scholarly journals Effects of Stephania hainanensis alkaloids on MSU-induced acute gouty arthritis in mice

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Hao-fei Fan ◽  
Xing-yue Fang ◽  
Hao-lin Wu ◽  
Yi-qian Xu ◽  
Li-chong Gong ◽  
...  

Abstract Background Gout is initiated by the precipitation of monosodium urate (MSU) crystals within the joints and soft tissues, and it can eventually cause acute or chronic arthritis. MSU crystals trigger, amplify, and maintain a strong inflammatory response through promoting proinflammatory activity. In this study, the therapeutic effects of Stephania hainanensis (S. hainanensis) total alkaloid (SHA) were tested and evaluated on MSU-induced acute gouty arthritis in a mouse model. Methods After oral administration of SHA (10 or 20 mg/kg) or the antigout medicine colchicine (0.5 mg/kg) once daily for 3 consecutive days, MSU crystals suspended in saline (2.5 mg/50 μl) were intradermally injected into the right paw of the mice. Then, SHA and colchicine were administered for another 2 days. During this period, swelling of the ankle and clinical scores were measured at 12, 24, and 48 h postinjection. After the mice were euthanized, inflammatory cytokine expression and paw tissue inflammation-related gene and protein expression, and a histopathological analysis was performed. Results SHA had obvious therapeutic effects on MSU-induced acute gouty arthritis in mice. SHA alleviated ankle swelling and inhibited the production of cytokines, such as IL-1β and TNF-α. In addition, NLRP3, Caspase-1 and IL-1β, which are activated by MSU were also suppressed by SHA. The histological evaluation showed that SHA relieved the infiltration of inflammation around the ankle. Conclusions These results suggest that SHA is capable of anti-inflammatory activities and may be useful for treating gouty arthritis.

2020 ◽  
Vol 2020 ◽  
pp. 1-13
Author(s):  
Rongmei Yao ◽  
Zihan Geng ◽  
Xin Mao ◽  
Yanyan Bao ◽  
Shanshan Guo ◽  
...  

Gouty arthritis is an inflammatory joint disease closely related to hyperuricemia. It is characterized by deposition of monosodium urate crystals in the joints, resulting in an intense inflammatory process and pain. Control of hyperuricemia and anti-inflammation treatments are the main therapeutic approaches. However, the commonly used drugs for inhibiting uric acid and acute gouty arthritis have obvious gastrointestinal and renal toxicity; thus, there is an urgency to develop new alternative therapeutic drugs. An extract of Tu-Teng-Cao (TTC), a compound drug used in traditional Chinese medicine, has been widely applied to the clinical treatment of arthritis. In this study, we investigated the therapeutic effects of TTC on gouty arthritis. In this study, an animal model of acute gouty arthritis with hyperuricemia was established using potassium oxonate and monosodium urate crystals. After treatment with TTC, the results showed obvious therapeutic effects on the rat model of acute gouty arthritis. The treatment significantly attenuated the degree of ankle swelling, inflammation, and dysfunction index, and the levels of proinflammatory cytokines. In addition, TTC has significant antihyperuricemia activity in rats with hyperuricemia induced by potassium oxonate. Histological evaluation showed that TTC relieved pathological damage in rats with acute gouty arthritis induced by monosodium urate crystals. All the groups treated with TTC showed improvement in cartilage degeneration, cell degeneration, synovial hyperplasia, and inflammatory cell invasion in the ankle joint of rats. TTC significantly alleviated swelling, inflammation, and bleeding of the renal corpuscle and convoluted tubules of rats. The results of this study suggest that TTC is capable of treating gouty arthritis and decreasing ankle injury through the control of uric acid and inflammation.


2021 ◽  
Author(s):  
Lizhen Shan ◽  
Di Yang ◽  
Fabo Feng ◽  
Danjie Zhu ◽  
Xiaolin Li

