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Current Drug Metabolism


ISSN (Print): 1389-2002
ISSN (Online): 1875-5453

Review Article

Salidroside - Can it be a Multifunctional Drug?

Author(s): Sri Krishna Jayadev Magani, Sri Durgambica Mupparthi, Bhanu Prakash Gollapalli, Dhananjay Shukla, AK Tiwari, Jyotsna Gorantala, Nagendra Sastry Yarla and Srinivasan Tantravahi*

Volume 21, Issue 7, 2020

Page: [512 - 524] Pages: 13

DOI: 10.2174/1389200221666200610172105

Price: $65


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
Kelly, G.S. Rhodiola rosea: a possible plant adaptogen. Altern. Med. Rev., 2001, 6(3), 293-302.
[PMID: 11410073]
Chiang, H.M.; Chen, H.C.; Wu, C.S.; Wu, P.Y.; Wen, K.C. Rhodiola plants: Chemistry and biological activity. Yao Wu Shi Pin Fen Xi, 2015, 23(3), 359-369.
[ ] [PMID: 28911692]
Sun, C.; Wang, Z.; Zheng, Q.; Zhang, H. Salidroside inhibits migration and invasion of human fibrosarcoma HT1080 cells. Phytomedicine, 2012, 19(3-4), 355-363.
[ ] [PMID: 21978886]
Wang, J.; Li, J.Z.; Lu, A.X.; Zhang, K.F.; Li, B.J. Anticancer effect of salidroside on A549 lung cancer cells through inhibition of oxidative stress and phospho-p38 expression. Oncol. Lett., 2014, 7(4), 1159-1164.
[ ] [PMID: 24944685]
Recio, M.C.; Giner, R.M.; Máñez, S. Immunmodulatory and antiproliferative properties of rhodiola species. Planta Med., 2016, 82(11-12), 952-960.
[ ] [PMID: 27224273]
Li, H.B.; Ge, Y.K.; Zheng, X.X.; Zhang, L. Salidroside stimulated glucose uptake in skeletal muscle cells by activating AMP-activated protein kinase. Eur. J. Pharmacol., 2008, 588(2-3), 165-169.
[ ] [PMID: 18501890]
Li, F.; Tang, H.; Xiao, F.; Gong, J.; Peng, Y.; Meng, X. Protective effect of salidroside from Rhodiolae Radix on diabetes-induced oxidative stress in mice. Molecules, 2011, 16(12), 9912-9924.
[ ] [PMID: 22134398]
Zhong, Z.; Han, J.; Zhang, J.; Xiao, Q.; Hu, J.; Chen, L. Pharmacological activities, mechanisms of action, and safety of salidroside in the central nervous system. Drug Des. Devel. Ther., 2018, 12, 1479-1489.
[ ] [PMID: 29872270]
Sun, M.Y.; Ma, D.S.; Zhao, S.; Wang, L.; Ma, C.Y.; Bai, Y. Salidroside mitigates hypoxia/reoxygenation injury by alleviating endoplasmic reticulum stress induced apoptosis in H9c2 cardiomyocytes. Mol. Med. Rep., 2018, 18(4), 3760-3768.
[ ] [PMID: 30132527]
Chauhan, K.; Kaur, G.; Kaur, S. Evaluation of antileishmanial efficacy of Salidroside against the SSG-sensitive and resistant strain of Leishmania donovani. Parasitol. Int., 2019., 72101928.
[ ] [PMID: 31108221]
Guo, N.; Hu, Z.; Fan, X.; Zheng, J.; Zhang, D.; Xu, T.; Yu, T.; Wang, Y.; Li, H. Simultaneous determination of salidroside and its aglycone metabolite p-tyrosol in rat plasma by liquid chromatography-tandem mass spectrometry. Molecules, 2012, 17(4), 4733-4754.
[ ] [PMID: 22525439]
Guo, N.; Zhu, M.; Han, X.; Sui, D.; Wang, Y.; Yang, Q. The metabolism of salidroside to its aglycone p-tyrosol in rats following the administration of salidroside. PLoS One, 2014, 9(8), e103648.
[ ] [PMID: 25101641]
Han, F.; Li, Y.T.; Mao, X.J.; Zhang, X.S.; Guan, J.; Song, A.H.; Yin, R. Metabolic profile of salidroside in rats using high-performance liquid chromatography combined with Fourier transform ion cyclotron resonance mass spectrometry. Anal. Bioanal. Chem., 2016, 408(7), 1975-1981.
