Hepatoprotective and Antioxidant Effects of Nanopiperine against Cypermethrin via Mitigation of Oxidative Stress, Inflammations and Gene Expression Using qRT-PCR.

Cypermethrin (Cyp) is a pyrethroid that has been associated with the toxicity of various organs. The aim of our study was to evaluate the hepatoprotective and antioxidant activities of nano-piperine (NP) against Cyp toxicity. Cyp (50 mg/kg) was administered orally in all animals of groups III-VI for 15 days. Groups IV-VI each received three doses of NP (125, 250, and 500 µg/kg/day) for 10 days after receiving the Cyp dosage, which was given after 1 h. A rise in serum biomarkers (ALT, AST, ALP, total protein, and albumin), which are indicators of toxicity alongside anomalous oxidative stress indices (lipid peroxidation (LPO), glutathione (GSH), superoxide dismutase (SOD) and catalase), was detected. After Cyp treatment, we observed upregulated cytokines, caspase expression, and histological analysis that the showed distortion of cell shape. However, the administration of NP dramatically reversed all of the Cyp-induced alterations, inducing reductions in serum marker levels, stress level, the production of cytokines, and caspase expression. Additionally, all of the histopathological alterations were minimized to values that were comparable to normal levels. The present findings suggested that NP exhibits potent antioxidant and anti-inflammatory activities that can protect rats' livers against Cyp-induced liver damage through hepatoprotective activities.

Cinnamon Oil Alleviates Acetaminophen-Induced Uterine Toxicity in Rats by Abrogation of Oxidative Stress, Apoptosis, and Inflammation.

Paracetamol, or acetaminophen (APAP), is one of the first-line medications that is used for fever and pain. However, APAP can induce uterine toxicity when overused. The mode of action of APAP toxicity is due to the production of free radicals. The main goal of our study is to determine uterine toxicity from APAP overdose and the antioxidative activity of cinnamon oil (CO) in female rats. The effect of different doses of CO (50-200 mg/kg b.w.) was assessed in the uterus toxicity induced by APAP. Additionally, the imbalance in oxidative parameters, interleukins, and caspases was evaluated for the protective effects of CO. A single dose of APAP (2 g/kg b.w.) resulted in uterus toxicity, indicated by a significant increase in the level of lipid peroxidation (LPO), inflammatory interleukins cytokines (IL-1 and 6), expression of caspases 3 and 9, and a marked change in uterus tissue architecture evaluated by histopathology. Co-treatment of CO resulted in a significant amelioration of all the parameters such as LPO, interleukins IL-1ß, IL-6, caspases 3 and 9 expression, and distortion of tissue architecture in a dose-dependent manner. Therefore, we can conclude that APAP-induced uterine injury due to oxidative stress can be restored by co-treatment with cinnamon oil (CO).

Neuroprotective Effects of Nano-Curcumin against Cypermethrin Associated Oxidative Stress and Up-Regulation of Apoptotic and Inflammatory Gene Expression in Rat Brains.

Cypermethrin (CPM) is the most toxic synthetic pyrethroid that has established neurotoxicity through oxidative stress and neurochemical agitation in experimental rats. The toxic effects are supposed to be mediated by modifying the sodium channels, reducing Na-K ATPase, acetylcholine esterase (AchE), and monoamine oxidase (MAO). The use of curcumin nanoparticles (NC) that have potent antioxidant, anti-inflammatory and antiapoptotic properties with improved bioavailability attenuates neurotoxicity in rat brains. To test this hypothesis, animals were divided into five groups, each having six animals. Group-I control received vehicle only, while Group-II was treated with 50 mg/kg CPM. Group-III and Group-IV received both CPM and NC 2.5 mg/kg and 5 mg/kg, respectively. Group-V received 5 mg of NC alone. The CPM and NC were given by oral route. Afterwards, brain antioxidant status was measured by assessing lipid peroxidation (LPO), 4-HNE, glutathione reduced (GSH), antioxidant enzyme catalase, and superoxide dismutase (SOD) along with neurotoxicity markers Na-K ATPase, AchE, and MAO. Inflammation and apoptosis indices were estimated by ELISA, qRT-PCR, and immunohistochemistry, while morphologic changes were examined by histopathology. Observations from the study confirmed CPM-induced neurotoxicity by altering Na-K ATPase, AchE, and MAO, and by decreasing the activity of antioxidant enzymes and GSH. Oxidative stress marker LPO and the level of inflammatory interleukins IL-6, IL-1ß, and TNF-α were notably high, and elevated expressions of Bax, NF-kB, and caspase-3 and -9 were reported in CPM group. However, NC treatment against CPM offers protection by improving antioxidant status and lowering LPO, inflammation, and apoptosis. The neurotoxicity marker's enzyme successfully attenuated after NC treatment. Therefore, this study supports the administration of NC effectively ameliorated CPM-induced neurotoxicity in experimental rats.

