Protocatechuic acid from chicory is bioavailable and undergoes partial glucuronidation and sulfation in healthy humans

Abstract

Protocatechuic acid exerts multiple health‐promoting effects such as anticancer, anti‐atherosclerosis, and neuroprotection in animal models. While protocatechuic acid produced in the lower gastrointestinal tract by microbial catabolism of several flavonoids is bioavailable, the pharmacokinetics of protocatechuic acid has not been evaluated so far in humans following its oral consumption. In this open‐label and single‐dose pharmacokinetic trial, 16 healthy adults followed a low‐phytochemical diet for three days. Next, after overnight fasting, participants consumed 150 g of chicory containing 248 μmol of protocatechuic acid. Blood, urine, and fecal samples were collected before and up to 24 hr after chicory consumption. Protocatechuic acid in the free and glucuronide/sulfate‐conjugated forms was almost undetectable in serum, urine, and fecal samples before chicory consumption. Chicory consumption increased the levels of protocatechuic acid and its glucuronide/sulfate conjugates in biological samples. The maximum serum concentrations of protocatechuic acid in the free‐, glucuronide‐, and sulfate‐conjugated forms were 3,273, 519, and 340 nmol/L, respectively. The recovery of total protocatechuic acid in blood circulation, urine, and feces was 23.79%, 12.17%, and 12.79% of the ingested dose, respectively. Moreover, glucuronide and sulfate conjugates of protocatechuic acid made up 34.79%, 60.15%, and 72.70% of its total recovery in blood circulation, urine, and feces, respectively. Collectively, protocatechuic acid from chicory is bioavailable and undergoes partial glucuronidation and sulfation in human adults, and its regular consumption may exert health‐promoting effects.

Bioaccessibility of phenolic compounds from sesame seeds ( Sesamum indicum L.) during in vitro gastrointestinal digestion and colonic fermentation

“…As shown in Table 1, protocatechuic and caftaric acid were only bioaccessible in black sesame seeds during intestinal digestion and colonic fermentation. Protocatechuic acid is the metabolite of some of flavonoids, such as anthocyanins, procyanidins, and quercetin (Zheng et al, 2019). Quercetin in black sesame seeds also became bioaccessible during the intestinal and colonic stage, which was consistent with the metabolism of protocatechuic acid.…”

New Cocrystal of Ubiquinol with High Stability to Oxidation

“…The coformer of the new cocrystal 3,4-dihydroxybenzoic acid (also known as protocatechuic acid) is a metabolite of polyphenols, such as anthocyanins, is found in more than 500 plants, 19 and is widely present in the human diet in grain brown rice, olive oil, plums, gooseberries, and white grapes. 20 Moreover, the European Food Safety Authority concluded that 3,4-dihydroxybenzoic acid does not give rise to safety concerns at its levels of dietary intake. 21 In vitro studies of antioxidant activity have been previously reported 22 and show higher activity in comparison ascorbic acid (recognized and accepted by the FDA as a dietary antioxidant 23 ).…”

Development of Dextran-Coated Magnetic Nanoparticles Loaded with Protocatechuic Acid for Vascular Inflammation Therapy

“…Commercial sources of the primary reagents and consumables used in this study were as follows: ferric chloride (FeCl 3 ·6H 2 O), ferrous chloride (FeCl 2 ·4H 2 O), 25% ammonium solution (25%), PCA, ammonium persulfate (APS), 2,7-bis(2-carboxyethyl)-5(6)-carboxyfluorescein acetoxymethyl ester (BCECF-AM), dexamethasone (Dexa), Dulbecco’s modified Eagle’s medium, ethylenediaminetetraacetic acid tetrasodium salt dihydrate (EDTA), glycerol, hydrochloric acid (HCl), lipopolysaccharides from Escherichia coli serotype O111:B, 2-mercaptoethanol, N , N , N ′, N ′-Tetramethyl ethylenediamine (TEMED), phenylmethylsulphonyl fluoride (PMSF), paraformaldehyde (PFA), Ponceau S solution, potassium hexacyanoferrate(II) trihydrate, RPMI-1640 medium, sodium dodecyl sulphate (SDS), Triton-X-100, and Tris-HCl, which were purchased from SIGMA-Aldrich (Merck KGaA, Darmstadt, Germany); fetal bovine serum and penicillin/streptomycin, which were purchased from Thermo Fisher Scientific (Waltham, MA, USA); recombinant human tumor necrosis factor-alpha (TNF-α) from R&D Systems, Inc. (Abingdon, UK); cell culture dishes, which were purchased from TPP ® (Trasadingen, Switzerland); the transparent/black 96-well micro test plates, F-bottom, which were purchased from Ratiolab (Ratiolab GmbH, Dreieich, Germany); and UV 96-well micro test plates, F-bottom, which were purchased from Corning Inc. (New York, NY, USA). Dextran was biosynthesized as exopolysaccharides from Weissella confusa , a yogurt-isolated lactic acid bacterium, as previously reported [ 20 ]. A culture medium consisting of DeMan-Rogosa-Sharpe (MRS) agar (55.3 g/L) and sucrose (80 g/L) dissolved in UHT milk was inoculated with Weissella confusa , and after 48 h of fermentation, the dextran was extracted and purified as detailed in [ 21 ].…”

“…Protocatechuic acid (3,4-dihydroxybenzoic acid; PCA), a phenolic acid found in medicinal plants such as Roselle ( Hibiscus sabdariffa L.) or Japanese ginkgo ( Ginkgo biloba L.), has several therapeutic effects associated with anti-oxidant, anti-bacterial, anti-aging, anti-fibrotic, and anti-inflammatory activity, or even anti-cancer properties at the appropriate concentrations [ 19 ]. Human studies reported that PCA, produced as a degradation metabolite by the intestinal microbiota from flavonoids such as anthocyanins or procyanidins, is bioavailable in serum after flavonoids intake [ 20 ]. After absorption through the intestinal epithelium, PCA may reach systemic blood circulation, delivered to the liver, where it may undergo structural modifications resulting in sulfated and glucuronidated forms that can be distributed to the tissues or excreted in the urine or feces.…”