: list of natural anti-inflammatory agents

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Hi and others, below are the antiinflammatories that work on some of the same pathways as ibuprofen (inhibition of cox-2 and prostaglandins), so hopefully some of them could have good effects in kids who do well on ibuprofen and who get hot easilyÉ Few things worth noting: some of these have shown inhibition of bad guy cox-2 in vitro, so not sure it is the same in vivoÉ also not much data on absorption etc É and that every kid is different etc etc. It is generally thought that cox-1 inhibition is not so good long term, this is probably why ibuprofen has those side effects as it inhibits both cox-1 and 2É few of these herbs in abstracts below also do that to some extent (at least in vitro) so it may be wise to avoid long termÉ - this is again speaking theoretically as no side effects on record, as opposed to ibuprofen.. This second abstract sounds particularly useful but sadly no access to full text ☹ So here is the list, in no particular order. Btw has anyone used resveratrol? Any benefits??ResveratrolFish oil / Omega-3s (interestingly since taking CLO my headaches have reduced considerably, also much much less need for ibuprofen, which I had to take a lot before CLO)Olive oilVitamins D3 and K2melatoninTMGGingerGreen teaPhyllantus à Rio Health does itScutellaria baicalensis à Solgar does itWillow barkTetrandra, luteolin à both in Inflammation Control by VRPRose hip (also seem to inhibit cox-1 = not good long-term??), rosemary, pycnogenol (also cox-1), garlic, ginko, ginseng, kava kava, st Õs worth, 3: Phytother Res. 2008 Feb;22(2):204-12.Lipid peroxidation and cyclooxygenase enzyme inhibitory activities of acidic aqueous extracts of some dietary supplements. Raman P, Dewitt DL, Nair MG. Bioactive Natural Products and Phytoceuticals, Department of Horticulture and National Food Safety and Toxicology Center, Michigan State University, East Lansing, MI 48824, USA. The botanical supplement market is growing at a fast pace with more and more people resorting to them for maintaining good health. Echinacea, garlic, ginkgo, ginseng, Siberian ginseng, grape seed extract, kava kava, saw palmetto and St 's wort are some of the popular supplements used for a variety of health benefits. These supplements are associated with various product claims, which suggest that they possess cyclooxygenase (COX) enzyme and lipid s inhibitory activities. COX enzymes are found to be at elevated levels in inflamed and cancerous cells. To test some of the product claims, selected supplements were analysed for their ability to inhibit COX-1 and -2 enzymes and lipid peroxidation in vitro. The supplements were extracted with acidified water (pH 2) at 37 degrees C to simulate the gastric environment. The supplements tested demonstrated varying degrees of COX enzyme inhibition (5-85% for COX-1 and 13-28% for COX-2). Interestingly, extracts of garlic (Meijer), ginkgo (Solaray), ginseng (Nature's Way), Siberian ginseng (GNC, Nutrilite, Solaray, Natrol), kava kava (GNC, Sundown, Solaray) and St 's wort (Nutrilite) selectively inhibited COX-2 enzyme. These supplements also inhibited lipid peroxidation in vitro (5-99%). The results indicated that the consumption of these botanical supplements studied possess health benefits. Copyright © 2007 Wiley & Sons, Ltd. PMID: 17726737 [PubMed - in process]10: J Herb Pharmacother. 