Dual Strategy for Improving the Oral Bioavailability of Resveratrol: Enhancing Water Solubility and Inhibiting Glucuronidation

Li, Yingchao; Zhang, Ran; Zhang, Qi; Luo, Meiling; Lu, Farong; Zhang, He; Jiang, Qikun; Zhang, Tianhong

doi:10.1021/acs.jafc.1c02602

Cited by 19 publications

(9 citation statements)

References 51 publications

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“…These include: (1) bioavailability and metabolism. Resveratrol demonstrates relatively low bioavailability and undergoes rapid liver metabolism, necessitating higher doses to achieve effective concentrations, thereby potentially escalating side effects and toxicity risks (Li et al, 2021; Vesely et al, 2021); (2) scarcity of clinical studies. The existing literature on resveratrol's effect on pain suffers from inconsistent evaluation criteria, hindering quantitative meta‐analysis due to limited data (Siddaway et al, 2019).…”

Section: Summary and Prospectmentioning

confidence: 99%

Deciphering resveratrol's role in modulating pathological pain: From molecular mechanisms to clinical relevance

Wang,

Jiang,

et al. 2023

Phytotherapy Research

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Pathological pain, a multifaceted and debilitating ailment originating from injury or post‐injury inflammation of the somatosensory system, poses a global health challenge. Despite its ubiquity, reliable therapeutic strategies remain elusive. To solve this problem, resveratrol, a naturally occurring nonflavonoid polyphenol, has emerged as a potential beacon of hope owing to its anti‐inflammatory, antioxidant, and immunomodulatory capabilities. These properties potentially position resveratrol as an efficacious candidate for the management of pathological pain. This concise review summaries current experimental and clinical findings to underscore the therapeutic potential of resveratrol in pathological pain, casting light on the complex underlying pathophysiology. Our exploration suggests that resveratrol may exert its analgesic effect by the modulating pivotal signaling pathways, including PI3K/Akt/mTOR, TNFR1/NF‐κB, MAPKs, and Nrf2. Moreover, resveratrol appears to attenuate spinal microglia activation, regulate primary receptors in dorsal root sensory neurons, inhibit pertinent voltage‐gated ion channels, and curb the expression of inflammatory mediators and oxidative stress responses. The objective of this review is to encapsulate the pharmacological activity of resveratrol, including its probable signaling pathways, pharmacokinetics, and toxicology pertinent to the treatment of pathological pain. Hopefully, we aim to map out promising trajectories for the development of resveratrol as a potential analgesic.

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Section: Summary and Prospectmentioning

confidence: 99%

Deciphering resveratrol's role in modulating pathological pain: From molecular mechanisms to clinical relevance

Wang,

Jiang,

et al. 2023

Phytotherapy Research

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“…A licorice flavonoid (licochalcone A) has been reported to be a potent inhibitor of several specific cytochrome P450 enzymes, while also showing strong inhibitory effects against UGT1A1, 1A3, 1A4, 1A6, 1A7, 1A9, and 2B7 and moderate inhibitory effects against UGT1A8, 1A10, 2B4, 2B15, and 2B17 (Xin et al., 2016). Another licorice extract (glycyrrhetic acid) was shown to be an effective inhibitor of cytochrome P450 in vitro, but was also able to reduce resveratrol glucuronidation by inhibiting UGTs (Li et al., 2021). Five major bioactive molecules (bavachin, neobavaisoflavone, isobavachalcone, bavachinin, and corylifol A) identified in an edible traditional Chinese herb ( Fructus Psoraleae ) were shown to inhibit UGT1A1 in human liver microsomes (Wang, Lv, et al., 2015).…”

Section: Current Strategies For Improving Bioavailability Of Nutraceu...mentioning

confidence: 99%

“…Eight flavonoids (quercetin, luteolin, dihydroquercetin, scutellarein, isorhamnetin, genistein, kaempferol, and epigallocatechin gallate) were investigated for their potential as competitive inhibitors of UGT1A1 and/or UGT1A9. Of these flavonoids, luteolin and isorhamnetin displayed the most and least inhibitory effects on glucuronidation of resveratrol in rat liver microsomes (Li et al., 2021). Recently, 56 flavonoids were collected to investigate structure–inhibition relationships of flavonoids as UGT1A1 inhibitors (Liu, Lv, et al., 2019).…”

