Ginsenosides In Ginseng Research Articles

Screening of GLP-1r agonists from natural products using affinity ultrafiltration screening coupled with UPLC-ESI-Orbitrap-MS technology: a case study of Panax ginseng

In our study, a method based on affinity ultrafiltration screening coupled with UPLC-ESI-Orbitrap-MS technology was established to select Glucagon-like peptide-1 receptor (GLP-1R) agonists from natural products, and as an example, the GLP-1R agonists from Panax ginseng was selected using our established method. As a result, total five GLP-1R agonists were selected from Panax ginseng for the first time. Our results indicated that activating GLP-1R to promote insulin secretion probably was another important hypoglycemia mechanism for ginsenosides in Panax ginseng, which had great influence on the study of the anti-diabetes effect of ginsenosides.

Integration of network pharmacology and proteomics analysis to identify key target pathways of Ginsenoside Re for myocardial ischemia

BackgroundClinically, various diseases cause myocardial ischemia (MI), which further induces severe cardiac injury and leads to high mortality in patients. Ginsenoside Re, one of the major ginsenosides in ginseng, can regulate the level of oxidative stress in the injured myocardium. Thus, it may attenuate MI injury, but the related mechanism has not been comprehensively studied. PurposeThis study aimed to investigate the anti-MI effect and comprehensively mechanisms of Ginsenoside Re. Study Design/MethodsOxygen–glucose deprivation (OGD), oxidative-induced cardiomyocyte injury, and isoproterenol-induced MI mice were used to explore their protective effect of Ginsenoside Re. An integrated approach of network pharmacology, molecular docking, and tandem mass tag proteomics was applied to determine the corresponding common potential targets of Ginsenoside Re against MI, such as target proteins and related pathways. The major anti-MI target proteins and related pathways were validated by immunofluorescence (IF) assay and Western blotting (WB). ResultsGinsenoside Re (1.32–168.93 µM) had low toxicity to normal cardiomyocytes, and increased the survival of oxidative stress-injured (OGD-induced injury or H2O2-induced injury) cardiomyocytes in this concentration range. It regulated the reactive oxygen species (ROS) level in OGD-injured cardiomyocytes; stabilized the nuclear morphology, mitochondrial membrane potential (MMP), and mitochondrial function; and reduced apoptosis. Meanwhile, Ginsenoside Re (5–20 mg/kg) alleviated cardiac injury in MI mice and maintained cardiac function. Through network pharmacology and proteomics, the relevant mechanisms revealed several key pathways of Ginsenoside Re anti-MI, including inhibition of MAPK pathway protein phosphorylation, downregulation of phosphorylated PDPK1, AKT, and STAT3, and upregulation of TGF-β3, ferroptosis pathway (upregulation of GPX4 and downregulation of phosphorylation level of MDM2) and AMPK pathway (regulating the synthesis of cholesterol in the myocardium by downregulation of HMGCR). The key proteins of these target pathways were validated by IF and/or WB. ConclusionGinsenoside Re may target MAPK, AKT, ferroptosis pathways and AMPK pathway to prevent and/or treat MI injury and protect cardiomyocytes from oxidative damage.

Review of Pharmacotherapeutic Targets in Alzheimer's Disease and Its Management Using Traditional Medicinal Plants.

Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by cognitive decline, memory loss, and impaired daily functioning. While there is currently no cure for AD, several pharmacotherapeutic targets and management strategies have been explored. Additionally, traditional medicinal plants have gained attention for their potential role in AD management. Pharmacotherapeutic targets in AD include amyloid-beta (Aβ) aggregation, tau protein hyperphosphorylation, neuroinflammation, oxidative stress, and cholinergic dysfunction. Traditional medicinal plants, such as Ginkgo biloba, Huperzia serrata, Curcuma longa (turmeric), and Panax ginseng, have demonstrated the ability to modulate these targets through their bioactive compounds. Ginkgo biloba, for instance, contains flavonoids and terpenoids that exhibit neuroprotective effects by reducing Aβ deposition and enhancing cerebral blood flow. Huperzia serrata, a natural source of huperzine A, has acetylcholinesterase-inhibiting properties, thus improving cholinergic function. Curcuma longa, enriched with curcumin, exhibits anti-inflammatory and antioxidant effects, potentially mitigating neuroinflammation and oxidative stress. Panax ginseng's ginsenosides have shown neuroprotective and anti-amyloidogenic properties. The investigation of traditional medicinal plants as a complementary approach to AD management offers several advantages, including a lower risk of adverse effects and potential multi-target interactions. Furthermore, the cultural knowledge and utilization of these plants provide a rich source of information for the development of new therapies. However, further research is necessary to elucidate the precise mechanisms of action, standardize preparations, and assess the safety and efficacy of these natural remedies. Integrating traditional medicinal-plant-based therapies with modern pharmacotherapies may hold the key to a more comprehensive and effective approach to AD treatment. This review aims to explore the pharmacotherapeutic targets in AD and assess the potential of traditional medicinal plants in its management.

