Product name: Acaciin
Synonym name: Buddleoside; linarin
Catalogue No.: BP0115
Cas No.: 480-36-4
Formula: C₂₈H₃₂O₁₄
Mol Weight: 592.55
Botanical Source: Occurs in Linaria vulgaris, Robinia and Micromeria spp. and other plants
Physical Description: Yellow powder
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, up to kilograms
Inquire for bulk scale.

Descriptions:
Linarin is a flavone glycoside in the plants Flos chrysanthemi indici, Buddleja officinalis, Cirsium setosum, Mentha arvensis and Buddleja davidii, possesses analgesic, antipyretic, anti-inflammatory and neuroprotective activities. [1]
Linarin is known to have anti-acetylcholinesterase effects, prevents Aβ(25-35)-induced neurotoxicity through the activation of PI3K/Akt, which subsequently inhibits GSK-3β and up-regulates Bcl-2, may be a potent therapeutic compound against Alzheimer's disease acting through both acetylcholinesterase inhibition and neuroprotection.[2]
Linarin has dose-dependent analgesic and anti-inflammatory activities.[3]
Linarin can protect osteoblasts against hydrogen peroxide-induced osteoblastic dysfunction and may exert anti-resorptive actions, at least in part, via the reduction of RANKL and oxidative damage.[4]
Linarin induces the osteogenic differentiation and mineralization of MC3T3-E1 osteoblastic cells by activating the BMP-2/RUNX2 pathway through PKA signalingin vitroand protected against OVX-induced bone lossin vivo, suggests that linarin is a useful natural alternative for the management of postmenopausal osteoporosis.[5]

References:
[1] Lou H, Fan P, Perez R G, et al. Bioorgan Med Chem, 2011, 19(13):4021-7.
[2] Martínez-Vázquez M, Ramírez Apan T O, Lastra A L, et al. Planta Medica, 1998, 64(2):134-7.
[3] Kim Y H, Lee Y S, Choi E M. Cell Immunol, 2011, 268(2):112-6.
[4] Feng X, Wang X, Liu Y, et al. Iran J Pharm Res, 2015, 14(3):949-54.
[5] Li J, Hao L, Wu J, et al. Int J Mol Med, 2016, 37(4):901-10.
[6] Guo Q, Fang H, Shen H. China Journal of Chinese Materia Medica, 2010, 35(9).

HPLC of Acaciin 

HNMR of Acaciin 

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

Introduction/Overview

Acaciin, also known as apigenin 7-O - α - L-rhamnose - (1 → 6) - β - D-glucoside, is a flavonoid carbon glycoside widely present in various medicinal plants. Its CAS number is 480-36-4. For a long time in the traditional medical system, its source plants, such as acacia and amaranth, are often used to treat eye inflammation, hypertension, diabetes and other diseases. Modern pharmacological research has gradually revealed that paeoniflorin not only has classic anti-inflammatory and antioxidant activities, but also exhibits unique potential in neuroprotection, metabolic regulation, and prevention and treatment of eye diseases. In recent years, with the development of systems pharmacology and molecular docking technology, the target and mechanism network of baicalin in complex diseases, especially in optic neurodegenerative diseases such as glaucoma, have become increasingly clear. This article aims to provide a systematic review of the chemical properties, plant sources, pharmacological activities, multi-target mechanisms of action, and medicinal properties of paeoniflorin. It also looks forward to its application prospects in clinical translation, in order to provide scientific basis for the deep development and utilization of this natural product.

Chemical structure and physicochemical properties

The molecular formula of paeoniflorin is C ₂₈ H ∝ ₂ O ₁₄, with a molecular weight of 592.5500. Its core structure is apigenin, a flavonoid compound. Its structural feature is that the 7th hydroxyl group of the apigenin nucleus is connected to a disaccharide chain - α - L-rhamnose - (1 → 6) - β - D-glucose through a glycosidic bond. This flavonoid carbon glycoside structure has stronger chemical stability and enzymatic resistance compared to common oxygen glycosides, which to some extent affects its metabolic processes in organisms.

