A promising drug combination of mangiferin and glycyrrhizic acid ameliorates disease severity of rheumatoid arthritis by reversing the disturbance of thermogenesis and energy metabolism

Mao, Xia; Liu, Yudong; Li, Weijie; Wang, Kexin; Li, Congchong; Wang, Qian; Chen, Wenjia; Ma, Zhaochen; Wang, Xiaoyue; Ding, Zihe; Zhang, Yanqiong; Lin, Na

doi:10.1016/j.phymed.2022.154216

Cited by 11 publications

(8 citation statements)

References 34 publications

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“…The Lpl–Ucp1–PPARGC1A signaling axis was identified as the candidate pathway involved in maintaining the balance of thermogenesis and energy metabolism. Higher expressions of the Lpl–Ucp1–PPARGC1 signaling axis were confirmed by higher levels of the cAMP, ChREBP-1, and AMPK signaling proteins involved in the mitochondrial biogenesis pathway [ 41 ].…”

Section: Discussionmentioning

confidence: 99%

Luteolin-7-O-rutinoside Protects RIN-5F Cells from High-Glucose-Induced Toxicity, Improves Glucose Homeostasis in L6 Myotubes, and Prevents Onset of Type 2 Diabetes

et al. 2023

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Luteolin-7-O-rutinoside (lut-7-O-rutin), a flavonoid commonly present in Mentha longifolia L. and Olea europaea L. leaves has been used as a flavoring agent with some biological activity. The present study is the first attempt to analyze the protective effect of lut-7-O-rutin on high-glucose-induced toxicity to RIN-5F cells in vitro. We found that lut-7-O-rutin improved insulin secretion in both normal and high-glucose conditions in a dose-dependent manner, without toxicity observed. In addition, 20 µmol of lut-7-O-rutin improves insulin sensitization and glucose uptake significantly (p ≤ 0.01) in L6 myotubes cultured in a high-glucose medium. Lut-7-O-rutin has shown a significant (p ≤ 0.05) effect on glucose uptake in L6 myotubes compared to the reference drug, rosiglitazone (20 µmol). Gene expression analysis confirmed significantly lowered CYP1A, TNF-α, and NF-κb expressions in RIN-5F cells, and increased mitochondrial thermogenesis-related LPL, Ucp-1 and PPARγC1A mRNA expressions in L6 myotubes after 24 h of lut-7-O-rutin treatment. The levels of signaling proteins associated with intracellular glucose uptakes, such as cAMP, ChREBP-1, and AMPK, were significantly increased in L6 myotubes. In addition, the levels of the conversion rate of glucose to lactate and fatty acids were raised in insulin-stimulated conditions; the rate of glycerol conversion was found to be higher at the basal level in L6 myotubes. In conclusion, lut-7-O-rutin protects RIN-5F cells from high-glucose-induced toxicity, stimulates insulin secretion, and promotes glucose absorption and homeostasis via molecular mechanisms.

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Section: Discussionmentioning

confidence: 99%

Luteolin-7-O-rutinoside Protects RIN-5F Cells from High-Glucose-Induced Toxicity, Improves Glucose Homeostasis in L6 Myotubes, and Prevents Onset of Type 2 Diabetes

et al. 2023

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“…Based on ETCM 2.0 database ( http://www.tcmip.cn/ETCM2/front/ #/) [ 13 ], we obtained the chemical composition of BHGZD and predicted the candidate target profile referring to our previous studies [ 11 ]. The interaction information between genes in the String database (version 10.0, http://string-db.org/ ) [ 14 ] was used to extract the interactions between BHGZD effective genes from both transcriptomic data and TCMIP v2.0 platform, and AIA-M-related genes from transcriptomic data, and then to construct the ‘‘ disease gene-drug target ’’ interactions network.…”

Section: Methodsmentioning

confidence: 99%

“…A total of 25 Lewis rats were randomly divided into five groups on average: (1) normal control group; (2) adjuvant induced arthritis (AIA) -wind-hot-dampness stimulation modified model group (AIA-M); (3) AIA-M-BHGZD treatment group (21.4 g/kg, 2 times of the RA patients clinical dosage, which had been proved to exert the most prominent therapeutic effects against RA among 0.5, 1 and 2 times the daily RA patient dosage in our previous studies) [ 10 , 11 , 21 ]; (4) AIA-M-BACs treatment group (MG, 0.6 mg/kg; GA, 1.185 mg/kg, comparable to the corresponding content in 21.4 g/kg BHGZD); (5) AIA-MTX treatment group (0.2 mg/kg).…”

Section: Methodsmentioning

confidence: 99%

“…In terms of HUVEC cells, cells were first inoculated in 10 cm culture medium, and after 24 h of drug treatment, VEGF at a final concentration of 20 ng/mL was added for 5 min for induction in all groups except the normal group, where an equal volume of medium was added. Western blot analysis was performed according to previous studies [ 11 ]. Detailed information of antibodies was provided in Additional file 1 : Table S1 Detailed information of antibodies to CD31, VEGFA, VEGFR2, SRC, PI3K, AKT1, p-VEGFR2, p-SRC, p-PI3K, p-AKT and GAPDH proteins.…”

