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1.
J Pharm Biomed Anal ; 220: 115007, 2022 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-36067594

RESUMO

Traditional Chinese medicine (TCM) plays a synergistic and comprehensive pharmacodynamic role of multi-channel and multi-target through its multi-components, showing unique therapeutic advantages in chronic and multi-gene complex diseases. Herb pair is a unique combination of two relatively fixed herbs, which embodies the integrity of TCM theory. In this study, untargeted fecal metabolomics based on MS was used to investigate the action mechanism of Radix ginseng and Schisandra chinensis (GS) herb pair on the complex disease of Alzheimer's disease (AD), and further analyze the therapeutic effects of small molecular components and saccharides of GS on AD. Quantitative analysis of bile acids (BAs) and short-chain fatty acids (SCFAs) further verified the conclusion of untargeted metabolomics. The results of the pharmacodynamics evaluation showed that the AD model was successfully constructed, and each TCM group had a different degree of improvement compared with the AD group. PCA analysis based on untargeted fecal metabolomics showed that the metabolic disorders in AD rats changed significantly over time, and there were different degrees of callback in each TCM group. The result indicated that the GS herb pair can regulate metabolic disorders of AD. Further analysis of therapeutic biomarkers showed that GS mainly regulated the metabolism of bile acid biosynthesis, sphingolipid metabolism, porphyrin and chlorophyll metabolism, etc. to treat AD. This study will help to further understand the pathogenesis of AD from metabolomics, and provide beneficial support for the further study of GS and the clinical treatment of complex diseases with TCM.


Assuntos
Doença de Alzheimer , Medicamentos de Ervas Chinesas , Panax , Porfirinas , Schisandra , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/metabolismo , Animais , Ácidos e Sais Biliares , Biomarcadores/metabolismo , Clorofila , Cromatografia Líquida de Alta Pressão/métodos , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/uso terapêutico , Metabolômica , Panax/metabolismo , Ratos , Schisandra/metabolismo , Esfingolipídeos/uso terapêutico
2.
Nutrients ; 14(17)2022 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-36079818

RESUMO

Ginseng (Panax ginseng Meyer) has been used in East Asian traditional medicine for a long time. Korean red ginseng (KRG) is effective against several disorders, including cancer. The cytotoxic effects of KRG extract in terms of autophagy- and apoptosis-mediated cell death and its mechanisms were investigated using human colorectal cancer lines. KRG induced autophagy-mediated cell death with enhanced expression of Atg5, Beclin-1, and LC3, and formed characteristic vacuoles in HCT-116 and SNU-1033 cells. An autophagy inhibitor prevented cell death induced by KRG. KRG generated mitochondrial reactive oxygen species (ROS); antioxidant countered this effect and decreased autophagy. KRG caused apoptotic cell death by increasing apoptotic cells and sub-G1 cells, and by activating caspases. A caspase inhibitor suppressed cell death induced by KRG. KRG increased phospho-Bcl-2 expression, but decreased Bcl-2 expression. Moreover, interaction of Bcl-2 with Beclin-1 was attenuated by KRG. Ginsenoside Rg2 was the most effective ginsenoside responsible for KRG-induced autophagy- and apoptosis-mediated cell death. KRG induced autophagy- and apoptosis-mediated cell death via mitochondrial ROS generation, and thus its administration may inhibit colon carcinogenesis.


Assuntos
Neoplasias , Panax , Apoptose , Autofagia , Proteína Beclina-1 , Humanos , Panax/metabolismo , Extratos Vegetais/farmacologia , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Espécies Reativas de Oxigênio/metabolismo
3.
Fish Shellfish Immunol ; 128: 19-27, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35921930

RESUMO

In the current study, white-leg shrimp (Litopenaeus vannamei) were fed on diets containing varying doses of Withania somnifera aqueous extract (WSAE) at a rate of 0 (control), 0.5, 1.0, and 2.0 g/kg feed for 56 days. After the feeding trial, shrimps in all groups were challenged with the exposure to Vibrio harveyi for ten days during which animals' mortality was observed. It is noted that the dietary WSAE linearly and quadratically stimulated shrimp's growth indices particularly at the treatment of 2.0 g/kg feed. Compared to the control group, the WSAE-fed L. vannamei had significantly higher villi length, villi width, and absorption area particularly in the treatment of 2.0 g/kg feed. Furthermore, L. vannamei fed on WSAE-enriched diets consumed more feed and exhibited higher total proteolytic activity, lipase, and α-amylase activities as compared with the control group. The dietary WSAE at escalating levels linearly and quadratically enhanced the antioxidant activity (serum superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), total antioxidant capacity, and reduced glutathione) and the immune response (total hemocyte counts, total protein, lysozyme, and phagocytic activity). Similarly, the mRNA expression levels of cMn-SOD, CAT, and GPx genes were linearly and quadratically upregulated in the hepatopancreas of L. vannamei fed on WSAE-enriched diets (especially in the 2.0 g/kg feed treatment), while their lowest levels were significantly observed in the control group. On the other hand, malondialdehyde levels were significantly decreased in WSAE-supplemented shrimp groups, and its highest levels were observed in animals fed on the control diet. After the bacterial exposure, the survival rates of L. vannamei fed on 1.0 and 2.0 g WSAE/kg feed (61.3% and 66.7%, respectively) were higher than those in the control animals. Taken together, the results obtained herein indicate that inclusion of WSAE in diets of L. vannamei effectively enhanced the growth, antioxidant biomarkers, immune response, and resistance to the V. harveyi infection, particularly at the treatment of 2.0 g/kg feed.