Hepatoprotective Effect of Curcumin Nano-Lipid Carrier against Cypermethrin Toxicity by Countering the Oxidative, Inflammatory, and Apoptotic Changes in Wistar Rats.

This study investigated the potential hepatoprotective activity of curcumin-incorporated nano-lipid carrier (Cur-NLC) against cypermethrin (Cyp) toxicity in adult Wistar male rats. All animals in groups III, IV, V, and VI were subjected to Cyp (50 mg/kg) toxicity for 15 days. Three different doses of Cur-NLC (1, 2.5, and 5 mg/kg/day) were administered orally for 10 days. The toxic effects were evaluated considering the increases in serum hepatic biomarkers alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), total protein and albumin, and lipid peroxidation (LPO), as well as a decrease in antioxidative activity (reduced glutathione (GSH), superoxide dismutase (SOD), and catalase) and the upregulation of inflammatory cytokines (IL-1ß, IL-6, and TNF-α). Immunohistochemistry studies of proteins (NF-κB, Apaf-1, 4-HNE, and Bax) showed enhanced expression, and histopathological examination revealed architectural changes in liver cells, indicating liver toxicity in animals. Toxicity was determined by quantitative and qualitative determinations of DNA fragmentation, which show massive apoptosis with Cyp treatment. The administration of Cur-NLC significantly ameliorates all changes caused by Cyp, such as a decrease in the levels of serum liver markers, an increase in antioxidative parameters, a decrease in expression of inflammatory cytokines (IL-1ß, IL-6, TNF-α, and NF-κB), and apoptosis (caspases-3, 9, Apaf-1, 4-HNE, and Bax), according to calorimetric and immunohistochemistry studies. The smear-like pattern of DNA is ameliorated similarly to the control at a high dose of Cur-NLC. Furthermore, all histopathological changes were reduced to a level close to the control. In conclusion, Cur-NLC could be a potent nutraceutical that exhibits a hepatoprotective effect against Cyp-induced hepatotoxicity in rats.

Role of cinnamon oil against acetaminophen overdose induced neurological aberrations through brain stress and cytokine upregulation in rat brain.

Acetaminophen (APAP) is a well-known antipyretic and analgesic medicine. It is safe at therapeutic suggested level while overdose initiates oxidative stress and inflammation mediated neurochemical alteration in the brain. The aim of this study was to investigate the role of cinnamon oil (CO), which possesses potent antioxidant and anti-inflammatory activities against an overdose of APAP that induced oxidative stress and inflammation in male albino rats. APAP treated rats showed significant elevation of thiobarbituric acid-reactive substances (TBARS) and decreased level of GSH in brain tissue, which is recognized as a biomarker of oxidative stress. Antioxidant enzymes GPx, GR, SOD, and CAT activity was depleted in APAP group along with neurotoxicity biomarkers such as Na+-K+-ATPase and increased activity of acetylcholinesterase (AchE), monoamine oxidase (MAO), and upregulated pro-inflammatory cytokine was observed. CO significantly protected the diminished activity of the antioxidant enzyme and suppressed the upregulated cytokines in brain tissue. CO also attenuated the activity of neurotoxicity biomarker enzyme, decreased TBARS content, and an increased level of GSH. The present findings perceptibly confirmed that the nutraceutical property of CO ameliorates APAP induced oxidative stress and inflammation. Therefore, our findings suggested that CO could be an alternative nutraceutical substitute in APAP overdose poisoning.

Renoprotective effects of cinnamon oil against APAP-Induced nephrotoxicity by ameliorating oxidative stress, apoptosis and inflammation in rats.

