T52 attenuates oncogenic STAT3 signaling and suppresses osteosarcoma.

BACKGROUND: T52 is a steroidal saponin extracted from the traditional Chinese herb Rohdea fargesii (Baill.), and it is reported to possess strong anti-proliferative capabilities in human pharyngeal carcinoma cell lines. However, whether T52 has anti-osteosarcoma properties, and its potential mechanism is remains unknown. PURPOSE: To examine the outcome and underlying mechanism of T52 in osteosarcomas (OS). METHODS/STUDY DESIGNS: The physiological roles of T52 in OS cells were examined using CCK-8, colony formation (CF), EdU staining, cell cycle/apoptosis and cell migration/invasion assays. The relevant T52 targets against OS were assessed via bioinformatics prediction, and the binding sites were analyzed by molecular docking. Western blot analysis was carried out to examine the levels of factors associated with apoptosis, cell cycle, and STAT3 signaling pathway activation. RESULTS: T52 markedly diminished the proliferation, migration, and invasion of OS cells, and promoted G2/M arrest and apoptosis in a dose-dependent fashion (DDF) in vitro. Mechanistically, molecular docking predicted that T52 stably associated with STAT3 Src homology 2 (SH2) domain residues. Western blot revealed that T52 suppressed the STAT3 signaling pathway, as well as the expression of the downstream targets, such as, Bcl-2, Cyclin D1, and c-Myc. In addition, the anti-OS property of T52 were partially reversed by STAT3 reactivation, which confirmed that STAT3 signaling is critical for regulating the anti-OS property of T52. CONCLUSION: We firstly demonstrated that T52 possessed strong anti-osteosarcoma property in vitro, which was brought on by the inhibition of the STAT3 signaling pathway. Our findings provided pharmacological support for treating OS with T52.

Total steroidal saponins from black nightshade (Solanum nigrum L.) overcome tumor multidrug resistance by inducing autophagy-mediated cell death in vivo and in vitro.

Multiple drug resistance (MDR) often occurs after prolonged chemotherapy, leading to refractory tumors and cancer recurrence. In this study, we demonstrated that the total steroidal saponins from Solanum nigrum L. (SN) had broad-spectrum cytotoxic activity against various human leukemia cancer cell lines, especially in adriamycin (ADR)-sensitive and resistant K562 cell lines. Moreover, SN could effectively inhibit the expression of ABC transporter in K562/ADR cells in vivo and in vitro. In vivo, by establishing K562/ADR xenograft tumor model, we demonstrated that SN might overcome drug resistance and inhibit the proliferation of tumors by regulating autophagy. In vitro, the increased LC3 puncta, the expression of LC3-II and Beclin-1, and the decreased expression of p62/SQSTM1 in SN-treated K562/ADR and K562 cells demonstrated autophagy induced by SN. Moreover, using the autophagy inhibitors or transfecting the ATG5 shRNA, we confirmed that autophagy induced by SN was a key factor in overcoming MDR thereby promoting cell death in K562/ADR cells. More importantly, SN-induced autophagy through the mTOR signaling pathway to overcome drug resistance and ultimately induced autophagy-mediated cell death in K562/ADR cells. Taken together, our findings suggest that SN has the potential to treat multidrug-resistant leukemia.

S-20, a steroidal saponin from the berries of black nightshade, exerts anti-multidrug resistance activity in K562/ADR cells through autophagic cell death and ERK activation.

Multidrug resistance (MDR) is a major cause of chemotherapy failure. Adriamycin (ADR) has been widely used to treat cancer, however, as a substrate of the adenosine triphosphate binding cassette (ABC) transporter, it is easy to develop drug resistance during the treatment. Here, we demonstrated that steroidal saponin S-20 isolated from the berries of black nightshade has comparable cytotoxicity in ADR-sensitive and resistant K562 cell lines. Autophagy is generally considered to be a protective mechanism to mediate MDR during treatment. However, we found that S-20-induced cell death in K562/ADR is associated with autophagy. We further explored the underlying mechanisms and found that S-20 induces caspase-dependent apoptosis in ADR-sensitive and resistant K562 cell lines. Most importantly, S-20-induced autophagy activates the ERK pathway and then inhibits the expression of drug resistance protein, which is the main reason to overcome K562/ADR resistance, rather than apoptosis. Taken together, our findings emphasize that S-20 exerts anti-multidrug resistance activity in K562/ADR cells through autophagic cell death and ERK activation, which may be considered as an effective strategy.

