Astragalus root (Astragalus membranaceus)

Astragalus belongs to a group of medicinal plants from the Leguminosae family. According to reports, there are > 3000 different types of A. membranaceus. The roots contain the medicinal components and are collected and dried for use.

Astragalus root (Astragalus membranaceus)

Uses

Astragalus has been known for centuries as a treatment for various diseases in traditional Chinese medicine. Such as in wound healing, diabetes, leukemia, hypertension, eye disease, nephritis, cirrhosis, uterine cancer. It is often used along with other herbs as a tonic to increase stamina, strength, and vitality. Extracts of astragalus are sold as dietary supplements to improve immune function and to decrease fatigue. Beneficial effects of astragalus are attributed to its polysaccharides and triterpenoid saponin compounds. In vitro and animal studies indicate that astragalus and its constituents have antioxidant, anti-inflammatory, and antiviral activities, along with exerting protective effects on the heart, kidney, bones, and the nervous system.

Chemistry/Pharmacology

The main bioactive components of the plant are saponins and flavonoids including calycosin, formononetin, astragaloside, and calycosin-7-Obeta-d-glucoside.

Clinical Studies

In small studies involving healthy individuals, astragalus exhibited sodium-excreting properties and produced a viral-type immune response. A formula containing astragalus as a major ingredient reduced fatigue in athletes; and as an adjuvant therapy, helped manage fatigue in stroke patients. In the injectable form, astragalus may benefit patients with IgA nephropathy, and when used in Chinese medicine, helped reduce diabetic ketoacidosis. In addition, an astragalus-based TCM formula was shown to preserve residual renal function in dialysis patients and to reduce proteinuria associated with idiopathic membranous nephropathy. A systematic review concluded that adjunctive use of astragalus in addition to conventional therapies may be effective for short-term reductions of albuminuria, proteinuria, and serum creatinine in patients with diabetic kidney disease.

Preclinical findings indicate that astragalus has anticancer effects against gastric, colon, hepatic and ovarian cancers, and concomitant treatment with aldesleukin potentiated tumoricidal activity while decreasing side effects. Astragalus also enhanced platinum-based chemotherapy and protected against oxaliplatin neurotoxicity. Its saponins were shown to reverse fluorouracil-associated toxicity and augment the therapeutic benefit of vinblastine while reducing neutropenic and anemic effects.

Astragalus may be useful in managing cancer-related fatigue. It has been associated with prolonged survival times in acute myeloid leukemia patients and may help reverse chemo-induced immunosuppression along with reducing chemo-induced side effects. The injectable forms of astragalus may also improve clinical outcomes in liver cancer patients and alleviate cancer symptoms and improve quality of life in patients with advanced and metastatic cancers. Whether orally administered astragalus exerts similar effects is not known. Meta-analyses have shown associations between astragalus and reductions in chemo-induced nausea and vomiting, chemo-induced gastrointestinal toxicity, and improvements in quality of life in patients with hepatocellular cancers.

Although astragalus is generally safe, due to its antioxidant and estrogenic activities, it may interfere with some chemotherapy drugs and/or affect hormone-sensitive cancers. However, these findings are based on preclinical studies and cannot be extrapolated to clinical recommendations. The physiological concentration used in these studies is unlikely to be achieved in humans, which makes it difficult to predict the downstream effects/interactions.

Biomechanical Mechanism

Polysaccharides, triterpenoid saponins, and flavonoids are the main constituents of astragalus with immunomodulating, antioxidant, anti-inflammatory, and anticancer effects. In vitro studies suggest the saponin astragaloside I promote osteoblastic differentiation by regulating the Wnt/beta-catenin signaling pathway. Cardioprotective effects from astragaloside IV may occur via the notch1/hes1 signaling pathway. In addition, it augments fibrinolytic potential via increases in tissue-type plasminogen activator (t-PA) synthesis and downregulation of PA inhibitor type 1 (PAI-1). Other anticoagulant activities are attributed to upregulation of KLF2 mRNA expression and inhibition of NF-kB signaling pathway.

Polysaccharides isolated from astragalus produce immunomodulating effects via activation of toll-like receptor 4 (TLR4)-related mitogen-activated protein kinase (MAPK) activities. In murine models, they reduced colitis via inhibition of NOD-like receptor protein 3 inflammasome, which decreases inflammatory factors such as interleukin (IL)-18 and IL-1beta, and reduced multiorgan iron overload via upregulated hepcidin and IL-6 expression and enhanced p38 MAPK phosphorylation. Cardioprotective effects with this constituent were attributed to anti-inflammatory properties and improved balance between reactive oxygen species (ROS) and NO. In a diabetic rat model, astragalus polysaccharides exerted effects on glucose and lipid metabolism and insulin resistance. Astragalus was also found to reduce the secretion of inflammatory cytokines via increasing levels of CD4+ CD25+ Foxp3+ T cells and by inhibiting the activation of NF-κB.

Benefits to counteract memory disorders were seen with astragalus due to its activity as a nerve-growth-promoting factor and due to its ability to increase M-cholinergic receptor density in senile rats.

In dialysis patients, an astragalus-based TCM formula enhanced NO production and transformed growth-factor-beta suppression. In IgA nephropathy patients, an astragalus injection decreased Core I β3-Gal-T-specific molecular chaperone gene expression and increased IgA1 O-glycosylation levels. In healthy individuals, a sublingual/ingested astragalus root extract produced increases in monocytes, neutrophils, lymphocytes, and platelets, as well as circulating cytokines levels, and self-reported symptoms like viral type immune responses such as fatigue, malaise, and headache. In another study, a formula containing astragalus reduced fatigue in athletes by increasing the uptake and utility of oxygen.

