Synonym name: Sodium New Houttuyfonate; Sodium Neohouttuyfonate
Catalogue No.: BP1319
Cas No.: 83766-73-8
Formula: C₁₂H₂₃NaO₅S
Mol Weight: 302.36
Botanical Source:

Purity: 95%~99%
Analysis Method: HPLC-DAD or/and HPLC-ELSD
Identification Method: Mass, NMR
Packing: Brown vial or HDPE plastic bottle
Can be supplied from milligrams to grams.

For Reference Standard and R&D, Not for Human Use Directly.
Inquire for bulk scale.

HPLC of  Sodium Houttuyfonate

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

Introduction/Overview

Sodium Houttuyfonate (SH), also known as sodium bisulfite of decanoyl acetaldehyde, with a CAS number of 83766-73-8, is a synthetic derivative of decanoyl acetaldehyde (Houttuynia cordata Thunb., commonly known as Houttuynia cordata Thunb.), the main active ingredient in traditional medicinal plants. Houttuynia cordata, as a traditional Chinese medicine with a long history in China, has been recorded in classics such as the Compendium of Materia Medica. It is commonly used for clearing heat and detoxifying, eliminating carbuncles and pus, and is commonly used in modern clinical practice to treat respiratory infections, inflammatory diseases, etc. Natural decanoyl acetaldehyde has unstable properties and is prone to polymerization failure, while sodium houttuynia cordata obtained through chemical modification has significantly improved water solubility and chemical stability, making it more suitable for drug development and application.

In recent years, with the increasing threat of new and recurrent infectious diseases, especially the frequent spread and mutation of influenza viruses, the development of new, efficient, and multi-target antiviral drugs has become an urgent need in the global public health field. Sodium Houttuynia cordata has attracted much attention due to its broad-spectrum antibacterial, antiviral, and anti-inflammatory activities. Numerous studies have shown that it exhibits significant inhibitory effects on multiple influenza virus strains in both in vitro and in vivo models. Its effects are not limited to directly targeting viral proteins, but also involve deep regulation of host immune and inflammatory pathways, reflecting the characteristics of multi pathway and multi-target intervention. This article aims to systematically review the chemical properties and pharmacological activities of sodium houttuyfonate, especially its anti influenza mechanism, molecular targets, drug properties, and clinical application prospects, in order to provide comprehensive scientific references for the in-depth research and development of this compound.

Chemical structure and physicochemical properties

The chemical structure of sodium Houttuynia cordata can be regarded as the addition product of decanoyl acetaldehyde (CH3 (CH ₂) ₈ COCH ₂ CHO) and sodium bisulfite (NaHSO3), forming a stable sulfonic acid salt form. Its molecular formula is C ₁₂ H ₂ ∝ NaO ₅ S, and its molecular weight is 280.3860. This modification is a crucial pharmaceutical improvement: the active aldehyde group in natural decanoyl acetaldehyde molecules is prone to self condensation or reaction with other nucleophiles, resulting in loss of activity; After addition with sodium bisulfite, the formed α - hydroxysulfonate structure greatly enhances the water solubility and chemical stability of the molecule, while retaining its basic pharmacological active skeleton.

From the analysis of physical and chemical properties, the calculated lipid water partition coefficient (LogP) is 1.3675, indicating that the molecule has a certain degree of lipophilicity, but overall leans towards amphiphilic properties. Its topological polar surface area (TPSA) is 91.6700 Å ², reflecting the large proportion of polar moieties (sulfonic acid groups, hydroxyl groups) in the molecule. The water solubility value is 3.3989 (usually referring to logS or related indicators, the larger the value, the worse the solubility. The specific scale needs to be combined with the context, but usually indicates good water solubility), which confirms its excellent water solubility characteristics as a sodium salt. These physicochemical parameters collectively determine the distribution, absorption, and metabolic characteristics of sodium houttuynia cordata in the body, providing the possibility for its oral or injection administration.

Plant sources and extraction methods

The direct plant source of sodium houttuynia cordata Thunb. is Houttuynia cordata Thunb. This plant is widely distributed in East Asia and Southeast Asia, and its whole plant is used as medicine. Fresh Houttuynia cordata contains volatile oil, and its main antibacterial and antiviral component is believed to be decanoyl acetaldehyde. However, the content of naturally extracted decanoyl acetaldehyde is low and extremely unstable.

Therefore, the sodium houttuynia cordata used in drugs is mainly prepared through chemical synthesis or semi synthesis methods. The classic synthetic route is to use methyl nonanone (or decanoic acid derivatives) as the starting material, undergo a series of reactions to generate decanoyl acetaldehyde intermediate, then undergo addition reaction with sodium bisulfite aqueous solution, and finally crystallize and purify to obtain pure sodium houttuyfonate. This process is mature and can achieve large-scale production, ensuring drug quality and stability. Although it originates from natural product structures, modern production processes have made it a standard chemical drug entity.

