Anti-Proliferative Activity of Triterpenoids and Sterols Isolated from Alstonia scholaris against Non-Small-Cell Lung Carcinoma Cells

Abstract

(1) Background: In China and South Asia, <i>Alstonia scholaris</i> (Apocynaceae) is an important medicinal plant that has been historically used in traditional ethnopharmacy to treat infectious diseases. Although various pharmacological activities have been reported, the anti-lung cancer components of <i>A. scholaris</i> have not yet been identified. The objective of this study is to evaluate the active components of the leaf extract of <i>A. scholaris</i><i>,</i> and assess the anti-proliferation effects of isolated compounds against non-small-cell lung carcinoma cells; (2) Methods: NMR was used to identify the chemical constitutes isolated from the leaf extract of <i>A. scholaris</i>. The anti-proliferative activity of compounds against non-small-cell lung carcinoma cells was assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay; (3) Results: Eight triterpenoids and five sterols were isolated from the hexane portion of <i>A. scholaris</i>, and structurally identified as: (<b>1</b>) ursolic acid, (<b>2</b>) oleanolic acid, (<b>3</b>) betulinic acid, (<b>4</b>) betulin, (<b>5</b>) 2β,3β,28-lup-20(29)-ene-triol, (<b>6</b>) lupeol, (<b>7</b>) β-amyrin, (<b>8</b>) α-amyrin, (<b>9</b>) poriferasterol, (<b>10</b>) epicampesterol, (<b>11</b>) β-sitosterol, (<b>12</b>) 6β-hydroxy-4-stigmasten-3-one, and (<b>1</b>3) ergosta-7,22-diene-3β,5α,6β-triol. Compound 5 was isolated from a plant source for the first time. In addition, compounds <b>9</b>, <b>10</b>, <b>12</b>, and <b>13</b> were also isolated from A. scholaris for the first time. Ursolic acid, betulinic acid, betulin, and 2β,3β,28-lup-20(29)-ene-triol showed anti-proliferative activity against NSCLC, with IC₅₀ of 39.8, 40.1, 240.5 and 172.6 μM, respectively.; (4) Conclusion: These findings reflect that pentacyclic triterpenoids are the anti-lung cancer chemicals in A. scholaris. The ability of ursolic acid, betulinic acid, betulin, and 2β,3β,28-lup-20(29)-ene-triol to inhibit the proliferative activity of NSCLC can constitute a valuable group of therapeutic agents in the future.