TPA-induced inflammation

Classical examples of anti-inflammatory Asteraceae are Arnica montana and Calendula officinalis, both used in European medicine to treat bruises and contusions. There is an expanding body of evidences to suggest that Asteraceae could be a useful source of anti-inflammatories, such as sesquiterpene lactones and/or triterpene alcohols, the latter being known to inhibit 12-O-tetra-decanoylphorbol-13-acetate (TPA)-induced inflammation in mice as efficiently as commercial indomethacine by possible inhibition of phospholipase A2 (10). 

The inhibitory effects of the sterols and triterpenoids on TPA-induced inflammatory ear edema in mice are shown in Table 2. The inhibitory effects of three reference compounds, quercetin (4), a known inhibitor of TPA-induced inflammation in mice, and of two commercially available anti-inflammatory drugs, indomethacin (5) and hydrocortisone (6), were included for comparison. As is evident from Table 2, most of the compounds examined exhibited activity almost equivalent to or higher than quercetin (4). Inhibitory effects on the other experimental models were also included in Table 2. 

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]. 

It has been reported that karounidiol and 7-oxo-dihydrokarounidiol have an inhibitory effect on TPA-induced inflammation [86]. Topically applied, they completely inhibited edema generation in a dose-dependent manner. The ID5o of karounidiol and 7-oxo-dihydrokarounidiol were 0.4 and 0.3 mg/ear, respectively. 

The MeOH extract of Rosmarinus officinalis (Lamiaceae) contains 16-20% of ursolic acid. Both the extract and the pure triterpene isolated from it were strong inhibitors of TPA-induced inflammation, ornithine decarboxylase (ODC) activity and tumour promotion in mouse skin. Some authors have suggested that the effects could be related to those of... 

Like many other antioxidants, rosemary and its polyphenols possess not only antioxidative activities, but also antitumorigenic activities. Huang et al. (5) investigated the inhibitory effects of rosemary extract, carnosol and ursolic acid on tumor formation in mouse skin. They found that topical application of rosemary inhibits B(a)P- and DMBA-induced initiation of tumor and TPA-induced tumor promotion in DMBA-initiated mice. Carnosol and ursolic acid were found to be strong inhibitors of TPA-induced inflammation, ornithine decarboxylase activity and tumor promotion in mouse skin (5). It was suggested that carnosol acted like other nonsteroidal phenolic anti-inflammatory agents, such as curcumin, which inhibited the metabolism of arachidonic acid. 

In humans, chronic inflammation of the liver is associated with hepatitis B virus (HBV) infections, and this inflammation is considered an important contributing event in HBV-induced liver cancer. In animal models, there is evidence that inflammation contributes to tumor promotion. Treatment of mouse skin with TPA produces an inflammatory response and increases the expression of proinflammatory mediators such as TNF-a, IL-la GM-CSF, and cyclooxygenase-2 (COX-2). Genetically modified mice deficient in TNFa or COX-2 are resistant to TPA-induced tumor promotion. These results indicate that the inflammatory effects of TPA are important in tumor promotion. 

Carragenin-induced paw edema and 12-0-tetradecanoylphorbol 13-acetate (TPA)-induced edema have been used as experimental models of acute inflammation. Gomisin A (49), gomisin J (140), and wuweizisu C (141) inhibited inflammation induced by TPA in mice [44], Diphyllin acetyl apioside (142) and diphyllin apioside (tuberculatin) (143) also showed an anti-inflammatory effect with IDjg values of 0.27 and 1.23 pM/ ear, respectively, in rabbit [98]. 

LaHann TR (1986). Effect of capsaicin on croton oil and TPA induced carcinogenesis and inflammation. J West Pharmacol Soc, 29, 145-149. 

Effect of theaflavin mixture on TPA-induced ear inflammation and levels of inflammatory mediators in female CD-I mice... 

The anti-inflammatory activity of the hydroalcoholic extract of P. cocos against some acute and chronic inflammatory processes was established recently. It reduced the TPA-induced edema (80% inhibition at 0.5 mg/ear), but its effect was milder against the AA-induced ear edema (40% inhibition at 0.5 mg/ear). When the extract was assayed in chronic experimental model of inflammation, it caused a 53% reduction in ear thickness together with a 73% decrease in myeloperoxidase (MPO) activity, which shows that leukocyte infiltration into the inflammation site could be prevented by a repeated dose of 1 mg/ear. The main constituents isolated from the extract were identified as pachymic and dehydrotumulosic acids. Topical administration of these lanostanes inhibited the TPA-induced edema with ID50 of 2.48 and 0.31 pg/ear, respectively. Reasons for the greater activity of dehydrotumulosic acid... 

Lonicera implexa Inflammation Loganic acid Anti-Inflammatory (p.o.) against carrageenan-induced mouse paw edema and (p.t.) against TPA-induced mouse ear edema Active 130]... 

From the methanol extract of Haplophyllum hispanicum (Rutaceae) two topical anti-inflammatory aryl naphthalide lignans were isolated and identified as diphyllin acetyl apioside and tuberculatin [284], The methanol extract was only active against the acute TPA-induced ear edema, whereas it was not active against the chronic inflammation induced by TPA or oxazolone-induced contact-delayed hypersensitivity in mouse ears. Diphyllin acetyl apioside was the most active of the isolated compounds on the acute TPA, with an ID50 of 0.27 pmol/ear, whereas tuberculatin gave an ID50 of 1.23 pmol/ear. 

When the rosemary extract was administered (i.g.) at lOOmg/kg/day for 5 consecutive days, the number and area of diethylnitrosamine-induced GST placental-form-positive (GST-P) hepatocellular foci were reduced in male F344 rats. A methanol extract of the leaves of rosemary was evaluated for its effects on tumor initiation and promotion in mouse skin carcinogenesis. Topical apphcation of the rosemary extract to mouse skin attenuated the covalent binding of BaP to epidermal DNA and inhibited tumor initiation by BaP and DMBA. Application of rosemary to mouse skin also inhibited TPA-induced ODC activity, inflammation, hyperplasia, and tumor promotion. Likewise, topical application of camosol or ursolic acid isolated from rosemary inhibited TPA-induced ear inflanunation, ODC activity, and tumor promotion. ... 

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