Abstract
Depression is the most prevalent mental disorder, affecting more than 300 million adults worldwide each year, which can lead to serious economic and social problems. Antidepressants are usually the first-line treatment for depression, however, traditional antidepressants on the market have the disadvantage of low remission rates and may cause side effects to patients, therefore, the current focus in the field of depression is to develop novel therapeutic agents with high remission rates and few side effects. In this context, the antidepressant effects of natural compounds have received attention. Baicalin (baicalein-7-O-glucuronide) and its aglycone baicalein (5,6,7-trihydroxyflavone) are flavonoid compounds extracted from the root of Scutellaria baicalensis. Although lacking the support of clinical data, they have been shown to have significantly promising antidepressant activity in many preclinical studies through various rodent models of depression. This paper reviews the antidepressant effects of baicalin and baicalein in experimental animal models, with emphasis on summarizing the molecular mechanisms of their antidepressant effects including regulation of the HPA axis, inhibition of inflammation and oxidative stress, reduction of neuronal apoptosis and promotion of neurogenesis, as well as amelioration of mitochondrial dysfunction. Controlled clinical trials should be conducted in the future to examine the effects of baicalin and baicalein on depression in humans.
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Malhi GS, Mann JJ (2018) Depression Lancet 392:2299–2312
Hammen C (2018) Risk factors for depression: an autobiographical review. Annu Rev Clin Psychol 14:1–28
Herrman H, Patel V, Kieling C, Berk M, Buchweitz C, Cuijpers P, Furukawa TA, Kessler RC, Kohrt BA, Maj M, McGorry P, Reynolds CF 3rd, Weissman MM, Chibanda D, Dowrick C, Howard LM, Hoven CW, Knapp M, Mayberg HS, Penninx B, Xiao S, Trivedi M, Uher R, Vijayakumar L, Wolpert M (2022) Time for united action on depression: a lancet-world psychiatric association commission. Lancet 399:957–1022
Chen ME, Su CH, Yang JS, Lu CC, Hou YC, Wu JB, Hsu YM (2018) Baicalin, Baicalein, and Lactobacillus Rhamnosus JB3 Alleviated Helicobacter pylori Infections in Vitro and in Vivo. J Food Sci 83:3118–3125
Zandi K, Musall K, Oo A, Cao D, Liang B, Hassandarvish P, Lan S, Slack RL, Kirby KA, Bassit L, Amblard F, Kim B, AbuBakar S, Sarafianos SG, Schinazi RF (2021) Baicalein and baicalin inhibit SARS-CoV-2 RNA-dependent-RNA polymerase. Microorganisms 9:893
Shi L, Hao Z, Zhang S, Wei M, Lu B, Wang Z, Ji L (2018) Baicalein and baicalin alleviate acetaminophen-induced liver injury by activating Nrf2 antioxidative pathway: The involvement of ERK1/2 and PKC. Biochem Pharmacol 150:9–23
Wang L, Feng T, Su Z, Pi C, Wei Y, Zhao L (2022) Latest research progress on anticancer effect of baicalin and its aglycone baicalein. Arch Pharm Res 45:535–557
El-Ela SRA, Zaghloul RA, Eissa LA (2022) Promising cardioprotective effect of baicalin in doxorubicin-induced cardiotoxicity through targeting toll-like receptor 4/nuclear factor-κB and Wnt/β-catenin pathways. Nutrition 102:111732
Dinda B, Dinda S, DasSharma S, Banik R, Chakraborty A, Dinda M (2017) Therapeutic potentials of baicalin and its aglycone, baicalein against inflammatory disorders. Eur J Med Chem 131:68–80
Wang Q, Timberlake MA 2nd, Prall K, Dwivedi Y (2017) The recent progress in animal models of depression. Prog Neuropsychopharmacol Biol Psychiatry 77:99–109
Steru L, Chermat R, Thierry B, Simon P (1985) The tail suspension test: a new method for screening antidepressants in mice. Psychopharmacology 85:367–370
