Abstract
Background: Salidroside is a glucoside of tyrosol found mostly in the roots of Rhodiola spp. It exhibits diverse biological and pharmacological properties. In the last decade, enormous research is conducted to explore the medicinal properties of salidroside; this research reported many activities like anti-cancer, anti-oxidant, anti-aging, anti-diabetic, anti-depressant, anti-hyperlipidemic, anti-inflammatory, immunomodulatory, etc.
Objective: Despite its multiple pharmacological effects, a comprehensive review detailing its metabolism and therapeutic activities is still missing. This review aims to provide an overview of the metabolism of salidroside, its role in alleviating different metabolic disorders, diseases and its molecular interaction with the target molecules in different conditions. This review mostly concentrates on the metabolism, biological activities and molecular pathways related to various pharmacological activities of salidroside.
Conclusion: Salidroside is produced by a three-step pathway in the plants with tyrosol as an intermediate molecule. The molecule is biotransformed into many metabolites through phase I and II pathways. These metabolites, together with a certain amount of salidroside may be responsible for various pharmacological functions. The salidroside based inhibition of PI3k/AKT, JAK/ STAT, and MEK/ERK pathways and activation of apoptosis and autophagy are the major reasons for its anti-cancer activity. AMPK pathway modulation plays a significant role in its anti-diabetic activity. The neuroprotective activity was linked with decreased oxidative stress and increased antioxidant enzymes, Nrf2/HO-1 pathways, decreased inflammation through suppression of NF-κB pathway and PI3K/AKT pathways. These scientific findings will pave the way to clinically translate the use of salidroside as a multi-functional drug for various diseases and disorders in the near future.
Keywords: Salidroside, tyrosol, cancer, diabetis, 4-hydroxyphenyl acetaldehyde (4-HPAA), glucronidation.
Graphical Abstract
[PMID: 11410073]
[http://dx.doi.org/10.1016/j.jfda.2015.04.007 ] [PMID: 28911692]
[http://dx.doi.org/10.1016/j.phymed.2011.09.070 ] [PMID: 21978886]
[http://dx.doi.org/10.3892/ol.2014.1863 ] [PMID: 24944685]
[http://dx.doi.org/10.1055/s-0042-107254 ] [PMID: 27224273]
[http://dx.doi.org/10.1016/j.ejphar.2008.04.036 ] [PMID: 18501890]
[http://dx.doi.org/10.3390/molecules16129912 ] [PMID: 22134398]
[http://dx.doi.org/10.2147/DDDT.S160776 ] [PMID: 29872270]
[http://dx.doi.org/10.3892/mmr.2018.9403 ] [PMID: 30132527]
[http://dx.doi.org/10.1016/j.parint.2019.101928 ] [PMID: 31108221]
[http://dx.doi.org/10.3390/molecules17044733 ] [PMID: 22525439]
[http://dx.doi.org/10.1371/journal.pone.0103648 ] [PMID: 25101641]
