Intergenerational Impact of Parental Zinc Deficiency on Metabolic and Redox Outcomes in Drosophila melanogaster.

Zinc deficiency is a common nutritional disorder with detrimental health consequences. Whether parental zinc deficiency induces intergenerational effects remains largely unknown. We investigated the effects of a combined maternal and paternal zinc deficiency on offspring's metabolic outcomes and gene expression changes in Drosophila melanogaster. The parent flies were raised on zinc-deficient diets throughout development, and their progeny were assessed. Offspring from zinc-deprived parents exhibited a significant (p < 0.05) increase in body weight and whole-body zinc levels. They also displayed disrupted glucose metabolism, altered lipid homeostasis, and diminished activity of antioxidant enzymes. Gene expression analysis revealed significant (p < 0.05) alterations in zinc transport genes, with increases in mRNA levels of dZIP1 and dZnT1 for female and male offspring, respectively. Both sexes exhibited reduced dZnT35C mRNA levels and significant (p < 0.05) increases in the mRNA levels of DILP2 and proinflammatory markers, Eiger and UPD2. Overall, female offspring showed higher sensitivity to parental zinc deficiency. Our findings underscore zinc's crucial role in maintaining health and the gender-specific responses to zinc deficiency. There is the need for further exploration of the underlying mechanisms behind these intergenerational effects.

Naringenin: its chemistry and roles in neuroprotection.

According to epidemiological research, as the population ages, neurological illnesses are becoming a bigger issue. Despite improvements in the treatment of these diseases, there are still widespread worries about how to find a long-lasting remedy. Several neurological diseases can be successfully treated with natural substances. As a result, current research has been concentrated on finding effective neuroprotective drugs with improved efficacy and fewer side effects. Naringenin is one potential treatment for neurodegenerative diseases. Many citrus fruits, tomatoes, bergamots, and other fruits are rich in naringenin, a flavonoid. This phytochemical is linked to a variety of biological functions. Naringenin has attracted a lot of interest for its ability to exhibit neuroprotection through several mechanisms. In the current article, we present evidence from the literature that naringenin reduces neurotoxicity and oxidative stress in brain tissues. Also, the literatures that are currently accessible shows that naringenin reduces neuroinflammation and other neurological anomalies. Additionally, we found several studies that touted naringenin as a promising anti-amyloidogenic, antidepressant, and neurotrophic treatment option. This review's major goal is to reflect on advancements in knowledge of the molecular processes that underlie naringenin's possible neuroprotective effects. Furthermore, this article also provides highlights of Naringenin with respect to its chemistry and pharmacokinetics.

L-alanine supplementation improves blood glucose level and biochemical indices in alloxan-induced diabetic rats.

Diabetes is a metabolic disorder whose complications are among the leading cause of death. In this study, the antidiabetic effect of L-alanine was tested in alloxan-induced diabetic rats. Thirty-five male albino Wistar rats were divided into five groups viz; Group I and II: nondiabetic and diabetic controls respectively; Group III and IV: 150 and 300 mg/kg b.w. L-alanine treated, respectively; Group V: glibenclamide (0.5 mg/kg b.w.) treated. Weight and blood glucose were monitored during the study, while liver and kidney functions, lipid profile, and antioxidant markers were examined at the end of the study. The outcomes indicate that 300 mg/kg L-alanine resulted to a significant decrease (p < .05) in weight and blood glucose. L-alanine restored tissue antioxidants, kidney, and liver functions by improving important parameters. Histopathological studies showed the potential of L-alanine in regeneration of the islets of Langerhans. These findings suggest that L-alanine has an alleviating effect on alloxan-induced diabetes. PRACTICAL APPLICATIONS: Several medicinal plants have been tested for their antidiabetic potentials, however, the isolation of the active compounds from these plants for medicinal use is often challenging. Here, we present data that suggests the potential use of a pure and harmless amino acid compound (L-alanine) for the management of diabetes. L-alanine is readily available, cheap and can also be found in many foods we eat. Therefore, L-alanine may be taken by diabetic patients as a food supplement for the treatment/management of diabetes or taken as part of foods rich in the amino acid such as meat, poultry, fish, eggs, and dairy products.

