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. 2024 Feb 26:8:100702.
doi: 10.1016/j.crfs.2024.100702. eCollection 2024.

Phytosterol organic acid esters: Characterization, anti-inflammatory properties and a delivery strategy to improve mitochondrial function

Xinyue Zou  1 , Ting Xu  2 , Tian Zhao  2 , Jing Xia  2 , Feifan Zhu  3 , Yu Hou  4 , Baiyi Lu  2 , Yunfei Zhang  1 , Xuan Yang  2
Affiliations

Phytosterol organic acid esters: Characterization, anti-inflammatory properties and a delivery strategy to improve mitochondrial function

Xinyue Zou et al. Curr Res Food Sci. .

Abstract

Phytosterol organic acid esters are important food resources and the components of biomembrane structure. Due to the lack of extraction and synthesis techniques, more research has been focused on phytosterols, and the research on phytosterol acid esters have encountered a bottleneck, but phytosterol acid esters confer substantial benefits to human health. In this study, stigmasteryl vanillate (VAN), stigmasteryl protocatechuate (PRO) and stigmasteryl sinapate (SIN) were prepared through the Steglich reaction. The processes are promotable and the products reach up to 95% purity. In addition, their stability was evaluated by differential scanning calorimetry and thermogravimetric analysis. HPLC analysis revealed an enhancement in water solubility after esterification with phenolic acid. In an in vitro digestion model, the bioaccessibility of stigmasteryl phenolates was significantly higher than that of stigmasterols (STIs). Regarding the anti-inflammatory properties, VAN, PRO, and SIN exhibit superior effects against TNF-α induced pro-inflammatory responses compared to STI. All stigmasteryl phenolates supplementation increased the ATP production, the basal, and maximal oxygen consumption rate in mitochondrial stress test. Overall, we present a synthesis method for stigmasteryl phenolates. It will contribute to the development and research of phytosterol acid ester analysis, functions and utilization in food. Moreover, the nutrient-stigmasterol hybrids tactic we have constructed is practical and can become a targeted mitochondrial delivery strategy with enhanced anti-inflammatory effects.

Keywords: Anti-inflammatory; Mitochondrial delivery strategy; Phenolic acids; Phytosterol esters; Steglich reaction; Stigmasterols.

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Conflict of interest statement

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Figures

Image 1
Graphical abstract
Fig. 1
Fig. 1
Preparation of stigmasteryl phenolates. (A) Synthesis of esterification of stigmasteryl benzoate. Stigmasterol reacted with phenolic acid in the presence of dicyclohexylcarbodiimide (DCC) and 4-dimethylamino pyridine (DMAP); (B) synthesis of ssterification of stigmasteryl styrylate. Step 1, sinapic acid was protected with acetic anhydride (Ac2O); step 2, stigmasterol reacted with protected sinapic acid in the presence of DCC and DMAP; step 3, deprotection with K2CO3.
Fig. 2
Fig. 2
FT-IR spectra of (A) stigmasterol (STI); (B) stigmasteryl vanillate (VAN); (C) stigmasteryl protocatechuate (PRO); (D) stigmasteryl sinapate (SIN).
Fig. 3
Fig. 3
DSC curves for (A) stigmasterol (STI); (B) stigmasteryl vanillate (VAN); (C) stigmasteryl protocatechuate (PRO); (D) stigmasteryl sinapate (SIN).
Fig. 4
Fig. 4
Experimental mass fraction of stigmasterol (STI), stigmasteryl vanillate (VAN), stigmasteryl protocatechuate (PRO), stigmasteryl sinapate (SIN) from thermogravimetric analysis.
Fig. 5
Fig. 5
The solubility and bioaccessibility characteristics of stigmasterol (STI), stigmasteryl vanillate (VAN), stigmasteryl protocatechuate (PRO) and stigmasteryl sinapate (SIN). (A) Solubility indexes of samples; (B) Bioaccessibility of samples at the entire phase of digestion. The data are presented as the means ± SD of three replications. Different characters indicate significant differences between the compared groups (p < 0.05).
Fig. 6
Fig. 6
The assessment of stigmasterol (STI), stigmasteryl vanillate (VAN), stigmasteryl protocatechuate (PRO) and stigmasteryl sinapate (SIN) against the TNF-a induced pro-inflammatory responses in HK-2 cells. (A) The HK-2 cell viability at different concentrations of phytosterol acid esters; (B) The cell viability of HEK293, MC38 and HeLa cell line under the different stigmasterol concentration. “*” indicates a significant difference (P < 0.05), and “***” indicates a significant difference (P < 0.005) compared with the MC38 model; (C) Schematic depicting approach of the treatment process of the experimental group and the control group followed by measure the absorbance of CCK-8 assay at 450–490 nm; (B) The HK-2 cell viability was determined after treatment. All the data were expressed as a percentage of the control. The data are presented as the means ± SD of five replications. Different characters indicate significant differences between the compared groups (p < 0.05).
Fig. 7
Fig. 7
The assessment of stigmasterol (STI), stigmasteryl vanillate (VAN), stigmasteryl protocatechuate (PRO) and stigmasteryl sinapate (SIN) against the mitochondrial stress test in HK-2 cells. (A) The oxygen consumption rate (OCR) changes of cultured cells after 24h treatment, measured by Seahorse analysis; (B) The basal OCR; (C) The ATP production; (D) The maximal OCR; All the data were expressed as a percentage of the control. The data are presented as the means ± SD of five replications. Different characters indicate significant differences between the compared groups (p < 0.05). (E) Diagram of the synthesis, physical and anti-inflammatory properties of the three novel stigmasteryl phenolates. Also, the nutrient-stigmasterol hybrids can be a potential low-toxic and stable targeted mitochondrial delivery strategy.
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