Protective and therapeutic effects of Scutellaria baicalensis and its main active ingredients baicalin and baicalein against natural toxicities and physical hazards: a review of mechanisms
Tóm tắt
Scutellaria baicalensis (SB) has been traditionally used to combat a variety of conditions ranging from ischemic heart disease to cancer. The protective effects of SB are due to the action of two main flavonoids baicalin (BA) and baicalein (BE). This paper aimed to provide a narrative review of the protective and antidotal effects of SB and its main constituents against natural toxicities and physical hazards. Scientific databases Medline, Scopus, and Web of Science were thoroughly searched, based on different keywords for in vivo, in vitro and clinical studies which reported protective or therapeutic effects of SB or its constituents in natural and physical toxicities. Numerous studies have reported that treatment with BE, BA, or total SB extract prevents or counteracts the detrimental toxic effects of various natural compounds and physical hazards. The toxic agents include mycotoxins, lipopolysaccharide, multiple plants and animal-derived substances as well as physical factors which negatively affected vital organs such as CNS, liver, kidneys, lung and heart. Increasing the expression of radical scavenging enzymes and glutathione content as well as inhibition of pro-inflammatory cytokines and pro-apoptotic mediators were important mechanisms of action. Different studies on the Chinese skullcap have exhibited that its total root extract, BA or BE can act as potential antidotes or protective agents against the damage induced by natural toxins and physical factors by alleviating oxidative stress and inflammation. However, the scarcity of high-quality clinical evidence means that further clinical studies are required to reach a more definitive conclusion.
Tài liệu tham khảo
Srinivas NR. Baicalin, an emerging multi-therapeutic agent: Pharmacodynamics, pharmacokinetics, and considerations from drug development perspectives. Xenobiotica. 2010;40:357–67.
Lu L, Guo Q, Zhao L. Overview of Oroxylin A: A Promising Flavonoid Compound. Phytother Res. 2016;30:1765–74.
Sharifi-Rad J, Herrera-Bravo J, Salazar LA, Shaheen S, Abdulmajid Ayatollahi S, Kobarfard F, et al. The Therapeutic Potential of Wogonin Observed in Preclinical Studies. Tan S, editor. Evidence-Based Complement Altern Med. 2021;2021:1–9.
Wozniak D, Drys A, Matkowski A. Antiradical and antioxidant activity of flavones from Scutellariae baicalensis radix. Nat Prod Res. 2015;29:1567–70.
Shieh DE, Liu LT, Lin CC. Antioxidant and free radical scavenging effects of baicalein, baicalin and wogonin. Anticancer Res Greece. 2000;20:2861–5.
Huang Y, Tsang SY, Yao X, Chen ZY. Biological properties of baicalein in cardiovascular system. Curr Drug Targets - Cardiovasc Haematol Disord. 2005;5:177–84.
Sowndhararajan K, Deepa P, Kim M, Park SJ, Kim S. Baicalein as a potent neuroprotective agent: A review. Biomed. Pharmacother. 2017;95:1021–32.
Sowndhararajan K, Deepa P, Kim M, Park SJ, Kim S. Neuroprotective and Cognitive Enhancement Potentials of Baicalin: A Review. Brain Sci. 2018;8:104.
Li Y, Zhao J, Hölscher C. Therapeutic Potential of Baicalein in Alzheimer’s Disease and Parkinson’s Disease. CNS Drugs. 2017;31:639–52.
Liang W, Huang X, Chen W. The effects of Baicalin and Baicalein on cerebral ischemia: A review. Aging Dis. 2017;8:850–67.
Liu H, Dong Y, Gao Y, Du Z, Wang Y, Cheng P, et al. The fascinating effects of baicalein on cancer: A review. Int J Mol. Sci. 2016;17:1681.
Donald G, Hertzer K, Eibl G. Baicalein - An Intriguing Therapeutic Phytochemical in Pancreatic Cancer. Curr Drug Targets. 2012;13:1772–6.
Li-Weber M. New therapeutic aspects of flavones: The anticancer properties of Scutellaria and its main active constituents Wogonin, Baicalein and Baicalin. Cancer Treat. Rev. 2009;35:57–68.
Chen H, Gao Y, Wu J, Chen Y, Chen B, Hu J, et al. Exploring therapeutic potentials of baicalin and its aglycone baicalein for hematological malignancies. Cancer Lett. 2014;354:5–11.
