In vivo assessment of black seed oil single dose on prednisolone pharmacokinetics.

OBJECTIVES: To investigate the effect of blackseed oil (BSO) single dose on prednisolone pharmacokinetics via p-gp inhibition. METHODS: Three groups of rats (n = 5) were orally administered the vehicle, verapamil (50 mg/kg) or BSO (5 ml/kg) 15 min prior to prednisolone (5 mg/kg) administration. Blood samples were collected over 24 h and quantified. Non-compartmental analysis was employed to calculate maximum plasma concentration (Cmax), area under the curve (AUC0-last), time to reach Cmax (Tmax), apparent clearance (CL/F), and half-life (t1/2). Statistical significance was considered at p<0.05. RESULTS: Prednisolone Cmax and AUC0-last decreased by 65% and 25% in the BSO group compared to the negative control (P < .0001, .0029, respectively) while they increased by 1.75-folds and 8-folds in verapamil group (P < .0001). Tmax was achieved at 0.16, 0.5, and 0.25 h in the negative control, verapamil, and BSO-treated groups, respectively. CL/F in the treatment group was 1.3-fold and 10-fold higher compared to the negative and positive control, respectively, whereas the t1/2 remained comparable. CONCLUSION: Administration of BSO decreased prednisolone Cmax and AUC0-last in rats indicating that there is a herb-drug interaction; however, p-gp inhibition cannot be concluded. Patients relying on folk medicine in chronic illnesses treatment might need to avoid combining BSO with prednisolone.

The perspective of pharmacist on pharmacovigilance and adverse drug reaction reporting in Asir region, Saudi Arabia.

OBJECTIVE: Adverse drug reactions (ADRs) are widespread worldwide, and their intervention is critical to patient safety and healthcare quality. Pharmacists are essential in monitoring and reporting ADRs, directly influencing patient care. This study aimed to examine the prevalence of ADRs among pharmacists and their knowledge regarding ADRs, including the factors affecting ADR reporting. SUBJECTS AND METHODS: From September 2021 to November 2021, a cross-sectional survey among pharmacists in the Asir area of Saudi Arabia was planned. This study involved contacting 97 pharmacists using a cluster sampling method. The study's goals were met using a 25-item self-administered questionnaire. Data analysis was done using SPSS version 25 (IBM Corp., Armonk, NY, USA). RESULTS: Ninety-seven pharmacists (male 53.6% and female 46.4%) completed the survey. More than three-fourths of the participants (78.4%) know the ADR reporting system. The survey was completed by 97 pharmacists (male 53.6% and female 46.4%). More than three-quarters of the participants (78.4%) were aware of the ADR reporting system, and the majority (70.8%) were aware that it is done using an online system. Still, only 56.7% knew that the Saudi FDA is the regulatory agency collecting ADR data in Saudi Arabia. Furthermore, 73.2% cited stress in the workplace as a critical deterrent to reporting. Most respondents (76.3%) had an unfavorable attitude about reporting ADRs. CONCLUSIONS: Pharmacists understand ADR reporting, but most lack the mentality to report the incidents. As a result, comprehensive and ongoing training for pharmacists is required to raise awareness of the need for ADR reporting.

Understanding the genetic aspects of resistance to antidepressants treatment.

