Polycyclic polyprenylated acylphloroglucinols(PPAPs)represent a distinct subclass of specialized metabolites predominantly found in the plant kingdom,particularly within the Guttiferae(Clusiaceae)family.These compound...Polycyclic polyprenylated acylphloroglucinols(PPAPs)represent a distinct subclass of specialized metabolites predominantly found in the plant kingdom,particularly within the Guttiferae(Clusiaceae)family.These compounds exhibit remarkable structural diversity and a wide range of biological activities.Seco-and nor-PPAPs,two unique variants of PPAPs with diverse skeletal structures,have been extensively investigated.As of June 2023,200 compounds have been isolated from four genera,with Hypericum being the primary source.Notably,115 of these compounds were identified in the past four years,indicating a significant increase in research activity.Seco-and nor-PPAPs can be categorized into six main subgroups based on the original PPAP scaffolds.Biological studies have revealed their potential in various therapeutic applications,including anti-cancer,anti-inflammatory,hepatoprotective,anti-Alzheimer’s disease(anti-AD),multidrug resistance(MDR)reversal,anti-depressant,neuroprotective,and immunosuppressive effects.This review provides a comprehensive overview of the occurrence,structures,and bioactivities of natural seco-and nor-PPAPs,offering valuable insights for the further development of PPAPs.展开更多
Hymoins A–C(1–3),three unusual polycyclic polyprenylated acylphloroglucinols(PPAPs)were isolated from the flowers of Hypericum monogynum.Hymoin A features the first intriguing 6/5/5/5/7 pentacyclic caged PPAP.Hymoin...Hymoins A–C(1–3),three unusual polycyclic polyprenylated acylphloroglucinols(PPAPs)were isolated from the flowers of Hypericum monogynum.Hymoin A features the first intriguing 6/5/5/5/7 pentacyclic caged PPAP.Hymoin B is characterized by an unprecedented rearranged 5/6/8 tricyclic ring system,while hymoin C represents the first rearranged PPAP with a fantastic spirocyclic 5/6/7 ring system.Their structures were established by extensive spectroscopic analysis,X-ray crystallography,and computational methods.The plausible biosynthetic routes for the compounds were also proposed.In oleic acid(OA)-induced HepG2 cells,all compounds exhibited significant lipid-lowering activity at the concentrations of 2–8μmol/L.Further mechanistic study implied that compound 1 exhibited excellent lipid-lowering activity in OA-induced HepG2 cells through inhibiting the proteins of free fatty acids synthesis and improving lipidolysis.展开更多
Hyparillums A(1)and B(2),two previously unidentified polycyclic polyprenylated acylphloroglucinols(PPAPs)with intricate architectures,were isolated from Hypericum patulum Thunb.Hyparillum A was the first PPAP with eig...Hyparillums A(1)and B(2),two previously unidentified polycyclic polyprenylated acylphloroglucinols(PPAPs)with intricate architectures,were isolated from Hypericum patulum Thunb.Hyparillum A was the first PPAP with eight-carbon rings based on an unprecedented 6/6/5/6/6/5/6/4 octocyclic system featuring a rare heptacyclo[10.8.1.11,10.03,8.08,21.012,19.014,17]docosane core.In contrast,hyparillum B featured a novel heptacyclic architecture(6/6/5/6/6/5/5)based on a hexacyclo[9.6.1.11,9.03,7.07,18.011,16]nonadecane motif.Furthermore,hyparillums A and B demonstrated promising inhibitory effects on the proliferation of murine splenocytes stimulated by anti-CD3/anti-CD28 monoclonal antibodies and lipopolysaccharide,exhibiting half-maximal inhibitory concentration(IC50)values ranging from 6.13±0.86 to 12.69±1.31μmol·L−1.展开更多
Polyprenylated acylphloroglucinols represent an important class of natural products found in many plants.Among them,the two related products oblongifolin C(Ob-C)and guttiferone K(Gt-K)isolated from Garcinia species(no...Polyprenylated acylphloroglucinols represent an important class of natural products found in many plants.Among them,the two related products oblongifolin C(Ob-C)and guttiferone K(Gt-K)isolated from Garcinia species(notably from edible fruits),have attracted attention due to their marked anticancer properties.The two compounds only differ by the nature of the C-6 side chain,prenyl(Gt-K)or geranyl(Ob-C)on the phloroglucinol core.Their origin,method of extraction and biological properties are presented here,with a focus on the targets and pathways implicated in their anticancer activities.Both compounds markedly reduce cancer cell proliferation in vitro,as well as tumor growth and metastasis in vivo.They are both potent inducer of tumor cell apoptosis,and regulation of autophagy flux is a hallmark of their mode of action.The distinct mechanism leading to autophagosome accumulation in cells and the implicated molecular targets are discussed.The specific role of the chaperone protein HSPA8,known to interact with Ob-C,is addressed.Molecular models of Gt-K and Ob-C bound to HSPA8 provide a structural basis to their common HSPA8-binding recognition capacity.The review shed light on the mechanism of action of these compounds,to encourage their studies and potential development.展开更多
