Induced Mouse Ear Edema Research Articles

Anti-inflammatory activity of Chrysanthemum indicum extract in acute and chronic cutaneous inflammation

Aim of the study Although Chrysanthemum indicum Linné (Compositae) has long been used in traditional Korean, Chinese, Japanese medicine to treat various immune-related diseases the underlying mechanism(s) by which these effects are induced remains to be defined in vivo model system. We investigated the effects of 70% ethanolic extract from Chrysanthemum indicum Linné (CIE) on skin inflammation in mice. Materials and methods Production of pro-inflammatory cytokines (TNF-α and IL-1β), activation of myeloperoxidase, and histological assessment were examined in acute and chronic skin inflammation using 12-O-tetradecanoyl-phorbol-13-acetate (TPA)-induced mouse ear edema. Results CIE inhibited topical edema in the mouse ear, following administration at 200 mg/kg (i.p.), leading to substantial reductions in skin thickness and tissue weight, inflammatory cytokine production, neutrophil-mediated myeloperoxidase activity, and various histopathological indicators. Furthermore, CIE was effective at reducing inflammatory damage induced by chronic TPA exposure. Conclusions These results demonstrate that CIE is an effective anti-inflammatory agent in murine phorbol ester-induced dermatitis, and suggest that the extract may have therapeutic potential in a variety of immune-related cutaneous diseases.

Anti-inflammatory, analgesic and wound healing activities of the leaves of Memecylon edule Roxb.

Aim of the study To determine the anti-inflammatory, analgesic and antioxidant activities of the leaves of Memecylon edule Roxb. used traditionally in Thailand. Materials and methods Hexane, (Hex), ethyl acetate (EtOAc), methanol (MeOH) and 50% methanol (MeOH50) fractions of the dry leaves were tested in vitro for their interleukin-10 production; the most active fraction was further studied in vivo for its anti-inflammatory and analgesic activities using the ethylphenylpropiolate (EPP)-induced mouse ear edema and the writhing test with mice. All fractions except Hex were tested for their radical scavenging activity towards 1′-diphenyl-2-picrylhydrazyl radical (DPPH ). Results The EtOAc showed the highest stimulation for interleukin-10 production. In the EPP test, this fraction was significantly active 30 min after topical application at all doses used (0.5, 1.0, 2.0 mg/ear); after 4 h and at 1.0 mg/ear EtOAc was slightly less active (inhibition 47.8%) than the reference, indomethacin, at the same dose (62.4%). At 200 mg/kg orally, the EtOAc caused a significant inhibition of the writhing response by 56.6% which was like indomethacin at 10 mg/kg. EtOAc, MeOH and MeOH50 exhibited radical scavenging activity. The order of IC 50 values was: ascorbic acid (9.1 μg/mL) > trolox (11.6 μg/mL) > MeOH (46.9 μg/mL) > MeOH50 (152.1 μg/mL) > EtOAc (1742.2 μg/mL). Conclusion The results provide support for the traditional use of Memecylon edule leaves in relieving inflammation and pain.

Anti-inflammatory effects of Asparagus cochinchinensis extract in acute and chronic cutaneous inflammation

Aims of study Although Asparagus cochinchinensis Merrill (Liliaceae) has long been used in traditional Korean and Chinese medicine to treat inflammatory diseases, the underlying mechanism(s) by which these effects are induced remains to be defined. We investigated the effects of 70% ethanolic extract from Asparagus cochinchinensis Merrill (ACE) on skin inflammation in mice. Materials and methods Production of pro-inflammatory cytokines (tumor necrosis factor (TNF)-α, interleukin (IL)-1β), activation of myeloperoxidase, and histological assessment were examined in acute and chronic skin inflammation using 12- O-tetradecanoyl-phorbol-13-acetate (TPA)-induced mouse ear edema. We also performed acetic acid-induced vascular permeability test. Results ACE inhibited topical edema in the mouse ear, following administration at 200 mg/kg (i.p.), leading to substantial reductions in skin thickness and tissue weight, inflammatory cytokine production, neutrophil-mediated myeloperoxidase (MPO) activity, and various histopathological indicators. Furthermore, ACE was effective at reducing inflammatory damage induced by chronic TPA exposure and evoked a significant inhibition of vascular permeability induced by acetic acid in mice. Conclusion These results demonstrate that ACE is an effective anti-inflammatory agent in murine phorbol ester-induced dermatitis, and suggest that the compound may have therapeutic potential in a variety of immune-related cutaneous diseases.