From the analysis of physical and chemical properties, the theoretical lipid water partition coefficient (LogP) of baicalin is 0.2998, indicating that it has a certain degree of hydrophilicity. Its topological polar surface area (TPSA) is as high as 217.9700 Å ², which is mainly attributed to the numerous oxygen atoms and sugar moieties in the molecule, resulting in strong polarity. The calculated water solubility value is 1.9686 mg/mL, which belongs to the range of slightly soluble to soluble. These parameters collectively determine the absorption and distribution characteristics of paeoniflorin in vivo: higher polarity and TPSA are usually unfavorable for passive transmembrane diffusion, which may limit its oral bioavailability. In addition, its ability to cross the blood-brain barrier (BBB) is predicted to be "low", suggesting that its direct action on the central nervous system may face challenges, but for diseases that primarily target the eye and peripheral tissues, such as glaucoma, this characteristic may not be an absolute disadvantage.

Plant sources and extraction methods

Menghua glycoside is widely distributed in nature, mainly found in various plants such as legumes, horsetails, and lips.
1. Main plant sources：
* Fabaceae The flowers of Robinia pseudoacacia are one of the most famous sources of anthocyanins, and Acaciin is named after it.
* Ma Qianke The dried flower buds of Buddleja officinalis are a traditional Chinese medicine, and paeoniflorin is one of its characteristic active ingredients, closely related to the traditional efficacy of "improving vision and eliminating shadows".
* Lipstick family Prunella vulgaris also contains anthocyanins in its entire plant, which are related to its anti-inflammatory and antihypertensive effects.
* Other sources It has also been detected in medicinal plants such as honeysuckle and chrysanthemum.

1. Extraction and Separation Methods：
   The extraction of paeoniflorin mainly adopts solvent extraction method. Common solvents include methanol, ethanol, and their aqueous solutions in different proportions. In order to improve extraction efficiency, modern technologies such as ultrasound assisted extraction (UAE), microwave-assisted extraction (MAE), and pressurized solvent extraction (PSE) have been widely used. These methods destroy plant cell walls through physical means, accelerate solvent penetration and component dissolution, and have the advantages of short time, high efficiency, and low solvent dosage.
   The crude extract after extraction needs to undergo further separation and purification. Macroporous adsorption resins (such as AB-8 and D101) are commonly used for enrichment, utilizing the polarity characteristics of anthocyanins for adsorption and elution. The final high-purity preparation relies on preparative high-performance liquid chromatography (Prep HPLC), which optimizes the mobile phase (usually methanol water or acetonitrile water system, with a small amount of formic acid or acetic acid added to adjust the pH) and chromatographic column (usually C18 reverse phase column) conditions to achieve efficient separation of monomeric compounds of anthocyanins.

Pharmacological activity research

A large number of in vitro and in vivo studies have confirmed that baicalin has multiple pharmacological activities, laying the foundation for its multi-target therapeutic potential.

1. Anti inflammatory and immune regulatory effects Menghua glycoside can significantly inhibit the excessive production of nitric oxide (NO), prostaglandin E2 (PGE2), tumor necrosis factor - α (TNF - α), interleukin-6 (IL-6) and other pro-inflammatory factors induced by lipopolysaccharide (LPS) and other factors in macrophages. Its function involves inhibiting the activation of nuclear factor kappa B (NF - κ B) and mitogen activated protein kinases (MAPKs) signaling pathways.

2. Antioxidant and neuroprotective effects As a flavonoid compound, paeoniflorin can directly scavenge free radicals such as DPPH and ABTS, and enhance the activity of endogenous antioxidant enzymes such as superoxide dismutase (SOD) and glutathione peroxidase (GSH Px). In neural cell injury models such as hydrogen peroxide, glutamate, or β - amyloid protein induction, paeoniflorin exhibits the ability to increase cell survival, reduce apoptosis, alleviate oxidative stress, and mitochondrial dysfunction, suggesting its protective potential against neurodegenerative diseases.

3. Eye protection and potential for reducing intraocular pressure This is a field that has received much attention in recent years regarding the production of anthocyanins. Research has shown that baicalin can alleviate eye inflammation in experimental dry eye and uveitis models. More importantly, in glaucoma related models, baicalin exhibits a trend of reducing intraocular pressure (IOP). The mechanism may involve inhibiting extracellular matrix remodeling of trabecular meshwork, improving the function of aqueous humor outflow pathway, and providing direct protection to retinal ganglion cells.

