Alkannin reverses lipopolysaccharides-induced inflammatory responses by suppressing mitogen-activated protein kinase and nuclear factor kappa-B signalling

Abstract

Rheumatoid arthritis (RA) is an inflammatory disease that seriously affects human health worldwide. Meanwhile, inflammation in RAW264.7 cells could lead to the progression of RA. Alkannin (ALK) is derived from Alkanna tinctoria and is known to exert anti-tumor effects. However, the function of ALK in inflammation of RAW264.7 cells remains unclear. Thus, this research sought to investigate the detailed function of ALK in inflammatory responses of RAW264.7 cells. To induce an inflammatory response, RAW264.7 cells were exposed to lipopolysaccharide (LPS). MTT assay was applied to examine cell viability. Enzyme-linked immunosorbent assay (ELISA) was used to assess the levels of inflammatory cytokines. Furthermore, the mechanism underlying ALK function in inflammatory responses was investigated using RT-qPCR and western blotting. The data revealed that LPS significantly increased the expression of cyclooxygenase 2 (COX-2), Interleukin (IL)-1β, inducible nitric oxide synthase (iNOS), tumor necrosis factor-α (TNF-α), and IL-6, whereas ALK reversed this effect. ALK also restored LPS-induced nuclear factor kappa-B (NF-κB) activation by inhibiting the downregulation of p-inhibitor kappa B alpha (IκBα). LPS elevated p-extracellular regulated protein kinases 1/2 (ERK1/2), phosphorylated p38 (p-p38), and phosphorylated -c-Jun N-terminal kinase (p-JNK) levels, which were markedly decreased in the presence of ALK. In summary, Alkannin attenuated LPS-induced inflammation by inhibiting NF-κB and MAPK signaling. Thus, our research might provide a new theoretical basis for exploring new strategies against RA.

Exploring the Pharmacological Potential of Lithospermum officinale L.: A Review of Phytochemicals and Ethnomedicinal Uses

“…In additi lipids exhibit anti-inflammatory, anticancer, and cardiovascular protective effects [4 These compounds, found abundantly in nature, offer a promising avenue for development of novel therapeutics. allantoin [48] antinociceptive and anti-inflammatory [49 wound healing [50], keratolytic [51] lithosenine [52] -acetyllithosenine [52] Molecules 2024, 29, x FOR PEER REVIEW 6 o acetyllithosenine [52] lycopsamine [53] toxic and potentially carcinogenic due to i hepatotoxicity [54] echimidine [53] toxic and potentially carcinogenic due to i hepatotoxicity [54] lycopsamine [53] Molecules 2024, 29, x FOR PEER REVIEW 6 o acetyllithosenine [52] lycopsamine [53] toxic and potentially carcinogenic due to i hepatotoxicity [54] echimidine [53] toxic and potentially carcinogenic due to i hepatotoxicity [54] toxic and potentially carcinogenic due to its hepatotoxicity [54] echimidine [53] acetyllithosenine [52] lycopsamine [53] toxic and potentially carcinogenic due to it hepatotoxicity [54] echimidine [53] toxic and potentially carcinogenic due to it hepatotoxicity [54] Quinones (naphthoquinones) alkannin [55] anti-inflammatory, antimicrobial, antioxida wound healing, anticancer [56] shikonin [57] anti-inflammatory, antioxidant, antimicrobi wound healing, anticancer, antidiabetic, antiallergic [58][59][60] Phenolics (phenolic acids) rosmarinic acid [48,61,62] anticancer [63], anti-inflammation, antioxidation, antidiabetes, antivirus, antitumor, neuroprotection, hepatoprotecti [64] toxic and potentially carcinogenic due to its hepatotoxicity…”