Abstract
Astragalus is a cosmopolitan genus characterised by a large number of species with an exceptional rate of diversification. Many of these species are used since ancient times in the Traditional Chinese Medicine (TCM) to cure a condition of general weakness known as “qi”-deficiency. The main phytochemical constituents of these species have been identified as imidazoline alkaloids, nitro toxins, selenium derivatives, polysaccharides, phenols and saponins. Among these, oleanane saponins and cycloartane glycosides are considered as the main responsible for the bioactivity of the plant crude extracts. However, although a plethora of literature data regarding the pharmacological activities of the Astragalus saponins is available, a clear understanding of their mode of action is still missing. In this review, a brief outline of the taxonomy, distribution and morphology of the Astragalus genus is presented along with a comprehensive description of the chemical features and the biological activities of the the saponins from it derived. Moreover, in an attempt to summarise the current mechanistic knowledge on these metabolites, we elaborated a detailed overview of the key signalling pathways that are known to be affected by Astragalus saponins. Finally, we dedicated a section to Astragaloside IV, the best-characterised cycloartane glycoside from Astragalus, to summarise its potentiality as a pharmacological agent. The ultimate goal of this review is to provide the foundations for future investigations, which would eventually enable the introduction of Astragalus saponins in the clinical setting.
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References
Agerer-Kirchhoff C (1976) Revision von Astragalus L. sect. Astragalus (Leguminosae). Boissiera 25:1–197
Agzamova MA, Isaev MI (1995) Astragalus triterpene glycosides and their genins. I. Structures of Cycloalpigenin and Cycloalpioside. Chem Nat Compd 31(5):589–595
Agzamova MA, Isaev MI, Gorovits MB, Abubakirov NK (1986) Triterpene glycosides of Astragalus and their genins. XXII. Cycloorbicoside A from Astragalus orbiculatus. Chem Nat Compd 22(6):671–676
Alaniya MD, Kavtaradze NSh, Skhirtladze AV, Aneli JN (2017) Cyclotanoside, a new cycloartane glycoside from flowers of Astragalus tanae. Chem Nat Compd 53:682–686
Andreotti F, Burzotta F, Manzoli A, Robinson K (2000) Homocysteine and risk of cardiovascular disease. J Thromb Thrombolysis 9(1):13–21
Aslanipour B, Gulcemal D, Nalbantsoy A, Yusufoglu H, Bedir E (2017a) Secondary metabolites from Astragalus karjaginii Boriss and the evaluation of their effects on cytokine release and hemolysis. Fitoterapia 122:26–33
Aslanipour B, Gülcemal D, Nalbantsoy A, Yusufoglu H, Bedir E (2017b) Cycloartane-type glycosides from Astragalus brachycalyx Fischer and their effects on cytokine release and hemolysis. Phytochem Lett 21:66–73
Auyeung KK, Cho CH, Ko JK (2009) A novel anticancer effect of Astragalus saponins: transcriptional activation of NSAID-activated gene. Int J Cancer 125(5):1082–1091
Auyeung KK, Woo PK, Law PC, Ko JK (2012) Astragalus saponins modulate cell invasiveness and angiogenesis in human gastric adenocarcinoma cells. J Ethnopharmacol 141(2):635–641
Auyeung KK, Law PC, Ko JK (2014) 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 66(4):662–674
Auyeung KK, Han QB, Ko JK (2016) Astragalus membranaceus: a review of its protection against inflammation and gastrointestinal cancers. Am J Chin Med 44(1):1–22
Avunduk S, Mitaine-Offer AC, Alankuş-Çalişkan Ö, Miyamoto T, Şenol SG, Lacaille-Dubois MA (2008) Triterpene glycosides from the roots of Astragalus flawescens. J Nat Prod 71:141–145
Azani N, Bruneau A, Wojciechowski MF, Zarre S (2017) Molecular phylogenetics of annual Astragalus (Fabaceae) and its systematic implications. Bot J Linn Soc 184:347–365
Bagheri A, Maassoumi AA, Ghahremaninejad F (2011) Additions to Astragalus sect. Hymenostegis (Fabaceae) in Iran. Iran J Bot 17:15–19
Bagi Z, Ungvari Z, Koller A (2002) Xanthine oxidase—derived reactive oxygen species convert flow-induced arteriolar dilation to constriction in Hyperhomocysteinemia Arteriosclerosis. Thromb Vasc Biol 22(1):28–33
Bao KF, Yu X, Wei X, Gui LL, Liu HL, Wang XY, Tao Y, Jiang GR, Hong M (2016) Astragaloside IV ameliorates allergic inflammation by inhibiting key initiating factors in the initial stage of sensitization. Sci Rep 6:38241
Barneby RC (1964) Atlas of North American Astragalus. Mem N Y Bot Gard 13:1–1188
Bedir E, Çalış İ, Aquino R, Piacente S, Pizza C (1999) Secondary metabolites from the roots of Astragalus trojanus. J Nat Prod 62:563–568
Bedir E, Pugh N, Calis I, Pasco DS, Khan IA (2000) Immunostimulatory effects of cycloartane-type triterpene glycosides from astragalus species. Biol Pharm Bull 23(7):834–837
Benchadi W, Haba H, Lavaud C, Harakat D, Benkhaled M (2013) Secondary metabolites of Astragalus cruciatus Link. and their chemotaxonomic significance. Rec Nat Prod 7:105–113
Boissier E (1872) Flora Orientalis 2:205–498
Bunge A (1869) Generis Astragali species gerontogeae. Mem Acad Imp Sci S Petersboug 15:1–254
Cai Z, Liu J, Bian H, Cai J (2016) Astragaloside IV ameliorates necrotizing enterocolitis by attenuating oxidative stress and suppressing inflammation via the vitamin D3-upregulated protein 1/NF-kappaB signaling pathway. Exp Ther Med 12(4):2702–2708
Cai T, Zhang C, Zhao Z, Li S, Cai H, Chen X, Cai D, Liu W, Yan Y, Xie K, Pan H, Zeng X (2018) The gastric mucosal protective effects of Astragaloside IV in mnng-induced GPL rats. Biomed Pharmacother 104:291–299
Calis I, Koyunoglu S, Yesilada A, Brun R, Ruedi P, Tasdemir D (2006) Antitrypanosomal cycloartane glycosides from Astragalus baibutensis. Chem Biodivers 3(8):923–929
Chaplin DD (2010) Overview of the immune response. J Allergy Clin Immunol 125(2Suppl2):3–23
Chaudhary LB, Rana TS, Anand KK (2008) Current status of the systematics of Astragalus L. (Fabaceae) with special reference to the himalayan species in India. Taiwania 53(4):338–355
Chen P, Xie Y, Shen E, Li GG, Yu Y, Zhang CB, Yang Y, Zou Y, Ge J, Chen R, Chen H (2011) Astragaloside IV attenuates myocardial fibrosis by inhibiting TGF-beta1 signaling in coxsackievirus B3-induced cardiomyopathy. Eur J Pharmacol 658(2–3):168–174