Acetaminophen (APAP) is used as a primary medication in relieving moderate pain and fever. However, APAP is associated with toxic effects in renal tissue that appear because of its free radicals property. The principle goal of the present work is to assess the kidney damage by APAP and its restore antioxidative property of cinnamon oil (CO). Animals were distributed into six animals each in six groups. Rats were administered with three varying doses of CO from 50 to 200 mg/kg b.w. respectively and only a single dose of APAP. APAP induced an alteration in serum biochemical markers, imbalance in oxidative parameters, morphological changes in kidney tissue along with increased interleukins cytokines (IL-1ß & 6) and caspase (3, 9) levels. CO administration significantly ameliorates all the parameters and histopathological changes were restored. Moreover, it also restored the activities of antioxidative enzymes. Our work proved that an variance of oxidative markers in the kidney by APAP is ameliorated by CO in rats. Thus, CO could be used in reducing APAP-induced nephrotoxicity.

Modulatory effect of zingerone against STZ-nicotinamide induced type-2 diabetes mellitus in rats.

The objective of this research was to explore the role of zingerone on hyperglycemia, hyperlipidemia, insulin level, oxidative biochemical markers and histological alterations in ß-cells of type-2 diabetic rats. The outcome of this study illustrates reduction in glucose and insulin levels significantly in zingerone-treated diabetic groups. Lipid parameters were resumed to normal in zingerone-treated diabetic group as demonstrated by significant reduction in triglycerides, cholesterols (total, low-density and very low-density) levels along with significant increase high-density cholesterols levels. Zingerone-treated diabetic groups exhibited significant reduction in LPO levels and restoration of GSH contents. Administration of zingerone to treated diabetic groups indicated improvement in antioxidant enzymes (GPx, GR, GST, SOD and CAT). Administration of zingerone to treated diabetic groups minimized degeneration of pancreatic ß-cells as witnessed from histopathological studies. Our results demonstrate that zingerone modulates hyperglycaemia, hyperlipidaemia, oxidative biochemical markers and degenerative changes in ß-cells of treated diabetic groups.

Phytochemical and spectral analysis of the methanolic extracts of leaves of Murraya koenigii of Jazan, Saudi Arabia.

The present study aimed to explore the biocomponents of Murraya koenigii leaves through hot continuous percolation method using methanol as solvent. The spectral analysis by GC-MS and FTIR study demonstrated the presence of alkaloids, tannins, fatty acids, and steroids. The extract was characterized by the presence of unique compounds such as epiyangambin, stigmasterol, α-terpineol, eucalyptol, ethyl cinnamate, fatty acids, and other steroids.

Solvent extraction, spectral analysis and antibacterial activity of the bioactive crystals of Sargassum aquifolium (Turner) C.Agardh from Red Sea.

The purpose of this study was to investigate the chemical composition and anti-bacterial properties of the bioactive principles of Sargassum aquifolium (Turner) C.Agardh, a brown seaweed in Red sea of Jazan province, Kingdom of Saudi Arabia. Crystals were obtained from the petroleum ether extract of Sargassum aquifolium and subjected to chemical tests, FTIR spectroscopic analysis and NMR analysis to identify their chemical composition, and to study their antibacterial properties against selected human pathogenic bacteria. In addition, GC-MS analysis was performed to identify the bioactive compounds in the crude petroleum ether extract. Results of the antibacterial effect of the crystal analyte showed a wide spectrum of activity against the screened human pathogenic bacteria.

Cinnamon oil against acetaminophen-induced acute liver toxicity by attenuating inflammation, oxidative stress and apoptosis.

Acetaminophen (APAP) is used as a primary drug due to its antipyretic and analgesic activity. The mechanism of action of APAP toxicity in the liver is due to the depletion of glutathione which elicited free radicals generation. Therefore, the objective of our work is to investigate the APAP induced liver damage and its repair by free radical scavenging activity of cinnamon oil (CO) in male Wistar rats. To investigate the effects of CO at different doses (50, 100 and 200 mg/kg b.w.), animals were given a single oral dose of CO per day for 14 days between 12:00-1:00 PM. The biochemical changes, imbalance in oxidative markers, interleukins, caspases and histopathological studies were determined for quantifying the hepatoprotective effect of CO. One dose of APAP (2 g/kg b.w.) results in significant hepatotoxicity and marked increase the serum markers alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), bilirubin, albumin, total protein, content of lipid peroxidation (LPO), interleukins (IL-1ß, IL-6), caspase-3, -9 expression, DNA fragmentation and histopathological changes were observed. Significant decrease in the levels of LPO, interleukins IL-1ß, IL-6, caspase-3, -9 expressions, qualitative as well as quantitative determination of DNA fragments and histopathological changes were reversed by the administration of CO dose dependently. Furthermore, it also restores the depleted activity of antioxidative enzymes. Our study shows that an imbalance in the oxidative parameter in the liver by APAP is restored by treating the animals with CO.

