A novel glycoglycerolipid from Holotrichia diomphalia Bates: Structure characteristics and protective effect against DNA damage

• Published in: International journal of biological macromolecules 2024-06, Vol.271 (Pt 1), p.132594, Article 132594
• Main Authors: Liu, Wen-Juan, Qiao, Yu-He, Wang, Shuyao, Wang, Yu-Bo, Nong, Qiu-Na, Xiao, Qianhan, Bai, Hong-Xin, Wu, Ke-Han, Chen, Jie, Li, Xiao-Qiang, Wang, Yu-Fan, Tan, Jin, Cao, Wei
• Format: Article
• Language: English
• Subjects: Animals; Antioxidants - chemistry; Antioxidants - pharmacology; Coleoptera; Cricetulus; DNA damage; DNA Damage - drug effects; Fatty acid; Glycolipids - chemistry; Glycolipids - pharmacology; Holotrichia diomphalia; Polysaccharide; Polysaccharides - chemistry; Polysaccharides - isolation & purification; Polysaccharides - pharmacology; Reactive Oxygen Species - metabolism; Structure
• ISSN: 0141-8130; 1879-0003; 1879-0003
• DOI: 10.1016/j.ijbiomac.2024.132594

A lipidated polysaccharide, HDPS-2II, was isolated from the dried larva of Holotrichia diomphalia, which is used in traditional Chinese medicine. The molecular weight of HDPS-2II was 5.9 kDa, which contained a polysaccharide backbone of →4)-β-Manp-(1 → 4,6)-β-Manp-(1 → [6)-α-Glcp-(1]n → 6)-α-Glcp→ with the side chain α-Glcp-(6 → 1)-α-Glcp-(6 → linked to the C-4 of β-1,4,6-Manp and four types of lipid chains including 4-(4-methyl-2-(methylamino)pentanamido)pentanoic acid, 5-(3-(tert-butyl)phenoxy)hexan-2-ol, N-(3-methyl-5-oxopentan-2-yl)palmitamide, and N-(5-amino-3-methyl-5-oxopentan-2-yl)stearamide. The lipid chains were linked to C-1 of terminal α-1,6-Glcp in carbohydrate chain through diacyl-glycerol. HDPS-2II exhibited DNA protective effects and antioxidative activity on H2O2- or adriamycin (ADM)-induced Chinese hamster lung cells. Furthermore, HDPS-2II significantly ameliorated chromosome aberrations and the accumulation of reactive oxygen species (ROS), reduced γ-H2AX signaling and the expressions of NADPH oxidase (NOX)2, NOX4, P22phox, and P47phox in ADM-induced cardiomyocytes. Mechanistically, HDPS-2II suppressed ADM-induced up-regulation of NOX2 and NOX4 in cardiomyocytes, but not in NOX2 or NOX4 knocked-down cardiomyocytes, indicating that HDPS-2II could relieve intracellular DNA damage by regulating NOX2/NOX4 signaling. These findings demonstrate that HDPS-2II is a new potential DNA protective agent.