Total saponins from Tupistra chinensis baker inhibits growth of human gastric cancer cells in vitro and in vivo.

ETHNOPHARMACOLOGICAL RELEVANCE: Tupistra chinensis Baker (syn. Rohdea chinensis), an antitumor folk herb mainly distributed in China, its rhizome has been historically used to treat gastric cancer. Studies showed that the steroidal saponins were the main bioactive components in the rhizome of T. chinensis. Our previous studies have confirmed that the steroidal saponins have a variety of anti-tumor activities. However, the underlying anti-tumor mechanism of the total steroidal saponins of T. chinensis (TCS) remains to be revealed. AIM OF THE STUDY: In the present study, we studied the potential anti-proliferative activity and anti-tumor mechanism of TCS on gastric cancer in vitro and in vivo. METHODS: In vitro, 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay was used to detect the proliferation ability of TCS on SGC-7901 cells and AGS cells. Flow cytometry were performed to analyze cell apoptosis, cell cycle, mitochondrial membrane potential and reactive oxygen species expression level. Western blotting was performed to validate the expression of proteins in related pathways. In vivo, a xenograft model was established by injecting SGC-7901 cells into nude mice. RESULTS: In vitro, TCS inhibited the proliferation of gastric cancer cells. TCS effectively induced apoptosis by PI3K/Akt/mTOR signaling pathway in SGC-7901 cells, and promoted apoptosis via p53-mediated pathway in AGS cells. TCS also exhibited inhibitory activity in blocking the migration of gastric cancer cells. In vivo, TCS significantly inhibited the growth of xenograft tumor. CONCLUSION: These results indicated that TCS exhibited significant anti-gastric cancer effects in vitro and in vivo.

A combination of Citrus reticulata peel and black tea inhibits migration and invasion of liver cancer via PI3K/AKT and MMPs signaling pathway.

Liver cancer, one of the most common malignancies, is the second leading cause of cancer death in the world. The citrus reticulate peel and black tea have been studied for their beneficial health effects. In spite of the many studies have been reported, the underlying molecular mechanisms underlying its health benefits are still not fully understood. In present study, we developed a unique citrus reticulate peel black tea (CRPBT) by combined citrus reticulate peel and black tea and assessed its active ingredients, anti-oxidant and anti-liver cancer effects in vitro. The results suggested that CRPBT exhibited antioxidant capacity and effectively inhibited proliferation and migration of liver cancer cells in a dose- and time- dependent manner. Mechanistically, CRPBT significantly down-regulated phosphorylation of PI3K and AKT, and up-regulated the ratio of Bax/Bcl-2, and suppressed the expression of MMP2/9, N-cadherin and Vimetin proteins in liver cancer cells. Taken together, CRPBT has good effect on inhibiting migration, invasion, proliferation, and inducing apoptosis in liver cancer cells.

Steroidal alkaloid glycosides and phenolics from the immature fruits of Solanum nigrum.

Solanum nigrum L. (also called as European black nightshade) has been traditionally used as folk medicine and food in some regions. Phytochemical investigations of the immature fruits of S. nigrum yielded five steroidal alkaloid glycosides (1-5), including an unprecedented nor-spirosolane type steroidal alkaloid with a five-membered ring A (1) and two novel spirosolane type steroidal alkaloid glycosides (2, 3), together with eight known phenolic compounds (6-13). Their structures were elucidated on the basis of spectroscopic and chemical methods, including IR, NMR, HR-ESI-MS, and GC analyses. Five steroidal alkaloid glycosides were tested for their potential antiproliferative effects against HL-60, U-937, Jurkat, K562, and HepG2 cell lines and inhibitory activities on nitric oxide (NO) production induced by lipopolysaccharide (LPS) in a macrophage cell line RAW 264.7. Compound 1 exhibited significant inhibition on NO production with an IC50 value of 23.4 ±â€¯2.0 µM, compared to positive control indomethacin (IC50, 47.40 ±â€¯4.50 µM). Compound 4 exhibited significant cytotoxicity against all tested cell lines.

