Hesperidin possesses myriads of pharmacological benefits, including anti-inflammatory and antioxidant properties. Herein, we speculated that the described pharmacological benefits of hesperidin might ...be due to its potentiating action on SIRT1; thereby, inhibition of NOX4. We developed diabetic neuropathy in Sprague-Dawley rats by feeding them a high-fat diet (HFD) for 12 weeks. We checked the effect of hesperidin on the level of oxidative stress, inflammatory markers, NOX4, and SIRT1 by biochemical analysis, histopathology, immunoblotting, immunocytochemistry, and real-time qPCR in HFD-fed rats and Palmitate encountered rat glial C6 cells. Hesperidin administration improved mechanical, thermal allodynia, and glucose homeostasis. There was a decrease in oxidative stress and inflammation and an enhanced level of antioxidant enzymes. Besides, the expression of NOX4 was down-regulated, while SIRT1 was upregulated. Interestingly, hesperidin treatment protected them from oxidative and inflammatory damage by upregulating SIRT1 and inhibiting NOX4 expression.
•Hesperidin improves mechanical and thermal sensitivity in diabetic neuropathic rats.•Hesperidin ameliorates hyperglycemia and hyperinsulinemia.•Hesperidin treatment protected from oxidative stress damage by inhibiting NADPH oxidase 4.•Hesperidin safeguards from NOX4 instigated inflammation by upregulating SIRT1 expression.
Endothelial dysfunction is related to the reduced bioavailability of nitric oxide (NO) and plays a significant role in developing hypertension. The intake of a diet rich in antioxidants decreases the ...threat of hypertension. Cissus quadrangularis possesses antioxidant, anti-inflammatory, and hypocholesterolemic activities. However, to date, no studies have been performed to explore this plant's antihypertensive and vasorelaxant activity. Herein, we investigated the chronic effect of C. quadrangularis on blood pressure as well as vascular function in hypertensive rats.
Male spontaneously hypertensive rats (SHR) were randomly divided into two groups. Normotensive Wistar rats were taken as the control group. The treatment was done using ethanolic extract of C. quadrangularis (EECQ) at a dose of 200 mg/kg.
The administration of EECQ for six weeks reduced the systolic blood pressure, mean arterial blood pressure, and heart rate. It also alleviated the cardiac and renal hypertrophy indices. Supplementation of EECQ improved the endothelium-dependent aortic vasodilation induced by acetylcholine. It restored the NO level and endothelial NO synthase expression in the aorta. Subsequently, the extract alleviates the oxidative stress and inflammatory markers in SHR rats.
Thus, in the present study, the chronic treatment of EECQ to genetically hypertensive rats improved endothelium-dependent relaxation in addition to its antihypertensive effect by eNOS activation and inhibition of ROS production, inflammation.
Breast cancer, one of the most significant tumors among all cancer cells, still has deficiencies for effective treatment. Moreover, substitute treatments employing natural products as bioactive ...metabolites has been seriously considered. The source of bioactive metabolites are not only the most numerous but also represent the richest source. A unique source is from the oceans or marine species which demonstrated intriguing chemical and biological diversity which represents an astonishing reserve for discovering novel anticancer drugs. Notably, marine sponges produce the largest amount of diverse bioactive peptides, alkaloids, terpenoids, polyketides along with many secondary metabolites whose potential is mostly therapeutic. In this review, our main focus is on the marine derived secondary metabolites which demonstrated cytotoxic effects towards numerous breast cancer cells and have been isolated from the marine sources such as marine sponges, cyanobacteria, fungi, algae, tunicates, actinomycetes, ascidians, and other sources of marine organisms.
Health promoting benefits of pongamol: An overview Jahan, Shamima; Mahmud, Md. Hasan; Khan, Zidan ...
Biomedicine & pharmacotherapy,
October 2021, 2021-Oct, 2021-10-00, 20211001, 2021-10-01, Letnik:
142
Journal Article
Recenzirano
Odprti dostop
Plant-derived chemicals are a source of novel chemotherapeutic agents. Throughout the human civilization, these novel chemicals have led to the discovery of new pharmacological active agents. ...Research on herbal medicine is of great importance, as most of the active agents used for treating numerous diseases are from natural sources, while other agents are either semisynthetic or synthetic. Pongamol, a flavonoid, which is the main constituent of Pongamia pinnata, is one such active agents, which exhibits diverse pharmacological activities. Various in vivo and in vitro studies revealed that pongamol is a potentially active agent, as it exerts anticancer, anti-inflammatory, antioxidant, antimicrobial, and anti-diabetic activities. Accordingly, the aim of the present review was to give an up-to-date overview on the chemistry, isolation, bioavailability, pharmacological activity, and health benefits of pongamol. This review focuses on the medicinal and health promoting activities of pongamol, along with possible mechanisms of action. For this purpose, this review summarizes the most recent literature pertaining to pongamol as a therapeutic agent against several diseases. In addition, the review covers information related to the toxicological assessment and safety of this phytochemical, and highlights the medicinal and folk values of this compound against various diseases and ailments.
