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The Compound of Mangiferin-Berberine Salt Has Potent Activities in Modulating Lipid and Glucose Metabolisms in HepG2 Cells.

Wang C, Jiang JD, Wu W, Kong WJ - Biomed Res Int (2016)

Bottom Line: The above activities of MB salt were AMPK dependent and were superior to those of M or B when administered at an equal molar concentration.MB salt enhanced basal and insulin-stimulated glucose consumption and suppressed gluconeogenesis more potently than M or B alone.Our results may support MB salt as a new kind of agent for the development of novel lipid or glucose-lowering drugs in the future.

View Article: PubMed Central - PubMed

Affiliation: Department of Virology, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China.

ABSTRACT
The mangiferin-berberine (MB) salt was synthesized by ionic bonding of mangiferin (M) and berberine (B) at an equal molecular ratio. This study aimed to investigate the activities of MB salt in modulating lipid and glucose metabolisms in HepG2 cells. After 24 h treatment of the studying compounds, cellular AMP-activated protein kinase α (AMPKα)/acetyl-CoA carboxylase (ACC) protein levels and carnitine palmitoyltransferase (CPT) 1 activities, intracellular lipid contents, mRNA expression levels of target genes, glucose consumption, and glucose production amounts were determined. Compound C (CC) was used in the blocking experiments. Our results showed that MB salt increased p-AMPKα (Thr172)/p-ACC (Ser79) levels and CPT1 activity and suppressed oleic acid- (OA-) induced lipid accumulation and upregulation of lipogenic genes potently in HepG2 cells. The above activities of MB salt were AMPK dependent and were superior to those of M or B when administered at an equal molar concentration. MB salt enhanced basal and insulin-stimulated glucose consumption and suppressed gluconeogenesis more potently than M or B alone. The inhibiting activity of MB salt on cellular gluconeogenesis was AMPK dependent. Our results may support MB salt as a new kind of agent for the development of novel lipid or glucose-lowering drugs in the future.

No MeSH data available.


Related in: MedlinePlus

Effects of MB salt on the expression levels of lipogenic transcription factors and their target genes. (a) HepG2 cells were left untreated or treated with OA or OA + MB salt as indicated. ∗∗∗p < 0.001 versus that of untreated cells; #p < 0.05 and ##p < 0.01 versus that of OA alone. (b) Cells were treated as described in Figure 4(a). ∗∗∗p < 0.001 versus that of untreated cells; ##p < 0.01 versus that of OA alone; $$p < 0.01 versus that of OA + MB salt. (c) Cells were treated as described in Figure 4(b). ∗∗∗p < 0.001 versus that of untreated cells; #p < 0.05 and ##p < 0.01 versus that of OA alone; $p < 0.05 versus that of OA + M or OA + B. After treatment for 24 h, cell total RNA was extracted for real-time RT-PCR determination of mRNA levels of indicated genes, which were normalized to that of GAPDH and plotted as fold of untreated cells. Values are mean ± SD of 3 separate experiments.
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fig5: Effects of MB salt on the expression levels of lipogenic transcription factors and their target genes. (a) HepG2 cells were left untreated or treated with OA or OA + MB salt as indicated. ∗∗∗p < 0.001 versus that of untreated cells; #p < 0.05 and ##p < 0.01 versus that of OA alone. (b) Cells were treated as described in Figure 4(a). ∗∗∗p < 0.001 versus that of untreated cells; ##p < 0.01 versus that of OA alone; $$p < 0.01 versus that of OA + MB salt. (c) Cells were treated as described in Figure 4(b). ∗∗∗p < 0.001 versus that of untreated cells; #p < 0.05 and ##p < 0.01 versus that of OA alone; $p < 0.05 versus that of OA + M or OA + B. After treatment for 24 h, cell total RNA was extracted for real-time RT-PCR determination of mRNA levels of indicated genes, which were normalized to that of GAPDH and plotted as fold of untreated cells. Values are mean ± SD of 3 separate experiments.

Mentions: In parallel with the development of steatosis, the mRNA expression levels of lipogenic transcription factors like sterol regulatory element-binding protein 1c (SREBP1c) and carbohydrate responsive element-binding protein (ChREBP) as well as their target genes like fatty acid synthase (FAS) and stearoyl-CoA desaturase 1 (SCD1) increased greatly after OA administration (Figure 5, p < 0.001 versus untreated). The MB salt suppressed the upregulation of the above genes in dose-dependent (Figure 5(a)) and AMPK-dependent (Figure 5(b)) manners. In agreement with its stimulating activity on AMPK and inhibiting activity on steatosis, the MB salt reduced the expression levels of lipogenic genes more effectively than M or B alone (p < 0.05, Figure 5(c)). Taken together, these results indicate that MB salt suppresses lipogenesis, steatosis, and TG accumulation in HpeG2 cells through AMPK activation, and its efficacies are more potent than M or B alone.