Ginsenoside CK Alleviates DSS-Induced IBD in Mice by Regulating Tryptophan Metabolism and Activating Aryl Hydrocarbon Receptor via Gut Microbiota Modulation.

Dysbiosis of gut microbiota is believed to be associated with inflammatory bowel disease (IBD). Ginsenoside compound K (CK), the main metabolite of Panax ginseng ginsenoside, has proven effective as an anti-inflammatory agent in IBD. However, the mechanisms by which CK modulates gut microbiota to ameliorate IBD remain poorly understood. Herein, CK demonstrated the potential to suppress the release of proinflammatory cytokines by gut microbiota modulation. Notably, supplementation with CK promoted the restoration of a harmonious balance in gut microbiota, primarily by enhancing the populations of Lactobacillus and Akkermansia. Furthermore, CK considerably elevated the concentrations of tryptophan metabolites derived from Lactobacillus that could activate the aryl hydrocarbon receptor. Overall, the promising alleviative efficacy of CK primarily stemmed from the promotion of Lactobacillus growth and production of tryptophan metabolites, suggesting that CK should be regarded as a prospective prebiotic agent for IBD in the future.

Exploring the allelopathic autotoxicity mechanism of ginsenosides accumulation under ginseng decomposition based on integrated analysis of transcriptomics and metabolomics.

Continuous cropping obstacles seriously constrained the sustainable development of the ginseng industry. The allelopathic autotoxicity of ginsenosides is the key "trigger" of continuous cropping obstacles in ginseng. During harvest, the ginseng plants could be broken and remain in the soil. The decomposition of ginseng residue in soil is one of the important release ways of ginsenosides. Therefore, the allelopathic mechanism of ginsenosides through the decomposed release pathway needs an in-depth study. To investigate this allelopathic regulation mechanism, the integrated analysis of transcriptomics and metabolomics was applied. The prototype ginsenosides in ginseng were detected converse to rare ginsenosides during decomposition. The rare ginsenosides caused more serious damage to ginseng hairy root cells and inhibited the growth of ginseng hairy roots more significantly. By high-throughput RNA sequencing gene transcriptomics study, the significantly differential expressed genes (DEGs) were obtained under prototype and rare ginsenoside interventions. These DEGs were mainly enriched in the biosynthesis of secondary metabolites and metabolic pathways, phytohormone signal transduction, and protein processing in endoplasmic reticulum pathways. Based on the functional enrichment of DEGs, the targeted metabolomics analysis based on UPLC-MS/MS determination was applied to screen endogenous differential metabolized phytohormones (DMPs). The influence of prototype and rare ginsenosides on the accumulation of endogenous phytohormones was studied. These were mainly involved in the biosynthesis of diterpenoid, zeatin, and secondary metabolites, phytohormone signal transduction, and metabolic pathways. After integrating the transcriptomics and metabolomics analysis, ginsenosides could regulate the genes in phytohormone signaling pathways to influence the accumulation of JA, ABA, and SA. The conclusion was that the prototype ginsenosides were converted into rare ginsenosides by ginseng decomposition and released into the soil, which aggravated its allelopathic autotoxicity. The allelopathic mechanism was to intervene in the response regulation of genes related to the metabolic accumulation of endogenous phytohormones in ginseng. This result provides a reference for the in-depth study of continuous cropping obstacles of ginseng.

