Administration Of Distilled Water Research Articles

Wound healing activity of hydromethanolic Dioscorea bulbifera extract on male wistar rat excision wound models

IntroductionWound healing is a complex physiological process that involves a series of coordinated events that recover structural and functional tissue integrity. The desire to promote nature-based solutions has led to the screening of various plants and herbs for their wound healing potentials with results showing the enhancement of various aspects of the wound healing process. Dioscorea bulbifera possesses a wide range of applications in folk remedies. In traditional Chinese medicine, it is used in the treatment of mumps, goitre, sore throat, gastric cancer and carcinoma of the rectum alone or in combination with other plants. The present study evaluated the effect of hydromethanolic extract of Dioscorea bulbifera (HEDB) on wound size, percentage of wound contraction and tissue hydroxyproline in male Wistar rat excision wound models. MethodsTwenty-five (25) male Wistar rats (180–200 g) were used for the study. They were divided into five (5) groups comprising five (5) animals per group. A circular excision wound (1.5–2 cm) was experimentally induced in each animal following ketamine anaesthesia. Groups I and II served as negative and positive controls and were treated with topical administration of distilled water and petroleum jelly respectively. Groups III, IV and V served as the experimental groups and were treated with 200, 400 and 800 mg/kg of HEDB topically. The diameter of the wound was measured and the wound area and percentage of wound contraction were calculated. Tissue hydroxyproline was determined using tissue excised from the healed portion of the dorsal surface of the animals via coulometric standard procedures. ResultsData from the study indicates that animals in the experimental groups (III, IV and V) had an earlier wound closure compared to the control. Animals treated with 200 mg/kg HEDB (Group III) showed complete wound closure by day 17, whereas animals treated with 400 mg/kg (Group IV) and 800 mg/kg HEDB (Group V) groups achieved complete wound closure by the 18th and 20th day of the experiment respectively. Similarly, all the animals in the experimental groups had significantly increased percentage of wound contraction compared to negative control (P < 0.05). Tissue hydroxyproline was significantly raised amongst the animals treated with 200 and 800 mg/kgHEDB compared to the negative control (p < 0.05). DiscussionEvidence from the study has shown that HEDB possesses potent wound healing activity as the present study has demonstrated that it reduced wound area, and increased wound contraction and tissue hydroxyproline on experimentally induced excision wound male Wistar rat models. These findings provide scientific evidence that validates the traditional medicinal application of Dioscorea bulbifera in promoting wound healing.

Hematological changes, oxidative stress assessment, and dysregulation of aquaporin-3 channel, prolactin, and oxytocin receptors in kidneys of lactating Wistar rats treated with monosodium glutamate.

High consumption of locally produced delicacies could expose nursing mothers to high monosodium glutamate (MSG) levels, frequently used as a necessary condiment in low-income countries. Thus, this study evaluated some novel preliminary changes in renal hormonal receptors, the aquaporin-3 channel, oxidative stress markers, and hematological indices induced by monosodium glutamate in lactating rats. Post-parturition, twenty-four (24) lactating Wistar rats were divided into four (4) groups of six rats each (n = 6). Oral administration of distilled water and MSG started three (3) days postpartum as follows: group 1: distilled water (1ml/kg BW), group 2: MSG (925mg/kg BW), group 3: MSG (1850mg/kg BW), and group 4: MSG (3700mg/kg BW). At the end of the experiment, which lasted fourteen (14) days, animals were sacrificed and samples of blood and tissues were obtained for biochemical analysis. MSG administration significantly (p < 0.05) increased ROS and MDA, with a significant (p < 0.05) decrease in kidney antioxidants. Serum creatinine, total, conjugated, and unconjugated bilirubin significantly (p < 0.05) increased with MSG administration. The prolactin receptor was significantly reduced (p < 0.05), while the oxytocin receptor and aquaporin-3 channel were significantly (p < 0.05) increased in the MSG-administered groups. There were significant (p < 0.05) changes in the hematological indices of the MSG-administered animals. Thus, the findings of this study suggest that high MSG consumption causes hematological alterations and may alter renal function via increased ROS production and dysregulation of the AQP-3 channel, prolactin, and oxytocin receptors in the kidneys of lactating Wistar rats.

Acute Antidepressant Activity Investigation of Selected African Medicinal Plants in Mice: A Preliminary Study

