A Botanical Composition Mitigates Cartilage Degradations and Pain Sensitivity in Osteoarthritis Disease Model

Abstract

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.

Aqueous Extracts of Morus alba Root Bark and Cornus officinalis Fruit Protect against Osteoarthritis Symptoms in Testosterone-Deficient and Osteoarthritis-Induced Rats

“…Furthermore, moracin, a flavonoid from Mores alba root bark protects against IL-1β-induced osteoarthritis by reducing inflammatory factors (TNF-α, IL-6, and COX2) via attenuating the NF-κB pathway [37]. Consistent with previous studies [35][36][37], the present study also demonstrated that MBW attenuated pain and proinflammatory activities in the articular cartilage along with preventing the reduction of serum testosterone concentrations in the testosterone-deficient rats with MIA-induced osteoarthritis. MBW inhibited the BMD loss only in the leg with osteoarthritis, and it was associated with the suppression of osteoarthritis progression.…”

“…It is also reported to facilitate weight loss by suppressing appetite and improving dyslipidemia [33,34]. Oral intake of a mixture of Acacia catechu water extract and Morus alba root bark ethanol extract (50 mg/kg BW) has anti-inflammatory (TNF-α and IL-1β), collagenase (MMP-13) inhibitory, and articular cartilage protective activities in MIA-induced arthritis [35,36]. Furthermore, moracin, a flavonoid from Mores alba root bark protects against IL-1β-induced osteoarthritis by reducing inflammatory factors (TNF-α, IL-6, and COX2) via attenuating the NF-κB pathway [37].…”

Calcitonin protects rat chondrocytes from IL‑1β injury via the Wnt/β‑catenin pathway

“…Osteoarthritis (OA) is a degenerative joint disease, pathologically characterized by the progressive loss of cartilage, osteophyte formation, subchondral sclerosis, matrix degradation and matrix synthesis imbalance (1–3). Symptoms of OA include inflammation, stiffness and loss of mobility (1). Currently, OA treatment is challenging due to its multiple etiologies and complex pathological processes (2).…”

UP1306: A Composition Containing Standardized Extracts of Acacia catechu and Morus alba for Arthritis Management

“…These properties of A. catechu and M. alba were indeed translated into beneficial applications for OA when their standardized composition, UP1306, was tested in vitro and in vivo. To mention a few tests, UP1306 was found to cause (a) suppression of inflammation and pain sensitivity in carrageenan induced rat paw edema model [27], (b) modulation of cyclooxygenase and lipoxygenase activities [27], (c) synergistic inhibition of glycosaminoglycan release ex vivo [27], and (d) increased cartilage sparing activities in monoiodoacetate-induced rat OA model [28]. In a randomized and double-blinded placebo-controlled clinical trial, UP1306 administered at 400 mg/day to arthritic subjects showed significant reduction in urinary C-telopeptides of type II collagen (CTX-II), when compared to placebo after 12 weeks of daily supplementation [29].…”