Scopoletin‐standardized Morinda elliptica leaf extract suppressed inflammation and cartilage degradation to alleviate osteoarthritis: A preclinical study

Abstract

The effect of scopoletin-standardized Morinda elliptica leaf extract against osteoarthritis was investigated in ex vivo explant culture and preclinical rodent model. Thirty male rats were grouped (n = 6) into untreated osteoarthritis (OA), OA + Diclofenac (5 mg/kg), and OA + extract (200 and 400 mg/kg) and compared with healthy control. Monosodium iodoacetate were injected into the right intra-articular knee joints to induce OA. The rats were evaluated for OA severity via physical (micro-CT and histological observations), biochemical, ELISA, and mRNA expression analysis (for inflammation and cartilage degradation biomarkers), after 28 days of treatment. The extract suppressed glycosaminoglycan release from the cartilage explant in the presence of Interleukin-1β. The 200 mg/kg dose appeared better than 400 mg/kg dose, at reducing cartilage and subchondral bone erosions in OA-induced rats, by significantly down-regulating the collagenases and aggrecanase. The extract dose-dependently reduced serum inflammation biomarkers and increased bone formation biomarkers to near normal levels in the OA-induced rats. M. elliptica leaf scopoletin-standardised extract alleviated OA progression and articular cartilage structure, by ameliorating cartilage degradation, nitric oxide levels, inflammation, bone /cartilage homeostasis, collagenase/aggrecanase activities, chondrocytes survival, subchondral bone structure and integrity.

Epicatechin and scopoletin richMorinda citrifolia(Noni) leaf extract supplementation, mitigated Osteoarthritis via anti-inflammatory, anti-oxidative, and anti-protease pathways

“…The MC400 extract chondro‐protective effect is further evidenced by the histological smooth articular cartilage surface. By suppressing the inflammatory cytokines, the extract subsequently reduced the cartilage degrading proteases, evidenced by the powerfully down‐regulated MMP1, MMP3, MMP13, and ADAMTS4 mRNA expressions in the tibia much better than that reported for Morinda elliptica (Wan Osman et al, ). The MMP1 breakdown ECM, while the MMP3 activates other MMPs, such as MMP1, MMP7, and MMP9 involved in connective tissue remodeling.…”

“…This study investigated the pathways by which scopoletin and epicatechin standardized MC leaf extract help prevent, mitigate or treat OA in cartilage ex‐plant and in vivo studies. The results were discussed in comparison with the earlier reported effect by scopoletin‐standardized Morinda elliptica leaf extract that did not contain epicatechin (Wan Osman, Lau, & Mohamed, ).…”

“…The MC400 extract chondro-protective effect is further evidenced by the histological smooth articular cartilage surface. By suppressing the inflammatory cytokines, the extract subsequently reduced the cartilage degrading proteases, evidenced by the powerfully down-regulated MMP1, MMP3, MMP13, and ADAMTS4 mRNA expressions in the tibia much better than that reported for F I G U R E 7 Summarized pathways by which Morinda citrifolia leaf mitigated osteoarthritis via reducing Nitric oxide (NO) production from chondrocytes to suppress inflammation, metalloproteinases and chondrocytes apoptosis [modified from (Abramson, 2008)] Morinda elliptica (Wan Osman et al, 2017). The MMP1 breakdown ECM, while the MMP3 activates other MMPs, such as MMP1, MMP7, and MMP9 involved in connective tissue remodeling.…”

“…The Diclofenac dose is based on the recommended dose for rats (Hasani, Soljakova, Jakupi, & Ustalar‐Ozgen, ). Osteoarthritis (OA) were induced by intra‐articular injection of monosodium iodoacetate (MIA 3 mg in 50 μl saline) into the right knee joint (Wan Osman et al, ). The extract was dissolved in deionized water and administered daily by oral gavage (2 ml/rat of the accordingly dissolved extract) for 28 days, 14 days after MIA injection (to enable OA development).…”

“…The Diclofenac dose is based on the recommended dose for rats (Hasani, Soljakova, Jakupi, & Ustalar-Ozgen, 2011). Osteoarthritis (OA) were induced by intra-articular injection of monosodium iodoacetate (MIA 3 mg in 50 μl saline) into the right knee joint (Wan Osman et al, 2017).…”