Furostanol saponins from Chinese onion induce G2/M cell-cycle arrest and apoptosis through mitochondria-mediate pathway in HepG2 cells.

Phytochemical investigations on the bulbs of Chinese onion led to the isolation of three new furostanol saponins (1, 2, 5) together with seven known furostanol saponins (3, 4, 6-10). Their chemical structures were elucidated on the basis of spectroscopic and chemical methods, including IR, MS, NMR, and GC analyses. The anti-proliferative and anti-inflammatory activities of the isolates were evaluated. Compounds 7-10 showed potential anti-proliferative activities against human cancer cell lines (HepG2, A549, SPC-A-1, MGC80-3, MDA-MB-231, SW620 and CNE-1) with IC50 values below 30 µM. Compounds 4 and 7 could induce G2/M cell-cycle arrest and apoptosis through mitochondria-mediate pathway in HepG2 cells. Compounds 7 and 10 showed strong inhibitory effects against LPS induced NO production in RAW264.7 cells with IC50 values of 2.01 ±â€¯1.40 µM and 2.49 ±â€¯1.54 µM, respectively.

Six types of tea reduce high-fat-diet-induced fat accumulation in mice by increasing lipid metabolism and suppressing inflammation.

A high-fat diet results in obesity because of white fat accumulation. Although tea extracts alleviate lipid metabolism disorders and decrease white fat accumulation, the mechanisms underlying the therapeutic actions of different types of Chinese tea are unclear. We established a murine model of obesity by feeding mice with a high-fat diet (HFD) and treating them with atorvastatin (positive control) or water extracts (WEATs) of different tea types. The food and water intake, body weight gain, white fat accumulation, and triglyceride (TG) and total cholesterol (TC) levels were evaluated to assess the effects of the WEATs on obesity. The levels of the lipid metabolism enzymes p-AMPK, CPT-1A and FAS and the pro-inflammatory factors iNOS and IL-6 were determined. The WEATs not only reduced the body weight and white fat accumulation in the HFD-induced obese mice, but also relieved hepatic steatosis. Comparing the effects of the six kinds of tea showed that white tea has the best anti-obesity effect. Yellow tea and raw pu-erh tea significantly up-regulated p-AMPK, green tea, white tea and raw pu-erh tea markedly inhibited FAS, and white tea, yellow tea and oolong tea up-regulated CPT-1. Therefore, it is possible that white tea, yellow tea and oolong tea inhibit obesity by increasing energy expenditure and fatty acid oxidation, while green tea, white tea and raw pu-erh tea exert their effects by inhibiting fatty acid synthesis. In addition, the WEATs also significantly decreased the levels of IL-6, while green tea, yellow tea and oolong tea significantly inhibited iNOS. Different types of tea have specific chemical compositions and can regulate different lipid metabolism related proteins. In conclusion, despite variations in its composition and mechanism of action, tea is a potent anti-obesity agent.

Tea Polypeptide Ameliorates Diabetic Nephropathy through RAGE and NF-κB Signaling Pathway in Type 2 Diabetes Mice.

Diabetic nephropathy (DN) is a major complication of type 2 diabetes (T2D), which is a key determinant of mortality in diabetic patients. Developing new therapeutic drugs which can not only control T2D but also prevent the development of DN is of great significance. We studied the therapeutic potential of Cuiyu tea polypeptides (TP), natural bioactive peptides isolated from a type of green tea, against DN and its underlying molecular mechanisms. TP (1000 mg/kg bw/day, p.o.) administration for 5 weeks significantly reduced the fasting blood glucose by 52.04 ± 9.23% in the high fat diet/streptozocin (HFD/STZ)-induced (30 mg/kg bw) diabetic mice. Compared to the model group, the serum insulin level of the TP group was decreased by 25.54 ± 6.06%, while at the same time, the HOMA-IR, HOMA-IS, and lipid levels showed different degrees of recovery ( p < 0.05). Moreover, in TP group mice the total urinary protein, creatinine, and urine nitrogen, all which can reflect the damage degree of the glomerular filtration function to a certain extent, dramatically declined by 34.51 ± 2.65%, 42.24 ± 15.24%, and 80.30 ± 6.01% compared to the model group, respectively. Mechanistically, TP stimulated the polyol PKCζ/JNK/NF-κB/TNF-α/iNOS and AGEs/RAGE/TGF-ß1 pathways, upregulated the expression of podocin in the glomeruli, and decreased the release of pro-inflammatory cytokines. These results strongly indicate the therapeutic potential of TP against DN.

