Steamed Panax Notoginseng Research Articles

An innovative processing driven efficient transformation of rare ginsenosides enhances anti-platelet aggregation potency of notoginseng by integrated analyses of processing-(chemical) profiling-pharmacodynamics

Ethnopharmacological relevancePanax notoginseng (Burk.) F. H. Chen, a valuable Chinese herb medicine, shows a characteristic bi-directional regulation of hemostasis and activating blood circulation with ginsenosides as the predominant bioactive compounds and is a typical representative of “processing triggered heteropotency”. Aim of the studyProcessing triggered heteropotency, one of the unique theories and practices in traditional Chinese medicine, refers to that the processing will lead to change in physical and chemical properties, and eventually disparate efficacy of the crude drugs, yet the optimum process and underlying mechanism remains unclear. In this study, using Panax notoginseng (PN) as a representative sample, a processing-(chemical) profiling-pharmacodynamics (3-P) relationship was proposed to investigate the processing mechanism of PN. Materials and methodsFirstly, a temperature programmed steaming process was designed to evaluate the steaming triggered chemical transformation of triterpene saponins and the corresponding enhancement in anti-platelet aggregation activity. The steaming process was programed from the conventional 100 °C–150 °C in a time course of 0–12 h, aiming to achieve the maximized conversion of rare ginsenosides (RGs), and dynamic profile of ginsenosides were constructed by a UPLC-Q-TOF-MS/MS analysis. Then, a processing-(chemical) profiling-pharmacodynamics (3-P) relationship was assessed by using the grey relational analysis (GRA) and orthogonal projections to latent structures (OPLS), and validated by bioactive fraction of 140 °C steamed PN. Subsequently, the P2Y12-ligand binding affinity of potential candidates was analyzed by molecular docking. Finally, the dynamic changes of ginsenosides during steaming of SPN were quantitatively detected by UPLC-QQQ-MS/MS. ResultsA total of 48 differential ginsenosides were characterized and monitored including the primary and secondarily transformed saponins. The higher temperature steaming especially at 140 °C induces not only the predominant production of the RGs, but also the stronger anti-platelet aggregation activity. The 3-P relationship showed the fraction (3) of 140 °C steamed PN rich in RGs exhibits the most predominant efficacy, in which, a series of RGs including ginsenosides Rg5, Rk1, 20(S/R)-Rg3 were proven to be potent components. Molecular docking analysis suggested that ginsenosides Rg5 and Rk1 showed more strong interaction with the platelet P2Y12 receptor. Quantitative analysis found 140 °C-2h PN possessed highest contents of Rk1 and Rg5 and total RGs. ConclusionsThe integrated 3-P strategy uncovered the promising ginsenosides with anti-platelet effect, thereby revealing the material basis of PN steaming, which could provide a new enlightenment for the investigation of processing mechanism of traditional Chinese medicines.

Homotherapy for heteropathy of Alzheimer's disease and anemia through reducing the expression of toll-like receptor and TNF by steamed Panax notoginseng

BackgroundOne of the effects of Steamed Panax notoginsen (SPN) is to replenish blood, which is mostly used to treat anemia in clinic. SPN has the effect of treating anemia and Alzheimer's disease (AD) in clinical and basic research. In traditional Chinese medicine, anemia and AD have the same characteristics, and their symptoms are qi and blood deficiency. MethodsFirst, data analysis was carried out through network pharmacology to predict the action targets of SPN homotherapy in the treatment of AD and anemia. Specifically, TCMSP and relevant literature were used to screen the main active ingredients of Panax notoginseng, and SuperPred was used to predict the action targets of the active ingredients. Disease targets related to AD and anemia were collected through Genecards database, and STRING and protein interaction (PPI) was used for enrichment analysis, Analyze the characteristics of the active ingredient target network on the Cytascape 3.9.0 platform, and use Metascape to enrich the gene ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes Pathway Enrichment (KEGG pathway). Then Drosophila was used as the AD animal model, and the effects of SPN on the climbing ability, olfactory memory and brain Aβ, with rats as anemia animal models, the improvement effect of SPN on blood routine and organ index of rats with blood deficiency induced by CTX and APH was analyzed to further explain the therapeutic effect of SPN on these two diseases. Finally, the regulatory effect of SPN on the key active target of allotherapy for AD and anemia was verified by PCR. ResultsAfter the screening, 17 active components and 92 action targets of SPN were obtained. The degree values of components and the first 15 targets are NFKB1, IL10, PIK3CA, PTGS2, SRC, ECFR, CASP3, MTOR, IL1B, ESR1, AKT1, HSP90AA1, IL6, TNF, and Toll-like receptor, it is mainly related to inflammatory response, immune regulation and antioxidation. SPN improved the climbing ability, olfactory memory ability, and Aβ42 content in the brain of Aβ flies, and significantly reduced the expression of TNF and Toll-like receptor in the brain after treatment. SPN can significantly improve the blood routine index and organ index of anemia rats, and also significantly reduce the expression of TNF and Toll-like receptor in the brain after treatment. ConclusionSPN can regulate the expression of TNF and Toll-like receptor to achieve the same treatment of AD and anemia.

