Limits...
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/M/B on glucose production. HepG2 cells were treated with different concentrations of MB salt (a) or an equal concentration of MB salt/M/B (b) for 24 h. Alternatively, cells were pretreated with CC for 30 min; then MB salt (c), M (d), or B (e) was added and incubated for 24 h. DMSO (0.1%) was used as control. After treatment, culture media were discarded; cells were loaded with the glucose production medium as described in Section 2. Four hours later, glucose levels in the supernatant were determined, normalized to protein concentrations, and presented as percentages of DMSO. Values are mean ± SD of 3 separate experiments; ∗p < 0.05 and ∗∗p < 0.01 versus that of DMSO; $p < 0.05 versus that of M alone or B alone in (b); #p < 0.05 and ##p < 0.01 versus that of MB salt alone (c), M alone (d), or B alone (e).
© Copyright Policy
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4829696&req=5

fig8: Effects of MB salt/M/B on glucose production. HepG2 cells were treated with different concentrations of MB salt (a) or an equal concentration of MB salt/M/B (b) for 24 h. Alternatively, cells were pretreated with CC for 30 min; then MB salt (c), M (d), or B (e) was added and incubated for 24 h. DMSO (0.1%) was used as control. After treatment, culture media were discarded; cells were loaded with the glucose production medium as described in Section 2. Four hours later, glucose levels in the supernatant were determined, normalized to protein concentrations, and presented as percentages of DMSO. Values are mean ± SD of 3 separate experiments; ∗p < 0.05 and ∗∗p < 0.01 versus that of DMSO; $p < 0.05 versus that of M alone or B alone in (b); #p < 0.05 and ##p < 0.01 versus that of MB salt alone (c), M alone (d), or B alone (e).

Mentions: AMPK activation was proved to inhibit gluconeogenesis [19], so we also determined the influences of these compounds on gluconeogenesis. As shown in Figure 8(a), MB salt inhibited glucose production dose-dependently in HepG2 cells. Accordingly, the expression levels of phosphoenolpyruvate carboxykinase (PEPCK)/glucose-6-phosphatase (G6Pase), two key enzymes of the gluconeogenesis pathway, were greatly downregulated by MB salt (Figure 9(a)). When administered at an equal molar concentration, MB salt had stronger activities in inhibiting glucose production (Figure 8(b)) and downregulating PEPCK/G6Pase (Figure 9(b)) than M or B alone (p < 0.05). Furthermore, unlike glucose consumption, the suppressing activities of MB salt/M/B on glucose production (Figures 8(c), 8(d), and 8(e)) and PEPCK/G6Pase expression (Figure 9(c) and data not shown) were totally abolished by CC. These results prove that MB salt suppresses gluconeogenesis in HepG2 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/M/B on glucose production. HepG2 cells were treated with different concentrations of MB salt (a) or an equal concentration of MB salt/M/B (b) for 24 h. Alternatively, cells were pretreated with CC for 30 min; then MB salt (c), M (d), or B (e) was added and incubated for 24 h. DMSO (0.1%) was used as control. After treatment, culture media were discarded; cells were loaded with the glucose production medium as described in Section 2. Four hours later, glucose levels in the supernatant were determined, normalized to protein concentrations, and presented as percentages of DMSO. Values are mean ± SD of 3 separate experiments; ∗p < 0.05 and ∗∗p < 0.01 versus that of DMSO; $p < 0.05 versus that of M alone or B alone in (b); #p < 0.05 and ##p < 0.01 versus that of MB salt alone (c), M alone (d), or B alone (e).
© Copyright Policy
Related In: Results  -  Collection

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

fig8: Effects of MB salt/M/B on glucose production. HepG2 cells were treated with different concentrations of MB salt (a) or an equal concentration of MB salt/M/B (b) for 24 h. Alternatively, cells were pretreated with CC for 30 min; then MB salt (c), M (d), or B (e) was added and incubated for 24 h. DMSO (0.1%) was used as control. After treatment, culture media were discarded; cells were loaded with the glucose production medium as described in Section 2. Four hours later, glucose levels in the supernatant were determined, normalized to protein concentrations, and presented as percentages of DMSO. Values are mean ± SD of 3 separate experiments; ∗p < 0.05 and ∗∗p < 0.01 versus that of DMSO; $p < 0.05 versus that of M alone or B alone in (b); #p < 0.05 and ##p < 0.01 versus that of MB salt alone (c), M alone (d), or B alone (e).
Mentions: AMPK activation was proved to inhibit gluconeogenesis [19], so we also determined the influences of these compounds on gluconeogenesis. As shown in Figure 8(a), MB salt inhibited glucose production dose-dependently in HepG2 cells. Accordingly, the expression levels of phosphoenolpyruvate carboxykinase (PEPCK)/glucose-6-phosphatase (G6Pase), two key enzymes of the gluconeogenesis pathway, were greatly downregulated by MB salt (Figure 9(a)). When administered at an equal molar concentration, MB salt had stronger activities in inhibiting glucose production (Figure 8(b)) and downregulating PEPCK/G6Pase (Figure 9(b)) than M or B alone (p < 0.05). Furthermore, unlike glucose consumption, the suppressing activities of MB salt/M/B on glucose production (Figures 8(c), 8(d), and 8(e)) and PEPCK/G6Pase expression (Figure 9(c) and data not shown) were totally abolished by CC. These results prove that MB salt suppresses gluconeogenesis in HepG2 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