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Research Article
Prophylactic or therapeutic administration of Holarrhena floribunda hydro ethanol extract suppresses Complete Freund’s Adjuvant-induced arthritis in Sprague-Dawley rats
Daniel Oduro-Mensah
Department of Biochemistry, Cell and Molecular Biology, School of Biological Sciences, University of Ghana
Corresponding Author
ORCiD: https://orcid.org/0000-0003-4492-2202
License:
This work is licensed under a CC BY 4.0 License. Read Full License
Declarations:
Declarations
- This study involved the use of non-human vertebrates.
- The author has confirmed that all appropriate ethical guidelines for the handling and use of animals in research have been followed and details of the oversight board have been included in the text.
- The author has confirmed that a statement listing potential conflicts of interest or lack thereof is included in the text.
Ethnopharmacological relevance In Ghanaian folk medicine, Holarrhena floribunda has anecdotal use for the treatment of inflammatory conditions. A hydro ethanol extract of the stem bark has previously been shown to be effective in the management of acute inflammation and anaphylaxis in rodents.
Aim of the study This study was aimed at evaluating the usefulness of H. floribunda stem bark hydro ethanol extract (HFE) for the management of chronic inflammation in a murine model.
Materials and Methods Anti-arthritic effect of the extract was evaluated using Complete Freund’s Adjuvant-induced arthritis in male Sprague-Dawley rats. Using both prophylactic and therapeutic treatment models, parameters assessed included oedema, serology of inflammatory response, radiology, bone tissue histology and haematology. Data were analysed by ANOVA followed by Tukey’s multiple comparisons post hoc test.
Results HFE at 50–500 mg/kg dose-dependently [P ≥ 0.0354 (prophylactic) and P ≥ 0.0001 (therapeutic)] inhibited swelling of the injected paw upon prophylactic [≤ 81.26 % (P < 0.0001)] or therapeutic [≤ 67.92 % (P < 0.01)] administration — and prevented spread of arthritis to the contralateral paw. Inflammation alleviation activity of HFE was further demonstrated by decrease in arthritis score, radiologic score and erythrocyte sedimentation rate. HFE at all doses significantly reduced serum IL-1α (P < 0.0197), and 500 mg/kg HFE reduced serum IL-6 (P = 0.0032). In contrast, serum concentrations of IL-10, protein kinase A and cyclic adenosine monophosphate were enhanced (P ≤ 0.0436). HFE consistently showed better prophylactic activity than when administered therapeutically.
Conclusions The data demonstrate that HFE suppresses CFA-induced arthritis and modulates regulators of inflammation; including IL-1α, -6 and -10 which also play mediatory roles in several immune response pathways. These make HFE a strong candidate for development as an agent for management and modulation of inflammation and the inflammatory response, including immune response-related adverse events such as seen in severe COVID-19.
Keywords
Arthritis, COVID-19, Cytokines, Holarrhena floribunda, Immunomodulation, Inflammation
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This is a list of supplementary files associated with this preprint. Click to download.
- Plate1.jpg
Plate 1: Effect of treatments on adjuvant-induced arthritis in Sprague-Dawley rats. The rats were injected sub plantar with IFA or CFA in the right hind paw. Vehicle, dexamethasone (0.3 mg/kg) or HFE treatment was administered 1 h before arthritis induction and daily thereafter until day 28 in the prophylactic model. In the therapeutic model, treatment was from day 14–28. (A) IFA/non-arthritic control; (B) CFA/arthritic control; (C) Dexamethasone (representative); (D–F) 50–500 mg/kg HFE prophylactic; (G–I) 50–500 mg/kg HFE therapeutic.
- Plate1.jpg
Plate 1: Effect of treatments on adjuvant-induced arthritis in Sprague-Dawley rats. The rats were injected sub plantar with IFA or CFA in the right hind paw. Vehicle, dexamethasone (0.3 mg/kg) or HFE treatment was administered 1 h before arthritis induction and daily thereafter until day 28 in the prophylactic model. In the therapeutic model, treatment was from day 14–28. (A) IFA/non-arthritic control; (B) CFA/arthritic control; (C) Dexamethasone (representative); (D–F) 50–500 mg/kg HFE prophylactic; (G–I) 50–500 mg/kg HFE therapeutic.
- Plate2.jpg
Plate 2: Radiographs of control and arthritic Sprague-Dawley rats. The rats were injected sub plantar with IFA or CFA in the right hind paw. Vehicle, dexamethasone (0.3 mg/kg) or HFE treatment was administered 1 h before arthritis induction and daily thereafter until day 28 in the prophylactic model. In the therapeutic model, treatment was from day 14–28. The rats were euthanized by cervical dislocation and radiographs were captured. (A) IFA/non-arthritic control; (B) CFA/arthritic control; (C) Dexamethasone; (D–F) 50–500 mg/kg HFE prophylactic; (G–I) 50–500 mg/kg HFE therapeutic.