[ ] [PMID: 26558763]
Hu, Z.; Wang, Z.; Liu, Y.; Wu, Y.; Han, X.; Zheng, J.; Yan, X.; Wang, Y. Metabolite profile of salidroside in rats by ultraperformance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry and high-performance liquid chromatography coupled with quadrupole-linear ion trap mass spectrometry. J. Agric. Food Chem., 2015, 63(41), 8999-9005.
[ ] [PMID: 26461036]
Luo, Z.; Ma, X.; Liu, Y.; Lu, L.; Yang, R.; Yu, G.; Sun, M.; Xin, S.; Tian, S.; Chen, X.; Zhao, H. An approach to characterizing the complicated sequential metabolism of salidroside in rats. Molecules, 2016, 21(6), 706.
[ ] [PMID: 27248984]
Ionescu, C.; Caira, M.R. Drug metabolism: current concepts; Springer: Dordrecht, Netherlands, 2005.
Belle, D.J.; Singh, H. Genetic factors in drug metabolism. Am. Fam. Physician, 2008, 77(11), 1553-1560.
[PMID: 18581835]
Zhou, S.F.; Liu, J.P.; Chowbay, B. Polymorphism of human cytochrome P450 enzymes and its clinical impact. Drug Metab. Rev., 2009, 41(2), 89-295.
[ ] [PMID: 19514967]
Zhang, Y.; Li, L.; Lin, L.; Liu, J.; Zhang, Z.; Xu, D.; Xiang, F. Pharmacokinetics, tissue distribution, and excretion of salidroside in rats. Planta Med., 2013, 79(15), 1429-1433.
[ ] [PMID: 24043591]
Li, L.; Qu, Y.; Jin, X.; Guo, X.Q.; Wang, Y.; Qi, L.; Yang, J.; Zhang, P.; Li, L.Z. Protective effect of salidroside against bone loss via hypoxia-inducible factor-1α pathway-induced angiogenesis. Sci. Rep., 2016, 6(6), 32131.
[ ] [PMID: 27558909]
Kawaguchi, T.; Osatomi, K.; Yamashita, H.; Kabashima, T.; Uyeda, K. Mechanism for fatty acid “sparing” effect on glucose-induced transcription: regulation of carbohydrate-responsive element-binding protein by AMP-activated protein kinase. J. Biol. Chem., 2002, 277(6), 3829-3835.
[ ] [PMID: 11724780]
Taiz, L.; Zeiger, E. Plant Physiology, 4th ed; Inc. Publishers: Sunderland, Massachusetts, 2006.
Shi, L.; Wang, L.; Zhang, Y.; Liu, Y. Approaches to biosynthesis of salidroside and its key metabolic enzymes. For. Stud. China, 2007, 9, 295-299.
Lan, X.; Chang, K.; Zeng, L.; Liu, X.; Qiu, F.; Zheng, W.; Quan, H.; Liao, Z.; Chen, M.; Huang, W.; Liu, W.; Wang, Q. Engineering salidroside biosynthetic pathway in hairy root cultures of Rhodiola crenulata based on metabolic characterization of tyrosine decarboxylase. PLoS One, 2013, 8(10), e75459.
[ ] [PMID: 24124492]
Chung, D.; Kim, S.Y.; Ahn, J.H. Production of three phenylethanoids, tyrosol, hydroxytyrosol, and salidroside, using plant genes expressing in Escherichia coli. Sci. Rep., 2017, 7(1), 2578.
[ ] [PMID: 28566694]
Torrens-Spence, M.P.; Pluskal, T.; Li, F-S.; Carballo, V.; Weng, J-K. Complete pathway elucidation and heterologous reconstitution of rhodiola salidroside biosynthesis. Mol. Plant, 2018, 11(1), 205-217.
[ ] [PMID: 29277428]
Day, A.J.; Cañada, F.J.; Díaz, J.C.; Kroon, P.A.; Mclauchlan, R.; Faulds, C.B.; Plumb, G.W.; Morgan, M.R.A.; Williamson, G. Dietary flavonoid and isoflavone glycosides are hydrolysed by the lactase site of lactase phlorizin hydrolase. FEBS Lett., 2000, 468(2-3), 166-170.
[ ] [PMID: 10692580]
Guo, N.; Ding, W.; Wang, Y.; Hu, Z.; Wang, Z.; Wang, Y. An LC-MS/MS method for the determination of salidroside and its metabolite p-tyrosol in rat liver tissues. Pharm. Biol., 2014, 52(5), 637-645.
[ ] [PMID: 24479765]
World Health Organization. Global Health Observatory.; World Health Organization :Geneva , 2018.Available at:
Hanahan, D.; Weinberg, R.A. The hallmarks of cancer. Cell, 2000, 100(1), 57-70.
