Cumambrin A from Chrysanthemum boreale attenuates inflammation and oxidative stress through TRIF-dependent signaling inhibition and Nrf2/HO-1 pathway activation.

ETHNOPHARMACOLOGICAL RELEVANCE: Chrysanthemum boreale (C. boreale) is applied in traditional Korean and Chinese medicine to treat fever, inflammation, and infectious diseases. Its dried flowers and aerial parts are often prepared as herbal teas or decoctions to reduce fever and inflammation. Phytochemical analysis attributes its medicinal properties with the presence of sesquiterpene lactones, flavonoids, and essential oils. Cumambrin A is one of the sesquiterpene lactones of C. boreale flowers. Despite numerous biological activities of cumambrin A reported, its effects on inflammation in lipopolysaccharide (LPS)-induced model remains to be determined.

AIM OF THE STUDY: The anti-inflammatory and antioxidant activities of cumambrin A were investigated along with elucidation of its molecular mechanisms in LPS-induced macrophage model.

MATERIALS AND METHODS: Cumambrin A was extracted and isolated from flowers of C. boreale. RAW264.7 macrophages stimulated with LPS were used to examine the effects of cumambrin A on inflammatory mediators such as nitric oxide (NO) and cytokines. Gene and protein expression related to inflammatory signaling were assessed by quantitative real-time PCR and Western blotting.

RESULTS: Cumambrin A significantly suppressed NO production (an IC50 value of 10.25 ± 3.68 μM), reactive oxygen species levels, and proinflammatory mediator expressions. Cumambrin A also effectively downregulated the expressions of signal transducer and activator of transcription (STAT)1, STAT3, and interferon regulatory factor 3 (IRF3) phosphorylation, consistent with inhibition of TIR-domain-containing adaptor-inducing interferon-β (TRIF)-dependent signaling. Moreover, cumambrin A upregulated nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) expression, indicating its antioxidant potential.

CONCLUSION: Our findings demonstrate that cumambrin A attenuates inflammatory activity and reduces oxidative stress via TRIF-dependent pathway modulation and Nrf2/HO-1 activation, respectively. This study provides the mechanistic basis of cumambrin A's bioactivity, supporting its potential as a promising lead compound derived from C. boreale.