Sesquiterpene Lactones from <i>Artemisia argyi</i>: Absolute Configuration and Immunosuppressant Activity

Reinhardt, Jakob K.; Zimmermann-Klemd, Amy Marisa; Danton, Ombeline; Mieri, Maria De; Smieško, Martin; Huber, Roman; Bürgi, Thomas; Gründemann, Carsten; Hamburger, Matthias

doi:10.1021/acs.jnatprod.8b00791

Cited by 42 publications

(39 citation statements)

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“…We recently found that an ethyl acetate extract of A. argyi suppressed the in vitro proliferation of human primary T lymphocytes in a concentration-dependent, non-cytotoxic manner (Figure 1) and we also isolated a series of compounds that were responsible for this activity (Reinhardt et al, 2019).…”

Section: Discussionmentioning

confidence: 80%

“…We previously showed that the A. argyi extract inhibited the proliferation of stimulated human T lymphocytes in vitro, and a series of related guaianolides and seco-guaianolides was found to be responsible for most of the inhibitory effects of the extract (Reinhardt et al, 2019). In the present study, we aimed to further substantiate the rationale for the use of A. argyi as an antiinflammatory herbal drug.…”

Section: Introductionmentioning

confidence: 80%

“…The compounds used in this work were isolated from A. argyi ethyl acetate extract in a previous study (Reinhardt et al, 2019).…”

Section: Tested Compoundsmentioning

confidence: 99%

“…Previously, we evaluated the effect of 435 plant extracts from a focused extract library of TCM plants on the proliferative capacity of primary expanded human T lymphocytes in vitro. The ethyl acetate extract of A. argyi inhibited the proliferation of human T lymphocytes in a concentration-dependent manner, with a half maximal inhibitory concentration (IC 50 ) of 16.2 µg/ ml (Reinhardt et al, 2019) ( Figure 1A). The focused library also comprised extracts from other plants of the Asteraceae family (Supplement 2), but none of these exhibited notable activity in the assay.…”

Section: Anti-proliferative Effects Of the A Argyi Extract On T Lympmentioning

confidence: 99%

“…We previously isolated a series of sesquiterpene lactones and flavones from the active extract ( Figure 7A), some of which showed significant inhibitory effects on T lymphocyte proliferation (Reinhardt et al, 2019) (Figure 1A). Several of the most-active compounds were tested: two stereoisomeric guaianolides, artecanin and canin (1 and 5), artanomaloide (2), arteglasin A (3) differing from 1 and 2 in the decoration of the 7membered ring, the moderately active flavone jaceosidin (4), and two stereoisomeric seco-guaianolides, seco-tanapartholides B and A (6 and 7) ( Figure 5).…”

Section: Effects Of Isolated a Argyi Compounds On The Activation Andmentioning

confidence: 99%

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Immunosuppressive Activity of Artemisia argyi Extract and Isolated Compounds

et al. 2020

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The need for novel drugs for the treatment of autoimmune diseases is high, since available pharmaceuticals often have substantial side effects and limited efficacy. Natural products are a good starting point in the development of immunosuppressive leads. Since enhanced T cell proliferation is a common feature of autoimmune diseases, we investigated the T cell proliferation inhibitory potential of an extract library of plants used in traditional Chinese medicine. Using a newly established cell-based screening platform, an ethyl acetate extract of Artemisia argyi H.Lév. & Vaniot (Asteraceae, A. argyi) was found to suppress the proliferation of human primary T lymphocytes in vitro in an IL-2-dependent manner. Flow cytometry-and ELISA-based techniques further demonstrated that the A. argyi extract reduced the activation and function of T cells. Transcription factor analysis and flow cytometric calcium influx investigations indicated that the immunomodulatory effect was based on specific modification of T cell signaling in a non-cytotoxic manner which is mediated via the NFAT pathway and a non-sequestrant inhibition of the calcium influx. A series of guaianolide and seco-guaianolide sesquiterpene lactones, as well as a flavonoid, were identified in a previous study as the bioactive compounds in the A. argyi extract. The effects of these bioactive compounds were compared to those of the crude extract. The tested sesquiterpene lactones act via the transcription factor NFAT and NF-kB, thereby exhibiting their immunosuppressive potential, but have an overall effect on T cell biology on a more-downstream level than the crude A. argyi extract.

