Journal of Traditional Chinese Medicine ›› 2024, Vol. 44 ›› Issue (6): 1217-1226.DOI: 10.19852/j.cnki.jtcm.20240409.001
• Research Articles • Previous Articles Next Articles
WANG Qixin1, XU Liting1, WU Jiangpeng2, HE Xueling1, TANG Huan1, CHENG Guangqing1, LU Tianming1, DAI Chuanhao1, GUO Qiuyan1(), WANG Jigang1,2()
Received:
2023-11-19
Accepted:
2024-03-11
Online:
2024-12-15
Published:
2024-04-09
Contact:
WANG Jigang, State Key Laboratory for Quality Ensurance and Sustainable Use of Dao-di Herbs, Artemisinin Research Center, and Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China. jgwang@icmm.ac.cn Telephone: +86-18211077872, +86-18260046833Supported by:
WANG Qixin, XU Liting, WU Jiangpeng, HE Xueling, TANG Huan, CHENG Guangqing, LU Tianming, DAI Chuanhao, GUO Qiuyan, WANG Jigang. Bailing capsule (百令胶囊) alleviates autoimmune thyroiditis via regulating peroxisome proliferator-activated receptor signaling pathway: a multi-omics analysis[J]. Journal of Traditional Chinese Medicine, 2024, 44(6): 1217-1226.
Figure 1 Influence of BL on body weight, thyroid function related antibody and hormone levels in AIT rats A: effect of BL on weight change of rats during the administration cycle; B: effect of BL on TPO-Ab of rats at the end of the administration; C: effect of BL on TG-Ab of rats at the end of the administration; D: effects of BL on serum concentration of FT3 in rats; E: effects of BL on serum concentration of FT4 in rats; F: effects of BL on serum concentration of TSH in rats; G: images of HE staining in thyroid tissue of BL-treated rats (× 40), G1: control, G2: model, G3: BL-low, G4: BL-high; H: images of thyroid ultrastructure in BL-treated rats, H1: control (× 300), H2: model (×300), H3: BL-low (× 300), H4: BL-high (× 300), H5: control (× 800), H6: model (× 800), H7: BL-low (× 800), H8: BL-high (× 800). Control treated with normal saline, model treated with 100 μL pTg (1 mg/mL) on days 0, 14, and 21, BL-low treated with 100 μL pTg (1 mg/mL) and BL (1 g/kg), BL-high treated with 100 μL pTg (1 mg/mL) and BL (5 g/kg). BL: Bailing capsule; AIT: autoimmune thyroiditis; pTg: porcine thyroglobulin; TPO-Ab: thyroid peroxidase antibody; TG-Ab: thyroglobulin antibody; FT3: triiodothyronine; FT4: free thyroxine; TSH: thyroid-stimulating hormone; Mv: microvillus; TJ: tight juactim; De: desmosome; Col: colloid; N: nucleus; M: mitochondrion; RER: rough endoplasmic reticulum; V: colloid vesicles; G: secretory granules; ASS: autolysosome; Go: golgi apparatus. Student t-test and one-way analysis of variance were used for comparison analysis. Statistical significance between the groups was determined by Dunnett's T3 analysis. Data are expressed as the mean ± standard deviation (n = 8). aP < 0.001, cP < 0.01, vs Model; bP < 0.001 vs Control.
Figure 2 Effect of BL on the serum cytokine levels of AIT rats A: effect of BL on inflammatory cytokines IFN-γ of rats; B: effect of BL on inflammatory cytokines IL-4 of rats; C: effect of BL on inflammatory cytokines IFN-γ/IL-4 values of rats; D: effect of BL on inflammatory cytokines IL-12 of rats; E: effect of BL on inflammatory cytokines IL-10 of rats; F: effect of BL on inflammatory cytokines IL-12/IL-10 values of rats. Control treated with normal saline, model treated with 100 μL pTg (1 mg/mL) on day 0, 14, and 21, BL-low treated with 100 μL pTg (1 mg/mL) and BL (1 g/kg), BL-high treated with 100 μL pTg (1 mg/mL) and BL (5 g/kg). BL: Bailing capsule; AIT: autoimmune thyroiditis; pTg: porcine thyroglobulin; IFN-γ: interferon-gamma; IL-4: interleukin-4; IL-10: interleukin-10; IL-12: interleukin-12. Student t-test and one-way analysis of variance were used for comparison analysis. Statistical significance between the groups was determined by Dunnett's T3 analysis. Data are expressed as the mean ± standard deviation (n = 8). aP < 0.001 vs Control; bP < 0.001, cP < 0.01 vs Model.
