<br>鳕鱼源肽的吸收和转运特性及其对去势小鼠骨丢失的保护作用,Food & Function

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鳕鱼源肽的吸收和转运特性及其对去势小鼠骨丢失的保护作用
Food & Function ( IF 5.1 ) Pub Date : 2024-03-11 , DOI: 10.1039/d3fo04819e
Meilian Yang ₁ , Shengpeng Su ₂ , Shuzhen Cheng ₁ , Zhenyu Wang ₁ , Ming Du ₁

Affiliation

从鳕鱼中鉴定出一种潜在的成骨十四肽，其氨基酸序列为 GETNPADSKPGSIR (P-GM-2)。本研究旨在利用 Caco-2/HT29-MTX 共培养单层阐明其吸收和运输特性，并利用卵巢切除小鼠模型评估其成骨活性。结果表明，P-GM-2可以通过TJ介导的被动旁细胞途径完整地跨越Caco-2/HT29-MTX共培养屏障，表观渗透系数为4.02 × 10 ^-6 cm s ^-1 。药代动力学结果显示，口服给药5分钟内即可在小鼠血液中检测到P-GM-2，并在30分钟时达到最大浓度。此外，连续三个月口服P-GM-2被发现可以有效调节骨转换关键标志物的分泌，从而防止卵巢切除小鼠的骨微结构退化和骨丢失。重要的是，没有观察到与治疗相关的毒性。总而言之，这些发现为 P-GM-2 的吸收和运输机制提供了宝贵的见解，突出了其作为预防骨质疏松症的安全有效活性成分的潜力。

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Absorption and transport properties of a codfish-derived peptide and its protective effect on bone loss in ovariectomized mice

A potential osteogenic tetradecapeptide with the amino acid sequence GETNPADSKPGSIR (P-GM-2) was identified from Gadus morhua. The present study aimed to elucidate its absorption and transport properties using Caco-2/HT29-MTX co-culture monolayers and to evaluate its osteogenic activity using an ovariectomized mouse model. The results showed that P-GM-2 could cross Caco-2/HT29-MTX co-culture barriers intactly with an apparent permeability coefficient of 4.02 × 10⁻⁶ cm s⁻¹ via the TJ-mediated passive paracellular pathway. Pharmacokinetic results revealed that P-GM-2 was detectable in the blood of mice within 5 min of oral administration and reached its maximum concentration at 30 min. Furthermore, the oral administration of P-GM-2 for a duration of three months has been found to effectively regulate the secretion of key markers of bone turnover, thereby protecting against bone microstructure degeneration and bone loss in ovariectomized mice. Importantly, no toxicity related to the treatment was observed. Taken together, these findings offer valuable insights into the absorption and transport mechanisms of P-GM-2, highlighting its potential as a safe and effective active ingredient for preventing osteoporosis.

更新日期：2024-03-11

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