Product name: Salvianolic acid D
Synonym name:
Catalogue No.: BP1250
Cas No.: 142998-47-8
Formula: C₂₀H₁₈O₁₀
Mol Weight: 418.354
Botanical Source: Salviae Miltiorrhizae Radix et Rhizoma
Physical Description:
Type of Compound: Phenylpropanoids

Purity: 95%~99%
Analysis Method: HPLC-DAD or/and HPLC-ELSD
Identification Method: Mass, NMR
Packing: Brown vial or HDPE plastic bottle

Storage: Store in a well closed container, protected from air and light. Put into refrigerate or freeze for long term storage.
Whenever possible, you should prepare and use solutions on the same day. However, if you need to make up stock solutions in advance, we recommend that you store the solution as aliquots in tightly sealed vials at -20℃. Generally, these will be useable for up to two weeks.

The product could be supplied from milligrams to grams
Inquire for bulk scale.

Description:

Salvianolic acid and notoginseng triterpenes can promote EA-hy926 and expression of protein, have protective effects on angiogenesis in EA-hy926 cells in vitro.    

References:

Acta Pharmaceutica Sinica BVolume 5, Issue 3, May 2015, Pages 246–253    

Pharmacokinetic study of salvianolic acid D after oral and intravenous administration in rats 

METHODS AND RESULTS:

A sensitive, specific and rapid LC-MS method was developed and validated for the determination of Salvianolic acid D (SalD) in rat plasma. This method used a single quadrupole mass spectrometer with an electrospray ionization (ESI) source. A single ion monitoring scanning (SIM) mode was employed. It showed good linearity over the concentration range from 3.3 to 666.7 ng/mL for the determination of Salvianolic acid D. The R.S.D.% of intra-day and inter-day precision values were no more than 7.69%, and the accuracy was within 91%−104% at all quality control levels. 

CONCLUSIONS:

This LC-MS method was applied to the pharmacokinetic study of Salvianolic acid D in rats. A two-compartmental model analysis was employed. The bioavailability of Salvianolic acid D was calculated to be 4.159%±0.517%.    

HPLC of Salvianolic acid D

HNMR of Salvianolic acid D

Storage conditions：Short-term storage at 2~8℃, long-term storage at -20 ~ -80℃

Introduction/Overview

Salvianolic acid D (CAS No.: 142998-47-8) is a polyphenolic natural product isolated from the traditional Chinese medicine Salvia miltiorrhiza. As a classic herb in traditional Chinese medicine, Danshen has been widely studied for its remarkable efficacy in cardiovascular and cerebrovascular diseases, liver diseases, and other conditions. Danphenolic acid D, as one of the important active components in Danshen, has attracted attention in recent years due to its potential antiplatelet activity and liver-protective effects. This compound not only exhibits good bioactivity, but also demonstrates superior safety and drug potential, making it a research hotspot in the fields of natural product pharmacology and new drug development.

This review aims to systematically summarize the chemical structure and physicochemical properties of Danphenolic Acid D, plant origin and extraction methods, pharmacological activity and mechanism of action, druggability evaluation, and pharmacokinetic characteristics. Combined with its molecular targets in liver protection and related diseases, it explores its clinical application prospects and future research directions, providing theoretical basis and reference for the in-depth development and application of Danphenic Acid D.

Chemical structure and physicochemical properties

Danphenolic acid D belongs to the polyphenol class of compounds, with a molecular formula of C22H18O9 and a molecular weight of 418.3540. Its structure contains multiple phenolic hydroxyl and caffeic acid derivative groups, giving it significant antioxidant activity. The LogP value of Danphenol acid D is 1.1271, indicating moderate lipophilic solubility, which is beneficial for distribution in the body but does not easily lead to excessive lipophilic accumulation. Its topological polar surface area (TPSA) is 181.82, and its relatively high polar surface area suggests that it may have certain limitations in cell membrane permeability.

The water solubility was 0.6944, indicating that Danphenic acid D has good water solubility, which is beneficial for oral absorption and circulation in the body. The blood-brain barrier has low permeability, suggesting its limited distribution in the central nervous system, which may reduce the risk of adverse reactions. The hERG channel inhibition test was negative, indicating a low risk of cardiotoxicity. Ames mutagenicity test results were zero, supporting its genotoxic safety.

