Labdane-Type Diterpenoids from the Rhizomes of Hedychium coronarium Inhibit Lipopolysaccharide-Stimulated Production of Pro-inflammatory Cytokines in Bone Marrow-Derived Dendritic Cells

Abstract

Key words Hedychium coronarium; hedycoronen A; hedycoronen B; tumor necrosis factor-α; interleukin-6; interleukin-12Numerous molecules are involved in the induction and maintenance of the inflammatory response. In addition to pivotal cytokines such as interleukin-1 (IL-1), -6, -12, and tumor necrosis factor-α (TNF-α), prostaglandins, and nitric oxide are important chemical mediators of inflammation. TNF-α is a well-characterized pro-inflammatory cytokine released primarily from monocytes and macrophages upon invasion of the host by a wide variety of pathogens. It plays a crucial role in host defense and in the inflammatory response. Although it has numerous beneficial roles in immune regulation, it has also been implicated in the pathogenesis of both acute and chronic inflammatory disease. 1)IL-6 is a particularly interesting molecule because it has both pro-and anti-inflammatory effects. It has been implicated in many inflammatory diseases in both adults and neonates.2)The IL-6 system promotes inflammatory events by stimulating the activation and proliferation of lymphocytes, differentiation of B cells, leukocyte recruitment, and the induction of an acute phase protein response in the liver. 3)IL-12 plays a central role in the initiation and regulation of cellular immunity. It is involved in type-1 helper T-cell-mediated inflammation as part of the normal immune response, as well as inflammatory diseases, including rheumatoid arthritis, asthma, psoriasis, and Crohn's disease. 4-6)Hedychium coronarium (Zingiberaceae) is widely cultivated in Vietnam, India, and Southeast Asian countries. It is a perennial rhizomatous herb growing at an altitude of 1000-2200 m. The rhizomes of H. coronarium have been used for the treatment of inflammation, skin diseases, headache, and sharp pain due to rheumatism in traditional medicine in Vietnam. Previous phytochemical investigation of H. coronarium has resulted in the identification of a number of labdane diterpenes, which were proved to be the main components.7-10) Labdane diterpenes occur in several plants of the Zingiberaceae family and have been reported to possess anti-inflammatory properties.11,12) Interestingly, our extensive phytochemical study of the rhizomes of H. coronarium led to the isolation of two new and four known labdane-type diterpenoids. These six labdanes (1-6) were evaluated for the lipopolysaccharide (LPS)-stimulated production of pro-inflammatory cytokines in bone marrow-derived dendritic cells. Results and DiscussionThe rhizomes of H. coronarium were extracted with methanol and fractionated with chloroform, ethyl acetate, and water. From the chloroform layer and by using combined chromatographic separations, two new and four known compounds were isolated. Their structures were elucidated using physicochemical and spectroscopic methods.Compound 1

Catalytic Carbonylative Spirolactonization of Hydroxycyclopropanols

“…The latter belong to a class of labdane derivaties which were recently found to inhibit LPS-induced nitric oxide (NO) production and LPS-stimulated production of pro-inflammatory cytokines. 15 …”

Micropropagation of Hedychium coronarium J. Koenig through rhizome bud

“…The plant is used in traditional system of medicine. The rhizome is used in the treatment of diabetes (Bhandary et al 1995), fever (as febrifuge) and headache (Jain et al 1995), arthritis, inflammation and skin diseases (Kiem et al 2012). The paste prepared from the rhizome is applied externally in cases of snakebite (Ray et al 2011).…”

Cancer chemoprevention activity of labdane diterpenes from rhizomes of Hedychium coronarium

“…The active compounds described by Girón et al (2008) bear one or two Michael acceptors as functional groups, whereas this feature is absent in the inactive structurallyrelated diterpenes. Recently, other labdane diterpenes isolated from H. coronarium, hedycoronen A and hedycoronen B, showed moderate inhibitory activity on TNF-production ( IC 50 46.0 ± 1.3 and 12.7 ± 0.3 μM, respectively), whereas the corresponding deoxymethyl derivatives were inactive (Kiem et al, 2012). This finding suggests that the inhibitory effect against some nuclear factors increases by introducing a methoxy or ethoxy group at the C-15/16 positions.…”

“…Remarkable inhibitory activity of nitric oxide (NO) production in LPS-activated mouse peritoneal macrophages has been reported for coronarin D and hedychilactone A, labdane diterpenes isolated from the rizhomes of H. coronarium Kiem et al, 2012).…”

“…NF-B activation is involved in inflammation, cell proliferation and oncogenic processes (Skehan et al, 1990;Matsuda et al, 2002;Pezzuto et al, 2005;Maiti et al, 2007;Kang et al, 2009;Kiem et al, 2012). Thus, agents that suppress NF-B activation can abrogate carcinogenesis.…”