The Antiaging Effect of Active Fractions and <i>Ent</i>-11α-Hydroxy-15-Oxo-Kaur-16-En-19-Oic Acid Isolated from <i>Adenostemma lavenia</i> (L.) O. Kuntze at the Cellular Level

• Main Authors: Irmanida Batubara, Rika Indri Astuti, Muhammad Eka Prastya, Auliya Ilmiawati, Miwa Maeda, Mayu Suzuki, Akie Hamamoto, Hiroshi Takemori
• Format: Article
• Language: English
• Published: MDPI AG 2020-08-01
• Series: Antioxidants
• Subjects: antiaging; <i>ent</i>-11α-hydroxy-15-oxo-kaur-16-en-19-oic acid; <i>Adenostemma lavenia</i>; <i>pap1</i>⁺ transcription factor; NRF2
• Online Access: https://www.mdpi.com/2076-3921/9/8/719

Background: The extract of <i>Adenostemma lavenia</i> (L.) O. Kuntze leaves has anti-inflammatory activities and is used as a folk medicine to treat patients with hepatitis and pneumonia in China and Taiwan. The diterpenoid <i>ent</i>-11α-hydroxy-15-oxo-kaur-16-en-19-oic acid (11αOH-KA) is the major ingredient in the extract and has wide-spectrum biological activities, such as antitumor and antimelanogenic activities, as well as anti-inflammatory activity. However, the physical and biological properties of this compound as an antioxidant or antiaging agent have not been reported yet. Methods: In addition to in vitro assays, we monitored antioxidative and antiaging signals in <i>Schizosaccharomyces pombe</i> (yeast) and mouse melanoma B16F10 cells. Results: <i>A. lavenia</i> water and chloroform fractions showed antioxidant properties in vitro. The <i>A. lavenia</i> extracts and 11αOH-KA conferred resistance to H₂O₂ to <i>S. pombe</i> and B16F10 cells and extended the yeast lifespan in a concentration-dependent manner. These materials maintained the yeast mitochondrial activity, even in a high-glucose medium, and induced an antioxidant gene program, the transcriptional factor <i>pap1</i>⁺ and its downstream <i>ctt1</i>⁺. Accordingly, 11αOH-KA activated the antioxidative transcription factor NF-E2-related factor 2, NRF2, the mammalian ortholog of <i>pap1</i>⁺, in B16F10 cells, which was accompanied by enhanced hemeoxygenase expression levels. These results suggest that 11αOH-KA and <i>A. lavenia</i> extracts may protect yeast and mammalian cells from oxidative stress and aging. Finally, we hope that these materials could be helpful in treating COVID-19 patients, because <i>A. lavenia</i> extracts and NRF2 activators have been reported to alleviate the symptoms of pneumonia in model animals.