Black tea affects obesity by reducing nutrient intake and activating AMP-activated protein kinase in mice.

The effects of certain tea components on the prevention of obesity in humans have been reported recently. However, whether Yinghong NO. 9 black tea consumption has beneficial effects on obesity are not known. Here, we obtained a Yinghong NO. 9 black tea infusion (Y9 BTI) and examined the anti-obesity effects of its oral administration. ICR mice were fed a standard diet supplemented with Y9 BTI at 0.5, 1.0, or 2.0 g/kg body weight for two weeks, and the body weight were recorded. HE staining was used to evaluate the effect of Y9 BTI on mice liver. Western blot analysis was used to detect the expression levels of related proteins in the mice liver and adipose. We found that the body weights of the mice in the control group were significantly higher than those of the mice in the middle and high dose groups. The results of western blot showed that Y9 BTI up-regulated the expression of liver kinase B1 (LKB1) and adenosine monophosphate-activated protein kinase (AMPK) and also increased in AMPK phosphorylation (p-AMPK) and LKB1 phosphorylation (p-LKB1). Y9 BTI significantly down-regulated Fas Cell Surface Death Receptor(FAS) and activated the phosphorylation of acetyl-CoA carboxylase (ACC). Furthermore, Y9 BTI (2.0 g/kg BW) down-regulated the expression of three factors (IL-1ß, Cox-2, and iNOS). Altogether, Y9 BTI supplementation reduced the feed intake of mice and may prevent obesity by inhibiting lipid absorption. These results suggest that Y9 BTI may regulate adipogenic processes through the LKB1/AMPK pathway.

Apoptosis and pro-death autophagy induced by a spirostanol saponin isolated from Rohdea chinensis (Baker) N. Tanaka (synonym Tupistra chinensis Baker) on HL-60 cells.

BACKGROUND: Our previous study has revealed that the spirostanol saponins isolated from the rhizomes of Rohdea chinensis (Baker) N. Tanaka (synonym Tupistra chinensis Baker) (Convallariaceae) (a reputed folk medicine) exhibited potent antiproliferative activity. However, the underlying mechanism of purified saponins remains unclear. More studies are necessary to assess the apoptosis and autophagy activities of the saponins from R. chinensis and clarify their antiproliferative mechanisms. PURPOSE: The present study certificated the potential antiproliferative activity and mechanism of 5ß-spirost-25(27)-en-1ß,3ß-diol-1-O-α-L-rhamnopyranosyl-(1→2)- ß-D-xylopyranosyl-3-O-α-L-rhamnopyranoside (SPD), a spirostanol saponin from R. chinensis, against human acute promyelocytic leukemia cells (HL-60). METHODS: The antiproliferative activity of SPD in vitro was evaluated by MTT assay compared with cis-dichlorodiammineplatinum (II). The autophagic activity was assessed using MDC staining and western blot, cell apoptosis inspection was detected by Annexin V-FITC/PI double staining and the mitochondrial membrane potential was detected by JC-1 fluorescence dye combined with flow cytometry. The potential mechanisms for protein levels of apoptosis and autophagy were evaluated by western blot. RESULTS: Treatment of HL-60 cells with SPD resulted in growth inhibition (IC50 value of 2.0 ± 0.2 µM, after 48 h treatment) and induction of apoptosis and autophagy. Results from Annexin V-FITC/PI double-staining assay and mitochondrial membrane potential detection showed that apoptosis was happened after SPD treatment. The regulation of caspase-3, Bax, Bcl-2, PARP following SPD treatment contributed to the induction of mitochondria-dependent apoptosis. Meanwhile, SPD induced autophagy related with Akt/mTOR/p70S6K signaling and activated of AMPK signaling pathway. Furthermore, blocking autophagy with bafilomycin A1 reduced the cytotoxicity of SPD in HL-60 cells. CONCLUSION: The antiproliferative, apoptosis and pro-death autophagy activities of SPD suggested that spirostanol saponins from R. chinensis would be a potential cytotoxic candidate against acute promyelocytic leukemia.

