Clinical and experimental investigations into the immune modulatory effects of Qianjinba polysaccharides on a rheumatoid arthritis mouse model: in vivo and in vitro studies

doi:10.5246/jcps.2024.10.067

Abstract

Abstract:

Qianjinba is derived from the dried root of a legume vine and is known for its plant polysaccharide, which has demonstrated anti-inflammatory, analgesic, and neuroprotective properties. Despite these known effects, its immunomodulatory potential remains underexplored. This study aimed to investigate the immunoregulatory effects of Qianjinba polysaccharide (QJBDT) in a murine model of rheumatoid arthritis (RA) and elucidate its mechanism of action in inhibiting the disease. To assess the immunomodulatory effects, RAW264.7 macrophage cells were stimulated with bacterial lipopolysaccharide (LPS) and subsequently treated with varying concentrations of QJBDT or total glucoside of paeonic acid (TGP). Cell proliferation and the expression levels of mitogen-activated protein kinase p38 and nuclear factor NF-κB proteins were evaluated. Following the successful modeling of RA in mice, different doses of QJBDT and TGP were administered via intragastric administration once daily for 21 d. Mice were divided into normal, model, QJBDT low-, medium-, and high-dose groups, along with a positive control group (TGP group), each comprising 10 mice. Organ coefficients were calculated, immune indexes in blood cells were determined, and alterations in T helper cell 17 (Th17) and regulatory T cells (Treg) were analyzed using flow cytometry. Compared to the normal group, cell proliferation rates significantly increased across all groups (P < 0.05). Elevated expressions of p38 and NF-κB proteins were observed in the model group, QJBDT low- and medium-dose groups (P < 0.05). Various systemic immune inflammation indexes, including systemic immune inflammation index (SII), total inflammation systemic index (AISI), and systemic inflammation response index (SIRI), platelet-to-lymphocyte ratio (PLR), neutrophil-to-lymphocyte ratio (NLR)，monocyte-to-lymphocyte ratio (MLR), showed increments (P < 0.05). Additionally, body weight and organ coefficients of the thymus, spleen, and liver decreased in both the model and low-dose groups (P < 0.05). Moreover, Th17 levels increased while Treg levels decreased across all groups (P < 0.05), resulting in a heightened Th17 to Treg ratio in the model and low-dose groups (P < 0.05). Notably, the QJBDT medium-dose, high-dose, and positive control groups demonstrated significant inhibitory effects on cell proliferation compared to the model group (P < 0.05), along with reduced expression levels of p38 and NF-κB (P < 0.05). Furthermore, various immune indicators from routine blood tests exhibited different degrees of decrease (P < 0.05), while immune indices displayed increases (P < 0.05). The low-, medium-, and high-dose groups of QJBDT, as well as the positive control group, showed decreased Th17 levels, elevated Treg levels, and diminished Th17 to Treg ratios (P < 0.05). Additionally, there was no statistically significant difference in efficacy between the QJBDT high-dose and TGP groups (P > 0.05). In conclusion, this study demonstrated that QJBDT exerted potent immunomodulatory effects on RA in mice in a dose-dependent manner. Its mechanism of action might involve the inhibition of NF-κB activation by suppressing the p38 MAPK signaling pathway.

Key words: Qianjin polysaccharide, Rheumatoid arthritis, Cell proliferation, p38, NF-κB, Th17, Treg

Supporting:

Yiwen Gao, Jucang Li, Nan Zhang, Shuang Li, Lili Wang, Haiguang Qin. Clinical and experimental investigations into the immune modulatory effects of Qianjinba polysaccharides on a rheumatoid arthritis mouse model: in vivo and in vitro studies[J]. Journal of Chinese Pharmaceutical Sciences, 2024, 33(10): 932-942.

