Natural Sources and Anti-in?ammatory Activity of Astragalin

Astragalin is a flavonoid compound with anti-inflammatory, antioxidant, anticancer, and antimicrobial activities. It inhibits cancer cell proliferation and migration while inducing apoptosis. Astragalin exhibits oral activity and offers neuroprotective, cardioprotective, and anti-osteoporotic effects. At concentrations of 20, 40, and 80 μM, Astragalin suppresses the viability and migration of cancer cells without exhibiting cytotoxicity toward normal human colonic epithelial cells (NCM460). When administered every two days for 25 days, Astragalin reduces tumor volume, weight, and tumor formation rate in a nude mouse model of human colon cancer, and also decreases the expression of p-NFκB and p-IKKα.

Figure1: Picture of Astragalin

Basic Introduction

Astragalin, a bioactive natural flavonoid also known as kaempferol-3-O-β-D-glucoside, has long been recognized for its medicinal importance. Astragalin has been reported to exhibit multiple pharmacological properties, including antioxidant, anti-inflammatory, anticancer, neuroprotective, and cardioprotective effects. Astragalin, isolated from flowers of Rosa chinensis Jacq., is a kind of flavonoid, with anti-inflammatory, antioxidant, antiviral, analgesic, antibacterial, antiallergic, and antihepatotoxic effects. However, no studies on the procoagulant effect of astragalin have been reported. This study aimed to investigate the procoagulant activity of astragalin and its mechanism. Its procoagulant effect was investigated by activated partial thromboplastin time (APTT), thrombin time (TT), prothrombin time (PT), and fibrinogen (FIB) in vitro, and a rat model established by heparin sodium was used to evaluate the mechanism for the procoagulant effect in vivo. The results showed that astragalin had good procoagulant effects compared with the control group in vitro.

Natural Sources

Astragalin, a naturally occurring flavonoid, has been identified in a variety of plants. It is found in Cuscuta chinensis Lam., a member of the Convolvulaceae family, which consists of approximately 60 genera and 1,650 species. The seeds of the genus Cuscuta are a rich source of astragalin and are traditionally used in folk medicine to treat osteoporosis in several Asian countries, including Pakistan. Among different species, C. chinensis exhibits high contents of astragalin, accounting for 29–34% of total phenolics. Astragalin is also present in Cassia alata, a member of the Fabaceae family—the largest family among angiosperms, comprising about 700 genera and 20,000 species. The leaves of C. alata are traditionally used in tropical regions such as Malaysia, Brazil, and Indonesia to treat skin conditions including eczema and chronic skin impurities. Additionally, astragalin has been isolated from plants belonging to the Ebenaceae, Rosaceae, and Eucommiaceae families. A summary of plants containing astragalin, the parts utilized, and their biological features is provided. Astragalin can also be produced in vivo through the glycosylation of kaempferol at the 3C-O position. [1]

Pharmacological effects

An increasing number of studies have demonstrated that Astragalin could prevent numerous types of cancers, especially those of the digestive system, skin, breast, lung, liver, and kidney. Remarkably, these findings partly uncover the underlying mechanisms, including promoting apoptosis and attenuating the growth of tumor cells via mediating the NF-κB, PI3K/AKT, MAPK, and JAK/STAT signaling pathways. Astragalin exerts its anticancer effects through these key pathways, further supporting its potential as a therapeutic agent. [2]

Increases Endogenous Estrogen

The flavonoid glycoside Astragalin has been shown to suppress gastric cancer cell growth, invasion, and migration by down-regulating gastric epithelium glycoprotein MUC1 and tumor-associated antigens. Mechanistically, Astragalin blocks the synthesis of Tn, sialyl Tn, and T antigens by suppressing specific glycosyltransferases and decreases NF-κB levels, suggesting the involvement of the NF-κB pathway in inhibiting glycosylation. Furthermore, Astragalin induces gastric cancer cell death and reduces tumor viability in xenograft models without obvious toxicity by promoting apoptosis and attenuating proliferation via up-regulating PARP and Bim and down-regulating Bcl-2, p-PI3K, and p-AKT. In colon cancer models, Astragalin prevents tumor growth by inactivating the NF-κB pathway, suppressing tumor volumes, and downregulating the phosphorylation of IKKα and NF-κB in vivo. In vitro, Astragalin restrains the growth and migration of HCT116 cells by down-regulating MMP-2 and MMP-9, induces G0/G1 phase cell cycle arrest via modulating cyclins and CDKs, and promotes apoptosis by regulating caspase family proteins, P53, and Bax. Additionally, Astragalin downregulates pro-inflammatory cytokines like TNF-α and IL-6. Collectively, these studies elucidate that Astragalin exhibits anti-tumor effects in the digestive system primarily by modulating the NF-κB and PI3K/AKT signaling pathways. [3]

