Terminalia bellirica (Gaertn.) Roxb. Extract and Gallic Acid Attenuate LPS‐Induced Inflammation and Oxidative Stress via MAPK/NF‐κ B and Akt/AMPK/Nrf2 Pathways

Tanaka, Miori; Kishimoto, Yoshimi; Sasaki, Mizuho; Sato, Akari; Kamiya, Tomoyasu; Kondo, Kazuo; Iida, Kaoruko

doi:10.1155/2018/9364364

Cited by 154Phytochemicals and Medicinal PlantsGenomics, phytochemicals, and oxidative stressMedicinal Plant Research

Terminalia bellirica (Gaertn.) Roxb. Extract and Gallic Acid Attenuate LPS‐Induced Inflammation and Oxidative Stress via MAPK/NF‐κ B and Akt/AMPK/Nrf2 Pathways

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Tanaka, Miori, Kishimoto, Yoshimi, Sasaki, Mizuho, Sato, Akari, Kamiya, Tomoyasu, Kondo, Kazuo, Iida, Kaoruko·2018·Oxidative Medicine and Cellular Longevity

DOI 10.1155/2018/9364364PMC PMC6250009

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Abstract

Excessive oxidative stress plays a critical role in the progression of various diseases. Recently, we showed that Terminalia bellirica (Gaertn.) Roxb. extract (TBE) inhibits inflammatory response and reactive oxygen species (ROS) production in THP‐1 macrophages. However, molecular mechanisms underlying anti‐inflammatory and antioxidant activities of TBE and its major polyphenolic compounds gallic acid (GA) and ellagic acid (EA) remain unclear. We found that TBE and GA attenuated LPS‐induced inflammatory mediator expression, ROS production, and activation of mitogen‐activated protein kinase (MAPK) and nuclear factor‐kappa B (NF‐κB) in RAW 264 macrophages. Furthermore, TBE and GA increased antioxidant enzyme expression along with upstream mediators nuclear factor erythroid‐2‐related factor 2 (Nrf2), Akt, and AMP‐activated protein kinase (AMPK). Importantly, knockdown of Nrf2 by siRNA and specific inhibition of Akt and AMPK significantly reduced antioxidant enzyme expression induced by TBE and GA. Finally, in vivo effects on histopathology and gene expression were assessed in tissues collected after intraperitoneal injection of LPS with or without TBE treatment. TBE enhanced antioxidant enzyme expression and improved acute kidney injury in LPS‐shock model mice. In conclusion, TBE and GA exert protective effects against inflammation and oxidative stress by suppressing MAPK/NF‐κB pathway and by activating Akt/AMPK/Nrf2 pathway. These results suggest that TBE and GA might be effective for the treatment of inflammation‐related diseases.

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Tanaka et al. reported that GA attenuated LPS-induced inflammatory mediator expression and reactive oxygen species production in RAW264.7 macrophages.
“Tanaka et al. reported that GA attenuated LPS-induced inflammatory mediator expression and reactive oxygen species production in RAW264.7 macrophages [71].”
From Exosome-functionalized magnesium-organic framework-based scaffolds with osteogenic, angiogenic and anti-inflammatory properties for accelerated bone regeneration. (2022) · cites this paper as [71]

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Authors: Tanaka, M., Kishimoto, Y., Sasaki, M., Sato, A., Kamiya, T., Kondo, K., & Iida, K.
Affiliations: Ochanomizu University (JP)
Toyo University (JP)
Corresponding author: Iida, Kaoruko
ORCID: Tanaka, Miori
Kishimoto, Yoshimi
Kondo, Kazuo
Iida, Kaoruko
Venue: Oxidative Medicine and Cellular Longevity
Publisher: Wiley
Published: 2018-01
Volume: 2018
Issue: 1
Pages: 9364364-9364364
ISSN: 1942-0994 (ISSN-L)
1942-0900
DOI: 10.1155/2018/9364364
PMC: PMC6250009
OpenAlex: W2899712363
Cited by: 154
References: 48
Citations by year: 2026: 10 · 2025: 13 · 2024: 26 · 2023: 26 · 2022: 28 · 2021: 22 · 2020: 20 · 2019: 9
FWCI: 17.50
Type: journal article
Language: en
Open access: hybrid
doi.org
Licence: cc-by
creativecommons.org/licenses/by/4.0/ (vor, 311 d)
Locations: Oxidative Medicine and Cellular Longevity (publishedVersion, cc-by)
Europe PMC (PubMed Central) (publishedVersion, cc-by)
PubMed Central (publishedVersion, cc-by)
PubMed (publishedVersion)
DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders: Japan Society for the Promotion of Science (JP16H03033, JP15H02895, JP18J13346)
Topics: Health Sciences › Medicine › Complementary and alternative medicine › Phytochemicals and Medicinal Plants
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics, phytochemicals, and oxidative stress
Life Sciences › Agricultural and Biological Sciences › Plant Science › Medicinal Plant Research
Keywords: Terminalia bellirica, gallic acid, ellagic acid, lipopolysaccharide-induced inflammation, oxidative stress, macrophages, reactive oxygen species, antioxidant enzymes, acute kidney injury, sepsis, anti-inflammatory activity
MeSH terms: RAW 264.7 Cells, Adenylate Kinase, Animals, Anti-Inflammatory Agents, Gallic Acid, Inflammation, Lipopolysaccharides, Male, Mice, Inbred ICR, Plant Extracts, Signal Transduction, NF-kappa B, Oxidative Stress, MAP Kinase Signaling System, Terminalia, Proto-Oncogene Proteins c-akt, NF-E2-Related Factor 2, Mice

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Terminalia bellirica (Gaertn.) Roxb. Extract and Gallic Acid Attenuate LPS‐Induced Inflammation and Oxidative Stress via MAPK/NF‐κ B and Akt/AMPK/Nrf2 Pathways

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