Abstract
Scutellaria baicalensis (SB), also known as the Chinese skullcap, has a long history of being used in Chinese medicine to treat a variety of conditions ranging from microbial infections to metabolic syndrome and malignancies. Numerous studies have reported that treatment with total SB extract or two main flavonoids found in its root and leaves, baicalin (BA) and baicalein (BE), can prevent or alleviate the detrimental toxic effects of exposure to various chemical compounds. It has been shown that BA and BE are generally behind the protective effects of SB against toxicants. This paper aimed to review the protective and therapeutic effects of SB and its main components BA and BE against chemical compounds that can cause intoxication after acute or chronic exposure and seriously affect different vital organs including the brain, heart, liver, and kidneys. In this review paper, we had a look into a total of 221 in vitro and in vivo studies from 1995 to 2021 from the scientific databases PubMed, Scopus, and Web of Science which reported protective or therapeutic effects of BA, BE, or SB against drugs and chemicals that one might be exposed to on a professional or accidental basis and compounds that are primarily used to simulate disease models. In conclusion, the protective effects of SB and its flavonoids can be mainly attributed to increase in antioxidants enzymes, inhibition of lipid peroxidation, reduction of inflammatory cytokines, and suppression of apoptosis pathway.
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Abbreviations
- AD:
-
Alzheimer’s disease
- Akt:
-
Protein kinase B
- ALP:
-
Alkaline phosphatase
- ALT:
-
Alanine aminotransferase
- APAP:
-
Acetaminophen
- AST:
-
Aspartate aminotransferase
- BA:
-
Baicalin
- BE:
-
Baicalein
- BaP:
-
Benzo(a)pyrene
- BLM:
-
Bleomycin
- BUN:
-
Blood urea nitrogen
- CAT:
-
Catalase
- Cd:
-
Cadmium
- CORT:
-
Corticosterone
- COX-2:
-
Cyclooxygenase-2
- DA:
-
Dopamine
- DOX:
-
Doxorubicin
- ERK:
-
Extracellular signal-regulated kinases
- ET-1:
-
Endothelin-1
- GSH:
-
Glutathione
- HO-1:
-
Heme oxygenase-1
- IκBα:
-
Nuclear factor of kappa light polypeptide gene enhancer in B cells inhibitor alpha
- IL:
-
Interleukin
- iNOS:
-
Inducible nitric oxide synthase
- i.p.:
-
Intraperitoneal
- JNK:
-
C-Jun N-terminal kinase
- Keap1:
-
Kelch-like epichlorohydrin–associated protein 1
- LDH:
-
Lactate dehydrogenase
- MAPK:
-
Mitogen-activated protein kinase
- MDA:
-
Malondialdehyde
- MMP:
-
Mitochondrial membrane potential
- MMPs:
-
Matrix metalloproteinases
- NF-κB:
-
Nuclear factor kappa-light-chain-enhancer of activated B cells
- NMDA:
-
N-methyl-d-aspartate
- NO:
-
Nitric oxide
- NQO-1:
-
NAD(P)H quinone dehydrogenase-1
- Nrf2:
-
Nuclear factor erythroid 2–related factor 2
- NTG:
-
Nitroglycerin
- Pb:
-
Lead
- PD:
-
Parkinson’s disease
- PI3K:
-
Phosphoinositide 3-kinase
- PPAR:
-
Peroxisome proliferator–activated receptor
- ROS:
-
Reactive oxygen species
- SB:
-
Scutellaria baicalensis
- SBE:
-
Scutellaria baicalensis extract
- Scr:
-
Serum creatinine
- SIRT1:
-
Sirtuin 1
- SOD:
-
Superoxide dismutase
- STZ:
-
Streptozotocin
- t-BHP:
-
Tert-Butyl hydroperoxide
- TCM:
-
Traditional Chinese medicine
- TG:
-
Triglyceride
- TGF:
-
Transforming growth factor
- Th:
-
T helper
- TLR:
-
Toll-like receptor
- TNF-α:
-
Tumor necrosis factor-α
- Treg:
-
T regulator
References
Akilah A, Balaha M, Abd-El Rahman MN, Hedya S (2018) Apigenin and baicalin, each alone or in low-dose combination, attenuated chloroquine induced male infertility in adult rats. Thai J Pharm Sci 42:118–128
Al-Oanzi ZH, Elasbali AM, Alruwaili NK et al (2020) Protective effect of baicalein alone and losartan–baicalein combination therapy on doxorubicin-induced hepatotoxicity in rats. Toxicol Environ Health Sci 12:45–54. https://doi.org/10.1007/s13530-020-00037-7
Asanuma M, Miyazaki I, Ogawa N (2003) Dopamine- or L-DOPA-induced neurotoxicity: the role of dopamine quinone formation and tyrosinase in a model of Parkinson’s disease. Neurotox Res 5:165–176. https://doi.org/10.1007/BF03033137
Aung HH, Dey L, Mehendale S et al (2003) Scutellaria baicalensis extract decreases cisplatin-induced pica in rats. Cancer Chemother Pharmacol 52:453–458. https://doi.org/10.1007/s00280-003-0694-9
Aung H, Mehendale S, Chang WT et al (2005) Scutellaria baicalensis decreases ritonavir-induced nausea. AIDS Res Ther 2:1–6. https://doi.org/10.1186/1742-6405-2-12
Baradaran Rahimi V, Askari VR, Hosseinzadeh H (2021) Promising influences of Scutellaria baicalensis and its two active constituents, baicalin, and baicalein, against metabolic syndrome: a review. Phythther Res 35:3558–3574. https://doi.org/10.1002/ptr.7046
Bartal M (2005) COPD and tobacco smoke. Monaldi Arch chest Dis = Arch Monaldi per le Mal del torace 63:213–225. https://doi.org/10.4081/monaldi.2005.623
Bertin G, Averbeck D (2006) Cadmium: cellular effects, modifications of biomolecules, modulation of DNA repair and genotoxic consequences (a review). Biochimie 88:1549–1559. https://doi.org/10.1016/j.biochi.2006.10.001
Campbell JH, Heikkila JJ (2018) Effect of hemin, baicalein and heme oxygenase-1 (HO-1) enzyme activity inhibitors on Cd-induced accumulation of HO-1, HSPs and aggresome-like structures in Xenopus kidney epithelial cells. Comp Biochem Physiol Part - C Toxicol Pharmacol 210:1–17. https://doi.org/10.1016/j.cbpc.2018.04.003
Cao J, Zhang Y, Wang T, Li B (2018) Endoplasmic reticulum stress is involved in baicalin protection on chondrocytes from patients with osteoarthritis. Dose-Response 16:1–8. https://doi.org/10.1177/1559325818810636
Chang WT, Li J, Haung HH et al (2011) Baicalein protects against doxorubicin-induced cardiotoxicity by attenuation of mitochondrial oxidant injury and JNK activation. J Cell Biochem 112:2873–2881
Chang Y, Lu CW, Lin TY et al (2016) Baicalein, a constituent of Scutellaria baicalensis, reduces glutamate release and protects neuronal cell against kainic acid-induced excitotoxicity in rats. Am J Chin Med 44:943–962
Chaudhuri TK, Paul S (2006) Protein-misfolding diseases and chaperone-based therapeutic approaches. FEBS J 273:1331–1349. https://doi.org/10.1111/j.1742-4658.2006.05181.x
Chen YC, Chow JM, Lin CW et al (2006) Baicalein inhibition of oxidative-stress-induced apoptosis via modulation of ERKs activation and induction of HO-1 gene expression in rat glioma cells C6. Toxicol Appl Pharmacol 216:263–273. https://doi.org/10.1016/j.taap.2006.05.008
Chen X, Zhang N, Zou H (2007) Protective effect of baicalin on mouse with Parkinson’s disease induced by MPTP. Chinese J Integr Tradit West Med 27:1010–1012
Chen H, Geng M, Hu Y, Wang J (2011) Effects of baicalin against oxidative stress injury of SH-SY5Y cells by up-regulating SIRT1. Acta Pharm Sin 46:1039–1044
Chen J, Zhao K, Bin LG (2013) Estrogen-induced cholestasis: pathogenesis and therapeutic implications. Hepatogastroenterology 60:1289–1296. https://doi.org/10.5754/hge121061
Chen H, Gao Y, Wu J et al (2014) Exploring therapeutic potentials of baicalin and its aglycone baicalein for hematological malignancies. Cancer Lett 354:5–11
Chen C, Li X, Gao P et al (2015a) Baicalin attenuates Alzheimer-like pathological changes and memory deficits induced by amyloid β1–42 protein. Metab Brain Dis 30:537–544. https://doi.org/10.1007/s11011-014-9601-9
