Pick To:Panax notoginseng is a commonly used bulk Chinese medicinal material in China, which has rich types of chemical components, including triterpenoid saponins, flavonoids, amino acids, polysaccharides, volatile oils and other components. Traditionally, triterpenoid saponins are considered as its main pharmacodynamic components. This paper reviews the research status of Panax notoginseng from the aspects of chemical components and pharmacological effects, and on this basis, according to the quality marker of traditional Chinese medicine（quality marker，Q-Marker）Theory, explore the genetic relationship of Panax medicinal plants, and combine the research of Panax notoginseng provenance, traditional efficacy, traditional medicinal properties, etcQ-MarkerConduct forecast analysis, forecastnotoginsenosideR1, ginsenosidesRg1, ginsenosidesRe, ginsenosidesRb1, ginsenosidesRg2, ginsenosidesRd, Panax notoginseng can be used asQ-MarkerIn order to provide a scientific basis for the quality control of Panax notoginseng and the formulation of new standards.
Panax notoginseng is a plant of AraliaceaePanax notoginseng (Burk.) F. H. ChenThe dry roots and rhizomes of Panax notoginseng are warm in nature, sweet and bitter in taste, belong to the liver and stomach meridians, have the effects of dispersing blood stasis, hemostasis, detumescence and pain, and are mainly used for the treatment of traumatic bleeding, chest and abdomen tingling, tumescent pain, etc. the content determination is based on Panax notoginseng saponinR1, ginsenosidesRg1And ginsenosidesRb1Is an indicator[1]Panax notoginseng is mainly distributed in Yunnan Province of China. Modern pharmacological studies have shown that it has hemostatic, blood activating, anti-inflammatory, immunomodulatory, antioxidant, anti-tumor, neuroprotective and other effects[2]. This paper systematically summarizes and analyzes its chemical components and pharmacological effects, and based on the quality marker of traditional Chinese Medicine（quality marker，Q-Marker）The theory of Panax notoginsengQ-MarkerMake predictions for its quality control research andQ-MarkerProvide the basis for the selection of.
1 chemical composition
1.1 Saponins
Saponins are the main chemical and effective components of Panax notoginseng. Saponins in Panax notoginseng can be divided into protopanaxadiol saponins（protopanaxadiol）Protopanaxatriol saponins（protopanaxatriol）, side chain changing saponins and other types of saponins. The parent nucleus structure and compound information of protopanaxadiol saponins found in Panax notoginseng are shown in Fig1And table1， 1And table2The parent nucleus structure and compound information of side chain changing saponins are shown in Fig2And table3See the figure for the parent nucleus structure and compound information of other saponins3And table4。
1.2 flavoneClass composition
Flavonoids are one of the main effective components of Panax notoginseng, and have a variety of pharmacological activities. At present, quercetin is the flavonoid obtained from Panax notoginseng[25]The quercetin structure is shown in Fig4。
1.3 amino acid
Panax notoginseng, a non protein amino acid component, is the main hemostatic active ingredient in Panax notoginseng[26]The structure of Panax notoginseng is shown in Fig5。
1.4 PolysaccharideClass composition
The sugars in Panax notoginseng mainly contain rhamnose, xylose, glucose, high glycans, etc.Ohtanietc.[27]A polysaccharide from Panax notoginsengsanchinan A, which has the effect of activating reticuloendothelial tissue system;Gaoetc.[28]Isolated from Panax notoginseng4Polysaccharides, respectively PF3111、PF3112、PBGA11andPBGA12In recent years,Liuetc.[29]andWangetc.[30]Isolated from Panax notoginseng2The polysaccharides with pharmacological activities werePNPS-0.3、PNPS-0.5M。
1.5 Other ingredients
The above compound types are the main compound types isolated from Panax notoginseng. With the in-depth study of the chemical constituents of Panax notoginseng, some special components have also been found, such as Polyhydroxypyrazine derivatives and nucleosides. . It has been reported that there is also a protein with antibacterial activity in Panax notoginsengpananotin[31]。Panax notoginseng alkynol compounds have important significance in anti-tumor, antioxidant and other aspects. Lin Qi et al[32]Ginseng alkynol and ginseng epoxy alkynol were isolated from the petroleum ether part of Panax notoginseng for the first time. Studies have reported that in the root of Panax notoginsengβ-Sitosterol[33]。
2 pharmacological action
Panax notoginseng has two-way regulation of activating blood circulation and hemostasis and anti-inflammatory effects. Modern pharmacological studies have found that Panax notoginseng has anti-tumor, neuroprotection, hypoglycemic and other aspectsIt also has pharmacological activity. The saponins in Panax notoginseng have a wide range of pharmacological effects, including activating blood circulation, anti-inflammatory, immune regulation, anti-oxidation, anti-tumor, neuroprotection, hypoglycemic and other aspects. Panax notoginseng is the main hemostatic component in Panax notoginseng. Panax notoginseng flavonoids mainly have blood activating and anti-inflammatory effects.
