Therapeutic Single Compounds for Osteoarthritis Treatment

Abstract

Osteoarthritis (OA) is an age-related degenerative disease for which an effective disease-modifying therapy is not available. Natural compounds derived from plants have been traditionally used in the clinic to treat OA. Over the years, many studies have explored the treatment of OA using natural extracts. Although various active natural extracts with broad application prospects have been discovered, single compounds are more important for clinical trials than total natural extracts. Moreover, although natural extracts exhibit minimal safety issues, the cytotoxicity and function of all single compounds in a total extract remain unclear. Therefore, understanding single compounds with the ability to inhibit catabolic factor expression is essential for developing therapeutic agents for OA. This review describes effective single compounds recently obtained from natural extracts and the possibility of developing therapeutic agents against OA using these compounds.

Role of Physical Exercise and Nutraceuticals in Modulating Molecular Pathways of Osteoarthritis

“…Eupatilin is an O-methylated flavonoid present in Artemisia asiatica (Asteraceae), which suppresses the expression of pro-inflammatory genes in chondrocytes through the reduction of JNK phosphorylation, NF-κB, and MAPK activation pathway [ 28 ].…”

“…Nowadays, other alternative therapeutic interventions to treat OA have come to the fore, such as nutraceuticals, defined as substances that can be considered as a food or part of a food and provides medical or health benefits, including OA prevention and treatment [ 24 , 25 ]. In vitro and in vivo studies showed that epigenetic changes are triggered by micronutrients commonly present in diets (e.g., vitamins, carotenoids, and flavonoids) that might modulate OA mediator pathways [ 26 , 27 , 28 ]. Indeed, myoblasts and chondrocytes seem to share similar pathological targets and pathways and close anatomical location, suggesting the possible existence of a paracrine network [ 29 ].…”

Mechanisms and Pharmaceutical Action of Lipid Nanoformulation of Natural Bioactive Compounds as Efficient Delivery Systems in the Therapy of Osteoarthritis

“…These studies reported the inhibition of TNF-α, IL-6 and IL-1β cytokines, decrease of PGE2 production, interference with eicosanoid biosynthesis and, finally, COX-2 inhibition and inflammation control. In addition, Tamus communis (Dioscoreaceae), Arnica montana (Asteraceae) and Symphytum officinalis (Boraginaceae) could suppress the expression of MMPs and COX-2, mainly through the blocking of the NF-kB pathway [ 85 ].…”

“…Certain anti-inflammatory polysaccharides from animal sources (GLU, CS, HA) and plant bioactive compounds (phenolic acids, flavonoids, phytoalexins, curcumin, tannins, alkaloids) are either orally or IA administered into OA knee, alone or in combination with NSAIDs or analgesics, serving as both prophylactic and therapeutic agents for the protection of the articular cartilage [ 85 ]. Novel formulations can be obtained by their loading in lipid nanostructures that could enhance their anti-inflammatory activity and improve OA therapy, due to better solubility and stability [ 146 ].…”

Xanthohumol Attenuated Inflammation and ECM Degradation by Mediating HO-1/C/EBPβ Pathway in Osteoarthritis Chondrocytes

“…Acacetin can significantly ameliorate IL-1β-induced matrix metalloproteinases expression in chondrocytes by inhibiting NF-κB signaling pathways in mice ( Chen et al, 2020a ). The therapeutic single compounds for osteoarthritis treatment have been reviewed recently ( Lee et al, 2021 ). Xanthohumol (XH), a natural prenylflavonoid isolated from hops and beer, has been preventing hyaluronan overproduction and subsequent response in the early stage of OA ( Stracke et al, 2011 ).…”