Figure 3 Expression profiling changes of genes in the thyroid A: the volcano plots indicated the relative expressions of DEGs in “Model vs Control”; B; the volcano plots indicated the relative expressions of DEGs in “BL-high vs Model”; C: KEGG analysis showed the relative expressions of DEGs and enriched pathways in “Model vs Control”; D: KEGG analysis showed the relative expressions of DEGs and enriched pathways in “BL-high vs Model”. Control treated with normal saline, model treated with 100 μL pTg (1 mg/mL) on days 0, 14, and 21, BL-high treated with 100 μL pTg (1 mg/mL) and BL (5 g/kg). pTg: porcine thyroglobulin; DEGs: differentially expressed genes; KEGG: kyoto encyclopedia of genes and genomes.
Figure 4 Identification of altered protein expression and functional pathways in response to BL A: the volcanic plot indicates the relative expressions of DEPs in “Model vs Control”; B; the volcano plots indicated the relative expressions of DEPs in “BL-high vs Model”; C: enrichment analysis of DEPs by KEGG in “Model vs Control”; D: enrichment analysis of DEPs by KEGG in “BL-high vs Model”; E: protein interaction analysis based on string database; F: determination of Fabp4 expression level in thyroid tissue; G: determination of Acsl1 expression level in thyroid tissue; H: determination of Acadl expression level in thyroid tissue; I: statistical result for the expression of Fabp4; G: statistical result for the expression of Acsl1; K: statistical result for the expression of Acadl. Control treated with normal saline, model treated with 100 μL pTg (1 mg/mL) on days 0, 14, and 21, BL-high treated with 100 μL pTg (1 mg/mL) and BL (5 g/kg). BL: Bailing capsule; DEGs: differentially expressed genes; KEGG: kyoto encyclopedia of genes and genomes; pTg: porcine thyroglobulin; Acsl1: acyl-coenzyme A synthetase long-chain family member 1; Acsl4: acyl-coenzyme A synthetase long-chain family member 4; Acsl5: acyl-coenzyme A synthetase long-chain family member 5; Fabp4: fatty acid-binding protein 4; Acadl: acyl-coenzyme A dehydrogenase long chain; Acadm: acyl-coenzyme A dehydrogenase middle chain; Pck1: phosphoenolpyruvate carboxykinase 1; Adipoq: adiponectin. Student t-test and one-way analysis of variance were used for comparison analysis. Statistical significance between the groups was determined by Dunnett's T3 analysis. Data was presented as the mean ± standard deviation (n = 3). aP < 0.01, cP < 0.05 vs Control; bP < 0.001, dP < 0.01, eP < 0.05 vs Model.
1. | Mincer DL, Jialal I. Hashimoto thyroiditis. Mather: In StatPearls, 2023: 1. |
2. |
Caturegli P, De Remigis A, Rose NR. Hashimoto thyroiditis: clinical and diagnostic criteria. Autoimmun Rev 2014; 13: 391-7.
DOI PMID |
3. |
Taylor PN, Albrecht D, Scholz A, et al. Global epidemiology of hyperthyroidism and hypothyroidism. Nat Rev Endocrinol 2018; 14: 301-16.
DOI PMID |
4. | Wang YZ, Zhang YY, Qiao JJ, Lu YY, Xia ZY. Protective effect of thyroid and restores of ovarian function of Buzhong Yiqi granule on experimental autoimmune thyroiditis in female rats. J Tradit Chin Med 2024; 44: 315-323. |
5. | Xu J, Yuan Q, Wu K, et al. Effects of Bailing capsule on diabetic nephropathy based on UPLC-MS urine metabolomics. RSC Adv 2019; 9: 35969-75. |
6. |
Shashidhar MG, Giridhar P, Udaya Sankar K, et al. Bioactive principles from Cordyceps sinensis: a potent food supplement - a review. J Funct Foods 2013; 5: 1013-30.
DOI PMID |
7. |
Zhou X, Gong Z, Su Y, et al. Cordyceps fungi: natural products, pharmacological functions and developmental products. J Pharm Pharmacol 2009; 61: 279-91.
