RESUMEN
Introduction: Black ginseng (BG) was processed by "steaming and drying" (generally nine times) repeatedly to produce "rare saponins" and secondary ginsenosides. Both ginseng (GS) and red ginseng (RG) were commonly used in treating heart failure (HF), and the latter was confirmed to be more potent, implying the presence of rare ginsenosides that contribute positively to the treatment of heart failure. Previous research indicated that rare ginsenosides are more abundant in BG than in RG. Consequently, this study aims to investigate the effects of BG and its components on HF to elucidate the active substances and their underlying mechanisms in the treatment of HF. Methods: The effects of BG and its fractions (water-eluted fraction (WEF), total saponin fraction (TSF), and alcohol-eluted fraction (AEF)) on rats with isoproterenol (ISO)-induced HF were explored, and steroids belonging to the hypothalamic-pituitary-adrenal (HPA) and hypothalamic-pituitary-gonadal (HPG) axes were determined quantitatively using the ultra-performance liquid chromatography-triple quadrupole tandem mass spectrometry (UPLC-QqQ-MS/MS) method. In addition, 16S rDNA sequencing was performed on the gut microbiota, followed by GC-MS analysis of short-chain fatty acids (SCFAs), and the biochemical indexes related to energy metabolism and the serum cyclic nucleotide system were also analyzed by ELISA. Results: Based on a thorough evaluation of energy metabolism and the endocrine system, it was observed that the effects of BG components on the hypothalamic-pituitary-thyroid (HPT) and HPA axes were more pronounced. Notably, the treatment efficacy of the low dose of the total saponin fraction (TSFL), water decoction (WD), and high dose of the polysaccharide fraction (PSFH) was superior based on pharmacodynamic indicators such as brain natriuretic peptide (BNP), creatine kinase (CK), and estradiol (E2)/T). Furthermore, the WD and BG components exhibited significant effects on androgens (T and androstenedione (A4)). The TSFL group exerts an anti-inflammatory effect by regulating Lactobacillus/Erysipelotrichales. The WD, PSFH, and TSFL may impact inflammatory cytokines through the gut microbiota (Lactobacillus/Erysipelotrichales) and their metabolites (acetate and butyrate), exerting an anti-inflammatory effect. Discussion: The BG and all its split components demonstrated varying levels of efficacy in alleviating HF, and TSF and PSF exhibited a significant protective effect on HF. The main active components in TSF were revealed to be ginsenosides Rk1, Rk3, 20-(S)-Rg3, and 20-(S)-Rh2 by the H9C2 cell experiment. The decoction of BG and its components exhibited a potent impact on androgen hormones, with an elevation trend. This phenomenon may be attributed to the activation of the eNOS-NO pathway through androgen regulation, thereby contributing to its anti-HF activities. The WD, PSFH, and TSFL may exert anti-inflammatory effects through the intestinal flora (Lactobacillaceae/Erysipelotrichaceae) and its metabolites (acetic acid and butyric acid), which affect the inflammatory factors. The different mechanisms of action of each component of HF also reflect the significance and necessity of the overall role of traditional Chinese medicine (TCM). Our research was the first to report that the E2/T is related to HF and can be used as an indicator to evaluate HF.
RESUMEN
This study developed a UPLC-PDA wavelength switching method to simultaneously determine the content of maltol and seventeen saponins in red and black ginseng and compared the quality differences of two different processed products of red and black ginseng. A Waters HSS T3 column(2. 1 mm×100 mm, 1. 8 µm) at 30 â was adopted, with the mobile phase of acetonitrile(A) and water containing 0. 1% phosphoric acid(B) under gradient elution, the flow rate of 0. 3 m L·min~(-1), and the injection volume of 2 µL.The wavelength switching was set at 273 nm within 0-11 min and 203 nm within 11-60 min. The content results of multiple batches of red and black ginseng samples were analyzed by the hierarchical cluster analysis(HCA) and principal component analysis(PCA) to evaluate the quality difference. The results showed that the 18 constituents exhibited good linear relationships within certain concentration ranges, with the correlation coefficients(r) greater than 0. 999 1. The relative standard deviations(RSDs) of precision,repeatability, and stability were all less than 5. 0%. The average recoveries ranged from 95. 93% to 104. 2%, with an RSD of 1. 8%-4. 2%. The content determination results showed that the quality of red and black ginseng samples was different, and the two types of processed products were intuitively distinguished by HCA and PCA. The method is accurate, reliable, and reproducible. It can be used to determine the content of maltol and seventeen saponins in red and black ginseng and provide basic information for the quality evaluation and comprehensive utilization of red and black ginseng.