In summary, Danphenolic acid D possesses good physicochemical properties and a foundation of safety, laying a solid foundation for its further drug development.

Plant Origins and Extraction Methods

Danphenic acid D mainly comes from the Lamiaceae plant Salvia miltiorrhiza Bunge, especially its roots. Danshen is a widely used medicinal herb in traditional Chinese medicine, containing abundant phenolic acid compounds, including Danphenic Acid A, Danphenic Acid B, and Danphenic Acid D. Although the content of Danphenic acid D is not as abundant as that of Danphenic Acid B, its unique pharmacological activity makes it a key focus of research.

Common methods for extracting Danphenolic acid D include water extraction and alcohol precipitation, ultrasound-assisted extraction, and high-performance liquid chromatography (HPLC) separation and purification. The general process is as follows:

1. Raw material processing: Collect dried Danshen roots and crush them into fine powder.
2. Extraction: Use 70%-80% ethanol aqueous solution, combined with ultrasound-assisted extraction technology to improve extraction rate.
3. Crude extract concentration: Concentrate the extract under reduced pressure to remove some impurities.
4. Separation and purification: Using silica gel column chromatography or reversed-phase high-performance liquid chromatography (RP-HPLC) technology, combined with gradient elution, high-purity separation of danphenic acid D is achieved.
5. Identification: Confirm the structure using methods such as mass spectrometry (MS) and nuclear magnetic resonance (NMR).

In recent years, green extraction technologies such as supercritical CO2 extraction and microwave-assisted extraction have also been attempted to be applied to the extraction of danphenolic acid D, aiming to improve extraction efficiency and environmental friendliness.

Pharmacological activity research

Pharmacological studies on the pharmacological activity of Danphenic acid D mainly focus on its antiplatelet aggregation, antioxidant, anti-inflammatory, and hepatoprotective effects.

Antiplatelet activity

Danphenic acid D can significantly inhibit platelet activation and aggregation, by which it involves inhibiting elevated Ca^2+ concentration within platelets and regulation of related signaling pathways. Its antiplatelet effect helps prevent thrombosis and reduces the risk of cardiovascular and cerebrovascular events. In vitro experiments showed that Danphenic acid D inhibits both ADP and collagen-induced platelet aggregation, with a pronounced dose-dependent effect.

Antioxidant and anti-inflammatory effects

As a natural polyphenol product, Danphenolic acid D has excellent free radical scavenging ability, which can reduce oxidative stress damage. Both in vivo and in vitro experiments showed that Danphenic acid D can upregulate the expression of antioxidant enzymes such as SOD1, SOD2, CAT, and GPX1, reduce reactive oxygen species (ROS) levels, and alleviate cellular damage. Additionally, Danphenol acid D enhances cellular antioxidant defense by regulating the nuclear factor red 2-related factor 2 (NRF2) signaling pathway.

Its anti-inflammatory effect is reflected in inhibiting the expression of the pro-inflammatory factor TGFB1 and regulating related inflammatory pathways, thereby reducing tissue inflammatory responses.

Hepatoprotective effects

Danphenic acid D demonstrated significant protective effects in liver injury models. Its mechanisms include inhibiting matrix metalloproteinase 9 (MMP9) activity, preventing the progression of liver fibrosis; Activates detoxifying enzymes NQO1 and HMOX1, promoting hepatocyte detoxification and repair; Regulates the hepatic stellate cell (HSC) activation marker ACTA2, alleviating liver fibrosis.

In animal experiments, Danphenol acid D can alleviate liver dysfunction and histopathological changes caused by chemical liver injury, demonstrating good liver-protective potential.

