Therapeutic potential of ethoxy mansonone G: A comprehensive exploration of its anticancer actions in breast cancer, colorectal cancer, and non-small cell lung carcinoma.

Mansonone G (MG), a 1,2-naphthoquinones with antiestrogenic, antimicrobial, and anti-adipogenic activities, is derived from the heartwood of Mansonia gagei Drumm. Ethoxy mansonone G (EMG), an essential derivative of MG, has anticancer and antioxidant agent. EMG also has antiestrogen activity and is demonstrated to lower estrogen receptor expression in endocrine-resistant cells. EMG significantly inhibits cell division, invasion, and anchorage-dependent growth in all cancer types. Through the stimulation of the tumor protein (p53) and extracellular signal-regulated kinase (ERK) signaling cascades, it also causes apoptosis. Moreover, it manifests its anti-cancerous effects in toll-like receptor pathways, c-Jun N-terminal kinase (c-JNK), and nuclear factor kappa B (NF-κB). EMG inhibits the phosphorylation of glycogen synthase kinase (GSK3), Erk, protein kinase B (Akt), and mammalian target of rapamycin (mTOR). By interfering with molecular cascades, EMG significantly reduces the metabolism of cancer cells. This paper focuses on the potential use of EMG in cancer treatment. Moreover, it states the methodology by which specific assays establish the anti-cancerous role of EMG. Breast cancer, non-small cell lung cancer, and colorectal cancer are only a few of the cancers for which EMG was shown to be effective. Through further research, EMG may be developed as a therapeutic solution to complications caused by cancer. This study presents EMG as a novel candidate for cancer therapy, offering a unique combination of pharmacological advantages and mechanistic insights that warrant further exploration and development toward addressing the complexities of cancer treatment.

Mansonone E from Mansonia gagei Inhibited α-MSH-Induced Melanogenesis in B16 Cells by Inhibiting CREB Expression and Phosphorylation in the PI3K/Akt Pathway.

Many natural products that inhibit melanogenesis, freckles, and hyperpigmentation have been selectively used in cosmetics because melanogenesis is linked to the multiple biogenesis cascades of melanin synthesis. However, some of these compounds have side effects that may result in their restriction in the future. We report here the isolation and structural elucidation of compounds extracted from Mansonia gagei and evaluate their activity on melanogenesis inhibition. We isolated five known compounds from M. gagei and identified them as mansonone E (1), mansorin I (2), populene F (3), mansonone G (4), and mansorin B (5). After evaluating the five compounds for cytotoxicity against B16 cells and inhibitory activity on α-melanocyte-stimulating hormone (α-MSH) induced melanogenesis, we determined that the cytotoxicity and melanogenesis-inhibitory effect of 1 were relatively low and high, respectively. Next, the effect of 1 on the expression of melanogenesis-related proteins was assessed; it was confirmed that 1 dose-dependently inhibited the expression levels of tyrosinase, tyrosinase-related protein 1 (TRP-1), TRP-2, cAMP response element binding protein (CREB), and microphthalmia-associated transcription factor (MITF) which were increased after stimulation by α-MSH. Furthermore, the effects of 1 on the phosphorylation levels of intracellular signaling pathway-related proteins were evaluated, and it was found that 1 dose-dependently rescued the phosphorylation of Akt and p38 mitogen-activated protein kinases (MAPK), which were up- or down-regulated after stimulation by α-MSH. In contrast, treatment with the phosphoinositide 3-kinase (PI3K)/Akt inhibitor wortmannin enhanced melanogenesis inhibition by mansonone E. Cumulatively, the data suggest that 1 suppresses α-MSH-induced melanogenesis in B16 cells by inhibiting both phosphorylation in the PI3K/Akt pathway and the expression of melanogenesis-related proteins.

Anticancer Profiling for Coumarins and Related O-Naphthoquinones from Mansonia gagei against Solid Tumor Cells In Vitro.

Napthoquinones and coumarins are naturally occurring compounds with potential anticancer activity. In the current study, two O-naphthoquinons (mansonone-G and mansonone-N) and six coumarins (mansorin-A, mansorin-B, mansorin-C, mansorins-I, mansorin-II, and mansorin-III) were isolated from the heartwood of Mansonia gagei family Sterculariaceae. Isolated compounds were examined for their potential anticancer activity against breast (MCF-7), cervix (HeLa), colorectal (HCT-116) and liver (HepG2) cancer cells using Sulfarhodamine-B (SRB) assay. Mansorin-II and mansorin-III showed relatively promising cytotoxic profile in all cell lines under investigation with inhibitory concentrations (IC50s) in the range of 0.74 µM to 36 µM and 3.95 µM to 35.3 µM, respectively. In addition, mansorin-B, mansorin-C, mansorin-II and mansorin-III significantly increased cellular entrapment of the P-glycoprotein (P-gp) substrate, doxorubicin, in colorectal cancer cells expressing the P-gp pump. The inhibitory effect of the isolated compounds on P-gp pump was examined using human recombinant P-gp molecules attached to ATPase subunit. Mansorin-B and mansonone-G were found to inhibit the P-gp attached ATPase subunit. On the other hand, mansorin-C, mansorin-III and mansorin-II inhibited P-gp pump via dual action (P-gp related ATPase subunit inhibition and P-gp substrate binding site occupation). However, mansorin II was examined for its potential chemomodulatory effect to paclitaxel (PTX) against colorectal cancer cells (HCT-116 and CaCo-2). Mansorin-II significantly reduced the IC50 of PTX in HCT-116 cells from 27.9 ± 10.2 nM to 5.1 ± 1.9 nM (synergism with combination index of 0.44). Additionally, Mansorin-II significantly reduced the IC50 of PTX in CaCo-2 cells from 2.1 ± 0.8 µM to 0.13 ± 0.03 µM (synergism with combination index of 0.18). Furthermore, cell cycle analysis was studied after combination of mansorin-II with paclitaxel using DNA flow cytometry analysis. Synergism of mansorin-II and PTX was reflected in increasing apoptotic cell population in both HCT-116 and CaCo-2 cells compared to PTX treatment alone. Combination of mansorin-II with PTX in CaCo-2 cells significantly increased the cell population in G2/M phase (from 2.9 ± 0.3% to 7.7 ± 0.8%) with reciprocal decrease in G0/G1 cell fraction from 52.1 ± 1.1% to 45.5 ± 1.0%. Similarly in HCT-116 cells, mansorin-II with PTX significantly increased the cell population in G2/M phase (from 33.4 ± 2.8% to 37.6 ± 1.3%) with reciprocal decrease in the S-phase cell population from 22.8 ± 1.7% to 20.2 ± 0.8%. In conclusion, mansorin-II synergizes the anticancer effect of paclitaxel in colorectal cancer cells, which might be partially attributed to enhancing its cellular entrapment via inhibiting P-gp efflux pump.

