Aronia Bioactive Fraction–Alginic Acid Nanocomplex–Modulates Tau Phosphorylation and Aggregation in Cell Models of Alzheimer’s Disease

Kang, Hye-Yeon; Jang, Bong-Keun; Yun, Seong-Hoon; Jeong, Hee-Yeong; Park, Eunkuk; Oh, Kang-Il; Jeong, Junhwan; Jeong, Seon-Yong

doi:10.3390/ijms27135748

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Aronia Bioactive Fraction–Alginic Acid Nanocomplex–Modulates Tau Phosphorylation and Aggregation in Cell Models of Alzheimer’s Disease

by

Hye-Yeon Kang

^1,2,3,†,

Bong-Keun Jang

^1,4,*,†,

Seong-Hoon Yun

¹

,

Hee-Yeong Jeong

¹,

Eunkuk Park

²

,

Kang-Il Oh

^2,3

,

Junhwan Jeong

^2,3

and

Seon-Yong Jeong

^2,3,*

¹

JBKLAB, Inc., 17 Techno 4-ro, Yuseoung-gu, Daejeon 34013, Republic of Korea

²

Department of Medical Genetics, Ajou University School of Medicine, Suwon 16499, Republic of Korea

³

BK21 R&E Initiative for Advanced Precision Medicine, Department of Biomedical Sciences, Graduate School of Ajou University, Suwon 16499, Republic of Korea

⁴

Department of Herbology, College of Korean Medicine, Kyung Hee University, 26 Kyungheedae-ro, Dongdaemun-gu, Seoul 02447, Republic of Korea

^*

Authors to whom correspondence should be addressed.

^†

These authors have contributed equally to this work.

Int. J. Mol. Sci. 2026, 27(13), 5748; https://doi.org/10.3390/ijms27135748 (registering DOI)

Submission received: 27 May 2026 / Revised: 18 June 2026 / Accepted: 24 June 2026 / Published: 25 June 2026

(This article belongs to the Special Issue Emerging Molecular Mechanisms and Therapeutic Targets in Neurodegenerative Diseases and Brain Cancers)

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Abstract

Preventing or reversing Tau hyperphosphorylation and aggregation represent critical objectives in the development of effective therapies for Alzheimer’s disease. The present study investigated the potential of a novel Aronia bioactive fraction—alginic acid nanocomplex (AANCP)—to simultaneously inhibit pathological features of Alzheimer’s disease. Evaluations of Aronia bioactive fraction (ABF) and low-molecular-weight alginic acid (LAA), utilized both individually and as AANCP, were conducted in HEK293-TauP301L and SH-SY5Y-TauP301L cell models of Alzheimer’s disease. Both ABF and LAA reduced the expression of total Tau and Tau phosphorylated at Ser396 in a concentration-dependent manner, with AANCP demonstrating significant synergistic activity of its components. Notably, the optimal AANCP ratio was 1:1 and 1:8 for inhibiting Tau phosphorylation and Tau aggregation, respectively. Mechanistically, AANCP inhibited Tau phosphorylation by upregulating p-Akt (phosphorylated protein kinase B) and p-GSK-3β (phosphorylated glycogen synthase kinase-3 beta), while also enhancing the activity of methylated PP2A, a key Tau phosphatase. Furthermore, AANCP exhibited superior efficacy in inhibiting heparin-induced Tau aggregation compared to the individual components. Analysis of autophagy markers indicated that the nanocomplex enhanced Tau clearance, as shown by increased LC3-II and Beclin-1 levels and reduced p62 levels. These results suggest AANCP as a promising therapeutic candidate that simultaneously reduces Tau phosphorylation and aggregation and facilitates autophagic Tau clearance, offering a potent, synergistic strategy for treating Alzheimer’s disease.

Keywords: Alzheimer’s disease; Aronia bioactive fraction–alginic acid nanocomplex (AANCP); Aronia melanocarpa; autophagy; glycogen synthase kinase-3β; Tau aggregation; Tau phosphorylation; tauopathy

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MDPI and ACS Style

Kang, H.-Y.; Jang, B.-K.; Yun, S.-H.; Jeong, H.-Y.; Park, E.; Oh, K.-I.; Jeong, J.; Jeong, S.-Y. Aronia Bioactive Fraction–Alginic Acid Nanocomplex–Modulates Tau Phosphorylation and Aggregation in Cell Models of Alzheimer’s Disease. Int. J. Mol. Sci. 2026, 27, 5748. https://doi.org/10.3390/ijms27135748

AMA Style

Kang H-Y, Jang B-K, Yun S-H, Jeong H-Y, Park E, Oh K-I, Jeong J, Jeong S-Y. Aronia Bioactive Fraction–Alginic Acid Nanocomplex–Modulates Tau Phosphorylation and Aggregation in Cell Models of Alzheimer’s Disease. International Journal of Molecular Sciences. 2026; 27(13):5748. https://doi.org/10.3390/ijms27135748

Chicago/Turabian Style

Kang, Hye-Yeon, Bong-Keun Jang, Seong-Hoon Yun, Hee-Yeong Jeong, Eunkuk Park, Kang-Il Oh, Junhwan Jeong, and Seon-Yong Jeong. 2026. "Aronia Bioactive Fraction–Alginic Acid Nanocomplex–Modulates Tau Phosphorylation and Aggregation in Cell Models of Alzheimer’s Disease" International Journal of Molecular Sciences 27, no. 13: 5748. https://doi.org/10.3390/ijms27135748

APA Style

Kang, H.-Y., Jang, B.-K., Yun, S.-H., Jeong, H.-Y., Park, E., Oh, K.-I., Jeong, J., & Jeong, S.-Y. (2026). Aronia Bioactive Fraction–Alginic Acid Nanocomplex–Modulates Tau Phosphorylation and Aggregation in Cell Models of Alzheimer’s Disease. International Journal of Molecular Sciences, 27(13), 5748. https://doi.org/10.3390/ijms27135748

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Aronia Bioactive Fraction–Alginic Acid Nanocomplex–Modulates Tau Phosphorylation and Aggregation in Cell Models of Alzheimer’s Disease

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