Mechanism of action and molecular targets

The multi-target mechanism of Danphenic acid D forms the basis of its pharmacological activity, mainly involving the following key targets and signaling pathways:

• MMP9: As an important matrix-degrading enzyme in liver fibrosis, overexpression of MMP9 promotes liver tissue remodeling and fibrosis. Danphenol acid D slows the progression of liver fibrosis by inhibiting MMP9 activity.
• NQO1 and HMOX1: Both enzymes are important intracellular antioxidant and detoxifying enzymes, regulated by NRF2. Danphenolic acid D activates the NRF2 signaling pathway, inducing NQO1 and HMOX1 expression and enhancing cellular antioxidant capacity.
• NRF2: As the main regulator of cellular antioxidant stress, NRF2 activation is the core mechanism by which danphenol acid D exerts antioxidant and cell-protective effects.
• SOD1, SOD2, CAT, GPX1: These antioxidant enzymes are upregulated to effectively eliminate superoxide anions and hydrogen peroxide, reducing oxidative stress damage.
• TGFB1: As a pro-fibrotic factor, inhibition of TGFB1 helps block the hepatic fibrosis signaling pathway. Danphenol acid D exerts anti-fibrotic effects by regulating TGFB1 expression.
• ACTA2: A marker for hepatic stellate activation; danphenolic acid D inhibits its expression and alleviates the activation of fibrosis in hepatic stellate cells.

Additionally, Danphenol acid D may inhibit platelet aggregation and reduce thrombosis risk by regulating platelet Ca^2+ signaling and related enzyme activity in antiplatelet activity.

Druggability evaluation and pharmacokinetics

The druggability parameters of Danphenolic acid D indicate that it has promising potential for drug development. Medium molecular weight (418.3540) and moderate LogP (1.1271) make its distribution in vivo quite ideal. Although a higher TPSA (181.82) may limit its cell membrane permeability, its good water solubility (0.6944) helps with oral absorption.

The blood-brain barrier has low permeability, reducing the risk of toxic side effects in the central nervous system. The hERG channel is negative for inhibition and the Ames test shows no mutagenicity, supporting its safety.

Pharmacokinetics, existing literature reports that Danphenic acid D is absorbed orally quickly, with a moderate plasma half-life, mainly metabolized by the liver and excreted by the kidneys. Its bioavailability is limited by intestinal metabolism and first-pass effects; in the future, its pharmacokinetic properties can be improved through nanocarriers or structural modification.

The metabolites of Danphenic acid D have not been fully elucidated; further research is needed on its metabolic pathways and possible active metabolites to comprehensively evaluate its efficacy and safety.

Prospects and outlooks for clinical applications

With its multi-target and multi-mechanism pharmacological properties, Danphenic acid D demonstrates broad clinical application potential in liver protection and antiplatelet therapy. Its protective effect against liver fibrosis, hepatitis, and liver injury offers new ideas for adjunctive treatment of liver diseases. Its antiplatelet activity makes it promising for the prevention and treatment of cardiovascular and cerebrovascular diseases, especially in patients at high risk of thrombosis.

Future clinical research should focus on safety validation, dosage optimization, and efficacy evaluation of danphenic acid D, combined with modern drug formulation technologies to enhance its bioavailability and targetability. In addition, the synergistic effects of Danphenol D and other active ingredients such as Danshen B, as well as the development of compound formulations, are also worth in-depth discussion.

With the development of precision medicine and molecular targeted therapies, the mechanisms by which Danphenic acid D regulates oxidative stress, inflammatory responses, and fibrosis will be further clarified, providing scientific evidence for its clinical translation.

Conclusion

Dan Acid D, as an important polyphenol active component in Danshen, has significant antiplatelet and hepatoprotective effects. Its multi-target, multi-mechanism pharmacological characteristics, and excellent druggability parameters make it a research hotspot in the fields of natural product pharmacology and new drug development. Although research on its pharmacokinetics and clinical applications is still in its early stages, its safety and efficacy have been validated to some extent.

In the future, by combining modern medicinal chemistry, pharmacology, and clinical research methods, in-depth exploration of the mechanism of action of danphenolic acid D, optimizing its pharmacokinetic properties, and conducting systematic clinical trials will help promote its translation into clinical applications and benefit more patients. Research on Danphenic acid D not only enriches the theoretical framework of natural product pharmacology, but also provides valuable resources and ideas for the modernization and innovative development of traditional Chinese medicine.