Compound Monograph

Notoginsenoside R1

Terpenoids Saponins Natural (plant-derived)

Notoginsenoside R1 (NGR1) is the signature saponin of notoginseng (Panax notoginseng / San Qi) — a protopanaxatriol-type dammarane found in essentially no other Panax species, which makes it the herb's authentication marker. It is the standardised component of the widely used Chinese cardiovascular injectables Xuesaitong and Xueshuantong, with a large but almost entirely preclinical anti-ischemic, endothelial-protective and neuroprotective literature; the human evidence is for the Panax notoginseng saponin (PNS) mixture, not isolated NGR1 taken by mouth.

Sources · 1

Where Does It Come From?

Notoginsenoside R1 is a naturally occurring dammarane triterpenoid saponin (protopanaxatriol group), found in Notoginseng. It is well tolerated orally (low toxicity).

Concentration

Content by Source

Reported concentrations across the plants that contain notoginsenoside R1 — the bar marks the typical level, the line shows the reported range.

Typical level Reported range % of total saponins

Literature figures for varying plant parts and preparations. Read them as a comparative guide, not exact assays.

Notoginsenoside R1 at a Glance

Notoginsenoside R1 (NGR1) is a dammarane triterpenoid saponin of the protopanaxatriol (PPT) group and the single most characteristic molecule of notoginseng (Panax notoginseng), the Chinese circulatory and trauma herb known as San Qi or Tian Qi. Unlike the ginsenosides it sits beside, NGR1 is found in essentially no other Panax species, so analysts use it as the botanical authentication marker that separates genuine notoginseng from Asian or American ginseng 1,2Reference 1Wang T et al. · 2016ReviewTraditional uses, botany, phytochemistry, pharmacology and toxicology of Panax notoginseng (Burk.) F.HView study →Reference 2Wang Q et al. · 2000Wang Q, Jiang YQ, Ma SP, Dang XD. (2000). [Determination of notoginsenoside R1 in radix notoginseng by HPLC-ELSD]. Zhongguo Zhong Yao Za Zhi (China Journal of Chinese Materia Medica). https://pubmed.ncbi.nlm.nih.gov/12516453/View study →.

Its research reputation is built on the cardiovascular and cerebrovascular system: in cell and rodent models NGR1 is anti-ischemic, endothelial-protective, antioxidant and anti-apoptotic, and it is the standardised saponin in the widely used Chinese injectables Xuesaitong and Xueshuantong 1,3,17Reference 1Wang T et al. · 2016ReviewTraditional uses, botany, phytochemistry, pharmacology and toxicology of Panax notoginseng (Burk.) F.HView study →Reference 3Yu Y et al. · 2016Cardioprotective effects of Notoginsenoside R1 against ischemia/reperfusion injuries by regulating oxidative stress- and endoplasmic reticulum stress-related signaling pathwaysView study →Reference 17Tong Q et al. · 2019Systematic reviewNotoginsenoside R1 for Organs Ischemia/Reperfusion Injury: A Preclinical Systematic ReviewView study →. The honest framing runs through this whole page: the substantial human clinical evidence belongs to the Panax notoginseng saponin (PNS) mixture given by injection — not to isolated NGR1 swallowed as a molecule 18,19Reference 18Feng L et al. · 2021Clinical trialEfficacy and Safety of Panax Notoginseng Saponins (Xueshuantong) in Patients With Acute Ischemic Stroke (EXPECT) Trial: Rationale and DesignView study →Reference 19Chen P et al. · 2024Meta-analysisEfficacy and safety of Panax notoginseng saponin injection in the treatment of acute myocardial infarction: a systematic review and meta-analysis of randomized controlled trialsView study →.

That distinction is not a technicality. NGR1 is very poorly absorbed by mouth (rat oral bioavailability well under 1%), which is exactly why the clinically studied products are injectables and why in-vitro potency cannot be assumed to reach human tissue after an oral dose 15,16Reference 15Zhang S et al. · 2019AnimalDose-dependent exposure profile and metabolic characterization of notoginsenoside R1 in rat plasma by ultra-fast liquid chromatography-electrospray ionization-tandem mass spectrometryView study →Reference 16Wen C et al. · 2025ReviewPharmacokinetics and Biological Activities of Notoginsenoside R1: A Systematical ReviewView study →.

The Notoginseng Marker

Notoginseng’s traditional reputation is a paradox that Chinese medicine states plainly: San Qi is the “wonder herb for blood” because it can both stop bleeding and move stagnant blood — hemostatic and circulation-promoting at once 1Reference 1Wang T et al. · 2016ReviewTraditional uses, botany, phytochemistry, pharmacology and toxicology of Panax notoginseng (Burk.) F.HView study →. The molecule most tied to the blood-stopping half is not a saponin at all but the non-protein amino acid dencichine; the saponins, including NGR1, sit on the blood-moving, anti-ischemic and vasoprotective side of that ledger 1Reference 1Wang T et al. · 2016ReviewTraditional uses, botany, phytochemistry, pharmacology and toxicology of Panax notoginseng (Burk.) F.HView study →.