Zhang XP, Zhang L, He JX, Zhang RP, Cheng QH, Zhou YF, et al. Experimental study of therapeutic efficacy of Baicalin in rats with severe acute pancreatitis. World J Gastroenterol. 2007;13:717–24.
Dinda B, Dinda S, DasSharma S, Banik R, Chakraborty A, Dinda M. Therapeutic potentials of baicalin and its aglycone, baicalein against inflammatory disorders. Eur J Med Chem. 2017;131:68–80.
Liu J, Wei Y, Luo Q, Xu F, Zhao Z, Zhang H, et al. Baicalin attenuates inflammation in mice with OVA-induced asthma by inhibiting NF-kappaB and suppressing CCR7/CCL19/CCL21. Int J Mol Med Greece. 2016;38:1541–8.
Kimura Y, Matsushita N, Yokoi-Hayashi K, Okuda H. Effects of baicalein isolated from Scutellaria baicalensis Radix on adhesion molecule expression induced by thrombin and thrombin receptor agonist peptide in cultured human umbilical vein endothelial cells. Planta Med. 2001;67:331–4.
Alsharairi NA. Scutellaria baicalensis and Their Natural Flavone Compounds as Potential Medicinal Drugs for the Treatment of Nicotine-Induced Non-Small-Cell Lung Cancer and Asthma. Int J Environ Res Public Health. 2021;18:5243.
Xiao J-R, Do C-W, To C-H. Potential Therapeutic Effects of Baicalein, Baicalin, and Wogonin in Ocular Disorders. J Ocul Pharmacol Ther. 2014;30:605–14.
Baradaran Rahimi V, Askari VR, Hosseinzadeh H. Promising influences of Scutellaria baicalensis and its two active constituents, baicalin, and baicalein, against metabolic syndrome: A review. Phytother Res. 2021;35:3558–74.
Tang Y-J, Zhou F-W, Luo Z-Q, Li X-Z, Yan H-M, Wang M-J, et al. Multiple Therapeutic Effects of Adjunctive Baicalin Therapy in Experimental Bacterial Meningitis. Inflammation. 2010;33:180–8.
Zhou R, Han X, Wang J, Sun J. Baicalin may have a therapeutic effect in attention deficit hyperactivity disorder. Med. Hypotheses. 2015;85:761–4.
Fang P, Yu M, Zhang L, Wan D, Shi M, Zhu Y, et al. Baicalin against obesity and insulin resistance through activation of AKT/AS160/GLUT4 pathway. Mol Cell Endocrinol. 2017;448:77–86.
Fang P, Sun Y, Gu X, Shi M, Bo P, Zhang Z, et al. Baicalin ameliorates hepatic insulin resistance and gluconeogenic activity through inhibition of p38 MAPK/PGC-1α pathway. Phytomedicine. 2019;64: 153074.
Yu M, Han S, Wang M, Han L, Huang Y, Bo P, et al. Baicalin protects against insulin resistance and metabolic dysfunction through activation of GALR2/GLUT4 signaling. Phytomedicine. 2022;95: 153869.
Liao P, Li Y, Li M, Chen X, Yuan D, Tang M, et al. Baicalin alleviates deoxynivalenol-induced intestinal inflammation and oxidative stress damage by inhibiting NF-κB and increasing mTOR signaling pathways in piglets. Food Chem Toxicol. 2020;140: 111326.
Xue D, Zhang W, Zhang Y, Wang H, Zheng B, Shi X. Adjusting Effects of Baicalin for Nuclear Factor-κB and Tumor Necrosis Factor-α on Rats With Caerulein-Induced Acute Pancreatitis. Mediators Inflamm. 2006;2006:1–6.
Sherwani MA, Yang K, Jani A, Abed RA, Taufique AK, Dosunmu TG, et al. Protective Effect of Baicalin Against TLR4-mediated UVA-induced Skin Inflammation. Photochem Photobiol. 2019;95:605–11.
Sui J, Feng Y, Li H, Cao R, Tian W, Jiang Z. Baicalin protects mouse testis from injury induced by heat stress. J Therm Biol. 2019;82:63–9.
Tavakkoli A, Ahmadi A, Razavi BM, Hosseinzadeh H. Black seed (Nigella sativa) and its constituent thymoquinone as an antidote or a protective agent against natural or chemical toxicities. Iran J Pharm Res. 2017;16:2–23.
