A method for improving the bioavailability of 5-heptadecylresorcinol

Abstract

The application discloses a method for improving bioavailability of 5-heptadecyl resorcinol, and belongs to the field of natural product health. Quercetin is added to 5-heptadecyl resorcinol, and the quercetin can promote the transport of 5-heptadecyl resorcinol by inhibiting the expression of P-gp transport gene. The promotion effect of 5-heptadecyl resorcinol transport is different due to different addition amounts of quercetin. 5-heptadecyl resorcinol has other beneficial health effects such as antioxidant, antitumor, neuroprotective, prevention of muscle atrophy, etc. The composition prepared by using quercetin and 5-heptadecyl resorcinol is applied to functional food, medicine and health products, and the bioavailability of 5-heptadecyl resorcinol can be significantly improved, so that the efficacy can be maximized. The application further verifies the promotion effect of quercetin on the transport of 5-heptadecyl resorcinol through cell experiments and animal experiments.

Description

Technical Field

[0001] This invention relates to a method for improving the bioavailability of 5-heptadecylresorcinol, belonging to the field of natural product health nutrition. Background Technology

[0002] Alkylresorcinols (ARs) have been found in various biological species in nature, such as plants, fungi, and bacteria, and are the most abundant phenolic lipid compounds. ARs are a class of amphiphilic 1,3-dihydroxyphenyl derivatives, a mixture of AR homologues, whose alkyl chains contain 13 to 27 odd-numbered carbon atoms. Similar to simple analogs of the 1,3-dihydroxy-5n-alkyl(enyl)benzene sequence, ARs possess both hydrophobic and hydrophilic regions associated with metabolism, absorption, and potential activity. The presence of lipophilic alkyl chains in ARs enhances their interaction with cellular sites, leading to stronger biological activity than resorcinol. The amphiphilicity of ARs and the differences in their structure and chain length endow them with various biological functions, such as antitumor and antioxidant effects. In recent years, they have gradually become a hot topic in nutritional and biomedical research.

[0003] Argan oils (ARs) are abundant in various higher plant species, with a particularly high proportion in cereal crops. It has been reported that black wheat has the highest AR content compared to wheat, barley, and oats. Notably, numerous reports conclude that ARs in cereals are primarily found in the bran, while the germ and endosperm do not contain ARs. The alkyl side chains of ARs in cereals are generally saturated carbon chains containing an odd number of carbon atoms (17–25). Furthermore, ARs are considered biomarkers for whole grain consumption; after ingestion, their homologues or metabolites can be detected in biological samples such as plasma, but they are undetectable in plasma and other biological samples when people consume a bran-free diet.

[0004] Compared to other AR homologues in cereals, 5-heptadecylrecorcinol (AR-C17) is considered the most important active monomer due to its potent bioactivity. AR-C17 has been reported to improve cognitive impairment and alleviate neuroinflammation in mice. Furthermore, AR-C17 is a promising adipocyte thermogenesis activator, potentially alleviating metabolic diseases associated with obesity and aging. Therefore, AR-C17 possesses significant potential for nutritional development. Despite numerous studies demonstrating the immeasurable benefits of AR-C17 for human health, its poor bioavailability limits the maximization of its functional benefits. Therefore, exploring methods to improve the bioavailability of AR-C17 is crucial for its application in the prevention and treatment of biological diseases. Summary of the Invention

[0005] The present invention aims to address the problem of poor bioavailability of 5-heptadecylresorcinol by providing a method and composition for improving the bioavailability of 5-heptadecylresorcinol, thereby solving the problem of low transport of 5-heptadecylresorcinol in intestinal epithelial cells and low bioavailability in vivo.

[0006] To achieve the above objectives, the present invention first provides a method for improving the bioavailability of 5-heptadecylresorcinol, wherein the method involves adding quercetin and / or quercetin derivatives to 5-heptadecylresorcinol.

[0007] Bioavailability refers to the extent and rate at which the active portion (drug or metabolite) of a composition enters the systemic circulation and subsequently reaches its site of action. In this composition, quercetin promotes the transport of 5-heptadecylresorcinol in intestinal epithelial cells, thereby enhancing its bioavailability in vivo.