Major depression disorder (MDD) is an extremely prevalent disorder and is expected to be the second leading cause of disease burden by 2020 according to the World Health Organisation (WHO). Moreover, this disease burden is predicted to rise in the next 20 years. Antidepressant medications are vital in the therapy of major depression. However, approximately 30-60% of patients treated with current antidepressant drugs fail to attain remission of depressive symptoms leading to drug resistance. Such patients account for a disproportionately great burden of disease, as supported by cost, augmented disability, and suicidal incidents. Antidepressants resistance remains to challenge mental health care professionals, and more relevant research relating newer medications is necessitated to enhance the quality of life of patients with depression. Enhancement in response rates continues the major challenge in antidepressant research, thus a wealth of potentials still exists concerning the antidepressant resistance for the management of major depression. However, the mechanisms causing resistance to antidepressant treatment remain unknown. Hence, clinical and basic research in understanding the fundamental mechanism of antidepressant resistance should remain a key priority. One potential source accounting for these differences in treatment outcome is genetic variations. The pharmacological mechanisms behind antidepressant response are only partly known but genetic factors play a significant role. Future research of risk factors should assist to advance the understanding of the mechanisms underlying drug resistance in mood disorders and contribute to progress their therapeutic management. Thus, psychiatrists could rely on more effective approaches to treat depressive episodes, reducing the incidence of further drug resistance. This review critically summarises the author's view on many aspects of treatment resistance, specific genetic biomarkers, potential strategies and clinical relevance from both clinical and preclinical studies in drug resistance to antidepressant therapies. Finally, this will allow us to suggest possible recommendations and innovative treatment strategies to improve therapeutic outcomes in managing antidepressant resistance.

Investigation on antimicrobial activity of root extracts of Thespesia populnea Linn.

Many medicinal plants have been used for centuries in daily life to treat microbial diseases all over the world. In this study, the in vitro antibacterial activity of aqueous and ethanol root extracts of Thespesia populnea Linn were investigated. Antimicrobial properties of T. populnea Linn was evaluated against five pathogenic bacteria and two fungi. Disc diffusion method and minimum inhibitory concentration (MIC) were determined by broth serial dilution method. The ciprofloxacin (5 µg/ml) and flucanozole (100 units/disc) were used as positive controls for bacteria and fungi respectively. Different concentrations (50, 100, 150 µg/ml) of ethanolic and aqueous root extracts of T. populnea were checked for the dose dependent antibacterial activity. Thespesia populnea showed broad spectrum antimicrobial activity against gram positive and gram negative bacteria and maximum inhibition by ethanolic extract was observed at higher dose (250 µg/ml) as 27±0.2mm. The MIC of the ethanol extract was 10 µg/ml for Staphylococcus aureus and 750 µg/ml for Candida albicans. The antifungal activity offered against S. aureus by the ethanolic extract is more than the aqueous extract. The results concluded that the anti-microbial activity of T. populnea was dose dependent. As the concentration increased the inhibition zone also increased. Flavonoids and tannins present in the extracts may be responsible for the antimicrobial activity.

Modulatory effect of polyphenolic extracts of Ichnocarpus frutescens on oxidative stress in rats with experimentally induced diabetes.

BACKGROUND & OBJECTIVES: The role of oxidative stress in the development of diabetes mellitus and its vascular complications are extensively studied. Hyperglycaemia causes oxidative damage by generation of reactive oxygen species and results in the development of complications. The present study was undertaken with the objective of exploring the anti-hyperglycaemic potential of polyphenolic enriched extract of Ichnocarpus frutescens in streptozotocin induced (n-STZ) neonatal diabetic rats (pups) for six weeks and to study oxidative stress and antioxidant status. METHODS: Two days old pups were rendered diabetic by single injection of streptozotocin (90 mg/kg body wt, ip). At the end of the treatment period, the level of blood glucose, serum biochemical markers, serum lipid levels and liver malondialdehyde, tissue antioxidant levels were measured. RESULTS: A marked rise was observed in the levels of fasting blood glucose (230.33 mg/dl), lipid profiles, lipid peroxidative products and a significant decrease in tissue antioxidants (superoxide dismuatase, catalase and reduced glutathione) and serum high density lipoprotein cholesterol levels in STZ treated rats. Oral administration of polyphenolic extract (150 and 300 mg/kg body wt, po) decreased fasting blood glucose levels (187.66 and 170.50 mg/dl, respectively) of STZ-treated diabetic rats significantly (P<0.01), when compared with control rats. In addition, the polyphenolic extract showed favourable effect (P<0.01) on the reduced tissues antioxidants level, liver glycogen level, high density lipoprotein level, with significant (P<0.01) reduction of elevated lipid peroxidation products. Histopathological study of the pancreas showed the protective role of polyphenolic extract. INTERPRETATION & CONCLUSIONS: Our study showed the antioxidant of effect polyphenolic extract of I. frutescens in STZ induced experimental diabetes. The results also suggested that this polyphenolic rich extract could be potentially useful for hyperglycaemia treatment to correct the diabetic state.

