed. Diclofenac at 10 mg/kg was used as a reference compound. Ex vivo proteoglycan protection model demonstrated 31.5%, 50.0%, and 54.8% inhibitions of proteoglycan degradations from UP1306 at concentrations of 50, 100, and 200 μg/mL, respectively. The merit of combining two bioflavonoid standardized extracts from A. catechu and M. alba was demonstrated in their Ex vivo synergistic proteoglycan protection activity. In the MIA in vivo OA model, administered orally at 500 mg/kg, UP1306 resulted in reductions of 17.5%, 29.0%, 34.4%, 33.5%, and 40.9% through week 1-5 in pain sensitivity, statistically significant improvements in articular cartilage matrix integrity, and minimal subchondral bone damage. Therefore, UP1306 could potentially be considered as an alternative remedy from natural sources for the management of OA and/or its associated symptoms.
Osteoarthritis (OA) is characterized by progressive articular cartilage degradation. Although there have been significant advances in OA management, to date, there are no effective treatment options to modify progression of the disease. We believe these unmet needs could be bridged by nutrients from natural products. Collagen induced arthritis in rats was developed and utilized to evaluate anti-inflammatory and cartilage protection activity of orally administered botanical composition, UP1306 (50 mg/kg) and Methotrexate (75 µg/kg) daily for three weeks. Objective arthritis severity markers, urine, synovial lavage, and serum were collected. At necropsy, the hock joint from each rat was collected for histopathology analysis. Urinary cartilage degradation marker (CTX-II), pro-inflammatory cytokines (tumor necrosis factor α (TNF-α), interleukin-1β (IL-1β), and IL-6), and proteases (Matrix Metallopeptidase 3 (MMP3) and 13) were measured. Rats treated with UP1306 showed statistically significant improvements in arthritis severity markers, including uCTX-II (91.4% vs. collagen-induced arthritis (CIA)), serum IL-1β, TNF-α, and IL-6 levels as well as synovial MMP-13. The histopathology data were also well aligned with the severity score of arthritis for both UP1306 and Methotrexate. UP1306, a botanical composition that contains a standardized blend of extracts from the heartwood of Acacia catechu and the root bark of Morus alba, could potentially be considered as a dietary supplement product for the management of arthritis.
Although there have been augmented advances in drug discovery, current OA management is inadequate due to the lack of successful therapies proven to be effective in modifying disease progression. For some, the risk outweighs the benefit. As a result, there is a desperate need for safe and efficacious natural alternatives. Here we evaluated a composition from Morus alba, Scutellaria baicalensis, and Acacia catechu in maintaining joint structural integrity and alleviating OA associated symptoms in monoiodoacetate- (MIA-) induced rat OA disease model. Study lasted for 6 weeks. 59.6%, 64.6%, 70.7%, 69.9%, and 70.3% reductions in pain sensitivity were observed for rats treated with the composition from week 1 to week 5, respectively. Statistically significant improvements in articular cartilage matrix integrity (maintained at 57.1% versus MIA + vehicle treated rats) were shown from the modified total Mankin score for animals treated with the composition. The composition showed a statistically significant reduction in uCTX-II level (54.1% reductions). The merit of combining these botanicals was also demonstrated in their synergistic analgesic activity. Therefore, the standardized blend of Morus alba, Scutellaria baicalensis, and Acacia catechu could potentially be considered as an alternative remedy from natural sources for the management of OA and/or its associated symptoms.
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