Lobetyolin(LBT)is a polyacetylene glycoside found in diverse medicinal plants but mainly isolated from the roots of Codo-nopsis pilosula,known as Radix Codonopsis or Dangshen.Twelve traditional Chinese medicinal prepa...Lobetyolin(LBT)is a polyacetylene glycoside found in diverse medicinal plants but mainly isolated from the roots of Codo-nopsis pilosula,known as Radix Codonopsis or Dangshen.Twelve traditional Chinese medicinal preparations containing Radix Codonopsis were identified;they are generally used to tonify spleen and lung Qi and occasionally to treat cancer.Here we have reviewed the anticancer properties of Codonopsis extracts,LBT and structural analogs.Lobetyolin and lobetyolinin are the mono-and bis-glucosylated forms of the polyacetylenic compound lobetyol.Lobetyol and LBT have shown activi-ties against several types of cancer(notably gastric cancer)and we examined the molecular basis of their activity.A down-regulation of glutamine metabolism by LBT has been evidenced,contributing to drug-induced apoptosis and tumor growth inhibition.LBT markedly reduces both mRNA and protein expression of the amino acid transporter Alanine-Serine-Cysteine Transporter 2(ASCT2).Other potential targets are proposed here,based on the structural analogy with other anticancer compounds.LBT and related polyacetylene glycosides should be further considered as potential anticancer agents,but more work is needed to evaluate their efficacy,toxicity,and risk-benefit ratio.展开更多
The steroidal alkaloid cyclovirobuxine D(Cvb-D)is the active principle of the oral drug huangyangning used for many years in China for the treatment of cardiovascular and cerebrovascular diseases.The drug is listed in...The steroidal alkaloid cyclovirobuxine D(Cvb-D)is the active principle of the oral drug huangyangning used for many years in China for the treatment of cardiovascular and cerebrovascular diseases.The drug is listed in the Chinese pharmacopeia.Recent studies have revealed that this unsung alkaloid also displays anticancer properties in vitro and in vivo.The drug activates several signaling pathways,and notably represses phosphorylation of proteins EGFR,ERK,Akt,mTOR.Thereby,Cvb-D exerts antiproliferative and antimetastatic activities.In the present review,the anticancer effects of Cvb-D and related natural products isolated from Buxus species have been analyzed.The molecular targets of Cvb-D are unknown at present,but hypotheses are formulated based on the signaling pathways modulated by the drug and the analogy with other compounds.Proteins EGFR and CTHRC1,implicated in the antiproliferative action of Cvb-D,could be considered as upstream targets.A bolder assumption is also formulated with the metastasis-associated protein S100A4 as a potential co-target for Cvb-D.This review aims to shed light on the anticancer properties of Cvb-D and to encourage further mechanistic studies with this drug with a good safety profile and a recognized anti-cardiovascular efficacy.展开更多
Biflavonoids are divided in two classes:C-C type compounds represented by the dimeric compound amentoflavone and C-O-C-type compounds typified by hinokiflavone(HNK)with an ether linkage between the two connected apige...Biflavonoids are divided in two classes:C-C type compounds represented by the dimeric compound amentoflavone and C-O-C-type compounds typified by hinokiflavone(HNK)with an ether linkage between the two connected apigenin units.This later sub-group of bisflavonyl ethers includes HNK,ochnaflavone,delicaflavone and a few other dimeric compounds,found in a variety of plants,notably Selaginella species.A comprehensive review of the anticancer properties and mechanism of action of HNK is provided,to highlight the anti-proliferative and anti-metastatic activities of HNK and derivatives,and HNK-containing plant extracts.The anticancer effects rely on the capacity of HNK to interfere with the ERK1-2/p38/NFκB signaling pathway and the regulation of the expression of the matrix metalloproteinases MMP-2 and MMP-9(with a potential direct binding to MMP-9).In addition,HNK was found to function as a potent modulator of pre-mRNA splicing,inhibit-ing the SUMO-specific protease SENP1.As such,HNK represents a rare SENP1 inhibitor of natural origin and a scaffold to design synthetic compounds.Oral formulations of HNK have been elaborated to enhance its solubility,to facilitate the compound delivery and to enhance its anticancer efficacy.The review shed light on the anticancer potential of C-O-C-type biflavonoids and specifically on the pharmacological profile of HNK.This compound deserves further attention as a regu-lator of pre-mRNA splicing,useful to treat cancers(in particular hepatocellular carcinoma)and other human pathologies.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
