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
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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 μg/mL) exhibited the greatest reductions in TNFα-stimulated lipolysis and IL-6 release in 3T3-L1 adipocytes, comparable to 5 μg/mL troglitazone. Pretreatment of 3T3-L1 adipocytes with this combination (5 μg/mL) also led to a 3-fold increase in insulin-stimulated glucose uptake that was comparable to 5 μg/mL pioglitazone or 901 μg/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.
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 μg/mL) exhibited the greatest reductions in TNFα-stimulated lipolysis and IL-6 release in 3T3-L1 adipocytes, comparable to 5 μg/mL troglitazone. Pretreatment of 3T3-L1 adipocytes with this combination (5 μg/mL) also led to a 3-fold increase in insulin-stimulated glucose uptake that was comparable to 5 μg/mL pioglitazone or 901 μg/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.
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