RESUMO
Six spirobiflavonoid stereoisomers including two new ones, spiropensilisols A (1) and B (2), were isolated from a mass-limited trunk barks of Glyptostrobus pensilis, an endangered conifer endemic to China. The new structures featuring a benzofuran-containing spirolactone and their absolute configurations were determined by extensive spectroscopic methods. All the isolates showed significant inhibitory activities against the human protein tyrosine phosphatase 1B (PTP1B) enzyme, a potential therapeutic target for diabetes and obesity, with IC50 values ranging from 3.3 to 17.1 µM. A preliminary SAR analysis with assistance of the molecular modeling approach was performed for the most potent compound (i.e., 1), to understand the nature of interactions governing the binding mode of spirobiflavonids within the active site of the PTP1B enzyme.
Assuntos
Inibidores Enzimáticos/química , Flavonoides/química , Proteína Tirosina Fosfatase não Receptora Tipo 1/antagonistas & inibidores , Traqueófitas/química , Sítios de Ligação , Domínio Catalítico , Inibidores Enzimáticos/metabolismo , Flavonoides/isolamento & purificação , Flavonoides/metabolismo , Humanos , Espectroscopia de Ressonância Magnética , Conformação Molecular , Simulação de Acoplamento Molecular , Proteína Tirosina Fosfatase não Receptora Tipo 1/metabolismo , Estereoisomerismo , Relação Estrutura-Atividade , Traqueófitas/metabolismoRESUMO
Ten diterpenoids including three new abietanes (1-3) were isolated from the twigs and needles of Podocarpus imbricatus, an endangered conifer growing in a Cantonese garden. The new structures were established by means of spectroscopic methods. Among the isolates, 3ß-hydroxy-abieta-8,11,13-trien-7-one (5), decandrin G (6), and 7,15-pimaradien-18-oic acid (8) showed significant anti-neuroinflammatory activities by inhibiting the overproduction of nitric oxide (NO) in lipopolysaccharide (LPS)-stimulated murine BV-2 microglial cells, with IC50 values of 3.7, 11.1, and 4.5 µM, respectively.
Assuntos
Abietanos/isolamento & purificação , Abietanos/farmacologia , Traqueófitas/química , Animais , Lipopolissacarídeos/farmacologia , Camundongos , Microglia/efeitos dos fármacos , Estrutura Molecular , Óxido Nítrico/biossínteseRESUMO
Nine unexpected new flavonol glycoside cyclodimers in the truxinate (1-7, biginkgosides A-G, respectively) or truxillate [biginkgosides H (8) and I (9)] forms were isolated as minor components from the extract of Ginkgo biloba leaves. The new dimers possess an unusual cyclobutane ring formed by a [2+2]-cycloaddition between two symmetric (for compounds 1-5 and 7-9) or nonsymmetric (for 6) flavonol coumaroyl glucorhamnosides. A plausible biosynthetic pathway for these new compounds based on the frontier molecular orbital theory of cycloaddition reactions is briefly discussed. An antineuroinflammatory screening revealed that biginkgosides E (5) and H (8) inhibited nitric oxide production in lipopolysaccharide-activated BV-2 microglial cells, with IC50 values of 2.91 and 17.23 µM, respectively. Additionally, biginkgoside F (6) showed a significant neuroprotective effect (34.3% increase in cell viability at 1 µM) against Aß25-35-induced cell viability decrease in SH-SY5Y neuroblastoma cells.
