Abstract
Scuellaria Root (SR, root of Scutellaria baicalensis), which has potent anti-inflammatory effects, is a component of useful Kampo formulae. Albeit a low frequency, SR induces serious interstitial pneumonia and liver dysfunction. In this study, to control the adverse effects of SR, we investigated the causal constituent responsible for its hepatocytotoxicity and aimed to develop a method to control it. As a result, we revealed that the hepatocytotoxicity of SR was correlated with its baicalin content, a major constituent in SR. It was confirmed by preparing a baicalin-free SR extract, which exhibited reduced hepatocytotoxicity. The addition of baicalin to the baicalin-free SR extract restored the hepatocytotoxicity, indicating that the hepatocytotoxicity of SR is dependent on its baicalin content. Thus, SR extract-induced hepatocytotoxicity can be controlled by regulating its baicalin content.
Graphical abstract
![](http://media.springernature.com/lw685/springer-static/image/art%3A10.1007%2Fs11418-024-01814-1/MediaObjects/11418_2024_1814_Figa_HTML.png)
![](http://media.springernature.com/m312/springer-static/image/art%3A10.1007%2Fs11418-024-01814-1/MediaObjects/11418_2024_1814_Fig1_HTML.png)
![](http://media.springernature.com/m312/springer-static/image/art%3A10.1007%2Fs11418-024-01814-1/MediaObjects/11418_2024_1814_Fig2_HTML.png)
![](http://media.springernature.com/m312/springer-static/image/art%3A10.1007%2Fs11418-024-01814-1/MediaObjects/11418_2024_1814_Fig3_HTML.png)
![](http://media.springernature.com/m312/springer-static/image/art%3A10.1007%2Fs11418-024-01814-1/MediaObjects/11418_2024_1814_Fig4_HTML.png)
![](http://media.springernature.com/m312/springer-static/image/art%3A10.1007%2Fs11418-024-01814-1/MediaObjects/11418_2024_1814_Fig5_HTML.png)
References
The Ministry of Health Labour and Welfare of Japan (2021) The Japanese Pharmacopoeia. The Ministry of Health Labour and Welfare of Japan, Japan
Puri KB, White N, Monro AJ (2019) The effect of supplementation with Scutellaria baicalensis on hepatic function. Med Hypotheses 133:109402. https://doi.org/10.1016/j.mehy.2019.109402
Lee W, Ku S, Bae J (2018) Anti-inflammatory effects of baicalin, baicalein, and wogonin in vitro and in vivo. Inflammation 38:110–125. https://doi.org/10.1007/s10753-014-0013-0
Oshima N, Narukawa Y, Hada N, Kiuchi F (2013) Quantitative analysis of anti-inflammatory activity of orengedokuto: importance of combination of flavonoids in inhibition of PGE2 production in mouse macrophage-like cell line J774.1. J Nat Med 67:281–288. https://doi.org/10.1007/s11418-012-0679-2
Oshima N, Shimizu T, Narukawa Y, Hada N, Kiuchi F (2018) Quantitative analysis of the anti-inflammatory activity of orengedokuto II: berberine is responsible for the inhibition of NO production. J Nat Med 72:706–714. https://doi.org/10.1007/s11418-018-1209-7
Shimizu T, Shibuya N, Narukawa Y, Oshima N, Hada N, Kiuchi F (2018) Synergistic effect of baicalein, wogonin and oroxylin A mixture: multistep inhibition of the NF-κB signalling pathway contributes to an anti-inflammatory effect of Scutellaria root flavonoids. J Nat Med 72:181–191. https://doi.org/10.1007/s11418-017-1129-y
González LT, Minsky NW, Espinosa LEM, Aranda RS, Meseguer JP, Pérez PC (2017) In vitro assessment of hepatoprotective agents against damage induced by acetaminophen and CCl4. BMC Complement Altern Med 17:39. https://doi.org/10.1186/s12906-016-1506-1
Yu Y, Pei M, Li L (2015) Baicalin induces apoptosis in hepatic cancer cells in vitro and suppresses tumor growth in vivo. Int J Clin Exp Med 8:8958–8967
Mahdi AO, Ehsaneh K, Farzaneh P, Fadhil SK, Mehdi Y, Bahman Y, Mohammad A, Khudaverdi G, Hossein SK (2021) Baicalin, a natural antimicrobial and anti-biofilm agent. J Herb Med 27:100432. https://doi.org/10.1016/j.hermed.2021.100432
Peng-fei L, Fu-gen H, Bin-bin D, Tian-sheng D, Xiang-lin H, Ming-qin Z (2013) Purification and antioxidant activities of baicalin isolated from the root of huangqin (Scutellaria baicalensis gcorsi). J Food Sci Technol 50:615–619. https://doi.org/10.1007/s13197-012-0857-y
Cui L, Feng L, Zhang ZH, Jia XB (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
Tarrago T, Kichik N, Claasen B, Prades R, Teixido M, Giralt E (2008) The natural product berberine is a human prolyl oligopeptidase inhibitor. Bioorg Med Chem 16:7516–7524. https://doi.org/10.1002/cmdc.200600303
Acknowledgements
We thank Renee Mosi, PhD, from Edanz (https://jp.edanz.com/ac) for editing a draft of this manuscript.
Funding
This work was supported by JSPS KAKENHI Grant Numbers 22K06676.
Author information
Authors and Affiliations
Contributions
Conceptualization, N.O.; methodology, N.O., K.K.; cytotoxicity evaluation, R.T., Y.K.; preparation of extracts, M.T., T.N. and K.O.; HPLC analysis, M.T., T.N. and K.O.; data curation, N.O., M.N. and N.H.; writing—original draft preparation, N.O.; writing—review and editing, K.K., K.O.; supervision, M.N. and N.H.; project administration, N.O.; funding acquisition, N.O. All authors have read and agreed to the manuscript.
Corresponding authors
Ethics declarations
Conflict of interest
The authors declare that they have no conflicts of interest.
Additional information
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
About this article
Cite this article
Oshima, N., Kusamori, K., Takasaki, R. et al. Scutellaria Root extract-induced hepatocytotoxicity can be controlled by regulating its baicalin content. J Nat Med (2024). https://doi.org/10.1007/s11418-024-01814-1
Received:
Accepted:
Published:
DOI: https://doi.org/10.1007/s11418-024-01814-1