Notoginsenoside R1 (NG-R1) Promoted Lymphatic Drainage Function to Ameliorating Rheumatoid Arthritis in TNF-Tg Mice by Suppressing NF-κB Signaling Pathway

Rheumatoid arthritis (RA) is a chronic autoimmune disease that is primarily characterized by synovial inflammation. Our previous studies demonstrated that the lymphatic system is critical for the development and maintenance of RA disease, and sufficient lymph drainage helps to improve joint inflammation. In this study, we found that NG-R1, the main active component in the traditional Chinese medicinal herb Sanchi, activating lymphatic function can attenuate synovial inflammation. According to histopathological staining of ankle sections, NG-R1 significantly decreased the area of inflammation and reduced bone destruction of ankle joints in TNF-Tg mice. Near infrared-indocyanine green (NIR-ICG) lymphatic imaging system has shown that NG-R1 significantly improved the lymphatic drainage function. However, the molecular mechanism of its activity is not properly understood. Our in-depth study demonstrates that NG-R1 reduced the inflammatory cytokine production of lymphatic endothelial cells (LECs) stimulated by TNF-α, and the mechanism ameliorated the phosphorylation of IKKα/β and p65, and the translocation of p65 into the nucleus. In summary, this study proved that NG-R1 promoted lymphatic drainage function to ameliorating rheumatoid arthritis in TNF-Tg mice by suppressing NF-κB signaling pathway.

[1]  Xun Sun,et al.  Targeted apoptosis of macrophages and osteoclasts in arthritic joints is effective against advanced inflammatory arthritis , 2021, Nature Communications.

[2]  J. Vencovský,et al.  The pre-clinical phase of rheumatoid arthritis: From risk factors to prevention of arthritis. , 2021, Autoimmunity reviews.

[3]  J. Isaacs,et al.  Targeting synovial fibroblast proliferation in rheumatoid arthritis (TRAFIC): an open-label, dose-finding, phase 1b trial , 2021, The Lancet. Rheumatology.

[4]  H. Madry,et al.  Nanomaterials for the Diagnosis and Treatment of Inflammatory Arthritis , 2021, International journal of molecular sciences.

[5]  E. Schwarz,et al.  Lymphatic muscle cells contribute to dysfunction of the synovial lymphatic system in inflammatory arthritis in mice , 2020, Arthritis Research & Therapy.

[6]  Qi Shi,et al.  Ginsenoside Rg1 promotes lymphatic drainage and improves chronic inflammatory arthritis , 2020, Journal of musculoskeletal & neuronal interactions.

[7]  Yanping Yang,et al.  Construction of a pH-responsive, Ultralow-dose Triptolide Nanomedicine for Safe Rheumatoid Arthritis Therapy. , 2020, Acta biomaterialia.

[8]  Hongwei Zhang,et al.  TRIM32 promotes inflammatory responses in rheumatoid arthritis fibroblast‐like synoviocytes , 2020, Scandinavian journal of immunology.

[9]  Hai Liu,et al.  Focus on Notoginsenoside R1 in Metabolism and Prevention Against Human Diseases , 2020, Drug design, development and therapy.

[10]  V. Hjortdal,et al.  Role of the lymphatic vasculature in cardiovascular medicine , 2019, Heart.

[11]  Q. Shen,et al.  Notoginsenoside R1 Protects db/db Mice against Diabetic Nephropathy via Upregulation of Nrf2-Mediated HO-1 Expression , 2019, Molecules.

[12]  Ilinka Acimovic The influence of health qigong on the subjectively expressed psychophysical state of patients with rheumatoid arthritis, rheum, osteoporosis, osteopenia , 2018 .

[13]  Guang Zhao,et al.  Notch-1 siRNA and Methotrexate towards a Multifunctional Approach in Rhematoid Arthritis Management: a Nanomedicine Approach , 2018, Pharmaceutical Research.

[14]  E. Schwarz,et al.  Targeting lymphatic function as a novel therapeutic intervention for rheumatoid arthritis , 2018, Nature Reviews Rheumatology.

[15]  Chun Li,et al.  Traditional uses, botany, phytochemistry, pharmacology and toxicology of Panax notoginseng (Burk.) F.H. Chen: A review. , 2016, Journal of ethnopharmacology.

[16]  Jingyi Zhang,et al.  Cardioprotective effects of Notoginsenoside R1 against ischemia/reperfusion injuries by regulating oxidative stress- and endoplasmic reticulum stress- related signaling pathways , 2016, Scientific Reports.

[17]  L. Xing,et al.  Peri-articular lymphatic system and "Bi" theory of Chinese medicine in the pathogenesis and treatment of arthritis , 2015, Chinese Journal of Integrative Medicine.

[18]  Xiao-Bo Sun,et al.  Notoginsenoside R1 attenuates cardiac dysfunction in endotoxemic mice: an insight into oestrogen receptor activation and PI3K/Akt signalling , 2013, British journal of pharmacology.