Abstract MiR-3146 plays an important role in the formation of neutrophil extracellular traps (NETs) during the pathogenesis of acute gouty arthritis (AGA).The aim of our study was to explore the underlying role and molecular mechanism of miR-3146 in the formation of neutrophil extracellular traps (NETs) during the pathogenesis of acute gouty arthritis (AGA). The expression of miR-3146 and sirtuin 1 (SIRT1) was determined by real-time PCR and western blot. The luciferase reporter assay was performed to identify the targeting relationship between miR-3146 and SIRT1. Reactive oxygen species (ROS) production was detected by fluorescent staining. NETs formation was demonstrated via immunofluorescence staining and ELISA method. AGA model was induced in rats to verify the effects of miR-3146 inhibition on histopathological changes and NETs. Here, we found miR-3146 expression was dramatically increased in neutrophils of patients with AGA, presenting higher levels of NETs. Monosodium urate (MSU) crystals significantly increased miR-3146 expression and ROS production in neutrophils. The NETs process was also triggered by MSU crystals. Furthermore, we verified the interaction between miR-3146 and SIRT1. Additionally, antagomir-3146-based therapy effectively inhibited the formation of NETs in rats with AGA. MiR-3146-mediated NETs formation may play a potential role in the pathogenesis of AGA.


Inflammation ◽  
2018 ◽  
Vol 41 (5) ◽  
pp. 1955-1964 ◽  
Author(s):  
Xiao-Juan Dai ◽  
Jin-Hui Tao ◽  
Xuan Fang ◽  
Yuan Xia ◽  
Xiao-Mei Li ◽  
...  

Author(s):  
Josephina A. Vossen

Chapter 35 discusses gout, a metabolic disorder in which hyperuricemia leads to deposition of monosodium urate (MSU) crystals in soft tissues and joints. Gout is the most common crystalline type of arthropathy in the United States. Gout is considered to have 4 phases, characterized by asymptomatic hyperuricemia, recurrent attacks of acute arthritis, intercritical gout and chronic tophaceous gout. Radiography is generally used in the initial evaluation of gouty arthritis. Characteristic of gout are well-defined, punched-out erosions with overhanging edges, with late preservation of the joint space, lack of periarticular osteopenia, asymmetrical involvement, and soft tissue nodules that may calcify.


Author(s):  
Nicola Dalbeth

The aetiopathogenesis of gout is initiated by urate overproduction and uric acid under-excretion, leading to hyperuricaemia. Foods such as seafood, red meat, beer, and sugar-sweetened beverages contribute to overproduction. Under-excretion is mediated by renal and gut uric acid transporters such as SLC2A9, ABCG2, and URAT1. In hyperurcaemia, there is formation of monosodium urate (MSU) crystals in joints, with acute gouty arthritis mediated by the innate immune system occurring in response to these crystals. Factors such as urate concentration, proteins present in synovial fluid, temperature, and pH control crystal nucleation and growth. Activation of the inflammasome by MSU crystals and production of interleukin-1ß‎ is central to acute gouty arthritis. Advanced gout occurs when there is persistent gouty arthritis and tophus with the tophus being an organized immune tissue response to MSU crystals that involves both innate and adaptive immune cells. Progression through the gout checkpoints (hyperuricaemia, MSU crystal formation, and immune response) is governed by inherited genetic variants, lifetime environmental exposures, and their interaction.


2021 ◽  
Vol 49 ◽  
Author(s):  
Mariana Correia Oliveira ◽  
Marcelo Jorge Chipitelli de Carvalho ◽  
Jade Manhãs de Souza Basto ◽  
Isabella Jennifer Viana Soares ◽  
Gabriela De Carvalho Cid ◽  
...  

