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Background: Geraniin, a dehydroellagitannin, is a major component of the aqueous extract of the aerial parts of Phyllanthus muellerianus (Kuntze) Exell. (Euphorbiaceae). Several Phyllanthus species are traditionally used for painful disorders. The anti-nociceptive effects of the aqueous extract of the aerial parts of P. muellerianus and of geraniin have been scientifically established. The aim of the paper is to determine whether a combination of geraniin and diclofenac or geraniin and morphine leads to better anti-nociceptive effects. Methods: The nature of the interactions of morphine and diclofenac with geraniin was evaluated by undertaking the isobolographic analysis. Mice were treated with geraniin (3–30 mg/kg), morphine (1–10 mg/kg), and diclofenac (10–100 mg/kg) to obtain the ED50 values of the agents in the formalin test. Dose-response curves were then obtained and analyzed after the co-administration of geraniin with morphine or diclofenac in fixed ratio (1:1) combinations based on specific fractions (1/2, 1/4, and 1/8) of their respective ED50 values for the formalin test. Results: Geraniin was less potent than morphine but more potent than diclofenac in the formalin-induced nociception. The isobolographic analysis of geraniin/morphine (G/M) and geraniin/diclofenac combinations (G/D) at different fractions revealed the potentiation of their anti-nociceptive effects. The degrees of potentiation, which were calculated as interaction indices, showed synergism for both combinations in both phase I (G/M: 0.040, G/D: 0.017) and phase II (G/M: 0.004, G/D: 0.002) of the formalin test. Conclusions: The present study demonstrates synergism for the co-administration of geraniin with both morphine and diclofenac. [ABSTRACT FROM AUTHOR]

This work was carried out with a view to determining the antioxidant, anti-inflammatory and anti-ulcer properties of the aqueous lyophilized extract of Markhamia lutea. In vitro proteinases inhibition, albumin denaturation, hemolysis of red blood cells by heat, inhibition of the proton pump H+/K+ATPase, FRAP (Ferric reducing antioxidant power) and DPPH (1,1-diphenyl-2-picrylhydrazyl) assays were performed. In vivo, cold water immersion-induced ulceration and methylene blue-induced ulceration was used to determine the anti-ulcer properties of the lyophilizate (100, 200 and 300 mg/kg). In vitro, the lyophilizate (400 μg/mL) significantly inhibited protein denaturation (66.65 %), hemolysis of red blood cells (56.54 %), proteinase activity (69.22 %); then the IC50 was 26.31 μg/mL on proton pump activity. It has also developed a strong ferric reducing antioxidant power (EC50=52.96 mmol FeSO4/g) as well as free radicals scavenging activity (EC50=22.38 μg/mL). In vivo, the aqueous lyophilizate (200 and 300 mg/kg) protected the gastric mucosa (70.68 and 79.00 % protection respectively) and reduced (p<0.05) acetylcholine, calcium and corticosterone concentrations. A decrease in malondialdehyde level, an increased glutathione level and an increased in catalase and SOD activities were recorded. In the methylene blue test, it significantly increased gastric fluid pH, while reducing gastric volume and improving hematological parameters in ulcer animals. In addition, the histological sections show that the aqueous lyophilizate of M. lutea protected the gastric mucosa from the deleterious effects of stress. The aqueous lyophilizate of M. lutea has anti-ulcer properties thanks to its anti-inflammatory, antioxidant and anti-secretory properties. [ABSTRACT FROM AUTHOR]

The ethanol extract of Persea americana seeds was found to inhibit the development of estrogen-dependent conditions in female Wistar rats, suggesting the ability of its secondary metabolites to interact with estrogen receptors (ERs), either as partial agonists or as antagonists. To test this hypothesis, the abovementioned extract was assessed for its ability to mimic and/or antagonize estradiol effects. Two experiments were conducted in ovariectomized (OVX) rats: (1) animals were treated with estradiol valerate (E2V; 1 mg/kg) or P. americana at doses of 25 and 50 mg/kg; (2) animals were treated with E2V alone (0.75 mg/kg) or in combination with P. americana at the abovementioned doses. Treatments were given orally for 3 days and animals were sacrificed for biochemical and histological analyses of the uterus and vagina. When administered alone, P. americana did not change the histomorphology of both organs (uterus and vagina). In combination with E2V, P. americana decreased uterine weight [30 % decrease (p<0.001) at 25 mg/kg and 24 % (p<0.01) at 50 mg/kg] and epithelium height (37 % decrease). This was associated with decreased estradiol levels (at least 86 % decrease, p<0.001) in the uterus. Similarly, vagina epithelium height decreased by at least 34 % (p<0.05) when E2V was co-administered with P. americana. The seed extract of P. americana contains ER antagonist secondary metabolites accounting for its ability to inhibit the development of estrogen-dependent conditions in female rats. [ABSTRACT FROM AUTHOR]

In Unani medicine, a comprehensive treatment plan has been delineated to deal with febrile illnesses using herbal drugs along with modified dietetics, which stands as a promising area of research. The present study was aimed at evaluating the antipyretic activity of the HAE of Artemisia absinthium L. whole plant as a standalone and as an adjuvant with barley water in an animal model of pyrexia to validate the age-old Unani principle of the treatment. The pyrexia was induced in all the groups except the plain control using Brewer's yeast. Group II did not receive any treatment, while group III received crocin, group IV received HAE of A. absinthium, group V administered Ma al-Sha'ir, and group VI was treated with the HAE of A. absinthium along with Ma al-Sha'ir by oral route. The rectal temperature of each rat was recorded at '0' h, 30 min, 60 min, and 180 min. The mean rectal temperature of group III went down from 101.82±0.20 °F to 100.4±0.57 °F over the period of (0–180) minutes, whereas the mean temperature in group IV went down from 102.45±0.60 °F to 100.14±0.57 °F. The mean rectal temperature of group V decreased from 100.62±0.11 °F to 99.55±0.51 °F, while the mean rectal temperature of group VI went down from 101.95±0.1 °F to 97.7±0.11 °F. It is concluded that the HAE of A. absinthium L. as a standalone and along with Ma al Sha'ir showed excellent antipyretic activity as compared to the standard drug in an animal model. [ABSTRACT FROM AUTHOR]

Nigeria ranks second in the global prevalence of diarrhoea with most cases concentrated in the Northern-region of the country. This research explored the antidiarrhoeal efficacy of the hydroethanolic extract of Piliostigma thonningii leaves (HEPTL), locally used to manage diarrhoeal conditions in Kebbi State, Nigeria. P. thonningii leaves were screened for their secondary metabolites and mineral constituents. Using 3 standard-diarrhoea models, female Wistar rats completely-randomised into six-groups of six animals each were utilised for probing the antidiarrhoeal activity of HEPTL. Animals in groups I and II served as the negative and positive controls, whereas the rats in groups III, IV and V respectively received 50, 100, and 200 mg/kg body weight-(bw) of HEPTL. Six secondary metabolites and eight minerals were found in the extract, with flavonoids and calcium being the most abundant while steroids and zinc were the least prevalent, respectively. High performance liquid chromatographic analysis revealed the presence of 19 bioactive substances. Furthermore, there was a significant (p<0.05) and dose-related reduction in diarrhoea onset, water content, and wet faeces count. Similarly, the amount of intestinal fluid and average distance traversed by the charcoal-meal were decreased dose-dependently by the HEPTL with a commensurate rise in the suppression of intestinal fluid accrual and peristalsis. Acetylcholinesterase, Na+/K+-ATPase, reduced glutathione, intestinal-alkaline phosphatase and protein levels increased significantly (p<0.05) whereas superoxide-dismutase, catalase, intestinal-nitric oxide and malondialdehyde levels all fell significantly (p<0.05). However, the level of intestinal glucose was not significantly altered. Overall, the HEPTL exhibited a profound effect in the alleviation of the severity of diarrhoea, notably at 200 mg/kg bw. [ABSTRACT FROM AUTHOR]

Markhamia lutea (M. lutea, Bignoniaceae) is mainly found in tropical/neotropical regions of America, Africa and Asia. The plant's leaves, stems or roots are used to treat anaemia, bloody diarrhoea, parasitic and microbial infections. This study evaluates anti-inflammatory properties (in vitro) of Markhamia lutea and their curative effects on paclitaxel-induced intestinal toxicity (in vivo). The anti-inflammatory potential of Markhamia lutea was tested over cytokines (TNF-alpha, IL-6, IL-1β, IL-10), reactive oxygen species (ROS) and enzymes (cyclooxygenase and 5-lipoxygenase). While in vivo, intestinal toxicity was induced for 10 days by oral administration of paclitaxel (3 mg/kg, 0.05 mL). Animals in each group were further treated with aqueous (300 mg/kg) and ethanolic (300 mg/kg) leaves extracts of Markhamia lutea during 7 days and clinical symptoms were recorded, hematological, biochemical and histological analysis were subsequently performed. In vitro, aqueous (250 μg/mL) and ethanolic (250 μg/mL) extracts of Markhamia lutea inhibited the activities of cyclooxygenase 1 (56.67 % and 69.38 %), cyclooxygenase 2 (50.67 % and 62.81 %) and 5-lipoxygenase (77.33 % and 86.00 %). These extracts inhibited the production of intracellular ROS, extracellular ROS and cell proliferation with maximum IC50 of 30.83 μg/mL, 38.67 μg/mL and 19.05 μg/mL respectively for the aqueous extract, then 25.46 μg/mL, 27.64 μg/mL and 7.34 μg/mL respectively for the ethanolic extract. The extracts also inhibited the production of proinflammatory cytokines (TNFα, IL-1β and IL-6) and stimulated the production of anti-inflammatory cytokines (IL-10). In vivo, after administration of paclitaxel, the aqueous and ethanolic extracts of Markhamia lutea significantly reduced the weight loss, the diarrheal stools and the mass/length intestines ratio of the treated animals compared to the animals of the negative control group. Biochemically, the extracts lead to a significant drop in serum creatinine and alanine aminotransferase levels, followed by a significant increase in alkaline phosphatase. In addition to bringing the haematological parameters back to normal values after disturbance by paclitaxel, the extracts caused tissue regeneration in the treated animals. In vitro, aqueous and ethanolic extracts of Markhamia lutea showed anti-inflammatory properties (inhibition of COX1, COX2, 5-LOX activities, inhibition of ROS production and cell proliferation); in vivo, the same extracts showed curative properties against intestinal toxicity caused by paclitaxel. [ABSTRACT FROM AUTHOR]