Section: Current Strategies For Improving Bioavailability Of Nutraceu...mentioning

confidence: 99%

“…In a Caco‐2 cell model, cereal flavone (apigenin) and pulse flavonol (quercetin) combinations showed synergistic downregulation of ABC transporter (BCRP, MDR1, MRP2, and MRP3) expression, and reduced the Phase II metabolism (methylation and glucuronidation) of quercetin and apigenin; as a result, a combination of cereal and pulse flavonoids enhanced their absorption (Ravisankar et al., 2019). Similarly, addition of glycyrrhetinic acid in resveratrol–phospholipid complexes protected resveratrol from glucuronidation and significantly improved its oral bioavailability (Li et al., 2021). However, strong inhibition of Phase I and II enzymes may trigger adverse intermolecular interactions and potential toxicity of xenobiotic compounds, or result in metabolic disorders of endobiotic metabolism, especially in the case of high doses of dietary inhibitors (Dominguez‐Avila et al., 2017; Lv, Xia, et al., 2019; Xin et al., 2016).…”

Section: Current Strategies For Improving Bioavailability Of Nutraceu...mentioning

confidence: 99%

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A review of recent progress in improving the bioavailability of nutraceutical‐loaded emulsions after oral intake

Chen

Liu

et al. 2022

Comp Rev Food Sci Food Safe

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Increasing awareness of the health benefits of specific constituents in fruits, vegetables, cereals, and other whole foods has sparked a broader interest in the potential health benefits of nutraceuticals. Many nutraceuticals are hydrophobic substances, which means they must be encapsulated in colloidal delivery systems. Oil‐in‐water emulsions are one of the most widely used delivery systems for improving the bioavailability and bioactivity of these nutraceuticals. The composition and structure of emulsions can be designed to improve the water dispersibility, physicochemical stability, and bioavailability of the encapsulated nutraceuticals. The nature of the emulsion used influences the interfacial area and properties of the nutraceutical‐loaded oil droplets in the gastrointestinal tract, which influences their digestion, as well as the bioaccessibility, metabolism, and absorption of the nutraceuticals. In this article, we review recent in vitro and in vivo studies on the utilization of emulsions to improve the bioavailability of nutraceuticals. The findings from this review should facilitate the design of more efficacious nutraceutical‐loaded emulsions with increased bioactivity.

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“…Poor water solubility and extensive metabolism lead to low bioavailability of RSV [ 6 ]. After oral administration, RSV is metabolized by phase II enzymes and form sulfate and glucuronide metabolites in the gastrointestinal tract and the liver, with trans-resveratrol-3-O-glucuronide and trans-resveratrol-3-sulfate the most abundant metabolites of RSV [ 7 , 8 ].…”

Section: Introductionmentioning

confidence: 99%

Gut Microbiota Composition in Relation to the Metabolism of Oral Administrated Resveratrol

et al. 2022

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Resveratrol (RSV) has been confirmed to confer multiple health benefits, and the majority of RSV tends to be metabolized in the gut microbiota after oral administration. In this study, the metabolism of RSV was investigated by using mouse models with distinct gut microbiota compositions: germ-free mice colonized with probiotics, conventional mouse, and DSS-induced colitis mouse models. The results demonstrated that in feces, the metabolites of RSV, including resveratrol sulfate (RES-sulfate), resveratrol glucuronide (RES-glucuronide), and dihydroresveratrol, significantly increased after probiotics colonized in germ-free mice. Furthermore, RES-sulfate and RES-glucuronide were below the detectable limit in the feces of conventional mice, with dihydroresveratrol being the dominant metabolite. Compared to the conventional mice, the ratio of Firmicutes/Bacteroides and the abundance of Lactobacillus genera were found significantly elevated in colitis mice after long-term ingestion of RSV, which shifted the metabolism of RSV in return. Our study provided critical implications in further application of RSV in foods and food supplements.

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Dual Strategy for Improving the Oral Bioavailability of Resveratrol: Enhancing Water Solubility and Inhibiting Glucuronidation

Cited by 19 publications

References 51 publications

Deciphering resveratrol's role in modulating pathological pain: From molecular mechanisms to clinical relevance

Deciphering resveratrol's role in modulating pathological pain: From molecular mechanisms to clinical relevance

A review of recent progress in improving the bioavailability of nutraceutical‐loaded emulsions after oral intake

Gut Microbiota Composition in Relation to the Metabolism of Oral Administrated Resveratrol

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