What makes NGR1 special is its specificity to the plant. The root of P. notoginseng is one of the most saponin-rich members of the ginseng family — roughly 12% total dammarane saponins by dry weight — and three of those dominate as official quality markers: ginsenoside Rg1, ginsenoside Rb1 and notoginsenoside R1 1Reference 1Wang T et al. · 2016ReviewTraditional uses, botany, phytochemistry, pharmacology and toxicology of Panax notoginseng (Burk.) F.HView study →. Rg1 and Rb1 are shared with Asian ginseng and American ginseng; NGR1 is not. Because it is effectively absent from the other Panax species, its presence (and the R1:Rg1:Rb1 fingerprint) is used to confirm true San Qi and detect adulteration — for instance substitution of cheaper Panax material, or of leaf/flower for root 1,2Reference 1Wang T et al. · 2016ReviewTraditional uses, botany, phytochemistry, pharmacology and toxicology of Panax notoginseng (Burk.) F.HView study →Reference 2Wang Q et al. · 2000Wang Q, Jiang YQ, Ma SP, Dang XD. (2000). [Determination of notoginsenoside R1 in radix notoginseng by HPLC-ELSD]. Zhongguo Zhong Yao Za Zhi (China Journal of Chinese Materia Medica). https://pubmed.ncbi.nlm.nih.gov/12516453/View study →. A dedicated HPLC-ELSD assay for NGR1 in Radix Notoginseng was published as early as 2000, and NGR1 remains one of the five saponins routinely quantified in modern pharmacopoeial quality control 2Reference 2Wang Q et al. · 2000Wang Q, Jiang YQ, Ma SP, Dang XD. (2000). [Determination of notoginsenoside R1 in radix notoginseng by HPLC-ELSD]. Zhongguo Zhong Yao Za Zhi (China Journal of Chinese Materia Medica). https://pubmed.ncbi.nlm.nih.gov/12516453/View study →.

So NGR1 plays two roles at once: a pharmacologically active saponin and a chemical passport for the herb it comes from.

Notoginsenoside R1 in Cardiovascular & Cerebrovascular Injectables

The reason NGR1 matters clinically is that it is a standardised component of Panax notoginseng saponin (PNS) injectables — the Chinese hospital products marketed as Xuesaitong, Xueshuantong and related preparations (also incorporated into oral formulas such as Naoxintong) 1,18Reference 1Wang T et al. · 2016ReviewTraditional uses, botany, phytochemistry, pharmacology and toxicology of Panax notoginseng (Burk.) F.HView study →Reference 18Feng L et al. · 2021Clinical trialEfficacy and Safety of Panax Notoginseng Saponins (Xueshuantong) in Patients With Acute Ischemic Stroke (EXPECT) Trial: Rationale and DesignView study →. These are PNS mixtures, standardised to a saponin profile in which NGR1 is a defined minor component alongside Rg1, Rb1, Rd and Re — not isolated-NGR1 drugs.

Given by injection, PNS bypasses the gut-absorption problem that cripples the oral saponins, and the human evidence is meaningful at the mixture level:

  • Ischemic stroke. PNS injectables (Xueshuantong/Xuesaitong) are among the most-studied traditional-medicine adjuncts for acute ischemic stroke; the multicentre, randomised, placebo-controlled EXPECT trial was designed specifically to test PNS (Xueshuantong) in acute ischemic stroke, and multiple randomised trials and meta-analyses report improved neurological-deficit and daily-living scores when PNS is added to standard care 18Reference 18Feng L et al. · 2021Clinical trialEfficacy and Safety of Panax Notoginseng Saponins (Xueshuantong) in Patients With Acute Ischemic Stroke (EXPECT) Trial: Rationale and DesignView study →.
  • Acute myocardial infarction. A 2024 systematic review and meta-analysis of 20 randomised trials (1,881 patients) found PNS injection, added to conventional treatment, improved the total effective rate and reduced major adverse cardiac events and infarct-related markers versus conventional treatment alone 19Reference 19Chen P et al. · 2024Meta-analysisEfficacy and safety of Panax notoginseng saponin injection in the treatment of acute myocardial infarction: a systematic review and meta-analysis of randomized controlled trialsView study →.

The load-bearing caveat: these are trials of the injected mixture, where NGR1 is one saponin among several and cannot be credited individually, and where the delivery route is the opposite of the poorly-absorbed oral molecule. NGR1’s own contribution — anti-ischemic, endothelial-protective, antioxidant, anti-thrombotic — is characterised in cells and animals 3,4,17Reference 3Yu Y et al. · 2016Cardioprotective effects of Notoginsenoside R1 against ischemia/reperfusion injuries by regulating oxidative stress- and endoplasmic reticulum stress-related signaling pathwaysView study →Reference 4Zeng JJ et al. · 2023AnimalNotoginsenoside R1 protects against myocardial ischemia/reperfusion injury in mice via suppressing TAK1-JNK/p38 signalingView study →Reference 17Tong Q et al. · 2019Systematic reviewNotoginsenoside R1 for Organs Ischemia/Reperfusion Injury: A Preclinical Systematic ReviewView study →. And the traditional hemostatic action that gives San Qi its fame is largely a different constituent’s story (dencichine), so an “anti-thrombotic + blood-stopping” herb is not a contradiction inside a single molecule — it is two different molecules doing two different jobs 1Reference 1Wang T et al. · 2016ReviewTraditional uses, botany, phytochemistry, pharmacology and toxicology of Panax notoginseng (Burk.) F.HView study →.

