Moringa oleifera Lam. Isothiocyanate Quinazolinone Derivatives Inhibit U251 Glioma Cell Proliferation through Cell Cycle Regulation and Apoptosis Induction.

A major active constituent of Moringa oleifera Lam. is 4-[(α-L-rhamnose oxy) benzyl] isothiocyanate (MITC). To broaden MITC's application and improve its biological activity, we synthesized a series of MITC quinazolinone derivatives and evaluated their anticancer activity. The anticancer effects and mechanisms of the compound with the most potent anticancer activity were investigated further. Among 16 MITC quinazolinone derivatives which were analyzed, MITC-12 significantly inhibited the growth of U251, A375, A431, HCT-116, HeLa, and MDA-MB-231 cells. MITC-12 significantly inhibited U251 cell proliferation in a time- and dose-dependent manner and decreased the number of EdU-positive cells, but was not toxic to normal human gastric mucosal cells (GES-1). Further, MITC-12 induced apoptosis of U251 cells, and increased caspase-3 expression levels and the Bax:Bcl-2 ratio. In addition, MITC-12 significantly decreased the proportion of U251 cells in the G1 phase and increased it in S and G2 phases. Transcriptome sequencing showed that MITC-12 had a significant regulatory effect on pathways regulating the cell cycle. Further, MITC-12 significantly decreased the expression levels of the cell cycle-related proteins CDK2, cyclinD1, and cyclinE, and increased those of cyclinA2, as well as the p-JNK:JNK ratio. These results indicate that MITC-12 inhibits U251 cell proliferation by inducing apoptosis and cell cycle arrest, activating JNK, and regulating cell cycle-associated proteins. MITC-12 has potential for use in the prevention and treatment of glioma.

Effects of UV/H2O2 degradation on Moringa oleifera Lam. leaves polysaccharides: Composition, in vitro fermentation and prebiotic properties on gut microorganisms.

Moringa oleifera Lam. leaves are a new raw food material rich in polysaccharides. These polysaccharides exhibit various biological properties, including antioxidant, hypoglycemic and immunoregulatory effects. However, the use of Moringa oleifera Lam. leaves polysaccharides (MOLP) may be limited by their large molecular weight (MW) and presence of numerous impurities, such as pigments. Research has indicated that degraded polysaccharides usually exhibit high biological activity because of changes in physical structure and chemical properties. In this study, we focused on the extraction of a degraded-modified fraction from MOLP using the Ultraviolet/ Hydrogen peroxide (UV/H2O2) method. Specifically, the physicochemical properties and glycosidic bond composition of a particular fraction (UV/H2O2 degraded Moringa oleifera Lam. leaves polysaccharides in 3 h called DMOLP-3) were investigated. In addition, in vitro simulated digestion experiments showed that DMOLP-3 was only partially degraded during gastrointestinal digestion, indicating that DMOLP-3 can be utilised by gut microorganisms. Furthermore, the prebiotic properties of MOLP and DMOLP-3 was studied using an in vitro faecal fermentation model. The results indicated that compared with MOLP, DMOLP-3 led to a decrease in both the colour and MW of the polysaccharides. In addition, this model exhibited enhanced solubility and antioxidant capabilities while also influencing the surface morphology. Moreover, DMOLP-3 can facilitate the proliferation of advantageous microorganisms and enhance the synthesis of short-chain fatty acids (SCFAs). These results provide valuable insights into the utilization of bioactive components in Moringa oleifera Lam. leaves for the intestinal health.

Alkaloid Extract of Moringa oleifera Lam. Exerts Antitumor Activity in Human Non-Small-Cell Lung Cancer via Modulation of the JAK2/STAT3 Signaling Pathway.