Background: Angiolipoma is a benign tumor composed of endothelial cells and mature adipocytes. Tumors reported in domestic species include two variants; infiltrative or non-infiltrative. Bitches and intact males seem predisposed. This mesenchyme tumor is commonly mistaken with lipoma due to its soft texture and subcutaneous site and often requires histopathology to confirm its diagnosis. Microscopic examination also enables the evaluation of surgical margins and rule out possible infiltrative sites. Complete surgical excision is usually curative. This study reports a case of non-infiltrating angiolipoma in a dog.Case: A 14-year-old mixed-breed dog was presented to a veterinary clinic in the city of Rio de Janeiro, RJ, Brazil. On palpation, a painless mass was noted, with high mobility and covered by intact hirsute skin in the right subcutaneous ventrolateral region. Computed tomography of the chest showed an expansive mass of uptake only from the edges of the soft tissues of the right subcutaneous ventrolateral region. The mass was homogeneous and well delimited, suggesting a neoplastic process. Subsequently, the mass was surgically removed, fixed in 10% buffered formalin, and sent for histopathological analysis. On macroscopic examination, the mass was well delimited, without skin coverage, and measured 2.3 × 1.9 × 0.6 cm. The consistency was smooth and unctuous in appearance with a compact cream-colored surface with blackish multifocal spots. Under microscopy, the histological sections showed neoplasm of mature adipocytes and of endothelial cells of blood vessels benign were filled with a marked amount of red blood cells. Multifocal fibrin thrombi and a mild inflammatory infiltrate composed of lymphocytes and rare mast cells were evident. There was no infiltration in the regional skeletal musculature. Thus, a diagnosis of non-infiltrative angiolipoma was established.Discussion: The diagnosis of non-infiltrating angiolipoma in this case was established through the results of histopathological examination. The occurrence of this neoplasm in dogs is uncommon, and the data reported in the veterinary medicine literature are scarce. However, in this study, it was found that the neoplasm on screening presented a behavior like that of lipomas, with noninvasive growth and the absence of local recurrence. The canine species does not commonly convey pain on palpation during a clinical examination, as observed in the present case. In humans, multiple angiolipoma nodules are common; this clinical presentation differs from that in animals, in which solitary nodules are generally observed. In dogs, as in the present case, they seem to have a predilection for the trunk. In animals, the pathogenesis of angiolipomas is not established, but in humans, it is based on theories that include the reaction to harmful stimuli and congenital malformation of adipose tissue. In humans, the presence of fibrin thrombi on the periphery of the region of cell proliferation are microscopic findings that can assist in the diagnosis of angiolipomas, an approach that was implemented in the present case. The occurrence of this neoplasm in dogs is uncommon, and the data reported in the veterinary medicine literature are scarce. The importance of an adequate description of angiolipomas is based on the need to provide information about its epidemiology, biological behavior, and prognosis.


2021 ◽  
Vol 2021 ◽  
pp. 1-15
Author(s):  
Yihua Fan ◽  
Wei Liu ◽  
Yue Jin ◽  
Xu Hou ◽  
Xuewu Zhang ◽  
...  

Background. The incidence of gout has been rapidly increasing in recent years with the changing of diet. At present, modern medications used in the clinical treatment of gout showed several side effects, such as gastrointestinal damage and the increased risk of cardiovascular disease. The traditional Chinese prescription Simiao Powder (SMP) has a long history in the treatment of acute gouty arthritis (AGA) and has a good curative effect. However, the mechanism and target of its therapeutic effects are still not completely understood. Methods. Potential active compounds (PACs) and targets of SMP were found in the TCMSP database, and the disease target genes related to AGA were obtained by searching CTD, DisGeNET, DrugBank, GeneCards, TTD, OMIM, and PharmGKB disease databases with “acute gouty arthritis” and “Arthritis, Gouty” as keywords, respectively. The network of “Traditional Chinese medicine (TCM)-PACs-potential targets of acute gouty arthritis” was constructed with the Cytoscape 3.7.2 software, and the target genes of acute gouty arthritis were intersected with genes regulated by active compounds of SMP. The resultant common gene targets were input into Cytoscape 3.7.2 software, and the BisoGenet plug-in was used to construct a PPI network. The GO functional enrichment analysis and KEGG pathway enrichment analysis of the intersecting target proteins were performed using R software and corresponding program packages. The molecular docking verification was carried out between the potentially active compounds of SMP and the core target at the same time. Results. 40 active components and 203 targets were identified, of which 95 targets were common targets for the drugs and diseases. GO function enrichment analysis revealed that SMP regulated several biological processes, such as response to lipopolysaccharide and oxidative stress, RNA polymerase II transcription regulator complex, protein kinase complex, and other cellular and molecular processes, including DNA-binding transcription factor binding. Results of KEGG pathway analysis showed that SMP was associated with AGA-related pathways such as interleukin-17 (IL-17), tumor necrosis factor (TNF), p53, and hypoxia-inducible factor 1 (HIF-1) signaling pathways. The results of molecular docking showed that active compounds in SMP exhibited strong binding to five core protein receptors (TP53, FN1, ESR1, CDK2, and HSPA5). Conclusions. Active components of SMP, such as quercetin, kaempferol, wogonin, baicalein, beta-sitosterol, and rutaecarpine, showed therapeutic effects on AGA. These compounds were strongly associated with core target proteins (such as TP53, FN1, ESR1, CDK2, and HSPA5). This study reveals that IL-17, TNF, p53, and HIF-1 signaling pathways mediate the therapeutic effects of SMP on AGA. These findings expand our understanding of the mechanism of SMP in the treatment of AGA.


