Antiulcerogenic effect of Cuphea ignea extract against ethanol-induced gastric ulcer in rats.

BACKGROUND: Cuphea ignea is one of the herbal resources belonging to Lythraceae family. Some species of this family have been used traditionally in South and Central America's folk medicine for treating stomach disorders. Therefore, the present study was performed to evaluate the gastropreventive effect of aqueous ethanolic extract of C. ignea aerial parts on ethanol-induced gastric ulcer. METHODS: Gastric ulcers were induced in Sprague Dawley rats using one oral dose of absolute ethanol (1.5 mL/rat). The C. ignea aerial parts extract at doses of 250 and 500 mg/kg body weight and ranitidine (a reference drug) at a dose of 30 mg/kg body weight were orally administrated daily for 7 days before ulcer induction. One hour after ethanol administration blood samples were collected and then stomachs of sacrificed rats were subjected to biochemical, macroscopic and microscopic studies. RESULTS: Oral administration of C. ignea extract significantly attenuated gastric ulcer as revealed by significant reduction in the gastric ulcer index and volume of gastric juice while significantly increased preventive percentage, gastric pH value and pepsin activity. Pre-treatment of C. ignea extract markedly improved the serum level of TNF-α, the gastric MPO activity and NO content. Furthermore, C. ignea pre-treatment significantly increased the gastric levels of enzymatic and non- enzymatic antioxidants namely CAT, SOD, GSH-Px, and GSH with concomitant reduction in MDA level compared with those in the ethanol group. These results were further supported by histopathological findings which revealed the curing effect of C. ignea on the hemorrhagic shock induced by ethanol toxicity. CONCLUSIONS: C. ignea extract showed a potential gastroprotective effect on ethanol-induced gastric ulcer, and its effect may be mediated through suppression of oxidative stress and gastric inflammation.

Lagerstroemia speciosa (L.) Pers Leaf Extract Attenuates Lung Tumorigenesis via Alleviating Oxidative Stress, Inflammation and Apoptosis.

One of the major etiological factors that account for lung cancer is tobacco use. Benzo(a)pyrene [B(a)P], one of the main constituents of tobacco smoke, has a key role in lung carcinogenesis. The present study was conducted to investigate the cytotoxicity of an aqueous ethanolic extract of Lagerstroemia speciosa (L.) Pers leaves (LLE) on human lung adenocarcinoma cells (A549), as well as its in vivo antitumor effect on a lung tumorigenesis mice model. Our results revealed that LLE possesses cytotoxic activity against the A549 cell line. Mice orally administered B(a)P (50 mg/kg body weight) showed an increase in relative lung weight with subsequent decrease in final body weight. Serum levels of tumor marker enzymes AHH, ADA and LDH and the inflammatory mediator NF-κB increased, while total antioxidant capacity (TAC) decreased. In addition, we observed the increased activity of metalloproteinases (MMP-2 and MMP-12) and levels of the tumor angiogenesis marker VEFG and the lipid peroxidation marker MDA, as well as decreased levels of the non-enzymatic antioxidant GSH and enzymatic antioxidants CAT and GSH-Px in lung tissues. Moreover, B(a)P administration up-regulated the expression of the COX-2 gene, pro-inflammatory cytokines TNF-α and IL-6, and an anti-apoptotic gene Bcl-2, and at the same time down-regulated expression of pro-apoptotic genes BAX and caspase-3 and the p53 gene. Pre- and post-treatment with LLE (250 mg/kg body weight) attenuated all these abnormalities. Histopathological observations verified the protective effect of LLE. Overall, the present data positively confirm the potent antitumor effect of L. speciosa leaves against lung tumorigenesis.

Antitumor activity of Cuphea ignea extract against benzo(a)pyrene-induced lung tumorigenesis in Swiss Albino mice.

Lung cancer has one of the highest mortality rates among various types of cancer and is the most frequent cancer in the world. The incidence of lung cancer is increasing rapidly, in parallel with an increased incidence of smoking. Effective chemoprevention may be an alternative strategy to control the incidence of lung cancer. Thus, the objective of current work was to ascertain the possible preventive and therapeutic efficacies of Cuphea ignea extract in a mouse model of lung tumorigenesis and its cytotoxicity toward the A549 human lung cancer cell line. Lung tumorigenesis was induced by the oral administration of benzo(a)pyrene (50 mg/kg b.w.) twice per week to Swiss albino mice for 4 weeks. Benzo(a)pyrene-treated mice were orally administered C. ignea (300 mg/kg body weight, 5 days/week) for 2 weeks before or 9 weeks after the first benzo(a)pyrene dose, for a total of 21 weeks. At the end of the administration period, various parameters were measured in the serum and lung tissues. The results revealed that the oral administration of benzo(a)pyrene resulted in increases in relative lung weight, serum levels of tumor markers (ADA, AHH, and LDH), and the inflammatory marker NF-κB, and a decreased total antioxidant capacity compared with the control. In addition, decreased levels of enzymatic and non-enzymatic antioxidants, with a concomitant increase in lipid peroxidation, metalloproteinases (MMP-2 and MMP-12), and the angiogenic marker VEGF were detected in lung tissues. Moreover, benzo(a)pyrene administration induced the upregulation of PKCα, COX-2, and Bcl-2 expression, with the downregulation of BAX and caspase-3 expression. C. ignea treatment alleviated all alterations in these parameters, which was further confirmed by the histopathological analysis of lung tissues. The findings of the current work provide the first verification of the preventive and therapeutic potentials of C. ignea extract against benzo(a)pyrene-induced lung tumorigenesis in mice.

Modulation of anticancer drug-induced P-glycoprotein expression by naringin.

Multidrug resistance (MDR) is a phenomenon that is often associated with decreased intracellular drug accumulation in the tumour cells of a patient, resulting from enhanced drug efflux. It is often related to the overexpression of P-glycoprotein (P-gp) on the surface of tumour cells, thereby reducing drug cytotoxicity. In the present study, naringin (the predominant flavonone found in grapefruit and other related citrus species) was tested for its potential ability to modulate the expression of P-gp in a short-term animal bioassay, in comparison with verapamil (a calcium channel blocker and positive MDR reversal agent). Western blot analysis showed that pre-treatment by i.p. administration of 5 mg naringin/kg body weight for 3 consecutive days prior to doxorubicin (the most common used anticancer drug which induces MDR) administration was able to significantly lower the P-gp expression reaching nearly the level of animals treated with verapamil. Moreover, pre-treatment with naringin prior to doxorubicin increased the sensitivity to the drug. Naringin inhibited the doxorubicin-stimulated ATPase activity demonstrating that naringin may interact directly with the transporter. In addition, the results demonstrated that induction of both glutathione (GSH) and glutathione-S-transferase (GST) by doxorubicin is consistent with an increased ATP-dependent doxorubicin transport. Thus, naringin seems to modulate the in vivo expression of P-gp. In summary, the present study describes the dual modulation of P-gp expression and function by the flavonoid naringin, which may be an attractive new agent for the chemosensitization of cancer cells.