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

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 Feb 17;116276. doi: 10.1016/j.jep.2023.116276.
Li Tang 1,  Xi Wang 2,  Rong Zhao 2,  Xiaomei Chen 2,  Feixia Wang 3,  Siwei Xia 3,  Qian Xiao 2,  Qiang Zhao 2,  Shiyan Yang 2,  Shanzhong Tan 4
Affiliations

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, 210001, 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.

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