Lung cancer is one of the most common malignant tumors diagnosed worldwide. Moringa oleifera Lam. is a valuable medicinal plant native to India and Pakistan. However, the antilung cancer activity of M. oleifera alkaloid extract (MOAE) is unknown. The present study aimed to evaluate the regulatory effect of MOAE on A549 cells by examination of the proliferation, apoptosis, cell cycle, and migration of cells and to elucidate the possible mechanism of action of MOAE. We tested five types of cancer cells and four types of lung cancer cells and found MOAE exerted the strongest growth inhibitory effect against A549 cells but had low toxicity to GES-1 cells (human gastric mucosal epithelial cells). Simultaneously, MOAE induced apoptosis and increased the expression of the apoptosis-related proteins caspase-3 and caspase-9 in A549 cells. Furthermore, MOAE induced cell cycle arrest in the S phase through a decrease in the expression of the proteins cyclin D1 and cyclin E and an increase in the expression of the protein p21. MOAE also inhibited the migratory ability of A549 cells and decreased the expression of the migration-related proteins, matrix metalloproteinase (MMP) 2 and MMP9. In addition, the phosphorylation level of JAK2 and STAT3 proteins was decreased in MOAE-treated A549 cells. Furthermore, AZD1480 (a JAK inhibitor) and MOAE inhibited the proliferation and migration of A549 cells and induced cell apoptosis, and the effects of MOAE and AZD1480 were not additive. These results indicated that MOAE inhibits the proliferation and migration of A549 cells and induces apoptosis and cell cycle arrest through a mechanism that is related to the inhibition of JAK2/STAT3 pathway activation. Thus, this extract has potential for preventing and treating lung cancer.

Corrigendum: Moringa oleifera Alkaloids Inhibited PC3 Cells Growth and Migration Through the COX-2 Mediated Wnt/ß-Catenin Signaling Pathway.

[This corrects the article DOI: 10.3389/fphar.2020.523962.].

Phylogenetic analyses of Lycium chinense (Solanaceae) and its coordinal species applying chloroplast genome.

Lycium chinense is an important edible and medicinal plant. Now, the complete chloroplast (cp) genome of L. chinense was assembled based on the Illumina sequencing reads. The cp genome of L. chinense was 155,736 bp long and contained two short inverted repeat regions (25,469 bp), which were separated by a small single-copy region (18,206 bp) and a large single-copy region (86,592 bp). The cp genome encodes 113 unique genes, including 79 protein-coding genes, 30 transfer RNA genes, and 4 ribosomal RNA genes. The topology of the phylogenetic tree showed that L. chinense is closely clustered with species Lycium ruthenicum and Lycium barbarum.

Chloroplast genome and phylogenetic analyses of Morus alba (Moraceae).

Morus alba is an important medicinal plant that is used to treat human diseases. The complete chloroplast (cp) genome of M. alba was assembled based on the Illumina sequencing reads. The cp genome of M. alba was 159,290 bp and contained two short inverted repeat regions (25,690 bp) which were separated by a small single copy region (19,845 bp) and a large single copy region (88,065 bp). The cp genome encodes 111 unique genes, including 77 protein-coding genes, 30 transfer RNA genes and four ribosomal RNA genes. The topology of the phylogenetic tree showed that M. alba is closely clustered with species M. cathayana and M. mongolica.

Chloroplast genome and phylogenetic analyses of Poncirus trifoliata (Rutaceae).

Poncirus trifoliata is an important medicinal plant that is used to treat human diseases. In this study, the complete chloroplast (cp) genome of P. trifoliata was assembled based on the Illumina sequencing reads. The cp genome of P. trifoliata was 160,260 bp and contained two short inverted repeat regions (27,029 bp) which were separated by a small single copy region (18,760 bp) and a large single copy region (87,442 bp). The cp genome encodes 113 unique genes, including 79 protein-coding genes, 30 transfer RNA genes and 4 ribosomal RNA genes. The topology of the phylogenetic tree showed that P. trifoliata is closely clustered with genus Citrus.

Moringa oleifera Alkaloids Inhibited PC3 Cells Growth and Migration Through the COX-2 Mediated Wnt/ß-Catenin Signaling Pathway.