[0008] In one embodiment of the present invention, the mass ratio of quercetin and / or quercetin derivatives to 5-heptadecylresorcinol is 3:1 to 1:3.

[0009] In one embodiment of the present invention, the mass ratio of quercetin and / or quercetin derivatives to 5-heptadecylresorcinol is 1:1.

[0010] The present invention also provides a composition for improving the bioavailability of 5-heptadecylresorcinol, the composition comprising quercetin and / or quercetin derivatives and 5-heptadecylresorcinol.

[0011] In one embodiment of the present invention, the composition further includes pharmaceutically acceptable excipients, such as solvents, propellants, solubilizers, cosolvents, emulsifiers, colorants, binders, disintegrants, fillers, lubricants, wetting agents, osmotic pressure regulators, stabilizers, flow aids, flavoring agents, preservatives, suspending agents, coating materials, fragrances, anti-adhesion agents, integrators, penetration enhancers, pH adjusters, buffers, plasticizers, surfactants, foaming agents, defoamers, thickeners, encapsulating agents, humectants, absorbents, diluents, flocculants and anti-flocculators, filter aids, release inhibitors, etc.

[0012] In one embodiment of the present invention, the mass ratio of quercetin and / or quercetin derivatives to 5-heptadecylresorcinol in the composition is 3:1 to 1:3.

[0013] In one embodiment of the present invention, the mass ratio of quercetin and / or quercetin derivatives to 5-heptadecylresorcinol in the composition is 1:1.

[0014] This invention also provides the application of the above composition in the preparation of functional foods, pharmaceuticals, or health products that enhance the bioavailability of 5-heptadecylresorcinol. In the composition, quercetin promotes the transport of 5-heptadecylresorcinol in intestinal epithelial cells, thereby improving its bioavailability. This is because the transport of 5-heptadecylresorcinol through intestinal epithelial cells is mainly regulated by P-gp efflux transporters, and quercetin, as a common flavonoid, is a typical inhibitor of P-gp. Quercetin can significantly inhibit the expression of P-gp transport genes, thereby assisting the intestinal transport of 5-heptadecylresorcinol and thus improving its bioavailability in vivo.

[0015] In one embodiment of the present invention, the functional food includes functional beverages, functional powders, functional effervescent tablets, functional biscuits, functional capsules, etc.

[0016] In one embodiment of the present invention, the medicine includes a drug for treating cancerous tumors, skeletal muscle injury, neuroinflammation, etc.

[0017] In one embodiment of the present invention, the health product includes health foods that have functions such as enhancing immunity, assisting in lowering blood lipids, assisting in lowering blood sugar, assisting in lowering blood pressure, anti-oxidation, weight loss, and regulating intestinal flora.

[0018] In one embodiment of the present invention, the quercetin is derived from sources such as black wheat, sophora japonica, and buckwheat.

[0019] The present invention also provides the use of quercetin and quercetin derivatives in improving the bioavailability of 5-heptadecylresorcinol.

[0020] In one embodiment of the invention, the use includes preparing compositions that enhance the bioavailability of 5-heptadecylresorcinol using quercetin and / or quercetin derivatives.

[0021] The beneficial effects of this invention are:

[0022] (1) Quercetin is widely found in widely cultivated plants such as black wheat, sophora japonica, and buckwheat, especially black wheat, which is widely cultivated in Xinjiang and other regions. This invention selects quercetin isolated from black wheat to assist in the transport of 5-heptadecylresorcinol, which has the advantages of wide availability of raw materials, affordable price, and no toxicity.

[0023] (2) 5-Heptadecanylresorcinol has other beneficial health effects such as anti-oxidation, anti-tumor, neuroprotection, and prevention of muscle atrophy. When quercetin is combined with 5-heptadecanylresorcinol to prepare a composition, the bioavailability of 5-heptadecanylresorcinol can be significantly improved when the composition is applied to functional foods, pharmaceuticals and health products, thereby maximizing the efficacy.

