Samples of the expressed fixed oil from different sources of Nigella sativa seeds were examined by thin-layer and gas chromatography for content of fixed oils and thymoquinone, and these substances were tested as possible inhibitors of eicosanoid generation and membrane lipid peroxidation. The crude fixed oil and pure thymoquinone both inhibited the cyclo-oxygenase and 5-lipoxygenase pathways of arachidonate metabolism in rat peritoneal leukocytes stimulated with calcium ionophore A23187, as shown by dose-dependent inhibition of thromboxane B₂ and leukotriene B₄, respectively. Thymoquinone was very potent, with approximate IC₅₀ values against 5-lipoxygenase and cyclo-oxygenase of <1 µg/ml and 3.5 µg/ml, respectively. Both substances also inhibited non-enzymatic peroxidation in ox brain phospholipid liposomes, but thymoquinone was about ten times more potent. However, the inhibition of eicosanoid generation and lipid peroxidation by the fixed oil of N. sativa is greater than is expected from its content of thymoquinone (ca. 0.2% w/v), and it is possible that other components such as the unusual C20:2 unsaturated fatty acids may contribute also to its anti-eicosanoid and antioxidant activity. These pharmacological properties of the oil support the traditional use of N. sativa and its derived products as a treatment for rheumatism and related inflammatory diseases.

The pentacyclic triterpene lupeol has been studied for its inhibitory effects on murine models of inflammation and peritoneal macrophage functions in-vitro. Lupeol (0.5 and 1 mg/ear) administered topically suppressed the mouse ear oedema induced by 12-O-tetradecanoyl-phorbol acetate (TPA), being less effective on ear oedema induced by arachidonic acid. Quantitation of the neutrophil specific marker myeloperoxidase demonstrated that its topical activity was associated with reduction in cell infiltration into inflamed tissues. When tested in-vitro, lupeol significantly reduced prostaglandin E2 (PGE2) production from A23187-stimulated macrophages, but failed to affect leukotriene C4 release. It was a weak inhibitor of nitrite release, but dose-dependently suppressed PGE2. Cytokine production (tumour necrosis factor-α and interleukin-1β) was inhibited in the range 10–100 μm in lipopolysaccharide-treated macrophages. This study demonstrated that lupeol possessed anti-inflammatory activity which was likely to depend on its ability to prevent the production of some pro-inflammatory mediators.

Natural products play a significant role in human health in relation to the prevention and treatment of inflammatory conditions. Among them, terpenoids (also referred to as terpenes), are the largest and most widespread class of secondary metabolites. They are found in higher plants, mosses, liverworts, algae and lichens, and also in insects, microbes or marine organisms. Some terpenoids have been used for therapeutic purposes for centuries as antibacterial, antiinflammatory, antitumoral agents, and in recent decades research activity into the clinical potential of this class of compounds has increased continuously as a source of pharmacologically interesting agents. In the present review, molecular basis of the anti-inflammatory action of diterpenoids is presented with special emphasis on their ability to modulate critical cell signaling pathways involved in the inflammatory response of the body such as nuclear transcription factor-kappaB (NF-κB) activation. NF-κB plays an important role in the regulation of immune and inflammatory responses. Indeed, deregulated NF-κB expression is a characteristic phenomenon in several inflammatory diseases and NF-κB has become a major target in drug discovery. Hence, this article also introduces our recently elucidated findings about the potential of labdane diterpenoids as anti-inflammatory agents due to their ability to inhibit NF-κB. The future development of this class of compounds as anti-inflammatory drugs requires the introduction of novel molecular targets of therapeutic relevance in addition to biotechnological approaches for the production of these molecules.

A sterol fraction composed of campesterol (7.6%), stigmasterol (28.4%) and beta-sitosterol (61.1%) was obtained by activity-guided fractionation of the acetone extract of Sideritis foetens Clem. This sterol fraction showed anti-inflammatory activity in in vivo murine models of inflammation. It decreased carrageenan paw oedema in mice after oral administration of 30 and 60 mg/kg and inhibited mouse ear oedema induced by 12-O-tetradecanoylphorbol acetate (TPA) after topical application. Quantitation of the neutrophil specific marker myeloperoxidase (MPO) demonstrated that its topical anti-inflammatory activity was associated with reduction in neutrophil infiltration into inflamed tissues. Non-cytotoxic concentrations of the sterol fraction inhibited leukocyte granular enzyme release (beta-glucuronidase) and superoxide generation. However, it did not shown any significant inhibitory effect on histamine release from mast cells. In vitro modulatory activity towards the classical pathway of the complement system shown by this fraction would correlate with the anti-inflammatory profile shown in vivo.

The anti-inflammatory activity of abietic acid, a diterpene isolated from Pimenta racemosa var. grissea (Myrtaceae), was evaluated in-vivo and in-vitro. This compound significantly inhibited rat paw oedema induced by carrageenan in a time- and dose-dependent manner, and mouse ear oedema induced by 12-O-tetradecanoylphorbol acetate, after oral or topical administration. The inhibition of myeloperoxidase enzyme showed that its topical activity was influenced by neutrophil infiltration into the inflamed tissues (ears). In addition, the effect of abietic acid on some macrophage functions was analysed in-vitro. Non-toxic concentrations of abietic acid inhibited prostaglandin E2 (PGE2) production in lipopolysaccharide-treated macrophages, whereas nitrite, tumour necrosis factor α and interleukin-1β production were only weakly affected by this diterpene. PGE2 production from A23187-stimulated macrophages was only inhibited at high doses (100 μM) and it failed to modify leukotriene C4 production. These results indicate that abietic acid exerts in-vivo anti-inflammatory activity after oral or topical administration and has partial ability to prevent the production of some inflammatory mediators.