Steamed Panax notoginseng and its Saponins Inhibit the Migration and Induce the Apoptosis of Neutrophils in a Zebrafish Tail-Fin Amputation Model.

Panax notoginseng (PN) is a Chinese medicinal herb that is traditionally used to treat inflammation and immune-related diseases. Its major active constituents are saponins, the types and levels of which can be changed in the process of steaming. These differences in saponins are causally relevant to the differences in the therapeutic efficacies of raw and steamed PN. In this study, we have prepared the extracts of steamed PN (SPNE) with 70% ethanol and investigated their immunomodulatory effect using a zebrafish tail-fin amputation model. A fingerprint-effect relationship analysis was performed to uncover active constituents of SPNE samples related to the inhibitory effect on neutrophil number. The results showed that SPNE significantly inhibited the neutrophil number at the amputation site of zebrafish larvae. And SPNE extracts steamed at higher temperatures and for longer time periods showed a stronger inhibitory effect. Ginsenosides Rh1, Rk3, Rh4, 20(S)-Rg3, and 20(R)-Rg3, of which the levels were increased along with the duration of steaming, were found to be the major active constituents contributing to the neutrophil-inhibiting effect of SPNE. By additionally investigating the number of neutrophils in the entire tail of zebrafish larvae and performing TUNEL assays, we found that the decreased number of neutrophils at the amputation site was due to both the inhibition of their migration and apoptosis-inducing effects of the ginsenosides in SPNE on neutrophils. Among them, Rh1 and 20(R)-Rg3 did not affect the number of neutrophils at the entire tail, suggesting that they only inhibit the migration of neutrophils. In contrast, ginsenosides Rk3, Rh4, 20(S)-Rg3, and SPNE did not only inhibit the migration of neutrophils but also promoted neutrophilic cell death. In conclusion, this study sheds light on how SPNE, in particular the ginsenosides it contains, plays a role in immune modulation.

Steamed Panax notoginseng attenuates renal anemia in an adenine-induced mouse model of chronic kidney disease

Ethnopharmacological relevancePanax notoginseng (PN) (Burk.) F. H. Chen is a medicinal herb used to treat blood disorders since ancient times, of which the steamed form exhibits the anti-anemia effect and acts with a “blood-tonifying” function according to the traditional use. However, its pharmacological effect and mechanism on alleviating renal anemia (RA) are still unclear. Aims of the studyThe study aims to investigate the effect of steamed Panax notoginseng (SPN) to attenuate RA and its underlying mechanism based on the model of adenine-induced RA mice. Materials and methodsSeventy mice were randomly divided into seven groups of ten: the control group, model group, the erythropoietin (EPO) group, the Fufang E'jiao Jiang (FEJ) group, the high-dose steamed PN (H-SPN) group, the middle-dose steamed PN (M-SPN) group, and the low-dose steamed PN (L-SPN) group. The adenine induction RA model was applied to assess the “blood enriching” function of SPN. The blood routine indexes, erythrocyte fragility, pathologic morphology of kidney tissue and the expression levels of related cytokines and proteins in the mice were detected after 3-week administration with SPN and positive drugs. ResultsOur study provided evidences that SPN could ameliorate RA. Compared with the control group, SPN could attenuate RA by significantly increasing the numbers of peripheral blood cells (p < 0.01), improving the erythrocyte fragility (p < 0.01), and restoring the expression of EPO mRNA in the kidneys and EPO receptor mRNA in bone marrow nucleated cells. The expression of TGF-β1 mRNA was declined and the expression of HGF mRNA was significantly increased in a dose-dependent way after the treatment of SPN. Additionally, the expression of Bcl-2 and Bcl-2/Bax ratio in the kidneys were significantly increased. In contrast, there was a highly significant decrease in the expression of Bax (p < 0.01), following SPN treatment. ConclusionSPN could alleviate RA by promoting the overall hematopoiesis and inhibiting the progress of renal injury in mice.