2.1 Promoting blood circulationeffect
Panax notoginseng saponins（Panax notoginseng saponins，PNS）Can increase peroxisome proliferator activated receptorsγProtein expression, activating platelet phosphatidylinositol-3-Hydroxykinase（phosphatidylinositol-3-hydroxykinase，PI3K）/protein kinaseB（protein kinase B，Akt）/Endothelial nitric oxide synthase（endothelial nitric oxide synthase，eNOS）[34]. ginsenosidesRg1canInhibition of thrombin induced platelet adhesion and aggregation[35]. ginsenosidesRe（cyclic adenosinemonophosphate，cAMP）Levels, and can inhibit adenosine diphosphate induced platelet aggregation[36]. ginsenosidesRg2It has certain antiplatelet aggregation activity and has potential coagulation factorsXInhibitory activity of[37]。
Vascular endothelial growth factor（vascular endothelial growth factor，VEGF）Considered to be the strongest factor in the formation of neovascularization, ginsenosidesRg1adoptPI3K/Akt/mTORSignaling pathway upregulationVEGFTo promote angiogenesis after ischemic stroke[38]. Panax notoginseng saponinR1Can up regulate ischemic myocardium in ratsVEGFExpression, promoting angiogenesis[39]. ginsenosidesRb1Can promoteVEGFAnd other pro angiogenic factors to improve blood circulation[40]。
In addition, the blood activating effect of Panax notoginseng is also manifested in promoting the fibrinolytic system and relaxing blood vessels. GinsenosidesRg1It can increase the activity of tissue plasminogen activator, increase the activity of fibrinolytic system, and promote fibrinolysis[41]. Panax notoginseng saponinR1Can upregulate inducible nitric oxide synthase（inducible nitric oxide synthase，iNOS）The expression of nitric oxide（NO）The increased synthesis of β - lactamase suggests that its vasodilatory mechanism may be related toNOAbout[42]. ginsenosidesReCan increase the concentration ofNOTo stimulate vasodilation[43]. ginsenosidesRg1By increasingeNOSPhosphorylation, activation ofPI3K/Akt/eNOSPathway increases endogenousNORelease of[44]Quercetin has a dose-dependent and endothelium-dependent vasodilatory effect on hypertensive rats, and its vasodilatory effect is similar to that of endotheliumNOAbout[45]。
2.2 hemostasiseffect
The main hemostatic component of Panax notoginseng is Panax notoginseng. Panax notoginseng acts through interaction with plateletsα-amino-3-hydroxyl-5-methyl-4-Isoxazole propionate receptor binding regulates platelet calcium influx andcAMPSynthesis, and increases ThromboxaneA2To enhance platelet activation in a paracrine manner[46]It significantly increases the number of reticular platelets and regulates thrombopoietin and interleukin-6（interleukin-6，IL-6）[47]. Shubin et al[48]When observing the hemostatic and procoagulant effects of Panax notoginseng for injection, it was found that it could significantly shorten the bleeding time of various animal models, promote blood coagulation, and reduce capillary permeability of model animals. At the same time, it played a hemostatic role by promoting blood coagulation and inhibiting fibrinolysis.
