Antiemetic activity of abietic acid possibly through the 5HT3 and muscarinic receptors interaction pathways.

The present study was designed to evaluate the antiemetic activity of abietic acid (AA) using in vivo and in silico studies. To assess the effect, doses of 50 mg/kg b.w. copper sulfate (CuSO4⋅5H2O) were given orally to 2-day-old chicks. The test compound (AA) was given orally at two doses of 20 and 40 mg/kg b.w. On the other hand, aprepitant (16 mg/kg), domperidone (6 mg/kg), diphenhydramine (10 mg/kg), hyoscine (21 mg/kg), and ondansetron (5 mg/kg) were administered orally as positive controls (PCs). The vehicle was used as a control group. Combination therapies with the referral drugs were also given to three separate groups of animals to see the synergistic and antagonizing activity of the test compound. Molecular docking and visualization of ligand-receptor interaction were performed using different computational tools against various emesis-inducing receptors (D2, D3, 5HT3, H1, and M1-M5). Furthermore, the pharmacokinetics and toxicity properties of the selected ligands were predicted by using the SwissADME and Protox-II online servers. Findings indicated that AA dose-dependently enhances the latency of emetic retching and reduces the number of retching compared to the vehicle group. Among the different treatments, animals treated with AA (40 mg/kg) exhibited the highest latency (98 ± 2.44 s) and reduced the number of retching (11.66 ± 2.52 times) compared to the control groups. Additionally, the molecular docking study indicated that AA exhibits the highest binding affinity (- 10.2 kcal/mol) toward the M4 receptors and an elevated binding affinity toward the receptors 5HT3 (- 8.1 kcal/mol), M1 (- 7.7 kcal/mol), M2 (- 8.7 kcal/mol), and H1 (- 8.5 kcal/mol) than the referral ligands. Taken together, our study suggests that AA has potent antiemetic effects by interacting with the 5TH3 and muscarinic receptor interaction pathways. However, additional extensive pre-clinical and clinical studies are required to evaluate the efficacy and toxicity of AA.

Revisiting luteolin: An updated review on its anticancer potential.

Numerous natural products found in our diet, such as polyphenols and flavonoids, can prevent the progression of cancer. Luteolin, a natural flavone, present in significant amounts in various fruits and vegetables plays a key role as a chemopreventive agent in treating various types of cancer. By inducing apoptosis, initiating cell cycle arrest, and decreasing angiogenesis, metastasis, and cell proliferation, luteolin is used to treat cancer. Its anticancer properties are attributed to its capability to engage with multiple molecular targeted sites and modify various signaling pathways in tumor cells. Luteolin has been shown to slow the spread of cancer in breast, colorectal, lung, prostate, liver, skin, pancreatic, oral, and gastric cancer models. It exhibits antioxidant properties and can be given to patients receiving Doxorubicin (DOX) chemotherapy to prevent the development of unexpected adverse reactions in the lungs and hematopoietic system subjected to DOX. Furthermore, it could be an excellent candidate for synergistic studies to overcome drug resistance in cancer cells. Accordingly, this review covers the recent literature related to the use of luteolin against different types of cancer, along with the mechanisms of action. In addition, the review highlights luteolin as a complementary medicine for preventing and treating cancer.

Quercetin increases the antidepressant-like effects of sclareol and antagonizes diazepam in thiopental sodium-induced sleeping mice: A possible GABAergic transmission intervention.