Hanahan, D.; Weinberg, R.A. Hallmarks of cancer: the next generation. Cell, 2011, 144(5), 646-674.
Liu, Z.; Li, X.; Simoneau, A.R.; Jafari, M.; Zi, X. Rhodiola rosea extracts and salidroside decrease the growth of bladder cancer cell lines via inhibition of the mTOR pathway and induction of autophagy. Mol. Carcinog., 2012, 51(3), 257-267.
[ ] [PMID: 21520297]
Zhao, G.; Shi, A.; Fan, Z.; Du, Y. Salidroside inhibits the growth of human breast cancer in vitro and in vivo. Oncol. Rep., 2015, 33(5), 2553-2560.
[ ] [PMID: 25814002]
Lv, C.; Huang, Y.; Liu, Z.X.; Yu, D.; Bai, Z.M. Salidroside reduces renal cell carcinoma proliferation by inhibiting JAK2/STAT3 signaling. Cancer Biomark., 2016, 17(1), 41-47.
[ ] [PMID: 27314291]
Li, T.; Xu, K.; Liu, Y. Anticancer effect of salidroside reduces viability through autophagy/PI3K/Akt and MMP-9 signaling pathways in human bladder cancer cells. Oncol. Lett., 2018, 16(3), 3162-3168.
[ ] [PMID: 30127910]
Shang, H.; Wang, S.; Yao, J.; Guo, C.; Dong, J.; Liao, L. Salidroside inhibits migration and invasion of poorly differentiated thyroid cancer cells. Thorac. Cancer, 2019, 10(6), 1469-1478.
[ ] [PMID: 31120636]
Kang, D.Y.; Sp, N.; Kim, D.H.; Joung, Y.H.; Lee, H.G.; Park, Y.M.; Yang, Y.M. Salidroside inhibits migration, invasion and angiogenesis of MDA MB 231 TNBC cells by regulating EGFR/Jak2/STAT3 signaling via MMP2. Int. J. Oncol., 2018, 53(2), 877-885.
[ ] [PMID: 29901185]
Huang, L.; Huang, Z.; Lin, W.; Wang, L.; Zhu, X.; Chen, X.; Yang, S.; Lv, C. Salidroside suppresses the growth and invasion of human osteosarcoma cell lines MG63 and U2OS in vitro by inhibiting the JAK2/STAT3 signaling pathway. Int. J. Oncol., 2019, 54(6), 1969-1980.
[ ] [PMID: 31081055]
Li, H.; Huang, D.; Hang, S. Salidroside inhibits the growth, migration and invasion of Wilms’ tumor cells through down-regulation of miR-891b. Life Sci., 2019, 222, 60-68.
[ ] [PMID: 30822424]
Yang, L.; Yu, Y.; Zhang, Q.; Li, X.; Zhang, C.; Mao, T.; Liu, S.; Tian, Z. Anti-gastric cancer effect of salidroside through elevating miR-99a expression. Artif. Cells Nanomed. Biotechnol., 2019, 47(1), 3500-3510.
[ ] [PMID: 31432697]
Ren, M.; Xu, W.; Xu, T. Salidroside represses proliferation, migration and invasion of human lung cancer cells through AKT and MEK/ERK signal pathway. Artif. Cells Nanomed. Biotechnol., 2019, 47(1), 1014-1021.
[ ] [PMID: 30880481]
Yu, G.; Li, N.; Zhao, Y.; Wang, W.; Feng, X.L. Salidroside induces apoptosis in human ovarian cancer SKOV3 and A2780 cells through the p53 signaling pathway. Oncol. Lett., 2018, 15(5), 6513-6518.
[ ] [PMID: 29616120]
Shi, X.; Zhao, W.; Yang, Y.; Wu, S.; Lv, B. Salidroside could enhance the cytotoxic effect of L OHP on colorectal cancer cells. Mol. Med. Rep., 2018, 17(1), 51-58.
[PMID: 29115408]
Ganesan, P.; Rajendranath, R.; Kandakumar, V.; Sagar, T.G. Treatment of chronic phase chronic myeloid leukemia with imatinib. Indian J. Pediatr., 2015, 82(3), 235-239.
[ ] [PMID: 24871078]
Ge, Chiyu.; Junli, Zhang. Feng, Feng Salidroside enhances the anti-cancerous effect of imatinib on human acute monocytic leukemia via the induction of autophagy-related apoptosis through AMPK activation. R. S. C. Adv, 2019, 9, 25022-25033.
Radha, V.; Mohan, V. Genetic predisposition to type 2 diabetes among Asian Indians. Indian J. Med. Res., 2007, 125(3), 259-274.
