TPA induced edema

FIGURE 2.2 Inhibitory effects of CS on TPA-induced edema and expression of VCAM-1 and COX-2 in mouse skin. Mice were treated topically with TPA (200 pL of 10 nmol of TPA dissolved in acetone) in the presence or absence of CS (1 or 2mg). Control animals were treated with acetone alone. (A) Skin section was stained with hematoxylin and eosin (original magnification, xlOO bar, 100 pm) (B) thickness of the skin (the thickness of the ear of each mouse was determined by averaging the values measured at five independent... 

Assays for the inhibition of croton oil-induced edema, teleosidin-induced edema, and 12-0-tetradecanoylphorbol-13-acetate (TPA)-induced edema in animals are used as rapid in vivo preliminary tests for screening antitumor-promoting substances [1],... 

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]. 

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... 

Figure 8 Illustration of inhibitory test of TPA-induced edema formation in mouse ears (A) and anti-inflammatory activities of nobiletin and indomethacin toward TPA-induced edema formation in ICR mouse skin (B). Five 7-week-old mice were used in each experiment. The test compound (810 nmol/20 pL in acetone) or acetone was...

Dibenzoylmethane (DBM) is a minor constituent of licorice and an analogue of curcumin. We previously reported that feeding 1% DBM in the diet strongly inhibited 7,12-dimethylbenzyla[a]anthracene (DMBA)-induced mammary tumorigenesis and formation of leukemias/lymphomas in Senear mice). In this report, we show that topical application of DBM to the backs of mice inhibited chemical- and ultraviolet light (UV)-induced inflammation, sunburn lesions, and formation of skin tumors in mice. Topical application of DBM inhibited TPA-induced edema of mouse ears and skin tumor promotion in CD-I mice in a dose-dependent manner. Topical application of 3 - 10 pmol DBM with 5 nmol TPA twice weekly for 16 weeks in CD-I mice previously treated with DMBA inhibited the number of skin tumors per mouse by 65 - 93%, and percent of mice with tumors was inhibited by 29 - 50%.. Topical application of 10 pmol DBM with mirex (a non-TP A type tumor promoter) 3 times a week for 18 weeks in... 

Anti-inflammatory activity of DBM was evaluated the ability of DBM to inhibit TPA-induced edema of mouse ear (Table I). Topical application of 1 nmol of TPA to mouse ear (24-26 days old) rapidly induced edema of mouse ear. Five hours after TPA application, the average weight of ear punches was increase from an average of 6.8 mg/punch (acetone control group) to 14.2 mg per punch (TPA-treated group). Topical application of DBM at 0.1, 0.3 or 1 pmol of DBM with 1 nmol TPA inhibited TPA-induced ear edema by 39, 45, or 71% respectively. DBM inhibited TPA-induced ear edema in a dose-dependent manner. 

Table I. Inhibitory Effect of DBM on TPA-induced Edema of Mouse Ear...

ZO095 Okuyama, T., M. Matsuda, Y. Masuda, et al. Studies on cancer bio-chemo-prevention of natural resources. X. Inhibitory effect of spices on TPA-en-hanced H-choline incorporation in phospholipid of C3H10T1/2 cells and on TPA induced ear edema. Zhonghua Yaoxue Zazhi 1995 47(5) 421-430. 

Assay for Iinhibition of TPA-induced Inflammatory Ear Edema in Mice... 

For screening antitumor-promoting agents, we used TPA-induced inflammatory ear edema in mice [Fig.(2)] [36,37,48]. TPA (lpg/ear) dissolved in acetone (20 pi) was applied to the right ear of ICR mice by means of a micropipette. A volume of 10 pi was delivered to both the inner and outer surfaces of the ear. The samples or their vehicles, methanol-chloroform-water (2 1 1,20 pi) or chloroform (20 pi), as control, were applied topically about 30 min before TPA treatment. For ear... 

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. 

Among five triterpenoids isolated from Calendula officinalis flowers, P-amyrin (119), faradiol (232), i /-taraxasterol (238), taraxasterol (239), and lupeol (238), the diol 232 was the most active. It showed a dose-dependent effect with a potency that equals that of indomethacin (5) in the topical anti-inflammatory assay with croton oil [33]. Esterification at C-3 of 232 with a fatty acid reduced the activity by more than 50% [33] consistent with our observation in the TPA-induced assay described above. The anti-inflammatory properties, as determined by croton oil-induced edema of mouse ear, of faradiol-3-O-myristate (233) and its 3-O-palmitate (234), the main components of lipophilic extracts of C. officinalis flowers, were shown to be contribute significantly to the pronounced antiphlogistic activity of the lipophilic extracts of C. officinalis flowers [34]. 

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. 

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. 

Numerous iridoids are involved in plant-animal interactions e.g. the defensive function of this type of compounds in ants. From the pharmacological standpoint, the applications of this class of compounds are rather limited. Some iridoids have anti-inflammatory activity, which is weak by the oral route and stronger by topical application e.g. 1 mg of aucubin, verbenalin, or loganin have an activity almost similar to that of 0.5 mg of indomethacin on the TPA-induced mouse ear edema. Some are ingredients in various forms of allopathic medications (valerian), others are typically, phytotherapeutic products (devil s claw, olive tree). Others receive attention for their non-pharmaceutical applications (yellow gentian). The hepatoprotective effects of picrosides I and II from kutkin, the crude active fraction in Picrorhiza kurroa is well known and documented. 

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