iridoids and Edema

Pain and inflammation are the major symptoms of almost every human disease. Herbal preparations from Morinda lucida are used to treat pain and inflammation in traditional medicine. However, the analgesic and anti-inflammatory activities of some of the plant's chemical constituents are not known.. The aim of this study is to evaluate the analgesic and anti-inflammatory activities and possible mechanisms of these activities of iridoids from Morinda lucida.. The compounds were isolated using column chromatography and characterized by NMR spectroscopy and LC-MS. Anti-inflammatory activity was evaluated using carrageenan-induced paw edema. Whereas, the analgesic activity was assessed in the hot plate and acetic acid-induced writhing assays. Mechanistic studies were conducted using pharmacological blockers, determination of antioxidant enzymes, lipid peroxidation, and docking studies.. The iridoid, ML2-2 exhibited inverse dose-dependent anti-inflammatory activity (42.62% maximum at 2 mg/kg p. o). ML2-3 produced dose-dependent anti-inflammatory activity (64.52% maximum at 10 mg/kg p. o.). Anti-inflammatory activity of diclofenac sodium was 58.60% at 10 mg/kg p. o. Furthermore, ML2-2 and ML2-3 produced analgesic activity (P < 0.01) of 44.44 ± 5.84 and 54.18 ± 19.01%. at 10 mg/kg p. o. respectively in the hot plate assay and 64.88 and 67.44% in the writhing assay. ML2-2 significantly elevated catalase activity. However, ML2-3 elevated SOD and catalase activity significantly. In the docking studies, both iridoids formed stable crystal complexes with delta and kappa opioid receptors, and the COX-2 enzyme with very low free binding energies (ΔG) from -11.2 to -14.0 kcal/mol. However, they did not bind with the mu opioid receptor. The lower bound RMSD of most of the poses were found to be ≤ 2. Several amino acids were involved in the interactions through various inter molecular forces.. These results indicate that ML2-2 and ML2-3 possessed very significant analgesic and anti-inflammatory activities via acting as both delta and kappa opioid receptor agonist, elevation of anti-oxidant activity and inhibition of COX-2.

Topics: Analgesics; Anti-Inflammatory Agents; Antioxidants; Carrageenan; Catalase; Cyclooxygenase 2; Edema; Humans; Inflammation; Iridoids; Morinda; Pain; Plant Extracts; Receptors, Opioid, delta; Rubiaceae; Superoxide Dismutase

Pterocephalus hookeri (C.B. Clarke) Höeck, one of the most popular Tibetan herbs, has been widely applied in Tibetan medicine prescriptions. Chemical investigations have led to the isolation of many bis-iridoids. However, the pharmacological activities of bis-iridoid constituents of this plant have never been reported before.. This study evaluated the anti-inflammatory and analgesic activities of afraction of bis-iridoid constituents of P. hookeri (BCPH) in order to provide experimental evidence for its traditional use, such as for cold, flu, and rheumatoid arthritis.. The analgesic effects of BCPH were investigated using the hot-plate test and acetic acid-induced writhing test. The anti-inflammatory activities were observed using the following models: carrageenin-induced edema of the hind paw of rats and xylene-induced ear edema in mice. The effects of dexamethasone administration were also studied.. BCPH significantly increased the hot-platepain threshold and reduced acetic acid-induced writhing response in mice. Moreover, BCPH remarkably inhibited xylene-induced ear edema and reduced the carrageenin-induced rat paw edema perimeter.. The results reveal that BCPH has central, peripheral analgesic activities as well as anti-inflammatory effects, supporting the traditional application of this herb in treating various diseases associated with inflammation and pain.

