Inhibition of Osteoarthritis-Related Molecules by Isomucronulatol 7-O-β-d-glucoside and Ecliptasaponin A in IL-1β-Stimulated Chondrosarcoma Cell Model

Abstract

Osteoarthritis (OA) is the common form of arthritis and is characterized by disability and cartilage degradation. Although natural product extracts have been reported to have anti-osteoarthritic effects, the potential bioactivity of Ryupunghwan (RPH), a traditional Korean medicinal botanical formula that contains Astragalus membranaceus, Turnera diffusa, Achyranthes bidentata, Angelica gigas, Eclipta prostrata, Eucommia ulmoides, and Ilex paraguariensis, is not known well. Therefore, the inhibitory effects of single compounds isolated from RPH on the OA-related molecules were investigated using IL-1β-stimulated chondrosarcoma SW1353 (SW1353) cell model. Two bioactive compounds, isomucronulatol 7-O-β-d-glucoside (IMG) and ecliptasaponin A (ES) were isolated and purified from RPH using column chromatography, and then the structures were analyzed using ESI-MS, 1H-NMR, and 13C-NMR spectrum. The expression or amount of matrix metalloproteinase 13 (MMP13), COX1/2, TNF-α, IL-1β or p65 was determined by RT-PCR, Western blot, and enzyme-linked immunosorbent assay (ELISA). RPH pretreatment reduced the expression and amounts of MMP13, and the expression of collagen II, COX1/2, TNF-α, IL-1β or p65, which were increased in IL-1β-stimulated SW1353 cells. IMG reduced the expression of all OA-related molecules, but the observed inhibitory effect was less than that of RPH extract. The other single compound ES showed the reduced expression of all OA-related molecules, and the effect was stronger than that in IMG (approximately 100 fold). Combination pretreatment of both single components remarkably reduced the expression of MMP13, compared to each single component. These synergic effects may provide potential molecular modes of action for the anti-osteoarthritic effects of RPH observed in clinical and animal studies.

<p>Resveratrol Exerts Anti-Osteoarthritic Effect by Inhibiting TLR4/NF-κB Signaling Pathway via the TLR4/Akt/FoxO1 Axis in IL-1β-Stimulated SW1353 Cells</p>

“…Thus, we hypothesized that TLR4/Akt/FoxO1 axis exists in OA and resveratrol may exert anti-osteoarthritic effect, at least in part by enhancing TLR4/Akt/FoxO1 axis, thereby decreasing TLR4 expression and subsequent TLR4/NF-κB signaling pathway suppression. To address this, in the present study, we mimic OA state by stimulating SW1353 cells with IL-1β 29 to verify our hypothesis "in vitro".…”

Cudratricusxanthone O Inhibits H2O2-Induced Cell Damage by Activating Nrf2/HO-1 Pathway in Human Chondrocytes

“…However, despite these various biological activities, prenylated xanthones have not been studied for OA. Previous studies have shown that hypoxia or inflammatory induction of SW1353 chondrocytes stimulated by IL-1β, monosodium iodoacetate (MIA), and H 2 O 2 is known as a representative in vitro model for OA studies [ 20 , 21 , 22 , 23 ]. In this study, we investigated the role of prenylated xanthones, cudratricusxanthone O (CTO), isolated from M. tricuspidata , on the suppression of H 2 O 2 -induced cell damage by promoting the Nrf2/HO-1 pathway in SW1353 cells.…”

Unraveling Natural Products’ Role in Osteoarthritis Management—An Overview

“…The formula contains a number of natural products, such as Astragalus membranaceus, Turnera diffusa, Achyranthes bidentata, Angelica gigas, Eclipta prostrata, Eucommia ulmoides, and Ilex paraguariensis, most of which are traditionally used in folk medicine. The formula was tested in the context of positive properties against OA, via in vitro experiments on cellular IL-1β-stimulated chondrosarcoma, SW1353 cell model [82]. As reported in this recent work, the pre-treatment with RPH had a suppressive effect on the mediators that contributed to the progression of osteoarthritis by inhibiting collagen 2, COX-1-2, MMP-13, TNF-α, and IL-13 expression [82].…”

“…In a recent study, Hong G.U. et al presented the OA modulating potential of a botanical formula, which is particularly common in Korea, mostly well known as Ryupunghwan (RPH) [82]. The formula contains a number of natural products, such as Astragalus membranaceus, Turnera diffusa, Achyranthes bidentata, Angelica gigas, Eclipta prostrata, Eucommia ulmoides, and Ilex paraguariensis, most of which are traditionally used in folk medicine.…”

“…The formula was tested in the context of positive properties against OA, via in vitro experiments on cellular IL-1β-stimulated chondrosarcoma, SW1353 cell model [82]. As reported in this recent work, the pre-treatment with RPH had a suppressive effect on the mediators that contributed to the progression of osteoarthritis by inhibiting collagen 2, COX-1-2, MMP-13, TNF-α, and IL-13 expression [82]. In the case of RPH formula, two components-isomucronulatol 7-O-β-d-glucoside and Ecliptasaponin A (Scheme 2)-were found to be present in higher concentration levels, and Ecliptasaponin A was further found to play a crucial role against OA, even higher than isomucronulatol 7-O-β-d-glucoside (IMG's) [82].…”