Effect of a nutraceutical drug in COPD condition: A pilot study of in vitro, in vivo and Clinical Trial

Background: Oxidative stress-mediated mitochondrial dysfunction is a key determinant of epithelial injury in COPD patients. Mitochondrial dysfunction as a drug target for COPD treatment is relatively under-explored. Objective: This study aimed to investigate the therapeutic potential of FDA-approved mitochondria-targeted antioxidant and neutraceutical, pyrroloquinoline quinone (PQQ) in COPD conditions. Methods: The therapeutic benefits of PQQ were evaluated in cigarette smoke extract (CSE) treated bronchial epithelial cells by examining epithelial cell integrity. Further, the effect of PQQ was evaluated in the mice model of COPD by giving PQQ orally. Finally, an open-labeled randomized clinical trial (RCT) was performed at the outpatient department of AIIMS, New Delhi. One group received standard therapy and the other received PQQ supplement along with standard therapy. The primary endpoint was the mean change from baseline in the SGRQ scores at the end of 12 weeks. Results: In CSE-treated epithelial cells, treatment with PQQ was found to restore the mitochondrial function, and reduce epithelial injury. Naïve mice treated with cigarette and biomass smoke exhibited inflammation and emphysematous changes. PQQ-mediated restoration of mitochondrial homeostasis attenuated smoke-induced emphysematous changes. In the case of RCT, PQQ treatment was associated with significant improvement in total SGRQ score after 12 weeks. Conclusions: Our results suggest the benefits of a mitochondrial-specific antioxidant therapy in COPD conditions. Hence the anti-inflammatory nature of mitochondria-targeted neutraceuticals could be a potential add-on treatment in patients with COPD.