Bioassay-guided isolation of anti-inflammatory and antinociceptive principles from a folk remedy, Rhododendron ponticum L. leaves

Ethnopharmacological relevance: Rhododendron ponticum L. (Ericaceae) is used for the treatment of inflammatory diseases and to alleviate rheumatic pain and against toothache in Turkish traditional medicine. Aim of the study: To evaluate the anti-inflammatory and antinociceptive effects of Rhododendron ponticum leaves using in vivo models, and isolation and chemical characterization of the biologically active constituents through bioassay-guided fractionation procedures. Material and Methods: Carrageenan-induced hind paw edema model was used for anti-inflammatory activity and p-benzoquinone induced abdominal contractions model for the antinociceptive activity assessment. Results: The ethylacetate fraction displayed marked anti-inflammatory (28.4-40.7% inhibition) and antinociceptive (50.7% inhibition) effects as compared to reference compounds. Through bioassay-guided fractionation and isolation procedures flavonol glycosides [a mixture of hyperoside and isoquercitrin (1) and quercitrin (2)] along with one flavanone glycoside [6-C-glycosylnaringenin (3)] were isolated as the active ingredients of ethylacetate extract against carrageenan-induced edema and p-benzoquinone-induced writhes and their structures were elucidated by spectral techniques. 1 and 2 also showed a significant anti-inflammatory activity against 12-O-tetradecanoyl-13-acetate (TPA)- induced mouse ear edema model. Conclusion: Results of the present study supported the utilization of the plant in Turkish folk medicine and revealed that flavones are the major anti-inflammatory and antinociceptive principles of the leaves.

Cancer chemoprotective effects of Curcuma xanthorrhiza

Curcuma xanthorrhiza Roxb. (Zingiberaceae) is a medicinal plant widely spread in South East Asia. In particular, it is commonly used not only for food and medicinal purposes in Indonesia, but also for the topical treatment of acne and skin inflammations as Thai traditional medicine. It was found that the methanol extract of C. xanthorrhiza inhibited significantly 7,12-dimethylbenz[a]anthracene (DMBA)-induced bacterial mutagenesis of Salmonella typhimurium TA98 and TA100 in the presence of S9, and the mutagenesis induced by H2O2 and tert-butylhydroperoxide in S. typhimurium TA102, respectively. In addition, 12-O-tetradecanolyphorbol-13-acetate(TPA)-induced mouse ear edema was markedly inhibited by pretreatment with C. xanthorrhiza extract. C. xanthorrhiza extract dose-dependently reduced ODC expression in mouse skin with TPA-induced acute inflammation. Furthermore, repeated treatment with 0.1% C. xanthorrhiza extract reduced the average number of tumors per mouse and the percentage of tumor-bearing mice in a multistage mouse skin carcinogenesis induced by DMBA and TPA. These results demonstrate that the methanol extract of C. xanthorrhiza possesses cancer chemopreventive potential.

