Advanced Search

Journal of Traditional Chinese Medicine >

2025 , Vol. 45 >Issue 4: 845 - 851

DOI: https://doi.org/10.19852/j.cnki.jtcm.2025.04.013

Original Articles

Study on the mechanism of Fuzi Lizhong decoction (附子理中汤) in the treatment of colorectal cancer of spleen kidney Yang deficiency from the perspective of intestinal flora and hypoxia inducible factor-1α signalling pathway

  • Lina ZHANG ,
  • Xiu LIN ,
  • Xin ZHAO ,
  • Wenjuan LI ,
  • Ye ZHAO
Expand
  • 1 Department of Oncology, Ruikang Hospital Affiliated Guangxi University of Chinese Medicine, Nanning 530011, China
    2 Department of Surgery, Guilin University of Technology Hospital, Guilin 541004, China; Department of Public Health, International College, Krirk University, Bangkok 10220, Thailand
    3 Medical Laboratory, the Second People's Hospital of Datong, Datong 037000, China; Department of Public Health, International College, Krirk University, Bangkok 10220, Thailand
    4 Department of Public Health, International College, Krirk University, Bangkok 10220, Thailand
ZHAO Ye, Department of Public Health, International College, Krirk University, Bangkok 10220, Thailand. zhao.ye@staff.krirk.ac.th
LIN Xiu, Department of Surgery, Guilin University of Technology Hospital, Guilin 541004, China; Department of Public Health, International College, Krirk University, Bangkok 10220, Thailand. xiulin@glut.edu.cn;

Received date: 2024-03-22

  Accepted date: 2024-10-17

  Online published: 2025-07-25

Supported by

Guangxi Natural Science Foundation “Controllable Synthesis of Ordered Mesoporous Seafoam-Loaded g-C3N4 Gomposites and Their Mechanism of Adsorption-Photocatalytic Degradation of Antidepressants in Water Bodies”(2017GXNSFBA198216);Open Fund for the Director of Guangxi Key Laboratory of Spatial Information and Geographic Information “Geographic Spatial Analysis of Regional Urinary Tract Stone Disease”(19-185-10-04)

Fold

Abstract

OBJECTIVE: To evaluate the effect of Fuzi Lizhong decoction (附子理中汤) on intestinal flora, serum inflammatory factors, and hypoxia inducible factor-1α (HIF-1α) in patients with colorectal cancer associated with spleen and kidney Yang deficiency.

METHODS: A total of 100 patients diagnosed with advanced colorectal cancer were randomly divided into two groups: a control group (CON, 50) and a Traditional Chinese Medicine (TCM) group (n = 50). The control group received treatment with the Capecitabine + Oxaliplatin (CAPEOX) regimen, while the TCM group received the same regimen along with Fuzi Lizhong decoction for six weeks. Changes in intestinal flora were assessed before and after six weeks in both groups. Serum markers, including HIF-1α, vascular endothelial growth factor (VEGF), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α), were measured using enzyme-linked immunosorbent assay. Adverse reactions, clinical efficacy, and TCM syndrome efficacy were also monitored.

RESULTS: After six weeks, the levels of Lactobacillus and Bifidobacterium were significantly higher, while the levels of Enterobacter and Enterococcus were significantly lower in the TCM group compared to the control group (P < 0.05). Serum levels of HIF-1α, VEGF, IL-6, and TNF-α were also significantly reduced in the TCM group compared to the control group (P < 0.05). Additionally, the incidence of adverse reactions was lower, and the clinical efficacy was higher in the TCM group compared to the control group (P < 0.05).

CONCLUSION: Fuzi Lizhong decoction effectively improves intestinal microbiota composition, reduces inflammatory factors and HIF-1α expression, alleviates chemotherapy-related adverse reactions, enhances clinical efficacy, and may inhibit tumor growth in patients with colorectal cancer.

Key words： colorectal neoplasms; gastrointestinal microbiome; vascular endothelial growth factors; hypoxia-inducible factor 1, alpha subunit; interleukin-6; tumor necrosis factor-alpha; Fuzi Lizhong decoction

Cite this article

Lina ZHANG , Xiu LIN , Xin ZHAO , Wenjuan LI , Ye ZHAO . Study on the mechanism of Fuzi Lizhong decoction (附子理中汤) in the treatment of colorectal cancer of spleen kidney Yang deficiency from the perspective of intestinal flora and hypoxia inducible factor-1α signalling pathway[J]. Journal of Traditional Chinese Medicine, 2025 , 45(4) : 845 -851 . DOI: 10.19852/j.cnki.jtcm.2025.04.013

