The anti‐hyperuricemic effect of flavonoid extract of saffron by‐product and its pharmacokinetics in rats after oral administration

Abstract

Only the dried stigma of the saffron, a flower deemed as the most valuable spice globally, is utilized for industrial production. Hence, there exists a growing interest in utilizing saffron floral bio‐residues. The anti‐hyperuricemic activity of a flavonoid extract from saffron floral bio‐residues was assessed in potassium oxonate‐induced hyperuricemia mice. In addition, an ultra‐high performance liquid chromatography‐triple quadrupole mass spectrometry method was established and validated to determine the pharmacokinetics of five main flavonoids and three phase‐II metabolites in rat plasma after oral administration of the flavonoid extract for the first time. Compared with pharmacokinetic parameters of kaempferol‐3‐O‐sophoroside, the most abundant flavonoid in the extract, and its aglycone kaempferol, we observed that coexisting compounds significantly reduced the absorption, accelerated the excretion of kaempferol‐3‐O‐sophoroside, while significantly increasing the absorption and prolonging the residence time of kaempferol in the flavonoid extract. These results suggest the promising potential of the flavonoid extract from saffron floral bio‐residues as an anti‐hyperuricemic agent. Kaempferol was absorbed in plasma at high concentrations owing to the biotransformation of kaempferol glycosides in vivo.

Flavonoid extract of saffron by‐product alleviates hyperuricemia via inhibiting xanthine oxidase and modulating gut microbiota

“…It is worth noting that kaempferol‐type flavonoids were the main compounds not only in SFB flavonoid extract but also in plasma of rats orally treated by SFB flavonoid extract, and kaempferol‐3‐ O ‐sophoroside lowered UA level in PO‐induced hyperuricemic mice in our previous work (Chen et al, 2022). These findings together with the reported pharmacological properties of kaempferol‐type flavonoids, such as antioxidant activity and antiinflammatory activity (Imran et al, 2019; Kim, Ku, Lee, & Bae, 2012; Plumb, Price, Rhodes, & Williamson, 1997), suggest that kaempferol‐type flavonoids are potential antihyperuricemic compounds of the SFB flavonoid extract.…”

“…Rats in the model group were then randomly divided into 5 groups ( n = 12 for each group) according to the UA value: model group, positive control group (allopurinol, 0.02 g/kg, per day), and SFB flavonoid extract‐treated groups (0.34 g/kg, 0.17 g/kg, 0.085 g/kg, per day, named H‐SFB, M‐SFB, and L‐SFB, respectively). The dosages of SFB flavonoid extract‐treated groups were calculated based on our previous experiment (Chen et al, 2022). Besides receiving PO (1.5 g/kg, per day) by oral gavage every morning, the 60 rats received distilled water, allopurinol, or SFB flavonoid by oral gavage every afternoon for 2 weeks, at the same time, rats in the control group received equal distilled water.…”

“…In our previous work, we prepared a flavonoid extract from SFB (Chen, Xiang, Liu, Li, & Yang, 2021) and evaluated its activity to prevent potassium oxonate (PO) induced hyperuricemia in mice, in which the mice first received the SFB flavonoid extract by oral gavage for 10 days and were injected with 3% PO 0.5 h before drug administration to establish hyperuricemia on day 10. The SFB flavonoid extract was found to lower the plasma level of UA in PO‐induced hyperuricemic mice, indicating the potential of SFB flavonoid extract to be an antihyperuricemia agent (Chen et al, 2022). However, the mechanism of SFB flavonoid extract on antihyperuricemia is unclear and further work needs to be studied.…”

Bioactive Components and Biological Activities of Crocus sativus L. Byproducts: A Comprehensive Review

“…64 Flavonoid extract from the bioresidues of saffron flowers can reduce the levels of uric acid and creatinine in plasma and also inhibit hepatic xanthine oxidase activity and regulate lipid levels in potassium oxonate-induced hyperuricemic mice. 65 The antidiabetic effects of flavonoids such as quercetin and kaempferol may include: (1) increasing the levels of endogenous antioxidants by upregulating the Nrf2 pathway, thus helping the heart to counteract the effects of oxidative stress induced by hyperglycemia, (2) inhibiting cardiac inflammation by the downregulation of NF-κB signaling pathway, (3) reducing glucose absorption by glucose transporter type 4, and (4) activating the AMPK signaling pathway to increase glucose uptake. 66,67 For example, the plasma level of glucose was decreased when animals were administrated with quercetin.…”

Ultra‐performance liquid chromatography‐quadrupole time‐of‐flight mass spectrometry‐based metabolomics to clarify the mechanism of color change of saffron floral bio‐residues

“…Saffron (the dried stigma of Crocus sativus L.) is a well‐known spice and traditional medicine widely used in the world. Saffron spice is very expensive since its isolation remains an extremely labor‐intensive process (7.4% w/w of the flower) (Serrano‐Diaz et al., 2014), and this is why it is known as the “gold of the plant kingdom.” The utilization of the rest 92.6% of the flower, that is, saffron floral bio‐residues (SFB) has hence attracted people's attention due to its economical and biological potential (Hosseini et al., 2018), such as antioxidant activities (Ahmadian‐Kouchaksaraie et al., 2016), anti‐inflammation (Chen et al., 2017), liver protection (Hosseini et al., 2018), anti‐hyperuricemic effect (Chen et al., 2022), etc. Recently, the search for a natural source of antioxidants and/or colorants to replace synthetic antioxidants and/or dyes has become important because it can provide health benefits through food products, for example, fortified food made from anthocyanin extract is currently attracting wide interest (Granados‐Balbuena et al., 2022; Zhang et al., 2020).…”