Medicinal fungus Phellinus igniarius alleviates gout in vitro by modulating TLR4/NF-kB/NLRP3 signaling

Abstract

Background:Phellinus igniarius (P. igniarius) is a valuable medicinal and edible fungus with various biological activities such as anti-inflammation, antioxidation, and immune regulation. In this study, we explored the effects of P. igniarius on a gout model in vitro.Methods: The DPPH, ABTS, and FRAP methods were combined to determine and compare the antioxidant activities of wild P. igniarius total polyphenols (WPP) and cultivated P. igniarius total polyphenols (CPP) in vitro. Spectrophotometry was used to compare the inhibitory effect of WPP and CPP on xanthine oxidase (XO) activity to evaluate anti-hyperuricemia activity in vitro. HUVECs were stimulated with monosodium urate (MSU) crystals for 24 h to establish an acute gouty inflammation model in vitro. The protective effects were compared by measuring cell viability; the contents of ICAM-1, IL-1β, IL-6 and VCAM-1; the protein expressions of TLR4 and NLRP3; reactive oxygen species production; and the nuclear translocation of NF-κB p65. UHPLC-QE-MS technology was used to explore the potential metabolic mechanism of P. igniarius against gout.Results: WPP and CPP had strong antioxidant capacity, and the antioxidant capacity of CPP was similar to that of WPP. In a comparative experiment of xanthine oxidase activity inhibition by WPP and CPP, the IC50 values were 88.19 μg/ml and 108.0 μg/ml, respectively. At a dose of 40 μg/ml, WPP and CPP significantly improved the decrease in cell viability induced by monosodium urate (150 μg/ml) and inhibited the increase in inflammatory factors such as ICAM-1, IL-1β, IL-6, and VCAM-1. The increase in TLR4 and NLRP3 protein expression induced by MSU crystals in HUVECs was also significantly inhibited by total polyphenols from wild and cultivated P. igniarius. In addition, both significantly improved MSU-induced ROS overproduction and NF-κB p65 nuclear translocation. WPP and CPP may primarily be involved in phenylalanine metabolism and lysophosphatidylcholine metabolism in their role in the treatment of gout.Conclusion: CPP and WPP both showed good antioxidant activity and xanthine oxidase inhibitory activity and had good therapeutic effects on the gout model in vitro. Furthermore, this study indicated that cultivated P. igniarius had a protective effect similar to that of wild P. igniarius, which would be expected to improve the shortage of wild P. igniarius and promote the development of the cultivated P. igniarius industry and product development.

LC-MS-based metabolomics reveals the mechanism of anti-gouty arthritis effect of Wuwei Shexiang pill

“…Thus, an integrated strategy combining network pharmacology with other approaches is increasingly being used. For instance, network pharmacology methodology is combined with multi-omics studies such as proteomics ( Cheng et al, 2022 ; Sun et al, 2022 ), metabolomics ( Pan et al, 2020 ; Zhou et al, 2020b ; Li et al, 2021 ), transcriptomics ( Xiao et al, 2021 ; Zhou et al, 2022a ), and lipidomics ( Chen et al, 2022 ). Furthermore, gut microbiomics ( Goo et al, 2021 ; Yao et al, 2022 ) and meta-analysis ( Yi et al, 2020 ) were adopted for overall analysis combined with network pharmacology methodology.…”

“…Phenylalanine metabolism is one of the important metabolic pathways of amino acids, which has also been reported to be closely associated with hyperuricemia and gout ( Jiang et al, 2017 ; Zhou et al, 2022 ). Phenylpyruvate and 2-hydroxycinnamic acid are products of the phenylalanine metabolic pathway, and phenylpyruvate can further generate phenylacetaldehyde, which generates phenylacetal-CoA, which is involved in the biosynthesis of pantothenic acid and CoA via Acetyl-CoA ( Wu et al, 2018 ).…”

Immune-enhancing activity of polysaccharides and flavonoids derived from Phellinus igniarius YASH1

“…Phellinus igniarius (P. igniarius) (Sanghuang) is a traditional Chinese medicinal fungus which has been widely used in traditional Chinese medicine for more than 2,000 years, and the natural products from P. igniarius have great potential for clinical application ( Zhou et al, 2022 ).…”

Network Pharmacology-Based Approach to Explore the Total Flavonoids of Phellinus igniarius against Hyperuricemia via Regulating the Nrf2/HO-1-ROS-ER Signaling Pathway

“…Moreover, ethanol extracts of P. igniarius have been reported to have a good renal protective efect against oteracil potassium-induced injury and could also regulate the gut microbiota to reduce blood UA levels [15]. Research on polysaccharides, favonoids, polyphenols, and other active ingredients from P. igniarius [16] have been reported on antitumor [17,18], antiinfammatory [19], antioxidative [20], and enhancing immunity [21]. Based on the antioxidant potential of P. igniarius and previous research foundations, this article will continue to use the MSU-induced HK-2 cell injury model as the research object.…”