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1.
Nutrients ; 16(12)2024 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-38931306

RESUMO

Sprout ginseng extract (ThinkGIN™) manufactured through a smart farm system has been shown to improve memory in preclinical studies. This study conducted a 12-week randomized, double-blind, placebo-controlled clinical trial to evaluate the efficacy and safety of ThinkGIN™ for improving memory in subjective memory impairment (SMI). Subjects aged 55 to 75 years with SMI participated in this study. A total of 80 subjects who met the inclusion/exclusion criteria were assigned to the ThinkGIN™ group (n = 40, 450 mg ThinkGIN™/day) or a placebo group (n = 40). Efficacy and safety evaluations were conducted before intervention and at 12 weeks after intervention. As a result of 12 weeks of ThinkGIN™ intake, significant differences in SVLT, RCFT, MoCA-K, PSQI-K, and AChE were observed between the two groups. Safety evaluation (AEs, laboratory tests, vital signs, and electrocardiogram) revealed that ThinkGIN™ was safe with no clinically significant changes. Therefore, ThinkGIN™ has the potential to be used as a functional food to improve memory.


Assuntos
Transtornos da Memória , Panax , Extratos Vegetais , Humanos , Panax/química , Método Duplo-Cego , Masculino , Extratos Vegetais/farmacologia , Extratos Vegetais/efeitos adversos , Pessoa de Meia-Idade , Feminino , Idoso , Transtornos da Memória/tratamento farmacológico , Resultado do Tratamento , Memória/efeitos dos fármacos
2.
Biomolecules ; 14(6)2024 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-38927118

RESUMO

Ginseng (Panax ginseng C. A. Meyer) is an ancient and valuable Chinese herbal medicine, and ginsenoside, as the main active ingredient of ginseng, has received wide attention because of its various pharmacological active effects. Cytochrome P450 is the largest family of enzymes in plant metabolism and is involved in the biosynthesis of terpenoids, alkaloids, lipids, and other primary and secondary plant metabolites. It is significant to explore more PgCYP450 genes with unknown functions and reveal their roles in ginsenoside synthesis. In this study, based on the five PgCYP450 genes screened in the pre-laboratory, through the correlation analysis with the content of ginsenosides and the analysis of the interactions network of the key enzyme genes for ginsenoside synthesis, we screened out those highly correlated with ginsenosides, PgCYP309, as the target gene from among the five PgCYP450 genes. Methyl jasmonate-induced treatment of ginseng adventitious roots showed that the PgCYP309 gene responded to methyl jasmonate induction and was involved in the synthesis of ginsenosides. The PgCYP309 gene was cloned and the overexpression vector pBI121-PgCYP309 and the interference vector pART27-PgCYP309 were constructed. Transformation of ginseng adventitious roots by the Agrobacterium fermentum-mediated method and successful induction of transgenic ginseng hairy roots were achieved. The transformation rate of ginseng hairy roots with overexpression of the PgCYP309 gene was 22.7%, and the transformation rate of ginseng hairy roots with interference of the PgCYP309 gene was 40%. Analysis of ginseng saponin content and relative gene expression levels in positive ginseng hairy root asexual lines revealed a significant increase in PPD, PPT, and PPT-type monomeric saponins Re and Rg2. The relative expression levels of PgCYP309 and PgCYP716A53v2 genes were also significantly increased. PgCYP309 gene promotes the synthesis of ginsenosides, and it was preliminarily verified that PgCYP309 gene can promote the synthesis of dammarane-type ginsenosides.


Assuntos
Sistema Enzimático do Citocromo P-450 , Ginsenosídeos , Panax , Panax/genética , Panax/metabolismo , Panax/enzimologia , Sistema Enzimático do Citocromo P-450/genética , Sistema Enzimático do Citocromo P-450/metabolismo , Ginsenosídeos/metabolismo , Ginsenosídeos/biossíntese , Regulação da Expressão Gênica de Plantas/efeitos dos fármacos , Raízes de Plantas/genética , Raízes de Plantas/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Oxilipinas/farmacologia , Oxilipinas/metabolismo , Acetatos/farmacologia , Acetatos/metabolismo , Ciclopentanos/farmacologia , Ciclopentanos/metabolismo
3.
Phytomedicine ; 130: 155537, 2024 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-38823344

RESUMO

BACKGROUND: Aberrant activation of autophagy in triple-negative breast cancer (TNBC) has led researchers to investigate potential therapeutic strategies targeting this process. The regulation of autophagy is significantly influenced by METTL3. Our previous research has shown that the Panax ginseng-derived compound, 20(R)-panaxatriol (PT), has potential as an anti-tumor agent. However, it remains unclear whether PT can modulate autophagy through METTL3 to exert its anti-tumor effects. OBJECTIVE: Our objective is to investigate whether PT can regulate autophagy in TNBC cells and elucidate the molecular mechanisms. STUDY DESIGN: For in vitro experiments, we employed SUM-159-PT and MDA-MB-231 cells. While in vivo experiments involved BALB/c nude mice and NOD/SCID mice. METHODS: In vitro, TNBC cells were treated with PT, and cell lines with varying expression levels of METTL3 were established. We assessed the impact on tumor cell activity and autophagy by analyzing autophagic flux, Western Blot (WB), and methylation levels. In vivo, subcutaneous transplantation models were established in BALB/c nude and NOD/SCID mice to observe the effect of PT on TNBC growth. HE staining and immunofluorescence were employed to analyze histopathological changes in tumor tissues. MeRIP-seq and dual-luciferase reporter gene assays were used to identify key downstream targets. Additionally, the silencing of STIP1 Homology And U-Box Containing Protein 1 (STUB1) explored PT's effects. The mechanism of PT's action on STUB1 via METTL3 was elucidated through mRNA stability assays, mRNA alternative splicing analysis, and nuclear-cytoplasmic mRNA separation. RESULTS: In both in vivo and in vitro experiments, it was discovered that PT significantly upregulates the expression of METTL3, leading to autophagy inhibition and therapeutic effects in TNBC. Simultaneously, through MeRIP-seq analysis and dual-luciferase reporter gene assays, we have demonstrated that PT modulates STUB1 via METTL3, influencing autophagy in TNBC cells. Furthermore, intriguingly, PT extends the half-life of STUB1 mRNA by enhancing its methylation modification, thereby enhancing its stability. CONCLUSION: In summary, our research reveals that PT increases STUB1 m6A modification through a METTL3-mediated mechanism in TNBC cells, inhibiting autophagy and further accentuating its anti-tumor properties. Our study provides novel mechanistic insights into TNBC pathogenesis and potential drug targets for TNBC.