How gaseous signalling molecules affect ion transport processes contributing to the physiological functions of the gastrointestinal tract under hypoxic conditions still needs to be clarified. The objective of the present study was to characterize the impact of gaseous signalling molecules on parameters of colonic ion transport during a hypoxia/reoxygenation cycle and the remaining secretory capacity of the epithelium after such a cycle. Short-circuit current (Isc) and tissue conductance (Gt) recordings in Ussing chamber experiments were performed on rat colon samples using CORM-2 (putative CO donor; 35 and 350 µM), sodium nitroprusside (NO donor; 100 µM), NaHS (fast H2S donor; 10 – 1,000 µM), GYY 4137 (slow H2S donor; 50 µM) and Angeli's salt (HNO donor; 100 µM) as donors for gasotransmitters. Inhibition of endogenous synthesis of H2S was operated by inhibitors of cystathionin-γ-lyase, i.e. dl-propargylglycine (1 mM) or β-cyano-l-alanine (5 mM), and the inhibitor of cystathionine-β-synthase, amino-oxyacetate (5 mM). The fast gasotransmitter donors NaHS, sodium nitroprusside and Angeli's salt, administered 5 min before the onset of hypoxia, induced an increase in Isc. The response to the subsequently applied hypoxia was characterized by a decrease in Isc, which tended to be reduced only in the presence of the lowest concentration of NaHS (10 µM) tested. Reoxygenation resulted in a slow increase in Isc, which was unaffected by all donors or inhibitors tested. The stable acetylcholine derivative carbachol (50 µM) was administered at the end of each hypoxia/reoxygenation cycle to test the secretory capacity of the epithelium. Pretreatment of the tissue with the putative CO donor CORM-2 suppressed the secretory response induced by carbachol. The same was observed when cystathionin-γ-lyase and cystathionin-γ-synthase were inhibited simultaneously. Under both conditions, Gt drastically increased suggesting an impaired tissue integrity. The present results demonstrate that none of the exogenous gasotransmitter releasing drugs significantly ameliorated the changes in epithelial ion transport during the hypoxia/reoxygenation cycle ex vivo. In contrast, the putative CO donor CORM-2 exerted a toxic effect on the epithelium. The endogenous production of H2S, however, seems to have a protective effect on the mucosal integrity and the epithelial transport functions, which – when inhibited – leads to a loss of the secretory ability of the mucosa. This observation together with the trend for improvement observed with a low concentration of the H2S donor NaHS suggests a moderate protective role of low concentrations of H2S under hypoxic conditions. [ABSTRACT FROM AUTHOR]

Xenobiotic detection systems-chemically activated luciferase expression (XDS-CALUX) bioassay in determining the toxic equivalency (TEQ) of PCDD/Fs from contaminated sites reported in several papers has been discussed in this study. CALUX bioassay method has been validated by an effective combined column clean-up system followed by addition of samples to monolayer cell cultures of H1L6.1c3 cell line in 96 well plates. Cultures are then examined under microscope after 24 h incubation followed by rinsing with 75 μL phosphate buffer saline and 30 μL of cell culture lysis. The response is observed in the luminometer and expressed in relative light unit (RLUs). CALUX-TEQ is estimated from a TCDD standard curve for unknown samples. Quality control in CALUX is done by selecting the range of CALUX values falling in the center of the linear standard curve. For developing nations CALUX biossay can be used as a cost effective and rapid screening technique for screening xenobiotic compounds from the hotspots like open solid waste burning sites, informal e-waste recycling workshops and industrial zones where constant monitoring for such compounds is required. [ABSTRACT FROM AUTHOR]

The hepatoprotective properties of scopoletin have been explored in carbon tetrachloride (CCl4) induced liver injury but not in drug-induced liver injury (DILI) scenarios. Only N-acetyl-cysteine (NAC) has proven efficacy in DILI treatment. Accordingly, we conducted a study to assess the hepatoprotective action of scopoletin in the anti-tubercular treatment (ATT)-DILI model in Wistar rats, if any. A total of 36 rats were evaluated, with six in each group. A 36-day ATT at 100 mg/kg dose for isoniazid, 300 mg/kg for rifampicin and 700 mg/kg for pyrazinamide were fed to induce hepatotoxicity in rats. Group I and II–VI received normal saline and ATT, respectively. Oral scopoletin (1,5 and 10 mg/kg) and NAC 150 mg/kg were administered in groups III, IV, V and VI, respectively, once daily for the last 15 days of the experiment. LFT monitoring was performed at baseline, days 21, 28, and 36. Rats were sacrificed for the histopathology examination. Aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP) and bilirubin levels were significantly increased in group II (receiving ATT) compared to normal control on day 28 and day 36 (p<0.05). All three doses of scopoletin and NAC groups led to the resolution of AST, ALT, ALP, and bilirubin changes induced by ATT medications effect beginning by day 28 and persisting on day 36 (p<0.01). An insignificant effect was observed on albumin and total protein levels. The effect was confirmed with antioxidants and histopathology analysis. The study confirms the hepatoprotective efficacy of scopoletin in a more robust commonly encountered liver injury etiology. [ABSTRACT FROM AUTHOR]

In this study, we determined the gastroprotective and ulcer-healing effects of extracts (aqueous and methanolic) of Nauclea pobeguinii stem-back. Gastroprotective and healing activity were evaluated following a HCl/ethanol and an indomethacin-induced acute ulcers models; acetic acid, pylorus-ligature, pylorus ligature/histamine and pylorus ligature/acetylcholine-induced chronic ulcers models. It emerges from this study that, at 100, 200 and 400 mg/kg, the extracts significantly reduced the various ulceration parameters. Compared to negative control male rats, the aqueous (100 mg/kg) and methanolic (400 mg/kg) extracts of Nauclea pobeguinii inhibited the ulcers induced by HCl/ethanol by 80.76 % and 100 % respectively, as well as ulcers induced by indomethacin by 88.28 % and 93.47 % respectively. Animals that received 200 mg/kg of both extracts showed a significant reduction in the levels of monocytes, lymphocytes, nitric oxide, MDA and a significant increase in the activities of SOD and catalase. Histological analysis showed repaired mucous epithelium at all doses of both extracts. Aqueous and methanol extracts inhibited ulceration indices by 89.33 % and 88.53 % for pylorus ligature, 83.81 % and 61.07 % for pylorus ligature/acetylcholine and 87.29 % and 99.63 % for pylorus ligature/histamine respectively. Both extracts protected the stomach lining with percentages inhibition of 79.49 % and 81.73 %, respectively in the ethanol test. The extracts induced a significant increase in mucus mass (p<0.001). The aqueous and methanol extracts of Nauclea pobeguinii healed ulcers thanks to their anti-inflammatory, anti-oxidant, anti-secretory and cytoprotective properties. [ABSTRACT FROM AUTHOR]

Vernonia amygdalina (VA) is a plant that consumed as vegetable by Indonesians contained numerous secondary metabolites. VA's pharmacological action, including its antioxidant properties, anticancer, antidiabetic, and hepatoprotective. The purpose of this research is to reveal the activity of Vernonia amygdalina. leafs aqueous fraction (VALAF) as a blood pressure-lowering agent in hypertensive model. Combination of prednisone and NaCl were used as hypertensive inducer. The animals were split into five different groups, normal control group treated with distilled water, treatment VALAF groups with dose of 10; 20 and 40 mg/kg BW respectively, while the last group was treated with captopril at dose of 2.25 mg/kg BW. All animals were given an oral treatment for 15 days. On days 5, 10, and 15, systolic and diastolic blood pressure, heart rate (HR), mean arterial pressure (MAP), and blood flow (BF) were all measured. On days 0 and 15, NO level were assessed. All data were analyzed using two-way ANOVA, and Duncan Multiple Range Test. The V. amygdalina leaf aqueous fraction has blood pressure lowering activity. The blood pressure parameter of the rats treated with VALAF were lower as compared to the normal control group (p<0.05). NO levels in the VALAF group were not significantly higher than in the normal control group (p>0.05). The VALAF 20 give the greatest percentage of decrease in blood pressure, heart rate and blood volume on the 15th day of examination. These study indicated that V. amygdalina leaf aqueous fraction has the potential to be an alternative therapy for managing blood pressure in hypertensive animal models. [ABSTRACT FROM AUTHOR]

