Lipoic acid-functionalized platycodin D nanocarrier improves mitochondrial dysfunction and reverses diabetes

• Published in: Chemical engineering journal (Lausanne, Switzerland : 1996) Switzerland : 1996), 2024-11, Vol.499, p.156422, Article 156422
• Main Authors: Shen, Qiong, Wang, Wen-Ting, Xing, Qiao-Yue, Bai, Yan, Li, Yan-Fei
• Format: Article
• Language: English
• Subjects: Gut microbiota; Insulin resistance; Mitochondrial dysfunction; Platycodin D; Targeting; Type 2 diabetes mellitus
• ISSN: 1385-8947
• DOI: 10.1016/j.cej.2024.156422

[Display omitted] •Mitochondrial functionalized nanocarriers (PANPs) were prepared by enzymatic reaction for the first time.•Cell experiments have shown that PANPs can effectively target mitochondria and reduce cellular oxidative damage.•Animal experiments have shown that PANPs effectively regulates glucose abnormalities in T2DM mice. The prevalence of metabolic syndrome, particularly type 2 diabetes mellitus (T2DM), is steadily increasing on a global scale. It is widely acknowledged that multi-organ insulin resistance serves as the central pathological mechanism underlying T2DM. Mitochondrial dysfunction is recognized as a significant contributor to insulin resistance, with a focus on maintaining homeostasis and addressing cellular functional impairments. In recent years, the emergence of natural compounds has shed light on the potential of platycodin D (PD) in the realm of diabetes management. However, optimizing its bioavailability and targeted delivery within the intricate gastrointestinal system remains a critical challenge. This study involved the development of PD nanocarriers (PD NPs) through an enzymatic reaction, followed by lipoic acid esterification onto PD NPs to create mitochondrial-functionalized nanocarriers (PA NPs). Cell experiments demonstrated that PA NPs effectively targeted mitochondria and mitigated cellular oxidative damage. In vitro simulations revealed that PA NPs successfully navigated the gastric environment and reached the intestinal tract for controlled release. Animal studies showcased that PA NPs improved islet morphology and function, and its mechanism may be achieved by regulating the GSK3-β/IRS1/AMPK signal pathway cascade. Furthermore, PA NPs modulated the gut microbiota derangement in STZ-induced diabetic mice, driving a healthier state, species evenness, and abundance.