The therapeutic gap arising from high global incidence of depressive disorders and the efficacy and toxicity shortcomings of existing antidepressant drugs indicate a need to further search the plant kingdom with the goal of discovering novel antidepressant pharmacotherapeutic agents. Crude 50% ethanol Terminalia catappa (CETC), Tapinanthus dodoneifolius (CETD) and Bryophyllum pinnatum (CEBP) leaf extracts were investigated for their acute antidepressant activity on the forced swim (FST) and tail suspension (TST) tests. Groups of mice (n = 6) were each exposed to the tests 1 hour following oral administration of distilled water (10 ml/kg), extracts (125, 250 and 500 mg/kg body weight) and fluoxetine (20 mg/kg), using the mean immobility time as endpoint. Qualitative phytochemical analysis of these crude extracts indicated the presence of alkaloids, cardiac glycosides, saponins, phenolic compounds, tannins, steroids, carbohydrates, flavonoids, terpenoids and anthraquinones. Compared to distilled water treatments (FST, 84.16 ±3.92; TST, 82.85 ±5.84), CETC (FST, 84.17 ±4.44, 71.67 ±1.89, &amp; 44.31 ±8.23*; TST, 79.03 ±2.62, 74.10 ±3.11, &amp; 52.57 ±6.00*) and CEBP (FST, 77.02 ±2.70, 66.11 ±4.42 &amp; 49.99 ±4.20*; TST, 69.51 ±7.24, 49.73 ±11.85* &amp; 46.39 ±5.68**) treatments caused dose-dependent and significant (P &lt; 0.05) reductions in the mean immobility times on both paradigms while CETD caused dose-dependent and significant (P &lt; 0.05) reductions of this parameter only on the TST. Overall, acute antidepressant activities at the highest dose level (500 mg/kg) of all extracts approximated that of the standard antidepressant fluoxetine (20 mg/kg). The findings of this study are a justification for the widespread ethnomedicinal uses of extracts of these plants. There is a need to further characterize their antidepressant and other neuropharmacological effects. 1.

Effect of taxifolin on clozapine-induced experimental oxidative and inflammatory heart damage in rats

AimClozapine is an atypical antipsychotic (AAP) drug used in treatment-resistant schizophrenia patients. The adverse effects of clozapine on the heart may result in death and require drug discontinuation. Inflammatory mechanisms are thought to be responsible for the negative effect of clozapine on the heart. This suggests that using an agent with anti-inflammatory and antioxidant properties, which may be specific to clozapine-induced heart damage, may prevent possible damage. The aim of our study is to evaluate the effect of taxifolin (3,5,7,3’,4’-pentahydroxy flavanone), an agent with known antioxidant and anti-inflammatory effects, on myocardial damage caused by clozapine with biochemical and histopathological data. Material and methodThe rats were divided into three equal groups: healthy control group (HC), clozapine-treated group (CLN), and taxifolin+clozapine-treated group (TCL). To perform this experiment, taxifolin was administered to TCL (n-6) rats at a dose of 50mg/kg orally by gavage into the stomach. In the HC (n-6) and CLN (n-6) groups, the same volume of distilled water was administered orally as a solvent. One hour after the administration of taxifolin and distilled water, clozapine was administered orally at a dose of 20mg/kg to the TCL and CLN groups once a day for 28 days. At the end of the period, troponin I (TP I) and creatine kinase MB (CK-MB) levels were measured in the venous blood of each group. Malondialdehyde (MDA), total glutathione (tGSH), TNF-α, NF-▪B, and IL-1β levels were measured in samples taken from heart tissues. Additionally, heart tissues were evaluated histopathologically. ResultsTroponin I, CK-MB, MDA, TNF-α, NF-▪B, and IL-1β levels, myocardial degeneration, myofiber irregularity, and congestion scores were significantly higher and tGSH levels were lower in the clozapine group than in the healthy control and taxifolin+clozapine groups (P<0.05). Compared with the healthy control group, troponin I, tGSH, and NF-KB levels were similar (P>0.05), CK-MB, MDA, TNF-α, and IL-1β levels were higher in the taxifolin+clozapine group, while they were significantly lower than the clozapine group (P<0.05). Histopathologically evaluated myocardial degeneration, myofiber irregularity, and congestion score were significantly lower in the taxifolin+clozapine group than in the clozapine group. In the clozapine group (CLN group), myofibers were found to have irregular patterns and were observed as irregular. In the taxifolin+clozapine group (TLC group), myofibrils generally showed a regular morphology. ConclusionWe found that taxifolin can ameliorate damage to myocardial tissue by regulating oxidant-antioxidant and proinflammatory cytokine levels. The data of our study suggest that taxifolin may be useful in the treatment of clozapine-induced myocardial injury.

Investigating the Preventive and Therapeutic Role of Costus afer in Acetaminophen Induced Liver Toxicity

The objective of this study was to determine the prophylatic and therapeutic role of Costus afer in acetaminophen poisoning in rats. The rats were equally divided into two groups; pre-treatment group and post-treatment group with each group have five sub-groups (negative control (NC), positive control (PC), A, B and C) of 5 rats each. NC was without any treatment; PC was treated with 800mg/kg of acetaminophen; A was treated with 200mg/kg of Costus afer; B was treated with 400mg/kg of Costus afer; C was treated with 800mg/kg of Costus afer. In the pre-treatment group, the PC was induced with acetaminophen 28 days after administration of distilled water, and “A”, “B” and “C” were induced with acetaminophen 28 days after Costus afer treatment while in the post-treatment group, the PC was induced with acetaminophen before commencing on 28 days administration of distilled water, and “A”, “B” and “C” were induced with acetaminophen before commencing on 28 days Costus afer treatment. After the treatment period, the rats were sacrificed and sample and liver organ were collected for laboratory analysis for liver enzymes and histological studies. The results showed that there was no significant change (p&gt;0.05) in liver enzymes in the A, B, C subgroups of the pre-treatment group after acetaminophen induction. In the post-treatment group, there was a significant decrease in the liver enzymes in A, B and C subgroups after Costus afer treatment. This study has proven that Costus afer has the potential to not only prevent acetaminophen liver toxicity but to also treat hepatotoxicity inflicted by acetaminophen in rats.