[http://dx.doi.org/10.1007/s00216-015-9080-9 ] [PMID: 26558763]
[http://dx.doi.org/10.1021/acs.jafc.5b04510 ] [PMID: 26461036]
[http://dx.doi.org/10.3390/molecules21060706 ] [PMID: 27248984]
[http://dx.doi.org/10.1007/1-4020-4142-X]
[PMID: 18581835]
[http://dx.doi.org/10.1080/03602530902843483 ] [PMID: 19514967]
[http://dx.doi.org/10.1055/s-0033-1350807 ] [PMID: 24043591]
[http://dx.doi.org/10.1038/srep32131 ] [PMID: 27558909]
[http://dx.doi.org/10.1074/jbc.M107895200 ] [PMID: 11724780]
[http://dx.doi.org/10.1007/s11632-007-0047-6]
[http://dx.doi.org/10.1371/journal.pone.0075459 ] [PMID: 24124492]
[http://dx.doi.org/10.1038/s41598-017-02042-2 ] [PMID: 28566694]
[http://dx.doi.org/10.1016/j.molp.2017.12.007 ] [PMID: 29277428]
[http://dx.doi.org/10.1016/S0014-5793(00)01211-4 ] [PMID: 10692580]
[http://dx.doi.org/10.3109/13880209.2013.863946 ] [PMID: 24479765]
[http://dx.doi.org/10.1016/S0092-8674(00)81683-9]
[http://dx.doi.org/10.1002/mc.20780 ] [PMID: 21520297]
[http://dx.doi.org/10.3892/or.2015.3857 ] [PMID: 25814002]
[http://dx.doi.org/10.3233/CBM-160615 ] [PMID: 27314291]
[http://dx.doi.org/10.3892/ol.2018.8982 ] [PMID: 30127910]
[http://dx.doi.org/10.1111/1759-7714.13096 ] [PMID: 31120636]
[http://dx.doi.org/10.3892/ijo.2018.4430 ] [PMID: 29901185]
[http://dx.doi.org/10.3892/ijo.2019.4781 ] [PMID: 31081055]
[http://dx.doi.org/10.1016/j.lfs.2019.02.052 ] [PMID: 30822424]
[http://dx.doi.org/10.1080/21691401.2019.1652626 ] [PMID: 31432697]
[http://dx.doi.org/10.1080/21691401.2019.1584566 ] [PMID: 30880481]
[http://dx.doi.org/10.3892/ol.2018.8090 ] [PMID: 29616120]
[PMID: 29115408]
[http://dx.doi.org/10.1007/s12098-014-1492-6 ] [PMID: 24871078]
[PMID: 17496355]
[http://dx.doi.org/10.3945/ajcn.2008.27249 ] [PMID: 19279076]
[http://dx.doi.org/10.1038/nature13478 ] [PMID: 24899308]
[http://dx.doi.org/10.1038/414782a ] [PMID: 11742409]
[http://dx.doi.org/10.1016/j.diabres.2013.11.002 ] [PMID: 24630390]
[PMID: 8011113]
[PMID: 19798452]
[http://dx.doi.org/10.1111/jfpp.13219]
[http://dx.doi.org/10.1002/biof.5520260306 ] [PMID: 16971752]
[http://dx.doi.org/10.1016/j.jep.2012.05.063 ] [PMID: 22683493]
[http://dx.doi.org/10.1016/j.phymed.2015.01.016 ] [PMID: 25925970]
[http://dx.doi.org/10.1111/bph.13120 ] [PMID: 25754463]
[http://dx.doi.org/10.1016/j.ejphar.2016.03.011 ] [PMID: 26948318]
[http://dx.doi.org/10.1186/s40360-017-0135-8 ] [PMID: 28441970]
[http://dx.doi.org/10.12659/MSM.906064 ] [PMID: 29679467]
[http://dx.doi.org/10.3736/jcim20040312 ] [PMID: 15339442]
[http://dx.doi.org/10.1016/j.vph.2015.07.004 ] [PMID: 26187353]
[http://dx.doi.org/10.1038/nrm.2017.95 ] [PMID: 28974774]
[http://dx.doi.org/10.1161/01.ATV.0000122852.22604.78 ] [PMID: 14976002]
[http://dx.doi.org/10.1111/j.1368-5031.2006.00825.x ] [PMID: 16494646]
[http://dx.doi.org/10.1055/s-2004-814489 ] [PMID: 15156413]