2004;4(2):11-8. Inhibition of COX isoforms by nutraceuticals. Seaver B, JR. University of Montana, 441 S. 6th E., Missoula, MT 59812, USA. Humans have two isoforms of Prostaglandin H Synthase or cyclooxygenase: COX-1 and COX-2. COX-1 is cytoprotective. COX-2 inhibitors reduce inflammation without the risk of ulceration and kidney damage. The ideal nutraceutical would inhibit COX-2 synthesis while preserving COX-1 synthesis. The hypothesis for this research was that COX inhibitors would fall primarily into three categories: COX-2 specific inhibition, non-specific inhibition (COX-1 and COX-2), and minimal inhibition. The human Cayman COX inhibitor screening assay was used to determine the inhibitory concentration 50 (IC50) of COX-1/ COX-2 activity of each nutraceutical. The assay was run, in duplicate, with three concentrations of a suspected inhibitor, a standard curve of eight concentrations, a non-specific binding sample, and a maximum binding sample. The inhibition and concentration of each sample was then put on a multiple regression best-fit line and the IC50 determined. For comparison, ibuprofen, rofecoxib, naproxen, and indomethacin were used. Positive results were seen for ipriflavone, resveratrol, MSV-60, amentoflavone, ruscus extract and notoginseng. Glucosamine, nexrutine, and berberine did not inhibit either isoform. PMID: 15364641 [PubMed - indexed for MEDLINE]J Med Food. 2007 Sep;10(3):442-51.A medicinal extract of Scutellaria baicalensis and Acacia catechu acts as a dual inhibitor of cyclooxygenase and 5-lipoxygenase to reduce inflammation. Burnett BP, Jia Q, Zhao Y, Levy RM. Primus Pharmaceuticals, Inc, sdale, AZ 85251, USA. A mixed extract containing two naturally occurring flavonoids, baicalin from Scutellaria baicalensis and catechin from Acacia catechu, was tested for cyclooxygenase (COX) and 5-lipoxygenase (5-LOX) inhibition via enzyme, cellular, and in vivo models. The 50% inhibitory concentration for inhibition of both ovine COX-1 and COX-2 peroxidase enzyme activities was 15 microg/mL, while the mixed extract showed a value for potato 5-LOX enzyme activity of 25 microg/mL. Prostaglandin E2 generation was inhibited by the mixed extract in human osteosarcoma cells expressing COX-2, while leukotriene production was inhibited in both human cell lines, immortalized THP-1 monocyte and HT-29 colorectal adenocarcinoma. In an arachidonic acid-induced mouse ear swelling model, the extract decreased edema in a dose-dependent manner. When arachidonic acid was injected directly into the intra-articular space of mouse ankle joints, the mixed extract abated the swelling and restored function in a rotary drum walking model. These results suggest that this natural, flavonoid mixture acts via "dual inhibition" of COX and LOX enzymes to reduce production of pro-inflammatory eicosanoids and attenuate edema in an in vivo model of inflammation. Publication Types: * Research Support, Non-U.S. Gov't PMID: 17887937 [PubMed - indexed for MEDLINE]2: Biochem Biophys Res Commun. 2007 Oct 26;362(3):606-11. Epub 2007 Aug 17.Inhibition of p38/CREB phosphorylation and COX-2 expression by olive oil polyphenols underlies their anti-proliferative effects. Corona G, Deiana M, Incani A, Vauzour D, Dess" MA, Spencer JP. Molecular Nutrition Group, School of Chemistry, Food and Pharmacy, University of Reading, Whiteknights Campus, Reading RG2 6AP, UK. We investigated the anti-proliferative effects of an olive oil polyphenolic extract on human colon adenocarcinoma cells. Analysis indicated that the extract contained hydroxytyrosol, tyrosol and the various secoiridoid derivatives, including oleuropein. This extract exerted a strong inhibitory effect on cancer cell proliferation, which was linked to the induction of a G2/M phase cell cycle block. Following treatment with the extract (50 microg/ml) the number of cells in the G2/M phase increased to 51.82+/-2.69% relative to control cells (15.1+/-2.5%). This G2/M block was mediated by the ability of olive oil polyphenols (50 microg/ml) to exert rapid inhibition of p38 (38.7+/-4.7%) and CREB (28.6+/-5.5%) phosphorylation which led to a downstream reduction in COX-2 expression (56.9+/-9.3%). Our data suggest that olive oil polyphenols may exert chemopreventative effects in the large intestine by interacting with signalling pathways