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•Pongamol, a flavonoid found in Pongamia pinnata, exhibits numerous pharmacological properties.•Pongamol exerts anticancer, anti-inflammatory, and anti-diabetic activities.•The current review highlights the medicinal and health promoting activities of pongamol.
Studies of the ethyl acetate extract bark extract of Olea ferruginea led to the isolation of one new compound Ferruginan A (1) in addition to two known compounds, Ferruginan (2) and cycloolivil (3). ...Structures of the isolated compounds were confirmed by mass spectrometry (MS) and NMR spectral data. The ethyl acetate fraction and compounds (1–3) were evaluated against breast cancer cell line (MCF-7) and as antioxidants using the free radical scavenging assay. Results revealed that compound 2 exhibits significant antioxidant activity with an IC50 value of 21.74 μg/mL. In addition, the ethyl acetate fraction showed good cytotoxic activity (79.31% inhibition at 250 μg/mL), whereas compounds 1–3 exerted mild cytotoxic activity (IC50=8.03–12.01 μg/mL) as compared to the standard (IC50=4.41 μg/mL) against MCF-7. Docking studies suggested that antioxidant activity is due to the chelation of compounds with copper present in the active site of tyrosinase. These results suggest that the extract exhibits considerable antioxidant activity, and the isolated compounds exert moderate anticancer activity.
•Cissus quadrangularis ameliorates insulin resistance and hyperlipidemia.•Cissus quadrangularis mitigates steatohepatitis and improves liver function.•Cissus quadrangularis decreases RAGE activation ...thereby down-regulates NOX4 expression.•Cissus quadrangularis mitigates ROS propagated oxidative stress and inflammation.
Cissus quadrangularis L. is commonly known as hadjod and traditionally used as a medicinal plant for the treatment of osteoporosis, dyspepsia, tumors, chronic ulcers, and hepatic diseases. Existing studies have proclaimed the proinflammatory property of NOX4 through instigating ROS and oxidative stress, which is considered to be one of the instrumental causes of steatohepatitis.
To investigate the protective effect of ethanolic extract of C. quadrangularis (EECQ) on the steatohepatitis associated with type 2 diabetes (DM) through inhibition of NOX4.
An experimental DM-induced steatohepatitis was developed by feeding a high-fat diet for 12 weeks in Sprague Dawley rats. Treatment of EECQ was given at a dose of 200 mg/kg (po), for six weeks. Glucose and insulin tolerance test was conducted. Hematoxylin and eosin and picrosirius red staining of liver sections was done. Steatosis and lobular inflammation were scored, and hepatocyte ballooning was assessed to confirm the NASH. qPCR, Immunofluorescence, and Immunoblotting determined the mRNA and protein expression of NOX4.
NASH group rats manifested features of DM, marked by aggravated glucose and insulin tolerance tests. Moreover, the DM rats exhibited the presence of steatohepatitis, characterized by elevated serum lipid content, aminotransferases, and presence of steatosis, lobular inflammation, and ballooning in the liver section. Nevertheless, EECQ treatment prevented all of these abnormalities. Besides, the level of AGEs and the expression of its receptor, RAGE was found to be increased in DM rats. Parallelly, the expression of NOX4 and the accompanying level of ROS, oxidative stress markers, and inflammatory cytokines were determined to be surged in palmitic acid exposed HepG2 cells and DM rats. However, EECQ treatment exemplified safeguards from the soared level of the aforementioned markers.
Collectively, the above findings propounded the protective effect of EECQ against steatohepatitis. Nonetheless, further studies on humans necessitate to scrutinize and reinforce its therapeutic potential so that it may be employed as a remedy for DM-induced steatohepatitis.
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Sustainable transportation systems play a key role in the socio-economic development of a country. Microscopic simulation models are becoming increasingly useful tools in designing, optimizing, and ...evaluating the sustainability of transportation systems and concerned management strategies. VISSIM, a microscopic traffic simulation software, has gained rapid recognition in the field of traffic simulation. However, default values for different input parameters used during simulation need to be tested to ensure a realistic replication for local traffic conditions. This paper attempts to model driving behavior parameters using the microscopic simulation software VISSIM through a case study in the Khobar-Dammam metropolitan areas in Saudi Arabia. VISSIM default values for different sensitive parameters such as lane change distances, additive and multiplicative parts of desired safety distances, the number of preceding vehicles spotted, amber signal decisions, and minimum headway were identified to be most sensitive and significant parameters to be calibrated to precisely replicate field conditions. The simulation results using default values produced higher link speed, larger queue length, and shorter travel times than those observed in the field. However, measures of effectiveness (MOEs) obtained from calibrated models over desired simulation runs were comparable to those obtained from field surveys. All compared MOEs used to validate the model matched within a range of 5–10% to the field-observed values.
Objective: To study association between spontaneous bacterial peritonitis and clinical symptoms in liver cirrhosis.
