Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Comparative Study
. 2020 Dec;58(1):1131-1139.
doi: 10.1080/13880209.2020.1844761.

Combination therapy of ginsenoside compound K and methotrexate was efficient in elimination of anaemia and reduction of disease activity in adjuvant-induced arthritis rats

Jingyu Chen  1 , Wu Wang  1 , Mengya Jiang  1 , Mei Yang  1 , Wei Wei  1
Affiliations
Comparative Study

Combination therapy of ginsenoside compound K and methotrexate was efficient in elimination of anaemia and reduction of disease activity in adjuvant-induced arthritis rats

Jingyu Chen et al. Pharm Biol. 2020 Dec.

Abstract

Context: Ginsenoside compound K (CK) has anti-inflammatory, immunoregulatory, and myelosuppressive protective effects. Methotrexate (MTX) is widely used in combination therapy for rheumatoid arthritis (RA).

Objective: To evaluate the effects of combination therapy of CK and MTX on anaemia and anti-arthritis in adjuvant-induced arthritis (AA) rats.

Materials and methods: AA was induced in rats by Complete Freund's adjuvant, and divided into five groups (n = 10): normal, AA, CK 80 mg/kg, combination therapy (80 mg/kg CK combined with 0.5 mg/kg MTX), and MTX 0.5 mg/kg. From day 12, CK (once a day for 15 days) or MTX (once every 3 days, five times) were intragastrically administered.

Results: Combination therapy showed increased haemoglobin to 148.5 ± 10.1 g/L compared with AA (129.8 ± 11.7 g/L) and MTX (128.8 ± 18.4 g/L), and decreased reticulocytes in peripheral blood to 4.9 ± 1.1% compared with MTX (9.3 ± 3.3%). In combination therapy group, paw swelling decreased to 5.6 ± 4.3 mL compared with CK (9.4 ± 3.9 mL) and MTX (13.5 ± 7.4 mL), and swollen joint count decreased to 1.4 ± 0.8 compared with CK (2.1 ± 1.0) and MTX (2.4 ± 1.2) at day 24. Combination therapy showed decreased IL-6 to 25.1 ± 17.2 pg/mL compared with MTX (44.9 ± 4.8 pg/mL), and decreased IL-17 to 5.8 ± 3.9 pg/mL compared with MTX (10.7 ± 4.2 pg/mL).

Conclusion: The anti-anaemia effect of CK deserves further study, and CK can be a candidate effective drug for combined treatment in RA with anaemia.

Keywords: Rheumatoid arthritis; anaemia of inflammation; natural products of ginsenosides.

PubMed Disclaimer

Conflict of interest statement

No potential conflict of interest was reported by the author(s).

Figures

Figure 1.
Figure 1.
Combined effects of CK and MTX on arthritis signs in AA rats. (A) global assessment; (B) arthritis index; (C) swollen joint counts; (D) paw swelling; Data are expressed as the mean ± SD, with 10 animals in each group. ##p < 0.01 vs. normal; *p < 0.05; **p < 0.01 vs. AA; ▽p < 0.05 vs. MTX; ●p < 0.05; ●●p < 0.01 vs. CK.
Figure 2.
Figure 2.
Combined effects of CK and MTX on joint erosion and FLS function in AA rats. (A) Photomicrographs of the rat joint (original magnification × 100, haematoxylin and eosin stain). (B) synoviocyte proliferation; (C) inflammatory cellular infiltration; (D) pannus formation; (E) bone erosion. (F) FLS proliferation; (G) the secretion of OPG from FLS; (H) the secretion of RANKL from FLS; (I) the secretion of TNF-α from FLS. Data are expressed as the mean ± SD. ##p < 0.01 vs. Normal; *p < 0.05; **p < 0.01 vs. AA. Data are expressed as the mean ± SD, with 6 animals in each group.
Figure 3.
Figure 3.
Combined effects of CK and MTX on erythrocyte and haemoglobin in AA rats. (A) number of peripheral blood erythrocyte; (B) haemoglobin concentration in peripheral blood; (C) number of reticulocytes in peripheral blood; (D) proportion of reticulocytes in peripheral blood. Data are expressed as the mean ± SD, with 6 animals in each group. ##p＜0.01 vs. Normal; *p＜0.05; **p＜0.01 vs. AA; ▽p＜0.05; ▽▽p＜0.05 vs. MTX.
Figure 4.
Figure 4.
Combined effects ofCK and MTX on spleen histopathology and proliferation of T cells and B cells. (A) Photomicrographs of the rat spleen (original magnification × 100, haematoxylin and eosin stain), (B) Lymphoid follicles, (C) Marginal zone, (D) the periarteriolar lymphoid sheaths, (E) T cell proliferation, (F) B cell proliferation. Data are expressed as the mean ± SD, with 6 animals in each group, ##p < 0.01 vs. Normal; *p < 0.05; **p < 0.01 vs. AA.
Figure 5.
Figure 5.
Combined effects of CK and MTX on pro-inflammatory cytokine in AA rats. pro-inflammatory cytokine in serum (A) IL-1β, (B) IL-2, (C) IL-6, (D) IL-17, (E) TNF-α, (F) IFN-γ, (G) PGE-2; (H) the secretion of PGE2 from macrophage; (I) the secretion of IL-17 from macrophage. Data are expressed as the mean ± SD, with 6 animals in each group. #p＜0.05; ##p＜0.01 vs. Normal; *p＜0.05; **p＜0.01 vs. AA; ▽p＜0.05 vs. MTX.
See this image and copyright information in PMC

References

    1. Alves CH, Farrell E, Vis M, Colin EM, Lubberts E.. 2016. Animal models of bone loss in inflammatory arthritis: from cytokines in the bench to novel treatments for bone loss in the bedside-a comprehensive review. Clin Rev Allergy Immunol. 51(1):27–47. - PMC - PubMed
    1. Chen J, Wang Q, Wu H, Liu K, Wu Y, Chang Y, Wei W.. 2016. The ginsenoside metabolite compound K exerts its anti-inflammatory activity by down regulating memory B cell in adjuvant-induced arthritis. Pharm Biol. 54(7):1280–1288. - PubMed
    1. Chen J, Wang Y, Wu H, Yan S, Chang Y, Wei W.. 2018. A modified compound from paeoniflorin, CP-25, suppressed immune responses and synovium inflammation in collagen-induced arthritis mice. Front Pharmacol. 9:563. - PMC - PubMed
    1. Chen J, Wu H, Wang Q, Chang Y, Liu K, Song S, Yuan P, Fu J, Sun W, Huang Q, et al. 2014. Ginsenoside metabolite compound k alleviates adjuvant-induced arthritis by suppressing T cell activation. Inflammation. 37(5):1608–1615. - PubMed
    1. Chen J, Wu H, Wang Q, Chang Y, Liu K, Wei W.. 2015. Ginsenoside metabolite compound K suppresses T-cell priming via modulation of dendritic cell trafficking and costimulatory signals, resulting in alleviation of collagen-induced arthritis. J Pharmacol Exp Ther. 353(1):71–79. - PubMed

Publication types

MeSH terms