DOI PMID |
8. | Zhang H, Li Y, Mi J, et al. GC-MS profiling of volatile components in different fermentation products of Cordyceps sinensis mycelia. Molecules 2017; 22: 1800. |
9. | Tian YY, Wang N, Hu JZ. Clinical observation on Bailing capsule in treatment of Hashimoto's thyroiditis. Shi Yong Zhong Yi Nei Ke Za Zhi 2020; 34: 75-8. |
10. | Xue YH, Li CX, Shang J, et al. Effect of Bailing capsule on Hashimoto's thyroiditis. Shenzhen Zhong Xi Yi Jie He Za Zhi 2021; 31: 62-4. |
11. | Yang ZY. Effects of Bailing capsules combined with Levothyroxine sodium in treatment autoimmune thyroiditis. Zhong Guo Min Kang Yi Xue 2022; 34: 24-7. |
12. |
Burek CL, Talor MV. Environmental triggers of autoimmune thyroiditis. J Autoimmun 2009; 33: 183-9.
DOI PMID |
13. |
Zhang C, Qin L, Sun B, et al. Transcriptome analysis of the effect of diosgenin on autoimmune thyroiditis in a rat model. Sci Rep 2021; 11: 6401.
DOI PMID |
14. | Zhang Q, Xiao X, Li M, et al. Bailing capsule (Cordyceps sinensis) ameliorates renal triglyceride accumulation through the PPARα pathway in diabetic rats. Front Pharmacol 2022; 13: 915592. |
15. | Zhao C, Yang D, Pang W. Immunomodulatory effect of Bailing capsule on thyroid follicular carcinoma in mice. Zhong Guo Yao Shi 2011; 14: 94-5. |
16. | Ragusa F, Fallahi P, Elia G, et al. Hashimotos' thyroiditis: epidemiology, pathogenesis, clinic and therapy. Best Pract Res Clin Endocrinol Metab 2019; 33: 101367. |
17. | Wang S, Liu Y, Zhao N, et al. IL-34 expression is reduced in Hashimoto's thyroiditis and associated with thyrocyte apoptosis. Front Endocrinol (Lausanne) 2018; 9: 629. |
18. | Kunadirek P, Pinjaroen N, Nookaew I, et al. Transcriptomic analyses reveal long non-coding RNA in peripheral blood mononuclear cells as a novel biomarker for diagnosis and prognosis of hepatocellular carcinoma. Int J Mol Sci 2022; 23: 7882. |
19. | Song XH, Zan RZ, Yu CH, et al. Effects of modified Haizao Yuhu decoction in experimental autoimmune thyroiditis rats. J Ethnopharmacol 2011; 135: 321-4. |
20. |
Mikoś H, Mikoś M, Obara-Moszyńska M, et al. The role of the immune system and cytokines involved in the pathogenesis of autoimmune thyroid disease (AITD). Endokrynol Pol 2014; 65: 150-5.
DOI PMID |
21. | Chao G, Zhu Y, Fang L. Correlation between Hashimoto's thyroiditis-related thyroid hormone levels and 25-hydroxyvitamin D. Front Endocrinol (Lausanne) 2020; 11: 4. |
22. | Pyzik A, Grywalska E, Matyjaszek-Matuszek B, et al. Immune disorders in Hashimoto's thyroiditis: what do we know so far? J Immunol Res 2015; 2015: 979167. |
23. |
Rydzewska M, Jaromin M, Pasierowska IE, et al. Role of the T and B lymphocytes in pathogenesis of autoimmune thyroid diseases. Thyroid Res 2018; 11: 2.
DOI PMID |
24. | Su XL, Zhang T, Guo S, et al. Efficacy of Wumei Baijiang prescription on regulatory T cells / helper T cells Immune balance in mice with ulcerative coliti. J Tradit Chin Med 2022; 42: 30-38. |
25. |
Ajjan RA, Watson PF, McIntosh RS, et al. Intrathyroidal cytokine gene expression in Hashimoto's thyroiditis. Clin Exp Immunol 1996; 105: 523-8.
PMID |
26. |
Martinenaite E, Ahmad SM, Bendtsen SK, et al. Arginase-1-based vaccination against the tumor microenvironment: the identification of an optimal T-cell epitope. Cancer Immunol Immunother 2019; 68: 1901-7.
DOI PMID |
27. | Dienz O, Eaton SM, Bond JP, et al. The induction of antibody production by IL-6 is indirectly mediated by IL-21 produced by CD4+ T cells. J Exp Med 2009; 206: 69-78. |
28. |
Raphael I, Nalawade S, Eagar TN, et al. T cell subsets and their signature cytokines in autoimmune and inflammatory diseases. Cytokine 2015; 74: 5-17.
DOI PMID |
29. | Ganesh BB, Bhattacharya P, Gopisetty A, et al. Role of cytokines in the pathogenesis and suppression of thyroid autoimmunity. J Interferon Cytokine Res 2011; 31: 721-31. |
30. |
Shearer BG, Billin AN. The next generation of PPAR drugs: do we have the tools to find them? Biochim Biophys Acta 2007; 1771: 1082-93.
