Potential of Phytomolecules in Sync with Nanotechnology to Surmount the Limitations of Current Treatment Options in the Management of Osteoarthritis

Abstract

Osteoarthritis (OA), a chronic degenerative musculoskeletal disorder, progressively increases with old age. It is characterized by progressive loss of hyaline cartilage followed by subchondral bone remodelling and inflammaging. To counteract the inflammation, synovium pours various inflammatory and immune mediators along with metabolic intermediates which further worsen the condition. However, even after recognizing the key molecular and cellular factors involved in the progression of OA, only disease-modifying therapies are available such as oral and topical NSAIDs (Non-steroidal anti-inflammatory drugs), Opioids, SNRIs (Serotonin-norepinephrine reuptake inhibitors), etc addressing symptomatic treatment and functional improvement in lieu of suppressing OA progression. Long term use of these therapies leads to various life-threatening complications. Interestingly, mother nature has numerous medicinal plants containing active phytochemicals that can act on various targets involved in the development and progression of OA. Phytochemicals have been used for millennia in traditional herbalism and are promising alternatives with a lower rate of adverse events and efficiency frequently comparable to synthetic molecules. Nevertheless, their mechanism of action in many cases are elusive and/or uncertain. Even though many in vitro and in vivo studies show promising results, clinical evidence is scarce. Studies suggests that, presence of carbonyl group at 2nd, chloro at 6th along with electron withdrawing group at the 7th position exhibited enhanced COX-2 (Cyclo-oxygenase-2) inhibition activity in OA. On the other hand, the presence of a double bond at C2-C3 position of C ring in flavonoids plays an important role in Nrf2 activation. Moreover, with the advancements in the understanding of OA progression, SARs (Structure activity relationships) of phytochemicals and integration with nanotechnology have given great opportunities to develop phytopharmaceuticals. Therefore, in the present review, we have discussed various promising phytomolecules, SAR as well as their nano-based delivery systems for the treatment of OA to motivate the future investigation of phytochemical based drug therapy.