Quercetin is the most common polyphenolic flavonoid present in fruits and vegetables demonstrating versatile health-promoting effects. This study aimed to examine the effects of quercetin (QR) and sclareol (SCL) on the thiopental sodium (TS)-induced sleeping and forced swimming test (FST) mouse models. SCL (1, 5, and 10 mg/kg, p.o.) or QR (50 mg/kg, p.o.) and/or diazepam (DZP) (3 mg/kg, i.p.) were employed. After 30 min of TS induction, individual or combined effects on the animals were checked. In the FST test, the animals were subjected to forced swimming after 30 min of administration of the test and/or controls for 5 min. In this case, immobility time was measured. In silico studies were conducted to evaluate the involvement of GABA receptors. SCL (5 and 10 mg/kg) significantly increased the latency and decreased sleeping time compared to the control in the TS-induced sleeping time study. DZP (3 mg/kg) showed a sedative-like effect in animals in both sleeping and FST studies. QR (50 mg/kg) exhibited a similar pattern of activity as SCL. However, its effects were more prominent than those of SCL groups. SCL (10 mg/kg) altered the DZP-3-mediated effects. SCL-10 co-treated with QR-50 significantly (p < 0.05) increased the latency and decreased sleep time and immobility time, suggesting possible synergistic antidepressant-like effects. In silico studies revealed that SCL and QR demonstrated better binding affinities with GABAA receptor, especially α2, α3, and α5 subunits. Both compounds also exhibited good ADMET and drug-like properties. In animal studies, the both compounds worked synergistically to provide antidepressant-like effects in a slightly different fashion. As a conclusion, the combined administration of SCL and QR may be used in upcoming neurological clinical trials, according to in vivo and in silico findings. However, additional investigation is necessary to verify this behavior and clarify the potential mechanism of action.

Longevity Spinach (Gynura procumbens) Ameliorated Oxidative Stress and Inflammatory Mediators in Cisplatin-Induced Organ Dysfunction in Rats: Comprehensive in†vivo and in silico Studies.

This study focused to assess the efficacy of Gynura procumbens (GP) leaf extract against cisplatin (CP)-induced hepatorenal complications in Wister albino rats. Additionally, it aims to detect polyphenolic compounds using high-performance liquid chromatography with diode-array detection (HPLC-DAD). The rats were treated intraperitoneally with CP (7.5 mg/kg) to mediate hepatorenal damage. They were then treated with GP extract (75 and 150 mg/kg, P.O.) for 7 consecutive days. Although GP extract significantly ameliorated CP-mediated hepatorenal biomarkers like alkaline phosphatase (ALP), alanine aminotransferase (ALT), aspartate aminotransferase (AST), creatinine, and blood urea nitrogen (BUN) levels in a dose-dependent manner, GP extract at 150 mg/kg dose normalized hepatorenal biomarkers ALP (45.11 U/L), ALT (34 U/L), AST (29 U/L), creatinine (10.3 mg/dl) and BUN (11.19 mg/dl) while comparing to control and disease group. Similarly, though it significantly reduced CP-induced oxidative stress inducers, including nitric oxide (NO) and advanced oxidative protein products (AOPP), higher dose (150 mg/kg) exhibited better activity in reducing NO (281.54 mmol/gm tissue in liver and 52.73 mmol/gm tissue in the kidney) and AOPP (770.95 mmol/mg protein in liver and 651.90 mmol/mg protein in the kidney). Besides, it showed better enhancement in the antioxidant enzymes superoxide dismutase, and glutathione levels at a higher dose (150 mg/kg). Histopathological studies showed that CP caused collagen accumulation in the liver and kidney tissues. GP extract drained the collagen mass and acted against hepatorenal damage. Ellagic acid, gallic acid, quercetin hydrate, kaempferol, and rutin hydrate were revealed in GP extract. In-silico modelling showed good docking scores of the polyphenolic compounds with molecular targets including CYP4502E1, NF-κB, caspase-3, and TNF-α. GP could be an effective therapeutic option for management of anticancer drugs' complications like CP-induced organ damage, although clinical studies are required to establish herbal formulation.

Reactive oxygen species in biological systems: Pathways, associated diseases, and potential inhibitors-A review.