Chen H, Xu Y, Wang J et al (2015) Baicalin ameliorates isoproterenol-induced acute myocardial infarction through iNOS, inflammation and oxidative stress in rat. Int J Clin Exp Pathol 8:10139–10147
Cheng Y, He G, Mu X et al (2008) Neuroprotective effect of baicalein against MPTP neurotoxicity: behavioral, biochemical and immunohistochemical profile. Neurosci Lett 441:16–20. https://doi.org/10.1016/j.neulet.2008.05.116
Cheng J-J, Zhao H-X, Guo K et al (2016) Flavonoid from Scutellaria Stems and Leaves Attenuates Composited Aβ-Induced Memory Impairment and Apoptosis in Rats 25:2627–2636
Choi J, Conrad CC, Malakowsky CA et al (2002) Flavones from Scutellaria baicalensis Georgi attenuate apoptosis and protein oxidation in neuronal cell lines. Biochim Biophys Acta - Gen Subj 1571:201–210. https://doi.org/10.1016/S0304-4165(02)00217-9
Choi EO, Jeong JW, Park C et al (2016) Baicalein protects C6 glial cells against hydrogen peroxide-induced oxidative stress and apoptosis through regulation of the Nrf2 signaling pathway. Int J Mol Med 37:798–806. https://doi.org/10.3892/ijmm.2016.2460
Cui L, Feng L, Zhang ZH, Bin JX (2014) The anti-inflammation effect of baicalin on experimental colitis through inhibiting TLR4/NF-κB pathway activation. Int Immunopharmacol 23:294–303. https://doi.org/10.1016/j.intimp.2014.09.005
Cui G, Chui Wah Luk S, Li RA et al (2015) Cytoprotection of baicalein against oxidative stress-induced cardiomyocytes injury through the Nrf2/Keap1 pathway. J Cardiovasc Pharmacol 65:39–46. https://doi.org/10.1097/FJC.0000000000000161
Dai D (2005) Mechanism of gentamicin induced ototoxicity and the neuroprotective effect mediated by baicalin. Chinese J Clin Rehabil 9:184–185
Dai S-X, Zou Y, Feng Y-L et al (2012) Baicalin down-regulates the expression of macrophage migration inhibitory factor (MIF) effectively for rats with ulcerative colitis. Phytother Res 26:498–504. https://doi.org/10.1002/ptr.3581
Dai C, Tang S, Wang Y et al (2017) Baicalein acts as a nephroprotectant that ameliorates colistin-induced nephrotoxicity by activating the antioxidant defence mechanism of the kidneys and down-regulating the inflammatory response. J Antimicrob Chemother 72:2562–2569
Dai C, Jiang S, Chu C et al (2019) Baicalin protects human retinal pigment epithelial cell lines against high glucose-induced cell injury by up-regulation of microRNA-145. Exp Mol Pathol 106:123–130. https://doi.org/10.1016/j.yexmp.2019.01.002
Dang Z, Li Q, Sun S et al (2019) The medicinal plant pair Bupleurum chinense-Scutellaria baicalensis – metabolomics and metallomics analysis in a model for alcoholic liver injury. Front Pharmacol 10:1–10. https://doi.org/10.3389/fphar.2019.00254
Ding H, Wang H, Zhao Y et al (2015) Protective effects of baicalin on Aβ1–42-induced learning and memory deficit, oxidative stress, and apoptosis in rat. Cell Mol Neurobiol 35:623–632. https://doi.org/10.1007/s10571-015-0156-z
Dong C, Anand KJS (2013) Developmental neurotoxicity of ketamine in pediatric clinical use. Toxicol Lett 220:53–60. https://doi.org/10.1016/j.toxlet.2013.03.030
Dong J, Zhang Y, Chen Y et al (2015) Baicalin inhibits the lethality of ricin in mice by inducing protein oligomerization. J Biol Chem 290:12899–12907. https://doi.org/10.1074/jbc.M114.632828
Dong Q, Chu F, Wu C et al (2016) Scutellaria baicalensis Georgi extract protects against alcohol-induced acute liver injury in mice and affects the mechanism of ER stress. Mol Med Rep 13:3052–3062. https://doi.org/10.3892/mmr.2016.4941
Dong Y, Xing Y, Sun J et al (2020) Baicalein alleviates liver oxidative stress and apoptosis induced by high-level glucose through the activation of the PERK/Nrf2 signaling pathway. Molecules 25:1–17. https://doi.org/10.3390/molecules25030599
Dorrigiv M, Zareiyan A, Hosseinzadeh H (2020) Garlic (Allium sativum) as an antidote or a protective agent against natural or chemical toxicities: a comprehensive update review. Phytother Res 34:1770–1797. https://doi.org/10.1002/ptr.6645
Dou W, Mukherjee S, Li H, et al (2012) Alleviation of gut inflammation by Cdx2/PXR pathway in a mouse model of chemical colitis. PLoS One 7https://doi.org/10.1371/journal.pone.0036075
Fan XX, Yao XJ, Xu SW et al (2015) (Z)3,4,5,4′-trans-tetramethoxystilbene, a new analogue of resveratrol, inhibits gefitinib-resistant non-small cell lung cancer via selectively elevating intracellular calcium level. Sci Rep 5:1–18. https://doi.org/10.1038/srep16348
Fanoudi S, Alavi MS, Karimi G, Hosseinzadeh H (2020) Milk thistle (Silybum marianum) as an antidote or a protective agent against natural or chemical toxicities: a review. Drug Chem Toxicol 43:240–254. https://doi.org/10.1080/01480545.2018.1485687
Feng J, Guo C, Zhu Y et al (2014) Baicalin down regulates the expression of TLR4 and NFkB-p65 in colon tissue in mice with colitis induced by dextran sulfate sodium. Int J Clin Exp Med 7:4063–4072
Fouad AEA, Fouad AA, Al-Melhim WN (2018) Protective effect of baicalin in rats exposed to arsenic-induced testicular toxicity. Indian J Forensic Med Toxicol 12:256–261. https://doi.org/10.5958/0973-9130.2018.00112.3
Furman D, Campisi J, Verdin E et al (2019) Chronic inflammation in the etiology of disease across the life span. Nat Med 25:1822–1832. https://doi.org/10.1038/s41591-019-0675-0
Gao Z, Huang K, Xu H (2001) Protective effects of flavonoids in the roots of Scutellaria baicalensis Georgi against hydrogen peroxide-induced oxidative stress in HS-SY5Y cells. Pharmacol Res 43:173–178. https://doi.org/10.1006/phrs.2000.0761
Gao Y, Lu J, Zhang Y et al (2013) Baicalein attenuates bleomycin-induced pulmonary fibrosis in rats through inhibition of miR-21. Pulm Pharmacol Ther 26:649–654
Gao L, Li C, Yang RY et al (2015) Ameliorative effects of baicalein in MPTP-induced mouse model of Parkinson’s disease: a microarray study. Pharmacol Biochem Behav 133:155–163. https://doi.org/10.1016/j.pbb.2015.04.004
Gao C, Du Q, Li W et al (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. https://doi.org/10.1007/s12035-018-1042-8
Gao L, Zhou F, Wang KX et al (2020) Baicalein protects PC12 cells from Aβ25–35-induced cytotoxicity via inhibition of apoptosis and metabolic disorders. Life Sci 248:117471. https://doi.org/10.1016/j.lfs.2020.117471
Ge GF, Shi WW, Yu CH et al (2017) Baicalein attenuates vinorelbine-induced vascular endothelial cell injury and chemotherapeutic phlebitis in rabbits. Toxicol Appl Pharmacol 318:23–32. https://doi.org/10.1016/j.taap.2017.01.013
Geng M, Chen H, Wang J et al (2010) Protective effects of baicalin on amyloid beta 25–35-induced apoptosis in human neuroblastoma SH-SY5Y cells. Neural Regen Res 5:1739–1744. https://doi.org/10.3969/j.issn.1673-5374.2010.22.010
Gong L, Zhu J (2018) Baicalin alleviates oxidative stress damage in trabecular meshwork cells in vitro. Naunyn Schmiedebergs Arch Pharmacol 391:51–58. https://doi.org/10.1007/s00210-017-1433-9
Gong WYI, Wu JF, Liu BJ et al (2014) Flavonoid components in Scutellaria baicalensis inhibit nicotine-induced proliferation, metastasis and lung cancer-associated inflammation in vitro. Int J Oncol 44:1561–1570. https://doi.org/10.3892/ijo.2014.2320
Guha G, Rajkumar V, Ashok Kumar R, Mathew L (2010) Aqueous extract of Phyllanthus amarus inhibits chromium(VI)-induced toxicity in MDA-MB-435S cells. Food Chem Toxicol 48:396–401
Guo C, Chen X (2011) Baicalin interferes with iron accumulation in C6 glioma cells*⋆. Neural Regen Res 6:2352–2356