2022 ◽  
Vol 12 ◽  
Author(s):  
Hongxing Li ◽  
Xinyue Zhang ◽  
Lili Gu ◽  
Qín Li ◽  
Yue Ju ◽  
...  

Background:Phellinus igniarius (P. igniarius) is an important medicinal and edible fungus in China and other Southeast Asian countries and has diverse biological activities. This study was performed to comparatively investigate the therapeutic effects of wild and cultivated P. igniarius on hyperuricaemia and gouty arthritis in rat models.Methods: UPLC-ESI-qTOF-MS was used to identify the chemical constituents of polyphenols from wild P. igniarius (WPP) and cultivated P. igniarius (CPP). Furthermore, WPP and CPP were evaluated in an improved hyperuricaemia rat model induced by yeast extract, adenine and potassium oxonate, which was used to examine xanthine oxidase (XO) activity inhibition and anti-hyperuricemia activity. WPP and CPP therapies for acute gouty arthritis were also investigated in a monosodium urate (MSU)-induced ankle swelling model. UHPLC-QE-MS was used to explore the underlying metabolic mechanisms of P. igniarius in the treatment of gout.Results: The main active components of WPP and CPP included protocatechuic aldehyde, hispidin, davallialactone, phelligridimer A, hypholomine B and inoscavin A as identified by UPLC-ESI-qTOF-MS. Wild P. igniarius and cultivated P. igniarius showed similar activities in reducing uric acid levels through inhibiting XO activity and down-regulating the levels of UA, Cr and UN, and they had anti-inflammatory activities through down-regulating the secretions of ICAM-1, IL-1β and IL-6 in the hyperuricaemia rat model. The pathological progression of kidney damage was also reversed. The polyphenols from wild and cultivated P. igniarius also showed significant anti-inflammatory activity by suppressing the expression of ICAM-1, IL-1β and IL-6 and by reducing the ankle joint swelling degree in an MSU-induced acute gouty arthritis rat model. The results of metabolic pathway enrichment indicated that the anti-hyperuricemia effect of WPP was mainly related to the metabolic pathways of valine, leucine and isoleucine biosynthesis and histidine metabolism. Additionally, the anti-hyperuricemia effect of CPP was mainly related to nicotinate and nicotinamide metabolism and beta-alanine metabolism.Conclusions: Wild P. igniarius and cultivated P. igniarius both significantly affected the treatment of hyperuricaemia and acute gouty arthritis models in vivo and therefore may be used as potential active agents for the treatment of hyperuricaemia and acute gouty arthritis.


Foods ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1638
Author(s):  
Xiaohong Li ◽  
Yue Liu ◽  
Yaming Shan ◽  
Yukun Wang ◽  
Zhandong Li ◽  
...  

We investigated the functions of microRNAs in the therapeutic effects of noni (Morinda citrifolia L.) fruit juice on mouse models of acute gouty arthritis induced with monosodium urate (MSU). Compared with the model group (treated with MSU), mice in both the positive control group (treated with both MSU and colchicine) and noni fruit juice group (treated with MSU and noni fruit juice) showed a significantly decreased degree of paw swelling in 5 days, as well as the contents of two types of proinflammatory cytokines (i.e., NALP3 and TNF-α). Based on the next-generation sequencing technology, a total of 3896 microRNAs (234 known and 3662 novel) were identified in mice treated with noni fruit juice. A large amount of differentially expressed miRNAs were identified in the noni fruit juice group, suggesting the significant effects of noni fruit juice on the mice with acute gouty arthritis, while the different patterns of change in the numbers of both upregulated and downregulated miRNAs in both noni fruit juice and positive control groups indicated that the mice of acute gouty arthritis may be regulated by differential mechanisms between the treatments of noni fruit juice and colchicine. The target genes of microRNAs involved in the pathogenesis and pathology of acute gouty arthritis in mice were identified and further annotated by both Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. Our results revealed the therapeutic effects of noni fruit juice on acute gouty arthritis in mice with a group of microRNAs involved in the pharmacological mechanisms of noni fruit juice, providing scientific evidence to support both the agricultural cultivation and pharmacological significance of noni plants.


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