Assuntos
Autofagia , Metiltransferases , Camundongos Endogâmicos BALB C , Camundongos Nus , Neoplasias de Mama Triplo Negativas , Ubiquitina-Proteína Ligases , Animais , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Humanos , Autofagia/efeitos dos fármacos , Feminino , Linhagem Celular Tumoral , Metiltransferases/metabolismo , Ubiquitina-Proteína Ligases/metabolismo , Camundongos SCID , Camundongos Endogâmicos NOD , Camundongos , Antineoplásicos Fitogênicos/farmacologia , Ensaios Antitumorais Modelo de Xenoenxerto , Panax/química , Adenosina/análogos & derivados , Adenosina/farmacologia
4.
Chem Biol Drug Des ; 103(6): e14567, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38858165

RESUMO

BACKGROUND: To explore the anti-tumor and anti-virus key active ingredients of Sini Decoction Plus Ginseng Soup (SNRS) and their mechanisms. METHODS: The main ingredients of SNRS were analyzed by network pharmacology, and quercetin was identified as the key active ingredient. Then, we obtained the targets of quercetin by using Drugbank, PharmMapper, and SwissTargetPrediction databases. Then, the targets of HBV-related hepatocellular carcinoma (HBV-related HCC) were obtained by using Genecards database. In addition, using the gene expression profiles of HBV-related HCC patients in GEO database and the genes with the greatest survival difference in GEPIA 2 database identified the potential targets of quercetin. In addition, the mechanism of potential genes was studied through GO, KEGG analysis, and PPI network. Using AUC and survival analysis to evaluate the diagnostic and prognostic value of cyclin-dependent kinase 1 (CDK1) and CCNB1. Finally, the effects of quercetin on proliferation of Hep3B and HepG2215 cells and the level of CDK1 and CCNB1 were verified in vitro. ELISA was used to measure the expression levels of hepatitis B surface antigen (HBsAg) and hepatitis B e antigen (HBeAg) after the intervention by quercetin for 24 h and 48 h in HepG2215 cell. RESULTS: The first 10 key ingredients of SNRS were identified, and quercetin was the most key ingredient. The 101 potential quercetin targets were identified for the treatment of HBV-related HCC. GO and KEGG showed that 101 potential target enrichment in cancer and cell cycle regulation. By Venn analysis, CDK1 and CCNB1 were intersection targets, which could be used as potential targets for the action of quercetin on HBV-related HCC. Moreover, the expression of CDK1 and CCNB1 was highly expressed in the high-risk group, while the OS rate was low. The 1-year, 3-year and 5-year area under the curve (AUC) curves of CDK1 and CCNB1 were 0.724, 0.676, 0.622 and 0.745, 0.678, 0.634, respectively. Moreover, experimental results also showed that quercetin inhibited cell proliferation and reduced CDK1 expression in Hep3B and HepG2215 cells. The expressions of HBsAg and HBeAg in HepG2215 cell supernatant and cell gradually decreased with the increase of intervention time of quercetin and CDK1 inhibitor. CONCLUSIONS: Quercetin is a key ingredient of anti-HBV-related HCC activity and inhibits HBV replication in SNRS by inhibiting CDK1.


Assuntos
Proteína Quinase CDC2 , Medicamentos de Ervas Chinesas , Neoplasias Hepáticas , Panax , Quercetina , Replicação Viral , Humanos , Antineoplásicos/química , Antineoplásicos/farmacologia , Antivirais/farmacologia , Antivirais/química , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/virologia , Proteína Quinase CDC2/efeitos dos fármacos , Proteína Quinase CDC2/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Ciclina B1/efeitos dos fármacos , Ciclina B1/metabolismo , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/química , Células Hep G2 , Vírus da Hepatite B/efeitos dos fármacos , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/virologia , Panax/química , Quercetina/farmacologia , Replicação Viral/efeitos dos fármacos
5.
BMC Plant Biol ; 24(1): 549, 2024 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-38872078

RESUMO

Ginseng (Panax ginseng C. A. Mey.) is an important and valuable medicinal plant species used in traditional Chinese medicine, and its metabolite ginsenoside is the primary active ingredient. The FAR1/FHY3 gene family members play critical roles in plant growth and development as well as participate in a variety of physiological processes, including plant development and signaling of hormones. Studies have indicated that methyl jasmonate treatment of ginseng adventitious roots resulted in a significant increase in the content of protopanaxadiol ginsenosides. Therefore, it is highly significant to screen the FAR1/FHY3 gene family members in ginseng and preliminarily investigate their expression patterns in response to methyl jasmonic acid signaling. In this study, we screened and identified the FAR1/FHY3 family genes in the ginseng transcriptome databases. And then, we analyzed their gene structure and phylogeny, chromosomal localization and expression patterns, and promoter cis-acting elements, and made GO functional annotations on the members of this family. After that, we treated the ginseng adventitious roots with 200 mM methyl jasmonate and investigated the trend of the expression of four genes containing the largest number of methyl jasmonate cis-acting elements at different treatment times. All four genes were able to respond to methyl jasmonate, the most significant change was in the PgFAR40 gene. This study provides data support for subsequent studies of this family member in ginseng and provides experimental reference for subsequent validation of the function of this family member under methyl jasmonic acid signaling.


