Rare Ginsenosides Research Articles

Construction of a hollow MOF with high sedimentation performance and co-immobilization of multiple-enzymes for preparing rare ginsenoside CK

1. Sna&β-G@H-Cu-BDC biocomposite was synthesized via the hydrogel-template method with larger size. 2. Sna and β-G were co-immobilized in the hollow Cu-BDC MOF to produce the rare ginsenoside CK with cascade catalysis. 3. The Sna&β-G@H-Cu-BDC biocomposite has good sedimentation performance.

Ginsenoside Rk1 Prevents UVB Irradiation-Mediated Oxidative Stress, Inflammatory Response, and Collagen Degradation via the PI3K/AKT/NF-κB Pathway In Vitro and In Vivo.

Long-term exposure to ultraviolet (UV) irradiation, especially UVB, can trigger destructive intracellular effects, including various types of DNA damage, oxidative stress, and inflammatory responses, leading to accelerated skin aging. Ginsenoside Rk1, a rare ginsenoside pertaining to panaxadiol saponins, has been certified to possess underlying anti-inflammatory effects. Nevertheless, the efficiency of Rk1 against the photoaging of human skin and the latent molecular mechanisms are still unclear. Here, UVB-irradiated HaCaT keratinocytes were used as an in vitro model, and UVB-irradiated BALB/c nude mouse dorsal skin was established as an in vivo model to explore the mechanism by which Rk1 protects skin. Consequently, we found that Rk1 administration significantly attenuated oxidative stress by suppressing reactive oxygen species (ROS) overproduction and strengthening the activities of antioxidant enzymes. The UVB-induced inflammatory response was alleviated by Rk1 application via regulation of the secretion of various proinflammatory cytokines. Additionally, western blot assays illustrated that Rk1 intervention inhibited collagen degradation by reducing the expression of matrix metalloproteinases. Further studies revealed that Rk1 could suppress the PI3K/AKT/NF-κB signaling pathways in vitro and in vivo. Molecular docking results indicated that Rk1 might effectively bind to the active pockets of PI3K, AKT, and NF-κB. The PI3K activator 740 Y-P clearly reversed the effects of Rk1 on oxidative stress, the inflammatory response, and collagen degradation in UVB-irradiated HaCaT cells. Moreover, histological and Masson staining verified that the administration of Rk1 to BALB/c nude mice remarkably ameliorated UVB-induced skin roughness, epidermal thickening, collagen fiber arrangement disorder, and wrinkles. Overall, the evidence provided in this study suggested that Rk1 could be applied for the development of effective natural antiphotoaging agents for skin health.

Discovery of enzymes to biotransform ginsenoside Rd into ginsenosides F2 and CK using metagenomics and genomic mining.

Ginsenosides are the main active components of ginseng, including many types and different contents. Among them, minor ginsenosides have better biological functions and pharmacological activities than those of the major ginsenosides. However, minor ginsenosides cannot be obtained in large quantities, but by means of enzymatic transformation technology, some major ginsenosides can be de-glycosylated at a specific position to generate minor ginsenosides. In this study, we report two glycosidase genes associated with the conversion of ginsenoside Rd to ginsenosides F2 or CK. SWMU-CK-1 was identified among the total genes extracted from the feces of plum deer by local Blast screening for putative ginsenoside conversion function, which could cause the conversion of ginsenoside Rd → F2 → CK. The other gene was found in the Bifidobacterium breve 689b SGAir 0764 chromosome genome, which might have the same function as the β-glucosidase gene testified by the gene matching, named SWMU-F2-2, and can achieve the Rd → F2 transformation. This study reports two genes that enable achieving the biotransformation of rare ginsenosides, while it provides a new insight and a promising approach to explore new genes and develop new functions of existing genes.