2.3 antiinflammatoryeffect
PNSCan significantly inhibit lipopolysaccharide inducedRAW 264.7Inflammatory factors in cellsNO、iNOSAnd can downregulateRAW 264.7Cellular phosphorylated nuclear factor-κB（nuclear factor-κB，NF-κB）Expression levels, which can be regulated byiNOS-NO-NF-κBsignaling pathway， Inhibit inflammatory response[49]. Panax notoginseng saponinR1It can down regulate the level of inflammatory cytokines in diabetic nephropathy rats by inhibiting transforming growth factorβ1（transforming growth factor-β1，TGF-β1）/Smad3Signaling pathway to regulate renal fibrosis in diabetic nephropathy rats[50]. ginsenosidesRb1Can reduce intestinal ischemia/The expression of inflammatory factors in rats with reperfusion model, through the activation ofPI3K/Akt/nuclear factorE2Correlation factor2（nuclear factor E2 related factor 2，Nrf2）Signaling pathway alleviates reperfusion injury[51]. ginsenosidesRdCan be reduced byIL-1β, tumor necrosis factor-β、IL-6, cyclooxygenase-2andiNOSExpression of, inhibition ofIL-1αInduced inflammatory response of chondrocytes[52]. ginsenosidesRg1It can down regulate the expression of inflammatory cytokines induced by lipopolysaccharide and reduceTollLike receptor4、NF-κBandNODLike receptor3To alleviate lipopolysaccharide induced myocardial inflammatory response and apoptosis[53]Quercetin is able to regulateNF-κBTo exert anti-inflammatory effects[54]。
2.4 Immunomodulationeffect
Panax notoginseng has a good application prospect in the treatment of immune diseases, and saponins are the main active ingredients of its immune regulation. The study found that,PNSCan upregulate asthma in miceβInterferon secretion, inhibitionIL-4Secretion, regulationTThe differentiation of cell subsets enablesTh1/Th2Restore balance and reduce airway inflammation[55]Cytokines play an important role in body immunity,Yangetc.[56]Through experimental observation, it was found that ginsenosidesRdCan enhance concanavalin induced splenocytes in miceIL-2、γInterferonIL-4andIL-10It can induce cellular and humoral immunity.
2.5 antioxidanteffect
. Some scholars have found through pharmacological experiments that,PNSIt can inhibit the accumulation of reactive oxygen species and reduceH2O2Induced astrocyte death in rats[57]; ginsenosideRg2Can enhanceEVC-304Antioxidation of cells[58]。
2.6 Antitumoreffect
Panax notoginseng saponins can up regulate the expression of cancer cell metastasis related genes and inhibit the metastasis of breast cancer cells[59]。TGF-βSignaling plays an important role in the occurrence and metastasis of breast cancer,Smad2In willTGF-βSignal transduction from cell surface receptors to the nucleus plays a key role, GinsenosideRdCan inhibitSmad2To inhibit the metastasis of breast cancer[60]。
2.7 Neuroprotection
Zhouetc.[61]Research shows that,PNSBy regulating glutamate metabolism, inhibition ofN-methyl-D-Aspartate receptor activation alleviates chemokinesCCL2Induced memory impairment in rats. ,β-Amyloid protein（amyloid β-protein，Aβ）It has a strong neurotoxic effect and is related to the degenerative lesions of neurons. Panax notoginseng saponinR1Can inhibit neuronal cellK+Channel, improve nerve impulse conduction, improve Alzheimer's disease（Alzheimer disease，AD）Memory ability of mice[62]; amyloid precursor protein is centrally expressed at neuronal synapses, which is associated withADOccurrence is closely related to ginsenosideRg1It has neuroprotective effect and can inhibitβ-Synthesis of proteases, reducingAβTo enhance memory[63]。
2.8 Hypoglycemic effect
Chenetc.[64]findPNSCan significantly maintain heritability2Type 2 diabetes mellitusKK-AyThe glucose homeostasis in mice significantly decreased the glucose load, insulin resistance index and serum triacylglycerol level.Yangetc.[65]Research shows that,PNSCan reduceKK-AyMouse fasting blood glucose, GinsenosideRb1yesPNSIt plays a major role in reducing blood glucose.