Assuntos
Acetatos , Ciclopentanos , Regulação da Expressão Gênica de Plantas , Família Multigênica , Oxilipinas , Panax , Filogenia , Proteínas de Plantas , Oxilipinas/farmacologia , Ciclopentanos/farmacologia , Panax/genética , Panax/metabolismo , Panax/efeitos dos fármacos , Acetatos/farmacologia , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Regulação da Expressão Gênica de Plantas/efeitos dos fármacos , Reguladores de Crescimento de Plantas/farmacologia , Reguladores de Crescimento de Plantas/metabolismo , Raízes de Plantas/genética , Raízes de Plantas/efeitos dos fármacos , Raízes de Plantas/metabolismo , Perfilação da Expressão Gênica , Genes de Plantas , Ginsenosídeos
6.
Phytomedicine ; 130: 155785, 2024 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-38823342

RESUMO

BACKGROUND: Oxidative stress is the main cause of many diseases, but because of its complex pathogenic factors, there is no clear method for treating it. Ginseng total saponin (GTS) an important active ingredients in Panax ginseng C.A. Mey (PG) and has potential therapeutic ability for oxidative stress due to various causes. However, the molecular mechanism of GTS in the treating oxidative stress damage in red blood cells (RBCs) is still unclear. PURPOSE: This study aimed to examine the protective effect of GTS on RBCs under oxidative stress damage and to determine its potential mechanism. METHODS: The oxidative stress models of rat RBCs induced by hydrogen peroxide (H2O2) and exhaustive swimming in vivo and in vitro was used. We determined the cell morphology, oxygen carrying capacity, apoptosis, antioxidant capacity, and energy metabolism of RBCs. The effect of tyrosine phosphorylation (pTyr) of Band 3 protein on RBCs glycolysis was also examined. RESULTS: GTS reduced the hemolysis of RBCs induced by H2O2 at the lowest concentration. Moreover, GTS effectively improved the morphology, enhanced the oxygen carrying capacity, and increased antioxidant enzyme activity, adenosine triphosphate (ATP) levels, and adenosine triphosphatase (ATPase) activity in RBCs. GTS also promoted the expression of membrane proteins in RBCs, inhibited pTyr of Band 3 protein, and further improved glycolysis, restoring the morphological structure and physiological function of RBCs. CONCLUSIONS: This study shows, that GTS can protect RBCs from oxidative stress damage by improving RBCs morphology and physiological function. Changes in pTyr expression and its related pTyr regulatory enzymes before and after GTS treatment suggest that Band 3 protein is the main target of GTS in the treating endogenous and exogenous oxidative stress. Moreover, GTS can enhance the glycolytic ability of RBCs by inhibiting pTyr of Band 3 protein, thereby restoring the function of RBCs.


Assuntos
Eritrócitos , Glicólise , Peróxido de Hidrogênio , Estresse Oxidativo , Panax , Ratos Sprague-Dawley , Saponinas , Tirosina , Estresse Oxidativo/efeitos dos fármacos , Panax/química , Eritrócitos/efeitos dos fármacos , Eritrócitos/metabolismo , Saponinas/farmacologia , Animais , Glicólise/efeitos dos fármacos , Tirosina/análogos & derivados , Tirosina/farmacologia , Tirosina/metabolismo , Masculino , Fosforilação/efeitos dos fármacos , Ratos , Hemólise/efeitos dos fármacos , Antioxidantes/farmacologia , Proteína 1 de Troca de Ânion do Eritrócito/metabolismo , Apoptose/efeitos dos fármacos
7.
Sensors (Basel) ; 24(11)2024 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-38894248

RESUMO

Red ginseng is widely used in food and pharmaceuticals due to its significant nutritional value. However, during the processing and storage of red ginseng, it is susceptible to grow mold and produce mycotoxins, generating security issues. This study proposes a novel approach using hyperspectral imaging technology and a 1D-convolutional neural network-residual-bidirectional-long short-term memory attention mechanism (1DCNN-ResBiLSTM-Attention) for pixel-level mycotoxin recognition in red ginseng. The "Red Ginseng-Mycotoxin" (R-M) dataset is established, and optimal parameters for 1D-CNN, residual bidirectional long short-term memory (ResBiLSTM), and 1DCNN-ResBiLSTM-Attention models are determined. The models achieved testing accuracies of 98.75%, 99.03%, and 99.17%, respectively. To simulate real detection scenarios with potential interfering impurities during the sampling process, a "Red Ginseng-Mycotoxin-Interfering Impurities" (R-M-I) dataset was created. The testing accuracy of the 1DCNN-ResBiLSTM-Attention model reached 96.39%, and it successfully predicted pixel-wise classification for other unknown samples. This study introduces a novel method for real-time mycotoxin monitoring in traditional Chinese medicine, with important implications for the on-site quality control of herbal materials.


Assuntos
Micotoxinas , Redes Neurais de Computação , Panax , Panax/química , Micotoxinas/análise , Micotoxinas/química , Imageamento Hiperespectral/métodos
8.
Molecules ; 29(12)2024 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-38930835

RESUMO

Ginseng (Panax ginseng C.A. Mey) is known for its rich saponin compounds and tonic effects. To better utilize the medicinal value of ginseng, this study investigated the extraction process, components, free radical scavenging ability, and immunomodulatory activity of total saponins of ginseng fibrous roots. The response surface methodology was employed to optimize the extraction process of total saponins, and Q-Orbitrap high-resolution liquid chromatography-mass spectrometry (LC-MS) was used to identify the chemical constituents in the total saponins extract of ginseng fibrous roots (GRS). The results showed that the optimal extraction process was achieved with an ethanol concentration of 68%, a material-solvent ratio of 1:25 mL/g, and an extraction time of 20 min, yielding a total saponin content of 6.34% under these conditions. The extract contained four terpenoid compounds and four polyphenolic compounds. GRS exhibited considerable scavenging activity against DPPH and ABTS radicals, with IC50 values of 0.893 and 0.210 mg/mL, respectively. Moreover, GRS restored immune suppression in mice by increasing white blood cell, red blood cell, and neutrophil counts, and improving the lymphocyte. It also promoted immune system recovery, as evidenced by elevated serum levels of IL-2, IFN-γ, TNF-α, and IL-1ß in mice. GRS is a natural compound with promising potential for developing antioxidants and immunomodulatory foods.


