Diterpenoids Isolated from Podocarpus macrophyllus Inhibited the Inflammatory Mediators in LPS-Induced HT-29 and RAW 264.7 Cells.

Choeen Kim,Ducdat Le,Mina Lee

doi:10.3390/molecules26144326

Abstract

Species of Podocarpus are used traditionally in their native areas for the treatment of fevers, asthma, coughs, cholera, chest pain, arthritis, rheumatism, and sexually transmitted diseases. To identify natural products having efficacy against inflammatory bowel disease (IBD), we identified a new, 16-hydroxy-4β-carboxy-O-β-D-glucopyranosyl-19-nor-totarol (4) together with three known diterpenoids from P. macrophyllus. Furthermore, all the extracts, fractions, and isolates 1–4 were investigated for their anti-inflammatory effects by assessing the expression on nitric oxide (NO) production and proinflammatory cytokines in lipopolysaccharide (LPS)-stimulated RAW 264.7 and HT-29 cells. Among them, nagilactone B (2) exhibited a potent anti-inflammatory effect against NO production on RAW 264.7 cells; therefore, nagilactone B was further assessed for anti-inflammatory activity. Western blot analysis revealed that nagilactone B significantly decreased the expression of LPS-stimulated protein, inducible nitric oxide synthase (iNOS), cyclooxygenase (COX)-2, and phosphorylated extracellular regulated kinase (pERK)1/2. In addition, nagilactone B downregulated tumor necrosis factor (TNF)-α, interleukin (IL)-6, and IL-8 levels in LPS-induced macrophages and colonic epithelial cells. To our best knowledge, this is the first report on the inhibitory effect of nagilactone B (pure state) and rakanmakilactone G against NO production in LPS-stimulated RAW 264.7 cells. Thus, diterpenoids isolated from P. macrophyllus could be employed as potential therapeutic phytochemicals for IBD.

Highlights

Inflammatory bowel disease (IBD) is a complex disease associated with environmental and genetic factors that lead to immunological reactions and inflammation in the intestine [1]
Both extracts displayed similar ABTS radical-scavenging effects, with IC50 values around 36 μg/mL (Table 1). These results suggest that the extract of P. macrophyllus leaves could be employed for further experiment
In summary, oxidant and inflammatory screening of crude extracts and fractions guided the isolation of four compounds (1–4) from leaves of P. macrophyllus

Summary

Introduction

Inflammatory bowel disease (IBD) is a complex disease associated with environmental and genetic factors that lead to immunological reactions and inflammation in the intestine [1]. Imbalances in the activation of proinflammatory and anti-inflammatory signaling pathways in the gut can lead to IBD, Crohn s disease (CD), and ulcerative colitis (UC) as chronic inflammatory conditions of the gastrointestinal system [2]. IBD prevalence has increased during the past decades, especially in Westernized countries with a prevalence as high as 1%. It is well-known that its prognosis is poor and that its medication is often ineffective [5]

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Conclusion