responsible for colorectal cancer development. Publication Types: * Research Support, Non-U.S. Gov't PMID: 17727817 [PubMed - indexed for MEDLINE]4: Phytother Res. 2007 Dec;21(12):1251-2.COX-1 and -2 activity of rose hip. JŠger AK, Eldeen IM, van Staden J. Department of Medicinal Chemistry, The Danish University of Pharmaceutical Sciences, 2 Universitetsparken, 2100 Copenhagen, Denmark. ankj@... The objective of this study was to investigate whether the clinically observed efficacy of rose hip in the treatment of osteoarthritis is due to inhibition of cyclooxygenase-1 and -2. Water, methanol, dichloromethane and hexane extracts of rose hip were tested for in vitro COX-1 and 2 activity. The organic solvent extracts showed good inhibition of both COX-1 and 2. The methanol extract was most active in both assays with IC(50) values of 12 microg/mL for COX-1 and 19 microg/mL for COX-2. The clinically observed effect might be due to inhibition of cyclooxygenase. Copyright © 2007 Wiley & Sons, Ltd. PMID: 17639563 [PubMed - in process]5: Oncol Rep. 2007 Jun;17(6):1525-31.Anti-proliferative and antioxidant properties of rosemary Rosmarinus officinalis. Cheung S, Tai J. Department of Pathology and Pediatrics, Center for Complementary Medicine Research, Child and Family Research Institute, British Columbia Children's and Women's Health Center, University of British Columbia, British Columbia V6H 3N4, Canada. Constituents in rosemary have shown a variety of pharmacological activities for cancer chemoprevention and therapy in in vitro and in vivo models. In order to further explore the chemopreventive properties of crude extracts of rosemary (Rosmarinus officinalis L), we studied its anti-proliferative property on several human cancer cell lines and its antioxidant and anti-inflammatory properties in vitro in a mouse RAW 264.7 macrophage/monocyte cell line. Our study shows that crude ethanolic rosemary extract (RO) has differential anti-proliferative effects on human leukemia and breast carcinoma cells. The 50% inhibitory concentration (IC50) was estimated at 1/700, 1/400, 1/150 and 1/500 dilutions, for the HL60, K562, MCF7 and MDA-MB-468 cells, respectively. Non-cytotoxic concentrations of RO at 1/1000 dilution minimally induced HL60 cell differentiation into granulocyte lineage at 9.5+/-2.2% compared to 2.8+/-0.8% in the untreated control (p<0.001), and did not induce HL60 cell differentiation into monocyte/macrophage lineage. The 6-hydroxy-2,5,7,8-tetramethyl-chroman-2-carboxylic acid (Trolox) equivalent antioxidant capacity assay showed that RO has substantial antioxidant activity with RO at 1/10 and 1/5 dilutions having 8.1 and 12.6 microM Trolox equivalents, respectively. RO at non-cytotoxic 1/2000 and 1/1000 dilutions did not affect nitric oxide (NO) production by non-stimulated RAW 264.7 cells. However, at the same dilutions RO significantly reduced NO production by lipopolysaccharide (LPS)-activated cells in a dose-dependent manner from 32.6+/-2.3 microM in the LPS-activated cells to 19.2+/-2.2 microM (p<0.01), and 7.7+/-1.2 microM (p<0.001), respectively. RT-PCR analyses showed that RAW 264.7 cells treated with 1/1000 and 1/500 dilutions for 5 h did not affect TNFalpha, IL-1beta, iNOS and COX-2 mRNA expression in these cells when compared to the untreated controls, nor did the 1/1000 dilution of RO affect TNFalpha, IL-1beta, iNOS and COX-2 mRNA expression in the LPS-activated cells. At 1/500 dilution, RO significantly reduced IL-1beta (p<0.01) and COX-2 (p<0.05) mRNA expression and non-significantly reduced TNFalpha and iNOS mRNA expression in the LPS-activated cells. In view of the chemopreventive potentials, further studies are needed to explore other biological properties of this popular spice used by many cultures in the world. Publication Types: * Research Support, Non-U.S. Gov't PMID: 17487414 [PubMed - indexed