Acute and sub-chronic toxicity studies of 5-methylcoumarin-4-β-glucoside isolated from &lt;i&gt;Vernonia glaberrima&lt;/i&gt; in Wistar rats

5-methylcoumarin-4-β-glucoside is a natural product isolated from Vernonia glaberrima – a plant used in African traditional medicine for the treatment of cancer and skin diseases. This compound possesses significant in-vitro antiproliferative potentials against colon cancer cell lines. However, safety assessment in several laboratory animals is required before commencing the in-vivo anticancer evaluation of the compound. This study is designed to evaluate the safety of 5-methylcoumarin-4-β-glucoside using 28 days sub-chronic toxicity model in Wistar rats. Acute toxicity study was carried out at a single oral dose of 10 mg/kg, 100 mg/kg and 1000 mg/kg body weight (phase 1) for 24 hours, and 1600 mg/kg, 2900 mg/kg, and 5000 mg/kg body weight (phase 2). Sub-chronic toxicity was conducted by oral administration of distilled water, 1%hydroxypropyl cellulose in distilled water as controls, and graded doses of 10 mg/kg, 50 mg/kg, and 100 mg/kg body weight of 5-methylcoumarin-4β-glucoside freshly prepared in 1% hydroxypropyl cellulose as vehicle to five groups of six rats each for 28 days. The result indicates that 5-methylcoumarin-4β-glucoside at a dose of 100 mg/kg body weight is non-toxic as serological indices like liver and kidney functioning test, serum lipid profile, oxidative stress markers and hematological indices remained in the normal range after the 28 days sub-chronic administration of the compound. Moreover, the histopathology findings revealed no alteration in the normal tissue architecture. Overall, the findings in Wistar rats corroborate the initial findings in mice. Conclusively, the compound 5-methylcoumarin-4β-glucoside is safe at the prescribed doses for further preclinical in vivo investigations.

Effect Of Gentamicin And Neomycin+Bacitracin On Deoxyribonuclease Activity I On The Quality Of Human DNA Of Salivary Origin

Deoxyribonucleic acid (DNA) can be found in saliva and various other sources. Saliva contains epithelial cells and leukocytes that are released into the oral cavity. Cells in saliva are potential sources of DNA for diagnostic purposes. DNA in saliva can be degraded due to the activity of deoxyribonuclease (DNase), an enzyme that catalyzes the hydrolysis of DNA. DNase I is expressed in exocrine cells while DNase II is expressed in macrophages. Inhibition of DNase activity will preserve DNA. Besides being able to kill bacteria, aminoglycosides (i.e. gentamicin and neomycin) can inhibit DNase. Saliva was collected from 8 subjects. Furthermore, saliva samples from each subject were divided into 4 groups, namely negative control (K1), positive control (K2), gentamicin (K3), and neomycin + bacitracin (K4). DNA was extracted from saliva using the spin column method. DNA from groups K3 and K4 were added to 1 mg/mL gentamicin and 20 mM neomycin + bacitracin, respectively, before adding 2.5 g/mL DNase I (DNA degradation assay). The quality of human genomic DNA from saliva was determined by the presence of the NOTCH2 gene amplicons (~704 bp). DNA was separated by 1% agarose gel electrophoresis and recorded using the gel documentation system. The DNA extracted from saliva using the spin column method had an average concentration of 26.49 + 30.70 ng/mL and an average purity of 1.819 + 0.122. The administration of distilled water as a negative control in the DNA degradation assay showed that no DNA was digested.

Gastrodin attenuates angiotensin II-induced vascular contraction and MLCK/p-MLC2 pathway activation

Context Gastrodin has been used as antihypertension therapy in China; however, the mechanisms underlying the effects of gastrodin have yet to be fully elucidated. Objective To explore the therapeutic efficiency of gastrodin as an antihypertensive and determine the mechanisms underlying this effect. Materials and methods C57BL/6 mice were continuously administered angiotensin II (Ang II) (500 ng/kg/min) to induce hypertension. Mice were randomly divided into control, Ang II and Ang II + gastrodin groups. Mice received intragastric administration of gastrodin (5 mg/kg) or double distilled water once a day for 4 weeks. Blood pressure, pulse wave velocity (PWV), thickness of the abdominal aorta, pathological morphology and differential expression transcripts (DETs) were assessed. Abdominal aorta rings and primary isolated vascular smooth muscle cells were subjected to Ang II stimulation to induce hypertension as ex vivo and in vitro models, respectively. Vascular ring tension, release of Ca2+ and levels of proteins involved in the myosin light chain kinase (MLCK)/phospho-myosin light chain 2 (p-MLC2) pathway were determined. Results Gastrodin treatment attenuated increases in blood pressure, PWV and thickness of the abdominal aorta. Treatment with gastrodin resulted in 2785 DETs and the enrichment of vascular contraction and calcium signalling pathways. Gastrodin treatment attenuated Ang II-induced vasoconstriction, produced a norepinephrine-precontracted vasodilation effect (attenuated by verapamil), and reduced intracellular Ca2+ release. Furthermore, gastrodin suppressed activation of the MLCK/p-MLC2 pathway in vivo and in vitro. Conclusions Gastrodin treatment lowers blood pressure, suppresses Ang II-induced vascular contraction and MLCK/p-MLC2 pathway activation, thereby demonstrating the mechanisms underlying the therapeutic efficacy of gastrodin as an antihypertensive.