The Compound of Mangiferin-Berberine Salt Has Potent Activities in Modulating Lipid and Glucose Metabolisms in HepG2 Cells.

Wang C, Jiang JD, Wu W, Kong WJ - Biomed Res Int (2016)

Effects of MB salt on the expression levels of lipogenic transcription factors and their target genes. (a) HepG2 cells were left untreated or treated with OA or OA + MB salt as indicated. ∗∗∗p < 0.001 versus that of untreated cells; #p < 0.05 and ##p < 0.01 versus that of OA alone. (b) Cells were treated as described in Figure 4(a). ∗∗∗p < 0.001 versus that of untreated cells; ##p < 0.01 versus that of OA alone; $$p < 0.01 versus that of OA + MB salt. (c) Cells were treated as described in Figure 4(b). ∗∗∗p < 0.001 versus that of untreated cells; #p < 0.05 and ##p < 0.01 versus that of OA alone; $p < 0.05 versus that of OA + M or OA + B. After treatment for 24 h, cell total RNA was extracted for real-time RT-PCR determination of mRNA levels of indicated genes, which were normalized to that of GAPDH and plotted as fold of untreated cells. Values are mean ± SD of 3 separate experiments.
© Copyright Policy
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC4829696&req=5

fig5: Effects of MB salt on the expression levels of lipogenic transcription factors and their target genes. (a) HepG2 cells were left untreated or treated with OA or OA + MB salt as indicated. ∗∗∗p < 0.001 versus that of untreated cells; #p < 0.05 and ##p < 0.01 versus that of OA alone. (b) Cells were treated as described in Figure 4(a). ∗∗∗p < 0.001 versus that of untreated cells; ##p < 0.01 versus that of OA alone; $$p < 0.01 versus that of OA + MB salt. (c) Cells were treated as described in Figure 4(b). ∗∗∗p < 0.001 versus that of untreated cells; #p < 0.05 and ##p < 0.01 versus that of OA alone; $p < 0.05 versus that of OA + M or OA + B. After treatment for 24 h, cell total RNA was extracted for real-time RT-PCR determination of mRNA levels of indicated genes, which were normalized to that of GAPDH and plotted as fold of untreated cells. Values are mean ± SD of 3 separate experiments.
Mentions: In parallel with the development of steatosis, the mRNA expression levels of lipogenic transcription factors like sterol regulatory element-binding protein 1c (SREBP1c) and carbohydrate responsive element-binding protein (ChREBP) as well as their target genes like fatty acid synthase (FAS) and stearoyl-CoA desaturase 1 (SCD1) increased greatly after OA administration (Figure 5, p < 0.001 versus untreated). The MB salt suppressed the upregulation of the above genes in dose-dependent (Figure 5(a)) and AMPK-dependent (Figure 5(b)) manners. In agreement with its stimulating activity on AMPK and inhibiting activity on steatosis, the MB salt reduced the expression levels of lipogenic genes more effectively than M or B alone (p < 0.05, Figure 5(c)). Taken together, these results indicate that MB salt suppresses lipogenesis, steatosis, and TG accumulation in HpeG2 cells through AMPK activation, and its efficacies are more potent than M or B alone.

Bottom Line: The above activities of MB salt were AMPK dependent and were superior to those of M or B when administered at an equal molar concentration.MB salt enhanced basal and insulin-stimulated glucose consumption and suppressed gluconeogenesis more potently than M or B alone.Our results may support MB salt as a new kind of agent for the development of novel lipid or glucose-lowering drugs in the future.

View Article: PubMed Central - PubMed

Affiliation: Department of Virology, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China.

ABSTRACT
The mangiferin-berberine (MB) salt was synthesized by ionic bonding of mangiferin (M) and berberine (B) at an equal molecular ratio. This study aimed to investigate the activities of MB salt in modulating lipid and glucose metabolisms in HepG2 cells. After 24 h treatment of the studying compounds, cellular AMP-activated protein kinase α (AMPKα)/acetyl-CoA carboxylase (ACC) protein levels and carnitine palmitoyltransferase (CPT) 1 activities, intracellular lipid contents, mRNA expression levels of target genes, glucose consumption, and glucose production amounts were determined. Compound C (CC) was used in the blocking experiments. Our results showed that MB salt increased p-AMPKα (Thr172)/p-ACC (Ser79) levels and CPT1 activity and suppressed oleic acid- (OA-) induced lipid accumulation and upregulation of lipogenic genes potently in HepG2 cells. The above activities of MB salt were AMPK dependent and were superior to those of M or B when administered at an equal molar concentration. MB salt enhanced basal and insulin-stimulated glucose consumption and suppressed gluconeogenesis more potently than M or B alone. The inhibiting activity of MB salt on cellular gluconeogenesis was AMPK dependent. Our results may support MB salt as a new kind of agent for the development of novel lipid or glucose-lowering drugs in the future.

No MeSH data available.


Related in: MedlinePlus