Undescribed Phyllocladane-Type Diterpenoids from <i>Callicarpa giraldii</i> Hesse ex Rehd. and Their Anti-Neuroinflammatory Activity.

Abstract

<i>Callicarpa giraldii</i> Hesse ex Rehd. is an endemic plant in China and has long been used as a traditional medicine in several provinces. Although the plant has been reported to contain flavonoids, triterpenes, and alkaloids, this study represents the first report of the isolation of phyllocladane-type diterpenoids, a relatively rare class of compounds. In this study, 18 new phyllocladane-type diterpenoids (<b>7</b>-<b>24</b>) were isolated and structurally elucidated, including eight uncommon 3,4-<i>seco</i> phyllocladane-type diterpenoids (<b>15</b>-<b>22</b>) and two unusual phyllocladane-type diterpene dimers (<b>23</b>-<b>24</b>), along with six known analogues (<b>1</b>-<b>6</b>). Their structures were elucidated by a comprehensive analysis of 1D and 2D NMR, IR, and HRESIMS data. The absolute configurations were determined by single crystal X-ray diffraction experiments, DFT NMR calculations, and TDDFT ECD calculations. Based on the obtained and reported spectroscopic data, we refined a rule to distinguish phyllocladane-type diterpenoids from their diastereomeric <i>ent</i>-kaurane-type compounds. Additionally, the isolated compounds were evaluated for their in vitro anti-neuroinflammatory activity against lipopolysaccharide (LPS)-induced inflammation in BV-2 microglial cells. Compounds <b>5</b>, <b>10</b>, <b>13</b>, <b>18</b>, <b>19</b>, and <b>20</b> showed moderate inhibitory activity at the concentration of 20 μM, with compounds <b>5</b> and <b>13</b> markedly reducing the mRNA levels of the pro-inflammatory cytokines IL-1<i>β</i>, IL-6, and TNF-<i>α</i> at this concentration.