A Protopanaxatriol Saponin

NGR1 belongs to the protopanaxatriol (PPT) branch of the dammarane saponins, the same aglycone family as ginsenoside Rg1 and Re. This matters for two reasons.

PPT vs. PPD. Dammarane ginsenosides split into two aglycone skeletons: protopanaxatriol (PPT) — Rg1, Re, NGR1 — and protopanaxadiol (PPD) — Rb1, Rc, Rd, Rg3, broadly the protopanaxadiol group. The two branches differ in hydroxylation, sugar attachment, absorption and, often, in the direction of their reported effects; NGR1 is a PPT-type saponin carrying an extra sugar relative to Rg1 1Reference 1Wang T et al. · 2016ReviewTraditional uses, botany, phytochemistry, pharmacology and toxicology of Panax notoginseng (Burk.) F.HView study →.

The bioavailability problem is real for NGR1. Like its PPT sibling Rg1, NGR1 is a large, multiply-glycosylated saponin that crosses the gut wall very badly — measured rat oral bioavailability is on the order of 0.25–0.29% in one careful UFLC-MS study, with poor Caco-2 permeability implying <1% absorption in humans 15,16Reference 15Zhang S et al. · 2019AnimalDose-dependent exposure profile and metabolic characterization of notoginsenoside R1 in rat plasma by ultra-fast liquid chromatography-electrospray ionization-tandem mass spectrometryView study →Reference 16Wen C et al. · 2025ReviewPharmacokinetics and Biological Activities of Notoginsenoside R1: A Systematical ReviewView study →. This is why the clinically used products are injectables, and why isolate-vs-plant honesty here also has to be isolate-vs-mixture honesty: almost none of the in-vitro pharmacology has been shown to occur after an oral dose of the pure molecule, and the human data are the injected PNS mixture, not oral NGR1 15,16,18Reference 15Zhang S et al. · 2019AnimalDose-dependent exposure profile and metabolic characterization of notoginsenoside R1 in rat plasma by ultra-fast liquid chromatography-electrospray ionization-tandem mass spectrometryView study →Reference 16Wen C et al. · 2025ReviewPharmacokinetics and Biological Activities of Notoginsenoside R1: A Systematical ReviewView study →Reference 18Feng L et al. · 2021Clinical trialEfficacy and Safety of Panax Notoginseng Saponins (Xueshuantong) in Patients With Acute Ischemic Stroke (EXPECT) Trial: Rationale and DesignView study →.

What It's Used For

NGR1’s preclinical profile is broad and internally consistent — anti-ischemic across several organs, converging on antioxidant, anti-apoptotic and anti-inflammatory signalling, frequently routed through estrogen receptors (NGR1 behaves as a phytoestrogen). The discipline of the compound page is the recurring caveat: almost all of it is cell and rodent work on the isolated molecule, and the human efficacy data are the PNS injectable mixture, not oral NGR1 15,16,17Reference 15Zhang S et al. · 2019AnimalDose-dependent exposure profile and metabolic characterization of notoginsenoside R1 in rat plasma by ultra-fast liquid chromatography-electrospray ionization-tandem mass spectrometryView study →Reference 16Wen C et al. · 2025ReviewPharmacokinetics and Biological Activities of Notoginsenoside R1: A Systematical ReviewView study →Reference 17Tong Q et al. · 2019Systematic reviewNotoginsenoside R1 for Organs Ischemia/Reperfusion Injury: A Preclinical Systematic ReviewView study →.

A genuine, multi-organ anti-ischemia signal (preclinical):isolated NGR1 reduces injury in myocardial, cerebral, renal and intestinal ischemia–reperfusion models, pooled in a preclinical systematic review of 25 studies — mainly through antioxidant, anti-apoptotic and anti-inflammatory mechanisms 17Reference 17Tong Q et al. · 2019Systematic reviewNotoginsenoside R1 for Organs Ischemia/Reperfusion Injury: A Preclinical Systematic ReviewView study →.
A phytoestrogen mechanism runs through much of it:several of NGR1’s protective effects (cerebral I/R, neonatal hypoxic-ischemia, diabetic cardiomyopathy) are abolished by the estrogen-receptor blocker ICI-182,780, marking ERα/ERβ-dependent activation of Akt/Nrf2 and related pathways 6,7,9Reference 6Meng X et al. · 2014Suppression of NADPH oxidase- and mitochondrion-derived superoxide by Notoginsenoside R1 protects against cerebral ischemia-reperfusion injury through estrogen receptor-dependent activation of Akt/Nrf2 pathwaysView study →Reference 7Wang Y et al. · 2016Notoginsenoside R1 Protects against Neonatal Cerebral Hypoxic-Ischemic Injury through Estrogen Receptor-Dependent Activation of Endoplasmic Reticulum Stress PathwaysView study →Reference 9Zhang B et al. · 2018Notoginsenoside R1 Protects Against Diabetic Cardiomyopathy Through Activating Estrogen Receptor α and Its Downstream SignalingView study →.
The honest human headline:the substantial clinical evidence is for injected Panax notoginseng saponins (Xuesaitong/Xueshuantong) in ischemic stroke and myocardial infarction — a mixture, given parenterally — not isolated oral NGR1 18,19Reference 18Feng L et al. · 2021Clinical trialEfficacy and Safety of Panax Notoginseng Saponins (Xueshuantong) in Patients With Acute Ischemic Stroke (EXPECT) Trial: Rationale and DesignView study →Reference 19Chen P et al. · 2024Meta-analysisEfficacy and safety of Panax notoginseng saponin injection in the treatment of acute myocardial infarction: a systematic review and meta-analysis of randomized controlled trialsView study →.
The bioavailability catch:oral NGR1 is absorbed at well under 1% in rats, so in-vitro potency should not be read as an achievable oral human effect 15,16Reference 15Zhang S et al. · 2019AnimalDose-dependent exposure profile and metabolic characterization of notoginsenoside R1 in rat plasma by ultra-fast liquid chromatography-electrospray ionization-tandem mass spectrometryView study →Reference 16Wen C et al. · 2025ReviewPharmacokinetics and Biological Activities of Notoginsenoside R1: A Systematical ReviewView study →.
Evidence by IndicationStrength of support · Beta