Assuntos
Sequestradores de Radicais Livres , Panax , Extratos Vegetais , Raízes de Plantas , Saponinas , Panax/química , Saponinas/farmacologia , Saponinas/química , Saponinas/isolamento & purificação , Sequestradores de Radicais Livres/farmacologia , Sequestradores de Radicais Livres/química , Raízes de Plantas/química , Animais , Camundongos , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Fatores Imunológicos/farmacologia , Fatores Imunológicos/química , Agentes de Imunomodulação/farmacologia , Agentes de Imunomodulação/química , Antioxidantes/farmacologia , Antioxidantes/química
9.
Plant Physiol Biochem ; 212: 108742, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38772166

RESUMO

Ginseng frequently encounters environmental stress during its growth and development. Late Embryogenesis Abundant (LEA) proteins play a crucial role in combating adversity stress, particularly against abiotic challenges In this study, 107 LEA genes from ginseng, spanning eight subfamilies, were identified, demonstrating significant evolutionary conservation, with the LEA2 subfamily being most prominent. Gene duplication events, primarily segmental duplications, have played a major role in the expansion of the LEA gene family, which has undergone strong purifying selection. PgLEAs were unevenly distributed across 22 chromosomes, with each subfamily featuring unique structural domains and conserved motifs. PgLEAs were expressed in various tissues, exhibiting distinct variations in abundance and tissue specificity. Numerous regulatory cis-elements, related to abiotic stress and hormones, were identified in the promoter region. Additionally, PgLEAs were regulated by a diverse array of abiotic stress-related transcription factors. A total of 35 PgLEAs were differentially expressed following treatments with ABA, GA, and IAA. Twenty-three PgLEAs showed significant but varied responses to drought, extreme temperatures, and salinity stress. The transformation of tobacco with the key gene PgLEA2-50 enhanced osmoregulation and antioxidant levels in transgenic lines, improving their resistance to abiotic stress. This study offers insights into functional gene analysis, focusing on LEA proteins, and establishes a foundational framework for research on ginseng's resilience to abiotic stress.


Assuntos
Regulação da Expressão Gênica de Plantas , Família Multigênica , Panax , Proteínas de Plantas , Estresse Fisiológico , Panax/genética , Panax/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Estresse Fisiológico/genética , Genoma de Planta/genética , Filogenia , Plantas Geneticamente Modificadas , Nicotiana/genética , Nicotiana/metabolismo
10.
J Microbiol Biotechnol ; 34(6): 1287-1298, 2024 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-38783703

RESUMO

Ulcerative colitis (UC) is an inflammatory bowel disease (IBD) that is currently difficult to treat effectively. Both Bacillus natto (BN) and ginseng-soluble dietary fiber (GSDF) are anti-inflammatory and helps sustain the intestinal barrier. In this study, the protective effects and mechanism of the combination of B. natto JLCC513 and ginseng-soluble dietary fiber (BG) in DSS-induced UC mice were investigated. Intervention with BG worked better than taking BN or GSDF separately, as evidenced by improved disease activity index, colon length, and colon injury and significantly reduced the levels of oxidative and inflammatory factors (LPS, ILs, and TNF-α) in UC mice. Further mechanistic study revealed that BG protected the intestinal barrier integrity by maintaining the tight junction proteins (Occludin and Claudin1) and inhibited the LPS/TLR4/NF-κB pathway in UC mice. In addition, BG increased the abundance of beneficial bacteria such as Bacteroides and Turicibacter and reduced the abundance of harmful bacteria such as Allobaculum in the gut microbiota of UC mice. BG also significantly upregulated genes related to linoleic acid metabolism in the gut microbiota. These BG-induced changes in the gut microbiota of mice with UC were significantly correlated with changes in pathological indices. In conclusion, this study demonstrated that BG exerts protective effect against UC by regulating the LPS/TLR4/NF-κB pathway and the structure and metabolic function of gut microbiota. Thus, BG can be potentially used in intestinal health foods to treat UC.


Assuntos
Bacillus , Colite Ulcerativa , Fibras na Dieta , Microbioma Gastrointestinal , Lipopolissacarídeos , NF-kappa B , Panax , Receptor 4 Toll-Like , Animais , Microbioma Gastrointestinal/efeitos dos fármacos , Receptor 4 Toll-Like/metabolismo , NF-kappa B/metabolismo , Camundongos , Fibras na Dieta/farmacologia , Panax/química , Colite Ulcerativa/microbiologia , Lipopolissacarídeos/metabolismo , Bacillus/metabolismo , Masculino , Transdução de Sinais , Modelos Animais de Doenças , Colo/microbiologia , Colo/metabolismo , Colo/patologia , Camundongos Endogâmicos C57BL , Probióticos/administração & dosagem , Probióticos/farmacologia , Sulfato de Dextrana , Anti-Inflamatórios/farmacologia
11.
Zhongguo Zhong Yao Za Zhi ; 49(10): 2585-2596, 2024 May.
Artigo em Chinês | MEDLINE | ID: mdl-38812159

