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, Alstonia scholaris (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 A. scholaris have not yet been identified. The objective of this study is to evaluate the active components of the leaf extract of A. scholaris, 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 A. scholaris. 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 A. scholaris, and structurally identified as: (1) ursolic acid, (2) oleanolic acid, (3) betulinic acid, (4) betulin, (5) 2β,3β,28-lup-20(29)-ene-triol, (6) lupeol, (7) β-amyrin, (8) α-amyrin, (9) poriferasterol, (10) epicampesterol, (11) β-sitosterol, (12) 6β-hydroxy-4-stigmasten-3-one, and (13) ergosta-7,22-diene-3β,5α,6β-triol. Compound 5 was isolated from a plant source for the first time. In addition, compounds 9, 10, 12, and 13 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.

Betulin Protects HT-22 Hippocampal Cells against ER Stress through Induction of Heme Oxygenase-1 and Inhibition of ROS Production

“…Since betulin can be easily converted to betulinic acid, several previous reports have compared the effects of betulin with those of betulinic acid in a broad spectrum of biological and pharmacological activities. 20,21 In particular, the antioxidant effect of betulin is more outstanding than betulin acid in hepatic stellate cell. 22 In our results, betulinic acid, a pentacyclic lupane-type triterpene derivative of betulin, exhibited mild cytotoxicity towards HT-22 hippocampal cells owing only to the structural difference of 28 carboxy substituents ( Figure 1b).…”

Diversity of medicinal plants utilized by To Manui ethnic of Central Sulawesi, Indonesia

“…With the main chemical compositions of alkaloids, iridoids, coumarin, flavonoids, saponins, tannins, steroids, phenols and leukoantosians, A. scholaris. reported to have various pharmacological activities such as antidiabetic, anti hyperlipidemia, antibacterial, antioxidant, anticancer, anti-inflammatory, analgesic, immunostimulant, antitussive, antiinflammatory, hepatoprotective, antidepressant and antidiarrheal (Pankti et al 2012;Wang et al 2017). With the current LC/LR/lc conservation status, it is necessary to regulate and limit the exploration and exploitation of A. scholaris for preventing conservation status increase to near threatened or even become vulnerable.…”

Naturally occurring anti-cancer compounds: shining from Chinese herbal medicine

“…(cranberry), Arctostaphylos uva-ursi (L.) Spreng (bearberry), Rhododendron hymenanthes Makino, Eriobotrya japonica, Rosemarinus officinalis, Calluna vulgaris, Eugenia jambolana and Ocimum sanctum, as well as in the wax-like protective coatings of fruits such as pears, apples and prunes [265]. UA has numerous biochemical and pharmacological effects including antiinflammatory, anti-oxidative, anti-proliferative, anti-atherosclerotic, anti-leukemic, anti-viral, and anti-diabetic effects [266][267][268][269][270][271][272]. It also exerts anti-cancer activities in ovarian, breast, gastric, prostate, lung, liver, bladder, pancreatic, and colorectal cancers [273][274][275][276][277][278][279][280][281].…”