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Background <p>Ulcerative colitis (UC) is the most common type of inflammatory bowel disease (IBD) whose pathogenesis may involve inflammation, oxidative stress, apoptosis and fibrosis. The aim of this study is to ameliorate UC pathogenic mechanisms by using perindopril (PER; 2&#xa0;mg/kg/day), an antihypertensive drug acting by inhibition of angiotensin-converting enzyme, and/or α-pinene (APN; 50&#xa0;mg/kg/day), a naturally occurring volatile organic compound known for its anti-inflammatory and antioxidant effects, in comparison with the traditional treatment sulfasalazine (SSZ; 100&#xa0;mg/kg/day) in acetic acid-induced UC in rats.</p> Results <p>The results showed that PER and/or APN improved UC macroscopic and microscopic lesions, while functionally decreasing the disease activity index. PER and/or APN also improved the oxidative status by decreasing malondialdehyde and nitric oxide while increasing reduced glutathione in UC-induced colons. Compared to UC group, animals treated with SSZ, PER, APN and PER + APN had increased levels of the anti-inflammatory cytokine IL-10 by 3.0, 1.9, 2.3 and 3.8 folds, respectively. Furthermore, compared to UC group, JAK-2 was declined by 51%, 39.2%, 42.8% and 60.7% and p-STAT3/STAT3 ratio was decreased by 41.4%, 46.5%, 50.9% and 58.6%, while SOCS3 levels were increased by 2.8, 2.0, 2.2 and 3.4 folds in SSZ, PER, APN and PER + APN groups, respectively. In addition, the pro-fibrotic marker MMP-9 was decreased by 51.7%, 58.2%, 55.1% and 66.13% and the pro-apoptotic markers also were decreased by 51.9%, 51.6%, 55.8% and 68.8% for c-caspase 3 and 47.7%, 53.8%, 54% and 67.6% for cytochrome C in SSZ, PER, APN and PER + APN groups, respectively. For MIR-98-5p, a microRNA known to have a role in IBD, it was decreased compared to UC group by 61.6%, 47.2%, 52.1% and 74% in SSZ, PER, APN and PER + APN groups, respectively.</p> Conclusion <p>In conclusion, to the best of our knowledge, this is the first study to demonstrate that PER and APN can modulate the JAK-STAT3-SOCS3 signaling axis and MIR-98-5p in UC model, to levels comparable to the traditional therapy with SSZ, and can be considered novel modulators of JAK-2/STAT3/SOCS3 and miR-98-5p in colon.</p> Graphical abstract <p></p>

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Perindopril and/or α‑pinene mitigate acetic acid-induced ulcerative colitis via regulation of JAK/STAT3/SOCS3 axis and miR-98-5p expression in rats

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年11月17日

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  • Basma M. A. Mohamed,
  • Mai A. Abd El Fattah,
  • Sara A. El Wakeel

摘要

Background

Ulcerative colitis (UC) is the most common type of inflammatory bowel disease (IBD) whose pathogenesis may involve inflammation, oxidative stress, apoptosis and fibrosis. The aim of this study is to ameliorate UC pathogenic mechanisms by using perindopril (PER; 2 mg/kg/day), an antihypertensive drug acting by inhibition of angiotensin-converting enzyme, and/or α-pinene (APN; 50 mg/kg/day), a naturally occurring volatile organic compound known for its anti-inflammatory and antioxidant effects, in comparison with the traditional treatment sulfasalazine (SSZ; 100 mg/kg/day) in acetic acid-induced UC in rats.

Results

The results showed that PER and/or APN improved UC macroscopic and microscopic lesions, while functionally decreasing the disease activity index. PER and/or APN also improved the oxidative status by decreasing malondialdehyde and nitric oxide while increasing reduced glutathione in UC-induced colons. Compared to UC group, animals treated with SSZ, PER, APN and PER + APN had increased levels of the anti-inflammatory cytokine IL-10 by 3.0, 1.9, 2.3 and 3.8 folds, respectively. Furthermore, compared to UC group, JAK-2 was declined by 51%, 39.2%, 42.8% and 60.7% and p-STAT3/STAT3 ratio was decreased by 41.4%, 46.5%, 50.9% and 58.6%, while SOCS3 levels were increased by 2.8, 2.0, 2.2 and 3.4 folds in SSZ, PER, APN and PER + APN groups, respectively. In addition, the pro-fibrotic marker MMP-9 was decreased by 51.7%, 58.2%, 55.1% and 66.13% and the pro-apoptotic markers also were decreased by 51.9%, 51.6%, 55.8% and 68.8% for c-caspase 3 and 47.7%, 53.8%, 54% and 67.6% for cytochrome C in SSZ, PER, APN and PER + APN groups, respectively. For MIR-98-5p, a microRNA known to have a role in IBD, it was decreased compared to UC group by 61.6%, 47.2%, 52.1% and 74% in SSZ, PER, APN and PER + APN groups, respectively.

Conclusion

In conclusion, to the best of our knowledge, this is the first study to demonstrate that PER and APN can modulate the JAK-STAT3-SOCS3 signaling axis and MIR-98-5p in UC model, to levels comparable to the traditional therapy with SSZ, and can be considered novel modulators of JAK-2/STAT3/SOCS3 and miR-98-5p in colon.

Graphical abstract