Yi-Qi-Jian-Pi formula ameliorates immune function in acute-on-chronic liver failure by upregulating autophagy and mitochondrial biogenesis in CD8+ T lymphocytes

Li Tang; Xi Wang; Rong Zhao; Xiaomei Chen; Feixia Wang; Siwei Xia; Qian Xiao; Qiang Zhao; Shiyan Yang; Shanzhong Tan

doi:10.1016/j.jep.2023.116276

Yi-Qi-Jian-Pi formula ameliorates immune function in acute-on-chronic liver failure by upregulating autophagy and mitochondrial biogenesis in CD8⁺ T lymphocytes

J Ethnopharmacol. 2023 May 23:308:116276. doi: 10.1016/j.jep.2023.116276. Epub 2023 Feb 17.

Authors

Li Tang¹, Xi Wang², Rong Zhao², Xiaomei Chen², Feixia Wang³, Siwei Xia³, Qian Xiao², Qiang Zhao², Shiyan Yang², Shanzhong Tan⁴

Affiliations

¹ Department of Integrated TCM and Western Medicine, Nanjing Hospital Affiliated to Nanjing University of Chinese Medicine, Nanjing, 210003, China; Department of Gastroenterology, Nanjing Hospital of Chinese Medicine Affiliated to Nanjing University of Chinese Medicine, Nanjing, 210022, China.
² Department of Integrated TCM and Western Medicine, Nanjing Hospital Affiliated to Nanjing University of Chinese Medicine, Nanjing, 210003, China.
³ Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Material Medical, School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, 210023, China.
⁴ Department of Integrated TCM and Western Medicine, Nanjing Hospital Affiliated to Nanjing University of Chinese Medicine, Nanjing, 210003, China. Electronic address: fsyy01455@njucm.edu.cn.

PMID: 36806340
DOI: 10.1016/j.jep.2023.116276

Abstract

Ethnopharmacological relevance: A key event in the pathogenesis of acute-on-chronic liver failure (ACLF) is the imbalance in the systemic immune response; immunosuppression in patients with ACLF contributes to poor prognosis. The Yi-Qi-Jian-Pi formula (YQJPF) may improve T lymphocyte immune function in patients with ACLF.

Aim of the study: To investigate the immune mechanism of YQJPF in vivo and in vitro.

Materials and methods: An ACLF rat model was established by injection of CCl₄, lipopolysaccharide, and D-galactosamine. We examined the effect of different doses of YQJPF (6.43, 12.87, 25.74 g/kg) on liver injury and immune function in the ACLF rat model. Magnetic-activated cell sorting was used to sort the CD8⁺ T lymphocytes in the spleen for lymphocyte function detection. In primary CD8⁺ T lymphocytes and Jurkat cell lines, the expression of mitochondrial function and biogenesis and autophagy related markers were detected using molecular biological methods and flow cytometry analysis.

Results: YQJPF improved the peripheral blood lymphocyte count and proportion of CD8⁺ T lymphocytes in ACLF rats, increased pro-inflammatory factors (IL-2, IFN-λ, and TNF-α), and reduced anti-inflammatory factors (IL-10 and TGF β1). YQJPF also improved metabolism and mitochondrial homeostasis in CD8⁺ T lymphocytes, alleviated lymphocyte immune dysfunction by promoting autophagy, upregulated mitochondrial biogenesis by promoting PGC-1α, NRF-1, and TFAM expression, and regulated the relationship between autophagy and mitochondrial biogenesis via PGC-1α.

Conclusions: Our results suggest that YQJPF could improve immune function in a rat model of ACLF, possibly via affecting the homeostasis of lymphatic mitochondria in CD8⁺ T lymphocytes. YQJPF may enhance lymphocyte mitochondrial biosynthesis and promote lymphocyte autophagy. PGC-1α is a possible upstream regulatory target of YQJPF.

Keywords: Acute-on-chronic liver failure; Autophagy; CD8(+) T lymphocytes; Mitochondrial biogenesis; Yi-Qi-Jian-Pi formula.

MeSH terms

Acute-On-Chronic Liver Failure* / pathology
Animals
Autophagy
CD8-Positive T-Lymphocytes
Immunity
Organelle Biogenesis
Rats