Porsolt RD, Bertin A, Jalfre M (1977) Behavioral despair in mice: a primary screening test for antidepressants. Arch Int Pharmacodyn Ther 229:327–336
Liu MY, Yin CY, Zhu LJ, Zhu XH, Xu C, Luo CX, Chen H, Zhu DY, Zhou QG (2018) Sucrose preference test for measurement of stress-induced anhedonia in mice. Nat Protoc 13:1686–1698
Liao H, Ye J, Gao L, Liu Y (2021) The main bioactive compounds of Scutellaria baicalensis Georgi. for alleviation of inflammatory cytokines: A comprehensive review. Biomed Pharmacother 133:110917
Huang T, Liu Y, Zhang C (2019) Pharmacokinetics and bioavailability enhancement of baicalin: a review. Eur J Drug Metab Pharmacokinet 44:159–168
Cherian K, Schatzberg AF, Keller J (2019) HPA axis in psychotic major depression and schizophrenia spectrum disorders: Cortisol, clinical symptomatology, and cognition. Schizophr Res 213:72–79
Li YC, Shen JD, Li J, Wang R, Jiao S, Yi LT (2013) Chronic treatment with baicalin prevents the chronic mild stress-induced depressive-like behavior: involving the inhibition of cyclooxygenase-2 in rat brain. Prog Neuropsychopharmacol Biol Psychiatry 40:138–143
Yu HY, Yin ZJ, Yang SJ, Ma SP (2014) Baicalin reverse AMPA receptor expression and neuron apoptosis in chronic unpredictable mild stress rats. Biochem Biophys Res Commun 451:467–472
Li YC, Wang LL, Pei YY, Shen JD, Li HB, Wang BY, Bai M (2015) Baicalin decreases SGK1 expression in the hippocampus and reverses depressive-like behaviors induced by corticosterone. Neuroscience 311:130–137
Yu H, Zhang F, Guan X (2019) Baicalin reverse depressive-like behaviors through regulation SIRT1-NF-kB signaling pathway in olfactory bulbectomized rats. Phytother Res 33:1480–1489
Zhao F, Tao W, Shang Z, Zhang W, Ruan J, Zhang C, Zhou L, Aiello H, Lai H, Qu R (2020) Facilitating granule cell survival and maturation in dentate gyrus with baicalin for antidepressant therapeutics. Front Pharmacol 11:556845
Zhang K, He M, Wang F, Zhang H, Li Y, Yang J, Wu C (2019) Revealing antidepressant mechanisms of Baicalin in hypothalamus through systems approaches in corticosterone- induced depressed mice. Front Neurosci 13:834
Pariante CM, Lightman SL (2008) The HPA axis in major depression: classical theories and new developments. Trends Neurosci 31:464–468
Myers B, McKlveen JM, Herman JP (2014) Glucocorticoid actions on synapses, circuits, and behavior: implications for the energetics of stress. Front Neuroendocrinol 35:180–196
Anacker C, Cattaneo A, Musaelyan K, Zunszain PA, Horowitz M, Molteni R, Luoni A, Calabrese F, Tansey K, Gennarelli M, Thuret S, Price J, Uher R, Riva MA, Pariante CM (2013) Role for the kinase SGK1 in stress, depression, and glucocorticoid effects on hippocampal neurogenesis. Proc Natl Acad Sci USA 110:8708–8713
Troubat R, Barone P, Leman S, Desmidt T, Cressant A, Atanasova B, Brizard B, El Hage W, Surget A, Belzung C, Camus V (2021) Neuroinflammation and depression: A review. Eur J Neurosci 53:151–171
Osimo EF, Pillinger T, Rodriguez IM, Khandaker GM, Pariante CM, Howes OD (2020) Inflammatory markers in depression: A meta-analysis of mean differences and variability in 5,166 patients and 5,083 controls. Brain Behav Immun 87:901–909
Shelton RC, Claiborne J, Sidoryk-Wegrzynowicz M, Reddy R, Aschner M, Lewis DA, Mirnics K (2011) Altered expression of genes involved in inflammation and apoptosis in frontal cortex in major depression. Mol Psychiatry 16:751–762
Köhler-Forsberg O, Hjorthøj C, Nordentoft M, Mors O, Benros ME (2019) Efficacy of anti-inflammatory treatment on major depressive disorder or depressive symptoms: meta-analysis of clinical trials. Acta Psychiatr Scand 139:404–419