Diarrhea, an abnormal state in which the individual has about three or more daily bowel movements, is now considered one of the most challenging global public health problems. Using plant products, such as Bridelia ferruginea is an alternative treatment option. The objective of this study was to investigate the antidiarrheal activity of B. ferruginea bark methanolic extract (BfME) and the mechanisms involved. BfME antidiarrheal activity was evaluated in mice model of castor oil-induced diarrhea and enteropooling. To evaluate motility, gastrointestinal transit time was carried out using phenol red meal, while intestinal activities of selected ATPases were also evaluated. Furthermore, the active components in BfME were detected by GC-MS analysis, while molecular docking of the most abundant compounds with muscarinic acetylcholine receptor (M3) and prostaglandin E2 receptor 3 (EP3) were conducted. BfME at 400 and 800 mg/kg showed antidiarrheal activity by delaying onset of diarrhea, reduced gastrointestinal transit and increased intestinal activities of Na+ K+-ATPase, Ca2+ Mg2+-ATPase and Mg2+-ATPase. Molecular docking revealed that γ-sitosterol, α-amyrin, and stigmasterol have outstanding binding affinity for M3 and EP3. In view of these results, the observed antidiarrheal activity possibly occurs via the activation of ATPases activities and inhibition of M3 and EP3. [ABSTRACT FROM AUTHOR]

Cardiovascular diseases, especially atherosclerosis, are the leading cause of human mortality in Indonesia. Ipomoea batatas (L.) is a food plant used in Indonesian traditional medicine to treat cardiovascular diseases and related conditions. We assessed the anti-atherosclerotic activity of the aqueous extract of I. batatas leaves in a rat model of high-fat diet-induced atherosclerosis and its mechanism. The presence of amino acid content in the I. batatas L. purple variant was determined by liquid chromatography high-resolution mass spectrometry (LC-HRMS). Thirty male Wistar rats were divided into five groups (n=6/group), i.e., standard diet group (SD), high-fat diet group (HF), and HF plus I. batatas L. extracts orally (625; 1,250; or 2,500 mg/kg) groups. The numbers of macrophages and aortic wall thickness were analyzed histologically. Immunohistochemical analyses were performed to assess foam cells-oxidized low-density lipoprotein (oxLDL), endothelial nitric oxide synthase (eNOS), and vascular endothelial growth factor (VEGF) expression in the aorta. LC-HRMS analysis showed nine amino acid content were identified from I. batatas L. In vivo study revealed that oral administration of I. batatas L. leaf extract alleviated foam cells-oxLDL formation and aortic wall thickness caused by high-fat diet atherosclerosis rats. Further, I. batatas L. leaf extract promoted the number of macrophages and modulated VEGF and eNOS expression in the aorta. I. batatas L. leaf extract shows a positive anti-atherosclerosis effect. Furthermore, the mechanism may promote the macrophages, eNOS, VEGF expressions, and inhibition of foam cells-oxLDL formation and aortic wall thickness with the best dosage at 2,500 mg/kg. This could represent a novel approach to prevent cardiovascular diseases. [ABSTRACT FROM AUTHOR]

Justicia gendarussa Burm.f, belonging to the family Acanthaceae, is widely used for various ailments traditionally. Antioxidant, anti-arthritic, anti-inflammatory, analgesic, anticancerous, properties of the plant have been widely reported. The present study analyzed the cardioprotective effect of J. gendarussa on doxorubicin (DOX) induced toxicity in mice. Ethanolic extract of J. gendarussa was administered orally for 7 consecutive days. The alterations in oxido-reduction status, biochemical and histopathological parameters were analyzed in heart tissue. DOX increased superoxide dismutase (SOD) and catalase activities to 3.4 ± 0.5 and 3.68 ± 1 from their normal values 2.43 ± 0.8 and 2.72 ± 0.88, respectively. The increased activities of both the enzymes were found reduced to 3.12 ± 0.24 and 3.41 ± 0.65 by the treatment of the extract. Similarly, DOX elevated glutathione peroxidase (GPx) activity to 44.6 ± 3.71 from the normal level 32.33 ± 3.41. DOX decreased the glutathione (GSH) level to 15.66 ± 2.51 from the normal values 31.66 ± 4.05. Upon treatment, GPx activity and GHS level found restored. The increased lipid peroxidation 2.53 ± 0.25 of DOX was also decreased to 2.0 ± 0.34 by the extract. Histopathology observations substantiate the protective effect of J. gendarussa extract. In conclusion, DOX-induced disturbance of oxido-reduction status and histopathology of heart attenuated closer to the normal indicating the protective effect of J. gendarussa against DOX-induced toxicity in cardiomyocytes. [ABSTRACT FROM AUTHOR]

Re-perfusion is the standard therapy for acute myocardial infarction, despite the associated pathologies that may contribute to irreversible myocardial injury. The present study aims to clarify the alterations in cardiac activities in response to experimental cardiac ischemic arrest followed by re-perfusion in isolated hearts perfused with nitric oxide (NO) donor, l-arginine, or NO inhibitor, Nω-Nitro-l-arginine methyl ester hydrochloride (l-NAME), to shed light on the possible role of NO in the re-perfusion process. Hearts isolated from adult Wistar rats were studied on Langendorff preparation under basal conditions and during 30 min re-perfusion following 30 min of total global ischemia. Rats were randomly divided into three groups; control and l-arginine or l-NAME infused heart groups. Cardiac tissue content of malondialdhyde, catalase and nitrite was also measured. Compared to the control group, both l-arginine and l-NAME infused hearts showed increased basal chronotropy and myocardial flow rate. Following ischemia and during the whole period of re-perfusion, the three groups demonstrated significant deterioration in the inotropic activity and compromised myocardial flow rate. l-arginine infused hearts revealed depressed inotropy and chronotropy, weak systolic and diastolic functions with compromised myocardial flow at early 5 min of re-perfusion, yet with significantly higher myocardial flow rate by the end of re-perfusion. Reducing NO availability by l-NAME revealed mild impact on the ischemia re-perfusion induced contractile dysfunction, whereas excess NO worsens cardiac performance at the early re-perfusion period. [ABSTRACT FROM AUTHOR]

This study aimed to investigate the potential of honey-supplemented medium (HSM) for expanding corneal keratocytes and its transplantation in a model of corneal laceration. Keratocytes were cultured in 1 % HSM- or 10 % fetal bovine serum (FBS)-supplemented medium for 24 h. The effect of HSM on keratocyte proliferation was evaluated using the MTT assay. The relative expression of Lum, Kera, and ALDH3A1, known markers of native keratocytes, was quantified by real-time PCR. The safety and efficacy of HSM-treated keratocyte intrastromal injection in a rabbit model of corneal laceration were also evaluated. The MTT assay showed that HSM treatment did not significantly affect cell viability compared to FBS-supplemented medium (84.71 ± 2.38 vs. 100.08 ± 10.92, respectively; p=0.076). Moreover, HSM-treated keratocytes had significantly increased expression of Lum, Kera, and ALDH3A1 compared to cells treated with FBS, while the expression of the proliferation biomarker Thy-1 did not significantly differ between the two treatments. Intrastromal injection of HSM-treated keratocytes in the laceration animal model was safe and uneventful, resulting in less stromal inflammation and neovascularization, and consequently, better final architecture with less residual haze compared to the group injected with FBS-treated keratocytes. These findings suggest that honey is a suitable supplement for keratocyte treatment and corneal cell therapy. The use of HSM may have potential applications in the treatment of corneal injuries and diseases. [ABSTRACT FROM AUTHOR]

Combining tamoxifen, the most common breast cancer hormonal therapy, with natural antitumor substances may prevent its hyperplastic effects on the uterine endometrium. Dacryodes edulis (DE) is traditionally recommended for the treatment of cancerous diseases. To investigate its antiproliferative properties, the present study was designed to assess the ability of the combined administration of tamoxifen with the aqueous extract of DE leaves to inhibit the trophic effect of this hormone therapy on rat uterine endometrium without compromising its non-proliferative effect on breast tissue. Ovariectomized (OVX) female Wistar rats were simultaneously treated with tamoxifen (10 mg/kg) intraperitoneally and DE leaves (at doses of 25, 50 and 100 mg/kgBW) by gavage. Control groups received either distilled water or tamoxifen alone. Treatments lasted 37 days. The 38th day, animals were sacrificed under anesthesia (diazepam: 10 mg/kgBW and ketamine: 50 mg/kgBW). The relative uterine weight was determined and the histological analysis of the uterus and mammary gland was performed. The oxidative status of the uterus was assessed and the levels of cholesterol and estradiol were evaluated in serum and uterus. Tamoxifen increased uterine weight and induced endometrial hyperplasia. This effect was associated with increased uterine levels of cholesterol (164.22%; p < 0.001), estradiol (927.5%; p < 0.001) and malondiadehyde (86%; p < 0.05), but unchanged antioxidant enzymes activities. The administration of DE leaves unchanged tamoxifen-increased uterine weight but reduced uterine epithelium hypertrophy (56.4%; p < 0.01). DE also increased uterine levels of malondiadehyde and antioxidant enzymes. The levels of estradiol and cholesterol in the uterus decreased while no changes were observed in the mammary gland of animals treated with tamoxifen alone or in co-administration with DE. D. edulis has antiproliferative properties and could complement endocrine therapy of estrogen-dependent breast cancer. [ABSTRACT FROM AUTHOR]