PMID |
31. | Michalik L, Wahli W. Peroxisome proliferator-activated receptors: three isotypes for a multitude of functions. Curr Opin Biotechnol 1999; 10: 564-70. |
32. | Zhang JM, Liang SL, Nie P, et al. Efficacy of Kushen decoction on high-fat-diet-induced hyperlipidemia in rats. J Tradit Chin Med 2022; 42: 364-71. |
33. | Blanquart C, Barbier O, Fruchart JC, et al. Peroxisome proliferator-activated receptors: regulation of transcriptional activities and roles in inflammation. J Steroid Biochem Mol Biol 2003; 85: 267-73. |
34. |
Michalik L, Desvergne B, Wahli W. Peroxisome-proliferator-activated receptors and cancers: complex stories. Nat Rev Cancer 2004; 4: 61-70.
DOI PMID |
35. | Diab A, Deng C, Smith JD, et al. Peroxisome proliferator-activated receptor-gamma agonist 15-deoxy-Delta (12,14)-prostaglandin J(2) ameliorates experimental autoimmune encephalomyelitis. J Immunol 2002; 168: 2508-15. |
36. |
Karger S, Berger K, Eszlinger M, et al. Evaluation of peroxisome proliferator-activated receptor-gamma expression in benign and malignant thyroid pathologies. Thyroid 2005; 15: 997-1003.
PMID |
37. |
Au AY, McBride C, Wilhelm KG Jr, et al. PAX8-peroxisome proliferator-activated receptor gamma (PPARgamma) disrupts normal PAX8 or PPARgamma transcriptional function and stimulates follicular thyroid cell growth. Endocrinology 2006; 147: 367-76.
PMID |
38. |
Marx N, Mach F, Sauty A, et al. Peroxisome proliferator-activated receptor-gamma activators inhibit IFN-gamma-induced expression of the T cell-active CXC chemokines IP-10, Mig, and I-TAC in human endothelial cells. J Immunol 2000; 164: 6503-8.
PMID |
39. |
Werion A, Joris V, Hepp M, et al. Pioglitazone, a PPARγ agonist, upregulates the expression of caveolin-1 and catalase, essential for thyroid cell homeostasis: a clue to the pathogenesis of Hashimoto's thyroiditis. Thyroid 2016; 26: 1320-31.
DOI PMID |
40. |
Antonelli A, Ferrari SM, Mancusi C, et al. Interferon-α, -β and -γ induce CXCL11 secretion in human thyrocytes: modulation by peroxisome proliferator-activated receptor γ agonists. Immunobiology 2013; 218: 690-5.
DOI PMID |
41. | Fallahi P, Ferrari SM, Corrado A, et al. Targeting chemokine (C-X-C motif) receptor 3 in thyroid autoimmunity. Recent Pat Endocr Metab Immune Drug Discov 2014; 8: 95-101. |
42. |
Montaigne D, Butruille L, Staels B. PPAR control of metabolism and cardiovascular functions. Nat Rev Cardiol 2021; 18: 809-23.
DOI PMID |
43. | Chen Q, Zhao JJ, Zheng DM, et al. The relationship between thyroid function and lipid metabolism: a clinical analysis. Jun Shi Yi Xue Ke Xue Yuan Yuan Kan 2010; 34: 364-6. |
44. | Chen CM, Liu J, Jia YM, et al. Correlation between serum thyroid-stimulating hormone and blood lipid in subjects with normal thyroid function. Zhong Guo Xin Xue Guan Za Zhi 2020; 25: 45-9. |
45. | Yu HY, Zhang MX, Cianflone K, et al. Influence of thyroid diseases on human serum adipocytokines. Hua Zhong Ke Ji Da Xue Xue Bao 2005; 34: 3. |
46. |
Wang F, Tan Y, Wang C, et al. Thyroid-stimulating hormone levels within the reference range are associated with serum lipid profiles independent of thyroid hormones. J Clin Endocrinol Metab 2012; 97: 2724-31.
DOI PMID |
47. | Lo MC, Lu CI, Chen MH, et al. Glycoxidative stress-induced mitophagy modulates mitochondrial fates. Ann N Y Acad Sci 2010; 1215: 1-7. |
Viewed | ||||||
Full text |
|
|||||
Abstract |
|
|||||
Sponsored by China Association of Chinese Medicine
& China Academy of Chinese Medical Sciences
16 Nanxiaojie, Dongzhimen Nei, Beijing, China. 100700 Email: jtcmen@126.com
Copyright 2020 Journal of Traditional Chinese Medicine. All rights reserved.