Search Results (4)

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 Aβ 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, Aβ 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 Aβ 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 Aβ aggregation, the inhibition of AChE function, and neuroprotection against oxidative stress and Aβ toxicity. The extracts could improve both the short- and long-term memory deficits induced by scopolamine in mice. Full article

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. Full article

Clausena indica fruits are routinely used for the culinary purpose as natural spices, whereas leaves and roots are folk medicine with various health benefits in southern China, South and Southeast Asia. In this study, the bioassay-guided fractionation by column chromatography yielded three pure compounds including dentatin, nordentatin, and clausine K and five active fractions (Re1-5) from C. indica roots. These known anticancer compounds were confirmed by X-ray diffraction, ¹H-, ¹³C-nuclear magnetic resonance (NMR), and electrospray ionization tandem mass spectrometric (ESI-MS-MS) analyses. Meanwhile, the phytochemical constituents from fractions were identified by gas chromatography-mass spectrometry (GC-MS). The isolates, fractions’ components and their biological activities were first time investigated on C. indica. By in vitro DPPH and ABTS scavenging assays, nordentatin (IC₅₀ = 49.2 and 69.9 µg/mL, respectively) and the fraction Re4 (32.4 and 38.5 µg/mL, respectively) showed the strongest antiradical activities, whereas clausine K presented a moderate and dentatin had negligible antioxidant activity, respectively. The anti-α-amylase activity of C. indica root extracts was mainly attributed to the fraction Re2 which inactivated the enzymatic assay with IC₅₀ of 573.8 µg/mL. Among tested samples, only nordentatin and clausine K were effective in the pancreatic elastase inhibition, however, their influences were trivial. Markedly, clausine K and Re4 performed the most remarkable tyrosinase inhibition with IC₅₀ values of 179.5 and 243.8 µg/mL, respectively, which were in turn 4 and 3 times stronger than myricetin (IC₅₀ = 735.6 µg/mL), a well-known tyrosinase inhibitor. This is the first report affirming clausine K to be a new strong tyrosinase inhibitor. Isolated compounds from C. indica roots were quantified by high-performance liquid chromatography (HPLC), of which, dentatin, nordentatin, and clausine K accounted for 14.74, 6.14, and 1.28 mg/g dry weight. The findings suggest that bioactive constituents from C. indica roots may be potentially employed for the development of antidiabetic, antiaging and cosmetic agents. Full article

Seven compounds, carbazole alkaloids (heptaphylline, 7-methoxyheptaphylline, 7-methoxymukonal) and coumarins (clausarin, dentatin, nordentatin, and xanthoxyletin), were isolated from the root bark of Clausena harmandiana. Antioxidation, cytotoxicity and apoptosis induction were evaluated in vitro. Results showed that clausarin exerted the highest DPPH radical scavenging and 7-methoxymukonal had the highest ferric reducing antioxidant power. In contrary, dentatin was the least DPPH radical scavenger, and heptaphylline was the least reducing antioxidant power. The isolated compounds showed different cytotoxicity. The hepatocellular carcinoma (HepG2) was generally more sensitive to the isolated compounds than lung cancer (SK-LU-1), colon cancer (HCT-116), and noncancerous (Vero) cell lines, respectively. Clausarin possessed the highest cytotoxicity selectively against cancer cell lines tested. 7-Methoxymukonal and 7-methoxyheptaphylline exhibited less cytotoxicity only in HepG2 cells and were inactive in the SK-LU-1 and HCT116 cells. Despite xantoxyletin possessing low antioxidant and low cytotoxic activity, it induced the highest apoptosis percentage with the lowest necrosis percentage of HepG2 cells after 24 h. In conclusion, xantoxyletin primarily show potential anticancer activity. The root bark of C. harmandiana is a good source of bioactive compounds or the lead for the development of new pharmaceutical agent. Full article