Topics: Acetic Acid; Analgesics; Animals; Anti-Inflammatory Agents; Caprifoliaceae; Carrageenan; Dexamethasone; Disease Models, Animal; Dose-Response Relationship, Drug; Edema; Female; Hot Temperature; Iridoids; Male; Mice, Inbred ICR; Nociceptive Pain; Phytotherapy; Plant Extracts; Plants, Medicinal; Rats, Sprague-Dawley; Xylenes

The analysis of the n-butanol extract of Linaria tingitana (BELT) by HPLC-DAD-ESI/MS allowed the identification of four iridoids structurally confirmed by NMR and ESI-MS/MS extensive experiments data. The subjection of BELT to the anti-inflammatory activity showed that it exhibited a concentration dependent stabilisation of HRBC membrane, inhibition of protein denaturation and nitric oxide scavenging effect in the in vitro process. These results were confirmed in the in vivo experiments which showed that BELT was found to be most pronounced at 200 mg/kg after carrageenan injection which significantly reduced the swelling in both early and late phases of carrageenan-evoked oedema, as well as a significant reduce at the accumulation of infiltrating cells, inhibition of the myeloperoxidase activity and suppressed the lipid peroxidation. These results were supported by the histological analysis which revealed the reduction of oedema and cells infiltration, this might be influenced by the synergistic action of the above isolated compounds.

Topics: 1-Butanol; Animals; Anti-Inflammatory Agents, Non-Steroidal; Carrageenan; Chromatography, High Pressure Liquid; Drug Evaluation, Preclinical; Edema; Humans; Iridoids; Linaria; Male; Nitric Oxide; Plant Extracts; Protein Denaturation; Rats, Wistar; Spectrometry, Mass, Electrospray Ionization; Tandem Mass Spectrometry

Castilleja tenuiflora (Orobanchaceae) has been used in Mexican traditional medicine as a treatment for cough, dysentery, anxiety, nausea and vomiting as well as hepatic and gastrointestinal diseases. The ethanolic extract of the aerial parts of Castilleja tenuiflora was separated by silica gel column chromatography. The fractions were evaluated using the induced edema acetate 12-O-tetradecanoylphorbol (TPA) anti-inflammatory activity model. The most active fraction was subjected to medium-pressure liquid chromatography (MPLC) with UV detection at 206 and 240 nm. The following iridoids were isolated: geniposidic acid, aucubin, bartioside, 8-epi-loganin, mussaenoside, and the phenylpropanoid verbascoside. The most active iridoid was geniposidic acid, which was more active than the control (indomethacin), and the least active iridoid was mussaenoside. 8-epi-Loganin, and mussaenoside have not been previously reported to be anti-inflammatory compounds. The results of these investigations confirm the potential of Mexican plants for the production of bioactive compounds and validate the ethnomedical use of Castilleja tenuiflora-like anti-inflammatory plants.

Topics: Acanthaceae; Animals; Anti-Inflammatory Agents; Edema; Glucosides; Inhibitory Concentration 50; Iridoids; Medicine, Traditional; Mice; Phenols; Plant Components, Aerial; Plant Extracts; Skin

