Nutr Res Pract.  2012 Oct;6(5):405-413.

Optimized mixture of hops rho iso-alpha acids-rich extract and acacia proanthocyanidins-rich extract reduces insulin resistance in 3T3-L1 adipocytes and improves glucose and insulin control in db/db mice

• Tripp ML
• Darland G
• Konda VR
• Pacioretty LM
• Chang JL
• Bland JS
• Babish JG

Abstract

Rho iso-alpha acids-rich extract (RIAA) from Humulus lupulus (hops) and proanthocyanidins-rich extracts (PAC) from Acacia nilotica exert anti-inflammatory and anti-diabetic activity in vitro and in vivo. We hypothesized that a combination of these two extracts would exert enhanced effects in vitro on inflammatory markers and insulin signaling, and on nonfasting glucose and insulin in db/db mice. Over 49 tested combinations, RIAA:PAC at 5:1 (6.25 microg/mL) exhibited the greatest reductions in TNFalpha-stimulated lipolysis and IL-6 release in 3T3-L1 adipocytes, comparable to 5 microg/mL troglitazone. Pretreatment of 3T3-L1 adipocytes with this combination (5 microg/mL) also led to a 3-fold increase in insulin-stimulated glucose uptake that was comparable to 5 microg/mL pioglitazone or 901 microg/mL aspirin. Finally, db/db mice fed with RIAA:PAC at 5:1 (100 mg/kg) for 7 days resulted in 22% decrease in nonfasting glucose and 19% decrease in insulin that was comparable to 0.5 mg/kg rosiglitazone and better than 100 mg/kg metformin. RIAA:PAC mixture may have the potential to be an alternative when conventional therapy is undesirable or ineffective, and future research exploring its long-term clinical application is warranted.

Keyword

Humulus lupulus; Acacia nilotica; phytochemicals; metabolic syndrome; anti-inflammatory

MeSH Terms

Acacia
Adipocytes
Animals
Aspirin
Chromans
Glucose
Humulus
Insulin
Insulin Resistance
Interleukin-6
Lipolysis
Metformin
Mice
Thiazolidinediones
Aspirin
Chromans
Glucose
Insulin
Interleukin-6
Metformin
Thiazolidinediones

Figure

• 

  Fig. 1 Dose-dependent, response surface representation of the interaction between RIAA and PAC on (A) free-fatty acids secretion as determined by glycerol release, and (B) IL-6 secretion. Detailed description of the response surface models (RSM) please refer to Methods. Values above the plane described a greater than expected stimulatory effect of the combination of components and values below the plane describe an inhibitory effect of the components greater than expected.

• 

  Fig. 2 RIAA, PAC and the 5:1 mixture of RIAA:PAC inhibit TNFα-stimulated FFA release in 3T3-L1 adipocytes. Data were analyzed using a one-way ANOVA; Fisher's least significant difference test was used to determine differences from the respective control. Data are presented as means ± 95% CI. *P < 0.05, **P < 0.01.

• 

  Fig. 3 RIAA:PAC at 5:1 effects on (A) IR, (B) IRS-1, and (C) PI3K in mature 3T3-L1 adipocytes. Both phosphorylated and total proteins were quantified and phosphoprotein content was normalized to total protein. Analysis was performed using the log-normal transformation of the mOD450 values per well or corrected for viable cells using crystal violet. Values presented represent the means ± 95% CIs. *P < 0.05, **P < 0.01 compared to DMSO.

• 

  Fig. 4 The 5:1 combination of RIAA:PAC on insulin-stimulated glucose uptake in 3T3-L1 adipocytes. For comparison across experiments with different positive controls, RFU were normalized to the PBS/solvent control and viable cells within each experiment. Data are presented as means ± 95% CI using pioglitazone and aspirin as the positive controls. *P < 0.05 compared to insulin alone.

• 

  Fig. 5 The effects of RIAA:PAC combinations on (A) nonfasting serum glucose, (B) insulin and (C) HOMA scores in db/db mice. Mean percent change from pre-test control values ± 95% CIs are shown. *P < 0.05, **P < 0.01 compared to controls alone.

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