Transcriptome-Wide Identification and Integrated Analysis of a UGT Gene Involved in Ginsenoside Ro Biosynthesis in Panax ginseng.

Panax ginseng as a traditional medicinal plant with a long history of medicinal use. Ginsenoside Ro is the only oleanane-type ginsenoside in ginseng, and has various pharmacological activities, including anti-inflammatory, detoxification, and antithrombotic activities. UDP-dependent glycosyltransferase (UGT) plays a key role in the synthesis of ginsenoside, and the excavation of UGT genes involved in the biosynthesis of ginsenoside Ro has great significance in enriching ginsenoside genetic resources and further revealing the synthesis mechanism of ginsenoside. In this work, ginsenoside-Ro-synthesis-related genes were mined using the P. ginseng reference-free transcriptome database. Fourteen hub transcripts were identified by differential expression analysis and weighted gene co-expression network analysis. Phylogenetic and synteny block analyses of PgUGAT252645, a UGT transcript among the hub transcripts, showed that PgUGAT252645 belonged to the UGT73 subfamily and was relatively conserved in ginseng plants. Functional analysis showed that PgUGAT252645 encodes a glucuronosyltransferase that catalyzes the glucuronide modification of the C3 position of oleanolic acid using uridine diphosphate glucuronide as the substrate. Furthermore, the mutation at 622 bp of its open reading frame resulted in amino acid substitutions that may significantly affect the catalytic activity of the enzyme, and, as a consequence, affect the biosynthesis of ginsenoside Ro. Results of the in vitro enzyme activity assay of the heterologous expression product in E. coli of PgUGAT252645 verified the above analyses. The function of PgUGAT252645 was further verified by the result that its overexpression in ginseng adventitious roots significantly increased the content of ginsenoside Ro. The present work identified a new UGT gene involved in the biosynthesis of ginsenoside Ro, which not only enriches the functional genes in the ginsenoside synthesis pathway, but also provides the technical basis and theoretical basis for the in-depth excavation of ginsenoside-synthesis-related genes.

Increased Accumulation of Ginsenosides in Panax ginseng Sprouts Cultivated with Kelp Fermentates

Currently, new agri-tech has been developed and adapted for the cultivation of crops using smart farming technologies, e.g., plant factories and hydroponics. Kelp (Laminaria japonica), which has a high industrial value, was considered as an alternative to chemicals for its eco-friendly and sustainably wide use in crop cultivation. In this study, a fermented kelp (FK) was developed for use in hydroponics. The FK contained various free and protein-bound amino acid compositions produced by fermenting the kelp with Saccharomyces cerevisiae. Supplementing FK as an aeroponic medium when cultivating ginseng sprouts (GSs) elevated the total phenolic and flavonoid contents. Additionally, seven ginsenosides (Rg1, Re, Rb1, Rc, Rg2, Rb2, and Rd) in GSs cultivated with FK in a smart-farm system were identified and quantified by a high-performance liquid chromatography-evaporative light scattering detector/mass spectrometry analysis. Administering FK significantly increased the ginsenosides in the GSs compared to the control group, which was cultivated with tap water. These results indicate the FK administration contributed to the increased accumulation of ginsenosides in the GSs. Overall, this study suggests that FK, which contains abundant nutrients for plant growth, can be used as a novel nutrient solution to enhance the ginsenoside content in GSs during hydroponic cultivation.

Identification and analysis of BAHD superfamily related to malonyl ginsenoside biosynthesis in Panax ginseng.

