Synonym name:
Catalogue No.: BP0704
Cas No.: 50816-24-5
Formula: C₁₇H₂₄O₁₁
Mol Weight: 404.368
Botanical Source: Verbena officinalis and Penstemon nitidus

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.

​Description:

Hastatoside and verbenalin are major sleep-promoting components of V. officinalis. Hastatoside has anti-inflammatory activity.

References:

Phytother Res. 2000 Sep;14(6):463-5.    

Antiinflammatory activity and chemical composition of extracts of Verbena officinalis.

METHODS AND RESULTS:

In an attempt to locate the biologically active fraction(s) of the plant Verbena officinalis Linn. (Verbenaceae), a preliminary screening of successive petroleum ether, chloroform and methanol extracts of aerial parts for antiinflammatory activity using carrageenan paw oedema model was carried out. All three extracts were found to exhibit antiinflammatory activity with the chloroform extract being the most active. Chemical investigations of petroleum ether and chloroform extracts led to the isolation of beta-sitosterol, ursolic acid, oleanolic acid, 3-epiursolic acid, 3-epioleanolic acid, and minor triterpenoids of derivatives of ursolic acid and oleanolic acids. 

CONCLUSIONS:

Chromatographic purification of the methanol extract yielded two iridoid glucosides, verbenalin and Hastatoside, a phenylpropanoid glycoside, verbascoside and beta-sitosterol-D-glucoside.    

Sleep & Biological Rhythms, 2009, 7(3):211–217.    

Hastatoside and verbenalin are sleep‐promoting components in Verbena officinalis   

Herbal tea made from Verbena officinalis (V. officinalis) has traditionally been used for the treatment of insomnia and other nervous conditions. 

METHODS AND RESULTS:

In this study, we examined the sleep-promoting activity of Hastatoside, verbenalin, and verbascoside, which are the major iridoids (Hastatoside and verbenalin) and polyphenol (verbascoside) components responsible for the pharmacological activity of V. officinalis, by electroencephalographic analysis of rats after oral administration of the compounds. Hastatoside (0.64 mmol/kg of body weight) and verbenalin (1.28 mmol/kg of body weight) increased the total time of non-rapid eye movement sleep during a 9-h period from 23.00 to 08.00 hours by 81% and 42%, respectively, with a lag time of about 3–5 h after the administration at 20.00 hours (lights-off time). Both compounds also increased the delta activity during non-rapid eye movement sleep. However, verbascoside had no effect on the amount of sleep. 

CONCLUSIONS:

Therefore, Hastatoside and verbenalin are major sleep-promoting components of V. officinalis.    

HPLC of Hastatoside

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

Introduction/Overview

Hastatoside is a typical cycloetherterpene glycoside natural product, first isolated from Verbena officinalis, a plant of the genus Verbena. As one of the representative compounds of cycloene ether terpene monoterpenes, verbena monophonoid glycoside has attracted widespread attention in the field of natural product pharmacology in recent years due to its unique chemical structure and diverse biological activities. Its main manifestations are its pharmacological effects such as promoting sleep, anti-inflammation, and liver protection, showing good development potential. This paper will systematically review the chemical structure, physicochemical properties, plant origin, and extraction methods of Verbena orchidoside, delve into its pharmacological activity and mechanism, evaluate its druggability and pharmacokinetic characteristics, and finally look ahead to its clinical application prospects.

Chemical structure and physicochemical properties

The chemical formula of Verbena Glycoside is C17H24O11, with a molecular weight of 404.3680. Its structure belongs to cycloalene ether terpene monoterpene glycosides, specifically including β-D-glucosides, methyl esters, cyclopentyran rings, α,β-unsaturated carboxylates, and other functional groups. This structure imparts high polarity, a large molecular surface area (TPSA, approximately 172.21 Á²), a LogP value of -1.2342, showing strong hydrophilicity and low lipid solubility. The water solubility was 27.7161, indicating a certain solubility in water, but the blood-brain barrier permeability was relatively low, suggesting that central nervous system action may be limited by drug delivery. The hERG channel inhibition test results were negative, and the Ames-related mutagenicity test score was only 0.3, indicating good safety and low mutagenic risk.