Reactive oxygen species (ROS) are produced under normal physiological conditions and may have beneficial and harmful effects on biological systems. ROS are involved in many physiological processes such as differentiation, proliferation, necrosis, autophagy, and apoptosis by acting as signaling molecules or regulators of transcription factors. In this case, maintaining proper cellular ROS levels is known as redox homeostasis. Oxidative stress occurs because of the imbalance between the production of ROS and antioxidant defenses. Sources of ROS include the mitochondria, auto-oxidation of glucose, and enzymatic pathways such as nicotinamide adenine dinucleotide phosphate reduced (NAD[P]H) oxidase. The possible ROS pathways are NF-κB, MAPKs, PI3K-Akt, and the Keap1-Nrf2-ARE signaling pathway. This review covers the literature pertaining to the possible ROS pathways and strategies to inhibit them. Additionally, this review summarizes the literature related to finding ROS inhibitors.

Composite of bacterial cellulose and gelatin: A versatile biocompatible scaffold for tissue engineering.

Synthesis of 0.4 ± 0.03 g/L per day of pure and porous bacterial cellulose (BC) scaffolds (scaffBC) and BC scaffolds modified with gelatin (scaffBC/Gel) was carried out using the Medusomyces gisevii Sa-28 bacterial strain. FT-IR spectroscopy and X-ray diffraction analysis showed that the scaffolds largely consist of crystalline cellulose I (Iα, Iß). Heating of BC with gelatin to 60 °C with subsequent lyophilization led to its modification by adsorption and binding of low-molecular fractions of gelatin and the formation of small pores between the fibers, which increased the biocompatibility and solubility of BC. The solubility of scaffBC and scaffBC/Gel was 20.8 % and 44.4 %, respectively, which enhances degradation in vivo. Light microscopy, scanning electron microscopy, and microcomputed tomography showed a uniform distribution of pores with a diameter of 100-500 µm. The chicken chorioallantoic membrane (CAM) model and subcutaneous implantation in rats confirmed low immunogenicity and intense formation of collagen fibers in both scaffolds and active germination of new blood vessels in scaffBC and scaffBC/Gel. The proliferative cellular activity of fibroblasts confirmed the safety of scaffolds. Taken together, the results obtained show that scaffBC/Gel can be used for the engineering of hard and soft tissues, which opens opportunities for further research.

Plant Polyphenols and Their Potential Benefits on Cardiovascular Health: A Review.

Fruits, vegetables, and other food items contain phytochemicals or secondary metabolites which may be considered non-essential nutrients but have medicinal importance. These dietary phytochemicals exhibit chemopreventive and therapeutic effects against numerous diseases. Polyphenols are secondary metabolites found in vegetables, fruits, and grains. These compounds exhibit several health benefits such as immune modulators, vasodilators, and antioxidants. This review focuses on recent studies on using dietary polyphenols to treat cardiovascular disorders, atherosclerosis, and vascular endothelium deficits. We focus on exploring the safety of highly effective polyphenols to ensure their maximum impact on cardiac abnormalities and discuss recent epidemiological evidence and intervention trials related to these properties. Kaempferol, quercetin, and resveratrol prevent oxidative stress by regulating proteins that induce oxidation in heart tissues. In addition, polyphenols modulate the tone of the endothelium of vessels by releasing nitric oxide (NO) and reducing low-density lipoprotein (LDL) oxidation to prevent atherosclerosis. In cardiomyocytes, polyphenols suppress the expression of inflammatory markers and inhibit the production of inflammation markers to exert an anti-inflammatory response. Consequently, heart diseases such as strokes, hypertension, heart failure, and ischemic heart disease could be prevented by dietary polyphenols.

Anxiolytic-like Effects by trans-Ferulic Acid Possibly Occur through GABAergic Interaction Pathways.