Guo C, Chen X, Xiong P (2014) Baicalin suppresses iron accumulation after substantia nigra injury: relationship between iron concentration and transferrin expression. Neural Regen Res 9:630–636. https://doi.org/10.4103/1673-5374.130108
Hashimoto M, Yamamoto S, Iwasa K et al (2017) The flavonoid baicalein attenuates cuprizone-induced demyelination via suppression of neuroinflammation. Brain Res Bull 135:47–52. https://doi.org/10.1016/j.brainresbull.2017.09.007
He G-R, Mu X, Li X-X et al (2015) Effect of baicalein on brain injury induced by 6-hydroxydopamine at different sites in rats. Chinese Pharmacol Bull 31:623–630. https://doi.org/10.3969/j.issn.1001-1978.2015.05.008
He F, Zhou A, Feng S et al (2018) Mesenchymal stem cell therapy for paraquat poisoning: a systematic review and meta-analysis of preclinical studies. PLoS ONE 13:e0194748. https://doi.org/10.1371/journal.pone.0194748
He P, Wu Y, Shun J, et al (2017) Baicalin ameliorates liver injury induced by chronic plus binge ethanol feeding by modulating oxidative stress and inflammation via CYP2E1 and NRF2 in mice. Oxid Med Cell Longev 2017https://doi.org/10.1155/2017/4820414
Heo H, Shin Y, Cho W et al (2009) Memory improvement in ibotenic acid induced model rats by extracts of Scutellaria baicalensis. J Ethnopharmacol 122:20–27. https://doi.org/10.1016/j.jep.2008.11.026
Hong T, Jin G-B, Cho S, Cyong J-C (2002) Evaluation of the anti-inflammatory effect of baicalein on dextran sulfate sodium-induced colitis in mice. Planta Med 68:268–271. https://doi.org/10.1055/s-2002-23143
Huang Y, Tsang SY, Yao X, Chen ZY (2005) Biological properties of baicalein in cardiovascular system. Curr Drug Targets - Cardiovasc Haematol Disord 5:177–184. https://doi.org/10.2174/1568006043586206
Huang HL, Wang YJ, Zhang QY et al (2012) Hepatoprotective effects of baicalein against CCl4-induced acute liver injury in mice. World J Gastroenterol 18:6605–6613. https://doi.org/10.3748/wjg.v18.i45.6605
Huang HH, Shao ZH, Li CQ et al (2014) Baicalein protects cardiomyocytes against mitochondrial oxidant injury associated with jnk inhibition and mitochondrial akt activation. Am J Chin Med 42:79–94. https://doi.org/10.1142/S0192415X14500050
Huang T, Wu T, Guo Y et al (2019) The concurrent treatment of Scutellaria baicalensis Georgi enhances the therapeutic efficacy of cisplatin but also attenuates chemotherapy-induced cachexia and acute kidney injury. J Ethnopharmacol 243:112075. https://doi.org/10.1016/j.jep.2019.112075
Huang X, He Y, Chen Y, et al (2016) Baicalin attenuates bleomycin-induced pulmonary fibrosis via adenosine A2a receptor related TGF-β1-induced ERK1/2 signaling pathway. BMC Pulm. Med. 16
Hung CH, Wang CN, Cheng HH et al (2018) Baicalin ameliorates imiquimod-induced psoriasis-like inflammation in mice. Planta Med 84:1110–1117. https://doi.org/10.1055/a-0622-8242
Hwang JM, Wang CJ, Chou FP et al (2005) Protective effect of baicalin on tert-butyl hydroperoxide-induced rat hepatotoxicity. Arch Toxicol 79:102–109. https://doi.org/10.1007/s00204-004-0588-6
Im HI, Joo WS, Nam E et al (2005) Baicalein prevents 6-hydroxydopamine-induced dopaminergic dysfunction and lipid peroxidation in mice. J Pharmacol Sci 98:185–189. https://doi.org/10.1254/jphs.SC0050014
Im H-I, Nam E, Lee E-S et al (2006) Baicalein protects 6-OHDA-induced neuronal damage by suppressing oxidative stress. Korean J Physiol Pharmacol 10:309–315
Irrera N, Pallio G, Mannino F et al (2020) Administration of a nutraceutical mixture composed by Aloe arborescens, Annona muricata, Morinda citrifolia, Beta rubra, Scutellaria baicalensis, and Vaccinium myrtillus reduces doxorubicin-induced side effects. Nutr Cancer 72:343–351. https://doi.org/10.1080/01635581.2019.1633364
Jang SI, Kim HJ, Hwang KM et al (2003) Hepatoprotective effect of baicalin, a major flavone from Scutellaria radix, on acetaminophen-induced liver injury in mice. Immunopharmacol Immunotoxicol 25:585–594. https://doi.org/10.1081/IPH-120026443
Jeong JY, Cha HJ, Choi EO et al (2019) Activation of the Nrf2/HO-1 signaling pathway contributes to the protective effects of baicalein against oxidative stress-induced DNA damage and apoptosis in HEI193 Schwann cells. Int J Med Sci 16:145–155. https://doi.org/10.7150/ijms.27005
Ji W, Liang K, An R, Wang X (2019) Baicalin protects against ethanol-induced chronic gastritis in rats by inhibiting Akt/NF-κB pathway. Life Sci 239:117064. https://doi.org/10.1016/j.lfs.2019.117064
Jia H, Chen X-L, Chen C et al (2010) Baicalin prevents the up-regulation of connective tissue growth factor in fibrotic lungs of rats. Acta Physiol Sin 62:535–540
Jiang H, Lv PF, Li JC et al (2013) Baicalin inhibits colistin sulfate-induced apoptosis of PC12 cells. Neural Regen Res 8:2597–2604. https://doi.org/10.3969/j.issn.1673-5374.2013.28.001
Jiang W-Y, Seo G, Kim Y-C, et al (2015) PF2405, standardized fraction of Scutellaria baicalensis, ameliorates colitis in vitro and in vivo. Arch Pharm Res 38https://doi.org/10.1007/s12272-015-0553-3
Jin XQ, Xu H, Shi HY et al (2007) Fluoride-induced oxidative stress of osteoblasts and protective effects of baicalein against fluoride toxicity. Biol Trace Elem Res 116:81–89
Jules-Elysee K, White DA (1990) Bleomycin-induced pulmonary toxicity. Clin Chest Med 11:1–20
Jung SH, Kang KD, Ji D et al (2008) The flavonoid baicalin counteracts ischemic and oxidative insults to retinal cells and lipid peroxidation to brain membranes. Neurochem Int 53:325–337. https://doi.org/10.1016/j.neuint.2008.09.004
Kang C, Wang L, Kang M et al (2019) Baicalin alleviates 6-hydroxydopamine-induced neurotoxicity in PC12 cells by down-regulation of microRNA-192-5p. Brain Res 1708:84–92. https://doi.org/10.1016/j.brainres.2018.12.015
Kim DH, Chung HY, Cho KH et al (2005) Cytoprotective mechanism of baicalin against endothelial cell damage by peroxynitrite. J Pharm Pharmacol 57:1581–1590. https://doi.org/10.1211/jpp.57.12.0008
Kim S-C, Lee S-D, Song S-H et al (2007) Effect of Scutellaria baicalensis Georgi. Extract on cisplatin-induced acute renal failure in rabbits. J Vet Clin 24:392–399
Kim S-H, Kim H-J, Jung J-Y (2009) Effects of baicalein on picryl chloride-induced contact dermatitis in BALB/c mice. J Korean Soc Food Sci Nutr 38:160–165. https://doi.org/10.3746/jkfn.2009.38.2.160
Kim KC, Kang SS, Lee J et al (2012) Baicalein attenuates oxidative stress-induced expression of matrix metalloproteinase-1 by regulating the ERK/JNK/AP-1 pathway in human keratinocytes. Biomol Ther 20:57–61. https://doi.org/10.4062/biomolther.2012.20.1.057
Kim DH, Sung B, Chung HY, Kim ND (2014) Modulation of colitis-associated colon tumorigenesis by baicalein and betaine. J Cancer Prev 19:152–160. https://doi.org/10.15430/jcp.2014.19.3.153
Kim TW, Choi JM, Kim MS et al (2016) Topical application of Scutellaria baicalensis suppresses 2,4-dinitrochlorobenzene-induced contact dermatitis. Nat Prod Res 30:705–709. https://doi.org/10.1080/14786419.2015.1038812
Ku SK, Bae JS (2015) Baicalin, baicalein and wogonin inhibits high glucose-induced vascular inflammation in vitro and in vivo. BMB Rep 48:519–524. https://doi.org/10.5483/BMBRep.2015.48.9.017
Kuang L, Cao X, Lu Z (2017) Baicalein protects against rotenone-induced neurotoxicity through induction of autophagy. Biol Pharm Bull 40:1537–1543. https://doi.org/10.1248/bpb.b17-00392
Kumar M, Kasala ER, Bodduluru LN et al (2016) Baicalein protects isoproterenol induced myocardial ischemic injury in male Wistar rats by mitigating oxidative stress and inflammation. Inflamm Res 65:613–622. https://doi.org/10.1007/s00011-016-0944-z