3 Q-MarkerPrediction analysis of
3.1 Based on the specificity of chemical compositionQ-MarkerPredictive analysis
Ginseng plants are distributed in eastern North America and eastern Asia, and there are6Species,3Varieties in North America2Species[66]Besides Panax notoginseng, ginseng is a commonly used medicinal plantP. ginseng C. A. Mey, American ginsengP. quinquefolius L., Panax japonicusP. japonicus C. A. Meyer. var. major (Burk.) C. Y. Wu et K. M. Frng, Panax japonicusP. japonicus (T. Nees) C. A. Mey.The formation of "specificity" of components is closely related to plant phylogeny, biosynthetic pathways of secondary metabolites, geographical distribution, medicinal parts, etc.
The types and existing rules of chemical components in ginseng are related to its phylogeny, origin and evolution, and geographical distribution. The taxa closely related to the ancestor species of Panax contain the original chemical components of the genus, and are distributed in the original species conservation area of the genus; The taxa far away from the ancestral species contain the nascent (evolutionary) chemical components of the genus and are distributed in the evolutionary center or diversity center of the genus[67]It should be noted that the conservation sites of the original species may be consistent with the centers of evolution or diversity[68]The origin center of ginseng plants is located in the Taihang Mountains in China and the mountains in southern Liaoning, belonging to East Asia-The flora of North America is intermittently distributed. The Hengduan Mountains in China and the central part, Southeast Yunnan and its adjacent areas are the evolutionary centers and diversity centers of the genus[69]. Panax spp4It migrated from the original center to all parts of China and through the Bering Strait and the Korean Strait to present North America and Japan before the millennium. After that, due to the dramatic environmental changes during the ice age, most of the ginseng plants were extinct, and only the existing ginseng plant survival areas survived. The taxa that migrated to southwest China maintained the original ploidy of their ancestors, and through continuous selection and evolution, formed many species now, such as Panax notoginseng, Panax japonicus, Panax japonicus (China). Panax notoginseng is3The species that are the first to differentiate and produce; Due to the higher latitude, the taxa that migrated to the Changbai Mountains, Siberia and other places doubled their ploidy in order to adapt to environmental changes, and formed existing species, such as ginseng, American ginseng and so on, due to geographical spacing[70-73]Panax notoginseng and ginseng are relict species that grow in natural shelters, and Panax notoginseng may be older than ginseng. ; The second group is considered to be an evolutionary group, with typical plants such as Panax japonicus and Panax japonicus[74]。
The characteristic component groups of ancient groups of ginseng include：①amino acid-Panax notoginseng；②Saponins mainly composed of dammarane type tetracyclic triterpenoid saponins[66]Panax notoginseng does not contain oleanane pentacyclic triterpene saponins, which is different from ginseng and American ginseng, and Panax notoginseng contains the unique saponin component Panax notoginseng saponinsR1Et al., consensus components (ginsenosidesRg1, ginsengsaponinRe, ginsenosidesRb1）There are significant differences in the proportion[75], ginsenosidesRg1、ReWithRb1The proportion in ginseng is about1.7︰1︰1.5, the proportion in American ginseng is about0.2︰1︰1.2, the proportion in Panax notoginseng is about8︰1︰7The content of Panax notoginseng in Panax notoginseng is the highest, followed by ginseng, and American ginseng is the lowest[76]。