Numerous previous studies reported that ferulic acid exerts anxiolytic activity. However, the mechanisms have yet to be elucidated. The current study aimed to investigate the anxiolytic effect of trans-ferulic acid (TFA), a stereoisomer of ferulic acid, and evaluated its underlying mechanism using in vivo and computational studies. For this, different experimental doses of TFA (25, 50, and 75 mg/kg) were administered orally to Swiss albino mice, and various behavioral methods of open field, hole board, swing box, and light-dark tests were carried out. Diazepam (DZP), a positive allosteric modulator of the GABAA receptor, was employed as a positive control at a dose of 2 mg/kg, and distilled water served as a vehicle. Additionally, molecular docking was performed to estimate the binding affinities of the TFA and DZP toward the GABAA receptor subunits of α2 and α3, which are associated with the anxiolytic effect; visualizations of the ligand-receptor interaction were carried out using various computational tools. Our findings indicate that TFA dose-dependently reduces the locomotor activity of the animals in comparison with the controls, calming their behaviors. In addition, TFA exerted the highest binding affinity (-5.8 kcal/mol) to the α2 subunit of the GABAA receptor by forming several hydrogen and hydrophobic bonds. Taken together, our findings suggest that TFA exerts a similar effect to DZP, and the compound exerts moderate anxiolytic activity through the GABAergic interaction pathway. We suggest further clinical studies to develop TFA as a reliable anxiolytic agent.

Anti-urolithiatic, antibacterial, anti-inflammatory and analgesic effects of Erica arborea flowers and leaves hydromethanolic extracts: An ethnopharmacological study.

Erica arborea L. is a medicinal plant vastly used in therapeutic purposes in several parts of the world for antimicrobial, anti-inflammatory, and diuretic purposes, and in treating urinary infections and kidney stones. The current investigation aimed to evaluate the medicinal use of E. arborea in Algeria's Bejaia region, and to examine the anti-urolithiatic, antibacterial, anti-inflammatory (in vivo), analgesic, and toxicity effects of E. arborea hydromethanolic extracts from leaves (EALE) and flowers (EALE) to give a justification for its use in the traditional medicine. The in vitro anti-urolithiathic activity of E. arborea leaf and flower hydromethanolic extracts nucleation and aggregation of crystals were measured using spectrophotometric methods. The agar disk diffusion assay and minimum inhibitory concentration (MIC) determination were employed to estimate the antibacterial effect of EAME against three Gram-positive and three Gram-negative bacterial strains in vitro. In addition, the xylene and croton oil-induced ear edema methods in mice were used to examine the topical and oral anti-inflammatory potential of the extracts. Similarly, the analgesic effect of the extract was assessed via the acetic acid-induced abdominal constriction in mice, whereas the acute toxicity of EAME was conducted following OECD guidelines. An ethnobotanical survey was conducted among 171 informants with 212 questionnaire cards. Results indicated that 28.04 % of people in the studied region used E. arborea in traditional folk medicine. Additionally, results revealed the presence of epicatechin, palmitic acid, and kaempferol-3-O-glucoside in the plant extracts. Results also showed that EAME exhibits significant and dose-dependent anti-urolithiatic activity in nucleation and aggregation assays. Furthermore, results revealed that the extracts exhibit significant antibacterial activity. The E. arborea flower extract (EAFE) showed maximum antibacterial activity, especially against P. aeruginosa, E. coli, S. gallinarum, and B. cereus. In addition, a greater minimum inhibitory concentration (MIC) in this extract was found at 1.60 mg/mL against M. luteus strain compared to the positive control. Moreover, the EAME caused a significant inhibition influence in the xylene and croton oil-induced edematous in mice. In contrast, the topical anti-inflammatory potential showed that extracts exhibit a considerable anti-edematogenic effect in both animal models. In the writhing reaction induced by the acetic acid model, the two extracts significantly reduced abdominal contractions. Finally, results of the toxicity assay showed that EAME is safe and no deaths or changes in mice behavior were observed even when doses as high as 5 g/kg DW were used. From the ethnopharmacological studies, our consequences endorse the benefit of E. arborea in folk medicine. Results of this investigation suggest that the leaf and flower extracts of E. arborea exhibit notable anti-urolithiatic, anti-inflammatory, analgesic, and antibacterial activities and are safe as a natural source of drugs with the above effects.

Hirsutine, an Emerging Natural Product with Promising Therapeutic Benefits: A Systematic Review.