[0024] (3) By adding a mixture of quercetin and 5-heptadecylresorcinol to an intestinal transport model, it was found that the addition of quercetin significantly increased the transport of 5-heptadecylresorcinol in intestinal epithelial cells. qPCR results showed that quercetin significantly inhibited the expression of the P-gp gene, facilitating the intestinal transport of 5-heptadecylresorcinol, and the transport amounts varied significantly at different concentration ratios. This invention was further validated in in vivo experiments. Mice were administered a mixture of quercetin and 5-heptadecylresorcinol at different concentrations via gavage. Compared with the control group, the groups with added quercetin showed a significant increase in the area under the curve (AUC) of 5-heptadecylresorcinol in plasma and a significant increase in the excretion rate of 5-heptadecylresorcinol's typical metabolites DHBA and DHPPA in urine. Furthermore, the results at different concentrations were correlated with in vitro cell experiments. This further validates that quercetin can assist in the transport of 5-heptadecylresorcinol, thereby further improving its bioavailability in vivo. Attached Figure Description

[0025] Figure 1 This is the chemical structural formula of AR-C17.

[0026] Figure 2 This study investigated the cotransport relationship between black wheat bran extracts containing different concentrations of 5-heptadecylresorcinol and 5-heptadecylresorcinol. Data are expressed as mean ± standard error, with each group analyzed in triplicate. (T-test)

[0027] Figure 3 This study identified the components of natural products in black wheat extract. Data are expressed as mean ± standard error, with each group having three replicates. *, P < 0.05; **, P < 0.01; ***, P < 0.001 (T-test).

[0028] Figure 4 This study investigated the effect of natural active ingredients from black wheat on the P-gp gene during the transport of 5-heptadecylresorcinol in CaCO₂ cells. The mRNA level of P-gp was analyzed using RT-qPCR. Data are presented as mean ± standard error, with five replicates per group. Compared with controls, *, P < 0.05; **, P < 0.01; ***, P < 0.001 (one-way ANOVA).

[0029] Figure 5 This study investigated the effect of the addition of natural active ingredients from black wheat on the transport of 5-heptadecylresorcinol in intestinal epithelial cells using a CaCO₂ model. Data are expressed as mean ± standard error, with each group having three replicates. Compared with control, *, P < 0.05; **, P < 0.01; ***, P < 0.001 (T-test).

[0030] Figure 6 To investigate the effect of different concentrations of quercetin on the transport of 5-heptadecylresorcinol during intestinal transit. Data are expressed as mean ± standard error, with each group having three replicates. Compared with control, ns, P>0.05; * / #, P<0.05; ** / ##, P<0.01; *** / ###, P<0.001 (T-test).

[0031] Figure 7 Effects of different concentrations of quercetin supplementation on the plasma pharmacokinetics of 5-heptadecylresorcinol. Data are expressed as mean ± standard error, with each group having three replicates. Compared with control, *, P < 0.05; **, P < 0.01; ***, P < 0.001 (T-test).

[0032] Figure 8 This study investigated the effect of different concentrations of quercetin supplementation on the urinary excretion rates of the 5-heptadecylresorcinol metabolites DHBA and DHPPA. Data are presented as mean ± standard error, with each group having three replicates. Compared with control, *, P < 0.05; **, P < 0.01; ***, P < 0.001 (T-test). Detailed Implementation

[0033] Example 1

[0034] Effects of black wheat natural product extract on AR-C17 in in vitro intestinal transport

[0035] 1. Experimental Methods

[0036] 1.1 Extraction and Component Identification of Natural Products from Black Wheat Bran Extract

[0037] Black wheat was pulverized, and 1.0 g of pulverized black wheat (passed through an 80-mesh sieve) was accurately weighed into a 50 mL centrifuge tube. 40 mL of ethyl acetate was added, and the mixture was thoroughly mixed. The centrifuge tube was placed in a constant temperature water bath shaking incubator and shaken at room temperature for 48 h. After centrifugation for 10 min (4000 r / min), the supernatant was collected and rotary evaporated at 45 °C until nearly dry. 5 mL of ethyl acetate was added to reconstitute the supernatant, which was then transferred to a 10 mL centrifuge tube. After drying with nitrogen, 1 mL of chromatographic grade methanol was added to reconstitute the supernatant. The solution was filtered through a 0.22 μm organic filter membrane and transferred to a sample vial for LC-MS component identification. The specific LC-MS conditions are as follows:

[0038] The Waters Acquity ultra-high performance liquid chromatography-tandem quadrupole mass spectrometry (UPLC-QQQ-MS) system was used.