Alavi MS, Fanoudi S, Ghasemzadeh Rahbardar M, Mehri S, Hosseinzadeh H. An updated review of protective effects of rosemary and its active constituents against natural and chemical toxicities. Phytother Res. 2021;35:1313–28.
Hosseini A, Hosseinzadeh H. Antidotal or protective effects of Curcuma longa (turmeric) and its active ingredient, curcumin, against natural and chemical toxicities: A review. Biomed Pharmacother. 2018;99:411–21.
Fouad AEA, Fouad AA, Al-Melhim WN. Protective effect of baicalin in rats exposed to arsenic-induced testicular toxicity. Indian J Forensic Med Toxicol. 2018;12:256–61.
Li XX, He GR, Mu X, Xu B, Tian S, Yu X, et al. Protective effects of baicalein against rotenone-induced neurotoxicity in PC12 cells and isolated rat brain mitochondria. Eur J Pharmacol. 2012;674:227–33.
Liu W, Chen X, Liu J, Chen C, Ai J. The effect of baicalein on bleomycin-induced fibrosis in lungs of rats. Chinese J Appl Physiol China. 2009;25:145–9.
Ueng YF, Shyu CC, Liu TY, Oda Y, Lin YL, Liao JF, et al. Protective effects of baicalein and wogonin against benzo[a]pyrene- and aflatoxin B1-induced genotoxicities. Biochem Pharmacol. 2001;62:1653–60.
De Boer JG, Quiney B, Walter PB, Thomas C, Hodgson K, Murch SJ, et al. Protection against aflatoxin-B 1 -induced liver mutagenesis by Scutellaria baicalensis. Mutat Res- Fundam Mol Mech Mutagen. 2005;578:15–22.
Kim BR, Kim DH, Park R, Kwon KB, Ryu DG, Kim YC, et al. Effect of an extract of the root of Scutellaria baicalensis and its flavonoids on aflatoxin B1 oxidizing cytochrome P450 enzymes. Planta Med. 2001;67:396–9.
Qiu J, Niu X, Dong J, Wang D, Wang J, Li H, et al. Baicalin protects mice from staphylococcus aureus pneumonia via inhibition of the cytolytic activity of-hemolysin. J Infect Dis. 2012;206:292–301.
Liu S, Liu B, Luo Z-Q, Qiu J, Zhou X, Li G, et al. The combination of osthole with baicalin protects mice from Staphylococcus aureus pneumonia. World J Microbiol Biotechnol. 2017;33:11.
Jia F, Ma W, Zhang X, Wang D, Zhou X. Matrine and baicalin inhibit apoptosis induced by Panton-Valentine leukocidin of Staphylococcus aureus in bovine mammary epithelial cells. J Dairy Sci. 2020;103:2731–42.
Dong J, Zhang Y, Chen Y, Niu X, Zhang Y, Yang C, et al. Baicalin inhibits the lethality of Shiga-like toxin 2 in mice. Antimicrob. Agents Chemother. 2015;59:7054–60.
Zhang Y, Qi Z, Liu Y, He W, Yang C, Wang Q, et al. Baicalin Protects Mice from Lethal Infection by Enterohemorrhagic Escherichia coli. Front Microbiol. 2017;8:395.
Vinh, Shinohara, Yamada, Duc, Nakayama, Ozawa, et al. Baicalein Inhibits Stx1 and 2 of EHE: Effects of Baicalein on the Cytotoxicity, Production, and Secretion of Shiga Toxins of Enterohaemorrhagic Escherichia coli. Toxins (Basel). 2019;11:505.
Dong J, Zhang Y, Chen Y, Niu X, Zhang Y, Li R, et al. Baicalin inhibits the lethality of ricin in mice by inducing protein oligomerization. J Biol Chem. 2015;290:12899–907.
Wang K, Feng C, Li C, Yao J, Xie X, Gong L, et al. Baicalin protects mice from aristolochic acid I-Induced kidney injury by induction of CYP1A through the aromatic hydrocarbon receptor. Int J Mol Sci. 2015;16:16454–68.
Liu LL, Gong LK, Wang H, Xiao Y, Wu XF, Zhang YH, et al. Baicalin protects mouse from Concanavalin A-induced liver injury through inhibition of cytokine production and hepatocyte apoptosis. Liver Int. 2007;27:582–91.