Bhatt S, Devadoss T, Jha NK, Baidya M, Gupta G, Chellappan DK, Singh SK, Dua K (2023) Targeting inflammation: a potential approach for the treatment of depression. Metab Brain Dis 38:45–59
Liu L, Dong Y, Shan X, Li L, Xia B, Wang H (2019) Anti-Depressive Effectiveness of Baicalin In Vitro and In Vivo. Molecules 24:326
Liu X, Liu C (2017) Baicalin ameliorates chronic unpredictable mild stress-induced depressive behavior: Involving the inhibition of NLRP3 inflammasome activation in rat prefrontal cortex. Int Immunopharmacol 48:30–34
Zhong J, Li G, Xu H, Wang Y, Shi M (2019) Baicalin ameliorates chronic mild stress-induced depression-like behaviors in mice and attenuates inflammatory cytokines and oxidative stress. Braz J Med Biol Res 52:e8434
Guo LT, Wang SQ, Su J, Xu LX, Ji ZY, Zhang RY, Zhao QW, Ma ZQ, Deng XY, Ma SP (2019) Baicalin ameliorates neuroinflammation-induced depressive-like behavior through inhibition of toll-like receptor 4 expression via the PI3K/AKT/FoxO1 pathway. J Neuroinflammation 16:95
Fu X, Jiao J, Qin T, Yu J, Fu Q, Deng X, Ma S, Ma Z (2021) A New Perspective on ameliorating depression-like behaviors: suppressing neuroinflammation by upregulating PGC-1α. Neurotox Res 39:872–885
Xia CY, Guo YX, Lian WW, Yan Y, Ma BZ, Cheng YC, Xu JK, He J, Zhang WK (2023) The NLRP3 inflammasome in depression: Potential mechanisms and therapies. Pharmacol Res 187:106625
Kaisho T, Akira S (2006) Toll-like receptor function and signaling. J Allergy Clin Immunol 117:979–987
Lee KM, Seong SY (2009) Partial role of TLR4 as a receptor responding to damage-associated molecular pattern. Immunol Lett 125:31–39
Xu X, Piao HN, Aosai F, Zeng XY, Cheng JH, Cui YX, Li J, Ma J, Piao HR, Jin X, Piao LX (2020) Arctigenin protects against depression by inhibiting microglial activation and neuroinflammation via HMGB1/TLR4/NF-κB and TNF-α/TNFR1/NF-κB pathways. Br J Pharmacol 177:5224–5245
Fan W, Morinaga H, Kim JJ, Bae E, Spann NJ, Heinz S, Glass CK, Olefsky JM (2010) FoxO1 regulates Tlr4 inflammatory pathway signalling in macrophages. Embo j 29:4223–4236
Brunet A, Bonni A, Zigmond MJ, Lin MZ, Juo P, Hu LS, Anderson MJ, Arden KC, Blenis J, Greenberg ME (1999) Akt promotes cell survival by phosphorylating and inhibiting a Forkhead transcription factor. Cell 96:857–868
Shen J, Qu C, Xu L, Sun H, Zhang J (2019) Resveratrol exerts a protective effect in chronic unpredictable mild stress-induced depressive-like behavior: involvement of the AKT/GSK3β signaling pathway in hippocampus. Psychopharmacology 236:591–602
Yang Y, Liu Y, Wang Y, Chao Y, Zhang J, Jia Y, Tie J, Hu D (2022) Regulation of SIRT1 and its roles in inflammation. Front Immunol 13:831168
Ryan KM, Patterson I, McLoughlin DM (2019) Peroxisome proliferator-activated receptor gamma co-activator-1 alpha in depression and the response to electroconvulsive therapy. Psychol Med 49:1859–1868
Kauppinen A, Suuronen T, Ojala J, Kaarniranta K, Salminen A (2013) Antagonistic crosstalk between NF-κB and SIRT1 in the regulation of inflammation and metabolic disorders. Cell Signal 25:1939–1948
Sokol CL, Luster AD (2015) The chemokine system in innate immunity. Cold Spring Harb Perspect Biol 7:a016303
McGrath T, Baskerville R, Rogero M, Castell L (2022) Emerging evidence for the widespread role of glutamatergic dysfunction in neuropsychiatric diseases. Nutrients 14:917
Chen F, Bertelsen AB, Holm IE, Nyengaard JR, Rosenberg R, Dorph-Petersen KA (2020) Hippocampal volume and cell number in depression, schizophrenia, and suicide subjects. Brain Res 1727:146546
Lucassen PJ, Fuchs E, Czéh B (2004) Antidepressant treatment with tianeptine reduces apoptosis in the hippocampal dentate gyrus and temporal cortex. Biol Psychiatry 55:789–796