In vivo anti-inflammatory and antinociceptive actions of some Lamium species

Ethnopharmacological relevance Several Lamium species have been used to relieve pain in arthritic ailments in Turkish folk medicine. Aim of the study To evaluate the anti-inflammatory and antinociceptive activities of different extracts prepared with methanol, dichloromethane, n-butanol and water from the aerial parts of some Lamium species of Turkish origin. Materials and methods Lamium eriocephalum subsp. eriocephalum, Lamium garganicum subsp. laevigatum, Lamium garganicum subsp. pulchrum and Lamium purpureum var. purpureum ( Lamiaceae); for the anti-inflammatory activity, carrageenan-induced hind paw edema model, PGE 2-induced hind paw edema model, and 12- O-tetradecanoyl-13-acetate (TPA)-induced mouse ear edema model and for the antinociceptive activity p-benzoquinone (PBQ)-induced writhing test in mice were employed. Results The n-butanol extracts of Lamium garganicum subsp. laevigatum (LGL-BuOH), Lamium garganicum subsp. pulchrum (LGP-BuOH), and Lamium purpureum var. purpureum (LPP-BuOH) exhibited notable inhibition (16.5–28.9, 14.5–26.9, 12.3–21.5%, resp.) in carrageenan-induced hind paw edema model at doses of 200 mg/kg without inducing any gastric damage. The LGL-BuOH (7.1–30.4%) and LGP-BuOH (5.9–24.1%) extracts also displayed potent anti-inflammatory activity against PGE 2-induced hind paw edema model. LGL-BuOH and LGP-BuOH were also found to exhibit remarkable antinociceptive activity in p-benzoquinone-induced abdominal constriction test at a dose of 200 mg/kg (25.0 and 24.3%, respectively). Conclusion The experimental data demonstrated that Lamium garganicum subsp. laevigatum and Lamium garganicum subsp. pulchrum displayed remarkable anti-inflammatory and antinociceptive activities.

Antinociceptive and Anti-inflammatory Activities of Seven Endemic Verbascum Species Growing in Turkey

The leaves, flowers, and whole aerial parts of Verbascum L. (Scrophulariaceae) species have been used to treat respiratory problems, eczema, and other types of inflammatory skin conditions in traditional Turkish medicine. Moreover, they have also been widely used as a folk medicine to produce a soothing and anti-inflammatory effect on the urinary tract. In order to evaluate their folkloric use, both antinociceptive and anti-inflammatory activities of seven endemic Verbascum species [V. chionophyllum Hub.-Mor., V. cilicicum Boiss., V. dudleyanum (Hub.-Mor.) Hub.-Mor., V. latisepalum Hub.-Mor., V. pycnostachyum Boiss. & Heldr., V. salviifolium Boiss., V. splendidum Boiss.] were investigated. Antinociceptive activity was investigated via p-benzoquinone–induced writhing test, and the anti-inflammatory activity was studied using carrageenan-induced hind paw edema, PGE2-induced hind paw edema, and 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced mouse ear edema models in mice. The methanol extracts of the flowers of V. chionophyllum and V. pycnostachyum, and the aerial parts of V. latisepalum and V. salviifolium, displayed significant antinociceptive and anti-inflammatory activity at 200 mg/kg oral dose without inducing any apparent acute toxicity or gastric damage. On the other hand, extracts from the rest of the species did not show any remarkable anti-inflammatory and antinociceptive activity. Results of the current study support the continued and expanded use of these plant species employed in Turkish folk medicine.

Anti-Inflammatory, Antinociceptive, and Sedating Effects of Lafoensia pacari. Aqueous Extract

The acetic acid–induced abdominal writhing, the tail flick, and the croton oil–induced mouse ear edema tests were used to study the anti-inflammatory effects of the aqueous extract from Lafoensia pacari. A. St.-Hil. (Lythraceae) stem bark. Pentobarbital-induced sleeping time was used to study the central nervous system depressant effect of the extract. The aqueous extract caused a dose-dependent inhibition of acetic acid–induced abdominal writhing and ear edema formation and produced a significant (p < 0.05) dose-related increase in the duration of sleep. The results suggest that Lafoensia pacari. stem bark contains compounds with anti-inflammatory, analgesic, and central depressant actions.