Chen T, Wang R, Jiang W, Wang H, Xu A, Lu G, Ren Y, Xu Y, Song Y, Yong S, Ji H, Ma Z (2016) Protective effect of Astragaloside IV against paraquat-induced lung injury in mice by suppressing Rho signaling. Inflammation 39(1):483–492
Cheng X, Gu J, Zhang M, Yuan J, Zhao B, Jiang J, Jia X (2014) Astragaloside IV inhibits migration and invasion in human lung cancer A549 cells via regulating PKC-α-ERK1/2-NF-κB pathway. Int Immunopharmacol 23(1):304–313
Cheng S, Yu P, Yang L, Shi H, He A, Chen H, Han J, Xie L, Chen J, Chen X (2016) Astragaloside IV enhances cardioprotection of remote ischemic conditioning after acute myocardial infarction in rats. Am J Transl Res 8(11):4657–4669
Choudhary MI, Jan S, Abbaskhan A, Musharraf SG, Samreen Sattar SA, Attaur R (2008) Cycloartane triterpenoids from Astragalus bicuspis. J Nat Prod 71(9):1557–1560
Chowdhery HJ, Rao RR (1992) Plant life in the Himalayan cold deserts: some adaptive strategies. Bull Bot Surv India 32:43–56
Chu H, Huang C, Gao Z, Dong J, Tang Y, Dong Q (2017) Reduction of ischemic brain edema by combined use of paeoniflorin and Astragaloside IV via down-regulating connexin 43. Phytother Res 31(9):1410–1418
Costa IM, Lima FOV, Fernandes LCB, Norrara B, Neta FI, Alves D, Cavalcanti J, Lucena EES, Cavalcante JS, Rego ACM, Filho IA, Queiroz DB, Freire MAM, Guzen FP (2018) Astragaloside IV supplementation promotes a neuroprotective effect in experimental models of neurological disorders: a systematic review. Curr Neuropharmacol. https://doi.org/10.2174/1570159X16666180911123341
Cui B, Inoue J, Takeshita T, Kinjo J, Nohara T (1992a) Triterpene glycosides from the seeds of Astragalus complanatus. Chem Pharm Bull 40(1):136–138
Cui B, Inoue J, Takeshita T, Kinjo J, Nohara T (1992b) Four new oleanene derivatives from seeds of Astragalus sinicus L. Chem Pharm Bull 40(12):3330–3333
Dai H, Jia G, Lu M, Liang C, Wang Y, Wang H (2017a) Astragaloside IV inhibits isoprenalineinduced cardiac fibrosis by targeting the reactive oxygen species/mitogenactivated protein kinase signaling axis. Mol Med Rep 15(4):1765–1770
Dai PC, Liu DL, Zhang L, Ye Y, Wang Q, Zhang HW, Lin XH, Lai GX (2017b) Astragaloside IV sensitizes non-small cell lung cancer cells to gefitinib potentially via regulation of SIRT6 Tumour Biol 39(4). https://doi.org/10.1177/1010428317697555
De Candolle AP (1802) Astragalogia nempe astragali, biserrulae et Oxytropidis nec non phacae, colutae et lessetriae historia iconibus illustrata. Parisiis J.B, Garney, p 369
De Tournefort JP (1700) Institutiones rei herbariae. Paris, France 3 vol. pp 697
Debelec-Butuner B, Ozturk MB, Tag O, Akgun IH, Yetik-Anacak G, Bedir E, Korkmaz KS (2018) Cycloartane-type sapogenol derivatives inhibit NFkappaB activation as chemopreventive strategy for inflammation-induced prostate carcinogenesis. Steroids 135:9–20
Deml I (1972) Revision der Sektionen Acanthophace Bunge und Aegacantha Bunge der Gattung Astragalus L. Boissiera 21:1–235
Dong H, Guo H, Liang Y, Wang X, Niu Y (2017a) Astragaloside IV synergizes with ferulic acid to suppress hepatic stellate cells activation in vitro. Free Radic Res 51(2):167–178
Dong Z, Zhang C, Chen Y, Yuan Z, Peng Y, Cao T (2017b) Astragaloside-IV protects against heat-induced apoptosis by inhibiting excessive activation of mitochondrial Ca2+ uniporter. Cell Physiol Biochem 42(2):480–494
Dong Z, Zhao P, Xu M, Zhang C, Guo W, Chen H, Tian J, Wei H, Lu R, Cao T (2017c) Astragaloside IV alleviates heart failure via activating PPARalpha to switch glycolysis to fatty acid beta-oxidation. Sci Rep 7(1):2691. https://doi.org/10.1038/s41598-017-02360-5
Dong Z, Zhou J, Zhang Y, Chen Y, Yang Z, Huang G, Chen Y, Yuan Z, Peng Y, Cao T (2017d) Astragaloside-IV alleviates heat-induced inflammation by inhibiting endoplasmic reticulum stress and autophagy. Cell Physiol Biochem 42(2):824–837
Du N, Xu Z, Gao M, Liu P, Sun B, Cao X (2018a) Combination of ginsenoside rg1 and Astragaloside IV reduces oxidative stress and inhibits TGF-beta1/Smads signaling cascade on renal fibrosis in rats with diabetic nephropathy. Drug Des Dev Ther 12:3517–3524
Du Q, Zhang S, Li A, Mohammad IS, Liu B, Li Y (2018b) Astragaloside IV inhibits adipose lipolysis and reduces hepatic glucose production via akt dependent PDE3B expression in HFD-fed mice. Front Physiol 9:15. https://doi.org/10.3389/fphys.2018.00015
Fan DD, Lin S, Song P, Wang ZY, Liu B, Gao SN, Fan YH, Zhu S, Li S, Jiang L (2016) Astragaloside IV protects rat gastric mucosa against aspirin-induced damage. Int Immunopharmacol 41:47–55
Gandalovicova A, Rosel D, Fernandes M, Vesely P, Heneberg P, Cermak V, Petruzelka L, Kumar S, Sanz-Moreno V, Brabek J (2017) Migrastatics-anti-metastatic and anti-invasion drugs: promises and challenges. Trends Cancer 3(6):391–406
Ghasemian-Yadegari J, Nazemiyeh H, Hamedeyazdan S, Fathiazad F (2017) Secondary metabolites from the roots of Astragalus maximus. Res J Pharmacogn 4:31–38
Gomez-Sosa E (1982) Novedades en el genero Astragalus, II (Leguminosae-Galegeae). Darwiniana 24:23–31
Gong L, Chang H, Zhang J, Guo G, Shi J, Xu H (2018) Astragaloside IV protects rat cardiomyocytes from hypoxia-induced injury by down-regulation of miR-23a and miR-92a. Cell Physiol Biochem 49(6):2240–2253
Gontscharov NF, Borissova AG, Gorshkova SG, Povov MG, Vasilchenko IT (1946) Astragalus. In: Komarov VL, Shishkin BK (eds) Flora of the U.S.S.R. 12:1–918
Gray A (1864) A revision and arrangement (mainly by the fruit) of the North American species of Astragalus and Oxytropis. Proc Am Acad Arts 6:188–236
Graziani V, Esposito A, Scognamiglio M, Chambery A, Russo R, Ciardiello F, Troiani T, Fiorentino A, Potenza N, D’Abrosca B (2019) Spectroscopic characterization and cytotoxicity assessment towards human colon cancer cell lines of acylated cycloartane glycosides from Astragalus boeticus L. Molecules. 24(9):1–17
Gülcemal D, Masullo M, Bedir E, Festa M, Karayıldırım T, Alankus-Caliskan O, Savran Piacente S (2012) Triterpene glycosides from Astragalus angustifolius. Planta Med 78:720–729