Computational prediction and experimental validation of the activator function of C2-ß-D-glucopyranosyl-1,3,6,7-tetrahydroxyxanthone on pancreatic and hepatic hexokinase.

This study identifies and validates hexokinase type 4 (HK4), an isozyme of hexokinase in the liver and pancreas, as an important target of C2-ß-D-glucopyranosyl-1,3,6,7-tetrahydroxyxanthone (ßdGT), a xanthone glucoside suggested to have antidiabetic property. In the study, we applied the computational pipeline of molecular docking followed by the molecular dynamics simulations to shortlist potential ßdGT protein targets. The analysis of protein dynamics and the binding free energy (ΔG) led us to the identification of HK4 as a key ßdGT target, whereby the binding mode and domain dynamics suggested the activator function of ßdGT. ßdGT bound to the allosteric site of the isozyme ∼13 Å away from the substrate (glucose)-binding site. The binding free energy of the ligand-protein complex was energetically feasible (ΔG, -41.61 kcal/mol) and the cleft angle deviation between the two (small and large) domains of HK4 revealed differential HK4 dynamics in response to ßdGT binding. 3D structure analysis of the isozyme-ligand complex highlighted the role of Arg63, Glu67 and Lys458 in ligand stabilization and hydrophobic interactions mediated by Tyr214 and Met235. Experimental validation of the results of computational analysis confirmed the activator function of ßdGT on HK4. The study has implication in diabetes as ßdGT may be used to lower the blood glucose level by activating hepatic and pancreatic hexokinase without the risk of hypoglycemia.Communicated by Ramaswamy H. Sarma.

Report: Anxiolytic, sedative and toxicological effect of hydromethanolic stem bark extract of Maerua angolensis DC. in Wister rats.

Maerua angolensis DC is traditionally used for the treatment of epilepsy and insomnia. The present study was designed to investigate the anxiolytic, sedative and toxicological effect of hydromethanolic stem bark extract of M. angolensis using animal model. Sub-chronic doses of the plant extract on liver and kidney function test were investigated. Elevated plus maze (EPM) and diazepam-induced sleeping time test was used in this investigation. The possible involvement of M. angolensis with GABAA receptor was also investigated using flumazenil. The results of acute toxicity studies showed LD50 to be greater than 5000mg/kg body weight. The test extract (40 and 80mg/kg) significantly (p<0.05) increased the number of open arm entries and time spent in the open arm entries. However, flumazenil with 80mg/kg plant extract showed no significant (p >0.01) difference in the number of entries into open arm when compared to control. The stem bark extract of M. angolensis significantly (p<0.01) increased the duration of sleep induced by diazepam in a dose-dependent manner. However, flumazenil with 80mg/kg extract showed no significant (p>0.01) sedative effect when compared to normal control. In conclusion, the result of our present findings revealed that M. angolensis may apparently be safe and non toxic at therapeutic dose. However, the plant may possess anxiolytic and sedative properties, which exert their effect on GABAA receptors.

Eugenol-rich Fraction of Syzygium aromaticum (Clove) Reverses Biochemical and Histopathological Changes in Liver Cirrhosis and Inhibits Hepatic Cell Proliferation.

