Top

BMC Complementary Medicine and Therapies

Published in:

Open Access 01-12-2021 | Colchicine | Research article

Effects of Stephania hainanensis alkaloids on MSU-induced acute gouty arthritis in mice

Authors: Hao-fei Fan, Xing-yue Fang, Hao-lin Wu, Yi-qian Xu, Li-chong Gong, Dao-rui Yu, Hao Jia, Xiao-liang Tang, Qi-bing Liu

Published in: BMC Complementary Medicine and Therapies | Issue 1/2021

Abstract

Background

Gout is initiated by the precipitation of monosodium urate (MSU) crystals within the joints and soft tissues, and it can eventually cause acute or chronic arthritis. MSU crystals trigger, amplify, and maintain a strong inflammatory response through promoting proinflammatory activity. In this study, the therapeutic effects of Stephania hainanensis (S. hainanensis) total alkaloid (SHA) were tested and evaluated on MSU-induced acute gouty arthritis in a mouse model.

Methods

After oral administration of SHA (10 or 20 mg/kg) or the antigout medicine colchicine (0.5 mg/kg) once daily for 3 consecutive days, MSU crystals suspended in saline (2.5 mg/50 μl) were intradermally injected into the right paw of the mice. Then, SHA and colchicine were administered for another 2 days. During this period, swelling of the ankle and clinical scores were measured at 12, 24, and 48 h postinjection. After the mice were euthanized, inflammatory cytokine expression and paw tissue inflammation-related gene and protein expression, and a histopathological analysis was performed.

Results

SHA had obvious therapeutic effects on MSU-induced acute gouty arthritis in mice. SHA alleviated ankle swelling and inhibited the production of cytokines, such as IL-1β and TNF-α. In addition, NLRP3, Caspase-1 and IL-1β, which are activated by MSU were also suppressed by SHA. The histological evaluation showed that SHA relieved the infiltration of inflammation around the ankle.

Conclusions

These results suggest that SHA is capable of anti-inflammatory activities and may be useful for treating gouty arthritis.

Available only for authorised users

Ragab G, Elshahaly M, Bardin T. Gout: an old disease in new perspective - a review. J Adv Res. 2017;8(5):495–511. https://doi.org/10.1016/j.jare.2017.04.008.CrossRefPubMedPubMedCentral

Pineda C, Fuentes-Gomez AJ, Hernandez-Diaz C, Zamudio-Cuevas Y, Fernandez-Torres J, Lopez-Macay A, et al. Animal model of acute gout reproduces the inflammatory and ultrasonographic joint changes of human gout. Arthritis Res Ther. 2015;17(1):37. https://doi.org/10.1186/s13075-015-0550-4.CrossRefPubMedPubMedCentral

Dehlin M, Jacobsson L, Roddy E. Global epidemiology of gout: prevalence, incidence, treatment patterns and risk factors. Nat Rev Rheumatol. 2020;16(7):380–90. https://doi.org/10.1038/s41584-020-0441-1.CrossRefPubMed

Yu Y, Yang J, Fu S, Xue Y, Liang M, Xuan D, et al. Leptin promotes monosodium urate crystal-induced inflammation in human and murine models of gout. J Immunol. 2019;202(9):2728–36. https://doi.org/10.4049/jimmunol.1801097.CrossRefPubMed

Yang Q, Zhang Q, Qing Y, Zhou L, Mi Q, Zhou J. miR-155 is dispensable in monosodium urate-induced gouty inflammation in mice. Arthritis Res Ther. 2018;20(1):144.CrossRefPubMedPubMedCentral

Aung T, Myung G, FitzGerald JD. Treatment approaches and adherence to urate-lowering therapy for patients with gout. Patient Prefer Adherence. 2017;11:795–800. https://doi.org/10.2147/PPA.S97927.CrossRefPubMedPubMedCentral

Schlesinger N. The safety of treatment options available for gout. Expert Opin Drug Saf. 2017;16(4):429–36. https://doi.org/10.1080/14740338.2017.1284199.CrossRefPubMed

Bardin T, Richette P. Impact of comorbidities on gout and hyperuricaemia: an update on prevalence and treatment options. BMC Med. 2017;15(1):123. https://doi.org/10.1186/s12916-017-0890-9.CrossRefPubMedPubMedCentral

Mehmood A, Ishaq M, Zhao L, Safdar B, Rehman AU, Munir M, et al. Natural compounds with xanthine oxidase inhibitory activity: a review. Chem Biol Drug Des. 2019;93(4):387–418. https://doi.org/10.1111/cbdd.13437.CrossRefPubMed

10.