Carascynol A,an unprecedented 4/9/8 ring system hybrid with a peroxide bridge,was characterized from Hyperi-cum ascyron.The architecture contains a caryophyllane-type moiety and a C_(6) unit derived from polyprenylate...Carascynol A,an unprecedented 4/9/8 ring system hybrid with a peroxide bridge,was characterized from Hyperi-cum ascyron.The architecture contains a caryophyllane-type moiety and a C_(6) unit derived from polyprenylated acylphloroglucinols.Its structure and absolute configuration were determined by comprehensive spectroscopic and X-ray diffraction data.Biologically,compound 1 inhibited cell proliferation in LoVo,SW480,and HCT116 cell lines(IC_(50)=12.30-24.57μM).展开更多
Two new type B polycyclic polyprenylated acylphloroglucinols(PPAPs)(1 and 2)and a known biogenetic precursor hyperbeanol Q(3)were isolated from the root extract of Hypericum beanii,a medicinal plant widespread in sout...Two new type B polycyclic polyprenylated acylphloroglucinols(PPAPs)(1 and 2)and a known biogenetic precursor hyperbeanol Q(3)were isolated from the root extract of Hypericum beanii,a medicinal plant widespread in southwest China.Their chemical structures were elucidated by 1 D/2 D NMR and HRESIMS data analysis,and absolute configurations were determined through detailed electric circular dichroism(ECD)analysis including ECD exciton chirality,Mo2(OAc)4-induced ECD,and ECD comparison.Of these compounds,hyperbeone A(1)is a typical[3.3.1]-type B PPAP with an unusual C-1 geranyl side chain,and hyperberin C(2)possesses a rare bicyclo[5.3.1]hendecane core.Taking compound 3 as a starting point,a plausible biosynthetic pathway to the bicyclic type B frameworks of 1 and 2 was proposed.展开更多
Hepatic ischemia/reperfusion injury(IRI)remains a critical complication contributing to graft dysfunction following liver surgery.As part of an ongoing search for hepatoprotective natural products,five previously unre...Hepatic ischemia/reperfusion injury(IRI)remains a critical complication contributing to graft dysfunction following liver surgery.As part of an ongoing search for hepatoprotective natural products,five previously unreported homoadamantane-type polycyclic polyprenylated acylphloroglucinols(PPAPs),named hyperhomanoons A-E(1-5),and one known analog,hypersampsone O(6),were isolated from Hypericum patulum.Among these,compound 6 demonstrated potent protective effects against CoCl_(2)-induced hypoxic injury in hepatocytes.Furthermore,in a murine model of hepatic IRI induced by vascular occlusion,pretreatment with 6 markedly alleviated liver damage and reduced hepatocyte apoptosis.This study is the first to identify PPAPs as promising scaffolds for the development of therapeutic agents targeting hepatic IRI,underscoring their potential as lead compounds in drug discovery efforts for ischemic liver diseases.展开更多
Hyphenrones R–X(1–7), seven new polyprenylated acylphloroglucinols derivatives, were isolated from the fruits of Hypericum henryi, together with eight know analogues. Compounds 1 and 2 were elucidated to possess com...Hyphenrones R–X(1–7), seven new polyprenylated acylphloroglucinols derivatives, were isolated from the fruits of Hypericum henryi, together with eight know analogues. Compounds 1 and 2 were elucidated to possess complex caged skeleton, while compounds 3–6 shared a common 3,9-epoxy moiety deriving from the normal polyprenylated acylphloroglucinols with a bicyclo[3.3.1]nonane-2,4,9-trione core. The new structures were elucidated on the basis of the interpretation of nuclear magnetic resonance(NMR) data, circular dichroism(CD) comparison, and single-crystal X-ray diffraction. In the bioassay, several compounds exhibited inhibitory activities against human tumor cell lines in vitro.展开更多
A series of dearomatized isoprenylated acylphloroglucinols derivatives,hyperhenols A-E(1-5),as well as seven known analogues(6-12),were characterized from Hypericum henryi.Their structures were determined by combinati...A series of dearomatized isoprenylated acylphloroglucinols derivatives,hyperhenols A-E(1-5),as well as seven known analogues(6-12),were characterized from Hypericum henryi.Their structures were determined by combination of NMR,ECD spectroscopy,and X-ray difraction analysis.Compounds 1 and 6-8 were tested to exhibit potential antitumor properties,of which 6 and 7 inhibited cell growth through inducing apoptosis and cell cycle arrest.In addition,these compounds could induce autophagy and PINK1/Parkin-mediated mitophagy in cancer cell lines,as well as suppress lung cancer A549 cells metastasis in vitro.展开更多
