Product name: Tiliroside
Synonym name: 6′′-O-trans-p-Coumaroylastragalin
Catalogue No.: BP1393
Cas No.: 20316-62-5
Formula: C₃₀H₂₆O₁₃
Mol Weight: 594.525
Botanical Source: Edgeworthia chrysantha Lindl.
Physical Description:
Type of Compound: Flavonoids

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:

Tiliroside possesses anti-inflammatory, antioxidant, anti-complement, anti-diabetic, anticarcinogenic and hepatoprotective activities. Tiliroside enhances fatty acid oxidation via the enhancement adiponectin signaling associated with the activation of both AMP-activated protein kinase and peroxisome proliferator-activated receptor α and ameliorates obesity-induced metabolic disorders.

References:

Fitoterapia. 2007 Jan;78(1):1-6.    

Tiliroside and gnaphaliin inhibit human low density lipoprotein oxidation.    

Two flavonoids, gnaphaliin and Tiliroside, isolated from Helichrysum italicum, were studied in vitro for their capacity to inhibit Cu(2+)-induced human low density lipoprotein (LDL) and diluted plasma oxidation. 

METHODS AND RESULTS:

LDL oxidation was monitored by conjugated diene, thiobarbituric acid-reactive substances (TBARS) formation and electrophoretic mobility on agarose gel. Gnaphaliin and Tiliroside increased the lag-phase for diene conjugate production in a dose-dependent manner. The reduction of TBARS production confirmed the antioxidant activity of gnaphaliin and Tiliroside with 50% inhibitory concentration (IC(50)) values of 8.0+/-3.9 microM and 7.0+/-2.6 microM respectively. Furthermore, the flavonoids negated the Cu(2+)-induced increase in electrophoretic mobility of LDL. Antioxidant activity of gnaphaliin and Tiliroside was significantly different when diluted plasma was oxidised by adding 1 mM CuSO(4). Although both flavonoids again reduced the TBARS production, Tiliroside showed higher activity than gnaphaliin (IC(50)=10.6+/-2.5 microM vs. IC(50)>50 microM). 

CONCLUSIONS:

In conclusion, Tiliroside and gnaphaliin are antioxidants against in vitro Cu(2+)-induced LDL oxidation in the same order of magnitude compared to that of the reference drug, probucol.    

Eur J Pharmacol. 2003 Feb 7;461(1):53-61.    

Assessment of the anti-inflammatory activity and free radical scavenger activity of tiliroside.   

Three flavonoids, gnaphaliin, pinocembrin and Tiliroside, isolated from Helichrysum italicum, were studied in vitro for their antioxidant and/or scavenger properties and in vivo in different models of inflammation. 

METHODS AND RESULTS:

In vitro tests included lipid peroxidation in rat liver microsomes, superoxide radical generation in the xanthine/xanthine oxidase system and the reduction of the stable radical 1,1-diphenyl-2-pycryl-hydrazyl (DPPH). Acute inflammation was induced by application of 12-O-tetradecanoylphorbol 13-acetate (TPA) to the mouse ear or by subcutaneous injection of phospholipase A(2) or serotonin in the mouse paw. Eczema provoked on the mouse ear by repeated administration of TPA was selected as a model of chronic inflammation. The flavonoids were assayed against sheep red blood cell-induced mouse paw oedema as a model of delayed-type hypersensitivity reaction. The most active compound, both in vitro and in vivo, was Tiliroside. It significantly inhibited enzymatic and non-enzymatic lipid peroxidation (IC(50)=12.6 and 28 microM, respectively). It had scavenger properties (IC(50)=21.3 microM) and very potent antioxidant activity in the DPPH test (IC(50)=6 microM). In vivo, Tiliroside significantly inhibited the mouse paw oedema induced by phospholipase A(2)(ED(50)=35.6 mg/kg) and the mouse ear inflammation induced by TPA (ED(50)=357 microg/ear). Pinocembrin was the only flavonoid that exhibited anti-inflammatory activity in the sheep red blood cell-induced delayed-type hypersensitivity reaction. However, only Tilirosidesignificantly reduced the oedema and leukocyte infiltration induced by TPA. 

CONCLUSIONS:

As in the case of other flavonoids, the anti-inflammatory activity of Tiliroside could be based on its antioxidant properties, although other mechanisms are probably involved.    

Mol Nutr Food Res. 2012 Mar;56(3):435-45.    