RESUMO

This study investigated the effects and mechanisms of total saponins of Panax japonicus(TSPJ) against liver injury induced by acetaminophen(APAP). Male Kunming mice were randomly divided into a blank control group, TSPJ group(200 mg·kg~(-1), ig), model group, APAP+ TSPJ low-dose group(50 mg·kg~(-1), ig), APAP+ TSPJ medium-dose group(100 mg·kg~(-1), ig), APAP+ TSPJ high-dose group(200 mg·kg~(-1), ig), and APAP+ N-acetyl-L-cysteine group(200 mg·kg~(-1), ip). The administration group received the corresponding medications via ig or ip once a day for 14 consecutive days. After the last administration for one hour, except for the blank control group and TSPJ group, all groups of mice were given 500 mg·kg~(-1) APAP by gavage. After 24 hours, mouse serum and liver tissue were collected for serum alanine aminotransferase(ALT), aspartate aminotransferase(AST), reactive oxygen species(ROS), tumor necrosis factor alpha(TNF-α), interleukin-1 beta(IL-1ß), cyclooxygenase-2(COX-2), IL-6, IL-4, IL-10, as well as lactate dehydrogenase(LDH), glutathione(GSH), superoxide dismutase(SOD), catalase(CAT), total antioxidant capacity(T-AOC), malondialdehyde(MDA), and myeloperoxidase(MPO) liver tissue. Hematoxylin-eosin staining was used to observe the morphological changes of liver tissue. The mRNA expression levels of lymphocyte antigen 6G(Ly6G), galectin 3(Mac-2), TNF-α, IL-1ß, COX-2, IL-6, IL-4, and IL-10 in liver tissue were determined by quantitative real-time polymerase chain reaction(PCR). Western blot was utilized to detect the protein expression levels of Ly6G, Mac-2, extracellular regulated protein kinases(ERK), phosphorylated extracellular regulated protein kinases(p-ERK), COX-2, inhibitor of nuclear factor κB protein α(IκBα), phosphorylated inhibitor of nuclear factor κB protein α(p-IκBα), and nuclear factor-κB subunit p65(NF-κB p65) in cytosol and nucleus in liver tissue. The results manifested that TSPJ dramatically reduced liver coefficient, serum ALT, AST, ROS, TNF-α, IL-1ß, IL-6, and COX-2 levels, LDH, MPO, and MDA contents in liver tissue, and mRNA expressions of TNF-α, IL-1ß, and IL-6 in APAP-induced liver injury mice. It prominently elevated serum IL-4 and IL-10 levels, GSH, CAT, SOD, and T-AOC contents, and mRNA expressions of IL-4 and IL-10 in liver tissue, improved the degree of liver pathological damage, and suppressed neutrophil infiltration and macrophage recruitment in liver tissue. In addition, TSPJ lessened the mRNA and protein expressions of neutrophil marker Ly6G, macrophage marker Mac-2, and COX-2 in liver tissue, protein expressions of p-ERK, p-IκBα, and NF-κB p65 in nuclear, and p-ERK/ERK and p-IκBα/p-IκBα ratios and hoisted protein expression of NF-κB p65 in cytosol. These results suggest that TSPJ has a significant protective effect on APAP-induced liver injury in mice, and it can alleviate APAP-induced oxidative damage and inflammatory response. Its mechanism may be related to suppressing ERK/NF-κB/COX-2 signaling pathway activation, thus inhibiting inflammatory cell infiltration, cytokine production, and liver cell damage.


Assuntos
Acetaminofen , Doença Hepática Induzida por Substâncias e Drogas , Ciclo-Oxigenase 2 , Fígado , NF-kappa B , Panax , Saponinas , Transdução de Sinais , Animais , Acetaminofen/efeitos adversos , Acetaminofen/toxicidade , Camundongos , Panax/química , Masculino , Saponinas/farmacologia , Saponinas/administração & dosagem , NF-kappa B/genética , NF-kappa B/metabolismo , Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológico , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Ciclo-Oxigenase 2/genética , Ciclo-Oxigenase 2/metabolismo , Fígado/efeitos dos fármacos , Fígado/metabolismo , Transdução de Sinais/efeitos dos fármacos , Humanos , Medicamentos de Ervas Chinesas/administração & dosagem , Medicamentos de Ervas Chinesas/farmacologia
12.
Zhongguo Zhong Yao Za Zhi ; 49(10): 2766-2775, 2024 May.
Artigo em Chinês | MEDLINE | ID: mdl-38812177

RESUMO

Panax ginseng is reputed to be capable of replenishing healthy Qi and bolstering physical strength, and P. notoginseng can resolve blood stasis and alleviate pain. P. ginseng and P. notoginseng are frequently employed to treat ischemic heart diseases caused by blockages in the heart vessels. Mitochondrial dysfunction often coexists with abnormal mitochondrial morphology, and mitochondrial plasticity and dynamics play key roles in cardiovascular diseases. In this study, primary neonatal rat cardiomyocytes were exposed to 4 hours of hypoxia(H) followed by 2 hours of reoxygenation(R). MitoTracker Deep Red and Hoechst 33342 were used to label mitochondria and nuclei, respectively. Fluorescence images were then acquired using ImageXpress Micro Confocal. Automated image processing and parameter extraction/calculation were carried out using ImagePro Plus. Subsequently, representative parameters were selected as indicators to assess alterations in mitochondrial morphology and function. The active compounds of P. ginseng and P. notoginseng were screened out and identified based on the UPLC-Triple-TOF-MS results and mitochondrial morphometric parameters. The findings demonstrated that RS-2, RS-4, SQ-1, and SQ-4 significantly increased the values of three key morphometric parameters, including mitochondrial length, branching, and area, which might contribute to rescuing morphological features of myocardial cells damaged by H/R injury. Among the active components of the two medicinal herbs, 20(R)-ginsenoside Rg_3, ginsenoside Re, and gypenoside ⅩⅦ exhibited the strongest protective effects on mitochondria in cardiomyocytes. Specifically, 20(R)-ginsenoside Rg_3 might upregulate expression of optic atrophy 1(OPA1) and mitofusin 2(MFN2), and ginsenoside Re and gypenoside ⅩⅦ might selectively upregulate OPA1 expression. Collectively, they promoted mitochondrial membrane fusion and mitigated mitochondrial damage, thereby exerting protective effects on cardiomyocytes. This study provides experimental support for the discovery of novel therapeutic agents for myocardial ischemia-reperfusion injury from P. ginseng and P. notoginseng and offers a novel approach for large-scale screening of bioactive compounds with cardioprotective effects from traditional Chinese medicines.