Nagilactones are tetracyclic natural products isolated from various Podocarpus species.These lactone-based compounds display a range of pharmacological effects,including antifungal,anti-atherosclerosis,anti-inflammato...Nagilactones are tetracyclic natural products isolated from various Podocarpus species.These lactone-based compounds display a range of pharmacological effects,including antifungal,anti-atherosclerosis,anti-inflammatory and anticancer activities reviewed here.The most active derivatives,such as nagilactones C,E and F,exhibit potent anticancer activities against different cancer cell lines and tumor models.A comprehensive analysis of their mechanism of action indicates that their anticancer activity mainly derives from three complementary action:(i)a drug-induced inhibition of cell proliferation coupled with a cell cycle perturbation and induction of apoptosis,(ii)a blockade of the epithelial to mesenchymal cell transi-tion contributing to an inhibition of cancer cell migration and invasion and(iii)a capacity to modulate the PD-L1 immune checkpoint.Different molecular effectors have been implicated in the antitumor activity,chiefly the AP-1 pathway blocked upon activation of the JNK/c-Jun axis.Nag-C is a potent inhibitor of protein synthesis binding to eukaryotic ribosomes and inhibition of different protein kinases,such as RIOK2 and JAK2,has been postulated with Nag-E.The literature survey on nagilactones highlights the therapeutic potential of these little-known terpenoids.The mechanistic analysis also provides useful information for structurally related compounds(podolactones,oidiolactones,inumakilactones)isolated from Podo-carpus plants.展开更多
The roots of the plant Cynanchum otophyllum C. K. Schneid(Apocynaceae), known as Qingyangshen in Chinese, are used for a long time as a traditional medicine by different ethnic communities in the Yunnan province(China...The roots of the plant Cynanchum otophyllum C. K. Schneid(Apocynaceae), known as Qingyangshen in Chinese, are used for a long time as a traditional medicine by different ethnic communities in the Yunnan province(China). The multiple properties and applications of this herbal medicine have been analyzed. C. otophyllum is a perennial herbal liana, nonedible, and generally wild harvested. A cultivation method has been proposed to increase the fruit set level. Qingyangshen is used essentially to treat epilepsy, rheumatism, or other inflammatory diseases. The plant can be found also in diverse polyherbal preparations used in cosmetic or as food supplement(detox products), and in phyto-preparations claimed to reduce hair loss. The plant is a rich reservoir of C-21 steroidal glycosides. Many bioactive compounds have been isolated from this plant and some of them have been pharmacologically characterized, such as otophyllosides, cynotophyllosides, cynanotins, cynotogenins, cynanchins, all briefly evocated here. The plant presents also interesting features in other domains. In particular, leave extracts of C. otophyllum C. K. Schneid contain proteases which are exploited for the local preparation of a cheese-like milk cake. Qingyangshen herbal preparation can be useful to treat epilepsy and inflammation. It has applications beyond medicine in the cosmetic and food industry.展开更多