The BAHD (benzylalcohol O-acetyl transferase, anthocyanin O-hydroxycinnamoyl transferase, N-hydroxycinnamoyl anthranilate benzoyl transferase and deacetylvindoline 4-O-acetyltransferase), has various biological functions in plants, including catalyzing the biosynthesis of terpenes, phenolics and esters, participating in plant stress response, affecting cell stability, and regulating fruit quality. Bioinformatics methods, real-time fluorescence quantitative PCR technology, and ultra-high-performance liquid chromatography combined with an Orbitrap mass spectrometer were used to explore the relationship between the BAHD gene family and malonyl ginsenosides in Panax ginseng. In this study, 103 BAHD genes were identified in P. ginseng, mainly distributed in three major clades. Most PgBAHDs contain cis-acting elements associated with abiotic stress response and plant hormone response. Among the 103 genes, 68 PgBAHDs are WGD (whole-genome duplication) genes. The significance of malonylation in biosynthesis has garnered considerable attention in the study of malonyltransferases. The phylogenetic tree results showed 34 PgBAHDs were clustered with genes that have malonyl characterization. Among them, seven PgBAHDs (PgBAHD4, 45, 65, 74, 90, 97, and 99) showed correlations > 0.9 with crucial enzyme genes involved in ginsenoside biosynthesis and > 0.8 with malonyl ginsenosides. These seven genes were considered potential candidates involved in the biosynthesis of malonyl ginsenosides. These results help elucidate the structure, evolution, and functions of the P. ginseng BAHD gene family, and establish the foundation for further research on the mechanism of BAHD genes in ginsenoside biosynthesis.

Characterization and In Vitro Antioxidant and Anti-Inflammatory Activities of Ginsenosides Extracted from Forest-Grown Wild Panax quinquefolius L.

American ginseng (Panax quinquefolius L.) is known for its health benefits, which are attributed to various terpenoids. However, the specific composition and activities of these terpenoids in forest-grown wild American ginseng remain understudied. This study aimed to characterize the terpenoid composition, particularly triterpene saponins, in forest-grown wild American ginseng. The analysis revealed that triterpene saponins, notably American ginseng ginsenosides (AGGs), are the predominant active components, as identified through LC-MS/MS and HPLC. A subsequent in vitro evaluation of AGGs showcased their potent antioxidant capabilities, displaying the dose-dependent scavenging of free radicals and reducing agents. Moreover, AGGs demonstrated efficacy in reducing oxidative injury and intracellular ROS levels in RAW 264.7 macrophages treated with H2O2. In addition to their antioxidant properties, AGGs exhibited anti-inflammatory effects, significantly inhibiting NO and inflammatory substance production in lipopolysaccharide-treated RAW 264.7 macrophages. These findings highlight the potential of AGG-rich forest-grown wild American ginseng as a functional food with promising implications for improving human health.

Non-destructive determination of ginsenosides in ginseng by combined hyperspectral and X-ray techniques based on ensemble learning

The potential of hyperspectral imaging and X-ray techniques for the non-destructive determination of the ginsenosides Rg1 + Re and Rb1 in ginseng was investigated. The random forest (RF) models were established using spectral information extracted from hyperspectral data to predict ginsenosides content. The RF model was optimized by data pre-processing methods and feature screening methods. Multiple feature screening methods combined with partial least squares regression models were used to find hyperspectral image feature information (color information and texture information) related to ginsenosides. A significant positive correlation between density extracted from X-ray images and the ginsenosides content was found by building the univariate linear regression models. Finally, the prediction performance of the integrated learning model based on the three data blocks was better than the model constructed by single data blocks (Rg1 + Re: R2p = 0.8691, RMSEP = 0.0439%; Rb1: R2p = 0.8291, RMSEP = 0.0803%). The results indicate that the developed method is highly feasible for non-destructive evaluation of ginseng quality.

Metabolic characteristics of ginsenosides from Panax ginseng in rat feces mediated by gut microbiota

Ginsenosides in Panax ginseng are regarded to be functional ingredients for diverse pharmacological effects and orally administrated with very low absorption in the gastrointestinal tract to be metabolized by gut microbiota. However, in vivo metabolic characteristics of ginsenosides mediated by gut microbiota are not well-known. This study aimed to explore the metabolic profiles of ginsenosides in rat feces mediated by gut microbiota. Ginsenosides and metabolites were identified and relatively quantified by ultra-performance liquid chromatography tandem/quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS/MS). As a result, eighty-four metabolites were identified in the normal control rat feces, while only thirty intermediates were found with very low yields in the pseudo-germ-free (GF) group. Similarly, the main bioconversion pathways of ginsenosides in vivo were the same deglycosylation reaction mediated by gut microbiota in vitro. The findings demonstrated significant differences in metabolic profiles between the normal control and pseudo-GF rats, which implied gut microbiota played an important role in the metabolism of ginsenosides.

