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. 2024 Apr 17;29(8):1830.
doi: 10.3390/molecules29081830.

Onosma bracteatum Wall Aqueous-Ethanolic Extract Suppresses Complete Freund's Adjuvant-Induced Arthritis in Rats via Regulation of TNF-α, IL-6, and C-Reactive Protein

Farah Zafar  1 , Ghazala Shaheen  1 , Hafiz Muhammad Asif  1 , Mohd Farhan  2   3 , Ghazala Muteeb  4 , Mohammad Aatif  5
Affiliations

Onosma bracteatum Wall Aqueous-Ethanolic Extract Suppresses Complete Freund's Adjuvant-Induced Arthritis in Rats via Regulation of TNF-α, IL-6, and C-Reactive Protein

Farah Zafar et al. Molecules. .

Abstract

Onosma bracteatum Wall (O. bracteatum) has been used traditionally for the management of arthritis; however, its therapeutic potential warrants further investigation. This study aimed to evaluate the anti-arthritic effects of the aqueous-ethanolic extract of O. bracteatum leaves (AeOB) in a rat model of complete Freund's adjuvant (CFA)-induced arthritis. Rats were treated with AeOB (250, 500, and 750 mg/kg), indomethacin (10 mg/kg), or a vehicle control from days 8 to 28 post-CFA injection. Arthritic score, paw diameter, and body weight were monitored at regular intervals. X-ray radiographs and histopathological analysis were performed to assess arthritic severity. Inflammatory cytokines tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and C-reactive protein (CRP) were quantified by qPCR and icromatography. Phytochemical analysis of AeOB revealed alkaloids, flavonoids, phenols, tannins, Saponins, and glycosides. AeOB also exhibited antioxidant potential with an IC50 of 73.22 µg/mL in a DPPH assay. AeOB and diclofenac exhibited anti-inflammatory and anti-arthritic activities. Rats treated with AeOB at 750 mg/kg and indomethacin showed significantly reduced arthritic symptoms and joint inflammation versus the CFA control. The AeOB treatment downregulated TNF-α and IL-6 and decreased CRP levels compared with arthritic rats. Radiography and histopathology also showed improved prognosis. These findings demonstrate the anti-arthritic potential of AeOB leaves.

Keywords: CFA; Onosma bracteatum wall; arthritis; inflammatory mediators; qRT-PCR.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
GC-MS chromatogram of aqueous–ethanolic extract of AeOB.
Figure 2
Figure 2
(A). Antioxidant potential of AeOB in DPPH assay. * shows p value is significant. Values shown are mean ± SD, n = 3. (B). Antioxidant potential of ascorbic acid in DPPH assay. Values shown are mean ± SD, n = 3.
Figure 3
Figure 3
(A). IC50 of AeOB in DPPH assay. Values shown are mean ± SD in triplicate (n = 3). (B). IC50 of ascorbic acid (standard) in DPPH assay. Solid and dash lines are the trend line that provides a visual representation of the concentration-response relationship and are essential for determining the potency, efficacy, and mechanism of action of compounds in pharmacological studies.
Figure 4
Figure 4
Percent inhibition by LOX inhibitory assay. * The mean difference is significant at the p ≤ 0.05 level. One-way ANOVA followed by LSD post hoc test was applied to check statistical significance.
Figure 5
Figure 5
Percent inhibition by HRBC membrane stabilization method. * The mean difference is significant at the p ≤ 0.05 level. One-way ANOVA followed by LSD post hoc test was applied to check statistical significance.
Figure 6
Figure 6
Percent inhibition by protein denaturation method. * The mean difference is significant at the p ≤ 0.05 level. One-way ANOVA followed by LSD post hoc test was applied to check statistical significance.
Figure 7
Figure 7
Visual illustration of CFA-induced rat paw on the 28th day: (A) Group-I (normal), (B) Group-II (arthritic control), (C) Group-III (standard), (D) Group-IV (AeOB, 250 mg/kg), (E) Group-V (AeOB, 500 mg/kg), and (F) Group-VI (AeOB, 750 mg/kg).
Figure 8
Figure 8
Reduction in paw diameter in different treatment groups compared with Group-II. Values are mean ± SD for n = 6. Stars indicate a comparison of Group-II with the treatment groups. At the * p ≤ 0.05 and *** p ≤ 0.001 levels, the mean difference is significant.
Figure 9
Figure 9
Reduction in arthritic score of different treatment groups compared with Group-II. Values are mean ± SD for n = 6. Stars indicate a comparison of Group-III and Group-VI with Group-II, respectively. The *** shows p ≤ 0.001, the mean difference is significant.
Figure 10
Figure 10
Paw withdrawal latency of different treatment groups compared with Group-II. Values are mean ± SD for n = 6. Stars indicate a comparison of Group-II with the other treatment groups. At the *** shows p ≤ 0.001 levels, the mean difference is significant.
Figure 11
Figure 11
X-ray of CFA-induced rat paws: (a) Group-I (normal), (b) Group-II (arthritic control), (c) Group-III (standard), (d) Group-IV (AeOB, 250 mg/kg), (e) Group-V (AeOB, 500 mg/kg), and (f) Group-VI (AeOB 750 mg/kg) on day 28.
Figure 12
Figure 12
Values are mean ± SD and n = 6 for body weights in CFA-induced arthritic rats, *** = p ≤ 0.001. Stars indicate a comparison of the treatment groups with Group-I. At the *** p ≤ 0.001 level, the mean difference is significant.
Figure 13
Figure 13
Values are mean ± SD and n = 6 for biochemical and hematological parameters in CFA-induced arthritic rats, where * = p ≤ 0.05, *** = p ≤ 0.001. Stars indicate a comparison of the arthritic control group with the other treatment groups.
Figure 14
Figure 14
Microscopic evaluation at ×10 of CFA-induced rat paws: (a) Group-I (normal), (b) Group-II (arthritic control), (c) Group-III (standard), (d) Group-IV (AeOB, 250 mg/kg), (e) Group-V (AeOB, 500 mg/kg), and (f) Group-VI (AeOB, 750 mg/kg) on day 28 of treatment.
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