Three new homo-adamantanyl type natural products were derived from polyprenylated polycyclic acylphloroglucinol.Hypercohones A-C(1-3),along with five other known hypercohones(4-8),were isolated from the aerial parts o...Three new homo-adamantanyl type natural products were derived from polyprenylated polycyclic acylphloroglucinol.Hypercohones A-C(1-3),along with five other known hypercohones(4-8),were isolated from the aerial parts of Hypericum cohaerens.The structures of 1-3 were elucidated on the basis of comprehensive spectroscopic analysis.The inhibitory activities of these isolates against five human cancer cell lines in vitro were tested.展开更多
Five new polycyclic polyprenylated acylphloroglucinols(1-5),ascyrones A-E,and four known compounds(6-9)were isolated from the aerial parts of Hypericum ascyron.All of the isolates containing a bicyclo[3.3.1]nonane-2,4...Five new polycyclic polyprenylated acylphloroglucinols(1-5),ascyrones A-E,and four known compounds(6-9)were isolated from the aerial parts of Hypericum ascyron.All of the isolates containing a bicyclo[3.3.1]nonane-2,4,9-trione core and a benzoyl group,belonged to type B bicyclic polyprenylated acylphloroglucinols(BPAPs).Their structures and absolute configurations were established based on spectroscopic analyses and calculated electronic circular dichroism(ECD)data.The anti-inflammatory,neuroprotective and cytotoxicity activities of compounds 1-4 and 6-9 were evaluated.Compound 6 exhibited obvious anti-inflammatory activity in lipopolysaccharide(LPS)-induced RAW264.7 cells.Compounds 1 and 9 exhibited slight cytotoxicity against Hep3B cells.Meanwhile,compound 1 showed mild neuroprotective activity against corticosterone(CORT)-induced PC 12 cell damage at 10 μmol-L^(-1).展开更多
Four new polycyclic polyprenylated acylphloroglucinol type metabolites,hypercohones D–G(1–4),along with four known analogues(5–8),were isolated from the aerial parts of Hypericum cohaerens.The structures of these i...Four new polycyclic polyprenylated acylphloroglucinol type metabolites,hypercohones D–G(1–4),along with four known analogues(5–8),were isolated from the aerial parts of Hypericum cohaerens.The structures of these isolates were elucidated by extensive spectroscopic methods.The inhibitory activities of these isolates against five human cancer cell lines in vitro were also tested.展开更多
Six new polyphenols with diferent isoprenylated xanthones,isoprenylated acylphloroglucinols,and chromone architectures,hyperfaberols A-F(1-6),were isolated from the whole plants of Hypericum faberi along with seven ot...Six new polyphenols with diferent isoprenylated xanthones,isoprenylated acylphloroglucinols,and chromone architectures,hyperfaberols A-F(1-6),were isolated from the whole plants of Hypericum faberi along with seven other related known compounds.In which hyperfaberols A/B(1/2)and 12-13 were isoprenylated xanthones,hyperfaberols C-E(3-5)and 8-11 were seven isoprenylated acylphloroglucinol derivatives,while 6-7 were two chromones.Their structures were elucidated by comprehensive analysis of their spectroscopic data as well as detailed comparison with the literature data.Compounds 1 and 11 showed cytotoxities against the human esophageal cancer cell line(ECA-109)and the pancreatic tumor cell line(PANC-1)in vitro,respectively.展开更多
Columnaris (caused by Flavobacterium columnare) is one of the most common bacterial diseases affecting the pond-raised channel catfish (Ictalurus punctatus) in the southeastern United States of America resulting in an...Columnaris (caused by Flavobacterium columnare) is one of the most common bacterial diseases affecting the pond-raised channel catfish (Ictalurus punctatus) in the southeastern United States of America resulting in annual losses of millions of dollars. As part of our continuing effort to discover environmentally benign compounds for the control of columnaris disease, acyl derivatives of phloroglucinol were synthesized and tested against F. columnare using a rapid bioassay. Among the analogs that were tested, diacyl analogs showed very high antibacterial activity against F. columnare in the laboratory bioassay. Diisovaleryl and diisobutyryl analogs were found to have the strongest activity against F. columnare (isolate ALM-00-173) based on 24-h 50% inhibitory concentration (IC50) and minimum inhibitory concentration (MIC). Diisovaleryl and diisobutyryl analogs had IC50 values 0.82 mg/L and 0.80 mg/L, respectively, whereas the drug control florfenicol had an IC50 value of 0.81 mg/L. Diisovaleryl and diisobutyryl analogs also had 24-h relative-to- drug-control IC50 values around 1.0 indicating activities similar to florfenicol, which is included in medicated feed and is one of the current management approach for columnaris.展开更多
