Investigation of Novel Aronia Bioactive Fraction-Alginic Acid Nanocomplex on the Enhanced Modulation of Neuroinflammation and Inhibition of Aβ Aggregation

Background/Objectives: Aronia extract or its active compounds, especially anthocyanin, have shown potential for Alzheimer’s disease (AD)-related pathologies, including neuroinflammation, fibrillogenesis of amyloid beta (Aβ), and cognitive impairment. However, there was still concern about their stru...

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Main Authors: Bong-Keun Jang, Soo Jung Shin, Hyun Ha Park, Vijay Kumar, Yong Ho Park, Jeom-Yong Kim, Hye-Yeon Kang, Sunyoung Park, Youngsun Kwon, Sang-Eun Shin, Minho Moon, Beom-Jin Lee
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Language:English
Published: MDPI AG 2024-12-01
Series:Pharmaceutics
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Online Access:https://www.mdpi.com/1999-4923/17/1/13
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author Bong-Keun Jang
Soo Jung Shin
Hyun Ha Park
Vijay Kumar
Yong Ho Park
Jeom-Yong Kim
Hye-Yeon Kang
Sunyoung Park
Youngsun Kwon
Sang-Eun Shin
Minho Moon
Beom-Jin Lee
author_facet Bong-Keun Jang
Soo Jung Shin
Hyun Ha Park
Vijay Kumar
Yong Ho Park
Jeom-Yong Kim
Hye-Yeon Kang
Sunyoung Park
Youngsun Kwon
Sang-Eun Shin
Minho Moon
Beom-Jin Lee
author_sort Bong-Keun Jang
collection DOAJ
description Background/Objectives: Aronia extract or its active compounds, especially anthocyanin, have shown potential for Alzheimer’s disease (AD)-related pathologies, including neuroinflammation, fibrillogenesis of amyloid beta (Aβ), and cognitive impairment. However, there was still concern about their structural instability in vivo and in vitro. To solve the instability of anthocyanins, we combined aronia bioactive factions (ABFs) and alginic acid via electrostatic molecular interactions and created an ABF–alginic acid nanocomplex (AANCP). We evaluated whether it is more stable and effective in cognitive disorder mice and neuroinflammation cell models. Methods: The physicochemical properties of the AANCP, such as nanoparticle size, structural stability, and release rate, were characterized. The AANCP was administered to scopolamine-injected Balb/c mice, and to BV2 microglia treated with lipopolysaccharide (LPS) and amyloid beta (Aβ). Inflammation responses were measured via qPCR and ELISA in vitro, and cognitive functions were measured via behavior tests in vivo. Results: The AANCP readily formed nanoparticles, 209.6 nm in size, with a negatively charged zeta potential. The AANCP exhibited better stability in four plasma samples (human, dog, rat, and mouse) and was slowly released in different pH conditions (pH 2.0, 7.4, and 8.0) compared with non-complexedABF. In vitro studies on microglial cells treated with AANCPs revealed a suppression of inflammatory cytokines (tumor necrosis factor-alpha and interleukin-6) induced by LPS. The AANCP increased microglial Aβ phagocytosis through the activation of triggering receptor expressed on myeloid cell 2 (TREM2)-related microglial polarization. The AANCP inhibited aggregation of Aβ in vitro and alleviated cognitive impairment in a scopolamine-induced in vivo dementia mouse model. Conclusions: Our data indicate that AANCPs are more stable than ABFs and effective for cognitive disorders and neuroinflammation via modulation of M2 microglial polarization.