Support is an experimental score — weighted by study type (human > animal > in vitro) and volume, tempered for isolate-vs-plant/mixture match and bioavailability. A beta, not a validated metric. Every row rests on isolated NGR1 in animals or cells (the human data are the injected PNS mixture), so scores are capped accordingly. Each application links to its write-up.

Mechanisms

Target / pathwayEffectRelevant to
Estrogen receptors α/β (phytoestrogen; ICI-182,780-sensitive)upstream switch for much of the neuro/cardio protection
cerebroprotectiondiabetic cardiomyopathy
NADPH oxidase / mitochondrial superoxide → Akt/Nrf2/HO-1↓ oxidative stress, ↑ antioxidant defence
cerebroprotectioncardioprotection
Endoplasmic-reticulum stress signallingattenuated ER-stress-driven apoptosis
cardioprotectionneonatal hypoxic-ischemia
TAK1 → JNK/p38suppressed → ↓ cardiomyocyte apoptosis
myocardial I/R
JAK2/STAT3activation → cardioprotection
myocardial infarction
BDNF/Akt/CREB↑ neurogenesis after cerebral I/R
cerebroprotection
PI3K/Akt ↑, NF-κB ↓; α3β1 integrin ↑podocyte protection, ↓ proteinuria
diabetic nephropathy
Nrf2 ↑ / NLRP3 inflammasome ↓antioxidant + anti-inflammatory
diabetic encephalopathy
Ang2/Tie2pro-angiogenic, endothelial
angiogenesisvascular

The recurring theme is an antioxidant, anti-apoptotic, endothelium-protective action, unusually often routed through the estrogen receptor — a phytoestrogen mechanism that ties the cerebral, cardiac and diabetic findings together 6,7,9Reference 6Meng X et al. · 2014Suppression of NADPH oxidase- and mitochondrion-derived superoxide by Notoginsenoside R1 protects against cerebral ischemia-reperfusion injury through estrogen receptor-dependent activation of Akt/Nrf2 pathwaysView study →Reference 7Wang Y et al. · 2016Notoginsenoside R1 Protects against Neonatal Cerebral Hypoxic-Ischemic Injury through Estrogen Receptor-Dependent Activation of Endoplasmic Reticulum Stress PathwaysView study →Reference 9Zhang B et al. · 2018Notoginsenoside R1 Protects Against Diabetic Cardiomyopathy Through Activating Estrogen Receptor α and Its Downstream SignalingView study →.

Pharmacokinetics

Poor oral bioavailability is the load-bearing fact, and it shapes how the whole molecule is used. As a large, multiply-glycosylated PPT saponin, NGR1 is highly water-soluble but crosses the intestinal wall badly: a dose-ranging UFLC-MS study in rats measured oral bioavailability at roughly 0.25–0.29% with a terminal half-life over ~8 h, and characterised seven metabolites formed chiefly by stepwise deglycosylation 15Reference 15Zhang S et al. · 2019AnimalDose-dependent exposure profile and metabolic characterization of notoginsenoside R1 in rat plasma by ultra-fast liquid chromatography-electrospray ionization-tandem mass spectrometryView study →. A systematic PK review reaches the same conclusion — low, dose-independent oral exposure and poor membrane permeability, with <1% absorption implied for humans — and notes that nanoparticle/formulation strategies are being explored precisely because the free molecule is so poorly absorbed 16Reference 16Wen C et al. · 2025ReviewPharmacokinetics and Biological Activities of Notoginsenoside R1: A Systematical ReviewView study →. The practical consequences are two: (1) the clinically studied products are injectables (PNS: Xuesaitong/Xueshuantong), which bypass the absorption barrier; and (2) in-vitro and injected-animal potency must not be read as what an oral dose delivers to human tissue 15,16Reference 15Zhang S et al. · 2019AnimalDose-dependent exposure profile and metabolic characterization of notoginsenoside R1 in rat plasma by ultra-fast liquid chromatography-electrospray ionization-tandem mass spectrometryView study →Reference 16Wen C et al. · 2025ReviewPharmacokinetics and Biological Activities of Notoginsenoside R1: A Systematical ReviewView study →.

