Berberine encapsulated PEG-coated liposomes attenuate Wnt1/β-catenin signaling in rheumatoid arthritis via miR-23a activation

Immunomodulatory effects of berberine on the inflamed joint reveal new therapeutic targets for rheumatoid arthritis management

“…Histologic analysis of joints from rodents with CIA or AIA indicated severe proliferation and hyperplasia of the synovium, with significant infiltration of inflammatory cells, pannus formation, narrowing of joint space, cartilage damage and bone erosion. Of note, berberine treatment inhibited these pathologic events and improved the joint rigidity in both CIA 22‐24 and AIA 25‐29 models.…”

“…In CIA rats, the levels of pro‐inflammatory mediators RANKL, TNF‐α, IL17, IL‐6 and IL‐1β were indicated to be increased in the blood and synovium, and berberine treatment significantly diminished the levels 24 . Similarly, berberine treatment decreased plasma levels of these proinflammatory mediators in AIA rats, which was accompanied with considerable suppression of pathological inflammatory signs and events in the joint 25,27,28 . Further studies on AIA rats showed that berberine reduced bone loss and increased calcium retainability by reducing the proteolytic activity of osteoclasts through reducing RANKL release in the joint region, 28 together with a reduction in the just‐mentioned pro‐inflammatory cytokines 25,27,28 …”

“…24 Similarly, berberine treatment decreased plasma levels of these proinflammatory mediators in AIA rats, which was accompanied with considerable suppression of pathological inflammatory signs and events in the joint. 25,27,28 Further studies on AIA rats showed F I G U R E 1 Schematic view of cellular pathways in the inflamed joint in rheumatoid arthritis that berberine reduced bone loss and increased calcium retainability by reducing the proteolytic activity of osteoclasts through reducing RANKL release in the joint region, 28 together with a reduction in the just-mentioned pro-inflammatory cytokines. 25,27,28 The suppressive effect of berberine on bone erosion is further supported by studies that show berberine can directly attenuate RANKL-mediated osteoclastogenic differentiation by inhibiting the nuclear factor κB (NF-κB) and Akt activation.…”

“…25,27,28 Further studies on AIA rats showed F I G U R E 1 Schematic view of cellular pathways in the inflamed joint in rheumatoid arthritis that berberine reduced bone loss and increased calcium retainability by reducing the proteolytic activity of osteoclasts through reducing RANKL release in the joint region, 28 together with a reduction in the just-mentioned pro-inflammatory cytokines. 25,27,28 The suppressive effect of berberine on bone erosion is further supported by studies that show berberine can directly attenuate RANKL-mediated osteoclastogenic differentiation by inhibiting the nuclear factor κB (NF-κB) and Akt activation. 31,32 RANKL induces the differentiation of osteoclast precursor cells, stimulates bone resorption by osteoclasts, and supports the survival of mature osteoclasts through activating the NF-κB pathway and phosphatidylinositide (PI) 3-kinase/Akt signalling.…”

“…Moreover, berberine can reduce the β‐catenin levels through the up‐regulation of miR‐23a that is found to be an LRP5 inhibitor. These effects further decrease the expression levels of various pro‐inflammatory cytokines (TNF‐α, IL‐1β, IL‐6 and IL‐23) and the release of RANKL, whereby reverse the excessive levels of inflammation, cartilage degradation and bone erosion, as well as pannus formation and immune cells infiltration at the joint space in AIA rats 28 . To sum up, the aforementioned findings revealing the crucial impact of the Wnt1/β‐catenin signalling pathway in RA progression and the inhibitory effect of berberine on this pathway accompanied by amelioration of RA clinical complications suggest the potential of Wnt1/β‐catenin signalling mediators as the effective therapeutic targets for treating RA.…”