ophiopogonin-d and Inflammation

The sustained activation of the nuclear factor κB (NF-κB) signaling pathway has been observed in human inflammatory bowel disease (IBD). Ophiopogonin D (OP-D) is a small molecular compound isolated from Ophiopogon japonicus, a widely used herbal remedy. In this study, dextran sodium sulfate was used to make a mouse model of experimental colitis and verify the effect of OP-D on the mouse model of experimental colitis. Small molecule-protein molecular docking approaches were also used to discover the mechanisms underlying the OP-D-induced regulation of colitis. In colitis, the OP-D can inhibit the apoptosis of intestinal mucosa cells, restore the intestinal barrier, and alleviate inflammation. The molecular docking simulations showed that OP-D had a high affinity with the REL-homology domain of NF-κB-p65 that affected its translocation to the nucleus. In a cell study, the effects of OP-D on inflammation and barrier dysfunction were significantly decreased by a small interfering RNA targeting NF-κB-p65. Further, the LPS-induced increase in NF-κB-p65 in the nucleus was also significantly inhibited by OP-D. OP-D alleviated experimental colitis by inhibiting NF-κB. New insights into the pathogenesis and treatment options of colitis are provided through this study.

Topics: Animals; Colitis; Dextran Sulfate; Inflammation; Mice; Mice, Inbred C57BL; Molecular Docking Simulation; NF-kappa B; Saponins; Signal Transduction; Spirostans

Atopic dermatitis (AD) can occur in both children and adults, and the symptoms include itching and eczema, which in turn cause patients to suffer. Ophiopogonin D (OP-D) is a steroidal glycoside from Radix Ophiopogon japonicus, which is well known as an effective anti-inflammatory herbal medicine in many Asian countries. In this study, we aimed to investigate the anti-inflammatory effects of OP-D, using an AD mouse model and inflamed HaCaT cells. Through a histopathological analysis, we were able to confirm the suppressive effects of OP-D on skin thickening and the mast cell activation in AD-like mouse back skin tissues stimulated by DNCB. In addition, we detected significant decreases in cytokine expression levels through multiplex assessment assays of the OP-D-treated mice blood. We observed the anti-inflammatory effect of OP-D in the spleen, causing weight loss in the spleen and in the mRNA expression levels related to diverse cytokines. In human keratinocytes inflamed by TNF-α, OP-D inhibited p38 and ERK protein activation and showed a reduction of NF-κB nuclear translocation. Furthermore, OP-D attenuated pro-inflammatory cytokine mRNA expressions in TNF-α-inflamed HaCaT cells. Accordingly, we came to the conclusion that OP-D is a potential natural drug which can be used in order to treat inflammatory skin diseases, such as AD.

Topics: Active Transport, Cell Nucleus; Animals; Cell Line; Cytokines; Dermatitis, Atopic; Dinitrochlorobenzene; Female; Humans; Inflammation; Keratinocytes; Mice; Mice, Inbred BALB C; Saponins; Skin; Spirostans; Spleen; Tumor Necrosis Factor-alpha

Ophiopogonin D (OP-D) is the principal pharmacologically active ingredient from Ophiopogon japonicas, which has been demonstrated to have numerous pharmacological activities. However, its protective effect against renal damage in streptozotocin (STZ)-induced diabetic nephropathy (DN) rats remains unclear. The present study was performed to investigate the protective effect of OP-D in the STZ-induced DN rat model. DN rats showed renal dysfunction, as evidenced by decreased serum albumin and creatinine clearance, along with increases in serum creatinine, blood urea nitrogen, TGF-β1, and kidney hypertrophy, and these were reversed by OP-D. In addition, STZ induced oxidative damage and inflammatory response in diabetic kidney tissue. These abnormalities were reversed by OP-D treatment. The findings obtained in the present study indicated that OP-D might possess the potential to be a therapeutic agent against DN via inhibiting renal inflammation and oxidative stress.

Topics: Animals; Diabetes Mellitus, Experimental; Diabetic Nephropathies; Inflammation; Male; Ophiopogon; Oxidative Stress; Rats; Rats, Sprague-Dawley; Saponins; Spirostans; Streptozocin

Ophiopogonin D (OPD) is the chief pharmacological active component of the traditional Chinese herbal prescription drug-Shenmai injection (SMI), which has been used to prevent and treat cardiovascular diseases. In the present study, we investigated whether OPD protectively relieve cardiac hypertrophy against inflammation via inhibiting the expression of NF-κB and examined whether cytochrome P450 2J3 (CYP2J3)was involved in this pathway. H9c2 cells were treated with Angiotensin II (Ang II). Hypertrophy in rat was induced by administration of Ang II infusion. To evaluate the effect of OPD on disease progression and the role of CYP2J3 in this way, inflammatory mediators (NF-κB), specific hypertrophic factors and pathological change were determined in this experiment. Ang II induced hypertrophy with the elevated expression of specific hypertrophy genes and NF-κB signaling molecules. However, these inductive effects were reversed by OPD in conjunction with Ang II. Overexpression of CYP2J3 prevented the excessive expression of NF-κB. In vivo, partial pathological cardiac hypertrophy injuries were relieved after OPD treatment. OPD exerts a positive effect on alleviating cardiac hypertrophy. The mechanism is probably through inhibiting the expression of NF-κB by upregulating CYP2J3 to suppress inflammation.

Topics: Animals; Anti-Inflammatory Agents; Cardiomegaly; Cytochrome P-450 Enzyme System; Down-Regulation; Inflammation; Male; NF-kappa B; Rats; Rats, Sprague-Dawley; Saponins; Spirostans; Up-Regulation

CYP2J2 is highly expressed in cardiovascular tissue including the heart and vascular endothelial cells. CYP2J2 and the EETs have been shown owning diverse biological effects. Our previous study found that ophiopogonin D (OP-D) suppressed drug-induced endoplasmic reticulum (ER) stress by upregulating the levels of CYP2J3/EETs in cardiomyocytes. The aim of this research was to investigate whether CYP2J2/EETs-PPARα pathway involved in endothelium protective effects of OP-D in human umbilical vein endothelial cells (HUVECs). The results showed that OP-D significantly inhibited Ang II induced NF-κB nuclear translocation, IκBα down-regulation and activation of pro-inflammatory cytokines (TNF-α, IL-6 and VCAM-1) by increasing the expression of CYP2J2/EETs and PPARα in HUVECs. Furthermore, treatment with exogenous 11,12-EET attenuated endothelial inflammation induced by Ang II as evidenced by inhibited NF-κB nuclear translocation, increased IκBα expression and decreased inflammation factor level. Finally, the activation of NF-κB nuclear translocation induced by Ang II was also markedly suppressed by fenofibrate. Co-incubation with 6-(2-proparglyloxyphenyl) hexanoic acid (PPOH) and PPARα inhibitor GW6471 before drug treatment abolished the endothelium protective effects of OP-D. Taken together, these data suggest that OP-D has the endothelial protective effect through activation of CYP2J and increasing EETs, and PPARα involves in this process.

Topics: 8,11,14-Eicosatrienoic Acid; Angiotensin II; Cells, Cultured; Human Umbilical Vein Endothelial Cells; Humans; Inflammation; NF-kappa B; PPAR alpha; Protein Transport; Saponins; Spirostans