The Study of Steaming Durations and Temperatures on the Chemical Characterization, Neuroprotective, and Antioxidant Activities of Panax notoginseng.

Panax notoginseng (PN) is one of the most valuable traditional Chinese medicines and has extensive pharmacological effects. Recent studies demonstrated that PN exhibited pharmacological effect related to Alzheimer's disease (AD). However, whether steaming process can boost its anti-AD activity is still unexplored. To fill this gap, effects of steaming durations and temperatures on the chemical characterization, neuroprotective and antioxidant activities of PN were systematically investigated in this study. HPLC fingerprint coupled with quantitative analysis demonstrated striking conversion of original saponins to less polar ones with the increase in the steaming time and temperature. In the viewpoint of anti-AD activity on neuroprotective and antioxidant effects, several steamed PN samples (110°C-6/8/10 h, 120°C ‐4/6 h samples) displayed a significant increase both in cell viability and oxygen radical absorption capacity (ORAC) values compared with the no steamed one (P < 0.01 or P < 0.005). Steaming temperature had the greater impact on the change of chemical composition and anti-AD activity of PN. Moreover, the spectrum-effect relationship analysis revealed that the transformed saponins were partially responsible for the increased neuroprotective and antioxidant effects of steamed PN. Therefore, steamed PN could be used as a potential crude drug for prevention and treatment of AD.

Comparative pharmacokinetic analysis of raw and steamed Panax notoginseng roots in rats by UPLC-MS/MS for simultaneously quantifying seven saponins

Context After being steamed, the restorative effects of Panax notoginseng (Burk.) F. H. Chen (Araliaceae) will be strengthened. However, the underlying mechanism remains elusive. Objective To compare the pharmacokinetics of ginsenosides Rg1, Rb1, Rd, Re, Rg5, Rk1, notoginsenoside R1 (GRg1, GRb1, GRd, GRe, GRg5, GRk1 and NGR1) in the raw and steam-processed P. notoginseng (RPN and SPN). Materials and methods The pharmacokinetics of seven components after oral administration of SPN and RPN extracts (1.0 g/kg) were investigated, respectively, in SD rats (two groups, n = 6) using UPLC-MS/MS. Results The approach elicited good linear regression (r 2 > 0.991). The accuracy, precision and stability were all within ± 15%. The extraction recoveries and matrix effects were 75.0–100.8% and 85.1–110.3%, respectively. Compared with the RPN group, AUC0– t of GRg1 (176.63 ± 42.49 ng/h/mL), GRb1 (5094.06 ± 1453.14 ng/h/mL), GRd (1396.89 ± 595.14 ng/h/mL), and NGR1 (135.95 ± 54.32 ng/h/mL), along with C max of GRg1 (17.41 ± 5.43 ng/mL), GRb1 (361.48 ± 165.57 ng/mL), GRd (62.47 ± 33.65 ng/mL) and NGR1 (23.97 ± 16.77 ng/mL) decreased remarkably with oral administration of the SPN extracts, while GRe showed no significantly difference. Of note, GRg5 and GRk1 could not be detected in the plasma. Conclusions Influence of the processing reduced the systemic exposure levels to GRg1, GRb1, GRd and NGR1. It is the first report of comparative pharmacokinetic study of multiple saponins analysis after oral administration of RPN and SPN extract, which might be helpful for further studies on its steam-processing mechanism.

Optimization of steaming process for polysaccharides from panax notoginseng by box-behnken response surface methodology and comparison of immunomodulatory effects of raw and steamed panax notoginseng polysaccharides