Assuntos
Cardiotônicos , Medicamentos de Ervas Chinesas , Miócitos Cardíacos , Panax notoginseng , Panax , Ratos Sprague-Dawley , Animais , Ratos , Panax/química , Panax notoginseng/química , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/química , Miócitos Cardíacos/efeitos dos fármacos , Miócitos Cardíacos/metabolismo , Cardiotônicos/farmacologia , Cromatografia Líquida de Alta Pressão , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Espectrometria de Massas
13.
Zhongguo Zhong Yao Za Zhi ; 49(7): 1717-1724, 2024 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-38812184

RESUMO

Panax ginseng, known as the "king of herbs", is a highly valued medicinal plant, and its medicinal parts include roots, stems, leaves, flowers, and fruits, among which the roots are the most commonly used. The main active components of this medicinal plant include triterpenoid saponins, polysaccharides, peptides, and volatile oils. The chemical components and active metabolites endow this herb with a variety of pharmacological effects, and thus this herb is used to treat various diseases and play healthcare roles. Currently, a wide range of preparations of P. ginseng have been officially registered and marketed, including tablets, oral liquids, and injections, which demonstrate good clinical efficacy in regulating immunity, adjuvant treatment of tumors, alleviating fatigue, delaying the aging process, improving glucose and lipid metabolism, treating cardiovascular diseases, and relieving inflammation and pain. The production process and quality standards of these drugs are of great significance to ensure their efficacy. According to the theory that Ginseng Radix et Rhizoma can greatly replenish original Qi, tonify the spleen and lung, promote fluid production to quench thirst, tranquilize mind and enrich the intelligence, this paper systematically summarized the clinical application progress of P. ginseng and rela-ted preparations on the market and prospected the further development of preparations from P. ginseng, providing a reference for further exploring the medicinal value and healthcare function of this herb. The above contents, as an important basis for the in-depth development of P. ginseng and related drugs, increase the possibilities for the application of P. ginseng.


Assuntos
Medicamentos de Ervas Chinesas , Panax , Panax/química , Humanos , Medicamentos de Ervas Chinesas/química , Animais
14.
Food Chem ; 454: 139802, 2024 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-38797098

RESUMO

Direct surface analysis in ambient conditions provides information on the position and chemical composition of an object at the time of investigation. An angled sampling probe is developed in this work for direct analysis in real time (DART) ionization high-resolution mass spectrometry. The DART ion source and the interface were modified for improved surface resolution, increased ion transfer efficiency, as well as enabling two-dimensional surface scanning. The angled probe DART-MS system was used for investigating a variety of food samples including fruit peels, ginseng root, plant leaves and sections of radish. Abundant signals and distinct chemical profiles are obtained in seconds, and spatial distribution of different molecules across the sample surfaces can be observed. In addition, the developed system can quickly identify the chemical changes when the surfaces were treated. The method is capable of directly evaluating food sample surfaces with different shapes, hardness, and conditions, without any sample pretreatments.


Assuntos
Frutas , Espectrometria de Massas , Espectrometria de Massas/métodos , Frutas/química , Produtos Biológicos/química , Produtos Biológicos/análise , Análise de Alimentos/métodos , Raphanus/química , Panax/química , Folhas de Planta/química , Raízes de Plantas/química
15.
Biochem Biophys Res Commun ; 719: 150027, 2024 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-38749089

RESUMO

Aging is a complex, degenerative process associated with various metabolic abnormalities. Ginsenosides (GS) is the main active components of Panax ginseng, which has anti-aging effects and improves metabolism. However, the anti-aging effect and the mechanism of GS in middle-aged mice has not been elucidated. In this study, GS after 3-month treatment significantly improved the grip strength, fatigue resistance, cognitive indices, and cardiac function of 15-month-old mice. Meanwhile, GS treatment reduced the fat content and obviously inhibited histone H2AX phosphorylation at Ser 139 (γ-H2AX), a marker of DNA damage in major organs, especially in the heart and liver. Further, the correlation analysis of serum metabolomics combined with aging phenotype suggested that myo-inositol (MI) upregulated by GS was positively correlated with left ventricular ejection fraction (LVEF) and left ventricular fractional shortening (LVFS), the main indicators of cardiac function. More importantly, liver tissue metabolomic analysis showed that GS increased MI content by promoting the synthesis pathway from phosphatidylcholine (PC) to MI for the inhibition of liver aging. Finally, we proved that MI reduced the percentage of senescence-associated ß-galactosidase staining, γ-H2AX immunofluorescence staining, p21 expression, and the production of reactive oxygen species in H2O2-induced cardiomyocytes. These results suggest that GS can enhance multiple organ functions, especially cardiac function for promoting the healthspan of aging mice, which is mediated by the conversion of PC to MI in the liver and the increase of MI level in the serum. Our study might provide new insights into the potential mechanisms of ginsenosides for prolonging the healthspan of natural aging mice.