Reactive oxygen and nitrogen species may be produced during inflammation leading to the formation of NO, H2S or HNO. Enzymes such as iNOS, CSE and CBS might also be responsible for polysulfide production. Since these signalling molecules might have an impact on colonic motility, the aim of this study was to compare their effect on rat colonic slow phasic contractions (SPC). Organ bath measurements with strips obtained from rat proximal colon were performed using the polysulfide Na2S3, sodium nitroprusside (NaNP), sodium hydrogen sulfide (NaHS), Angeli's salt as NO, H2S, and HNO donors, respectively. TTX (1 µM) was used to block neuronal activity. All four molecules, concentration-dependently, inhibited the amplitude and frequency of SPC both in the circular and longitudinal muscle layer. The relative potency was NaNP>Angeli's salt>NaHS>Na2S3. The inhibitory response induced by NaNP (1 µM) and Angeli's salt (50 µM) was reversed by ODQ (10 µM) whereas the inhibitory effect of NaHS (1 mM) was reversed by apamin (1 µM) and glibenclamide (10 µM). Na2S3 (1 mM) response was partially reversed by apamin (1 µM) and glibenclamide (10 µM). High concentrations of Na2S3 caused an increase in tone. Low concentrations of NaHS or Na2S3 did not potentiate NaNP responses. All signalling molecules inhibit SPC in both muscle layers. The effect is independent of neural activity and involves guanylyl cyclase (NO and HNO) and SKCa and KATP channels (NaHS or Na2S3). Other pathways might also be involved in Na2S3 responses. Accordingly, complementary mechanisms of inhibition might be attributable to these signalling molecules. [ABSTRACT FROM AUTHOR]

A polyherbal formulation with hepatoprotective and choleretic properties combining pharmacological potential of eight medicinal plants was developed in Nargiz Medical center (Republic of Azerbaijan) for the use as herbal tea. To explore the effect of polyherbal composition on the metabolism of LPS-stimulated macrophages in vitro. The qualitative and quantitative phytochemical analysis was conducted using specific color reactions and gas chromatography-mass spectrometry (GC–MS). Nitric oxide (NO) assay was determined using the Griess reaction. Reactive oxygen species (ROS) generation was measured using ROS-sensitive fluorescence indicator, H2DCFDA, by flow cytometry. Arginase activity was examined by colorimetric method. The studied polyherbal formulation exerted anti-inflammatory activity in LPS-stimulated macrophages which was evidenced by dose-dependent decrease of ROS generation and by shift of arginine metabolism to the increase of arginase activity and decrease of NO release. Our findings suggest that the herbal tea reduces macrophage inflammatory activity, that provide an important rationale to utilize it for the attenuation of chronic inflammation typical of hepatobiliary disorders. [ABSTRACT FROM AUTHOR]

Artocarpus is a tropical plant known for its high concentration of secondary metabolites, especially flavonoids and phenolics. This study aims to evaluate the potential use of ethanol extracts obtained from three species of Artocarpus (Artocarpus altilis, Artocarpus champeden, and Artocarpus heterophyllus) as gastroprotective agents. The gastroprotective potential of the extracts at concentrations of 100, 200, and 400 mg/kg BW was studied in an animal model induced by absolute ethanol. The animals were subjected to extract pre-treatment for 14 days. Subsequently, the gastroprotective potential was evaluated based on the area of the lesion, the volume of gastric fluid, gastric pH, total acidity, gastric wall mucus content, and microscopic lesions. There was a significant decrease in the lesion area and gastric fluid volume in the animals that received pre-treated extracts of A. altilis, A. Champeden, and A. heterophyllus, as well as a significant increase in the pH and gastric wall mucus secretion when compared to the ethanol group (p<0.05), rather than the omeprazole or the normal group (p>0.05). Both macroscopic and microscopic examinations revealed a significant decrease in necrotic lesions. Extracts of A. altilis, A. Champeden, and A. heterophyllus are effective in lowering the risk of peptic ulcers since they have the potential to be used as natural gastroprotective agents. [ABSTRACT FROM AUTHOR]

Although Sanguisorba minor has been used as herbal medicine, no study has ever examined its potential toxicity. This study investigated acute and subacute toxicities of S. minor hydroalcoholic extract (SE). In the acute toxicity test, a single oral dose (300, 2,000, and 3,000 mg/kg) of SE was given to mice. The oral administration of SE (100, 200, and 400 mg/kg for 4 weeks) was performed to evaluate subacute toxicity. After the treatments, neurobehavioral, histopathology, hematological, and biochemical parameters were monitored. In vitro cytotoxicity was also assessed. Moreover, high-performance liquid chromatography fingerprint was done for the standardization of SE. The no-observed-adverse-effect level of SE was up to 2,000 mg/kg, and the LD50 of the prepared extract was over 3,000 mg/kg. The rats exposed to the extract did not show any marked change in their body weight. The extract at used doses did not affect neuromuscular coordination. According to the hematological, biochemical, and histological examinations, no significant treatment-related adverse effect of the extract was observed, even at 400 mg/kg. Only 48 h exposure to 400 μg/mL of SE reduced the viability of PC12 cells. The findings revealed that this plant could be well-tolerated, regarded safe, and used as herbal medicine. [ABSTRACT FROM AUTHOR]

This study aimed to evaluate the antibiofilm activity and toxicity of the glycolic extract of Persea americana "P. americana" over multidrug-resistant strains of Acinetobacter baumannii "A. baumannii" as alternative therapy to be investigated. A bacterial inoculum of each bacterial strain (4a, 5a, 9a, 12a, ATCC 19606) of A. baumannii was prepared and adjusted by the spectrophotometer. The microdilution broth method was performed to determine the minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC). P. americana glycolic extracts were obtained of the tree stalk and leaves. The biofilm viability was tested by MTT assay after 5 min exposure. The toxicity of the extracts was tested by invertebrate model Galleria mellonella. The data were analyzed by ANOVA, Tukey test and log-rank method (α=0.05). The extract showed an inhibitory and bactericidal action over all the tested strains with the lowest MIC value observed for the reference strain (3.12 mg/mL). The extract did not demonstrate toxicity in any of the tested concentrations (12.5, 25 and 50 mg/mL) in Galleria mellonella larvae, with a survival percentage above 80% after 168 h. The glycolic extract of P. americana has microbicidal and antibiofilm activity on multidrug-resistant clinical strains of A. baumannii and showed low toxicity for the invertebrate model G. mellonella. [ABSTRACT FROM AUTHOR]

To validate the concept of abadāl-i-adwiya (drug substitution) by evaluation of physicochemical standardization and hepatoprotective activity of Aristolochia rotunda & its substitute, Curcuma Zedoaria in albino Wistar rats. Physicochemical standardization by estimation of moisture content, ash values and extractive values were carried out using standard methods. Hepatotoxicity was induced in albino Wistar rats using CCl4 1 mL/kg s. c. on alternate day for 14 days. Group I was served as Plain control and Group II as Negative control. Group III was administered silymarin 50 mg/kg p. o. while Group IV received HAE of A. rotunda 89.64 mg/kg p. o., and Group V was administered HAE of C. Zedoaria 45.73 mg/kg p. o. At the end of the study, serum bilirubin, AST (SGOT), ALT (SGPT) and ALP were estimated. The histopathology of liver was also carried out. The physicochemical parameters of both test drugs viz. moisture content, total ash, acid insoluble ash and water soluble ash were found within normal limit. The total serum bilirubin, direct bilirubin, AST (SGOT), ALT (SGPT) levels were significantly decreased in Test groups A and B when compared to the Negative and Standard controls. The microscopic examination of liver collected from animals of Group IV and Group V revealed significant recovery from hepatic toxicity compared to the Negative control. The study experimentation has revealed that C. Zedoaria may be used as a substitute for A. rotunda in the treatment of liver diseases. However, the outcome has to be further corroborated with phytochemical evaluation and clinical trials of both the drugs. Furthermore, the concept of drug substitute in Unani system of medicine is also validated in the light of above study. [ABSTRACT FROM AUTHOR]

Doxorubicin (DOX) is a commonly used chemotherapeutic drug. However, its non-target organ toxicities pose a serious problem. This study is to assess the protective role of Clerodendrum volubile leaf extract (CVE) against DOX-induced toxicities in rats. In addition, the inhibitory activities of three phytochemical compounds (Rutin, Gallic acid and Rosmarinic acid) from CVE against Carbonyl reductase 1 (CBR1) were examined. Rats were randomly divided into 5 groups: (a) Control group rats were given 0.9% NaCl as vehicle, (b) DOX group: A single dose of DOX (25 mg/kg; i.p.) was administered and rats were sacrificed 4 days after DOX injection, while groups (c–e) CVE-treated DOX rat groups were given 125, 250 and 500 mg/kg body weight of extracts orally for 12 consecutive days; 8 days before, and 4 days after the DOX administration. Computational techniques were used to determine the inhibitory activities of the compounds against CBR1. DOX intoxication caused a significant increase (p<0.05) in serum marker enzymes: ALT, AST, ALP, LDH, CK activities. The levels of liver and heart tissues antioxidant parameters: GPx, SOD, CAT, and GSH were significantly (p<0.05) decreased in DOX-intoxicated rats with concomitant elevation of malondialdehyde levels. Pretreatment with CVE reversed the above trends. From the structural analysis, Rutin and RSA exhibited the highest binding free energies against CBR1, and also exhibited structural stability when bound with CBR1. Our study indicates the protective effect of CVE when used in combination with doxorubicin thus improving its chemotherapeutic application via inhibition of CBR-mediated metabolism. [ABSTRACT FROM AUTHOR]

