Biochanin A attenuates zymosan-induced arthritis in mice similarly to 17-β estradiol: an alternative to hormone replacement therapy?

Biochanin A Regulates Key Steps of Inflammation Resolution in a Model of Antigen-Induced Arthritis via GPR30/PKA-Dependent Mechanism

“…To date, BCA has been well-known for its anti-inflammatory effects. By reducing neutrophil recruitment and production of the inflammatory cytokines, BCA attenuated the development of zymosan-induced arthritis in mice (Felix et al, 2020), which correlates with the lower expression of adhesion molecules (VCAM-1, ICAM-1, and E-selectin) in neutrophils treated with BCA in vitro (Ming et al, 2015). However, effects of the BCA on the clearance of neutrophils have not been investigated yet.…”

“…Previous studies have established that BCA induces apoptosis in cancer cells via regulation of a variety of signaling molecules, such as activating the cleavage of caspase-3 and caspase-9, the release of cytochrome c (Hsu et al, 2018), and decreasing expression of antiapoptotic proteins, B-cell lymphoma protein 2 (Bcl-2), and B-cell lymphoma extra-large (Bcl-xL) Mansoor et al, 2011;Puthli et al, 2013). Recently, we showed that BCA induces neutrophil apoptosis in vitro (Felix et al, 2020). In the current study, we demonstrated that the reduction in the accumulation of neutrophils in the arthritic synovial cavity was associated with the apoptosis of these cells and that this mechanism was caspasedependent, as confirmed by the reduction of apoptosis by treatment with a pan-caspase inhibitor, zVAD-fmk.…”

“…In addition to joint pain, neutrophils are the main responsible for tissue damage (Fattori et al, 2016). Previous studies have shown that BCA potentially inhibit pro-inflammatory cytokines production including TNF-α and IFN-γ in neutrophils (Felix et al, 2020) and IL-6 and IL-1β in macrophages (Kole et al, 2011;Qiu et al, 2012). Furthermore, BCA has been described to inhibit neuropathic pain in diabetic rats (Chundi et al, 2016).…”

“…BCA is known for a wide spectrum of pharmacological characteristics, mainly for its anti-inflammatory effects during arthritis and osteoporosis (Felix et al, 2020;Liao et al, 2021), asthma (Ko et al, 2011), and neuropathic pain (Chundi et al, 2016), by inhibiting pro-inflammatory signaling and transcription factors, such as reducing the activation of NF-κB (nuclear factor kappa beta) and blocking the levels of TNF-α (tumor-necrosis factor-alpha), IL-1β (interleukin 1 beta), and IL-2. In addition, the antitumor effect of BCA is correlated with its ability to stimulate cell apoptosis (Puthli et al, 2013;Hsu et al, 2018).…”

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“…In addition, the antitumor effect of BCA is correlated with its ability to stimulate cell apoptosis (Puthli et al, 2013;Hsu et al, 2018). Recently, we showed that BCA induced neutrophilic apoptosis in vitro (Felix et al, 2020). However, BCA's ability to influence pro-resolving pathways is currently lacking.…”