Study Design: cross-sectional study.
Place and Duration of Study: Combined Military ...Hospital Kharian, from Jul 2019 to Apr 2020.
Methodology: A total of 122 patients of liver cirrhosis (irrespective of aetiology), presented with various clinical symptoms such as fever, pain abdomen and hepatic encephalopathy were randomly selected. Patients between 18-80 years of age, were included in the study. Asymptomatic patients, with ascites other than liver cirrhosis were excluded. Spontaneous Bacterial Peritonitis was defined as positive ascitic fluid culture and/or ascitic polymorphonuclear leukocyte ≥250 cells/mm3 in ascitic fluid.
Results: Of the 122 randomly selected patients, the mean age was 56.5 ± 20.2 years. Forty-Five (46.8%) were male and 67 (54.2%) patients were female. Chronic Hepatitis C was the commonest cause of liver cirrhosis (92%). The frequency of spontaneous bacterial peritonitis was 37.7%. Majority, (83%) of the culture positive ascitic isolate was Gram negative bacilli and E.coli (72%) being the commonest organism isolated. Severe ascites, high International Normalized Ratio (INR), hepatic encephalopathy, fever, low ascetic fluid protein count, high serum bilirubin and creatinine were considered to be independent predictor of Spontaneous Bacterial Peritonitis.
Conclusion: Clinical symptoms of fever, hepatic encephalopathy, severe ascites, International Normalized ratio high and deranged renal profile was highly suggestive of Spontaneous Bacterial Peritonitis in cirrhotic patients.
S009-0629 methyl-8-(methylthio)-2-phenyl-6-p-tolyl-4,5-dihydro-2H-benzoeindazole-9-carboxylate is a novel antidiabetic agent with PTP1B inhibitory activity. In this study, we have investigated the in ...vitro metabolic stability, plasma protein binding, blood partitioning, and oral pharmacokinetic study of S009-0629 in rats. The plasma protein binding, blood partitioning, and metabolic stability were determined by HPLC method. The oral pharmacokinetic study was analyzed by liquid chromatography coupled mass spectrometry (LC-MS/MS) method. The plasma protein binding of S009-0629 using modified charcoal adsorption method at 5 and 10 µg/mL was 80.58 ± 1.04% and 81.95 ± 1.15%, respectively. The K
of S009-0629 was independent of concentration and time. The in-vitro half-life of S009-0629 at 5 and 10 µM using rat liver microsomes was determined as 273 ± 24.46 and 281.67 ± 26.53 min, respectively. After oral administration, S009-0629 exhibited C
55.51 ± 1.18 ng/mL was observed at 18 hr (t
). S009-0629 was found to have the large apparent volume of distribution (1,894.93 ± 363.67 L/kg). Oral in-vivo t
of S009-0629 was found to be 41.23 ± 5.96 hr. A rapid and highly sensitive LC-MS/MS method was validated for S009-0629 in rat plasma. S009-0629 has high plasma protein binding and low hepatic extraction. S009-0629 has no affinity with human P-gp and BCRP in ATPase assay. After oral dosing, S009-0629 has slow absorption and elimination in rats.
•LC-MS/MS method has been developed and validated for quantification of analytes.•LLOQ of all analytes was 10 ng/mL except for OMEP (1 ng/mL) and r2 > 0.994.•ACET, THEO, OMEP, MTX, MP administered ...either alone or in combination with EECO.•Dose adjustment would be required when ACET, MP, MTX are co-administered with EECO.•EECO had inhibitory effects on CYP1A2, CYP2C9 and CYP3A4.
Traditionally Cassia occidentalis L. extract is used for the treatment of several diseases including fever, bone diseases, fracture, kidney and digestive diseases. Ethanolic extract of Cassia occidentalis L. (EECO) is being developed as a phytopharmaceutical for corticosteroid-induced osteoporosis.
This study was aimed to investigate the effect of EECO on the pharmacokinetics of acetaminophen (ACET), theophylline (THEO), omeprazole (OMEP), methotrexate (MTX), and methylprednisolone (MP).
Interaction studies were performed in Sprague Dawley (SD) rats. ACET (100 mg/kg), THEO (25 mg/kg), OMEP (40 mg/kg), MTX (5 mg/kg), or MP (5 mg/kg) was administered with and without EECO (250 mg/kg) separately.
The LLOQ of all analytes was 10 ng/mL except for OMEP (1 ng/mL) and r2 > 0.994. The intra-day and inter-day RSD (%) were ≤12.13 and accuracy (%) was between 89.19 and 112.67 at four QC levels. Our results suggested that EECO caused interaction when coadministered with ACET, MTX and MP. No changes were found in the bioavailability of THEO and OMEP. EECO had inhibitory effects on CYP1A2, CYP2C9 and CYP3A4.
Based on these results, dose adjustment may be required when ACET, MP and MTX are coadministered with EECO. These results would be useful for phase 1 clinical trial of EECO.
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