Multiple Beneficial Effects of Aloesone from <i>Aloe vera</i> on LPS-Induced RAW264.7 Cells, Including the Inhibition of Oxidative Stress, Inflammation, M1 Polarization, and Apoptosis
Aloesone is a major metabolic compound in <i>Aloe vera</i>, which has been widely used as a food source and therapeutic agent in several countries. Our recent study demonstrated that aloesone has anti-epileptic effects on glutamate-induced neuronal injury by suppressing the production of...
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MDPI AG
2023-02-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/28/4/1617 |
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| author | Yan Wang Zhongyv Xiong Chang Li Dong Liu Xiaogang Li Junyv Xu Niangen Chen Xuesong Wang Qifu Li Youbin Li |
| author_facet | Yan Wang Zhongyv Xiong Chang Li Dong Liu Xiaogang Li Junyv Xu Niangen Chen Xuesong Wang Qifu Li Youbin Li |
| author_sort | Yan Wang |
| collection | DOAJ |
| description | Aloesone is a major metabolic compound in <i>Aloe vera</i>, which has been widely used as a food source and therapeutic agent in several countries. Our recent study demonstrated that aloesone has anti-epileptic effects on glutamate-induced neuronal injury by suppressing the production of reactive oxygen species (ROS). Unless ROS are naturally neutralized by the endogenous antioxidant system, they lead to the activation of inflammation, polarization, and apoptosis. This study aimed to identify the multiple beneficial effects of aloesone and explore its molecular mechanism in macrophages. Hence, the murine macrophage cell line RAW264.7 was pretreated with aloesone and then exposed to lipopolysaccharides (LPS). The results demonstrated that aloesone, within a dosage range of 0.1–100 µM, dramatically decreased the LPS-induced elevation of ROS production, reduced nitric oxide (NO) release, inhibited the M1 polarization of RAW264.7 cells, and prevented cells from entering the LPS-induced early and late phases of apoptosis in a dose-dependent manner. Simultaneously, aloesone significantly decreased the mRNA expression of inflammation-related genes (iNOS, IL-1ꞵ, TNF-α) and increased the expression of antioxidant enzymes (Gpx-1 and SOD-1). The core genes HSP90AA1, Stat3, Mapk1, mTOR, Fyn, Ptk2b, and Lck were closely related to these beneficial effects of aloesone. Furthermore, immunofluorescence staining and flow cytometry data confirmed that aloesone significantly repressed the activation of mTOR, p-mTOR, and HIF-1α induced by LPS and inhibited the protein expression of TLR4, which is the target of LPS. In conclusion, aloesone demonstrated multiple protective effects against LPS-induced oxidative stress, inflammation, M1 polarization, and apoptosis in macrophages, suggesting its potential as a prodrug. |
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| last_indexed | 2024-03-11T08:22:26Z |
| publishDate | 2023-02-01 |
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| series | Molecules |
| spelling | doaj.art-9c3c03a64b6345b381ec1bd624d593512023-11-16T22:20:57ZengMDPI AGMolecules1420-30492023-02-01284161710.3390/molecules28041617Multiple Beneficial Effects of Aloesone from <i>Aloe vera</i> on LPS-Induced RAW264.7 Cells, Including the Inhibition of Oxidative Stress, Inflammation, M1 Polarization, and ApoptosisYan Wang0Zhongyv Xiong1Chang Li2Dong Liu3Xiaogang Li4Junyv Xu5Niangen Chen6Xuesong Wang7Qifu Li8Youbin Li9Key Laboratory of Tropical Translational Medicine of Ministry of Education, Hainan Key Laboratory for Research and Development of Tropical Herbs, Key Laboratory of Li Nationality Medicine, School of Pharmacy, Department of Neurology, The First Affiliated Hospital of Hainan Medical University, Hainan Medical University, Haikou 571199, ChinaKey Laboratory of Tropical Translational Medicine of Ministry of Education, Hainan Key Laboratory for Research and Development of Tropical Herbs, Key Laboratory of Li Nationality Medicine, School of Pharmacy, Department of Neurology, The First Affiliated Hospital of Hainan Medical University, Hainan Medical University, Haikou 571199, ChinaKey Laboratory of Tropical Translational Medicine of Ministry of Education, Hainan Key Laboratory for Research and Development of Tropical Herbs, Key Laboratory of Li Nationality Medicine, School of Pharmacy, Department of Neurology, The First Affiliated Hospital of Hainan Medical University, Hainan Medical University, Haikou 571199, ChinaKey Laboratory of Tropical Translational Medicine of Ministry of Education, Hainan Key Laboratory for Research and Development of Tropical Herbs, Key Laboratory of Li Nationality Medicine, School of Pharmacy, Department of Neurology, The First Affiliated Hospital of Hainan Medical University, Hainan Medical University, Haikou 571199, ChinaKey Laboratory of Tropical Translational Medicine of Ministry of Education, Hainan Key Laboratory for Research and Development of Tropical Herbs, Key Laboratory of Li Nationality Medicine, School of Pharmacy, Department of Neurology, The First Affiliated Hospital of Hainan Medical University, Hainan Medical University, Haikou 571199, ChinaKey Laboratory of Tropical Translational Medicine of Ministry of Education, Hainan Key Laboratory for Research and Development of Tropical Herbs, Key Laboratory of