PNSGinsenoside is the main component ofRb1, ginsenosidesRg1, NotoginsenosideR1Isodammarane type tetracyclic triterpenoid saponins. At present, the biosynthetic pathway of dammarane type tetracyclic triterpenoid saponins in plants has been preliminarily understood. Studies suggest that the synthesis of dammarane type tetracyclic triterpenoid saponins in plants is mainly through acetic acid/Mevalonate pathway [77], see Fig6. generally, it can be divided into3Stages: ① synthesis of isopentenyl pyrophosphate（isopentenyldiphosphate，IPP）And dimethylallyl pyrophosphate（dimethylallylpyrophosphate，DMAPP）; ② Catalyzed by isopentenyl transferases and terpene cyclasesIPPandDMAPPformation2,3-Squalene oxide; 2,3-Oxidized squalene is cyclized, hydroxylated, and glycosylated to form triterpenoid saponins, but the glycosylation steps remain to be identified. At present, it has been identified that Panax notoginseng8Saponins (Panax notoginseng saponinsR1, ginsenosidesRg1、Rd、Rb1、F1、Rh2、CK、Rg3）Glycosyltransferases of biosynthetic pathways（pn3-29、pn3-31、pn3-32、pn3-32-i5Et al.)[78]Panax notoginseng is mainly distributed in Lathyrus, ginseng and other plants. Previous studies have shown that LathyrusLathyrussativus L.Panax notoginseng fromβ-differentOxazoline -5-Ketoalanine synthesis. While it was not detected in Panax notoginsengβ-differentOxazoline -5-The precursor of ketoalanine is heteroAzole-5-Ketone, indicating that the biosynthesis of notoginseng in Panax notoginseng may be different from Lathyrus sativus[79]The potential synthesis pathway of Panax notoginseng in Panax notoginseng is shown in Fig7. it can be seen that NotoginsenosideR1, ginsenosidesRg1, ginsenosidesRb1And Panax notoginseng are in the downstream position of the biogenic pathway, with strong specificity.
The biosynthesis of secondary metabolites in medicinal plants has tissue and organ specificity. Panax notoginseng is the root and rhizome of its original plant, of which the main root is the main clinical medicinal part. In addition, the medicinal parts of Panax notoginseng also include lateral roots and fibrous roots. In addition, Panax notoginseng leaves and flowers are also used in folk. The above ground part of Panax notoginseng is mainly protopanaxadiol saponin, while the underground part is mainly protopanaxatriol saponin, and Panax notoginseng saponinR1Is a characteristic ingredient[80-81]。
Through the analysis of component specificity, Panax notoginseng saponins and Panax notoginseng saponins wereR1, ginsenosidesRg1, ginsenosidesRe, ginsenosidesRb1As Panax notoginsengQ-MarkerSelected objects for.
3.2 Based on the evidence of chemical composition and effectivenessQ-MarkerPredictive analysis
3.2.1 Correlation between chemical composition and traditional efficacy Traditional efficacy (functional indications) is the generalization of the effectiveness of traditional Chinese medicine and the basis of clinical medication.Q-MarkerAs the main index to evaluate and control the effectiveness of traditional Chinese medicine, it must be combined with the effectiveness. Panax notoginseng has the effects of dispersing blood stasis, hemostasis, detumescence and pain relief. notoginsenosideR1, ginsenosidesRg1, ginsenosidesRb1, ginsenosidesRg2, ginsenosidesRdSaponins have the effects of dilating blood vessels, inhibiting platelet aggregation, prolonging coagulation time, and anti-inflammatory. Panax notoginseng is the main active ingredient of Panax notoginseng to exert hemostatic effect. Quercetin has blood activating and anti-inflammatory effects. Therefore, Panax notoginsengPanax notoginseng, quercetin, Panax notoginseng saponins inR1, ginsenosidesRg1, ginsenosidesRb1, ginsenosidesRg2, ginsenosidesRdAvailable asQ-MarkerThe main choice of.