References

1. Bray F, Laversanne M, Weiderpass E, Soerjomataram I. The ever-increasing importance of cancer as a leading cause of premature death worldwide. Cancer 2021; 127: 3029-30.
2. Sung H, Ferlay J, Siegel RL, et al. Global Cancer Statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 2021; 71: 209-49.
3. Siegel RL, Miller KD, Wagle NS, Jemal A. Cancer statistics, 2023. CA Cancer J Clin 2023; 73: 17-48.
4. Sawicki T, Ruszkowska M, Danielewicz A, Nied?wiedzka E, Ar?ukowicz T, Przyby?owicz KE. A review of colorectal cancer in terms of epidemiology, risk factors, development, symptoms and diagnosis. Cancers (Basel) 2021; 13: 2025.
5. Haverkamp D, Redwood D, Roik E, Vindigni S, Thomas T. Elevated colorectal cancer incidence among American Indian/Alaska Native persons in Alaska compared to other populations worldwide. Int J Circumpolar Health 2023; 82: 2184749.
6. Cao W, Chen HD, Yu YW, Li N, Chen WQ. Changing profiles of cancer burden worldwide and in China: a secondary analysis of the global cancer statistics 2020. Chin Med J (Engl) 2021; 134: 783-91.
7. Waldmann E, Kammerlander AA, Gessl I, et al. Association of adenoma detection rate and adenoma characteristics with colorectal cancer mortality after screening colonoscopy. Clin Gastroenterol Hepatol 2021; 19: 1890-8.
8. Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 2018; 68: 394-424.
9. Wieszczy P, Kaminski MF, Franczyk R, et al. Colorectal cancer incidence and mortality after removal of adenomas during screening colonoscopies. Gastroenterology 2020; 158: 875-83.e5.
10. Kaminski MF, Wieszczy P, Rupinski M, et al. Increased rate of adenoma detection associates with reduced risk of colorectal cancer and death. Gastroenterology 2017; 153: 98-105.
11. Xi Y, Xu P. Global colorectal cancer burden in 2020 and projections to 2040. Transl Oncol 2021; 14: 101174.
12. Hsiao WL, Liu L. The role of traditional Chinese herbal medicines in cancer therapy-from TCM theory to mechanistic insights. Planta Med 2010; 76: 1118-31.
13. Yang J, Ma W, Mei Q, et al. Protective Effect of Fuzi Lizhong decoction against non-alcoholic fatty liver disease via anti-inflammatory response through regulating p53 and PPARG signaling. Biol Pharm Bull 2020; 43: 1626-33.
14. Yue LY, Zhu CL, Gao C, Wang C, Chen XY, Tian TD. Roles of three classic TCM formulae in inhibiting gastric cancer growth in mice. J Tradit Chin Med Sci 2017; 4: 65-70.
15. The Ministry of Health of the People's Republic of China, Department of Medical Science,ed. Chinese norms for the diagnosis and treatment of common malignant tumours (in Chinese). Beijing: Beijing Medical University and Peking Union Medical College Joint Publishing House 1991: 1-793. (in Chinese).
16. Li Kk, Xu YF, Zhang L, et al. Exploring the clinical experience of Chinese medical master Hong Guangxiang in treating advanced lung cancer based on the theory of "Yang transforming Qi, Yin forming". Zhong Hua Zhong Yi Yao Za Zhi 2025; 40: 1203-6.
17. Wang Y, Liu P, Fang Y, et al. The effect of long-term Traditional Chinese Medicine treatment on survival time of colorectal cancer based on propensity score matching: a retrospective cohort study. Evid Based Complement Alternat Med 2020; 2020: 7023420.
18. He WT, Zhang T, Yang YF, Zhang HL. Meta-analysis of clinical efficacy and evidence-based analysis of Chinese medicine for colorectal cancer. Zhong Yi Za Zhi 2018; 59: 1929-36.
19. Pei JW. Professor Jiang Shiqing's experience in treating malignant tumours using the warm-Yang method. Henan Zhong Yi Yao 2009; 29: 129-30.
20. Wang QQ, Liu JY, Zhang ZL, Zhou GQ, Hao WS. Interpretation of the classics of Traditional Chinese Medicine. Beijing: China Traditional Chinese Medicine Press, 2012: 261-73.
21. Feng LZ, He WP, Ye XW, Zhang SF, Huang HT, Liu XH. Clinical and experimental study on myelosuppression induced by chemotherapeutic drugs by strengthening spleen and replenishing blood formula. Zhong Yi Zhong Liu Xue Za Zhi 2019; 1: 28-37.
22. Si H, Yang Q, Hu H, Ding C, Wang H, Lin X. Colorectal cancer occurrence and treatment based on changes in intestinal flora. Semin Cancer Biol 2021; 70: 3-10.
23. Ghosh S, Pramanik S. Structural diversity, functional aspects and future therapeutic applications of human gut microbiome. Arch Microbiol 2021; 203: 5281-308.