Tumor necrosis factor-α(TNF-α)is a promising target for inflammatory and autoimmune diseases.Spirohypertones A(1)and B(2),two unprecedented polycyclic polyprenylated acylphloroglucinols with highly rearranged skelet...Tumor necrosis factor-α(TNF-α)is a promising target for inflammatory and autoimmune diseases.Spirohypertones A(1)and B(2),two unprecedented polycyclic polyprenylated acylphloroglucinols with highly rearranged skeletons,were isolated from Hypericum patulum.The structures of 1 and 2 were confirmed through comprehensive spectroscopic analysis,single-crystal X-ray diffraction and electronic circular dichroism calculations.Importantly,2 showed remarkable TNF-αinhibitory activity,which could protect L929 cells from death induced by co-incubation with TNF-αand actinomycin D.It also demonstrated the ability to suppress the inflammatory response in HaCaT cells stimulated with TNF-α.Notably,in an imiquimod-induced psoriasis murine model,2 restrained symptoms of epidermal hyperplasia associated with psoriasis,presenting anti-inflammatory and antiproliferative effects.This discovery positions 2 as a potent TNF-αinhibitor,providing a promising lead compound for developing an antipsoriatic agent.展开更多
Objective To study the chemical constituents from the aerial parts of Hypericum beani/. Methods Various chromatographic techniques were used to separate the constituents and their structures were elucidated on the bas...Objective To study the chemical constituents from the aerial parts of Hypericum beani/. Methods Various chromatographic techniques were used to separate the constituents and their structures were elucidated on the basis of extensive spectroscopic interpretation. Results Fifteen compounds were isolated from the aerial parts of H. beanii. Their structures were identified as hyperbeanol E （1）, （E）-Iinalool-l-oic acid （2）, （4S,5R）-5-（4＇-methyl-3＇-pentenyl）-4-hydroxy-5-methyl- dihydrofuran-2-one （3）, benzoic acid （4）, 4-（3-O-3＂）-3＂-methylbutenyl-6-phenyl- pyran-2-one （5）, 4-hydroxy-4a,7-dimethoxy-4,4a-dihydrodibenzo-p-dioxJn-2（3H）- one （6）, isoimperatorin （7）, 2,3-dimethoxyxanthone （8）, 3,4-dihydroxy-2- methoxyxanthone （9）, osajaxanthone （10）, nigrolineaxanthone F （1 1）, hypercohone G （12）, betulinic acid （1 3）, oleanolic acid 3.13-caffeate （14）, and isoastilbin （1 5）. Conclusion Compound 1 is a new menthane monoterpene derivative which owns an extra lactone ring. Compounds 2-7 and 10-1 5 are isolated from genus Hypericum Linn. for the first time and the other compounds are first obtained from the plants in H. beanii.展开更多
基金supported by the National Natural Science Foundation for Distinguished Young Scholars(No.81725021)the National Natural Science Foundation of China(Nos.82003633,32100321,and 32300335)+1 种基金the National Natural Science Foundation of Hubei Province(Nos.2023AFB791 and 2023AFB530)the Knowledge Innovation Project of Wuhan Science and Technology Bureau(No.2023020201020534).
文摘Polycyclic polyprenylated acylphloroglucinols(PPAPs)represent a distinct subclass of specialized metabolites predominantly found in the plant kingdom,particularly within the Guttiferae(Clusiaceae)family.These compounds exhibit remarkable structural diversity and a wide range of biological activities.Seco-and nor-PPAPs,two unique variants of PPAPs with diverse skeletal structures,have been extensively investigated.As of June 2023,200 compounds have been isolated from four genera,with Hypericum being the primary source.Notably,115 of these compounds were identified in the past four years,indicating a significant increase in research activity.Seco-and nor-PPAPs can be categorized into six main subgroups based on the original PPAP scaffolds.Biological studies have revealed their potential in various therapeutic applications,including anti-cancer,anti-inflammatory,hepatoprotective,anti-Alzheimer’s disease(anti-AD),multidrug resistance(MDR)reversal,anti-depressant,neuroprotective,and immunosuppressive effects.This review provides a comprehensive overview of the occurrence,structures,and bioactivities of natural seco-and nor-PPAPs,offering valuable insights for the further development of PPAPs.