Phytocannabinoids beyond the Δ9-tetrahy-drocannabinol have shown anticonvulsive effects. Also, alkylamides from Echinacea purpurea have been proved as cannabinomimetics. We examined the effect of the hydroalcoholic root extract of E. purpurea on pentylenetetrazol (PTZ)-induced tonic–clonic seizures and kindling model of epileptogenesis and the involvement of CB2 receptors as the mediator of this effect. Male Wistar rats (200 ± 20 g) were used. Single intraperitoneal (i.p.) injection of PTZ (80 mg/kg) was used to induce tonic–clonic seizures. The kindling model of epileptogenesis was induced by daily injections of PTZ (37 mg/kg; i.p. for 15 days). Latency and duration of the stages were monitored for analysis. The hydroalcoholic root extract of E. purpurea was injected (i.p.) 20 min before seizure induction at the doses of 10, 50, 100 and 200 mg/kg. CB2 receptor antagonist SR144528 was injected (0.1 mg/kg; i.p.) 20 min before the Echinacea injection. In the tonic–clonic model, pretreatment with E. purpurea at the doses of 100 and 200 mg/kg significantly increased latencies to S2–S6, while it significantly decreased S6 duration and mortality rate. SR144528 injection before the injection of 100 mg/kg of E. purpurea significantly prevented the effects of the extract on S4–S6 latencies. In the kindling model, E. purpurea at the doses of 100 and 200 mg/kg significantly delayed epileptogenesis and decreased mortality rate, while SR144528 injection before the injection of 100 mg/kg of E. purpurea significantly blocked this effect of the extract. These findings revealed the anticonvulsive and antiepileptogenesis effects of the E. purpurea root extract, which can be mediated by CB2 receptors. [ABSTRACT FROM AUTHOR]

The article highlights a study to compare between olive oil and almond oil to ameliorate blood parameters, liver function, blood and liver antioxidants and DNA, and liver histology in favism rats. It discusses that Almond oil restored blood parameters, liver function, blood and liver antioxidants and DNA, and liver histology more efficiently than olive oil in favism.

The article highlights a study to evaluate the effect of Ficus glumosa on phenylhydrazineinduced hemolytic anemia and hepatic damage in rats. It discusses that the leaves of F. glumosa contain important antioxidant(s) that could effectively reduce hemolytic anemia and hepatic damage, especially during phenylhydrazine-induced toxicity.

The article highlights a study which demonstrated the enhancing actions of probiotic on the antitrypanosomal effects of diminazene aceturate in dogs experimentally infected with Trypanosoma brucei brucei. It discusses that : The administration of multispecies probiotic to infected dogs enhanced the antitrypanosomal effects of diminazene aceturate.

Cynometra travancorica, endemic to Western Ghats of India is pharmacologically similar to Saraca asoca and occasionally used as substitute in a well-known Ayurvedic uterine tonic Asokarishta. S. asoca possess various biological properties, but there are no reports on C. travancorica. The present study evaluated the pharmacological properties of C. travancorica and its efficacy in attenuating the sodium fluoride (NaF) induced oxidative stress in mice. Antioxidant potential of methanolic extract of C. travancorica (CTE) stem bark was evaluated using DPPH, superoxide radical scavenging and total antioxidant assays. The effect of CTE on mitigating NaF deteriorated redox status in the liver tissue of mice was evaluated. Functional groups in CTE were analyzed by FTIR analysis. CTE effectively scavenged the free radicals in in vitro condition. CTE could augment catalase (46.6%), superoxide dismutase (53.8%) activities and GSH level (48.1%) against NaF induced decline in the liver tissue of mice. The peroxidation of lipids was found to be decreased by 44.9% and tissue damage abated as inferred by histopathology. FTIR analysis revealed the presence of biologically active functional groups in CTE. The study revealed the ameliorative effect of C. travancorica against NaF induced deleterious effect in experimental animals by its potent antioxidant potential. [ABSTRACT FROM AUTHOR]

Acute lung injury (ALI) is a life-threatening pulmonary dysfunction associated with severe inflammation. There are still no effective pharmacological therapies for the treatment of ALI. In this concern, several anti-inflammatory agents could be used as add-on therapy to inhibit inflammation. Achillea wilhelmsii (AW) C. Koch is a well-known medicinal plant in the Iranian ethnomedical practices with anti-inflammatory activity. This study was aimed to evaluate the efficacy of ethanolic extract of AW on lipopolysaccharide (LPS)-induced ALI in mice. The ALI model was established via the intra-tracheal (i.t.) administration of LPS (2 mg/kg) to male BALB/c mice. The ALI mice were divided into four groups (n=8 each) which intra-peritoneally (i.p.) treated with repeated doses of saline (model), dexamethasone (2 mg/kg), and AW (150–300 mg/kg) 1, 11 and 23 h post LPS administration. Twenty-four hours after the LPS challenge, bronchoalveolar lavage fluid (BALF) and lung tissue were evaluated for inflammatory cell influx, level of tumor necrosis factor-α (TNF-α) and histopathological changes. The AW (150–300 mg/kg) treated mice showed lower inflammatory cells infiltration in BALF and TNF-α level when compared to the model group. In addition, LPS induced several pathological alterations such as edema, alveolar hemorrhage and inflammatory cell infiltration into the interstitium and alveolar spaces. Treatment with AW significantly reduced LPS-induced pathological injury. Taken together, the data here indicated that AW may be considered as a promising add-on therapy for ALI. [ABSTRACT FROM AUTHOR]

Increasing hypertension incidence in Sub-Sahara Africa and the current cost of management of the metabolic disorder has necessitated research on medicinal plants employed in African Traditional Medicine for hypertension. Thus, this study evaluated antihypertensive effect of Annona muricata leaves or Curcuma longa rhizomes in experimentally-induced hypertensive male Wistar rats (n=70) which were unilaterally nephrectomized and daily loaded with 1% salt. Cardiovascular and haematological changes, as well as urinalysis were determined. Rats were uninephrectomized and NaCl (1%) included in drinking water for 42 days. Extract-treated hypertensive rats were compared to normotensive, untreated hypertensive and hypertensive rats treated with lisinopril (5 mg/70 kg) or hydrochlorothiazide (12.5 mg/70 kg). A. muricata extract or C. longa extract were administered at 100, 200 or 400 mg/kg. Blood pressure (systolic, diastolic and mean arterial) and electrocardiogram was measured on day 41. Twenty-four-hour urine samples were collected from day 42. Blood samples were collected on day 43 for haematology (PCV, red cell indices, WBC and its differentials, and platelets). A. muricata or C. longa extracts caused a decline in elevated blood pressure of hypertensive rats. Heart rate and QT segment reduction coupled with prolonged QRS duration were reversed in extract-treated rats, with significant increases in hemogram parameters indicating increased blood viscosity. Also, leukocyturia, proteinuria and ketonuria with increased urine alkalinity, urobilinogen and specific gravity which are classical indicators of poor prognostic outcomes in hypertension were reversed in extract-treated rats. In conclusion, A. muricata and C. longa have cardioprotective effect with reversal of derangements in haemogram and urinalysis associated with hypertension. [ABSTRACT FROM AUTHOR]

Teucrium polium (TP) has been traditionally used for treatment of the diabetes mellitus, kidney and liver diseases, and inflammations but some studies have reported the hepatotoxicity effects of this plant. Therefore, this study was conducted to investigate the effect of TP aqueous extract on the liver of the diabetic rats. Adult male Wistar rats were randomly divided into five groups: (Control) Normal rats that were gavaged with normal saline (1 mL), (TP100) Normal rats (Non-diabetic) that were gavaged with TP (100 mg/kg), (DM) diabetic model rats, which became diabetic by intraperitoneal injection of streptozotocin (50 mg/kg), (DTP100) diabetic rats that were gavaged with TP (100 mg/kg), and (DTP200) diabetic rats that were gavaged with TP (200 mg/kg). The effects of the aqueous extract on the blood glucose, body weight, the activities of enzyme markers of liver damage (Aspartate Aminotransferase (AST) and Alanine Aminotransferase (ALT)) were investigated in the serum of the control and treated groups. At the end of study liver histopathology and the total antioxidant activity (TAA) test were evaluated. Finally, obtained data were analyzed by the SPSS software (version 16). Results showed that the AST and ALT levels were significantly increased in the diabetic rats (p<0.001). A comparison of 100 mg/kg and 200 mg/kg doses of TP administration in diabetic rats also showed a significant difference (p=0.01), indicating a better performance of 100 mg/kg dose. No significant difference was found between the control group and rats treated by the TP (TP100) (p=0.382). Also, triglyceride (TG) and cholesterol levels were significantly decreased in the treated groups compared to the diabetic untreated group. Findings of the study revealed no hepatotoxicity, and the hepatoprotective effects of the TP were proved in the present study. [ABSTRACT FROM AUTHOR]

