Chemoprevention has come of age as an effective cancer control modality; however, the search for novel agent(s) for the armamentarium of cancer chemoprevention continues. We argue that agents capable of intervening at more than one critical pathway in the carcinogenesis process will have greater advantage over other single-target agents. Pomegranate fruit extract (PFE) derived from the tree Punica granatum possesses strong antioxidant and antiinflammatory properties. Pomegranate fruit was extracted with acetone and analyzed based on matrix-assisted laser desorption/ionization time-of-flight mass spectrometry and found to contain anthocyanins, ellagitannins and hydrolyzable tannins. We evaluated whether PFE possesses antitumor-promoting effects. We first determined the effect of topical application of PFE to CD-1 mice against 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced conventional markers and other novel markers of skin tumor promotion. We found that topical application of PFE (2 mg/mouse) 30 min prior to TPA (3.2 nmole/mouse) application on mouse skin afforded significant inhibition, in a time-dependent manner, against TPA-mediated increase in skin edema and hyperplasia, epidermal ornithine decarboxylase (ODC) activity and protein expression of ODC and cyclooxygenase-2. We also found that topical application of PFE resulted in inhibition of TPA-induced phosphorylation of ERK1/2, p38 and JNK1/2, as well as activation of NF-kappaB and IKKalpha and phosphorylation and degradation of IkappaBalpha. We next assessed the effect of skin application of PFE on TPA-induced skin tumor promotion in 7,12-dimethylbenz(a)anthracene-initiated CD-1 mouse. The animals pretreated with PFE showed substantially reduced tumor incidence and lower tumor body burden when assessed as total number of tumors per group, percent of mice with tumors and number of tumors per animal as compared to animals that did not receive PFE. In TPA-treated group, 100% of the mice developed tumors at 16 weeks on test, whereas at this time in PFE-treated group, only 30% mice exhibited tumors. Skin application of PFE prior to TPA application also resulted in a significant delay in latency period from 9 to 14 weeks and afforded protection when tumor data were considered in terms of tumor incidence and tumor multiplicity. The results of our study provide clear evidence that PFE possesses antiskin-tumor-promoting effects in CD-1 mouse. Because PFE is capable of inhibiting conventional as well as novel biomarkers of TPA-induced tumor promotion, it may possess chemopreventive activity in a wide range of tumor models. Thus, an in-depth study to define active agent(s) in PFE capable of affording antitumor-promoting effect is warranted.

https://onlinelibrary.wiley.com/doi/pdf/10.1002/ijc.20587

Anthocyanin‐ and hydrolyzable tannin‐rich pomegranate fruit extract modulates MAPK and NF‐κB pathways and inhibits skin tumorigenesis in CD‐1 mice

Chemoprevention has become an effective cancer control modality; however, the search for novel agent(s) for the armamentarium of cancer chemoprevention continues We argue that agents capable for inhibition of promotion stage of tumorigenesis with the ability to intervene at several critical pathways in the tumorigenesis process will have greater advantage over other single-target agents Lupeol, a triterpene, is the principal constituent of common fruit plants such as olive, mango, fig and medicinal herbs that have been used to treat skin aliments Lupeol has been reported to possess a wide range of medicinal properties that include strong antioxidant, antimutagenic, anti-inflammatory and antiarthritic effects In the present study, we show that Lupeol possesses antitumor-promoting effects in a mouse skin tumorigenesis model We first determined the effect of topical application of Lupeol to CD-1 mouse against 12-O-tetradecanoyl-phorbol-13-acetate (TPA)-induced conventional markers and other novel markers of skin tumor promotion We found that topical application of Lupeol (1–2 mg/mouse) 30 min prior to TPA (32 nmol/mouse) application onto the skin of CD-1 mice afforded significant inhibition, in a time- and dose-dependent manner, against TPA-mediated increase in (i) skin edema and hyperplasia, (ii) epidermal ornithine decarboxylase (ODC) activity, and (iii) protein expression of ODC, cyclo-oxygenase-2 and nitric oxide synthase As of the role of nuclear factor kappa B (NF-κB) and phosphatidyl inositol 3-kinase (PI3K)/Akt signaling in tumor promotion, we next determined the effect of topical application of Lupeol to mouse skin against these signaling pathways We found that Lupeol treatment to mouse skin resulted in the inhibition of TPA-induced (i) activation of PI3K, (ii) phosphorylation of Akt at Thr308, (iii) activation of NF-κB and IKKα, and (iv) degradation and phosphorylation of IκBα The animals pretreated with Lupeol showed significantly reduced tumor incidence, lower tumor body burden and a significant delay in the latency period for tumor appearance At the termination of the experiment at 28 weeks, 100% of the animals in TPA-treated group exhibited seven to eight tumors/mouse, whereas only 53% of the mice receiving Lupeol prior to TPA treatment exhibited one to three tumors/mouse These results for the first time provide evidence that Lupeol possesses antiskin tumor-promoting effects in CD-1 mouse and inhibits conventional as well as novel biomarkers of tumor promotion We suggest that Lupeol is an attractive antitumor-promoting agent that must be evaluated in tumor models other than skin carcinogenesis

Lupeol modulates NF-κB and PI3K/Akt pathways and inhibits skin cancer in CD-1 mice

Medicinal herbs for the treatment of rheumatic disorders--a survey of European herbals from the 16th and 17th century.