Fruits and vegetables are used not only for nutritional purposes but also as therapeutics to treat various diseases and ailments. These food items are prominent sources of phytochemicals that exhibit chemopreventive and therapeutic effects against several diseases. Hirsutine (HSN) is a naturally occurring indole alkaloid found in various Uncaria species and has a multitude of therapeutic benefits. It is found in foodstuffs such as fish, seafood, meat, poultry, dairy, and some grain products among other things. In addition, it is present in fruits and vegetables including corn, cauliflower, mushrooms, potatoes, bamboo shoots, bananas, cantaloupe, and citrus fruits. The primary emphasis of this study is to summarize the pharmacological activities and the underlying mechanisms of HSN against different diseases, as well as the biopharmaceutical features. For this, data were collected (up to date as of 1 July 2023) from various reliable and authentic literature by searching different academic search engines, including PubMed, Springer Link, Scopus, Wiley Online, Web of Science, ScienceDirect, and Google Scholar. Findings indicated that HSN exerts several effects in various preclinical and pharmacological experimental systems. It exhibits anti-inflammatory, antiviral, anti-diabetic, and antioxidant activities with beneficial effects in neurological and cardiovascular diseases. Our findings also indicate that HSN exerts promising anticancer potentials via several molecular mechanisms, including apoptotic cell death, induction of oxidative stress, cytotoxic effect, anti-proliferative effect, genotoxic effect, and inhibition of cancer cell migration and invasion against various cancers such as lung, breast, and antitumor effects in human T-cell leukemia. Taken all together, findings from this study show that HSN can be a promising therapeutic agent to treat various diseases including cancer.

Quercetin Antagonizes the Sedative Effects of Linalool, Possibly through the GABAergic Interaction Pathway.

Sedatives promote calmness or sleepiness during surgery or severely stressful events. In addition, depression is a mental health issue that negatively affects emotional well-being. A group of drugs called anti-depressants is used to treat major depressive illnesses. The aim of the present work was to evaluate the effects of quercetin (QUR) and linalool (LIN) on thiopental sodium (TS)-induced sleeping mice and to investigate the combined effects of these compounds using a conventional co-treatment strategy and in silico studies. For this, the TS-induced sleeping mice were monitored to compare the occurrence, latency, and duration of the sleep-in response to QUR (10, 25, 50 mg/kg), LIN (10, 25, 50 mg/kg), and diazepam (DZP, 3 mg/kg, i.p.). Moreover, an in silico investigation was undertaken to assess this study's putative modulatory sedation mechanism. For this, we observed the ability of test and standard medications to interact with various gamma-aminobutyric acid A receptor (GABAA) subunits. Results revealed that QUR and LIN cause dose-dependent antidepressant-like and sedative-like effects in animals, respectively. In addition, QUR-50 mg/kg and LIN-50 mg/kg and/or DZP-3 mg/kg combined were associated with an increased latency period and reduced sleeping times in animals. Results of the in silico studies demonstrated that QUR has better binding interaction with GABAA α3, ß1, and γ2 subunits when compared with DZP, whereas LIN showed moderate affinity with the GABAA receptor. Taken together, the sleep duration of LIN and DZP is opposed by QUR in TS-induced sleeping mice, suggesting that QUR may be responsible for providing sedation-antagonizing effects through the GABAergic interaction pathway.

Food Polyphenols and Type II Diabetes Mellitus: Pharmacology and Mechanisms.