Acute Toxicity and Anxiolytic Activity Screening of Hydroalcoholic Leaf Extracts of Bryophyllum pinnatum, Terminalia catappa and Tapinanthus dodoneifolius Growing on Terminalia catappa Tree in MIce

Aims: Hydroalcoholic T. dodoneifolius, B.pinnatum and T. catappa leaf extracts were investigated for their acute toxicity and anxiolytic activities. Study Design: Acute toxicity (LD50) was determined using the limit dose acute and Anxiolytic activities were assessed by open-field field behavioural testing in mice. Place and Duration of Study: The study took place in the Neurobehavioural room of Department of Pharmacology &amp; Therapeutics, Faculty of Pharmacy, Ahmadu Bello University, Zaria in late December 2022. Methodology: Groups of mice (n=6; equal sexes) were each exposed to the open-field paradigm (OFT) following 1 hour of single oral administration of distilled water, extracts (125, 250, and 500 mg/kg) and diazepam (0. 5 mg/kg) using the behavioural indices of mean centre zone time (M%CZT), centre zone re-entry (MCZR) and defeaction/urination frequency (MD/UF). Results: Acute toxicity testing shows that the three extracts are safe with LD50 of 5g/kg. Behavioural results indicate, compared to the distilled water treatment (M%CZT, 6.39±1.53; MCZR, 4.67±1.15, &amp; MU/UF, 4.83±0.75), single acute T. dodoneifolius (M%CZT, 7.50±1.73, 13.72±2.43, &amp; 20.94±3.91*; MCZR, 7.33±0.88, 9.50±0.76, &amp; 11.50±1.6*; MD/UF, 4.17±0.48, 3.17±0.54, &amp; 1.83±0.60*), and B.pinnatum (M%CZT, 9.72±1.91, 9.78±1.32, &amp; 19.67±2.01*; MCZR, 6.00±1.15, 10.50±0.76, &amp; 12.50±1.72*; MD/UF, 3.17±0.79, 2.33±0.42, &amp; 1.33±0.49*) extract treatments demonstrated consistent dose-dependency in their anxiolytic activity across the three parameters with T. catappa extract (M%CZT, 6.95±1.27, 12.17±2.01, &amp; 16.84±1.49*; MCZR, 8.17±1.60, 10.17±1.67, &amp; 10.83±1.96; MD/UF, 2.83±0.60, 2.00±0.73, &amp; 3.67±0.42) exhibiting dose-pendent anxiolytic effect only on the M%CZT. However, at the highest dose level of 500 mg/kg, all plant extract treatments caused anxiolytic effects that are comparable with those of 0.5 mg/kg diazepam treatments (M%CZT, 22.61±1.31*; MCZR, 12.17±1.66*; &amp; MD/UF, 2.62±0.21*). Conclusion: These findings justify the traditional use of these medicinal plant extracts in the remediation of nervous and related disorders.

Bushen Huoxue Fang improves recurrent miscarriage in mice by down-regulating the JAK2/STAT3 pathway

To investigate the efficacy of Bushen Huoxue Fang (BSHXF, a traditional Chinese medicine formula) for improving recurrent spontaneous abortion (RSA) in mice and the role of tyrosine kinase (JAK2) and transcriptional activator (STAT3) signaling pathway in its therapeutic mechanism. Female CBA/J mice were caged with male DBA/2 mice to establish RSA mouse models, which were randomly divided into model group, dydrogesterone group and BSHXF group, with the female mice caged with male BALB/c mice as the control group (n=6). From the first day of pregnancy, the mice were subjected to daily intragastric administration of BSHXF, dydrogesterone, or distilled water (in control and model groups) for 12 days. After the treatments, serum levels of antithrombin III (AT-III), activated protein C (APC), tissue plasminogen activator (t-PA), progesterone, human chorionic gonadotropin (HCG), and estradiol (E2) were detected in each group using ELISA. HE staining was used to observe the morphological changes of the endometrium of the mice. Western blotting was performed to determine the expressions of p-JAK2, p-Stat3 and Bcl-2 in the placenta of the mice. Compared with the control mice, the mouse models of RSA showed a significantly increased embryo loss rate with decreased serum levels of AT-III, T-PA, progesterone, APC and HCG, increased placental expressions of p-JAK2, p-STAT3 and Bax, and decreased expression of Bcl-2 (P < 0.05). Treatments with BSHXF and dydrogesterone both increased serum levels of AT-III, t-PA and HCG in the mouse models; Serum APC level was significantly reduced in BSHXF group and serum progesterone level was significantly increased in dydrogesterone group (P < 0.05). BSHXF can improve the prethrombotic state and inhibit cell apoptosis by downregulating the JAK2/STAT3 pathway to increase the pregnancy rate in mouse models of RSA.