Tiliroside, a glycosidic flavonoid, inhibits carbohydrate digestion and glucose absorption in the gastrointestinal tract.   

Recent studies have reported that Tiliroside, a glycosidic flavonoid, possesses anti-diabetic activities. In the present study, we investigated the effects of Tiliroside on carbohydrate digestion and absorption in the gastrointestinal tract. 

METHODS AND RESULTS:

This study showed that Tiliroside inhibits pancreatic α-amylase (IC₅₀ = 0.28 mM) in vitro. Tiliroside was found as a noncompetitive inhibitor of α-amylase with K(i) values of 84.2 μM. In male ICR mice, the increase in postprandial plasma glucose levels was significantly suppressed in the Tiliroside-administered group. Tiliroside treatment also suppressed hyperinsulinemia after starch administration. Tiliroside administration inhibited the increase of plasma glucose levels in an oral glucose tolerance test, but not in an intraperitoneal glucose tolerance test. In human intestinal Caco-2 cells, the addition of Tiliroside caused a significant dose-dependent inhibition of glucose uptake. The inhibitory effects of both sodium-dependent glucose transporter 1 (SGLT1) and glucose transporter 2 (GLUT2) inhibitors (phlorizin and phloretin, respectively) on glucose uptake were significantly inhibited in the presence of Tiliroside, suggesting that Tiliroside inhibited glucose uptake mediated by both SGLT1 and GLUT2. 

CONCLUSIONS:

These findings indicate that the anti-diabetic effects of Tiliroside are at least partially mediated through inhibitory effects on carbohydrate digestion and glucose uptake in the gastrointestinal tract.   

Bioorg Med Chem. 2002 Mar;10(3):707-12.    

Hepatoprotective principles from the flowers of Tilia argentea (linden): structure requirements of tiliroside and mechanisms of action.    

The methanolic extract from the flowers of Tilia argentea (linden) was found to show a hepatoprotective effect against D-galactosamine (D-GalN)/lipopolysaccharide (LPS)-induced liver injury in mice. 

METHODS AND RESULTS:

By bioassay-guided separation using in vitro D-GalN-induced damage to hepatocytes, five flavonol glycosides were isolated as the hepatoprotective constituents of the methanolic extract. Tiliroside, the principal flavonol glycoside, strongly inhibited serum GPT and GOT elevations at doses of 25-100 mg/kg (p.o.) in D-GalN/LPS-treated mice. By comparing the inhibitory effects of Tiliroside with those of its components alone, the kaempferol 3-O-beta-D-glucopyranoside moiety was found to be essential for the activity, and its effect was suggested to depend on the inhibition of tumor necrosis factor-alpha (TNF-alpha) production, decreased sensitivity of hepatocytes to TNF-alpha, and on the protection of hepatocytes against D-GalN.    

HPLC of Tiliroside

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

Introduction/Overview

Tiliroside, also known as linden glycoside, is a glycoside flavonoid compound widely found in various plants. Since its initial isolation and identification, silver linden has attracted significant attention from the natural product pharmacology community due to its diverse biological activities, especially its potential applications in anti-diabetes and anti-inflammatory fields. In recent years, as the incidence of metabolic diseases and chronic inflammation-related diseases has continued to rise, research into the pharmacological mechanisms and druggability of silver linden has deepened, providing important scientific basis for developing new natural medicines.

As a non-competitive inhibitor of α-amylase (α-amylase), silver linden can effectively inhibit carbohydrate digestion and glucose absorption, thereby exerting antidiabetic effects. Moreover, it involves several key molecular targets in regulating inflammatory responses, such as IL-6, STAT3, and TNF, demonstrating strong anti-inflammatory activity. This paper will systematically review the chemical structure and physicochemical properties of silver linadin, plant origin and extraction methods, pharmacological activity and mechanism of action, druggability evaluation, and pharmacokinetic characteristics, and finally explore its clinical application prospects and future research directions.

Chemical structure and physicochemical properties

The chemical structure of silver linden belongs to the glycoside flavonoids, with a molecular formula of C_30H_26O_13 and a molecular weight of 594.5250. Its core structure is the flavonoid nucleus, connected to glycoside chains, specifically quercetin or similar flavonoids binding to sugars such as glucose and arabinose. Its structure contains multiple hydroxyl and phenolic hydroxyl groups, giving it strong antioxidant capacity.