Moringa oleifera Lam. (M. oleifera) is valuable plant distributed in many tropical and subtropical countries. It has a number of medicinal uses and is highly nutritious. M. oleifera has been shown to inhibit tumor cell growth, but this effect has not been demonstrated on prostate cancer cells. In this study, we evaluated the inhibitory effect of M. oleifera alkaloids (MOA) on proliferation and migration of PC3 human prostate cancer cells in vitro and in vivo. Furthermore, we elucidated the mechanism of these effects. The results showed that MOA inhibited proliferation of PC3 cells and induced apoptosis and cell cycle arrest. Furthermore, MOA suppressed PC3 cell migration and inhibited the expression of matrix metalloproteinases (MMP)-9. In addition, MOA significantly downregulated the expression of cyclooxygenase 2 (COX-2), ß-catenin, phosphorylated glycogen synthase 3ß, and vascular endothelial growth factor, and suppressed production of prostaglandin E2 (PGE2). Furthermore, FH535 (ß-catenin inhibitor) and MOA reversed PGE2-induced PC3 cell proliferation and migration, and the effects of MOA and FH535 were not additive. In vivo experiments showed that MOA (150 mg/kg) significantly inhibited growth of xenograft tumors in mice, and significantly reduced the protein expression levels of COX-2 and ß-catenin in tumor tissues. These results indicate that MOA inhibits the proliferation and migration, and induces apoptosis and cell cycle arrest of PC3 cells. Additionally, MOA inhibits the proliferation and migration of PC3 cells through suppression of the COX-2 mediated Wnt/ß-catenin signaling pathway.

Moringa oleifera Leaf Petroleum Ether Extract Inhibits Lipogenesis by Activating the AMPK Signaling Pathway.

In recent years, obesity has become a key factor affecting human health. Moringa oleifera Lam. is a perennial tropical deciduous tree, which is widely used in human medicine due to its nutritional and unique medicinal value. It has a cholesterol-lowering effect, but its mechanism of action is unclear. In this study, we elucidated the inhibitory effect of M. oleifera leaf petroleum ether extract (MOPEE) on lipid accumulation by in vitro and in vivo experiments, and we described its mechanism of action. MOPEE suppressed adipogenesis in 3T3-L1 adipocytes in a dose-dependent manner and had no effect on cell viability at doses up to 400 µg/ml. Furthermore, MOPEE (400 µg/ml) significantly downregulated the expression of adipogenesis-associated proteins [peroxisome proliferator-activated receptor γ (PPARγ), CCAAT/enhancer-binding proteins α and ß (C/EBPα and C/EBPß), and fatty acid synthase (FAS)] and upregulated the expression of a lipolysis-associated protein [hormone-sensitive lipase (HSL)] in 3T3-L1 adipocytes. Additionally, MOPEE (400 µg/ml) significantly increased the degree of phosphorylation of AMP-activated protein kinase α (AMPKα) and acetyl-CoA carboxylase (ACC). An AMPK inhibitor reversed the MOPEE-induced activation of AMPKα and ACC in 3T3-L1 adipocytes. Animal experiments showed that, in high-fat diet (HFD) mice, MOPEE [0.5 g/kg body weight (BW)] effectively decreased BW; relative epididymal, perirenal, and mesenteric fat weight and fat tissue size; and hepatic fat accumulation. Furthermore, MOPEE markedly reduced the serum levels of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and aspartate aminotransferase (AST). Moreover, MOPEE significantly downregulated the expression of adipogenesis-associated proteins (PPARγ and FAS) and upregulated the expression of a lipolysis-associated protein [adipose triglyceride lipase (ATGL)] in HFD mice hepatic and epididymal fat tissue. Additionally, MOPEE markedly increased the degree of phosphorylation of AMPKα and ACC in HFD mice hepatic and epididymal fat tissue. Following ultrahigh-performance liquid chromatography quadrupole time-of-flight tandem mass spectrometry (UPLC-QTOF-MS/MS) analysis, three phytocompounds (isoquercitrin, chrysin-7-glucoside, and quercitrin) were identified as compounds with relatively high levels in MOPEE. Among them, quercitrin showed excellent fat accumulation inhibitory activity, and the three compounds had synergistic effects in inhibiting adipogenesis. Taken together, MOPEE inhibits fat accumulation by inhibiting the adipogenesis and promoting the lipolysis, and this process is related to AMPK activation.