Gülcemal D, Masullo M, Napolitano A, Karayıldırım T, Bedir E, Alankuş-Çalışkan O, Piacente S (2013) Oleanane glycosides from Astragalus tauricolus: isolation and structural elucidation based on a preliminary liquid chromatography-electrospray ionization tandem mass spectrometry profiling. Phytochemistry 86:184–194
Gülcemal D, Aslanipour B, Bedir E (2019) Secondary metabolites from Turkish Astragalus species. In: Ozturk M, Hakeem KR (eds) Plant and human health, vol 2: Phytochemistry and molecular aspects. Springer International Publishing, pp 43–97
Guo H, Cao A, Chu S, Wang Y, Zang Y, Mao X, Wang H, Wang Y, Liu C, Zhang X, Peng W (2016) Astragaloside IV attenuates podocyte apoptosis mediated by endoplasmic reticulum stress through upregulating sarco/endoplasmic reticulum Ca(2+)-ATPase 2 expression in diabetic nephropathy. Front Pharmacol 7:500. https://doi.org/10.3389/fphar.2016.00500
Guo H, Wang Y, Zhang X, Zang Y, Zhang Y, Wang L, Wang H, Wang Y, Cao A, Peng W (2017) Astragaloside IV protects against podocyte injury via SERCA2-dependent ER stress reduction and AMPKalpha-regulated autophagy induction in streptozotocin-induced diabetic nephropathy. Sci Rep 7(1):6852. https://doi.org/10.1038/s41598-017-07061-7
Haiyan H, Rensong Y, Guoqin J, Xueli Z, Huaying X, Yanwu X (2016) Effect of Astragaloside IV on neural stem cell transplantation in alzheimer’s disease rat models. Evid Complement Alternat Med. https://doi.org/10.1155/2016/3106980
Hao M, Liu Y, Chen P, Jiang H, Kuang HY (2018) Astragaloside IV protects RGC-5 cells against oxidative stress. Neural Regen Res 13(6):1081–1086
He CS, Liu YC, Xu ZP, Dai PC, Chen XW, Jin DH (2016) Astragaloside IV enhances cisplatin chemosensitivity in non-small cell lung cancer cells through inhibition of B7-H3. Cell Physiol Biochem 40(5):1221–1229
He KQ, Li WZ, Chai XQ, Yin YY, Jiang Y, Li WP (2018) Astragaloside IV prevents kidney injury caused by iatrogenic hyperinsulinemia in a streptozotocin induced diabetic rat model. Int J Mol Med 41(2):1078–1088
Hoesel B, Schmid JA (2013) The complexity of NF-kappaB signaling in inflammation and cancer. Mol Cancer 12:86. https://doi.org/10.1186/1476-4598-12-86
Horo I, Bedir E, Perrone A, Ozgökçe F, Piacente S, Alankuş-Çalışkan O (2010) Triterpene glycosides from Astragalus icmadophilus. Phytochemistry 71:956–963
Horo I, Bedir E, Masullo M, Piacente S, Ozgökçe F, Alankuş-Çalışkan O (2012) Saponins from Astragalus hareftae (NAB.) SIRJ. Phytochemistry 84:147–153
Hu T, Fei Z, Wei N (2017) Chemosensitive effects of Astragaloside IV in osteosarcoma cells via induction of apoptosis and regulation of caspase-dependent Fas/FasL signalling. Pharmacol Rep 69(6):1159–1164
Huang R, Li M (2016) Protective effect of Astragaloside IV against sepsis-induced acute lung injury in rats. Saudi Pharm J 24(3):341–347
Huang H, Lai S, Wan Q, Qi W, Liu J (2016a) Astragaloside IV protects cardiomyocytes from anoxia/reoxygenation injury by upregulating the expression of Hes1 protein. Can J Physiol Pharmacol 94(5):542–553
Huang P, Lu X, Yuan B, Liu T, Dai L, Liu Y, Yin H (2016b) Astragaloside IV alleviates E. coli-caused peritonitis via upregulation of neutrophil influx to the site of infection. Int Immunopharmacol 39:377–382
Huang F, Lan Y, Qin L, Dong H, Shi H, Wu H, Zou Q, Hu Z, Wu X (2018) Astragaloside IV promotes adult neurogenesis in hippocampal dentate gyrus of mouse through CXCL1/CXCR1 signaling. Molecules. https://doi.org/10.3390/molecules23092178
Ionkova I (1991) Producing triterpene saponins by conventional and genetically transformed cultures of Astragalus hamosus L. (Fabaceae). Probl Farmakol Farmat 5:32–38
Ionkova I, Momekov G, Proksch P (2010) Effects of cycloartane saponins from hairy roots of Astragalus membranaceus Bge on human tumor cell targets. Fitoterapia 81(5):447–451
Ionkova I, Shkondrov A, Krasteva I, Ionkov T (2014) Recent progress in phytochemistry, pharmacology and biotechnology of Astragalus saponins. Phytochem Rev 13(2):343–374
Ji C, Luo Y, Zou C, Huang L, Tian R, Lu Z (2018) Effect of Astragaloside IV on indoxyl sulfate-induced kidney injury in mice via attenuation of oxidative stress. BMC Pharmacol Toxicol 19(1):53. https://doi.org/10.1186/s40360-018-0241-2
Jia L, Lv D, Zhang S, Wang Z, Zhou B (2018) Astragaloside IV inhibits the progression of non-small cell lung cancer. Oncol Res. https://doi.org/10.3727/096504018x15344989701565
Jiang K, Lu Q, Li Q, Ji Y, Chen W, Xue X (2017a) Astragaloside IV inhibits breast cancer cell invasion by suppressing Vav3 mediated Rac1/MAPK signalling. Int Immunopharmacol 42:195–202
Jiang XG, Sun K, Liu YY, Yan L, Wang MX, Fan JY, Mu HN, Li C, Chen YY, Wang CS, Han JY (2017b) Astragaloside IV ameliorates 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis implicating regulation of energy metabolism. Sci Rep 7:41832. https://doi.org/10.1038/srep41832
Jin H, Wang L, Li B, Cai C, Ye J, Xia J, Ma S (2017) Astragaloside IV ameliorates airway inflammation in an established murine model of asthma by inhibiting the mTORC1 signaling pathway. Evid Complement Alternat Med. https://doi.org/10.1155/2017/4037086
Johnston IM (1947) Astragalus in Argentina, Bolivia and Chile. J Arnold Arboretum 28:336–409
Jones ME (1923) Revision of North American species of Astragalus. Utah, Salt Lake City, p 288
Ju Y, Su Y, Chen Q, Ma K, Ji T, Wang Z, Li W, Li W (2018) Protective effects of Astragaloside IV on endoplasmic reticulum stress-induced renal tubular epithelial cells apoptosis in type 2 diabetic nephropathy rats. Biomed Pharmacother 109:84–92
Kalluri R, Weinberg RA (2009) The basics of epithelial-mesenchymal transition. J Clin Investig 119:1420–1428
Kazempour OS, Maassoumi AA, Murakani N (2003) Molecular systematics of the genus Astragalus L. (Fabaceae): phylogenetic analysis of nuclear ribosomal DNA internal transcribed spacers and chloroplast gene ndhF sequences. Plant Syst Evol 242:1–32
Kazempour OS, Maassoumi AA, Murakani N (2005) Molecular systematics of the Old world Astragalus (Fabaceae) as inferred from nrDNA ITS sequence data. Brittonia 57:367–381
Khan MT, Choudhary MI, Attaur R, Mamedova RP, Agzamova MA, Sultankhodzhaev MN, Isaev MI (2006) Tyrosinase inhibition studies of cycloartane and cucurbitane glycosides and their structure-activity relationships. Bioorg Med Chem 14(17):6085–6088