[0039] Liquid chromatography conditions: Column: HSST3 column (2.1 mm × 100 mm, 1.8 μm). Gradient elution was used to separate phenolic compounds. Mobile phase A was ultrapure water / acetic acid (99.9:0.1, v / v), and mobile phase B was acetonitrile. Gradient elution program: 0–0.5 min, 2% B; 0.5–10.5 min, 2–20% B; 10.5–18.5 min, 20–100% B; 18.5–20 min, 100% B; 20–20.5 min, 100–2% B; 20.5–23 min, 2% B. Column oven temperature: 40℃; total system flow rate: 0.3 mL / min; injection volume: 1 μL.

[0040] Mass spectrometry conditions: Multiple reaction monitoring (MRM) was used to detect and analyze the identified polyphenols in negative ion mode, and full scan mode was used for auxiliary analysis. Scan range: m / z 100~1000; capillary voltage: 3kV, cone voltage: 40V, extraction cone voltage: 3V, desolvation gas (N2) flow rate: 650L / h, cone gas (He) flow rate: 50L / h, desolvation gas temperature: 350℃, ion source temperature: 120℃.

[0041] 1.2 Effect of different concentrations of AR-C17 black wheat bran extract on the in vitro transport of AR-C17.

[0042] (1) Cell culture and seeding: CaCO-2 cells were cultured in DMEM medium (containing 10% fetal bovine serum, 1% antibiotic solution and 1% non-essential amino acids) in cell culture flasks until the logarithmic growth phase (the medium was changed every 1-2 days). The cells were digested with trypsin containing 0.25% EDTA for 3-5 minutes. The cells were observed under an inverted microscope. When the cell edges retracted and the cells no longer connected to each other, the medium was added to disperse the cells. The cells were then passaged at a ratio of 1:3 between primary cells and daughter cells.

[0043] (2) To obtain a differentiated monolayer cell membrane, CaCO₂ cells were subjected to a reaction at a concentration of 4 × 10⁻⁶ cells / mL. 5 cells / cm 2 The cells were seeded at a density in 24-well Transwell chambers. The medium was changed every two days for the first two weeks, and then once a day thereafter. After culturing for 21 to 24 days, a fully differentiated CaCO-2 monolayer was obtained.

[0044] (3) Evaluation of the synergistic effect of the extract on the transport of 5-heptadecylresorcinol in intestinal epithelial cells. For the transport process from the villous surface (AP) to the basal surface (BL), 0.3 mL of extract based on different AR-C17 concentrations (AR-C17 concentrations of 0.5 μg / mL, 1 μg / mL, and 2 μg / mL) was added to the AP side, and 0.6 mL of HBSS (blank control) was added to the BL side; for the transport process from the basal surface (BL) to the villous surface (AP), 0.6 mL of extract based on different AR-C17 concentrations (AR-C17 concentrations of 0.5 μg / mL, 1 μg / mL, and 2 μg / mL) was added to the BL side, and 0.3 mL of HBSS was added to the AP side. After placing the culture plate in a constant temperature shaker at 37°C and 50 rpm for 150 min, 200 μL of receiving solution was aspirated from the receiving chamber, and 200 μL of HBSS was added simultaneously. The content of 5-heptadecylresorcinol in the receiving solution was determined by LC-MS.

[0045] An investigation into promoting the transport of 5-heptadecylresorcinol in intestinal epithelial cells and thereby improving its bioavailability.

[0046] 1 Experimental Methods

[0047] 1.1 Cell Experiments

[0048] (1) Cell culture and seeding: CaCO-2 cells were cultured in DMEM medium (containing 10% fetal bovine serum, 1% antibiotic solution and 1% non-essential amino acids) in cell culture flasks until the logarithmic growth phase (the medium was changed every 1-2 days). The cells were digested with trypsin containing 0.25% EDTA for 3-5 minutes. The cells were observed under an inverted microscope. When the cell edges retracted and the cells no longer connected to each other, the medium was added to disperse the cells. The cells were then passaged at a ratio of 1:3 between primary cells and daughter cells.