Zhang Y, Shan L, Hua Y, Wang D, Zeng H, Liu R, et al. Baicalein Selectively Induces Apoptosis in Activated Lymphocytes and Ameliorates Concanavalin A-Induced Hepatitis in Mice. PLoS One. 2013;8:e69592.
Im AR, Kim YH, Uddin MR, Lee HW, Chae SW, Kim YH, et al. Scutellaria baicalensis extracts and flavonoids protect rat l6 cells from antimycin a-induced mitochondrial dysfunction. Evidence-based Complement Altern Med. 2012;2012:517965.
Huan SK-H, Wang K-T, Yeh S-D, Lee C-J, Lin L-C, Liu D-Z, et al. Scutellaria baicalensis Alleviates Cantharidin-Induced Rat Hemorrhagic Cystitis through Inhibition of Cyclooxygenase-2 Overexpression. Molecules. 2012;17:6277–89.
Zhang SF, Dong YC, Zhang XF, Wu XG, Cheng JJ, Guan LH, et al. Flavonoids from Scutellaria attenuate okadaic acid-induced neuronal damage in rats. Brain Inj. 2015;29:1376–82.
Li D, Shi G, Wang J, Zhang D, Pan Y, Dou H, et al. Baicalein ameliorates pristane-induced lupus nephritis via activating Nrf2/HO-1 in myeloid-derived suppressor cells. Arthritis Res Ther. 2019;21:1–14.
Zhang J, Sheng Y, Shi L, Zheng Z, Chen M, Lu B, et al. Quercetin and baicalein suppress monocrotaline-induced hepatic sinusoidal obstruction syndrome in rats. Eur J Pharmacol Netherlands. 2017;795:160–8.
Schultze AE, Roth RA. Chronic pulmonary hypertension-the monocrotaline model and involvement of the hemostatic system. J Toxicol Environ Heal Part B. 1998;1:271–346.
Hsu WL, Lin YC, Jeng JR, Chang HY, Chou TC. Baicalein Ameliorates Pulmonary Arterial Hypertension Caused by Monocrotaline through Downregulation of ET-1 and ET AR in Pneumonectomized Rats. Am J Chin Med. 2018;46:769–83.
Shi R, Zhu D, Wei Z, Fu N, Wang C, Liu L, et al. Baicalein attenuates monocrotaline-induced pulmonary arterial hypertension by inhibiting endothelial-to-mesenchymal transition. Life Sci. 2018;207:442–50.
Shi R, Wei Z, Zhu D, Fu N, Wang C, Yin S, et al. Baicalein attenuates monocrotaline-induced pulmonary arterial hypertension by inhibiting vascular remodeling in rats. Pulm Pharmacol Ther England. 2018;48:124–35.
Zhang Z, Zhang L, Sun C, Kong F, Wang J, Xin Q, et al. Baicalin attenuates monocrotaline-induced pulmonary hypertension through bone morphogenetic protein signaling pathway. Oncotarget. 2017;8:63430–41.
Yan G, Wang J, Yi T, Cheng J, Guo H, He Y, et al. Baicalin prevents pulmonary arterial remodeling in vivo via the AKT/ERK/NF-kappaB signaling pathways. Pulm Circ. United States; 2019;9:2045894019878599.
Luan Y, Chao S, Ju ZY, Wang J, Xue X, Qi TG, et al. Therapeutic effects of baicalin on monocrotaline-induced pulmonary arterial hypertension by inhibiting inflammatory response. Int. Immunopharmacol. 2015;26:188–93.
Gal Y, Mazor O, Falach R, Sapoznikov A, Kronman C, Sabo T. Treatments for pulmonary ricin intoxication: Current aspects and future prospects. Toxins (Basel). 2017;9:311.
Liu J, Zhu X, Kim SJ, Zhang W. Antimycin-type depsipeptides: discovery, biosynthesis, chemical synthesis, and bioactivities. Nat Prod Rep. 2016;33:1146–65.
Xiao GL, Zhang CH, Liu GD, Liu FY, Liu ZY, Hu SY, et al. Clinical study of the effects of baicalin on arrhythmia induced by aconitine poisoning. J Med Plants Res. 2011;5:88–92.
Xue X, Zhang S, Jiang W, Wang J, Xin Q, Sun C, et al. Protective effect of baicalin against pulmonary arterial hypertension vascular remodeling through regulation of TNF-α signaling pathway. Pharmacol Res Perspect. 2021;9: e00703.