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Section: Discussionmentioning

confidence: 80%

Section: Introductionmentioning

confidence: 80%

“…The compounds used in this work were isolated from A. argyi ethyl acetate extract in a previous study (Reinhardt et al, 2019).…”

Section: Tested Compoundsmentioning

confidence: 99%

Section: Anti-proliferative Effects Of the A Argyi Extract On T Lympmentioning

confidence: 99%

Section: Effects Of Isolated a Argyi Compounds On The Activation Andmentioning

confidence: 99%

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Immunosuppressive Activity of Artemisia argyi Extract and Isolated Compounds

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New Indole Diketopiperazine Alkaloids from Soft Coral‐Associated Epiphytic Fungus Aspergillus sp. EGF 15‐0‐3

Xia

Chen

Wang

et al. 2020

Chemistry & Biodiversity

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Three new indole diketopiperazine alkaloids, 11-methylneoechinulin E and variecolorin M, and (+)-variecolorin G, along with 12 known analogs, were isolated from a soft coral-associated epiphytic fungus Aspergillus sp. EGF 15-0-3. The structures of the new compounds were unambiguously established by extensive spectroscopic analyses including HR-ESI-MS, 1D and 2D NMR spectroscopy and optical rotation measurements. The absolute configurations of (+)-and (À )-variecolorin G were determined by experimental and quantum-chemical ECD investigations and single-crystal X-ray diffraction analysis. Variecolorin G is a pair of enantiomeric mixtures with a ratio of 1 : 2. Moreover, (+)-neoechinulin A is firstly reported as a natural product. The cytotoxic activities of all the isolated compounds against NCI-H1975 gefitinib resistance (NCI-H1975/GR) cell lines were preliminarily evaluated by MTT method.

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Artematrovirenolides A—D and Artematrolides S—Z, Sesquiterpenoid Dimers with Cytotoxicity against Three Hepatoma Cell Lines from Artemisia atrovirens

et al. 2021

Chin. J. Chem.

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Comprehensive Summary Inspired by the intriguing structures and remarkable activities of sesquiterpenoid dimers, 12 new sesquiterpenoid dimers, artematrovirenolides A—D (1—4) and artematrolides S—Z (8—12), were isolated from the EtOAc fraction of Artemisia atrovirens through a bioactivity‐guided approach. Their structures were elucidated by comprehensive spectroscopic data and absolute configuration was assigned based on single crystal X‐ray diffraction data and ECD calculations. Structurally, all compounds are presumably formed via [4+2] cycloaddition involving three connecting model. Compounds 1—4 are four novel hetero‐dimeric [4+2] Diels–Alder adducts dimerized from a rotundane‐type unit and a guaiane‐type monomer, and compounds 5—12 are eight new homo‐dimeric [4+2] adducts derived from two guaianolide moieties. A putative biosynthetic pathway for compounds 1—4 was also proposed. Compounds 4, 6, 7, and 10 demonstrated moderate cytotoxicity against HepG2, SMMC‐7721, and Huh7 cell lines with IC50 values ranging from 9.3 to 62.3 μmol/L. Interestingly, compounds 5 and 11 manifested cytotoxicity with IC50 values of 13.6 and 12.8 (HepG2), 18.5 and 13.1 (SMMC‐7721), and 16.5 and 19.4 μmol/L (Huh7), respectively, which were equivalent to the positive control, sorafenib. This investigation suggests that compounds 5 and 11 might be considered as potent antihepatoma candidates and deserve further structural modification and mechanism study.

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Sesquiterpene Lactones from Artemisia argyi: Absolute Configuration and Immunosuppressant Activity

Cited by 42 publications

References 25 publications

Immunosuppressive Activity of Artemisia argyi Extract and Isolated Compounds

Immunosuppressive Activity of Artemisia argyi Extract and Isolated Compounds

New Indole Diketopiperazine Alkaloids from Soft Coral‐Associated Epiphytic Fungus Aspergillus sp. EGF 15‐0‐3

Artematrovirenolides A—D and Artematrolides S—Z, Sesquiterpenoid Dimers with Cytotoxicity against Three Hepatoma Cell Lines from Artemisia atrovirens

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