基金financially supported by the National Natural Science Foundation of China(Nos.32270413,82060631,82160808,and 82360035)the Science and Technology Department of Guizhou Province(Nos.QKHJC 2020–1Z076,QKHJC-ZK[2023]YB156,QKHJC-ZK[2021]YB569,and QKHPTRC[2020]5008)+4 种基金Excellent Young Talents Plan of Guizhou Medical University(2023,No.106)the 13thbatch of outstanding young scientific and technological talents in Guizhou Province(No.QKHPTRC[2021]5633)Guizhou Science and Technology Innovation Talent Team(No.QKHPTRC–CXTD[2022]007)High-level Innovative Talents in Guizhou Province(Thousand Levels of Talent for Chunmao Yuan in 2018)the project of State Key Laboratory of Functions and Applications of Medicinal Plants,Guizhou Medical University(Nos.FAMP202102K and QJJ[2023]113)。
文摘Hymoins A–C(1–3),three unusual polycyclic polyprenylated acylphloroglucinols(PPAPs)were isolated from the flowers of Hypericum monogynum.Hymoin A features the first intriguing 6/5/5/5/7 pentacyclic caged PPAP.Hymoin B is characterized by an unprecedented rearranged 5/6/8 tricyclic ring system,while hymoin C represents the first rearranged PPAP with a fantastic spirocyclic 5/6/7 ring system.Their structures were established by extensive spectroscopic analysis,X-ray crystallography,and computational methods.The plausible biosynthetic routes for the compounds were also proposed.In oleic acid(OA)-induced HepG2 cells,all compounds exhibited significant lipid-lowering activity at the concentrations of 2–8μmol/L.Further mechanistic study implied that compound 1 exhibited excellent lipid-lowering activity in OA-induced HepG2 cells through inhibiting the proteins of free fatty acids synthesis and improving lipidolysis.
基金supported by the Program for Changjiang Scholars of Ministry of Education of the People’s Republic of China(No.T2016088)the National Natural Science Foundation for Distinguished Young Scholars(No.81725021)+5 种基金the National Science and Technology Project of China(No.2018ZX09201001-001-003)the National Natural Science Foundation of China(Nos.82003633,32100321,and 32300335)the Research and Development Program of Hubei Province(No.2020BCA058)the Open Foundation of Hubei Key Laboratory of Wudang Local Chinese Medicine Research(No.WDCM2022003)the National Natural Science Foundation of Hubei Province(No.2023AFB530)the Knowledge Innovation Project of Wuhan Science and Technology Bureau(No.2023020201020534).
文摘Hyparillums A(1)and B(2),two previously unidentified polycyclic polyprenylated acylphloroglucinols(PPAPs)with intricate architectures,were isolated from Hypericum patulum Thunb.Hyparillum A was the first PPAP with eight-carbon rings based on an unprecedented 6/6/5/6/6/5/6/4 octocyclic system featuring a rare heptacyclo[10.8.1.11,10.03,8.08,21.012,19.014,17]docosane core.In contrast,hyparillum B featured a novel heptacyclic architecture(6/6/5/6/6/5/5)based on a hexacyclo[9.6.1.11,9.03,7.07,18.011,16]nonadecane motif.Furthermore,hyparillums A and B demonstrated promising inhibitory effects on the proliferation of murine splenocytes stimulated by anti-CD3/anti-CD28 monoclonal antibodies and lipopolysaccharide,exhibiting half-maximal inhibitory concentration(IC50)values ranging from 6.13±0.86 to 12.69±1.31μmol·L−1.
文摘Polyprenylated acylphloroglucinols represent an important class of natural products found in many plants.Among them,the two related products oblongifolin C(Ob-C)and guttiferone K(Gt-K)isolated from Garcinia species(notably from edible fruits),have attracted attention due to their marked anticancer properties.The two compounds only differ by the nature of the C-6 side chain,prenyl(Gt-K)or geranyl(Ob-C)on the phloroglucinol core.Their origin,method of extraction and biological properties are presented here,with a focus on the targets and pathways implicated in their anticancer activities.Both compounds markedly reduce cancer cell proliferation in vitro,as well as tumor growth and metastasis in vivo.They are both potent inducer of tumor cell apoptosis,and regulation of autophagy flux is a hallmark of their mode of action.The distinct mechanism leading to autophagosome accumulation in cells and the implicated molecular targets are discussed.The specific role of the chaperone protein HSPA8,known to interact with Ob-C,is addressed.Molecular models of Gt-K and Ob-C bound to HSPA8 provide a structural basis to their common HSPA8-binding recognition capacity.The review shed light on the mechanism of action of these compounds,to encourage their studies and potential development.