From a molecular structure perspective, the cycloene ether terpene skeleton binding glycoside of verbenamide glycosides may interact with biological targets through hydrogen bonds and van der Waals forces, affecting its pharmacological activity. α, the β-unsaturated carboxylate structure may participate in covalent binding with enzyme active sites, regulating related signaling pathways.

Plant Origins and Extraction Methods

Verbena glycoside is mainly found in Verbena officinalis, especially in Verbena officinalis. This plant is widely distributed across Europe, Asia, and North America, and has traditionally been used to treat insomnia, anxiety, and liver diseases. As one of its main active ingredients, Verbena glycoside has been extensively researched and utilized in recent years.

The extraction of Verbena orchidoside is usually done using polar solvents such as methanol or ethanol aqueous solutions for extraction. The specific steps include:

1. Dry and crush the raw materials, then sift and set aside.
2. Use 70%-80% ethanol aqueous solution for reflux extraction, generally 2-4 hours, repeating 2-3 times to improve extraction rate.
3. The extract is filtered and concentrated to an appropriate volume.
4. High-purity verbena glycoside is obtained by liquid-liquid separation, silica gel column chromatography, or high-performance liquid chromatography (HPLC).
5. Pure products are identified for structure through methods such as mass spectrometry and nuclear magnetic resonance (NMR).

In recent years, the application of ultrasound-assisted extraction and microwave-assisted extraction technologies has significantly improved the extraction efficiency and purity of Verbena orchidoside, reduced solvent usage and extraction time, and aligned with the concept of green chemistry.

Pharmacological activity research

Research on the pharmacological activity of Verbena orchidoside covers multiple aspects, mainly including promoting sleep, anti-inflammatory, and liver-protective effects.

Promotes sleep

Multiple in vivo experiments have shown that Verbena glycoside can significantly shorten sleep latency and extend sleep duration. Its mechanism of action may be related to regulating the γ-aminobutyric acid (GABA) receptor and 5-hydroxytryptamine (5-HT) system in the central nervous system. In animal models, Verbena glycoside promotes sleep by enhancing inhibitory nerve transmission mediated by GABA_A receptors, reducing neural excitability. Additionally, its regulatory effect on 5-HT receptors also helps improve sleep structure and quality.

Anti-inflammatory effects

Verbena glycoside exhibits significant anti-inflammatory activity, able to inhibit the expression and release of various inflammatory mediators. Both in vitro cell models and in vivo inflammation models have confirmed that it reduces inflammatory responses by downregulating pro-inflammatory cytokines such as IL-6, TNF-α, and related signaling pathways like NF-κB and STAT3. It inhibits inflammation-related enzymes such as PTGS1, PTGS2 (COX-1, COX-2), and induced nitric oxide synthase (NOS2), reducing the generation of inflammatory mediators. Additionally, Verbena glycoside regulates the TRPV1 and TRPA1 plasma channels, reducing neuroinflammation and pain.

Liver-protective effects

Verbena glycoside has shown good effects in liver protection. Experimental studies have shown that it can reduce liver cell damage and inhibit liver inflammation and fibrosis. Its mechanism involves antioxidant stress, suppression of inflammatory factor release, and regulation of hepatocyte apoptosis-related proteins such as CASP1. Through multi-target synergistic action, Verbena Glycoside effectively alleviates inflammation and fibrosis in liver tissues, promoting liver function recovery.

Mechanism of action and molecular targets

The multiple pharmacological effects of Verbena Glycoside are attributed to its regulation of various molecular targets, mainly involving inflammatory signaling pathways and neurotransmitter systems.