Assuntos
Envelhecimento , Ginsenosídeos , Inositol , Metabolômica , Panax , Fosfatidilcolinas , Animais , Panax/química , Ginsenosídeos/farmacologia , Envelhecimento/efeitos dos fármacos , Envelhecimento/metabolismo , Fosfatidilcolinas/metabolismo , Camundongos , Masculino , Inositol/farmacologia , Fígado/metabolismo , Fígado/efeitos dos fármacos , Camundongos Endogâmicos C57BL
16.
Front Immunol ; 15: 1353614, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38698858

RESUMO

Intestinal inflammatory imbalance and immune dysfunction may lead to a spectrum of intestinal diseases, such as inflammatory bowel disease (IBD) and gastrointestinal tumors. As the king of herbs, ginseng has exerted a wide range of pharmacological effects in various diseases. Especially, it has been shown that ginseng and ginsenosides have strong immunomodulatory and anti-inflammatory abilities in intestinal system. In this review, we summarized how ginseng and various extracts influence intestinal inflammation and immune function, including regulating the immune balance, modulating the expression of inflammatory mediators and cytokines, promoting intestinal mucosal wound healing, preventing colitis-associated colorectal cancer, recovering gut microbiota and metabolism imbalance, alleviating antibiotic-induced diarrhea, and relieving the symptoms of irritable bowel syndrome. In addition, the specific experimental methods and key control mechanisms are also briefly described.


Assuntos
Microbioma Gastrointestinal , Ginsenosídeos , Panax , Ginsenosídeos/farmacologia , Ginsenosídeos/uso terapêutico , Panax/química , Humanos , Animais , Microbioma Gastrointestinal/efeitos dos fármacos , Mucosa Intestinal/imunologia , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/metabolismo , Mucosa Intestinal/patologia , Anti-Inflamatórios/uso terapêutico , Anti-Inflamatórios/farmacologia , Doenças Inflamatórias Intestinais/tratamento farmacológico , Doenças Inflamatórias Intestinais/imunologia , Doenças Inflamatórias Intestinais/metabolismo , Sistema Imunitário/efeitos dos fármacos , Sistema Imunitário/metabolismo , Sistema Imunitário/imunologia , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico
17.
Molecules ; 29(9)2024 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-38731522

RESUMO

Cardiovascular disease has become a common ailment that endangers human health, having garnered widespread attention due to its high prevalence, recurrence rate, and sudden death risk. Ginseng possesses functions such as invigorating vital energy, enhancing vein recovery, promoting body fluid and blood nourishment, calming the nerves, and improving cognitive function. It is widely utilized in the treatment of various heart conditions, including palpitations, chest pain, heart failure, and other ailments. Although numerous research reports have investigated the cardiovascular activity of single ginsenoside, there remains a lack of systematic research on the specific components group that predominantly contribute to cardiovascular efficacy in ginseng medicinal materials. In this research, the spectrum-effect relationship, target cell extraction, and BP neural network classification were used to establish a rapid screening system for potential active substances. The results show that red ginseng extract (RGE) can improve the decrease in cell viability and ATP content and inhibit the increase in ROS production and LDH release in OGD-induced H9c2 cells. A total of 70 ginsenosides were identified in RGE using HPLC-Q-TOF-MS/MS analysis. Chromatographic fingerprints were established for 12 batches of RGE by high-performance liquid chromatography (HPLC). A total of 36 common ingredients were found in 12 batches of RGE. The cell viability, ATP, ROS, and LDH of 12 batches RGE were tested to establish gray relationship analysis (GRA) and partial least squares discrimination analysis (PLS-DA). BP neural network classification and target cell extraction were used to narrow down the scope of Spectral efficiency analysis and screen the potential active components. According to the cell experiments, RGE can improve the cell viability and ATP content and reduce the oxidative damage. Then, seven active ingredients, namely, Ginsenoside Rg1, Rg2, Rg3, Rb1, Rd, Re, and Ro, were screened out, and their cardiovascular activity was confirmed in the OGD model. The seven ginsenosides were the main active substances of red ginseng in treating myocardial injury. This study offers a reference for quality control in red ginseng and preparations containing red ginseng for the management of cardiovascular diseases. It also provides ideas for screening active ingredients of the same type of multi-pharmacologically active traditional Chinese medicines.


Assuntos
Sobrevivência Celular , Ginsenosídeos , Redes Neurais de Computação , Panax , Extratos Vegetais , Panax/química , Extratos Vegetais/farmacologia , Extratos Vegetais/química , Ginsenosídeos/farmacologia , Ginsenosídeos/química , Ginsenosídeos/isolamento & purificação , Sobrevivência Celular/efeitos dos fármacos , Ratos , Animais , Linhagem Celular , Espécies Reativas de Oxigênio/metabolismo , Miócitos Cardíacos/efeitos dos fármacos , Miócitos Cardíacos/metabolismo , Cromatografia Líquida de Alta Pressão , Humanos , Espectrometria de Massas em Tandem
18.
Nutrients ; 16(10)2024 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-38794654

RESUMO

Hexavalent chromium is a common pollutant in the environment. Long-term exposure to hexavalent chromium can cause damage to multiple organs. The kidney is one of the main organs that metabolizes heavy metal toxicity, and the accumulation of Cr (VI) in the body can lead to serious damage to kidney function. Studies have shown that ginseng polysaccharides have the function of preventing cisplatin-induced endoplasmic reticulum stress, inflammatory response, and apoptosis in renal cells, but their efficacy and mechanisms against hexavalent chromium-induced nephrotoxicity need to be explored. The aim of this study was to explore the efficacy and mechanism of ginseng polysaccharide against hexavalent chromium-induced nephrotoxicity. The results of pharmacodynamic experiments showed that ginseng polysaccharide could significantly reduce the kidney index, urea nitrogen (BUN), and serum creatinine (Cre) values of K2Cr2O7-treated mice. The results of mechanistic experiments showed that ginseng polysaccharides could alleviate oxidative stress, apoptosis, and biofilm damage in renal tissues caused by Cr (VI). Lipidomic correlation analysis showed that ginseng polysaccharides could protect the organism by regulating the expression of differential lipids. This study opens new avenues for the development of alternative strategies for the prevention of kidney injury caused by hexavalent chromium.