Assuntos
Panax , Penaeidae , Withania , Ração Animal/análise , Animais , Antioxidantes/metabolismo , Biomarcadores , Catalase , Dieta/veterinária , Suplementos Nutricionais , Resistência à Doença , Glutationa , Glutationa Peroxidase/metabolismo , Imunidade Inata , Lipase , Malondialdeído , Muramidase/metabolismo , Panax/genética , Panax/metabolismo , RNA Mensageiro , Superóxido Dismutase/metabolismo , Withania/genética , Withania/metabolismo , alfa-Amilases/farmacologia
4.
Biomater Adv ; 137: 212814, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35929253

RESUMO

In order to increase the bioavailability of mountain ginseng (MG), gold nanoparticles (MG-AuNPs) were biologically synthesized from MG extract, and an oil-in-water (O/W) nanoemulsion (SMG-AuNEs) was prepared from MG-AuNPs and a phytochemical silydianin. The physical stability of SMG-AuNEs were monitored and optimized in terms of particle size, pH value, zeta potential, and polydispersity index. The chemicostructural properties of the prepared MG-AuNPs and SMG-AuNEs were characterized using various spectrometric and microscopic analyses, such as EDX spectroscopy, FT-IR spectroscopy, and TEM. The effect of both nanomaterial samples on the anti-inflammatory activity and their underlying mechanism was compared in LPS-stimulated RAW 264.7 cells. SMG-AuNEs did not show toxic effects against RAW 264.7 macrophages, HaCaT keratinocytes, and normal dermal fibroblasts. SMG-AuNEs exhibited significantly higher inhibition of pro-inflammatory genes and proteins, including IL-1ß, IL-6, and TNF-α, compared with those of MG-AuNPs and silydianin. Western blotting analysis revealed that the MAPK and NF-κB signalings were highly inhibited by SMG-AuNEs treatment. Hence, this study shows that nano-emulsification of gold nanoparticles prepared from MG is a useful method for augmenting the anti-inflammatory potential of MG. This study may serve as a foundation for using MG as a functional ingredient in anti-inflammatory agents. Our results may implicate the use of nanoemulsions to develop new anti-inflammatory products using MG.


Assuntos
Nanopartículas Metálicas , Panax , Anti-Inflamatórios/farmacologia , Ouro/farmacologia , Lipopolissacarídeos/farmacologia , Nanopartículas Metálicas/química , NF-kappa B , Panax/metabolismo , Transdução de Sinais , Silimarina , Espectroscopia de Infravermelho com Transformada de Fourier
5.
Gen Physiol Biophys ; 41(4): 329-338, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35938966

RESUMO

This study aims to explore the effect and mechanism of arginyl-fructosyl-glucose (AFG) on TGF-ß1-induced epithelial-mesenchymal transition (EMT) of renal tubular epithelial cells. HK-2 cells were induced by TGF-ß1 and then co-cultured with AFG at different concentrations (0, 25, 50, and 100 µmol/l) for 48 h. The morphology of HK-2 cells was observed under an inverted microscope and the expressions of α-SMA, Vimentin, and E-cadherin were assessed by qRT-PCR, Western blot, and immunofluorescence. The mRNA expressions of ERK and STAT3 were also examined by qRT-PCR, and the protein levels of ERK, STAT3, p-ERK, and p-STAT3 were measured by Western blot. Finally, CCK-8 and transwell assays were used to detect cell proliferation and invasion. TGF-ß1 treatment significantly induced EMT in HK-2 cells. The expressions of p-ERK and p-STAT3 were signally increased after TGF-ß1 induction, while Mogrol treatment inhibited p-ERK, p-STAT3, α-SMA, and Vimentin expression levels, enhanced E-cadherin expression, and suppressed cell proliferation and invasion. AFG exposure could also inhibit p-ERK, p-STAT3, α-SMA, and Vimentin expressions, promote E-cadherin expression, and markedly inhibit HK-2 cell proliferation and invasion. AFG inhibited TGF-ß1-induced EMT of renal tubular epithelial cells by regulating phosphorylation of ERK and STAT3.