[PMID: 17496355]
Qi, L.; Cornelis, M.C.; Zhang, C.; van Dam, R.M.; Hu, F.B. Genetic predisposition, Western dietary pattern, and the risk of type 2 diabetes in men. Am. J. Clin. Nutr., 2009, 89(5), 1453-1458.
[ ] [PMID: 19279076]
Perry, R.J.; Samuel, V.T.; Petersen, K.F.; Shulman, G.I. The role of hepatic lipids in hepatic insulin resistance and type 2 diabetes. Nature, 2014, 510(7503), 84-91.
[ ] [PMID: 24899308]
Zimmet, P.; Alberti, K.G.; Shaw, J. Global and societal implications of the diabetes epidemic. Nature, 2001, 414(6865), 782-787.
[ ] [PMID: 11742409]
Guariguata, L.; Whiting, D.R.; Hambleton, I.; Beagley, J.; Linnenkamp, U.; Shaw, J.E. Global estimates of diabetes prevalence for 2013 and projections for 2035. Diabetes Res. Clin. Pract., 2014, 103(2), 137-149.
[ ] [PMID: 24630390]
Cheng, X.J.; Di, L.; Wu, Y.; Zhao, Q.C.; Du, G.Z.; Liu, Y.Q. [Studies on the hypoglycemic effect of Rhodiola sachalinensis A. Bor. polysaccharides]. Zhongguo Zhongyao Zazhi, 1993, 18(9), 557-559, 575.
[PMID: 8011113]
Gao, D.; Li, Q.; Liu, Z.; Feng, J.; Li, J.; Han, Z.; Duan, Y. Antidiabetic potential of Rhodiola sachalinensis root extract in streptozotocin-induced diabetic rats. Methods Find. Exp. Clin. Pharmacol., 2009, 31(6), 375-381.
[PMID: 19798452]
Mao, Y. Hypoglycemic and hypolipidaemic activities of polysaccharides from Rhodiolarosea in KKAy mice. J. Food Process. Preserv., 2017, 41(6), 13219.
Kim, S.H.; Hyun, S.H.; Choung, S.Y. Antioxidative effects of Cinnamomi cassiae and Rhodiola rosea extracts in liver of diabetic mice. Biofactors, 2006, 26(3), 209-219.
[ ] [PMID: 16971752]
Wang, J.; Rong, X.; Li, W.; Yang, Y.; Yamahara, J.; Li, Y. Rhodiola crenulata root ameliorates derangements of glucose and lipid metabolism in a rat model of the metabolic syndrome and type 2 diabetes. J. Ethnopharmacol., 2012, 142(3), 782-788.
[ ] [PMID: 22683493]
Lee, S.Y.; Lai, F.Y.; Shi, L.S.; Chou, Y.C.; Yen, I.C.; Chang, T.C. Rhodiola crenulata extract suppresses hepatic gluconeogenesis via activation of the AMPK pathway. Phytomedicine, 2015, 22(4), 477-486.
[ ] [PMID: 25925970]
Zheng, T.; Yang, X.; Wu, D.; Xing, S.; Bian, F.; Li, W.; Chi, J.; Bai, X.; Wu, G.; Chen, X.; Zhang, Y.; Jin, S. Salidroside ameliorates insulin resistance through activation of a mitochondria-associated AMPK/PI3K/Akt/GSK3β pathway. Br. J. Pharmacol., 2015, 172(13), 3284-3301.
[ ] [PMID: 25754463]
Zhang, X.R.; Fu, X.J.; Zhu, D.S.; Zhang, C.Z.; Hou, S.; Li, M.; Yang, X.H. Salidroside-regulated lipid metabolism with down-regulation of miR-370 in type 2 diabetic mice. Eur. J. Pharmacol., 2016, 779(779), 46-52.
[ ] [PMID: 26948318]
Ma, Y.G.; Wang, J.W.; Bai, Y.G.; Liu, M.; Xie, M.J.; Dai, Z.J. Salidroside contributes to reducing blood pressure and alleviating cerebrovascular contractile activity in diabetic Goto-Kakizaki Rats by inhibition of L-type calcium channel in smooth muscle cells. BMC Pharmacol. Toxicol., 2017, 18(1), 30.
[ ] [PMID: 28441970]
Zhang, P.; Li, Y.; Guo, R.; Zang, W. Salidroside protects against advanced glycation end products-induced vascular endothelial dysfunction. Med. Sci. Monit., 2018, 24(24), 2420-2428.
[ ] [PMID: 29679467]
Wang, S.H.; Wang, W.J.; Wang, X.F.; Chen, W.H. [Effects of salidroside on carbohydrate metabolism and differentiation of 3T3-L1 adipocytes]. J. Chin. Integr. Med., 2004, 2(3), 193-195.