Inflammation-related targets

• IL-6 and TNF-α: Verbena glycoside inhibits the expression of pro-inflammatory cytokines IL-6 and TNF-α, reduces inflammatory responses, and lowers excessive activation of immune cells.
• STAT3 and NF-κB: As key transcription factors, STAT3 and NF-κB regulate the expression of various inflammatory genes. Verbena glycoside blocks inflammatory signal transmission by inhibiting its activation.
• CASP1: This caspase is involved in the maturation of the inflammatory mediator IL-1β. Verbena glycoside reduces the release of inflammatory mediators by inhibiting CASP1 activity.
• PTGS1/PTGS2 (COX-1/COX-2): Verbena glycoside inhibits cyclooxygenase activity, reduces prostaglandin synthesis, and relieves inflammation and pain.
• NOS2: Induced nitric oxide synthase produces large amounts of NO during inflammation. Verbena glycoside reduces oxidative stress and inflammatory damage by inhibiting NOS2 expression.
• TRPV1/TRPA1: These two ion channels are involved in pain and inflammation signaling. Verbena glycoside alleviates neuroinflammation by modulating its activity.

Nervous system targets

Verbena glycoside in the leaf positively modulates GABA_A receptors, enhancing inhibitory neural transmission and promoting sleep. Additionally, its regulatory effect on the 5-HT receptor improves sleep structure and alleviates symptoms of anxiety and depression.

Druggability evaluation and pharmacokinetics

The druggability evaluation of Verbena glycoside indicates that it has certain development potential. Moderate molecular weight and strong hydrophilicity (LogP -1.2342) indicate good solubility in vivo, but may limit its ability to cross lipid membranes, especially with low blood-brain barrier permeability, suggesting that central action may depend on specific delivery mechanisms or dosage formulation design.

Its higher polarity (TPSA 172.21 Ų) matches the characteristics of polysaccharide natural products, which may result in lower oral bioavailability and require improved absorption through structural modification or nanocarrier techniques. The negative inhibition and low mutagenicity of hERG channels (Ames test 0.3) indicate good safety and suitability for further drug development.

Currently, pharmacokinetic data on Verbena glycoside are limited. Preliminary studies show that it is slowly absorbed orally, has a moderate plasma half-life, and is mainly metabolized by the liver and excreted by the kidneys. In the future, systematic studies of its metabolic pathways, distribution in vivo, and excretion characteristics are needed to optimize the administration regimen.

Prospects and outlooks for clinical applications

As a versatile natural product, Verbena lutein has broad clinical application prospects. Its sleep-promoting effects provide natural drug candidates for treating insomnia and related sleep disorders; Anti-inflammatory and liver-protective effects provide new ideas for adjunctive treatment of chronic inflammatory diseases and liver diseases.

Future research directions should focus on:

1. Pharmacodynamics and safety evaluation: Systematic preclinical toxicology and long-term safety studies are conducted to clarify the spectrum of toxic side effects.
2. Dosage Form Development: To address its low lipid solubility and poor blood-brain barrier permeability, new delivery systems such as nanocarriers, liposomes, or transdermal formulations are being developed to improve bioavailability and targeting.
3. Clinical trial design: Conduct multicenter, randomized, double-blind controlled clinical trials to verify their sleep-promoting and anti-inflammatory effects, clarify indications and medication regimens.
4. Structural optimization: Chemical modification improves pharmacokinetic properties, enhancing oral absorption and targeting capabilities.
5. In-depth Mechanism Research: Using multi-omics techniques and molecular simulations to further reveal its interaction mechanisms with targets, guiding precise drug administration.

Conclusion

As a typical cycloeneetherterpenoid glycoside natural product, Eugenerana leaf demonstrates significant pharmacological potential in promoting sleep, anti-inflammation, and liver protection due to its unique chemical structure and diverse biological activities. Its excellent safety profile and multi-target mechanism of action provide a solid foundation for new drug development. However, current research on its pharmacokinetics and clinical applications remains limited, urgently requiring systematic and in-depth research support. In the future, through multidisciplinary collaboration, Verbena glycoside is expected to become a major breakthrough in the development of natural product drugs, bringing new hope for the treatment of related diseases.