Kinjo J, Udayama M, Okawa M, Nohara T (1999) Study of structure–hepatoprotective relationships of oleanene-type triterpenoidal glucuronides obtained from several fabaceous plants on rat primary hepatocyte cultures. Biol Pharm Bull 22(2):203–206
Kitagawa I, Wang HK, Yoshikawa M (1983a) Saponin and sapogenol. XXXVII. Chemical constituents of astragali radix, the root of Astragalus membranaceus Bunge. 4. Astragalosides VII and VIII. Chem Pharm Bull 31:716–722
Kitagawa I, Wang HK, Saito M, Takagi A, Yoshikawa M (1983b) Saponin and sapogenol. XXXV. Chemical constituents of astragali radix, the root of Astragalus membranaceus Bunge. 2. Astragalosides I, II and IV, acetylastragaloside I and isoastragalosides I and II. Chem Pharm Bull 31:698–708
Ko (1998) Astragalus saponins induce apoptosis via an ERK-independent NF-κB signaling pathway in the human hepatocellular HepG2 cell line. Int J Mol Med 23:189–196
Krasteva I, Nikolov S, Kaloga M, Mayer G (2007) A new saponin lactone from Astragalus corniculatus. Nat Prod Res 21:941–945
Krastevaa I, Nikolov S, Kaloga M, Mayer G (2006) Triterpenoid saponins from Astragalus corniculatus. Z Naturforsch 61b:1166–1169
Lacaille-Dubois M (2005) Bioactive saponins with cancer related and immunomodulatory activity: recent developments. Stud Nat Prod Chem 32(L):209–246
Lee S, Nguyen MT (2015) Recent advances of vaccine adjuvants for infectious diseases. Immune Netw 15(2):51–57
Lee S, Jeong JS, Kwon HJ, Hong SP (2017) Quantification of isoflavonoids and triterpene saponins in Astragali Radix, the root of Astragalus membranaceus, via reverse-phase high-performance liquid chromatography coupled with integrated pulsed amperometric detection. J Chromatogr 1070:76–81
Leng B, Tang F, Lu M, Zhang Z, Wang H, Zhang Y (2018) Astragaloside IV improves vascular endothelial dysfunction by inhibiting the TLR4/NF-kappaB signaling pathway. Life Sci 209:111–121
Li X, He D, Zhang L, Cheng X, Sheng B, Luo Y (2006) A novel antioxidant agent, Astragalosides, prevents shock wave-induced renal oxidative injury in rabbits. Urol Res 34(4):277–282
Li M, Qu YZ, Zhao ZW, Wu SX, Liu YY, Wei XY, Gao L, Gao GD (2012) Astragaloside IV protects against focal cerebral ischemia/reperfusion injury correlating to suppression of neutrophils adhesion-related molecules. Neurochem Int 60(5):458–465
Li M, Ma RN, Li LH, Qu YZ, Gao GD (2013) Astragaloside IV reduces cerebral edema post-ischemia/reperfusion correlating the suppression of MMP-9 and AQP4. Eur J Pharmacol 715(1–3):189–195
Li X, Qu L, Dong Y, Han L, Liu E, Fang S, Zhang Y, Wang T (2014) A review of recent research progress on the Astragalus Genus. Molecules 19:18850–18880
Li B, Wang F, Liu N, Shen W, Huang T (2017a) Astragaloside IV inhibits progression of glioma via blocking MAPK/ERK signaling pathway. Biochem Biophys Res Commun 491(1):98–103
Li K, Chen Y, Jiang R, Chen D, Wang H, Xiong W, Li D, Liu Z, Li X, Li J, Yuan K (2017b) Protective effects of Astragaloside IV against ovalbumin-induced allergic rhinitis are mediated by T-box protein expressed in T cells/GATA-3 and forkhead box protein 3/retinoic acid-related orphan nuclear receptor gammat. Mol Med Rep 16(2):1207–1215
Li L, Hou X, Xu R, Liu C, Tu M (2017c) Research review on the pharmacological effects of Astragaloside IV. Fundam Clin Pharmacol 31(1):17–36
Li LC, Xu L, Hu Y, Cui WJ, Cui WH, Zhou WC, Kan LD (2017d) Astragaloside IV improves bleomycin-induced pulmonary fibrosis in rats by attenuating extracellular matrix deposition. Front Pharmacol 8:513. https://doi.org/10.3389/fphar.2017.00513
Li M, Li H, Fang F, Deng X, Ma S (2017e) Astragaloside IV attenuates cognitive impairments induced by transient cerebral ischemia and reperfusion in mice via anti-inflammatory mechanisms. Neurosci Lett 639:114–119
Li Y, Meng T, Hao N, Tao H, Zou S, Li M, Ming P, Ding H, Dong J, Feng S, Li J, Wang X, Wu J (2017f) Immune regulation mechanism of Astragaloside IV on RAW264.7 cells through activating the NF-kappaB/MAPK signaling pathway. Int Immunopharmacol 49:38–49
Li XZ, Ding YZ, Wu HF, Bian ZP, Xu JD, Gu CR, Chen XJ, Yang D (2017g) Astragaloside IV prevents cardiac remodeling in the apolipoprotein E-deficient mice by regulating cardiac homeostasis and oxidative stress. Cell Physiol Biochem 44(6):2422–2438
Li C, Yang F, Liu F, Li D, Yang T (2018a) NRF2/HO-1 activation via ERK pathway involved in the anti-neuroinflammatory effect of Astragaloside IV in LPS induced microglial cells. Neurosci Lett 666:104–110
Li H, Wang P, Huang F, Jin J, Wu H, Zhang B, Wang Z, Shi H, Wu X (2018b) Astragaloside IV protects blood–brain barrier integrity from LPS-induced disruption via activating Nrf2 antioxidant signaling pathway in mice. Toxicol Appl Pharmacol 340:58–66
Li H, Zhang Y, Min J, Gao L, Zhang R, Yang Y (2018c) Astragaloside IV attenuates orbital inflammation in Graves’ orbitopathy through suppression of autophagy. Inflamm Res 67(2):117–127
Li L, HuangW Wang S, Sun K, Zhang W, Ding Y, Zhang L, Tumen B, Ji L, Liu C (2018d) Astragaloside IV attenuates acetaminophen-induced liver injuries in mice by activating the Nrf2 signaling pathway. Molecules 23:2032–2040
Li Y, Ye Y, Chen H (2018e) Astragaloside IV inhibits cell migration and viability of hepatocellular carcinoma cells via suppressing long noncoding RNA ATB. Biomed Pharmacother 99:134–141
Linnaeus C (1753) Species plantarum. Stockholm, Sweden. pp 755–762
Liston A (1992) Variation in the chloroplast genes rpoC1 and rpoC2 of the genus Astragalus (Fabaceae): evidence from restriction site mapping of a PCR amplified fragment. Am J Bot 79:953–961
Liu HS, Shi HL, Huang F, Peterson KE, Wu H, Lan YY, Zhang BB, He YX, Woods T, Du M, Wu XJ, Wang ZT (2016a) Astragaloside IV inhibits microglia activation via glucocorticoid receptor mediated signaling pathway. Sci Rep 6:19137
Liu R, Jiang H, Tian Y, Zhao W, Wu X (2016b) Astragaloside IV protects against polymicrobial sepsis through inhibiting inflammatory response and apoptosis of lymphocytes. J Surg Res 200(1):315–323
Liu J, Meng Q, Jing H, Zhou S (2017a) Astragaloside IV protects against apoptosis in human degenerative chondrocytes through autophagy activation. Mol Med Rep 16(3):3269–3275