Aim: We aimed to optimize the steaming process of Pana notoginseng using response surface methodology (RSM). Materials and Methods: The yield and immune activity of steamed P. notoginseng polysaccharides (s-PNPs) was used as the indicators to optimize the steaming parameters: wetting time, steaming time, and temperature. After this, chromatogram and spectroscopy were used to analyze the effect of steaming on the structure of polysaccharides. Then, our study evaluated the immunological activities between s-PNPs and raw P. notoginseng polysaccharides (r-PNPs) in vivo and in vitro. Results: The optimal parameters of processing technology were as follows: wetting time was 25 h, steaming time was 4 h, and steaming temperature was 110°C. The s-PNPs yield reached a maximum of 13.67 ± 0.39%, and the cell proliferation rate was 22.87 ± 0.015% under these conditions. The chemical analysis method showed that the polysaccharide content was slightly increased, the protein content was decreased and the monosaccharide composition analysis indicated that the glucose content in s-PNPs was significantly increased than r-PNPs. Moreover, Fourier transform infrared spectroscopy analysis showed that the functional groups of polysaccharides changed partially between s-PNPs and r-PNPs. In addition, the immunological activity of s-PNPs was better than that of r-PNPs in vivo and in vitro. Conclusion: These studies showed that polysaccharides content was increased, and the immune function of s-PNPs was enhanced after applying steaming, making this approach meaningful for the development and application of P. notoginseng with its immunomodulatory.

Analyzing Active Constituents and Optimal Steaming Conditions Related to the Hematopoietic Effect of Steamed Panax notoginseng by Network Pharmacology Coupled with Response Surface Methodology.

During hundreds of years of medication, it is believed that the steamed Panax notoginseng (SPN) can enrich and regulate the blood, replenish the body, and improve the health. The aim of this study was to optimize the steaming conditions of SPN which are related to the hematopoietic effect. In the study, network pharmacology and pharmacological experiments were used to predict and verify the potential hematopoietic active ingredients of SPN. Three variables including the steaming time (2-10 h), steaming temperature (90-130°C), and different producing areas of PN were investigated by using single-factor analysis. Box-Behnken design response surface methodology (BBD-RSM) was performed to explore the optimized steaming conditions which are responsible for the hematopoietic effect of SPN. Furthermore, the hematopoietic effect of the optimized SPN was evaluated. Results demonstrated that ginsenoside Rd, Rh1, Rh4, Rk3, and 20(S)-Rg3 can significantly increase blood routine parameters and expressions of hematopoietic factors in anemia mice. The total contents of the five ginsenosides were selected as evaluation indexes of the response surface method. We found that the PN from Wenshan steamed at 120°C for 5 h could significantly increase the levels of blood routine parameters and hematopoietic factor expression compared with the model group. The study not only provides data support for the determination of hematinic effect-related markers for SPN but also gives a scientific reference for the processing of SPN which has a better hematopoietic effect. The underlying mechanisms require further research.

Steamed Panax notoginseng Attenuates Anemia in Mice With Blood Deficiency Syndrome via Regulating Hematopoietic Factors and JAK-STAT Pathway.

Panax notoginseng (Burk.) F. H. Chen is a medicinal herb used to treat blood disorders since ancient times, of which the steamed form exhibits the anti-anemia effect and acts with a “blood-tonifying” function according to traditional use. The present study aimed to investigate the anti-anemia effect and underlying mechanism of steamed P. notoginseng (SPN) on mice with blood deficiency syndrome induced by chemotherapy. Blood deficiency syndrome was induced in mice by cyclophosphamide and acetylphenylhydrazine. A number of peripheral blood cells and organs (liver, kidney, and spleen) coefficients were measured. The mRNA expression of hematopoietic function-related cytokines in the bone marrow of mice was detected by RT-qPCR. The janus kinase-signal transducer and activator of transcription (JAK-STAT) signaling pathway was screened based on our previous analysis by network pharmacology. The expression of related proteins and cell cycle factors predicted in the pathway was determined by Western blot and RT-qPCR. SPN could significantly increase the numbers of peripheral blood cells and reverse the enlargement of spleen in a dose-dependent manner. The quantities of related hematopoietic factors in bone marrow were also increased significantly after SPN administration. SPN was involved in the cell cycle reaction and activation of immune cells through the JAK-STAT pathway, which could promote the hematopoiesis.

Unveiling Active Constituents and Potential Targets Related to the Hematinic Effect of Steamed Panax notoginseng Using Network Pharmacology Coupled With Multivariate Data Analyses.