Tsai C, Lin Y, Wang H, Chou T. Baicalein, an active component of Scutellaria baicalensis, protects against lipopolysaccharide-induced acute lung injury in rats. J Ethnopharmacol. 2014;153:197–206.
Deng J, Wang DX, Liang AL, Tang J, Xiang DK. Effects of baicalin on alveolar fluid clearance and α-ENaC expression in rats with LPS-induced acute lung injury. Can J Physiol Pharmacol. 2017;95:122–8.
Long Y, Xiang Y, Liu S, Zhang Y, Wan J, Yang Q, et al. Baicalin Liposome Alleviates Lipopolysaccharide-Induced Acute Lung Injury in Mice via Inhibiting TLR4/JNK/ERK/NF-κB Pathway. Mediators Inflamm. 2020;2020:8414062.
Chen H, Zhang Y, Zhang W, Liu H, Sun C, Zhang B, et al. Inhibition of myeloid differentiation factor 2 by baicalein protects against acute lung injury. Phytomedicine. 2019;63:152997.
Ding XM, Pan L, Wang Y, Xu QZ. Baicalin exerts protective effects against lipopolysaccharide-induced acute lung injury by regulating the crosstalk between the CX3CL1-CX3CR1 axis and NF-B pathway in CX3CL1-knockout mice. Int J Mol Med. 2016;37:703–15.
Meng X, Hu L, Li W. Baicalin ameliorates lipopolysaccharide-induced acute lung injury in mice by suppressing oxidative stress and inflammation via the activation of the Nrf2-mediated HO-1 signaling pathway. Naunyn Schmiedebergs Arch Pharmacol. 2019;392:1421–33.
Huang KL, Chen CS, Hsu CW, Li MH, Chang H, Tsai SH, et al. Therapeutice effects of baicalin on lipopolysaccharide-induced acute lung injury in rats. Am J Chin Med. 2008;36:301–11.
Dong S, Zhong Y, Lu W, Li G, Jiang H, Mao B. Baicalin Inhibits Lipopolysaccharide-Induced Inflammation Through Signaling NF-kappaB Pathway in HBE16 Airway Epithelial Cells. Inflammation. 2015;38:1493–501.
Feng T, Zhou L, Gai S, Zhai Y, Gou N, Wang X, et al. Acacia catechu (L.f.) Willd and Scutellaria baicalensis Georgi extracts suppress LPS‐induced pro‐inflammatory responses through NF‐кB, MAPK, and PI3K‐Akt signaling pathways in alveolar epithelial type II cells. Phytother Res. 2019;33:3251–60.
Chen JJ, Huang CC, Chang HY, Li PY, Liang YC, Deng JS, et al. Scutellaria baicalensis Ameliorates Acute Lung Injury by Suppressing Inflammation in Vitro and in Vivo. Am J Chin Med. 2017;45:137–57.
Chen HM, Liou SF, Hsu JH, Chen TJ, Cheng TL, Chiu CC, et al. Baicalein inhibits HMGB1 release and MMP-2/-9 expression in lipopolysaccharide-induced cardiac hypertrophy. Am J Chin Med. 2014;42:785–97.
Li MF, Hu XY, Chen LW, Lian J, Zhao GJ, Hong GL, et al. Baicalin regulates STIM1-mediated calcium overload and reduces apoptosis of cardiomyocytes induced by lipopolysaccharide. Chin Med J (Engl). China; 2019;99:3176–82.
Liu X, Wang S, Zhao G. Baicalin relieves lipopolysaccharide-evoked inflammatory injury through regulation of miR-21 in H9c2 cells. Phytother Res. 2020;34:1134–41.
Wan JY, Gong X, Zhang L, Li HZ, Zhou YF, Zhou QX. Protective effect of baicalin against Lipopolysaccharide/d-galactosamine-induced liver injury in mice by up-regulation of Heme oxygenase-1. Eur J Pharmacol. 2008;587:302–8.
Liu A, Wang W, Fang H, Yang Y, Jiang X, Liu S, et al. Baicalein protects against polymicrobial sepsis-induced liver injury via inhibition of inflammation and apoptosis in mice. Eur J Pharmacol. 2015;748:45–53.
Wang C, Nie H, Li K, Zhang Y-X, Shu K-G, Chen X-J. Protective effect of baicalin solid dispersion on D-galactosamine induced acute hepatic injury in mice. Chinese J Integr Tradit West Med. 2014;34:71–4.