Yuan J, Murrell GA, Trickett A, Wang MX (2003) Involvement of cytochrome c release and caspase-3 activation in the oxidative stress-induced apoptosis in human tendon fibroblasts. Biochim Biophys Acta 1641:35–41
Brown R (1997) The bcl-2 family of proteins. Br Med Bull 53:466–477
Ma Z, Feng D, Rui W, Wang Z (2023) Baicalin attenuates chronic unpredictable mild stress-induced hippocampal neuronal apoptosis through regulating SIRT1/PARP1 signaling pathway. Behav Brain Res 441:114299
Banaudha K, Marini AM (2000) AMPA prevents glutamate-induced neurotoxicity and apoptosis in cultured cerebellar granule cell neurons. Neurotox Res 2:51–61
Liu SJ, Zukin RS (2007) Ca2+-permeable AMPA receptors in synaptic plasticity and neuronal death. Trends Neurosci 30:126–134
Mahajan SS, Thai KH, Chen K, Ziff E (2011) Exposure of neurons to excitotoxic levels of glutamate induces cleavage of the RNA editing enzyme, adenosine deaminase acting on RNA 2, and loss of GLUR2 editing. Neuroscience 189:305–315
Lauterborn JC, Lynch G, Vanderklish P, Arai A, Gall CM (2000) Positive modulation of AMPA receptors increases neurotrophin expression by hippocampal and cortical neurons. J Neurosci 20:8–21
Ha HC, Snyder SH (2000) Poly(ADP-ribose) polymerase-1 in the nervous system. Neurobiol Dis 7:225–239
Ordway GA, Szebeni A, Hernandez LJ, Crawford JD, Szebeni K, Chandley MJ, Burgess KC, Miller C, Bakkalbasi E, Brown RW (2017) Antidepressant-like actions of inhibitors of poly(ADP-Ribose) polymerase in rodent models. Int J Neuropsychopharmacol 20:994–1004
Luccarini I, Pantano D, Nardiello P, Cavone L, Lapucci A, Miceli C, Nediani C, Berti A, Stefani M, Casamenti F (2016) The Polyphenol oleuropein aglycone modulates the PARP1-SIRT1 interplay: an in vitro and in vivo study. J Alzheimers Dis 54:737–750
Ribeiro FF, Xapelli S (2021) An overview of adult neurogenesis. Adv Exp Med Biol 1331:77–94
Zhang K, Pan X, Wang F, Ma J, Su G, Dong Y, Yang J, Wu C (2016) Baicalin promotes hippocampal neurogenesis via SGK1- and FKBP5-mediated glucocorticoid receptor phosphorylation in a neuroendocrine mouse model of anxiety/depression. Sci Rep 6:30951
Xiao Z, Cao Z, Yang J, Jia Z, Du Y, Sun G, Lu Y, Pei L (2021) Baicalin promotes hippocampal neurogenesis via the Wnt/β-catenin pathway in a chronic unpredictable mild stress-induced mouse model of depression. Biochem Pharmacol 190:114594
Wang Z, Cheng YT, Lu Y, Sun GQ, Pei L (2023) Baicalin ameliorates corticosterone-induced depression by promoting neurodevelopment of hippocampal via mTOR/GSK3 β pathway. Chin J Integr Med 29:405
Mayer JL, Klumpers L, Maslam S, de Kloet ER, Joëls M, Lucassen PJ (2006) Brief treatment with the glucocorticoid receptor antagonist mifepristone normalises the corticosterone-induced reduction of adult hippocampal neurogenesis. J Neuroendocrinol 18:629–631
Egeland M, Zunszain PA, Pariante CM (2015) Molecular mechanisms in the regulation of adult neurogenesis during stress. Nat Rev Neurosci 16:189–200
Zhang S, Cheon M, Park H, Kim T, Chung C (2022) Interaction between glucocorticoid receptors and FKBP5 in regulating neurotransmission of the hippocampus. Neuroscience 483:95–103
Gao C, Chen X, Xu A, Cheng K, Shen J (2018) Adaptor Protein APPL2 affects adult antidepressant behaviors and hippocampal neurogenesis via regulating the sensitivity of glucocorticoid receptor. Mol Neurobiol 55:5537–5547
Gao C, Du Q, Li W, Deng R, Wang Q, Xu A, Shen J (2018) Baicalin modulates APPL2/Glucocorticoid receptor signaling cascade, promotes neurogenesis, and attenuates emotional and olfactory dysfunctions in chronic corticosterone-induced depression. Mol Neurobiol 55:9334–9348