Pharmacological activity research

Sodium Houttuynia cordata has a wide range of pharmacological activities, including antibacterial, antiviral, anti-inflammatory, and immune regulatory aspects. Among them, its anti influenza virus activity has been a research focus in recent years.

1. Broad spectrum antibacterial activity Early studies have confirmed that it has inhibitory effects on various Gram positive bacteria (such as Staphylococcus aureus and Streptococcus pneumoniae) and Gram negative bacteria (such as Haemophilus influenzae), and its mechanism may be related to the destruction of bacterial cell membrane integrity.
2. Antiviral activity：
   • Anti influenza virus This is the most extensively studied area of activity for sodium houttuynia cordata. Both in vitro and in vivo experiments have shown that it can effectively inhibit the replication of influenza A viruses (such as H1N1, H3N2, H5N1, H7N9, etc.) and influenza B viruses. In cell models, it can reduce viral titers and alleviate cytopathic effects; In a mouse influenza model, it can reduce viral load in lung tissue, alleviate inflammatory damage and edema in lung tissue, and significantly improve survival rate.
   • Anti other viruses The study also showed that it has certain inhibitory potential against respiratory syncytial virus (RSV), herpes simplex virus (HSV), human immunodeficiency virus (HIV), etc., but the research depth is not as deep as influenza virus.
3. Anti inflammatory and immune regulatory activity Sodium Houttuynia cordata can significantly inhibit the excessive inflammatory response of macrophages and epithelial cells caused by stimuli such as lipopolysaccharide (LPS), and reduce the expression of key pro-inflammatory factors such as tumor necrosis factor - α (TNF - α), interleukin-6 (IL-6), and interleukin-1 β (IL-1 β). At the same time, it can also regulate the function of immune cells, promote beneficial immune responses in viral infections, and suppress excessive inflammatory storms. This "immune homeostasis" regulatory effect is crucial for controlling the severity of viral infections such as influenza.

Mechanism of action and molecular targets

The mechanism of action of Houttuynia cordata sodium against influenza is complex, showing the characteristics of multi-target and multi pathway synergy, which can be divided into direct antiviral effect and indirect host directed effect.

1. Directly acting on the virus：

   • Inhibit virus adsorption and entry Research has shown that SH may interfere with the binding of virus hemagglutinin (HA) protein to host cell surface receptors, or affect the virus membrane fusion process, thereby blocking the initial invasion step of the virus.
   • Key protein for inhibiting virus replication Evidence suggests that SH may interfere with the neuraminidase (NA) activity, nucleoprotein (NP) function, and RNA polymerase complex (PB2, PB1, PA) activity of influenza virus, affecting the transcription and replication of the virus genome. There may also be regulatory effects on the viral ion channel protein M2.

2. Regulating host cell signaling pathways (core mechanism)：

   • Activate NRF2/antioxidant response pathway Nuclear factor E2 related factor 2 (NFE2L2/NRF2) is a key transcription factor for cellular antioxidant stress. SH can activate NRF2 and promote the expression of downstream antioxidant enzymes such as heme oxygenase-1 (HO-1) and quinone oxidoreductase 1 (NQO1). This not only alleviates the oxidative damage caused by the virus, but also products such as HO-1 have been proven to have direct antiviral and anti-inflammatory effects.
   • Regulating the MAPK signaling pathway The mitogen activated protein kinase (MAPK) pathway, particularly p38 MAPK (MAPK14) and JNK (MAPK8), plays a central role in the inflammatory cytokine storm induced by influenza virus. SH can effectively inhibit the phosphorylation of p38 and JNK activated by viruses, thereby downstream inhibiting the activity of transcription factors such as AP-1 and significantly reducing the excessive production of pro-inflammatory cytokines.
   • Regulating interferon signaling The interferon (IFN) system is the core of antiviral innate immunity. SH can upregulate the expression of type I interferon (IFN - α/β) and its stimulating genes (ISGs). Further research has found that it may enhance the cell's response to interferon by stabilizing or positively regulating the signaling of interferon receptors (IFNAR1/2), thereby establishing a stronger antiviral state.
   • Other potential targets The study also involves the regulation of pathways such as NF - κ B and PI3K/Akt, which together form a network of anti-inflammatory and cell protective effects.

In summary, the mode of action of Sodium Houttuynia cordata is not simply a "virus killer", but rather achieves a dual effect of "strengthening the body and eliminating evil" by moderately enhancing the host cell's defense capabilities (such as NRF2 and interferon pathways), while inhibiting harmful overreactions caused by viruses (such as p38/JNK mediated inflammatory storms).

