Carum carvi Modulates Acetaminophen-Induced Hepatotoxicity: Effects on TNF-α, NF-κB, and Caspases

Carum carvi is a well-known herb traditionally used as a spice in Asian countries. Acetaminophen is a known marketed drug mainly used as an analgesic. It has been scientifically proven that consumption of acetaminophen (paracetamol) is associated with liver toxicity if taken in high doses without medical supervision. The present study evaluated the in vivo antioxidant and hepatoprotective efficacy of Carum carvi against acetaminophen-induced hepatotoxicity in Wistar rats. Our results demonstrate that Carum carvi, at doses (mg/kg) of 100 (D1) and 200 (D2), showed inhibitory properties for DNA-sugar damage, lipid peroxidation, DPPH scavenging, and increased reducing potential in a concentration-dependent manner. Our results also confirm that liver toxicity associated with paracetamol, such as depletion of reduced glutathione and antioxidant enzyme levels, as well as induction of cytochrome P450, oxidative stress, apoptosis, and inflammatory cytokines, was efficiently restored by Carum carvi treatment in rats. Moreover, the expression of redox-sensitive transcription factors, namely, NF-κB and TNF-α levels, was also modulated by Carum carvi in the rats. In summary, our study confirms that Carum carvi inhibits inflammation and oxidative stress, thereby protecting liver cells from paracetamol prompted hepatotoxicity

Box–Behnken Response Surface Design of Polysaccharide Extraction from Rhododendron arboreum and the Evaluation of Its Antioxidant Potential

© 2020 by the authors. In the present investigation, the ultrasound-assisted extraction (UAE) conditions and optimization of Rhododendron arboreum polysaccharide (RAP) yield were studied by a Box–Behnken response surface design and the evaluation of its antioxidant potential. Three parameters that affect the productivity of UAE, such as extraction temperature (50–90 ◦C), extraction time (10–30 min), and solid–liquid ratio (1–2 g/mL), were examined to optimize the yield of the polysaccharide percentage. The chromatographic analysis revealed that the composition of monosaccharides was found to be glucose, galactose, mannose, arabinose, and fucose. The data were fitted to polynomial response models, applying multiple regression analysis with a high coefficient of determination value (R2 = 0.999). The data exhibited that the extraction parameters have significant effects on the extraction yield of polysaccharide percentage. Derringer’s desirability prediction tool was attained under the optimal extraction conditions (extraction temperature 66.75 ◦C, extraction time 19.72 min, and liquid–solid ratio 1.66 mL/g) with a desirability value of 1 yielded the highest polysaccharide percentage (11.56%), which was confirmed through validation experiments. An average of 11.09 ± 1.65% of polysaccharide yield was obtained in optimized extraction conditions with a 95.43% validity. The in vitro antioxidant effect of polysaccharides of R. arboreum was studied. The results showed that the RAP extract exhibited a strong potential against free radical damage

Neuroprotective and Cardiometabolic Role of Vitamin E: Alleviating Neuroinflammation and Metabolic Disturbance Induced by AlCl₃ in Rat Models

Cardiovascular diseases (CVDs) and neurodegenerative disorders, such as diabetes mellitus and Alzheimer’s disease, share a common pathophysiological link involving insulin resistance (IR), inflammation, and hypertension. Aluminium chloride (AlCl3), a known neurotoxicant, has been associated with neurodegeneration, cognitive impairment, and various organ dysfunctions due to the production of reactive oxygen species (ROS) and oxidative stress. In this study, we aimed to investigate the potential protective effects of metformin and vitamin E against AlCl3-induced neuroinflammation and cardiometabolic disturbances in rat models. Rats were divided into five groups: a normal control group, an AlCl3-treated diseased group without any treatment, and three groups exposed to AlCl3 and subsequently administered with metformin (100 mg/kg/day) alone, vitamin E (150 mg/kg/day) orally alone, or a combination of metformin (100 mg/kg/day) and vitamin E (150 mg/kg/day) for 45 days. We analyzed serum biomarkers and histopathological changes in brain, heart, and pancreatic tissues using H&E and Masson’s trichrome staining and immunohistochemistry (IHC). Electrocardiogram (ECG) patterns were observed for all groups. The AlCl3-treated group showed elevated levels of inflammatory biomarkers, MDA, and disturbances in glycemic and lipid profiles, along with reduced insulin levels. However, treatment with the combination of metformin and vitamin E resulted in significantly reduced glucose, cholesterol, LDL, and TG levels, accompanied by increased insulin and HDL levels compared to the individual treatment groups. Histopathological analyses revealed that combination therapy preserved neuronal structures, muscle cell nuclei, and normal morphology in the brain, heart, and pancreatic tissues. IHC demonstrated reduced amyloid plaques and neurofibrillary tangles in the combination-treated group compared to the AlCl3-treated group. Moreover, the combination group showed a normal ECG pattern, contrasting the altered pattern observed in the AlCl3-treated group. Overall, our findings suggest that metformin and vitamin E, in combination, possess neuroprotective and cardiometabolic effects, alleviating AlCl3-induced neuroinflammation and metabolic disturbances

