Anti-inflammatory agent triterpenes

Widespread reports indicate that, in addition to their anti-inflammatory role, triterpenes have other activities. Triterpenoids have been found to possess cytotoxic, antimicrobial and interesting effects on metabolism. Triterpenoids with antitumour activity include oleanane, lanostane, lupane, friedelane, hopane and quassionoid types. Glycyrrhetinic acid has been described as an antiviral, hypolipidemic and anti-atherosclerotic agent. Cucurbitacins B and E, and oleanolic acid possess a potent protective action on the liver, and ganoderic acid and its derivatives have been shown to be inhibitors of cholesterol biosynthesis. Lanostane derivatives, like suberosol, have also been found to inhibit HIV replication in H9 lymphocytes [1,3]. 

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 D C-friedooleanane triterpene type is the main kind of compound contained in the seeds of Trichoscmthes kirilomi (Cucurbitaceae) a species employed in Chinese medicine as an anti-inflammatory agent. Some of the isolated compounds were evaluated for their topical anti-edematous activity against TPA-induced inflammation in mice. 3-Epikarounidiol, 7-oxoisomultiflorenol and 3-epibryonolol gave ID50 ranging from 0.2 to 0.6 mg/ear, and these values approach that of karounidiol 3-O-benzoate. In any case, the anti-inflammatory potency of these triterpenes was lower than that of hydrocortisone [85]. 

A study was recently undertaken [90] to enlarge our understanding of the mechanism of action of triterpenes as topical anti-inflammatory agents... 

Most saponins have a bitter taste, but some sweet saponins are known as well. Glycyrrhizic acid from licorice root (Glycyrrhiza glabra), a P-amyrine type triterpene linked to two molecules of glucuronic acid (Fig. 33), is 50 times sweeter than sucrose (table sugar). Licorice extracts are used to prepare candies (licorice) and as a sweetener. They are also used as mild expectorant and as anti-inflammatory agent. The anti-inflammatory effect is caused by inhibition of an enzyme that inactivates cortisol. On the other hand, this may also lead to side effects such as sodium retention, excretion of potassium, water retention and increased blood pressure. 

The fruits, kernel and leaves of loquat are all used for medicinal purpose. The leaf of loquat is a well known Traditional Chinese Medicine used as anti-tussive and anti-inflammatory agent for acute and chronic bronchitis. Phytochemical studies 1-5) with this species have led to the isolation of many natural products including flavonoids, triterpenes and sesquiterpene glycoside. Some of the components have been found to have antioxidant (2), antiviral (4), cytotoxic (/) and hypoglycemic (5) properties. In the course of ongoing search for anti-tussive and anti-inflammatory components from this plant, an ethanolic extract of the leaves of . japonica was examined. We report here the isolation and structural determination of three new components as well as seventeen known compounds. 

Several examples of bioassay-guided isolation are given in the literature. Recio et al [47] used a topical irritant agent to track the activity during the isolation of the anti-inflammatory triterpenes from Diospyros leucomelas, whereas Cuellar et al. [48] employed a combined system of in vivo and in vitro experiments, consisting of the inhibition of an enzyme activity Fig. (1) . Other authors prefer in vitro models. Ammon and Safayhi [49] used the inhibition of leukotriene formation in rat peritoneal neutrophils to isolate the boswellic acids of gum resin exudate of Boswellia serrata, whereas Takaishi et al. [42] studied the inhibition of interleukin-1 secretion, and Jain et al. [50] studied the in vitro inhibition of phospholipase A2 activity. The main results of these studies are summarised in the pharmacological activity section of this chapter. 

The triterpene sapogenins betulinic acid, oleanolic acid and ursolic acid show cytotoxic and anti-inflammatory effects, and based on their structures novel chemopreventive and anticancer agents are being developed (Liby et al., 2007). A derivative of betulinic acid, beviri-mat, is the first member of a new class of anti HIV therapeutics, maturase inhibitors. These... 

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