Section: Methodsmentioning

confidence: 99%

“…Our previous studies reported that BHGZD may relieve RA through exerting its immunomodulatory and anti-inflammatory activities [ 10 ] and reversing energy metabolism disturbance during the disease progression [ 11 ]. Angiogenesis has been indicated to be a pivotal driver for RA, and the imbalance of pro-/anti-angiogenic factors may lead to excessive synovial vascularization, subsequently promoting inflammatory cell infiltration into the joints and exacerbating cartilage and bone destruction.…”

Section: Introductionmentioning

confidence: 99%

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Extensive preclinical evaluation of combined mangiferin and glycyrrhizic acid for restricting synovial neovascularization in rheumatoid arthritis

Mao,

Yan,

et al. 2023

Chin Med

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Background Synovial neovascularization promotes rheumatoid arthritis (RA) progression. Baihu guizhi decoction (BHGZD) has a potential in restricting this pathological change of RA. Purpose To identify bioactive compounds (BACs) of BHGZD and to elucidate the underlying mechanisms in restricting synovial neovascularization of RA. Method Through transcriptomic profiling, the chemical profiling of BHGZD and its effective transcriptomic profiling against RA were identified. Then, candidate targets and the corresponding BACs against synovial neovascularization were screened by “disease gene-drug target” interaction network analysis and in silico molecular docking. The binding affinities of candidate BAC-target pairs were verified using surface plasmon resonance, and the pharmacokinetic characteristics of BACs in vivo after BHGZD administration at different time points were detected by Ultra Performance Liquid Chromatography-Mass spectrum/Mass spectrum. After that, in vivo experiments based on adjuvant-induced arthritis (AIA-M) rats, and in vitro experiments based on human umbilical vein endothelial cells (HUVEC) and arthritic synovial fibroblasts (MH7A) were carried out to evaluate the pharmacological effects of BHGZD and the two-BACs-combination, and to verify the associated mechanisms. Result VEGFA/VEGFR2/SRC/PI3K/AKT signal axis was screened as one of the key network targets of BHGZD against synovial neovascularization in RA. Mangiferin (MG) and glycyrrhizic acid (GA) were identified as the representative BACs of BHGZD for their strong binding affinities with components of the VEGFA/VEGFR2/SRC/PI3K/AKT signal axis, and their high exposed quantity in vivo. Both BHGZD and the two-BAC combination of MG and GA were demonstrated to be effective in restricting disease severity, reducing synovial inflammation and decreasing the formation of vascular opacities in AIA-M rats, and also reducing the migrative and invasive activities of HUVEC and MH7A cells and attenuating the lumen formation ability of HUVEC cells significantly. Mechanically, both BHGZD and the two-BAC combination markedly reduced the expression of VEGFA in synovial tissues, the serum levels of VEGF and NO, and the enzymatic activity of eNOS, increased the content of endostatin, and also reversed the abnormal alterations in the VEGFA/VEGFR2/SRC/PI3K/AKT signal axis in vivo and in vitro. Conclusion MG and GA may be the representative BACs of BHGZD for restricting excessive synovial vascularization in RA via regulating VEGFA/VEGFR2/SRC/PI3K/AKT signal axis.

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Mangiferin: A natural bioactive immunomodulating glucosylxanthone with potential against cancer and rheumatoid arthritis

Akkewar,

Mishra,

Sethi

2024

J Biochem & Molecular Tox

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Mangiferin is a naturally occurring glucosylxanthone that has shown promising immunomodulatory effects. It is generally isolated from the leaves, peels, bark, and kernels of Mangifera indica Linn. Mangiferin is like a miraculous natural bioactive molecule that has an immunomodulatory function that makes it a potential therapeutic candidate for the treatment of rheumatoid arthritis (RA) and cancer. The anticancer activity of mangiferin acts by blocking NF‐κB, as well as regulating the β‐catenin, EMT, MMP9, MMP2, LDH, ROS, and NO, and also by the activation of macrophages. It has no cytotoxic effect on grown chondrocytes and lowers matrix metalloproteinase levels. Additionally, it has a potent proapoptotic impact on synoviocytes. The precise molecular mechanism of action of mangiferin on RA and malignancies is still unknown. This comprehensive review elaborates on the immunomodulatory effect of mangiferin and its anticancer and anti‐RA activity. This also explained the total synthesis of mangiferin and its in vitro and in vivo screening models.

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A promising drug combination of mangiferin and glycyrrhizic acid ameliorates disease severity of rheumatoid arthritis by reversing the disturbance of thermogenesis and energy metabolism

Cited by 11 publications

References 34 publications

Luteolin-7-O-rutinoside Protects RIN-5F Cells from High-Glucose-Induced Toxicity, Improves Glucose Homeostasis in L6 Myotubes, and Prevents Onset of Type 2 Diabetes

Luteolin-7-O-rutinoside Protects RIN-5F Cells from High-Glucose-Induced Toxicity, Improves Glucose Homeostasis in L6 Myotubes, and Prevents Onset of Type 2 Diabetes

Extensive preclinical evaluation of combined mangiferin and glycyrrhizic acid for restricting synovial neovascularization in rheumatoid arthritis

Mangiferin: A natural bioactive immunomodulating glucosylxanthone with potential against cancer and rheumatoid arthritis

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