Huang-Lian-Jie-Du-Tang (HLJDT), a famous traditional Chinese prescription with wide anti-inflammatory applications, is an aqueous extract of four herbal materials: Rhizoma coptidis, Radix scutellariae, Cortex phellodendri, and Fructus gardeniae. Its effects on the cyclooxygenase (COX)-2 and 5-lipoxygenase (5-LOX) pathways are thought to be responsible for its anti-inflammatory activity. However, our previous work found that the inhibitory effects of HLJDT act on the 5-LOX pathway but not on the COX pathway. The possibility that HLJDT inhibits COX-2- or 5-LOX-catalyzed eicosanoid generation by downregulating enzyme expression requires further investigation.. To observe the effects of HLJDT and its four major components (baicalin, baicalein, berberine and geniposide) on COX-2- or 5-LOX-catalyzed eicosanoid generation and to distinguish the effects of HLJDT on enzyme activity from those on enzyme expression.. The topical anti-inflammatory activities and inhibition of eicosanoid formation of HLJDT and its components were observed in an arachidonic acid (AA)-induced mouse ear edema model. Macrophage-based systems were established to observe the effects of the drugs on enzyme activity and enzyme expression of COX-2 and 5-LOX. Further experiments were carried out to confirm these effects at the mRNA and protein levels.. Topical treatment of HLJDT significantly inhibited AA-induced mouse ear edema and reduced PGE(2) and LTB(4) release in the edematous ears. Baicalein, geniposide, and berberine also ameliorated the symptoms and suppressed eicosanoid generation with varying efficacies. Cell-based assays showed that HLJDT and baicalein inhibited the PGE(2) levels by decreasing COX-2 enzyme expression without affecting COX-2 enzyme activity in RAW 246.7 murine macrophages. The other experiments on rat peritoneal macrophages indicated that HLJDT and baicalein exerted significant inhibition on LTB(4) production by decreasing 5-LOX enzyme activity. The real-time PCR and western blotting data demonstrated that HLJDT and baicalein reduced COX-2 expression at the mRNA and protein levels, whereas no inhibition on 5-LOX expression was observed.. HLJDT can suppress eicosanoid generation via both the COX and LOX pathways, which definitely contributes to its topical anti-inflammatory activity. We have confirmed that its dual inhibition on the COX and LOX pathways mainly result from the downregulation of COX-2 expression and direct inhibition of 5-LOX activity, respectively. Baicalein worked as a potent active component in most of the tests. These findings about the different inhibitory effects of HLJDT on COX-2 and 5-LOX help to better understand the mechanism of HLJDT and promote safer applications of drug.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Arachidonate 5-Lipoxygenase; Arachidonic Acid; Berberine; Cell Line; Cyclooxygenase 2; Cyclooxygenase 2 Inhibitors; Dinoprostone; Drugs, Chinese Herbal; Edema; Flavanones; Flavonoids; Iridoids; Leukotriene B4; Lipoxygenase Inhibitors; Male; Mice; Mice, Inbred ICR; Rats; Rats, Sprague-Dawley; RNA, Messenger

Penstemon gentianoides (Kunth) Poir. and Penstemon campanulatus (Cav.) Willd. (Plantaginaceae) are important medicinal plants in Mexico used by indigenous people for their anti-inflammatory effects and to also reduce rheumatic pains.. In addition to radical scavenging activity, the anti-inflammatory activity of the extracts, fractions and compounds of these plants were investigated and reported here for the first time.. The anti-inflammatory activities of MeOH, CH(2)Cl(2), and ethyl acetate extracts and iridoid, flavonoids, and phenylpropanoids from Penstemon gentianoides and P. campanulatus were studied in the TPA-induced mouse ear edema model. In addition, antioxidant activity against DPPH, crocin and β-carotene were investigated.. All extracts were tested and a selection of known compounds significantly (p <0.05) inhibited mouse ear edema. The results showed that CH(2)Cl(2) extracts of roots and stems from P. gentianoides and ethyl acetate extracts of leaves from P. gentianoides and P. campanulatus, as well as luteolin, diosmetin, penstemide and verbascoside produced the most positive results. Of all substances tested, the CH(2)Cl(2) extract of P. gentianoides roots was the most powerful inhibitor (ED(50)=0.07 mg/ear), with activity comparable to that of indomethacin. These extracts, compounds purified, as well as known compounds, inhibited oxidation of β-carotene and crocin.. These findings showed that the iridoid monoterpenes, flavonoids and phenylpropanoids present in these plants species may all contribute to the observed anti-inflammatory activity. Additionally, the observed antioxidant activity is correlated with the anti-inflammatory activity of these plants and the phytochemicals derived from them.

Topics: Animals; Anti-Inflammatory Agents; Antioxidants; Disease Models, Animal; Edema; Flavonoids; Indomethacin; Inflammation; Iridoids; Male; Medicine, Traditional; Mexico; Mice; Penstemon; Plant Extracts; Rats; Rats, Wistar; Solvents