Gupta K, Gupta R, Bhatia MS, Tripathi AK, Gupta LK (2017) Effect of agomelatine and fluoxetine on HAM-D score, serum brain-derived neurotrophic factor, and tumor necrosis factor-α level in patients with major depressive disorder with severe depression. J Clin Pharmacol 57:1519–1526
Einat H, Yuan P, Gould TD, Li J, Du J, Zhang L, Manji HK, Chen G (2003) The role of the extracellular signal-regulated kinase signaling pathway in mood modulation. J Neurosci 23:7311–7316
Jia Z, Yang J, Cao Z, Zhao J, Zhang J, Lu Y, Chu L, Zhang S, Chen Y, Pei L (2021) Baicalin ameliorates chronic unpredictable mild stress-induced depression through the BDNF/ERK/CREB signaling pathway. Behav Brain Res 414:113463
Pontrello CG, Sun MY, Lin A, Fiacco TA, DeFea KA, Ethell IM (2012) Cofilin under control of β-arrestin-2 in NMDA-dependent dendritic spine plasticity, long-term depression (LTD), and learning. Proc Natl Acad Sci U S A 109:E442-451
Lu Y, Sun G, Yang F, Guan Z, Zhang Z, Zhao J, Liu Y, Chu L, Pei L (2019) Baicalin regulates depression behavior in mice exposed to chronic mild stress via the Rac/LIMK/cofilin pathway. Biomed Pharmacother 116:109054
Wang J, Zhai HR, Ma SF, Shi HZ, Zhang WJ, Yun Q, Liu WJ, Liu ZZ, Zhang WN (2022) FOXG1 contributes adult hippocampal neurogenesis in mice. Int J Mol Sci 23:14979
Tang MM, Lin WJ, Zhang JT, Zhao YW, Li YC (2017) Exogenous FGF2 reverses depressive-like behaviors and restores the suppressed FGF2-ERK1/2 signaling and the impaired hippocampal neurogenesis induced by neuroinflammation. Brain Behav Immun 66:322–331
Zhang R, Ma Z, Liu K, Li Y, Liu D, Xu L, Deng X, Qu R, Ma Z, Ma S (2019) Baicalin exerts antidepressant effects through Akt/FOXG1 pathway promoting neuronal differentiation and survival. Life Sci 221:241–248
Duda P, Hajka D, Wójcicka O, Rakus D, Gizak A (2020) GSK3β: A Master Player in Depressive Disorder Pathogenesis and Treatment Responsiveness. Cells 9
Pérez-Domper P, Palomo V, Gradari S, Gil C, de Ceballos ML, Martínez A, Trejo JL (2017) The GSK-3-inhibitor VP2.51 produces antidepressant effects associated with adult hippocampal neurogenesis. Neuropharmacology 116:174–187
Garza JC, Guo M, Zhang W, Lu XY (2012) Leptin restores adult hippocampal neurogenesis in a chronic unpredictable stress model of depression and reverses glucocorticoid-induced inhibition of GSK-3β/β-catenin signaling. Mol Psychiatry 17:790–808
Ignácio ZM, Réus GZ, Arent CO, Abelaira HM, Pitcher MR, Quevedo J (2016) New perspectives on the involvement of mTOR in depression as well as in the action of antidepressant drugs. Br J Clin Pharmacol 82:1280–1290
Park SW, Lee JG, Seo MK, Lee CH, Cho HY, Lee BJ, Seol W, Kim YH (2014) Differential effects of antidepressant drugs on mTOR signalling in rat hippocampal neurons. Int J Neuropsychopharmacol 17:1831–1846
Bhatt S, Nagappa AN, Patil CR (2020) Role of oxidative stress in depression. Drug Discov Today 25:1270–1276
Palta P, Samuel LJ, Miller ER 3rd, Szanton SL (2014) Depression and oxidative stress: results from a meta-analysis of observational studies. Psychosom Med 76:12–19
Zhang CY, Zeng MJ, Zhou LP, Li YQ, Zhao F, Shang ZY, Deng XY, Ma ZQ, Fu Q, Ma SP, Qu R (2018) Baicalin exerts neuroprotective effects via inhibiting activation of GSK3β/NF-κB/NLRP3 signal pathway in a rat model of depression. Int Immunopharmacol 64:175–182
Bansal Y, Kuhad A (2016) Mitochondrial Dysfunction in Depression. Curr Neuropharmacol 14:610–618
Popov LD (2020) Mitochondrial biogenesis: An update. J Cell Mol Med 24:4892–4899
Cantó C, Auwerx J (2009) PGC-1alpha, SIRT1 and AMPK, an energy sensing network that controls energy expenditure. Curr Opin Lipidol 20:98–105
Lu S, Li C, Jin X, Zhu L, Shen J, Bai M, Li Y, Xu E (2022) Baicalin improves the energy levels in the prefrontal cortex of mice exposed to chronic unpredictable mild stress. Heliyon 8:e12083