In terms of physicochemical properties, the LogP value of silver linden is 1.6902, indicating moderate lipid solubility, which benefits cell membrane permeability but is not easily deposited in lipid environments. Its polar surface area (TPSA) is 216.58 Ų, indicating good water solubility, with a water solubility of about 0.2002, suitable for dispersion in aqueous systems. Silver linden has relatively low blood-brain barrier permeability, suggesting its limited distribution in the central nervous system and potentially reducing the risk of central side effects. The hERG channel inhibition test was negative, indicating a low risk of cardiotoxicity, while the Ames test was 0.0, indicating no significant genotoxicity.

The non-competitive inhibitory characteristic of silver linden showed an inhibition constant (Ki) of 84.2 μM against α-amylase, demonstrating its effectiveness in regulating enzyme activity. The synergistic action between glycosyls and flavonoid nuclei in its structure ensures binding ability to target enzymes while also affecting bioavailability and metabolic stability.

Plant Origins and Extraction Methods

Silver linden is widely found in various plants, especially in the flowers, leaves, and bark of Tilia spp. (Tilia spp.) plants, where the content is relatively high. Additionally, silver linden can also be detected in medicinal plants such as Impatiens balsamina, ginkgo leaves, and hawthorn. Its abundant plant sources provide a natural raw material foundation for large-scale extraction and application.

Traditional methods for extracting silver linden mainly use organic solvent extraction, such as ethanol or methanol aqueous solutions (50%-80%), for reflux or ultrasonic-assisted extraction of plant materials. The extract is concentrated, separated, and purified by column chromatography to obtain high-purity silver linadin. In recent years, with the development of green extraction technologies, new techniques such as supercritical CO_2 extraction, microwave-assisted extraction, and enzyme-assisted extraction have been introduced into silver linden extraction, significantly improving extraction efficiency and purity, while reducing the use of organic solvents, in line with the concept of green chemistry.

During extraction, parameters such as pH, temperature, solvent polarity, and extraction time significantly affect the extraction rate of silver lindan. Optimizing process conditions not only increases yield but also ensures the structural integrity and bioactivity stability of silver linadin.

Pharmacological activity research

Antidiabetic effects

As a non-competitive inhibitor of α-amylase, silver linden can significantly inhibit the breakdown of carbohydrates in the gastrointestinal tract, delay the release and absorption of glucose, and reduce postprandial blood sugar peaks. In vitro enzyme activity tests showed that silver linden inhibitory activity on α-amylase was stable and dose-dependent, with a Ki value of 84.2 μM, indicating good enzyme inhibition activity.

Animal experiments further confirmed that silver linadin can improve blood sugar levels in diabetic rats, enhance insulin sensitivity, and alleviate diabetes-related oxidative stress and inflammatory responses. Additionally, silver linden can regulate the expression of genes related to glycolipid metabolism, improve the function of pancreatic islet β cells, and demonstrate its multi-target, multi-mechanism anti-diabetic potential.

Anti-inflammatory effects

Silver linden demonstrates significant anti-inflammatory activity across various inflammation models. Its targets cover several key molecules in inflammatory signaling pathways, including pro-inflammatory cytokines IL-6 and TNF-α, transcription factor NF-κB (NFKB1), inflammatory enzymes PTGS1 (COX-1), PTGS2 (COX-2), and induced nitric oxide synthase NOS2. By inhibiting the expression and activity of these targets, silver linden can effectively alleviate inflammatory responses.

Silver linden also regulates inflammation-related signaling pathways such as STAT3 and CASP1, inhibiting the activation of inflammasomes and reducing the release of inflammatory mediators. Additionally, silver linden has a regulatory effect on pain-related ion channels such as TRPV1 and TRPA1, showing certain analgesic effects.

Other pharmacological activities

In addition to anti-diabetic and anti-inflammatory effects, silver linden also possesses antioxidant, antibacterial, and antitumor biological activities. Its antioxidant effect mainly comes from the phenolic hydroxyl structure of the flavonoid nucleus, which can scavenge free radicals and reduce oxidative stress damage. Some studies show that silver linden inhibits certain pathogenic bacteria and may exert anti-tumor effects by regulating apoptosis-related signaling pathways.

