scholarly journals Bergenin Reduces Experimental Painful Diabetic Neuropathy by Restoring Redox and Immune Homeostasis in the Nervous System

2020 ◽  
Vol 21 (14) ◽  
pp. 4850 ◽  
Author(s):  
Cristiane F. Villarreal ◽  
Dourivaldo S. Santos ◽  
Pedro S. S. Lauria ◽  
Kelly B. Gama ◽  
Renan F. Espírito-Santo ◽  
...  

Diabetic neuropathy is a frequent complication of diabetes. Symptoms include neuropathic pain and sensory alterations—no effective treatments are currently available. This work characterized the therapeutic effect of bergenin in a mouse (C57/BL6) model of streptozotocin-induced painful diabetic neuropathy. Nociceptive thresholds were assessed by the von Frey test. Cytokines, antioxidant genes, and oxidative stress markers were measured in nervous tissues by ELISA, RT-qPCR, and biochemical analyses. Single (3.125–25 mg/kg) or multiple (25 mg/kg; twice a day for 14 days) treatments with bergenin reduced the behavioral signs of diabetic neuropathy in mice. Bergenin reduced both nitric oxide (NO) production in vitro and malondialdehyde (MDA)/nitrite amounts in vivo. These antioxidant properties can be attributed to the modulation of gene expression by the downregulation of inducible nitric oxide synthase (iNOS) and upregulation of glutathione peroxidase and Nrf2 in the nervous system. Bergenin also modulated the pro- and anti-inflammatory cytokines production in neuropathic mice. The long-lasting antinociceptive effect induced by bergenin in neuropathic mice, was associated with a shift of the cytokine balance toward anti-inflammatory predominance and upregulation of antioxidant pathways, favoring the reestablishment of redox and immune homeostasis in the nervous system. These results point to the therapeutic potential of bergenin in the treatment of painful diabetic neuropathy.

2021 ◽  
Vol 22 (7) ◽  
pp. 3671
Author(s):  
Magdalena Ulanowska ◽  
Beata Olas

Eugenol is a phenolic aromatic compound obtained mainly from clove oil. Due to its known antibacterial, antiviral, antifungal, anticancer, anti-inflammatory and antioxidant properties, it has long been used in various areas, such as cosmetology, medicine, and pharmacology. However, high concentrations can be toxic. A dose of 2.5 mg/kg body weight is regarded as safe. This paper reviews the current state of knowledge regarding the activities and application of eugenol and its derivatives and recent research of these compounds. This review is based on information concerning eugenol characteristics and recent research from articles in PubMed. Eugenol remains of great interest to researchers, since its multidirectional action allows it to be a potential component of drugs and other products with therapeutic potential against a range of diseases.


Biomedicines ◽  
2021 ◽  
Vol 9 (6) ◽  
pp. 615
Author(s):  
Shang-En Huang ◽  
Erna Sulistyowati ◽  
Yu-Ying Chao ◽  
Bin-Nan Wu ◽  
Zen-Kong Dai ◽  
...  

Osteoarthritis is a degenerative arthropathy that is mainly characterized by dysregulation of inflammatory responses. KMUP-1, a derived chemical synthetic of xanthine, has been shown to have anti-inflammatory and antioxidant properties. Here, we aimed to investigate the in vitro anti-inflammatory and in vivo anti-osteoarthritis effects of KMUP-1. Protein and gene expressions of inflammation markers were determined by ELISA, Western blotting and microarray, respectively. RAW264.7 mouse macrophages were cultured and pretreated with KMUP-1 (1, 5, 10 μM). The productions of TNF-α, IL-6, MMP-2 and MMP- 9 were reduced by KMUP-1 pretreatment in LPS-induced inflammation of RAW264.7 cells. The expressions of iNOS, TNF-α, COX-2, MMP-2 and MMP-9 were also inhibited by KMUP-1 pretreatment. The gene expression levels of TNF and COX families were also downregulated. In addition, KMUP-1 suppressed the activations of ERK, JNK and p38 as well as phosphorylation of IκBα/NF-κB signaling pathways. Furthermore, SIRT1 inhibitor attenuated the inhibitory effect of KMUP-1 in LPS-induced NF-κB activation. In vivo study showed that KMUP-1 reduced mechanical hyperalgesia in monoiodoacetic acid (MIA)-induced rats OA. Additionally, KMUP-1 pretreatment reduced the serum levels of TNF-α and IL-6 in MIA-injected rats. Moreover, macroscopic and histological observation showed that KMUP-1 reduced articular cartilage erosion in rats. Our results demonstrated that KMUP-1 inhibited the inflammatory responses and restored SIRT1 in vitro, alleviated joint-related pain and cartilage destruction in vivo. Taken together, KMUP-1 has the potential to improve MIA-induced articular cartilage degradation by inhibiting the levels and expression of inflammatory mediators suggesting that KMUP-1 might be a potential therapeutic agent for OA.