Liu X, Wang W, Song G, Wei X, Zeng Y, Han P, Wang D, Shao M, Wu J, Sun H, Xiong G, Li S (2017b) Astragaloside IV ameliorates diabetic nephropathy by modulating the mitochondrial quality control network. PLoS One 12(8):e0182558
Liu X, Zhang J, Wang S, Qiu J, Yu C (2017c) Astragaloside IV attenuates the H2O2-induced apoptosis of neuronal cells by inhibiting alpha-synuclein expression via the p38 MAPK pathway. Int J Mol Med 40(6):1772–1780
Liu ZH, Liu HB, Wang J (2018) Astragaloside IV protects against the pathological cardiac hypertrophy in mice. Biomed Pharmacother 97:1468–1478
Lock JM, Schrire BD (2005) Tribe Galegeae. In: Lewis G, Schire B, Mackinder B, Lock M (eds) Legumes of the world. Royal Botanic Gardens, Kew
Lu M, Leng B, He X, Zhang Z, Wang H, Tang F (2018) Calcium sensing receptor-related Pathway contributes to cardiac injury and the mechanism of Astragaloside IV on cardioprotection. Front Pharmacol 9:1163. https://doi.org/10.3389/fphar.2018.01163
Luo Y, Qin Z, Hong Z, Zhang X, Ding D, Fu JH, Zhang WD, Chen J (2004) Astragaloside IV protects against ischemic brain injury in a murine model of transient focal ischemia. Neurosci Lett 363(3):218–223
Luo X, Huang P, Yuan B, Liu T, Lan F, Lu X, Dai L, Liu Y, Yin H (2016) Astragaloside IV enhances diabetic wound healing involving upregulation of alternatively activated macrophages. Int Immunopharmacol 35:22–28
Luo H, Yao L, Zhang Y, Li R (2017) Liquid chromatography-mass spectrometry-based quantitative proteomics analysis reveals chondroprotective effects of Astragaloside IV in interleukin-1beta-induced SW1353 chondrocyte-like cells. Biomed Pharmacother 91:796–802
Ma Y, Qiao G, Yin Y, Zhang Y, Yu Y, Yu X (2018) Protective effects of Astragaloside IV on delayed cerebral vasospasm in an experimental rat model of subarachnoid haemorrhage. World Neurosurg 118:e443–e448. https://doi.org/10.1016/j.wneu.2018.06.212
Maassoumi AAR (1998) Old world check-list of Astragalus. Research Institute of Forests and Rangelands, Tehran
Mamedova RP, Isaev MI (2004) Triterpenoids from Astragalus plants. Chem Nat Compd 40(4):303–357
Mann J (2002) Natural products in cancer chemotherapy: past, present and future. Nat Rev Cancer 2:143–148
Mao S, Yang G, Li W, Zhang J, Liang H, Li J, Zhang M (2016) Gastroprotective effects of Astragaloside IV against acute gastric lesion in rats. PLoS One. https://doi.org/10.1371/journal.pone.0148146
McDowell IF, Lang D (2000) Homocysteine and endothelial dysfunction: a link with cardiovascular disease. J Nutr 130(2S):369S–372S
Meiqian Z, Leying Z, Chang C (2018) Astragaloside IV inhibits cigarette smoke-induced pulmonary inflammation in mice. Inflammation 41(5):1671–1680
Mitaine-Offer AC, Miyamoto T, Semmar N, Jay M, Lacaille-Dubois MA (2006) A new oleanane glycoside fro m the roots of Astragalus caprinus. Magn Reson Chem 44(7):713–716
Murata I, Abe Y, Yaginuma Y, Yodo K, Kamakari Y, Miyazaki Y, Baba D, Shinoda Y, Iwasaki T, Takahashi K, Kobayashi J, Inoue Y, Kanamoto I (2017) Astragaloside-IV prevents acute kidney injury and inflammation by normalizing muscular mitochondrial function associated with a nitric oxide protective mechanism in crush syndrome rats. Ann Intensive Care 7(1):90. https://doi.org/10.1186/s13613-017-0313-2
Nalbantsoy A, Nesil T, Erden S, Calis I, Bedir E (2011) Adjuvant effects of Astragalus saponins macrophyllosaponin B and Astragaloside VII. J Ethnopharmacol 134(3):897–903
Nalbantsoy A, Nesil T, Yilmaz-Dilsiz O, Aksu G, Khan S, Bedir E (2012) Evaluation of the immunomodulatory properties in mice and in vitro anti-inflammatory activity of cycloartane type saponins from Astragalus species. J Ethnopharmacol 139(2):574–581
Oh YS (2016) Bioactive compounds and their neuroprotective effects in diabetic complications. Nutrients 8(8):472
Ozipek M, Doenmez AA, Calis I, Brun R, Rueedi P, Tasdemir D (2005) Leishmanicidal cycloartane-type triterpene glycosides from astragalus oleifolius. Phytochemistry 66:1168–1173
Paterson I, Anderson EA (2005) Chemistry. The renaissance of natural products as drug candidates. Science 310:451–453
Pignatti S (2017) Flora d’Italia vol. 2 Edagricole pp 1–1778
Pistelli L, Bertoli A, Lepori E, Morelli I, Panizzi L (2002) Antimicrobial and antifungal activity of crude extracts and isolated saponins from Astragalus verrucosus. Fitoterapia 73(4):336–339
Podlech D (1986) Taxonomic and phytogeographical problems in Astragalus of old world and southwest Asia. Proc R Soc Edinburgh 89:37–43
Podlech D (1998) Phylogeny and progression of characters in Old World Astragali (Leguminosae). In: Zhang A, Wu S (eds) Floristic characteristics and diversity of East Asian Plants. China Higher Education Press China, pp 405–407
Podlech D (1999) http://www.botanik/biologie.uni-muenchen.de/botsyst/thesau1.html
Podlech D (2008) The genus Astragalus L. (Fabaceae) in Europe with exclusion of the former Soviet Union. Feddes Repertorium 119(5–6): 310–387
Podlech D, Xu LR (2004) New species and combinations in Astragalus (Leguminosae) from China and the Himalayas. Novon 14:216–226
Podlech D, Xu LR (2007) New species and new combination in Astragalus (Leguminosae) from China. Novon 17:228–254
Podlech D, Zarre S (2013) A taxonomic revision of the genus Astragalus L. (Leguminosae) in the Old World, vol 1–3. Naturhistorisches Museum, Wien
Populo H, Lopes JM, Soares P (2012) The mTOR signalling pathway in human cancer. Int J Mol Sci 13(2):1886–1918
Qi LW, Yu QT, Yi L, Ren MT, Wen XD, Wang YX, Li P (2008) Simultaneous determination of 15 marker constituents in various radix Astragali preparations by solid-phase extraction and high-performance liquid chromatography. J Sep Sci 31(1):97–106
Qi Y, Gao F, Hou L, Wan C (2017) Anti-inflammatory and immunostimulatory activities of Astragalosides. Am J Chin Med 45(6):1157–1167
Qian W, Cai X, Qian Q, Zhang W, Wang D (2018) Astragaloside IV modulates TGF-beta1-dependent epithelial-mesenchymal transition in bleomycin-induced pulmonary fibrosis. J Cell Mol Med 22(9):4354–4365
Qiao Y, Fan CL, Tang MK (2017) Astragaloside IV protects rat retinal capillary endothelial cells against high glucose-induced oxidative injury. Drug Des Dev Ther 11:3567–3577