Li Nationality Medicine, School of Pharmacy, Department of Neurology, The First Affiliated Hospital of Hainan Medical University, Hainan Medical University, Haikou 571199, ChinaKey Laboratory of Tropical Translational Medicine of Ministry of Education, Hainan Key Laboratory for Research and Development of Tropical Herbs, Key Laboratory of Li Nationality Medicine, School of Pharmacy, Department of Neurology, The First Affiliated Hospital of Hainan Medical University, Hainan Medical University, Haikou 571199, ChinaKey Laboratory of Tropical Translational Medicine of Ministry of Education, Hainan Key Laboratory for Research and Development of Tropical Herbs, Key Laboratory of Li Nationality Medicine, School of Pharmacy, Department of Neurology, The First Affiliated Hospital of Hainan Medical University, Hainan Medical University, Haikou 571199, ChinaKey Laboratory of Tropical Translational Medicine of Ministry of Education, Hainan Key Laboratory for Research and Development of Tropical Herbs, Key Laboratory of Li Nationality Medicine, School of Pharmacy, Department of Neurology, The First Affiliated Hospital of Hainan Medical University, Hainan Medical University, Haikou 571199, ChinaKey Laboratory of Tropical Translational Medicine of Ministry of Education, Hainan Key Laboratory for Research and Development of Tropical Herbs, Key Laboratory of Li Nationality Medicine, School of Pharmacy, Department of Neurology, The First Affiliated Hospital of Hainan Medical University, Hainan Medical University, Haikou 571199, ChinaAloesone is a major metabolic compound in <i>Aloe vera</i>, which has been widely used as a food source and therapeutic agent in several countries. Our recent study demonstrated that aloesone has anti-epileptic effects on glutamate-induced neuronal injury by suppressing the production of reactive oxygen species (ROS). Unless ROS are naturally neutralized by the endogenous antioxidant system, they lead to the activation of inflammation, polarization, and apoptosis. This study aimed to identify the multiple beneficial effects of aloesone and explore its molecular mechanism in macrophages. Hence, the murine macrophage cell line RAW264.7 was pretreated with aloesone and then exposed to lipopolysaccharides (LPS). The results demonstrated that aloesone, within a dosage range of 0.1–100 µM, dramatically decreased the LPS-induced elevation of ROS production, reduced nitric oxide (NO) release, inhibited the M1 polarization of RAW264.7 cells, and prevented cells from entering the LPS-induced early and late phases of apoptosis in a dose-dependent manner. Simultaneously, aloesone significantly decreased the mRNA expression of inflammation-related genes (iNOS, IL-1ꞵ, TNF-α) and increased the expression of antioxidant enzymes (Gpx-1 and SOD-1). The core genes HSP90AA1, Stat3, Mapk1, mTOR, Fyn, Ptk2b, and Lck were closely related to these beneficial effects of aloesone. Furthermore, immunofluorescence staining and flow cytometry data confirmed that aloesone significantly repressed the activation of mTOR, p-mTOR, and HIF-1α induced by LPS and inhibited the protein expression of TLR4, which is the target of LPS. In conclusion, aloesone demonstrated multiple protective effects against LPS-induced oxidative stress, inflammation, M1 polarization, and apoptosis in macrophages, suggesting its potential as a prodrug.https://www.mdpi.com/1420-3049/28/4/1617aloesoneanti-apoptosisanti-inflammationanti-M1 polarizationantioxidant stressK |
| spellingShingle | Yan Wang Zhongyv Xiong Chang Li Dong Liu Xiaogang Li Junyv Xu Niangen Chen Xuesong Wang Qifu Li Youbin Li Multiple Beneficial Effects of Aloesone from <i>Aloe vera</i> on LPS-Induced RAW264.7 Cells, Including the Inhibition of Oxidative Stress, Inflammation, M1 Polarization, and Apoptosis Molecules aloesone anti-apoptosis anti-inflammation anti-M1 polarization antioxidant stressK |
| title | Multiple Beneficial Effects of Aloesone from <i>Aloe vera</i> on LPS-Induced RAW264.7 Cells, Including the Inhibition of Oxidative Stress, Inflammation, M1 Polarization, and Apoptosis |
| title_full | Multiple Beneficial Effects of Aloesone from <i>Aloe vera</i> on LPS-Induced RAW264.7 Cells, Including the Inhibition of Oxidative Stress, Inflammation, M1 Polarization, and Apoptosis |
| title_fullStr | Multiple Beneficial Effects of Aloesone from <i>Aloe vera</i> on LPS-Induced RAW264.7 Cells, Including the Inhibition of Oxidative Stress, Inflammation, M1 Polarization, and Apoptosis |
| title_full_unstemmed | Multiple Beneficial Effects of Aloesone from <i>Aloe vera</i> on LPS-Induced RAW264.7 Cells, Including the Inhibition of Oxidative Stress, Inflammation, M1 Polarization, and Apoptosis |
| title_short | Multiple Beneficial Effects of Aloesone from <i>Aloe vera</i> on LPS-Induced RAW264.7 Cells, Including the Inhibition of Oxidative Stress, Inflammation, M1 Polarization, and Apoptosis |
| title_sort | multiple beneficial effects of aloesone from i aloe vera i on lps induced raw264 7 cells including the inhibition of oxidative stress inflammation m1 polarization and apoptosis |
| topic | aloesone anti-apoptosis anti-inflammation anti-M1 polarization antioxidant stressK |
| url | https://www.mdpi.com/1420-3049/28/4/1617 |
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