Molecules ◽  
2020 ◽  
Vol 25 (10) ◽  
pp. 2351 ◽  
Author(s):  
Daniel Cervantes-García ◽  
Armida I. Bahena-Delgado ◽  
Mariela Jiménez ◽  
Laura E. Córdova-Dávalos ◽  
Vanessa Ruiz-Esparza Palacios ◽  
...  

Nonsteroidal anti-inflammatory drug (NSAID)-induced enteropathy is considered a serious and increasing clinical problem without available treatment. Glycomacropeptide (GMP) is a 64-amino acid peptide derived from milk κ-casein with numerous biological activities. The aim of this study was to investigate the protective effect of GMP on NSAID enteropathy in rats. Enteropathy was induced by seven days oral indomethacin administration. Rats were orally GMP treated from seven days previous and during the establishment of the enteropathy model. Changes in metabolism, hematological and biochemical blood alterations, intestinal inflammation and oxidative damage were analyzed. Integrity barrier markers, macroscopic intestinal damage and survival rate were also evaluated. GMP treatment prevented anorexia and weight loss in animals. Furthermore, prophylaxis with GMP ameliorated the decline in hemoglobin, hematocrit, albumin and total protein levels. The treatment had no therapeutic efficacy on the decrease of occludin and mucin (MUC)-2 expression in intestinal tissue. However, GMP markedly decreased neutrophil infiltration, and CXCL1, interleukin-1β and inducible nitric oxide synthase expression. Nitric oxide production and lipid hydroperoxide level in the small intestine were also diminished. These beneficial effects were mirrored by preventing ulcer development and increasing animal survival. These results suggest that GMP may protect against NSAID enteropathy through anti-inflammatory and antioxidant properties.


2021 ◽  
Vol 11 (10) ◽  
pp. 4711
Author(s):  
Woo Jin Lee ◽  
Wan Yi Li ◽  
Sang Woo Lee ◽  
Sung Keun Jung

Until now, the physiological effects of Soroseris hirsuta were primarily unknown. Here we have evaluated the anti-inflammatory and antioxidant effects of Soroseris hirsuta extract (SHE) on lipopolysaccharide (LPS)-activated murine macrophages RAW 264.7 cells. SHE inhibited nitric oxide expression and inducible nitric oxide synthase expression in RAW 264.7 cells treated with LPS. Moreover, SHE suppressed LPS-induced phosphorylation of IκB kinase, inhibitor of kappa B, p65, p38, and c-JUN N-terminal kinase. Western blot and immunofluorescence analyses showed that SHE suppressed p65 nuclear translocation induced by LPS. Furthermore, SHE inhibited the reactive oxygen species in LPS-treated RAW 264.7 cells. SHE significantly increased heme oxygenase-1 expression and the nuclear translocation of nuclear factor erythroid 2-related factor 2. SHE suppressed LPS-induced interleukin-1β mRNA expression in RAW 264.7 cells. Thus, SHE is a promising nutraceutical as it displays anti-inflammatory and antioxidant properties.


2018 ◽  
Vol 19 (12) ◽  
pp. 3746 ◽  
Author(s):  
Ye Jeong ◽  
Mi-Young Lee

Populus deltoides, known as eastern cottonwood, has been commonly used as a medicinal plant. The aim of the present study was to investigate the mechanism underlying the anti-inflammatory activity of P. deltoides leaf extract (PLE). PLE effectively inhibited the expression of inducible nitric oxide synthase (iNOS) and nitric oxide (NO) production in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells, but not that of cyclooxygenase-2 (COX-2) and prostaglandin E2. Proinflammatory tumor necrosis factor alpha (TNF-α) levels were also reduced by the extract. PLE inhibited the phosphorylation of nuclear factor-kappa B (NF-κB) and inhibitor of Kappa Bα (IκBα), and blunted LPS-triggered enhanced nuclear translocation of NF-κB p65. In mitogen-activated protein kinase (MAPK) signaling, PLE effectively decreased the phosphorylation of p38 and c-Jun N-terminal protein kinase (JNK), but not of extracellular signal-regulated kinase 1/2 (ERK1/2). Taken together, these results suggest that anti-inflammatory activity of P. deltoides leaf extract might be driven by iNOS and NO inhibition mediated by modulation of the NF-κB and p38/JNK signaling pathways.


