Natural Polyphenol Corilagin Enhances Osteogenesis and Chondrogenesis Differentiation of Mesenchymal Stem Cells - Implications for Bone and Cartilage Regeneration

Sep 30, 2026

Corilagin, a hydrolyzable ellagitannin polyphenol found in longan and medicinal plants, was examined for its ability to regulate bone marrow mesenchymal stem cell (BM-MSC) differentiation. The study evaluated BM-MSC viability, protein-binding interactions, and lineage-specific differentiation toward osteogenic and chondrogenic pathways. Corilagin preserved synovial SW-982 cell viability over 1.56–50 µg/mL for 48 h but reduced viability with longer exposure. In BM-MSCs, it dose-dependently enhanced osteogenesis and chondrogenesis, increasing mineral deposition and cartilage matrix formation and upregulating Runx2/OPN and Sox9/aggrecan, supporting regenerative potential.

LanguageEnglish

CategoryHealthcare

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Reading Time40 min

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1. Introduction

Article Natural Polyphenol Corilagin Enhances Osteogenesis and Chondrogenesis Differentiation of Mesenchymal Stem Cells: Implications for Bone and Cartilage Regeneration Thitianan Kulsirirat 1, Sittisak Honsawek 2, Mariko Takeda-Morishita 3 and Korbtham Sathirakul 4, * Academic Editor: George Grant Received: 28 November 2025 Revised: 27 December 2025 Accepted: 30 December 2025 Published: 5 January 2026 Corrected: 26 January 2026 Copyright: © 2026 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license. 1 Department of Biopharmacy, Faculty of Pharmacy, Srinakharinwirot University, Nakhon Nayok 26120, Thailand; [thitianan@g.swu.ac.th](thitianan@g.swu.ac.th) 2 Center of Excellence in Osteoarthritis and Musculoskeleton, Department of Biochemistry, Faculty of Medicine, Chulalongkorn University, King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Bangkok 10330, Thailand; [sittisak.h@chula.ac.th](sittisak.h@chula.ac.th) 3 Laboratory of Drug Delivery Systems, Faculty of Pharmaceutical Sciences, Kobe Gakuin University, Kobe 650-8586, Hyogo, Japan; [mmtakeda@pharm.kobegakuin.ac.jp](mmtakeda@pharm.kobegakuin.ac.jp) 4 Department of Pharmacy, Faculty of Pharmacy, Mahidol University, Bangkok 10400, Thailand * Correspondence: [korbtham.sat@mahidol.edu or pyksk2001@yahoo.com.sg](korbtham.sat@mahidol.edu or pyksk2001@yahoo.com.sg); Tel.: +66-2644-8677-91; Fax: +66-2644-8694 Abstract Corilagin is a hydrolyzable ellagitannin and naturally occurring polyphenolic compound widely distributed in medicinal plants. It is also present in longan (Dimocarpus longan), known as lumyai in Thailand, a subtropical fruit extensively cultivated across China and Southeast Asia. Corilagin has been reported to exhibit strong antioxidant, antiinflammatory, hepatoprotective, and anticancer activities through modulation of multiple cellular signaling pathways. However, despite these well-established pharmacological properties, its potential role in regulating bone marrow mesenchymal stem cell (BM-MSC) differentiation has not been fully explored in biomedical applications. In this study, we investigated the effects of corilagin on BM-MSC viability, protein-binding interactions, and lineage-specific differentiation toward osteogenic and chondrogenic pathways. Cytotoxicity assessment using human synovial SW-982 cells demonstrated that corilagin maintained cell viability at concentrations ranging from 1.56 to 50 µg/mL within 48 h, whereas prolonged exposure resulted in a time-dependent reduction in viability. In BM-MSCs, corilagin significantly enhanced osteogenic and chondrogenic differentiation in a dose-dependent manner, as evidenced by increased mineral deposition and cartilage matrix formation, as revealed by Alizarin Red S, Toluidine Blue, and Alcian Blue staining. Quantitative analyses further showed the upregulation of key lineage-specific genes, including Runx2 and osteopontin (OPN) for osteogenesis and Sox9 and aggrecan for chondrogenesis. Protein-binding assays confirmed the molecular interaction capacity of corilagin, supporting its biological activity. Overall, these findings demonstrate that corilagin promotes MSC-mediated osteogenic and chondrogenic differentiation while maintaining acceptable cytocompatibility, highlighting its potential as a natural small-molecule candidate for bone and cartilage tissue engineering and other biomedical fields with regenerative medicine applications. Keywords: corilagin; medicinal plants; mesenchymal stem cells; biomarkers; biomedical fields; regenerative medicine 1. Introduction Bone and cartilage degeneration represent major clinical challenges worldwide, particularly in aging societies where musculoskeletal disorders such as osteoarthritis, osteoporosis, and cartilage injuries are increasingly prevalent [1] . These conditions significantly imp

FAQs

What is corilagin and why is it relevant to bone and cartilage regeneration?

Corilagin is a hydrolyzable ellagitannin polyphenol naturally present in medicinal plants and longan. It is investigated here for regulating BM-MSC differentiation toward osteogenic and chondrogenic lineages, which are key for bone and cartilage regeneration.

How did corilagin affect cell viability in the study?

Corilagin maintained synovial SW-982 cell viability at 1.56–50 µg/mL within 48 h. Prolonged exposure led to a time-dependent reduction in viability.

What evidence shows corilagin promotes osteogenesis and chondrogenesis in BM-MSCs?

Corilagin increased mineral deposition and cartilage matrix formation using Alizarin Red S, Toluidine Blue, and Alcian Blue staining. It also upregulated osteogenic genes (Runx2, osteopontin/OPN) and chondrogenic genes (Sox9, aggrecan).

What role did protein-binding assays play in the findings?

Protein-binding assays confirmed corilagin’s molecular interaction capacity, supporting its ability to drive biological activity related to MSC differentiation.

Sep 30, 2026

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