HYPOTHESIS/ PURPOSE: To compare the anti-inflammatory activities and the anti-nociceptive properties of RG and BG.
METHODS: Nitric Oxide (NO) and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazoliumbromide (MTT) assay, quantitative Reverse Transcriptase-Polymerase Chain Reaction (qRT-PCR), western blot, xylene-induced ear edema, carrageenan-induced paw edema RESULTS: The ginsenoside contents were confirmed using high-performance liquid chromatography (HPLC) and has been altered through increased processing. The highest concentration of these extracts inhibited NO production to near-basal levels in lipopolysaccharide (LPS)-stimulated RAW 264.7 without exhibiting cytotoxicity. Pro-inflammatory cytokine expression at the mRNA level was investigated using qRT-PCR. Comparatively, BG exhibited better inhibition of pro-inflammatory mediators, iNOS and COX-2 and pro-inflammatory cytokines, IL-1β, IL-6 and TNF-α. Protein expression was determined using western blot analysis and BG exhibited stronger inhibition. Xylene-induced ear edema model in mice and carrageenan-induced paw edema in rats were carried out and tested with the effects of ginseng as well as dexamethasone and indomethacin - commonly used drugs. BG is a more potent anti-inflammatory agent, possesses anti-nociceptive properties, and has a strong potency comparable to the NSAIDs.
CONCLUSION: BG has more potent anti-inflammatory and anti-nociceptive effects due to the change in ginsenoside component with increased processing.
MATERIALS AND METHODS: The influx of immune cells, release of pro-inflammatory cytokines and subsequent accumulation of synovial fluid (swelling) and pain manifest into the disease. The present study used CFA induced Balb/c mice model and treated them intraperitoneally with andrographolide and dexamethasone (used as a positive control) on alternate days for six days. After 6 days, blood and peritoneal macrophages were collected to evaluate the expression of various arthritic markers and paw edema was measured on all days.
RESULTS: The in vitro and ex vivo experiments showed that andrographolide treated animal group had reduced paw edema, cell cytotoxicity and nitric oxide production than dexamethasone treated animal group. Further, the study revealed the mechanistic role of andrographolide in treatment of arthritis by suppressing battery of molecules like COX-2, NF-κB, p-p38, CD40, TNF-α, IL-1β and IL-6 involved in arthritis.
CONCLUSION: The study showed the potent anti-arthritic effects of andrographolide and warrants further investigations on andrographolide for the development of safe and effective anti-arthritic drug.
AIMS: The aims of this study were to determine the efficacy of rectal diclofenac in preventing PEP and to evaluate any adverse events.
METHODS: This was a randomized, open-label, two-arm, prospective clinical trial. Only patients at high risk of developing PEP were recruited. They received 100 mg rectal diclofenac or no intervention immediately after ERCP. The patients were reviewed 30 days after discharge to evaluate any adverse event.
RESULTS: Among 144 recruited patients, 69 (47.9%) received diclofenac and 75 (52.1%) had no intervention. Eleven patients (7.6%) developed PEP, in which seven were from the diclofenac group and four were in the control group. Eight cases of PEP (5.5%) were mild and three cases (2.1%) were moderate. The differences in pancreatitis incidence and severity between both groups were not statistically significant. There were 11 adverse events reported. Clinically significant bleeding happened in four patients (2.8%): one from the diclofenac group and three from the control group. Other events included cholangitis: two patients (2.9%) from the diclofenac group and four (5.3%) from the control group. One patient from the diclofenac group (1.4%) had a perforation which was treated conservatively.
CONCLUSIONS: In summary, prophylactic rectal diclofenac did not significantly decrease the incidence of PEP among patients at high risk for developing PEP. However, the administration of diclofenac was fairly safe with few clinical adverse events.