Assuntos
Panax , Fator de Crescimento Transformador beta1 , Arginina/análogos & derivados , Caderinas/metabolismo , Linhagem Celular , Células Epiteliais , Transição Epitelial-Mesenquimal , Glucose , Panax/metabolismo , Fator de Crescimento Transformador beta1/metabolismo , Vimentina/metabolismo
6.
Biogerontology ; 23(4): 485-497, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35939242

RESUMO

Ginseng volatile oil (GVO) is one of the main components of ginseng and has antibacterial and anti-inflammatory properties. In this study, gas chromatography-mass spectrometry (GC-MS) was applied to characterize GVO chemical composition, and 73 volatile components were detected from GVO. Caenorhabditis elegans was used as animal model to further elucidate the antioxidant and anti-aging effects of GVO in vivo. The results suggested that GVO significantly prolonged the lifespan of C. elegans and promoted its health without damaging its reproductive capacity. In addition, GVO increased the antioxidant capacity and survival rate of nematodes after heat shock. Transcriptional sequencing showed that autophagy-related genes atg-4.2, atg-7, lgg-2, and cyd-1 were up-regulated, and superoxide dismutase 1 (sod-1) expression was increased after GVO pretreatment. Considering the role of autophagy and antioxidant in aging, the expression of autophagy substrate P62 protein in BC12921 strain was analyzed and found to decrease by more than 50.00% after treatment with GVO. In addition, the lifespan of SOD-1 mutant nematodes was not significantly different from that of the control group. SOD activity and autophagy were activated, which is a clear expression of hormesis. All these results suggest that GVO prolongs the lifespan and healthspan of C. elegans, and its biological functions may be related to hormesis.


Assuntos
Proteínas de Caenorhabditis elegans , Óleos Voláteis , Panax , Animais , Antioxidantes/metabolismo , Antioxidantes/farmacologia , Caenorhabditis elegans , Proteínas de Caenorhabditis elegans/genética , Proteínas de Caenorhabditis elegans/metabolismo , Longevidade , Proteínas Associadas aos Microtúbulos/metabolismo , Proteínas Associadas aos Microtúbulos/farmacologia , Óleos Voláteis/metabolismo , Óleos Voláteis/farmacologia , Estresse Oxidativo , Panax/metabolismo , Superóxido Dismutase/metabolismo
7.
BMC Plant Biol ; 22(1): 320, 2022 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-35787249

RESUMO

Jilin ginseng (Panax ginseng C. A. Meyer) has a long history of medicinal use worldwide. The quality of ginseng is governed by a variety of internal and external factors. Nuclear factor Y (NF-Y), an important transcription factor in eukaryotes, plays a crucial role in the plant response to abiotic stresses by binding to a specific promoter, the CCAAT box. However, the NF-Y gene family has not been reported in Panax ginseng. In this study, 115 PgNF-Y transcripts with 40 gene IDs were identified from the Jilin ginseng transcriptome database. These genes were classified into the PgNF-YA (13), PgNF-YB (14), and PgNF-YC (13) subgroups according to their subunit types, and their nucleotide sequence lengths, structural domain information, and amino acid sequence lengths were analyzed. The phylogenetic analysis showed that the 79 PgNF-Y transcripts with complete ORFs were divided into three subfamilies, NF-YA, NF-YB, and NF-YC. PgNF-Y was annotated to eight subclasses under three major functions (BP, MF, and CC) by GO annotation, indicating that these transcripts perform different functions in ginseng growth and development. Expression pattern analysis of the roots of 42 farm cultivars, 14 different tissues of 4-year-old ginseng plants, and the roots of 4 different-ages of ginseng plants showed that PgNF-Y gene expression differed across lineages and had spatiotemporal specificity. Coexpression network analysis showed that PgNF-Ys acted synergistically with each other in Jilin ginseng. In addition, the analysis of the response of PgNF-YB09, PgNF-YC02, and PgNF-YC07-04 genes to salt stress treatment was investigated by fluorescence quantitative PCR. The expression of these genes increased after salt stress treatment, indicating that they may be involved in the regulation of the response to salt stresses in ginseng. These results provide important functional genetic resources for the improvement and gene breeding of ginseng in the future.Conclusions: This study fills a knowledge gap regarding the NF-Y gene family in ginseng, provides systematic theoretical support for subsequent research on PgNF-Y genes, and provides data resources for resistance to salt stress in ginseng.


