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Planta Med 2023; 89(12): 1170-1177
DOI: 10.1055/a-2090-0733
Natural Product Chemistry and Analytical Studies
Original Papers

Lyonensinols A – C, 24-Norursane-Type Triterpenoids from the Twigs and Leaves of Lyonia doyonensis and Their Potential Anti-inflammatory and PTP1B Inhibitory Activities

Ming-Zhu Zhang‡
1   School of Pharmacy, Nanchang University, Nanchang, Peopleʼs Republic of China
,
Meng-Yuan Jiang‡
1   School of Pharmacy, Nanchang University, Nanchang, Peopleʼs Republic of China
,
Ling-Ping Kong
1   School of Pharmacy, Nanchang University, Nanchang, Peopleʼs Republic of China
,
Cai-Ying Liu
1   School of Pharmacy, Nanchang University, Nanchang, Peopleʼs Republic of China
,
Huai-Xin Kang
2   The Hospital of Nanchang University, Nanchang, Peopleʼs Republic of China
,
Ai-Hong Liu
3   Center of Analysis and Testing, Nanchang University, Nanchang, Peopleʼs Republic of China
,
Bin Wang
1   School of Pharmacy, Nanchang University, Nanchang, Peopleʼs Republic of China
,
Shui-Chun Mao
1   School of Pharmacy, Nanchang University, Nanchang, Peopleʼs Republic of China
› Author AffiliationsThis work was financially supported by the National Natural Science Foundation of China (Nos. 82060633, 81860616, and 21362024) and the Natural Science Foundation of Jiangxi Province, China (Nos. 20212ACB206034, 20202BAB206084, and 20181BAB205086). We acknowledge Dr. G.-D. Li (Yunnan University of Chinese Medicine). We are also grateful to Prof. J. Li (Shanghai Institute of Materia Medica, CAS) for the bioassay help.
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Abstract

Lyonia doyonensis is a deciduous shrub native to high-altitude regions of Asia. So far, there is no report on any chemical and biological properties of L. doyonensis. An EtOH extract of L. doyonensis twigs and leaves showed inhibitory activities on protein tyrosine phosphatase 1B and lipopolysaccharide-induced inflammation in BV-2 microglial cells. A phytochemical investigation of this extract led to the isolation of a, so far only ambiguously described, 24-norursane-type triterpenoid, now named lyonensinol A (1), along with its two new derivatives, lyonensinols B and C (2 and 3), and six known triterpenoids (4 – 9). Their structures were elucidated by detailed analysis of spectroscopic data. A combination of chemical conversions, electronic circular dichroism, and Mo2(OAc)4-induced electronic circular dichroism was used to confirm their absolute configurations. Lyonensinols B (2) and C (3) represent the first examples of norursane-type triterpenoids acylated with a p-coumaroyl moiety. The potential anti-inflammatory and protein tyrosine phosphatase 1B inhibitory activities of all the isolates were evaluated. Compounds 3, 7, and 8 at 10 µM showed potent inhibitory activities on lipopolysaccharide-induced nitric oxide production in BV-2 microglial cells, with nitric oxide levels decreasing to 31.5, 41.9, and 27.1%, respectively, while compounds 3, 4, 7, and 8 exhibited notable inhibitory activities against protein tyrosine phosphatase 1B, with IC50 values ranging from 1.7 to 18.2 µM. Interestingly, compounds 3 and 8, bearing a C-3 trans-p-coumaroyl group, showed not only more potent anti-inflammatory effects, but also exhibited stronger protein tyrosine phosphatase 1B inhibition than their respective stereoisomers (2 and 7) with a cis-p-coumaroyl group.

Key words

Ericaceae - Lyonia doyonensis - 24-norursane-type triterpenoids - anti-inflammatory activity - PTP1B inhibition

Supporting Information

    NMR data of 4 – 9, key ROESY correlations of 2 and 3, HRESIMS, IR, UV, 1D and 2D NMR spectra of 1 – 3, structures of two known 24-norursanes structurally related to 1, and dose-response curves of the PTP1B inhibitors 3, 4, 7, 8, and oleanolic acid are available as Supporting Information.