Asunto(s)
Panax , Pironas , Saponinas , Panax/química , Saponinas/análisis , Saponinas/química , Cromatografía Líquida de Alta Presión/métodos , Pironas/análisis , Medicamentos Herbarios Chinos/química , Medicamentos Herbarios Chinos/análisisRESUMEN
BACKGROUND: Our objective in this study was to evaluate the effectiveness of oligosaccharides extracted from black ginseng (OSBG), innovatively prepared by a low-temperature steam-heating process, in the improvement of learning and memory impairment in mice, as well as the mechanism(s). RESULTS: Eight carbohydrates involving isomaltose and maltotetraose were detected in black gensing; monosaccharide residues including mannose and rhamnose were also discovered. OSBG-treated mice showed significant amelioration in recognition and spatial memory deficits compared to the scopolamine group. OSBG could decrease acetylcholinesterase activity in a tissue-dependent fashion but not in a dose-dependent manner. Furthermore, in contrast, OSBG administration resulted in significant upregulation superoxide dismutase, glutathione, glutathione peroxidase (GPx), and Kelch-like ECH-associated protein 1, downregulation of malondialdehyde and nuclear factor erythroid 2-related factor 2 in the tissues. Finally, at the genus level, we observed that the OSBG interventions increased the relative abundance of probiotics (e.g., Barnesiella, Staphylococcus, Clostridium_XlVb) and decreased pernicious bacteria such as Eisenbergiella and Intestinimonas, compared to the Alzheimer's disease mouse model group. Herein, our results demonstrate that OSBG restores the composition of the scopolamine-induced intestinal microbiota in mice, providing homeostasis of gut microbiota and providing evidence for microbiota-regulated therapeutic potential. CONCLUSION: Our results showed for the first time a clear role for OSBG in improving scopolamine-induced memory impairment by inhibiting cholinergic dysfunction in a tissue-dependent manner. Additionally, OSBG administration relieved oxidative stress by activating the Keap-1/Nrf2 pathway and modulating the gut microbiota. Collectively, OSBG may be a promising target for neuroprotective antioxidants for improving memory and cognition in Alzheimer's disease patients. © 2024 Society of Chemical Industry.
Asunto(s)
Enfermedad de Alzheimer , Disfunción Cognitiva , Proteína 1 Asociada A ECH Tipo Kelch , Factor 2 Relacionado con NF-E2 , Oligosacáridos , Panax , Extractos Vegetales , Animales , Enfermedad de Alzheimer/metabolismo , Enfermedad de Alzheimer/tratamiento farmacológico , Ratones , Factor 2 Relacionado con NF-E2/metabolismo , Factor 2 Relacionado con NF-E2/genética , Panax/química , Masculino , Oligosacáridos/química , Oligosacáridos/administración & dosificación , Oligosacáridos/farmacología , Disfunción Cognitiva/tratamiento farmacológico , Disfunción Cognitiva/metabolismo , Proteína 1 Asociada A ECH Tipo Kelch/metabolismo , Proteína 1 Asociada A ECH Tipo Kelch/genética , Humanos , Extractos Vegetales/química , Extractos Vegetales/administración & dosificación , Extractos Vegetales/farmacología , Vapor , Modelos Animales de Enfermedad , Microbioma Gastrointestinal/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Calor , Superóxido Dismutasa/metabolismo , Glutatión Peroxidasa/metabolismoRESUMEN
HPLC analysis determined six small-molecule organic acids, maltol, 5-hydroxymethylfurfural (5-HMF), 17 ginsenosides, four oligosaccharides, and 20 amino acids in black ginseng samples with different processing times. Based on the content determination results, the differential ingredients in the processing of black ginseng were screened by multivariate statistical analysis. Network pharmacological methods obtained the core targets and pathways of the above ingredients against prostate cancer. Finally, the entropy weight method was used to assign values to the above ingredients, targets, and pathways, and the vector space network pharmacology method was established to study the anti-prostate cancer mechanism of black ginseng in the process of "nine steaming and nine sun-drying". Based on principal component analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS-DA), fructose, glucose, dencichin, glutamate, ginsenoside 20 (S)-Rg3, 20 (R)-Rg3, 20 (S)-Rh2, Rg1, Re, and Rc were the main differential ingredients in various steaming and sun-drying cycle periods of black ginseng. The results of vector space network pharmacology showed that the main reason for the change in the anti-prostate cancer pathway of black ginseng with the number of steaming and sun-drying was the different regulatory ability of black ginseng on the PI3K-Akt signaling pathway and chemical carcinogenesis-receptor activation pathway. It gave researchers a fresh perspective for exploring the anti-prostate cancer active components of black ginseng and the change in the mechanism of the effect of traditional Chinese medicine in processing.