Clinical Trials

There are no controlled efficacy trials of isolated notoginsenoside R1. The human evidence is entirely at the Panax notoginseng saponin (PNS) mixture level — injectable Xueshuantong/Xuesaitong in ischemic stroke (including the multicentre placebo-controlled EXPECT trial) and acute myocardial infarction (a meta-analysis of 20 RCTs) — where NGR1 is one standardised saponin among several and cannot be credited individually 18,19Reference 18Feng L et al. · 2021Clinical trialEfficacy and Safety of Panax Notoginseng Saponins (Xueshuantong) in Patients With Acute Ischemic Stroke (EXPECT) Trial: Rationale and DesignView study →Reference 19Chen P et al. · 2024Meta-analysisEfficacy and safety of Panax notoginseng saponin injection in the treatment of acute myocardial infarction: a systematic review and meta-analysis of randomized controlled trialsView study →. The isolated-molecule literature is preclinical, pooled in a 25-study animal systematic review 17Reference 17Tong Q et al. · 2019Systematic reviewNotoginsenoside R1 for Organs Ischemia/Reperfusion Injury: A Preclinical Systematic ReviewView study →.

CompletedPlannedTerminatedPreclinical
None(isolated NGR1); PNS-mixture RCTs exist (stroke, MI)None identified (isolated NGR1)NoneExtensive(multi-organ I/R, diabetic complications)

Last checked: July 2026.

Isolate vs. Plant (and Mixture) Studies

NGR1 needs a three-way honesty, not the usual two. The mechanism evidence is the isolate: the myocardial I/R, cerebral I/R, neonatal hypoxic-ischemia, diabetic-organ and angiogenesis studies all test purified NGR1 (or NG-R1) directly in cells and rodents — a genuine, internally consistent preclinical base 3,4,6,7,9,13,17Reference 3Yu Y et al. · 2016Cardioprotective effects of Notoginsenoside R1 against ischemia/reperfusion injuries by regulating oxidative stress- and endoplasmic reticulum stress-related signaling pathwaysView study →Reference 4Zeng JJ et al. · 2023AnimalNotoginsenoside R1 protects against myocardial ischemia/reperfusion injury in mice via suppressing TAK1-JNK/p38 signalingView study →Reference 6Meng X et al. · 2014Suppression of NADPH oxidase- and mitochondrion-derived superoxide by Notoginsenoside R1 protects against cerebral ischemia-reperfusion injury through estrogen receptor-dependent activation of Akt/Nrf2 pathwaysView study →Reference 7Wang Y et al. · 2016Notoginsenoside R1 Protects against Neonatal Cerebral Hypoxic-Ischemic Injury through Estrogen Receptor-Dependent Activation of Endoplasmic Reticulum Stress PathwaysView study →Reference 9Zhang B et al. · 2018Notoginsenoside R1 Protects Against Diabetic Cardiomyopathy Through Activating Estrogen Receptor α and Its Downstream SignalingView study →Reference 13Zhong J et al. · 2020Notoginsenoside R1 activates the Ang2/Tie2 pathway to promote angiogenesisView study →Reference 17Tong Q et al. · 2019Systematic reviewNotoginsenoside R1 for Organs Ischemia/Reperfusion Injury: A Preclinical Systematic ReviewView study →. The human efficacy evidence is neither the isolate nor the simple whole plant — it is the standardised PNS mixture, given by injection (Xuesaitong/Xueshuantong), in which NGR1 is a defined minor component 18,19Reference 18Feng L et al. · 2021Clinical trialEfficacy and Safety of Panax Notoginseng Saponins (Xueshuantong) in Patients With Acute Ischemic Stroke (EXPECT) Trial: Rationale and DesignView study →Reference 19Chen P et al. · 2024Meta-analysisEfficacy and safety of Panax notoginseng saponin injection in the treatment of acute myocardial infarction: a systematic review and meta-analysis of randomized controlled trialsView study →. And the whole herb (powdered San Qi root) is a third thing again, carrying the saponins plus the hemostatic amino acid dencichine and other constituents 1Reference 1Wang T et al. · 2016ReviewTraditional uses, botany, phytochemistry, pharmacology and toxicology of Panax notoginseng (Burk.) F.HView study →. The correct read: strong isolate mechanism + meaningful clinical evidence for the injected mixture + a traditional whole-root practice — three evidence bases that are not interchangeable, bridged only loosely because oral NGR1 is barely absorbed 15,16Reference 15Zhang S et al. · 2019AnimalDose-dependent exposure profile and metabolic characterization of notoginsenoside R1 in rat plasma by ultra-fast liquid chromatography-electrospray ionization-tandem mass spectrometryView study →Reference 16Wen C et al. · 2025ReviewPharmacokinetics and Biological Activities of Notoginsenoside R1: A Systematical ReviewView study →.