Aged Oolong Tea Reduces High-Fat Diet-Induced Fat Accumulation and Dyslipidemia by Regulating the AMPK/ACC Signaling Pathway.

While oolong tea (OT) has been shown to induce weight loss and reduce fat accumulation, the mechanisms remain poorly defined, especially for aged OT. In this study, five groups of mice (n = 9/group) were used including a normal diet with vehicle treatment, and a high-fat diet (HFD) with vehicle or the water extracts from aged OTs (EAOTs, three different storage years) by oral gavage at 1000 mg/kg·BW for 6 weeks. Body weight, fat accumulation, and serum biochemical parameters were used to evaluate obesity. The morphology of hepatocytes and adipocytes was analyzed by being stained with hematoxylin and eosin. The levels of p-AMPK, p-ACC (and non-phosphorylated versions), CPT-1 and FAS were determined by Western blotting and immunohistochemistry. EAOTs decreased HFD-induced body weight, fat accumulation, serum levels of triglyceride, total cholesterol, and low-density lipoprotein cholesterol, while enhancing the serum high-density lipoprotein cholesterol level. At the same time, EAOTs clearly alleviated fatty liver and reduced the size of adipocytes in the epididymal fat, especially in the 2006 group. Most importantly, EAOTs increased the phosphorylation of AMPK and ACC, and up-regulated the expression of CPT-1 but down-regulated the expression of fatty acid synthase, TNF-α and iNOS. Thus, EAOTs may inhibit obesity by up-regulating energy expenditure and fatty acid oxidation while inhibiting fatty acid synthesis and inflammation.

Potential Anti-inflammatory Steroidal Saponins from the Berries of Solanum nigrum L. (European Black Nightshade).

Solanum nigrum L. or European black nightshade (Solanum genus) is a common weed of crops and gardens. The berries and leaves of S. nigrum L. are consumed as food or vegetable in some regions and reported to possess a range of biological activities. In this study, nine new steroidal saponins, solanigrosides Y1-Y9 (1-6, 10-12), together with seven known congeners, were isolated from the berries of S. nigrum. Their potential inhibitory effects on nitric oxide (NO) and IL-6 and IL-1ß production induced by lipopolysaccharide (LPS) in macrophages cell line RAW 264.7 were evaluated. Compound 1 exhibited significant inhibition on NO production with an IC50 value of 9.7 µM, and some compounds exhibited significant inhibition effects on the LPS-induced IL-6 and IL-1ß production. These results suggest that the steroidal saponins from berries of S. nigrum demonstrated pronounced anti-inflammatory activity and might be explored as a healthy benefit agent.

Antiproliferative and anti-inflammatory polyhydroxylated spirostanol saponins from Tupistra chinensis.

