Xuedan Huang

Effect of Zizyphus jujuba Extract on the Inhibition of Adipogenesis in 3T3-L1 Preadipocytes

Obesity, the leading metabolic disease in the world, is a serious health problem in industrialized countries. The Zizyphus jujuba fruit has been used as traditional Chinese medicinal herb and considered to affect various physiological functions in the body for thousands of years. We investigated the anti-obesity effect of Z. jujuba on adipocyte differentiation of 3T3-L1 preadipocytes and found that treatment with an extract of Z. jujuba suppressed lipid accumulation and glycerol-3-phosphate dehydrogenase (GPDH) activity without affecting cell viability. Further fractionation of the initial Z .jujuba extract with organic solvent revealed that the chloroform fraction (CHCl(3)-F) elicited the most inhibitory effect, which involved significant attenuation of the expression of key adipogenic transcription factors, including peroxisome proliferator-activated receptor (PPAR)gamma and CCAAT enhancer binding proteins (C/EBPs) at the protein level. These results suggest that CHCl(3)-F may block adipogenesis, at least in part, by decreasing the expression of PPARgamma, C/EBPalpha and beta.

Green tea extract enhances the selective cytotoxic activity of Zizyphus jujuba extracts in HepG2 cells.

Anticarcinogenic effects attributed to phytochemicals may be based on synergistic, additive, or antagonistic interactions of many compounds. In our previous study, we demonstrated that the chloroform fraction (CHCl(3)-F) from Z. jujuba has anticancer activity in HepG2 cells. In China, many people drink jujuba tea and believe in the synergic effects of jujuba and tea for better health. We therefore investigated the effects of CHCl(3)-F and green tea extract (GTE), and their underlying mechanisms of action in HepG2 cells. Our results showed that GTE enhanced the effect of CHCl(3)-F on cell viability in HepG2 cells, without cytotoxicity in rat hepatocytes, which was used as a normal cell model. Furthermore, combination of CHCl(3)-F and GTE caused an effect on G1 phase arrest but not on apoptosis. Interestingly, the mechanism of the G1 arrest was associated, not with an increase in p27(Kip1) levels and the hypohosphorylation of Rb, which are pathways used by CHCl(3)-F on G1 arrest in HepG2 cells, but with increases in p53 and p21(Waf1/Cip1) levels, and a decrease in cyclin E levels. Collectively, our findings suggest that combination of CHCl(3)-F and GTE produces an enhanced cell growth inhibition effect, and that the resultant G1 arrest was caused via a different mechanism as that of CHCl(3)-F treatment alone.

Anticancer Activities and Mechanisms of Blumea balsamifera Extract in Hepatocellular Carcinoma Cells

Blumea balsamifera (also known as sambong), a medicinal plant, is known to improve physiological disorders such as rheumatism and hypertension. However, its anticancer activity has not been well elucidated. In this study, we found that Blumea balsamifera MeOH extract (BME) induced growth inhibitory activity in rat and human hepatocellular carcinoma cells (McA-RH7777, HepG2, respectively) without cytotoxicity as in with rat hepatocytes used as a normal cell model. BME induced cell cycle arrest at G1 phase via decreases in expression of cyclin-E and phosphorylation of retinoblastoma (Rb) protein in both dose- and time-dependent manners. Furthermore, BME reduced the level of a proliferation related ligand (APRIL) which stimulates tumor cell growth. The anti-proliferative effect of BME was improved slightly but significantly by the treatment with recombinant human APRIL. These findings suggest that BME may have a possible therapeutic potential in hepatoma cancer patients and the depletion of cellular APRIL may be one of the important mechanisms on the growth inhibitory effect of BME.

Anti-obesity effect of Blumea balsamifera extract in 3T3-L1 preadipocytes and adipocytes.

Obesity, the leading metabolic disease in the world, is a serious health problem in industrialized countries. We investigated the anti-obesity effect of Blumea balsamifera extract on adipocyte differentiation of 3T3-L1 preadipocytes and anti-obesity effect of 3T3-L1 adipocytes. We found that treatment with an extract of Blumea balsamifera suppressed lipid accumulation and glycerol-3-phosphate dehydrogenase (GPDH) activity without affecting cell viability in 3T3-L1 preadipocytes and adipocytes. Furthermore, Blumea balsamifera extract brought significant attenuation of expressions of key adipogenic transcription factors, including peroxisome proliferator-activated receptor (PPAR)gamma, CCAAT element binding protein (C/EBPs) and leptin, however, induced up-regulation of adiponectin at the protein level in 3T3-L1 preadipocytes and adipocytes. These results suggest that Blumea balsamifera extract may block adipogenesis, at least in part, by decreasing key adipogenic transcription factors in 3T3-L1 preadipocytes and may have antiatherogenic, anti-inflammatory, and antidiabetic effects through up-regulation of adiponectin in 3T3-L1 adipocytes.

Combination of Zizyphus jujuba and green tea extracts exerts excellent cytotoxic activity in HepG2 cells via reducing the expression of APRIL.