3.2.2 Correlation between chemical composition and traditional medicinal properties Property is one of the core contents of the basic attributes and effectiveness of traditional Chinese medicine, which should also beQ-MarkerOne of the basis for determination. 《Chinese Pharmacopoeia》2020Annual EditionThe nature of Panax notoginseng is sweet, slightly bitter and warm; Return to liver and stomach channels. Sweet "can be tonic, slow, and harmonious", and bitter "can be cathartic, dry, and firm". Chang Xuehui et al[82]It is believed that sweet drugs contain glycosides, amino acids and other components, which correspond to saponins and amino acids in Panax notoginseng. Yanyongqing et al[83]Through research460According to the chemical constituents of commonly used bitter traditional Chinese medicine, it was found that bitter traditional Chinese medicine contained alkaloids, followed by terpenoids and glycosides, which corresponded to saponins in Panax notoginseng. [84]According to the analysis of chemical components in guiganjing traditional Chinese medicine, flavonoids, organic acids, volatile oils, terpenes, glycosides, alkaloids, sugars are the main components of guiganjing traditional Chinese medicine. According to the above analysis, saponins, amino acids and flavonoids in Panax notoginseng should be the main material basis of its "flavor" and should also beQ-MarkerThe main choice of.
3.3 Based on the measurability of chemical compositionQ-MarkerPredictive analysis
The measurability of chemical composition is alsoQ-MarkerImportant basis for determination. 《Chinese Pharmacopoeia》2020Ginsenosides in Panax notoginsengRg1, ginsenosidesRb1And Panax notoginseng saponinsR1Determination method and limit requirements of[1]. zhenglihua et al[85]HPLC was used to determine the content of total saponins of Panax notoginseng5Components (NotoginsenosideR1, ginsenosidesRg1, ginsenosidesRe, ginsenosidesRb1And ginsenosidesRd）A simultaneous assay was performed. Cuixiuming et al[86]adoptHPLCObjective to analyze the content of Panax notoginseng and its different parts in different producing areas, different specifications, different harvest times. In conclusion, saponins and notoginseng in Panax notoginseng can be quantitatively detected by certain analytical methods. Q-MarkerAccording to the differences of different chemical compositions, the specific determination method should be established to provide a scientific basis for the establishment of quality evaluation standards.
4 epilogue
Panax notoginseng is collected in the herbal works of past dynasties and various editions of Chinese Pharmacopoeia. It has a wide range of pharmacological activities. In recent years, great progress has been made in the research of Panax notoginseng. Its various medicinal values make its development and utilization promising. Panax notoginseng is a commonly used bulk Chinese herbal medicine in China. The market demand is increasing, and adulteration of Panax notoginseng occurs from time to time in the market. .
The quality of traditional Chinese medicine reflects and characterizes the effectiveness and safety of traditional Chinese medicine, which is an important basis for the clinical use of traditional Chinese medicine and the effectiveness control of Chinese patent medicine. In this paper, the chemical constituents, pharmacological effects2This paper summarizes the research status of Panax notoginseng from three aspects. Based on the review of chemical components and pharmacological effects, traditional Chinese MedicineQ-MarkerAccording to the phylogenetic relationship of Panax species and the biogenic pathway of secondary metabolites, effective components, components related to drug properties, and measurable components of Panax notoginsengQ-MarkerThe screening and determination of were performed by literature analysis for itsQ-MarkerOf which Panax notoginseng saponinsR1, ginsenosidesRg1, ginsenosidesRe, ginsenosidesRb1, ginsenosidesRg2, ginsenosidesRdAnd Panax notoginseng can be considered as candidates for Panax notoginsengQ-Marker。
References (omitted) chart(omitted) common original documents.
Come ; Jun, Lin Juan, Zhang Hongbing, hanyanqi, wangdeqin, lichuyuan, liuchangxiao. Research progress and quality marker prediction analysis of Panax notoginseng [J] . Chinese herbal medicine, 2021, 52 (9): 2733-2745