Steamed Panax notoginseng (SPN) has been used as a tonic to improve the blood deficiency syndrome (BDS) in the theory of traditional Chinese medicine. Here, we aim to unveil active constituents and potential targets related to the hematinic effect of SPN, which has not been answered before. In the study a constituent-target-disease network was constructed by combining the SPN-specific and anemia-specific target proteins with protein-protein interactions. And the network pharmacology was used to screen out the underlying targets and mechanisms of SPN treating anemia. Also, the multivariate data analyses were performed for the double screening. According to the results, 11 targets related to chemical constituents of SPN were found to be closely associated with the hematinic effect of SPN. Among them, the direct target protein of mitochondrial ferrochelatase (FECH) had the major role through the metabolic pathway. Meanwhile, Rk3 and 20(S)-Rg3 were predicted to be major constituents related to the hematinic effect of SPN by both multivariate data analyses and network pharmacology. And it was been validated by the pharmacologic tests that Rk3 and 20(S)-Rg3 could significantly increase the levels of blood routine parameters, FECH and its downstream protein of heme in mice with BDS. The study provides evidences for the mechanism understanding and drug development of SPN for the treatment of anemia.

Identification of anti-inflammatory components of raw and steamed Panax notoginseng root by analyses of spectrum-effect relationship.

To identify bioactive components of Panax notoginseng (PN) roots in raw and steamed forms, chemometrics analyses including bivariate correlation analysis and partial least squares regression were used to establish the relationships between the chromatograms and anti-inflammatory effect of PN samples. The chemical fingerprints of PN were obtained by high performance liquid chromatography. The anti-inflammatory activity was evaluated by the TNF-α and IL-6 inhibiting test. According to the results, raw PN (RPN) displayed a stronger anti-inflammatory effect compared with steamed PN (SPN) samples. Chemometrics analyses showed that notoginsenoside R1, ginsenosides Rg1, Re and Rb1 were the major anti-inflammatory components of RPN, whereas ginsenosides 20(S)-Rg3 was the active one of SPN treating inflammation. The pharmacologic verification was consistent with the predicted results. In addition, the contents of anti-inflammatory components in RPN were higher than those in SPN, which might be the reason that RPN exhibited stronger effect on the inflammation induced by lipopolysaccharide in RAW264.7 cells. These findings could be beneficial for choosing differential markers for the quality control of RPN and SPN.

Pharmacokinetic Characteristics of Steamed Notoginseng by an Efficient LC-MS/MS Method for Simultaneously Quantifying Twenty-three Triterpenoids.

Steamed Panax notoginseng (SNG) has been widely used as a restorative medicine instead of the raw one, but its pharmacokinetic profile is entirely unknown. To address this, we've developed an LC-MS/MS method with high efficiency and sensitivity for simultaneous quantification of 23 triterpenoids (notoginsenosides Fa, Fc, R1, 20( S)-R2, 20( R)-R2, ginsenosides F4, Rb1, Rg1, Rd, Re, Rb2, 20( S)-Rh1, 20( R)-Rh1, Rh4, R k1, R k3, 20( S)-Rg2, 20( S)-Rg3, 20( R)-Rg3, Rg5, C-K, 20( S)-PPT, 20( S)-PPD) from SNG in rat plasma. This validated approach exhibits great linearity, precision, accuracy, recovery, and stability for all analytes. Furthermore, we, for the first time, applied this method to the pharmacokinetic study of SNG and proposed Rb1, Fa, Rd, R k1, Rg5, R k3, Rh4, and 20( S)-PPD to be suitable pharmacokinetic markers of SNG due to their high exposure levels of systemic plasma. Hence, this developed approach would be a powerful tool for future in vivo investigation of various sources of notoginseng-related samples.

Optimisation of Ethanol-Reflux Extraction of Saponins from Steamed Panax notoginseng by Response Surface Methodology and Evaluation of Hematopoiesis Effect.

The present study aims to optimize the ethanol-reflux extraction conditions for extracting saponins from steamed Panax notoginseng (SPN). Four variables including the extraction time (0.5–2.5 h), ethanol concentration (50–90%), water to solid ratio (W/S, 8–16), and times of extraction (1–5) were investigated by using the Box-Behnken design response surface methodology (BBD-RSM). For each response, a second-order polynomial model with high R2 values (>0.9690) was developed using multiple linear regression analysis and the optimum conditions to maximize the yield (31.96%), content (70.49 mg/g), and antioxidant activity (EC50 value of 0.0421 mg/mL) for saponins extracted from SPN were obtained with a extraction time of 1.51 h, ethanol concentration of 60%, extraction done 3 times, and a W/S of 10. The experimental values were in good consistency with the predicted ones. In addition, the extracted SPN saponins could significantly increase the levels of blood routine parameters compared with the model group (p < 0.01) and there was no significant difference in the hematopoiesis effect between the SPN group and the SPN saponins group, of which the dose was 15 times lower than the former one. It is suggested that the SPN saponins extracted by the optimized method had similar functions of “blood tonifying” at a much lower dose.