[0049] (2) To obtain a differentiated monolayer cell membrane, CaCO₂ cells were subjected to a reaction at a concentration of 4 × 10⁻⁶ cells / mL. 5 cells / cm 2 The cells were seeded at a density in 24-well Transwell chambers. The medium was changed every two days for the first two weeks, and then once a day thereafter. After culturing for 21 to 24 days, a fully differentiated CaCO-2 monolayer was obtained.

[0050] (3) To evaluate the inhibitory effects of natural extracts quercetin (Que), catechin (Cat), p-coumaric acid (p-co), syringic acid (Syn), ferulic acid (Fer), and caffeic acid (Caf) from black wheat bran extract on P-gp in intestinal epithelial cells. CaCO₂ cells cultured in plates were stimulated with a concentration ratio of 3:1 (corresponding natural extract: AR-C17) for 6 h, 12 h, and 24 h, followed by RNA extraction. Total RNA was extracted using Trizol reagent (1 mL / cell). The concentration and purity of RNA were quantified using a nanodrop (Thermo Fisher Scientific). After RNA purification and cDNA synthesis, qRT-PCR was performed. qRT-PCR was conducted on an ABI 7900 qRT-PCR system. Primers designed for gene amplification are shown in Table 1 below. Each sample was performed in triplicate, and the RT-PCR primer sequences used are shown in Table 1 below.

[0051] Table 1

[0052]

[0053] (4) To evaluate the synergistic effect of natural extracts of black wheat bran extract, including quercetin (Que), catechin (Cat), p-coagulant (p-co), syringic acid (Syn), ferulic acid (Fer), and caffeic acid (Caf), on the transport of 5-heptadecylresorcinol in intestinal epithelial cells. For the transport process from the acuminate (AP) to the basal (BL) side, 0.3 mL of extract containing different natural extracts (quercetin, catechin, p-coumaric acid, syringic acid, ferulic acid, and caffeic acid) was added to the AP side, with a natural extract to AR-C17 concentration ratio of 3:1. 0.6 mL of HBSS (blank control) was added to the BL side. For the transport process from the basal (BL) to the acuminate (AP) side, 0.6 mL of extract containing different natural extracts (quercetin, catechin, p-coumaric acid, syringic acid, ferulic acid, and caffeic acid) was added to the BL side, with a natural extract to AR-C17 concentration ratio of 3:1. 0.3 mL of HBSS was added to the AP side. After placing the culture plate in a 37°C, 50 rpm air bath shaker for 150 min, 200 μL of receiving solution was aspirated from the receiving chamber, and 200 μL of HBSS was added simultaneously. The content of 5-heptadecylresorcinol in the receiving solution was determined by LC-MS.

[0054] (5) Screening the optimal synergistic concentration ratio of quercetin to promote the transport of 5-heptadecylresorcinol in intestinal epithelial cells. The procedure is the same as in (4), except that different concentration ratios (3:1, 2:1, 1:1, 1:2, and 1:3) of mixed working solution of quercetin and 5-heptadecylresorcinol were added to the AP and BL sides, respectively. After incubation in an air bath with shaking for 150 min, 200 μL of the receiving solution was taken from the receiving chamber, and the 5-heptadecylresorcinol content was measured.