RESUMEN
Black ginseng (BG) is processed ginseng traditionally made in Korea via the steaming and drying of ginseng root through three or more cycles, leading to changes in its appearance due to the Maillard reaction on its surface, resulting in a dark coloration. In this study, we explored markers for differentiating processed ginseng by analyzing the chemical characteristics of BG. We elucidated a new method for the structural identification of ginsenoside metabolites and described the features of processed ginseng using UPLC-QTOF-MS in the positive ion mode. We confirmed that maltose, glucose, and fructose, along with L-arginine, L-histidine, and L-lysine, were the key compounds responsible for the changes in the external quality of BG. These compounds can serve as important metabolic markers for distinguishing BG from conventionally processed ginseng. The major characteristics of white ginseng, red ginseng, and BG can be distinguished based on their high-polarity and low-polarity ginsenosides, and a precise method for the structural elucidation of ginsenosides in the positive ion mode is presented.
RESUMEN
BACKGROUND: Continuous exposure of the skin to ultraviolet B (UVB) rays can cause inflammation and photodamage. In previous studies, we observed that the upregulation of nc886, a noncoding RNA (ncRNA), can alleviate UVB-induced inflammation through suppression of the protein kinase RNA (PKR) pathway. We aim to investigate the effect of fermented black ginseng extract (FBGE), which has been shown to increase the expression of nc886, on UVB-induced inflammation in keratinocytes. METHODS: To confirm the cytotoxicity of FBGE, MTT assay was performed, and no significant cytotoxicity was found on human keratinocytes. The efficacies of FBGE were assessed through qPCR, Western blotting, and ELISA analysis which confirmed regulation of UVB-induced inflammation. RESULTS: The analysis results showed that FBGE inhibited the decrease in nc886 expression and the increase in the methylated nc886 caused by UVB. It also prevented the UVB-induced increase of metalloproteinase-9 (MMP-9), metalloproteinase-1 (MMP-1), cyclooxygenase-2 (COX-2), prostaglandin E2 (PGE2), interleukin-8 (IL-8) and tumor necrosis factor-α (TNF-α). Additionally, FBGE suppressed the PKR-MAPK pathways activated by UVB. CONCLUSION: These results implicate that FBGE can alleviate UVB-induced inflammation through regulation of the nc886-PKR pathway.
Asunto(s)
Queratinocitos , Panax , Humanos , Queratinocitos/metabolismo , Piel , Inflamación/metabolismo , Metaloproteasas/metabolismo , Metaloproteasas/farmacología , Rayos Ultravioleta/efectos adversosRESUMEN
Korean ginseng (Panax ginseng) contains various ginsenosides as active ingredients, and they show diverse biological activities. Black ginseng is manufactured by repeated steaming and drying of white ginseng, which alters the polarity of ginsenosides and improves biological activities. The aim of the present investigation was to examine the anti-neuroinflammatory effects of the ethanolic extract of black ginseng (BGE) in lipopolysaccharide (LPS)-induced BV2 microglial cells. Pre-treatment with BGE inhibited the overproduction of pro-inflammatory mediators including nitric oxide (NO), prostaglandin E2 (PGE2), inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) in LPS-induced BV2 cells. In addition, BGE reduced the activation of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), p38 mitogen-activated protein kinase (MAPK), and c-jun N-terminal kinase (JNK) MAPK signaling pathways induced by LPS. These anti-neuroinflammatory effects were mediated through the negative regulation of the toll-like receptor 4 (TLR4)/myeloid differentiation primary response 88 (MyD88) signaling pathway. Among the four ginsenosides contained in BGE, ginsenosides Rd and Rg3 inhibited the production of inflammatory mediators. Taken together, this investigation suggests that BGE represents potential anti-neuroinflammatory candidates for the prevention and treatment of neurodegenerative diseases.