Ajuga bracteosa Wall Ex Benth. (Labiateae) is described in Ayurveda for the treatment of rheumatism, gout, palsy and amenorrhea.. The aim of present investigation is to study anti-inflammatory activity of Ajuga bracteosa, to understand possible mechanism of action and to identify the constituents responsible for its activity.. The anti-inflammatory activity of 70% ethanolic extract was evaluated in TPA-induced mouse ear edema assay and in vitro cyclooxygenase (COX)-1 and COX-2 inhibitory activity was determined using EIA kits employing appropriate reference standards. Aajugarin I, lupulin A, withaferin A, reptoside and 6-deoxyharpagide were isolated from the 70% ethanolic extract by silica gel column chromatography.. The 70% ethanol extract of whole plants of Ajuga bracteosa showed a significant (p<0.05) and dose-dependent anti-inflammatory activity in an acute inflammation model at the dose of 0.5 and 1.0 mg/ear. The extract also exhibited a strong in vitro COX-1 and COX-2 inhibitory activity at 25 and 50 μg/mL concentration. Among the isolated compounds 6-deoxyharpagide exhibited highest COX-2 inhibition while rest of the compounds exhibited weak to moderate COX-1 and COX-2 inhibition at 30 μM concentration.. The results suggest that the 70% ethanol extract of Ajuga bracteosa possesses promising anti-inflammatory activity, which is possibly mediated through inhibition of COX-1 and COX-2 enzymes. The isolated constituents could be responsible in part for its anti-inflammatory and COX inhibitory activity. The study supports traditional use of Ajuga bracteosa for inflammatory diseases.

Topics: Ajuga; Animals; Anti-Inflammatory Agents; Cyclooxygenase 2 Inhibitors; Cyclooxygenase Inhibitors; Diterpenes; Edema; Ethnopharmacology; Female; Humans; In Vitro Techniques; India; Iridoid Glycosides; Iridoids; Medicine, Ayurvedic; Mice; Phytotherapy; Plant Extracts; Plants, Medicinal; Pyrans; Withanolides

Lamiophlomis rotata (Benth.) Kudo is a perennial herb (Labiatae) used as the Tibetan traditional medicine with the effects of alleviating pain, detumescence, hemostasis, promoting blood circulation to remove blood stasis and reinforcing marrow. In this study, we investigated the antinociceptive and anti-inflammatory activities of iridoid glycosides extract of L. rotata (IGLR) in mice. Our results showed that the iridoid glycosides extract could decrease acetic-acid-induced writhings times and formalin-induced lickings times, inhibit carrageenan-induced hind paw edema and xylene-induced ear swelling, and suppress peritoneal capillary permeability and leukocyte infiltration also induced by acetic acid in mice. All of these results suggested that the iridoid glycosides extract possesses the significant antinociceptive and anti-inflammatory activities.

Topics: Acetic Acid; Analgesics; Animals; Anti-Inflammatory Agents; Behavior, Animal; Capillary Permeability; Ear Diseases; Edema; Formaldehyde; Glycosides; Iridoids; Lamiaceae; Mice; Mice, Inbred BALB C; Neutrophil Infiltration; Pain; Peritoneal Cavity; Phytotherapy; Plant Components, Aerial; Plant Extracts; Xylenes

Swertiamarin, a secoiridoid isolated from the ethyl acetate extract of Enicostemma axillare, was evaluated for antiedematogenic activity using carrageenan-, formalin-, and histamine-induced paw edema methods in rats. In the carrageenan-induced method, the percentages of edema inhibition obtained after 5 h induction were 38.60, 52.50, and 45.44, respectively, for 100 and 200 mg/kg bw swertiamarin and 100 mg/kg bw of standard diclofenac sodium given orally. The activity of swertiamarin at 200 mg/kg bw was found to be superior to that of standard diclofenac sodium in all these methods. Swertiamarin was also screened for IN VITRO antioxidant activity using seven different methods: good activity was observed in ABTS and hydrogen peroxide methods, and moderate activity was observed in hydroxyl radical by deoxyribose and lipid peroxidation methods, with IC50 values of 2.83, 5.70, 52.56, and 78.33 microg/mL, respectively. The total antioxidant capacity was found to be 4.51 mM of ascorbic acid per gram of swertiamarin. Swertiamarin possesses antiedematogenic and in vitro antioxidant activities, and it may be the active constituent responsible for the anti-inflammatory activity of E. AXILLARE.