Cardiovascular diseases (CVDs) are highly prevalent in various countries, and heart failure accounts for the majority of deaths. The present study focuses on determining the protective effect of ethanol extract of leaves of Tamarindus indica (TIEE) by in vitro and in vivo methods. In vitro cardiotonic activity was determined using Langendorff's heart perfusion assembly. In vivo studies were performed using Doxorubicin (1.5 mg/kg, i.p for seven days) induced cardiotoxicity in rats. These animals were simultaneously treated with the TIEE at a low dose (200 mg/kg, p.o), high dose (400 mg/kg, p.o) and standard drug Digoxin (100 μg/kg, p.o) for seven days. At the end of the study, various parameters like electrocardiogram (ECG) recording, serum levels of serum glutamic pyruvic transaminase (SGPT), lactate dehydrogenase (LDH), creatinine phosphokinase (CPK), and presence of cardiac troponin (cTnI) were determined. Isolated hearts were subjected to histopathological studies. The TIEE at a concentration of 60 μg/mL showed a significant cardiotonic effect in vitro that was evident by increased force of contraction, heart rate, and cardiac output. In vivo studies revealed that the TIEE decreased the prolongation of QT and RR interval of ECG, lowered the serum enzyme levels like LDH, CPK indicating cardiac protection, and the same was established by the absence of cTnI in blood. Histopathological examinations of heart tissue sections showed improved architecture in the treatment groups when compared with diseased groups. The study revealed the cardioprotective activity of T. indica leaf extract by both in vitro and in vivo methods. [ABSTRACT FROM AUTHOR]

This study examined the possible protective roles of exogenous glycine (Gly) and L-Arginine (l-Arg) against Diclofenac (DIC)-induced gastro-duodenal damage in rats. Rats were divided into Group A (control), Group B (DIC group) and Groups C–F which were pre-treated for five days with Gly1 (250 mg/kg), Gly2 (500 mg/kg), l-Arg1 (200 mg/kg) and l-Arg2 (400 mg/kg), respectively, before co-treatment with DIC for another three days. Hematological, biochemical and histopathological analyses were then carried out. DIC produced significant (p<0.05) reduction in PCV (13.82%), Hb (46.58%), RBC (30.53%), serum total protein (32.72%), albumin (28.44%) and globulin (38.01%) along with significant (p<0.05) elevation of serum MPO activity (83.30%), when compared with control. In addition, DIC increased gastric H2O2 and MDA levels by 33.93 and 48.59%, respectively, while the duodenal levels of the same parameters increased by 19.43 and 85.56%, respectively. Moreover, SOD, GPx and GST activities in the DIC group were significantly (p<0.05) reduced in the stomach (21.12, 24.35 and 51.28%, respectively) and duodenum (30.59, 16.35 and 37.90%, respectively), compared to control. Treatment with Gly and l-Arg resulted in significant amelioration of the DIC-induced alterations although l-Arg produced better amelioration of RBC (29.78%), total protein (10.12%), albumin (9.93%) and MPO (65.01%), compared to the DIC group. The protective effects of both amino acids against oxidative stress parameters and histological lesions were largely similar. The data from this study suggest that Gly or l-Arg prevented DIC-induced gastro-duodenal toxicity and might, therefore be useful in improving the therapeutic index of DIC. [ABSTRACT FROM AUTHOR]

Protocatechuic acid (PCA) possesses numerous pharmacological activities, including antioxidative and anti-inflammatory activities. This study seeks to investigate its underlying mechanism of action in the liver and brain toxicity induced by CCl4 in male albino rats. Rats were given PCA at 10 and 20 mg/kg daily and orally as a pretreatment for seven days. A single injection of CCl4 was given 2 h later to induce brain and liver toxicity. CCl4 moderately elevated the activities of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP). PCA lowered AST level significantly when compared to control. Total protein and albumin levels presented insignificant changes (p>0.05) in all groups while lipid profile showed increased total cholesterol level and reduced high-density lipoprotein (HDL) by CCl4. PCA (10 mg/kg) significantly reduced the cholesterol level while the 20 mg/kg dose moderately prevented HDL reduction. There was an increased MDA production with a corresponding low GSH level in the group treated with CCl4. Activities of superoxide dismutase, catalase, and glutathione-S-transferase in both organs also declined. PCA, especially at 10 mg/kg attenuated lipid peroxidation by increasing GSH level in the organs. Biochemical assays revealed the improvement of antioxidant enzyme activities by PCA in these organs. Furthermore, PCA lowered the level of proinflammatory cytokine COX 2 in the brain and liver while NF-kB expression was inhibited in the brain. Histopathology reports validated the effects of PCA. PCA exhibited protection against toxicity in these tissues through antioxidant and anti-inflammatory activities and the potential mechanism might be through modulation of the NF-κB/COX-2 pathway. [ABSTRACT FROM AUTHOR]

Comparative evaluation of cardioprotective activity of Gala and Fuji apple juice against isoprenaline induced cardiotoxicity in rats. Rats (125–150 g) were orally administered Gala (GA) and Fuji (FA) apple juice (3 mL/day, per oral) for 13 days. Myocardial injury was inducted on 14th and 15th day by the administration of Isoprenaline (85 mg/kg/day, subcutaneous). In treated group i.e. GA and FA, aspartate aminotransferase (AST), alanine transaminase (ALT), lactate dehydrogenase (LDH), creatine kinase (CK), Troponin-I level and malondialdehyde (MDA) content was reduced while glutathione (GSH), superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) level was significantly increased. Marked reduction in cholesterol, triglyceride, phospholipids, low-density lipoprotein (LDL) and very low-density lipoprotein (VLDL) was observed while high-density lipoprotein (HDL) level increased significantly. In tissue and serum total serum protein (TSP) level, Albumin, Globulin and A/G ratio increased very significantly in the treated group while the level of white blood corpuscles (WBC), haemoglobin (Hb), erythrocyte sedimentation rate (ESR), total fibrinogen (TF), bleeding time (BT), c-reactive protein (C-rP), red blood corpuscles (RBC), clotting time (CT) and prothrombin time (PT) showed a significant rise in the level. The level of Sialic acid, hexose, fucose and hexosamine was highly significantly increased, there was an increase in the level of K+ and glycogen while a significant reduction in electrolyte and glucose level was observed when all these parameters were compared to Isoprenaline (ISO) group. The above findings were supported by histopathological examination of hearts. Cardioprotective activity was compared with standard drug, metoprolol. On comparative analysis of both juices, GA juices have found more effective when compared to FA juice. The study was concluded that Gala and Fuji apple possessed significant prophylactic and protective effects against Isoprenaline-induced cardiotoxicity in rats through maintaining inhibiting lipid peroxidation, endogenous antioxidant enzyme activities and cytokine levels. [ABSTRACT FROM AUTHOR]

Early diagnosis and management of known cardiovascular disease risk attributes such as hypertension lessens morbidity and mortality as well as increase quality of life of patients. This present study was modelled to investigate the ameliorative effect of Kolaviron, an extract of Garcinia kola Heckel seeds, in ethanol- and sucrose-induced hypertension. Test animals were divided into six groups of six animals each for each hypertensive model. Animals were treated daily with distilled water (10 ml/kg); 35% ethanol (3 g/kg) or sucrose (5–7%); Kolaviron (50, 100 and 200 mg/kg) separately plus ethanol or sucrose and Amlodipine (0.14 mg/kg) separately plus ethanol or sucrose for 8 weeks. Systolic, diastolic and mean arterial pressures were determined using non-invasive BP system after 8 weeks. Blood was obtained for the assessment of biochemical parameters, lipid profile and antioxidant indices. Vital organs were collected for approximation of tissue antioxidant levels. Results show that Kolaviron at various doses and Amlodipine significantly reduced (p<0.05–0.001) the elevated systolic, diastolic, and mean arterial pressures produced by ethanol and sucrose administration. Additionally, Kolaviron and Amlodipine significantly overturned (p<0.05–0.001) the reduction in GSH, SOD and CAT, and elevation in MDA levels elicited by ethanol and sucrose. Furthermore, Kolaviron and Amlodipine produced significant reduction (p<0.001) in levels of cholesterol, triglycerides and low-density lipoproteins, as well as significant increase (p<0.01–0.001) in levels of high-density lipoproteins. Results from this study demonstrate that Kolaviron possibly possesses significant antihypertensive effect which may possibly be attributed to its antioxidant effects and relative improvement of lipid profile. [ABSTRACT FROM AUTHOR]