[0055] 1.2 Animal Experiments

[0056] (1) Twenty-four 5-week-old SPF-grade C57BL / 6 mice were pre-acclimatized for one week (acclimatized by feeding according to SPF-grade feed standards for one week) and then randomly divided into a control group (150 mg / kg ARs by gavage), a 150 mg / kg ARs + quercetin gavage group (concentration ratio 1:1), a 150 mg / kg ARs + quercetin gavage group (concentration ratio 2:1), and a 150 mg / kg ARs + quercetin gavage group (concentration ratio 1:2). Mice were fasted for 12 hours before gavage (water was allowed). Blood was collected from the tail vein at 0h, 0.5h, 1h, 2h, 4h, 6h, 8h, 10h, 12h, 16h, and 24h. Urine was collected from the metabolic cage at 0-6h, 6-12h, 12-18h, and 18-24h. Animal experiments were then conducted. Finally, isoflurane anesthetic was used, which was evaporated by an oxygen flow. Anesthesia was induced using a concentration of 2-3%, and maintained at 1.5-2%. After anesthesia, blood was collected from the eyeballs, and the mice were killed by cervical dislocation. Corresponding tissues were collected.

[0057] (2) Accurately pipette 100 μL of the heparin-anticoagulated mouse plasma sample to be tested, add 1 mL of anhydrous ethanol solution, vortex mix, centrifuge at 4℃ and 16000 r / min for 10 min, take the supernatant, blow dry with nitrogen, add 100 μL of anhydrous ethanol to the dried sample to reconstitute the sample, vortex mix, centrifuge at 4℃ and 16000 r / min for 10 min, take the supernatant, and determine the content of 5-heptadecylresorcinol by LC-MS.

[0058] (3) Accurately measure 2 mL of urine and add 2 mL of methanol to precipitate proteins. After centrifugation at 17000 rpm for 5 min, transfer the supernatant to a vial for LC-MS analysis. To quantify the content of its typical metabolites 3,5-dihydroxybenzoic acid (DHBA) and 3-(3,5-dihydroxyphenyl)propanoic acid (DHPPA) in urine, syringic acid was added as an internal standard. 2 mL of urine was treated with 6 mL of PBS (50 mmol / L, pH 6.8) containing β-glucanuronidase (250 U) and sulfatase (3 U) at 37 °C for 24 h. After incubation, the urine was diluted 5-fold with methanol containing 0.2% acetic acid, and the supernatant obtained by centrifugation was used to determine the metabolite content by LC-MS.

[0059] The time procedure for determining 5-heptadecylresorcinol is as follows:

[0060] ACQMITYMPLC BEN C 18 Chromatographic column (2.1 mm × 100 mm, 1.7 μm); column temperature 30 ℃; injection volume 5 μL; mobile phase: phase A is 0.1% ammonia, phase B is acetonitrile; flow rate 0.5 mL / min; elution gradient: 0–2 min, 100%–15% A, 0%–85% B; 2–4 min, 15%–10% A, 85%–90% B; 4–8 min, 10%–5% A, 90%–95% B; 8–9 min, 5%–15% A, 95%–85% B;

[0061] The time procedure for determining DHBA and DHPPA is as follows:

[0062] Gemini-NX C18 column (3 mm × 150 mm, 5 μm); column temperature 30 ℃; injection volume 10 μL; mobile phase: phase A is water containing 0.2% acetic acid, phase B is methanol containing 0.2%; flow rate 0.3 mL / min; elution gradient: 0–5 min, 100% A, 0% B; 5–20 min, 100%–60% A, 0%–40% B; 20–30 min, 60%–20% A, 40%–80% B; 30–40 min, 20%–0% A, 80%–100% B; 40–55 min, 0% A, 100% B; 55–65 min, 100% A, 0% B;

[0063] 2. Experimental Results

[0064] 2.1 Cotransport relationship between black wheat bran extracts containing different concentrations of 5-heptadecylresorcinol and 5-heptadecylresorcinol

[0065] from Figure 2 It can be seen that when the concentration of AR-C17 in the extract is 0.5 μg / mL, 1 μg / mL and 2 μg / mL, the amount of 5-heptadecylresorcinol transported in the black wheat bran extract is significantly increased compared with the pure 5-heptadecylresorcinol sample. This also indicates that there is a synergistic supplement in the extract that can promote the transport of 5-heptadecylresorcinol.

[0066] 2.1 Analysis and identification of natural active ingredients in black wheat bran extract

[0067] To investigate the specific synergistic agents in the extract, we identified its components. From... Figure 3 It can be seen that, in addition to 5-heptadecylresorcinol, the main natural active ingredients detected in the black wheat bran extract are quercetin (Que), catechin (Cat), p-coumaric acid (p-co), syringic acid (Syn), ferulic acid (Fer), and caffeic acid (Caf). Specifically, except for ferulic acid and caffeic acid, the content of the others is approximately more than three times that of AR-C17.