Type II diabetes mellitus and its related complications are growing public health problems. Many natural products present in our diet, including polyphenols, can be used in treating and managing type II diabetes mellitus and different diseases, owing to their numerous biological properties. Anthocyanins, flavonols, stilbenes, curcuminoids, hesperidin, hesperetin, naringenin, and phenolic acids are common polyphenols found in blueberries, chokeberries, sea-buckthorn, mulberries, turmeric, citrus fruits, and cereals. These compounds exhibit antidiabetic effects through different pathways. Accordingly, this review presents an overview of the most recent developments in using food polyphenols for managing and treating type II diabetes mellitus, along with various mechanisms. In addition, the present work summarizes the literature about the anti-diabetic effect of food polyphenols and evaluates their potential as complementary or alternative medicines to treat type II diabetes mellitus. Results obtained from this survey show that anthocyanins, flavonols, stilbenes, curcuminoids, and phenolic acids can manage diabetes mellitus by protecting pancreatic ß-cells against glucose toxicity, promoting ß-cell proliferation, reducing ß-cell apoptosis, and inhibiting α-glucosidases or α-amylase. In addition, these phenolic compounds exhibit antioxidant anti-inflammatory activities, modulate carbohydrate and lipid metabolism, optimize oxidative stress, reduce insulin resistance, and stimulate the pancreas to secrete insulin. They also activate insulin signaling and inhibit digestive enzymes, regulate intestinal microbiota, improve adipose tissue metabolism, inhibit glucose absorption, and inhibit the formation of advanced glycation end products. However, insufficient data are available on the effective mechanisms necessary to manage diabetes.

Collaterally Sensitive ß-Lactam Drugs as an Effective Therapy against the Pre-Existing Methicillin Resistant Staphylococcus aureus (MRSA) Biofilms.

Methicillin-resistant Staphylococcus aureus (MRSA) is among the leading causes of nosocomial infections and forms biofilms, which are difficult to eradicate because of their increasing resistance to antimicrobial agents. This is especially true for pre-existing biofilms. The current study focused on evaluating the efficacy of three ß-lactam drugs, meropenem, piperacillin, and tazobactam, alone and in combination against the MRSA biofilms. When used individually, none of the drugs exhibited significant antibacterial activity against MRSA in a planktonic state. At the same time, the combination of meropenem, piperacillin, and tazobactam showed a 41.7 and 41.3% reduction in planktonic bacterial cell growth, respectively. These drugs were further assessed for biofilm inhibition and removal. The combination of meropenem, piperacillin, and tazobactam caused 44.3% biofilm inhibition, while the rest of the combinations did not show any significant effects. Results also revealed that piperacillin and tazobactam exhibited the best synergy against the pre-formed biofilm of MRSA, with 46% removal. However, adding meropenem to the piperacillin and tazobactam combination showed a slightly reduced activity towards the pre-formed biofilm of MRSA and removed 38.7% of it. Although the mechanism of synergism is not fully understood, our findings suggest that these three ß-lactam drugs can be used in combination as very effective therapeutic agents for the treatment of pre-existing MRSA biofilms. The in vivo experiments on the antibiofilm activity of these drugs will pave the way for applying such synergistic combinations to clinics.

Cardioprotective and hypotensive mechanistic insights of hydroethanolic extract of Cucumis melo L. kernels in isoprenaline-induced cardiotoxicity based on metabolomics and in silico electrophysiological models.

Background: Cardiovascular diseases (CVD) continue to threaten health worldwide, and account for a significant portion of deaths and illnesses. In both developing and industrialized nations, they challenge their health systems. There are several traditional uses of Cucurbitaceae seeds in Pakistan, India, Iran, and China, including treating cardiovascular, neurological, and urogenital diseases. Methods: In the present work, integrated techniques of metabolomics profiling and computational cardiomyocyte stimulation were used to investigate possible mechanisms of C. melo in isoprenaline (ISO)-induced myocardial infarction. In vitro, vasoconstrictions, paired atria, and in vivo invasive blood pressure measurement models were performed to explore the mechanism of action of C. melo hydroethanolic seed extract (Cm-EtOH). Results: Results showed that Cm-EtOH demonstrates NO-based endothelium-derived relaxing factor (EDRF) vasorelaxant response, negative chronotropic and inotropic response in the atrium, and hypotensive effects in normotensive rats. Results also revealed that Cm-EtOH decreases cardiomyocyte hypertrophy and reverts the altered gene expressions, biochemical, and metabolites in ISO-induced myocardial infarction (MI) rats. The extract additionally reversed ISO-induced MI-induced oxidative stress, energy consumption, and amino acid metabolism. Moreover, C. melo seeds increased EDRF function, energy production, and antioxidant capacity to treat myocardial and vascular disorders. In computational cardiomyocyte simulation, gallic acid reduced action potential duration, upstroke velocity (dV/dtmax), and effective refractory period. Conclusion: This study highlights the therapeutic potential of C. melo seeds to treat cardiovascular diseases and provides mechanistic insight into its antihypertensive and cardioprotective activities.