Valuation of anti-inflammatory and antinociceptive activities of Erica species native to Turkey

Erica L. species (Ericaceae) have been popularly used as antirheumatic, diuretic, astringent and treatment of urinary infections. In order to evaluate this information, anti-inflammatory and antinociceptive activities of different extracts prepared with methanol, chloroform, ethyl acetate, n-butanol and water from the aerial parts of Erica arborea L., Erica manipuliflora Salisb., Erica bocquetii (Peşmen) P.F. Stevens and Erica sicula Guss. subsp. libanotica (C.&W. Barbey) P.F. Stevens (Ericaceae) of Turkish origin were investigated by using in vivo methods. For the anti-inflammatory activity, carrageenan-induced hind paw edema model, PGE 2-induced hind paw edema model, and 12- O-tetradecanoyl-13-acetate (TPA)-induced mouse ear edema model and for the antinociceptive activity p-benzoquinone-induced writhing test in mice were employed. The ethyl acetate extracts of Erica arborea (EAE), Erica bocquetii (EBE) and Erica manipuliflora (EME) exhibited notable inhibition against carrageenan-induced (24.1–32.3%, 23.8–36.1%, 29.2–35.1%, respectively) and PGE 2-induced (21.2–37.7%, 6.8–29.7%, and 6.2–34.1%, respectively) hind paw edema as well as TPA-induced mouse ear edema models in mice, while the ethyl acetate extract of Erica sicula subsp. libanotica (ESE) (10.7–29.7%) displayed potent anti-inflammatory activity only on the PGE 2-induced hind paw edema model. However, the remaining extracts were found to be inactive against inflammatory models. Same extracts, i.e., EAE, EBE and EME were also found to exhibit remarkable antinociceptive activity in p-benzoquinone-induced abdominal constriction test at a dose of 100 mg/kg (46.5%, 27.7% and 36.3%, respectively).

Assessment of anti-inflammatory and antinociceptive activities of Daphne pontica L. (Thymelaeaceae)

The n-hexane, diethylether, ethyl acetate and methanol extracts from roots, leaves, stems and flowers with young leaves of Daphne pontica L. (Thymelaeaceae) were investigated for their in vivo anti-inflammatory and antinociceptive activities. For the anti-inflammatory activity assessment, carrageenan-induced hind paw edema, PGE 2-induced hind paw edema and 12- O-tetradecanoyl-13-acetate (TPA)-induced mouse ear edema models and for the antinociceptive activity, p-benzoquinone-induced abdominal constriction test were used. Only ethyl acetate extracts of the roots showed significant anti-inflammatory activity on carrageenan-induced (22.7–32.0% inhibition) and PGE 2-induced hind paw edema (3.2–27.3% inhibition) as well as 12- O-tetradecanoyl-13-acetate (TPA)-induced mouse ear edema (47.8–43.3% inhibition) models at 50 mg/kg dose without inducing any apparent gastric lesion or acute toxicity, whereas the other extracts were shown to be ineffective. In addition to roots, ethyl acetate extracts of the stems exhibited 19.5–29.9%; 5.3–23.9%; 36.6–28.1% inhibition on carrageenan-induced and PGE 2-induced hind paw edema as well as 12- O-tetradecanoyl-13-acetate (TPA)-induced mouse ear edema models, respectively. On the other hand, none of the extracts showed any significant antinociceptive activity.

Antimicrobial, Antinociceptive and Anti-inflammatory Activity Studies on Pseudevernia furfuracea