for MEDLINE]6: Biol Pharm Bull. 2006 May;29(5):985-90.reventive effect of Ginkgo biloba extract (GBB) on the lipopolysaccharide-induced expressions of inducible nitric oxide synthase and cyclooxygenase-2 via suppression of nuclear factor-kappaB in RAW 264.7 cells. Park YM, Won JH, Yun KJ, Ryu JH, Han YN, Choi SK, Lee KT. Department of Biochemistry, College of Pharmacy, Kyung-Hee University, Seoul, South Korea. During our ongoing efforts to identify bioactive natural products with anti-inflammatory activity, we produced an extract from Ginkgo biloba (GBB) which contains higher levels of the active principles terpene and biflavonoid than EGb, the standard commercially available extract. In the present study, we examined and compared the effects of these two extracts on lipopolysaccharide (LPS)-induced nitric oxide (NO) and prostaglandin E2 (PGE2) production by the RAW 264.7 macrophage cell line. Our data indicate that GBB is a more potent inhibitor of NO and PGE2 production than EGb 761, and it also significantly decreased tumor necrosis factor (TNF)-alpha release. Consistent with these observations, the protein and mRNA expression levels of inducible NO synthase (iNOS) and cyclooxygenase-2 (COX-2) were found to be inhibited by GBB in a dose-dependent manner. Furthermore, GBB inhibited the LPS-induced DNA binding activity of nuclear factor-kappaB (NF-kappaB), which was associated with the prevention of IkappaB degradation, and subsequently with decreased p65 protein level in the nucleus. These results suggest that GBB inhibits LPS-induced iNOS, COX-2 and TNF-alpha expressions through the down-regulation of NF-kappaB-DNA binding activity. Publication Types * Research Support, Non-U.S. Gov't PMID: 16651732 [PubMed - indexed for MEDLINE]7: Biomed Pharmacother. 2006 Jan;60(1):5-9. Epub 2005 Oct 26. Inhibition of COX-1 and COX-2 activity by plasma of human volunteers after ingestion of French maritime pine bark extract (Pycnogenol). SchŠfer A, Chovanov‡ Z, Muchov‡ J, Sumegov‡ K, Lipt‡kov‡ A, Durackov‡ Z, Hšgger P. Institut fŸr Pharmazie und Lebensmittelchemie, Bayerische Julius-Maximilians-UniversitŠt, WŸrzburg, Germany. There is evidence from several studies that supplementation with French maritime pine bark extract (Pycnogenol) improves inflammatory symptoms in vivo. However, the molecular pharmacological basis for the observed effects has not been fully uncovered yet. Direct inhibitory effects of plant extracts or components upon cyclooxygenase (COX) activity have been repeatedly reported, but the question remained whether sufficiently high in vivo concentrations of bioactive compounds could be achieved in humans. The purpose of the present study was to determine a possible inhibition of the enzymatic activity of COX-1 and COX-2 by serum samples of human volunteers after intake of French maritime pine bark extract. This methodology considered that the serum samples would contain any bioavailable active principle. Therefore, we obtained blood samples before and after 5 days administration of 200 mg Pycnogenol to five healthy humans. The plasma moderately inhibited both COX-1 and COX-2 activities ex vivo. In a second approach, 10 volunteers received a single dose of 300 mg Pycnogenol. Only 30 min after ingestion of the pine bark extract the serum samples induced a statistically significant increase in the inhibition of both COX-1 (P < 0.02) and COX-2 (P < 0.002). This suggests a strikingly rapid bioavailability of bioeffective compounds after oral intake of the extract. Thus, we provide evidence that Pycnogenol exerts effects by inhibition of eicosanoid generating enzymes which is consistent with reported clinical anti-inflammatory and platelet inhibitory effects in vivo. The next challenge is to identify the active principle(s) that are rapidly bioavailable in human plasma. Publication Types: * Clinical Trial * Research