Topics: Animals; Anti-Inflammatory Agents; Carrageenan; Diclofenac; Edema; Female; Formaldehyde; Free Radical Scavengers; Free Radicals; Gentianaceae; Glucosides; Histamine; Iridoid Glucosides; Iridoids; Male; Pyrones; Rats; Rats, Wistar

We have studied scrovalentinoside, an iridoid with anti-inflammatory properties isolated from Scrophularia auriculata ssp. pseudoauriculata, as an anti-inflammatory agent in different experimental models of delayed-type hypersensitivity. We found that scrovalentinoside reduced the edema induced by oxazolone at 0.5 mg/ear and sheep red blood cells at 10 mg/kg. The observed effect occurred during the last phase or inflammatory response; during the earlier phase or induction of the delayed-type hypersensitivity reaction, no significant activity was noted. Thus, scrovalentinoside reduced both the edema and cell infiltration in vivo and reduced lymphocyte proliferation in vitro, affecting the cycle principally during the first 48 h. Whereas cells stimulated with phytohemagglutinin changed from the G(0)/G(1) phase to the S and G(2)/M phases, when these same cells were treated with scrovalentinoside (100 microM), they remained in the G(0)/G(1) phase. Finally, scrovalentinoside inhibited the production of the pro-inflammatory mediators' TNF-alpha, IFN-gamma, IL-1beta, IL-2, IL-4, LTB(4), and NO, but had no effect on the production of the anti-inflammatory cytokine IL-10.

Topics: Animals; Anti-Inflammatory Agents; Blotting, Western; Cell Cycle; Cell Proliferation; Disease Models, Animal; Edema; Female; Glycosides; Humans; Hypersensitivity, Delayed; Inflammation Mediators; Iridoid Glycosides; Iridoids; Macrophages; Mice; Oxazolone; Phytohemagglutinins; Plant Preparations; Plants, Medicinal; Rats; Receptors, Glucocorticoid; Scrophularia; T-Lymphocytes

Infusions of Verbascumlasianthum flowers have been used for hemorrhoids in Turkish folk medicine. In order to evaluate the scientific basis for this practice, in vivo anti-inflammatory and antinociceptive activities of Verbascum lasianthum Boiss. ex Bentham flowers were investigated. A methanolic extract of the flowers was shown to possess significant inhibitory activity in the carrageenan-induced hind paw edema model and in p-benzoquinone-induced writhings in mice. Through bioassay-guided fractionation and isolation procedures eight compounds, 6-O-(4'''-O-trans-p-coumaroyl)-alpha-L-rhamnopyranosylaucubin (1), 6-O-(4'''-O-trans-p-methoxycinnamoyl)-alpha-L-rhamnopyranosylaucubin (2), sinuatol (3), aucubin (4), geniposidic acid (5), catalpol (6), ajugol (7) and ilwensisaponin A (8) were isolated and their structures were elucidated by spectral techniques. An iridoid glucoside, aucubin (4) and a triterpenoid saponin, ilwensisaponin A (8) were found to possess significant antinociceptive and anti-inflammatory activities, per os without inducing any apparent acute toxicity or gastric damage. Results of the present study support the continued and expanded utilization of plants employed in Turkish folk medicine.

Topics: Analgesics; Animals; Anti-Inflammatory Agents; Biological Assay; Edema; Flowers; Hemorrhoids; Iridoids; Male; Medicine, Traditional; Mice; Pain; Pain Measurement; Phytotherapy; Plant Extracts; Plants, Medicinal; Spectrum Analysis; Turkey; Verbascum

Gardenia fruit has been traditionally used as a folk medicine for centuries in Asian countries. Extraction with ethanol was used to obtain an extract (GFE) that contains two known constituents, geniposide and genipin, which were subsequently evaluated for anti-inflammatory activity. GFE, genipin, and geniposide showed acute anti-inflammatory activities in carrageenan-induced rat paw edema. In a dose-dependent manner, GFE also inhibited vascular permeability induced by acetic acid. Both genipin and geniposide inhibited production of exudate and nitric oxide (NO) in the rat air pouch edema model. However, genipin possessed stronger anti-inflammatory activity than geniposide, as demonstrated by the results with carrageenan-induced rat paw edema, carrageenan-induced air pouch formation, and measurement of NO content in the exudates. GFE caused a dose-dependent inhibition of acetic acid-induced abdominal writhing in mice. Collectively, genipin, rather than geniposide, is the major anti-inflammatory component of gardenia fruit.