Prevalence in Nature

NGR1 is, for practical purposes, a single-species molecule. It is a principal saponin of Panax notoginseng root — about 10% of the root’s total saponins, which themselves run near 12% of the dried root — but it is not a meaningful constituent of Panax ginseng (Asian ginseng) or Panax quinquefolius (American ginseng) 1Reference 1Wang T et al. · 2016ReviewTraditional uses, botany, phytochemistry, pharmacology and toxicology of Panax notoginseng (Burk.) F.HView study →. That near-exclusivity is the whole basis of its use as an authentication marker: finding NGR1 (and the R1/Rg1/Rb1 fingerprint) is chemical evidence that the material is true San Qi rather than a cheaper Panax substitute 1,2Reference 1Wang T et al. · 2016ReviewTraditional uses, botany, phytochemistry, pharmacology and toxicology of Panax notoginseng (Burk.) F.HView study →Reference 2Wang Q et al. · 2000Wang Q, Jiang YQ, Ma SP, Dang XD. (2000). [Determination of notoginsenoside R1 in radix notoginseng by HPLC-ELSD]. Zhongguo Zhong Yao Za Zhi (China Journal of Chinese Materia Medica). https://pubmed.ncbi.nlm.nih.gov/12516453/View study →. Within the plant, the saponin profile varies with plant part (root vs. leaf vs. flower), age and processing (raw vs. steamed), but the root is the drug and the marker source 1Reference 1Wang T et al. · 2016ReviewTraditional uses, botany, phytochemistry, pharmacology and toxicology of Panax notoginseng (Burk.) F.HView study →.

Discovery & Synthesis

Notoginsenoside R1 was isolated and characterised from the root of Panax notoginseng during the phytochemical work that mapped the herb’s dammarane saponins, and it took its name from the plant (notoginseng) — the “R1” following the ginsenoside-style saponin nomenclature 1Reference 1Wang T et al. · 2016ReviewTraditional uses, botany, phytochemistry, pharmacology and toxicology of Panax notoginseng (Burk.) F.HView study →. Its practical debut in analytical chemistry came with quality-control methods: a dedicated HPLC-ELSD assay for NGR1 in Radix Notoginseng was published in 2000, formalising the molecule’s role as a marker 2Reference 2Wang Q et al. · 2000Wang Q, Jiang YQ, Ma SP, Dang XD. (2000). [Determination of notoginsenoside R1 in radix notoginseng by HPLC-ELSD]. Zhongguo Zhong Yao Za Zhi (China Journal of Chinese Materia Medica). https://pubmed.ncbi.nlm.nih.gov/12516453/View study →. There is no commercially important total synthesis: NGR1 is obtained by extraction and chromatographic purification from notoginseng root (the same material that feeds the PNS injectables), because the plant is a rich and specific source and de-novo synthesis of a multiply-glycosylated dammarane saponin is not competitive with extraction 1,16Reference 1Wang T et al. · 2016ReviewTraditional uses, botany, phytochemistry, pharmacology and toxicology of Panax notoginseng (Burk.) F.HView study →Reference 16Wen C et al. · 2025ReviewPharmacokinetics and Biological Activities of Notoginsenoside R1: A Systematical ReviewView study →.

Patents: not yet researched.

Toxicity & Safety

Isolated NGR1 carries a low toxicity flag. It is a saponin with low acute toxicity in animal studies, and its very poor oral absorption keeps systemic exposure low after ingestion, further limiting the chance of reaching harmful levels by mouth 15,16Reference 15Zhang S et al. · 2019AnimalDose-dependent exposure profile and metabolic characterization of notoginsenoside R1 in rat plasma by ultra-fast liquid chromatography-electrospray ionization-tandem mass spectrometryView study →Reference 16Wen C et al. · 2025ReviewPharmacokinetics and Biological Activities of Notoginsenoside R1: A Systematical ReviewView study →. The meaningful safety context is not the pure molecule at all but the route and the mixture:

Safety at a Glance
Low / no toxicity
  • Low acute toxicity for the isolate. A poorly-absorbed dammarane saponin; oral exposure to the free molecule is low, and preclinical work reports a wide safety margin 15,16Reference 15Zhang S et al. · 2019AnimalDose-dependent exposure profile and metabolic characterization of notoginsenoside R1 in rat plasma by ultra-fast liquid chromatography-electrospray ionization-tandem mass spectrometryView study →Reference 16Wen C et al. · 2025ReviewPharmacokinetics and Biological Activities of Notoginsenoside R1: A Systematical ReviewView study →.
  • Bleeding/antiplatelet caution belongs to the herb & PNS products, not the isolate. Notoginseng and its saponins influence platelets and circulation; caution with anticoagulant/antiplatelet drugs and around surgery is a whole-herb / PNS consideration 1Reference 1Wang T et al. · 2016ReviewTraditional uses, botany, phytochemistry, pharmacology and toxicology of Panax notoginseng (Burk.) F.HView study →.
  • Human data are for injected PNS, not oral NGR1. Efficacy and adverse-event information come from the standardised Panax notoginseng saponin mixture given parenterally (Xuesaitong/Xueshuantong), where injection-related reactions belong to the product, not to isolated NGR1 18,19Reference 18Feng L et al. · 2021Clinical trialEfficacy and Safety of Panax Notoginseng Saponins (Xueshuantong) in Patients With Acute Ischemic Stroke (EXPECT) Trial: Rationale and DesignView study →Reference 19Chen P et al. · 2024Meta-analysisEfficacy and safety of Panax notoginseng saponin injection in the treatment of acute myocardial infarction: a systematic review and meta-analysis of randomized controlled trialsView study →.
  • Phytoestrogen activity. NGR1 acts through estrogen receptors in several models; a theoretical consideration in hormone-sensitive conditions, though no human signal is established for the isolate 6,9Reference 6Meng X et al. · 2014Suppression of NADPH oxidase- and mitochondrion-derived superoxide by Notoginsenoside R1 protects against cerebral ischemia-reperfusion injury through estrogen receptor-dependent activation of Akt/Nrf2 pathwaysView study →Reference 9Zhang B et al. · 2018Notoginsenoside R1 Protects Against Diabetic Cardiomyopathy Through Activating Estrogen Receptor α and Its Downstream SignalingView study →.

