<p>Asthma is a complex condition associated with increased morbidity, mortality, healthcare costs, and a diminished quality of life. It is now understood as a heterogeneous disease with various clinical manifestations rather than a single entity. Campesterol, a plant sterol, has demonstrated anti-inflammatory and antioxidant properties in animal models. Allergic asthma was induced in BALB/c mice using ovalbumin through intraperitoneal sensitization on the 1st and 14th days of the study, followed by intranasal challenges from the 15th to the 21st day. The mice were then treated with three different doses of campesterol and the standard drug methylprednisolone for 7&#xa0;days post-intranasal challenge. The mRNA expression levels of IL-4, IL-5, AQP-1, and AQP-5 were assessed using real-time polymerase chain reaction (qPCR). Histopathological analysis of lung tissues was conducted using hematoxylin and eosin (H&amp;E) staining. Differential and total leukocyte counts were measured in bronchoalveolar lavage fluid (BALF) and blood using an automatic hematology analyzer. The data were statistically analyzed using one-way ANOVA and post hoc Tukey’s test. In silico molecular docking was performed to assess the binding affinity and interaction profiles of campesterol with target proteins, including JAK2, TNF-α, and NF-κB, which are involved in inflammatory pathways. Treatment with campesterol led to a reduction in total leukocyte count (TLC) and differential leukocyte count (DLC), as well as suppression of inflammatory cell infiltration. There was a significant decrease in the expression levels of IL-4 and IL-5, while the expression levels of AQP-1 and AQP-5 were significantly increased. Additionally, the lung wet/dry ratio was significantly reduced following campesterol treatment. In summary, the reduction in inflammation may be linked to decreased expression levels of IL-4 and IL-5 expression levels, while the reduction in pulmonary edema may be associated with increased expression levels of aquaporin 1 and aquaporin 5. The molecular docking revealed that campesterol exhibited stronger binding affinity across target proteins. The study suggests that campesterol could serve as an alternative therapy for treating allergic asthma. These findings may contribute to improved patient compliance by reducing inflammation and potentially offering a new avenue for asthma management. The docking results exhibited that campesterol has a stronger and more stable interaction profile with key pro-inflammatory and anti-inflammatory targets.</p>

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Campesterol attenuates airway inflammation in allergic asthma: insights from a murine model and molecular docking analysis

  • Hafsa Abid,
  • Aisha Mobashar,
  • Arham Shabbir,
  • Hossam Kamli,
  • Ammara Saleem,
  • Narmeen Mehmood,
  • Amir Ali,
  • Shoaib Kakar,
  • Mohammed Dauelbait,
  • Amir Bouallegue,
  • Mohammad Khalid,
  • Omar A. Almohammed

摘要

Asthma is a complex condition associated with increased morbidity, mortality, healthcare costs, and a diminished quality of life. It is now understood as a heterogeneous disease with various clinical manifestations rather than a single entity. Campesterol, a plant sterol, has demonstrated anti-inflammatory and antioxidant properties in animal models. Allergic asthma was induced in BALB/c mice using ovalbumin through intraperitoneal sensitization on the 1st and 14th days of the study, followed by intranasal challenges from the 15th to the 21st day. The mice were then treated with three different doses of campesterol and the standard drug methylprednisolone for 7 days post-intranasal challenge. The mRNA expression levels of IL-4, IL-5, AQP-1, and AQP-5 were assessed using real-time polymerase chain reaction (qPCR). Histopathological analysis of lung tissues was conducted using hematoxylin and eosin (H&E) staining. Differential and total leukocyte counts were measured in bronchoalveolar lavage fluid (BALF) and blood using an automatic hematology analyzer. The data were statistically analyzed using one-way ANOVA and post hoc Tukey’s test. In silico molecular docking was performed to assess the binding affinity and interaction profiles of campesterol with target proteins, including JAK2, TNF-α, and NF-κB, which are involved in inflammatory pathways. Treatment with campesterol led to a reduction in total leukocyte count (TLC) and differential leukocyte count (DLC), as well as suppression of inflammatory cell infiltration. There was a significant decrease in the expression levels of IL-4 and IL-5, while the expression levels of AQP-1 and AQP-5 were significantly increased. Additionally, the lung wet/dry ratio was significantly reduced following campesterol treatment. In summary, the reduction in inflammation may be linked to decreased expression levels of IL-4 and IL-5 expression levels, while the reduction in pulmonary edema may be associated with increased expression levels of aquaporin 1 and aquaporin 5. The molecular docking revealed that campesterol exhibited stronger binding affinity across target proteins. The study suggests that campesterol could serve as an alternative therapy for treating allergic asthma. These findings may contribute to improved patient compliance by reducing inflammation and potentially offering a new avenue for asthma management. The docking results exhibited that campesterol has a stronger and more stable interaction profile with key pro-inflammatory and anti-inflammatory targets.