Figures/Tables 5

References 33

[1]	Zhou, W.; Liu, Z.G.; Song, W.Z. Effect of triptolide on bone erosion in mice with rheumatoid arthritis. Chin. J. Clin. Pharmacol. 2021, 37, 2476–2480.
[2]	Yang, D.Q. Interpretation of Qijinbao, single side needle and Jinying root of ethnic medicine. J. Jishou Univ. 2023, 44, 84–89.
[3]	Zhuo, S.; Qin, H.G.; Chen, J. Effects of Qianjinbao on immune function in mice. Chin. Med. 2014, 25, 2641–2643.
[4]	Huang, Y.M.; Lan, M.L.; Tu, D.P. The textual research and modern research on the herbal medicine of the law of Qianjinba. J. Zhuangyao Pharma. Res. 2022, 01, 80–87.
[5]	Du, P.L.; Zhou, Y.Q.; Huang, G.H. Progress of clinical application research on pharmacological effects of chemical components of the plant. Anhui Agric. Sci. 2017, 45, 109–111.
[6]	Wei, L.J.; Chen, H.M.; Wang, J.H. Effects research of flemingia decoction on immuno-endocrine of ovariectomized rat. Guangxi J. Tradit. Chin. Med. 2009, 32, 46–49.
[7]	Yang, F.; Xi, W.; Xie, Y.X.; Li, Y.D.; Luo, X.L.; Kuang, Z.P.; Wu, J.N.; Li, L. The effect of gekko gecko peptides on immune functions of immunosuppression mice. J. Guangxi Med. Univ. 2011, 28, 342–344.
[8]	Chen, P.; Weng, J.B.; Yin, H. Research progress on extraction technology and pharmacological action of the plant. Shaanxi Tradit. Chin. Med. 2013, 34, 247–249.
[9]	Zhao, B.; Zhang, Y.L.; Tong, J.M. Effects of polysaccharide from the fruit of thladiantha dubia bunge on the immunefunctions of immunosuppressed mice. Lishizhen Med. Mater. Med. Res. 2010, 21, 1627–1629.
[10]	Ye, Y.X.; Lin, L.; Zhao, J.X. Effects of polysaccharides from Eucommia Ulmoides leaves on immune function in immunosuppressed mice. Chin. Materia Medica. 2015, 38, 1496–1498.
[11]	Zhuo, S.; Qiao, X.; Qin, H.G. Effects of different extraction parts of Qianjinbao on immune function of mice. J. Youjiang Med. Coll. Nat. 2015, 37, 682–683.
[12]	Zhuo, S.; Qiao, X.; Yang, Z.M. The regulatory effects of polysaccharide on immune function in mice. J. Guangxi Botany. 2017, 37, 1213–1218.
[13]	Qiao, X.; Zhuo, S.; Yang, Z.M. Extraction purification and structure identification of polysaccharide from the plant. J. Guangxi Botany. 2017, 37, 265–270.
[14]	Li, S.G.; Jia, C.; Song, Y.Y. Effect and mechanism of IL-37b on CD39/ATP axis of dendritic cells inhibiting inflammatory response in rats with rheumatoid arthritis. J. Immunol. 2022, 38, 51–58.
[15]	Zhu, X.W.; Zhao, W.T.; Chen, Y. Effect of Sanshui Baihu Decoction on human TNF-α transgenic mouse model of rheumatoid arthritis. Chin. J. Integr. Med. 2020, 40, 480–484.
[16]	Schett, G.; Gravallese, E. Bone erosion in rheumatoid arthritis: mechanisms, diagnosis and treatment. Nat. Rev. Rheumatol. 2012, 8, 656–664.
[17]	Bin, B.; Deng, X.Y.; Lu, H.W. Research progress of Zhuangyao Qianjin Bao; The First Chinese and Western Medicine Collaborative Innovation Forum for Men’s Health and the Third National Andrology Youth Academic Forum for Integrated Chinese and Western Medicine, Nanchang, Jiangxi, China, F, 2019 [C].
[18]	Wang, M.J.; Wang, Y.L.; Zhang, Y.J. Analysis of therapeutic effect and influence of cytokines on rheumatoid arthritis. Lishizhen Med. Mater. Med. Res. 2019, 30, 2172–2175.
[19]	Zhuo, S.; Qin, H.G.; Chen, J. Effects of Qianjinbao on immune function in mice. Lishizhen Med. Mater. Med. Res. 2014, 25, 2641–2643.