Integrated Mechanisms of Polarity-Based Extracts of Cucumis melo L. Seed Kernels for Airway Smooth Muscle Relaxation via Key Signaling Pathways Based on WGCNA, In Vivo, and In Vitro Analyses.

The present study aimed to determine the mechanisms responsible for calcium-mediated smooth muscle contractions in C. melo seeds. The phytochemicals of C. melo were identified and quantified with the aid of Liquid Chromatography Electrospray Ionization Tandem Mass Spectrometric (LC/ESI-MS/MS) and high-performance liquid chromatography (HPLC), and then tested in-vitro and in vivo to confirm involvement in smooth muscle relaxation. Allergic asthma gene datasets were acquired from the NCBI gene expression omnibus (GEO) and differentially expressed gene (DEG) analysis, weighted gene co-expression network analysis (WGCNA), and functional enrichment analysis were conducted. Additionally, molecular docking of key genes was carried out. Kaempferol, rutin, and quercetin are identified as phytochemical constituents of C. melo seeds. Results indicated that C. melo seeds exhibit a dose-dependent relaxant effect for potassium chloride (80 mM)- induced spastic contraction and calcium antagonistic response in calcium dose-response curves. The functional enrichment of WGCNA and DEG asthma-associated pathogenic genes showed cytokine-mediated pathways and inflammatory responses. Furthermore, CACNA1A, IL2RB, and NOS2 were identified as key genes with greater binding affinity with rutin, quercitrin, and kaempferol in molecular docking. These results show that the bronchodilator and antidiarrheal effects of C. melo were produced by altering the regulatory genes of calcium-mediated smooth muscle contraction.

Cytotoxic and mutagenic effects of the food additive tartrazine on eukaryotic cells.

BACKGROUND: Among the food additives used in the food industry, food dyes are considered the most toxic. For instance, tartrazine (TRZ) is a food colorant commercially available with conflicting data regarding its cytotoxic, genotoxic, and mutagenic effects. Therefore, this study aimed to evaluate the cytotoxic and mutagenic potential of TRZ using different eukaryotic cells (in vitro). METHODS: This study employed 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT), brine shrimp lethality, Allium cepa and Saccharomyces cerevisiae tests. Different concentrations of TRZ and different exposure times were used in this study. RESULTS: The results demonstrate that TRZ induced a concentration-dependent toxic effect on the test systems. It also exerted cytotoxicity in fibroblasts and human gastric cells. In addition, TRZ showed mutagenic effects on the A. cepa test system. However, its toxicogenic effects may not relate to the oxidizing activity, which was confirmed by the S. cerevisiae test model. CONCLUSION: Taken together, TRZ exerted toxicogenic effects on the test systems. Therefore, it may be harmful to health, especially its prolonged use may trigger carcinogenesis.

Hepatoprotective activity of andrographolide possibly through antioxidative defense mechanism in Sprague-Dawley rats.

