Inhibitory lipáz

Acanthopanax sessiliflorus

• Sessiloside and chiisanoside
• Lupine-type saponins
• Leaves of A. sessiliflorus
• In vitro studies
• Inhibit HPL activity in a dose-dependent manner
• Simultaneous administration of oil and chiisanoside
• Decreased plasma TG levels
• Increased the amount of undigested TG in the intestinal lumen [12]

Aesculus turbinata escins

• A. turbinata (Japanese horse chestnut)
• Saponins extracted from the seeds are called escins
• Inhibition of pancreatic lipase activity
• Increase in the levels of undigested fat in the mice feces confirmed effective inhibition of fat digestion in vivo [12]

Berry polyphenols

• Anthocyanins
• Ellagitannins
• Reduce postprandial hyperglycemia
• Directly induce secretion of insulin from pancreatic cells
• Inhibition of alpha-glucosidase and alpha-amylase
• Also exerts inhibitory activity on pancreatic lipase [12]

Ellagitannin-rich extracts

• Raspberry
• Strawberry
• Cloudberry
• Arctic bramble
• Seem to be the most effective at inhibiting lipase
• Some published data extract-induced fecal lipid excretion
• Associated with reductions in weight gain
• Changes in TG metabolism [12]
• Other studies report no significant correlations
• Compensatory increases in lipase secretion
• Similar to those seen in studies on condensed tannins in rats [12]

Chinese tea plant saponins

• Camellia sinensis
• Accelerate GI transit
• Inhibitory effect on pancreatic lipase
• Chakasaponins I, II, and III which inhibit pancreatic lipase [12]

Carnosic acid and carnosol

• Compounds extracted from the leaves of Salvia officinalis L. (sage)
• Inhibitory activity on pancreatic lipase
• Carnosol
• Stronger inhibitory activity in vitro
• Carnosic acid
• 20 mg/kg/day, by mouth to mice fed a high fat diet
• Reduced body weight gain and the accumulation of epididymal fat [12]

Cassia mimosoides L. var nomame Makino (Nomame Herba)

• C. mimisoides
• Leguminous plant grown in Japan and China
• Ethanol extract, CT-II, possesses a dose dependent inhibitory action on porcine lipase
• In rats fed high fat diets
• CT-II (1% to 3.5% of diet) dose dependently suppressed body weight gain
• Lowered parametrial fat and liver weight [12]

Cetilistat

• ATL-962, Alizyme®; Takeda Pharmaceutical
• Aim of creating a drug similar to orlistat without its side effects
• Shown inhibitory activity for both rat and human pancreatic lipase
• Cetilistat increases fecal fat excretion in a similar way to orlistat
• Phase IIb studies
• 180 to 720 mg/day to obese individuals with and without type II diabetes on a hypocaloric moderate fat diet
• Significant weight loss compared to subjects receiving placebo
• Adverse effects were similar to those in the placebo group [12]

Crocin and crocetin

• Gardeniae fructus
• Used as a Chinese traditional medicine
• Geniposide and crocin as main components
• Crocin and its metabolite crocetin
• Potently inhibit pancreatic lipase
• Most potent inhibitor was crocetin
• Inhibited the incremental increase in body weight compared with that of the control group
• Reduced epididymal fat pad mass
• 50 mg/kg is comparable with that of orlistat at a dose of 10 mg/kg [12]

Dioscorea nipponica

• D. nipponica Makino
• In the mountainous areas of the Korean peninsula
• Inhibit porcine pancreatic lipase activity
• Dioscin and its aglycone diosgenin
• Result of further purification processes
• Rats fed a high fat diet containing 5% of D. nipponica had significantly
• Lower body weight gain that their control counterparts
• Decreases in blood TG
• Very-low-density lipoproteins (VLDL) and LDL [12]

Ebelactones

• From Streptomyces aburaviensis
• Potent inhibition of pancreatic lipase
• Inhibited fat intestinal absorption in a dose-dependent manner
• Decreased plasmatic levels of TG and cholesterol [12]

