Novel serotonin-boosting effect of incense smoke from Kynam agarwood in mice: The involvement of multiple neuroactive pathways

J Ethnopharmacol. 2021 Jul 15:275:114069. doi: 10.1016/j.jep.2021.114069. Epub 2021 Mar 29.


Ethnopharmacological relevance: Stress is a state of feeling that inhibits one from responding properly in the face of a threat. Agarwood smoke has been used in traditional medicine as a sedative anti-anxious, and anti-restless therapy. Its scent emitted from heat induces people to enter a stable state; however, the underlying molecular effect is still unclear.

Aim of the study: This study analyzed novel biological events and gene expression signatures induced by agarwood incense smoke in mice.

Materials and methods: Incense smoke was produced by heating at 150 °C for 30 min in a headspace autosampler oven. We treated mice with exposure to incense smoke from Kynam agarwood for 45 min/day for 7 consecutive days. After a 7-day inhalation period, the potent agarwood smoke affected-indicators in serum were measured, and the RNA profiles of the mouse brains were analyzed by microarray to elucidate the biological events induced by agarwood incense smoke.

Results: Chemical profile analysis showed that the major component in the incense smoke of Kynam was 2-(2-phenylethyl) chromone (26.82%). Incense smoke from Kynam induced mice to enter a stable state and increased the levels of serotonin in sera. The emotion-related pathways, including dopaminergic synapse, serotonergic synapse, GABAergic synapse, long-term depression and neuroactive ligand-receptor interaction, were significantly affected by incense smoke. Moreover, the expression of Crhr2 and Chrnd genes, involved with neuroactive ligand-receptor interaction pathway, was upregulated by incense smoke.

Conclusions: By a newly-established incense smoke exposure system, we first identified that anti-anxious and anti-depressant effects of agarwood incense smoke were likely associated with the increase of serotonin levels and multiple neuroactive pathways in mice.

Keywords: Agarwood; Gene expression profile; Incense smoke; Serotonin.

MeSH terms

  • Animals
  • Anti-Anxiety Agents / chemistry
  • Anti-Anxiety Agents / pharmacology*
  • Anti-Anxiety Agents / therapeutic use
  • Antidepressive Agents / chemistry
  • Antidepressive Agents / pharmacology*
  • Antidepressive Agents / therapeutic use
  • Behavior, Animal / drug effects
  • Brain / drug effects
  • Emotions / drug effects
  • Flavonoids / pharmacology
  • Flavonoids / therapeutic use
  • Gene Expression / drug effects
  • Hypnotics and Sedatives / chemistry
  • Hypnotics and Sedatives / pharmacology*
  • Hypnotics and Sedatives / therapeutic use
  • Male
  • Medicine, Traditional
  • Mice
  • Mice, Inbred BALB C
  • Plant Extracts / chemistry
  • Plant Extracts / pharmacology*
  • Plant Extracts / therapeutic use
  • Receptors, Cholinergic / genetics
  • Receptors, Cholinergic / metabolism
  • Receptors, Corticotropin-Releasing Hormone / genetics
  • Receptors, Corticotropin-Releasing Hormone / metabolism
  • Serotonin / metabolism*
  • Signal Transduction / drug effects
  • Smoke / analysis*
  • Up-Regulation / drug effects
  • Wood / chemistry*


  • Anti-Anxiety Agents
  • Antidepressive Agents
  • CRF receptor type 2
  • Chrnd protein, mouse
  • Flavonoids
  • Hypnotics and Sedatives
  • Plant Extracts
  • Receptors, Cholinergic
  • Receptors, Corticotropin-Releasing Hormone
  • Smoke
  • Serotonin
  • 2-(2-phenylethyl)chromone