24. Keku TO, Dulal S, Deveaux A, Jovov B, Han X. The gastrointestinal microbiota and colorectal cancer. Am J Physiol Gastrointest Liver Physiol 2015; 308: G351-63.
25. Xing C, Zhihao L, Ji D. Diagnostic value of fecal Fusobacterium nucleatum in colorectal cancer. Arch Med Sci 2023; 19: 1929-33.
26. Jiang X, Yang HX, Zhang FC. Role of intestinal flora metabolites in autoimmune diseases. Xie He Yi Xue Za Zhi 2022; 13: 747-52.
27. Jiang WW, Liu YL. Intestinal flora and common liver diseases. Zhong Hua Gan Bing Za Zhi 2013, 21: 5-6.
28. Font-Burgada J, Sun B, Karin M. Obesity and cancer: the oil that feeds the flame. Cell Metab 2016; 23: 48-62.
29. Alhinai EA, Walton GE, Commane DM. The role of the gut microbiota in colorectal cancer causation. Int J Mol Sci 2019; 20: 5295.
30. Ding YF, Peng ZX, Ding L, Peng YR. Baishouwu extract suppresses the development of hepatocellular carcinoma via TLR4/MyD88/NF-κB pathway. Front Pharmacol 2019; 10: 389.
31. Yu LX, Schwabe RF. The gut microbiome and liver cancer: mechanisms and clinical translation. Nat Rev Gastroenterol Hepatol 2017; 14: 527-39.
32. Chen HB, Zhou HK, Li WT, Li MH, Cheng HB, Wu MH. Prevention and treatment of colon cancer based on intestinal flora and its relationship with the theory of cancer toxicity and pathogenesis. Zhong Yi Za Zhi 2019; 34: 5796-800.
33. Cheng HB, Zhou ZY, Li L, et al. Discussion on the clinical identification and treatment system of Chinese medicine tumours based on the theory of cancer-toxicity pathogenesis. Zhong Yi Za Zhi 2015; 56: 1989-92.
34. Zhang CJ, Chen XJ, Wen J, Jing YP, Wei JS. Study on the effects of compound Sijunzi Tang and Codonopsis ginseng polysaccharide in regulating the intestinal flora of mice with ulcerative colitis//Chinese Society of Immunology. The 12th National Immunology Academic Conference Sessions Exchange Report Collection. Lanzhou: Lanzhou University, 2017: 142-3.
35. Zhang XD. Effect of Sini decoction on colon cancer induced by AOM-DSS in mice and its impact on the intestinal microbiota of mice. Jilin: Jilin University, 2018: 65.
36. Han Y, Jo H, Cho JH, Dhanasekaran DN, Song YS. Resveratrol as a tumor-suppressive nutraceutical modulating tumor micro-environment and malignant behaviors of cancer. Int J Mol Sci 2019; 20: 925.
37. Lai W, Wang B, Huang R, Zhang C, Fu P, Ma L. Ferroptosis in organ fibrosis: from mechanisms to therapeutic medicines. J Transl Int Med 2024;12: 22-34.
38. Fu HJ, Zhou M, Huang ZH, Chen YX, Wu XX. Severe acute hepatitis of unknown origin in children: clinical issues of concern. J Transl Int Med 2023; 11: 19-23.
39. Chen YF, Hu DJ, Zhang X, Li YZ, Shen BY. Analysis of serum OPN, YKL-40, HGF and VEGF-A levels and their risk factors in patients with colorectal cancer liver metastases. Modern Biomedical Progress 2020; 20: 2891-5.
40. Ning X, Wang Y, Yan W, Li G, Sang N. Chitin synthesis inhibitors promote liver cancer cell metastasis via interfering with hypoxia-inducible factor 1α. Chemosphere 2018; 206: 231-7.
41. Lu L, Pan F, Zhao C, Sun ZG, Zhang N. Relationship of hypoxia-inducible factor-1α and vascular endothelial growth factor with clinicopathological features and prognosis in non-small cell lung cancer. Lin Chuang Fei Ke Za Zhi 2021; 26: 411-7.
42. Wang G, Wang J, Li X, Wu Q, Yao R, Luo X. Hypoxia and TNF-α synergistically induce expression of IL-6 and IL-8 in human fibroblast-like synoviocytes via enhancing TAK1/NF-κB/HIF-1α signaling. Inflammation 2023; 46: 912-24.
43. Luo H, Gui FQ, Liu H, Zhang M, Zhao Y. Correlation study of silencing HIF-1α with TNF-α and IL-6 under hypoxic conditions and changes in biological behaviour of human dermal microvascular endothelial cells. Zhong Guo Xi Bao Sheng Wu Xue Xue Bao 2018; 40: 62-70.
44. Qu XL, Duan GJ, Zhao B, et al. Anti-inflammatory, antioxidant and anti-apoptotic protective effects and mechanism of Radix et Rhizoma Polygonati Odorati-Ginger on acute myocardial ischaemia in rats. Zhong Yao Yao Li Yu Lin Chuang 2022; 38: 31-7.
45. Zhang H, Wang X, Zhang J, He Y, Yang X, Nie Y, Sun L. Crosstalk between gut microbiota and gut resident macrophages in inflammatory bowel disease. J Transl Int Med 2023; 11: 382-92.
46. Zhai YC, Xia SS, Wang X, Zang KH, Han T. Study on the mechanism of anti-inflammatory effect of the pair of Radix et Rhizoma Pinelliae and Radix et Rhizoma Drynariae on mice with chronic ulcerative colitis. Zhong Hua Zhong Yi Yao Za Zhi 2022; 37: 1914-8.
Options
Outlines

/

〈 〉