- Plate2.jpg
Plate 2: Radiographs of control and arthritic Sprague-Dawley rats. The rats were injected sub plantar with IFA or CFA in the right hind paw. Vehicle, dexamethasone (0.3 mg/kg) or HFE treatment was administered 1 h before arthritis induction and daily thereafter until day 28 in the prophylactic model. In the therapeutic model, treatment was from day 14–28. The rats were euthanized by cervical dislocation and radiographs were captured. (A) IFA/non-arthritic control; (B) CFA/arthritic control; (C) Dexamethasone; (D–F) 50–500 mg/kg HFE prophylactic; (G–I) 50–500 mg/kg HFE therapeutic.
- Plate3.jpg
Plate 3: Photomicrographs of paw sections of control and arthritic Sprague-Dawley rats. The paw sections were stained with hematoxylin-eosin. (A) Control IFA rats; (B) arthritis (CFA) control rats; (C) 0.3 mg/kg dexamethasone-treated rats; (D–F) 50–500 mg/kg HFE prophylactic; (G–I) 50–500 mg/kg HFE therapeutic. Magnification: ×100.
- Plate3.jpg
Plate 3: Photomicrographs of paw sections of control and arthritic Sprague-Dawley rats. The paw sections were stained with hematoxylin-eosin. (A) Control IFA rats; (B) arthritis (CFA) control rats; (C) 0.3 mg/kg dexamethasone-treated rats; (D–F) 50–500 mg/kg HFE prophylactic; (G–I) 50–500 mg/kg HFE therapeutic. Magnification: ×100.
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Research Article
Prophylactic or therapeutic administration of Holarrhena floribunda hydro ethanol extract suppresses Complete Freund’s Adjuvant-induced arthritis in Sprague-Dawley rats
Daniel Oduro-Mensah
Department of Biochemistry, Cell and Molecular Biology, School of Biological Sciences, University of Ghana
Corresponding Author
ORCiD: https://orcid.org/0000-0003-4492-2202
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
History
CURRENT STATUS: Posted
Version 1
Posted 16 Dec, 2020
No community comments so far
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
License:
This work is licensed under a CC BY 4.0 License. Read Full License
Declarations:
Declarations
- This study involved the use of non-human vertebrates.
- The author has confirmed that all appropriate ethical guidelines for the handling and use of animals in research have been followed and details of the oversight board have been included in the text.
- The author has confirmed that a statement listing potential conflicts of interest or lack thereof is included in the text.
Ethnopharmacological relevance In Ghanaian folk medicine, Holarrhena floribunda has anecdotal use for the treatment of inflammatory conditions. A hydro ethanol extract of the stem bark has previously been shown to be effective in the management of acute inflammation and anaphylaxis in rodents.
Aim of the study This study was aimed at evaluating the usefulness of H. floribunda stem bark hydro ethanol extract (HFE) for the management of chronic inflammation in a murine model.
Materials and Methods Anti-arthritic effect of the extract was evaluated using Complete Freund’s Adjuvant-induced arthritis in male Sprague-Dawley rats. Using both prophylactic and therapeutic treatment models, parameters assessed included oedema, serology of inflammatory response, radiology, bone tissue histology and haematology. Data were analysed by ANOVA followed by Tukey’s multiple comparisons post hoc test.
Results HFE at 50–500 mg/kg dose-dependently [P ≥ 0.0354 (prophylactic) and P ≥ 0.0001 (therapeutic)] inhibited swelling of the injected paw upon prophylactic [≤ 81.26 % (P < 0.0001)] or therapeutic [≤ 67.92 % (P < 0.01)] administration — and prevented spread of arthritis to the contralateral paw. Inflammation alleviation activity of HFE was further demonstrated by decrease in arthritis score, radiologic score and erythrocyte sedimentation rate. HFE at all doses significantly reduced serum IL-1α (P < 0.0197), and 500 mg/kg HFE reduced serum IL-6 (P = 0.0032). In contrast, serum concentrations of IL-10, protein kinase A and cyclic adenosine monophosphate were enhanced (P ≤ 0.0436). HFE consistently showed better prophylactic activity than when administered therapeutically.
Conclusions The data demonstrate that HFE suppresses CFA-induced arthritis and modulates regulators of inflammation; including IL-1α, -6 and -10 which also play mediatory roles in several immune response pathways. These make HFE a strong candidate for development as an agent for management and modulation of inflammation and the inflammatory response, including immune response-related adverse events such as seen in severe COVID-19.
Figure 1
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Figure 2
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Figure 3
Figure 3
Figure 4
Figure 4