[http://dx.doi.org/10.1002/cbdv.200790043 ] [PMID: 17372953]
[http://dx.doi.org/10.1016/0014-5793(87)80292-2 ] [PMID: 2889619]
[http://dx.doi.org/10.1038/nrc2676 ] [PMID: 19629071]
[PMID: 659409]
[http://dx.doi.org/10.1146/annurev.nutr.28.061807.155434 ] [PMID: 18598135]
[http://dx.doi.org/10.1038/s41419-019-1413-8]
[http://dx.doi.org/10.1016/j.phymed.2010.02.002 ] [PMID: 20378318]
[http://dx.doi.org/10.1016/j.bbr.2013.01.037 ] [PMID: 23396166]
[PMID: 16837437]
[http://dx.doi.org/10.1007/s12031-017-0951-8 ] [PMID: 28741143]
[http://dx.doi.org/10.1016/S1474-4422(18)30499-X ] [PMID: 30879893]
[http://dx.doi.org/10.1016/S0188-4409(01)00316-2 ] [PMID: 11578751]
[http://dx.doi.org/10.1081/IPH-120024498 ] [PMID: 19180794]
[http://dx.doi.org/10.1002/ptr.6335 ] [PMID: 30848530]
[http://dx.doi.org/10.1002/jcp.28124 ] [PMID: 30656690]
[http://dx.doi.org/10.1002/bab.1719 ] [PMID: 30548933]
[http://dx.doi.org/10.1155/2019/6073496 ] [PMID: 31223467]
[http://dx.doi.org/10.1007/s10753-019-01045-7 ] [PMID: 31230155]
[http://dx.doi.org/10.1186/1471-2148-4-2 ] [PMID: 15005799]
[http://dx.doi.org/10.1007/BF02705126 ] [PMID: 12799498]
[http://dx.doi.org/10.2174/1568026617666161116141334 ] [PMID: 27848900]
[http://dx.doi.org/10.1016/j.bbrc.2010.06.033 ] [PMID: 20541529]
[http://dx.doi.org/10.3892/or.2018.6381 ] [PMID: 29693192]
[http://dx.doi.org/10.18632/oncotarget.9918 ] [PMID: 27285767]
[http://dx.doi.org/10.1016/j.ejphar.2009.01.046 ] [PMID: 19326475]
[http://dx.doi.org/10.1016/j.ebiom.2018.10.069 ] [PMID: 30396856]
[http://dx.doi.org/10.12659/MSM.897640 ] [PMID: 27794583]
[http://dx.doi.org/10.1016/j.ccell.2014.04.008 ] [PMID: 25169691]
[PMID: 29434685]
[http://dx.doi.org/10.1155/2019/8212868 ] [PMID: 30805019]
[http://dx.doi.org/10.1016/j.jphs.2018.05.011 ] [PMID: 29960844]
[http://dx.doi.org/10.1155/2017/3530281 ] [PMID: 28798798]
[http://dx.doi.org/10.1016/j.biopha.2018.04.184 ] [PMID: 29864934]
[PMID: 26175977]
[http://dx.doi.org/10.3389/fncel.2016.00098 ] [PMID: 27147970]
[http://dx.doi.org/10.1615/CritRevEukarGeneExpr.v20.i2.20 ] [PMID: 21133841]
[http://dx.doi.org/10.1016/j.fct.2013.09.019 ] [PMID: 24055767]
[http://dx.doi.org/10.1016/S0140-6736(05)67698-2 ] [PMID: 16291066]
[http://dx.doi.org/10.3389/fendo.2014.00086 ] [PMID: 24936198]
[http://dx.doi.org/10.1016/S0140-6736(05)67700-8 ] [PMID: 16291068]
[http://dx.doi.org/10.2337/db12-1822 ] [PMID: 23423568]
[http://dx.doi.org/10.1002/sctm.18-0143 ] [PMID: 30624028]
[http://dx.doi.org/10.1016/j.brainres.2008.07.094 ] [PMID: 18708034]
[http://dx.doi.org/10.1016/j.bcp.2018.08.015 ] [PMID: 30114387]
[http://dx.doi.org/10.1016/j.transproceed.2008.10.004 ] [PMID: 19100373]
[http://dx.doi.org/10.1039/c3fo00013c ] [PMID: 23507802]
[http://dx.doi.org/10.3109/01480540903373654 ] [PMID: 20307149]