The impact of irradiation on ginsenoside variations in red ginseng and its hypoglycemic effects in type 1 diabetic mice

This study aimed to investigate the impact of irradiation on the saponin content in red ginseng extract (ISERG) and its hypoglycemic effects using high-performance liquid chromatography and in vivo experiments. The results revealed a significant increase in the levels of red ginseng ginsenosides Rh4 and CK by 75.56% and 59.32% respectively after exposure to 15 kGy 60Co-γ irradiation. Furthermore, the administration of 500 mg/kg·BW 15 kGy 60Co-γ irradiated ISERG for 32 days demonstrated notable reductions in blood sugar levels and increased insulin levels in Type 1 Diabetes Mellitus (T1DM) mice. Moreover, it effectively improved glucose and lipid metabolism, organ coefficient, and antioxidant related indicators in T1DM mice. The study also observed improvements in the expression levels of InsR, IRS1, and Sirt6 proteins, suggesting their potential in diabetes treatment. These findings highlight the promising application of irradiated red ginseng in the future.

Prediction performance and reliability evaluation of three ginsenosides in Panax ginseng using hyperspectral imaging combined with a novel ensemble chemometric model

Panax ginseng C. A. Meyer (PG) is a health-promoting food, and its ginsenosides (Rb1, Rg1, Re) content, as the quality indicator, is affected by the planting modes (garden or forest ginsengs) and years. Effective prediction of this content remains to be investigated. In this study, hyperspectral (HSI) combined with ensemble model (CGRU-GPR) including the convolutional neural network (CNN), gate recurrent unit (GRU), and Gaussian process regression (GPR) realized a comprehensive evaluation of the prediction performance and predictive uncertainty. With effective wavelengths, the proposed CGRU-GPR model improved operation efficiency and obtained satisfactory prediction results with relative percent deviation (RPD) values all higher than 2.70 in three ginsenosides. Meanwhile, the interval prediction with a high prediction interval coverage probability (PICP) of 0.97 – 1.0 and a low mean width percentage (MWP) of 0.7 – 1.66 indicated a low prediction uncertainty. This study provides a rapid and reliable method for predicting ginsenosides contents in PG.

β-Glucosidase and Its Application in Bioconversion of Ginsenosides in Panax ginseng.

Ginsenosides are a group of bioactive compounds isolated from Panax ginseng. Conventional major ginsenosides have a long history of use in traditional medicine for both illness prevention and therapy. Bioconversion processes have the potential to create new and valuable products in pharmaceutical and biological activities, making them both critical for research and highly economic to implement. This has led to an increase in the number of studies that use major ginsenosides as a precursor to generate minor ones using β-glucosidase. Minor ginsenosides may also have useful properties but are difficult to isolate from raw ginseng because of their scarcity. Bioconversion processes have the potential to create novel minor ginsenosides from the more abundant major ginsenoside precursors in a cost-effective manner. While numerous bioconversion techniques have been developed, an increasing number of studies have reported that β-glucosidase can effectively and specifically generate minor ginsenosides. This paper summarizes the probable bioconversion mechanisms of two protopanaxadiol (PPD) and protopanaxatriol (PPT) types. Other high-efficiency and high-value bioconversion processes using complete proteins isolated from bacterial biomass or recombinant enzymes are also discussed in this article. This paper also discusses the various conversion and analysis methods and their potential applications. Overall, this paper offers theoretical and technical foundations for future studies that will be both scientifically and economically significant.