The traditional Chinese medicine,Xihuang pills(XHP),has long been used for the management of cancers,both to limit tumor cells proliferation and dissemination,and to protect nontumor cells from damages induced by conv...The traditional Chinese medicine,Xihuang pills(XHP),has long been used for the management of cancers,both to limit tumor cells proliferation and dissemination,and to protect nontumor cells from damages induced by conventional therapeutic agents.XHP is made from two plant extracts(from Boswellia carteri and Commiphora myrrha)and two animal-derived products(from Moschus moschiferus and Calculus bovis).Recent advances into the mechanism of action of XHP and its clinical efficacy are reviewed here to highlight its potential to treat breast and colon cancers in particular.The immunoregulatory effects of XHP are underlined.Similar traditional medicinal preparations containing Boswellia and Commiphora are discussed,as well as the activities of the major natural products found in XHP including abietic acid,acetyl-keto-boswellic acid,and muscone.Pharmacological and clinical studies of XHP and similar medicinal preparations,such as the Korean medicine Hang Am Dan-B,are encouraged.展开更多
The dried fruits of the plant Forsythia suspensa(Forsythia Fructus: Lianqiao in Chinese) are used in many herbal preparations to treat various diseases or the associated symptoms. Forsythia extracts contain phenyletha...The dried fruits of the plant Forsythia suspensa(Forsythia Fructus: Lianqiao in Chinese) are used in many herbal preparations to treat various diseases or the associated symptoms. Forsythia extracts contain phenylethanoid glycosides(Ph Gs) such as the forsythosides(Fst A-to-P). The leading products, Fst-A,-B and-F(arenarioside), can be found also in >90 other plants inventoried here. The pharmacological properties of Fst are reviewed, with emphasis on their anticancer, antiviral, and antibacterial activities, which essentially derive from their anti-inflammatory and antioxidant effects. Fst-B functions as a potential binder of the repressor protein Kelch-like ECH-association protein 1(Keap 1), thus promoting the nuclear translocation of the transcription factor Nuclear factor erythroid 2-related factor 2(Nrf2) implicated in the subsequent activation of the production of antioxidant enzymes and repression of the oxidative stress. The regulation of the Nrf2/Heme oxygenase-1 pathway is the central piece of the multifaceted mechanism of action of Fst-A/B. Their prominent antioxidant and anti-inflammatory effects support the use of these compounds in different inflammation-related diseases and conditions, from sepsis to neuroprotection and many other pathologies discussed here. In addition, these properties contribute to the antiviral action of the compounds. Fst-A/B displays activities against the influenza A virus and different Fst-containing traditional Chinese medicinal(TCMs) have revealed beneficial effects to combat the current COVID-19 pandemic. The mechanisms whereby Fst-A/B could inhibit viral multiplication are discussed. Ph Gs likely contribute to the anti-COVID-19 activities reported with several TCM such as Shuang-Huang-Lian oral liquid, Lianhua-Qingwen capsules, and others. This review highlights the pharmacological profile of Fst and illustrates health benefits associated with the use of Forsythia Fructus.展开更多
文摘Lobetyolin(LBT)is a polyacetylene glycoside found in diverse medicinal plants but mainly isolated from the roots of Codo-nopsis pilosula,known as Radix Codonopsis or Dangshen.Twelve traditional Chinese medicinal preparations containing Radix Codonopsis were identified;they are generally used to tonify spleen and lung Qi and occasionally to treat cancer.Here we have reviewed the anticancer properties of Codonopsis extracts,LBT and structural analogs.Lobetyolin and lobetyolinin are the mono-and bis-glucosylated forms of the polyacetylenic compound lobetyol.Lobetyol and LBT have shown activi-ties against several types of cancer(notably gastric cancer)and we examined the molecular basis of their activity.A down-regulation of glutamine metabolism by LBT has been evidenced,contributing to drug-induced apoptosis and tumor growth inhibition.LBT markedly reduces both mRNA and protein expression of the amino acid transporter Alanine-Serine-Cysteine Transporter 2(ASCT2).Other potential targets are proposed here,based on the structural analogy with other anticancer compounds.LBT and related polyacetylene glycosides should be further considered as potential anticancer agents,but more work is needed to evaluate their efficacy,toxicity,and risk-benefit ratio.
基金Chemical compound studied in this article:Cyclovirobuxine D(PubChem CID:260439).
