Background: Excessive production and/or reduced excretion of uric acid could lead to hyperuricemia, which could be a major cause of disability. Hyperuricemia has received increasing attention in the last few decades due to its global prevalence. Cichorium intybus L., commonly known as chicory, is a perennial herb of the asteraceae family. It was previously shown to exert potent hypouricemic effects linked with decreasing uric acid formation in the liver by down-regulating the activity of xanthine oxidase, and increasing uric acid excretion by up-regulating the renal OAT3 mRNA expression. The present study aimed to evaluate its extra-renal excretion and possible molecular mechanism underlying the transporter responsible for intestinal uric acid excretion in vivo. Methods: Chicory was administered intragastrically to hyperuricemic rats induced by drinking 10% fructose water. The uricosuric effect was evaluated by determining the serum uric acid level as well as the intestinal uric acid excretion by HPLC. The location and expression levels of ATP-binding cassette transporter, sub-family G, member 2 (ABCG2) in jejunum and ileum were analyzed. Results: The administration of chicory decreased the serum uric acid level significantly and increased the intestinal uric acid excretion obviously in hyperuricemic rats induced by 10% fructose drinking. Staining showed that ABCG2 was expressed in the apical membrane of the epithelium and glands of the jejunum and ileum in rats. Further examination showed that chicory enhanced the mRNA and protein expressions of ABCG2 markedly in a dose-dependent manner in jejunum and ileum. Conclusion: These findings indicate that chicory increases uric acid excretion by intestines, which may be related to the stimulation of intestinal uric acid excretion via up-regulating the mRNA and protein expressions of ABCG2.

Background: The production and maturation of interleukin (IL)-1β, regulated by the NF-κB and NLRP3 signaling pathways, lie at the core of gout. This study aimed to evaluate the antigout effect of Cichorium intybus L. (also known as chicory) in vivo and in vitro. Methods: A gout animal model was established with monosodium urate (MSU) crystal injections. Rats were orally administered with chicory extract or colchicine. Levels of ankle edema, inflammatory activity, and IL-1β release were observed. Several essential targets of the NF-κB and NLRP3 signaling pathways were detected. Primary macrophages were isolated to verify the antigout mechanism of chicory extract as well as chicoric acid in vitro. Results: Improvements of swelling degree, inflammatory activity, and histopathological lesion in MSU-injected ankles were observed in the treatment with chicory extract. Further, the chicory extract significantly decreased IL-1β release by suppressing the NF-κB and NLRP3 signaling pathways in gout rats. Similar to the in vivo results, IL-1β release was also inhibited by chicory extract and chicoric acid, a specific effective compound in chicory, through the NF-κB and NLRP3 signaling pathways. Conclusion: This study suggests that chicory extract and chicoric acid may be used as promising therapeutic agents against gout by inhibiting the NF-κB and NLRP3 signaling pathways.

Rheumatoid arthritis (RA) is an autoimmune disease characterized by bone and joint degeneration. Existing anti-inflammatory chemotherapy drugs offer temporary relief but come with undesirable side effects. Herbal medications have shown positive effects on RA symptoms with minimal adverse reactions. In this study, we investigated the potential of Nyctanthes arbor-tristis (NAT) through in vitro and in silico research. Hydroethanolic extracts of harsingar were prepared using the reflux method, containing alkaloids, phenol, saponin, steroids, proteins, tannins, terpenoids, carbohydrates, glycosides, and flavonoids, which exhibited TPC (98.56 ± 0.46 mg GAE/g) and TFC (34.51 ± 0.45 mg CE/g). LC–MS/MS analyzes the active compounds in the extract. NAT exhibited the best scavenging capabilities at 1 mg/mL in anti-oxidant and anti-arthritic activity. Maximum splenocyte proliferation occurred at 250 µg/mL. In vitro cell splenocyte studies revealed the downregulation of TNF-α and the upregulation of IL-10. Additionally, an in silico study demonstrated that bioactive constituents and targets bind with favorable binding affinity. These findings demonstrate the potential of Nyctanthes arbor-tristis in exerting anti-arthritic effects, as supported by in vitro and in silico studies. Further mechanistic research is necessary to validate the therapeutic potential of all phytoconstituents in RA treatment.