Suppress gastric cancer cells growth

Astragalin has been shown to suppress gastric cancer cell growth, invasion, and migration by down-regulating gastric epithelium glycoprotein MUC1 and tumor-associated antigens. Specifically, it was observed that Astragalin blocked the synthesis of Tn antigen, sialyl Tn antigen, and T antigen by suppressing the expression of the glycosyltransferases ppGalNAcT2, ST6GalNAcT2, C1GalT1, St3Gal-IV, and FUT4 in AGS cells. Moreover, Astragalin also decreased the level of NF-κB, suggesting that the NF-κB signaling pathway might be involved in the inhibition of the glycosylation process. In addition, Astragalin was reported to induce the death of gastric cancer cells and reduce cancer cell viability in a gastric cancer cell-based xenograft mouse model without obvious toxicity. Astragalin administration promoted cell apoptosis and attenuated cell proliferation by up-regulating PARP and Bim and down-regulating Bcl-2, p-PI3K, and p-AKT, indicating that modulating the PI3K/AKT signaling is a key mechanism of Astragalin in preventing gastric cancer. [2]

Anti-inflammatory Activity

Inflammation is an immediate response of the body to tissue damage caused by pathogens and toxic stimuli such as physical or chemical injury. Although the inflammatory response serves as a defense mechanism, when persistent, it can lead to multiple pathological conditions including cancer, allergy, atherosclerosis, and autoimmune diseases. The adverse effects associated with nonsteroidal anti-inflammatory drugs have created a need among researchers to identify effective and safer alternatives. Plant extracts enriched with flavonoids have been recognized for their anti-inflammatory activity. Astragalin, a bioactive natural flavonoid, has been shown to mitigate inflammation in LPS-induced murine models of mastitis and lung injury by reducing myeloperoxidase activity and decreasing the expression of IL-1β, IL-6, and TNF-α. The anti-inflammatory response of astragalin proceeds through inhibition of LPS-induced activation of NF-κB, as it actively prevents the degradation of IκBα and restricts the nuclear translocation of NF-κB. Another investigation on LPS-stimulated expression of inflammatory mediators in macrophages confirmed that astragalin actively inhibits the expression of pro-inflammatory mediators by suppressing the NF-κB signaling pathway. [2]

Toxicity

The acute toxicity of Astragalin, when administered as part of a polyherbal mixture, was evaluated in rats at oral doses of 10 g/kg, 20 g/kg, 40 g/kg, and 80 g/kg of the mixture. The results showed that only one out of five rats in the 80 g/kg group developed mild diarrhea within the first 24 hours following administration, whereas no toxic effects were observed in the other groups. In chronic toxicity studies involving the polyherbal mixture, Astragalin did not induce any obvious histological changes in the pancreas, kidney, or liver of treated rats. However, Astragalin was associated with a significant reduction in body weight, a slight decrease in blood glucose levels, and increases in total cholesterol and HDL levels compared to the control group. In another study, a plant extract rich in Astragalin was administered to rats at a dose of 2000 mg/kg, and Astragalin did not cause any alterations in vital organ tissues. Furthermore, an in silico study predicted that Astragalin possesses multiple pharmacological activities and is unlikely to exhibit acute toxicity. Collectively, these findings suggest that Astragalin may be non-toxic, although further studies are required to support its development as a novel therapeutic agent or functional food. [3]

Reference

[1] Riaz A, Rasul A, Hussain G, et al. Astragalin: a bioactive phytochemical with potential therapeutic activities[J]. Advances in Pharmacological and Pharmaceutical Sciences, 2018, 2018(1): 9794625.

[2] Chen J, Zhong K, Qin S, et al. Astragalin: A food-origin flavonoid with therapeutic effect for multiple diseases[J]. Frontiers in pharmacology, 2023, 14: 1265960.

[3] Wei M, Mahady G B, Liu D, et al. Astragalin, a flavonoid from Morus alba (mulberry) increases endogenous estrogen and progesterone by inhibiting ovarian granulosa cell apoptosis in an aged rat model of menopause[J]. Molecules, 2016, 21(5): 675.

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