RESUMO
Ganoderma mushrooms are of great nutritious and medicinal values. This study was designed to characterize compounds from the fruiting bodies of Ganoderma cochlear and investigate their protective effects against kidney disorders. Six novel meroterpenoids cochlearoids F-K (1-6) were isolated by utilizing phytochemical approaches. Their structures were identified on the basis of extensive spectroscopic data and calculation methods. Biological evaluation shows that compounds 1-4 and 6 exhibit potent inhibitory activity on fibronectin overproduction in TGF-ß1-induced HKC-8 cells.
Assuntos
Carpóforos/química , Ganoderma/química , Rim/efeitos dos fármacos , Substâncias Protetoras/farmacologia , Terpenos/química , Terpenos/farmacologia , Linhagem Celular , Fibronectinas/metabolismo , Humanos , Rim/metabolismo , Terpenos/isolamento & purificação , Fator de Crescimento Transformador beta1/metabolismoRESUMO
The morphological characteristic of Dendrobium moschatum (Buch.-Ham.) Sw. 1805 is very distinctive among Dendrobium Sw. 1799, and it has high medicinal and ornamental values. Here, we reported the first complete chloroplast genome of D. moschatum. The complete genome of D. moschatum was 159,701 bp in length with 130 genes, including 38 tRNA, 8 rRNA, and 84 protein-coding genes. Phylogenetic analysis showed that D. moschatum was strongly allied with D. denneanum Kerr. 1933.
RESUMO
Twelve previously undescribed phenolic meroterpenoids, cochlearols N-Y, along with two known analogs, ganocochlearins B and C, were isolated from the fruiting bodies of Ganoderma cochlear. Most of these substances were isolated as racemic mixtures. The structures of cochlearols N-Y were assigned based upon spectroscopic data and theoretical calculations. The renoprotective activities of these compounds were evaluated using normal and diseased rat renal interstitial fibroblast cells (NRK-49F). The results show that ganocochlearins S, U, X and Y display potent inhibitory activities against fibronectin overproduction in TGF-ß1-induced NRK-49F cells.
Assuntos
Citoproteção/efeitos dos fármacos , Ganoderma/química , Rim/citologia , Fenóis/química , Terpenos/química , Terpenos/farmacologia , Animais , Linhagem Celular , Carpóforos/química , Rim/efeitos dos fármacos , Modelos Moleculares , Conformação Molecular , RatosRESUMO
Nine multifarious new meroterpenoids, cochlearols E-M (1-9), along with seven known meroterpenoids 10-16, were isolated from the fruiting bodies of Ganoderma cochlear. Racemic 1, 6-8, 10 and 13 were separated by chiral HPLC. The structures were elucidated based on detailed spectroscopic analyses (HRESIMS, 1D/2D-NMR) and calculated electronic circular dichroism (ECD). Their biological activities against renal fibrosis were evaluated by using rat normal and diseased renal interstitial fibroblast cells (NRK49F). The results show that compounds 7a, 7b, and 10a exhibit potent proliferation inhibition in TGF-ß1-induced NRK-49F cells.
Assuntos
Fibroblastos/efeitos dos fármacos , Ganoderma/química , Terpenos/farmacologia , Animais , Linhagem Celular , China , Fibrose , Carpóforos/química , Rim/citologia , Estrutura Molecular , Ratos , Terpenos/isolamento & purificaçãoRESUMO
T-type calcium channel (TTCC) inhibitors hold great potential for the treatment of a variety of neurological disorders. Cochlearoids A-E (1-5), five pairs of dimeric meroterpenoid enantiomers, and cochlearines A (6) and B (7), two pairs of enantiomeric hybrid metabolites, were isolated and characterized from Ganoderma cochlear. Biological evaluation found that compounds (+)-1, (-)-3, and (±)-6 significantly inhibited Cav3.1 TTCC and showed noticeable selectivity against Cav1.2, Cav2.1, Cav2.2, and Kv11.1 (hERG) channels.