4. Anti diabetes and prevention of complications Menghua glycoside can inhibit alpha glucosidase activity, delay carbohydrate absorption, and help reduce postprandial blood sugar. At the same time, it can improve insulin resistance, and reduce the accumulation of sorbitol in tissues by inhibiting the activity of aldose reductase (AKR1B1), thus preventing and treating complications such as diabetes cataract and neuropathy.

5. Other activities The study also reported that baicalin has anti anxiety, anti fibrosis, anti-tumor and other activities, but its strength and mechanism of action need further clarification.

Mechanism of action and molecular targets

Based on network pharmacology and molecular docking research, the therapeutic effect of baicalin on diseases such as glaucoma exhibits the characteristics of "multi-component multi-target multi pathway". The mechanism of action of the target list you provided can be analyzed as follows:

1. Regulating aqueous humor dynamics and reducing intraocular pressure：

   • Carbonic Anhydrase II (CA2)Monteverdin may inhibit CA2 activity, reduce the generation of bicarbonate ions in aqueous humor, and thus decrease aqueous humor secretion, which is the target of classical intraocular pressure lowering drugs such as Dozomib.
   • Matrix metalloproteinase-9 (MMP9)Menghua glycoside may inhibit the overexpression of MMP9, prevent abnormal degradation and remodeling of extracellular matrix in trabecular meshwork, and maintain the normal structure and function of aqueous humor outflow channels.
   • Muscarinic acetylcholine receptor M3 (CHRM3)Regulating CHRM3 may affect the contraction and relaxation of the ciliary muscle, indirectly affecting the resistance to aqueous humor outflow.

2. Protecting the optic nerve and retinal ganglion cells：

   • β - amyloid precursor protein (APP) and histone demethylase (KDM1A)Menghua glycoside may reduce the production of neurotoxic substances and promote the survival and plasticity of nerve cells by regulating APP metabolism and epigenetic regulation of KDM1A.
   • Cholinergic receptor (CHRNA7) and acetylcholinesterase (ACHE)Regulating the alpha 7 subtype of nicotinic acetylcholine receptors and inhibiting ACHE can enhance cholinergic neurotransmission, which is crucial for maintaining the normal function of retinal ganglion cells and resisting damage.
   • Purine/pyrimidine free endonuclease 1 (APEX1)As a key DNA repair enzyme, the activation of APEX1 helps to repair oxidative DNA damage in nerve cells, and baicalin may exert neuroprotective effects through this pathway.

3. Antioxidant and anti-inflammatory properties：

   • Xanthine dehydrogenase/oxidase (XDH)Inhibition of XDH can reduce the production of superoxide and uric acid, which is an important antioxidant target.
   • Aldehyde reductase (AKR1B1)As mentioned above, inhibiting AKR1B1 is the core of preventing and treating complications of diabetes. At the same time, oxidative stress is also part of the pathological process of glaucoma. This target has cross protective significance.

In summary, through synergistic effects on multiple targets mentioned above, Montenegrin has constructed a comprehensive prevention and treatment network for glaucoma from three aspects: reducing intraocular pressure (etiological intervention), antioxidant and anti-inflammatory (pathological process intervention), and direct neuroprotection (outcome intervention).

Evaluation of drug properties and pharmacokinetics

Based on the provided pharmacological parameters and existing research, the preliminary evaluation of the pharmacological properties of baicalin is as follows:

1. Absorption, Distribution, Metabolism, and Excretion (ADME)：

   • absorb The high TPSA and polarity of paeoniflorin may lead to its low oral bioavailability. Flavonoid glycosides usually need to be hydrolyzed into aglycones (apigenin) by gut microbiota or intestinal mucosal enzymes before being absorbed. However, as a carbon glycoside, baicalin is more stable to hydrolysis and may be partially absorbed in its original form, but the absorption rate and degree may be limited. New drug delivery systems, such as nano formulations and phospholipid complexes, are effective strategies for improving their absorption.
   • distribution The predicted low blood-brain barrier permeability limits its distribution to the central nervous system, but ocular tissues (such as aqueous humor and retina) have unique blood aqueous and blood retinal barriers, and their distribution characteristics require specific experimental verification. Higher water solubility is beneficial for its distribution in the systemic circulation.
   • Metabolism Menghua glycoside mainly undergoes phase II metabolic reactions in the body, such as glucuronidation, sulfation, etc., generating more water-soluble metabolites that are excreted through the kidneys or bile. Its glycosidic bonds are relatively stable, but may be metabolized by specific bacterial communities in the colon.