Quality evaluation of commercial Ginseng Radix et Rhizoma Rubra based on multi-component quantitative analysis

To comprehensively evaluate the quality of commercial Ginseng Radix et Rhizoma Rubra, 43 batches of commercial Ginseng Radix et Rhizoma Rubra were collected to determine the content of nine ginsenosides Rg_1, Re, Rb_1, Rk_3, Rh_4, 20(S)-Rg_3, 20(R)-Rg_3, Rk_1, and Rg_5 by high performance liquid chromatography(HPLC). The quality of the commercial Ginseng Radix et Rhizoma Rubra was evaluated by correlation analysis, principal component analysis, factor analysis, analysis of variance(ANOVA), and cluster heatmap analysis. The content determination indicated that the content of common ginsenosides in commercial Ginseng Radix et Rhizoma Rubra were higher while that of rare ginsenosides were lower. Multivariate statistical analysis revealed that ginsenosides Rg_1 and Rb_1 were significantly positively correlated with rare ginsenosides, and Rg_1, Rb_1 and rare ginsenosides played an important role in evaluating the quality of commercial Ginseng Radix et Rhizoma Rubra. In combination with the processing principle and current quality situation of Ginseng Radix et Rhizoma Rubra, it is recommended to improve the content limit of Rb_1 in the existing quality standards.

Investigation of the protection from liver injury and pharmacokinetics of baijiu with fermented ginseng in rat and zebrafish models

Ginsenosides in Shen Quan baijiu (SQJ) with fermented ginseng were identified by ultrahigh-performance liquid chromatography coupled to quadrupole Orbitrap high-resolution mass spectrometry (UHPLC-Q-Exactive Orbitrap MS). Their pharmacokinetic behavior in rats and effects on zebrafish liver were investigated, and their anti-alcoholic and liver-protecting ingredients in SQJ were further explored. Twenty rats were randomly divided into five groups and administered with different samples. Serum samples were collected at different time points within 48 h, and the ethanol content in the rat serum was detected by gas chromatography (GC). The ginsenosides of SQJ and commercial ginseng baijiu were identified by UHPLC-Q-Exactive Orbitrap MS to explore their differential components. An alcoholic liver disease (ALD) zebrafish model was established for the detection of malondialdehyde (MDA) content and glutathione peroxidase (GSH-PX) and superoxide dismutase (SOD) activities. For the rat model, ethanol was not detected in the serum of the SQJ group at the 3rd h. In addition, the half-life of alcohol metabolism and the time to reach the maximum ethanol concentration in serum were both short. For the zebrafish model, the active ingredients in SQJ significantly enhanced the GSH-PX and SOD activities and reduced the MDA production in the liver. MS results revealed that the most abundant component of SQJ was ginsenoside Rg5/Rk1. Compared with those in commercial ginseng baijiu, the types of ginsenoside compound and the content of rare ginsenosides in SQJ increased significantly, especially ginsenoside Rg5/Rk1. This work was the first to use two biological models, rat and zebrafish. The findings serve as a basis for elucidating the protective mechanism of fermented ginseng components against ALD.

Inhibitory Activities of Rare Ginsenoside Rg4 on Cecal Ligation and Puncture-Induced Sepsis.

Sepsis is an uncontrolled response to inflammatory infection and is associated with high levels of mortality and morbidity. Rg4 is a rare ginsenoside mainly found in the leaves of Panax ginseng C. A. Meyer and the major protopanaxatriol-type ginsenoside of black ginseng. In this study, we determined whether Rg4 affects cecal ligation and puncture (CLP)-induced sepsis. Animals were separated into the following six groups: control group, CLP-operated group, CLP plus maslinic acid (MA), and CLP plus Rg4 (5, 10, or 15 mg/kg). Survival rate, body weight changes, inflammatory cytokines, and histological analyses were assessed. Human endothelial cells were activated with the high-mobility group box 1 (HMGB1) protein and Rg4. Cell viability was determined using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Enzyme-linked immunosorbent assay (ELISA) and Western blot analysis were used to assess inflammation and gene expression, respectively. After CLP surgery, the Rg4-administered group exhibited a higher survival rate and body weight compared with the untreated control group. Rg4 treatment reduced cytokine levels, including tumor necrosis factor (TNF)-α and interleukin (IL)-1β, as well as nitric oxide (NO) levels and renal inflammation. After Rg4 treatment of HMGB1-activated cells, the expressions of toll-like receptor (TLR) 4 and TNF-α were decreased, and the activation of phosphoinositide 3-kinase (PI3K)/AKT signaling increased cell viability. In summary, Rg4 inhibited inflammation and exhibited a protective effect against CLP-induced sepsis, thereby reinforcing cell survival against septic responses.