[0068] 2.2 Effects of different natural active ingredients in black wheat bran extract on the P-gp gene

[0069] from Figure 4 It can be seen that, compared with catechin, p-coumaric acid, syringic acid, ferulic acid, and caffeic acid, quercetin supplementation significantly inhibited P-gp mRNA levels, and the inhibitory effect increased significantly over time. This demonstrates that quercetin supplementation can inhibit P-gp gene expression.

[0070] 2.3 Effects of different natural active ingredients in black wheat bran extract on the transport of 5-heptadecanoylresorcinol in intestinal epithelial cells

[0071] from Figure 5 As can be seen, compared with the control group and other natural active ingredient groups, the transport of 5-heptadecylresorcinol on the BL→AP side was significantly reduced and the efflux ratio (ER) was significantly decreased after supplementation with a certain proportion of quercetin (quercetin: 5-heptadecylresorcinol = 3:1). Combined with the results and analysis in section 2.2, it can be concluded that quercetin supplementation can assist the transport of 5-heptadecylresorcinol in intestinal epithelial cells by inhibiting the expression of the P-gp gene.

[0072] 2.4 Screening of the optimal concentration ratio for quercetin-assisted 5-heptadecanoylresorcinol transport

[0073] from Figure 6 It can be seen that the ER value changes significantly with different concentration ratios of quercetin and 5-heptadecylresorcinol. The ER value is lowest when the concentration ratio is 1:1, meaning that the higher the concentration of 5-heptadecylresorcinol is transported from the intestinal lumen into the bloodstream under the regulation of the P-gp transporter.

[0074] 2.5 Effect of quercetin on the pharmacokinetics of 5-heptadecanoylresorcinol in mouse plasma

[0075] The effect of quercetin on the transport of 5-heptadecylresorcinol was further verified in mice, and the results are as follows: Figure 7 As shown in the figure. The results showed that after gavage administration of a mixture of quercetin and 5-heptadecylresorcinol at different concentration ratios, the concentration of 5-heptadecylresorcinol in mouse plasma exhibited a similar trend, and the AUC values ​​showed significant differences. Consistent with the results of in vitro cell experiments, when the concentration ratio was 1:1, the higher the AUC value of 5-heptadecylresorcinol in mouse plasma, the greater the amount of 5-heptadecylresorcinol transported through the intestine, and the higher its bioavailability in vivo.

[0076] 2.6 Effect of quercetin on the excretion rate of 5-heptadecanoylresorcinol metabolites in mouse urine

[0077] The excretion rate of 5-heptadecanoylresorcinol metabolites in urine was detected, and the results are as follows: Figure 8 As shown, when the concentration ratio is 1:1, DHBA and DHPPA have the highest excretion rates, which also means that the more 5-heptadecylresorcinol involved in metabolism, the higher the bioavailability.

[0078] Although the present invention has been disclosed above with reference to preferred embodiments, it is not intended to limit the present invention. Anyone skilled in the art can make various modifications and alterations without departing from the spirit and scope of the present invention. Therefore, the scope of protection of the present invention should be determined by the claims.

Claims

1. Use of quercetin for the preparation of a composition for increasing the bioavailability of 5-heptadecylresorcinol, characterized in that, The composition comprises 5-heptadecyl resorcinol and quercetin, a mass ratio of quercetin to 5-heptadecyl resorcinol is 1:1, and the improvement of the bioavailability of 5-heptadecyl resorcinol comprises promoting the transport of 5-heptadecyl resorcinol in the intestinal epithelial cells, inhibiting the expression of P-gp transport gene, improving the pharmacokinetic parameters of 5-heptadecyl resorcinol in the blood plasma, and improving the excretion rate of metabolites of 5-heptadecyl resorcinol in the urine.

2. Use according to claim 1, characterized in that, The composition further comprises a pharmaceutically acceptable adjuvant.

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