Xanthones from <i>Securidaca inappendiculata</i> antagonized the antirheumatic effects of methotrexate <i>in vivo</i> by promoting its secretion into urine.

Wang, Dandan; Li, Yan; Wu, Youliang; Wu, Yilai; Han, Jun Hyun; Olatunji, Opeyemi Joshua; Wang, Li; Zuo, Jian

doi:10.1080/17425255.2021.1843634

Cited by 12 publications

(4 citation statements)

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“…Securidaca inappendiculata Hassk (SI) is a plant native to tropical America and it is widely grown in the tropical regions of China, especially Guangdong, Guangxi, Hainan and Yunnan provinces. SI is extensively used in Chinese folk medicine for treating inflammatory related diseases particularly rheumatic arthritis ( Wang et al, 2021 ). In addition to its anti-inflammatory effects, SI has been reported to possess other pharmacological effects including antidiabetic, antioxidant, anticancer, hepatoprotective and cytotoxic effects ( Zha et al, 2015 ; Ji et al, 2019 ; Olatunji et al, 2021 ).…”

Section: Introductionmentioning

confidence: 99%

Securidaca inappendiculata Polyphenol Rich Extract Counteracts Cognitive Deficits, Neuropathy, Neuroinflammation and Oxidative Stress in Diabetic Encephalopathic Rats via p38 MAPK/Nrf2/HO-1 Pathways

2021

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Diabetic encephalopathy is one of the serious emerging complication of diabetes. Securidaca inappendiculata is an important medicinal plant with excellent antioxidant and anti-inflammatory properties. This study investigated the neuroprotective effects of S. inappendiculata polyphenol rich extract (SiPE) against diabetic encephalopathy in rats and elucidated the potential mechanisms of action. Type 2 diabetes mellitus (T2DM) was induced using high fructose solution/intraperitoneal injection of streptozotocin and the diabetic rats were treated with SiPE (50, 100 and 200 mg/kg) for 8 weeks. Learning and memory functions were assessed using the Morris water and Y maze tests, depressive behaviour was evaluated using forced swimming and open field tests, while neuropathic pain assessment was assessed using hot plate, tail immersion and formalin tests. After the experiments, acetylcholinesterase (AChE), oxidative stress biomarkers and proinflammatory cytokines, caspase-3 and nuclear factor kappa-light-chain-enhancer of activated B (NF-κB) were determined by ELISA kits. In addition, the expression levels of p38, phospho-p38 (p-p38), nuclear factor erythroid 2–related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) were determined by western blot analyses. The results indicated that SiPE administration significantly lowered blood glucose level, attenuated body weight loss, thermal/chemical hyperalgesia, improved behavioural deficit in the Morris water maze, Y maze test and reduced depressive-like behaviours. Furthermore, SiPE reduced AChE, caspase-3, NF-κB, malonaldehyde malondialdehyde levels and simultaneously increased antioxidant enzymes activity in the brain tissues of diabetic rats. SiPE administration also significantly suppressed p38 MAPK pathway and upregulated the Nrf2 pathway. The findings suggested that SiPE exerted antidiabetic encephalopathy effects via modulation of oxidative stress and inflammation.

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Section: Introductionmentioning

confidence: 99%

Securidaca inappendiculata Polyphenol Rich Extract Counteracts Cognitive Deficits, Neuropathy, Neuroinflammation and Oxidative Stress in Diabetic Encephalopathic Rats via p38 MAPK/Nrf2/HO-1 Pathways

2021

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“… 12 Besides, these observations suggested the different therapeutic mechanisms of MTX and XRF on RA/CIA, a hypothesis supported by our recent study. 13 MTX suppresses several classic pro-inflammatory pathways in immune cells by activating adenosine receptors. 14 Therefore, XRF could induce MMP3 decrease in CIA rats through a mechanism that is largely independent from JNK and NF-κB pathways.…”

Section: Resultsmentioning

confidence: 99%

Securidaca inappendiculata-Derived Xanthones Protected Joints from Degradation in Male Rats with Collagen-Induced Arthritis by Regulating PPAR-γ Signaling