Lichens are a large group of organisms which are represented by approximately 18 000 species worldwide. Lichens form an interesting group of lower plants featuring algae and fungi symbiotically combined. Aliphatic, cycloaliphatic, aromatic and terpenic compounds were reported as their secondary metabolites. Lichens and their metabolits have some biological activities such as antimicrobial, antitumor, antioxidant, anti-inflammatory, analgesic and antipyretic, enzyme inhibiting and cytotoxic. Pseudevernia furfuracea (L.) Zopf (Parmeliaceae) is a common epiphytic lichen in the conifer-hardwood forest of Anatolia. This lichen is used in traditional medicine as a treatment for wound, eczema and hemorrhoids in Turkey. In the present study, methanolic extract from thallus of P. furfuracea and its fractions were investigated for its in vitro antimicrobial, and in vivo anti-inflammatory and antinociceptive activities. Significant antimicrobial activities were observed against Gram (+) microorganisms and Candida krusei. For the anti-inflammatory activity assessment, carrageenan-induced hind paw edema, 12-O-tetradecanoyl-13-acetate (TPA)-induced mouse ear edema and for the antinociceptive activity, p-benzoquinone-induced abdominal constriction tests were used. Methanolic extract of the plant was found to possess significant inhibitory activity on the carrageenan-induced hind paw edema model in mice whereas the other fractions did not show any activity. While CH2Cl2 and EtOAc fractions showed notable anti-inflammatory activity on carrageenan-induced hind paw edema model without inducing any apparent acute toxicity or gastric damage, these fractions did not show against 12-O-tetradecanoyl-13-acetate (TPA)-induced mouse ear edema model and antinociceptive activity. 2,4-dihydroxy-3,6-dimethyl-benzoic acid methyl ester (=atraric acid) [1], methyl hematommate [2], and methyl chlorohematommate [3] were isolated from the active fractions as the main compounds. The structures of 1–3 were elucidated by spectroscopical (NMR, MS) means.

Antiinflammatory activity of the aqueous leaf extract of Byrsocarpus coccineus

The antiinflammatory effect of the aqueous leaf extract of Byrsocarpus coccineus was evaluated using the carrageenan and egg albumin induced rat paw edema, xylene induced mouse ear edema and formaldehyde induced arthritis inflammation tests. The extract administered orally at doses of 50, 100, 200 and 400 mg/kg b.w produced a significant ( P < 0.05) dose dependent inhibition of edema formation in all four methods used. The results obtained suggest that the aqueous leaf extract of B. coccineus is endowed with effective antiinflammatory activity mediated via either inhibition of phospholipase A 2 (PLA 2) activity or cyclooxygenase cascade and by blocking the release of vasoactive substances (histamine, serotonin and kinins). These findings seem to justify the use of the plant in traditional African medicine in the treatment of inflammation, including arthritic conditions.

Anti-inflammatory and antinociceptive potential of Maclura pomifera (Rafin.) Schneider fruit extracts and its major isoflavonoids, scandenone and auriculasin

The aqueous, ethanolic and chloroform extracts and two prenylated isoflavones: scandenone ( I) and auriculasin ( II), isolated from the fruits of Maclura pomifera (Rafin.) Schneider, were investigated for their in vivo anti-inflammatory and antinociceptive activity. For the anti-inflammatory activity, both carrageenan-induced hind paw edema and 12- O-tetradecanoyl-13-acetate (TPA)-induced mouse ear edema models and for the antinociceptive activity, p-benzoquinone-induced abdominal constriction test were used. Scandenone, the chloroform and the ethanolic extracts were shown to possess antinociceptive activity and anti-inflammatory activity on carrageenan-induced hind paw edema model at 100 mg/kg dose. The same compound and the extract were also found to be highly active in (TPA)-induced mouse ear edema model whereas auriculasin and the H 2O extract showed to be inactive in all of the assays.

Anti-Inflammatory and Antiallergic Activityin vivoof LipophilicIsatis tinctoriaExtracts and Tryptanthrin

