The role of lipid and carbohydrate digestive enzyme inhibitors in the management of obesity: a review of current and emerging therapeutic agents

Figures & data

Table 1 Effective in vitro doses and target enzymes of inhibitors

Product	Dose	Effect	Ref
Cetilistat	54.8 nmol/L 5.95 nmol/L	Inhibits rat pancreatic lipase Inhibits HPL	^Citation46
Platycodin D1 saponin	0.18–0.03 mM	Inhibits pancreatic lipase	^Citation82
Sabiosaponin prosapogenin 1b	0.12 mg/mL	Inhibits pancreatic lipase	^Citation87
Acanthopanax sessiliflorus sessiloside and chiisanoside	0.36 and 0.75 mg/mL, respectively	Inhibit pancreatic lipase	^Citation53
Acanthopanax senticosus triterpenoid saponins	0.22–0.29 mM	Inhibit pancreatic lipase Inhibits glucose 6-phosphatase and lipogenic enzymes in liver	^Citation52,Citation61
Panax japonicum chikusetsusaponin	125–500 μg/mL	Inhibits pancreatic lipase	^Citation76
Dioscorea nipponica extract	5–10 mg/mL	Inhibits pancreatic lipase	^Citation72
Kochia scoparia alcohol extract and saponins	0.25 mg/mL	Inhibit pancreatic lipase	^Citation213
Aesculus turbinata escins	20–100 μM	Inhibit pancreatic lipase	^Citation70
Sapindus rarak extract and saponins	Extract: IC50 = 614 μg/mL Rarasaponins I IC50 = 131 μM and II 172 μM	Inhibit pancreatic lipase	^Citation86
Oolong tea saponins (theasaponins E1 and E2)	Km and Vmax values of 1.42 mg/mL and 476.2 nkat/L respectively. The Ki value of theasaponin is 0.25 mg/mL	Inhibit pancreatic lipase	^Citation73,Citation74
Chinese tea saponins chakasaponins I, II, and III	IC50 of 0.091 mg/mL IC50 values of 0.17–0.53 mM	Inhibit pancreatic lipase	^Citation71
Oolong tea catechins	05–2 g/L	Inhibit pancreatic lipase	^Citation73,Citation203
epigallocatechin 3-O-gallate(−)	0.34 μM	Inhibit pancreatic lipase
epigallocatechin-3,5-digallate	0.09 μM	Inhibit pancreatic lipase
Green tea catechins	5–30 μM	Inhibit adipocytes differentiation Inhibit gastric and pancreatic lipase Inhibit α-amylase and α-glucosidase	^Citation187^–^Citation189,Citation191,Citation192
Cyclocarya paliurus	5 μg/mL 9.1 μg/mL	Inhibits α-glucosidase Inhibits pancreatic lipase	^Citation180,Citation181
Salacia reticulata polyphenol extracts salacinol and kotalanol	IC50 of 264 mg/L	Inhibit pancreatic lipase Inhibit α-glucosidase	^Citation210
Apple polyphenol procyanidin fractions	IC50 of 5.6 μg/mL IC50 of 1.4 μg/mL	Inhibit pancreatic lipase	^Citation97
Grape seed extract	1 mg/mL 80% inhibition	Inhibits pancreatic lipase	^Citation101
Nelumbo nucifera extract	IC50 of 0.46 mg/mL IC50 of 0.82 mg/mL	Inhibits lipase Inhibits α-amylase	^Citation199
Cassia mimosoides CT-IIa extract	0.1–0.71 mg/μmL	50% inhibition porcine lipase	^Citation98
Peanut shell extract	10 mg/mL	92% inhibition of human lipase	^Citation207
Carnosic acid and carnasol	IC50 of 36 μM IC50 of 13 and μM	Inhibit pancreatic lipase	^Citation104
Crocetin	IC50 of 2.1 mg/mL	Inhibits pancreatic lipase	^Citation109
Lipstatin	IC50 of 0.14 μM	Inhibits pancreatic lipase	^Citation110
Panclicins A, B, C, D E	2.9, 2.6, 0.62, 0.66, and 0.89 μM	Inhibit pancreatic lipase	^Citation131
Vibralactone	IC50 of 0.4 μg/mL	Inhibits pancreatic lipase	^Citation133

a ethanol extract.

Abbreviations: HPL, triacylglycerol acyl hydrolase.

Table 2 Enzyme inhibitors: doses and in vivo effects

Product	Dose	Effect	Ref
Cetilistat	3–100 mg/kg; DIO rats 80–720 mg/day; humans	↓ TG plasma levels ↑ Fat excretion Suppression of body weight gain ↓ White adipose tissue ↓ Body weight	^Citation46,Citation48,Citation49
Acanthopanax sessiliflorus	100–300 mg/kg; VO, mice	↓ TG plasma levels ↑ TG in intestinal lumen	^Citation66
Acanthopanax senticosus extracts	12 mg/kg; DIO mice	↓ TG in liver and serum ↓ LDL in serum ↑ HDL	^Citation63
Panax japonicum total chikusetsusaponins	1%–3% of diet; DIO mice	Suppression of body weight gain ↓ Parametrial adipose tissue weight	^Citation76
Dioscorea nipponica dioscin and diosgenin	100 mg/kg; VO, mice 5% of high fat diet, rats	↓ TG in plasma Suppression of body weight gain ↓ VLDL and LDL in plasma	^Citation72
Aesculus turbinata	0.1%–0.5% of diet; DIO mice	Suppression of body weight gain ↓ Parametrial adipose tissue weight ↓ TG in plasma	^Citation68
Cyclocarya paliurus extract	250 mg/kg; VO, mice	↓ Increase in blood glucose after sucrose administration ↓ TG in plasma	^Citation180,Citation181
Salacia reticulata extract	125 mg/kg; VO, Zucker and HFD rats	Suppression of body weight gain	^Citation210
Apple polyphenol and procyanidin fractions	200 mg/kg; VO, mice 600 mg; VO, humans	↓ TG in plasma after corn oil loading Inhibition of TG increase after TG load	^Citation97
Nelumbo nucifera	5% of diet; mice	↓ Body weight ↓ TG in plasma ↓ Parametrial adipose tissue weight	^Citation199
Cassia mimosoides CT-IIa extract	1%–3.5% of diet; DIO rats	Suppression of body weight gain ↓ Parametrial adipose tissue weight	^Citation98
Peanut shell extract	1% of diet; DIO rats	Suppression of body weight gain	^Citation207
Carnosic acid	20 mg/kg; VO, DIO mice	Suppression of body weight gain	^Citation104
Crocetin and crocin	50 mg/kg; VO, mice	Suppression of body weight gain ↓ Epididymal fat pad	^Citation109
Lipstatin	375–750 mg/day; humans	↑ Fat excretion	^Citation118
Green tea catechins	5–80 mg; VO, rats	Inhibition of α-amylase and α-glucosidase	^Citation191

a Note: ethanol extract.

Abbreviations: DIO, diet-induced obesity; HFD, high-fat diet; HDL, high-density lipoprotein cholesterol; LDL, low-density lipoprotein cholesterol; TG, triglycerides; VLDL, very-low-density lipoprotein cholesterol; VO, volume overload.

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