Journal of ethnopharmacology · 2025
In vitro and in vivo anti-inflammatory and chondroprotective effects of standardized hot water extract from Hydrangea serrata (Thunb.) Ser. via modulation of NF-κB and MAPK pathways.
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Heo Huy-Seoung, Cho Min Hyung, Chung Kyung-Sook, Lee Chae-Won, Yoon Young-Seo, Lee Sun-Hee, An Hyo-Jin, Lee Kyung-Tae
Аннотация
ETHNOPHARMACOLOGICAL RELEVANCE: Arthritis is an inflammatory disorder characterized by cartilage degradation and excessive inflammatory mediator production. Hydrangea leaves have been consumed as a medicine and tea in the far-east Asian countries, such as Korea, China, and Japan.
AIM OF THE STUDY: To clarify the mechanisms responsible for the pharmacological activities of Hydrangea serrata (Thunb.) Ser., we investigated anti-inflammatory and anti-arthritic properties of standardized hot water extract (WHS) of H. serrata leaves.
MATERIALS AND METHODS: The anti-arthritic effects of WHS were evaluated using RAW 264.7 murine macrophages and SW1353 human chondrocytes (in vitro) and carrageenan-induced paw edema and adjuvant-induced arthritis (AIA) models (in vivo). Clinical parameters including paw volume, arthritis score, and inflammatory pain were monitored. Histological analyses of ankle joints were performed using safranin-O staining and Mankin scoring. The anti-inflammatory effects of WHS were determined by NO and PGE2 assay. The expression levels of inflammation-related genes and proteins were analyzed by qRT-PCR and Western blotting, respectively. Additionally, untargeted LC-MS/MS metabolomic profiling of WHS was conducted to identify bioactive compounds, followed by functional characterization using cheminformatics tools and literature-based evidence integration.
RESULTS: WHS significantly inhibited prostaglandin E2 and cyclooxygenase-2 production and suppressed the expression of pro-inflammatory cytokines (IL-1β, IL-6, TNF-α) in RAW 264.7 macrophages and SW1353 chondrocytes. In carrageenan-induced paw edema and adjuvant-induced arthritis models, WHS reduced inflammatory swelling and pain. Mechanistically, WHS inhibited p38 MAPK activation, which attenuated NF-κB activation by reducing p65 phosphorylation, thereby downregulating MMP-13 and pro-inflammatory cytokine expression. LC-MS/MS metabolomic analysis identified hydrangenol as a key bioactive metabolite.
CONCLUSION: These findings suggest that WHS, with hydrangenol as a major metabolite, is a promising therapeutic candidate for arthritis and inflammatory joint diseases.
AIM OF THE STUDY: To clarify the mechanisms responsible for the pharmacological activities of Hydrangea serrata (Thunb.) Ser., we investigated anti-inflammatory and anti-arthritic properties of standardized hot water extract (WHS) of H. serrata leaves.
MATERIALS AND METHODS: The anti-arthritic effects of WHS were evaluated using RAW 264.7 murine macrophages and SW1353 human chondrocytes (in vitro) and carrageenan-induced paw edema and adjuvant-induced arthritis (AIA) models (in vivo). Clinical parameters including paw volume, arthritis score, and inflammatory pain were monitored. Histological analyses of ankle joints were performed using safranin-O staining and Mankin scoring. The anti-inflammatory effects of WHS were determined by NO and PGE2 assay. The expression levels of inflammation-related genes and proteins were analyzed by qRT-PCR and Western blotting, respectively. Additionally, untargeted LC-MS/MS metabolomic profiling of WHS was conducted to identify bioactive compounds, followed by functional characterization using cheminformatics tools and literature-based evidence integration.
RESULTS: WHS significantly inhibited prostaglandin E2 and cyclooxygenase-2 production and suppressed the expression of pro-inflammatory cytokines (IL-1β, IL-6, TNF-α) in RAW 264.7 macrophages and SW1353 chondrocytes. In carrageenan-induced paw edema and adjuvant-induced arthritis models, WHS reduced inflammatory swelling and pain. Mechanistically, WHS inhibited p38 MAPK activation, which attenuated NF-κB activation by reducing p65 phosphorylation, thereby downregulating MMP-13 and pro-inflammatory cytokine expression. LC-MS/MS metabolomic analysis identified hydrangenol as a key bioactive metabolite.
CONCLUSION: These findings suggest that WHS, with hydrangenol as a major metabolite, is a promising therapeutic candidate for arthritis and inflammatory joint diseases.