| Summary: | <i>Platycodon grandiflorus</i> (balloon flower), used as a food reserve as well as in traditional herbal medicine, is known for its multiple beneficial effects. In particular, this plant is widely used as a vegetable in Republic of Korea. We examined the ameliorative effects of <i>P. grandiflorus</i> on alloxan-induced pancreatic islet damage in zebrafish. The aerial part treatment led to a significant recovery in pancreatic islet size and glucose uptake. The efficacy of the aerial part was more potent than that of the root. Eight flavonoids (<b>1</b>–<b>8</b>) were isolated from the aerial part. Structures of two new flavone glycosides, designated dorajiside I (<b>1</b>) and II (<b>2</b>), were elucidated to be luteolin 7-<i>O</i>-α-L-rhamno-pyranosyl (1 → 2)-(6-<i>O</i>-acetyl)-β-D-glucopyranoside and apigenin 7-<i>O</i>-α-L-rhamnopyranosyl (1 → 2)-(6-<i>O</i>-acetyl)-β-D-glucopyranoside, respectively, by spectroscopic analysis. Compounds <b>1</b>, <b>3</b>, <b>4</b> and <b>6</b>–<b>8</b> yielded the recovery of injured pancreatic islets in zebrafish. Among them, compound <b>7</b> blocked K<sub>ATP</sub> channels in pancreatic β-cells. Furthermore, compounds <b>3</b>, <b>4</b>, <b>6</b> and <b>7</b> showed significant changes with respect to the mRNA expression of <i>GCK</i>, <i>GCKR</i>, <i>GLIS3</i> and <i>CDKN2B</i> compared to alloxan-induced zebrafish. In conclusion, the aerial part of <i>P. grandiflorus</i> and its constituents conferred a regenerative effect on injured pancreatic islets.
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