Radix rehmanniae and its active ingredients ameliorate CFA-induced inflammation by attenuating macrophage-mediated localized response and nitrative damage

Abstract

Osteoarthritis(OA)-related Inflammatory pain is a prevalent symptom in degenerative diseases affecting mature individuals, often presenting as persistent joint pain and impaired daily functioning. This pain is closely linked to tissue damage and immune cell infiltration. Targeting macrophage polarization, a process influenced by the local microenvironment emerges as a promising strategy for managing inflammatory pain.

Radix Rehmanniae (RR), also known as Sheng Di Huang in Chinese, is a traditional Chinese medicinal herb that has been utilized for centuries to treat various ailments, including inflammation-related conditions. In recent years, scientific research has been dedicated to comprehending the mechanisms and therapeutic potential of RR and its active compounds in the context of inflammatory pain and OA. However, its immuno-modulatory effects and anti-inflammatory properties in the context of inflammatory pain still need to be explored.

This study examined the in vivo and in vitro anti-inflammatory and antioxidant effects of RR and its active ingredients, as well as the role of macrophage polarization in attenuating OA-related inflammatory pain. Using the CFA-induced pain model, which effectively induces localized inflammation and pain, mirroring the symptomatic profile observed in conditions like OA. The results revealed that RR and its active ingredients had the significant analgesic effect, RR has exhibited the capacity to substantially reduce pain-associated behaviors, including heightened sensitivity to mechanical and thermal stimuli. These effects collectively enhance the overall quality of life for individuals grappling with inflammatory pain.

The production of reactive nitrogen and oxygen species, such as peroxynitrite, can result in oxidative and nitrative stress, which can cause damage to the cellular components. Our research delved into the effects of RR and its active compounds, intending to reduce nitrative damage and oxidative stress. This could aid in safeguarding the tissues from further harm and foster the resolution of inflammation.

Contributions to inflammatory pain and tissue damage are the activation and polarization of macrophages, the pivotal immune cells that regulate inflammation. Macrophages exhibit different activation states, with the M1-like phenotype linked to pro-inflammatory responses and the M2-like phenotype associated with anti-inflammatory processes and tissue repair. RR and its active compounds have demonstrated the ability to modulate macrophage polarization, favoring a transition from the M1-like to the M2-like phenotype. Further in vitro evaluations of RR and active ingredient effects on macrophage polarization were conducted using optimized culture systems. The result suggests that RR's inhibitory effects on macrophage-derived nitrative damage are linked to suppressing the TLR4-MyD88- nuclear factor kappa-light chain enhancer of activated B cells (NF-κB) pathway. Macrophage polarization and antioxidant effects were explored concerning mir155-mediated mechanisms.

In summary, this research highlights that macrophage-induced inflammation leads to localized nitration and assembly, contributing to tissue damage and inflammatory cell infiltration in OA pathogenesis. Targeting macrophage-mediated inflammation offers a promising OA therapeutic strategy. RR and its active ingredients show potential as therapeutic agents to alleviate macrophage-mediated localized inflammatory microenvironments and nitrative damage in OA treatment. Further investigations are warranted to comprehend the precise mechanisms and clinical applicability of RR and its active compounds in managing inflammatory pain and OA.