Pregnancy/lactation is a per-herb / per-supplement decision and is not adjudicated on this molecule page; notoginseng the herb is traditionally avoided in pregnancy for its blood-moving activity, and no isolate-specific reproductive dataset exists for NGR1 1Reference 1Wang T et al. · 2016ReviewTraditional uses, botany, phytochemistry, pharmacology and toxicology of Panax notoginseng (Burk.) F.HView study →.

Dosage

There is no established human dose of isolated notoginsenoside R1. Efficacy figures come only from preclinical work — rodent cardio- and neuroprotection studies typically dose NGR1 in the low milligrams-per-kilogram range by injection (e.g. ~25 mg/kg i.p. in mouse myocardial I/R), chosen for the experiment, not validated for people 3,4Reference 3Yu Y et al. · 2016Cardioprotective effects of Notoginsenoside R1 against ischemia/reperfusion injuries by regulating oxidative stress- and endoplasmic reticulum stress-related signaling pathwaysView study →Reference 4Zeng JJ et al. · 2023AnimalNotoginsenoside R1 protects against myocardial ischemia/reperfusion injury in mice via suppressing TAK1-JNK/p38 signalingView study →. Because oral NGR1 is absorbed at well under 1%, an oral milligram figure does not map onto delivered exposure 15,16Reference 15Zhang S et al. · 2019AnimalDose-dependent exposure profile and metabolic characterization of notoginsenoside R1 in rat plasma by ultra-fast liquid chromatography-electrospray ionization-tandem mass spectrometryView study →Reference 16Wen C et al. · 2025ReviewPharmacokinetics and Biological Activities of Notoginsenoside R1: A Systematical ReviewView study →. In practice, human intake of NGR1 happens two ways, neither of them as the isolate:

RouteFormWhat it is
Injectable (studied clinically)PNS injectables — Xuesaitong / XueshuantongStandardised Panax notoginseng saponin mixture; NGR1 a defined minor component 18,19Reference 18Feng L et al. · 2021Clinical trialEfficacy and Safety of Panax Notoginseng Saponins (Xueshuantong) in Patients With Acute Ischemic Stroke (EXPECT) Trial: Rationale and DesignView study →Reference 19Chen P et al. · 2024Meta-analysisEfficacy and safety of Panax notoginseng saponin injection in the treatment of acute myocardial infarction: a systematic review and meta-analysis of randomized controlled trialsView study →
Oral (traditional)Powdered / decocted San Qi rootWhole-herb notoginseng; saponins poorly absorbed, plus dencichine and other constituents 1Reference 1Wang T et al. · 2016ReviewTraditional uses, botany, phytochemistry, pharmacology and toxicology of Panax notoginseng (Burk.) F.HView study →

These are doses and preparations studied in research and traditional practice, and are not a personal recommendation.