Grape seed extracts and skins

• Contain a variety of health-promoting polyphenols
• Condensed tannins
• Proanthocyanidins
• Grape seed extract at a concentration of 1 mg/mL inhibits 80% of lipase activity
• In vivo these extracts seem to lack toxicity [12]

Green tea

• Widely consumed and for centuries
• Long-term consumption of green tea and its extract (GTE) associated with weight loss
• Mainly through a thermogenic mechanism
• Derived from an oxidation-free process
• High levels of catechins are retained [12]
• Full fermentation processes used to produce black tea
• Significantly reduce catechins levels
• Main active ingredients in GTE:
• Catechins epigallocatechin gallate (EGCG; Teavigo®)
• Epigallocatechin (EGC)
• Epicatechin gallate (ECG)
• Epicatechin (EC) [12]
• Inhibition of adipocyte division and maturation
• Reduce glucose and fat absorption by inhibiting GI enzymes involved in nutrient digestion
• Green tea extract AR25 (Exolise®; standardized at 25% catechins)
• Effectively inhibited gastric and pancreatic lipase activities
• Tea polyphenols
• Inhibit alpha-amylase and alpha-glucosidase in vitro [12]
• Green tea catechins reduced alpha-amylase and sucrase activities in rat intestine
• Streptozotocin-induced diabetic rats
• Green tea extracts to the diet (0.01% and 0.2% of diet) significantly reduced
• Maltase (both doses)
• Saccharase
• Lactase (higher dose) [12]
• Green tea extract (3% of diet) to rats fed a high fat diet
• Decreased body weight gain and visceral fat accumulation
• Increase in fecal lipids
• Administration of AR25 for 3 months human obese
• Decreased body weight and waist circumference [12]

Jablka

• All extracts from apples exhibited more than 70% inhibitory activity [12]
• Several phenolic substances
• Chlorogenic acid
• (+)-catechin
• Epicatechin
• Phloridzin
• Rutin
• Procyanidins (condensed tannins)
• Mainly composed of various polymerized catechins [12]
• Inhibited pancreatic lipase activity in a dose-dependent manner
• Procyanidin fractions
• Inhibited pancreatic lipase activity in a dose-dependent manner
• In mice 200 mg/kg significantly decreased plasma TG after corn oil loading
• Inhibit TG absorption [12]
• Apple polyphenols - AP (600 mg) containing capsules to humans
• Inhibited TG elevation after TG load compared to subjects receiving placebo
• No side effects were reported [12]

Lipstatin

• Isolated from Streptomyces toxytricini
• Very potent and selective irreversible inhibitor of pancreatic lipase

Tetrahydrolipstatin or orlistat

• THL, Ro 18-0647, Xenical®; Hoffmann-La Roche, Basel, Switzerland
• Highly lipophilic hydrogenated derivative of lipstatin

Orlistat

• Potent inhibitor of most mammalian lipases
• Therapeutic doses of orlistat generally achieve around 35% inhibition of lipid digestion
• Undigested fat is not absorbed but excreted
• Does not significantly diminish the activity of other intestinal enzymes
• Less than 1% of orlistat itself is absorbed
• At doses between 375 and 750 mg/day to humans
• Decreased fat absorption
• Increased fat elimination
• Caused side effects related to the amount of fat in the diet
• Evaluated in many clinical studies for obesity treatment
• After 1 year treatment orlistat (120 mg 3xd before feeding) + hypocaloric diet
• Higher weight loss compared with placebo
• Weight reduction from baseline no greater than 10%
• 4% placebo subtracted
• Orlistat significantly decreased
• Glycemia, glycated hemoglobin
• Insulin resistance
• Hyperlipidemia
• High blood pressure [12]
• Orlistat should not be continuously used for more than 24 months
• XENDOS study - continuously for 48 months
• Slightly impair the absorption of liposoluble vitamins A, E, and beta-carotene
• Vitamin supplementation is only required in a minority of patients
• Orlistat accelerates gastric emptying
• Could lead to exaggerated postprandial hyperglycemia
• Presence of undigested fat in the bowels causes side effects
• Diarrhea, abdominal pain, oily stools and fecal spotting [12]
• Irritable bowel syndrome are clear contraindications for its use
• A half dose of orlistat (Alli®, 60 mg rather than 120 mg 3 times daily)
• Approved in Australasia, USA and the EU for over-the-counter use
• To overweight and obese participants significantly
• Reduced their body weight (5.96 kg vs 3.91 kg) waist circumference
• Visceral fat (15.7% vs 9.4%) [12]