A preliminary study on combination therapy of artemisinin dimer oxime and topotecan against nonsmall cell lung cancer in mice

Background: Artemisinin dimer oxime – dimer molecule synthesized from artemisinin possesses high bioavailability and marked in vitro anticancer activities against solid tumor-derived cell lines, endothelial cell proliferation, migration, and angiogenic processes. Numerous murine models have been developed to study human cancer. The most widely used models are the human tumor xenograft mouse model. Materials and Methods: In this study, human tumor cells (NCI-H640, 1 × 107 in 100 μL) are implanted subcutaneously, or 1 × 107 in 50 μL in the thoracic cavity, in athymic nude mice (nu/nu). The implanted cells were allowed to grow for 10 days before initiation of drug treatment (dimer oxime and topotecan, ip). Tumor volume and thoracic/body weight ratio were recorded. Results: We successfully established subcutaneous and thoracic xenografts with human nonsmall cell lung cancer cell line xenografts in athymic nude mice in only 10 days. Using these models, we attempted treatment of xenografts with topotecan – a known anticancer drug and artemisinin dimer oxime or combination of these two drugs. Combination therapy showed a significant reduction in tumor volume and tumor/body weight. Treatments with combination of topotecan and dimer oxime resulted in the reduced mortality rates in comparison with untreated mice. Conclusions: Xenograft tumor models are useful for preclinical screening of new pharmacophores. From this preliminary study, it appears that combination of dimer oxime and topotecan may be used as chemotherapeutic agents against nonsmall cell lung cancer. Further studies are needed to evaluate other combination treatment regimens as well as the mechanism(s) of action

Metabolomics Analysis and Biochemical Profiling of Arsenic-Induced Metabolic Impairment and Disease Susceptibility

Our study aimed to conduct a comprehensive biochemical profiling and metabolomics analysis to investigate the effects of arsenic-induced metabolic disorders, with a specific focus on disruptions in lipid metabolism, amino acid metabolism, and carbohydrate metabolism. Additionally, we sought to assess the therapeutic potential of resveratrol (RSV) as a remedy for arsenic-induced diabetes, using metformin (MF) as a standard drug for comparison. We measured the total arsenic content in mouse serum by employing inductively coupled plasma mass spectrometry (ICP-MS) after administering a 50-ppm solution of sodium arsenate (50 mg/L) in purified water. Our findings revealed a substantial increase in total arsenic content in the exposed group, with a mean value of 166.80 ± 8.52 ppb (p p p p < 0.05). However, the level of MDA was significantly increased. Molecular analysis of gene expression indicated significant upregulation of key enzymes involved in lipid metabolism, such as carnitine palmitoyl-transferase-I (CPT-I), carnitine palmitoyl-transferase-II (CPT-II), lecithin–cholesterol acyltransferase (LCAT), and others. Additionally, alterations in gene expression related to glucose transporter-2 (GLUT-2), glucose-6-phosphatase (G6PC), and glucokinase (GK), associated with carbohydrate metabolism, were observed. Amino acid analysis revealed significant decreases in nine amino acids in arsenic-exposed mice. Metabolomics analysis identified disruptions in lipid metabolomes, amino acids, and arsenic metabolites, highlighting their involvement in essential metabolic pathways. Histopathological observations revealed significant changes in liver architecture, hepatocyte degeneration, and increased Kupffer cells in the livers of arsenic-exposed mice. In conclusion, these findings enhance our comprehension of the impact of environmental toxins on metabolic health and offer potential avenues for remedies against such disruptions

Efficacy of Prosopilosidine from Prosopis glandulosa var. glandulosa against Cryptococcus neoformans Infection in a Murine Model