[ ] [PMID: 15339442]
Xing, S.S.; Yang, X.Y.; Zheng, T.; Li, W.J.; Wu, D.; Chi, J.Y.; Bian, F.; Bai, X.L.; Wu, G.J.; Zhang, Y.Z.; Zhang, C.T.; Zhang, Y.H.; Li, Y.S.; Jin, S. Salidroside improves endothelial function and alleviates atherosclerosis by activating a mitochondria-related AMPK/PI3K/Akt/eNOS pathway. Vascul. Pharmacol., 2015, 72, 141-152.
[ ] [PMID: 26187353]
Herzig, S.; Shaw, R.J. AMPK: guardian of metabolism and mitochondrial homeostasis. Nat. Rev. Mol. Cell Biol., 2018, 19(2), 121-135.
[ ] [PMID: 28974774]
Ceriello, A.; Motz, E. Is oxidative stress the pathogenic mechanism underlying insulin resistance, diabetes, and cardiovascular disease? The common soil hypothesis revisited. Arterioscler. Thromb. Vasc. Biol., 2004, 24(5), 816-823.
[ ] [PMID: 14976002]
Wright, E., Jr; Scism-Bacon, J.L.; Glass, L.C. Oxidative stress in type 2 diabetes: the role of fasting and postprandial glycaemia. Int. J. Clin. Pract., 2006, 60(3), 308-314.
[ ] [PMID: 16494646]
Santilli, F.; Cipollone, F.; Mezzetti, A.; Chiarelli, F. The role of nitric oxide in the development of diabetic angiopathy. Horm. Metab. Res., 2004, 36(5), 319-335.
[ ] [PMID: 15156413]
Yu, P.; Hu, C.; Meehan, E.J.; Chen, L. X-ray crystal structure and antioxidant activity of salidroside, a phenylethanoid glycoside. Chem. Biodivers., 2007, 4(3), 508-513.
[ ] [PMID: 17372953]
Carling, D.; Zammit, V.A.; Hardie, D.G. A common bicyclic protein kinase cascade inactivates the regulatory enzymes of fatty acid and cholesterol biosynthesis. FEBS Lett., 1987, 223(2), 217-222.
[ ] [PMID: 2889619]
Shackelford, D.B.; Shaw, R.J. The LKB1-AMPK pathway: metabolism and growth control in tumour suppression. Nat. Rev. Cancer, 2009, 9(8), 563-575.
[ ] [PMID: 19629071]
McGarry, J.D.; Leatherman, G.F.; Foster, D.W. Carnitine palmitoyltransferase I. The site of inhibition of hepatic fatty acid oxidation by malonyl-CoA. J. Biol. Chem., 1978, 253(12), 4128-4136.
[PMID: 659409]
Saggerson, D. Malonyl-CoA, a key signaling molecule in mammalian cells. Annu. Rev. Nutr., 2008, 28, 253-272.
[ ] [PMID: 18598135]
Yang, Y.; Wang, H.; Kouadir, M.; Song, H.; Shi, F. Recent advances in the mechanisms of NLRP3 inflammasome activation and its inhibitors. Cell Death Dis., 2019, 10(2), 128.
Panossian, A.; Wikman, G.; Sarris, J. Rosenroot (Rhodiola rosea): traditional use, chemical composition, pharmacology and clinical efficacy. Phytomedicine, 2010, 17(7), 481-493.
[ ] [PMID: 20378318]
Zhang, J.; Zhen, Y.F. Pu-Bu-Ci-Ren; Song, L.G.; Kong, W.N.; Shao, T.M.; Li, X.; Chai, X.Q. Salidroside attenuates beta amyloid-induced cognitive deficits via modulating oxidative stress and inflammatory mediators in rat hippocampus. Behav. Brain Res., 2013, 244, 70-81.
[ ] [PMID: 23396166]
Kwon, Y.I.; Jang, H.D.; Shetty, K. Evaluation of Rhodiola crenulata and Rhodiola rosea for management of type II diabetes and hypertension. Asia Pac. J. Clin. Nutr., 2006, 15(3), 425-432.
[PMID: 16837437]
Park, C.; Lee, J.S. Mini review: natural ingredients for diabetes which are approved by Korean FDA. Biomed. Res., 2013, 24(1), 164-169.
Ni, G.L.; Cui, R.; Shao, A.M.; Wu, Z.M. Salidroside ameliorates diabetic neuropathic pain in rats by inhibiting neuroinflammation. J. Mol. Neurosci., 2017, 63(1), 9-16.