This study aimed to explore the spectrum-effect relationships between high-performance liquid chromatography fingerprints and the uric acid-lowering activities of chicory. Chemical fingerprints of chicory samples from ten different sources were determined by high-performance liquid chromatography, and then investigated by similarity analysis and hierarchical clustering analysis. Pharmacodynamics experiments were conducted in animals to obtain the uric acid-lowering activity information of each chicory sample. The spectrum-effect relationships between chemical fingerprints and the uric acid-lowering activities of chicory were established by canonical correlation analysis. The structures of potential effective peaks were identified by liquid chromatography with tandem mass spectrometry. The results showed that a close correlation existed between the spectrum and effect of chicory. Aesculin, chlorogenic acid, chicoric acid, isochlorogenic acid A/B/C and 13,14-seco-stigma5(6),14(15)-diene-3α-ol might be the main effective constituents. This work provides a general model of the combination of high-performance liquid chromatography and uric acid-lowering activities to study the spectrum-effect relationships of chicory, which can be used to discover the principle components responsible for the bioactivity.

Hyperuricemia (HUA) is a metabolic disorder characterized by abnormal purine metabolism and/or reduced uric acid (UA) excretion. Chicory (Cichorium intybus L.), recognized in Traditional Chinese Medicine, is noted for its anti-HUA effects, particularly in enhancing intestinal UA excretion, though the underlying mechanisms remain unclear. Studies indicate that disruptions in gut microbiota and its metabolites are associated with HUA, and chicory has been demonstrated to ameliorate gut microbiota dysbiosis. Among gut microbiota-derived metabolites, butyrate, a short-chain fatty acid, plays a crucial role in gut functions and is linked to HUA. Therefore, butyrate may be pivotal in elucidating the mechanism by which chicory promotes intestinal UA excretion. This study aims to investigate whether chicory facilitates intestinal UA excretion through gut microbiota-derived butyrate and to elucidate the underlying mechanism. We employed an integrated methodology combining network biology with the NHANES database analysis to explore the pathological relationship between butyrate and HUA. Our findings were subsequently validated through animal experiments. We administered chicory to rats with HUA to ascertain whether butyrate serves as the key gut microbiota metabolite through which chicory promotes intestinal UA excretion. Furthermore, we utilized western blotting to assess the expression of core targets within the PPARγ-ABCG2 pathway associated with butyrate under conditions where animals received butyrate supplements and PPARγ agonists separately. The network biology indicates that butyrate is a crucial short-chain fatty acid influencing HUA. Analyses of NHANES data and animal experiments further confirm a significant negative correlation between butyrate and serum uric acid (SUA) levels. HUA rats exhibited intestinal barrier damage, impaired intestinal UA excretion, reduced butyrate levels, and decreased expression of PPARγ and ABCG2 proteins. Intervention with chicory in HUA rats repaired intestinal barrier damage, enhanced intestinal UA excretion, and increased both butyrate levels and the expression of PPARγ and ABCG2 proteins. Similarly, interventions with butyrate supplements or PPARγ agonists in HUA rats effectively promoted intestinal UA excretion and increased the expression of PPARγ and ABCG2 proteins. This study demonstrates that butyrate is a key metabolite produced by gut microbiota, through which chicory regulates gut microbiota to enhance intestinal UA excretion. The underlying mechanism involves the activation of the PPARγ-ABCG2 pathway, which is facilitated by elevated butyrate levels in the intestine.

Background: Gout is a chronic inflammatory condition characterized by elevated uric acid levels in the blood, which can precipitate acute gout attacks in individuals with genetic susceptibility, existing medical conditions, and dietary influences. Genetic predispositions, comorbid medical conditions, nutritional choices, and environmental factors increasingly recognize the multifactorial etiology of the disease. Methods: Recent research has highlighted the potential of phytochemicals, particularly flavonoids, saponins, and alkaloids, to manage hyperuricemia (HUA) and its associated complications. Results: Plant’s natural compounds have garnered attention for their anti-inflammatory, antioxidant, and uric acid-lowering properties, suggesting their role in alternative and complementary medicine. Phytochemicals have demonstrated promise in mitigating gout symptoms and potentially modifying the disease course by addressing different aspects of hyperuricemia and inflammation. Herbal remedies, with their complex phytochemical profiles, offer a unique advantage by potentially complementing conventional pharmacological treatments. The integration of herbal therapies with standard medications could lead to enhanced therapeutic outcomes through synergistic effects, optimizing disease management, and improving patient quality of life. Conclusions: This review examines the current understanding of the multifaceted etiology of gout, explores the role of phytochemicals in managing hyperuricemia, and discusses the potential benefits of combining herbal remedies with conventional treatments to improve patient care and therapeutic efficacy.