D-limonene (5 (one-methyl-four-[1-methylethenyl]) cyclohexane) diminishes CCl4-induced cardiac toxicity by alleviating oxidative stress, inflammatory and cardiac markers.

Background: The cardiovascular crisis is advancing rapidly throughout the world. A large number of studies have shown that plant polyphenols affect major mechanisms involved in cardiovascular events through their action on the antioxidant system, signaling, and transcription pathways. D-limonene, a monocyclic monoterpene obtained from citrus fruits, is reported to possess many pharmacological activities.Methods: The experiment was designed to determine the protective effect of D-limonene against cardiac injury induced by CCl4 in Wistar rats. Rats were treated with two doses of D-limonene against cardiac injury induced by CCl4. Serum toxicity markers, cardiac toxicity biomarker enzymes, inflammatory mediators, anti-oxidant armory, lipid peroxidation, lipid profile, and histology were done.Results: CCl4 intoxication resulted in a substantial rise in FFA, TC, TG, PL, LDL, VLDL, and a reduction in HDL, restoring these changes with the administration of D-limonene at a dosage of 200 mg/kg. CCl4 administration also resulted in lipid oxidation and decreased antioxidant activity. At the same time, D-limonene at a dosage of 200 mg/kg body weight inhibited LPO and restored in vivo antioxidant components to normal. CCl4 intoxication also resulted in a significant increase in inflammatory markers like IL-6, TNF-α, high sensitivity Corticotropin Releasing Factor (Hs-CRF), and biomarkers of cardiac toxicity like alanine aminotransferase (ALT), lactate dehydrogenase (LDH), creatine kinase (CK), creatine kinase MB (CKMB), and Troponin I & troponin-t activities. D-limonene reversed all these changes to normal. Histology further confirmed our obtained results.Conclusion: These findings indicate that D-limonene can ameliorate cardiac injury at a 200 mg/kg body weight dosage. Henceforth, D-Limonene intervenes in mediating CCl4 induced toxicity by various signaling pathways.

Chemopreventive efficacy zingerone (4-[4-hydroxy-3-methylphenyl] butan-2-one) in experimental colon carcinogenesis in Wistar rats.

Colorectal cancer is one of the most common cancers worldwide. Development of naturally occurring inexpensive and safe alternatives can be effective in suppressing colon related proliferations. Zingerone (4-[4-hydroxy-3-methylphenyl] butan-2-one), a polyphenolic alkanone of ginger, has massive pharmacological properties and thus can be used as promising candidate against various ailments. In the current study, we aimed at demonstrating the protective effect of zingerone against experimental colon carcinogenesis and elucidating its possible mechanism by studying inflammatory and Nrf-2 signaling cascade. Four groups of animals (I-IV) were made with six animals each. Group I (control) was given normal saline orally. Group II was given 1,2-dimethylhydrazine (DMH) at the dose rate of 20 mg/kg body weight. Group III and IV were treated with DMH at the dose rate of 20 mg/kg body weight and also received oral treatment of zingerone at a dose rate of 50 and 100 mg/kg body weight, respectively, for first 5 weeks and animals were euthanized after 16 weeks. Our results reveal that DMH treated rats exhibited elevated ROS and MDA levels, increased activity of cytochrome P450 2E1 and serum marker enzyme carcinoembreyonic antigen (CEA), increased no of aberrant crypts of foci (ACF), and elevated expression of inflammatory and proliferative proteins. Nrf-2 was downregulated by DMH treatment. Treatment with zingerone to DMH treated rats, resulted in alterations in the activity of the cytochrome P450 2E1 and CEA. In addition, immunostaining of NF-kB-p65, COX-2, iNOS, and PCNA, Ki-67 was suppressed by zingerone. Furthermore, zingerone administration also attenuated the level of IL-6 and TNF-α and it also helps in preserving mucous layer. Thus, zingerone could be considered as a good chemopreventive agent in experimental model of colon carcinogenesis. Further studies are required to study other pathways involved in colon carcinogenesis and their modulation buy zingerone.

Antioxidant and Antimutagenic Activities of Different Fractions from the Leaves of Rhododendron arboreum Sm. and Their GC-MS Profiling.

In this era of urbanization and environmental pollution, antioxidants and antimutagens derived from plants are promising safeguards for human health. In the current investigation, we analyzed the antioxidant and antimutagenic effects of the hexane, chloroform, and ethyl acetate fractions of Rhododendron arboreum Sm. leaves and determined their chemical composition. The different fractions inhibited lipid peroxidation, repressed the production of nitric oxide radicals, and prevented deoxyribose degradation. The antimutagenic activity of the leaf fractions was analyzed against 4-nitro-O-phenylenediamine, sodium azide and 2-aminofluorene mutagens in two test strains (TA-98 and TA-100) of Salmonella typhimurium. The experiment was conducted using pre- and co-incubation modes. The best results were obtained in the pre-incubation mode, and against indirect acting mutagen. The presence of a number of bioactive constituents was confirmed in the different fractions by GC-MS analysis. The study reveals the strong antioxidant and antimutagenic activity of R. arboreum leaves. We propose that those activities of R. arboreum might correspond to the combined effect of the phytochemicals identified by GC-MS analysis. To the best of our knowledge, this is the first report on the antimutagenic activity of R. arboreum leaves.

Nepeta deflersiana attenuates isoproterenol-induced myocardial injuries in rats: Possible involvement of oxidative stress, apoptosis, inflammation through nuclear factor (NF)-κB downregulation.

