Suppressive, Curative, and Prophylactic Effects of Maesa lanceolata Forssk. against Rodent Malaria Parasite Plasmodium berghei.

The artemisinin partial resistance is believed to be spread to artemisinin-based combination therapy partner drugs. As a result, new antiplasmodial compounds are required to treat resistant malaria infections. In the invention of antimalarial substances, claimed medical plants are precious resources. So, the current study was designed to assess the antiplasmodial effects of Maesa lanceolata in mice. In this study, preliminary phytoconstituent and in vivo acute oral toxicity tests were done. Early infection, established infection, and residual infection tests were employed to determine the antimalarial effects of the test drugs. Three doses (200, 400, and 600 mg/kg) of the extracts were provided orally to the test mice. Analysis of variance (one-way) followed by post hoc Tukey's test was used to analyze the difference between and within groups. Terpenoids, tannins, saponins, flavonoids, and alkaloids were detected in the phytochemical constituent analysis. Both 80% methanolic crude extract and solvent fractions had no toxic result at the 2000 mg/kg dose. All test drug doses suppressed parasite levels in a significant manner at all tests. The activity of chloroform fraction (maximum percentage suppression, 81.28%) overwhelms the crude extract activity. The curative effects of 80% methanolic crude extract, with a maximum of 80.22% parasitemia suppression, were greater than its suppressive and prophylactic effects. The 400 mg/kg dose of chloroform fraction resulted in a maximum survival period (18 days) than other doses of tested materials. The results of this investigation provide support for the activity of M. lanceolata leaf extract against malaria.

Ebola Entry Inhibitors Discovered from Maesa perlarius.

Ebola virus disease (EVD), a disease caused by infection with Ebola virus (EBOV), is characterized by hemorrhagic fever and a high case fatality rate. With limited options for the treatment of EVD, anti-Ebola viral therapeutics need to be urgently developed. In this study, over 500 extracts of medicinal plants collected in the Lingnan region were tested against infection with Ebola-virus-pseudotyped particles (EBOVpp), leading to the discovery of Maesa perlarius as an anti-EBOV plant lead. The methanol extract (MPBE) of the stems of this plant showed an inhibitory effect against EBOVpp, with an IC50 value of 0.52 µg/mL, which was confirmed by testing the extract against infectious EBOV in a biosafety level 4 laboratory. The bioassay-guided fractionation of MPBE resulted in three proanthocyanidins (procyanidin B2 (1), procyanidin C1 (2), and epicatechin-(4ß→8)-epicatechin-(4ß→8)-epicatechin-(4ß→8)-epicatechin (3)), along with two flavan-3-ols ((+)-catechin (4) and (-)-epicatechin (5)). The IC50 values of the compounds against pseudovirion-bearing EBOV-GP ranged from 0.83 to 36.0 µM, with 1 as the most potent inhibitor. The anti-EBOV activities of five synthetic derivatives together with six commercially available analogues, including EGCG ((-)-epigallocatechin-3-O-gallate (8)), were further investigated. Molecular docking analysis and binding affinity measurement suggested the EBOV glycoprotein could be a potential molecular target for 1 and its related compounds.

Alkenylbenzoquinones and other compounds from the fruit of Maesa lanceolata exhibited potent cytotoxic, antibacterial, and antiradical scavenging activities§.

A phytochemical study of the methanol extract of the fruit of Maesa lanceolata resulted in the isolation of a new alkenylbenzoquinone (1), alongside the known compounds (Z)-2,5-dihydroxy-6-methyl-3-(pentadec-10'-enyl)-1,4-benzoquinone (2), 2,5-dihydroxy-6-methyl-3-(nonadec-14'-enyl)-1,4-benzoquinone (3), 2,5-dihydroxy-6-methyl-3-(tridecyl)-1,4-benzoquinone (4), (2S,3S,4R,2'R,9E)-[2'-hydroxytetraeicosanoyl]-2-aminooctadec-9-ene-1,3,4-triol (5), monopalmitin (glyceryl palmitate) (6), lupeol (7), and 3-O-(ß-D-glucopyranoside)-ß-sitosterol (8). The structures of the compounds were established by the means of spectroscopic (1 D- and 2 D-NMR) and spectrometric techniques (MS). The isolated compounds were assessed for their antibacterial, cytotoxic, and antiradical activities. Compound 2 showed moderate activity against Staphylococcus warneri (DSMZ 20036), while the other compounds were inactive. The two quinones 1 and 2 were significantly cytotoxic, with IC50 values of 0.005 µM and 12.5 µM respectively, and were weakly active towards DPPH radical (IC50 >250 µg/mL).

New Polyesterified Ursane Derivatives from Leaves of Maesa membranacea and Their Cytotoxic Activity.

Maesa membranacea A. DC. (Primulaceae) is a plant species that has been frequently used by practitioners of the traditional ethnobotany knowledge from northern and central Vietnam. However, the chemical constituents of the plant remained unknown until recently. Chromatographic separation of a chloroform-soluble fraction of extract from leaves of M. membranacea led to the isolation of two new polyesterified ursane triterpenes (1-2) and two known apocarotenoids: (+)-dehydrovomifoliol (3) and (+)-vomifoliol (4). The chemical structures of the undescribed triterpenoids were elucidated using 1D and 2D MNR and HRESIMS spectral data as 2α,6ß,22α-triacetoxy-11α-(2-methylbutyryloxy)-urs-12-ene-3α,20ß-diol (1) and 2α,6ß,22α-triacetoxy-urs-12-ene-3α,11α,20ß-triol (2). The newly isolated triterpenoids were tested for their cytotoxic activity in vitro against two melanoma cell lines (HTB140 and A375), normal skin keratinocytes (HaCaT), two colon cancer cell lines (HT29 and Caco-2), two prostate cancer cell lines (DU145 and PC3) and normal prostate epithelial cells (PNT-2). Doxorubicin was used as a reference cytostatic drug. The 2α,6ß,22α-triacetoxy-11α-(2-methylbutyryloxy)-urs-12-ene-3α,20ß-diol demonstrated cytotoxic activity against prostate cancer cell lines (Du145-IC50 = 35.8 µg/mL, PC3-IC50 = 41.6 µg/mL), and at a concentration of 100 µg/mL reduced viability of normal prostate epithelium (PNT-2) cells by 41%.