In vitro anticholinergic and antihistaminic activities of Acorus calamus Linn. leaves extracts.

The present investigation was aimed at determining the effects of hexane, acetone, methanol and aqueous extracts of Acorus calamus leaves (ACHE, ACAE, ACME and ACAQE) on cholinergic and histaminic system using isolated frog rectus abdominis muscle and guinea pig ileum. A dose dependent potentiation of Ach response (anticholinesterase like effect) was found with ACAE and ACME at 0.25, 0.5, 0.75 and 1 mg/ml, but at higher dose of ACAE, ACME, ACAQE and ACHE (5, 20 mg/ml) inhibit the Ach response (antinicotinic effect). These results revealed biphasic effect of Acorus calamus leaves extracts on acetylcholine induced contractile response in isolated frog rectus abdominis muscle preparation (i.e. potentiation effect at lower dose and inhibitory effect at higher dose). Studies on isolated guinea pig ileum demonstrated antihistaminic effect in a dose dependent manner (100-1000 µg/ml) with ACAE, ACME and ACAQE. In addition, the dose dependent inhibition of Ach response (antimuscarinic effect) was observed with ACAE and ACME. In conclusion, Acorus calamus leaves extracts exerts antinicotinic, anticholinesterase like activities in isolated frog rectus abdominis muscle and antihistaminic, antimuscarinic effect in guinea pig ileum. It has been suggested that these observed activities can be further studied for therapeutic potential of Acorus calamus leaves in the treatment of cognitive disorders and asthma.

Effect of Biophytum sensitivum on streptozotocin and nicotinamide-induced diabetic rats.

OBJECTIVE: To investigate the effect of aqueous solution of Biophytum sensitivum leaf extract (BSEt) on normal and streptozotocin (STZ)-nicotinamide-induced diabetic rats. METHODS: Diabetes was induced in adult male Wistar rats by the administration of STZ-nicotinamide (40, 110 mg/kg b.w., respectively) intraperitoneally. BSEt (200 mg/kg) was administered to diabetic rats for 28 days. The effect of extract on blood glucose, plasma insulin, total haemoglobin, glycosylated haemoglobin, liver glycogen and carbohydrate metabolism regulating enzymes of liver was studied in diabetic rats. RESULTS: BSEt significantly reduced the blood glucose and glycosylated haemoglobin levels and significantly increased the total haemoglobin, plasma insulin and liver glycogen levels in diabetic rats. It also increased the hexokinase activity and decreased glucose-6-phosphatase, fructose-1, 6-bisphosphatase activities in diabetic rats. CONCLUSIONS: The results of our study suggest that BSEt possesses a promising effect on STZ-nicotinamide-induced diabetes.

Antioxidant activity of polyphenolic extracts of Ichnocarpus frutescens.

In the present study antioxidant activities by (1,1-diphenyl-2-picrylhydrazyl radical (DPPH), hydrogen peroxide, hydroxyl radical inhibition, hemolysis by hydrogen peroxide assay, reducing power and total antioxidant activities of polyphenolic extract of Ichnocarpus frutescens leaves were investigated. The flavonoids and total polyphenolic contents of the extract were also determined using standard methods. Phytochemical analyses revealed the presence of flavonoids, polyphenols, anthocyanins and simple phenolic acids. The results of antioxidant activities of polyphenol extract obtained by different in vitro methods were varied depending on the method used. Nevertheless, polyphenol extract showed significant inhibitory activities in all in vitro reactive oxygen species scavenging, might be attributed due to the high level of polyphenolic compound. Also, these various antioxidant activities were compared to α-tocopherol and l-ascorbic acid as reference antioxidant compounds. These findings provide evidence that the polyphenolic extract of I. frutescens is a natural source of antioxidant against oxidative damage.