Nelumbo nucifera extract (NNE)

• Large aquatic herb
• Widely found in India and China
• NNE inhibits lipase and alpha-amylase activity
• Effect was dependent upon the phenolic compounds present
• Mice NNE (5% of diet) and exercise
• Decreased body weight
• Parametrial adipose tissue weight
• Liver TG levels [12]
• Streptozotocin-induced diabetic rats
• Reduced blood sugar levels when compared with control animals
• NNE administration improved glucose tolerance and potentiated the action of exogenously injected insulin [12]

Oolong tea catechins

• Inhibiting small intestine micelle formation
• Limiting the absorption of sugars
• Inhibiting alpha-glucosidase activity
• Epigallocatechin 3-O-gallate (EGCG)
• Main polyphenols in oolong tea
• Inhibits pancreatic lipase
• Flavan-3-ol digallate esters
• (-)-epigallocatechin-3,5-digallate
• Inhibitory lipase activity [12]
• Oolong tea catechins
• Suppressed increases in body weight
• Parametrial adipose tissue weights
• Adipose cell size
• Delaying the absorption of dietary fat from the intestine
• By inhibiting pancreatic lipase activity [12]
• Double-blind, placebo-controlled study, 12 weeks daily oolong tea
• Containing 690 mg of catechins
• Normal and overweight males significant reduction
• In body weight (1.5%)
• BMI (1.5%)
• Waist circumference (2.0%)
• Body fat mass (3.7%) [12]

Oolong tea saponins

• Green and oolong tea have been reported to exert anti-obesity and hypolipidemic actions
• Teas contain several different active ingredients that may exert anti-obesity actions through various mechanisms
• Oolong tea contains two saponins
• Theasaponins E1 and E2
• Seem to competitively inhibit pancreatic lipase activity [12]

Panax japonicus chikusetsusaponins

• Rhizomes of P. japonicus C.A. Meyer - Japanese name- Chikusetsuninjin
• Chikusetsusaponins
• Chikusetsusaponin III
• 28-deglucosyl-chikusetsusaponin IV
• 28-deglucosylchikusetsusaponin
• Inhibit pancreatic lipase activity
• Chikusetsusaponins (1% to 3% in diet)
• Significantly suppressed weight gain in DIO mice
• Independent of energy intake
• Correlated with a significant reduction in parametrial adipose tissue weight
• Reduction of plasma TG levels was observed [12]

Panciclins A, B, C, D, and E

• Pancreatic lipase inhibitors
• Isolated from Streptomyces sp. NR 0619.
• Panclicins A, B, C, D, and E are analogs (but not irreversible inhibitors) of tetrahydrolipstatin
• Contains a ß-lactone and an N-formyl leucine ester [12]

Peanut and peanut shell extract (PSE)

• Aqueous extract of peanut cotyledons
• Specific inhibitory activity towards pancreatic and human salivary alpha-amylases and lipases
• Peanut shell extract
• Inhibitory effects on human lipase
• 10 mg/mL inhibiting 92% of activity [12]
• 1% of a high fat diet, PSE reduced weight gain in normal adult rats without altering food consumption [12]

Platycodin saponins

• Main constituents of Platycodi radix
• Root of Platycodon grandiflorum A. DC (Campanulaceae)
• Known as Doraji
• Platycodi radix extracts
• Saponin-rich fraction of Platycodi radix
• Inhibitory effect on HPL
• Correlate with anti-obesity actions
• Platycodin D
• Strongest HPL inhibitory activity
• In rats, the decrease in body weight
• Platycodin saponins
• Reduce gastric secretion
• Slow gastric digestion
• Decreasing subsequent food intake [12]