Lebeau A, Esclaire F, Rostène W, Pélaprat D (2001) Baicalein protects cortical neurons from β-amyloid (25–35) induced toxicity. NeuroReport 12:2199–2202. https://doi.org/10.1097/00001756-200107200-00031
Lee HJ, Noh YH, Lee DY et al (2005) Baicalein attenuates 6-hydroxydopamine-induced neurotoxicity in SH-SY5Y cells. Eur J Cell Biol 84:897–905. https://doi.org/10.1016/j.ejcb.2005.07.003
Lee B, Sur B, Shim I et al (2014) Baicalin improves chronic corticosterone-induced learning and memory deficits via the enhancement of impaired hippocampal brain-derived neurotrophic factor and cAMP response element-binding protein expression in the rat. J Nat Med 68:132–143
Lee E, Park HR, Ji ST et al (2014) Baicalein attenuates astroglial activation in the 1-methyl-4-phenyl-1,2,3,4-tetrahydropyridine-induced Parkinson’s disease model by downregulating the activations of nuclear factor-κB, ERK, and JNK. J Neurosci Res 92:130–139. https://doi.org/10.1002/jnr.23307
Li HT, Wu XD, Davey AK, Wang J (2011) Antihyperglycemic effects of baicalin on streptozotocin - nicotinamide induced diabetic rats. Phytother Res 25:189–194. https://doi.org/10.1002/ptr.3238
Li L, Bao H, Wu J et al (2012) Baicalin is anti-inflammatory in cigarette smoke-induced inflammatory models in vivo and in vitro: a possible role for HDAC2 activity. Int Immunopharmacol 13:15–22. https://doi.org/10.1016/j.intimp.2012.03.001
Li XX, He GR, Mu X et al (2012) Protective effects of baicalein against rotenone-induced neurotoxicity in PC12 cells and isolated rat brain mitochondria. Eur J Pharmacol 674:227–233
Li YC, Wang LL, Pei YY et al (2015) Baicalin decreases SGK1 expression in the hippocampus and reverses depressive-like behaviors induced by corticosterone. Neuroscience 311:130–137. https://doi.org/10.1016/j.neuroscience.2015.10.023
Li X, Lee YJ, Kim HY et al (2016) Beneficial effects of Scutellaria baicalensis on penile erection in streptozotocin-induced diabetic rats. Am J Chin Med 44:305–320. https://doi.org/10.1142/S0192415X1650018X
Li M, Han Y, Wang H-L et al (2017) Inhibitory effects of Bupleurum chinense-Scutellaria baicalensis decoction on activation of rat HSC induced by CCl4. Chinese Pharmacol Bull 33:729–732. https://doi.org/10.3969/j.issn.1001-1978.2017.05.026
Li Y, Zhao J, Hölscher C (2017) Therapeutic potential of baicalein in Alzheimer’s disease and Parkinson’s disease. CNS Drugs 31:639–652
Li P, Wang X, Zhang J (2018) Baicalein administration protects against pentylenetetrazole-induced chronic epilepsy in rats. Trop J Pharm Res 17:293–298. https://doi.org/10.4314/tjpr.v17i2.14
Li Q, Li QQ, Jia JN et al (2019) Baicalein exerts neuroprotective effects in FeCl3-induced posttraumatic epileptic seizures via suppressing ferroptosis. Front Pharmacol 10:1–13. https://doi.org/10.3389/fphar.2019.00638
Li Q, Yu Z, Xiao D et al (2020) Baicalein inhibits mitochondrial apoptosis induced by oxidative stress in cardiomyocytes by stabilizing MARCH5 expression. J Cell Mol Med 24:2040–2051. https://doi.org/10.1111/jcmm.14903
Li J, Ling Y, Yin S, et al (2020a) Baicalin serves a protective role in diabetic nephropathy through preventing high glucose‑induced podocyte apoptosis. Exp Ther Med 367–374 https://doi.org/10.3892/etm.2020a.8701
Liao CC, Day YJ, Lee HC et al (2016) Baicalin attenuates il-17-mediated acetaminophen-induced liver injury in a mouse model. PLoS ONE 11:1–19. https://doi.org/10.1371/journal.pone.0166856
Liao ZJ, Liang RS, Shi SS et al (2016) Effect of baicalin on hippocampal damage in kainic acid-induced epileptic mice. Exp Ther Med 12:1405–1411. https://doi.org/10.3892/etm.2016.3461
Liao C-C, Day Y-J, Lee H-C et al (2017) ERK signaling pathway plays a Key role in baicalin protection against acetaminophen-induced liver injury. Am J Chin Med 45:105–121. https://doi.org/10.1142/S0192415X17500082
Lichterfeld M, Nischalke HD, Bergmann F et al (2002) Long-term efficacy and safety of ritonavir/indinavir at 400/400 mg twice a day in combination with two nucleoside reverse transcriptase inhibitors as first line antiretroviral therapy. HIV Med 3:37–43. https://doi.org/10.1046/j.1464-2662.2001.00091.x
Liguori I, Russo G, Curcio F et al (2018) Oxidative stress, aging, and diseases. Clin Interv Aging 13:757–772. https://doi.org/10.2147/CIA.S158513
Lin AMY, Ping YH, Chang GF et al (2011) Neuroprotective effect of oral S/B remedy (Scutellaria baicalensis Georgi and Bupleurum scorzonerifolfium Willd) on iron-induced neurodegeneration in the nigrostriatal dopaminergic system of rat brain. J Ethnopharmacol 134:884–891. https://doi.org/10.1016/j.jep.2011.01.056
Lin M, Li L, Zhang Y et al (2014) Baicalin ameliorates H2O2 induced cytotoxicity in HK-2 cells through the inhibition of ER stress and the activation of Nrf2 signaling. Int J Mol Sci 15:12507–12522. https://doi.org/10.3390/ijms150712507
Liu J-F, Peng H-L (2011) Effect of baicalin on serum glucose, cholesterol and activation of AMPK in streptozotocin-induced type 2 diabetic rats. Chinese J Pharmacol Toxicol 25:145–150. https://doi.org/10.3867/j.issn.1000-3002.2011.02.004
Liu J, Ma Y, Shi H et al (2006) Effect of baicalin on expression of heme oxygenase-1 in lung injury of rats associated with paraquat poisoning. Chinese J Ind Hyg Occup Dis 24:337–340
Liu W, Chen X, Liu J et al (2009) The effect of baicalein on bleomycin-induced fibrosis in lungs of rats. Zhongguo Ying Yong Sheng Li Xue Za Zhi 25:145–149
Liu JH, Wann H, Chen MM et al (2010) Baicalein significantly protects human retinal pigment epithelium cells against H2O2-induced oxidative stress by scavenging reactive oxygen species and downregulating the expression of matrix metalloproteinase-9 and vascular endothelial growth factor. J Ocul Pharmacol Ther 26:421–429. https://doi.org/10.1089/jop.2010.0063
Liu B, Jian Z, Li Q et al (2012) Baicalein protects human melanocytes from H2O 2-induced apoptosis via inhibiting mitochondria-dependent caspase activation and the p38 MAPK pathway. Free Radic Biol Med 53:183–193. https://doi.org/10.1016/j.freeradbiomed.2012.04.015
Liu X-Y, Zhang C-Y, Wang Y-Y, Che Q-M (2012) Protective effects of baicalein 6, 7-diacetate on CCl 4 or D-GalN induced hepatic injury in mice. Chinese J New Drugs 21:1517-1522+1527
Liu YF, Gao F, Li XW et al (2012) The anticonvulsant and neuroprotective effects of baicalin on pilocarpine-induced epileptic model in rats. Neurochem Res 37:1670–1680
Liu S, Lv X, Sun Z, Su R (2015) Hepatoprotective and antioxidant effects of baicalin against CCl4-induced hepatotoxicity. J Chinese Pharm Sci 24:538–544. https://doi.org/10.5246/jcps.2015.08.068
Liu T, Dai W, Li C et al (2015) Baicalin alleviates silica-induced lung inflammation and fibrosis by inhibiting the Th17 response in C57BL/6 mice. J Nat Prod 78:3049–3057
Liu Y-Y, Yeh P-H, Wang G-J, et al (2006b) Baicalein reverses the methamphetamine-induced striatal dopaminergic neurotoxicity in mice. J Food Drug Anal 14:
Li-Weber M (2009) New therapeutic aspects of flavones: the anticancer properties of Scutellaria and its main active constituents Wogonin. Baicalein and Baicalin Cancer Treat Rev 35:57–68
Lixuan Z, Jingcheng D, Wenqin Y et al (2010) Baicalin attenuates inflammation by inhibiting NF-κB activation in cigarette smoke induced inflammatory models. Pulm Pharmacol Ther 23:411–419. https://doi.org/10.1016/j.pupt.2010.05.004