The effects of a supercritical CO2 (SFE) extract, a dichloromethane (DCM) extract from Isatis tinctoria leaf and the alkaloidal constituent tryptanthrin were studied in acute and subchronic experimental models of inflammation. The SFE and DCM extracts showed anti-inflammatory activity in the carrageenan-induced acute mouse paw oedema (ED50 values of 78 mg/kg and 165 mg/kg P. O., respectively) and in the acute tetradecanoylphorbol acetate (TPA)-induced mouse ear oedema in oral (62% and 32% oedema reduction at 100 and 125 mg/kg, respectively) and topical application (37% and 33% reduction of oedema at 0.5 mg/ear). In contrast, tryptanthrin showed no significant anti-inflammatory effect. The DCM extract inhibited oedema formation and neutrophil infiltration in subchronic inflammation in mice induced by repeated application of TPA. The extract showed activity after oral and topical administration by reducing the various parameters of the inflammatory response. The DCM extract (1 mg/ear) inhibited the delayed-type hypersensitivity (DTH) reaction induced by application of dinitrofluorobenzene (DNFB) after topical application. The response during the induction phase (24 h) was decreased by 48%, and the inflammatory phase (48 to 96 h) was reduced by 53 to 56%. The extract had no effect in this model when administered orally. The DCM extract (200 mg/kg P. O.) inhibited the acetic acid-induced writhing by 49%.

M.637 Menstrual cycle length and blood lipids in a cohort of mediterranean women

Although the expression of the prototypic secretory phospholipase A2 (sPLA2), group IIA (sPLA2-IIA), is known to be up-regulated during inflammation, it remains uncertain if other sPLA2 enzymes display similar or distinct profiles of induction under pathological conditions. In this study, we investigated the expression of several sPLA2s in rodent inflammation models. In lipopolysaccharide (LPS)-treated mice, the expression of sPLA2-V, and to a lesser extent that of sPLA2-IID, -IIE, and -IIF, were increased, whereas that of sPLA2-X was rather constant, in distinct tissues. 12-O-Tetradecanoylphorbol-13-acetate (TPA)-induced mouse ear edema, in which the expression of sPLA2-IID, -IIF and -V was increased, was significantly reduced by YM-26734, a competitive sPLA2-IIA inhibitor that turned out to inhibit sPLA2-IID, -IIE, -V and -X as well. In contrast, sPLA2-IIA was dominant in carageenin-induced pleurisy in rats, where the accumulation of exudate fluids and leukocytes was significantly ameliorated by YM-26734. These results indicate that distinct sPLA2s can participate in inflammatory diseases according to tissues, animal species, and types of inflammation.

Synthesis and anti-inflammatory activity of fructigenine a derivatives

Several derivatives were synthesized from fructigenine A, which was isolated fromPenicillium fructigenum. The anti-inflammatory properties of fructigenine A was evaluatedin vivo with a 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced mouse ear edema model and a carrageenan-induced rat paw edema model. Results showed that the anti-in flammatory activity was significantly higher with fructigenine derivatives than with indomethacin, which was used as a standard. We concluded that fructigenine derivatives could exert an anti-inflammatory effect.

Taraxer-14-en-3beta-ol, an anti-inflammatory compound from Sterculia foetida L.

Taraxer-14-en-3beta-ol ( 1) was shown to be the active ingredient in the leaves of Sterculia foetida L. The alcohol 1, its acetate and ketone showed anti-inflammatory activity against TPA induced mouse ear oedema with inhibition ratios of 60.0, 58.57 and 40.57 at 0.5 mg/ear, respectively. The percentage inhibition of inflammation increased with dose for each compound.

Induction of distinct sets of secretory phospholipase A 2 in rodents during inflammation

Although the expression of the prototypic secretory phospholipase A 2 (sPLA 2), group IIA (sPLA 2-IIA), is known to be up-regulated during inflammation, it remains uncertain if other sPLA 2 enzymes display similar or distinct profiles of induction under pathological conditions. In this study, we investigated the expression of several sPLA 2s in rodent inflammation models. In lipopolysaccharide (LPS)-treated mice, the expression of sPLA 2-V, and to a lesser extent that of sPLA 2-IID, -IIE, and -IIF, were increased, whereas that of sPLA 2-X was rather constant, in distinct tissues. 12- O-Tetradecanoylphorbol-13-acetate (TPA)-induced mouse ear edema, in which the expression of sPLA 2-IID, -IIF and -V was increased, was significantly reduced by YM-26734, a competitive sPLA 2-IIA inhibitor that turned out to inhibit sPLA 2-IID, -IIE, -V and -X as well. In contrast, sPLA 2-IIA was dominant in carageenin-induced pleurisy in rats, where the accumulation of exudate fluids and leukocytes was significantly ameliorated by YM-26734. These results indicate that distinct sPLA 2s can participate in inflammatory diseases according to tissues, animal species, and types of inflammation.

