Citation: Fei-Yan Gao, Yan Wu, Ling Yang, Zhong-Yi Ma, Yi Chen, Xiao-Man Mao, Xu-Fei Bian, Pei Tang, Chong Li. Orally delivered berberine derivatives for dual therapy in diabetic complications with MRSA infections[J]. Chinese Chemical Letters, ;2025, 36(4): 109917. doi: 10.1016/j.cclet.2024.109917 shu

Orally delivered berberine derivatives for dual therapy in diabetic complications with MRSA infections

Fei-Yan Gao ^{a, 1} ,
Yan Wu ^{b, 1} ,
Ling Yang ^{a, 1} ,
Zhong-Yi Ma ^a ,
Yi Chen ^c ,
Xiao-Man Mao ^a ,
Xu-Fei Bian ^a ,
Pei Tang ^{c, *,} ,
Chong Li ^{a, *,}

a.
Engineering Research Center of Coptis Development & Utilization, Ministry of Education, College of Pharmaceutical Sciences, Southwest University, Chongqing 400715, China
b.
West China Hospital of Stomatology, Sichuan University, Chengdu 610041, China
c.
Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy, Sichuan University, Chengdu 610041, China

peitang@scu.edu.cn

chongli@swu.edu.cn

Received Date: 3 February 2024
Revised Date: 15 April 2024
Accepted Date: 22 April 2024
Available Online: 22 April 2024

Figures(6)

Diabetes mellitus (DM) is a serious health problem in the world, and infections are common complications in diabetic patients, particularly methicillin-resistant Staphylococcus aureus (MRSA) infections, which substantially increases mortality in patients. In clinical practice, the treatment of diabetic complication-related infections involves multiple issues such as drug resistance when combining antidiabetic drugs with antibiotics. In this study, a series of derivatives were synthesized with alkyl radicals with different chain lengths substituted at the C8 and C12 positions of berberine, with compounds CY1 and CY3 with good antidiabetic and antibacterial activities screened out after identification. Then, oral liposomes (CY1-Lip and CY3-Lip) were prepared, and their particle sizes, stability, and pharmacokinetics were investigated. In acquired mouse models of diabetes, induced with an acute MRSA lung infection, we demonstrate that CY1-Lip and CY3-Lip can effectively reduce levels of fasting blood glucose (FBG), fasting insulin (FINS), and insulin resistance index among diabetic mice with pneumonia, thus exerting their multi-targets effects. Furthermore, both preparations significantly reduced lung MRSA loads and improved lung tissue lesions, reduced high infiltration of M1 macrophages in lung, and suppressed the expression levels of pro-inflammatory factors such as necrosis factor-α (TNF-α) and interleukin-6 (IL-6). This provides new insights into the clinical treatment of diabetes complicated with pulmonary infections.
- 8-Alkyl berberine derivatives,
- Type-2 diabetes mellitus,
- Methicillin-resistant Staphylococcus aureus,
- Lung infections,
- Immunoregulation
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