Systematic Review on Future Therapeutic Targeting SIRT-1, NRF2, HO-1 Pathway with Natural and Synthetic Molecules in Management of Asthma

Asthma is a persistent inflammatory respiratory condition that entails airway hyperreactivity, hypersecretion of mucus, obstructed airflow, and airway remodeling. One of the mechanisms of asthma development is oxidative stress, since the excessive production of ROS (reactive oxygen species) leads to exacerbation of inflammation and structural damage to airway epithelium. Currently, one of the most promising therapeutic targets is the SIRT1/NRF2/HO-1 signaling pathway, which is responsible for the regulation of oxidative stress and inflammation. The present systematic review discusses the opportunities for treatment of asthma associated with the modulation of the SIRT1/NRF2/HO-1 signaling pathway. Bioactive natural substances such as resveratrol, curcumin, quercetin, sulforaphane, berberine, and carnosic acid show substantial antioxidant, anti-inflammatory, and cytoprotective activities by upregulation of SIRT1 and NRF2 pathways resulting in induction of HO-1 and prevention of oxidative stress. Unfortunately, their clinical use is hindered by low bioavailability and instability due to rapid metabolism and unfavorable pharmacokinetics. Synthetic agents like SRT1720, SRT2104, dimethyl fumarate (DMF), bardoxolone methyl, and others as NRF2 agonists provide higher stability and efficacy in comparison with natural counterparts and can be considered as promising candidates for further translational studies and clinical application. Future directions include nanotechnologies for targeted drug delivery and combinatorial therapy. While several preclinical studies have yielded positive outcomes, clinical translation has been hindered by variations in experimental methods, disparities in dosage regimes, and a lack of well-conducted human clinical trials. In summary, modulation of the SIRT1/NRF2/HO-1 signaling pathway is an innovative and attractive approach towards achieving a disease-modifying treatment for asthma. Clinical research is required to determine the safety and efficacy of natural and artificial molecules in the modulation of this pathway in asthma therapy.

Asthma, SIRT1, NRF2, HO-1, Oxidative Stress, Natural and Synthetic Molecules

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