Yao R, Geng Z, Mao X, Bao Y, Guo S, Bao L, et al. Tu-Teng-Cao extract alleviates monosodium urate-induced acute gouty arthritis in rats by inhibiting uric acid and inflammation. Evid Based Complement Alternat Med. 2020;2020:3095624.PubMedPubMedCentral

11.

China ECoFo. Flora of China. Beijing: Science Press; 1996.

12.

Commission CP. Pharmacopoeia of the People’s republic of China. Beijing: China medical science press; 2015.

13.

He J, Liu Y, Kang Y, Yang P, Wang Y, Guo J, et al. Identification of alkaloids in Stephania hainanensis by liquid chromatography coupled with quadrupole time-of-flight mass spectrometry. Phytochem Anal. 2016;27(3–4):206–16. https://doi.org/10.1002/pca.2618.CrossRefPubMed

14.

Semwal DK, Badoni R, Semwal R, Kothiyal SK, Singh GJ, Rawat U. The genus Stephania (Menispermaceae): chemical and pharmacological perspectives. J Ethnopharmacol. 2010;132(2):369–83. https://doi.org/10.1016/j.jep.2010.08.047.CrossRefPubMed

15.

M. C, Zhu Y, Dong Z, Zhao Y, Yang J. Analgesic and anti-inflammatory effects of total alkaloids from Stephania hainanensis in Hainan and it's acute toxicity. China Trop Med. 2011;11(6):719–21.

16.

Lee YM, Shon EJ, Kim OS, Kim DS. Effects of Mollugo pentaphylla extract on monosodium urate crystal-induced gouty arthritis in mice. BMC Complement Altern Med. 2017;17(1):447. https://doi.org/10.1186/s12906-017-1955-1.CrossRefPubMedPubMedCentral

17.

Mariotte A, De Cauwer A, Po C, Abou-Faycal C, Pichot A, Paul N, et al. A mouse model of MSU-induced acute inflammation in vivo suggests imiquimod-dependent targeting of Il-1beta as relevant therapy for gout patients. Theranostics. 2020;10(5):2158–71. https://doi.org/10.7150/thno.40650.CrossRefPubMedPubMedCentral

18.

Dalbeth N, Choi HK, Joosten LAB, Khanna PP, Matsuo H, Perez-Ruiz F, et al. Gout. Nat Rev Dis Prime. 2019;5(1):69. https://doi.org/10.1038/s41572-019-0115-y.CrossRef

19.

Vedder D, Gerritsen M, Duvvuri B, van Vollenhoven RF, Nurmohamed MT, Lood C. Neutrophil activation identifies patients with active polyarticular gout. Arthritis Res Ther. 2020;22(1):148. https://doi.org/10.1186/s13075-020-02244-6.CrossRefPubMedPubMedCentral

20.

Yokose K, Sato S, Asano T, Yashiro M, Kobayashi H, Watanabe H, et al. TNF-alpha potentiates uric acid-induced interleukin-1beta (IL-1beta) secretion in human neutrophils. Mod Rheumatol. 2018;28(3):513–7. https://doi.org/10.1080/14397595.2017.1369924.CrossRefPubMed

21.

Yin C, Liu B, Wang P, Li X, Li Y, Zheng X, et al. Eucalyptol alleviates inflammation and pain responses in a mouse model of gout arthritis. Br J Pharmacol. 2020;177(9):2042–57. https://doi.org/10.1111/bph.14967.CrossRefPubMedPubMedCentral

22.

Song N, Li T. Regulation of NLRP3 Inflammasome by phosphorylation. Front Immunol. 2018;9:2305. https://doi.org/10.3389/fimmu.2018.02305.CrossRefPubMedPubMedCentral

23.

