Artocarpus lakoocha Extract Inhibits LPS-Induced Inflammatory Response in RAW 264.7 Macrophage Cells

Abstract

Artocarpus lakoocha Roxb. (AL) has been known for its high content of stilbenoids, especially oxyresveratrol. AL has been used in Thai traditional medicine for centuries. However, the role of AL in regulating inflammation has not been elucidated. Here we investigated the molecular mechanisms underlying the anti-inflammation of AL ethanolic extract in RAW 264.7 murine macrophage cell line. The HPLC results revealed that this plant was rich in oxyresveratrol, and AL ethanolic extract exhibited anti-inflammatory properties. In particular, AL extract decreased lipopolysaccharide (LPS)-mediated production and secretion of cytokines and chemokine, including IL-6, TNF-α, and MCP-1. Consistently, the extract inhibited the production of nitric oxide (NO) in the supernatants of LPS-stimulated cells. Data from the immunofluorescence study showed that AL extract suppressed nuclear translocation of nuclear factor-kappa B (NF-κB) upon LPS induction. Results from Western blot analysis further confirmed that AL extract strongly prevented the LPS-induced degradation of IκB which is normally required for the activation of NF-κB. The protein expression of iNOS and COX-2 in response to LPS stimulation was significantly decreased with the presence of AL extract. AL extract was found to play an anti-inflammatory role, in part through inhibiting LPS-induced activation of Akt. The extract had negligible impact on the activation of mitogen-activated protein kinase (MAPK) pathways. Specifically, incubation of cells with the extract for only 3 h demonstrated the rapid action of AL extract on inhibiting the phosphorylation of Akt, but not ERK1/2. Longer exposure (24 h) to AL extract was required to mildly reduce the phosphorylation of ERK1/2, p38, and JNK MAPKs. These results indicate that AL extract manipulates its anti-inflammatory effects mainly through blocking the PI3K/Akt and NF-κB signal transduction pathways. Collectively, we believe that AL could be a potential alternative agent for alleviating excessive inflammation in many inflammation-associated diseases.

Oxyresveratrol Inhibits IL-1β-Induced Inflammation via Suppressing AKT and ERK1/2 Activation in Human Microglia, HMC3

“…Natural polyphenolic phytochemicals have emerged as possible anti-neuroinflammatory agents. In particular, our previous study demonstrated that the Artocarpus lakoocha Roxb, containing a high amount of oxyresveratrol (OXY), could suppress lipopolysaccharide (LPS)-induced inflammatory response via inhibiting PI3K/AKT, MAPK, and NF-κB cascades in murine macrophages [ 10 ]. In our current study, we focused mainly on investigating anti-neuroinflammatory effects of OXY, reported to pass the blood–brain barrier (BBB) and exert neuroprotective effects in rodents [ 12 , 15 , 23 ].…”

“…Oxyresveratrol ( trans -2,3′,4,5′-tetrahydroxystilbene, OXY) is a polyphenolic molecule, and it can be extracted from different plants, including Artocarpus lakoocha ( A. lakoocha ) [ 10 , 11 ]. Furthermore, OXY exerts several pharmacological activities, especially anti-inflammatory effects.…”

Oxyresveratrol Inhibits R848-Induced Pro-Inflammatory Mediators Release by Human Dendritic Cells Even When Embedded in PLGA Nanoparticles

“…(Moraceae), which has been used in Thai traditional medicine as an antioxidant and to treat inflammatory and parasitic diseases [ 30 , 31 , 32 ]. Recently, many studies have been performed to investigate the pharmacological effects of oxyresveratrol: in particular, it has been reported to suppress lipopolysaccharide-induced inflammatory response in murine models [ 31 , 33 , 34 ] and to exert its anti-inflammatory effects mainly by downregulating the release of various cytokines [ 12 , 13 , 14 , 15 ]. As far as we know, no investigations have been made on the effect of oxyresveratrol on the functional activity of human DCs, which play an essential role in activation of inflammation and immune reaction [ 1 , 2 , 3 ].…”

Human neutrophil elastase inhibitory dihydrobenzoxanthones and alkylated flavones from the Artocarpus elasticus root barks

“…The therapeutic effect is associated with the abundance of phenolics, such as flavonoids, stilbenoids, dihydrochalcones, dihydrobenzoxanthones and prenylated flavonoids [12]. Single metabolites reported in vivo antimalarial [13], inhibition of LPS-induced inflammation [14], α-glucosidase inhibitory [15], TRAILresistance overcoming with antiviral [16], and anticancer [17] activities. Alkylated flavonoid Artonin E from A. elasticus also revealed considerable cytotoxic effect in MCF-7 human breast cancer cells by ROS mediated mitochondrial pathway [18,19].…”