[20]	Zhu, L.; Wei, W.; Zheng, Y.Q. Effect and mechanism of total glucosides of Paeony on synovial cells in collagen-induced arthritis rats. Acta Pharmacol. Sin. 2006, 02, 166–170.
[21]	Yang, P.; Qian, F.Y.; Zhang, M.F.; Xu, A.L.; Wang, X.; Jiang, B.P.; Zhou, L.L. Th17 cell pathogenicity and plasticity in rheumatoid arthritis. J. Leukoc. Biol. 2019, 106, 1233–1240.
[22]	Scheinecker, C.; Göschl, L.; Bonelli, M. Treg cells in health and autoimmune diseases: new insights from single cell analysis. J. Autoimmun. 2020, 110, 102376.
[23]	Feng, J.J.; Shao, C.; Li, J.Q. Inhibition of p38 mitotin-activated protein kinase pathway regulates Th17 and Treg imbalance to reduce lipopolysaccharids-induced acute lung injury in mice. Chin. J. Respirat. Crit. Care. 2023, 22, 44–51.
[24]	Yasuda, S.; Sugiura, H.; Tanaka, H.; Takigami, S.; Yamagata, K. p38 MAP kinase inhibitors as potential therapeutic drugs for neural diseases. Cent. Nerv. Syst. Agents Med. Chem. 2011, 11, 45–59.
[25]	Karunakaran, S.; Ravindranath, V. Activation of p38 MAPK in the substantia nigra leads to nuclear translocation of NF-κB in MPTP-treated mice: implication in Parkinson’s disease. J. Neurochem. 2009, 109, 1791–1799.
[26]	Wang, G.; Pan, J.; Chen, S.D. Kinases and kinase signaling pathways: potential therapeutic targets in Parkinson’s disease. Prog. Neurobiol. 2012, 98, 207–221.
[27]	Niranjan, R.; Rajasekar, N.; Nath, C.; Shukla, R. The effect of guggulipid and nimesulide on MPTP-induced mediators of neuroinflammation in rat astrocytoma cells, C6. Chem. Biol. Interact. 2012, 200, 73–83.
[28]	Huang, C.P.; Yang, H.P.; Zhang, Z.X.; Xu, Y.J. Role of p38 mitogen-activated protein kinase in the activation of nuclear factor-кB in lipopolysaccharide-stimulated alveolar macrophage. Acta Med. Univ. Sci. Technol. Huazhong. 2007, 36, 804–807.
[29]	Liu, Y.R.; Yan, X.; Yu, H.X.; Yao, Y.; Wang, J.Q.; Li, X.F.; Chen, R.N.; Xu, Q.Q.; Ma, T.T.; Huang, C.; Li, J. NLRC5 promotes cell proliferation via regulating the NF-κB signaling pathway in Rheumatoid arthritis. Mol. Immunol. 2017, 91, 24–34.
[30]	Huang, M.C.; Wang, L.H.; Zeng, S.; Qiu, Q.; Zou, Y.Y.; Shi, M.H.; Xu, H.S.; Liang, L.Q. Indirubin inhibits the migration, invasion, and activation of fibroblast-like synoviocytes from rheumatoid arthritis patients. Inflamm. Res. 2017, 66, 433–440.
[31]	Yue, P.Y.K.; Ha, W.Y.; Lau, C.C.; Cheung, F.M.F.; Lee, A.W.M.; Ng, W.T.; Ngan, R.K.C.; Yau, C.C.; Kwong, D.L.W.; Lung, H.L.; Mak, N.K.; Lung, M.L.; Wong, R.N.S. MicroRNA profiling study reveals miR-150 in association with metastasis in nasopharyngeal carcinoma. Sci. Rep. 2017, 7, 12012.
[32]	Mao, J.D.; Qi, S.R.; Cui, Y.J.; Dou, X.X.; Luo, X.M.; Liu, J.X.; Zhu, T.; Ma, Y.F.; Wang, H.F. Lactobacillus rhamnosus GG attenuates lipopolysaccharide-induced inflammation and barrier dysfunction by regulating MAPK/NF-κB signaling and modulating metabolome in the piglet intestine. J. Nutr. 2020, 150, 1313–1323.
[33]	Li, L.L.; Chen, J.T.; Lin, L.; Pan, G.X.; Zhang, S.; Chen, H.; Zhang, M.J.; Xuan, Y.X.; Wang, Y.; You, Z.Q. Quzhou Fructus Aurantii Extract suppresses inflammation via regulation of MAPK, NF-κB, and AMPK signaling pathway. Sci. Rep. 2020, 10, 1593.