MATERIALS AND METHODS: An in vitro monocyte recruitment model utilizing THP-1 and HUVECs was developed to evaluate TNF-α-induced monocyte adhesion and trans-endothelial migration. To study the role of Nrf2 for MA-mediated anti-inflammatory effects, Nrf2 inhibitor ML385 was used as the pharmacological inhibitor. The expression of Nrf2, monocyte chemoattractant protein-1 (MCP-1), vascular cell adhesion molecule 1 (VCAM-1), cluster of differentiation 36 (CD36), and scavenger receptor type A (SR-A) in HUVECs and THP-1 macrophages were investigated using RT-qPCR and Western blotting. The NF-κB activity was determined using NF-κB (p65) Transcription Factor Assay Kit.
KEY FINDINGS: The results showed opposing effects of MA on Nrf2 expression in HUVECs and THP-1 macrophages. MA suppressed TNF-α-induced Nrf2 expression in HUVECs, but enhanced its expression in THP-1 macrophages. Combined effects of MA and ML385 suppressed MCP-1, VCAM-1, and SR-A expressions. Intriguingly, at the protein level, ML385 selectively inhibited SR-A but enhanced CD36 expression. Meanwhile, ML385 further enhanced MA-mediated inhibition of NF-κB activity in HUVECs. This effect, however, was not observed in THP-1 macrophages.
SIGNIFICANCE: MA attenuated foam cell formation by suppressing VCAM-1, MCP-1, and SR-A expression, as well as NF-κB activity, possibly through Nrf2 inhibition. The involvement of Nrf2 for MA-mediated anti-inflammatory effects however differs between HUVECs and macrophages. Future investigations are warranted for a detailed evaluation of the contributing roles of Nrf2 in foam cells formation.
METHODS: Maximal non-toxic dose (MNTD) of methanol extract of P. ginseng root culture on BV2 microglia cells was first determined via 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, followed by treatment and LPS stimulation of cells, and the measurement of NO using Griess assay and TNF-α, IL-6, and IL-10 using ELISA assay.
RESULTS: The MNTD of P. ginseng root extract was determined to be (587 ± 57) µg/mL. Following that, NO and IL-6 levels were found to be insignificantly reduced by 6.88% and 0.14% respectively in stimulated cells upon treatment with MNTD. Treatment with MNTD yielded similar insignificant result, with only a reduction of 3.58% and 0.08% in NO and IL-6 levels respectively. However, TNF-α and IL-10 levels were significantly downregulated by 15.64% and 34.96% respectively upon treatment with P. ginseng root extract at MNTD.
CONCLUSION: Methanol extract of P. ginseng root culture did not show any significant anti-inflammatory effects on NO and IL-6 levels, but might potentially possess both anti-neuroinflammatory and pro-neuroinflammatory properties through the downregulation of TNF-α and IL-10 respectively.
METHODS: The antibacterial activity of four NSAIDs (aspirin, ibuprofen, diclofenac and mefenamic acid) were tested against ten pathogenic bacterial strains using the microdilution broth method. The interaction between NSAIDs and antibiotics (cefuroxime/chloramphenicol) was estimated by calculating the fractional inhibitory concentration (FICI) of the combination.
RESULTS: Aspirin, ibuprofen and diclofenac exhibited antibacterial activity against the selected pathogenic bacteria. The interaction between ibuprofen/aspirin with cefuroxime was demonstrated to be synergistic against methicillin-sensitive S. aureus (MSSA) and the MRSA reference strain, whereas for MRSA clinical strains additive effects were observed for both NSAIDs and cefuroxime combinations. The combination of chloramphenicol with ibuprofen/aspirin was synergistic against all of the tested MRSA strains and displayed an additive effect against MSSA. A 4-8192-fold reduction in the cefuroxime minimum inhibitory concentration (MIC) and a 4-64-fold reduction of the chloramphenicol MIC were documented.
CONCLUSIONS: Overall, the NSAIDs ibuprofen and aspirin showed antibacterial activity against strains of S. aureus. Although individually less potent than common antibiotics, these NSAIDs are synergistic in action with cefuroxime and chloramphenicol and could potentially be used as adjuvants in combating multidrug-resistant MRSA.