Madhulai Manappagu – a well-known sastric and widely prescribed Siddha herbal syrup formulation indicated for treating Veluppu Noi (Anaemia especially Iron deficiency Anaemia) has been in day today practice in Tamil Nadu for a quite longer decades. The syrup is a herbal preparation which has a sweet pleasant odour and a palatable taste, contain the juice of pomegranate (Punica granatum L.) as the main ingredient. Though the formulation is a fruit juice, the safety profile of the syrup is not established and is being marketed without toxicological evaluation. The study is aimed at ascertaining the acute and sub-acute toxicity assessment of Madhulai Manappagu in Wistar Albino rats. The acute and sub-acute (28day repeated oral) toxicity studies were performed as per the guidelines mentioned in the Organization for Economic Cooperation and Development (OECD) 423 (adopted on December 2001) and TG 407 (adopted on October 2008) with slight modifications respectively. For acute toxicity study, three female rats were randomly selected as control; three female rats were randomly selected and were administered a single dose of 5,000 mg/kg body weight per oral route. For sub-acute (28day repeated oral) toxicity studies, three doses of test drug MM of 500 mg/kg/day (low dose), 750 mg/kg/day (intermittent dose) and 1,000 mg/kg/day (high dose) were selected for administration. Both sexes of Wistar Albino rats were randomized into four groups of 10 animals each (five males, five females). Group I was kept as control group. Group II, III and IV served as low, intermittent and high doses of MM respectively. Animals were observed for mortality, morbidity, body weight changes, feed and water intake. Haematology, clinical biochemistry, electrolytes, gross pathology, relative organ weight and histopathological examination were performed. In the acute toxicity study, rats showed no toxicological signs on behavior, gross pathology and body weight of rats when treated with a single dose of 5,000 mg/kg body weight per oral route. In the subacute (28 days repeated oral) toxicity study, rats have showed no significant changes on behavior, gross pathology, body weight, and hematological and biochemical parameters when treated with Madhulai Manappagu in three different doses. The toxicity studies which include both acute and 28 days repeated (subacute) oral toxicity studies, revealed no observed adverse effect level (NOAEL) of Madhulai Manappagu in animals. Thus the safety of the drug in human usage was ensured. [ABSTRACT FROM AUTHOR]

Parshioshan (Adiantum capillus-veneris L.), Duqu (Peucedanum grande C.B. Clarke), Kaknaj (Physalis alkekengi L.) and Kharekhasak (Tribulus terresteris L.) have been selected for this study as they have been associated with medicinal actions for litholytic activity. The experiment was carried out in Sprague Dawley rats divided into seven groups, serving as plain control, disease control, standard control, curative A and B and preventive A and B groups. Animals of plain control received distilled water. Remaining six groups received Ethylene glycol 0.75% and Ammonium chloride 1% by adding in the drinking water for the first three days followed by 0.75% Ethylene glycol for 18 days. From 8th day till 21st day, standard control received Cystone in the dose of 750 mg/kg. Preventive and curative test groups were treated with hydroalcoholic extract of the test drug in the dose of 132 mg/kg and 264 mg/kg from 1st to 21st day and 8th to 21st day of calculi induction. Test drug reduced the number of calcium oxalate crystals in the urine; the level of urinary calcium, creatinine, magnesium, phosphorus, sodium and chloride decreased significantly in standard and test groups. The urine volume increased significantly in all the test groups. The level of serum calcium, urea, phosphorus and creatinine were significantly reduced in all the test groups. These results indicated that the test drug reduced and prevented the growth of urinary stones. Moreover, the test drug also possessed significant antiurolithiatic activity. However, the protective effect was found more than its curative effect. [ABSTRACT FROM AUTHOR]

This study was designed to evaluate the ameliorative effect of almond (Terminalia catappa) leaf (ALE) and stem bark (ABE) extracts on the enzyme activities and oxidative stress markers in the brain and liver tissues of cyclosporine-A (CsA) stressed male albino rats. Eighty-eight adult male rats weighing between 200 and 220 g were randomly distributed to into 11 groups (n=8) and different doses (100 and 200 mg/kg bwt.) of ALE and ABE were administered through oral gavages to the normal rats and 50 mg/kg/bwt/day CsA-stressed, while normal control rats was given a saline solution (p.o), and the treatment lasted for 14 days. Blood plasma, liver and brain tissues were prepared for biochemical analysis. Neuronal [acetylcholinesterase (AChE) and butrylcholinesterase (BChE) and arginase] enzyme activities and thiobarbituric acid reactive species (TBARS) level, plasma aspartate transferase (AST), alanine aminotransferase (ALT) and alkaline phosphatase (ALP) activities, liver non-protein thiol (NPSH) level were analyzed. The results revealed that, the administration of CsA induced a significant increase in neuronal AChE, BChE, arginase, TBARS level, but decreased nitric oxide (NO) level. CsA also increased ALT, AST, and ALP activities in the blood plasma of CsA stress rats compared to normal control, but were significantly reversed respectively (p<0.001) upon treatment with the ALE and ABE dose-dependently. The study revealed that ALE and ABE could prevent neuronal dysfunction and liver toxicity induced by CsA administration, however, higher dose (200 mg/kg) of the studied extracts appears to be more potent. [ABSTRACT FROM AUTHOR]

The liver is one of the primary biorepositories of cadmium (Cd) and it has been implicated in the pathogenesis of hepatic diseases. Quassia amara stem bark has been reputed to have strong antimalarial, antimicrobial, antiulcerative and amoebicidal properties. This study aims to determine the effects of Q. amara on Cd-induced hepatotoxicity and lipid profile in male Wistar rats. The animals were divided into three groups of five animals each. Group 1 served as control while group 2 received Cd (5 mg/kg) for 4 weeks. Prior to Cd treatment, group 3 was treated with Q. amara extract (200 mg/kg) for 2 weeks and received the Q. amara and Cd simultaneously for 4 weeks. Cadmium caused significant increase in serum total cholesterol and low-density lipoprotein (LDL) as well as increased hepatic malondialdehyde (MDA) when compared with the control group. On the other hand, Cd caused a decrease in serum high-density lipoprotein (HDL) and hepatic superoxide dismutase (SOD) when compared with control. However, treatment with Q. amara prevented Cd-induced changes in the lipid profile, augmented Cd-induced decline in SOD and also ameliorated the Cd-induced increase in MDA. Catalase level was however comparable across the groups. Q. amara ameliorated the Cd-induced damage to liver by preventing dyslipidemia and oxidative damage in the hepatic tissue. [ABSTRACT FROM AUTHOR]

Pre-pregnancy obesity is a serious epidemics concern that negatively affects the neurodevelopmental of the offspring. Elateriospermum tapos (E. tapos) commonly used to enhance weight loss in obesity treatment. This study was aimed to investigate the influence of E. tapos supplement in obese maternal prior pregnancy on the offspring's bodyweight, lipid metabolism and memory function. Thirty female Sprague Dawley rats were used. Six rats were assigned to the normal diet group (DND). The remaining rats were fed with a high-fat and cafeteria diet (HFCD) to generate obesity for 5 weeks. Obese rats were further divided into four groups: Negative Control (DNC; HFCD), Positive Control (DPC; Orlistat 200 mg/kg), treatment 1 (DTX1; E. tapos seed 200 mg/kg) and treatment 2 (DTX2, E. tapos shell 200 mg/kg) were given daily, for 6 weeks prior to mating. At weaning, offspring of both genders were designated into six groups according to their dam's group (n=6/group). All groups were fed with a cafeteria diet except for the control group. Memory tasks for object and place recognition were conducted on offspring at eighth weeks of age. The offspring were cull at the 12th week of age for their blood sample. Both offspring genders from DTX2 significantly reduce bodyweight, calorie intake and triglyceride level. In memory tasks, offspring from DTX2 showed a significant increase in exploration rate in place test as compared to offspring from the DNC group. This study highlights E. tapos shell as an anti-obesity agent and protecting memory deficit in obese dam's offspring. [ABSTRACT FROM AUTHOR]

Nanotechnology is an exciting field for investigators. Green zinc oxide nanoparticles (ZnO NPs) with Camellia sinensis extract complex are proved to be used in the treatment of the toxicity of monosodium glutamate (MSG) in the liver, kidney, and testis of rats. Therefore, the synthesized complex of green nanoparticles using green tea extract (GTE) was tested against the toxicity of MSG on the pancreas. The glucose and insulin levels were estimated as well as some biochemical parameters for evaluating the antioxidant status of the pancreas tissue. The histopathological change of the pancreas also has been determined. It indicates the biomedical capability of ZnO NPs/GTE to act as potent antidiabetic through decreasing blood glucose and increasing serum insulin also, inhibition of lipid peroxidation and enhancement of the antioxidant parameters. The ZnO NPs/GTE enhanced the pancreatic cell and Langerhans islets as well lowered the sugar levels and stimulated insulin. [ABSTRACT FROM AUTHOR]

Rauvolfia vomitoria is a medicinal plant used traditionally in Africa in the management of several human diseases including psychosis. However, there is inadequate scientific information on the potency of the phenolic constituents of R. vomitoria leaf in the management of neurodegeneration. Therefore, this study characterized the phenolic constituents and investigated the effects of aqueous and methanolic extracts of R. vomitoria leaf on free radicals, Fe2+-induced lipid peroxidation, and critical enzymes linked to neurodegeneration in rat's brain in vitro. The polyphenols were evaluated by characterizing phenolic constituents using high-performance liquid chromatography coupled with diode array detector (HPLC-DAD). The antioxidant properties were assessed through the extracts ability to reduce Fe3+ to Fe2+; inhibit ABTS, DPPH, and OH radicals and Fe2+-induced lipid peroxidation. The effects of the extracts on AChE and MAO were also evaluated. The phenolic characterization of R. vomitoria leaf revealed that there were more flavonoids present. Both aqueous and methanolic extracts of R. vomitoria leaf had inhibitory effects with the methanolic extract having higher significant (p≤0.05) free radicals scavenging ability coupled with inhibition of monoamine oxidases. However, there was no significant (p≤0.05) difference obtained in the inhibition of lipid peroxidation and cholinesterases. This study suggests that the rich phenolic constituents of R. vomitoria leaf might contribute to the observed antioxidative and neuroprotective effects. The methanolic extract was more potent than the aqueous extract; therefore, extraction of R. vomitoria leaf with methanol could offer better health-promoting effects in neurodegenerative condition. [ABSTRACT FROM AUTHOR]