Chemical and bioactive comparison of Panax notoginseng root and rhizome in raw and steamed forms

BackgroundThe root and rhizome are historically and officially utilized medicinal parts of Panax notoginseng (PN) (Burk.) F. H. Chen, which in raw and steamed forms are used differently in practice. MethodsTo investigate the differences in chemical composition and bioactivities of PN root and rhizome between raw and steamed forms, high-performance liquid chromatography analyses and pharmacologic effects evaluated by tests of anticoagulation, antioxidation, hemostasis, antiinflammation, and hematopoiesis were combined. ResultsWith the duration of steaming time, the contents of ginsenosides Rg1, Re, Rb1, Rd, and notoginsenoside R1 in PN were decreased, while those of ginsenosides Rh1, 20(S)-Rg3, 20(R)-Rg3, Rh4, and Rk3 were increased gradually. Raw PN samples steamed for 6 h at 120°C with stable levels of most constituents were used for the subsequent study of bioeffects. Raw PN showed better hemostasis, anticoagulation, and antiinflammation effects, while steamed PN exhibited stronger antioxidation and hematopoiesis activities. For different parts of PN, contents of saponins in PN rhizome were generally higher than those in the root, which could be related to the stronger bioactivities of rhizome compared with the same form of PN root. ConclusionThis study provides basic information about the chemical and bioactive comparison of PN root and rhizome in both raw and steamed forms, indicating that the change of saponins may have a key role in different properties of raw and steamed PN.

Uncovering Active Constituents Responsible for Different Activities of Raw and Steamed Panax notoginseng Roots.

Although Panax notoginseng (PN) roots in raw and steamed forms were historically supposed to be different in the efficacies, the raw materials and steamed ones were often undifferentiated in the use and market circulation, which might bring unstable curative effects or even adverse reactions. To uncover chemical constituents responsible to different activities of raw and steamed PN, chemometrics analyses including partial least squares regression (PLSR) and multi-linear regression analysis (MLRA) were used to establish the relationships between the chromatographic fingerprints and activities of PN samples. Chemical fingerprints of PN were determined by HPLC. Anticoagulant and antioxidant activities were evaluated by the thromboplastin inhibiting test and hydroxyl radical scavenging assay, respectively. Results showed that there was a significant difference in the chemical composition between raw and steamed PN, which could be discriminated by principle component analysis according to different steaming temperatures. Compared with the steamed PN, raw PN exhibited stronger anticoagulation and weaker antioxidation. By chemometrics analyses, notoginsenoside R1, ginsenosides Rg1, Re, Rb1, and Rd were found to be the major active constituents of raw PN, whereas ginsenosides Rh1, Rk3, Rh4, and 20(R)-Rg3 had the key role in the activities of steamed PN, which could be used as new markers for the quality control (QC) of steamed PN.

Identification of saponins from Panax notoginseng in metabolites of rats

UPLC-QTOF-MS/MS was used to identify metabolites in rat blood, urine and feces after the administration of n-butanol extract derived from steamed notoginseng. The metabolic process of saponins came from steamed notoginseng was analyzed. The metabolites were processed by PeakView software, and identified according to the structural characteristics of prototype compounds and the accurate qualitative and quantitative changes of common metabolic pathways. Four saponins metabolites were identified based on MS/MS information of metabolites, namely ginsenoside Rh₄, Rk₃, Rk₁, Rg₅,and their 15 metabolites were verified. The metabolic pathways of the four ginsenosides in n-butanol extract included glucuronidation, desugar, sulfation, dehydromethylation, and branch loss. The metabolites of main active saponin components derived from steamed Panax notoginseng were analyzed from the perspective of qualitative analysis. And the material basis for the efficacy of steamed notoginseng was further clarified.

A new two-dimensional chromatographic method for separation of saponins from steamed Panax notoginseng

The root and rhizome of Panax notoginseng (PNG) are used as folk medicine. Recent studies have reported PNG to possess immunomodulatory, cardioprotective, hepatoprotective, anti-diabetic and anticancer activities among a host of other pharmacological effects. The main active constituents responsible for these pharmacological effects are saponins. It has also been proven that the chemical constituents of steamed PNG differs from the raw form. Traditional methods of separating individual components in crude extracts are usually tedious, almost irreproducible and time-consuming. In this study, an automated multi-step preparative separation system, known as Sepbox afforded a quick, reproducible and fast separation of saponins from PNG. With Sepbox, a total of 11 saponins of high purity were obtained in a short period of time. The separated compounds were identified as notoginsenosides R1, T5, ginsenosides Rb1, Rg1, Rg2, Rh1, Rh4, Rd, 20 (S) −Rg3 and a mixture of ginsenosides Rk1 and Rg5.