Evaluation of drug properties and pharmacokinetics

Based on its physical and chemical properties and relevant experimental data, the preliminary evaluation of the pharmacological properties of sodium houttuynia cordata is as follows:

• Absorption, distribution, metabolism, excretion (ADME)As a small molecule with good water solubility, oral absorption studies have shown certain bioavailability, but specific parameters vary depending on the research. Animal pharmacokinetic studies have shown that it is widely distributed in the body and has a high concentration in lung tissue, which is consistent with its efficacy in combating respiratory infections. The predicted blood-brain barrier permeability is' low ', indicating a lower risk of central nervous system related side effects. The metabolic pathway may involve the conversion of sulfonic groups and the β - oxidation of fatty acid chains, mainly excreted through the kidneys.
• Preliminary evaluation of safety：
  • HERG inhibition The predicted or experimental results indicate 'no', suggesting a low risk of potential cardiac toxicity (causing QT interval prolongation), which is an important drug safety advantage.
  • Genotoxicity The Ames test result is 0.9 (usually expressed in the form of the ratio or conclusion of the number of revertant colonies relative to the control, which needs to be interpreted in conjunction with the specific experimental system, but generally less than 2 and without dose correlation can be considered a negative tendency), indicating that it has no significant mutagenicity.
  • Preclinical toxicity Acute and subchronic toxicity tests have shown that within the effective dose range, the toxicity of sodium Houttuynia cordata is relatively low, and the main adverse reactions may be related to local injection irritation or gastrointestinal reactions at high doses.

Overall, sodium Houttuynia cordata exhibits good potential for medicinal properties: moderate molecular weight, good water solubility, and positive preliminary safety signals. However, its complete pharmacokinetic characteristics, metabolic fate in the human body, and interactions with other drugs still need to be elucidated through more systematic and rigorous preclinical and clinical studies.

Clinical application prospects and prospects

Sodium Houttuynia cordata is currently used in clinical practice in China in the form of injections, oral preparations, etc. It is mainly used as an adjuvant therapy for bacterial or viral inflammatory diseases such as respiratory infections, bronchitis, pneumonia, etc. Based on its unique anti influenza virus mechanism, its clinical application prospects are as follows:

1. As an anti influenza medication Existing anti influenza drugs such as neuraminidase inhibitor (oseltamivir) and polymerase inhibitor (mabaroxavir) are facing resistance issues. The multi-target and host directed mechanism of sodium houttuynia cordata makes it less likely to induce virus resistance and may be effective against drug-resistant virus strains. It is expected to be developed into a new type of anti influenza drug, especially suitable for cases with treatment needs for both influenza and secondary inflammation.
2. Combination therapy strategy Combining with existing direct antiviral drugs may result in synergistic effects. For example, the combination of SH (regulating host immunity and inflammation) and oseltamivir (inhibiting virus release) theoretically can more effectively clear the virus, control lung inflammation, and reduce the severity rate, which has important clinical exploration value.
3. Dealing with the inflammatory storm In severe influenza or COVID-19 and other viral infections, cytokine storm is the key to cause acute respiratory distress syndrome (ARDS) and multiple organ failure. The strong anti-inflammatory and immune regulatory effects of SH make it a potential candidate drug for inhibiting inflammatory storms and as an adjuvant therapy for critically ill patients.
4. Formulation optimization and exploration of new indications Further development of its novel drug delivery system (such as inhalers, lung targeted agents) can be carried out to increase lung drug concentration and reduce systemic exposure. Its anti-inflammatory and immunomodulatory effects also suggest its potential for exploration in non infectious inflammatory diseases such as asthma, chronic obstructive pulmonary disease, and autoimmune diseases.

The challenges faced mainly include: although the mechanism of action network has been preliminarily mapped, the most precise direct molecular targets (such as interaction sites with specific viral proteins or host proteins) still need to be further identified; Large scale, randomized double-blind clinical trials are needed to confirm its efficacy and safety advantages in treating influenza; As a derivative of natural products, its chemical composition is clear, but the quality control standards still need to be in line with international standards to promote international application.

Conclusion

Sodium Houttuynia cordata is a successful example derived from the traditional Chinese medicine Houttuynia cordata. It overcomes the stability problem of natural ingredients through chemical modification and has developed into a modern medicine with a clear chemical structure. Its anti influenza pharmacological activity is outstanding, and its mechanism of action is profound. It exerts its effects through a dual pathway of directly inhibiting the virus and indirectly regulating host defense and inflammatory response. The core involves precise regulation of the NRF2, MAPK (p38/JNK), and interferon signaling pathways. The preliminary pharmacological evaluation shows that it has good water solubility and safety potential.

In the future, with the further deepening of molecular target research, the accumulation of high-quality clinical evidence, and the application of new formulation technologies, sodium houttuynia cordata is expected to evolve from a widely used anti infective adjuvant drug to an important treatment option for viral respiratory infectious diseases such as influenza, especially in clinical situations where both antiviral and anti-inflammatory needs are met. Its research and development process also fully reflects the value of drug development that draws inspiration from traditional medical wisdom and applies modern scientific technology for innovation and validation.