Abstract
Lycopodii herba (SJC), a traditional Chinese medicine, has the effect of dispelling wind and eliminating dampness (a therapeutic principle and method of traditional Chinese medicine for rheumatoid arthritis), relaxing tendon and activating collaterals. However, the major effective components and its therapeutic mechanism were unclear. In this study, different SJC samples with slightly different compositions were prepared by extracting with different concentrations of ethanol. Then, the therapeutic effects on rheumatoid arthritis (RA) of different SJC samples were evaluated. Finally, the spectrum–effect relationship between UPLC-Q-TOF/MS fingerprints and the effect of RA was explored to screen the effective components. Western blotting was used to study the potential mechanism. The volume of hind paw and the level of RF, TNF-α, and IL-1β were lower after administrating with different SJC samples, compared with the model group. Histopathological findings also confirmed that SJC could relieve the symptoms of RA. Combined with identification of the components in plasm from SJC, lycojaponicumin C, des-N-methyl-α-obscurine, 8β-acetoxy-12β-hydroxy-lycopodine or 8β-acetoxy-11α-hydroxy-lycopodine or 8β-hydroxy-11α-acetoxylycopodine were considered to be the major effective components. The mechanism may be related to AChE/NF-κB signaling pathway. This work provides a general method to screen the potential effective components of herb medicines and would be benefit to understand the mechanism of SJC for the treatment of RA.
Similar content being viewed by others
Data Availability
Data is available when required.
References
Tracy, A., C.D. Buckley, and K. Raza. 2017. Pre-symptomatic autoimmunity in rheumatoid arthritis: when does the disease start? Seminars in Immunopathology 39: 423–435.
Guo, Q., Y. Wang, D. Xu, J. Nossent, N.J. Pavlos, and J. Xu. 2018. Rheumatoid arthritis: pathological mechanisms and modern pharmacologic therapies. Bone Research 6: 15.
Mandik-Nayak, L., J.B. DuHadaway, J. Mulgrew, E. Pigott, K. Manley, S. Sedano, G.C. Prendergast, and L.D. Laury-Kleintop. 2017. RhoB blockade selectively inhibits autoantibody production in autoimmune models of rheumatoid arthritis and lupus. Disease Models & Mechanisms 10: 1313–1322.
Littlejohn, E.A., and S.U. Monrad. 2018. Early Diagnosis and Treatment of Rheumatoid Arthritis. Primary Care 45: 237–255.
Kyei, S., G.A. Koffuor, and J.N. Boampong. 2012. Antiarthritic effect of aqueous and ethanolic leaf extracts of Pistia stratiotes in adjuvant-induced arthritis in Sprague-Dawley rats. Journal of Experimental Pharmacology 4: 41–51.
Horta-Baas, G., M.D.S. Romero-Figueroa, A.J. Montiel-Jarquin, M.L. Pizano-Zarate, J. Garcia-Mena, and N. Ramirez-Duran. 2017. Intestinal Dysbiosis and Rheumatoid Arthritis: A Link between Gut Microbiota and the Pathogenesis of Rheumatoid Arthritis. Journal of Immunology Research 2017: 4835189.
Taylor, P., J. Gartemann, J. Hsieh, and J. Creeden. 2011. A systematic review of serum biomarkers anti-cyclic citrullinated Peptide and rheumatoid factor as tests for rheumatoid arthritis. Autoimmune Diseases 2011: 815038.
Corvaisier, M., Y. Delneste, H. Jeanvoine, L. Preisser, S. Blanchard, E. Garo, E. Hoppe, B. Barré, M. Audran, B.A. Bouvard, J.-P. Saint-André, and P. Jeannin. 2012. IL-26 Is Overexpressed in Rheumatoid Arthritis and Induces Proinflammatory Cytokine Production and Th17 Cell Generation. PLoS Biology 10: e1001395.
Lu, S., S. Dong, D. Xu, J. Duan, G. Li, Y. Guo, H. Kuang, and Q. Wang. 2017. Spectrum-Effect Relationships between Fingerprints of Caulophyllum robustum Maxim and Inhabited Pro-Inflammation Cytokine Effects. Molecules 22(11): 1826.
Shabbir, A., S.A. Batool, M.I. Basheer, M. Shahzad, K. Sultana, R.B. Tareen, J. Iqbal, and H. Saeed Ul. 2018. Ziziphora clinopodioides ameliorated rheumatoid arthritis and inflammatory paw edema in different models of acute and chronic inflammation. Biomedicine & Pharmacotherapy = Biomedecine & Pharmacotherapie 97: 1710–1721.
Zamora-Legoff, J.A., M.L. Krause, C.S. Crowson, J.H. Ryu, and E.L. Matteson. 2017. Progressive Decline of Lung Function in Rheumatoid Arthritis-Associated Interstitial Lung Disease. Arthritis & Rheumatology 69: 542–549.
Kaeley, N., S. Ahmad, M. Pathania, and R. Kakkar. 2019. Prevalence and patterns of peripheral neuropathy in patients of rheumatoid arthritis. Journal of Family Medicine And Primary Care 8: 22–26.
Liu, J., and R.L. Liu. 2011. The potential role of Chinese medicine in ameliorating extra-articular manifestations of rheumatoid arthritis. Chinese Journal of Integrative Medicine 17: 735–737.
Giles, J.T. 2019. Extra-articular Manifestations and Comorbidity in Rheumatoid Arthritis: Potential Impact of Pre-Rheumatoid Arthritis Prevention. Clinical Therapeutics 41: 1246–1255.