References

  1. Wang T, Guo R, Zhou G, Zhou X, Kou Z, Sui F, Li C, Tang L, Wang Z. (2016). Traditional uses, botany, phytochemistry, pharmacology and toxicology of Panax notoginseng (Burk.) F.H. Chen: A review. Journal of Ethnopharmacology. https://pubmed.ncbi.nlm.nih.gov/27154405/
  2. Wang Q, Jiang YQ, Ma SP, Dang XD. (2000). [Determination of notoginsenoside R1 in radix notoginseng by HPLC-ELSD]. Zhongguo Zhong Yao Za Zhi (China Journal of Chinese Materia Medica). https://pubmed.ncbi.nlm.nih.gov/12516453/
  3. Yu Y, Sun G, Luo Y, Wang M, Chen R, Zhang J, Ai Q, Xing N, Sun X. (2016). Cardioprotective effects of Notoginsenoside R1 against ischemia/reperfusion injuries by regulating oxidative stress- and endoplasmic reticulum stress-related signaling pathways. Scientific Reports. https://pubmed.ncbi.nlm.nih.gov/26888485/
  4. Zeng JJ, Shi HQ, Ren FF, Zhao XS, Chen QY, Wang DJ, Wu LP, Chu MP, Lai TF, Li L. (2023). Notoginsenoside R1 protects against myocardial ischemia/reperfusion injury in mice via suppressing TAK1-JNK/p38 signaling. Acta Pharmacologica Sinica. https://pubmed.ncbi.nlm.nih.gov/36721009/
  5. Xu H, Zhang X, Shi Y, Yu K, Jiang Y. (2022). Notoginsenoside R1 relieves the myocardial infarction via activating the JAK2/STAT3 signaling pathway in vivo and in vitro. Bioengineered. https://pubmed.ncbi.nlm.nih.gov/35263202/
  6. Meng X, Wang M, Wang X, Sun G, Ye J, Xu H, Sun X. (2014). Suppression of NADPH oxidase- and mitochondrion-derived superoxide by Notoginsenoside R1 protects against cerebral ischemia-reperfusion injury through estrogen receptor-dependent activation of Akt/Nrf2 pathways. Free Radical Research. https://pubmed.ncbi.nlm.nih.gov/24720662/
  7. Wang Y, Tu L, Li Y, Chen D, Wang S. (2016). Notoginsenoside R1 Protects against Neonatal Cerebral Hypoxic-Ischemic Injury through Estrogen Receptor-Dependent Activation of Endoplasmic Reticulum Stress Pathways. Journal of Pharmacology and Experimental Therapeutics. https://pubmed.ncbi.nlm.nih.gov/26892460/
  8. Zhu T, Wang L, Xie W, Meng X, Feng Y, Sun G, Sun X. (2021). Notoginsenoside R1 Improves Cerebral Ischemia/Reperfusion Injury by Promoting Neurogenesis via the BDNF/Akt/CREB Pathway. Frontiers in Pharmacology. https://pubmed.ncbi.nlm.nih.gov/34025400/
  9. Zhang B, Zhang J, Zhang C, Zhang X, Ye J, Kuang S, Sun G, Sun X. (2018). Notoginsenoside R1 Protects Against Diabetic Cardiomyopathy Through Activating Estrogen Receptor α and Its Downstream Signaling. Frontiers in Pharmacology. https://pubmed.ncbi.nlm.nih.gov/30450046/
  10. Zhai Y, Meng X, Luo Y, Wu Y, Ye T, Zhou P, Ding S, Wang M, Lu S, Zhu L, Sun G, Sun X. (2018). Notoginsenoside R1 ameliorates diabetic encephalopathy by activating the Nrf2 pathway and inhibiting NLRP3 inflammasome activation. Oncotarget. https://pubmed.ncbi.nlm.nih.gov/29507694/
  11. Gui D, Wei L, Jian G, Guo Y, Yang J, Wang N. (2014). Notoginsenoside R1 ameliorates podocyte adhesion under diabetic condition through α3β1 integrin upregulation in vitro and in vivo. Cellular Physiology and Biochemistry. https://pubmed.ncbi.nlm.nih.gov/25503068/
  12. Huang G, Lv J, Li T, Huai G, Li X, Xiang S, Wang L, Qin Z, Pang J, Zou B, Wang Y. (2016). Notoginsenoside R1 ameliorates podocyte injury in rats with diabetic nephropathy by activating the PI3K/Akt signaling pathway. International Journal of Molecular Medicine. https://pubmed.ncbi.nlm.nih.gov/27571993/
  13. Zhong J, Lu W, Zhang J, Huang M, Lyu W, Ye G, Deng L, Chen M, Yao N, Li Y, Liu G, Liang Y, Fu J, Zhang D, Ye W. (2020). Notoginsenoside R1 activates the Ang2/Tie2 pathway to promote angiogenesis. Phytomedicine. https://pubmed.ncbi.nlm.nih.gov/32823242/
  14. Pei X, Zhang L, Liu D, Wu Y, Li X, Cao Y, Du X. (2023). Notoginsenoside R1 attenuates brain injury in rats with traumatic brain injury: Possible mediation of apoptosis via ERK1/2 signaling pathway. PLoS One. https://pubmed.ncbi.nlm.nih.gov/38109303/
  15. Zhang S, Ju Z, Guan H, Yu L, Wang Z, Zhao Y. (2019). Dose-dependent exposure profile and metabolic characterization of notoginsenoside R1 in rat plasma by ultra-fast liquid chromatography-electrospray ionization-tandem mass spectrometry. Biomedical Chromatography. https://pubmed.ncbi.nlm.nih.gov/31368122/
  16. Wen C, Liao X, Ye X, Lai W. (2025). Pharmacokinetics and Biological Activities of Notoginsenoside R1: A Systematical Review. The American Journal of Chinese Medicine. https://pubmed.ncbi.nlm.nih.gov/39880667/
  17. Tong Q, Zhu PC, Zhuang Z, Deng LH, Wang ZH, Zeng H, Zheng GQ, Wang Y. (2019). Notoginsenoside R1 for Organs Ischemia/Reperfusion Injury: A Preclinical Systematic Review. Frontiers in Pharmacology. https://pubmed.ncbi.nlm.nih.gov/31680976/
  18. Feng L, Han F, Zhou L, Wu S, Du Y, Zhang D, Zhang C, Gao Y. (2021). Efficacy and Safety of Panax Notoginseng Saponins (Xueshuantong) in Patients With Acute Ischemic Stroke (EXPECT) Trial: Rationale and Design. Frontiers in Pharmacology. https://pubmed.ncbi.nlm.nih.gov/33967788/
  19. Chen P, Gao Z, Guo M, Pan D, Zhang H, Du J, Shi D. (2024). Efficacy and safety of Panax notoginseng saponin injection in the treatment of acute myocardial infarction: a systematic review and meta-analysis of randomized controlled trials. Frontiers in Pharmacology. https://pubmed.ncbi.nlm.nih.gov/38576488/