Mechanisms by which astragalus and its constituents may exert anticancer effects have also been examined. In human colorectal cancers cell lines, astragalus suppressed chromosome organization, histone modification, and regulation of macromolecule metabolism, as well as several cancer signaling pathways. Saponins induced S phase and G2/M arrest and suppressed p21 expression and cyclin-dependent kinase activity. Modulation of mTOR signaling and COX2 downregulation also occurred, which in turn can reduce VEGF levels to suppress angiogenesis. In gastric adenocarcinoma cells, caspase 3 activation, G2/M phase cell cycle arrest, cyclin B1, p21 and c-myc regulation, and downregulation of vascular endothelial growth factor (VEGF) and metalloproteinase (MMP)-2 and MMP-9 occurred. Combined with vinblastine, saponins boosted downregulation of proangiogenic and proliferative factors while attenuating neutropenia and anemia seen with this chemotherapy.

In combination with calpain inhibitors, these saponins may also exert more pronounced apoptotic effects. Polysaccharides potentiate the immune-mediated antitumor activity of interleukin-2 in vitro, improve lymphocyte responses, enhance natural killer cell activity, potentiate monocyte activity, increase phagocytosis perhaps by regulating tumor necrosis factor production, and activate macrophages to release nitric oxide and tumor necrosis factor-alpha, which directly blocks growth of breast cancer cells. Apoptotic effects by polysaccharides in hepatocellular carcinoma cells were attributed to decreased Notch1 expression.

Sources/Articles

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Auyeung KK, Woo PK, Law PC, Ko JK. Astragalus saponins modulate cell invasiveness and angiogenesis in human gastric adenocarcinoma cells. J Ethnopharmacol. 2012;141(2):635-41.

Auyeung KK, Law PC, Ko JK. Combined therapeutic effects of vinblastine and Astragalus saponins in human colon cancer cells and tumor xenograft via inhibition of tumor growth and proangiogenic factors. Nutr Cancer. 2014;66(4):662-674.

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Cheng X, Wei B, Sun L, et al. Astragaloside I Stimulates Osteoblast Differentiation Through the Wnt/beta-catenin Signaling Pathway. Phytother Res. Jul 10 2016.Dun C, Liu J, Qiu F, et al. Effects of Astragalus polysaccharides on memory impairment in a diabetic rat model. Neuropsychiatr Dis Treat. 2016;12:1617-1621.

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Han R, Tang F, Lu M, et al. Protective effects of Astragalus polysaccharides against endothelial dysfunction in hypertrophic rats induced by isoproterenol. Int Immunopharmacol. Sep 2016;38:306-312.

Hsieh CH, Lin CY, Hsu CL, et al. Incorporation of Astragalus polysaccharides injection during concurrent chemoradiotherapy in advanced pharyngeal or laryngeal squamous cell carcinoma: preliminary experience of a phase II double-blind, randomized trial. J Cancer Res Clin Oncol. 2020 Jan;146(1):33-41.

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Huang H, Lai S, Wan Q, et al. Astragaloside IV protects cardiomyocytes from anoxia/reoxygenation injury by upregulating the expression of Hes1 protein. Can J Physiol Pharmacol. May 2016;94(5):542-553.

Huang WH, Liao WR, Sun RX. Astragalus polysaccharide induces the apoptosis of human hepatocellular carcinoma cells by decreasing the expression of Notch1. Int J Mol Med. Aug 2016;38(2):551-557.

Huang WC, Kuo KT, Bamodu OA, et al. Astragalus polysaccharide (PG2) Ameliorates Cancer Symptom Clusters, as well as Improves Quality of Life in Patients with Metastatic Disease, through Modulation of the Inflammatory Cascade. Cancers (Basel). 2019 Jul 25;11(8). pii: E1054.

Ji L, Chen X, Zhong X, et al. Astragalus membranaceus up-regulate Cosmc expression and reverse IgA dys-glycosylation in IgA nephropathy. BMC Complement Altern Med. 2014 Jun 18;14:195. doi: 10.1186/1472-6882-14-195.

Law PC, Auyeung KK, Chan LY, et al. Astragalus saponins downregulate vascular endothelial growth factor under cobalt chloride-stimulated hypoxia in colon cancer cells. BMC Complement Altern Med. 2012;12:160.

Li W, Song K, Wang S, et al. Anti-tumor potential of astragalus polysaccharides on breast cancer cell line mediated by macrophage activation. Mater Sci Eng C Mater Biol Appl. 2019 May;98:685-695.

Lu MC, Yao CH, Wang SH, et al. Effect of Astragalus membranaceus in rats on peripheral nerve regeneration: in vitro and in vivo studies. J Trauma. 2010 Feb;68(2):434-40.

Lui SL, Zhu D, Cheng SW, et al. Effects of Astragalus membranaceus-based Chinese Medicine Formulae on Residual Renal Function in Patients on Peritoneal Dialysis. Perit Dial Int. Sep-Oct 2015;35(5):595-597.

Meng LQ, Tang JW, Wang Y, et al. Astragaloside IV synergizes with ferulic acid to inhibit renal tubulointerstitial fibrosis in rats with obstructive nephropathy. Br J Pharmacol. Apr 2011;162(8):1805-1818.

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Qun L, Luo Q, Zhang ZY, et al. Effects of astragalus on IL-2/IL-2R system in patients with maintained hemodialysis. Clin Nephrol. 1999 Nov;52(5):333-4.

Ren F, Qian XH, Qian XL. Astragalus polysaccharide upregulates hepcidin and reduces iron overload in mice via activation of p38 mitogen-activated protein kinase. Biochem Biophys Res Commun. Mar 25 2016;472(1):163-168.

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