Assuntos
Panax , Fator de Ligação a CCAAT , Regulação da Expressão Gênica de Plantas , Panax/genética , Panax/metabolismo , Filogenia , Melhoramento Vegetal , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Plantas/genética , Estresse Salino , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Transcriptoma
8.
Zhongguo Zhong Yao Za Zhi ; 47(14): 3756-3764, 2022 Jul.
Artigo em Chinês | MEDLINE | ID: mdl-35850832

RESUMO

A total of 8 bHLH transcription factors were cloned from Panax quinquefolius and the response of them to methyl jasmonate(MeJA) was studied.To be specific, based on the preliminary transcriptome screening, 8 bHLH transcription factors were cloned with seedlings which had been cultured for 3 weeks.The content of ginsenosides Rg_1, Re, and Rb_1, and total saponins in the adventitious roots of P.quinquefolius was determined at different time of MeJA treatment by high performance liquid chromatography(HPLC) and spectrophotometry.Real-time quantitative polymerase chain reaction(PCR) was used to detect the relative expression of 8 transcription factors after MeJA treatment.The correlation between the relative expression of the 8 transcription factors and the saponin content after MeJA treatment was checked by Pearson's correlation analysis.The results showed that the PCR products(Pq-bHLH21-Pq-bHLH28) of the 8 bHLH transcription factors were 762-2 013 bp in length.They were submitted to NCBI to obtain the Genbank access numbers.The proteins yielded from Pq-bHLH21-Pq-bHLH28 showed amino acid sequence identity of 24.90%, and each amino acid sequence had the bHLH(Basic Helix-loop-helix) conserved domain and belonged to the bHLH family.The 5 amino acid sequences of Pq-bHLH22 and Pq-bHLH24-Pq-bHLH27 contained the bHLH-MYC N domain, which belonged to the MYC transcription factors.Pq-bHLH21-Pq-bHLH28 responded to MeJA within 48 h of treatment.At 72 h, the expression of Pq-bHLH24 reached 106.53 folds the highest in the treatment group.Pq-bHLH25, Pq-bHLH27, and Pq-bHLH28 showed synergic expression.Pq-bHLH21 may re-gulate the biosynthetic pathway of ginsenoside Rb_1, while Pq-bHLH22, Pq-bHLH25, and Pq-bHLH28 were in significantly positive correlation with the biosynthetic pathway of ginsenoside Re.The result lays a foundation for further verifying the regulation of ginsenoside biosynthesis by bHLH transcription factors.


Assuntos
Ginsenosídeos , Panax , Saponinas , Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Clonagem Molecular , Panax/genética , Panax/metabolismo , Raízes de Plantas/genética , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo
9.
Wound Manag Prev ; 68(6): 28-37, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35895033

RESUMO

BACKGROUND: Red ginseng (Rg) is an herbal product that has been used in traditional medicine in Asian and European countries for many years. PURPOSE: To study the effects of Rg extract on wound healing when used systemically, locally, or in combination in rats with experimentally induced diabetes. METHODS: A total of 60 rats were randomly divided into 4 groups: saline (control), local Rg (LRg), systemic Rg (SRg), and local + systemic = combined Rg (CRg). A full-thickness wound (2 cm × 1 cm) was created on the back of the rats, and treatment protocols were carried out for 14 days. Wound areas of all rats were measured on days 0 and 14. Tissue samples were taken from the wound areas for histopathologic evaluation of inflammation, epithelialization, and fibrosis. Vascular endothelial growth factor (VEGF), CD4+, and CD8+ expressions were examined by immunohistochemistry. RESULTS: Wound contraction measurements were 63.8%, 80.5%, 88.5%, and 86.6% in the control, LRg, SRg and CRg groups, respectively. Although significant differences were observed for all treated groups (LRg, SRg, and CRg) compared with the control group in terms of wound contraction, there was no difference among the treatment groups. VEGF-positive vessel/mm2 was observed 4.00 ± 0.75, 5.93 ± 0.70, 5.93 ± 1.93, and 7.93 ± 0.70 in the control, LRg, SRg and CRg groups, respectively. There was no difference between LRg and SRg in terms of VEGF expression, but there was significant difference for all other groups compared with each other. CONCLUSION: All usage methods of Rg extract increased wound contraction, and differences were observed compared with the control group. However, the authors believe that the combined usage was more effective due to higher VEGF expression levels and lower CD4+:CD8+ ratio.