Efficacy of Artemisia annua Linné in improving cognitive impairment in a chronic cerebral hypoperfusion-induced vascular dementia animal model

BackgroundVascular dementia (VaD) is the second most common type of dementia after Alzheimer's disease. Currently, no FDA-approved drugs are available for the treatment of VaD. Artemisia annua Linné (AA) is known to have antioxidant properties, but its effects and mechanisms of action on cognitive impairment are still unknown. PurposeIn this study, the improvement in cognitive impairment by AA in terms of protection against oxidative stress, neuroinflammation, and preservation of the integrity of the neurovascular unit (NVU) was assessed in an animal model of VaD with bilateral common carotid artery occlusion (BCCAO). MethodsEight-week-old male Wistar rats were allowed to adapt for four weeks, and BCCAO was induced at 12 weeks of age. The rats were randomly assigned into four groups, with seven rats in each group: sham group without BCCAO, VaD group that received oral administration of distilled water after BCCAO surgery, and two AA groups that received oral administration of 150 mg/kg or 750 mg/kg AA after BCCAO surgery for 8 weeks. Nine weeks after BCCAO surgery, the cognitive function of the rats was evaluated and accumulated oxidative stress was assessed by immunohistochemistry, immunofluorescence, and western blotting. Damage to the components of the NVU was evaluated, and sirtuin (Sirt) 1 and 2 expression and nuclear factor-erythrocyte 2-associated factor 2 (Nrf2)/Kelch-like ECH-associated protein1 (Keap1) activation were investigated to assess the reduction in cell signaling and antioxidant pathways. ResultsBCCAO-induced cerebral perfusion decreased memory function and induced neuroinflammation and oxidative stress. But AA treatment mitigated cognitive impairment and reduced neuroinflammation and oxidative stress caused by chronic cerebral hypoperfusion. AA extracts activated the Nrf2/Keap1/activating antioxidant response elements pathway and maintained Sirt 1 and 2, subsequently leading to the maintenance of neurons, improved construct of microvessels, increased platelet-derived growth factor receptor beta, and platelet-endothelial cell adhesion molecule-1 associated with the blood-brain barrier integrity. ConclusionAA is effective in alleviating BCCAO-induced cognitive decline and its administration may be a useful therapeutic approach for VaD.

Preclinical study of goat milk kefir as an antihyperglycemic food

Background: Goat milk kefir is a functional food with numerous health benefits, including blood sugar control, cholesterol reduction, and improved digestive health. This study aims to determine the effect of kefir consumption on blood glucose levels in hyperglycaemic mice (Mus musculus) without affecting another blood chemistry. This study compared goat milk kefir products to other processed milk products considered to be capable of controlling and reducing blood sugar levels. Objective:This study aimed to compare goat milk kefir products to other processed food products considered to be capable of controlling and reducing blood sugar levels.Methods: Twenty-one mice, as experimental animals, were induced for 21 days with the high-fat and high fructose diet to increase blood sugar levels. After induction, mice were divided into 3 groups according to treatment, namely oral administration of additional distilled water (placebo), diabetasol® (positive control), and goat's milk kefir with each group consisting of 9 individuals. Results: Treatment showed significant effect on the blood glucose and β-ketone level. Diabetasol® and Goat kefir supplemented mice had a lower blood glucose level than control (p &lt; 0.05) and goat kefir supplemented mice had lower blood β-ketone level than control and Diabetasol® (p&lt; 0.05). Meanwhile, hematocrit and hemoglobin levels did not show significant differences between treatments.Conclusion: The results suggested that goat milk kefir has preclinical potential as an antihyperglycemic functional food without affecting other blood chemistry profiles.Keywords: Antihyperglycemic, blood sugar, goat kefir

Protective Effect of Hydroalcoholic Extract of Clove on Thioacetamide-Induced Hepatotoxicity Animal Model: Effects Hydroalcoholic Extract of Clove Against Hepatotoxicity.

The drug-induced liver injury (DILI) has a wide range of clinical presentations, from asymptomatic liver enzyme elevations to cirrhosis. Herbal dietary supplements may be beneficial to reduce the risk of hepatotoxicity. This study aimed to evaluate the effects of different doses of clove extracts on humoral factors in rats with hepatotoxicity induced by thioacetamide. In this experimental study, rats were divided into nine groups (10 rats per each). The Control group received no treatment. The Sham group was treated with oral administration of distilled water (0.5 ml) for 21 days. The positive control group received thioacetamide (50 mg/kg for three days) intraperitoneally. The clove group was divided into three subgroups and given daily oral administrations of 50, 150, and 300 mg/kg of clove hydroalcoholic extracts (for 21 days). Rats in the experimental group were divided into three subgroups and subjected to 50 mg/kg thioacetamide injection after receiving hydroalcoholic extracts of clove (50, 150, and 300 mg/kg, respectively) for 21 days in the last three days. All rats were sacrificed after 48 hours to measure liver function parameters (aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, total plasma protein, and albumin). The rats that received thioacetamide showed liver damage by increased serum liver biomarkers and decreased levels of total plasma protein and albumin compared to the control group. The different doses of clove extract resulted in a significant improvement of liver damage by reduced serum liver enzymes levels and increased total plasma protein and albumin. Oral administration of the different doses of the clove extract (50, 150, and 300 mg/kg) for 21 consecutive days could significantly improve the changes associated with serum biomarkers of hepatotoxicity. [GMJ.2022;11:e1603].