2020 ◽  
Vol 10 (6-s) ◽  
pp. 103-108
Author(s):  
Komlatsè Togbenou ◽  
Kokou Idoh ◽  
Kossivi Dosseh ◽  
Tchazou Kpatcha ◽  
Amégnona Agbonon

Introduction: Annona senegalensis Pers (Annonaceae) and Piliostigma thonningii (Schum.) (Leguminoseae)  are two medicinal plants used, often in combination, in traditional Togolese medicine for the treatment of diseases with an inflammatory component. Objective: The aim of this study is to evaluate the anti-inflammatory effect of the hydro-ethanolic extract (EHEM) of the combination of A. senegalensis and P. thonningii (1: 1, m: m). Methods: The ovalbumin-induced allergic airway asthma model was used. Animals made asthmatic were treated with EHEM at doses of 250 and 500 mg / kg. Inflammation markers including histamine, nitric oxide (NO), vascular leakage, leukocyte infiltration in the airways, and malondialdehyde (MDA), were measured. Results: Compared to the SNT group, EHEM inhibits the infiltration of the airways by leukocytes (850,00 × 103 ± 50 cells / mL vs 1830 × 103 ± 53,85 cells / mL for ST500 mg / kg, P <0,05). It inhibited vascular permeability to Evans Blue (10,40 ± 0,270 μg / mL vs ST500, p<0,05). It inhibited histamine release (13,95 ± 0,937 μg / mL vs 32,78 ± 1,044 μg / mL, p<0,05) and NO production (0,211 ± 0,008 Μm vs 0,315 ± 0,022 μM, p<0,05). It finally inhibited MDA production (14,66 ± 0,533 nM / mL vs 9,014 ± 0,366 nM / mL and 7,149 ± 0,300 nM / mL, p<0,05) in lung tissue. Conclusion: Our results suggest that EHEM inhibits OVA-induced inflammation. These results justify the use of this combination of plants in traditional Togolese medicine. Keywords: Inflammation, malondialdehyde, Annona senegalensis, Piliostigma thonningii.


Author(s):  
Fatima Khan ◽  
Mohd Nayab ◽  
Abdul Nasir Ansari

Ginger has been appreciated for over 2500-3000 years in many parts of the world due to its numerous scientific properties. The ginger plant (Zingiber officinale Roscoe) belongs to the Zingiberaceae family. It is a known food and flavoring ingredient reputed for its wide range of medicinal properties that have been widely used in Chinese, Ayurvedic, and Unāni Tibb worldwide, since antiquity. Ginger has long been used to cure a variety of ailments, including diarrhea, stomach discomfort, indigestion, and nausea. It is a versatile herb with phenomenal phytotherapeutic and medicinal properties. Active ingredients available in ginger such as 6-gingerol, 6-shogaol, 6-paradol, and zingerone are responsible for upgrading enzyme actions and balancing circulation through rejuvenating the body with physical re-strengthening. Gingerols, the key phenolic plant secondary metabolites responsible for its distinct flavor and health benefits, are found in the rhizome of ginger Extensive study has been undertaken over the last two decades to uncover bioactive ingredients and the therapeutic potential of ginger. This review considers ginger's chemical composition and the most recent study findings on its possible health advantages, such as analgesic, anti-inflammatory, antibacterial, and antioxidant properties due to its phytochemistry. Overall, clinical trials are needed to confirm these prospective various health advantages of ginger in human subjects and the most efficacious dosage, based on the current body of scientific literature.


2014 ◽  
Vol 2014 ◽  
pp. 1-10 ◽  
Author(s):  
Yung-Hsiang Chen ◽  
Yu-Ning Lin ◽  
Wen-Chi Chen ◽  
Wen-Tsong Hsieh ◽  
Huey-Yi Chen

Stress urinary incontinence (SUI) is a common disorder in middle-aged women and the elderly population. Although surgical treatment of SUI has progressed, pharmacological therapies remain unelucidated. We screened potential herbal medicines against SUI with anex vivoorgan bath assay.Ramulus Cinnamomiand its major constituent cinnamaldehyde cause a high contractile force of the urethra and a low contractile force of blood vessels. Cinnamaldehyde dose-dependently reduced lipopolysaccharide-induced nitric oxide (NO) production and inducible nitric oxide synthase (iNOS) expression in RAW 264.7 cells. In the vaginal distension- (VD-) induced SUI model in mice, cinnamaldehyde significantly reversed the VD-induced SUI physical signs and reduced blood pressure. Cinnamaldehyde may offer therapeutic potential against SUI without the possible side effect of hypertension. The modulation of several SUI-related proteins including myosin, iNOS, survival motor neuron (SMN) protein, and superoxide dismutase 3 (SOD3) may play some crucial roles in the therapeutic approach against SUI. This information may offer clues to the pathogenesis of SUI and open additional avenues for potential therapy strategies.