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spelling doaj-art-83f0405ab1054183beef4ef772b250302025-01-24T13:45:34ZengMDPI AGPharmaceutics1999-49232024-12-011711310.3390/pharmaceutics17010013Investigation of Novel Aronia Bioactive Fraction-Alginic Acid Nanocomplex on the Enhanced Modulation of Neuroinflammation and Inhibition of Aβ AggregationBong-Keun Jang0Soo Jung Shin1Hyun Ha Park2Vijay Kumar3Yong Ho Park4Jeom-Yong Kim5Hye-Yeon Kang6Sunyoung Park7Youngsun Kwon8Sang-Eun Shin9Minho Moon10Beom-Jin Lee11Department of Pharmacy, College of Pharmacy, Ajou University, Suwon 16499, Republic of KoreaDepartment of Biochemistry, College of Medicine, Konyang University, 158, Gwanjeodong-ro, Seo-gu, Daejeon 35365, Republic of KoreaDepartment of Biochemistry, College of Medicine, Konyang University, 158, Gwanjeodong-ro, Seo-gu, Daejeon 35365, Republic of KoreaDepartment of Biochemistry, College of Medicine, Konyang University, 158, Gwanjeodong-ro, Seo-gu, Daejeon 35365, Republic of KoreaDepartment of Biochemistry, College of Medicine, Konyang University, 158, Gwanjeodong-ro, Seo-gu, Daejeon 35365, Republic of KoreaJBKLAB, Inc., 17 Techno 4-ro, Yuseoung-gu, Daejeon 34013, Republic of KoreaJBKLAB, Inc., 17 Techno 4-ro, Yuseoung-gu, Daejeon 34013, Republic of KoreaJBKLAB, Inc., 17 Techno 4-ro, Yuseoung-gu, Daejeon 34013, Republic of KoreaJBKLAB, Inc., 17 Techno 4-ro, Yuseoung-gu, Daejeon 34013, Republic of KoreaJBKLAB, Inc., 17 Techno 4-ro, Yuseoung-gu, Daejeon 34013, Republic of KoreaDepartment of Biochemistry, College of Medicine, Konyang University, 158, Gwanjeodong-ro, Seo-gu, Daejeon 35365, Republic of KoreaDepartment of Pharmacy, College of Pharmacy, Ajou University, Suwon 16499, Republic of KoreaBackground/Objectives: Aronia extract or its active compounds, especially anthocyanin, have shown potential for Alzheimer’s disease (AD)-related pathologies, including neuroinflammation, fibrillogenesis of amyloid beta (Aβ), and cognitive impairment. However, there was still concern about their structural instability in vivo and in vitro. To solve the instability of anthocyanins, we combined aronia bioactive factions (ABFs) and alginic acid via electrostatic molecular interactions and created an ABF–alginic acid nanocomplex (AANCP). We evaluated whether it is more stable and effective in cognitive disorder mice and neuroinflammation cell models. Methods: The physicochemical properties of the AANCP, such as nanoparticle size, structural stability, and release rate, were characterized. The AANCP was administered to scopolamine-injected Balb/c mice, and to BV2 microglia treated with lipopolysaccharide (LPS) and amyloid beta (Aβ). Inflammation responses were measured via qPCR and ELISA in vitro, and cognitive functions were measured via behavior tests in vivo. Results: The AANCP readily formed nanoparticles, 209.6 nm in size, with a negatively charged zeta potential. The AANCP exhibited better stability in four plasma samples (human, dog, rat, and mouse) and was slowly released in different pH conditions (pH 2.0, 7.4, and 8.0) compared with non-complexedABF. In vitro studies on microglial cells treated with AANCPs revealed a suppression of inflammatory cytokines (tumor necrosis factor-alpha and interleukin-6) induced by LPS. The AANCP increased microglial Aβ phagocytosis through the activation of triggering receptor expressed on myeloid cell 2 (TREM2)-related microglial polarization. The AANCP inhibited aggregation of Aβ in vitro and alleviated cognitive impairment in a scopolamine-induced in vivo dementia mouse model. Conclusions: Our data indicate that AANCPs are more stable than ABFs and effective for cognitive disorders and neuroinflammation via modulation of M2 microglial polarization.https://www.mdpi.com/1999-4923/17/1/13anthocyaninaronia bioactive fraction–alginic acid nanocomplexelectrostatic interactionnanoparticlesenhanced stabilityneuroinflammation
spellingShingle Bong-Keun Jang
Soo Jung Shin
Hyun Ha Park
Vijay Kumar
Yong Ho Park
Jeom-Yong Kim
Hye-Yeon Kang
Sunyoung Park
Youngsun Kwon
Sang-Eun Shin
Minho Moon
Beom-Jin Lee
Investigation of Novel Aronia Bioactive Fraction-Alginic Acid Nanocomplex on the Enhanced Modulation of Neuroinflammation and Inhibition of Aβ Aggregation
Pharmaceutics
anthocyanin
aronia bioactive fraction–alginic acid nanocomplex
electrostatic interaction
nanoparticles
enhanced stability
neuroinflammation
title Investigation of Novel Aronia Bioactive Fraction-Alginic Acid Nanocomplex on the Enhanced Modulation of Neuroinflammation and Inhibition of Aβ Aggregation
title_full Investigation of Novel Aronia Bioactive Fraction-Alginic Acid Nanocomplex on the Enhanced Modulation of Neuroinflammation and Inhibition of Aβ Aggregation
title_fullStr Investigation of Novel Aronia Bioactive Fraction-Alginic Acid Nanocomplex on the Enhanced Modulation of Neuroinflammation and Inhibition of Aβ Aggregation
title_full_unstemmed Investigation of Novel Aronia Bioactive Fraction-Alginic Acid Nanocomplex on the Enhanced Modulation of Neuroinflammation and Inhibition of Aβ Aggregation
title_short Investigation of Novel Aronia Bioactive Fraction-Alginic Acid Nanocomplex on the Enhanced Modulation of Neuroinflammation and Inhibition of Aβ Aggregation
title_sort investigation of novel aronia bioactive fraction alginic acid nanocomplex on the enhanced modulation of neuroinflammation and inhibition of aβ aggregation
topic anthocyanin
aronia bioactive fraction–alginic acid nanocomplex
electrostatic interaction
nanoparticles
enhanced stability
neuroinflammation
url https://www.mdpi.com/1999-4923/17/1/13
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