Product name: Shanzhiside methylester
Synonym name:
Catalogue No.: BP1300
Cas No.: 64421-28-9
Formula: C₁₇H₂₆O₁₁
Mol Weight: 406.384
Botanical Source: Mussaenda parviflora and Salvia digitaloides
Physical Description: Powder
Type of Compound: Iridoids

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, up to kilograms
Inquire for bulk scale.

Descriptions:
Shanzhiside methylester, the principle effective iridoid glycoside from the analgesic herb Lamiophlomis rotata , reduces neuropathic pain by activating spinal GLP-1 receptors and subsequently stimulating microglial β-endorphin expression via the p38 MAPK signaling; stimulation of the endogenous β-endorphin expression may be a novel and effective strategy for the discovery and development of analgesics for the long-term treatment of chronic pain. [1]

References:
[1] Fan H, Li T F, Gong N, et al. Neuropharmacol, 2015, 101:98-109.
[2] Xi H E, Mao X, Fan P C, et al. Chinese J Exp Trad Med Formulae. 2010, 16(07):50-2

HPLC of Shanzhiside methylester

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

Introduction/Overview

Shanzhiside methylester (CAS No.: 64421-28-9) is a natural cycloetherterpenoid monoterpene glycoside with significant bioactivity, attracting attention due to its unique chemical structure and diverse pharmacological effects. As one of the common active ingredients in traditional Chinese medicine, methyl gardeniside shows promising application potential in anti-inflammatory, analgesic, and neuroprotective fields. In recent years, with the deepening of natural product pharmacology, the molecular mechanisms and targets of methyl gardeniside have gradually been revealed, especially its regulatory role in inflammation-related diseases, which has attracted widespread research interest. This paper will systematically review the chemical structure, plant origin, pharmacological activity, mechanism of action, druggability evaluation, and clinical application prospects of methyl gardeniside ester, aiming to provide scientific basis and theoretical support for further development and application of this natural product.

Chemical structure and physicochemical properties

Methyl gardeniside is a monoterpene glycoside of the cycloalkene ether terpene class, with a molecular formula of C19H30O10 and a molecular weight of 406.3840. Its chemical structure includes a core backbone of a cycloalene etherterpene and a glycosidic group. Its complex structure includes polyhydroxyl and methyl substituents, giving it excellent water solubility and bioactivity. According to calculations, the LogP value of methyl gardeniside is -1.5453, indicating strong hydrophilicity; the polar surface area (TPSA) is 175.3700, indicating high molecular polarity, which may affect cell membrane permeability and bioavailability. Additionally, the water solubility of methyl gardeniside reaches 43.2892, which facilitates its dissolution and distribution in the body. Notably, this compound has a relatively low blood-brain barrier penetration ability, suggesting its direct effect on the central nervous system may be limited, but this also reduces the risk of central nervous system side effects. The hERG channel inhibition test was negative, indicating that methyl gardeniside carries a low risk of cardiotoxicity; The Ames test result was 0.0, indicating no significant mutagenicity and relatively high safety.

Plant Origins and Extraction Methods

Methyl gardeniside is mainly found in various traditional Chinese medicinal materials, with gardenia jasminoides Ellis being the primary source. As a traditional Chinese medicinal herb, gardenia has long been used for clearing heat and detoxifying, promoting dampness, and reducing jaundice. Methyl gardenia glycoside is one of its important active ingredients. Besides gardenia, the compound can also be detected in some other plants rich in cyclic oleether terpenes, but at relatively low levels.

Common methods for extracting methyl gardeniside ester include solvent extraction, ultrasound-assisted extraction, and high-performance liquid chromatography (HPLC) separation and purification. Generally, ethanol or methanol is used as the solvent for crude extraction, followed by enrichment and purification through liquid-liquid distribution and column chromatography techniques. In recent years, green extraction technologies such as supercritical CO2 extraction and microwave-assisted extraction have also been attempted to improve extraction efficiency and purity. Purified methyl gardeniside ester is often identified for structural identification and content determination using modern analytical methods such as mass spectrometry (MS) and nuclear magnetic resonance (NMR).

Pharmacological activity research

Pharmacological activity studies of methyl gardeniside mainly focus on its anti-inflammatory, analgesic, and neuroprotective effects. A large number of in vitro cell models and in vivo animal experiments have shown that methyl gardeniside can significantly inhibit the expression of inflammatory factors, reduce inflammatory responses, and improve the pathological status of related diseases.

1. Anti-inflammatory effects
   Methyl gardeniside regulates inflammatory signaling pathways through multiple targets, significantly reducing the expression of pro-inflammatory cytokines such as IL-6 and TNF-α and inhibiting the release of inflammatory mediators. It inhibits cyclooxygenases (PTGS1, PTGS2) and induced nitric oxide synthase (NOS2), reducing the production of prostaglandins and NO, and alleviating inflammatory responses. In animal models, methyl gardeniside demonstrates protective effects against various inflammatory diseases such as arthritis and enteritis.

2. Analgesic effect
   Methyl gardeniside esters regulate pain-related ion channels such as TRPV1 and TRPA1, alleviating neuropathic and inflammatory pain. By inhibiting the overactivation of these ion channels, it reduces neuronal excitability and alleviates pain symptoms.

3. Neuroprotective effects
   In neurological disease models, methyl gardeniside can reduce nerve cell damage and promote neurological function recovery by inhibiting inflammatory responses and regulating the apoptosis-related protein CASP1. Its regulation of the STAT3 and NFKB1 signaling pathways helps suppress neuroinflammation and protect neuronal survival.