基金supported by the NSFC-Joint Foundation of Yunnan Province (Grant No.U1902213)the Second Tibetan Plateau Scientific Expedition and Research (STEP)program (Grant No.2019QZKK0502-0303)+2 种基金Natural Science Foundation of Yunnan (Grant No.2019FA003)CAS Interdisciplinary Innovation Team of CAS“Light of West China”Programthe Fund of State Key Laboratory of Phytochemistry and Plant Resources in West China (Grant No.E0230211Z1).
文摘Carascynol A,an unprecedented 4/9/8 ring system hybrid with a peroxide bridge,was characterized from Hyperi-cum ascyron.The architecture contains a caryophyllane-type moiety and a C_(6) unit derived from polyprenylated acylphloroglucinols.Its structure and absolute configuration were determined by comprehensive spectroscopic and X-ray diffraction data.Biologically,compound 1 inhibited cell proliferation in LoVo,SW480,and HCT116 cell lines(IC_(50)=12.30-24.57μM).
基金the National Natural Science Foundation of China(No.31900287)the Drug Innovation Major Project(2018ZX09711-001-007)the China Postdoctoral Science Foundation(2017M621889)。
文摘Two new type B polycyclic polyprenylated acylphloroglucinols(PPAPs)(1 and 2)and a known biogenetic precursor hyperbeanol Q(3)were isolated from the root extract of Hypericum beanii,a medicinal plant widespread in southwest China.Their chemical structures were elucidated by 1 D/2 D NMR and HRESIMS data analysis,and absolute configurations were determined through detailed electric circular dichroism(ECD)analysis including ECD exciton chirality,Mo2(OAc)4-induced ECD,and ECD comparison.Of these compounds,hyperbeone A(1)is a typical[3.3.1]-type B PPAP with an unusual C-1 geranyl side chain,and hyperberin C(2)possesses a rare bicyclo[5.3.1]hendecane core.Taking compound 3 as a starting point,a plausible biosynthetic pathway to the bicyclic type B frameworks of 1 and 2 was proposed.
基金supported by the National Natural Science Foundation for Distinguished Young Scholars(No.81725021)the National Natural Science Foundation of China(Nos.82003633 and 82173705)。
文摘Hepatic ischemia/reperfusion injury(IRI)remains a critical complication contributing to graft dysfunction following liver surgery.As part of an ongoing search for hepatoprotective natural products,five previously unreported homoadamantane-type polycyclic polyprenylated acylphloroglucinols(PPAPs),named hyperhomanoons A-E(1-5),and one known analog,hypersampsone O(6),were isolated from Hypericum patulum.Among these,compound 6 demonstrated potent protective effects against CoCl_(2)-induced hypoxic injury in hepatocytes.Furthermore,in a murine model of hepatic IRI induced by vascular occlusion,pretreatment with 6 markedly alleviated liver damage and reduced hepatocyte apoptosis.This study is the first to identify PPAPs as promising scaffolds for the development of therapeutic agents targeting hepatic IRI,underscoring their potential as lead compounds in drug discovery efforts for ischemic liver diseases.
基金supported by the Natural Sciences Foundation of Yunnan Province (2015FA032)Foundation of State Key Laboratory of Phytochemistry and Plant Resources in West China (P2015-ZZ07)+1 种基金the foundation from Youth Innovation Promotion Association CAS to X.W. Yang and G. Xuthe West Light Foundation of the Chinese Academy of Sciences to X.W. Yang
文摘Hyphenrones R–X(1–7), seven new polyprenylated acylphloroglucinols derivatives, were isolated from the fruits of Hypericum henryi, together with eight know analogues. Compounds 1 and 2 were elucidated to possess complex caged skeleton, while compounds 3–6 shared a common 3,9-epoxy moiety deriving from the normal polyprenylated acylphloroglucinols with a bicyclo[3.3.1]nonane-2,4,9-trione core. The new structures were elucidated on the basis of the interpretation of nuclear magnetic resonance(NMR) data, circular dichroism(CD) comparison, and single-crystal X-ray diffraction. In the bioassay, several compounds exhibited inhibitory activities against human tumor cell lines in vitro.