Modification of low-density lipoprotein by myeloperoxidase-derived oxidants and reagent hypochlorous acid.

Cyclooxygenases in the skin: pharmacological and toxicological implications.

Artemisia asiatica Nakai has been used in traditional Asian medicine for the treatment of inflammatory and other disorders. Previous studies have revealed that the formulated ethanol extract (DA-9601) of A. asiatica has pronounced antioxidative and antiinflammatory activities and exhibits cytoprotective effects against experimentally induced gastrointestinal, hepatic and pancreatic damage. In the present study, we assessed the inhibitory effect of DA-9601 on tumor promotion, which is closely linked to inflammatory tissue damage. As an initial approach to evaluating the possible antitumor-promoting potential of DA-9601, its effects on TPA-induced ear edema were examined in female ICR mice. Pretreatment of the inner surface of the mouse ear with DA-9601 30 min prior to topical application of TPA inhibited ear edema at 5 hr. TPA-stimulated expression of epidermal COX-2 and iNOS was also mitigated by topical application of the same extract. Moreover, DA-9601 abrogated the TPA-mediated activation of NF-κB/Rel and AP-1 in mouse epidermis. Suppression of epidermal NF-κB by DA-9601 appeared to be mediated in part through inhibition of IκBα degradation, thereby blocking the nuclear translocation of p65, the functional subunit of NF-κB. DA-9601 also significantly suppressed TPA-induced ODC activity and papilloma formation in mouse skin. Taken together, these findings suggest that DA-9601 derived from A. asiatica possesses potential chemopreventive activities. © 2002 Wiley-Liss, Inc.

https://onlinelibrary.wiley.com/doi/pdf/10.1002/ijc.10489

Inhibitory effects of the standardized extract (DA‐9601) of Artemisia asiatica Nakai on phorbol ester–induced ornithine decarboxylase activity, papilloma formation, cyclooxygenase‐2 expression, inducible nitric oxide synthase expression and nuclear transcription factor κB activation in mouse skin

We had previously reported that the protective effect of taurine against indomethacin-induced gastric mucosal injury was due to its antioxidant effects, which inhibited lipid peroxidation and neutrophil activation. In this study, we examined the effect of taurine on reducing the inflammatory parameters of trinitrobenzene sulfonic acid (TNBS)-induced inflammatory bowel disease (IBD) in rats. In order to induce IBD, ethanolic TNBS was given to rats intracolonically. Then they received 500 mg/kg/day of taurine orally and were sacrificed one week after IBD induction. While ulceration and inflammation of distal colon with formation of granuloma in the vehicle-treated IBD rats two days after administration of TNBS were observed, treatment with taurine ameliorated colonic damage and decreased the incidence of diarrhea and adhesion. Also, colon weight as an index of tissue edema, which was markedly increased in the IBD rats, became significantly lower after taurine treatment. Myeloperoxidase (MPO) activity in the vehicle-treated IBD rats was substantially increased, compared with that of normal control. The taurine-treated animals significantly reduced MPO activity (35% lower) when compared with that of the vehicle-treated animals. Taurine treatment decreased both basal and formyl-methionyl leucyl phenylalanine-stimulated reactive oxygen generation from colonic tissue in the IBD rats. These results suggest that the administration of taurine reduce the inflammatory parameters in this IBD rat model by increasing defending capacity against oxidative damage.

Protective effect of taurine on TNBS-induced inflammatory bowel disease in rats

Taurine, or 2-aminoethane sulfonic acid, is an intracellular amino acid and has been suggested to have a function in protecting biological systems from oxidative tissue damage. The aim of this study w

Effects of taurine on cerulein-induced acute pancreatitis in the rat.

The present invention relates to a pharmaceutical composition for forming a film directly on a wound to accelerate wound healing, a use for the same, a treatment method using the same, and a method for preparing the same. The film-forming composition according to the present invention forms a film directly on the wound to increase the adhesion to the wound. The formed thin hydrophilic film protects the wound surface to prevent infection of the wound surface, retains the physiologically active substance useful for wound healing on the wound surface to promote the wound healing, and allow drugs to be continuously delivered to the wound surface. Therefore, the composition according to the present invention has excellent wound healing effect and has excellent usability as it is not absorbed into clothing, bandage, etc., thus effectively replacing conventional gel or ointment formations for delivering physiologically active substances.

Film-forming pharmaceutical composition for wound healing and method for preparing the same

The present invention relates to herbal extracts of Sinapis Semen, Corydalis Tuber, Pharbitidis Seed and Strychni Ignatii Semen, and a composition containing the same for treating and preventing gastrointestinal motility disorder. The extracts of the present invention have a remarkable effect of promoting gastrointestinal motility through HT3 receptor antagonism and/or HT4 receptor agonism.

Extract of herbal and the composition containing the same

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Protective effect of taurine on TNBS-induced inflammatory bowel disease in rats

Effects of taurine on cerulein-induced acute pancreatitis in the rat.

Film-forming pharmaceutical composition for wound healing and method for preparing the same

Extract of herbal and the composition containing the same