[ ] [PMID: 28741143]
GBD 2016 Neurology Collaborators. Global, regional, and national burden of neurological disorders, 1990-2016: a systematic analysis for the Global Burden of Disease Study 2016. Lancet Neurol., 2019, 18(5), 459-480.
[ ] [PMID: 30879893]
Maccioni, R.B.; Muñoz, J.P.; Barbeito, L. The molecular bases of Alzheimer’s disease and other neurodegenerative disorders. Arch. Med. Res., 2001, 32(5), 367-381.
[ ] [PMID: 11578751]
Jang, S.I.; Pae, H.O.; Choi, B.M.; Oh, G.S.; Jeong, S.; Lee, H.J.; Kim, H.Y.; Kang, K.J.; Yun, Y.G.; Kim, Y.C.; Chung, H.T. Salidroside from Rhodiola sachalinensis protects neuronal PC12 cells against cytotoxicity induced by amyloid-beta. Immunopharmacol. Immunotoxicol., 2003, 25(3), 295-304.
[ ] [PMID: 19180794]
Cho, S.H.; Chen, J.A.; Sayed, F.; Ward, M.E.; Gao, F.; Nguyen, T.A.; Krabbe, G.; Sohn, P.D.; Lo, I.; Minami, S.; Devidze, N.; Zhou, Y.; Coppola, G.; Gan, L. SIRT1 deficiency in microglia contributes to cognitive decline in aging and neurodegeneration via epigenetic regulation of IL-1β. J. Neurosci., 2015, 1435(2), 807-818.
Xu, N.; Huang, F.; Jian, C.; Qin, L.; Lu, F.; Wang, Y.; Zhang, Z.; Zhang, Q. Neuroprotective effect of salidroside against central nervous system inflammation-induced cognitive deficits: A pivotal role of sirtuin 1-dependent Nrf-2/HO-1/NF-κB pathway. Phytother. Res., 2019, 33(5), 1438-1447.
[ ] [PMID: 30848530]
Su, Y.; Zong, S.; Wei, C.; Song, F.; Feng, H.; Qin, A.; Lian, Z.; Fu, F.; Shao, S.; Fang, F.; Wu, T.; Xu, J.; Liu, Q.; Zhao, J. Salidroside promotes rat spinal cord injury recovery by inhibiting inflammatory cytokine expression and NF-κB and MAPK signaling pathways. J. Cell. Physiol., 2019, 234(8), 14259-14269.
[ ] [PMID: 30656690]
Zhou, F.; Ju, J.; Fang, Y.; Fan, X.; Yan, S.; Wang, Q.; Wei, P.; Duan, F.; Miao, F.; Hu, Z.; Wang, M. Salidroside protected against MPP+ -induced Parkinson’s disease in PC12 cells by inhibiting inflammation, oxidative stress and cell apoptosis. Biotechnol. Appl. Biochem., 2019, 66(2), 247-253.
[ ] [PMID: 30548933]
Li, R.; Wang, S.; Li, T.; Wu, L.; Fang, Y.; Feng, Y.; Zhang, L.; Chen, J.; Wang, X. Salidroside Protects Dopaminergic Neurons by Preserving Complex I Activity via DJ-1/Nrf2-Mediated Antioxidant Pathway. Parkinsons Dis., 2019., 20196073496.
[ ] [PMID: 31223467]
Zhang, X.; Lai, W.; Ying, X.; Xu, L.; Chu, K.; Brown, J.; Chen, L.; Hong, G. Salidroside reduces inflammation and brain injury after permanent middle cerebral artery occlusion in rats by regulating PI3K/PKB/Nrf2/NFκB signaling rather than complement C3 activity. Inflammation, 2019, 42(5), 1830-1842.
[ ] [PMID: 31230155]
Hedges, S.B.; Blair, J.E.; Venturi, M.L.; Shoe, J.L. A molecular timescale of eukaryote evolution and the rise of complex multicellular life. BMC Evol. Biol., 2004, 4, 2.
[ ] [PMID: 15005799]
Bonner, J.T. On the origin of differentiation. J. Biosci., 2003, 28(4), 523-528.
[ ] [PMID: 12799498]
Li, Y.; Wu, J.; Shi, R.; Li, N.; Xu, Z.; Sun, M. Antioxidative effects of Rhodiola genus: phytochemistry and pharmacological mechanisms against the diseases. Curr. Top. Med. Chem., 2017, 17(15), 1692-1708.
[ ] [PMID: 27848900]
Hu, X.; Zhang, X.; Qiu, S.; Yu, D.; Lin, S. Salidroside induces cell-cycle arrest and apoptosis in human breast cancer cells. Biochem. Biophys. Res. Commun., 2010, 398(1), 62-67.