Support, Non-U.S. Gov't PMID: 16330178 [PubMed - indexed for MEDLINE]8: J Altern Complement Med. 2004 Dec;10(6):1009-13.Ginger extract inhibits beta-amyloid peptide-induced cytokine and chemokine expression in cultured THP-1 monocytes. Grzanna R, Phan P, Polotsky A, Lindmark L, Frondoza CG. RMG Biosciences, Inc., Baltimore, MD, USA. INTRODUCTION: Neuritic plaques, a neuropathologic hallmark of Alzheimer's disease, are extracellular deposits of beta-amyloid peptides (Abeta). In the central nervous system neuritic plaques are surrounded by activated microglial cells expressing proinflammatory cytokines, chemokines, and neurotoxic mediators. Long-term activation of microglial cells is suspected to contribute to the neuron loss in Alzheimer's disease. OBJECTIVE: This study was conducted to determine whether a ginger (Zingiber officinale and Alpinia galanga) extract (GE) can dampen the activation of THP-1 cells by lipopolysaccharide, proinflammatory cytokines, and fibrillar amyloid peptide Abeta(1-42), a major component of neuritic plaques. METHODS: THP-1 cells, a human monocytic cell line with properties similar to human microglial cells, were incubated with GE or control medium alone for 1 hour, and then with reincubated lipopolysaccharide (LPS), tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta) or fibrillar Abeta(1-42) for an additional hour. The extent of THP-1 cell activation was determined by measuring mRNA levels of TNF-alpha and IL-1beta, cyclooxygenase-2 (COX-2), macrophage inflammatory protein 1alpha (MIP-1alpha), monocyte chemoattractant protein-1 (MCP-1), and interferon-gamma inducible protein 10 (IP-10). RESULTS: The results document that the GE used in this study inhibits LPS, cytokine, and amyloid Abeta peptide-induced expression of the proinflammatory genes TNF-alpha, IL-1beta, COX-2, MIP-alpha, MCP-1, and IP-10. The data provide experimental evidence that ginger can inhibit the activation of human monocytic THP-1 cells by different proinflammatory stimuli and reduce the expression of a wide range of inflammation-related genes in these microglial-like cells. CONCLUSIONS: The findings suggest that GE may be useful in delaying the onset and the progression of neurodegenerative disorders involving chronically activated microglial cells in the central nervous system. PMID: 15673995 [PubMed - indexed for MEDLINE]9: Phytother Res. 2004 Sep;18(9):723-8.Reversal of LPS-induced immobility in mice by green tea polyphenols: possible COX-2 mechanism. Singal A, Tirkey N, Chopra K. Pharmacology Division, University Institute of Pharmaceutical Sciences, Panjab University, Chandigarh-160014, India. An endotoxin (lipopolysaccharide, LPS) is known to activate the hypothalamo-pituitary adrenocortical axis, as well as norepinephrine and indolamine metabolism. Systemically administered LPS produces depression in the forced swimming-induced despair behaviour model in mice. The present study was designed to investigate the effect of green tea extract (GTE) on LPS-induced despair behaviour and to explore the mechanism involved in modulation of LPS-induced immobility by GTE. GTE (10-100 mg/kg) pretreatment reversed LPS-induced immobility in a dose-dependent manner. Rofecoxib (2 mg/kg) and nimesulide (2 mg/kg), COX-2 inhibitors, also reversed the LPS-induced immobility, which was significantly potentiated by concomitant administration of GTE. On the other hand, GTE did not show any potentiating effect on immobility with naproxen (10 mg/kg), which is a nonselective COX blocker. Interestingly the antioxidant, carvedilol (2 mg/kg) did not produce any effect on immobility either in normal or in LPS treated mice. The results of the study implicate the role of COX-2 inhibition by GTE in the reversal of LPS-induced immobility. Copyright © 2004 Wiley & Sons, Ltd. PMID: 15478205 [PubMed - indexed for MEDLINE]11: J Altern Complement