Assuntos
Diabetes Mellitus , Panax , Animais , Panax/metabolismo , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Ratos , Fator A de Crescimento do Endotélio Vascular/metabolismo , Fator A de Crescimento do Endotélio Vascular/farmacologia , Cicatrização
10.
Food Funct ; 13(16): 8605-8615, 2022 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-35894549

RESUMO

The effects of ginseng oligosaccharides (GSOs) on neuronal oxidative injury induced by glutamate (GLU) and the molecular mechanisms involved were investigated. Cell damage was assessed using MTT assays, and the lactate dehydrogenase (LDH) release rate and flow cytometry were used to detect the accumulation of reactive oxygen species (ROS) and mitochondrial membrane potential respectively. The levels of catalase (CAT) and glutathione (GSH) were measured in PC12 cells and Drosophila brain tissue. The climbing ability of Drosophila was observed. Levels of proteins, including Cyt C, Bcl-2/BAX, and Nrf2/HO-1-associated proteins, were determined by western blotting and immunofluorescence. It was found that GSOs reversed GLU-induced reductions in cell viability and the LDH release rate, and rescued ROS accumulation. GSOs also mitigated the deleterious effects of GLU on the mitochondrial membrane potential and Cyt C release, thus alleviating mitochondrial dysfunction, and increased GSH levels and CAT activity in both cells and Drosophila brain tissue. The climbing index in GSO-treated Drosophila was significantly higher than that in the tert-butyl-hydroperoxide-treated flies. Furthermore, GSOs protected cells against GLU-induced apoptosis by reducing the expression of the mitochondrial apoptosis-associated Bcl-2 family effector proteins and protected cells from GLU-induced oxidative damage by increasing the nuclear translocation of Nrf2 and HO-1 expression. These findings indicate that GSOs protect against GLU-induced neuronal oxidative damage through Nrf2/HO-1 activation.


Assuntos
Fator 2 Relacionado a NF-E2 , Panax , Animais , Apoptose , Drosophila/metabolismo , Ácido Glutâmico/metabolismo , Glutationa/metabolismo , Heme Oxigenase-1/genética , Heme Oxigenase-1/metabolismo , Fator 2 Relacionado a NF-E2/genética , Fator 2 Relacionado a NF-E2/metabolismo , Neurônios/metabolismo , Oligossacarídeos/farmacologia , Estresse Oxidativo , Panax/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Ratos , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais
11.
J Integr Plant Biol ; 64(9): 1739-1754, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35731022

RESUMO

The ginsenoside Rg3 found in Panax species has extensive pharmacological properties, in particular anti-cancer effects. However, its natural yield in Panax plants is limited. Here, we report a multi-modular strategy to improve yields of Rg3 in a Panax ginseng chassis, combining engineering of triterpene metabolism and overexpression of a lignin biosynthesis gene, phenylalanine ammonia lyase (PAL). We first performed semi-rational design and site mutagenesis to improve the enzymatic efficiency of Pq3-O-UGT2, a glycosyltransferase that directly catalyzes the biosynthesis of Rg3 from Rh2 . Next, we used clustered regularly interspaced palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) gene editing to knock down the branch pathway of protopanaxatriol-type ginsenoside biosynthesis to enhance the metabolic flux of the protopanaxadiol-type ginsenoside Rg3 . Overexpression of PAL accelerated the formation of the xylem structure, significantly improving ginsenoside Rg3 accumulation (to 6.19-fold higher than in the control). We combined overexpression of the ginsenoside aglycon synthetic genes squalene epoxidase, Pq3-O-UGT2, and PAL with CRISPR/Cas9-based knockdown of CYP716A53v2 to improve ginsenoside Rg3 accumulation. Finally, we produced ginsenoside Rg3 at a yield of 83.6 mg/L in a shake flask (7.0 mg/g dry weight, 21.12-fold higher than with wild-type cultures). The high-production system established in this study could be a potential platform to produce the ginsenoside Rg3 commercially for pharmaceutical use.


Assuntos
Ginsenosídeos , Panax , Ginsenosídeos/metabolismo , Lignina/metabolismo , Panax/química , Panax/genética , Panax/metabolismo , Fenilalanina Amônia-Liase/genética , Fenilalanina Amônia-Liase/metabolismo
12.
Sci Rep ; 12(1): 10165, 2022 06 17.
Artigo em Inglês | MEDLINE | ID: mdl-35715520

RESUMO

The C2H2 zinc finger protein (C2H2-ZFP) gene family plays important roles in response to environmental stresses and several other biological processes in plants. Ginseng is a precious medicinal herb cultivated in Asia and North America. However, little is known about the C2H2-ZFP gene family and its functions in ginseng. Here, we identified 115 C2H2-ZFP genes from ginseng, defined as the PgZFP gene family. It was clustered into five groups and featured with eight conserved motifs, with each gene containing one to six of them. The family genes are categorized into 17 gene ontology subcategories and have numerous regulatory elements responsive to a variety of biological process, suggesting their functional differentiation. The 115 PgZFP genes were spliced into 228 transcripts at seed setting stage and varied dramatically in expression across tissues, developmental stages, and genotypes, but they form a co-expression network, suggesting their functional correlation. Furthermore, four genes, PgZFP31, PgZFP78-01, PgZFP38, and PgZFP39-01, were identified from the gene family that were actively involved in plant response to salt stress. These results provide new knowledge on origin, differentiation, evolution, and function of the PgZFP gene family and new gene resources for C2H2-ZFP gene research and application in ginseng and other plant species.