(20S) Ginsenoside Rh2-Activated, Distinct Apoptosis Pathways in Highly and Poorly Differentiated Human Esophageal Cancer Cells.

Ginsenoside Rh2 (G-Rh2), a rare ginsenoside isolated from red ginseng, has considerable anti-cancer activity and induces apoptosis in a variety of cancer cells, but its activity in esophageal cancer cells is unclear. In this study, we examined the cytotoxic activity of (20S) G-Rh2 in highly differentiated esophageal squamous ECA109 cells and poorly differentiated esophageal squamous TE-13 cells. (20S) G-Rh2 exerted intense cytotoxicity in ECA109 and TE-13 cells with an IC50 of 2.9 and 3.7 μg/mL, respectively. After treatment with G-Rh2, Bcl-2, and Bcl-xL, the two main anti-apoptosis Bcl-2 family proteins upregulated, and Bax and Bak, the two key pro-apoptosis proteins translocated to mitochondria in both cell lines. At the same time, cytochrome c and Smac released from mitochondria, followed by caspase-9 activation, indicating that a mitochondria-mediated intrinsic apoptosis pathway was activated in both cell lines upon treatment with (20S) G-Rh2. It is noteworthy that (20S) G-Rh2 upregulated the transcription and protein expression of two death receptors, Fas and DR5, and subsequently activated Caspase-8 in the TE-13 cells but not in the ECA109 cells. Taken together, we demonstrated the potent anti-esophageal cancer cell activity of (20S) G-Rh2 and showed its working mechanism in two differentiated esophageal cancer cells, which can provide important evidence for developing an effective strategy for anti-esophageal cancer treatment.

Ultrahigh-performance liquid chromatography coupled to ion mobility quadrupole time-of-flight mass spectrometry profiling and unveiling the transformation of ginsenosides by the dual conditions of citric acid and high-pressure steaming.

Many methods have been reported for the production of rare ginsenosides, including heat treatment, acid hydrolysis, alkaline hydrolysis, enzymatic hydrolysis, and microbial transformation. However, the conversion of original ginsenosides to rare ginsenosides under the dual conditions of citric acid and high-pressure steam sterilization has rarely been reported. In this study, a method involving ultrahigh-performance liquid chromatography coupled to ion mobility quadrupole time-of-flight mass spectrometry was developed for analysis of chemical transformation of protopanaxatriol (PPT)-type ginsenosides Rg1 and Re, protopanaxadiol (PPD)-type ginsenoside Rb1 , and total ginsenosides in the dual conditions of citric acid and high-pressure steam sterilization. An internal ginsenoside database containing 126 known ginsenosides and 18 ginsenoside reference compounds was established to identify the transformation products and explore possible transformation pathways and mechanisms. A total of 54 ginsenosides have been preliminarily identified in the transformation products of PPD-type ginsenosides Rg1 and Re, PPD-type ginsenoside Rb1 , and total ginsenosides, and the possible transformation pathways were as follows: Rg1 , Re → 20(S)-Rh12 , 20(R)-Rh12 ; Rg1 , Re → 20(S)-Rh1 , 20(R)-Rh1 → Rk3 , Rh4 , Rh5 ; Rb1 → gypenoside LXXV; Rb1 → 20(S)-Rg3 , 20(R)-Rg3 → Rk1 , Rg5 ; Re → 20(S)-Rg2 , 20(R)-Rg2 → 20(S)-Rf2 , 20(R)-Rf2 , Rg4 , F4 . The results elucidated the possible transformation pathways and mechanisms of ginsenosides in the dual conditions of citric acid and high-pressure steam sterilization, which were helpful for revealing the mechanisms of ginsenosides and enhanced safety and quality control of pharmaceuticals and nutraceuticals. Meanwhile, a simple, efficient, and practical method was developed for the production of rare ginsenosides, which has the potential to produce diverse rare ginsenosides on an industrial scale.