Qin S, Huang K, Fang Z, Yin J, Dai R (2017) The effect of Astragaloside IV on ethanol-induced gastric mucosal injury in rats: involvement of inflammation. Int Immunopharmacol 52:211–217
Qiu LH, Xie XJ, Zhang BQ (2010) Astragaloside IV improves homocysteine-induced acute phase endothelial dysfunction via antioxidation. Biol Pharm Bull 33(4):641–646
Qiu X, Guo Q, Xiong W, Yang X, Tang YQ (2016) Therapeutic effect of Astragaloside-IV on bradycardia is involved in up-regulating klotho expression. Life Sci 144:94–102
Rajput ZI, Hu SH, Xiao CW, Arijo AG (2007) Adjuvant effects of saponins on animal immune responses. J Zhejiang Univ Sci B 8(3):153–161
Ren S, Zhang H, Mu Y, Sun M, Liu P (2013) Pharmacological effects of Astragaloside IV: a literature review. J Tradit Chin Med 33(3):413–416
Rios JL, Waterman PG (1997) A review of the pharmacology and toxicology of Astragalus. Phytother Res 11(6):411–418
Rydberg PA (1929) Astragalanae. N Am Flora 24:251–462
Sanderson MJ, Doyle JJ (1993) Phylogenetic relationships in North American Astragalus L. (Fabaceae) based on choloroplast DNA restriction site variation. Syst Bot 18:395–408
Sanderson MJ, Wojciechowski MF (2000) Improved bootstrap confidence limits in large-scale phylogenies with an example from Neo-Astragalus (leguminosae). Syst Biol 49:671–685
Sarraj-Laabidi A, Lacaille-Dubois MA, Semmar N (2018) Structural organization of cycloartane-based saponins in the genus Astragalus (Fabaceae). Phytochem Rev 17:431–452
Savran T, Gülcemal D, Masullo M, Karayıldırım T, Polat E, Piacente S, Alankuş-Çalışkan Ö (2012) Cycloartane glycosides from Astragalus erinaceus. Rec Nat Prod 6:230–236
Scherson RA, Vidal R, Sanderson MJ (2008) Phylogeny, biogeography, and rates of diversification of new world Astragalus (leguminosae) with an emphasis on South American radiations. Am J Bot 95(8):1030–1039
Shkondrov A, Krasteva I, Bucar F, Kunert O, Kondeva-Burdina M, Ionkova I (2018) A new tetracyclic saponin from Astragalus glycyphyllos L. and its neuroprotective and hMAO-B inhibiting activity. Nat Prod Res. https://doi.org/10.1080/14786419.2018.1491040
Sinclair S (1998) Chinese herbs: a clinical review of Astragalus, Ligusticum, and Schizandrae. Altern Med Rev 3(5):338–344
Song G, Han P, Sun H, Shao M, Yu X, Wang W, Wang D, Yi W, Ge N, Li S, Yi T (2018) Astragaloside IV ameliorates early diabetic nephropathy by inhibition of MEK1/2-ERK1/2-RSK2 signaling in streptozotocin-induced diabetic mice. J Int Med Res 46(7):2883–2897
Sun H, Wang W, Han P, Shao M, Song G, Du H, Yi T, Li S (2016a) Astragaloside IV ameliorates renal injury in db/db mice. Sci Rep 6:32545. https://doi.org/10.1038/srep32545
Sun J, Chen XL, Zheng JY, Zhou JW, Ma ZL (2016b) Astragaloside IV protects new born rats from anesthesia-induced apoptosis in the developing brain. Exp Ther Med 12(3):1829–1835
Sun B, Rui R, Pan H, Zhang L, Wang X (2018) Effect of combined use of Astragaloside IV (AsIV) and atorvastatin (AV) on expression of PPAR-gamma and inflammation-associated cytokines in atherosclerosis rats. Med Sci Monit 24:6229–6236
Sun P, Liu Y, Wang Q, Zhang B (2019) Astragaloside IV inhibits human colorectal cancer cell growth. Front Biosci (Landmark Ed) 24:597–606
Taeb F, Zarre S, Podlech D, Tillich HJ, Osaloo SK, Maassoumi AA (2007) A contribution to the phylogeny of annual species of Astragalus (Fabaceae) in the Old World using hair micromorphology and other morphological characters. Feddes Repert 118:206–227
Taeb F, Ekici M, Podlech D (2012) Taxonomic revision of annual species of Astragalus (Fabaceae) in Turkey. Feddes Repert 123:1–26
Tang B, Zhang G, Tan HY, Wei XQ (2018) Astragaloside IV inhibits ventricular remodeling and improves fatty acid utilization in rats with chronic heart failure. Biosci Rep. https://doi.org/10.1042/bsr20171036
Tietz S, Zarre SH (1994) Revision von Astragalus L. sect. Megalocystis Bunge (Fabaceae). Sendtnera 2:287–363
Tin MM, Cho CH, Chan K, James AE, Ko JK (2007) Astragalus saponins induce growth inhibition and apoptosis in human colon cancer cells and tumor xenograft. Carcinogenesis 28(6):1347–1355
Torrey J, Gray A (1838) Tribe Astragaleae. Flora N Am 1:328–353
Tutin TG, Heywood VH, Burges NA, Moore DM, Valentine SM, Walters SM, Webb DA (2010) Flora Europea, Cambridge University Press vol 2, pp 469
Un R, Horo I, Masullo M, Falco A, Senol SG, Piacente S, Alankuş-Çalıskan Ö (2016) Cycloartane and oleanane-type glycosides from Astragalus pennatulus. Fitoterapia 109:254–260
Ungvari Z, Csiszar A, Bagi Z, Koller A (2002) Impaired nitric oxide-mediated flow-induced coronary dilation in hyperhomocysteinemia: morphological and functional evidence for increased peroxynitrite formation. Am J Pathol 161(1):145–153
van Helvert S, Storm C, Friedl P (2018) Mechanoreciprocity in cell migration. Nat Cell Biol 20(1):8–20
Verotta L, El-Sebakhy N (2001) Cycloartane and oleanane saponins from Astragalus sp studies in natural products. Chemistry 25(F):179–234
Viqar UA, Faryal VM & Rasool BT (2018) Laceioside, a new cycloartane saponin from Astragalus tephrosioides Boiss. var. lacei (Ali) Kirchoff. Nat Prod Res https://doi.org/10.1080/14786419.2018.1455042
Wan Y, Xu L, Wang Y, Tuerdi N, Ye M, Qi R (2018) Preventive effects of Astragaloside IV and its active sapogenin cycloastragenol on cardiac fibrosis of mice by inhibiting the NLRP3 inflammasome. Eur J Pharmacol 833:545–554
Wang Y, Auyeung KK, Zhang X, Ko JK (2014) Astragalus saponins modulates colon cancer development by regulating calpain-mediated glucose-regulated protein expression. BMC Complement Altern Med 14:401
Wang T, Ruan J, Li X, Chao L, Shi P, Han L, Zhang Y, Wang T (2016a) Bioactive cyclolanstane-type saponins from the stems of Astragalus membranaceus (Fisch.) Bge. var. mongholicus (Bge.) Hsiao J Nat Med 70:198–206
Wang Y, Ren T, Zheng L, Chen H, Ko JK, Auyeung KK (2016b) Astragalus saponins inhibits lipopolysaccharide-induced inflammation in mouse macrophages. Am J Chin Med 44(3):579–593
Wang C, Li Y, Yang X, Bi S, Zhang Y, Han D, Zhang D (2017a) Tetramethylpyrazine and Astragaloside IV synergistically ameliorate left ventricular remodeling and preserve cardiac function in a rat myocardial infarction model. J Cardiovasc Pharmacol 69(1):34–40