Asunto(s)
Ginsenósidos , Panax , FN-kappa B/metabolismo , Lipopolisacáridos/farmacología , Factor 88 de Diferenciación Mieloide/metabolismo , Microglía/metabolismo , Receptor Toll-Like 4/metabolismo , Ginsenósidos/farmacología , Ginsenósidos/metabolismo , Antiinflamatorios/farmacología , Antiinflamatorios/metabolismo , Panax/metabolismo , Transducción de Señal , Enfermedades Neuroinflamatorias , Mediadores de Inflamación/metabolismo , Óxido Nítrico/metabolismoRESUMEN
New dammarane-type triterpenoid saponin, named 22(R)-notoginsenoside Ab1 (1), together with thirteen known dammarane-type triterpenoid saponins (2-14) was isolated from the EtOH extract of black ginseng and their structures were elucidated on the basis of one- and two-dimensional NMR (including 1H-NMR, 13C-NMR, HSQC, HMBC, ROESY) and calculated ECD. Among them, compounds 1-2 and 6-8 were isolated for the first time from ginseng and black ginseng. Besides, the absolute structure of 22(R)- and 22(S)- notoginsenoside Ab1 were distinguished by ECD for the first time.
RESUMEN
OBJECTIVE: This study aimed to explore the mechanism of total saponin of black ginseng (TSBG) in treating heart failure (HF) in DOX-induced HF model rats. METHODS: Rats with HF induced by the intraperitoneal injection of DOX were treated with TSBG (low dose, 30 mg/kg/day; medium dose, 60 mg/kg/day; high dose, 120 mg/kg/day) and shakubar trivalsartan (80 mg/kg/day, positive control) for four weeks. Serum BNP and ANP levels were tested by ELISA, and pathological tissue sections were examined. Serum metabolites were measured using nontargeted metabolomic techniques. The expression of Akt/mTOR autophagy-associated proteins in heart tissue was detected using Western blot, including Beclin1, p62, LCII and LC3I. RESULTS: Compared with the model group, rats in the TSBG-H group had a significantly lower heart index (p < 0.05), significantly lower serum levels of BNP (p < 0.01) and ANP (p < 0.01) and significantly fewer cardiac histopathological changes. Metabolomic results showed that TSBG significantly back-regulated 12 metabolites (p < 0.05), including cholesterol, histamine, sphinganine, putrescine, arachidonic acid, 3-sulfinoalanine, hypotaurine, gluconic acid and lysoPC (18:0:0). These metabolite changes were involved in taurine and hypotaurine metabolism, arachidonic acid metabolism, sphingolipid metabolism, etc. The protein expression level of p-Akt/Akt and p-mTOR/mTOR was significantly up-regulated (p < 0.001), whereas that of Beclin1, p62 (p < 0.001) and LCII/LC3I was down-regulated (p < 0.05). CONCLUSION: TSBG has an excellent therapeutic effect on DOX-induced HF in rats, probably by regulating the Akt/mTOR autophagy signalling pathway, resulting in the improvement of taurine and hypotaurine metabolism, arachidonic acid metabolism and sphingolipid metabolism, which may provide a reference for elucidating the potential mechanism of action of TSBG against HF.