Chung YH, Kim DH, Lee WW. Monosodium urate crystal-induced pro-interleukin-1beta production is post-transcriptionally regulated via the p38 signaling pathway in human monocytes. Sci Rep. 2016;6(1):34533. https://doi.org/10.1038/srep34533.CrossRefPubMedPubMedCentral

24.

Martinon F, Petrilli V, Mayor A, Tardivel A, Tschopp J. Gout-associated uric acid crystals activate the NALP3 inflammasome. Nature. 2006;440(7081):237–41. https://doi.org/10.1038/nature04516.CrossRefPubMed

25.

Kingsbury SR, Conaghan PG, McDermott MF. The role of the NLRP3 inflammasome in gout. J Inflamm Res. 2011;4:39–49. https://doi.org/10.2147/JIR.S11330.CrossRefPubMedPubMedCentral

26.

MN C, Z D, Y Z, GB C. Qualitative and quantitative study of Stephania hainanensis H. S. Lo et Y. Tsoong. Chin J Pharm Anal. 2012;32(1):116–9.

27.

Li S, Liu X, Chen X, Bi L. Research Progress on anti-inflammatory effects and mechanisms of alkaloids from Chinese medical herbs. Evid Based Complement Altern Med. 2020;2020:1303524.

28.

Amaral FA, Costa VV, Tavares LD, Sachs D, Coelho FM, Fagundes CT, et al. NLRP3 inflammasome-mediated neutrophil recruitment and hypernociception depend on leukotriene B (4) in a murine model of gout. Arthritis Rheum. 2012;64(2):474–84. https://doi.org/10.1002/art.33355.CrossRefPubMed

29.

Joosten LA, Netea MG, Mylona E, Koenders MI, Malireddi RK, Oosting M, et al. Engagement of fatty acids with toll-like receptor 2 drives interleukin-1beta production via the ASC/caspase 1 pathway in monosodium urate monohydrate crystal-induced gouty arthritis. Arthritis Rheum. 2010;62(11):3237–48. https://doi.org/10.1002/art.27667.CrossRefPubMedPubMedCentral

30.

Reber LL, Marichal T, Sokolove J, Starkl P, Gaudenzio N, Iwakura Y, et al. Contribution of mast cell-derived interleukin-1beta to uric acid crystal-induced acute arthritis in mice. Arthritis Rheumatol. 2014;66(10):2881–91. https://doi.org/10.1002/art.38747.CrossRefPubMedPubMedCentral

Title: Effects of Stephania hainanensis alkaloids on MSU-induced acute gouty arthritis in mice
Authors: Hao-fei Fan
Xing-yue Fang
Hao-lin Wu
Yi-qian Xu
Li-chong Gong
Dao-rui Yu
Hao Jia
Xiao-liang Tang
Qi-bing Liu
Publication date: 01-12-2021
Publisher: BioMed Central
Keywords: Colchicine
Alkaloids
Alkaloids
Arthritis
Cytokines
Published in: BMC Complementary Medicine and Therapies / Issue 1/2021
Electronic ISSN: 2662-7671
DOI: https://doi.org/10.1186/s12906-021-03364-5

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Effects of Stephania hainanensis alkaloids on MSU-induced acute gouty arthritis in mice

Abstract

Background

Methods

Results

Conclusions

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

Please log in to get access to this content

Other articles of this Issue 1/2021

Echinacea purpurea (L.) Moench treatment of monocytes promotes tonic interferon signaling, increased innate immunity gene expression and DNA repeat hypermethylated silencing of endogenous retroviral sequences

Synergistic antifungal evaluation of over-the-counter antifungal creams with turmeric essential oil or Aloe vera gel against pathogenic fungi

The antioxidant and anti-inflammatory effects of Carica Papaya Linn. seeds extract on CCl4-induced liver injury in male rats

Correction to: Hepatoprotective effect of silymarin on fructose induced nonalcoholic fatty liver disease in male albino wistar rats

Acculturation and use of traditional medicine among African migrant women in Sydney: a mixed method study

Neuroprotective potentials of selected natural edible oils using enzyme inhibitory, kinetic and simulation approaches