Exploring the mechanism of active components from ginseng to manage diabetes mellitus based on network pharmacology and molecular docking

A large body of literature has shown that ginseng had a role in diabetes mellitus management. Ginsenosides are the main active components of ginseng. But what ginsenosides can manage in diabetic are not systematic. The targets of these ginsenosides are still incomplete. Our aim was to identify which ginsenosides can manage diabetes mellitus through network pharmacology and molecular docking. To identify the targets of these ginsenosides. In this work, we retrieved and screened ginsenosides and corresponding diabetes mellitus targets across multiple databases. PPI networks of the genes were constructed using STRING, and the core targets were screened out through topological analysis. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses were performed by using the R language. Finally, molecular docking was performed after bioinformatics analysis for verification. Our research results showed that 28 ginsenosides in ginseng might be against diabetes mellitus by modulating related proteins such as VEGFA, Caspase 3, and TNF-α. Among the 28 ginsenosides, 20(R)-Protopanaxatriol, 20(R)-Protopanaxadiol, and Ginsenoside Rg1 might play a significant role. Kyoto Encyclopedia of Genes and Genomes and Gene Ontology enrichment analysis showed that the management of diabetes mellitus by ginsenosides may be related to the positive regulation of reactive oxygen metabolic processes, associated with the insulin signaling pathway, TNF signaling pathway, and AMPK signaling pathway. Molecular docking results and molecular dynamics simulation showed that most ginsenosides could stably bind to the core target, mainly hydrogen bonding and hydrophobic bond. This study suggests the management of ginseng on diabetes mellitus. We believe that our results can contribute to the systematic study of the mechanism of ginsenosides for the management of diabetes mellitus. At the same time, it can provide a theoretical basis for subsequent studies on the management of ginsenosides in diabetes mellitus.

Characterization of ginsenoside structural isomers from mixtures using in situ methylation with direct analysis in real-time ionization tandem mass spectrometry

Characterization of structural isomers of bioactive molecules is important for recognizing their functions, but it has been challenging due to their highly similar structures. As the main bioactive constituents of Panax ginseng, ginsenosides have different structural isomers attributed to the aglycone structure and glycosylation sites as well as stereochemistry of sugar groups attached. This work demonstrated a simple and robust in situ methylation reaction with tetramethylammonium hydroxide (TMAH) using ambient ionization source of direct analysis in real time (DART) to characterize saponin structural isomers. The DART ion source provides favorable conditions to methylate hydroxyl groups of ginsenoside instantaneously with TMAH, and it can ionize the methylated products at the same time. Methylated ginsenoside stereoisomers even with subtle structure differences generated very different mass signals from full-scan MS and tandem MS. High-resolution mass spectrometry aided the assignment of molecular structures of the various precursor and fragment ions from different ginsenosides, which provided structural information for both the aglycone skeleton and the sugar moieties in ginsenosides. The presented method was successfully used for the identification of ginsenosides in Panax ginseng, and saponin isomers were characterized without the need for chromatographic separation and/or tedious offline sample pretreatment.

Classification of three types of ginseng samples based on ginsenoside profiles: appropriate data normalization improves the efficiency of multivariate analysis

BackgroundIt is well known that ginsenosides are the main active ingredients in ginseng, and they have also been important indexes for assessing the quality of ginseng. However, the absolute contents of ginsenosides in ginseng were shown to be varied with the origin, cultivated type, cultivated year and climate. It is a great challenge to distinguish the commercial types of ginsengs according to the content of one or several ginsenosides. MethodsThe common commercial types of ginsengs are white ginseng (WG), red ginseng (RG), American ginseng (AG). To clearly illustrate the differences among WG, RG and AG at the ginsenosides level, we established a strategy for the detection and identification of ginsenosides based on an optimized LC-Q-Orbitrap MS/MS method coupled with an in-house database of ginsenosides. Before and after the normalization, the ginsenosides datasheet was analyzed and compared using several state-of-the-art multivariate statistical analysis methods. ResultsHere, 81 ginsenosides were identified in different ginseng samples. The majority of the ginsenosides (59 in 81) were all shared by WG, RG and AG. When the shared ginsenosides datasheet was normalized by the level of ginsenoside Ro, our analysis strategy clearly divided the ginseng samples into three groups (i.e., WG, RG and AG groups). We found that the ginsenoside profiles in RG and WG were significantly different from those in AG. The potential markers and multivariate diagnostic models differentiating the three types of ginsengs were also indicated. ConclusionOur novel methodology based on ginsenoside profiles is more robust than existing methods, and data normalization is required to improve the efficiency of multivariate statistical analysis.