Allyl and prenyl ethers of mansonone G, new potential semisynthetic antibacterial agents.

Four natural 1,2-naphthoquinones: mansonones C, E, G, and H were isolated from the dichloromethane extract of Mansonia gagei Drumm. heartwoods. Mansonone G was further converted to eight ether and four ester analogues. The structures of mansonones and the analogues were well-confirmed by spectroscopic techniques. All compounds were evaluated for their antibacterial activity against Gram-positive and negative bacteria. Further modification of mansonone G furnished certain analogues displaying better activity than natural mansonones. Particularly, allyl and prenyl ethers of mansonone G exhibited better activity against Staphylococcus aureus with MIC sixty-four times better than their natural compound.

Identification and α-glucosidase inhibitory activity evaluation of two new coumarins derived from Mansonia gagei J. R. Drumm.

Five coumarins were isolated from the heartwood of Mansonia gagei, which included two newly discovered compounds, namely 11-hydroxypopulene E (1) and mansorin D (2), along with three previously identified compounds. The structures were determined through the utilisation of comprehensive spectroscopic data, ECD calculations, and a thorough comparison with existing literature data. The α-glucosidase inhibitory activities of all isolated compounds were assessed in yeast. Out of the compounds tested, compound 2 exhibited the most significant activity, displaying a percentage inhibition of 34.33% at a concentration of 200 µM.

α-Glucosidase inhibition of sesquiterpenoids from the heartwood of Mansonia gagei.

Nine undescribed sesquiterpenoids, along with ten known compounds, were isolated from the ethyl acetate extract of Mansonia gagei heartwood. Their structures were determined by spectroscopic data analysis (FTIR, 1D, 2D NMR, and HRESIMS), and their absolute configurations were established by ECD calculation. The isolated compounds were evaluated for their inhibitory effect against α-glucosidase from yeast. The results showed that mansonone U, mansonialactam, heliclactone and mansonone S exhibited exceptionally potent activities when compared to the positive control, acarbose, with IC50 values of 12.38 ± 0.71, 0.20 ± 0.05, 13.12 ± 2.85, and 12.05 ± 1.91 µM, respectively. Among them, mansonialactam possessed the most potent inhibitory activity against yeast α-glucosidase, and it showed an uncompetitive inhibition mode.

Gagones A-F: Six prenylated chalcones from the heartwood of Mansonia gagei.

Six undescribed prenylated chalcones gagones A-F were isolated from the acetone fraction of Mansonia gagei heartwood. Their structures were unambiguously established based on spectroscopic analysis (HRESIMS, 1D and 2D NMR), as well as comparison to literature data. Their absolute configurations were elucidated using DP4 and electronic circular dichroism calculations. Isolated compounds were evaluated for their inhibitory activity against α-glucosidase and DPPH assay. All of the tested compounds exhibited better activity than that of acarbose (IC50 93.6 ± 0.5 µM). Among them, gagone D exhibited the highest α-glucosidase inhibitory with the IC50 value of 3.6 ± 0.4 µM. For antioxidant activity, gagones A-C, and E showed more active than that of ascorbic acid (IC50 30.2 ± 0.5 µM) with the IC50 values of 13.2 ± 0.7, 20.1 ± 0.4, 19.3 ± 0.5 and 12.8 ± 0.2 µM, respectively.

A new neolignan and a new phenolic acid from the heartwood of Mansonia gagei J.R. Drumm.

One new neolignan (1) and one new phenolic compound (2), together with four known compounds (3-6) were isolated from the heartwood of Mansonia gagei. Their structures were elucidated by extensive spectroscopic analyses, including 1D and 2D NMR and HRESIMS. The absolute configuration of 2 was established based on the DP4+ protocol and by comparison of experimental and calculated ECD spectra. All isolated compounds were evaluated by DPPH assay for antioxidant activity, while compounds 3-6 were assayed using the MTT-based colorimetric assay for cytotoxicity against lung cancer cell line A549. In terms of antioxidant activity, 1 and 3 exhibited stronger activity (IC50 14.91 ± 1.10 and 17.46 ± 0.16 µM, respectively) than the positive control, ascorbic acid (IC50 30.20 ± 0.47 µM). Among the compounds tested for cytotoxicity, compound 3 showed the highest activity, with an IC50 value of 26.04 ± 2.95 µM.