Zuo¹,

Tao²,

Wu³

et al. 2021

JIR

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Background The bark of Securidaca inappendiculata Hassk. is traditionally used for treating inflammatory diseases and bone fractures in China. We have previously validated the xanthone-enriched fraction (XRF) of S. inappendiculata with anti-rheumatic potentials, but mechanism underlying the joints protective effects is still largely unknown. Materials and Methods The male rats with collagen-induced arthritis (CIA) were treated with XRF. The therapeutic efficacy of XRF was evaluated by arthritis score changes, morphological observation of paws, histological examinations and serological analyses. Protein expression in tissues and cells was investigated by either immunohistochemical or immunoblotting methods, while levels of mRNA expression were investigated by RT-qPCR. Metabolites in serum were detected by LC-MS approach. The joints homogenates were used for analyzing possible targeted genes by genome microarray analyses. Results Treatment with XRF and methotrexate (MTX) led to significant decrease in arthritis scores, and alleviated deformation of paws in CIA rats. In addition, XRF and MTX reduced circulating TNF-α, IL-1β and IL-17α in the serum and down-regulated TLR4/NF-κB and JNK pathways in joints of CIA rats. Compared to MTX, XRF-loading microemulsion significantly protected joints, which was accompanied by dramatic decrease in MMP3. Differential genes-based KEGG enrichment and metabolomics analysis suggested that XRF reduced fatty acids biosynthesis by regulating PPAR-γ signaling. S inappendiculata -derived 1,7-dihydroxy-3,4-dimethoxyxanthone (XAN) up-regulated PPAR-γ expression in macrophages, but suppressed it in pre-adipocytes in vitro, which was synchronized with SIRT1 changes. Adiponectin production and SCD-1 expression in pre-adipocytes were also decreased. Aside the direct inhibition on MMP3 expression in synovioblast, the presence of XAN in macrophages-pre-adipocytes co-culture system further reinforced this effect. Conclusion This study revealed the joint protective advantages of the bioactive fraction from S. inappendiculata in CIA rats over MTX, and demonstrated that S. inappendiculata -derived xanthones suppressed the erosive nature of synovioblast acquired under inflammatory circumstances by regulating PPAR-γ signaling-controlled metabolism-immunity feedback.

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“…As a therapeutic target, tyrosinase is one important metal enzyme containing two copper, which widely presents in the organism (Min et al, 2023;Fan et al, 2017). Tyrosinase has been confirmed to be involved in the synthesis of melanin (Li et al, 2023;Hassan et al, 2023;Li J. et al, 2021). The first reaction process is monophenolase activity, in which L-tyrosine is hydroxylated into L-dopa and the second reaction process is diphenolase activity, in which L-dopa is subsequently oxidized into dopaquinone (Djafarou et al, 2023;Lee et al, 2023;Zargaham et al, 2023).…”

Section: Introductionmentioning

confidence: 99%

“…Inhibition of tyrosinase activity would reduce melanin generation, thence, the finding on novel tyrosinase inhibitors is attracting more attention due to their potential application in medicine and cosmetics fields ( Wang and Mu, 2021 ). Although kojic acid and arbutin ( Figure 1 ) are applied as tyrosinase inhibitors in the medical and industrial fields, they still have been found to lots of adverse side effects ( Wang et al, 2021 ; Esma et al, 2023 ). Now, to find novel tyrosinase inhibitors is essential for treatment of melanin synthesis ( Romagnoli et al, 2022 ; Nasab et al, 2023 ).…”

Section: Introductionmentioning

confidence: 99%

Inhibition mechanism investigation of quercetagetin as a potential tyrosinase inhibitor

Liang

2024

Front. Chem.

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Tyrosinase is one important rate limiting enzyme in melanin synthesis, directly affecting the melanin synthesis. Quercetagetin is one active ingredient from marigold. Thence, the inhibition effects of quercetagetin against tyrosinase were investigated. The results showed quercetagetin could inhibit tyrosinase activity with IC50 value of 0.19 ± 0.01 mM and the inhibition type was a reversible mixed-type. Results of fluorescence quenching showed quercetagetin could quench tyrosinase fluorescence in static process. CD and 3D fluorescence results showed the interaction of quercetagetin to tyrosinase could change tyrosinase conformation to inhibit activity. Moreover, docking revealed details of quercetagetin’s interactions with tyrosinase.

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Xanthones from Securidaca inappendiculata antagonized the antirheumatic effects of methotrexate in vivo by promoting its secretion into urine.

Cited by 12 publications

References 27 publications

Securidaca inappendiculata Polyphenol Rich Extract Counteracts Cognitive Deficits, Neuropathy, Neuroinflammation and Oxidative Stress in Diabetic Encephalopathic Rats via p38 MAPK/Nrf2/HO-1 Pathways

Securidaca inappendiculata Polyphenol Rich Extract Counteracts Cognitive Deficits, Neuropathy, Neuroinflammation and Oxidative Stress in Diabetic Encephalopathic Rats via p38 MAPK/Nrf2/HO-1 Pathways

Securidaca inappendiculata-Derived Xanthones Protected Joints from Degradation in Male Rats with Collagen-Induced Arthritis by Regulating PPAR-γ Signaling

Inhibition mechanism investigation of quercetagetin as a potential tyrosinase inhibitor

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