Dendritic cells maturation promoted by M1 and M4, end products of steroidal ginseng saponins metabolized in digestive tracts, drive a potent Th1 polarization

Takei, Masao; Tachikawa, Eiichi; Hasegawa, Hideo; Lee, Je‐Jung

doi:10.1016/j.bcp.2004.04.015

Cited by 57 publications

(38 citation statements)

References 27 publications

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“…Surprisingly, me-AntK treatment of DC facilitates their ability to induce T cells to differentiate toward a Th2 phenotype. The Th1 promotion and inhibitory effect of ginsenosides, triterpenoids isolated from the medicinal herb ginseng, have been reported on DC [31,32]. Thus, this is the first example of a natural triterpenoid can activate DC to induce Th2 responses.…”

Section: Discussionmentioning

confidence: 78%

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A triterpenoid methyl antcinate K isolated from Antrodia cinnamomea promotes dendritic cell activation and Th2 differentiation

Chen

Shen

et al. 2009

Eur J Immunol

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Dendritic cells (DC) play a central role in the initiation and regulation of immune responses.Increasing evidence has indicated that manipulation of DC can serve as a therapeutic mechanism for immunomodulation. In this study we tested some unique compounds isolated from Antrodia cinnamomea, a medicinal fungus in Taiwan, on mouse bone marrowderived DC activation. A triterpenoid methyl antcinate K (me-AntK) promoted DC maturation by enhancing the expression of MHC class II, CD86, and reducing the endocytosis. TNF-a, MCP-1, and MIP-1b were secreted by DC after me-AntK treatment, indicating augmentation of innate immunity by me-AntK. Interestingly, the me-AntK-activated DC induced Ag-specific T-cell proliferation and facilitated Th2 differentiation. Examining signaling responses, we found that me-AntK treatment uniquely activated JNK and ERK in DC. Our results demonstrate that me-AntK is the first natural triterpenoid to promote the ability of DC to prime Th2 responses. This suggests that me-AntK can potentially be applied to enhance immune responses and modulate DC function in immunotherapy.Key words: DC . Immunomodulation . Th2 . Triterpenoid Supporting Information available online Introduction DC are specialized leukocytes which take up and process Ag in peripheral tissues and then transport and present Ag to activate T cells in secondary lymphoid organs [1,2]. DC are heterogeneous but all subsets have intrinsic and cooperative Ag-presenting function [3,4]. Exposure of DC to pathogen products or pro-inflammatory stimuli induces DC maturation, which dramatically enhances the ability of DC to activate Ag-specific T cells [5]. TLR are important receptors involved in detection of PAMP in DC. TLR ligation induces the activation of NF-kB and MAP kinase pathways, resulting in DC maturation, which is characterized by upregulation of MHC class II and costimulatory molecule expression as well as cytokine and chemokine production [6]. Befitting the key regulatory role of DC in 2482immune responses, DC are being developed for the treatment of cancers, allergies, and viral infections, and as adjuvants for potent new vaccines to prevent or treat cancers and infectious diseases [7,8]. Thus, DC are manipulated as pharmacological targets for discovering novel biological modifiers of immune responses [9][10][11].Natural products and their derivatives have historically been a rich source of therapeutic agents and lead molecules in drug discovery [12]. A number of biologically active natural products have been isolated from Aphyllophorales, many of which are known as polypores. Polypores are a large group of terrestrial fungi of the phylum Basidiomycota (basidiomycetes), and they are a major source of pharmacologically active substances [13]. For example, Ganoderma lucidum (Ling Zhi or Reishi), a wellknown fungus that has been used for medicinal purposes for centuries, has been studied extensively [14,15]. A precious basidiomycete Antrodia cinnamomea [syn. A. camphorata] (Ac) restrictively grows in a unique host, the endemic and en...

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Section: Discussionmentioning

confidence: 78%

“…Studies have shown that triterpenoids can modulate the function of immune cells [27][28][29]. Although the effect of some triterpenoids on DC has been reported [30][31][32], many triterpenoid compounds still remain to be examined. Several triterpenoids have been isolated from Ac previously [33,34].…”

Section: Introductionmentioning

confidence: 99%

A triterpenoid methyl antcinate K isolated from Antrodia cinnamomea promotes dendritic cell activation and Th2 differentiation

Chen

Shen

et al. 2009

Eur J Immunol

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“…The generation of human monocyte-derived DC was carried out as described previously [11]. Recombinant human IL-4 (IL-4), recombinant human granulocyte-macrophage colony-stimulating factor (GM-CSF) and recombinant human TNF-a (TNF-a) were purchased from R&D systems (Minneapolis, MN).…”

Section: Generation Of Monocyte-derived DCmentioning

confidence: 99%

“…Determination of naïve T cell polarization by DC Determination of naïve T cell polarization by DC was carried out as described previously [11].…”

Section: Generation Of Monocyte-derived DCmentioning

confidence: 99%

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Triterpene esters from Uncaria rhynchophylla drive potent IL-12-dependent Th1 polarization

et al. 2010

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Dendritic cells (DC) are key antigen-presenting cells that link innate and adaptive immunity and ultimately activate antigen-specific T cells. In the current study, we demonstrated that two triterpene esters, uncarinic acid C (1) and uncarinic acid D (2), which are isolated from the hooks of Uncaria rhynchophylla, activate phenotypic and cytokine production alterations in DC. We also show that 1 and 2 modulate human DC function in a fashion that favors Th1 cell polarization. The effect of 1 (E configuration at the 2' position) was approximately 20 times more potent than that of 2 (Z configuration at 2'). These results indicated that the configuration of the 2' double bond greatly effects activity. Thus, 1 and 2 may prove useful as DC-based vaccines for cancer immunotherapy.

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Leukocyte modulation by natural products from herbal medicines and potential as cancer immunotherapy

Yang

Wang²,

Zhang

2022

Journal of Leukocyte Biology

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Cancer constitutes a kind of life‐threatening disease that is prevalent throughout the world. In light of limitations in conventional chemotherapies or radiotherapies, cancer immunotherapy has emerged as a potent strategy in treating cancer. In cancer immunotherapy, preliminary studies have demonstrated that cancer immune surveillance serves a crucial role in tumor initiation, progression, and metastasis. Herbal medicines and natural products, which serve as alternative medicines, are involved in the modulation of tumor immunosurveillance to enhance antitumor activity. Accordingly, this review aimed to summarize the modulation function of herbal medicines and natural products on tumor immunosurveillance while providing scientific insight into further research on its molecular mechanism and potential clinical applications.

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Dendritic cells maturation promoted by M1 and M4, end products of steroidal ginseng saponins metabolized in digestive tracts, drive a potent Th1 polarization

Cited by 57 publications

References 27 publications

A triterpenoid methyl antcinate K isolated from Antrodia cinnamomea promotes dendritic cell activation and Th2 differentiation

A triterpenoid methyl antcinate K isolated from Antrodia cinnamomea promotes dendritic cell activation and Th2 differentiation

Triterpene esters from Uncaria rhynchophylla drive potent IL-12-dependent Th1 polarization

Leukocyte modulation by natural products from herbal medicines and potential as cancer immunotherapy

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