2. Preliminary evaluation of safety：

   • HERG inhibition The predicted result is' no ', indicating that the risk of Montmorillonite causing QT interval prolongation and apical torsion ventricular tachycardia is low, which is an important positive signal for the cardiovascular safety of the drug.
   • Genotoxicity (Ames test)The predicted value is 0.9 (usually with 0.8 or 0.9 as the positive judgment threshold edge), which is a computer prediction and needs to be further confirmed through experiments (such as in vitro Ames test) to determine whether it has mutagenicity. At present, the data suggests a low risk, but careful evaluation is still needed.

3. Challenges and optimization of drug development The main challenge is that oral bioavailability may be low. Future research needs to determine its absolute bioavailability through experiments and explore prodrug modification, eutectic technology, or the development of non oral administration routes (such as eye drops and ocular implants) to overcome this bottleneck. Its good water solubility and preliminary safety prediction provide a favorable foundation for its further development.

Clinical application prospects and prospects

The clinical application prospects of baicalin mainly focus on the field of chronic complex diseases, especially glaucoma.

1. As a candidate drug for multi-target treatment of glaucoma Existing glaucoma drugs mostly target a single target (such as prostaglandin analogs, beta blockers). Menghua glycoside has the potential to have dual effects of lowering intraocular pressure and neuroprotection, which is in line with the concept of modern glaucoma treatment shifting from "lowering intraocular pressure" to "protecting the optic nerve". Developing eye drops or sustained-release formulations containing paeoniflorin is expected to become a new type of comprehensive anti glaucoma drug.

2. Treatment of diabetes and its complications: Based on its AKR1B1 inhibition and α - glucosidase inhibitory activity, montmorillonite or its structural optimization can be used to develop drugs or functional food for preventing and treating diabetes cataract, neuropathy and assisting in reducing blood sugar.

3. Potential in neurodegenerative diseases Its antioxidant, anti-inflammatory, and neuroprotective effects suggest that it may be beneficial for conditions such as Alzheimer's disease and Parkinson's disease. Although its BBB permeability is low, it can be bypassed through strategies such as intranasal administration or explored by developing prodrugs of its aglycone apigenin.

4. Outlook and Future Research Directions：

   • In depth mechanism research It is necessary to use gene knockout/knock in animal models, CRISPR-Cas9 and other technologies to empirically demonstrate the contribution of the predicted targets and elucidate their dominant pathways of action.
   • Pharmacokinetic study Systematically conduct ADME studies on the pharmacological characteristics, absolute bioavailability, and major metabolites of paeoniflorin in animals and humans.
   • Pharmaceutical research Focus on developing delivery systems that can improve their ocular bioavailability or oral absorption, such as nanoparticles, microemulsions, cyclodextrin inclusion complexes, etc.
   • Preclinical and clinical research: After completing the standardized toxicological evaluation of GLP, promote its clinical trials in glaucoma, diabetes complications and other indications, and verify its safety and effectiveness.
   • Structural modification and optimization Based on its pharmacophore, reasonable structural modifications can be made to improve its pharmacokinetic properties (such as increasing lipid solubility and BBB permeability) while retaining multi-target activity.

Conclusion

Menghua glycoside, as a natural flavonoid carbon glycoside with abundant sources, has shown great potential in the prevention and treatment of complex diseases such as glaucoma due to its unique pharmacological properties of anti-inflammatory, antioxidant, neuroprotective, and multi-target regulation. Preliminary studies in systems pharmacology have revealed the molecular network of its action on multiple key targets such as APP, CA2, MMP9, AKR1B1, providing a theoretical basis for its therapeutic advantage of "multi-target synergy". Despite facing challenges in drug development, especially in oral absorption and BBB permeability, its good water solubility and preliminary predicted cardiovascular safety lay a positive foundation for its further development. In the future, through in-depth mechanism verification, pharmacokinetic research and advanced preparation technology, it is expected that montmorillonite will be successfully transformed from a traditional plant active ingredient into an innovative drug candidate for the treatment of glaucoma, diabetes complications and other diseases, providing a model for the modernization and accurate use of natural products.