Mechanism of action and molecular targets

The pharmacological mechanism of silver linden involves coordinated regulation of multiple targets and multiple pathways. Its antidiabetic effect mainly relies on non-competitive inhibition of α-amylase, blocking the enzymatic hydrolysis of carbohydrates, reducing glucose absorption, and lowering blood sugar levels. This mechanism avoids direct stimulation of insulin secretion and reduces the risk of hypoglycemia.

In terms of anti-inflammation, silver ligaside blocks the inflammatory signaling cascade by inhibiting the activity of pro-inflammatory cytokines (such as IL-6, TNF-α) and key transcription factor NF-κB. Its regulation of STAT3 affects cell proliferation and apoptosis, further reducing chronic inflammation. CASP1 inhibition reduces cytokine release mediated by inflammasomes, decreasing tissue damage.

Additionally, silver linden regulates TRPV1 and TRPA1, reducing inflammation-related pain perception. The inhibitory effects of PTGS1 and PTGS2 reduce prostaglandin synthesis and relieve inflammation symptoms. Inhibition of NOS2 reduces excessive nitric oxide production, alleviating oxidative stress and inflammation.

The multi-target action of silver linden enables it to exhibit comprehensive regulatory effects in complex disease states, offering high potential for clinical translation.

Druggability evaluation and pharmacokinetics

The druggability parameters of silver linden indicate its promising potential for drug development. Although the molecular weight of 594.5250 is slightly high, it is still within an acceptable range. A moderate LogP (1.6902) and a higher TPSA (216.58) suggest that it has some water solubility and polarity in vivo, which benefits its distribution in the bloodstream but may limit passive diffusion of cell membranes.

Its water solubility is 0.2002, making it suitable for oral formulation design, but attention must be paid to the impact of solubility limits on bioavailability. The blood-brain barrier has low permeability, reducing the risk of central nervous system side effects. The hERG channel inhibits negative and non-genotoxic (Ames test 0.0) to provide good safety assurance.

Pharmacokinetic studies show that silver linden is absorbed quickly after oral administration, but its bioavailability is limited by the hydrolysis and metabolism of its glycoside structure. Gut microbes and hepatic enzyme systems have a significant impact on the metabolism of silver lindan, mainly releasing flavonoid nuclei through glycoside hydrolase, followed by corresponding phase I and phase II metabolic reactions.

The metabolites of silver linden have certain biological activity in the body and may work synergistically with parent compounds. It has a moderate half-life and is widely distributed throughout the body, mainly excreted through the kidneys and bile. In the future, further optimization of administration methods and dosage forms is needed to improve oral bioavailability and targeting.

Prospects and outlooks for clinical applications

As a naturally derived glycoside flavonoid, silver linden has broad clinical application prospects due to its remarkable anti-diabetic and anti-inflammatory activities. By modulating multiple targets and multi-signal pathways, it offers a new strategy for treating metabolic syndrome, chronic inflammatory diseases, and related complications.

Currently, clinical research on silver linden is still in the early stages, mainly focusing on in vitro and animal model validation. Systematic clinical trials should be conducted in the future to evaluate its safety, efficacy, and pharmacokinetic characteristics, and to clarify its therapeutic dosage and administration regimen.

In addition, formulation development and drug delivery technology innovation for silver linden are also key research priorities for the future. Using nanocarriers, liposomes, or other drug delivery systems is expected to improve bioavailability and targeting, enhancing therapeutic outcomes.

The multi-target mechanism of silver ligandine offers possibilities for combination therapy, especially in synergistic use with existing antidiabetic or anti-inflammatory drugs, potentially enhancing efficacy and reducing side effects.

In summary, as a representative natural product drug, silver linden has good pharmacological activity and safety, and is expected to become an important candidate for treating metabolic and inflammation-related diseases in the future.

Conclusion

As a glycoside flavonoid with multiple biological activities, silver linden demonstrates significant research value in the field of natural product pharmacology due to its anti-diabetic and anti-inflammatory effects. Its unique chemical structure endows it with excellent physicochemical properties and multi-target regulation capabilities, promoting its potential applications in the treatment of metabolic diseases and inflammation.

Although significant progress has been made in current research on silver linadine, further exploration of its pharmacokinetic characteristics, clinical safety, and effective dose range is still needed. In the future, optimizing its extraction and purification processes and drug delivery systems through new technologies will further promote the clinical translation of silver lindan.

In summary, as a natural product with broad pharmacological activity, silver linden has promising drug development potential and application prospects, and deserves ongoing attention and investment in basic research and clinical development.