文摘The steroidal alkaloid cyclovirobuxine D(Cvb-D)is the active principle of the oral drug huangyangning used for many years in China for the treatment of cardiovascular and cerebrovascular diseases.The drug is listed in the Chinese pharmacopeia.Recent studies have revealed that this unsung alkaloid also displays anticancer properties in vitro and in vivo.The drug activates several signaling pathways,and notably represses phosphorylation of proteins EGFR,ERK,Akt,mTOR.Thereby,Cvb-D exerts antiproliferative and antimetastatic activities.In the present review,the anticancer effects of Cvb-D and related natural products isolated from Buxus species have been analyzed.The molecular targets of Cvb-D are unknown at present,but hypotheses are formulated based on the signaling pathways modulated by the drug and the analogy with other compounds.Proteins EGFR and CTHRC1,implicated in the antiproliferative action of Cvb-D,could be considered as upstream targets.A bolder assumption is also formulated with the metastasis-associated protein S100A4 as a potential co-target for Cvb-D.This review aims to shed light on the anticancer properties of Cvb-D and to encourage further mechanistic studies with this drug with a good safety profile and a recognized anti-cardiovascular efficacy.
基金This research did not receive any specific grant from funding agencies in the public,commercial,or not-for-profit sectors。
文摘Biflavonoids are divided in two classes:C-C type compounds represented by the dimeric compound amentoflavone and C-O-C-type compounds typified by hinokiflavone(HNK)with an ether linkage between the two connected apigenin units.This later sub-group of bisflavonyl ethers includes HNK,ochnaflavone,delicaflavone and a few other dimeric compounds,found in a variety of plants,notably Selaginella species.A comprehensive review of the anticancer properties and mechanism of action of HNK is provided,to highlight the anti-proliferative and anti-metastatic activities of HNK and derivatives,and HNK-containing plant extracts.The anticancer effects rely on the capacity of HNK to interfere with the ERK1-2/p38/NFκB signaling pathway and the regulation of the expression of the matrix metalloproteinases MMP-2 and MMP-9(with a potential direct binding to MMP-9).In addition,HNK was found to function as a potent modulator of pre-mRNA splicing,inhibit-ing the SUMO-specific protease SENP1.As such,HNK represents a rare SENP1 inhibitor of natural origin and a scaffold to design synthetic compounds.Oral formulations of HNK have been elaborated to enhance its solubility,to facilitate the compound delivery and to enhance its anticancer efficacy.The review shed light on the anticancer potential of C-O-C-type biflavonoids and specifically on the pharmacological profile of HNK.This compound deserves further attention as a regu-lator of pre-mRNA splicing,useful to treat cancers(in particular hepatocellular carcinoma)and other human pathologies.
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.
文摘Nagilactones are tetracyclic natural products isolated from various Podocarpus species.These lactone-based compounds display a range of pharmacological effects,including antifungal,anti-atherosclerosis,anti-inflammatory and anticancer activities reviewed here.The most active derivatives,such as nagilactones C,E and F,exhibit potent anticancer activities against different cancer cell lines and tumor models.A comprehensive analysis of their mechanism of action indicates that their anticancer activity mainly derives from three complementary action:(i)a drug-induced inhibition of cell proliferation coupled with a cell cycle perturbation and induction of apoptosis,(ii)a blockade of the epithelial to mesenchymal cell transi-tion contributing to an inhibition of cancer cell migration and invasion and(iii)a capacity to modulate the PD-L1 immune checkpoint.Different molecular effectors have been implicated in the antitumor activity,chiefly the AP-1 pathway blocked upon activation of the JNK/c-Jun axis.Nag-C is a potent inhibitor of protein synthesis binding to eukaryotic ribosomes and inhibition of different protein kinases,such as RIOK2 and JAK2,has been postulated with Nag-E.The literature survey on nagilactones highlights the therapeutic potential of these little-known terpenoids.The mechanistic analysis also provides useful information for structurally related compounds(podolactones,oidiolactones,inumakilactones)isolated from Podo-carpus plants.
