Multifunctionality of Clausena harmandiana Extract and Its Active Constituents against Alzheimer's Disease.

This study was designed to investigate the effects of the root-bark extract of Clausena harmandiana (CH) and its active constituents (nordentatin and 7-methoxyheptaphylline) on pharmacological activities regarding selected targets associated with AD, namely, its antioxidant activity, inhibition of Aß aggregation, acetylcholinesterase (AChE) activity, and neuroprotective effects. The effect of the CH extract on the cognitive impairment induced by scopolamine was also evaluated in mice. The effects of the CH extract and its active constituents on radical scavenging, Aß aggregation, and AChE activity were investigated with a 2,2'-azino-bis(3-ethylbenzthiazoline-6-sulfonic acid (ABTS) assay, a thioflavin-T assay, and Ellman's method. The neuroprotective effects of the extract against hydrogen-peroxide and Aß toxicity were evaluated with a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay. In addition, the effects on cognitive impairment induced by scopolamine in mice were evaluated using Morris-water-maze and modified-Y-maze test models. The results of the present study demonstrate that the root-bark extract of CH shows multimodal actions relevant to the AD pathological cascade, including antioxidant effects, the inhibition of Aß aggregation, the inhibition of AChE function, and neuroprotection against oxidative stress and Aß toxicity. The extracts could improve both the short- and long-term memory deficits induced by scopolamine in mice.

Acridone Derivatives from Atalantia monophyla Inhibited Cancer Cell Proliferation through ERK Pathway.

The present study aimed to investigate the effect of acridone alkaloids on cancer cell lines and elucidate the underlying molecular mechanisms. The ten acridone alkaloids from Atalantia monophyla were screened for cytotoxicity against LNCaP cell lines by a WST-8 assay. Then, the most potential acridone, buxifoliadine E, was evaluated on four types of cancer cells, namely prostate cancer (LNCaP), neuroblastoma (SH SY5Y), hepatoblastoma (HepG2), and colorectal cancer (HT29). The results showed that buxifoliadine E was able to significantly inhibit the proliferation of all four types of cancer cells, having the most potent cytotoxicity against the HepG2 cell line. Western blotting analysis was performed to assess the expression of signaling proteins in the cancer cells. In HepG2 cells, buxifoliadine E induced changes in the levels of Bid as well as cleaved caspase-3 and Bax through MAPKs, including Erk and p38. Moreover, the binding interaction between buxifoliadine E and Erk was investigated by using the Autodock 4.2.6 and Discovery Studio programs. The result showed that buxifoliadine E bound at the ATP-binding site, located at the interface between the N- and C-terminal lobes of Erk2. The results of this study indicate that buxifoliadine E suppressed cancer cell proliferation by inhibiting the Erk pathway.

Nordentatin Inhibits Neuroblastoma Cell Proliferation and Migration through Regulation of GSK-3 Pathway.

Cancer is caused by abnormal cell changes leading to uncontrolled cell growth. The specific characteristics of cancer cells, including the loss of apoptotic control and the ability to migrate into and invade the surrounding tissue, result in cancer cell metastasis to other parts of the body. Therefore, the inhibition of the proliferation, migration, and invasion of cancer cells are the principal goals in the treatment of cancer. This study aimed to investigate the inhibitory activity of nordentatin, a coumarin derivative isolated from Clausena harmandiana, regarding the proliferation and migration of human neuroblastoma cells (SH-SY5Y). Nordentatin at a concentration of 100 µM showed cell cytotoxicity toward SH-SY5Y that was significantly different from that of the control group (p < 0.01) at 24, 48, and 72 h. Moreover, nordentatin inhibited SH-SY5Y proliferation by inhibiting the antiapoptotic protein Mcl-1, leading to the cleavage of caspase-3 and resulting in the inhibition of a migratory protein, MMP-9, through the GSK-3 pathway (compared with cells treated with a GSK inhibitor). These results suggest that nordentatin inhibited the proliferation and migration of neuroblastoma cells through the GSK-3 pathway.

Candidone Inhibits Migration and Invasion, and Induces Apoptosis in HepG2 Cells.

The aim of the study was to investigate the inhibitory activity of candidone, the active constituent of Derris (D.) indica, on the proliferation, migration, and invasiveness of human hepatoblastoma (HepG2) cells. Cancer cell death was assessed using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, and apoptosis-associated morphological changes were observed by phase contrast microscopy. Additionally, Western blotting was used to study protein expression following treatment with candidone, and transwell migration and invasion assays were used for observing cancer cell migration and invasiveness, respectively. The results suggest that candidone possesses potent inhibitory activity against HepG2 cells (concentration, 100 µM; 24 h treatment). Cancer cells treated with candidone exhibited apoptosis-associated changes, including detachment, cell shrinkage and death. Furthermore, candidone was shown to promote cell death by activating caspase-3 and -9, and decreasing the expression of antiapoptotic proteins, including p65, induced myeloid leukemia cell differentiation protein Mcl-1, B-cell lymphoma 2 (Bcl2), Bcl2-associated agonist of cell death and survivin. Moreover, candidone inhibited the migration and invasion abilities of HepG2 cells and decreased the levels of proteins associated with these processes, including phospho-p38 and active matrix metallopeptidase 9. Collectively, the results of the present study indicate that candidone is able to inhibit the proliferation, migration and invasive potential of HepG2 cells.

Determination of the Marker Diarylheptanoid Phytoestrogens in Curcuma comosa Rhizomes and Selected Herbal Medicinal Products by HPLC-DAD.

A method for quantification of diarylheptanoids in Curcuma comosa rhizomes and selected pharmaceutical preparations was established by using HPLC-diode array detector (DAD). The chromatographic separation of three diarylheptanoids [(3S)-1-(3,4-dihydroxy-phenyl)-7-phenyl-(6E)-6-hepten-3-ol (1), (3R)-1,7-diphenyl-(4E,6E)-4,6-heptadien-3-ol (2), and (3S)-1,7-diphenyl-(6E)-6-hepten-3-ol (3)] was performed on a Luna C18 analytical column using gradient elution with 0.5% acetic acid in water and acetonitrile with a flow rate of 1 mL/min and a column temperature of 35°C. The calibration curves for the analytes showed good linearity (R2>0.999), high precision (relative standard deviation (RSD) <2%) and acceptable recovery (98.35-103.90%, RSD <2%). The limit of detection (LOD) and limit of quantification (LOQ) were 0.06-0.22 and 0.18-0.69 µg/mL, respectively. The results of all validated parameters were within the limits according to the International Conference on Harmonization (ICH) Guidelines. The established method was successfully applied for qualitative and quantitative determination of the three constituents in different samples of C. comosa and some commercial products in capsules. The simplicity, rapidity, and reliability of the method could be useful for the fingerprint analysis and standardization of diarylheptanoids, which are responsible for the estrogenic activity in raw materials and herbal medicinal products of C. comosa.

Flavonols from Bauhinia malabarica.

Bauhinia malabarica Roxb. has been used in Thai traditional medicine for wound healing, as a diuretic, to fight dysentery and as an emmenagogue. Seven flavonols, including 6,8-di-C-methylkaempferol 3-methyl ether, kaempferol, afzelin, quercetin, isoquercitrin, quercitrin, and hyperoside were isolated from the methanol extract of leaves.

Novel biflavonoids from the stem bark of Ochna integerrima.

Two new biflavonoids, namely, 6'"-hydroxylophirone B (1) and 6'"-hydroxylophirone B 4"'-O-beta-glucoside (2), were isolated from the stem bark of Ochna integerrima, together with five known compounds. The structures of 1 and 2 were determined by spectral data interpretation.