[ ] [PMID: 20541529]
Kong, Y.H.; Xu, S.P. Salidroside prevents skin carcinogenesis induced by DMBA/TPA in a mouse model through suppression of inflammation and promotion of apoptosis. Oncol. Rep., 2018, 39(6), 2513-2526.
[ ] [PMID: 29693192]
Chen, X.; Kou, Y.; Lu, Y.; Pu, Y. Salidroside ameliorated hypoxia-induced tumorigenesis of BxPC-3 cells via downregulating hypoxia-inducible factor (HIF)-1α and LOXL2. J. Cell. Biochem., 2019, 1-9.
Park, J.S.; Lee, J.H.; Lee, Y.S.; Kim, J.K.; Dong, S.M.; Yoon, D.S. Emerging role of LOXL2 in the promotion of pancreas cancer metastasis. Oncotarget, 2016, 7(27), 42539-42552.
[ ] [PMID: 27285767]
Zhang, J.; Liu, A.; Hou, R.; Zhang, J.; Jia, X.; Jiang, W.; Chen, J. Salidroside protects cardiomyocyte against hypoxia-induced death: a HIF-1alpha-activated and VEGF-mediated pathway. Eur. J. Pharmacol., 2009, 607(1-3), 6-14.
[ ] [PMID: 19326475]
Qin, Y.; Liu, H.J.; Li, M.; Zhai, D.H.; Tang, Y.H.; Yang, L.; Qiao, K.L.; Yang, J.H.; Zhong, W.L.; Zhang, Q.; Liu, Y.R.; Yang, G.; Sun, T.; Yang, C. Salidroside improves the hypoxic tumor microenvironment and reverses the drug resistance of platinum drugs via HIF-1α signaling pathway. EBioMedicine, 2018, 38, 25-36.
[ ] [PMID: 30396856]
Hu, Y.; Lv, X.; Zhang, J.; Meng, X. comparative study on the protective effects of salidroside and hypoxic preconditioning for attenuating anoxia-induced apoptosis in pheochromocytoma (PC12) cells. Med. Sci. Monit., 2016, 22, 4082-4091.
[ ] [PMID: 27794583]
Lipp, L.L. Brain perfusion and oxygenation. Crit. Care Nurs. Clin. North Am., 2014, 26(3), 389-398.
[ ] [PMID: 25169691]
Xu, L.; Jia, L.; Wang, Q.; Hou, J.; Li, S.; Teng, J. Salidroside attenuates hypoxia/reoxygenation-induced human brain vascular smooth muscle cell injury by activating the SIRT1/FOXO3α pathway. Exp. Ther. Med., 2018, 15(1), 822-830.
[PMID: 29434685]
Cao, X.B.; Jiang, Z.H.; Dong, L.; Zheng, Y.; Li, Y. Effects of modulation of ion channel currents by salidroside in H9C2 myocardial cells in hypoxia and reoxygenation. Evid. Based Complement. Alternat. Med., 2019., 20198212868.
[ ] [PMID: 30805019]
Sun, Y.; Xun, L.; Jin, G.; Shi, L. Salidroside protects renal tubular epithelial cells from hypoxia/reoxygenation injury in vitro. J. Pharmacol. Sci., 2018, 137(2), 170-176.
[ ] [PMID: 29960844]
Zhang, X.; Zhao, J.F.; Zhao, F.; Yan, J.F.; Yang, F.; Huang, X.J.; Chen, G.; Fu, H.Y.; Lv, B.D. The protective effect of salidroside on hypoxia-induced Corpus cavernosum smooth muscle cell phenotypic transformation. Evid. Based Complement. Alternat. Med., 2017., 20173530281.
[ ] [PMID: 28798798]
Yan, R.; Xu, H.; Fu, X. Salidroside protects hypoxia-induced injury by up-regulation of miR-210 in rat neural stem cells. Biomed. Pharmacother., 2018, 103, 1490-1497.
[ ] [PMID: 29864934]
Trgovcevic, S.; Milicevic, M.; Nedovic, G.; Jovanic, G. Health condition and quality of life in persons with spinal cord injury. Iran. J. Public Health, 2014, 43(9), 1229-1238.
[PMID: 26175977]
Hall, E.D.; Braughler, J.M.F. Molecular and Cellular Approaches to the Treatment of Brain Diseases; Waxman Raven Press: New York, 1993, pp. 81-105.
Anwar, M.A.; Al Shehabi, T.S.; Eid, A.H. Inflammogenesis of secondary spinal cord injury. Front. Cell. Neurosci., 2016, 10, 98.