Tupistra chinensis is widely distributed in southwestern China and its rhizome is a famous folk medicine for the treatment of carbuncles and pharyngitis. Its chemical identity of potent antiproliferative and anti-inflammatory constituents has been carried out in this study. Twenty-three polyhydroxylated spirostanol saponins, including nine novels, were isolated and identified. The new spirostanol saponins were elucidated as spirost-25(27)-en-1ß,2ß,3ß,4ß,5ß-pentol-2-O-ß-D-xylopyranoside (1), spirost-25(27)- en-1ß,2ß,3ß,4ß,5ß-pentol-2-O-α-L-arabinopyranoside (2), spirost-25(27)-en- 1ß,3α,5ß-triol (12), spirost-25(27)-en-1ß,3α,4ß,5ß,6ß-pentol (13), spirost-25(27)-en- 1ß,2ß,3ß,5ß-tetraol-5-O-ß-D-glucopyranoside (16), 5ß-spirost-25(27)-en-1ß,3ß-diol- 3-O-ß-D-glucopyranosyl-(1 → 4)-ß-D-glucopyranoside (17), (25R)-5ß-spirostan- 1ß,3ß-diol-3-O-ß-D-glucopyranosyl-(1 → 6)-ß-D-glucopyranoside (18), (25R)-5ß- spirostan-1ß,3ß-diol-3-O-ß-D-fructofuranosyl-(2 → 6)-ß-D-glucopyranoside (19), 5ß-spirost-25(27)-en-3ß-ol-3-O-ß-D-glucopyranosyl-(1 → 4)-ß-D-glucopyranoside (20). The antiproliferative effects against seven human cancer cell lines and inhibitory activities on nitric oxide (NO) production induced by lipopolysaccharide (LPS) in a macrophage cell line RAW 264.7 were assayed for all the isolated compounds. Compounds 17, 19 and 21 exhibited potential antiproliferative activities against all of human cancer cell lines tested. Compounds 21 showed significant inhibition on NO production with IC50 values of 11.5 µM. These results showed that the spirostanol saponins isolated from the dried rhizomes of T. chinensis have potent antiproliferative and anti-inflammatory activities and T. chinensis might be used as anticancer and.anti-inflammatory supplement.

Extracts of Tsai Tai (Brassica chinensis): enhanced antioxidant activity and anti-aging effects both in vitro and in Caenorhabditis elegans.

Tsai Tai is one of the most widely consumed Brassica vegetables in Asian countries because of its good taste and its nutritional benefits. This study evaluated the antioxidant capacity and possible associated health benefits of 3 Tsai Tai (Brassica chinensis) varieties, namely, Hon Tsai Tai, Pak Choi and Choi Sum. The DPPH radical scavenging ability and reducing power assays were performed to evaluate the in vitro activities of the extracts. Caenorhabditis elegans was used as an in vivo model for evaluation of beneficial health effects, including antioxidant activity and delayed aging. In vitro, the Hon Tsai Tai extract exhibited higher antioxidant activities than Pak Choi and Choi Sum, and the total phenolic contents were significantly correlated with the DPPH and RP values. In vivo, the three assayed Tsai Tai extracts significantly increased resistance against paraquat-induced oxidative stress with an increase in survival rates from 15% to 28% compared with controls. However, only the extract from Hon Tsai Tai significantly prolonged the lifespan of Caenorhabditis elegans, with an 8% increase in the mean lifespan with respect to controls. Further evidence of antioxidant protection was obtained by assessing ROS production via the DCF assay. The analyses of intracellular SOD activity and MDA content confirmed the existence of an antioxidant protective effect. These results suggest that Tsai Tai might serve as a good source of natural antioxidants, and in particular, Hon Tsai Tai could be explored as a potential dietary supplement to retard aging.

A novel triterpenoid isolated from apple functions as an anti-mammary tumor agent via a mitochondrial and caspase-independent apoptosis pathway.

A novel triterpenoid, named 3ß-trans-cinnamoyloxy-2α-hydroxy-urs-12-en-28-oic acid (CHUA), was one of the main components of apple peels and showed potent in vitro antitumor activity against human tumor cells. In vivo antitumor experiments showed that CHUA could significantly inhibit the growth of mammary tumor in a nude mouse xenograft model at a dose of 50 mg/kg/day without body weight loss and mortality. In vitro, CHUA could induce apoptosis in MDA-MB-231 cells through the detection of DNA fragments and LDH activity. Simultaneously, mitochondrial transmembrane potential was markedly reduced and the release of cytochrome c was increased after CHUA treatment. It also up-regulated the expression ratio of mitochondrial Bax/Bcl-2 regulated by SIRT1 and p53. Interestingly, z-VAD-fmk and z-DEVD-fmk augmented cell death after CHUA treatment. Other protease(s) different from caspase-3 might be responsible for the degradation of PARP. These results suggested that the pro-apoptotic activity of CHUA may be adjusted by mitochondrial and caspase-independent pathways.