Topics: Animals; Anti-Inflammatory Agents; Carrageenan; Dose-Response Relationship, Drug; Edema; Female; Fruit; Gardenia; Inflammation; Iridoid Glycosides; Iridoids; Male; Mice; Nitrates; Plant Extracts; Pyrans; Rats; Rats, Sprague-Dawley

To study the effect of geniposide on serum IL-1beta and TNF-alpha levels of rheumatoid arthritis rats, as well as the mechanism of this drug.. To establish an experimental rat model of type II collagen-induced arthritic (CIA). The inhibitory effects on paw edema were observed, and serum IL-1beta and TNF-alpha levels were determined in experimental rats.. Compared with the model, geniposide delayed the starting time of right paw edema significantly, and the levels of serum IL-1beta and TNF-alpha were significantly decreased by geniposide at high dose or medium dose (P < 0.01).. Geniposide can lower serum IL-1beta and TNF-alpha levels in rheumatoid arthritis rats. The effect may be close related to inhibitory development of rheumatoid arthritis by the agent.

Topics: Animals; Arthritis, Rheumatoid; Collagen Type II; Dose-Response Relationship, Drug; Edema; Gardenia; Hindlimb; Interleukin-1; Iridoids; Male; Plants, Medicinal; Pyrans; Rats; Rats, Wistar; Tumor Necrosis Factor-alpha

Genipin, the aglycone of geniposide, is metabolically produced from the geniposide in body tissues. The purpose of this study is to clarify some pharmacological actions of genipin. Genipin showed concentration-dependent inhibition on lipid peroxidation induced by Fe++/ascorbate in rat brain homogenate. Genipin exhibited significant topical antiinflammatory effect shown as an inhibition of croton oil-induced ear edema in mice. Nitric oxide (NO) synthesis by inducible nitric oxide synthase (iNOS) is increased in inflammatory diseases and leads to cellular injury. Genipin concentration-dependently (50-300 microM) inhibited NO production and iNOS expression upon stimulation by lipopolysaccharide/interferon-gamma (IFN-gamma) in RAW 264.7, a murine macrophage cell line. Genipin markedly blocked lipopolysaccharide-evoked degradation of inhibitor-kappaB-beta (IkappaB-beta), indicating that it exhibits inhibitory effect on NO production through the inhibition of nuclear factor-kappaB (NF-kappaB) activation. It was also shown to contain potent antiangiogenic activity in a dose-dependent manner, which was detected by chick embryo chorioallantoic membrane assay. In summary, we demonstrate that genipin possesses antiinflammatory and is a specific hydroxyl radical scavenger. Its antiangiogenic and NO production-inhibitory properties are also presented.

Topics: Angiogenesis Inhibitors; Animals; Anti-Inflammatory Agents; Antioxidants; Brain; Cell Line; Cell Survival; Chorioallantoic Membrane; Dose-Response Relationship, Drug; Ear; Edema; Female; Gardenia; Immunoblotting; Interferon-gamma; Iridoid Glycosides; Iridoids; Lipid Peroxidation; Lipopolysaccharides; Macrophages; Male; Mice; Mice, Inbred ICR; Nitric Oxide; Nitric Oxide Synthase; Nitric Oxide Synthase Type II; Pyrans; Rats; Rats, Sprague-Dawley