BACKGROUND: Nepeta deflersiana (Lamiaceae) is a perennial herb used in the Saudi and Yemeni folk medicine as an anti-inflammatory, carminative, and antirheumatic agent. PURPOSE: This study explores the phytochemistry of the plant and the cardioprotective effect of N. deflersiana ethanolic extract (NDEE) against isoproterenol (ISP)-induced myocardial injury in rats. DESIGN/METHODS: Cardiac function, serum cardiac enzymes, myocardial antioxidants, inflammatory, and apoptotic biomarkers, and histopathological parameters were studied in ISP-injured Wistar rat heart tissues. RESULTS: To the best of our knowledge, this is the first study to report the isolation of nine secondary metabolites from this plant: 1α-hydroxy-7α,14α,18-triacetoxy-isopimara-8,15-diene (1), ß-sitosterol (2), lupeol (3), ursolic acid (4), 2,3-dihydroxy ursolic acid (5), caffeic acid (6), methyl rosmarinate (7), rosmarinic acid (8), and an irridoid glucoside 8-epi-7-deoxyloganic acid (9). To explain the mechanisms underlying the cardioprotective effect of NDEE, we evaluated the redox-sensitivity of NDEE in ISP-induced cardiac injury. The oral administration of NDEE (50 and 100 mg/kg b.w) prevented the depletion of endogenous antioxidants (CAT, SOD, NP-SH, and NO) and myocyte injury marker enzymes and inhibited lipid peroxidation (MDA, MPO). Moreover, NDEE downregulated the expression of pro-inflammatory cytokines (TNFα, IL-6, and IL-10) and apoptotic markers (caspase-3 and Bax) and upregulated the anti-apoptotic protein Bcl2. Furthermore, NDEE pretreatment significantly downregulated cardiac NF-κB (p65) expression, NF-κB-DNA binding activity, and MPO activity. Histological data showed that NDEE pretreatment reduced myonecrosis, edema, and infiltration of inflammatory cells and restored the architecture of cardiomyocytes. CONCLUSION: NDEE demonstrated strong antioxidant, cardioprotective, anti-inflammatory, and anti-apoptotic potential against myocardial damage. This further endorses the use of N. deflersiana in Yemeni folk medicine against cardiovascular diseases.

Hepatoprotective effect of Quercetin supplementation against Acrylamide-induced DNA damage in wistar rats.

BACKGROUND: Quercetin (QR), is a polyphenolic flavonoid compound which is found in large amounts in certain foods, and protects against oxidative stress. The current study was conducted to determine whether Quercetin can possibly exert hepatoprotective and antioxidant activity against acrylamide (ACR) induced toxicity in rats. METHODS: Four groups of Wistar rats consisting of six rats each: (i) control group; (ii) ACR treated group (50 mg/kg bw); (iii) QR group: rats were treated with QR (10 mg/kg bw); (iv) QR (10 mg/kg bw) was given i.p. for 5 days followed by ACR (50 mg/kg bw) on 5th day (single dose). RESULTS: ACR caused an elevation in 8-OH guanosine level and a reduction in Glutahione S-transferase (GST) activity. Administration of QR significantly protected liver tissue against hepatotoxic effect of acrylamide from amelioration of the marker enzyme (p < 0.05) and DNA damage (p < 0.01) as evident by comet assay and, besides some indices of histopathological alterations. CONCLUSION: It is concluded that QR could protect the liver against DNA damage induced by ACR probably is thus capable of ameliorating ACR-induced changes in the rat livers.

Ameliorative effect of methanol extract of Rumex vesicarius on CCl4-induced liver damage in Wistar albino rats.

CONTEXT: Rumex vesicarius L. (Polygonaceae), an edible plant, is reported to have many bioactive phytochemicals, especially flavonoids and anthraquinones with antioxidant and detoxifying properties. OBJECTIVE: This study evaluated the methanolic extract of R. vasicarius (MERV) for hepatoprotective activity in rats against CCl4-induced liver damage. MATERIALS AND METHODS: The whole plant extract was prepared and investigated for its hepatoprotective activity. Rats were pretreated with MERV (100 and 200 mg/kg, p.o.) for 7 d prior to the induction of liver damage by CCl4. Animals were then sacrificed 24 h after CCl4 administration for the biochemical (AST, ALT, and ALP activity in serum; lipid peroxidation (LPO) and glutathione (GSH) levels in liver tissue) and histological analyses. RESULTS: CCl4-induced hepatotoxicity was confirmed by an increase (p < 0.05) in serum AST (4.55-fold), ALT (3.51-fold), and ALP (1.82-fold) activities. CCl4-induced hepatotoxicity was also manifested by an increase (p < 0.05) in LPO (3.88-fold) and depletion of reduced glutathione (3.14-fold) activity in liver tissue. The multiple dose MERV administration at 200 mg/kg showed promising hepatoprotective activity as evident from significant decrease levels of serum AST (230.01 ± 13.21), serum ALT (82.15 ± 5.01), serum ALP (504.75 ± 19.72), hepatic LPO (3.38 ± 0.33), and increased levels of hepatic glutathione (0.34 ± 0.04) towards near normal. Further, biochemical results were confirmed by histopathological changes as compared with CCl4-intoxicated rats. DISCUSSION AND CONCLUSION: The results obtained from this study indicate hepatoprotective activity of Rumex plant against CCl4-induced liver toxicity; hence, it can be used as a hepatoprotective agent.