Assuntos
Peptídeos beta-Amiloides/farmacologia , Medicamentos de Ervas Chinesas/isolamento & purificação , Medicamentos de Ervas Chinesas/farmacologia , Flavonóis/isolamento & purificação , Flavonóis/farmacologia , Ginkgo biloba/química , Glicosídeos/isolamento & purificação , Glicosídeos/farmacologia , Fármacos Neuroprotetores/farmacologia , Folhas de Planta/química , Peptídeos beta-Amiloides/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Medicamentos de Ervas Chinesas/química , Ésteres , Flavonóis/química , Glicosídeos/química , Lipopolissacarídeos/farmacologia , Macrófagos/metabolismo , Estrutura Molecular , Neuroblastoma/tratamento farmacológico , Fármacos Neuroprotetores/química , Fármacos Neuroprotetores/isolamento & purificação , Óxido Nítrico/biossíntese , Ressonância Magnética Nuclear Biomolecular , Fragmentos de Peptídeos/efeitos dos fármacos , Extratos Vegetais/farmacologiaRESUMO
The genus Fagopyrum (Polygonaceae), currently comprising 15 species of plants, includes three important buckwheat species: Fagopyrum esculentum (F. esculentum) Moench. (common buckwheat), Fagopyrum tataricum (F. tataricum) (L.) Gaertn. (tartary buckwheat) and Fagopyrum dibotrys (F. dibotrys) (D. Don) Hara. (perennial buckwheat), which have been well explored due to their long tradition of both edible and medicinal use. This review aimed to present an up-to-date and comprehensive analysis of the phytochemistry and pharmacology of the three Fagopyrum buckwheats. In addition, the scope for future research was also discussed. All available references included in this paper were compiled from major databases, such as MEDLINE, Pubmed, Scholar, Elsevier, Springer, Wiley and CNKI. A total of 106 compounds isolated from three Fagopyrum buckwheats can be mainly divided into six classes: flavonoids, phenolics, fagopyritols, triterpenoids, steroids and fatty acids. Flavonoids and phenolic compounds were considered to be the major active components. Considerable pharmacological experiments both in vitro and in vivo have validated that Fagopyrum buckwheats possess antitumor, anti-oxidant, anti-inflammatory, hepatoprotective, anti-diabetic activities, etc. All reported data lead us to conclude that Fagopyrum buckwheats have convincing medicinal potential. However, further research is needed to explore its bioactive constituents, the relationship to their structural activities and the molecular mechanisms of action.
Assuntos
Fagopyrum/química , Compostos Fitoquímicos/química , Antialérgicos/química , Antialérgicos/isolamento & purificação , Antialérgicos/farmacologia , Antibacterianos/química , Antibacterianos/isolamento & purificação , Antibacterianos/farmacologia , Anti-Inflamatórios/química , Anti-Inflamatórios/isolamento & purificação , Anti-Inflamatórios/farmacologia , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/isolamento & purificação , Antineoplásicos Fitogênicos/farmacologia , Antioxidantes/química , Antioxidantes/isolamento & purificação , Antioxidantes/farmacologia , Fadiga/tratamento farmacológico , Hipoglicemiantes/química , Hipoglicemiantes/isolamento & purificação , Hipoglicemiantes/farmacologia , Compostos Fitoquímicos/isolamento & purificação , Compostos Fitoquímicos/farmacologia , Substâncias Protetoras/química , Substâncias Protetoras/isolamento & purificação , Substâncias Protetoras/farmacologiaRESUMO
Based on bioactivity-oriented isolation, the EtOAc extract of a culture broth of the endophytic fungus Perenniporia tephropora Z41 from Taxus chinensis var. mairei, with strong anti-Pyricularia oryzae activity, afforded a new sesquiterpenoid, perenniporin A (1), together with three known compounds, ergosterol (2), rel-(+)-(2aR,5R,5aR,8S,8aS,8bR)-decahydro-2,2,5,8-tetramethyl-2H-naphtho[1,8-bc]genfuran-5-ol (3), and albicanol (4). Their structures were elucidated by means of spectroscopic methods. All the isolated compounds and the EtOAc extract of P. tephropora Z41 (EPT) were evaluated for their cytotoxic activity against three human cancer cell lines (HeLa, SMMC-7721, and PANC-1). EPT demonstrated significant cytotoxicity with IC(50) values ranging from 2 to 15 µg/mL. Compound 2 was the most cytotoxic constituent against the tested cell lines with IC(50) values of 1.16, 11.63, and 11.80 µg/mL, respectively, while compounds 1, 3, and 4 exhibited moderate cytotoxicity with IC(50) values ranging from 6 to 58 µg/mL. We conclude that the endophytic fungus P. tephropora is a promising source of novel and cytotoxic metabolites.