Comparison of oral administration of fructose and glucose on food intake and physiological parameters in broiler chicks

Like glucose, fructose is a monosaccharide, but the mechanisms of its absorption and metabolism in the body are very different between the 2 molecules. In this study, we investigated the effects of oral administration of glucose and fructose on food intake, diencephalic gene expression, and plasma metabolite concentrations in broiler chicks. The animals used in this study were 4-day-old male broiler chicks (Ross 308). They were given glucose, fructose (200 mg/ 0.5 mL/ bird), or a similar volume of distilled water orally after 6 h fasting. After treatment, measurements of food intake (at 0, 30, and 60 min), and blood glucose as well as insulin concentrations were measured over time; however, diencephalic (hypothalamus) gene expression and plasma metabolites were measured at 30 min. The results showed that glucose administration suppressed food intake, but fructose administration did not suppress food intake and it was at the same level as distilled water administration. In addition, fructose administration did not increase plasma glucose and insulin levels as did glucose administration. In the diencephalon, expression levels of genes related to the melanocortin system were unaffected by the treatment, while gene expression levels related to intracellular energy regulation, such as AMP-activated protein kinase were affected by the glucose treatment in the fasted chicks. These results suggest that fructose administration does not suppress feeding behavior as a result of possible reduction in the energy levels in the diencephalon and associated energy metabolism.

Fertility protective effect of taxifolin in cisplatin-induced ovarian damage.

The aim of our study was to investigate the protective effect of taxifolin on ovarian damage and reproductive dysfunction created by cisplatin administration. A total of 36 albino Wistar female adult rats were equally divided into 3 groups as cisplatin administered only (CIS), taxifolin+cisplatin (T+C) and healthy control group (HG). Taxifolin 50 mg/kg was administered orally by gavage in the T+C (n=12) group. In the HG (n=12) and CIS (n=12) groups, the same volume of distilled water as a solvent was orally administered. One hour after administration of taxifolin or distilled water, animals in the T+C and CIS groups were injected with cisplatin at a dose of 2.5 mg/kg intraperitoneally. This procedure was repeated once a day for 14 days. Six animals from each group were sacrificed on day 15, and their ovaries were removed for histopathological and biochemical analysis. Ovarian tissue malondialdehyde (MDA), total Glutathione (tGSH), Nuclear Factor-Kappa B (NF-kB), Tumor Necrosis Factor-α (TNF-α), Interleukin 1 beta (IL-1β), and Interleukin-6 (IL-6) levels were measured. The remaining animals (n=6 in each group) were kept in the laboratory with mature male rats for two months to breed. CIS administration led to an increase in inflammatory molecules and membrane lipid peroxidation products, and decreased the synthesis of antioxidant molecules. Compared to the CIS group, the ovarian tissue MDA, NF-kB, TNF-α, IL-1β and IL-6 levels were found to be significantly decreased in the T+C group (p<0.001 for all comparisons). On the other hand, the tGSH levels of the T+C group were significantly higher than the CIS group (p<0.001). Milder ovarian necrosis, fibrosis and follicle damage were detected in animals which were given taxifolin. Four out of the six rats (67%) treated with taxifolin gave birth within 27 days. We demonstrated, for the first time, that taxifolin ameliorates cisplatin-induced ovarian injury by decreasing MDA and proinflammatory cytokines and increasing the antioxidant enzyme. The fact that more than half of the animals receiving taxifolin became pregnant suggests that the cytoprotective effect of taxifolin is strong enough to preserve fertility.

Effects of subacute cadmium exposure and subsequent deferiprone treatment on cadmium accumulation and on the homeostasis of essential elements in the mouse brain

