Triterpene, anti-inflammatory activity

ABSTRACT This chapter reviews the natural triterpenes with anti-inflammatory activity, including the traditional ones and the new compounds isolated over the last six years. 

The root of the Bupleurum species has been used in China as a traditional remedy for inflammatory diseases [20]. The main constituents of this drug are oligoglycosides of oleanane triterpenes called saikosaponin a-f. Saikosaponins cause a reduction in histamine secretion and enhance the anti-inflammatory actions of glucocorticoids [22]. Some of them have been shown to inhibit prostaglandin E2 production in the macrophage culture system [23]. It has recently been reported that the saikosaponins present in Heteromorpha trifoliata, which are structurally related to those of Bupleurum falcatum (saiko in Japanese), have anti-inflammatory activity. One in vivo study concluded that the isolated saikosaponins act by a mechanism close to that of steroids, but do not involve the glucocorticoid receptor [24]. 

To isolate active compounds it is necessary to monitor the activity during fractionation and isolation. In the case of triterpenes as anti-inflammatory agents, different kinds of tests are employed. Subplantar administration of carrageenan in rats was commonly used in earlier studies to establish the anti-inflammatory activity of orally administered plant extracts or fractions, but a large amount of sample was necessary. Topical application of inflammatory agents is more useful in screening extracts and pure compounds, because the amount of sample is smaller than with oral application and it is easier to track the activity. The introduction of in vitro tests could be an alternative way to monitor the anti-inflammatory activity. 

In the last few years, interest in triterpenes as anti-inflammatory agents and their mechanisms of action has also increased greatly. Oleanolic acid and ursolic acid have been recognised to have anti-inflammatory activity in carrageenan-induced paw edema in rats or mice, adjuvant-induced arthritis in rats, etc. Oleanolic acid, in addition, was able to suppress the delayed hypersensitivity reaction in mice induced by dinitrochlorobenzene (DNCB). These effects are attributable to different mechanisms of action ranging from the inhibition of histamine release to inhibition of complement activity [1,58]. 

The triterpene-enriched fraction of the supercritical CO2 extract of the dried flowers of Calendula officinalis (Asteraceae) inhibited the croton oil-induced ear edema in mice. Of the identified compounds, the faradiol monoesters, lupeol, F-taraxasterol and a mixture of taraxasterol/ 5-amyrin were tested for their anti-inflammatory activity. Faradiol, obtained by hydrolysis of the extract, was the most active compound. It showed a dose-dependent effect with a potency that equals that of indomethacin at 0.14 fimol/cm2 (48% and 47% edema inhibition, respectively). The esterification of faradiol resulted in a reduction of more than 50% in the activity (only 31% inhibition was observed at 0.14 pmol/cm2), whereas 4/-taraxasterol, a C-16P dehydroxylated derivative of faradiol, was less active (47% inhibition at a dose of 0.28 pmol/cm2) [43]. 

Yasukawa et al. [84] demonstrated the anti-inflammatory activity of some sterols and triterpenes on the TPA-induced ear edema test in mouse. Among them, karounidiol 3-O-benzoate, a D C-friedooleanane triterpene, showed an interesting inhibitory effect (95%) of the edema formation at a dose of 2 mg/ear its ID50 was 0.4 pmol/ear. 

In a bioassay-oriented fractionation of Calendula officinalis flower extracts, the most potent anti-inflammatory activity was found to he in the free triterpenes, rather than the saponins. While several active triterpenes were identified, the most active was faradiol monoester (Della Loggia et al. 1994). 

Anti-inflammatory and antiarthritic activities have been established in vitro and in the carrageenan-induced paw edema test, in arthritic rats and in dogs with inflammatory joint and spinal disease. The anti-inflammatory activity is apparently mediated through inhibition of TNF-a, IL-ip, NO, MAPK, and 5-LO, as well as P-selectin-mediated recruitment of inflammatory cells. Earlier clinical trials in India have been conducted on arthritis patients with positive results, and boswellic acid and other related pentacycUc triterpene acids are marketed as antiarthritic drugs in India. More recent trials have demonstrated the efficacy of olibanum prepara-... 

A P. cocos preparation, a hydroalcoholic extract, as well as some of the triterpene acids displayed anti-inflammatory activities in different in vivo models. Polysaccharides isolated from P. cocos were found to induce NF-kB and nitric oxide production, as well as iNOS expression. ... 

The triterpenes of R. rugosa have antinociceptive and anti-inflammatory properties in mice and rats. Anti-inflammatory activity was also displayed by a galactolipid isolated from R. canina. Preparations made from the powdered rose hips were effective in reducing the painful symptoms of knee and hip osteoarthritis in human patients. ... 

The structure-activity relation of triterpene QMs on the anti-inflammatory effect has been investigated with a series of analogues by comparing inhibition of the IL-1 (3 production in the LPS-induced monocytes.93-94 Clearly, the conjugated QM structure with alkenes is essential for the observed inhibition, and similar inhibitory effect was found with derivatives that are capable to form the conjugated QM through hydrolysis and/or oxidation.93-94 Also, the presence of the E ring in the triterpene QM structure is an additional contributor. 

Mentha piperita subsp. citrata Briq. -horteia Tranquilizer Branch (infusion, ingested) Caboclos [57] Essential oils [138,139] flavonoid glycosides [140,141] menthol [142] menthofurolactone [143,144] pyridine-derivatives [145] mintlactone [146] flavones [147] triterpenes [148] terpenoids [149] sesquiterpenic hydrocarbons [150] menthofuran [151,152], Antimicrobial and antioxidant activities [138,265] antiallergic effect [140] anti-nociceptive and anti-inflammatory effects [266]... 

A wide range of biological activities has been described for triterpenes and nor-triterpene quinonemethides. These include anti-inflammatory, anti-hyperlipidemic, antitumour-promotion, hepatoprotective, anti-ulcer, anti-microbial and hypoglycemic activitiy, among others [16,35]. Among the compound mentioned previously in this review, antitumour-promotion, anti-inflammatory, inmunosuppressive, anti-tumour, insecticide and anti-AIDS activities were found and are described below. 

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