Polyphenols

• Presence of more than one phenol unit or building block per molecule
• Fruit skins contain high levels of polyphenols
• Able to inhibit digestive enzymes
• Catechins and condensed tannins from various plant sources
• Inhibit digestive enzymes
• Including lipase
• Alpha-amylase [12]

Salacia reticulata

• Climber found in Sri Lanka and India
• Stems and roots are used for diabetes treatment
• Food supplement that suppresses postprandial hyperglycemia
• Alpha-glucosidase inhibition
• Salacinol
• Kotalanol
• Polyphenol extracts
• Inhibit pancreatic lipase
• Catechins showed potent inhibitory activity [12]

Sapindus rarak DC

• Tree found in South and Southeast Asian countries
• Pericarps have anti-pruritic actions
• Methanolic extract from S. rarak pericarps exerts pancreatic lipase inhibitory activity
• Rarasaponins I and II
• Raraoside A
• Inhibited pancreatic lipase [12]

Saponins

• Phytochemicals
• Roots and rhizomes of most vegetables, beans and herbs
• Glycosides known for their soap-like foaming ability when mixed with water
• Combination of a lipophylic sapogenin and a hydrophilic sugar part [12]

• Oleanane
• Lupine
• Dammarane [12]

• Can inhibit pancreatic lipase activity
• Have potential as treatments effective for obesity [12]

Scabiosaponins

• Scabiosa tschiliensis Grun. (Dipsacaceae)
• Perennial herb widely distributed in Mongolia and China
• Scabiosaponins E, F, G and I,
• Hookeroside A and B
• Prosapogenin 1b
• Greater inhibitory activity at a concentration of 0.12 mg/mL
• Inhibit HPL
• Scabiosaponins E, F, and G have been successfully synthesized [12]

Acanthopanax senticosus (Rupr. Maxim) Harms

• A. senticosus
• Siberian Ginseng
• Eleutherococcus senticosus
• Crude A. senticosus extracts
• Triterpenoid saponins have been isolated
• Exhibit pancreatic lipase inhibitory activity in vitro
• With IC50 values ranging from 0.22 to 0.29 mM:
• Leaves and fruits
• Ciwujianoside C1
• Tauroside H1
• 3-O- alphja-L-rhamnopyranosyl-(1›2)- alpha-L-arabinopyranosyl mesembryanthemoidigenic acid
• Acanthopanaxoside C
• Acanthopanaxoside E
• Silphioside F
• Copteroside B
• Hederagenin 3-O- beta-D glucuronopyranoside 6'-O-methyl ester
• Gypsogenin 3-O- beta-D-glucuronide
• Sessiloside
• Chiisanoside

• A. senticosus extract (12 mg/kg for 12 weeks)
• Decreased the deposition of abdominal fat
• Improved associated lipid parameters
• Increasing serum high-density lipoprotein (HDL) cholesterol
• Decreasing serum TG and low-density lipoprotein (LDL) cholesterol
• A. senticosus (1500 mg/day for 6 months) to postmenopausal women
• Decreased serum LDL levels and LDL/HDL ratios
• Without associated side effects

• Several mechanisms of action
• Inhibition of hepatic lipogenic enzymes
• Glucose 6-phosphatase
• Reduction of LDL levels is probably the result of a combination of effects [12]

Vibralactone

• Compound isolated from the culture broth of the polypore Boreostereum vibrans
• Inhibits pancreatic lipase [12]

Brassicaceae, Ericaceae, Fabaceae, Rosaceae and Solanaceae

• All extracts showed inhibitory activity
• Majority of extracts, 100 in total
• Some degree of inhibitory activity
• 26 extracts
• Inhibited lipase activity by at least 40%
• 10 exhibited
• Over 70% inhibitory activity [12]