Assuntos
Dedos de Zinco CYS2-HIS2 , Panax , Dedos de Zinco CYS2-HIS2/genética , Regulação da Expressão Gênica de Plantas , Panax/genética , Panax/metabolismo , Filogenia , Proteínas de Plantas/metabolismo , Estresse Salino , Dedos de Zinco/genética
13.
ACS Synth Biol ; 11(7): 2394-2404, 2022 07 15.
Artigo em Inglês | MEDLINE | ID: mdl-35687875

RESUMO

Panax notoginseng is one of the most famous valuable medical plants in China, and its broad application in clinical treatment has an inseparable relationship with the active molecules, ginsenosides. Ginsenosides are glycoside compounds that have varied structures for the diverse sugar chain. Although extensive work has been done, there are still unknown steps in the biosynthetic pathway of ginsenosides. Here, we screened candidate glycosyltransferase genes based on the previous genome and transcriptome data of P. notoginseng and cloned the full length of 27 UGT genes successfully. Among them, we found that PnUGT33 could catalyze different ginsenoside substrates to produce higher polarity rare ginsenosides by extending the sugar chain. We further analyzed the enzymatic kinetics and predicted the catalytic mechanism of PnUGT33 by simulating molecular docking. After that, we reconstructed the biosynthetic pathway of rare ginsenoside Rg3 and gypenoside LXXV in yeast. By combining the Golden Gate method and overexpressing the UDPG biosynthetic genes, we further improved the yield of engineering yeast strain. Finally, the shake-flask culture yield of Rg3 reached 51 mg/L and the fed-batch fermentation yield of gypenoside LXXV reached 94.5 mg/L, which was the first and highest record.


Assuntos
Ginsenosídeos , Panax notoginseng , Panax , Ginsenosídeos/genética , Ginsenosídeos/metabolismo , Glicosiltransferases/genética , Glicosiltransferases/metabolismo , Engenharia Metabólica/métodos , Simulação de Acoplamento Molecular , Panax/química , Panax/genética , Panax/metabolismo , Panax notoginseng/genética , Panax notoginseng/metabolismo , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/metabolismo , Saponinas , Açúcares/metabolismo , Triterpenos
14.
J Microbiol Biotechnol ; 32(7): 902-910, 2022 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-35719083

RESUMO

The ginsenoside compound K (C-K) is widely used in traditional medicines, nutritional supplements, and cosmetics owing to its diverse pharmacological activities. Although many studies on C-K production have been conducted, fermentation is reported to produce C-K with low concentration and productivity. In the present study, addition of an inducer and optimization of the carbon and nitrogen sources in the medium were performed using response surface methodology to increase the C-K production via fermentation by Aspergillus tubingensis, a generally recognized as safe fungus. The optimized inducer and carbon and nitrogen sources were 2 g/l rice straw, 10 g/l sucrose, and 10 g/l soy protein concentrate, respectively, and they resulted in a 3.1-fold increase in the concentration and productivity of C-K (0.22 g/l and 1.52 mg/l/h, respectively) compared to those used before optimization without inducer (0.071 g/l and 0.49 mg/l/h, respectively). The feeding methods of American ginseng extract (AGE), including feeding timing, feeding concentration, and feeding frequency, were also optimized. Under the optimized conditions, A. tubingensis produced 3.96 mM (2.47 g/l) C-K at 144 h by feeding two times with 8 g/l AGE at 48 and 60 h, with a productivity of 17.1 mg/l/h. The concentration and productivity of C-K after optimization of feeding methods were 11-fold higher than those before the optimization (0.22 g/l and 1.52 mg/l/h, respectively). Thus, the optimization for the feeding methods of ginseng extract is an efficient strategy to increase C-K production. To our knowledge, this is the highest reported C-K concentration and productivity via fermentation reported so far.


Assuntos
Panax , Aspergillus , Carbono , Fermentação , Ginsenosídeos , Nitrogênio , Panax/metabolismo , Extratos Vegetais/metabolismo
15.
Pharm Biol ; 60(1): 1038-1046, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-35634656