Triterpenoids of sour jujube show pronounced inhibitory effect on human tumor cells and antioxidant activity.

Sour jujube is a common fruit and traditional medicine in China. Bioactivity-guided fractionation of sour jujube was used to determine the chemical identity of potent antiproliferative and antioxidant constituents. Four novel ursane-type triterpenoids, together with 8 known were isolated and identified. The new triterpenoids were elucidated to be 2α,3ß,13ß,23-tetrahydroxy-urs-11-en-28-oic acid (3), 2α,3ß-dihydroxy-urs-20(30)-en-28-oic acid (9), 2α,3ß,28-trihydroxy-urs-20(30)-ene (10), and 3ß,12ß,13ß-trihydroxy-ursan-28-oic acid (11). Among the triterpenoids isolated, 2α,3ß,19α-trihydroxy-urs-12-en-28-oic acid (7), 9 and 10 showed high potent inhibitory activity toward the proliferation of HepG2 cells, which the IC50 values were lower than 5 µM. Compounds 9 and 10 also exhibited pronounced activity against MCF-7 cells, with IC50 value of 0.8 ± 0.03 and 1.5 ± 0.1 µM, respectively. Compound 10 showed high antioxidant activity with an EC50 of 0.8 ± 0.02 µM, which was 18.9 times higher than ascorbic acid in antioxidant capacity.

Antidiabetic and antioxidant effects and phytochemicals of mulberry fruit (Morus alba L.) polyphenol enhanced extract.

The antidiabetic and antioxidant activities of the ethyl acetate-soluble extract (MFE) of mulberry fruit (Morus alba L.) were investigated. In vitro, MFE showed potent α-glucosidase inhibitory activity and radical-scavenging activities against DPPH and superoxide anion radicals. In vivo, MFE could significantly decrease fasting blood glucose (FBG) and glycosylated serum protein (GSP), and increase antioxidant enzymatic activities (SOD, CAT, GSH-Px) in streptozotocin (STZ)-induced diabetic mice. Bioactivity-guided fractionation of the MFE led to the isolation of 25 phenolic compounds, and their structures were identified on the basis of MS and NMR data. All the 25 compounds were isolated from mulberry fruit for the first time. Also, the α-glucosidase inhibitory activity and antioxidant activity of the phenolics were evaluated. Potent α-glucosidase inhibitory and radical-scavenging activities of these phenolics suggested that they may be partially responsible for the antidiabetic and antioxidant activities of mulberry fruit.

Cytotoxic ceramides and glycerides from the roots of Livistona chinensis.

A 70% ethanol extract of the roots of Livistona chinensis has been investigated, led to the isolation of 13 compounds, including a new ceramide, (2S,3S,4R,9Z)-2-[(2R)-2-hydroxytricosanoylamino]-9-octadecene-1,3,4-triol (2), a new glycosyl ceramide, 1-O-ß-D-glucopyranosyl-(2S,3S,4R,9Z)-2-[(2R)-2-hydroxydocosanoylamino]-9-octadecene-1,3,4-triol (3), three new monoacylglycerols, 1-(34-hydroxytetratriacontanoyl)-sn-glycerol (9), 1-[nonadeca-(9Z,12Z)-dienoyl]-sn-glycerol (10), and 1-[12-hydroxypentatriaconta-(13E,15Z)-dienoyl]-sn-glycerol (11), a new diacylglycerol, 1-(heptadeca-6Z,9Z-dienoyl)-3-(octadeca-6Z,9Z,12Z-trienoyl)-sn-glycerol (12), as well as a new diacylglycerol aminoglycoside, 1-octadecanoyl-2-nonadecanoyl-3-O-(6-amino-6-deoxy)-ß-D-glucopyranosyl-sn-glycerol (13). The structures of new compounds were elucidated, based on spectroscopic, zymologic and chemical methods. Among the compounds tested, compounds 3, 4 and 13 showed significantly antiproliferative effects against the human tumor cell lines (K562, HL-60, HepG2, and CNE-1) with the IC50 of 10-65 µM. To our knowledge, this is first report of the occurrence of ceramides and acylglycerols in the genus Livistona.