Hepatocellular carcinoma is a type of tumor highly resistant to available chemotherapeutic agents. The treatment of hepatocellular carcinoma remains a challenge that needs new approaches in the future. In a previous study, we demonstrated that the chloroform fraction (CHCl(3)-F) from Z. jujuba has anticancer activity in human liver cancer cells (HepG2), and that combining CHCl(3)-F with green tea extracts (GTE) results in enhanced effects of anticancer activity in the cells. To further understand the mechanism of the anticancer activity of combining CHCl(3)-F and GTE in HepG2 cells, we investigated whether the addition of a mixture of CHCl(3)-F and GTE would affect the expression of APRIL (a proliferation-inducing ligand), which was expressed in HepG2 cells from 4 hours of incubation in vitro. We have shown that CHCl(3)-F and GTE enhanced anti-cancer activity by reducing the expression of APRIL. We speculate that the CHCl(3)-F and GTE mixture might provide a lead to a new drug design to treat hepatocellular carcinoma in the future.

Synergistic Effect of Green Tea Polyphenols on Their Protection Against FK506-Induced Cytotoxicity in Renal Cells

FK506 (tacrolimus) is a widely used immunosuppressant first employed in the management of rejection in organ transplantation, but now used for autoimmune disease. However, the nephrotoxicity induced by FK506 remains a serious clinical problem. We previously demonstrated that FK506 caused a significant increase in apoptosis of LLC-PK1 cells, a porcine proximal tubule cell line, but the addition of green tea extract and its polyphenolic components suppressed the cell death. Here, we examined the synergistic effect of tea polyphenols on the protection of FK506-induced cell death. The combined treatment with 5 microM (-)-epigallocatechin-gallate (EGCG) and 5 microM of (+)-catechin (C), (-)-epicatechin (EC), (-)-epigallocatechin (EGC) or (-)-epicatechin-gallate (ECG) reduced FK506-induced cytotoxicity in LLC-PK1. Similarly, the combined treatment with 5 microM EGC and 5 microM of C, EC, EGCG or ECG also reduced the cytotoxicity. These results showed that the co-treatments with EGCG and EGC, EGCG or ECG, and EGC and ECG have stronger synergistic effects on the protection of FK506-induced cell death. Furthermore, the combined treatment of EGCG (5 microM) and EGC (5 microM) showed a significant time-dependent suppression of the increased intracellular ROS levels 15 min after the addition of FK506, as well as on caspase activation. The results of these synergistic effects of the constituents of green tea extract suggest that its protective effects may reside in more than just one of its constituent.

Synergistic Anticancer Activities of Natural Substances in Human Hepatocellular Carcinoma

Hepatocellular carcinoma (HCC) is highly resistant to currently available chemotherapeutic agents. The clinical outcome of HCC treatment remains unsatisfactory. Therefore, new effective and well-tolerated therapy strategies are needed. Natural products are excellent sources for the development of new medications for disease treatment. Recently, we and other researchers have suggested that the combined effect of natural products may improve the effect of chemotherapy treatments against the proliferation of cancer cells. In addition, many combination treatments with natural products augmented intracellular reactive oxygen species (ROS). In this review we will demonstrate the synergistic anticancer effects of a combination of natural products with chemotherapeutic agents or natural products against human HCC and provide new insight into the development of novel combination therapies against HCC.

Cytotoxic activity of two natural sesquiterpene lactones, isobutyroylplenolin and arnicolide D, on human colon cancer cell line HT-29

In this study, we found that two sesquiterpene lactones, isobutyroylplenolin and arnicolide D, from Centipeda minima L. (Compositae) exerted stronger cytotoxic activity than cisplatin on the human colon carcinoma HT-29 cell line. Furthermore, the cytotoxicity of these two compounds on normal cells was weaker than that of cisplatin. Treatment with isobutyroylplenolin and arnicolide D increased the levels of intracellular reactive oxygen species and decreased the levels of nuclear factor-κB protein, resulting in cell cycle arrest in G1 phase and apoptosis. We also discuss the difference in structure and activity between these two compounds.

Anti-steatosis compounds from leaves of Mallotus furetianus

Abstract There is no drug administration-approved therapy for non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH). In this study, eight compounds, gallic acid (1), methyl gallate (2), corilagin (3), 3,4,8,9,10-pentahydroxydibenzo[b,d]pyran-6-one (4), repandinin B (5), (Z)-3-hexenyl-β-D-glucopyranoside (6), (+)-lyoniresinol-3α-O-α-L-rhamnopyranoside (7) and mallophenol A (8) were isolated from the active fractions of Mallotus furetianus. Three compounds, (6, 7 and 8) revealed potent anti-steatosis activity in the oleic acid (OA)-induced steatosis cell model, with the minimum effective concentration of 0.05 (6), 0.0005 (7) and 0.0005 (8) μg/mL, which were much lower than the control compound, fibrate (72.4 μg/mL).

The Effects of Bairesi Complex Prescription (a Uyghur Medicine Prescription) and Its Five Crude Herbal Extracts on Melanogenesis in G-361 Cells

Vitiligo is considered a preimmune stage of a disease that is not well clarified. This condition is difficult to treat because there is no definite cure. Uyghur medicine is an important part of traditional Chinese medicine. There are many types of prescriptions that are used for the treatment of vitiligo. Bairesi complex prescription is one of the active prescriptions for vitiligo that is used in the clinic. However, the intensities of melanogenesis due to uses of Bairesi complex prescription and its five constituent crude herbs have not been reported yet. In the present study, we found that the hot water extracts of Bairesi complex prescription and the crude herbs were more effective in eliciting melanin production in G-361 cells than the EtOH extracts. Furthermore, the Bairesi complex prescription exhibited less cytotoxicity and was more effective in melanin formation than the five crude herbal extracts. In the present study, we also discuss the mechanisms of melanogenesis due to the use of the Bairesi complex prescription and its single crude herbal extracts.