Assuntos
Apoptose , Cromo , Rim , Estresse Oxidativo , Panax , Polissacarídeos , Panax/química , Cromo/toxicidade , Animais , Polissacarídeos/farmacologia , Camundongos , Rim/efeitos dos fármacos , Rim/metabolismo , Rim/patologia , Apoptose/efeitos dos fármacos , Masculino , Estresse Oxidativo/efeitos dos fármacos , Nefropatias/induzido quimicamente , Nefropatias/prevenção & controle , Extratos Vegetais/farmacologia , Creatinina/sangue
19.
Sci Rep ; 14(1): 12109, 2024 05 27.
Artigo em Inglês | MEDLINE | ID: mdl-38802411

RESUMO

Chronic Heart Failure (CHF) is a significant global public health issue, with high mortality and morbidity rates and associated costs. Disease modules, which are collections of disease-related genes, offer an effective approach to understanding diseases from a biological network perspective. We employed the multi-Steiner tree algorithm within the NeDRex platform to extract CHF disease modules, and subsequently utilized the Trustrank algorithm to rank potential drugs for repurposing. The constructed disease module was then used to investigate the mechanism by which Panax ginseng ameliorates CHF. The active constituents of Panax ginseng were identified through a comprehensive review of the TCMSP database and relevant literature. The Swiss target prediction database was utilized to determine the action targets of these components. These targets were then cross-referenced with the CHF disease module in the STRING database to establish protein-protein interaction (PPI) relationships. Potential action pathways were uncovered through Gene Ontology (GO) and KEGG pathway enrichment analyses on the DAVID platform. Molecular docking, the determination of the interaction of biological macromolecules with their ligands, and visualization were conducted using Autodock Vina, PLIP, and PyMOL, respectively. The findings suggest that drugs such as dasatinib and mitoxantrone, which have low docking scores with key disease proteins and are reported in the literature as effective against CHF, could be promising. Key components of Panax ginseng, including ginsenoside rh4 and ginsenoside rg5, may exert their effects by targeting key proteins such as AKT1, TNF, NFKB1, among others, thereby influencing the PI3K-Akt and calcium signaling pathways. In conclusion, drugs like dasatinib and midostaurin may be suitable for CHF treatment, and Panax ginseng could potentially mitigate the progression of CHF through a multi-component-multi-target-multi-pathway approach. Disease module analysis emerges as an effective strategy for exploring drug repurposing and the mechanisms of traditional Chinese medicine in disease treatment.


Assuntos
Reposicionamento de Medicamentos , Insuficiência Cardíaca , Simulação de Acoplamento Molecular , Panax , Panax/química , Panax/metabolismo , Insuficiência Cardíaca/tratamento farmacológico , Insuficiência Cardíaca/metabolismo , Humanos , Reposicionamento de Medicamentos/métodos , Mapas de Interação de Proteínas/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Doença Crônica/tratamento farmacológico , Ginsenosídeos/farmacologia , Ginsenosídeos/uso terapêutico , Medicamentos de Ervas Chinesas/uso terapêutico , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/química
20.
Phytomedicine ; 129: 155625, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38692077

RESUMO

BACKGROUND: Shengmai Formula (SMF), a classic formula in treating Qi-Yin deficiency, is composed of Ginseng Radix et Rhizoma Rubra (GRR), Ophiopogon Radix (OR), and Schisandra chinensis Fructus (SC), and has been developed into various dosage forms including Shengmai Yin Oral Liquid (SMY), Shengmai Capsules (SMC), and Shengmai Injection (SMI). The pharmacological effects of compound Chinese medicine are attributed to the integration of multiple components. Yet the quality criteria of SMF are limited to monitoring schisandrol A or ginsenosides Rg1 and Re, but none for OR. Since the complexity of raw materials and preparations, establishing a economical and unified method for SMF is challenging. It is urgent to simultaneously quantify multiple components with different structures using a universal method for quality control of SMF. Charged aerosol detector (CAD) overcame the above shortcomings owing to its characteristics of high responsiveness, nondiscrimination, and low cost. PURPOSE: We aimed to establish a versatile analysis strategy using HPLC-CAD for simultaneously quantifying the structurally diverse markers in quality control of SMF from raw materials to preparations. METHOD: By optimizing the column, mobile phase, column temperature, flow rate, and CAD parameters, a HPLC-CAD method that integrated multi-component characterization, authenticity identification, transfer information of raw materials and quantitative determination of Shengmai preparations was established. RESULTS: In total 50 components from SMF were characterized (28 in GRR, 13 in SC, and 9 in OR). The differences in raw materials between species of SC and Schisandrae sphenantherae Fructus (SS), processing methods of Ginseng Radix (GR) and GRR, and locations of OR from Sichuan (ORS) and Zhejiang (ORZ) were compared. Fourteen components in 19 batches of SMY, SMC and SMI from different manufacturers were quantified, including 11 ginsenosides and 3 lignans. The multivariate statistical analysis results further suggested that Rb1, Rg1 and Ro were the main differences among Shengmai preparations. CONCLUSION: The established versatile analysis strategy based on HPLC-CAD was proven sensitive, simple, convenient, overcoming the discriminatory effect of UV detector, revealing the composition and transfer information of SMF and applicable for authentication of the ingredient herbs and improving the quality of Shengmai preparations.


Assuntos
Combinação de Medicamentos , Medicamentos de Ervas Chinesas , Controle de Qualidade , Schisandra , Cromatografia Líquida de Alta Pressão/métodos , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/análise , Medicamentos de Ervas Chinesas/normas , Schisandra/química , Ginsenosídeos/análise , Ginsenosídeos/química , Lignanas/análise , Ciclo-Octanos/análise , Ciclo-Octanos/química , Panax/química
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