IntroductionCadmium (Cd) is а hazardous multi-organ toxin. In this study, we provide the first results about the effect of oral administration of deferiprone (DFP) on Cd accumulation and on the homeostasis of essential elements in the brain of Cd-exposed mice. MethodsAdult Institute of Cancer Research (ICR) male mice were randomized into four experimental groups: untreated controls – administered distilled water for 28 days; Cd-exposed group – exposed to 18 mg/kg body weight (b.w.) Cd(II) acetate for 14 days followed by the administration of distilled water for two weeks; Cd + DFP (low dose) – Cd-intoxicated mice subsequently treated with 19 mg/kg b.w. DFP for two weeks; and Cd + DFP (high dose) – Cd-exposed mice administered high-dose DFP (135 mg/kg b.w.) for 14 days. Brains were subjected to inductively coupled plasma-mass spectrometry (ICP-MS) and histological analysis. ResultsThe results revealed that exposure of mice to Cd for 14 days significantly increased Cd concentration and significantly decreased magnesium (Mg), phosphorus (P), and zinc (Zn) contents in the brain compared to untreated controls. This effect was accompanied by necrotic-degenerative changes in both the cerebrum and cerebellum. Oral administration of low-dose DFP to Cd-exposed mice decreased the concentration of the toxic metal in the brain by 16.37% and restored the concentration of the essential elements to normal control values. Histological analysis revealed substantially improved cerebral and cerebellar histoarchitectures. In contrast, oral administration of high-dose DFP increased Cd content and significantly decreased selenium (Se) concentration in the brain. Necrotic neurons and Purkinje cells were still observed in the cerebral and cerebellar cortices. ConclusionThe results demonstrated that oral administration of DFP at low doses has a better therapeutic potential for the treatment of Cd-induced brain damage compared to high doses.

E.faecium QH06 alleviates TNBS-induced colonic mucosal injury in rats

To investigate the effect of Enterococcus faecium QH06 on TNBS-induced ulcerative colitis (UC) in rats and explore the mechanisms in light of intestinal flora and intestinal immunity. Thirty-six male Wistar rats were randomized equally into control group, UC model group, and E.faecium QH06 intervention group. The rats in the latter two groups were subjected to colonic enema with 5% TNBS/ethanol to induce UC, followed by treatment with intragastric administration of distilled water or E.faecium QH06 at the dose of 0.21 g/kg. After 14 days of treatment, the rats were examined for colon pathologies with HE staining. The mRNA and protein expression levels of IL-4, IL-10, IL-12, and IFN-γ in the colon tissues were detected using RT-qPCR and ELISA, and the expression of TLR2 protein was detected with immunohistochemistry and ELISA. Illumina Miseq platform was used for sequencing analysis of the intestinal flora of the rats with bioinformatics analysis. The correlations of the parameters of the intestinal flora with the expression levels of TLR2 and cytokines were analyzed. The rats with TNBS- induced UC showed obvious weight loss (P < 0.01) and severe colon tissue injury with high pathological scores (P < 0.01). The protein expression levels of IFN-γ, IL-12, and TLR2 (P < 0.01) and the mRNA expression levels of IFN-γ, IL-12 and IL-10 (P < 0.05) were significantly increased in the colon tissues of the rats with UC. Illumina Miseq sequence analysis showed that in UC rats, the Shannon index (P < 0.05) ACE (P < 0.01)and Chao (P < 0.05) index for the diversity of intestinal flora both decreased with a significantly increased abundance of Enterobacteriaceae (P < 0.01) and a lowered abundance of Burkholderiaceae (P < 0.05). Compared with the UC rats, the rats treated with E. faecium QH06 showed obvious body weight gain (P < 0.05), lessened colon injuries, lowered pathological score of the colon tissue (P < 0.05), decreased protein expressions of IFN- γ, IL- 12, and TLR2 and mRNA expressions of IFN- γ and IL-12 (P < 0.01 or 0.05), and increased protein expressions of IL- 4 (P < 0.05). The Shannon index ACE (P < 0.05) and Chao (P < 0.05) index of intestinal microflora were significantly increased, the abundance of Enterobacteriaceae was lowered and that of Burkholderiaceae and Rikenellaceae was increased in E.faecium QH06- treated rats (P < 0.01 or 0.05). Correlation analysis showed that IFN-γ was positively correlated with the abundance of Enterobacteriaceae, and IFN-γ was negatively correlated with the abundance of Prevotellaceae, Desulfovibrionaceae, norank_o_Mollicutes_RF39 and Clostridiales_vadinBB60_group; TLR2 was negatively correlated with Clostridiales_vadinBB60_group, norank_o_Mollicutes_RF39 and Prevotellaceae. E.faecium QH06 can alleviate TNBS-induced colonic mucosal injury in rats, and its effect is mediated possibly by increasing the abundance of SCFA-producing bacteria such as Prevotellaceae and inhibiting abnormal immune responses mediated by TLR2.

Antifatigue effects of the composition of Moringa oleifera leaves and Polygonatum polysaccharide and its mechanisms