Assuntos
Antineoplásicos/química , Antineoplásicos/isolamento & purificação , Endófitos/química , Endófitos/isolamento & purificação , Polyporaceae/química , Polyporaceae/isolamento & purificação , Taxus/microbiologia , Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Análise por Conglomerados , DNA Fúngico/química , DNA Fúngico/genética , DNA Ribossômico/química , DNA Ribossômico/genética , DNA Espaçador Ribossômico/química , DNA Espaçador Ribossômico/genética , Endófitos/classificação , Endófitos/genética , Genes de RNAr , Humanos , Concentração Inibidora 50 , Dados de Sequência Molecular , Estrutura Molecular , Filogenia , Polyporaceae/classificação , Polyporaceae/genética , RNA Fúngico/genética , RNA Ribossômico 5,8S/genética , Análise de Sequência de DNA , Análise EspectralRESUMO
Given the limitations of existing therapeutic agents for treatment of postmenopausal osteoporosis, there still remains a need for more options with both efficacy and less adverse effects. Cistanche deserticola Y. C. Ma is known as a popular tonic herb traditionally used to treatment deficiency of kidney energy including muscle weakness in minority area of Asian counties. Based on the theory of "kidney dominate bone," an ovariectomized (OVX) rat model of postmenopausal osteoporosis was used to evaluate the therapeutic effect of C. deserticola extract (CDE) on bone loss. Forty eight female Sprague-Dawley rats, aged about 12 weeks, were randomly assigned into six groups including sham group orally administrated with 0.5% carboxymethyl cellulose sodium (CMC-Na) (sham), positive group treated with 1 mg/kg of estradiol valerate (EV), low, moderate, and high dosage groups orally administrated with 200, 400, and 800 mg/kg/day of CDE, respectively. After 3 months of continuous intervention, CDE exhibited significant anti-osteoporotic activity evidenced by the enhanced total bone mineral density, ameliorated bone microarchitecture; increased alkaline phosphatase activity; decreased deoxypyridinoline, cathepsin K, tartrate-resistant acid phosphatase, and malondialdehyde levels; whereas the body, uterus, and vagina weights in OVX rats were not influenced by CDE intervention. In addition, a seemed contradictory phenomenon on levels of calcium and phosphorus between OVX and sham rats were observed and elucidated. Mechanistically, CDE significantly down-regulated the levels of TRAF6, RANKL, RANK, NF-κB, IKKß, NFAT2, and up-regulated the phosphatidylinositol 3-kinase (PI3K), AKT, osteoprotegerin, and c-Fos expressions, which implied CDE could suppress RANKL/RANK-induced activation of downstream NF-κB and PI3K/AKT pathways, and ultimately, preventing activity of the key osteoclastogenic proteins NFAT2 and c-Fos. All of the data suggested CDE possessed potential anti-osteoporotic activity and this effect was, at least in part, involved in modulation of RANKL/RANK/TRAF6-mediated NF-κB and PI3K/AKT signaling as well as c-Fos and NFAT2 levels. Therefore, CDE may represent a useful promising remedy candidate for treatment of postmenopausal osteoporosis.
RESUMO
During a further and comprehensive phytochemical investigation on the shed trunk barks of the critically endangered plant Abies beshanzuensis, one new (1) and ten known (2-11) lignans with diverse structures were isolated. On the basis of spectroscopic methods, the new structure was established to be (7S,8R,8'R)-4'-methoxyl-α-conidendrin (1). Among the isolated lignans, (-)-matairesinol (5) and (-)-arctigenin (6) showed significant anti-neuroinflammatory activities by inhibiting the overproduction of nitric oxide in lipopolysaccharide-stimulated murine BV-2 microglial cells, with IC50 values of 11.5 and 19.0 µM, respectively.
