Dendrobium officinale extends lifespan in yeast and Drosophila via context-dependent PI3K-AKT modulation

  • J Ethnopharmacol. 2026 Sep 15:368:121777. doi: 10.1016/j.jep.2026.121777.
Zhengqiong Sun  1 ,  Min Jiang  2 ,  Lei Li  3 ,  Yongxing Chen  4 ,  Lichun Zhao  5 ,  Lei Zhang  6
Affiliations
  • 1. Institute of Interdisciplinary Integrative Medicine Research, Medical College of Nantong University, Nantong, 226019, China; Department of Pharmaceutical Botany, School of Pharmacy, Naval Medical University, Shanghai, 200433, China.
  • 2. Key Laboratory of Ethnic Medicine Resource Development and Utilization in Guizhou Province, School of Chinese Ethnic Medicine, Guizhou Minzu University, Guiyang, 550025, China.
  • 3. Department of Pharmaceutical Botany, School of Pharmacy, Naval Medical University, Shanghai, 200433, China.
  • 4. College of Pharmacy, Fujian University of Traditional Chinese Medicine, Fuzhou, 350122, China.
  • 5. College of Pharmaceutical Sciences, Guizhou University of Traditional Chinese Medicine. Guiyang, 550025, China. Electronic address: [email protected].
  • 6. Institute of Interdisciplinary Integrative Medicine Research, Medical College of Nantong University, Nantong, 226019, China; Department of Pharmaceutical Botany, School of Pharmacy, Naval Medical University, Shanghai, 200433, China. Electronic address: [email protected].
PMID: 42069158 DOI: 10.1016/j.jep.2026.121777
Abstract

Ethnopharmacological relevance: Dendrobium officinale Kimura et Migo (Tiepi Shihu), a yin-nourishing tonic in traditional Chinese medicine, has been historically used for health maintenance and longevity promotion.

Aim of the study: We evaluated the Anti-aging effects of D. officinale whole powder (DOP) and a non-polysaccharide fraction (DOE) and explored underlying mechanisms focusing on conserved PI3K-AKT signaling.

Materials and methods: Network pharmacology was applied to predict aging-related targets and enriched pathways. Anti-aging activity was assessed in yeast (Saccharomyces cerevisiae) and female flies (Drosophila melanogaster) using lifespan and healthspan assays, a high-sugar diet challenge, and pathway readouts via qRT-PCR and Western blotting. In RAW264.7 macrophages, the PI3K Inhibitor LY294002 and the Akt Inhibitor MK-2206 were used to evaluate pathway dependence.

Results: Network pharmacology identified 355 overlapping targets, enriched in PI3K-AKT, MAPK, Ras, and HIF-1 pathways. We found that dihydroconiferyl alcohol, homovanillyl alcohol, and taxifolin extended yeast lifespan, and these effects were abolished in yeast mutants defective in key aging-related genes. In flies, DOP extended female lifespan, improved climbing performance, and mitigated high-sugar diet-induced lifespan loss and hyperglycemia, accompanied by reduced Akt phosphorylation under dietary stress and enhanced FOXO-associated responses. DOE also extended lifespan, increased Akt/S6K phosphorylation and reduced FOXO in flies. D. officinale was associated with context-dependent modulation of innate immune-related gene expression. However, DOE suppressed Akt activity and increased FOXO in RAW264.7 cells; co-treatment with MK-2206 abolished DOE-induced changes.

Conclusions: D. officinale exerts Anti-aging effects in yeast and Drosophila models, while mammalian macrophages support a mechanistic role for context-dependent PI3K-AKT signaling regulation. Its distinct fractions act in a context-dependent manner, with Akt serving as a central regulatory node and FOXO-associated responses, supporting its ethnopharmacological use as a longevity-promoting herb.

Keywords
Anti-Aging; Dendrobium officinale; Drosophila melanogaster; FOXO; Network pharmacology; PI3K-AKT signaling.
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