Phytochemical analysis and biological effects of Zingiber cassumunar extract and three phenylbutenoids: targeting NF-κB, Akt/MAPK, and caspase-3 pathways

Abstract Background Zingiber cassumunar Roxb., belonging to the Zingiberaceae family, is a medicinal herb commonly found in tropical regions, particularly in Southeast Asia. This research aims to investigate the preventive effects and anti-inflammatory properties of a phenylbutenoid extract (PE) obt...

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Main Authors: Thidaporn Gundom, Wanida Sukketsiri, Pharkphoom Panichayupakaranant
Format: Article
Language:English
Published: BMC 2025-05-01
Series:BMC Complementary Medicine and Therapies
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Online Access:https://doi.org/10.1186/s12906-025-04907-w
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author Thidaporn Gundom
Wanida Sukketsiri
Pharkphoom Panichayupakaranant
author_facet Thidaporn Gundom
Wanida Sukketsiri
Pharkphoom Panichayupakaranant
author_sort Thidaporn Gundom
collection DOAJ
description Abstract Background Zingiber cassumunar Roxb., belonging to the Zingiberaceae family, is a medicinal herb commonly found in tropical regions, particularly in Southeast Asia. This research aims to investigate the preventive effects and anti-inflammatory properties of a phenylbutenoid extract (PE) obtained from the rhizomes of Z. cassumunar. Method The PE extract was prepared using green microwave extraction and subsequently analyzed by high-performance liquid chromatography. To evaluate its anti-inflammatory activity, lipopolysaccharide (LPS)-stimulated RAW264.7 cell models were used to measure the release of nitric oxide (NO), tumor necrosis factor-α (TNF-α), and interleukin-1β (IL-1β) using the Griess assay and enzyme-linked immunosorbent assay, respectively. Additionally, the inhibitory effects of PE on apoptosis and reactive oxygen species (ROS) production were evaluated in hydrogen peroxide-induced C2C12 myoblast cells. The expression of inflammation- and apoptosis-related proteins was evaluated using western blotting. Results The results indicated that the PE was enriched with (E)-(3,4-dimethoxyphenyl)butadiene (DMPBD), (E)-1-(3,4-dimethoxyphenyl)but-3-en-1-ol (compound D), and (E)-1-(3,4-dimethoxyphenyl)but-3-en-1-yl acetate (compound D acetate). The PE contained a total phenylbutenoid content of 1.42% w/w. The PE exhibited potent anti-inflammatory properties, with half maximal inhibitory concentration (IC50) values of 7.2 µg/mL for NO, 23.4 µg/mL for TNF-α, and 19.8 µg/mL for IL-1β. In comparison, DMPBD exhibited lower activity against NO and TNF-α (IC50 values of 16.3 and 37.2 µg/mL, respectively) but similar efficacy against IL-1β (IC50 of 17.7 µg/mL) in LPS-induced RAW264.7 cells. All test compounds significantly decreased the percentage of apoptotic cells and suppressed intracellular ROS production in hydrogen peroxide-induced C2C12 myoblast cells. Notably, PE exhibited the highest potency in reducing apoptotic cells, with the lowest IC50 value of 11.6 µg/mL. PE inhibited the expression of p-p38/p38, pERK/ERK, and pAkt/Akt in the LPS-induced inflammatory response in RAW264.7 cells. Additionally, PE significantly suppressed the cleaved/pro-caspase-3 ratio without affecting Bax and Bcl-2 protein levels. Conclusion These findings suggest that PE and its phenylbutenoids exhibit anti-inflammatory effects through the inhibition of p38, ERK, and Akt signaling pathways, and anti-apoptotic effects via the inhibition of the caspase-3 pathway, highlighting their therapeutic potential for managing inflammatory and degenerative conditions. Clinical trial number Not applicable.