Med. 2002 Oct;8(5):567-72.Anticancer activity of Scutellaria baicalensis and its potential mechanism. Ye F, Xui L, Yi J, Zhang W, Zhang DY. Department of Pathology, Mount Sinai School of Medicine, New York University, New York, NY 10021, USA. OBJECTIVE: Scutellaria baicalensis is a widely used Chinese herbal medicine that historically is used in anti-inflammatory and anticancer therapy. The aim of the study is to determine its ability to inhibit human cancer cells in vitro and to determine whether its anticancer activity is because of the inhibition of prostaglandin E(2) (PGE(2)) production that is derived from arachidonic acid through cyclooxygenase-2 (COX-2) pathway. METHODS: Cell lines from the most common human cancers, including squamous cell carcinoma (SCC-25, KB), breast cancer (MCF-7), hepatocellular carcinoma (HepG2), prostate carcinoma (PC-3 and LNCaP), and colon cancer (KM-12 and HCT-15) were tested. The cells were treated with various concentrations of Scutellaria baicalensis (0.1-100 mg/mL) for 72 hours. Percentage of viable cells after treatment was assessed using a trypan blue dye exclusion assay and the level of PGE(2) production was determined by enzyme immunoassay (EIA). RESULTS: Scutellaria baicalensis demonstrated a strong dose-dependent growth inhibition in all cell lines. Inhibition concentration at 50% (IC(50)) for HepG2, MCF-7, PC-3, LNCaP, KM-12, HCT-15, KB and SCC-25 cells was 1.1, 0.9, 0.52, 0.82, 1.1, 1.5, 1.0, and 1.2 mg/mL, respectively. Three cell lines (KB, SCC-25, and HepG2) were assessed for the production of PGE(2) and a high level of extracellular (KB and SCC-25) and intracellular PGE(2) (HepG2) was noted. In the presence of Scutellaria baicalensis extract, there was a significant decrease of PGE(2) in a dose-dependent fashion. CONCLUSIONS: Scutellaria baicalensis strongly inhibits cell growth in all cancer cell lines tested. However, prostate and breast cancer cells (PC-3, LNCaP, and MCF-7) are slightly more sensitive than other type of cancer cells. It also inhibits PGE(2) production, indicating that suppression of tumor cell growth may be due to its ability to inhibit COX-2 activity. This study supports the notion of using Scutellaria baicalensis as a novel anticancer agent to treat various cancers. Publication Types: * In Vitro PMID: 12470437 [PubMed à indexed for MEDLINE]12: Wien Med Wochenschr. 2002;152(15-16):354-9. [Willow bark extract--effects and effectiveness. Status of current knowledge regarding pharmacology, toxicology and clinical aspects] [Article in German] MŠrz RW, Kemper F. Medizinischen Forschung von Bionorica AG, Deutschland, Kerschensteinerstrasse 11-15, D-92318 Neumarkt/Opf., Deutschland. reinhard.maerz@... New pharmacological and clinical studies show that standardized willow bark extracts (WRE) is not only the natural form of salicylic acid. Willow bark extract has comparable antiinflammatory activities as higher doses of acetylsalicylic acid (ASS), and it shows antinociceptive and antipyretic activities. Under the pharmacologically active doses, no adverse effects regarding the stomach mucosa was observed, in contrast to acetylsalicylic acid. A daily dose of 1572 mg willow bark extract of a proprietary preparation (Assalix; standardised to 15.2% salicin, i.e. 240 mg salicin per day) was significantly superior to placebo in patients with osteoarthritis of the hip and the knee and in patients with exacerbations of chronic low back pain. In 2 open studies against active treatments as controls, willow bark extract exhibited advantages against a routinely prescribed treatment scheme of orthopedic specialists based on nonsteroidal antirheumatic drugs and rather similar efficacy as the COX-2-inhibitor refecoxib. Willow bark extract also displays an activity regarding the thrombocyte function, but the activity is clearly weaker. Publication Types: * English Abstract