Asunto(s)
Insuficiencia Cardíaca , Panax , Saponinas , Ratas , Animales , Ratas Sprague-Dawley , Proteínas Proto-Oncogénicas c-akt/metabolismo , Proteínas Proto-Oncogénicas c-akt/uso terapéutico , Saponinas/farmacología , Beclina-1 , Panax/metabolismo , Ácido Araquidónico , Insuficiencia Cardíaca/inducido químicamente , Insuficiencia Cardíaca/tratamiento farmacológico , Serina-Treonina Quinasas TOR/metabolismo , Metabolómica , Taurina , Esfingolípidos/uso terapéuticoRESUMEN
Asthma is a chronic inflammatory lung disease that causes respiratory difficulties. Black ginseng extract (BGE) has preventative effects on respiratory inflammatory diseases such as asthma. However, the pharmacological mechanisms behind the anti-asthmatic activity of BGE remain unknown. To investigate the anti-asthmatic mechanism of BGE, phorbol 12-myristate 13-acetate plus ionomycin (PMA/Iono)-stimulated mouse EL4 cells and ovalbumin (OVA)-induced mice with allergic airway inflammation were used. Immune cells (eosinophils/macrophages), interleukin (IL)-4, -5, -13, and serum immunoglobulin E (IgE) levels were measured using an enzyme-linked immunosorbent assay. Inflammatory cell recruitment and mucus secretion in the lung tissue were estimated. Protein expression was analyzed via Western blotting, including that of inducible nitric oxide synthase (iNOS) and the activation of protein kinase C theta (PKCθ) and its downstream signaling molecules. BGE decreased T helper (Th)2 cytokines, serum IgE, mucus secretion, and iNOS expression in mice with allergic airway inflammation, thereby providing a protective effect. Moreover, BGE and its major ginsenosides inhibited the production of Th2 cytokines in PMA/Iono-stimulated EL4 cells. In EL4 cells, these outcomes were accompanied by the inactivation of PKCθ and its downstream transcription factors, such as nuclear factor of activated T cells (NFAT), nuclear factor kappa B (NF-κB), activator of transcription 6 (STAT6), and GATA binding protein 3 (GATA3), which are involved in allergic airway inflammation. BGE also inhibited the activation of PKCθ and the abovementioned transcriptional factors in the lung tissue of mice with allergic airway inflammation. These results highlight the potential of BGE as a useful therapeutic and preventative agent for allergic airway inflammatory diseases such as allergic asthma.
Asunto(s)
Antiasmáticos , Asma , Hipersensibilidad , Panax , Animales , Ratones , Antiasmáticos/farmacología , Antiasmáticos/uso terapéutico , Interleucina-4/metabolismo , Asma/metabolismo , Pulmón/metabolismo , Citocinas/metabolismo , Hipersensibilidad/metabolismo , Transducción de Señal , Inflamación/metabolismo , Inmunoglobulina E , Panax/metabolismo , Ovalbúmina , Ratones Endogámicos BALB C , Modelos Animales de EnfermedadRESUMEN
Black ginseng is a new type of processed ginseng that is traditionally used in herbal medicine in East Asian countries. It is prepared from fresh, white, or red ginseng by undergoing a process of steaming and drying several times. However, the chemical differentiation of black ginseng with different processing levels is not well understood. The aim of this study was to propose a new method for discriminating and quantifying black ginseng. Six ginsenosides from black ginseng were accurately quantified, and based on this, the black ginseng samples were divided into incomplete and complete black ginseng. Ultrahigh-performance liquid chromatography-quadrupole-time of flight/mass spectrometry (UPLC-Q-TOF/MS) combined with a multivariate statistical analysis strategy was then employed to differentiate the two groups. A total of 141 ions were selected as analytical markers of black ginseng, with 45 of these markers being annotated by matching precise m/z and MS/MS data from prior studies.