Wang HL, Zhou QH, Xu MB, Zhou XL, Zheng GQ (2017b) Astragaloside IV for experimental focal cerebral ischemia: preclinical evidence and possible mechanisms. Oxid Med Cell Longev 2017:8424326
Wang N, Siu F, Zhang Y (2017c) Effect of Astragaloside IV on diabetic gastric mucosa in vivo and in vitro. Am J Transl Res 9(11):4902–4913
Wang PP, Luan JJ, Xu WK, Wang L, Xu DJ, Yang CY, Zhu YH, Wang YQ (2017d) Astragaloside IV downregulates the expression of MDR1 in Bel7402/FU human hepatic cancer cells by inhibiting the JNK/cJun/AP1 signaling pathway. Mol Med Rep 16(3):2761–2766
Wang ZF, Ma DG, Zhu Z, Mu YP, Yang YY, Feng L, Yang H, Liang JQ, Liu YY, Liu L, Lu HW (2017e) Astragaloside IV inhibits pathological functions of gastric cancer-associated fibroblasts. World J Gastroenterol 23(48):8512–8525
Wang C, Li Y, Hao M, Li W (2018a) Astragaloside IV inhibits triglyceride accumulation in insulin-resistant HepG2 Cells via AMPK-induced SREBP-1c phosphorylation. Front Pharmacol 9:345
Wang S, Mou J, Cui LX, Wang X, Zhang Z (2018b) Astragaloside IV inhibits cell proliferation of colorectal cancer cell lines through down-regulation of B7-H3. Biomed Pharmacother 102:1037–1044
Wang X, Gao Y, Tian N, Zou D, Shi Y, Zhang N (2018c) Astragaloside IV improves renal function and fibrosis via inhibition of miR-21-induced podocyte dedifferentiation and mesangial cell activation in diabetic mice. Drug Des Dev Ther 12:2431–2442
Wenninger J (1991) Revision von Astragalus L. sect. Chlorostachys Bunge, sect. Phyllolobium Bunge und sect. Skythropos Simpson (Leguminosae). Mitt Bot Staatss München 30:1–196
Wink M (2013) Evolution of secondary metabolites in legumes (Fabaceae) South Afr J Bot 89:164–75
Wojciechowski MF (2005) Astragalus (Fabaceae): a molecular phylogenetic perspective. Brittonia 57:382–396
Wojciechowski MF, Sanderson MJ, Baldwin BG, Donoghue MJ (1993) Monophyly of aneuploid Astragalus (Fabaceae): Evidence from nuclear ribosomal DNA internal transcribed spacer sequences. Am J Bot 80:711–722
Wojciechowski MF, Sanderson MJ, Hu JM (1999) Evidence on the monophyly of Astragalus (Fabaceae) and its major subgroups based on nuclear ribosomal DNA ITS and chloroplast DNA trnL intron data. Syst Bot 24:409–437
Wu H, Gao Y, Shi HL, Qin LY, Huang F, Lan YY, Zhang BB, Hu ZB, Wu XJ (2016) Astragaloside IV improves lipid metabolism in obese mice by alleviation of leptin resistance and regulation of thermogenic network. Sci Rep 6:30190
Xia L, Guo D, Chen B (2017) Neuroprotective effects of Astragaloside IV on Parkinson disease models of mice and primary astrocytes. Exp Ther Med 14(6):5569–5575
Xie T, Li Y, Li SL, Luo HF (2016) Astragaloside IV enhances cisplatin chemosensitivity in human colorectal cancer via regulating NOTCH3. Oncol Res 24(6):447–453
Xu L, Podlech D (2010) Astragalus. In: Wu ZY, Raven HP, Hong DY (eds) Flora of China Vol. 10 (Fabaceae). Science Press: Beijing, and Missouri Botanical Garden Press, St. Louis
Xu C, Tang F, Lu M, Yang J, Han R, Mei M, Hu J, Wang H (2016a) Pretreatment with Astragaloside IV protects human umbilical vein endothelial cells from hydrogen peroxide induced oxidative stress and cell dysfunction via inhibiting eNOS uncoupling and NADPH oxidase—ROS—NF-kappaB pathway. Can J Physiol Pharmacol 94(11):132–1140
Xu C, Tang F, Lu M, Yang J, Han R, Mei M, Hu J, Zhou M, Wang H (2016b) Astragaloside IV improves the isoproterenol-induced vascular dysfunction via attenuating eNOS uncoupling-mediated oxidative stress and inhibiting ROS-NF-kappaB pathways. Int Immunopharmacol 33:119–127
Xu H, Wang CY, Zhang HN, Lv CY, Wang YZ (2016c) Astragaloside IV suppresses inflammatory mediator production in synoviocytes and collageninduced arthritic rats. Mol Med Rep 13(4):3289–3296
Xu F, Cui WQ, Wei Y, Cui J, Qiu J, Hu LL, Gong WY, Dong JC, Liu BJ (2018) Astragaloside IV inhibits lung cancer progression and metastasis by modulating macrophage polarization through AMPK signaling. J Exp Clin Cancer Res 37(1):207
Yan W, Xu Y, Yuan Y, Tian L, Wang Q, Xie Y, Shao X, Zhang M, Ni Z, Mou S (2017) Renoprotective mechanisms of Astragaloside IV in cisplatin-induced acute kidney injury. Free Radic Res 51(7–8):669–683
Yang ZG, Sun HX, Fang WH (2005) Haemolytic activities and adjuvant effect of Astragalus membranaceus saponins (AMS) on the immune responses to ovalbumin in mice. Vaccine 23(44):5196–5203
Yang LP, Shen JG, Xu WC, Li J, Jiang JQ (2013) Secondary metabolites of the genus Astragalus: structure and biological-activity update. Chem Biodivers 10(6):1004–1054
Yang L, Xing F, Han X, Li Q, Wu H, Shi H, Wang Z, Huang F, Wu X (2018) Astragaloside IV regulates differentiation and induces apoptosis of activated CD4(+) T cells in the pathogenesis of experimental autoimmune encephalomyelitis. Toxicol Appl Pharmacol 362:105–115
Yao XM, Liu YJ, Wang M, Wang H, Zhu BB, Liang YP, Yao WG, Yu H, Wang NS, Zhang XM, Peng W (2016) Astragaloside IV prevents high glucose-induced podocyte apoptosis via downregulation of TRPC6. Mol Med Rep 13(6):5149–5156
Ye Q, Su L, Chen D, Zheng W, Liu Y (2017) Astragaloside IV induced miR-134 expression reduces EMT and increases chemotherapeutic sensitivity by suppressing CREB1 signaling in colorectal cancer cell line SW-480. Cell Physiol Biochem 43(4):1617–1626
Yesilada E, Bedir E, Calis I, Takaishi Y, Ohmoto Y (2005) Effects of triterpene saponins from Astragalus species on in vitro cytokine release. J Ethnopharmacol 96(1–2):71–77
Yin X, Zhang Y, Yu J, Zhang P, Shen J, Qiu J, Wu H, Zhu X (2006) The antioxidative effects of astragalus saponin I protect against development of early diabetic nephropathy. J Pharmacol Sci 101(2):166–173
Yin B, Hou XW, Lu ML (2019) Astragaloside IV attenuates myocardial ischemia/reperfusion injury in rats via inhibition of calcium-sensing receptor-mediated apoptotic signaling pathways. Acta Pharmacol Sin 40(5):599–607
Yoshikawa M, Wang HK, Kayakiri H, Taniyama T, Kitagawa I (1985) Saponin and sapogenol. XL. Structure of sophoraflavoside I, a bisdesmoside of soyasapogenol B, from Sophorae Radix, the root of Sophora flavescens Aiton. Chem Pharm Bull 33:4267–4274