Conigliaro, P., P. Triggianese, E. De Martino, G.L. Fonti, M.S. Chimenti, F. Sunzini, A. Viola, C. Canofari, and R. Perricone. 2019. Challenges in the treatment of Rheumatoid Arthritis. Autoimmunity Reviews 18: 706–713.
Fischbach, W. 2019. Drug-induced gastrointestinal bleeding. Der Internist 60: 597–607.
Gomes, A., S. Bhattacharya, M. Chakraborty, P. Bhattacharjee, R. Mishra, and A. Gomes. 2010. Anti-arthritic activity of Indian monocellate cobra (Naja kaouthia) venom on adjuvant induced arthritis. Toxicon: Official Journal of the International Society on Toxinology 55: 670–673.
Kalantar, M., H. Kalantari, M. Goudarzi, L. Khorsandi, S. Bakhit, and H. Kalantar. 2019. Crocin ameliorates methotrexate-induced liver injury via inhibition of oxidative stress and inflammation in rats. Pharmacological Reports: PR 71: 746–752.
Garcia, D.S., E.I. Saturansky, D. Poncino, Y. Martinez-Artola, S. Rosenberg, G. Abritta, C. Ascimani-Pena, and A. Cravero. 2019. Hepatic toxicity by methotrexate with weekly single doses associated with folic acid in rheumatoid and psoriatic arthritis. What is its real frequency? Annals of Hepatology 18(5): 765–769.
Zhuo-ya, C., Z. Zi-gui, L. Ping, and Q. Yong. 2015. Advances in studies on chemical constituents in Lycopodii Herba and their pharmacological activities. Chinese Traditional and Herbal Drugs 46: 297–304.
Chen, B., H. Zhan, M. Chung, X. Lin, M. Zhang, J. Pang, and C. Wang. 2015. Chinese Herbal Bath Therapy for the Treatment of Knee Osteoarthritis: Meta-Analysis of Randomized Controlled Trials. Evidence-based Complementary and Alternative Medicine : eCAM 2015: 949172.
Hanif, K., M. Kumar, N. Singh, and R. Shukla. 2015. Effect of homeopathic Lycopodium clavatum on memory functions and cerebral blood flow in memory-impaired rats. Homeopathy : The Journal of the Faculty of Homeopathy 104: 24–28.
Li, X., M. Kang, N. Ma, T. Pang, Y. Zhang, H. Jin, Z. Yang, and L. Song. 2019. Identification and Analysis of Chemical Constituents and Rat Serum Metabolites in Lycopodium clavatum Using UPLC-Q-TOF/MS Combined with Multiple Data-Processing Approaches. Evidence-based Complementary and Alternative Medicine 2019: 1–8.
Liang, J., Y. Chen, G. Ren, W. Dong, M. Shi, L. Xiong, J. Li, J. Dong, F. Li, and J. Yuan. 2017. Screening Hepatotoxic Components in Euodia rutaecarpa by UHPLC-QTOF/MS Based on the Spectrum-Toxicity Relationship. Molecules 22(8): 1264.
Cooles, F.A.H., A.E. Anderson, A. Skelton, A.G. Pratt, M.S. Kurowska-Stolarska, I. McInnes, C.M.U. Hilkens, and J.D. Isaacs. 2018. Phenotypic and Transcriptomic Analysis of Peripheral Blood Plasmacytoid and Conventional Dendritic Cells in Early Drug Naive Rheumatoid Arthritis. Frontiers in Immunology 9: 755.
Sasso, O., M. Migliore, D. Habrant, A. Armirotti, C. Albani, M. Summa, G. Moreno-Sanz, R. Scarpelli, and D. Piomelli. 2015. Multitarget fatty acid amide hydrolase/cyclooxygenase blockade suppresses intestinal inflammation and protects against nonsteroidal anti-inflammatory drug-dependent gastrointestinal damage. FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology 29: 2616–2627.
Montesinos, M.C., A. Desai, and B.N. Cronstein. 2006. Suppression of inflammation by low-dose methotrexate is mediated by adenosine A2A receptor but not A3 receptor activation in thioglycollate-induced peritonitis. Arthritis Research & Therapy 8: R53.
Funding
This work was supported by Tianjin Education Commission Research Project in China [grant number: 2017KJ132] and the National Natural Science Foundation of China [grant number: 8180141249].
Author information
Authors and Affiliations
Contributions
Zhen Yang: methodology, writing-original draft preparation and writing-reviewing and editing. Qingsheng Yin: methodology. Jing Ma: methodology and writing-original draft preparation. Changshuo Yang and Yuanyuan Sheng: data curation. Lili Song: visualization. Tan Pang: investigation. Pengwei Zhuang, Hong Guo, and Yanjun Zhang: conceptualization and supervision.
Corresponding authors
Ethics declarations
Conflicts of Interest
The authors declare that they have no competing interests.
Ethics Approval
The experimental protocol used in this study was approved by the Ethics Committee for Animal Experimentation of Tianjin University of Traditional Chinese Medicine (TCM-2016-015-E03) and was conducted according to the NIH Guide for the Care and Use of Laboratory Animals.
Consent to Participate
Not applicable.
Consent for Publication
Not applicable.
Code Availability
PLSR was selected to explore the spectrum–effect relationship between UPLC-Q-TOF/MS fingerprints and the effect of RA to screen the effective components of it for RA.
Additional information
Publisher’s Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
About this article
Cite this article
Yang, Z., Yin, Q., Ma, J. et al. Screen the Effective Components of Lycopodii herba on Rheumatoid Arthritis with the Aid of Spectrum-Effect Relationship and Uncover its Potential Mechanism. Inflammation 43, 2087–2097 (2020). https://doi.org/10.1007/s10753-020-01276-z
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10753-020-01276-z