The aims of this study to assess the efficiency of AGL against acetaminophen (APAP)-induced hepatic toxicity that was generated by mitochondrial oxidative stress and glutathione depletion. Free radical scavenging potentiality was analyzed by using 2, 2-diphenyl-1-picrylhydrazyl (DPPH), hydrogen peroxide, nitric oxide, and hydroxyl radical scavenging assays. APAP-induced liver toxicity was formed at a dose level of 640 mg/kg mg/kg BW each, p.o. for 14 days for all experimental rats except the vehicle control group. AGL (5 and 10 mg/kg) were treated orally with negative control and negative control silymarin (50 mg/kg) group. To assess the protective effect, we looked at the levels of serum biochemical markers, liver histoarchitecture, and hepatic antioxidant enzyme activity. AGL showed in vitro anti-oxidant potentialities by scavenging radicals in the respective assays. As evidenced by serum biochemical indicators and relative liver weight, AGL co-administration substantially reduced toxicant-induced hepatic damage. APAP-intoxication increased the malondialdehyde (MDA) level and declined in cellular endogenous antioxidant enzymes such as reduced catalase, superoxide dismutase, and glutathione, where, AGL treatment amended their level. In the same way, histopathological evaluation further verified that AGL protected the hepatocyte from APAP-induced damage. As AGL scavenges toxic free radicals, thereby protects mitochondria and other organelles from reactive oxygen and nitrogen species-mediated stress and its eventual consequence necrosis. Therefore, we propose the hepatoprotective activity of AGL through its antioxidant mechanism.

Targeting mTOR as a Cancer Therapy: Recent Advances in Natural Bioactive Compounds and Immunotherapy.

The mammalian target of rapamycin (mTOR) is a highly conserved serine/threonine-protein kinase, which regulates many biological processes related to metabolism, cancer, immune function, and aging. It is an essential protein kinase that belongs to the phosphoinositide-3-kinase (PI3K) family and has two known signaling complexes, mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC2). Even though mTOR signaling plays a critical role in promoting mitochondria-related protein synthesis, suppressing the catabolic process of autophagy, contributing to lipid metabolism, engaging in ribosome formation, and acting as a critical regulator of mRNA translation, it remains one of the significant signaling systems involved in the tumor process, particularly in apoptosis, cell cycle, and cancer cell proliferation. Therefore, the mTOR signaling system could be suggested as a cancer biomarker, and its targeting is important in anti-tumor therapy research. Indeed, its dysregulation is involved in different types of cancers such as colon, neck, cervical, head, lung, breast, reproductive, and bone cancers, as well as nasopharyngeal carcinoma. Moreover, recent investigations showed that targeting mTOR could be considered as cancer therapy. Accordingly, this review presents an overview of recent developments associated with the mTOR signaling pathway and its molecular involvement in various human cancer types. It also summarizes the research progress of different mTOR inhibitors, including natural and synthetised compounds and their main mechanisms, as well as the rational combinations with immunotherapies.

Pharmacological Properties of Trichostatin A, Focusing on the Anticancer Potential: A Comprehensive Review.

Trichostatin A (TSA), a natural derivative of dienohydroxamic acid derived from a fungal metabolite, exhibits various biological activities. It exerts antidiabetic activity and reverses high glucose levels caused by the downregulation of brain-derived neurotrophic factor (BDNF) expression in Schwann cells, anti-inflammatory activity by suppressing the expression of various cytokines, and significant antioxidant activity by suppressing oxidative stress through multiple mechanisms. Most importantly, TSA exhibits potent inhibitory activity against different types of cancer through different pathways. The anticancer activity of TSA appeared in many in vitro and in vivo investigations that involved various cell lines and animal models. Indeed, TSA exhibits anticancer properties alone or in combination with other drugs used in chemotherapy. It induces sensitivity of some human cancers toward chemotherapeutical drugs. TSA also exhibits its action on epigenetic modulators involved in cell transformation, and therefore it is considered an epidrug candidate for cancer therapy. Accordingly, this work presents a comprehensive review of the most recent developments in utilizing this natural compound for the prevention, management, and treatment of various diseases, including cancer, along with the multiple mechanisms of action. In addition, this review summarizes the most recent and relevant literature that deals with the use of TSA as a therapeutic agent against various diseases, emphasizing its anticancer potential and the anticancer molecular mechanisms. Moreover, TSA has not been involved in toxicological effects on normal cells. Furthermore, this work highlights the potential utilization of TSA as a complementary or alternative medicine for preventing and treating cancer, alone or in combination with other anticancer drugs.