2012 ◽  
Vol 32 (suppl_1) ◽  
Author(s):  
Taiki Kida ◽  
Yoshiki Tsubosaka ◽  
Masatoshi Hori ◽  
Hiroshi Ozaki ◽  
Takahisa Murata

Objective TGR5, a membrane-bound, G-protein-coupled receptor for bile acids, is known to be involved in regulation of energy homeostasis and inflammation. However, little is known about the function of TGR5 in vascular endothelial cells. In the present study, we examined whether TGR5 agonism represents anti-inflammatory effects in vascular endothelial cells focusing on nitric oxide (NO) production. Methods and Results In human umbilical vein endothelial cells (HUVECs), treatment with taurolithocholic acid (TLCA), which has the highest affinity to TGR5 among various bile acids, significantly reduced tumor necrosis factor (TNF)-α-induced vascular cell adhesion molecule (VCAM)-1 protein expression and adhesion of human monocytes, U937. These effects were abrogated by a NO synthase (NOS) inhibitor, N G -Monomethyl-L-arginine (L-NMMA). In bovine aortic endothelial cells (BAECs), treatment with TLCA as well as lithocholic acid, which also has high affinity to TGR5, significantly increased the NO production. In contrast, deoxycholic acid and chenodeoxycholic acid, which possess low affinity to TGR5, did not affect the NO production. Gene depletion of TGR5 by siRNA transfection abolished TLCA-induced NO production in BAECs. TLCA-induced NO production was also observed in HUVECs measured as intracellular cGMP accumulation. We next investigated the signal pathways responsible for the TLCA-induced NO production in endothelial cells. Treatment with TLCA increased endothelial NOS (eNOS) ser1177 phosphorylation in HUVECs. This response was accompanied by increased Akt ser473 phosphorylation and intracellular Ca 2+ ([Ca 2+ ] i ). Treatment with phosphoinositide 3-kinase (PI3K) inhibitor, LY294002, or blockade of calcium channel with La 3+ , significantly decreased TLCA-induced eNOS ser1177 phosphorylation and subsequent NO production. Conclusion These results indicate that TGR5 agonism can mediate anti-inflammatory responses by suppressing VCAM-1 expression and monocytes adhesion to endothelial cells. This function is dependent on NO production via Akt activation and [Ca 2+ ] i increase.


Molecules ◽  
2018 ◽  
Vol 23 (9) ◽  
pp. 2124 ◽  
Author(s):  
Erna Sulistyowati ◽  
Mei-Yueh Lee ◽  
Lin-Chi Wu ◽  
Jong-Hau Hsu ◽  
Zen-Kong Dai ◽  
...  

Heat shock cognate protein 70 (HSC70), a molecular chaperone, is constitutively expressed by mammalian cells to regulate various cellular functions. It is associated with many diseases and is a potential therapeutic target. Although HSC70 also possesses an anti-inflammatory action, the mechanism of this action remains unclear. This current study aimed to assess the anti-inflammatory effects of HSC70 in murine macrophages RAW 264.7 exposed to lipopolysaccharides (LPS) and to explain its pathways. Mouse macrophages (RAW 264.7) in 0.1 µg/mL LPS incubation were pretreated with recombinant HSC70 (rHSC70) and different assays (Griess assay, enzyme-linked immune assay/ELISA, electrophoretic mobility shift assay/EMSA, gelatin zymography, and Western blotting) were performed to determine whether rHSC70 blocks pro-inflammatory mediators. The findings showed that rHSC70 attenuated the nitric oxide (NO) generation, tumor necrosis factor α (TNF-α) and interleukin 6 (IL-6) expressions in LPS-stimulated RAW264.7 cells. In addition, rHSC70 preconditioning suppressed the activities and expressions of matrix metalloproteinase-2 (MMP-2) and MMP-9. Finally, rHSC70 diminished the nuclear translocation of nuclear factor-κB (NF-κB) and reduced the phosphorylation of extracellular-signal regulated kinases 1/2 (ERK1/2), c-Jun N-terminal kinase (JNK), p38 mitogen-activated protein kinases (MAPK), and phosphatidylinositol-3-kinase (PI3K/Akt). We demonstrate that rHSC70 preconditioning exerts its anti-inflammatory effects through NO production constriction; TNF-α, and IL-6 suppression following down-regulation of inducible nitric oxide synthase (iNOS), cyclooxygenase 2 (COX-2), and MMP-2/MMP-9. Accordingly, it ameliorated the signal transduction of MAPKs, Akt/IκBα, and NF-κB pathways. Therefore, extracellular HSC70 plays a critical role in the innate immunity modulation and mechanisms of endogenous protective stimulation.


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