Yu Q, Qi L, Li P, Yi L, Zhao J, Bi Z (2007) Determination of seventeen main flavonoids and saponins in the medicinal plant Huang-qi (Radix Astragali) by HPLC-DAD-ELSD. J Sep Sci 30:1292–1299
Yu WN, Sun LF, Yang H (2016) Inhibitory effects of Astragaloside IV on bleomycin-induced pulmonary fibrosis in rats via attenuation of oxidative stress and inflammation. Inflammation 39(5):1835–1841
Zarre SH (2000) Systematic revision of Astragalus sect. Adiaspastus, sect. Macrophyllium and sect. Pterophorus Englera 18:1–219
Zarre S, Azani N (2013) Perspectives in taxonomy and phylogeny of the genus Astragalus (Fabaceae): a review. Prog Biol Sci 3(1):1–6
Zarre SH, Podlech D (1997) Problems in the taxonomy of tragacanthic Astragali. Sendtnera 4:243–250
Zhang WJ, Wojta J, Binder BR (1997) Regulation of the fibrinolytic potential of cultured human umbilical vein endothelial cells: Astragaloside IV downregulates plasminogen activator inhibitor-1 and upregulates tissue-type plasminogen activator expression. J Vasc Res 34(4):273–280
Zhang WD, Zhang C, Wang XH, Gao PJ, Zhu DL, Chen H, Liu RH, Li HL (2006) Astragaloside IV dilates aortic vessels from normal and spontaneously hypertensive rats through endothelium-dependent and endothelium-independent ways. Planta Med 72(7):621–626
Zhang BQ, Hu SJ, Qiu LH, Zhu JH, Xie XJ, Sun J, Zhu ZH, Xia Q, Bian K (2007) Effects of Astragalus membranaceus and its main components on the acute phase endothelial dysfunction induced by homocysteine. Vascul Pharmacol 46(4):278–285
Zhang J, Xie X, Li C, Fu P (2009) Systematic review of the renal protective effect of Astragalus membranaceus (root) on diabetic nephropathy in animal models. J Ethnopharmacol 126(2):189–196
Zhang L, Liu Q, Lu L, Zhao X, Gao X, Wang Y (2011) Astragaloside IV stimulates angiogenesis and increases hypoxia-inducible factor-1alpha accumulation via phosphatidylinositol 3-kinase/Akt pathway. J Pharmacol Exp Ther 338(2):485–491
Zhang Y, Hu G, Li S, Li ZH, Lam CO, Hong SJ, Kwan YW, Chan SW, Leung GP, Lee SM (2012) Pro-angiogenic activity of Astragaloside IV in HUVECs in vitro and zebrafish in vivo. Mol Med Rep 5(3):805–811
Zhang Y, Li X, Ruan J, Wang T, Dong Y, Hao J, Liu E, Han L, Gao X, Wang T (2016a) Oleanane type saponins from the stems of Astragalus membranaceus (Fisch.) Bge. var. mongholicus (Bge.) Hsiao. Fitoterapia 109:99–105
Zhang Y, Guo YQ, Li XX, Ruan JY, Wang TT, Li J, Han LF, Yu HY, Wang T (2016b) Rearranged oleanane type saponins, astraisoolesaponins A1–A3 and B, from the stems of Astragalus membranaceus (Fisch.) Bge. var. mongholicus (Bge.) Hsiao Tetrahedron 72: 7008–7013
Zhang S, Tang D, Zang W, Yin G, Dai J, Sun YU, Yang Z, Hoffman RM, Guo X (2017) Synergistic inhibitory effect of traditional Chinese medicine Astragaloside IV and curcumin on tumor growth and angiogenesis in an orthotopic nude-mouse model of human hepatocellular carcinoma. Anticancer Res 37(2):465–473
Zhang C, Cai T, Zeng X, Cai D, Chen Y, Huang X, Gan H, Zhuo J, Zhao Z, Pan H, Li S (2018a) Astragaloside IV reverses MNNG-induced precancerous lesions of gastric carcinoma in rats: regulation on glycolysis through miRNA-34a/LDHA pathway. Phytother Res 32(7):1364–1372
Zhang X, Chen J, Xu P, Tian X (2018b) Protective effects of Astragaloside IV against hypoxic pulmonary hypertension. Medchemcomm 9(10):1715–1721
Zhang XP, Li YD, Luo LL, Liu YQ, Li Y, Guo C, Li ZD, Xie XR, Song HX, Yang LP, Sun SB, An FY (2018c) Astragalus saponins and liposome constitute an efficacious adjuvant formulation for cancer vaccines. Cancer Biother Radiopharm 33(1):25–31
Zhang Z, Cheng X, Ge D, Wang S, Qi B (2018d) Protective effects of Astragaloside IV combined with budesonide in bronchitis in rats by regulation of Nrf2/Keap1. Pathway Med Sci Monit 24:8481–8488
Zhao Z, Wang W, Wang F, Zhao K, Han Y, Xu W, Tang L (2009) Effects of Astragaloside IV on heart failure in rats Chin Med 4:6
Zheng Q, Zhu JZ, Bao XY, Zhu PC, Tong Q, Huang YY, Zhang QH, Zhang KJ, Zheng GQ, Wang Y (2018) A preclinical systematic review and meta-analysis of Astragaloside IV for myocardial ischemia/reperfusion injury. Front Physiol 9:795
Zheng Y, Dai Y, Liu W, Wang N, Cai Y, Wang S, Zhang F, Liu P, Chen Q, Wang Z (2019) Astragaloside IV enhances taxol chemosensitivity of breast cancer via caveolin-1-targeting oxidant damage. J Cell Physiol 234(4):4277–4290
Zhou Y, Tong X, Ren S, Wang X, Chen J, Mu Y, Sun M, Chen G, Zhang H, Liu P (2016) Synergistic anti-liver fibrosis actions of total astragalus saponins and glycyrrhizic acid via TGF-beta1/Smads signaling pathway modulation. J Ethnopharmacol 190:83–90
Zhou B, Zhou DL, Wei XH, Zhong RY, Xu J, Sun L (2017a) Astragaloside IV attenuates free fatty acid-induced ER stress and lipid accumulation in hepatocytes via AMPK activation. Acta Pharmacol Sin 38(7):998–1008
Zhou X, Sun X, Gong X, Yang Y, Chen C, Shan G, Yao Q (2017b) Astragaloside IV from Astragalus membranaceus ameliorates renal interstitial fibrosis by inhibiting inflammation via TLR4/NF-small ka. CyrillicB in vivo and in vitro Int Immunopharmacol 42:18–24
Zhu D, Tuo W (2016) QS-21: a potent vaccine adjuvant. Nat Prod Chem Res. https://doi.org/10.4172/2329-6836.1000e113
Zhu J, Wen K (2018) Astragaloside IV inhibits TGF-beta1-induced epithelial-mesenchymal transition through inhibition of the PI3 K/Akt/NF-kappaB pathway in gastric cancer cells. Phytother Res 32(7):1289–1296
Zhu R, Zheng J, Chen L, Gu B, Huang S (2016) Astragaloside IV facilitates glucose transport in C2C12 myotubes through the IRS1/AKT pathway and suppresses the palmitate-induced activation of the IKK/IkappaBalpha pathway. Int J Mol Med 37(6):1697–1705
Zhu X, Chen Y, Du Y, Wan Q, Xu Y, Wu J (2018) Astragaloside IV attenuates penicillin-induced epilepsy via inhibiting activation of the MAPK signaling pathway. Mol Med Rep 17(1):643–647
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Graziani, V., Scognamiglio, M., Esposito, A. et al. Chemical diversity and biological activities of the saponins isolated from Astragalus genus: focus on Astragaloside IV. Phytochem Rev 18, 1133–1166 (2019). https://doi.org/10.1007/s11101-019-09626-y
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DOI: https://doi.org/10.1007/s11101-019-09626-y