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Micranthin B alleviates metabolic dysfunction-associated steatohepatitis by targeting G3BP1 to improve stress granule-mediated endoplasmic reticulum stress 认领 引用
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作者 Yang Cheng Jingyi Wang +6 位作者 Mengmeng He Enyi Wu Shengtao Ye Ying Zheng Yanqiu Zhang Lingyi Kong Hao Zhang 《Chinese Journal of Natural Medicines》 SCIE CAS CSCD 2026年第6期757-768,共12页
Ras-GTPase activating protein SH3 domain-binding protein 1(G3BP1),a core component of stress granules(SGs),is highly expressed in several liver diseases.SG assembly has also been observed in metabolic disorders,sugges... Ras-GTPase activating protein SH3 domain-binding protein 1(G3BP1),a core component of stress granules(SGs),is highly expressed in several liver diseases.SG assembly has also been observed in metabolic disorders,suggesting that this process may be a promising therapeutic target.Using a high-content drug screening approach based on G3BP1 expression,we identified Micranthin B(MB),a diterpenoid from Isodon lophanthoides(Buch.-Ham.ex D.Don)Hara,as a compound that alleviates metabolic dysfunction-associated steatohepatitis(MASH)by targeting G3BP1 and inhibiting SG formation.MB administration significantly alleviated MASH progression in both high-fat,high-cholesterol(HFHC)diet-induced mouse model and palmitic acid(PA)-stimulated hepatocytes.Mechanistically,MB inhibited histone deacetylase 6(HDAC6)-mediated deacetylation of G3BP1,thereby suppressing SG formation.This prevented SG-mediated recruitment of the N-glycosylation-related proteins SEC61 translocon subunit beta(SEC61B)and calnexin(CANX),reduced the accumulation of misfolded or unfolded proteins,and alleviated endoplasmic reticulum(ER)stress.These findings suggest that MB has therapeutic potential in the treatment of MASH. 展开更多
关键词 MASH Micranthin B G3BP1 Stress granule Endoplasmic reticulum homeostasis
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Isodons A-H,seco-abietane and abietane-type diterpenoids from Isodon lophanthoides:isolation,structural elucidation,and anti-cholestatic activity 认领 引用 被引量：2
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作者 Huiling Zhou Mingzhu Han +6 位作者 Miaomiao Nan Yingrong Leng Weiming Huang Shengtao Ye Lingyi Kong Wenjun Xu Hao Zhang 《Chinese Journal of Natural Medicines》 SCIE CAS CSCD 2025年第9期1133-1142,共10页
Eight new diterpenoids,Isodons A-H(1-8),comprising seco-abietane and abietane-type structures,together with 13 known analogues(9-21),were isolated from Isodon lophanthoides(Buch.-Ham.ex D.Don)Hara.The compounds(+)-3/(... Eight new diterpenoids,Isodons A-H(1-8),comprising seco-abietane and abietane-type structures,together with 13 known analogues(9-21),were isolated from Isodon lophanthoides(Buch.-Ham.ex D.Don)Hara.The compounds(+)-3/(-)-3,(+)-4/(-)-4,and(+)-5/(-)-5 were identified as three enantiomeric pairs.The planar structures and absolute configurations of 1-8 were determined through high-resolution electrospray ionization mass spectrometry(HR-ESI-MS),1D&2D nuclear magnetic resonance(NMR)spectroscopy,electronic circular dichroism(ECD)calculations,and X-ray diffraction crystallography.A cholesterol 7α-hydroxylase(Cyp7a1)luciferase reporter assay revealed significant anti-cholestatic activities for compounds 1,(+)-4,6,7,12-14,and 16.Additionally,compound 6 demonstrated anti-cholestatic effects through the farnesoid X receptor(FXR)-associated signaling pathways in vitro and in vivo.These findings suggest potential applications for I.Lophanthoides in pharmaceutical development. 展开更多
关键词 Isodon lophanthoides Diterpenoids Anticholestatic effect FXR Cyp7a1
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Hyperbenzones A and B,two 1,2-seco and rearranged polycyclic polyprenylated acylphloroglucinols from Hypericum beanii 认领 引用 被引量：2
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作者 Weijia Lu Yanqiu Zhang +4 位作者 Yawei Li Shengtao Ye Jun Luo Lingyi Kong Wenjun Xu 《Chinese Chemical Letters》 SCIE CAS CSCD 2022年第8期4121-4125,共5页
Two novel seco-polycyclic polyprenylated acylphloroglucinols(PPAPs),hyperbenzones A(1)and B(2),were isolated from the roots of Hypericum beanii,together with one known biosynthetic congener 3.Compound 1 incorporates a... Two novel seco-polycyclic polyprenylated acylphloroglucinols(PPAPs),hyperbenzones A(1)and B(2),were isolated from the roots of Hypericum beanii,together with one known biosynthetic congener 3.Compound 1 incorporates a 6/5/5 ring system with an unprecedented spiro[bicyclo[3.3.0]octane-3,1'-cyclohexane]-2,2'-dione motif.The structures of 1 and 2 were determined by a combination of high resolution electrospray ionization mass spectroscopy(HRESIMS),nuclear magnetic resonance(NMR)spectroscopic analyses,gage-independent atomic orbital(GIAO)NMR chemical shift calculation with DP4+analyses,electronic circular dichroism(ECD)calculation,and X-ray diffraction analysis.A 1,2-seco retroClaisen rearrangement from a bicyclo[3.3.1]nonane PPAP precursor and following chemodivergent radical cascade cyclizations are proposed as the key steps in the biosynthetic pathway to yield compounds 1 and2.Biological investigations indicated that compounds 1 and 3 could decrease intracellular lipid accumulation in a palmitic acid-induced nonalcoholic steatohepatitis(NASH)cell model. 展开更多
关键词 seco-PPAPs Hypericum beanii Hyperbenzones A and B NASH 1 2-seco-Bicyclic derivatives
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