文摘The roots of the plant Cynanchum otophyllum C. K. Schneid(Apocynaceae), known as Qingyangshen in Chinese, are used for a long time as a traditional medicine by different ethnic communities in the Yunnan province(China). The multiple properties and applications of this herbal medicine have been analyzed. C. otophyllum is a perennial herbal liana, nonedible, and generally wild harvested. A cultivation method has been proposed to increase the fruit set level. Qingyangshen is used essentially to treat epilepsy, rheumatism, or other inflammatory diseases. The plant can be found also in diverse polyherbal preparations used in cosmetic or as food supplement(detox products), and in phyto-preparations claimed to reduce hair loss. The plant is a rich reservoir of C-21 steroidal glycosides. Many bioactive compounds have been isolated from this plant and some of them have been pharmacologically characterized, such as otophyllosides, cynotophyllosides, cynanotins, cynotogenins, cynanchins, all briefly evocated here. The plant presents also interesting features in other domains. In particular, leave extracts of C. otophyllum C. K. Schneid contain proteases which are exploited for the local preparation of a cheese-like milk cake. Qingyangshen herbal preparation can be useful to treat epilepsy and inflammation. It has applications beyond medicine in the cosmetic and food industry.
文摘The traditional Chinese medicine,Xihuang pills(XHP),has long been used for the management of cancers,both to limit tumor cells proliferation and dissemination,and to protect nontumor cells from damages induced by conventional therapeutic agents.XHP is made from two plant extracts(from Boswellia carteri and Commiphora myrrha)and two animal-derived products(from Moschus moschiferus and Calculus bovis).Recent advances into the mechanism of action of XHP and its clinical efficacy are reviewed here to highlight its potential to treat breast and colon cancers in particular.The immunoregulatory effects of XHP are underlined.Similar traditional medicinal preparations containing Boswellia and Commiphora are discussed,as well as the activities of the major natural products found in XHP including abietic acid,acetyl-keto-boswellic acid,and muscone.Pharmacological and clinical studies of XHP and similar medicinal preparations,such as the Korean medicine Hang Am Dan-B,are encouraged.
文摘The dried fruits of the plant Forsythia suspensa(Forsythia Fructus: Lianqiao in Chinese) are used in many herbal preparations to treat various diseases or the associated symptoms. Forsythia extracts contain phenylethanoid glycosides(Ph Gs) such as the forsythosides(Fst A-to-P). The leading products, Fst-A,-B and-F(arenarioside), can be found also in >90 other plants inventoried here. The pharmacological properties of Fst are reviewed, with emphasis on their anticancer, antiviral, and antibacterial activities, which essentially derive from their anti-inflammatory and antioxidant effects. Fst-B functions as a potential binder of the repressor protein Kelch-like ECH-association protein 1(Keap 1), thus promoting the nuclear translocation of the transcription factor Nuclear factor erythroid 2-related factor 2(Nrf2) implicated in the subsequent activation of the production of antioxidant enzymes and repression of the oxidative stress. The regulation of the Nrf2/Heme oxygenase-1 pathway is the central piece of the multifaceted mechanism of action of Fst-A/B. Their prominent antioxidant and anti-inflammatory effects support the use of these compounds in different inflammation-related diseases and conditions, from sepsis to neuroprotection and many other pathologies discussed here. In addition, these properties contribute to the antiviral action of the compounds. Fst-A/B displays activities against the influenza A virus and different Fst-containing traditional Chinese medicinal(TCMs) have revealed beneficial effects to combat the current COVID-19 pandemic. The mechanisms whereby Fst-A/B could inhibit viral multiplication are discussed. Ph Gs likely contribute to the anti-COVID-19 activities reported with several TCM such as Shuang-Huang-Lian oral liquid, Lianhua-Qingwen capsules, and others. This review highlights the pharmacological profile of Fst and illustrates health benefits associated with the use of Forsythia Fructus.