基金supported by the NSFC-Joint Foundation of Yunnan Province(U1902213)Chongqing Municipal Natural Science Foundation(cstc2018jcyjAX0388)+3 种基金the Second Tibetan Plateau Scientific Expedition and Research(STEP)program(2019QZKK0502)Southeast Asia Biodiversity Research Institute,CAS(2017CASSEABRIQG003)State Key Laboratory of Phytochemistry and Plant Resources in West China(P2017-KF02 and P2019-ZZ05)the Natural Sciences Foundation of Yunnan Province(2019FA003).
文摘A series of dearomatized isoprenylated acylphloroglucinols derivatives,hyperhenols A-E(1-5),as well as seven known analogues(6-12),were characterized from Hypericum henryi.Their structures were determined by combination of NMR,ECD spectroscopy,and X-ray difraction analysis.Compounds 1 and 6-8 were tested to exhibit potential antitumor properties,of which 6 and 7 inhibited cell growth through inducing apoptosis and cell cycle arrest.In addition,these compounds could induce autophagy and PINK1/Parkin-mediated mitophagy in cancer cell lines,as well as suppress lung cancer A549 cells metastasis in vitro.
基金The work was financially supported by the foundations from NSFC(20972167)the Young Academic Leader Raising Foundation of Yunnan Province(No.2009CI073)the foundation from CAS to Dr Gang Xu.
文摘Three new homo-adamantanyl type natural products were derived from polyprenylated polycyclic acylphloroglucinol.Hypercohones A-C(1-3),along with five other known hypercohones(4-8),were isolated from the aerial parts of Hypericum cohaerens.The structures of 1-3 were elucidated on the basis of comprehensive spectroscopic analysis.The inhibitory activities of these isolates against five human cancer cell lines in vitro were tested.
基金This work was supported by the National Natural Science Foundation of China(No.31800279).
文摘Five new polycyclic polyprenylated acylphloroglucinols(1-5),ascyrones A-E,and four known compounds(6-9)were isolated from the aerial parts of Hypericum ascyron.All of the isolates containing a bicyclo[3.3.1]nonane-2,4,9-trione core and a benzoyl group,belonged to type B bicyclic polyprenylated acylphloroglucinols(BPAPs).Their structures and absolute configurations were established based on spectroscopic analyses and calculated electronic circular dichroism(ECD)data.The anti-inflammatory,neuroprotective and cytotoxicity activities of compounds 1-4 and 6-9 were evaluated.Compound 6 exhibited obvious anti-inflammatory activity in lipopolysaccharide(LPS)-induced RAW264.7 cells.Compounds 1 and 9 exhibited slight cytotoxicity against Hep3B cells.Meanwhile,compound 1 showed mild neuroprotective activity against corticosterone(CORT)-induced PC 12 cell damage at 10 μmol-L^(-1).
基金the foundations from NSFC(20972167)the Young Academic Leader Raising Foundation of Yunnan Province(No.2009CI073)the foundation from CAS to Dr G.Xu.
文摘Four new polycyclic polyprenylated acylphloroglucinol type metabolites,hypercohones D–G(1–4),along with four known analogues(5–8),were isolated from the aerial parts of Hypericum cohaerens.The structures of these isolates were elucidated by extensive spectroscopic methods.The inhibitory activities of these isolates against five human cancer cell lines in vitro were also tested.
基金supported by the foundations from Kunming Institute of Botany(KIB2017001)Southeast Asia Biodiversity Research Institute(2017CASSEABRIQG003)CAS,and Yunnan Key Laboratory of Natural Medicinal Chemistry(S2017-ZZ11 and 2015-ZZ07).
文摘Six new polyphenols with diferent isoprenylated xanthones,isoprenylated acylphloroglucinols,and chromone architectures,hyperfaberols A-F(1-6),were isolated from the whole plants of Hypericum faberi along with seven other related known compounds.In which hyperfaberols A/B(1/2)and 12-13 were isoprenylated xanthones,hyperfaberols C-E(3-5)and 8-11 were seven isoprenylated acylphloroglucinol derivatives,while 6-7 were two chromones.Their structures were elucidated by comprehensive analysis of their spectroscopic data as well as detailed comparison with the literature data.Compounds 1 and 11 showed cytotoxities against the human esophageal cancer cell line(ECA-109)and the pancreatic tumor cell line(PANC-1)in vitro,respectively.
