New Diterpenoids from Mesona procumbens with Antiproliferative Activities Modulate Cell Cycle Arrest and Apoptosis in Human Leukemia Cancer Cells

Abstract

Mesona procumbens is a popular material used in foods and herbal medicines in Asia for clearing heat and resolving toxins. However, phytochemical research on this plant is very rare. In this study, eleven new diterpenoids, mesonols A-K (1–11), comprising seven ent-kauranes, three ent-atisanes, and one sarcopetalane, were isolated from its methanolic extract. Structural elucidation of compounds 1–11 was performed by spectroscopic methods, especially 2D NMR, HRESIMS, and X-ray crystallographic analysis. All isolates were assessed for their antiproliferative activity, and compounds 1–4 showed potential antiproliferative activities against A549, Hep-3B, PC-3, HT29, and U937 cancer cells, with IC50 values ranging from 1.97 to 19.86 µM. The most active compounds, 1 and 2, were selected for further investigation of their effects on cell cycle progression, apoptosis, and ROS generation in U937 human leukemia cancer cells. Interestingly, it was found that compounds 1 and 2 induced antiproliferative effects in U937 cells through different mechanisms. Compound 1 caused cell cycle arrest at the G2/M phase and subsequent cell death in a dose- and time-dependent manner. However, 2-mediated antiproliferation of U937 cells triggered ROS-mediated mitochondrial-dependent apoptosis. These results provide insight into the molecular mechanism involved in the antiproliferative activities of compounds 1 and 2 in U937 cells. Altogether, the study showed that new diterpenoid compounds 1 and 2 from M. procumbens are potent and promising anticancer agents.

Functionality and Health-Promoting Properties of Polysaccharide and Plant-Derived Substances from Mesona chinensis

“…Ethanolic extracts of M. chinensis, at concentrations of 1560-100,000 µg/mL and 390-3130 µg/mL, showed significant inhibition effects against the viability of CT-26 (colorectal cancer cell line) and HT-29 (Human colon cancer cells) colorectal cancer cell lines, respectively [79]. The protective effect of a methanolic extract of M. chinensis on human leukemia cancer cells was reported by Huang et al [28]. The methanolic extract revealed 11 new diterpenoid compounds, mesonols 1-11, and mesonols 1-4 compounds, which provided antiproliferative activities against five cancer cell lines (human lung carcinoma (A549), human liver carcinoma (Hep-3B), human prostate carcinoma (PC-3), human colon carcinoma (HT29), and human monoblastic leukemia (U937)), with reduced toxicity against the RAW 264.7 cell line.…”

“…The ethanolic M. chinensis extraction yielded rosmarinic acid, apigenin, 7-hydroxycoumarin, ferulic acid, and rutin [16]. Eleven novel diterpenoids were reported as resulting from the methanolic extraction of M. chinensis after isolation with n-hexane and CH 2 Cl 2 , including seven ent-kauranes, three ent-atisanes, and one sarcopetalane [28]. Bioactive compounds of M. chinensis ethanolic extracts and their fractions, named as F0, F10, F20, F30, F40, F50, and MTFs (Mesona total flavonoids) (including aqueous extract (AE)) and detected using high performance liquid chromatography with mass spectrometry (HPLC-MS) analysis, mainly contained caffeic acid, quercetin 3-O-galactoside, isoquercetin, astragalin, rosmarinic acid, aromadendrin-3-O-rutinoside, rosmarinic acid-3-O-glucoside, and kaempferol-7-O-glucoside.…”

“…This review discussed the recent scientific information on the Mesona plant regarding the composition of its phytochemicals and its alteration of gut microbiota, as well as its health benefits. Several bioactive compounds and polysaccharide components have been reported to have various pharmacological effects including antioxidant activities [25], hypoglycemic and hypolipidemic activities [26,27], antiproliferative activities [28], a growth inhibitory effect on hepatocellular carcinoma (HepG2) cells [15], anti-dyslipidemia activities [29], renalprotective activities [30], antihypertensive [31] and DNA damage-protective activities [32], anti-inflammatory activities [33], antimutagenic effects [34], and antibiosis activities [35].…”

New Diterpenes with Potential Antitumoral Activity Isolated from Plants in the Years 2017–2022

“…From Mesona procumbens Hemsl. (Lamiaceae) whole plant, a traditional Chinese herb, it was possible to isolate seven new ent-kauranes, named mesonols A-G, by methanolic extraction and subsequent partitioning with n-hexane and CH 2 Cl 2 [130]. Their structures were determined by spectroscopic methods, especially 2D NMR, HRESIMS, and X-ray crystallographic analysis.…”