Impact of GNB3-C825T, ADRB3-Trp64Arg, UCP2-3′UTR 45 bp del/ins, and PPARγ-Pro12Ala Polymorphisms on Bofutsushosan Response in Obese Subjects: A Randomized, Double-Blind, Placebo-Controlled Trial

Abstract

Obesity is known to be influenced by a number of genes, including the β3 subunit of G protein (GNB3), β3-adrenergic receptor (ADRB3), uncoupling protein 2 (UCP2), and peroxisome proliferator activated receptor gamma (PPARγ). The single nucleotide polymorphisms (SNPs) of the above genes, such as GNB3-C825T, ADRB3-Trp64Arg, UCP2-3'UTR 45 bp del/ins, and PPARγ-Pro12Ala, are associated with obesity and body mass index. The present study evaluates the impact of Bofutsushosan, a traditional Eastern Asian herbal medicine with known anti-obesity properties, on obese subjects according to the presence of the above-mentioned SNPs. Upon randomization, the volunteers were allocated to receive Bofutsushosan (n=55) or placebo (n=56) treatments for 8 weeks. Following the treatment schedule, significant reductions in total cholesterol and significant improvement in the Korean version of obesity-related quality of life scale were seen in the Bofutsushosan-treated group, but not in placebo. Bofutsushosan exerted significant anti-obesity effects on a number of parameters in the carriers of the GNB3-825T allele, but only on waist circumference in the GNB3-C/C homozygote. Significant anti-obesity impact of Bofutsushosan was also seen on a number of obesity-indices in both ADRB3-Arg64 carriers and ADRB3-Trp64 homozygotes, as well as in UCP2-D/D carriers, but not in UCP2-D/I+I/I variants. The effect of Bofutsushosan was more pronounced in PPARγ-Pro/Pro genotype compared to PPARγ-Pro/Ala variants. Thus, the results revealed differential responses of the subjects to the anti-obesity effects of Bofutsushosan treatment according to the polymorphism of the vital obesity-related genes. Our study provides new insight into individualized clinical applications of Bofutsushosan for obesity.

Traditional Herbal Formula Oyaksungi-San Inhibits Adipogenesis in 3T3-L1 Adipocytes

“…Several herbal formulas have been reported to have remarkable antiobesity effects in vitro and in vivo . For example, Hwangryunhaedok-tang (Orengedokuto) had inhibitory effects in 3T3-L1 cell adipogenesis [ 4 ], and Boiogito improved serum triglyceride contents in obese patients without different gene polymorphisms [ 5 ]. Another herbal formula, Bangpungtonse-oun-san (Bofu-tsusho-san), was shown to attenuate hyperlipidemia [ 6 , 7 ] and body fat accumulation [ 8 ].…”

Influence of G-protein β-Polypeptide 3 C825T Polymorphism on Antihypertensive Response to Telmisartan and Amlodipine in Chinese Patients

“…[ 21 ] There is increasing interest in pharmacogenetics of this polymorphism in therapeutic drugs targeting GPCRs such as hydralazine, isosorbide dinitrate, sildenafil, and bofutsushosan. [ 23 24 25 ] We are the first to investigate the association of C825T polymorphism with drug response to telmisartan and amlodipine. The significantly higher posttreatment DBP and MAP levels in 825TT homozygotes by telmisartan therapy while the baseline DBP and MAP levels were comparable among genotypes, our findings indicate that the polymorphism is associated with decreased telmisartan response.…”

“…Our findings are in contrast to the findings of better drug responses in TT homozygotes or carriers of the 835T allele for hydralazine, isosorbide dinitrate, sildenafil, and bofutsushosan as reported previously. [ 23 24 25 ] The 825TT genotype is associated with greater therapeutic effects with isosorbide dinitrate and hydralazine combined therapy in heart failure patients[ 23 ] and better improvement in posttreatment parameters and longer time to clinical worsening in pulmonary hypertension patients treated with sildenafil,[ 24 ] and better anti-obesity response to bofutsushosan, a traditional herbal medicine. [ 25 ]…”

Systematic Review on Herbal Treatment for Obesity in Adults

“…최종적으로 선정된 13편의 무작위 대조군 임상연구에 서 사용한 한약은 방풍통성산과 위약을 비교한 임상연구 4편 [9][10][11][12] , 태음조위탕 2편 13,14) , 방기황기탕 1편 15) , 방풍통성 산과 방기황기탕을 각각의 군에 배정한 논문 1편이었다 16) .…”