  • Supporting Information


Publication History

Received: 05 January 2023

Accepted after revision: 08 May 2023

Accepted Manuscript online:
09 May 2023

Article published online:
21 June 2023

© 2023. Thieme. All rights reserved.

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  • References

  • 1 Sun N, Li D, Chen X, Wu P, Lu YJ, Hou N, Chen WH, Wong WL. New applications of oleanolic acid and its derivatives as cardioprotective agents: A review of their therapeutic perspectives. Curr Pharm Des 2019; 25: 3740-3750
    CrossrefPubMedGoogle Scholar
  • 2 Yu JH, Yu ZP, Wang YY, Bao J, Zhu KK, Yuan T, Zhang H. Triterpenoids and triterpenoid saponins from Dipsacus asper and their cytotoxic and antibacterial activities. Phytochemistry 2019; 162: 241-249
    CrossrefPubMedGoogle Scholar
  • 3 Jang DS, Kim JM, Kim JH, Kim JS. 24-nor-Ursane type triterpenoids from the stems of Rumex japonicus . Chem Pharm Bull 2005; 53: 1594-1596
    CrossrefPubMedGoogle Scholar
  • 4 Zeng N, Shen Y, Li LZ, Jiao WH, Gao PY, Song SJ, Chen WS, Lin HW. Anti-inflammatory triterpenes from the leaves of Rosa laevigata . J Nat Prod 2011; 74: 732-738
    CrossrefPubMedGoogle Scholar
  • 5 Tian Y, Feng L, Li B, Hu J, Xie J, Xiao W, Nie L, Wu J. Rosanortriterpene C, a 3, 24-dinor-2, 4-seco-ursane triterpene from the fruits of Rosa laevigata var. leiocapus . Chem Pharm Bull 2019; 67: 1255-1258
    CrossrefPubMedGoogle Scholar
  • 6 Xu W, Tan J, Mu Y, Zheng D, Huang X, Li L. New antimicrobial terpenoids and phloroglucinol glucosides from Syzygium szemaoense . Bioorg Chem 2020; 103: 104242
    CrossrefPubMedGoogle Scholar
  • 7 Wu Y, Lu J, Lu X, Li R, Guo J, Guo F, Li Y. Monoterpenoids and triterpenoids from Pterocephalus hookeri with NF-κB inhibitory activity. Phytochem Lett 2015; 13: 30-34
    CrossrefPubMedGoogle Scholar
  • 8 Wang HQ, Ma SG, Zhang D, Li YH, Qu J, Li Y, Liu YB, Yu SS. Oxygenated pentacyclic triterpenoids from the stems and branches of Enkianthus chinensis . Bioorg Chem 2021; 111: 104866
    CrossrefPubMedGoogle Scholar
  • 9 Na MK, Thuong PT, Hwang IH, Bae KH, Kim BY, Osada H, Ahn JS. Protein tyrosine phosphatase 1B inhibitory activity of 24-norursane triterpenes isolated from Weigela subsessilis . Phytother Res 2010; 24: 1716-1719
    CrossrefPubMedGoogle Scholar
  • 10 Zhang H, Peng X, Zheng X, Li S, Teng Y, Liu J, Zou C, Yao G. Lanostane triterpene glycosides from the flowers of Lyonia ovalifolia var. hebecarpa and their antiproliferative activities. Bioorg Chem 2020; 96: 103598
    CrossrefPubMedGoogle Scholar
  • 11 Qu KJ, Wang B, Jiang CS, Xie BG, Liu AH, Li SW, Guo YW, Li J, Mao SC. Rearranged Diels-Alder adducts and prenylated flavonoids as potential PTP1B inhibitors from Morus nigra . J Nat Prod 2021; 84: 2303-2311
    CrossrefPubMedGoogle Scholar
  • 12 Liu AH, Liu DQ, Liang TJ, Yu XQ, Feng MT, Yao LG, Fang Y, Wang B, Feng LH, Zhang MX, Mao SC. Caulerprenylols A and B, two rare antifungal prenylated para-xylenes from the green alga Caulerpa racemosa . Bioorg Med Chem Lett 2013; 23: 2491-2494