Identification and chemical profiling of anti-alcoholic liver disease biomarkers of ginseng Huang jiu using UPLC-Q-Orbitrap-HRMS and network pharmacology-based analyses

This study investigated the mechanism of characteristic non-volatile organic compounds (NVOCs) from ginseng Huang jiu (GH) in the treatment of alcoholic liver disease through UPLC-Q-Orbitrap-HRMS and network pharmacological analyses. Changes in NVOC contents in ginseng Huang jiu and ginseng-soaked wine fermented by different processing technologies were analyzed through liquid chromatography–mass spectrometry (LC-MS). A total of 96 ginsenosides were identified in ginseng Huang jiu throughout the fermentation process, which included 37 protopanaxadiol-type ginsenosides, 47 protopanaxatriol-type ginsenosides, and 4 oleanolic acid-type ginsenosides. Orthogonal partial least squares-discriminant analysis (OPLS-DA) revealed that 20(R)-Rg2, Gypenoside XVII, 20(S)-Rf3, CK, Rg5, Rh2, and other rare ginsenosides in ginseng Huang jiu could be the potential index for determining ginseng Huang jiu. In addition, ginseng Huang jiu could improve alcoholic liver disease by regulating the GSTP1, HRAS, AKR1B1, GSTA1, Androgen receptor (AR), GSR, and LDHB genes through bioinformatics analysis. This study provides new insights into improving the industrial production of ginseng Huang jiu and treating alcoholic liver disease with medicinal and food products.

Ginsenoside Rh3 Inhibits Lung Cancer Metastasis by Targeting Extracellular Signal-Regulated Kinase: A Network Pharmacology Study.

Lung cancer has a high mortality rate and is very common. One of the main reasons for the poor prognosis of patients with lung cancer is the high incidence of metastasis. Ginsenoside Rh3, a rare ginsenoside extracted from Panax notoginseng, exhibits excellent anti-inflammatory and anti-tumor effects. Nonetheless, the inhibitory potential of Rh3 against lung cancer remains unknown. The target genes of Rh3 were screened by the PharmMapper database; the proliferation of lung cancer cells was detected by MTT assay; the migration and invasion of cells were detected by the Transwell method; and the expression of extracellular signal-regulated kinase (ERK) and EMT-related proteins in vivo and in vitro were detected by Western blotting. In addition, we established a lung metastasis model in nude mice using A549 cells to assess the effect of Rh3 on NSCLC tumor metastasis in vivo. Our findings suggest that Rh3 significantly inhibited lung cancer metastasis both in vivo and in vitro. It was determined by flow cytometry analysis that Rh3 notably inhibited cell proliferation by blocking the G1 phase. In addition, Rh3 inhibited metastasis in lung cancer cells and regulated the expression of metastasis-related proteins under hypoxia. Mechanistic studies suggested that Rh3 targeted ERK to inhibit lung cancer metastasis. The ERK inhibitor U0126 or siRNA-mediated knockdown of ERK had an enhanced effect on Rh3’s ability to inhibit lung cancer metastasis. The studies revealed that the inhibitory effect of Rh3 on the metastatic ability of lung cancer cells may be supported by ERK-related signaling pathways.

Key Glycosyltransferase Genes of Panax notoginseng: Identification and Engineering Yeast Construction of Rare Ginsenosides.

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

Mass spectrometry-based profiling and imaging strategy, a fit-for-purpose tool for unveiling the transformations of ginsenosides in Panax notoginseng during processing

BackgroundPanax notoginseng, a valuable medicinal plant, is traditionally used to treat trauma, body pain, and cardiovascular diseases in two clinical forms including raw (crude) and processed form. Processing-triggered compound transformation is responsible for the distinct bioactivity between raw and processed Panax notoginseng. Nevertheless, investigating the chemical diversity and dynamic transformation pattern of processed Panax notoginseng is challenging. MethodsA new approach, which integrates multi-components characterization, processing trajectory depiction, discovery of differential markers, transformation mechanism of metabolites, in situ spatial distribution and transformation of metabolites, was established to elucidate the role of processing on the holistic chemical transformations of Panax notoginseng (PN). ResultsIn this study, 136 ginsenosides (mainly rare ginsenosides) were identified or tentatively characterized and the temperature-dependent chemical variation trajectory was depicted via principal component analysis (PCA). Nineteen processing-associated markers were confirmed by orthogonal partial least squares-discriminant analysis (OPLS-DA). For the first time, the transformation pathway of ginsenosides during processing were elucidated by integrating the precursor ion scan (PIS) and mimic processing strategy that involves with deglycosylation, dehydration, hydration, acetylation, and isomerization. Results of mass spectrometry imaging (MSI) revealed the major ginsenosides M-Rb1, R1, Rg1, Rb1, Rd, and Re exhibited distinct spatial distribution pattern that are highly abundant in the xylem and showed a downward trend during processing. We firstly depicted the spatial distribution of processing-triggered rare ginsenosides (Rg3, Rk1, Rg5, etc.), and in situ transformation of ginsenosides was discovered in the process of steaming. Additionally, this variation trend was consistent with untargeted metabolomics results. ConclusionThis study comprehensively revealed chemical diversity and dynamic transformation pattern and depicted the spatial distribution of ginsenosides of PN during processing. It could provide a clue for the distinct bioactivities between raw and processed PN and elucidate the role of processing on the holistic chemical transformations of natural products, more importantly, the proposed strategy is valuable for the quality evaluation and control of the processing of natural product.

