2. Academic Validation
  3. An arabinogalactan isolated from Cynanchum atratum promotes lymphangiogenesis and lymphatic vessel remodeling to alleviate secondary lymphedema

An arabinogalactan isolated from Cynanchum atratum promotes lymphangiogenesis and lymphatic vessel remodeling to alleviate secondary lymphedema

  • Int J Biol Macromol. 2024 Jun 10;273(Pt 2):133061. doi: 10.1016/j.ijbiomac.2024.133061.
Ning Li 1,  Ming Ruan 1,  Weihao Chen 2,  Yunxi Han 1,  Kunru Yang 1,  Hao Xu 1,  Songshan Shi 2,  Shunchun Wang 2,  Huijun Wang 3,  Yongjun Wang 4,  Qianqian Liang 5
Affiliations

Affiliations

  • 1 Longhua Hospital, Shanghai University of Traditional Chinese Medicine, 725 Wan-Ping South Road, Shanghai 200032, China; Spine Institute, Shanghai University of Traditional Chinese Medicine, 725 Wan-Ping South Road, Shanghai 200032, China.
  • 2 The MOE Key Laboratory for Standardization of Chinese Medicines and the SATCM Key Laboratory for New Resources and Quality Evaluation of Chinese Medicines, Shanghai Key Laboratory of Compound Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, 1200 Cailun Road, Shanghai 201203, China.
  • 3 The MOE Key Laboratory for Standardization of Chinese Medicines and the SATCM Key Laboratory for New Resources and Quality Evaluation of Chinese Medicines, Shanghai Key Laboratory of Compound Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, 1200 Cailun Road, Shanghai 201203, China. Electronic address: huijun.wang@outlook.com.
  • 4 Longhua Hospital, Shanghai University of Traditional Chinese Medicine, 725 Wan-Ping South Road, Shanghai 200032, China; Spine Institute, Shanghai University of Traditional Chinese Medicine, 725 Wan-Ping South Road, Shanghai 200032, China. Electronic address: wangyongjun@shutcm.edu.cn.
  • 5 Longhua Hospital, Shanghai University of Traditional Chinese Medicine, 725 Wan-Ping South Road, Shanghai 200032, China; Spine Institute, Shanghai University of Traditional Chinese Medicine, 725 Wan-Ping South Road, Shanghai 200032, China. Electronic address: liangqianqiantcm@126.com.
PMID: 38866272 DOI: 10.1016/j.ijbiomac.2024.133061
Abstract

Secondary lymphedema is a chronic and incurable disease lacking satisfactory therapeutic drugs. It primarily results from lymphatic vessel dysfunction resulting from factors such as tumor-related surgery, injury, or Infection. Promoting lymphangiogenesis and lymphatic vessel remodeling is crucial for restoring tissue fluid drainage and treating secondary lymphedema. In this study, we discovered that the oral administration of a type-II arabinogalactan (CAPW-1, molecular weight: 64 kDa) significantly promoted lymphangiogenesis and alleviated edema in mice with secondary lymphedema. Notably, the tail diameter of the CAPW-1200 group considerably decreased in comparison to that of the lymphedema group, with an average diameter difference reaching 0.98 mm on day 14. CAPW-1 treatment also reduced the average thickness of the subcutaneous area in the CAPW-1200 group to 0.37 mm (compared with 0.73 mm in the lymphedema group). It also facilitated the return of injected indocyanine green (ICG) from the tail tip to the sciatic lymph nodes, indicating that CAPW-1 promoted lymphatic vessel remodeling at the injury site. In addition, CAPW-1 enhanced the proliferation and migration of lymphatic endothelial cells. This phenomenon was associated with the activation of the Toll-like Receptor 4 (TLR4)/nuclear factor-κB (NF-κB) signaling pathway, thereby promoting the expression of vascular endothelial growth factor-C (VEGF-C), which can be abolished using a TLR4 Antagonist. Despite these findings, CAPW-1 did not alleviate the symptoms of lymphedema or restore lymphatic drainage in VEGFR3/Flt-4flox/flox/Prox1-CreERT2 mice. In summary, CAPW-1 alleviates secondary lymphedema by promoting lymphangiogenesis and lymphatic vessel remodeling through the activation of the TLR4/NF-κB/VEGF-C signaling pathway, indicating its potential as a therapeutic lymphangiogenesis agent for patients with secondary lymphedema.

Keywords

Arabinogalactan; Lymphangiogenesis; Lymphatic vessel remodeling; Secondary lymphedema; TLR4/NF-κB/VEGF-C pathway.

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