Long Y, Xiang Y, Liu S et al (2020) Baicalin liposome alleviates lipopolysaccharide-induced acute lung injury in mice via inhibiting TLR4/JNK/ERK/NF-κB pathway. Mediators Inflamm 2020:8414062. https://doi.org/10.1155/2020/8414062
Lu Y, Wu X, Dong Y et al (2010) Anesthetic sevoflurane causes neurotoxicity differently in neonatal naïve and Alzheimer disease transgenic mice. Anesthesiology 112:1404–1416. https://doi.org/10.1097/ALN.0b013e3181d94de1
Lu W, Meng X, Jia G et al (2012) Baicalin normalizes blood glucose level in streptozotocin-induced diabetic rats. Lat Am J Pharm 31:214–219
Luo X, Yu Z, Deng C et al (2017) Baicalein ameliorates TNBS-induced colitis by suppressing TLR4/MyD88 signaling cascade and NLRP3 inflammasome activation in mice. Sci Rep 7:1–14. https://doi.org/10.1038/s41598-017-12562-6
Ma AT, Zhong XH, Liu ZM et al (2009) Protective effects of baicalin against bromocriptine induced abortion in mice. Am J Chin Med 37:85–95
Ma R-L, Wang W-P, Jiang X-G et al (2011) Effects of total flavonoids of Scutellaria baicalensis Georgi (TFSB) on bleomycin-induced pulmonary fibrosis in rats. Chinese Pharmacol Bull 27:537–542. https://doi.org/10.3969/j.issn.1001-1978.2011.04.023
Ma J, Li S, Zhu L et al (2018) Baicalein protects human vitiligo melanocytes from oxidative stress through activation of NF-E2-related factor2 (Nrf2) signaling pathway. Free Radic Biol Med 129:492–503. https://doi.org/10.1016/j.freeradbiomed.2018.10.421
Ma L, Li XP, Ji HS et al (2018) Baicalein protects rats with diabetic cardiomyopathy against oxidative stress and inflammation injury via phosphatidylinositol 3-kinase (Pl3K)/AKT pathway. Med Sci Monit 24:5368–5375. https://doi.org/10.12659/MSM.911455
Mehendale S, Aung H, Wang C-Z et al (2007) Scutellaria baicalensis and a constituent flavonoid, baicalein, attenuate ritonavir-induced gastrointestinal side-effects. J Pharm Pharmacol 59:1567–1572. https://doi.org/10.1211/jpp.59.11.0015
Mohammadzadeh N, Mehri S, Hosseinzadeh H (2017) Berberis vulgaris and its constituent berberine as antidotes and protective agents against natural or chemical toxicities. Iran J Basic Med Sci 20:538–551. https://doi.org/10.22038/ijbms.2017.8678
Moslehi M, Meshkini A, Yazdanparast R (2012) Flavonoid baicalein modulates H2O2-induced mitogen-activated protein kinases activation and cell death in SK-N-MC cells. Cell Mol Neurobiol 32:549–560. https://doi.org/10.1007/s10571-011-9795-x
Mu X, He G, Cheng Y et al (2009) Baicalein exerts neuroprotective effects in 6-hydroxydopamine-induced experimental parkinsonism in vivo and in vitro. Pharmacol Biochem Behav 92:642–648. https://doi.org/10.1016/j.pbb.2009.03.008
Mu X, He GR, Yuan X et al (2011) Baicalein protects the brain against neuron impairments induced by MPTP in C57BL/6 mice. Pharmacol Biochem Behav 98:286–291. https://doi.org/10.1016/j.pbb.2011.01.011
Nan J-X, Park E-J, Kim Y-C et al (2002) Scutellaria baicalensis inhibits liver fibrosis induced by bile duct ligation or carbon tetrachloride in rats. J Pharm Pharmacol 54:555–563. https://doi.org/10.1211/0022357021778673
Naveenkumar C, Asokkumar S, Raghunandhakumar S et al (2012) Potent antitumor and antineoplastic efficacy of baicalein on benzo(a)pyrene-induced experimental pulmonary tumorigenesis. Fundam Clin Pharmacol 26:259–270. https://doi.org/10.1111/j.1472-8206.2010.00910.x
Naveenkumar C, Raghunandakumar S, Asokkumar S et al (2014) Mitigating role of baicalein on lysosomal enzymes and xenobiotic metabolizing enzyme status during lung carcinogenesis of Swiss albino mice induced by benzo(a)pyrene. Fundam Clin Pharmacol 28:310–322. https://doi.org/10.1111/fcp.12036
Niu C, Wan J, Bian Y et al (2017) Baicalein and its underlying mechanism as a protector against liver injury induced by cisplatin in mice. Biotechnol Biotechnol Equip 31:193–199. https://doi.org/10.1080/13102818.2016.1257924
Pan Y, Chen D, Lu Q et al (2017) Baicalin prevents the apoptosis of endplate chondrocytes by inhibiting the oxidative stress induced by H2O2. Mol Med Rep 16:2985–2991. https://doi.org/10.3892/mmr.2017.6904
Pan Y, Song D, Zhou W, et al (2019) Baicalin inhibits C2C12 myoblast apoptosis and prevents against skeletal muscle injury. Mol Med Rephttps://doi.org/10.3892/mmr.2019.10298
Pang C, Jiang P, Ji L-L (2014) Baicalein induced Nrf2 activation and its protection against hepatotoxicity. Chinese Pharmacol Bull 30:546–549. https://doi.org/10.3969/j.issn.1001-1978.2014.04.023
Papanastasiou DA, Vayenas DV, Vassilopoulos A, Repanti M (2000) Concentration of iron and distribution of iron and transferrin after experimental iron overload in rat tissues in vivo: study of the liver, the spleen, the central nervous system and other organs. Pathol Res Pract 196:47–54. https://doi.org/10.1016/S0344-0338(00)80021-7
Park SW, Lee CH, Yeong SK et al (2008) Protective effect of baicalin against carbon tetrachloride-induced acute hepatic injury in mice. J Pharmacol Sci 106:136–143. https://doi.org/10.1254/jphs.FP0071392
Park C, Choi EO, Kim GY et al (2019) Protective effect of baicalein on oxidative stress-induced DNA damage and apoptosis in RT4-D6P2T Schwann cells. Int J Med Sci 16:8–16. https://doi.org/10.7150/ijms.29692
Peng XD, Dai LL, Huang CQ et al (2009) Correlation between anti-fibrotic effect of baicalin and serum cytokines in rat hepatic fibrosis. World J Gastroenterol 15:4720–4725. https://doi.org/10.3748/wjg.15.4720
Perez CA, Wei Y, Guo M (2009) Iron-binding and anti-Fenton properties of baicalein and baicalin. J Inorg Biochem 103:326–332
Psotová J, Chlopčíkova Š, Miketová P et al (2004) Chemoprotective effect of plant phenolics against anthracycline-induced toxicity on rat cardiomyocytes. Part III. Apigenin, baicalelin, kaempherol, luteolin and quercetin. Phytother Res 18:516–521. https://doi.org/10.1002/ptr.1462
Pu W, ling, Bai R yu, Zhou K, et al (2019) Baicalein attenuates pancreatic inflammatory injury through regulating MAPK, STAT 3 and NF-κB activation. Int Immunopharmacol 72:204–210. https://doi.org/10.1016/j.intimp.2019.04.018
Qiao H, Han H, Hong D et al (2011) Protective effects of baicalin on carbon tetrachloride induced liver injury by activating PPARγ and inhibiting TGFβ1. Pharm Biol 49:38–45. https://doi.org/10.3109/13880209.2010.493179
Qiu L, Chen J, Lin J et al (2017) Baicalin alleviates H2O2-induced injury of H9c2 cardiomyocytes through suppression of the Wnt/β-catenin signaling pathway. Mol Med Rep 16:9251–9255. https://doi.org/10.3892/mmr.2017.7748
Rashedinia M, Lari P, Abnous K, Hosseinzadeh H (2013) Proteomic analysis of rat cerebral cortex following subchronic acrolein toxicity. Toxicol Appl Pharmacol 272:199–207. https://doi.org/10.1016/j.taap.2013.05.029
Rezaee Khorasany A, Razavi M, Taghiabadi E et al (2020) Effect of crocin, an active saffron constituent, on ethanol toxicity in the rat: histopathological and biochemical studies. Iran J Basic Med Sci 23:51–62. https://doi.org/10.22038/ijbms.2019.37133.8845
Sahebkar A (2012) Baicalin as a potentially promising drug for the management of sulfur mustard induced cutaneous complications: a review of molecular mechanisms. Cutan Ocul Toxicol 31:226–234. https://doi.org/10.3109/15569527.2011.633950
Sahu BD, Kumar JM, Kuncha M et al (2016) Baicalein alleviates doxorubicin-induced cardiotoxicity via suppression of myocardial oxidative stress and apoptosis in mice. Life Sci 144:8–18