Cheng P, Wang T, Li W, Muhammad I, Wang H, Sun X, et al. Baicalin alleviates lipopolysaccharide-induced liver inflammation in chicken by suppressing TLR4-mediated NF-κB pathway. Front Pharmacol. 2017;8:1–12.
Huang Y, Sun M, Yang X, Ma A, Ma Y, Zhao A. Baicalin relieves inflammation stimulated by lipopolysaccharide via upregulating TUG1 in liver cells. J Physiol Biochem. 2019;75:463–73.
Wu Y, Lian L, Wan Y, Nan J. Chemico-Biological Interactions Baicalein inhibits nuclear factor- B and apoptosis via c-FLIP and MAPK in d -GalN / LPS induced acute liver failure in murine models. Chem Biol Interact. 2010;188:526–34.
Thanh HN, Minh HPT, Le TA, Ly HDT, Huu TN, Duc LV, et al. Ethanol extracts of Scutellaria baicalensis protect against lipopolysaccharideinduced acute liver injury in mice. Asian Pac J Trop Biomed. 2015;5:761–7.
Liao S, Li P, Wang J, Zhang Q, Xu D, Yang M, et al. Protection of baicalin against lipopolysaccharide induced liver and kidney injuries based on 1H NMR metabolomic profiling. Toxicol Res (Camb). 2016;5:1148–59.
Sun Y, Liu MW, Zhao YH, Lu YX, Wang YA, Tong CW. Baicalin attenuates lipopolysaccharide-induced renal tubular epithelial cell injury by inhibiting the TXNIP/NLRP3 signalling pathway via increasing miR-223–3p expression. J Biol Regul Homeost Agents. 34:69–82.
Yeh J-H, Chiu H-F, Wang J-S, Lee J-K, Chou T-C. Protective Effect of Baicalein Extracted from Scutellaria baicalensis against Lipopolysaccharide-Induced Glomerulonephritis in Mice. Int J Pharmacol. 2010;6:81–8.
Hwang YK, Jinhua M, Choi BR, Cui CA, Jeon WK, Kim H, et al. Effects of Scutellaria baicalensis on chronic cerebral hypoperfusion- induced memory impairments and chronic lipopolysaccharide infusion-induced memory impairments. J Ethnopharmacol. 2011;137:681–9.
Shah M-A, Park D-J, Kang J-B, Kim M-O, Koh P-O. Baicalin attenuates lipopolysaccharide-induced neuroinflammation in cerebral cortex of mice via inhibiting nuclear factor kappa B (NF-κB) activation. J Vet Med Sci. 2019;81:1359–67.
Shah M-A, Park D-J, Kang J-B, Kim M-O, Koh P-O. Baicalin alleviates lipopolysaccharide-induced neuroglial activation and inflammatory factors activation in hippocampus of adult mice. Lab Anim Res. 2020;36:32.
Wang G, Wu J, Wang J. Effects of baicalin from traditional Chinese medicine against lipopolysaccharide-induced inflammation in BV2 cells in vitro. Lat Am J Pharm. 2019;38:204–8.
Yan J-J, Du G-H, Qin X-M, Gao L. Baicalein attenuates the neuroinflammation in LPS-activated BV-2 microglial cells through suppression of pro-inflammatory cytokines, COX2/NF-kappaB expressions and regulation of metabolic abnormality. Int Immunopharmacol. Netherlands; 2020;79:106092.
Li F-Q, Wang T, Pei Z, Liu B, Hong J-S. Inhibition of microglial activation by the herbal flavonoid baicalein attenuates inflammation-mediated degeneration of dopaminergic neurons. J Neural Transm Austria. 2005;112:331–47.
Chen C-J, Raung S-L, Liao S-L, Chen S-Y. Inhibition of inducible nitric oxide synthase expression by baicalein in endotoxin/cytokine-stimulated microglia. Biochem Pharmacol. 2004;67:957–65.
Tsai CC, Lin MT, Wang JJ, Liao JF, Huang WT. The antipyretic effects of baicalin in lipopolysaccharide-evoked fever in rabbits. Neuropharmacology. 2006;51:709–17.
Ye L, Tao Y, Wang Y, Feng T, Li H. The effects of baicalin on the TLR2/4 signaling pathway in the peripheral blood mononuclear cells of a lipopolysaccharide-induced rat fever model. Int Immunopharmacol. 2015;25:106–11.