    CrossrefPubMedGoogle Scholar
  • 13 Feng MT, Wang T, Liu AH, Li J, Yao LG, Wang B, Guo YW, Mao SC. PTP1B inhibitory and cytotoxic C-24 epimers of Δ 28-24-hydroxy stigmastane-type steroids from the brown alga Dictyopteris undulata Holmes. Phytochemistry 2018; 146: 25-35
    CrossrefPubMedGoogle Scholar
  • 14 Mahato SB, Kundu AP. Review article number 98: 13C NMR spectra of pentacyclic triterpenoids – a compilation and some salient features. Phytochemistry 1994; 37: 1517-1575
    CrossrefPubMedGoogle Scholar
  • 15 Takahashi K, Kawaguchi S, Nishimura K, Kubota K, Tanabe Y, Takani M. Constituents of medicinal plants. XIII. Constituents of the pericarps of the capsules of Euscaphis japonica . Chem Pharm Bull 1974; 22: 650-653
    CrossrefPubMedGoogle Scholar
  • 16 Ojinnaka CM, Okogun JI, Okorie DA. Myrianthic acid: A triterpene acid from the rootwood of Myrianthus arboreus . Phytochemistry 1984; 23: 1125-1127
    CrossrefPubMedGoogle Scholar
  • 17 Yagi A, Okamura N, Haraguchi Y, Noda K, Nishioka I. Studies on the constituents of Zizyphi fructus. II.: Structure of new p-coumaroylates of maslinic acid. Chem Pharm Bull 1978; 26: 3075-3079
    CrossrefPubMedGoogle Scholar
  • 18 Taniguchi S, Imayoshi Y, Kobayashi E, Takamatsu Y, Ito H, Hatano T, Sakagami H, Tokuda H, Nishino H, Sugita D, Shimura S, Yoshida T. Production of bioactive triterpenes by Eriobotrya japonica calli. Phytochemistry 2002; 59: 315-323
    CrossrefPubMedGoogle Scholar
  • 19 Longue Ekon JP, Bissoue AN, Fomani M, Toze FAA, Waffo Kamdem AF, Sewald N, Wansi JD. Cytotoxic 24-nor-ursane-type triterpenoids from the twigs of Mostuea hirsuta . Z Naturforsch 2015; 70: 837-842
    CrossrefPubMedGoogle Scholar
  • 20 Frelek J, Ikekawa N, Takatsuto S, Snatzke G. Application of [Mo2(OAc)4] for determination of absolute configuration of brassinosteroid vic-diols by circular dichroism. Chirality 1997; 9: 578-582
    CrossrefPubMedGoogle Scholar
  • 21 Snatzke G, Wagner U, Wolff HP. Circulardichroism–LXXV: Cottonogenic derivatives of chiral bidentate ligands with the complex [Mo2(O2CCH3)4]. Tetrahedron 1981; 37: 349-361
    PubMedGoogle Scholar
  • 22 Ren FC, Li GY, Nama N, Liu ZH, Yang L, Zhou J, Hu JM. 13, 27-Cycloursane, ursane and oleanane triterpenoids from the leaves of Lucuma nervosa . Fitoterapia 2019; 136: 104178
    CrossrefPubMedGoogle Scholar
  • 23 Nandi S, Saxena M. Potential inhibitors of protein tyrosine phosphatase (PTP1B) enzyme: promising target for type-II diabetes mellitus. Curr Top Med Chem 2020; 20: 2692-2707
    CrossrefPubMedGoogle Scholar
  • 24 Xia MJ, Zhang M, Li SW, Cai ZF, Zhao TS, Liu AH, Luo J, Zhang HY, Li J, Guo YW, Wang B, Mao SC. Anti-inflammatory and PTP1B inhibitory sesquiterpenoids from the twigs and leaves of Aglaia lawii . Fitoterapia 2022; 162: 105260
    CrossrefPubMedGoogle Scholar
  • 25 Garzon-Porras AM, Bertuzzi DL, Lucas K, da Silva LCE, de Oliveira MG, Ornelas C. Nitric oxide releasing polyamide dendrimer with anti-inflammatory activity. ACS Appl Polym Mater 2020; 2: 2027-2034
    CrossrefPubMedGoogle Scholar