Sahu BD, Kumar JM, Sistla R (2015) Baicalein, a bioflavonoid, prevents cisplatin- Induced acute kidney injury by up-regulating antioxidant defenses and down-regulating the MAPKs and NF-κB Pathways. PLoS One 10
Sang WL, Geun SS, Chae HK, Yong KK (2005) Beneficial effect of flavonoid baicalein in cisplatin-induced cell death of human glioma cells. Neurosci Lett 382:71–75
Sarkar P, Nath K, Banu S (2019) Modulatory effect of baicalein on gene expression and activity of antioxidant enzymes in streptozotocin-nicotinamide induced diabetic rats. Brazilian J Pharm Sci 55https://doi.org/10.1590/s2175-97902019000118201
Sawicka E, Srednicka D, Dlugosz A (2010) Baicalin inhibits free radicals processes initiated by chromium ions. Acta Pol Pharm 67:706–709
Sawicka E, Długosz A, Rembacz KP, Guzik A (2013) The effects of coenzyme Q10 and baicalin in cisplatin-induced lipid peroxidation and nitrosative stress. Acta Pol Pharm - Drug Res 70:977–985
Shang YZ, Qin BW, Cheng JJ, Miao H (2006) Prevention of oxidative injury by flavonoids from stems and leaves of Scutellaria baicalensis Georgi in PC12 cells. Phytother Res 20:53–57. https://doi.org/10.1002/ptr.1802
Shang YZ, Qin BW, Cheng JJ, Miao H (2008) Effect of Scutellaria flavonoids on KCN-induced damages in rat pheochromocytoma PC12 cells. Indian J Med Res 127:610–615
Sherer TB, Betarbet R, Testa CM et al (2003) Mechanism of toxicity in rotenone models of Parkinson’s disease. J Neurosci 23:10756–10764. https://doi.org/10.1523/JNEUROSCI.23-34-10756.2003
Sherwani MA, Yang K, Jani A et al (2019) Protective effect of baicalin against TLR4-mediated UVA-induced skin inflammation. Photochem Photobiol 95:605–611. https://doi.org/10.1111/php.13021
Shi Q, Godschalk RWL, van Schooten FJ (2017) Inflammation and the chemical carcinogen benzo[a]pyrene: partners in crime. Mutat Res 774:12–24. https://doi.org/10.1016/j.mrrev.2017.08.003
Shi L, Hao Z, Zhang S, et al (2018) Baicalein and baicalin alleviate acetaminophen-induced liver injury by activating Nrf2 antioxidative pathway: the involvement of ERK1/2 and PKC. Biochem Pharmacolhttps://doi.org/10.1016/j.bcp.2018.01.026
Shieh DE, Liu LT, Lin CC (2000) Antioxidant and free radical scavenging effects of baicalein, baicalin and wogonin. Anticancer Res 20:2861–2865
Shimizu I (2000) Sho-saiko-to: Japanese herbal medicine for protection against hepatic fibrosis and carcinoma. J Gastroenterol Hepatol 15(Suppl):D84-90. https://doi.org/10.1046/j.1440-1746.2000.02138.x
Shimizu I, Ma YR, Mizobuchi Y et al (1999) Effects of Sho-saiko-to, a Japanese herbal medicine, on hepatic fibrosis in rats. Hepatology 29:149–160. https://doi.org/10.1002/hep.510290108
Siddarth M, Chawla D, Raizada A et al (2019) Ameliorating effect of baicalin in cadmium induced kidney fibrosis. Drug Metab Pharmacokinet 34:S18–S19. https://doi.org/10.1016/j.dmpk.2018.09.082
Singh J, Chaudhari BP, Kakkar P (2017) Baicalin and chrysin mixture imparts cyto-protection against methylglyoxal induced cytotoxicity and diabetic tubular injury by modulating RAGE, oxidative stress and inflammation. Environ Toxicol Pharmacol 50:67–75. https://doi.org/10.1016/j.etap.2017.01.013
Sohail A, Bhat WF, Bhat SA et al (2018) Investigating the preventive effects of baicalin and gallocatechin against glyoxal-induced cystatin aggregation. J Biomol Struct Dyn 36:3791–3802. https://doi.org/10.1080/07391102.2017.1400470
Song J, Zheng H, Seo HJ, Ji GE (2012) Effect of oral administration of Scutellaria baicalensis root extract on atopic dermatitis-like skin lesion induced by oxazolone in hairless mice. J Korean Soc Appl Biol Chem 55:175–181. https://doi.org/10.1007/s13765-012-1047-3
Song J-W, Long J-Y, Xie L et al (2020) Applications, phytochemistry, pharmacological effects, pharmacokinetics, toxicity of Scutellaria baicalensis Georgi and its probably potential therapeutic effects on COVID-19: a review. Chin Med 15:102. https://doi.org/10.1186/s13020-020-00384-0
Song JX, Choi MYM, Wong KCK, et al (2012b) Baicalein antagonizes rotenone-induced apoptosis in dopaminergic SH-SY5Y cells related to Parkinsonism. Chin. Med. 7
Sowndhararajan K, Deepa P, Kim M et al (2018) Neuroprotective and cognitive enhancement potentials of baicalin: a review. Brain Sci 8:104. https://doi.org/10.3390/brainsci8060104
Srinivas NR (2010) Baicalin, an emerging multi-therapeutic agent: pharmacodynamics, pharmacokinetics, and considerations from drug development perspectives. Xenobiotica 40:357–367. https://doi.org/10.3109/00498251003663724
Stein A, Voigt W, Jordan K (2010) Chemotherapy-induced diarrhea: pathophysiology, frequency and guideline-based management. Ther Adv Med Oncol 2:51–63. https://doi.org/10.1177/1758834009355164
Su G, Chen G, An X et al (2017) Metabolic profiling analysis of the alleviation effect of treatment with baicalin on cinnabar induced toxicity in rats urine and serum. Front Pharmacol 8:1–9. https://doi.org/10.3389/fphar.2017.00271
Sun H, Che QM, Zhao X, Pu XP (2010) Antifibrotic effects of chronic baicalein administration in a CCl4 liver fibrosis model in rats. Eur J Pharmacol 631:53–60. https://doi.org/10.1016/j.ejphar.2010.01.002
Sun YY, Zhang WJ, Dong CL et al (2017) Baicalin alleviates nitroglycerin-induced migraine in rats via the trigeminovascular system. Phytother Res 31:899–905. https://doi.org/10.1002/ptr.5811
Takasuna K, Kasai Y, Kitano Y et al (1995) Protective effects of kampo medicines and baicalin against intestinal toxicity of a new anticancer camptothecin derivative, irinotecan hydrochloride (CPT-11), in rats. Japanese J Cancer Res 86:978–984. https://doi.org/10.1111/j.1349-7006.1995.tb03010.x
Takeshima M, Murata M, Urasoe N et al (2011) Protective effects of baicalein against excess L-DOPA-induced dopamine quinone neurotoxicity. Neurol Res 33:1050–1056. https://doi.org/10.1179/1743132811Y.0000000032
Tanaka Y, Ito T, Tsuji G, Furue M (2020) Baicalein inhibits benzo[a]pyrene-induced toxic response by downregulating src phosphorylation and by upregulating nrf2-hmox1 system. Antioxidants 9:1–20. https://doi.org/10.3390/antiox9060507
Tang Y-J, Zhou F-W, Luo Z-Q et al (2010) Multiple therapeutic effects of adjunctive baicalin therapy in experimental bacterial meningitis. Inflammation 33:180–188. https://doi.org/10.1007/s10753-009-9172-9
Thompson LA, Darwish WS (2019) Environmental chemical contaminants in food: review of a global problem. J Toxicol 2019:2345283. https://doi.org/10.1155/2019/2345283
Tousian H, Razavi BM, Hosseinzadeh H (2020) Effects of alpha-mangostin on memory senescence induced by high glucose in human umbilical vein endothelial cells. Iran J Basic Med Sci 23:1261–1267. https://doi.org/10.22038/ijbms.2020.40651.9612
Tsai C-L, Tsai C-W, Chang W-S et al (2021) Protective effects of baicalin on arsenic trioxide-induced oxidative damage and apoptosis in human umbilical vein endothelial cells. In Vivo 35:155–162. https://doi.org/10.21873/invivo.12243
Tu L, Wu ZY, Yang XL et al (2019) Neuroprotective effect and mechanism of baicalin on Parkinson’s disease model induced by 6-OHDA. Neuropsychiatr Dis Treat 15:3615–3625. https://doi.org/10.2147/NDT.S165931
Ueng YF, Shyu CC, Liu TY et al (2001) Protective effects of baicalein and wogonin against benzo[a]pyrene- and aflatoxin B1-induced genotoxicities. Biochem Pharmacol 62:1653–1660
Waisundara VY, Hsu A, Huang D, Tan BKH (2008) Scutellaria baicalensis: enhances the anti-diabetic activity of metformin in streptozotocin-induced diabetic wistar rats. Am J Chin Med 36:517–540. https://doi.org/10.1142/S0192415X08005953