Neuroprotective Properties of Kempferol Derivatives from Maesa membranacea against Oxidative Stress-Induced Cell Damage: An Association with Cathepsin D Inhibition and PI3K/Akt Activation.

As components of the human diet with potential health benefits, flavonols are the subject of numerous studies, confirming their antioxidant, free radical scavenging and anti-inflammatory activity. Taking into consideration the postulated pathogenesis of certain CNS dysfunctions characterized by neuronal degradation, flavonols may prevent the decay of neurons in multiple pathways. Leaves of Maesa membranacea yielded several flavonol glycosides including α-rhamnoisorobin (kaempferol 7-O-α-rhamnoside) and kaempferitrin (kaempferol 3,7-di-O-α-rhamnoside). The latter compound was a major constituent of the investigated plant material. Neuroprotective effects of kaempferitrin and α-rhamnoisorobin were tested in vitro using H2O2-, 6-OHDA- and doxorubicin-induced models of SH-SY5Y cell damage. Both undifferentiated and differentiated neuroblastoma cells were used in the experiments. α-Rhamnoisorobin at a concentration range of 1-10 µM demonstrated cytoprotective effects against H2O2-induced cell damage. The compound (at 1-10 µM) was also effective in attenuating 6-OHDA-induced neurotoxicity. In both H2O2- and 6-OHDA-induced cell damage, kaempferitrin, similar to isoquercitrin, demonstrated neuroprotective activity at the highest of the tested concentrations (50 µM). The tested flavonols were not effective in counteracting doxorubicin-induced cytotoxicity. Their caspase-3- and cathepsin D-inhibitory activities appeared to be structure dependent. Inhibition of the PI3-K/Akt pathway abolished the neuroprotective effect of the investigated flavonols.

Effects of hydro-ethanolic extract of leaves of Maesa lanceolata (Mursinaceae) on acetic acid-induced ulcerative colitis in rats.

Ulcerative colitis is a form of inflammatory bowel disease that is characterized by acute and chronic inflammation. The aim of this work was to evaluate the efficacy of hydroethanolic extract of Maesa lanceolata leaves on acetic acid-induced colitis in rats. Colitis was induced by rectal administration of 1 mL of acetic acid (4%) in 25 male rats except the normal control group which received distilled water after 18 h of fasting followed by Ketamine (50 mg/kg)/Valium (10 mg/kg) anesthesia. Five hours later, the normal control and the negative control received distilled water, the positive control received prednisolone (5 mg/kg) and the three test groups received extract at 100, 200 and 400 mg/kg bw for eight days. During treatment, rectal temperature, the number and quality of the stools, and changes in body weight were assessed. At the end of the treatment, the animals were sacrificed, blood, colon, liver and spleen were collected for evaluation of hematological, inflammatory, antioxidant and histological parameters. Rectal temperature and the number of diarrheal, mucus and bloody stools were significantly reduced (P < 0.01) during treatment in the test and positive control groups with an increase in body weight change. The extract significantly (P < 0.01) reduced myeloperoxidase, TNF-α, interleukin 6, NO and MDA levels and significantly (P < 0.01) increased SOD levels, of GSH and catalase activity in the colon and blood. This extract also increased (P < 0.01) levels of red blood cells, hemoglobin, hematocrit, total white blood cells and blood platelets, prevented leukocyte infiltration in the liver and colon.

Discovery of New Triterpenoid Saponins Isolated from Maesa japonica with Antifungal Activity against Rice Blast Fungus Magnaporthe oryzae.

While searching for new antifungal compounds, we revealed that a methanol extract of plant species Maesa japonica has a potent antifungal activity in vivo against rice blast fungus Magnaporthe oryzae. To identify the antifungal substances, the methanol extract of M. japonica was extracted by organic solvents, and consequently, six active compounds were isolated from the n-butanol layer. The isolated compounds were five new acylated triterpenoid saponins including maejaposide I (1), maejaposides C-1, C-2, and C-3 (2-4), and maejaposide A-1 (5), along with a known one, maejaposide A (6). These chemical structures were determined by NMR and a comparison of their NMR and MS data with those reported in the literature. Based on the in vitro antifungal bioassay, the five compounds (2-6) exhibited strong antifungal activity against M. oryzae with MIC values ranging from 4 to 32 µg/mL, except for maejaposide I (1) (MIC > 250 µg/mL). When the compounds were evaluated at concentrations of 125, 250, and 500 µg/mL for an in vivo antifungal activity against rice blast, compounds 2-6 strongly reduced the development of blast by at least 85% to 98% compared to the untreated control. However, compound 1 did not show any in vivo antifungal activity up to a concentration of 500 µg/mL. Taken together, our results suggest that the methanol extract of M. japonica and the new acylated triterpenoid saponins can be used as a source for the development of natural fungicides.