Overview of Anti-Inflammatory and Anti-Nociceptive Effects of Polyphenols to Halt Osteoarthritis: From Preclinical Studies to New Clinical Insights

Abstract

Knee osteoarthritis (OA) is one of the most multifactorial joint disorders in adults. It is characterized by degenerative and inflammatory processes that are responsible for joint destruction, pain and stiffness. Despite therapeutic advances, the search for alternative strategies to target inflammation and pain is still very challenging. In this regard, there is a growing body of evidence for the role of several bioactive dietary molecules (BDMs) in targeting inflammation and pain, with promising clinical results. BDMs may be valuable non-pharmaceutical solutions to treat and prevent the evolution of early OA to more severe phenotypes, overcoming the side effects of anti-inflammatory drugs. Among BDMs, polyphenols (PPs) are widely studied due to their abundance in several plants, together with their benefits in halting inflammation and pain. Despite their biological relevance, there are still many questionable aspects (biosafety, bioavailability, etc.) that hinder their clinical application. This review highlights the mechanisms of action and biological targets modulated by PPs, summarizes the data on their anti-inflammatory and anti-nociceptive effects in different preclinical in vitro and in vivo models of OA and underlines the gaps in the knowledge. Furthermore, this work reports the preliminary promising results of clinical studies on OA patients treated with PPs and discusses new perspectives to accelerate the translation of PPs treatment into the clinics.

Chinese herbal compound Xinfeng capsule inhibits cartilage extracellular matrix degradation and inflammation in osteoarthritis by modulating circ_0032131 and the miR-502-5p/TRAF2 axis

“…A previous study reported that quercetin could alleviate osteoarthritis in rats by inhibiting in ammation reaction and apoptosis of chondrocytes [32] . Because of its anti-in ammatory and antiinjurious qualities, formononetin may offer a great deal of promise in the treatment of OA [33] . Kaempferol can further protect bones by reducing in ammation, osteoclast autophagy, oxidative stress, and osteoblast apoptosis [34] .…”

Protective and Pain-Killer Effects of AMC3, a Novel N-Formyl Peptide Receptors (FPRs) Modulator, in Experimental Models of Rheumatoid Arthritis

“…Our findings highlighted the beneficial properties of AMC3 on changes in the RA chondrocytic gene expression profile induced by pro-inflammatory IL-1β. Especially since its inhibitory effects are emerged through an iNOS overproduction, an enzyme primarily linked with the chronic and progressive inflammation [ 54 ]; on COX-2, a remarkable enzyme involved in prostaglandin biosynthesis—in particular, that of Prostaglandin E 2 (PGE 2 ), which is responsible for a matrix metalloproteinase unbalance [ 55 ]; and an increase in the expression of the angiogenic factor VEGF-A [ 56 ], that contributes to inflammatory hyperalgesia [ 57 , 58 ], effects potentially promoted by the suppression of NF-κB activity [ 59 ]; as well as of the influence exerted by the activation of these receptors on MAPK pathways, including ERK, p38 MAPK, and JNK [ 60 ]. The present results are consistent with the data reported in the literature about the FPR2-mediated anti-inflammatory and pain-relieving effects of two endogenously generated agonists, like Annexin1 (ANXA1) [ 61 , 62 ] and lipoxins (LX) A4 [ 63 ].…”

“…Angiogenic activity amplifies inflammation, joint damage, and pain [ 69 , 70 , 71 , 72 , 73 ]. In recent years, accumulating evidence has suggested the pathological involvement of VEGF-A and its signaling pathways in the disease progression and associated pain in various rheumatic diseases, including RA, applying this growth factor as a hallmark of chronic pain and intensifying the study of VEGF-A and its cognate receptors, VEGFR-1 and VEGFR-2, as a therapeutic target for pain treatment [ 57 , 74 ].…”

A standardized nutraceutical supplement contributes to pain relief, improves quality of life and regulates inflammation in knee osteoarthritis patients; A randomized clinical trial

“…Extensive research has examined the effects of individual polyphenols (i.e. resveratrol, curcumin, quercetin) in vitro , in vivo , as well as in some clinical trials, on OA settings [ 12 , 13 ]. Of interest is the possible synergistic action of polyphenols in restraining OS and inflammation and eventually alleviating pain, stiffness and edema in OA patients [ 14 ].…”