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spelling doaj-art-33d9bf2a66dc499c86ccb6f016b7d9492025-08-20T02:32:05ZengBMCBMC Complementary Medicine and Therapies2662-76712025-05-0125111910.1186/s12906-025-04907-wPhytochemical analysis and biological effects of Zingiber cassumunar extract and three phenylbutenoids: targeting NF-κB, Akt/MAPK, and caspase-3 pathwaysThidaporn Gundom0Wanida Sukketsiri1Pharkphoom Panichayupakaranant2Department of Pharmacognosy and Pharmaceutical Botany, Faculty of Pharmaceutical Sciences, Prince of Songkla UniversityDivision of Health and Applied Sciences, Faculty of Science, Prince of Songkla UniversityDepartment of Pharmacognosy and Pharmaceutical Botany, Faculty of Pharmaceutical Sciences, Prince of Songkla UniversityAbstract Background Zingiber cassumunar Roxb., belonging to the Zingiberaceae family, is a medicinal herb commonly found in tropical regions, particularly in Southeast Asia. This research aims to investigate the preventive effects and anti-inflammatory properties of a phenylbutenoid extract (PE) obtained from the rhizomes of Z. cassumunar. Method The PE extract was prepared using green microwave extraction and subsequently analyzed by high-performance liquid chromatography. To evaluate its anti-inflammatory activity, lipopolysaccharide (LPS)-stimulated RAW264.7 cell models were used to measure the release of nitric oxide (NO), tumor necrosis factor-α (TNF-α), and interleukin-1β (IL-1β) using the Griess assay and enzyme-linked immunosorbent assay, respectively. Additionally, the inhibitory effects of PE on apoptosis and reactive oxygen species (ROS) production were evaluated in hydrogen peroxide-induced C2C12 myoblast cells. The expression of inflammation- and apoptosis-related proteins was evaluated using western blotting. Results The results indicated that the PE was enriched with (E)-(3,4-dimethoxyphenyl)butadiene (DMPBD), (E)-1-(3,4-dimethoxyphenyl)but-3-en-1-ol (compound D), and (E)-1-(3,4-dimethoxyphenyl)but-3-en-1-yl acetate (compound D acetate). The PE contained a total phenylbutenoid content of 1.42% w/w. The PE exhibited potent anti-inflammatory properties, with half maximal inhibitory concentration (IC50) values of 7.2 µg/mL for NO, 23.4 µg/mL for TNF-α, and 19.8 µg/mL for IL-1β. In comparison, DMPBD exhibited lower activity against NO and TNF-α (IC50 values of 16.3 and 37.2 µg/mL, respectively) but similar efficacy against IL-1β (IC50 of 17.7 µg/mL) in LPS-induced RAW264.7 cells. All test compounds significantly decreased the percentage of apoptotic cells and suppressed intracellular ROS production in hydrogen peroxide-induced C2C12 myoblast cells. Notably, PE exhibited the highest potency in reducing apoptotic cells, with the lowest IC50 value of 11.6 µg/mL. PE inhibited the expression of p-p38/p38, pERK/ERK, and pAkt/Akt in the LPS-induced inflammatory response in RAW264.7 cells. Additionally, PE significantly suppressed the cleaved/pro-caspase-3 ratio without affecting Bax and Bcl-2 protein levels. Conclusion These findings suggest that PE and its phenylbutenoids exhibit anti-inflammatory effects through the inhibition of p38, ERK, and Akt signaling pathways, and anti-apoptotic effects via the inhibition of the caspase-3 pathway, highlighting their therapeutic potential for managing inflammatory and degenerative conditions. Clinical trial number Not applicable.https://doi.org/10.1186/s12906-025-04907-wAnti-inflammatoryApoptosisPhenylbutenoidZingiber cassumunar
spellingShingle Thidaporn Gundom
Wanida Sukketsiri
Pharkphoom Panichayupakaranant
Phytochemical analysis and biological effects of Zingiber cassumunar extract and three phenylbutenoids: targeting NF-κB, Akt/MAPK, and caspase-3 pathways
BMC Complementary Medicine and Therapies
Anti-inflammatory
Apoptosis
Phenylbutenoid
Zingiber cassumunar
title Phytochemical analysis and biological effects of Zingiber cassumunar extract and three phenylbutenoids: targeting NF-κB, Akt/MAPK, and caspase-3 pathways
title_full Phytochemical analysis and biological effects of Zingiber cassumunar extract and three phenylbutenoids: targeting NF-κB, Akt/MAPK, and caspase-3 pathways
title_fullStr Phytochemical analysis and biological effects of Zingiber cassumunar extract and three phenylbutenoids: targeting NF-κB, Akt/MAPK, and caspase-3 pathways
title_full_unstemmed Phytochemical analysis and biological effects of Zingiber cassumunar extract and three phenylbutenoids: targeting NF-κB, Akt/MAPK, and caspase-3 pathways
title_short Phytochemical analysis and biological effects of Zingiber cassumunar extract and three phenylbutenoids: targeting NF-κB, Akt/MAPK, and caspase-3 pathways
title_sort phytochemical analysis and biological effects of zingiber cassumunar extract and three phenylbutenoids targeting nf κb akt mapk and caspase 3 pathways
topic Anti-inflammatory
Apoptosis
Phenylbutenoid
Zingiber cassumunar
url https://doi.org/10.1186/s12906-025-04907-w
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