Asunto(s)
Ginsenósidos , Panax , Cromatografía Liquida/métodos , Espectrometría de Masas en Tándem/métodos , Cromatografía Líquida de Alta Presión/métodos , Panax/química , Extractos Vegetales/química , Ginsenósidos/químicaRESUMEN
Viral infections are known as one of the major factors causing death. Ginseng is a medicinal plant that demonstrated a wide range of antiviral potential, and saponins are the major bioactive ingredients in the genus Panax with vast therapeutic potential. Studies focusing on the antiviral activity of the genus Panax plant-derived agents (extracts and saponins) and their mechanisms were identified and summarized, including contributions mainly from January 2016 until January 2022. P. ginseng, P. notoginseng, and P. quinquefolius were included in the review as valuable medicinal herbs against infections with 14 types of viruses. Reports from 9 extracts and 12 bioactive saponins were included, with 6 types of protopanaxadiol (PPD) ginsenosides and 6 types of protopanaxatriol (PPT) ginsenosides. The mechanisms mainly involved the inhibition of viral attachment and replication, the modulation of immune response by regulating signaling pathways, including the Janus kinase (JAK)/signal transducer and activator of transcription (STAT) pathway, cystathionine γ-lyase (CSE)/hydrogen sulfide (H2S) pathway, phosphoinositide-dependent kinase-1 (PDK1)/ protein kinase B (Akt) signaling pathway, c-Jun N-terminal kinase (JNK)/activator protein-1 (AP-1) pathway, and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) pathway. This review includes detailed information about the mentioned antiviral effects of the genus Panax extracts and saponins in vitro and in vivo, and in human clinical trials, which provides a scientific basis for ginseng as an adjunctive therapeutic drug or nutraceutical.
RESUMEN
In recent years, black ginseng, a new type of processed ginseng product, has attracted the attention of scholars globally. Ginsenoside and ginseng polysaccharide, the main active substances of black ginseng, have been shown to carry curative effects for many diseases. This article focuses on the mechanism of their action in anti-inflammatory response, which is mainly divided into three aspects: activation of immune cells to exert immune regulatory response; participation in inflammatory response-related pathways and regulation of the expression level of inflammatory factors; effect on the metabolic activity of intestinal flora. This study identifies active anti-inflammatory components and an action mechanism of black ginseng showing multi-component, multi-target, and multi-channel characteristics, providing ideas and a basis for a follow-up in-depth study of its specific mechanism.
Asunto(s)
Ginsenósidos , Panax , Antiinflamatorios/farmacología , Ginsenósidos/química , Ginsenósidos/farmacología , Panax/química , Extractos Vegetales/farmacología , Polisacáridos/farmacologíaRESUMEN
Black ginseng (BG) is one type of ginseng product, which is produced from fresh ginseng by steaming and drying several times. To characterize the differences in saponin composition of BG and white ginseng (WG), the ultra-high performance liquid chromatography Quadrupole-Orbitrap mass spectrometry (UHPLC-Q-Orbitrap-MS) was used to analyze the ginseng samples. A total of 53 saponins were successfully identified, and the possible transformation pathways of several ginsenosides were described. Multivariate statistical analysis methods were used to perform the pattern recognition and further to select the marker compounds of samples. Twenty ginsenosides were considered to contribute most to the sample classification, six of which including Rg3, Rk1, Rh4, Rs3, Rs5, and Rk2 increased significantly in BG, while the other fourteen ginsenosides were greatly elevated in WG. The changes of ginsenoside in BG and WG were characterized by UHPLC-Q-Orbitrap-MS, which is of great significance for its quality control and effect evaluation.
RESUMEN
Black ginseng is a novel manufactured ginseng product, and the application of black ginseng products in market is increasing in recent years. Black ginseng is prepared by steaming and fermentation, but not as mature as processing red ginseng. Therefore, complete proposals for preparation techniques are firstly presented. Additionally, there are also abundant chemical components in black ginseng, including ginsenosides, polysaccharides, amino acids, polyphenols, flavonoids, etc. Among them, ginsenosides, polysaccharides and phenolic compounds are the main ingredients, making health benefits of black ginseng stronger than other ginseng products. Therefore, black ginseng as a functional food has come to the market in various forms, such as candies, tea, porridge, soup, etc. The improvement in nutrition, flavor, and safety has exhibited a broad prospect for black ginseng products in food industry. Accordingly, preparation technologies, phytochemistry, health benefits and application of black ginseng are comprehensively evaluated.