Assuntos
Bloqueadores dos Canais de Cálcio/farmacologia , Canais de Cálcio Tipo N/química , Canais de Cálcio Tipo T/química , Ganoderma/química , Inibição Neural/efeitos dos fármacos , Terpenos/síntese química , Terpenos/farmacologia , Bloqueadores dos Canais de Cálcio/química , Canais de Cálcio Tipo N/metabolismo , Canais de Cálcio Tipo T/metabolismo , Humanos , Estrutura Molecular , Inibição Neural/fisiologia , Terpenos/químicaRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Several Ganoderma fungi are well-known for their medical uses to treat cancer, insomnia and kidney disease in East Asia. Triperpenoids and polysaccharides have been considered for a long time to be the major active components of the genus Ganoderma. The present study is to examine the effects of lingzhilactones from G. lingzhi on adriamycin-induced nephropathy in mice. MATERIALS AND METHODS: A combination of various chromatography led to the isolation of lingzhilactones A-C, their structures were identified by spectroscopic and computational methods. The intracellular reactive oxygen species (ROS) was detected with the carboxymethyl-H2-dichlorofluorescein diacetate fluoroprobe. The fibrotic markers were analyzed by real-time RT-PCR and Western blot analyses. Detection of SEAP was conducted with the chemiluminescent. Urine albumin was measured using an ELISA assay. Histology and immunohistochemical staining was used to assess fibrotic lesions in mice. RESULTS: Three new lingzhilactones A-C (1-3) containing a fused lactone moiety were isolated from G. lingzhi. We found that 2 could inhibit ROS generation in a dose-dependent manner, inhibit mRNA expression of collagen IV, fibronectin, IL-6 and increase expression of Nrf2 in rat tubular epithelial cells. Furthermore, we found that 2 could reduce urinary albumin levels, abrogate myofibroblastic activation and inhibit the phosphorylation of Smad3 in adriamycin-induced mice. CONCLUSIONS: The in vitro and in vivo results suggested that lingzhilactone B could protect against renal injuries by increasing the activities of antioxidants and inhibiting inflammation. The inhibition of Smad3 phosphorylation suggested that this substance displays in vivo antifibrotic activity by a mechanism that is dependent on disruption of Smad3. These results promote understanding of the traditional usage of G. lingzhi and provide promising findings which may be beneficial for anti-kidney disease drug design.
Assuntos
Anti-Inflamatórios/uso terapêutico , Ganoderma , Nefropatias/tratamento farmacológico , Lactonas/uso terapêutico , Animais , Anti-Inflamatórios/isolamento & purificação , Anti-Inflamatórios/farmacologia , Linhagem Celular , Colágeno Tipo IV/genética , Doxorrubicina , Fibronectinas/genética , Interleucina-6/genética , Nefropatias/induzido quimicamente , Nefropatias/metabolismo , Lactonas/isolamento & purificação , Lactonas/farmacologia , Masculino , Células Mesangiais/efeitos dos fármacos , Células Mesangiais/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Fator 2 Relacionado a NF-E2/genética , RNA Mensageiro/metabolismo , Ratos , Espécies Reativas de Oxigênio/metabolismo , Proteína Smad3/genética , Proteína Smad3/metabolismoRESUMO
(+)- and (-)-cochlearols A (1) and B (2), two meroterpenoids with novel polycyclic skeletons, were isolated from the fruiting bodies of the fungus Ganoderma cochlear. Their structures and stereochemistry were determined by using spectroscopic, computational and single-crystal X-ray diffraction methods. Cochlearol A is a new normeroterpenoid containing a naturally unusual dioxaspiro[4.5]decane motif. Biological studies showed that (-)-2 is a strong inhibitor of p-Smads, exhibiting renoprotective activities in TGF-ß1 induced rat renal proximal tubular cells.