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Total flavonoids from Tetrastigma hemsleyanum ameliorates inflammatory stress in concanavalin A-induced autoimmune hepatitis mice by regulating Treg/Th17 immune homeostasis

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Abstract

Objective

Tetrastigma hemsleyanum, a rare and endangered medicinal plant, has attracted much attention due to its immunoregulatory and hepatoprotective activities. This study aimed to evaluate the anti-inflammatory effects and underlying mechanisms of total flavonoids from T. hemsleyanum(TFT)on Con A-induced hepatitis in mice.

Methods

TFT (1, 2 and 4 g/kg) and a positive control drug bifendate (200 mg/kg) were administered intragastrically to mice once daily for 10 consecutive days. On the 10th day, the model autoimmune of hepatitis was established by intravenous injection of Con A (20 mg/kg) 1 h after drug administration. Liver injury was assessed by serum levels of alanine amino transferase (ALT and AST) and histopathology 8 h after Con A injection. The levels of pro-inflammatory Th17 cytokines (IL-17, IL-6) and anti-inflammatory Treg cytokines (IL-10, TGF-β1) in serum were evaluated by ELISA, the levels of Th17 and Treg cells infiltrated into spleen were investigated by flow cytometry methods, and hepatic tissue transcription factor Foxp3 and RORγt mRNA were determined using quantitative real-time PCR.

Results

Pretreatment with TFT and bifendate significantly reduced the serum levels of ALT and AST, and attenuated histopathological alterations in Con A-induced liver injury. With respect to samples treated with Con A alone, TFT and bifendate pretreatments differentially attenuated the increase of serum inflammatory factors interleukin (IL)-17 and IL-6 levels, the proportions of Th17 cells in spleen and the expression of RORγt in hepatic tissues. Meanwhile, TFT and bifendate pretreatments could enhance the percentage of Treg cells in spleen and the expression of Foxp3 in hepatic tissues, as well as the levels of transforming growth factor (TGF)-β1, IL-10 in serum.

Conclusion

The anti-inflammatory effects of TFT was mediated by regulating Treg/Th17 immune homeostasis, which, therefore, suppressed the inflammatory immune response. This study provided scientific basis for the further researches and clinical applications of Tetrastigma hemsleyanum.

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Abbreviations

ALT:

Alanine aminotransferase

AST:

Aspartate aminotransferase

Con A:

Concanavalin A

ELISA:

Enzyme-linked immunosorbent assay

Foxp3:

Forkhead box protein3

HE:

Haematoxylin and eosin

IFN-γ:

Interferon-γ

IL:

Interleukin

RORγt:

Retinoid-related orphan nuclear receptor-γt

TFT:

Total flavonoids from Tetrastigma hemsleyanum

TGF-β1:

Transforming growth factor-β

Th:

T helper type

TNF-α:

Tumor necrosis factor-α

Treg:

T regulatory

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Acknowledgements

This work was supported by the Natural Science Foundation of Ningbo City (Grant no. 2018A610430), the New Shoot Talents Program of Zhejiang Province (Grant no. 2017R435001), the Science Foundation of Zhejiang education department (Grant no. Y201534579), the Science and technology projects of Zhejiang Food and Drug Administration (YP201603), the Leading and top talent training project of Ningbo City (Grant no. NBLJ201801011), Key Laboratory of Ningbo, China (no. 2016b22002).

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  1. Institute of Biopharmaceutical, Zhejiang Pharmaceutical College, Ningbo, 315100, Zhejiang, People’s Republic of China

    Weiwei Ji, Xin Peng, Tianling Lou, Juan Wang & Wenyu Qiu

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  1. Weiwei Ji
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  2. Xin Peng
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Ji, W., Peng, X., Lou, T. et al. Total flavonoids from Tetrastigma hemsleyanum ameliorates inflammatory stress in concanavalin A-induced autoimmune hepatitis mice by regulating Treg/Th17 immune homeostasis. Inflammopharmacol 27, 1297–1307 (2019). https://doi.org/10.1007/s10787-019-00599-0

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