RESUMO

CONTEXT: Panax ginseng C. A. Meyer (Araliaceae) is a famous Asian medicine. Ginsenoside Rc is a component isolated from Panax ginseng. OBJECTIVE: This study evaluates the effect of ginsenoside Rc on myocardial ischaemic injury. MATERIALS AND METHODS: Male Swiss mice were subcutaneously injected with 50 mg/kg isoproterenol once a day for three days. Ginsenoside Rc (10, 20, or 40 mg/kg) was intragastrically administered 1 h after isoproterenol injection. The mice in the control group were subcutaneously injected with normal saline and intragastrically given 0.5% CMC-Na. CK-MB and troponin T were assayed. Histopathological examination of myocardium was conducted. The expression of Nrf2, GCLC, GCLM and HO-1 in heart tissues was evaluated by Western blot. RESULTS: In myocardial ischaemic mice, ginsenoside Rc reduced the levels of CK-MB (197.1 ± 15.7, 189.9 ± 19.0, 184.0 ± 14.4 vs. 221.6 ± 27.9) and troponin T (10.3 ± 1.7, 9.5 ± 1.3, 8.7 ± 1.7 vs. 13.4 ± 2.4). Ginsenoside Rc attenuated the necrosis and inflammatory cells infiltration in myocardium. Furthermore, ginsenoside Rc not only decreased the contents of MDA, TNF-α but also increased GSH level in the heart tissues. The expression of Nrf2, GCLC, GCLM and HO-1 was significantly increased in the animals treated with ginsenoside Rc. ML385, an Nrf2 inhibitor, blocked partially the ginsenoside Rc-mediated cardioprotective effect. Ginsenoside Rc attenuated myocardial ischaemic injury in mice, which may be, in part, through its antioxidative and anti-inflammatory effects. CONCLUSIONS: This study indicated that ginsenoside Rc might be a novel candidate for treatment of myocardial ischaemia.


Assuntos
Antioxidantes , Panax , Animais , Anti-Inflamatórios/farmacologia , Antioxidantes/farmacologia , Ginsenosídeos , Isoproterenol , Masculino , Camundongos , Fator 2 Relacionado a NF-E2/metabolismo , Panax/metabolismo , Troponina T
16.
Nutrients ; 14(9)2022 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-35565712

RESUMO

Sarcopenia and obesity are serious health problems that are highly related to several metabolic diseases. Sarcopenic obesity, a combined state of sarcopenia and obesity, results in higher risks of metabolic diseases and even mortality than sarcopenia or obesity alone. Therefore, the development of therapeutic agents for sarcopenic obesity is crucial. C57BL/6 mice were fed with a high-fat diet (HFD) for 9 weeks. Then, mice were administered with Panax ginseng berry extract (GBE) for an additional 4 weeks, with continuous HFD intake. GBE significantly decreased the food efficiency ratio, serum lipid and insulin levels, adipose tissue weights, and adipocyte size. It significantly increased the grip strength, muscle masses, and myofiber cross-sectional area. It deactivated the protein kinase C (PKC) theta and zeta, resulting in activation of the phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) pathway, which is known to regulate muscle synthesis and degradation. Furthermore, it inhibited the production of inflammatory cytokines in the muscle tissue. GBE attenuated both obesity and sarcopenia. Thus, GBE is a potential agent to prevent or treat sarcopenic obesity.


Assuntos
Panax , Sarcopenia , Animais , Dieta Hiperlipídica/efeitos adversos , Frutas/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Obesidade/complicações , Obesidade/tratamento farmacológico , Obesidade/metabolismo , Panax/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Sarcopenia/tratamento farmacológico , Sarcopenia/metabolismo , Sarcopenia/prevenção & controle
17.
Integr Cancer Ther ; 21: 15347354221101203, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35615883

RESUMO

Ginsenosides, as the most important constituents of ginseng, have been extensively investigated in cancer chemoprevention and therapeutics. Among the ginsenosides, Compound K (CK), a rare protopanaxadiol type of ginsenoside, has been most broadly used for cancer treatment due to its high anticancer bioactivity. However, the functional mechanism of CK in cancer is not well known. This review describes the structure, transformation and pharmacological activity of CK and discusses the functional mechanisms of CK and its metabolites, which regulate signaling pathways related to tumor growth and metastasis. CK inhibits tumor growth by inducing tumor apoptosis and tumor cell differentiation, regulates the tumor microenvironment by suppressing tumor angiogenesis-related proteins, and downregulates the roles of immunosuppressive cells, such as myeloid-derived suppressor cells (MDSCs). There is currently much research on the potential development of CK as a new strategy when administered alone or in combination with other compounds.