Objective: To investigate the anti-fatigue effects of composition of Moringa oleifera leaves and Polygonatum polysaccharide, and to explore the mechanisms. Methods: Thirty male Kunming mice were randomly divided into control (C) and composition of Moringa oleifera leaves and Polygonatum polysaccharide group (MP). There were 15 mice in each group. Group C was given distilled water and the group MP was given composition intragastriclly every day. The volume was 0.5 ml. After 14 days of treatment, weight-bearing swimming experiment was conducted, and exhaustive swimming time was recorded. The bearing weight was 3% of the body weight. In another experiment, 48 male Kunming mice were randomly divided into quiet control group (QC), swimming control group (SC) and composition group (MP). There were 16 mice in each group. The QC and SC groups were given distilled water intragastrically, and the group MP was treated with composition every day for 14 days. The volume was 0.5 ml. On the day 15, 30 minutes after intragastriclly administration of distilled water, blood, liver and hind leg muscle of the QC group were collected immediately. The SC and MP groups were subjected non-weight-bearing swimming experiment, and blood, liver and hind leg muscle were collected after swimming. The fatigue related indexes, oxidant/antioxidant parameters and energy metabolism indicators in serum and tissues were determined by commercial kits. Results: The exhaustive swimming time of mice in MP group was significantly longer than that in the C group (P<0.05). Compared with the control group, non-weight-bearing swimming decreased the contents of serum glucose and GSH, the contents of hepatic glycogen and ATP, the hepatic activities of SOD, LDH and ATPase, and muscle activity of GSH-Px (P< 0.05). However, serum levels of BUN and MDA were increased (P<0.05). Compared with the SC group, the composition remarkably increased the contents of serum glucose and hepatic glycogen, increased serum content of GSH, enhanced hepatic activities of SOD, LDH and ATPase and muscle activity of GSH-Px, and increased the hepatic content of ATP (P<0.05). However, the serum level of BUN was decreased (P<0.05). Conclusion: The Moringa oleifera leaves and Polygonatum polysaccharide composition possesses anti-fatigue effects. Anti-oxidant and improving energy metabolism could be the important mechanisms.

Ameliorating Effects of Phytotherapy on Body Weight and Serum Lipid Profiles in Menopause-Induced Rat Model

ObjectivesPhytotherapy-based materials as a natural source of alternatives to estrogen therapy has drawn keen attention for treating menopausal dyslipidemia. The objective of this study was to investigate the anti-menopausal dyslipidemia of herbal medicine extract: Kyung-Ok-Go, which is mixture of Rehmannia glutinosa, Panax ginseng, Wolfiporia extensa and Apis cerana Fabricius, supplementation on body weight and lipid profiles of serum in menopause-induced rats. MethodsTwenty 9-week-old female Sprague-Dawley rats were randomly divided into 4 groups after a week adaptation (n = 5 each): Control group (C), Ovariectomized group (OVX), OVX + 17β-Acetylestradiol group (OVX + positive control; OP) and OVX + herb extracts group (OHE). At the age of 10 weeks, bilateral ovariectomy was performed on group OVX, OP and OHE, and two weeks of recovery period was followed. After recovery, all groups were treated with oral gavage administration of distilled water (C, OVX), 50μ/kg b.w. of 17beta-Acetylestradiol (OP) and 1200mg/kg b.w. of herbal extract (OHE) respectively for 9 weeks. Serum triglyceride (TG), total cholesterol (TC) levels were analyzed using ELISA kits and assays were conducted. ResultsAfter oral administration for 9 weeks, the final body weight and body weight gain of OVX, OP and OHE groups increased compared to the control group. However, the final body weight and body weight gain of OP and OHE groups were significantly reduced compared to the OVX group (p = 0.000). In serum biochemical assays, the OHE group showed lower triglyceride (TG) and total cholesterol (TC) levels compared with other ovariectomized groups (p = 0.000), and in particular, TG levels were ranked at the same level as the control group (p < 0.005). ConclusionsIn this study, it was confirmed that continuous intake of herbal medicine extracts may ameliorate menopause syndromes such as dyslipidemia, obesity and lipid accumulation at a similar level to hormone therapy like estrogen intake. Moreover, further analysis of finding mechanism of the ameliorating effects is in progress. Funding SourcesThis research was funded by Kwang-dong Pharmaceutical Co., Ltd..

Ameliorative effects of Liv-52 on doxorubicin-induced oxidative damage in rat liver

ABSTRACT Hepatotoxicity is a common side effect of doxorubicin (Dox) treatment of cancer. Liv-52 is an ayurvedic medicine that is reported to ameliorate liver injury due to oxidative stress. We investigated the effects of Liv-52 on Dox induced oxidative damage to liver tissues of rats using biochemical and histopathological techniques. Thirty male rats were assigned randomly into three equal groups: control (CG), Dox group (DG) Liv-52 + Dox group (LD). Rats in the LD group received 50 mg/kg Liv-52 in distilled water via gastric gavage. Distilled water was given via the same route to the rats in the DG and CG groups. Rats in the LD and DG groups were injected intraperitoneally with 5 mg/kg Dox 1 h after administration of Liv-52 or distilled water. The procedure was repeated daily for 7 days. On day 8, the animals were sacrificed, and serum and tissue biochemical and histopathological assays were performed. The malondialdehyde level was increased significantly in the DG group, while glutathione and superoxide dismutase levels were significantly lower in the DG group compared to the LD and CG groups. The highest levels of alanine aminotransferase, aspartate aminotransferase and lactate dehydrogenase were found in the DG group, while the lowest levels were found in the CG group, which exhibited levels similar to those of the LD group. Treatment with Liv-52 prior to Dox treatment reduced the histopathologic changes in the Dox group. Therefore, pre-treatment with Liv-52 protected against Dox induced oxidative stress and hepatotoxicity.