Antitumor effects of dammarane-type saponins from steamed Notoginseng.

Six dammarane-type saponins were extracted from steamed Panax notoginseng. Their chemical structures were identified spectroscopically as ginsenosides Rh1 (1), Rg1 (2), 20 (S)-Rg3 (3), 20 (R)-Rg3 (4), Rb3 (5), and Rb1 (6). Compounds (0.1-10 μM) were tested for inhibition of tumor necrosis factor-α (TNF)-induced nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) luciferase reporter activity using a human kidney 293T cell-based assay. Ginsenoside Rb3 (5) showed the most significant activity with an IC50 of 8.2 μM. This compound also inhibited the induction of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) messenger Ribonucleic acid (mRNA) in a dose-dependent manner after HepG2 cells had been treated with TNF-α (10 ng/mL).

Ultra-high performance liquid chromatography/time-of-flight mass spectrometry (UHPLC/TOFMS) for time-dependent profiling of raw and steamed Panax notoginseng

The metabolic profiles of Panax notoginseng and its associated therapeutic values are critically affected by the duration of steaming. The time-dependent steaming effect of P. notoginseng is not well-characterized and there is also no official guideline on its duration of steaming. In this paper, a UHPLC/TOFMS-based metabolomic platform was developed for the qualitative profiling of multiparametric metabolic changes of raw P. notoginseng during the steaming process. Our method was successful in discriminating the differentially processed herbs. Both the unsupervised principal component analysis (PCA) score plot ( R 2 X = 0.664, Q 2 (cum) = 0.622, and PCs = 2) and the supervised partial least square-data analysis (PLS-DA) model ( R 2 X = 0.708, R 2 Y = 0.461, and Q 2 Y = 0.271) demonstrated strong classification and clear trajectory patterns with regard to the duration of steaming. The PLS-DA model was validated for its robustness via a prediction set, confirming that the UHPLC/TOFMS metabolic profiles of the raw and differentially steamed P. notoginseng samples were highly reproducible. Based on our method, the minimum durations of steaming for the maximum production of bioactive ginsenosides such as Rg3 and Rh2 were also predicted. Our novel time-dependent metabolic profiling approach represents the paradigm shift in the quality control of P. notoginseng products.

Antiplatelet and anticoagulant effects of Panax notoginseng: Comparison of raw and steamed Panax notoginseng with Panax ginseng and Panax quinquefolium

Ethnopharmacological significance Panax notoginseng (Burk.) F. H. Chen (Araliacea) is traditionally used for its hemostatic and cardiovascular effects when raw and as a tonic when steamed. Aim of the study This study aims to compare the effects of raw and steamed Panax notoginseng, Panax ginseng C. A. Meyer and Panax quinquefolium Linn. on platelet aggregation and plasma coagulation. Materials and methods Effects on collagen-induced platelet aggregation were investigated using a platelet aggregometer, while the plasma coagulation times (prothrombin time, activated partial thromboplastin time and thrombin time) were determined using a blood coagulation analyzer. The data was corroborated with ex vivo platelet aggregation and in vivo rat bleeding time. Results Raw and steamed Panax notoginseng significantly inhibit platelet aggregation and plasma coagulation. Steamed Panax notoginseng has significantly more potent antiplatelet and anticoagulant effects than the raw extract, and the antiplatelet and anticoagulant effects increase with increasing steaming durations. Comparing the three common Panax species, Panax notoginseng has higher antiplatelet effect than Panax ginseng and Panax quinquefolium. The in vitro antiplatelet and anticoagulant effects are positively translated into a prolongation of in vivo rat bleeding time after oral administration of the raw and steamed extracts. Conclusion The results indicate that the three common Panax species affect platelet aggregation and plasma coagulation differently, with steamed Panax notoginseng showing the greatest antiplatelet and anticoagulant effects. Panax notoginseng may be a good source of lead compounds for novel antiplatelet and anticoagulant therapeutics.