Luo W, Wang CY, Jin L. Baicalin Downregulates Porphyromonas gingivalis Lipopolysaccharide-Upregulated IL-6 and IL-8 Expression in Human Oral Keratinocytes by Negative Regulation of TLR Signaling. PLoS ONE. 2012;7:1–9.
Wang J, Luo H, Yang L, Li Y. Baicalein induces apoptosis and reduces inflammation in LPS-stimulated keratinocytes by blocking the activation of NF-κB: implications for alleviating oral lichen planus. Cell Mol Biol (Noisy-le-grand). 2016;62:55–60.
Wu Q, Ye H, Zhu Y-Z, Guo M, He X-X, Zheng X-B. Protective effect of baicalin against LPS-induced intestinal injury. China J Chinese Mater medica. 2013;38:2854–8.
Chen J, Zhang R, Wang J, Yu P, Liu Q, Zeng D, et al. Protective effects of baicalin on LPS-induced injury in intestinal epithelial cells and intercellular tight junctions. Can J Physiol Pharmacol. 2015;93:233–7.
Chen YC, Shen SC, Chen LG, Lee TJF, Yang LL. Wogonin, baicalin, and baicalein inhibition of inducible nitric oxide synthase and cyclooxygenase-2 gene expressions induced by nitric oxide synthase inhibitors and lipopolysaccharide. Biochem Pharmacol. 2001;61:1417–27.
Cheng PY, Lee YM, Wu YS, Chang TW, Jin JS, Yen MH. Protective effect of baicalein against endotoxic shock in rats in vivo and in vitro. Biochem Pharmacol. 2007;73:793–804.
Lee YM, Cheng PY, Chim LS, Kung CW, Ka SM, Chung MT, et al. Baicalein, an active component of Scutellaria baicalensis Georgi, improves cardiac contractile function in endotoxaemic rats via induction of heme oxygenase-1 and suppression of inflammatory responses. J Ethnopharmacol. 2011;135:179–85.
Liu LL, Gong LK, Wang H, Xiao Y, Wu XF, Zhang YH, et al. Baicalin inhibits macrophage activation by lipopolysaccharide and protects mice from endotoxin shock. Biochem Pharmacol. 2008;75:914–22.
He X, Wei Z, Zhou E, Chen L, Kou J, Wang J, et al. Baicalein attenuates inflammatory responses by suppressing TLR4 mediated NF-κB and MAPK signaling pathways in LPS-induced mastitis in mice. Int Immunopharmacol. 2015;28:470–6.
Yang W, Li H, Cong X, Wang X, Jiang Z, Zhang Q, et al. Baicalin attenuates lipopolysaccharide induced inflammation and apoptosis of cow mammary epithelial cells by regulating NF-κB and HSP72. Int Immunopharmacol. 2016;40:139–45.
Wang X, Zhao Y, Zhong X. Protective effects of Baicalin on decidua cells of LPS-induced mice abortion. J Immunol Res. 2014;2014:1–7.
Ma J, Wang R, Yan H, Xu R, Xu A, Zhang J. Protective Effects of Baicalin on Lipopolysaccharide-Induced Injury in Caenorhabditis elegans. Pharmacology Switzerland. 2020;105:109–17.
Zhao Y, Bao Y, Shi W, Wang X, Zhong X. Protective effects of baicalin on lipopolysaccharide (LPS)-induced implantation failure and the uterine endometrium in mice. African J Pharm Pharmacol. 2011;5:1661–8.
Min W, Lin XF, Miao X, Wang BT, Yang ZL, Luo D. Inhibitory effects of Baicalin on ultraviolet B-induced photo-damage in keratinocyte cell line. Am J Chin Med. 2008;36:745–60.
Zhou B-R, Luo D, Wei F-D, Chen X-E, Gao J. Baicalin protects human fibroblasts against ultraviolet B-induced cyclobutane pyrimidine dimers formation. Arch Dermatol Res. 2008;300:331–4.
Zhang JA, Yin Z, Ma LW, Yin ZQ, Hu YY, Xu Y, et al. The protective effect of baicalin against UVB irradiation induced photoaging: An in vitro and in vivo study. PLoS One. 2014;9:e99703.
Chang W-S, Lin E-Y, Hsu S-W, Hu P-S, Chuang C-L, Liao C-H, et al. Baicalin Scavenged Reactive Oxygen Species and Protected Human Keratinocytes Against UVB-induced Cytotoxicity. In Vivo (Brooklyn). 2016;30:605–10.