[ ] [PMID: 27147970]
Coulibaly, M.O.; Sietsema, D.L.; Burgers, T.A.; Mason, J.; Williams, B.O.; Jones, C.B. Recent advances in the use of serological bone formation markers to monitor callus development and fracture healing. Crit. Rev. Eukaryot. Gene Expr., 2010, 20(2), 105-127.
[ ] [PMID: 21133841]
Chen, J.J.; Zhang, N.F.; Mao, G.X.; He, X.B.; Zhan, Y.C.; Deng, H.B.; Song, D.Q.; Li, D.D.; Li, Z.R.; Si, S.Y.; Qiu, Q.; Wang, Z. Salidroside stimulates osteoblast differentiation through BMP signaling pathway. Food Chem. Toxicol., 2013, 62, 499-505.
[ ] [PMID: 24055767]
Boulton, A.J.; Vileikyte, L.; Ragnarson-Tennvall, G.; Apelqvist, J. The global burden of diabetic foot disease. Lancet, 2005, 366(9498), 1719-1724.
[ ] [PMID: 16291066]
Davey, G.C.; Patil, S.B.; O’Loughlin, A.; O’Brien, T. Mesenchymal stem cell-based treatment for microvascular and secondary complications of diabetes mellitus. Front. Endocrinol. (Lausanne), 2014, 5, 86.
[ ] [PMID: 24936198]
Falanga, V. Wound healing and its impairment in the diabetic foot. Lancet, 2005, 366(9498), 1736-1743.
[ ] [PMID: 16291068]
O’Loughlin, A.; Kulkarni, M.; Creane, M.; Vaughan, E.E.; Mooney, E.; Shaw, G.; Murphy, M.; Dockery, P.; Pandit, A.; O’Brien, T. Topical administration of allogeneic mesenchymal stromal cells seeded in a collagen scaffold augments wound healing and increases angiogenesis in the diabetic rabbit ulcer. Diabetes, 2013, 62(7), 2588-2594.
[ ] [PMID: 23423568]
Ariyanti, A.D.; Zhang, J.; Marcelina, O.; Nugrahaningrum, D.A.; Wang, G.; Kasim, V.; Wu, S. Salidroside-pretreated mesenchymal stem cells enhance diabetic wound healing by promoting paracrine function and survival of mesenchymal stem cells under hyperglycemia. Stem Cells Transl. Med., 2019, 8(4), 404-414.
[ ] [PMID: 30624028]
Zhan, X.; Kim, C.; Sharp, F.R. Very brief focal ischemia simulating transient ischemic attacks (TIAs) can injure brain and induce Hsp70 protein. Brain Res., 2008, 1234, 183-197.
[ ] [PMID: 18708034]
Zhang, X.; Du, Q.; Yang, Y.; Wang, J.; Liu, Y.; Zhao, Z.; Zhu, Y.; Liu, C. Salidroside alleviates ischemic brain injury in mice with ischemic stroke through regulating BDNK mediated PI3K/Akt pathway. Biochem. Pharmacol., 2018, 156, 99-108.
[ ] [PMID: 30114387]
Kosieradzki, M.; Rowiński, W. Ischemia/reperfusion injury in kidney transplantation: mechanisms and prevention. Transplant. Proc., 2008, 40(10), 3279-3288.
[ ] [PMID: 19100373]
Yuan, Y.; Wu, S.J.; Liu, X.; Zhang, L.L. Antioxidant effect of salidroside and its protective effect against furan-induced hepatocyte damage in mice. Food Funct., 2013, 4(5), 763-769.
[ ] [PMID: 23507802]
Aksenova, R.A.; Zotova, M.I.; Nekhoda, M.F.; Cherdintsev, S.G. Comparative characteristics of the stimulating and adaptogenic effects of Rhodiola rosea preparations. In: Stimulants of the Central Nervous System; Saratikov, A.S., Ed.; Tomsk University Press: Tomsk, 1968; Vol. 2, pp. 3-12.
Zhu, Y-P.; Zhang, T-B.; Wan, X.; Ma, X.; Tian, Y.; Zheng, Y.; Zhu, J. Genetic toxicity of rhodioside injection. Pharm Care Res., 2009, 9(4), 279-282.
Zhu, J.; Wan, X.; Zhu, Y.; Ma, X.; Zheng, Y.; Zhang, T. Evaluation of salidroside in vitro and in vivo genotoxicity. Drug Chem. Toxicol., 2010, 33(2), 220-226.
[ ] [PMID: 20307149]
Zh, Y-P.; Zhu, J-B.; Ma, X-L.; Tian, Y-J.; Wan, X-Y.; Zhang, T-B. Evaluation for developmental toxicity of rhodioside injection in rats. Zhongguo Xin Yao Zazhi, 2009, 18(21), 2068-2071.

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