柑橘果胶中的 5-mer低聚半乳糖醛酸(OG DP5)对不同类型人体细胞的抗炎、免疫调节和抗增殖作用。治疗特应性皮炎和牛皮癣等皮肤病的前景

Q3 Pharmacology, Toxicology and Pharmaceutics Phytomedicine Plus Pub Date : 2024-11-01 DOI:10.1016/j.phyplu.2024.100666
Lény Teyssier , Lamotte Olivier , Bonnin Estelle , Crépeau Marie-Jeanne , Cussac Didier , Jeandroz Sylvain , Wendehenne David , Pelloux Jérôme , Jean-Louis Connat
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引用次数: 0

摘要

背景寡聚半乳糖醛酸(OG)是天然植物细胞壁果胶衍生产品,具有不同的聚合度(DP)和甲基化度(M)(见 Yu 等人,2022 年)。研究设计在培养的人外周血单核细胞(PBMC)上测试了不同甲基化程度(M:0、5、30 和 70)的 5-mer OG(DP5)的不同浓度,以了解它们是否能减少 LPS 诱导的 IL-1β 释放。然后,用代表几种病症的特异性激动剂刺激不同的人体细胞组合,测试活性最强的 OG DP5M0(甲基化为 0)的效果。结果 DP5M0 可剂量依赖性地减少 LPS 诱导的人外周血单核细胞(PBMC)释放 IL-1β。而 DP5M30 和 DP5M70 则没有这种效果。在对代表已知病理的 12 种不同人体细胞系统(BioMAP 系统)进行测试时,DP5M0 也比泼尼松龙更有效。由 B 细胞和 PBMC 等量组合而成的 T BioMAP 系统对 DP5M0 的反应灵敏度最高。鉴于所有这些细胞因子都参与角质形成细胞的增殖和分化,该模型系统符合 DP5M0 对特应性皮炎和银屑病可能产生的有益影响。DP5M0 还在 5 种不同的细胞系统中显示出抗增殖特性。通过比较 DP5M0 与抗炎产品泼尼松龙和双氯芬酸的 BioMAP 图谱,可以看出它们的作用模式不同。这些数据表明,DP5M0 可用于治疗牛皮癣疾病,在患者不能耐受其他已开发药物时,可作为这些药物的替代策略。
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Anti-inflammatory, immuno-modulatory, and anti-proliferative effects of 5-mer Oligogalacturonides (OG DP5) from citrus pectin on different types of human cells. Perspectives for treatment of dermal diseases such as atopic dermatitis and psoriasis

Background

Oligogalacturonides (OG) are natural plant cell wall pectin-derived products with different degrees of polymerisation (DP) and methylation (M) (see Yu et al. 2022). Their effects as stimulators of plant defence are well documented and they are also known for their potent effects on human health.

Purpose

Here, we investigated the anti-inflammatory effects of OG extracted from Citrus on different types of human cells and cell systems representative of several pathologies.

Study design

Different concentrations of 5-mer OG (DP5) with different methylation degrees (M: 0, 5, 30 and 70) were tested on cultured human peripheral blood mononuclear cells (PBMC) to see if there were able to decrease LPS-induced IL-1β release. Then, different human cell combination stimulated by specific agonists representative of several pathologies were used to test the effect of the most active OG DP5M0 (0 methylation).

Methods

IL-1β was monitored in the PBMC culture medium with ELISA and effects on bio-markers typical of pathologies were studied using the BioMAP Diversity PLUS® method (Eurofins, France).

Results

DP5M0 dose-dependently reduced LPS-induced IL-1β release by cultured human peripheral blood mononuclear cells (PBMC). This was not observed for DP5M30 or DP5M70. DP5M0 was also more efficient than prednisolone when tested on 12 different human cell systems representative of known pathologies (BioMAP systems). The T BioMAP system, which consists in an equal combination of B cells and PBMC, shows the best response sensitivity to DP5M0. This latter induces a dose-dependent decrease of the biomarkers of inflammation and of those of immune responses (IL-6, IL-8, IL-2, IL-17A, IL-17F and TNF-α).

Conclusion

In view that all these cytokines are involved in keratinocytes proliferation and differentiation, this model system fits with a possible beneficial effect of DP5M0 on atopic dermatitis and psoriasis. DP5M0 also showed anti-proliferative properties in 5 different cell systems. The comparison of the BioMAP profiles of DP5M0 and anti-inflammatory products prednisolone and diclofenac indicates that their modes of action are different. These data argue for a possible use of DP5M0 for treatments of psoriasis diseases as alternative strategy to other developed medicines when the patients do not tolerate them.
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来源期刊
Phytomedicine Plus
Phytomedicine Plus Medicine-Complementary and Alternative Medicine
CiteScore
3.70
自引率
0.00%
发文量
178
审稿时长
81 days
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