PMID: 12244878 [PubMed - indexed for MEDLINE]Biol Pharm Bull. 2007 Dec;30(12):2244-9. Betaine modulates age-related NF-kappaB by thiol-enhancing action. Go EK, Jung KJ, Kim JM, Lim H, Lim HK, Yu BP, Chung HY. Department of Pharmacy, College of Pharmacy, Pusan National University, Gumjung-ku, Busan 609-735, Korea. Depletion of glutathione levels and perturbations in redox status are considered to play a crucial role in aging and chronic inflammatory processes through the activation of redox sensitive transcription factors, including nuclear factor-kappaB (NF-kappaB). In the current study, we assessed the regulatory action of dietary betaine in the suppression of NF-kappaB by comparing kidney tissue from old, betaine-supplemented rats or non-betaine-supplemented rats (age 21 months) and 7 month-old rats. In addition, cultured HEK 293T cells were utilized for the molecular assessment of betaine's restorative ability of redox status when treating cells with potent glutathione (GSH)-depleting agents. Results showed that in old rats a short-term feeding (10 d) with betaine attenuated the age-related decrease in thiol levels, increase in reactive species and TNFalpha expression via NF-kappaB activation, compared to the young controls. These findings were verified in the cell-cultured system. Further investigations found that redox imbalance due to thiol depletion caused increased NF-kappaB activation, and cyclooxygenase (COX)-2 and TNFalpha levels, both of which were suppressed by betaine treatment. Based on both in vivo and in vitro data, we concluded that betaine exerts its efficacy by maintaining thiol status in the regulation of COX-2 and TNFalpha via NF-kappaB activation during aging. PMID: 18057706 [PubMed - indexed for MEDLINE]J Hepatol. 2003 Mar;38(3):289-97. Phyllanthus amarus has anti-inflammatory potential by inhibition of iNOS, COX-2, and cytokines via the NF-kappaB pathway. Kiemer AK, Hartung T, Huber C, Vollmar AM. Department of Pharmacy, Center of Drug Research, University of Munich, Butenandtstr. 5-13, 81377 Munich, Germany. alexandra.kiemer@... BACKGROUND/AIMS: Phyllanthus amarus is a herbal medicine traditionally applied in the treatment of viral hepatitis. Aim of this study was to investigate potential anti-inflammatory properties of standardized P. amarus extracts concerning a potential influence of P. amarus on endotoxin-induced nitric oxide synthase (iNOS), cyclooxygenase (COX-2), and cytokine production in vivo and in vitro. METHODS: Investigations were performed in rat Kupffer cells (KC), in RAW264.7 macrophages, in human whole blood, and in mice. Cells were stimulated with lipopolysaccharides (LPS) in the presence or absence of P. amarus extracts (hexane, EtOH/H(2)O), mice were treated with galactosamine/LPS as a model for acute toxic hepatitis. Nitrite was measured by Griess assay, prostaglandin E(2) (PGE(2)) by radioimmunoassay, and cytokines by enzyme-linked immunosorbent assay. iNOS and COX-2 were determined by Western blot, activation of NF-kappaB and AP-1 by EMSA. RESULTS: P. amarus EtOH/H(2)O and hexane extracts showed an inhibition of LPS-induced production of NO and PGE(2) in KC and in RAW264.7. The extracts also attenuated the LPS-induced secretion of tumor necrosis factor (TNF-alpha) in RAW264.7 as well as in human whole blood. Both extracts reduced expression of iNOS and COX-2 and inhibited activation of NF-kappaB, but not of AP-1. P. amarus inhibited induction of interleukin (IL)-1beta, IL-10, and interferon-gamma in human whole blood and reduced TNF-alpha production in vivo. CONCLUSIONS: This work shows that standardized extracts of P. amarus inhibit the induction of iNOS, COX-2, and TNF-alpha. Therefore, we report for the first time an anti-inflammatory potential of this traditionally employed herbal medicine both in vitro and in vivo. PMID: 12586294 [PubMed - indexed for MEDLINE]