Comparison of the Saponins in Three Processed American Ginseng Products by Ultra-High Performance Liquid Chromatography-Quadrupole Orbitrap Tandem Mass Spectrometry and Multivariate Statistical Analysis

A method with ultrahigh performance liquid chromatography Quadrupole-Orbitrap tandem mass spectrometry (UHPLC-Q-Orbitrap-MS/MS) was applied for the quality evaluation of different processing and drying of American ginseng, including natural drying (ND), steam drying (SD), and vacuum freeze-drying (VFD). A total of 51 saponins were successfully identified in three processed products. Three processed American ginseng products were well-differentiated in orthogonal partial least-squares discriminant analysis (OPLS-DA). The S-plot also identified the marker compounds in each product, while the major ginsenosides of ND (malonyl (M)-Rd, M-Rb1, Rg1), SD (20 (S)-Rg3, 20 (S)-Rg2), and VFD (M-Rd, M-Rb1) were found. The results indicate that the method by vacuum freeze-drying can retain the content of rare ginsenosides and malonyl-ginsenosides. The marker compounds selected will benefit the holistic evaluation of related American ginseng products.

Study on the Biochemical Characterization and Selectivity of Three β-Glucosidases From Bifidobacterium adolescentis ATCC15703.

Three β-glucosidases from Bifidobacterium adolescentis ATCC15703, namely, BaBgl1A, BaBgl3A, and BaBgl3B, were overexpressed in Escherichia coli. The recombinant β-glucosidases were sufficiently purified using Ni2+ affinity chromatography, and BaBgl1A exhibited the best purification efficiency with a purification factor of 2.3-fold and specific activity of 71.2 U/mg. Three recombinant β-glucosidases acted on p-nitrophenyl-β-glucopyranoside (pNPβGlc) at around pH 7.0 and 30–50°C. The results of the substrate specificity assay suggested that BaBgl1A acted exclusively as β-1,2-glucosidase, while BaBgl3A and BaBgl3B acted mostly as β-1,3-glucosidase and β-1,4-glucosidase, respectively. The substrate specificity of the three recombinant enzymes was further studied using the ginsenosides Rb1 and Rd as substrates. The results of thin-layer chromatography and high-performance liquid chromatography analyses showed that BaBgl1A exhibited the highest bioconversion ability on Rb1 and Rd, where it hydrolyzed the outer C-3 glucose moieties of Rb1 and Rd into the rare ginsenosides Gypenoside XVII and F2; BaBgl3A exhibited medium bioconversion ability on Rb1, where it hydrolyzed both the outer C-3 and C-20 glucose moieties of Rb1 into Gyp XVII and Rd; and BaBgl3B was not active on Rb1 and Rd. These β-glucosidases will act as new biocatalytic tools for transforming ginsenosides and preparing active glycosides and aglycone.