文摘Columnaris (caused by Flavobacterium columnare) is one of the most common bacterial diseases affecting the pond-raised channel catfish (Ictalurus punctatus) in the southeastern United States of America resulting in annual losses of millions of dollars. As part of our continuing effort to discover environmentally benign compounds for the control of columnaris disease, acyl derivatives of phloroglucinol were synthesized and tested against F. columnare using a rapid bioassay. Among the analogs that were tested, diacyl analogs showed very high antibacterial activity against F. columnare in the laboratory bioassay. Diisovaleryl and diisobutyryl analogs were found to have the strongest activity against F. columnare (isolate ALM-00-173) based on 24-h 50% inhibitory concentration (IC50) and minimum inhibitory concentration (MIC). Diisovaleryl and diisobutyryl analogs had IC50 values 0.82 mg/L and 0.80 mg/L, respectively, whereas the drug control florfenicol had an IC50 value of 0.81 mg/L. Diisovaleryl and diisobutyryl analogs also had 24-h relative-to- drug-control IC50 values around 1.0 indicating activities similar to florfenicol, which is included in medicated feed and is one of the current management approach for columnaris.
基金supported by the Program for Changjiang Scholars of Ministry of Education of the People's Republic of China(T2016088)the National Natural Science Foundation for Distinguished Young Scholars(81725021,China)the National Natural Science Foundation of China(Nos.82003633,32100321 and 32300335)+4 种基金the National Natural Science Foundation of Hubei Province(2023AFB791 and 2023AFB530,China)Knowledge Innovation Project of Wuhan Science and Technology Bureau(2023020201020534,China)the Research and Development Program of Hubei Province(2020BCA058,China)the Open Foundation of Hubei Key Laboratory of Wudang Local Chinese Medicine Research(WDCM2023010,China)Funded by Open Research Fund Program of State Key Laboratory of Biocatalysis and Enzyme Engineering(SKLBEE2023003,China).
文摘Tumor necrosis factor-α(TNF-α)is a promising target for inflammatory and autoimmune diseases.Spirohypertones A(1)and B(2),two unprecedented polycyclic polyprenylated acylphloroglucinols with highly rearranged skeletons,were isolated from Hypericum patulum.The structures of 1 and 2 were confirmed through comprehensive spectroscopic analysis,single-crystal X-ray diffraction and electronic circular dichroism calculations.Importantly,2 showed remarkable TNF-αinhibitory activity,which could protect L929 cells from death induced by co-incubation with TNF-αand actinomycin D.It also demonstrated the ability to suppress the inflammatory response in HaCaT cells stimulated with TNF-α.Notably,in an imiquimod-induced psoriasis murine model,2 restrained symptoms of epidermal hyperplasia associated with psoriasis,presenting anti-inflammatory and antiproliferative effects.This discovery positions 2 as a potent TNF-αinhibitor,providing a promising lead compound for developing an antipsoriatic agent.
基金National Natural Science Foundation of China(31300293,81422046)General Project of Applied Foundation Research,Yunnan Province(2013FB067)+2 种基金Basic Research Project of Ministry of Science and Technology of China(2012FY110300)Major State Basic Research Development Program(2010CB951704)Youth Innovation Promotion Association CAS and SRF for ROCS,SEM to WL.Xiao
文摘Objective To study the chemical constituents from the aerial parts of Hypericum beani/. Methods Various chromatographic techniques were used to separate the constituents and their structures were elucidated on the basis of extensive spectroscopic interpretation. Results Fifteen compounds were isolated from the aerial parts of H. beanii. Their structures were identified as hyperbeanol E （1）, （E）-Iinalool-l-oic acid （2）, （4S,5R）-5-（4＇-methyl-3＇-pentenyl）-4-hydroxy-5-methyl- dihydrofuran-2-one （3）, benzoic acid （4）, 4-（3-O-3＂）-3＂-methylbutenyl-6-phenyl- pyran-2-one （5）, 4-hydroxy-4a,7-dimethoxy-4,4a-dihydrodibenzo-p-dioxJn-2（3H）- one （6）, isoimperatorin （7）, 2,3-dimethoxyxanthone （8）, 3,4-dihydroxy-2- methoxyxanthone （9）, osajaxanthone （10）, nigrolineaxanthone F （1 1）, hypercohone G （12）, betulinic acid （1 3）, oleanolic acid 3.13-caffeate （14）, and isoastilbin （1 5）. Conclusion Compound 1 is a new menthane monoterpene derivative which owns an extra lactone ring. Compounds 2-7 and 10-1 5 are isolated from genus Hypericum Linn. for the first time and the other compounds are first obtained from the plants in H. beanii.