Assuntos
Ginsenosídeos , Neoplasias , Panax , Apoptose , Ginsenosídeos/farmacologia , Humanos , Neoplasias/tratamento farmacológico , Neovascularização Patológica , Panax/metabolismo , Microambiente Tumoral
18.
Molecules ; 27(9)2022 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-35565992

RESUMO

Chronic rhinosinusitis (CRS) is characterized by chronic inflammation of the sinonasal mucosa with epithelial dedifferentiation toward the mesenchymal phenotype, known as the epithelial-mesenchymal transition (EMT). Asian sand dust (ASD) can induce nasal mucosal inflammation and cause the development of EMT. Korean red ginseng (KRG) and ginsenoside Rg3 have been used as traditional herbal medicines to treat various diseases. The aim of this study was to investigate their effect on ASD-induced EMT in nasal epithelial cells. Primary nasal epithelial cells were incubated with ASD with or without KRG or Rg3, and the production of transforming growth factor-ß1 (TGF-ß1) and interleukin (IL)-8 was measured. EMT markers were determined by RT-PCR, Western blot analysis, and confocal microscopy, and transcription factor expression by Western blot analysis. The effect on cell migration was evaluated using the wound scratch assay. Results showed ASD-induced TGF-ß1 production, downregulation of E-cadherin, and upregulation of fibronectin in nasal epithelial cells. KRG and Rg3 suppressed TGF-ß1 production (31.7% to 43.1%), upregulated the expression of E-cadherin (26.4% to 88.3% in mRNA), and downregulated that of fibronectin (14.2% to 46.2% in mRNA and 52.3% to 70.2% in protein). In addition, they suppressed the ASD-induced phosphorylation of ERK, p38, and mTOR, as well as inhibiting the ASD-induced migration of nasal epithelial cells (25.2% to 41.5%). The results of this study demonstrate that KRG and Rg3 inhibit ASD-induced EMT by suppressing the activation of ERK, p38, and mTOR signaling pathways in nasal epithelial cells.


Assuntos
Transição Epitelial-Mesenquimal , Panax , Caderinas/metabolismo , Movimento Celular , Poeira , Células Epiteliais , Fibronectinas/metabolismo , Ginsenosídeos , Humanos , Inflamação/metabolismo , Panax/metabolismo , RNA Mensageiro/metabolismo , Areia , Serina-Treonina Quinases TOR/metabolismo , Fator de Crescimento Transformador beta1/metabolismo
19.
Biomolecules ; 12(4)2022 03 28.
Artigo em Inglês | MEDLINE | ID: mdl-35454101

RESUMO

It is well known that ginsenosides-major bioactive constituents of Panax ginseng-are attracting more attention due to their beneficial pharmacological activities. Ginsenoside Rd, belonging to protopanaxadiol (PPD)-type ginsenosides, exhibits diverse and powerful pharmacological activities. In recent decades, nearly 300 studies on the pharmacological activities of Rd-as a potential treatment for a variety of diseases-have been published. However, no specific, comprehensive reviews have been documented to date. The present review not only summarizes the in vitro and in vivo studies on the health benefits of Rd, including anti-cancer, anti-diabetic, anti-inflammatory, neuroprotective, cardioprotective, ischemic stroke, immunoregulation, and other pharmacological effects, it also delves into the inclusion of potential molecular mechanisms, providing an overview of future prospects for the use of Rd in the treatment of chronic metabolic diseases and neurodegenerative disorders. Although biotransformation, pharmacokinetics, and clinical studies of Rd have also been reviewed, clinical trial data of Rd are limited; the only data available are for its treatment of acute ischemic stroke. Therefore, clinical evidence of Rd should be considered in future studies.


Assuntos
Ginsenosídeos , AVC Isquêmico , Panax , Biotransformação , Ginsenosídeos/metabolismo , Ginsenosídeos/farmacologia , Ginsenosídeos/uso terapêutico , Humanos , Panax/metabolismo
20.
Nat Commun ; 13(1): 2224, 2022 04 25.
Artigo em Inglês | MEDLINE | ID: mdl-35468919

RESUMO

Araliaceae species produce various classes of triterpene and triterpenoid saponins, such as the oleanane-type triterpenoids in Aralia species and dammarane-type saponins in Panax, valued for their medicinal properties. The lack of genome sequences of Panax relatives has hindered mechanistic insight into the divergence of triterpene saponins in Araliaceae. Here, we report a chromosome-level genome of Aralia elata with a total length of 1.05 Gb. The loss of 12 exons in the dammarenediol synthase (DDS)-encoding gene in A. elata after divergence from Panax might have caused the lack of dammarane-type saponin production, and a complementation assay shows that overexpression of the PgDDS gene from Panax ginseng in callus of A. elata recovers the accumulation of dammarane-type saponins. Tandem duplication events of triterpene biosynthetic genes are common in the A. elata genome, especially for AeCYP72As, AeCSLMs, and AeUGT73s, which function as tailoring enzymes of oleanane-type saponins and aralosides. More than 13 aralosides are de novo synthesized in Saccharomyces cerevisiae by overexpression of these genes in combination. This study sheds light on the diversity of saponins biosynthetic pathway in Araliaceae and will facilitate heterologous bioproduction of aralosides.


Assuntos
Aralia , Panax , Saponinas , Triterpenos , Aralia/metabolismo , Panax/metabolismo , Saponinas/genética , Triterpenos/metabolismo
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