Psoriasis is an autoimmune, inflammatory disease that needs a reliable animal model. Imiquimod (IMQ)-induced psoriasis is a widely used preclinical tool for psoriasis research. However, this model is sensitive to the genetic variation of mice. The present study explores mice's genetic background on disease stability and severity induced by IMQ. Three distinct strains of mice (Balb/c, C57BL/6, and Swiss albino) were divided into four groups (Vaseline, IMQ, IMQ+Clobetasol, and IMQ+Curcumin). Psoriasis area severity index (PASI) score, ear/back skin thickness, body weight alterations, and histopathological examination were employed to analyze disease severity. The spleen index studied the systemic effect. Strain effect on oxidative stress induced by IMQ was evaluated by estimating antioxidant factors, superoxide dismutase (SOD), catalase, and glutathione (GSH). IMQ application resulted in increased PASI score, thickness, and alterations in body weight, confirming disease development in all the mice. However, the disease stability/severity between these strains was not identical. Although IMQ application caused splenomegaly, IMQ+curcumin treated C57BL/6 mice demonstrated a synergistic effect of IMQ and curcumin on the spleen resulting in increased splenomegaly. Decreased cellular enzyme activity in SOD, Catalase, and levels of GSH was observed in IMQ challenged mice, indicating the participation of the redox system in the genesis of the disease that was comparable among the strains. These results indicate the existence of strain-dependent development of the disease. The Swiss model was found to be better in terms of disease severity and stability than other models. Further, a detailed mechanistic study might help to explain the pathological difference between these strains. [ABSTRACT FROM AUTHOR]

Terminalia arjuna (TA) has been widely used as folk medicine since ancient times. Apart from its therapeutic properties it also has anti-spermatogenic activity, but its effectiveness and mode of action on male gonadal activity remains to be revealed. TA bark extract was dissolved in 1% dimethyl sulfoxide and applied in primary Leydig cell culture from rat testis in dose dependent manner. After 24 h of treatment cellular toxicity marker, cytokines, steroid 5-alpha-reductase 1 (SRD5A1) and androgen receptor (AR) were measured. Present study first proposed the cytotoxic impacts of TA on Leydig cells via leakage of lactate dehydrogenase and inflammatory responses by altering the pro- and anti-inflammatory cytokines in dose-dependent-manner. Furthermore, down regulation of SRD5A1 and AR indicated inhibition of normal steroidogenesis which well corroborated with cytotoxity and inflammation related parameters to promote damage of Leydig cell function. Nevertheless, it can be speculated that the inhibition of normal steroidogenesis and thereby spermatogenesis induced by TA is possibly due to the presence of β-sitosterol. Therefore, the dose and duration of treatment should be carefully monitored in cases of its medicinal uses and longer duration should be avoided to protect reproductive health and fertility. [ABSTRACT FROM AUTHOR]

Ghee is widely considered as the Indian name for clarified butterfat and processing of ghee with therapeutic herbs i.e., ghrita is renowned for augmenting their medicinal properties. The wound is considered as a challenging clinical problem with early and late complications. To reduce the burden of wounds with the shortest period and minimum scaring, an attempt was made to prepare and evaluate the wound healing potential of ghee based polyherbal formulation. Based on local ethnic tribal claims, Semecarpus anacardium L., Argemone mexicana L., Cocculus hirsutus L., and Woodfordia fruticosa K. were collected from Western Ghats of India. The polyherbal Bhallatakadi Ghrita (BG) formulation was prepared as per Ayurvedic procedure and assessed for its wound healing potential using incision and excision wound animal models. BG treated group showed a complete contraction of wounds (99.82 ± 0.10%) (p<0.001) with 15.17 ± 0.40 days re-epithelization time and breaking strength (531.50 ± 5.89) (p<0.05). The hydroxyproline content of BG was found to be significantly higher i.e., 4.23 ± 0.21 (p<0.05). Quantitative estimation of BG exhibited 54.7 ± 3.7 mg100 g−1 of polyphenols and 42.3 ± 5.4 mg.100 g−1 flavonoids in terms of gallic acid and quercetin respectively. HPLC analysis revealed the presence of gallic acid and quercetin whereas the presence of fatty acids was confirmed by GC-MS analysis. It may conclude that the presence of quercetin, gallic acid, and fatty acids could have accelerated the healing rate of the ghrita formulation, as they have already been known for their potential wound healing properties. [ABSTRACT FROM AUTHOR]

Neera, non-fermented coconut inflorescence sap (NFCIS) and its fermented form, toddy (FCIS) are the two well-known traditional drinks in South India. Both the saps show high rejuvenation effect and NFCIS is used for the curing of bronchial suffocation, anemia, tuberculosis and piles in traditional medicine. But, a few scientific studies have been reported on their health benefits so far. Presently, the antioxidant effect of both non-fermented (NFCIS) and fermented form (FCIS) of coconut inflorescence were analyzed in experimental animals. The free radical scavenging property of FCIS and NFCIS was analyzed in vitro. The effect of these saps on mitigating sodium fluoride (NaF) deteriorated redox status was evaluated in mice. NFCIS exhibited high antioxidant activity than its fermented form. NFCIS reduces metal ions and scavenge hydroxyl and DPPH radicals with IC50 values 6.5 ± 1.9 and 44 ± 3.14 µL/mL, respectively. Supplementation of NFCIS for 14 days increased SOD, CAT and GPx activities and GSH level in liver by 51.67, 52, 27.88 and 35.77%, respectively against NaF induced decline with a concomitant decrease in lipid peroxidation to 40.76%. Saps rich in minerals indicate pharmaceutical and nutritional value. The study revealed the antioxidant efficacy of non-alcoholic natural drink, Neera and recommends an alternative for synthetic carbonated soft drinks. The regular consumption of Neera may protect the body from various chronic diseases especially where the oxidative stress played as a key role. [ABSTRACT FROM AUTHOR]

Native Bacillus thuringiensis BK5.2, isolated from soil of Baluran National Park, East Java, Indonesia, has been shown to be toxic against Aedes aegypti larvae. This study aims to determine the strength and the speed of the toxicity of B. thuringiensis BK5.2 against A. aegypti larvae in lethal concentration (LC) and lethal time (LT), as well as detection of toxin structure and parasporal inclusion. LC values were determined by the mortality of A. aegypti third instar larvae after 24 and 48 h exposure to five various concentrations of B. thuringiensis BK5.2, while LT values were determined based on the mortality of A. aegypti third instar larvae due to exposure to LC90 concentration at 0; 0.5; 1; 2; 4; 8; 10; 20; 24; and 48 h. Larvicidal toxicity was determined based on value of LC50 and LC90 (CFU/mL), as well as LT50 and LT90 (hours) analysed ​​with Probit analysis. Parasporal inclusion was detected using transmission electron microscope (TEM) and scanning electron microscope (SEM). Based on bioassay, LC50 and LC90 values ​​were 11.6 × 106 and 22.7 × 106 CFU/mL, respectively, at 24 h exposure, as well as 8.3 × 106 and 15.4 × 106 CFU/mL, respectively, at 48 h exposure, while the value of LT50 and LT90 were 19.0 and 26.6 h, respectively. Morphological observation of the dead larvae showed there was damage on abdomen and thorax region. Detection by TEM and SEM showed there was cuboidal parasporal inclusion. Native B. thuringiensis BK5.2 has high toxicity against A. aegypti larvae and detected flatcuboidal toxin in parasporal inclusion. [ABSTRACT FROM AUTHOR]

Several studies establish the therapeutic properties of various plants which are sometimes a source of minerals, vitamins and phytochemical compounds. However, many studies evoked potential toxic of some. In Cameroon, Crassocephalum crepidioides (C.c) is used in folk medicine to treat several diseases, but there are not much informations about its toxicity. This study evaluate its acute and sub-acute toxicity. Our study was undertaken to evaluate acute and sub-acute toxicity of aqueous leaves extract of C.c. The study was conducted using the OECD guidelines about oral toxicity's study. For acute toxicity, rats were administrated single oral dose of 5,000 mg/kg body weight (b.w) and monitored for death and weight impairment during seven days. In sub-acute toxicity, experimental rats received daily doses of 250,500 and 1,000 mg/kg b.w during 28 consecutive days. The toxics effects of the extract were assessed using anthropometric, haematological, biochemical parameters as well as histology of vital body's organs (liver, kidneys, lungs and spleen). lethal dose 50 (LD50) was find to be greater than 5,000 mg/kg b.w in rats. In sub-acute toxicity, we observed significant increase of body weight, food and water consumption with the maximums of 15.14, 24.52 and 28.86% respectively at 1,000 mg/kg b.w. There was no significant change in haematological parameters. However, we observed significant change in biochemical parameters. Furthermore, structural disorders were noticed in liver and kidneys of animals treated with C.c. Data obtained suggesting that C.c extract could be safe in single administration, but with toxic effects in repeated treatment. [ABSTRACT FROM AUTHOR]