Osteoarthritis (OA) is a leading cause of musculoskeletal disorders that mainly affects the elderly
population. Some herbal medicines have the potential to alleviate the pain associated with OA and improve
physical activity mostly through anti-inflammatory and anti-oxidative properties. The aim of this study was to
investigate the effects of herbal medicines, especially topical types, on osteoarthritis.
In this systematic review, the keywords “osteoarthritis”, “herbal compounds”, “herbal medicine”, “topical drug”,
“hydrogels”, “cream” and “treatment” were used to search publications published from 2010 to 2019 and indexed
in databases including PubMed, SCOPUS, Web of Science and Google Scholar. After screening of titles and
abstracts and detection of duplicate publications, 38 eligible articles were included in the main review. We also
included herbal formulations in vivo.
Bioactive fractions of herbal medicines mostly worked on OA through suppression of interleukin-1β (IL-1β),
inducing nuclear factor-κB (NF-κB) activation by inhibition of inhibitor of NF-κB (IκBα) phosphorylation, IκBα
degradation, p65 phosphorylation, and p65 nuclear translocation, downregulation of NF-κB targets including
COX-2 and MMPs, upregulation of collagen type II, cartilage-specific proteoglycans (CSPGs), β1-integrin, and
expression of cartilage-specific transcription factor SOX-9 protein. Noticeably, herbal medicines do not produce
desirable effects, thereby using their combinations with other therapeutic agents seem to exert substantial clinical
Herbal gels have demonstrated robustly significant healing effects on knee pain, stiffness and mobility. It is worth
considering that because OA is a chronic disease, longer duration of the studies/trials would even lead to obtaining
more reliable judgments regarding topical treatment tolerability, safety and efficacy and clarify local or systemic
adverse effects. Stability and standardization of a defined amount or concentrations of herbal gels would
give promising effects on OA treatment and pain relief.