Six new iridoid glucosides, 6'-O-trans-feruloylnegundoside (1), 6'-O-trans-caffeoylnegundoside (2), 2'-O-p-hydroxybenzoyl-6'-O-trans-caffeoylgardoside (3), 2'-O-p-hydroxybenzoyl-6'-O-trans-caffeoyl-8-epiloganic acid (4), 2'-O-p-hydroxybenzoyl gardoside (5), and 2'-O-p-hydroxybenzoyl-8-epiloganic acid (6), along with two known iridoids, agnuside and negundoside, have been isolated from the ethyl acetate extractive of the leaves of Vitex altissima. The structures of these compounds were elucidated on the basis of spectral data interpretation. These isolates did not exhibit significant 5-lipoxygenase enzyme inhibitory activity, but compounds 2-4 showed potent antioxidant activity by both the superoxide (NBT riboflavin photoreduction) free-radical-scavenging and DPPH-radical-scavenging methods. Compounds 1, 2, and negundoside were evaluated in a rat paw edema assay.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Biphenyl Compounds; Edema; Enzyme Inhibitors; Free Radical Scavengers; Glucosides; India; Iridoids; Lipoxygenase Inhibitors; Molecular Structure; Picrates; Plant Leaves; Plants, Medicinal; Rats; Rats, Wistar; Vitex

Five iridoid glycosides, including the two new compounds scropolioside-D(2) (1) and harpagoside-B (2), were isolated from the aerial parts of Scrophularia deserti DEL (Scrophulariaceae). Their structures were elucidated on the basis of spectral data to be 6-O-[2",4"-di-O-acetyl-3"-O-trans-cinnamoyl)-alpha-L-rhamnopyranosyl]-8 alpha-hydroxymethyl-1 alpha,5 beta,6 alpha,7 alpha,9 beta-pentahydro-7(8)-epoxy-2-oxaind-3-ene-1-O-beta-D-glucopyranoside-6'-O-acetate (1) and 5-O-beta-hydroxy-8-O-beta-trans-cinnamoyl-8 alpha-methyl-1,6,7,9-tetrahydro-2-oxaind-3-ene-1-O-beta-D-glucopyranoside (2), respectively. In addition, three more iridoid glycosides, scropolioside-D (3), koelzioside (4), and 8-O-acetyl-harpagide (5), were also isolated and characterized from this source. The biological activity and the structure activity relationship of the compounds were also studied, and scropolioside-D (3) and harpagoside-B (2) were found to possess significant antidiabetic and antiinflammatory activity, respectively.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Diabetes Mellitus, Experimental; Edema; Female; Glycosides; Hypoglycemic Agents; Iridoid Glucosides; Iridoids; Male; Mice; Plant Components, Aerial; Plant Extracts; Pyrans; Rats; Rats, Wistar; Scrophularia

The activity of the four glycoterpenoids: two saponins, verbascosaponin A and verbascosaponin, and two iridoids, scropolioside A and scrovalentinoside, isolated from Scrophularia auriculata ssp. pseudoauriculata, were studied in different models of acute and chronic inflammation. Both saponins significantly inhibited the mouse paw edema induced by carrageenan and ear edema induced by single and multiple doses of 12-O-tetradecanoylphorbol 13-acetate (TPA). Verbascosaponin A showed a potency twice as high as that of indomethacin in the acute TPA model. Verbascosaponin A and scropolioside A were active after a long latency period against ethyl phenylpropiolate edema, as are glucocorticoids. When the putative corticoid-like mechanism of the two compounds was studied, verbascosaponin A activity was notably reduced by the mRNA synthesis inhibitor, actinomycin D, while the effect of scropolioside A was partially interfered with by the anti-glucocorticoid drugs used. Both iridoids were active on the delayed type hypersensitivity reaction. They significantly reduced the inflammatory lesion and suppressed the cellular infiltration.

Topics: Animals; Anti-Inflammatory Agents; Capillary Permeability; Ear; Edema; Female; Glucosides; Glycosides; Hypersensitivity, Delayed; Iridoid Glycosides; Iridoids; Mice; Plants, Medicinal; Pyrans; Saponins; Serotonin; Terpenes; Tetradecanoylphorbol Acetate; Triterpenes