Asunto(s)
Ginsenósidos , Panax , Ginsenósidos/química , Extractos Vegetales/química , Panax/química , Aminoácidos , Polisacáridos/químicaRESUMEN
Black ginseng (BG) shows beneficial effects on liver injury, but the related mechanism has not been fully revealed. This study attempted to investigate the protective effects and associated mechanisms of BG against nonalcoholic steatohepatitis (NASH). Twelve ginsenosides in BG were annotated by ultrahigh performance liquid chromatography combined with high resolution mass spectrometry (UHPLC-HRMS). The Western diet (WD) together with the low-dose CCl4 was given to mice to create the NASH model. Histopathological examination and liver/serum biochemical analysis revealed that the NASH mice displayed severe steatosis and liver damage compared with control mice. After BG administration, the serum and liver triglycerides (TG) concentrations and the serum level of low-density lipoprotein (LDL) were dramatically reduced. Besides, the BG treatment greatly decreased the serum values of interleukin 6 (IL-6) and tumor necrosis factor-α (TNF-α), and the hepatic expression of fibrotic-related genes, such as alpha-smooth muscle actin (α-SMA) and collagen type I alpha 1 (Col1α1). We further discovered that BG administration could block the protein expression of toll-like receptor 4 (TLR4) and the phosphorylation of nuclear factor-kappa B p65 (NF-κB p65), indicating that BG exerted a liver protective effect via regulating the TLR4/NF-κB pathway. This study demonstrated the therapeutic efficacy and the associated mechanism of BG in the treatment of NASH, giving evidence for BG as a potential functional food to prevent NASH. PRACTICAL APPLICATIONS: BG is a type of processed ginseng product that has been used as diet supplementation and has shown favorable effects on liver injury. However, the pharmacological impact of BG on NASH has not been studied in depth. The present study showed that BG could effectively reduce WD-induced liver fibrosis and inflammation through the TLR4/NF-κB axis, which indicated that BG has the potential to be utilized as a functional herb to attenuate liver injury.
Asunto(s)
Enfermedad del Hígado Graso no Alcohólico , Panax , Ratones , Animales , Enfermedad del Hígado Graso no Alcohólico/tratamiento farmacológico , Enfermedad del Hígado Graso no Alcohólico/etiología , Enfermedad del Hígado Graso no Alcohólico/metabolismo , FN-kappa B/genética , FN-kappa B/metabolismo , Dieta Occidental , Receptor Toll-Like 4/genética , Receptor Toll-Like 4/metabolismo , Panax/metabolismo , Transducción de SeñalRESUMEN
This study aimed to investigate the therapeutic effect of black ginseng (BG) on non-alcoholic fatty liver disease (NAFLD) using network pharmacology combined with the molecular docking strategy. The saponin composition of BG was analyzed by liquid chromatography-mass spectrometry (LC/MS) instrument. Then the network pharmacology was applied to explore the potential targets and related mechanisms of BG in the treatment of NAFLD. After screening out key targets, molecular docking was used to predict the binding modes between ginsenoside and target. Finally, a methionine and choline deficiency (MCD) diet-induced NAFLD mice model was established to further confirm the therapeutic effect of BG on NAFLD. Twenty-four ginsenosides were annotated based on the MS and tandem MS information. Ten proteins were screened out as key targets closely related to BG treatment of NAFLD. The molecular docking showed that most of the ginsenosides had good binding affinities with AKT1. The validation experiment revealed that BG administration could reduce serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels and improve the MCD diet-induced histological changes in liver tissue. Moreover, BG could upregulate the phosphorylation level of AKT in the liver of NAFLD mice, thereby exerting the therapeutic effect on NAFLD. Further studies on the active ginsenosides as well as their synergistic action on NAFLD will be required to reveal the underlying mechanisms in-depth. This study demonstrates that network pharmacological prediction in conjunction with molecular docking is a viable technique for screening the active chemicals and related targets of BG, which can be applied to other herbal medicines.
