UP3005, a Botanical Composition Containing Two Standardized Extracts ofUncaria gambirandMorus alba, Improves Pain Sensitivity and Cartilage Degradations in Monosodium Iodoacetate-Induced Rat OA Disease Model

Abstract

Osteoarthritis (OA) is a multifactorial disease primarily noted by cartilage degradation in association with inflammation that causes significant morbidity, joint pain, stiffness, and limited mobility. Present-day management of OA is inadequate due to the lack of principal therapies proven to be effective in hindering disease progression where symptomatic therapy focused approach masks the actual etiology leading to irreversible damage. Here, we describe the effect of UP3005, a composition containing a proprietary blend of two standardized extracts from the leaf of Uncaria gambir 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. Pain sensitivity, micro-CT, histopathology, and glycosaminoglycans (GAGs) level analysis were conducted. Diclofenac at 10 mg/kg was used as a reference compound. UP3005 resulted in almost a complete inhibition in proteoglycans degradation, reductions of 16.6% (week 4), 40.5% (week 5), and 22.0% (week 6) in pain sensitivity, statistically significant improvements in articular cartilage matrix integrity, minimal visual subchondral bone damage, and statistically significant increase in bone mineral density when compared to the vehicle control with MIA. Therefore, UP3005 could potentially be considered as an alternative therapy from natural sources for the treatment of OA and/or its associated symptoms.

<b><i>Morus alba</i></b> L. Stem Extract Attenuates Pain and Articular Cartilage Damage in the Anterior Cruciate Ligament Transection-Induced Rat Model of Osteoarthritis

“…As a result, alternative treatments that offer a superior safety profile such as plant-based dietary supplements have recently become the focus of attention in OA research [10,11] . For instance, medicinal plants containing phenolic compounds reportedly have a protective effect against the progression of OA as well as alleviating OA pain [10][11][12] .…”

“…In Thailand, major parts of mulberry trees that are used are the leaves and fruits, while the other parts are left unused. This plant has been reported to have anti-nociceptive, anti-inflammatory and antioxidant activities with these pharmacological properties derived from extracts of the leaves [13,14] , twigs [15] and root barks [12,15,16] . However, little attention has been paid to the stem, despite the fact that it has a much higher content of oxyresveratrol compared with twigs and leaves, respectively [17] .…”

Evaluation of Toxicity and Antimicrobial Activity of an Ethanolic Extract from Leaves of Morus alba L. (Moraceae)

“…Diels-Alder adducts and prenylated flavanones isolated from the root bark of M. alba showed cytotoxic activity against human tumor cells [ 13 ]. In another study, a composition containing a blend of standardized extracts from Uncaria gambir leaves and M. alba root bark was reported to be useful as an alternative therapy for alleviating osteoarthritis and its associated symptoms [ 14 ]. Kim et al [ 15 ] reported that extracts from M. alba leaves and fruits were able to reduce cognitive deficits in mice induced by the high-fat diet.…”

Phytochemical Analysis and Anti-Inflammatory and Anti-Osteoarthritic Bioactive Potential of Verbascum thapsus L. (Scrophulariaceae) Leaf Extract Evaluated in Two In Vitro Models of Inflammation and Osteoarthritis

“…In fact, pharmacological therapies, with anti-inflammatory and chondroprotective effects, aim at reducing pain and preserving matrix integrity, thus improving the patient’s joint activity and quality of life. Recently, several studies have suggested a potential adjuvant role for natural extracts, such as curcumin, resveratrol, pomegranate, as well as genistein and soy protein, on OA progression, in terms of moderating chondrocyte inflammation and following cartilage injury resulting in the improvement of joint pain [ 5 , 6 ]. Moreover, the traditional use of Harpagophytum procumbens (Burch.)…”