Thymoquinone and fluoxetine alleviate depression via attenuating oxidative damage and inflammatory markers in type-2 diabetic rats.

The study was designed to find out the effect of thymoquinone (TQ) alone and combination of TQ + fluoxetine in depression of type-2 diabetic rats. Glucose level was significantly decreased in TQ alone treated group, whereas no significant change was recorded when TQ was combined with fluoxetine. Administration of TQ alone and combination of TQ and fluoxetine significantly decreased immobility time, increased latency to immobility and increased locomotor activity. Treatment with TQ alone significantly decreased level of TBARS, increased GSH and restored the activities of antioxidant enzymes (GPx, GR & CAT). However, TQ and fluoxetine combination reduced TBARS level, increased GSH content but no change in the antioxidant enzymes activities. Inflammatory markers (IL-1ß, IL-6 & TNF-α) levels were significantly reduced after the administration of TQ alone and TQ + fluoxetine. The study suggests that combination of TQ and fluoxetine can be used to control depression in type-2 diabetes mellitus.

The combination of canagliflozin and omega-3 fatty acid ameliorates insulin resistance and cardiac biomarkers via modulation of inflammatory cytokines in type 2 diabetic rats.

The present study was carried out with the hypothesis that combination of canagliflozin and omega-3 fatty acid may have potential effect on insulin level, insulin resistance, cardiac biomarkers, inflammatory cytokines and histological studies in type 2 diabetes mellitus (DM). Type 2 DM was induced by injecting nicotinamide (120 mg/kg, i.p.) 15 min before STZ (60 mg/kg) injection. Canagliflozin (5 and 10 mg/kg) and omega-3 fatty acid (300 mg/kg) were given for 28 days after confirmation of diabetes. Biochemical estimations revealed elevated levels of glucose, insulin, HOMA-R and inflammatory cytokines in diabetic group. Daily dosing of alone canagliflozin and omega-3 fatty acid slightly reduced elevated levels of glucose, insulin, HOMA-R and inflammatory cytokines (IL-1ß, IL-2, and TNFα), whereas canagliflozin and omega-3 fatty acid combination has reduced these biochemical parameters significantly when compared with diabetic group. Similarly in diabetic group the levels of cardiac biomarkers such as lipid profile, LDH, CKMB and troponin were significantly increased. Elevated levels of cardiac biomarkers were significantly reduced after daily dosing of alone canagliflozin and omega-3 fatty acid. Canagliflozin and omega-3 fatty acid combination has offered better improvement in cardiac biomarkers compared to alone canagliflozin and omega-3 fatty acid. Histopathological analysis also supported the above hypothesis that combination therapy (canagliflozin and omega-3 fatty acid) offered better protection against degenerative changes in ß-cells of pancreas as compared to alone treatment with these drugs. Thus the present study revealed that canagliflozin and omega-3 fatty acid can be used as potential combination therapy in type 2 DM along with cardiac complication.

Therapeutic potential of Vanillylacetone against CCl4 induced hepatotoxicity by suppressing the serum marker, oxidative stress, inflammatory cytokines and apoptosis in Swiss albino mice.