Waisundara VY, Hsu A, Tan BKH, Huang D (2009) Baicalin reduces mitochondrial damage in streptozotocin-induced diabetic Wistar rats. Diabetes Metab Res Rev 25:671–677
Waisundara VY, Hsu A, Tan BKH, Huang D (2009) Baicalin improves antioxidant status of streptozotocin-induced diabetic Wistar rats. J Agric Food Chem 57:4096–4102. https://doi.org/10.1021/jf8028539
Wang J (2019) Protective effects of baicalein against cadmium-induced oxidative stress in rat testes. Pak Vet J 39:216–220. https://doi.org/10.29261/pakvetj/2019.025
Wang S, Zhou Y (2018) Baicalein inhibits neuroapoptosis via pathways in sevoflurane induced rats. Transl Neurosci 9:88–98. https://doi.org/10.1515/tnsci-2018-0015
Wang SY, Wang HH, Chi CW et al (2004) Effects of baicalein on β-amyloid peptide-(25–35)-induced amnesia in mice. Eur J Pharmacol 506:55–61. https://doi.org/10.1016/j.ejphar.2004.10.029
Wang R, Shen X, Xing E et al (2013) Scutellaria baicalensis stem-leaf total flavonoid reduces neuronal apoptosis induced by amyloid beta-peptide (25–35). Neural Regen Res 8:1081–1090. https://doi.org/10.3969/j.issn.1673-5374.2013.12.003
Wang S, Zang W, Yang Y et al (2013) Tanshinone IIA and baicalin inhibiting the formation of benzo[a]pyrene and benzo[a]pyrene induced cytotoxicity: correlation with scavenging free radical. Environ Toxicol Pharmacol 36:403–410. https://doi.org/10.1016/j.etap.2013.05.003
Wang YH, Yu HT, Pu XP, Du GH (2013) Baicalein prevents 6-hydroxydopamine-induced mitochondrial dysfunction in SH-SY5Y cells via inhibition of mitochondrial oxidation and up-regulation of DJ-1 protein expression. Molecules 18:14726–14738. https://doi.org/10.3390/molecules181214726
Wang H, Zhang Y, Bai R et al (2016) Baicalin attenuates alcoholic liver injury through modulation of hepatic oxidative stress, inflammation and sonic hedgehog pathway in rats. Cell Physiol Biochem 39:1129–1140. https://doi.org/10.1159/000447820
Wang SF, Liu LF, Wu MY et al (2017) Baicalein prevents 6-OHDA/ascorbic acid-induced calcium-dependent dopaminergic neuronal cell death. Sci Rep 7:1–8. https://doi.org/10.1038/s41598-017-07142-7
Wang YF, Tang ZH, Li T et al (2017) Baicalein protects tert-butyl hydroperoxide-induced hepatotoxicity dependent of reactive oxygen species removal. Mol Med Rep 16:8392–8398. https://doi.org/10.3892/mmr.2017.7592
Wang X, Chang X, Zhan H, et al (2020) Curcumin and baicalin ameliorate ethanol-induced liver oxidative damage via the Nrf2/HO-1 pathway. J Food Biochem e13425. https://doi.org/10.1111/jfbc.13425
Wei D, Tang J, Bai W et al (2014) Ameliorative effects of baicalein on an amyloid-β induced Alzheimer’s disease rat model: a proteomics study. Curr Alzheimer Res 11:869–881
Wen YF, Zhao JQ, Bhadauria M, Nirala SK (2013) Baicalin prevents cadmium induced hepatic cytotoxicity, oxidative stress and histomorphometric alterations. Exp Toxicol Pathol 65:189–196
Wong YK, Chou MK, Shen YC et al (2014) Preventive effect of baicalein on methamphetamine-induced amnesia in the passive avoidance test in mice. Pharmacology 93:278–285. https://doi.org/10.1159/000365008
Wozniak D, Drys A, Matkowski A (2015) Antiradical and antioxidant activity of flavones from Scutellariae baicalensis radix. Nat Prod Res 29:1567–1570. https://doi.org/10.1080/14786419.2014.983920
Wu PH, Shen YC, Wang YH et al (2006) Baicalein attenuates methamphetamine-induced loss of dopamine transporter in mouse striatum. Toxicology 226:238–245. https://doi.org/10.1016/j.tox.2006.06.015
Wu J, Li H, Li M (2015) Effects of baicalin cream in two mouse models: 2,4-dinitrofluorobenzene-induced contact hypersensitivity and mouse tail test for psoriasis. Int J Clin Exp Med 8:2128–2137
Xiao W, Cao X-L, Zhang R et al (2017) Baicalin attenuates Aβ25-35 induced learning and memory disorders in mice and its possible mechanism. Chinese J Pharmacol Toxicol 31:59–64. https://doi.org/10.3867/j.issn.1000-3002.2017.01.007
Xie X, Shen Q, Ma L et al (2018) Chronic corticosterone-induced depression mediates premature aging in rats. J Affect Disord 229:254–261. https://doi.org/10.1016/j.jad.2017.12.073
Xiong P, Chen X, Guo C et al (2012) Baicalin and deferoxamine alleviate iron accumulation in different brain regions of Parkinson’s disease rats. Neural Regen Res 7:2092–2098. https://doi.org/10.3969/j.issn.1673-5374.2012.27.002
Xiong J, Wang C, Chen H et al (2014) Aβ-induced microglial cell activation is inhibited by baicalin through the JAK2/STAT3 signaling pathway. Int J Neurosci 124:609–620. https://doi.org/10.3109/00207454.2013.865027
Xu Y, Feng Y, Li H, Gao Z (2012) Ferric citrate CYP2E1-independently promotes alcohol-induced apoptosis in HepG2 cells via oxidative/nitrative stress which is attenuated by pretreatment with baicalin. Food Chem Toxicol 50:3264–3272. https://doi.org/10.1016/j.fct.2012.05.061
Xue D, Zhang W, Zhang Y et al (2006) Adjusting effects of baicalin for nuclear factor-κB and tumor necrosis factor-α on rats with caerulein-induced acute pancreatitis. Mediators Inflamm 2006:1–6. https://doi.org/10.1155/MI/2006/26295
Yang WK, Kim SH, Jung IC, Park YC (2019) Effects of Scutellaria baicalensis extract on cigarette smoke-induced airway inflammation in a murine model of chronic obstructive pulmonary disease. J Med Food 22:87–96. https://doi.org/10.1089/jmf.2018.4200
Yang J, Xiang D, Xiang D et al (2020) Baicalin protects against 17α-ethinylestradiol-induced cholestasis via the sirtuin 1/hepatic nuclear receptor-1α/farnesoid X receptor pathway. Front Pharmacol 10:1–15. https://doi.org/10.3389/fphar.2019.01685
Yang H, Lu Y, Zeng XF, et al (2018) Antichronic gastric ulcer effect of zinc-baicalin complex on the acetic acid-induced chronic gastric ulcer rat model. Gastroenterol Res Pract 2018https://doi.org/10.1155/2018/1275486
Yao J, Cao X, Zhang R et al (2016) Protective effect of baicalin against experimental colitis via suppression of oxidant stress and apoptosis. Pharmacogn Mag 12:225–234. https://doi.org/10.4103/0973-1296.186342
Yao J, Liu T, Chen RJ et al (2020) Sphingosine-1-phosphate signal transducer and activator of transcription 3 signaling pathway contributes to baicalein-mediated inhibition of dextran sulfate sodium-induced experimental colitis in mice. Chin Med J (engl) 133:292–300. https://doi.org/10.1097/CM9.0000000000000627
Yeh CH, Ma KH, Liu PS et al (2015) Baicalein decreases hydrogen peroxide-induced damage to NG108-15 cells via upregulation of Nrf2. J Cell Physiol 230:1840–1851. https://doi.org/10.1002/jcp.24900
Yin F, Liu J, Ji X et al (2011) Baicalin prevents the production of hydrogen peroxide and oxidative stress induced by Aβ aggregation in SH-SY5Y cells. Neurosci Lett 492:76–79. https://doi.org/10.1016/j.neulet.2011.01.055
Yoon JJ, Jeong JW, Choi EO et al (2017) Protective effects of Scutellaria baicalensis Georgi against hydrogen peroxide-induced DNA damage and apoptosis in HaCaT human skin keratinocytes. EXCLI J 16:426–438. https://doi.org/10.17179/excli2016-817
Yu Z, Li Q, Wang Y, Li P (2020) A potent protective effect of baicalein on liver injury by regulating mitochondria-related apoptosis. Apoptosis 25:412–425. https://doi.org/10.1007/s10495-020-01608-2
Yun J, Jung YS (2014) A Scutellaria baicalensis radix water extract inhibits morphine-induced conditioned place preference. Pharm Biol 52:1382–1387. https://doi.org/10.3109/13880209.2014.892514