Polyphenolic extract of Ichnocarpus frutescens attenuates diabetic complications in streptozotocin-treated diabetic rats.

Diabetic nephropathy is one of the major complications of diabetes. Oxidative stress is implicated as an important mechanism by which diabetes causes nephropathy. The aim of the study was to examine the involvement of oxidative stress in the progression of nephropathy in STZ diabetic animals and to evaluate the potential of polyphenolic extract (PPE) in the treatment of diabetes mellitus. In this study, we examined whether prolonged oral administration of polyphenolic extract of Ichnocarpus frutescens could prevent the progress or improve the outcome of diabetic nephropathy induced by oxidative stress in STZ diabetic rats. Intraperitoneal glucose tolerance test (IPGTT) revealed a significant decrease in blood glucose levels at 180 min after glucose loading in Wistar albino rats fed with PPE. During the eight weeks of experimental period, diabetic rats exhibited wide range of symptoms, including loss of body weight, hyperglycemia, polyuria, proteinuria, renal enlargement, and total renal dysfunction. A significant increase in TBARS level was observed in diabetic kidney, which was accompanied by a significant decrease in enzymatic and non-enzymatic antioxidant levels. After eight weeks, PPE-treated groups showed a lower level of blood glucose compared with non-treated STZ diabetic rats. The increases in urinary albumin and protein after eight weeks of treatment were significantly inhibited by prolonged treatment with PPE. In addition, PPE attenuates the adverse effects on hepatic biomarkers. We found that PPE can effectively protect against aldose reductase activity and protein damage (albumin glycation), and showed that its action was mainly due to enriched polyphenolic content. Our results also showed that treatment with PPE normalized the increase in hyperalgesia (i.e., the response to thermal stimuli) associated with the induction of diabetes by STZ. PPE administration in diabetic rats clearly ameliorated diabetic complications, suggesting not only a natural antioxidant but also supportive therapy for the treatment of type II diabetes.

Antitumor activity of polyphenolic extract of Ichnocarpus frutescens.

AIM: Phytochemical and dietary antioxidants are known to decrease the risk of many diseases such as cancer and cardiovascular diseases. In this study polyphenolic extract (PPE) of leaves of Ichnocarpus frutescens was evaluated for antitumor activity in vivo. MATERIALS AND METHODS: Murine Ehrlich ascites carcinoma (EAC) model was used to assess PPE antitumor activity in vivo. PPE cytotoxicity was determined in vitro in U-937 monocytoid leukemia and K-562 erythroleukemia cell lines. PPE also have been assessed for the free radical scavenging activity against superoxide and nitric oxide radicals. Acute oral toxicity was performed by acute toxic classic method. The total phenolics content was quantified by the Folin-Ciocalteu method. RESULTS: Results of in vivo study showed a significant decrease in tumor volume, viable tumor cell count and a significant increase of life span in the PPE treated group compared to untreated one: the life span of PPE treated animals increased by 53.41% (50 mg PPE/kg) and 73.95% (100 mg PPE/kg). PPE (5, 10 and 20 microg/mL) effectively inhibits in vitro proliferation of U-937 and K-562 cell lines. PPE exhibited pronounced radical scavenging activity with an inhibitory concentration (IC(50)) value of 167.46 microg/mL and 158.52 microg/mL against superoxide and nitric oxide radicals, respectively. CONCLUSION: PPE of Ichnocarpus frutescens possesses strong free radical scavenging activity and anti-tumor activity in vitro and in vivo.

BRONCHODILATOR EFFECT OF ALCOHOLIC EXTRACT OF Euphorbia hirta linn.

The bronchodilator effect of alcoholic extract of Euphorbia hirta Linn was evaluated at different doses (50,100 and 200mg/kg,p.o), using histamine aerosol test model. A dose dependent bronchodilator effect was observed in E. hirta pretreated animals. The extract of E. hirta at a dose of 200mg/kg was found to be more effective in histamine induced broncho constriction and a significant (p<0.001) effect was observed.