BACKGROUND: Dried flower bud of Syzygium aromaticum (clove) is rich in eugenol, an antioxidant and antiinflammatory compound that can protect liver against injury. Clove, besides eugenol, also contains other pharmacologically active phytochemicals such as ß-sitosterol and ascorbic acid. This study reports the effect of eugenol-rich fraction (ERF) of clove on liver cirrhosis induced by thioacetamide. METHODS: Cirrhosis of the liver, which predisposes to hepatocellular carcinoma, was induced by administering thioacetamide (0.03%) in drinking water for 16 weeks. Cirrhotic animals were divided into two groups; the treated group was administered ERF for 9 weeks, one week after discontinuation of thioacetamide, while the other group received normal saline for a similar duration of time. RESULTS: The treatment with ERF, as determined by histopathology and through a battery of biochemical markers of hepatic injury, oxidative stress and drug metabolizing enzymes, significantly ameliorated the signs of liver cirrhosis. It lowered the elevated levels of alkaline phosphatase, γ-glutamyl transferase and other biochemical changes in liver cirrhosis. Histopathology of the liver corroborated the effect of ERF with biochemical findings. ERF treatment further inhibited cell proliferation, as demonstrated by reduced [(3)H]-thymidine uptake. CONCLUSIONS: Data provide evidence supporting the protective action of ERF on liver cirrhosis. The study assumes significance because cirrhosis predisposes the liver to cancer, which is characterized by abnormal cell proliferation. ERF in this study is reported to inhibit hepatic cell proliferation and at the same time decrease oxidative stress, which might be the mechanism of protection against liver cirrhosis.

Mineral pitch stimulates humoral, cellular and innate immune responses in mice.

CONTEXT: Mineral pitch (MP), a traditional medicine, is proposed to boost immunity in conditions that suppress Th1 cytokines such as AIDS/HIV, tuberculosis, leishmaniasis and cancer. OBJECTIVE: This study investigates the immunoregulatory mechanisms of MP in innate, humoral and cell-mediated immunity. MATERIALS AND METHODS: Mice given MP (100, 200, 300 or 400 mg/kg, orally) for 10 consecutive days were immunized intravenously with goat RBC or ovalbumin, and investigated for plaque-forming cells (PFC), hemagglutination titer, hypersensitivity response, lymphocyte proliferation and macrophage function. RESULTS: MP increased PFC (330.2 versus 182.2/106 splenocytes) in mice immunized with goat RBC and elicited ovalbumin-specific IgG titer at 400 mg/kg. Increase in Th1 immunity was correlated with the increased level of IFN-γ (724 versus 470 pg/ml) and decreased IL-4 (96 versus 178 pg/ml). CD4⁺/CD3⁺ ratio and delayed-type hypersensitivity response also increased to, respectively, 20.62 ± 0.59 (versus 16.47 ± 0.72) and 1.59 ± 0.12 (versus 0.87 ± 0.10 mm) in MP-treated mice. MP increased lymphocyte proliferation (11.14 ± 0.60 versus 5.81 ± 0.40 SI) and macrophage phagocyte response (0.24 ± 0.02 versus 0.15 ± 0.009), expressed as absorbance at 570 nm, but decreased nitrite production (17.4 ± 1.10 versus 24.3 ± 1.30 µM/106 cells). We also observed an increased bone marrow cellularity (24.5 ± 1.10 versus 17.10 ± 0.70 cells/femur) and WBC count (12 667 ± 377 versus 9178 ± 213 cells/mm³) following MP treatment. There was no sign of toxicity at 400 mg/kg, 1/12th of reported LD50. CONCLUSION: MP elicits a dose-dependent Th1 immune response.

Aqueous Extract of Dried Flower Buds of Syzygium aromaticum Inhibits Inflammation and Oxidative Stress.

This study reports the beneficial effect of aqueous extract of dried flower buds of Syzygium aromaticum (clove) in acute and chronic inflammation. Inflammation was induced in rats by injecting carrageenan in hind paw or implanting cotton pellet in the axilla. Administration of the extract (1 g/kg body weight) inhibited the formation of oedema induced by carrageenan and decreased granuloma in cotton pellet granuloma model. The extract, when compared with the disease control, is reported to decrease the elevated levels of succinate dehydrogenase (p<0.001), xanthine oxidase (p<0.05) and lipid peroxidation, and increase the activity of catalase (p<0.001) and glutathione peroxidase (p<0.01) in the two animal models. Potential role of xanthine oxidase in inflammation and the ability of the extract to alleviate oxidative stress and inflammation is discussed. The study advocates the use of aqueous extract, rather than the isolated bioactive principle for various reasons.