Zhai H, Kang Z, Zhang H et al (2019) Baicalin attenuated substantia nigra neuronal apoptosis in Parkinson’s disease rats via the mTOR/AKT/GSK-3β pathway. J Integr Neurosci 18:423–429. https://doi.org/10.31083/j.jin.2019.04.192
Zhang X, Yu J (2019) Baicalin attenuates gentamicin-induced cochlear hair cell ototoxicity. J Appl Toxicol 39:1208–1214. https://doi.org/10.1002/jat.3806
Zhang Y, Li H, Zhao Y, Gao Z (2006) Dietary supplementation of baicalin and quercetin attenuates iron overload induced mouse liver injury. Eur J Pharmacol 535:263–269. https://doi.org/10.1016/j.ejphar.2006.01.067
Zhang S, Ye J, Dong G (2010) Neuroprotective effect of baicalein on hydrogen peroxide-mediated oxidative stress and mitochondrial dysfunction in PC12 cells. J Mol Neurosci 40:311–320. https://doi.org/10.1007/s12031-009-9285-5
Zhang XW, Li WF, Li WW et al (2011) Protective effects of the aqueous extract of Scutellaria baicalensis against acrolein-induced oxidative stress in cultured human umbilical vein endothelial cells. Pharm Biol 49:256–261. https://doi.org/10.3109/13880209.2010.501803
Zhang Y, Gao Z, Liu J, Xu Z (2011) Protective effects of baicalin and quercetin on an iron-overloaded mouse: comparison of liver, kidney and heart tissues. Nat Prod Res 25:1150–1160
Zhang Y, Huang Y, Deng X et al (2012) Iron overload-induced rat liver injury: involvement of protein tyrosine nitration and the effect of baicalin. Eur J Pharmacol 680:95–101
Zhang Z, Cui W, Li G et al (2012) Baicalein protects against 6-OHDA-induced neurotoxicity through activation of Keap1/Nrf2/HO-1 and involving PKCα and PI3K/AKT signaling pathways. J Agric Food Chem 60:8171–8182. https://doi.org/10.1021/jf301511m
Zhang J, Li P, Wang Y et al (2013) Ameliorative effects of a combination of baicalin, jasminoidin and cholic acid on ibotenic acid-induced dementia model in rats. PLoS ONE 8:e56658. https://doi.org/10.1371/journal.pone.0056658
Zhang CL, Zhang S, He WX et al (2017) Baicalin may alleviate inflammatory infiltration in dextran sodium sulfate-induced chronic ulcerative colitis via inhibiting IL-33 expression. Life Sci 186:125–132. https://doi.org/10.1016/j.lfs.2017.08.010
Zhang X, Yang Y, Du L et al (2017) International immunopharmacology baicalein exerts anti-neuroinflammatory effects to protect against rotenone-induced brain injury in rats. Int Immunopharmacol 50:38–47. https://doi.org/10.1016/j.intimp.2017.06.007
Zhang XF, Zhang WJ, Dong CI et al (2017) Analgesia effect of baicalein against NTG-induced migraine in rats. Biomed Pharmacother 90:116–121. https://doi.org/10.1016/j.biopha.2017.03.052
Zhang Z, Gao X, Guo M et al (2017) The protective effect of baicalin against lead-induced renal oxidative damage in mice. Biol Trace Elem Res 175:129–135. https://doi.org/10.1007/s12011-016-0731-2
Zhang B, Sun W, Yu N et al (2018) Anti-diabetic effect of baicalein is associated with the modulation of gut microbiota in streptozotocin and high-fat-diet induced diabetic rats. J Funct Foods 46:256–267. https://doi.org/10.1016/j.jff.2018.04.070
Zhang K, He M, Wang F et al (2019) Revealing antidepressant mechanisms of baicalin in hypothalamus through systems approaches in corticosterone-induced depressed mice. Front Neurosci 13:1–10. https://doi.org/10.3389/fnins.2019.00834
Zhang J, Deng Y, Cheng B et al (2020) Protective effects and molecular mechanisms of baicalein on thioacetamide-induced toxicity in zebrafish larvae. Chemosphere 256:127038. https://doi.org/10.1016/j.chemosphere.2020.127038
Zhang Z, Zhong M, Wang J et al (2020) Synthesis of baicalein modified cerium oxide nanoparticles for inhibitory activation of NF-κB and mitogen-activated protein kinase signals in rotenone-induced Parkinsonian rats. Sci Adv Mater 12:93–100. https://doi.org/10.1166/sam.2020.3594
Zhang X, Du L, Zhang W, et al (2017b) Therapeutic effects of baicalein on rotenone-induced Parkinson’s disease through protecting mitochondrial function and biogenesis. Sci. Rep. 7
Zhang S, Xu L, Liang R, et al (2020b) Baicalin suppresses renal fibrosis through microRNA-124/TLR4/NF-κB axis in streptozotocin-induced diabetic nephropathy mice and high glucose-treated human proximal tubule epithelial cells. J Physiol Biochemhttps://doi.org/10.1007/s13105-020-00747-z
Zhao Y, Li H, Gao Z, Xu H (2005) Effects of dietary baicalin supplementation on iron overload-induced mouse liver oxidative injury. Eur J Pharmacol 509:195–200. https://doi.org/10.1016/j.ejphar.2004.11.060
Zhao Y, Li H, Gao Z et al (2006) Effects of flavonoids extracted from Scutellaria baicalensis Georgi on hemin-nitrite-H2O2 induced liver injury. Eur J Pharmacol 536:192–199. https://doi.org/10.1016/j.ejphar.2006.02.045
Zhao WZ, Wang HT, Huang HJ et al (2018) Neuroprotective effects of baicalein on acrolein-induced neurotoxicity in the nigrostriatal dopaminergic system of rat brain. Mol Neurobiol 55:130–137. https://doi.org/10.1007/s12035-017-0725-x
Zhao H, Li C, Li L et al (2020) Baicalin alleviates bleomycin-induced pulmonary fibrosis and fibroblast proliferation in rats via the PI3K/AKT signaling pathway. Mol Med Rep 21:2321–2334. https://doi.org/10.3892/mmr.2020.11046
Zhao Y, Wang H-L, Li T-T et al (2020b) Baicalin ameliorates dexamethasone-induced osteoporosis by regulation of the RANK/RANKL/OPG signaling pathway. Drug Des Devel Ther 14:195–206. https://doi.org/10.2147/DDDT.S225516
Zheng WX, Wang F, Cao XL et al (2014) Baicalin protects PC-12 cells from oxidative stress induced by hydrogen peroxide via anti-apoptotic effects. Brain Inj 28:227–234. https://doi.org/10.3109/02699052.2013.860469
Zheng XP, Nie Q, Feng J et al (2020) Kidney-targeted baicalin-lysozyme conjugate ameliorates renal fibrosis in rats with diabetic nephropathy induced by streptozotocin. BMC Nephrol 21:1–17. https://doi.org/10.1186/s12882-020-01833-6
Zhong X, Surh Y-J, Do S-G et al (2019) Baicalein inhibits dextran sulfate sodium-induced mouse colitis. J Cancer Prev 24:129–138. https://doi.org/10.15430/jcp.2019.24.2.129
Zhou L, Tan S, Shan YL et al (2016) Baicalein improves behavioral dysfunction induced by Alzheimer’s disease in rats. Neuropsychiatr Dis Treat 12:3145–3152. https://doi.org/10.2147/NDT.S117469
Zhou HC, Wang H, Shi K, et al (2019) Hepatoprotective effect of baicalein against acetaminophen-induced acute liver injury in mice. Molecules 24https://doi.org/10.3390/molecules24010131
Zhu L, Shen H, Gu P, et al (2020) Baicalin alleviates TNBS‑induced colitis by inhibiting PI3K/AKT pathway activation. Exp Ther Med 581–590https://doi.org/10.3892/etm.2020.8718
Zou Y, Dai S-X, Chi H-G, et al (2014) Baicalin attenuates TNBS-induced colitis in rats by modulating the Th17/Treg paradigm. Arch Pharm Res 38https://doi.org/10.1007/s12272-014-0486-2
Zuo D, Lin L, Liu Y et al (2016) Baicalin attenuates ketamine-induced neurotoxicity in the developing rats: involvement of PI3K/Akt and CREB/BDNF/Bcl-2 pathways. Neurotox Res 30:159–172. https://doi.org/10.1007/s12640-016-9611-y
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Ahmadi, A., Mortazavi, Z., Mehri, S. et al. Scutellaria baicalensis and its constituents baicalin and baicalein as antidotes or protective agents against chemical toxicities: a comprehensive review. Naunyn-Schmiedeberg's Arch Pharmacol 395, 1297–1329 (2022). https://doi.org/10.1007/s00210-022-02258-8
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DOI: https://doi.org/10.1007/s00210-022-02258-8