In addition, methyl gardeniside also exhibits multiple pharmacological effects such as antioxidant and immunomodulatory properties, demonstrating broad therapeutic potential.

Mechanism of action and molecular targets

The pharmacological action of methyl gardeniside depends on its regulation of multiple key molecular targets and involves complex signal transduction networks.

• IL-6 and STAT3 pathways
  IL-6 is a typical pro-inflammatory cytokine that mediates inflammatory responses and cell proliferation by activating the STAT3 signaling pathway. Methyl gardeniside can inhibit IL-6 expression and STAT3 phosphorylation, blocking activation of this pathway and reducing inflammation and related pathological changes.

• CASP1 (caspase 1)
  CASP1 is a key enzyme for activating inflammasomes and is involved in the maturation and release of the pro-inflammatory cytokine IL-1β. Methyl gardeniside inhibits CASP1 activity, blocks the activation of inflammatory bodies, and reduces the release of inflammatory mediators.

• TRPV1 and TRPA1 ion channels
  TRPV1 and TRPA1 play important roles in pain and inflammation perception. Methyl gardeniside regulates the activity of these two channels, reduces excessive neuronal excitability, and relieves pain and inflammation.

• PTGS1 and PTGS2 (cyclooxygenases 1 and 2)
  PTGS enzymes catalyze the synthesis of prostaglandins and are important mediators of inflammatory responses. Methyl gardeniside inhibits PTGS1 and PTGS2, reduces prostaglandin production, and alleviates inflammatory symptoms.

• TNF and NOS2
  TNF-α is another important pro-inflammatory factor, and excess nitric oxide produced by NOS2 exacerbates inflammation. Methyl gardeniside further exerts anti-inflammatory effects by inhibiting the expression of both.

• NFKB1 (Nuclear factor κB)
  NFKB1 is a key transcription factor regulating the expression of inflammatory genes. Methyl gardeniside can block NFKB1 activation, inhibit the transcription of inflammatory genes, and reduce inflammatory responses.

In summary, methyl gardeniside regulates inflammation- and pain-related signaling networks through multi-target and multi-pathway synergistic effects, exerting its pharmacological effects.

Druggability evaluation and pharmacokinetics

From the perspective of druggability, methyl gardeniside demonstrates certain advantages and challenges. Its molecular weight is 406.3840, classifying it as a medium-weight compound, with a LogP value of -1.5453, indicating strong hydrophilicity, which is beneficial for dissolution and distribution in body fluids, but may limit its cell membrane penetration. A higher TPSA (175.3700) suggests greater polarity, which may affect oral absorption and bioavailability.

Low blood-brain barrier penetration means that methyl gardeniside has a limited direct effect on the central nervous system, but this also reduces the potential risk of CN toxicity. The hERG channel was inhibited negatively and the Ames test showed no mutagenicity, indicating good safety and low risks of cardiotoxicity and genotoxicity.

Pharmacokinetics, current research is limited, but based on its physicochemical properties, its oral bioavailability may be limited. Its metabolism in the body mainly occurs through hepatic enzyme systems, and the activity and toxicity of metabolites require further research. In the future, structural modification or drug carrier technologies will be needed to improve their pharmacokinetic properties, enhancing in vivo stability and targeting.

Prospects and outlooks for clinical applications

Based on the significant activity of methyl gardeniside in anti-inflammatory, analgesic, and neuroprotective aspects, it has great potential for application in various inflammation-related diseases. Especially in adjunctive treatments for rheumatoid arthritis, inflammatory bowel disease, neuropathic pain, and certain neurodegenerative diseases, methyl gardeniside ester is expected to become a candidate for novel natural medicines.

Future research should focus on the following aspects:

1. In-depth analysis of pharmacological mechanisms
   Further elucidation was made to clarify the mechanism of methyl gardeniside at the cellular and molecular levels, especially its regulatory network of inflammatory signaling pathways.

2. Pharmacokinetics and pharmacodynamics research
   Systematically evaluate its absorption, distribution, metabolism, and excretion characteristics in vivo to optimize administration regimens and improve bioavailability.

3. Structural optimization and dosage form development
   Chemical modification or nanocarrier technology can improve the properties of the drug, enhancing targeting and efficacy.

4. Preclinical and clinical research
   Conducting animal models and human clinical trials to verify their safety and efficacy, driving their clinical translation.

5. Combination medication strategies
   Exploring the synergistic effects of methyl gardeniside ester with other drugs to expand its clinical indications.

In summary, as a natural product with multi-target anti-inflammatory effects, methyl gardeniside has promising development prospects and is worthy of further in-depth research and clinical development.

Conclusion

Methyl gardeniside glycoside, as a monoterpene glycoside of cyclo-enyl ether terpenes, has become a hot topic in natural product pharmacology research due to its unique chemical structure and significant anti-inflammatory and analgesic activity. By regulating multiple inflammation-related signaling pathways such as IL-6/STAT3, CASP1, TRPV1/TRPA1, PTGS1/PTGS2, TNF, NOS2, and NFKB1, it exerts multi-target synergistic anti-inflammatory effects, demonstrating broad medicinal value. Although its druggability is somewhat limited, its good safety and diverse pharmacological effects provide a solid foundation for its clinical application. In the future, through structural optimization, pharmacokinetic improvements, and advancement of clinical research, methyl shanxiside is expected to become an important natural drug for treating inflammation and related diseases, contributing new natural drug resources to human health.