Zhang JA, Luan C, Huang D, Ju M, Chen K, Gu H. Induction of autophagy by baicalin through the AMPK-mTOR pathway protects human skin fibroblasts from ultraviolet B radiation-induced apoptosis. Drug Des Devel Ther. 2020;14:417–28.
Min W, Liu X, Qian Q, Lin B, Wu D, Wang M, et al. The effects of baicalin against UVA-induced photoaging in skin fibroblasts. Am J Chin Med. 2014;42:709–27.
Zhou BR, Yin H Bin, Xu Y, Wu D, Zhang ZH, Zhi-Qiang Yin, et al. Baicalin protects human skin fi broblasts from ultraviolet A radiation-induced oxidative damage and apoptosis. Free Radic Res. 2012;46:1458–71.
Wang S-C, Chen S-F, Lee Y-M, Chuang C-L, Bau D-T, Lin S-S. Baicalin scavenges reactive oxygen species and protects human keratinocytes against UVC-induced cytotoxicity. In Vivo (Brooklyn). 2013;27:707–14.
Manca ML, Mir-Palomo S, Caddeo C, Nacher A, Díez-Sales O, Peris JE, et al. Sorbitol-penetration enhancer containing vesicles loaded with baicalin for the protection and regeneration of skin injured by oxidative stress and UV radiation. Int J Pharm. 2019;555:175–83.
Bing-Rong Z, Song-Liang J, Xiao-E C, Xiang-Fei L, Bao-Xiang C, Jie G, et al. Protective effect of the Baicalin against DNA damage induced by ultraviolet B irradiation to mouse epidermis. Photodermatol Photoimmunol Photomed. 2008;24:175–82.
Zhou BR, Liu WL, Luo D. Protective effect of baicalin against multiple ultraviolet b exposure-mediated injuries in C57BL/6 mouse skin. Arch Pharm Res. 2011;34:261–8.
Oh MC, Piao MJ, Fernando PMDJ, Han X, Hewage SRKM, Park JE, et al. Baicalein protects human skin cells against ultraviolet B-induced oxidative stress. Biomol Ther. 2016;24:616–22.
Lu J, Zhong Y, Lin Z, Lin X, Chen Z, Wu X, et al. Baicalin alleviates radiation-induced epithelial-mesenchymal transition of primary type II alveolar epithelial cells via TGF-β and ERK/GSK3β signaling pathways. Biomed Pharmacother. 2017;95:1219–24.
Yang SJ, Jo H, Kim JG, Jung SH. Baicalin attenuates laser-induced choroidal neovascularization. Curr Eye Res. 2014;39:745–51.
Jang H, Lee J, Park S, Kim JS, Shim S, Lee S, et al. Baicalein mitigates radiation-induced enteritis by improving endothelial dysfunction. Front Pharmacol. 2019;10:1–13.
Lee EK, Kim JM, Choi J, Jung KJ, Kim DH, Chung SW, et al. Modulation of NF-κB and FOXOs by baicalein attenuates the radiation-induced inflammatory process in mouse kidney. Free Radic Res. 2011;45:507–17.
Wang M, Dong Y, Wu J, Li H, Zhang Y, Fan S, et al. Baicalein ameliorates ionizing radiation-induced injuries by rebalancing gut microbiota and inhibiting apoptosis. Life Sci. Netherlands; 2020;261:118463.
Gandhi NM. Baicalein protects mice against radiation-induced DNA damages and genotoxicity. Mol Cell Biochem. 2013;379:277–81.
Guo X, Chi S, Cong X, Li H, Jiang Z, Cao R, et al. Baicalin protects sertoli cells from heat stress-induced apoptosis via activation of the Fas/FasL pathway and Hsp72 expression. Reprod Toxicol. 2015;57:196–203.
Kang TH, Hong BN, Park C, Kim SY, Park R. Effect of baicalein from Scutellaria baicalensis on prevention of noise-induced hearing loss. Neurosci Lett. 2010;469:298–302.
Rodriguez I, Hong BN, Nam YH, Kim EY, Park GH, Ji MG, et al. Bioconversion of Scutellaria baicalensis extract can increase recovery of auditory function in a mouse model of noise-induced hearing loss. Biomed Pharmacother. 2017;93:1303–9.