Asunto(s)
Deficiencia de Colina , Ginsenósidos , Enfermedad del Hígado Graso no Alcohólico , Panax , Ratones , Animales , Enfermedad del Hígado Graso no Alcohólico/tratamiento farmacológico , Alanina Transaminasa , Panax/metabolismo , Ginsenósidos/farmacología , Ginsenósidos/uso terapéutico , Simulación del Acoplamiento Molecular , Proteínas Proto-Oncogénicas c-akt/metabolismo , Farmacología en Red , Deficiencia de Colina/metabolismo , Deficiencia de Colina/patología , Aspartato Aminotransferasas , Hígado , Metionina/metabolismo , Metionina/farmacologíaRESUMEN
Cellular senescence, one of the hallmarks of aging, refers to permanent cell cycle arrest and is accelerated during the aging process. Black ginseng (BG), prepared by a repeated steaming and drying process nine times from fresh ginseng (Panax ginseng C.A. Meyer), is garnering attention for herbal medicine due to its physiological benefits against reactive oxygen species (ROS), inflammation, and oncogenesis, which are common cues to induce aging. However, which key nodules in the cellular senescence process are regulated by BG supplementation has not been elucidated yet. In this study, we investigated the effects of BG on cellular senescence using in vitro and aged mouse models. BG-treated primary mouse embryonic fibroblasts (MEFs) in which senescence was triggered by ionizing radiation (IR) expressed less senescence-associated ß-galactosidase (SA-ß-gal)-positive stained cells. In our aged mice (18 months old) study, BG supplementation (300 mg/kg) for 4 weeks altered hepatic genes involved in the aging process. Furthermore, we found BG supplementation downregulated age-related inflammatory genes, especially in the complement system. Based on this observation, we demonstrated that BG supplementation led to less activation of the canonical senescence pathway, p53-dependent p21 and p16, in multiple metabolic organs such as liver, skeletal muscle and white adipose tissue. Thus, we suggest that BG is a potential senolytic candidate that retards cellular senescence.
RESUMEN
Cigarette smoke (CS) is a risk factor that can induce airway enlargement, airway obstruction, and airway mucus hypersecretion. Although studies have shown that Korean black ginseng extract (BGE) has potent anti-inflammatory and antioxidant activities, the CS-induced inflammatory responses and molecular mechanisms are yet to be examined. The aim of this study was to examine the effect of BGE on the airway inflammatory response and its molecular mechanisms, using CS/lipopolysaccharides (LPS)-exposed animals and PMA-stimulated human airway epithelial NCI-H292 cells. The results show that BGE inhibited the recruitment of immune cells and the release of inflammatory mediators, such as tumor necrosis factor (TNF)-α and interleukin (IL)-6, monocyte chemoattractant protein (MCP)-1, elastase, and reactive oxygen species (ROS) in the airways of CS/LPS-exposed animals. BGE inhibited mucus secretion and the expression of Mucin 5AC (MUC5AC). Furthermore, BGE exhibited an anti-inflammatory effect by downregulating a signaling pathway mediated by transforming growth factor-ß-activated kinase (TAK) 1, an important protein that accelerates inflammation by cigarette smoke (CS). Overall, the findings show that BGE inhibits lung inflammation and mucus secretion by decreasing the activation of TAK1 both in human epithelial cells and in CS/LPS-exposed animals, and could be a potential adjuvant in the treatment and prevention of airway inflammatory diseases caused by airway irritants such as CS.
RESUMEN
Background: Ginseng has been used in Korea for a long time as a restorative herbal medicine. Black ginseng (BG) is made from red or white ginseng by multiple steamy and dry processes. Although BG has been reported to have anti-inflammatory potential, studies on its influence on inflammatory skin disorders are lacking. Objective: To investigate the effects of BG under the inflammatory conditions of cultured sebocytes and outer root sheath (ORS) cells. Methods: The cultured cells were treated with 0.1% dimethyl sulfoxide, 5 µg/ml lipopolysaccharide (LPS) or 5 µg/ml LPS+50 µg/ml BG for 6 hours and 24 hours. Reverse transcription-polymerase chain reaction (RT-PCR), real-time PCR, enzyme-linked immunosorbent assay, western blotting, immunofluorescence staining and Nile red staining were performed for analysis of inflammatory biomarkers and sebum-related biomarkers. Results: BG brought out the increased gene and protein expression of inflammatory biomarkers such as interleukin (IL)-1ß, IL-6, IL-8, and tumor necrosis factor-α, in the LPS-treated sebocytes and ORS cells. In addition, BG induced increased expression of TLR4, p-c-jun, p-JNK and p-iκB in LPS-treated sebocytes and ORS cells. Furthermore, it significantly increased the expression of LL-37 and the production of sebum in LPS-treated sebocytes. Conclusion: It may be possible for BG to increase the expression of inflammatory biomarkers in inflammatory skin disorders, such as acne.