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Astragalin: pharmacokinetics and biological activities

Sep 18,2023

General Description

Astragalin is a bioactive compound that exhibits various biological activities. It is absorbed into the bloodstream after oral administration and undergoes metabolism primarily through phase II enzymes. The drug has a relatively low oral bioavailability and is rapidly eliminated from the body through urine. Astragalin demonstrates potent anti-inflammatory activity by reducing inflammation and inhibiting the activation of NF-κB. It also possesses significant antioxidant activity, scavenging free radicals and protecting against oxidative stress. Additionally, astragalin exhibits neuroprotective effects by maintaining cerebral redox homeostasis, reducing neurodegeneration, and enhancing antioxidant enzyme activities. It shows potential as a therapeutic agent for neurodegenerative diseases.

Figure 1. Astragalin.png

Figure 1. Astragalin

Pharmacokinetics

After oral administration, astragalin is absorbed into the bloodstream and circulates freely in the plasma. Its pharmacokinetic parameters are dose-dependent, showing biphasic absorption with an initial rapid phase followed by slower sustained release. The absolute oral bioavailability of astragalin is relatively low, typically around 20-30%. Astragalin undergoes metabolism primarily through phase II enzymes, such as glucuronidation and sulfation, leading to the formation of water-soluble metabolites that can be easily excreted. The drug has a relatively short elimination half-life of 1 to 3 hours in humans, indicating rapid elimination from the body. Urine is the primary route of excretion for astragalin and its metabolites. The pharmacokinetics of astragalin can be influenced significantly by various factors including age, sex, race/ethnicity, disease state, and concomitant medications. In summary, the pharmacokinetics of astragalin are complex and variable among different populations. Understanding the factors affecting its absorption, distribution, metabolism, and excretion is vital for optimizing its therapeutic use and minimizing potential adverse effects in clinical settings. 1

Biological activities

Anti-inflammatory activity

Astragalin has been shown to possess potent anti-inflammatory properties in various animal models. It reduces inflammation in LPS-induced murine models of mastitis and lung injury by reducing myeloperoxidase activity and the expression of pro-inflammatory cytokines. Astragalin achieves its anti-inflammatory effect by inhibiting LPS-induced activation of NF-κB, which alleviates the deterioration of IkBα and restricts the nuclear translocation of NF-κB. In addition, astragalin can halt the MAPK and NF-κB pathways in leptospira-induced uterine and epithelial inflammation in mice. It also inhibits the production of prostaglandin E2 (PGE2) in periodontal pathogen-induced periodontitis and downregulates the production of cellular nitrite oxide and IL-6 in LPS-stimulated cells. Furthermore, astragalin has been shown to significantly reduce eosinophil count and retrieved IgE, IL-4, IL-5, and IL-13 in bronchoalveolar lavage fluid of mouse models of allergic asthma. Overall, astragalin possesses robust anti-inflammatory activity in various animal models. 2

Antioxidant activity

Astragalin exhibits significant antioxidant activity, which is crucial for neutralizing harmful free radicals and maintaining cellular function. Free radicals such as hydroxyl radicals, superoxide anion, singlet oxygen, and reactive oxygen species (ROS) can lead to various pathological conditions when their production exceeds the body's antioxidant capacity. Astragalin acts as a potent antioxidant by scavenging free radicals, donating electrons, and chelating free catalytic metals in biological systems.  Furthermore, astragalin has been found to inhibit endotoxin-induced oxidative stress, preventing epithelial apoptosis and eosinophilia. It antagonizes endotoxin-induced oxidative stress by modulating the LPS-TLR signaling network. In addition, astragalin protects against neurotoxicity and oxidative stress in models such as Caenorhabditis elegans and ischemic brain injury in rats. It achieves this by modulating apoptosis-related pathways and enhancing the expression of NCam in the hippocampus region. Overall, astragalin demonstrates potent antioxidant activity, providing protection against oxidative damage and potential therapeutic benefits for various pathological conditions associated with oxidative stress. 3

Neuroprotective activity

Astragalin exhibits neuroprotective effects by maintaining cerebral redox homeostasis and scavenging free radicals generated during neurotoxicity and oxidative stress in neuronal cells. It has been shown to decrease neurodegeneration and increase lifespan in C. elegans models stimulated by 6-OHDA. Astragalin reduces levels of reactive oxygen species (ROS), inhibits lipid peroxidation, and enhances the activities of antioxidant enzymes superoxide dismutase (SOD) and glutathione peroxidase (GPx). Moreover, astragalin enhances acetylcholinesterase (AChE) activity and decreases the expression of the proapoptotic gene egl-1, which is associated with neuronal cell death. Additionally, when applied through the leaves extract of Eucommia ulmoides, astragalin exhibits positive effects on metabolism, prolongs convulsion latency, and diminishes convulsion rates, indicating its hypnotic effect on the central nervous system (CNS). Astragalin also suppresses carrageenan-stimulated paw edema in rats. Furthermore, in ischemic brain injury rat models, astragalin improves neural function. These findings highlight the potential of astragalin as a neuroprotective agent against neurodegenerative diseases and its ability to alleviate oxidative stress-induced damage in neuronal cells. 4

Reference

1. Tao Y, Bao J, Zhu F, Pan M, Liu Q, Wang P. Ethnopharmacology of Rubus idaeus Linnaeus: A critical review on ethnobotany, processing methods, phytochemicals, pharmacology and quality control. J Ethnopharmacol, 2023, 302(Pt A):115870.

2. Li F, Liang D, Yang Z, Wang T, Wang W, Song X, Guo M, Zhou E, Li D, Cao Y, Zhang N. Astragalin suppresses inflammatory responses via down-regulation of NF-κB signaling pathway in lipopolysaccharide-induced mastitis in a murine model. Int Immunopharmacol, 2013, 17(2):478-482.

3. Cho IH, Gong JH, Kang MK, Lee EJ, Park JH, Park SJ, Kang YH. Astragalin inhibits airway eotaxin-1 induction and epithelial apoptosis through modulating oxidative stress-responsive MAPK signaling. BMC Pulm Med, 2014, 14:122.

4. Li H, Shi R, Ding F, Wang H, Han W, Ma F, Hu M, Ma CW, Huang Z. Astragalus Polysaccharide Suppresses 6-Hydroxydopamine-Induced Neurotoxicity in Caenorhabditis elegans. Oxid Med Cell Longev, 2016, 2016:4856761.

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