Transformation Mechanism of Rare Ginsenosides in American Ginseng by Different Processing Methods and Antitumour Effects

The mechanism by which ginsenosides from Panax quinquefolium L. transform into rare saponins by different processing methods and their antitumour effects have yet to be fully elucidated. Our study aimed to detect the effect of amino acids and processing methods on the conversion of ginsenosides in American ginseng to rare ginsenosides, using 8 monomeric ginsenosides as substrates to discuss the reaction pathway and mechanism. S180 tumour-bearing mice were established to study the antitumour effects of American ginseng total saponins (AGS-Q) or American ginseng total saponins after transformation (AGS-H) synergistic CTX. The results showed that aspartic acid was the best catalyst, and the thermal extraction method had the best effect. Under the optimal conditions, including a reaction temperature of 110°C, an aspartic acid concentration of 5%, a reaction time of 2.5 h and a liquid-solid ratio of 30 mL/g, the highest conversion of Rk1 and Rg5 was 6.58 ± 0.11 mg/g and 3.74 ± 0.05 mg/g, respectively. In the reaction pathway, the diol group saponins participated in the transformation process, and the triol group saponins basically did not participate in the transformation process. AGS-Q or AGS-H synergistic CTX, or AGS-H synergistic CTX/2 could significantly increase the tumour inhibition rate, spleen index and white blood cell count, had a significant upregulation effect on IL-2 and IL-10 immune cytokines; significantly restored the ratio of CD4+/CD8+; and significantly inhibited the level of CD4+CD25+. AGS-Q or AGS-H synergistic with CTX or CTX/2 can significantly upregulate the expression of Bax and cleaved-Caspase-3 and inhibit the expression of antiapoptotic protein Bcl-2. AGS synergistic CTX in the treatment of S180 tumour-bearing mice can improve the efficacy and reduce toxicity.

Ginsenoside Rg3 determination using an electro-synthesized molecularly imprinted polymer on MWCNT-Ti3C2Tx nanocomposite modified electrode

Rare ginsenoside Rg3 is a main active ingredient in ginseng, which is more easily absorbed by human body and plays its role. Determination of Rg3 in edible and medicinal samples is a key factor for quality evaluation and effective monitoring of adulteration. In this study, an electrochemical sensor was developed based on molecularly imprinted polymer (MIP) and nanomaterial amplification. MIP was achieved by electro-polymerization with Rg3 as the template molecule and the functional monomer was o-phenylenediamine. Multi-walled carbon nanotubes (MWCNT) and titanium carbide (Ti3C2Tx) nanocomposites formed an excellent porous structure, which exhibited the advantages of increasing the specific surface area and electrical conductivity. The prepared sensor presented a great linear relation of Rg3 in the range of 10–2000 μg mL−1 with a limit of detection (LOD) of 0.34 μg mL−1. Importantly, the sensor was successfully utilized to detect ginsenoside Rg3 in different real samples.

Chemical Distance Measurement and System Pharmacology Approach Uncover the Novel Protective Effects of Biotransformed Ginsenoside C-Mc against UVB-Irradiated Photoaging.

Long-term exposure to ultraviolet light induces photoaging and may eventually increase the risk of skin carcinogenesis. Rare minor ginsenosides isolating from traditional medicine Panax (ginseng) have shown biomedical efficacy as antioxidation and antiphotodamage agents. However, due to the difficulty of component extraction and wide variety of ginsenoside, the identification of active antiphotoaging ginsenoside remains a huge challenge. In this study, we proposed a novel in silico approach to identify potential compound against photoaging from 82 ginsenosides. Specifically, we calculated the shortest distance between unknown and known antiphotoaging ginsenoside set in the chemical space and applied chemical structure similarity assessment, drug-likeness screening, and ADMET evaluation for the candidates. We highlighted three rare minor ginsenosides (C-Mc, Mx, and F2) that possess high potential as antiphotoaging agents. Among them, C-Mc deriving from American ginseng (Panax quinquefolius L.) was validated by wet-lab experimental assays and showed significant antioxidant and cytoprotective activity against UVB-induced photodamage in human dermal fibroblasts. Furthermore, system pharmacology analysis was conducted to explore the therapeutic targets and molecular mechanisms through integrating global drug-target network, high quality photoaging-related gene profile from multiomics data, and skin tissue-specific expression protein network. In combination with in vitro assays, we found that C-Mc suppressed MMP production through regulating the MAPK/AP-1/NF-κB pathway and expedited collagen synthesis via the TGF-β/Smad pathway, as well as enhanced the expression of Nrf2/ARE to hold a balance of endogenous oxidation. Overall, this study offers an effective drug discovery framework combining in silico prediction and in vitro validation, uncovering that ginsenoside C-Mc has potential antiphotoaging properties and might be a novel natural agent for use in oral drug, skincare products, or functional food.