Jin X, Zhu L, Lu S, Li C, Bai M, Xu E, Shen J, Li Y (2023) Baicalin ameliorates CUMS-induced depression-like behaviors through activating AMPK/PGC-1α pathway and enhancing NIX-mediated mitophagy in mice. Eur J Pharmacol 938:175435
Yu HY, Yin ZJ, Yang SJ, Ma SP, Qu R (2016) Baicalin Reverses depressive-like behaviours and regulates apoptotic signalling induced by olfactory bulbectomy. Phytother Res 30:469–475
Xiong Z, Jiang B, Wu PF, Tian J, Shi LL, Gu J, Hu ZL, Fu H, Wang F, Chen JG (2011) Antidepressant effects of a plant-derived flavonoid baicalein involving extracellular signal-regulated kinases cascade. Biol Pharm Bull 34:253–259
Lee B, Sur B, Park J, Kim SH, Kwon S, Yeom M, Shim I, Lee H, Hahm DH (2013) Chronic administration of baicalein decreases depression-like behavior induced by repeated restraint stress in rats. Korean J Physiol Pharmacol 17:393–403
Liu HT, Lin YN, Tsai MC, Wu YC, Lee MC (2022) Baicalein exerts therapeutic effects against endotoxin-induced depression-like behavior in mice by decreasing inflammatory cytokines and increasing brain-derived neurotrophic factor levels. Antioxidants (Basel) 11:947
Wu H, Long X, Yuan F, Chen L, Pan S, Liu Y, Stowell Y, Li X (2014) Combined use of phospholipid complexes and self-emulsifying microemulsions for improving the oral absorption of a BCS class IV compound, baicalin. Acta Pharm Sin B 4:217–226
Kang MJ, Ko GS, Oh DG, Kim JS, Noh K, Kang W, Yoon WK, Kim HC, Jeong HG, Jeong TC (2014) Role of metabolism by intestinal microbiota in pharmacokinetics of oral baicalin. Arch Pharm Res 37:371–378
Zhang R, Cui Y, Wang Y, Tian X, Zheng L, Cong H, Wu B, Huo X, Wang C, Zhang B, Wang X, Yu Z (2017) Catechol-O-Methyltransferase and UDP-glucuronosyltransferases in the metabolism of baicalein in different species. Eur J Drug Metab Pharmacokinet 42:981–992
Zhang L, Xing D, Wang W, Wang R, Du L (2006) Kinetic difference of baicalin in rat blood and cerebral nuclei after intravenous administration of Scutellariae Radix extract. J Ethnopharmacol 103:120–125
Zhang J, Cai W, Zhou Y, Liu Y, Wu X, Li Y, Lu J, Qiao Y (2015) Profiling and identification of the metabolites of baicalin and study on their tissue distribution in rats by ultra-high-performance liquid chromatography with linear ion trap-Orbitrap mass spectrometer. J Chromatogr B Analyt Technol Biomed Life Sci 985:91–102
Li M, Shi A, Pang H, Xue W, Li Y, Cao G, Yan B, Dong F, Li K, Xiao W, He G, Du G, Hu X (2014) Safety, tolerability, and pharmacokinetics of a single ascending dose of baicalein chewable tablets in healthy subjects. J Ethnopharmacol 156:210–215
Pang H, Xue W, Shi A, Li M, Li Y, Cao G, Yan B, Dong F, Xiao W, He G, Du G, Hu X, Cheng G (2016) Multiple-ascending-dose pharmacokinetics and safety evaluation of baicalein chewable tablets in healthy chinese volunteers. Clin Drug Investig 36:713–724
Cai Y, Ma W, Xiao Y, Wu B, Li X, Liu F, Qiu J, Zhang G (2017) High doses of baicalin induces kidney injury and fibrosis through regulating TGF-β/Smad signaling pathway. Toxicol Appl Pharmacol 333:1–9
Perez-Caballero L, Torres-Sanchez S, Romero-López-Alberca C, González-Saiz F, Mico JA, Berrocoso E (2019) Monoaminergic system and depression. Cell Tissue Res 377:107–113
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Wang, C., Gao, MQ. Research Progress on the Antidepressant Effects of Baicalin and Its Aglycone Baicalein: A Systematic Review of the Biological Mechanisms. Neurochem Res 49, 14–28 (2024). https://doi.org/10.1007/s11064-023-04026-3
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DOI: https://doi.org/10.1007/s11064-023-04026-3