Synthesis and structure-activity relationships of cis-tetrahydrophthalazinone/pyridazinone hybrids: a novel series of potent dual PDE3/PDE4 inhibitory agents.

In this study, the synthesis and in vitro and in vivo pharmacological investigations of a new series of phthalazinone/pyridazinone hybrids with both PDE3 and PDE4 inhibitory activities are described. These compounds combine the pharmacophores of recently discovered 4a,5,8,8a-tetrahydro-2H-phthalazin-1-one-type inhibitors of PDE4 and the well-known 2H-pyridazin-3-one-type PDE3 inhibitors such as the tetrahydrobenzimidazoles. Most of the synthesized compounds are pharmacologically spoken PDE3/PDE4 hybrids. All hybrids show potent PDE4 inhibitory activity (pIC(50) = 7.0-8.7), whereas the pIC(50) values for inhibition of PDE3 vary from 5.4 to 7.5. In general, analogues with a 5-methyl-4,5-dihydropyridazinone moiety exhibit the highest PDE3 inhibitory activities. The highest in vivo antiinflammatory activity is displayed by phthalazinones 43 and 44 showing, at a dose of 30 micromol/kg po, 46% inhibition of arachidonic acid (AA) induced mouse ear edema. No correlation was found between the in vitro PDE3 and/or PDE4 inhibitory activity and the in vivo antiinflammatory capacity after oral dosing.

Novel selective phosphodiesterase (PDE4) inhibitors. 4. Resolution, absolute configuration, and PDE4 inhibitory activity of cis-tetra- and cis-hexahydrophthalazinones.

Recently, we reported that 4-catechol-substituted cis-(+/-)-4a,5,6,7,8,8a-hexa- and cis-(+/-)-4a,5,8,8a-tetrahydro-2H-phthalazin-1-ones show potent inhibition of phosphodiesterase (PDE4) activity, while the corresponding trans racemic mixtures exhibit only weak to moderate activity. To determine the absolute configuration and PDE4 inhibitory activity of the individual cis-enantiomers, several optically active phthalazinones have been synthesized. The enantiomers of the various gamma-keto acids, used as starting materials, were resolved in a classical way by the formation of diastereomeric salts, and each was converted to optically active phthalazinone in an enantioselective manner. The absolute configuration of the (+)-enantiomer of cis-hexahydrophthalazinone (+)-12 was determined by X-ray crystallography. The carbon atoms at the 4a and 8a positions were found to have the S- and R-configuration, respectively. In the present series of hexa- and tetrahydrophthalazinones, stereoselectivity for PDE4 inhibition is observed; the cis-(+)-enantiomers of the phthalazinones display high inhibitory activity, whereas their (-)-counterparts exhibit only weak to moderate activity. It is likely that all cis-(+)-phthalazinones have a (4aS,8aR)-configuration and vice versa for the cis-(-)-analogues. In the current series, the N-adamantan-2-yl analogue (+)-14 shows the most potent inhibition of PDE4 (pIC(50) = 9.3); the corresponding (-)-enantiomer is 250-fold less active. In addition, the N-substituted tetrahydrophthalazinones under study were investigated for their in vivo antiinflammatory activities by examining the suppression of arachidonic acid (AA) induced mouse ear edema formation. In this assay analogues (+)-14 and (+)-15 were found to be potent antiinflammatory agents showing about 50% inhibition at 30 micromol/kg po.