Complexation mechanism between 20(R, S)-ginsenoside Rh1 and serum albumin: Multi-spectroscopy, in vitro cytotoxicity, and in silico investigations.

As rare ginsenosides, 20(R, S)-ginsenoside Rh1 [20(R, S)-Rh1] are isomers and have been reported to exhibit multiple biological effects. However, the application of 20(R, S)-Rh1 is still limited due to their poor solubilities and low bioavailabilities. Here, the complexation mechanism between 20(R, S)-Rh1 and serum albumin (SA) was explored by a combination of multi-spectroscopy and in silico investigations. Results of spectra experiments showed that 20(R, S)-Rh1 could form complexes with bovine serum albumin (BSA) and quench its intrinsic fluorescence. In addition, the influence of BSA on the anti-cancer activity of 20(R, S)-Rh1 was also evaluated in A549 cells. The result of the MTT assay indicated that anti-cancer activity of 20(R, S)-Rh1 was enhanced when combined with BSA. The results of molecular docking and dynamics simulation demonstrated that the subtle structural differences of 20(R, S)-Rh1 at the 20-carbon atom may be responsible for their different binding capacities and binding stabilities with human serum albumin. The cytotoxicity assay for 20(R, S)-Rh1 alone and their complexes with BSA demonstrated the enhancement effect of BSA for inhibition of cell proliferation. In conclusion, this work provided insight into the complexation mechanism between 20(R, S)-Rh1 and SA. PRACTICAL APPLICATION: The complexation mechanism between 20(R, S)-ginsenoside Rh1 [20(R, S)-Rh1] and serum albumin (SA) was explored by a combination of multi-spectroscopy and in silico investigations in this work. The cytotoxicity assay for 20(R, S)-Rh1 alone and their complexes with bovine serum albumin (BSA) demonstrates the enhancement effect of BSA for inhibition of cell proliferation. Hence, this work provided insight into the complexation mechanism between 20(R, S)-Rh1 and SA.

A narrative review of the pharmacology of ginsenoside compound K.

Background and ObjectiveThe ginsenoside compound K [20-o-beta-dglucopyranosyl-20 (S)-protopanaxadiol; CK] is the main deglycosylated metabolite of ginsenoside. As a rare ginsenoside converted from the active substance of ginseng by intestinal bacteria, CK has higher biological activity than other ginsenosides. It has demonstrated diverse and intriguing biological activities, including anti-carcinogenic, anti-diabetic, anti-inflammation, anti-allergy, anti-angiogenesis, anti-aging, neuroprotective, and hepatoprotective effects. The purpose of this review was to elucidate the rich pharmacological activities and related mechanisms of ginsenoside CK in vivo and in vitro, as well as the potential therapeutic value of CK as a drug in a variety of systemically related diseases.MethodsThe PubMed database was searched for articles published in English from February 2008 to December 2021 using related keywords such as “Ginsenoside compound K”, “compound K”, and “CK”. About 140 research papers and reports written in English were identified. These papers mainly concentrated on the pharmacological activities of CK in cancer prevention, immune regulation, diabetic improvement, central nervous system (CNS) protection, cardiovascular protection, skin improvement, and hepatoprotection.Key Content and FindingsThis paper describes the synthesis, pharmacokinetics, and adverse reactions of CK, as well as great detailed summarized of the relevant pharmacological activities. Such diverse intriguing biological properties of CK have been found.ConclusionsOn account of CK’s numerous pharmacological activities and anti-carcinogenic, anti-inflammation, antiallergic, anti-diabetic, anti-angiogenesis, anti-aging, neuroprotective, and hepatoprotective effects, strong evidence is available for CK as a preventive or therapeutic agent for various diseases. However, further studies are needed to evaluate the safety and effectiveness of CK as a drug and its application in the medical field.

Sustainable production of rare oleanane-type ginsenoside Ro with an artificial glycosylation pathway in Saccharomyces cerevisiae

S. cerevisiae was genetically reprogrammed to produce ginsenoside Ro with seven exogenous enzymes from five species. This study also paved a good way for the synthesis of other complex glycosides of triterpenoids.