In this study, 2,3-dihydro-1H-indolizinium alkaloid-prosopilosidine (PPD), that was isolated from Prosopis glandulosa, was evaluated against C. neoformans in a murine model of cryptococcosis. In vitro and in vivo toxicity of indolizidines were also evaluated. Mice were infected via the tail vein with live C. neoformans. Twenty-four hours post-infection, the mice were treated with PPD once a day (i.p.) or twice a day (bid) orally, or with amphotericin B (Amp B) intraperitoneally (IP), or with fluconazole (Flu) orally for 5 days. The brains of all of the animals were aseptically removed and the numbers of live C. neoformans were recovered. In vitro toxicity of indolizidine alkaloids was determined in HepG2 cells. PPD showed to be potent in vivo activity against C. neoformans at a dose of 0.0625 mg/kg by eliminating ~76% of the organisms compared to ~83% with Amp B (1.5 mg/kg). In addition, PPD was found to be equally efficacious, but less toxic, at either 0.125 or 0.0625 mg/kg compared to Amp B (1.5 mg/kg) when it was administered bid (twice a day) by an i.p. route. When tested by an oral route, PPD (10 mg/kg) showed potent activity in this murine model of cryptococcosis with ~82% of organisms eliminated from the brain tissue, whereas Flu (15 mg/kg) reduced ~90% of the infection. In vitro results suggest that quaternary indolizidines were less toxic as compared to those of tertiary bases. PPD (20 mg/kg) did not cause any alteration in the plasma chemistry profiles. These results indicated that PPD was active in eliminating cryptococcal infection by oral and i.p. routes at lower doses compared to Amp B. or Flu

A Multitarget Approach to Evaluate the Efficacy of Aquilaria&nbsp;sinensis Flower Extract against Metabolic Syndrome

Aquilaria sinensis (Lour.) Spreng is known for its resinous secretion (agarwood), often secreted in defense against injuries. We investigated the effects of A. sinensis flower extract (AF) on peroxisome proliferator-activated receptors alpha and gamma (PPAR&alpha; and PPAR&gamma;), liver X receptor (LXR), glucose uptake, and lipid accumulation (adipogenesis). Activation of PPAR&alpha;, PPAR&gamma; and LXR was determined in hepatic (HepG2) cells by reporter gene assays. Glucose uptake was determined in differentiated muscle (C2C12) cells using 2-NBDG (2-deoxy-2-[(7-nitro-2,1,3-benzoxadiazol-4-yl)amino]-D-glucose). Adipogenesis was determined in adipocytes (3T3-L1 cells) by Oil red O staining. At a concentration of 50 &micro;g/mL, AF caused 12.2-fold activation of PPAR&alpha; and 5.7-fold activation of PPAR&gamma;, while the activation of LXR was only 1.7-fold. AF inhibited (28%) the adipogenic effect induced by rosiglitazone in adipocytes and increased glucose uptake (32.8%) in muscle cells at 50 &mu;g/mL. It was concluded that AF acted as a PPAR&alpha;/&gamma; dual agonist without the undesired effect of adipogenesis and exhibited the property of enhancing glucose uptake. This is the first report to reveal the PPAR&alpha;/&gamma; dual agonistic action and glucose uptake enhancing property of AF along with its antiadipogenic effect, indicating its potential in ameliorating the symptoms of metabolic syndrome

TLR4/NFκB-Mediated Anti-Inflammatory and Antioxidative Effect of Hexanic and Ethanolic Extracts of <i>Curcuma longa</i> L. in Buffalo Mammary Epithelial Cells

Mastitis is the commonest disease of bovines imposing a great economic setback and a drastic public health concern worldwide. Antibiotic resistance is the preliminary con of excessive antibiotics use for disease treatment. Studies validate an alarming increase in the antibiotic resistance of both humans and animals. For ages, medicinal plants have been used to treat a number of ailments in humans and animals, including mastitis. Curcuma longa, or turmeric, is the prerequisite in Indian cooking and has been used in traditional medicine for its magical properties. The rhizome of C. longa possesses significant anti-inflammatory, antibacterial, antifungal, and antioxidative properties. In the current study, we evaluated the hexanic and ethanolic extracts of C. longa for their anti-inflammatory and antioxidative potential against LPS-induced inflammation in buffalo mammary epithelial cells (BuMECs). Pretreatment with the extracts downregulated the expression of proinflammatory cytokine TNFα via the TLR4/NFκB-mediated signaling pathway. However, IL-6 was downregulated in only the hexanic C. longa-pretreated group. A significant upregulation of NRF2 mRNA expression was seen in both hexanic- and ethanolic-treated groups. A GC-MS/MS study of the extracts revealed the presence of important sesqueterpenoids and phenolics as the main bioactive phytoconstituents in the extracts. Sesqueterpenoids, such as turmerone, ar-turmerone, curlone, and atlantone, and phenols, such as guaiacol (2-Hydroxyanisole phenol, 2-methoxy), and ethyl ferulate/ethyl 4′-hydroxy-3′methoxycinnamate, were found in C. longa extracts. The protective role of C. longa in BuMECs against LPS-induced inflammation and oxidant insult might be due to the presence of bioactive compounds, such as terpenoid and phenolic compounds. However, we further propose the isolation of these phytoconstituents and their analysis using HPLC and NMR studies