Assuntos
Abies/química , Anti-Inflamatórios/isolamento & purificação , Lignanas/isolamento & purificação , Animais , Anti-Inflamatórios/farmacologia , Células Cultivadas , Furanos/farmacologia , Lignanas/química , Lignanas/farmacologia , Camundongos , Microglia/efeitos dos fármacos , Óxido Nítrico/biossíntese , Casca de Planta/químicaRESUMO
Our study aimed to investigate the antiosteoporotic properties of the ethanol extract of Podocarpium podocarpum (DC.) Yang et Huang (PE) in ovariectomized (OVX) rats and to characterize the active constituents. As a result, PE significantly inhibited the increased urinary Ca excretion and activity of bone resorption markers including tartrate-resistant acid phosphatase (TRAP), deoxypyridinoline crosslinks and cathepsin K in OVX rats, whereas exhibited little effects on the body, uterus and vagina weight. Detailed micro-CT analysis showed that PE notably enhanced bone quality, with increased bone mineral content (BMC), bone volume fraction (BVF), connectivity density (CD), tissue mineral content (TMC), tissue mineral density (TMD) and trabecular number (Tb. N), and decreased trabecular separation (Tb. Sp), in OVX animal. Those findings implied that PE had notable antiosteoporotic effect, especially effective in preventing bone resorption, with little side-effects on reproductive tissue. Further chemical investigation led to the isolation of 17 flavonoids, most of which showed significantly stimulatory effect on osteoblastic proliferation, ALP activity and mineralized nodes formation as well as inhibitory effect on osteoclastic TRAP activity in osteoblastic and osteoclastic cells. Our results indicated that PE, with abundant flavonoids, had remarkable antiosteoporotic activity and therefore can be a promising candidate for the treatment of postmenopausal osteoporosis induced by estrogen deficiency through herbal remedy.
Assuntos
Densidade Óssea/efeitos dos fármacos , Fabaceae/química , Osteoporose/tratamento farmacológico , Extratos Vegetais/farmacologia , Fosfatase Ácida/metabolismo , Fosfatase Alcalina/metabolismo , Animais , Células Cultivadas , Modelos Animais de Doenças , Feminino , Fêmur/efeitos dos fármacos , Flavonoides/isolamento & purificação , Flavonoides/farmacologia , Isoenzimas/metabolismo , Estrutura Molecular , Osteoblastos/efeitos dos fármacos , Osteoclastos/efeitos dos fármacos , Ovariectomia , Ratos , Ratos Sprague-Dawley , Fosfatase Ácida Resistente a TartaratoRESUMO
Hypertrophic scarring, a common proliferative disorder of dermal fibroblasts, results from an overproduction of fibroblasts and excessive deposition of collagen. Although treatment with surgical excision or steroid hormones can modify the symptoms, numerous treatment-related complications have been described. In view of this, we investigated the therapeutic effects of essential oil (EO) from rhizomes of Ligusticum chuanxiong Hort. (Umbelliferae) on formed hypertrophic scars in a rabbit ear model. EO was prepared as a liposomal formulation (liposome-enveloped essential oil, LEO) and a rabbit ear model with hypertrophic scars was established. LEO (2.5, 5, and 10%) was applied once daily to the scars for 28 days. On postoperative day 56, the scar tissue was excised for masson's trichrome staining, detection of fibroblast apoptosis, assays of the levels of collagens I and III, and analysis of the mRNA expression of matrix metalloproteinase-1 (MMP-1), caspase-3 and -9, and transforming growth factor beta 1 (TGF-ß(1)). In addition, the scar elevation index (SEI) was also determined. As a result, LEO treatment significantly alleviated formed hypertrophic scars on rabbit ears. The levels of TGF-ß(1), MMP-1, collagen I, and collagen III were evidently decreased, and caspase -3 and -9 levels and apoptosis cells were markedly increased in the scar tissue. SEI was also significantly reduced. Histological findings exhibited significant amelioration of the collagen tissue. These results suggest that LEO possesses the favorable therapeutic effects on formed hypertrophic scars in the rabbit ear model and may be an effective cure for human hypertrophic scars.