Effect of Ginseng Extract Supplementation on Procalcitonin Level, Neutrophil, and Length of Stay In Patients With Community Acquired Pneumonia

Background: Pneumonia is an acute inflammation of the lung parenchyma caused by microorganisms (bacteria, viruses, fungi, parasites) and causes of high morbidity and mortality. Ginsenoside in ginseng have anti-inflammatory effects, potentially as adjunctive therapy in community-acquired pneumonia (CAP) patients. As much as 43% of patients at dr. Moewardi Hospital in 2016 were hospitalized have passed away. The aim of this study was to determine the effect of ginseng extract on levels of procalcitonin, neutrophils, and length of stay of community-acquired pneumonia patients. Method: The quasi-experimental clinical trial with the pretest posttest design approach was conducted on 26 community acquired pneumonia patients who were hospitalized in Dr. Moewardi Hospital Surakarta from October until November 2019 using consecutive sampling. The control group (n=13) received standard antibiotics while the treatment group (n=13) received additional ginseng extract 2x100 mg/day for 14 days. Procalcitonin was measured at admission, third and fourteenth day; neutrophils are measured at admission and third day; length of stay is based on the number of days of treatment in hospital. Results: There was a significant difference (P=0.001) towards decreased of serum procalcitonin levels between treatment group (-0.63±0.06) compared to control group (-0.38±0.07). There was a significant difference (P<0.001) towards decreased of neutrophil levels between treatment group (-6.68±1.34) compared to control group (-3.51±0.88). There was a significant difference (P=0.001) towards decreased of length of stay between treatment group (5.69±0.95) compared to control group (7.15±0.99). Conclusion: Ginseng extract containing ginsenoside as its main ingredient, can act as an anti-inflammatory which can be used as adjunctive therapy in community-acquired pneumonia patients who are hospitalized to accelerate clinical improvement and shorten the length of stay.

Pathway elucidation of bioactive rhamnosylated ginsenosides in Panax ginseng and their de novo high-level production by engineered Saccharomyces cerevisiae

Rg2 and Re are both rhamnose-containing ginsenosides isolated exclusively from Panax plants, which exhibit broad spectrum of pharmacological activities. However, limitations of current plant-relied manufacturing methods have largely hampered their medical applications. Here, we report elucidation of the complete biosynthetic pathway of these two ginsenosides by the identification of a rhamnosyltransferase PgURT94 from Panax ginseng. We then achieve de novo bio-production of Rg2 and Re from glucose by reconstituting their biosynthetic pathways in yeast. Through stepwise strain engineering and fed-batch fermentation, the maximum yield of Rg2 and Re reach 1.3 and 3.6 g/L, respectively. Our work completes the identification of the last missing enzyme for Rg2 and Re biosynthesis and achieves their high-level production by engineered yeasts. Once scaled, this microbial biosynthesis platform will enable a robust and stable supply of Rg2 and Re and facilitate their food and medical applications.

Effects of Different Extraction Methods in Pharmacopoeia on the Content and Structure Transformation of Ginsenosides.

Ginseng (Panax ginseng C. A. Meyer), a perennial herb, possesses immunostimulatory, anticarcinogenic, antiemetic, and antioxidative biological activities. In recent years, more and more people have paid attention to the extraction methods and quality evaluation of ginseng. China, the United States, Europe, Japan, and Korea have all had the quality standards and content determination methods of ginseng. The different treatment methods are adopted before the determination of ginseng samples and the content limits of the index components, such as ginsenoside Rb1, ginsenoside Rg1, and ginsenoside Re exist differences. The similarities and differences of ginseng content detection methods in pharmacopoeias of different countries have been analyzed by a research group, but the comparison of the effects of different methods on the ginsenoside content and structural transformation has not been reported. In this paper, ginsenosides in ginseng were extracted according to four national pharmacopoeias and analyzed quantitatively and qualitatively by UPLC-Q-Exactive-MS and HPLC-UV. It was illustrated that the pretreatment method has a significant influence on the content determination of ginseng. The yield of rare saponins was increased by heating concluded from both the qualitative and quantitative comparison. Finally, a simple and feasible extraction method was optimized by response surface method at room temperature. The analysis of the preparation method and process optimization of the four pharmacopoeias can provide important reference information for the revision of ginseng standards.