The aim of this research was to investigate the therapeutic potential of Vanillylacetone against carbon tetrachloride (CCl4) induced hepatotoxicity in mice through understanding the serum marker, oxidative stress mechanism and cytokine networks. Carbon tetrachloride is highly hepatotoxic used as research based on animal model. The mice were classified into five groups and each had eight mice. Group-I was controlled and the vehicle was given orally. Group-II was toxic and carbon tetrachloride (1.5 ml/kg) twice a week for 15 days was administered by intra-peritoneal injections. Group- III and IV were pre-treated with Vanillylacetone 50 & 100 mg kg-1 body weight given every day p.o. while, Group-V received only Vanillylacetone (100 mg kg-1 body weight) for 15 days orally. The finding indicates that the administration of CCl4 causes significant elevation of enzyme markers, oxidative stress, inflammatory cytokine and apoptotic markers in Group-II as compared to Group-I. The administration of Vanillylacetone (50 and100 mg kg-1) significantly suppresses the elevated serum enzymes, oxidative stress (TBARS), an inflammatory cytokine (IL2 and TNFα) and apoptotic markers (Caspase-3 and 9) in Group-III and IV as compared to Group-II. It was also noticed that the higher dose of Vanillylacetone (100 mg) is more effective than lower dose of Vanillylacetone (50 mg). There were no significant changes observed with higher dose of Vanillylacetone (100 mg kg-1) in Group-V as compared to Group-I. Histopathological analysis also supported the above findings. Overall, this results shows that Vanillylacetone has a good antioxidant and therapeutic properties which can help in preventing the chemically (CCl4) induced hepatotoxicity.

Thymoquinone Ameliorates Doxorubicin-Induced Cardiotoxicity in Swiss Albino Mice by Modulating Oxidative Damage and Cellular Inflammation.

Thymoquinone is the active constituent of Nigella sativa, having antioxidant and anti-inflammatory actions. In present study, we have analyzed the effects of thymoquinone on doxorubicin (DOX) induced cardiotoxicity in mice. In this experiment, thirty mice (25-35 gm) were divided into five groups (Groups A, B, C, D, and E) each containing six animals. Normal saline was given to a control group (Group A) for 14 days. Cardiotoxicity was induced by DOX (15 mg/kg, i.p.) in Group B, once on the 13th day of the study, and Groups C and D also received DOX (15 mg/kg, i.p.) and were then treated with thymoquinone (10 and 20 mg/kg, b/w, p.o.), respectively, for 14 days. Group E was given only thymoquione (20 mg/kg b/w, p.o.). A blood serum marker (AST, ALT, CK-MB, and LDH) and oxidative stress marker (LPO, GSH, CAT, SOD, GPx, GR, and GST) were evaluated. Results revealed that serum enzyme marker like aspartate aminotransferase (AST), creatinine kinase-MB (CKMB), and lactate dehydrogenase (LDH) were significantly elevated in Group B as compare to Group A. Similarly, the oxidative stress marker lipid peroxidation (LPO) was also elevated in Group B while the antioxidant enzyme catalase, superoxide dismutase, glutathione peroxidase, glutathione reductase, and glutathione S-transferase (CAT, SOD, GPx, GR, and GST) were also decreased in Group B. The treatment with thymoquinone 10 and 20 mg/kg resulted in a significant decrease in the serum marker and increase in the antioxidant enzymes. In this study, we have found that thymoquinone prevented DOX-induced cardiotoxicity by accelerating heart antioxidant defense mechanisms and down regulating the LPO levels towards normalcy in Groups C and D. The effect of doxorubicin increases the inflammatory cytokine (IL2) in Group B as compared to Group A, and it overcomes by the thymoquinone in Groups C and D. Thus, thymoquinone may have utility as a potential drug for cardiomyopathy.

Potency of nano-antibacterial formulation from Sargassum binderi against selected human pathogenic bacteria

Seaweeds constitutes an abundant marine reserve that can be harnessed as source of new pharmaceutical agents. Sargassum binderi Sonder ex J. Agardh is a brown seaweed that is predominantly available from December to March in the Red Sea, Jazan, Kingdom of Saudi Arabia (KSA). In this study, three extracts were isolated using three different techniques, and were subjected to antibacterial assay. The petroleum ether extract of Sargassum binderi was more effective against selected human pathogenic bacteria than the other extracts. Therefore, further studies were focused on developing oleic acid vesicles entrapped with the petroleum ether extract of Sargassum binderi, with the aim of enhancing its penetration property. Oleic acid vesicles were prepared by entrapping petroleum ether extract of Sargassum binderi using film hydration technique. The formulated vesicles were in nanoscale, and so were termed phyto-nanovesicles (PNVs). The spectrum of antibacterial activity of PNVs showed that it is a promising formulation against S. aureus, S. pyogenes, B. subtilis, E. coli, K. pneumoniae and P. aeruginosa. The microbial sensitivities to the PNVs was in the order E.coli > B. subtilis > S. aureus > S. pyogenes > K. pneumoniae > P. aeruginosa. Thus, the PNV formulation possesses promising and effective antimicrobial potential against human pathogenic bacteria