Thrombosis is one of the major cardiovascular diseases that occur when the platelets become activated inappropriately within the circulation under pathological conditions. Currently, anti-platelet drugs such as aspirin and clopidogrel are used to treat these conditions. However, these drugs are associated with serious side effects, especially bleeding. Therefore, development of improved therapeutics to treat thrombotic diseases is an important strategy to combat cardiovascular diseases. In this study, we investigate the effects of 1,8 cineole in the modulation of platelet function, thrombosis and haemostasis.

Methods: To determine the modulatory effects of 1,8 cineole in platelet activation, aggregation assays were performed using platelet-rich plasma by optical aggregometry in the presence or absence of different concentrations (6.2, 12.5, 25, 50 and 100 μM) of 1,8 cineole. Platelets were pre-treated with 1,8 cineole for 5 minutes prior to stimulation with various agonists such as CRP-XL, collagen, thrombin and ADP. Furthermore, the level of fibrinogen binding (as a marker for integrin aIIbb3) and P-selectin exposure (as a marker for a-granule secretion) on the platelet surface were measured by flow cytometry using human platelets.

Results: Our findings demonstrate the inhibitory activities of 1,8 cineole on human platelets.  Indeed, 1,8 cineole affected platelet aggregation in a dose-dependent manner when activated by various agonists. Similarly, the level of fibrinogen binding and P-selectin exposure upon stimulation with CRP-XL was significantly inhibited by 1,8 cineole. These results suggest that 1, 8 cineole may have modulatory effects on platelet function and thereby thrombosis, and therefore this might be useful in controlling thrombotic diseases.

Platelets, small circulating blood cells play indispensable roles in the regulation of haemostasis via blood clotting. However, their unwarranted activation in blood vessels leads to thrombosis, which obstructs blood flow to major organs such as heart and brain resulting in heart attack and stroke, respectively. Hence, platelets act as a promising target to treat/ prevent cardiovascular diseases (primarily thrombotic diseases). Direct relationships between cardiovascular health and dietary flavonoids have been long established. Nevertheless, numerous challenges are associated with the use of dietary components in biological systems for the prevention and treatment of diseases due to their poor absorption in the intestine, the reduced bioavailability in blood stream, inability to readily cross the cell membranes and their modest stability in biological systems. Here, we report the design, synthesis, chemical characterisation and biological evaluation of Ruthenium complexes of chrysin (a natural flavonoid), and its synthesised thio-flavone and their Ruthenium derivatives for the modulation of platelet function and thrombus formation. Our results demonstrate that Ruthenium-based synthetic chrysin derivatives exert enhanced inhibitory effects in platelets under physiological conditions. Furthermore, we explored the structure-activity relationships of flavonoids with platelets through a systematic analysis of structurally-related flavones with the view of advancing the current knowledge on structure-activity relationships of flavonoids. For this, we investigated a panel of 16 synthetic flavones containing hydroxy or methoxy groups at C-7,8 positions on the A-ring with a phenyl group or its bioisosteres as the B-ring along with their thio-analogues possessing a sulfur molecule at the 4th carbon position in the C-ring for their anti-platelet efficacies. The results demonstrate that the hydroxyl groups in flavonoids are important for optimum platelet inhibitory activities. In addition, the 4-C=O and B ring phenyl groups are less critical for the anti-platelet activity of these flavonoids. Overall, our results demonstrate that Ru-thio-chrysin could serve as a promising template for the development of novel anti-thrombotic agents and this structure-activity relationship for flavonoids on platelet function may guide the design, optimisation and development of flavonoid scaffolds as anti-platelet agents.

Statement of the Problem: Because of increasing side effects of synthetic medicines, the scientific research is being diverted toward the discovery of some better alternatives in pharmaceutical preparations from natural sources. The aim of current research work was to study the effect of Mucuna pruriens (MP) seed extract on liver enzymes, serum proteins and reproducive hormone levels in male albino rats.

Methodology & Theoretical Orientation: Seeds extract of M. pruriens was prepared in methanolic solvent and the potential effect was evaluated by administering into male albino rats for 42 days. The rats were divided into six groups of four rats in each group; as control (normal saline), Carbon tetrachloride injected (0.5 mL 20% CCl₄ /Kg bw twice a week), Testosterone treated (0.5 mL 20% CCl₄ + 2.5 mg testoverone/Kg bw twice a week) and MP-treated A, B & C (0.5 mL 20% CCl₄ twice a week + 50, 100 & 200 mg extract/Kg bw daily, respectively) groups. Body, testis and relative testis weight of male rats were recorded. Liver enzymes and serum proteins were measured by photometric method using commercially available assay kits. Serum testosterone was determined by ELISA kit method. Histological changes in liver and testicular sections were observed through microscopy by H & E staining.

Findings: Significant (p<0.05) increase in body, testis and relative testis weight was observed in extract treated rats compared to normal and CCl₄ intoxicated rats. Significant (p<0.05) dose dependent improvement in ALT and AST activity was observed extract treated rats while not in ALP activity compared to control and CCl₄ treated rats. Serum proteins particularly albumin concentration vary significantly (p<0.05) in extract treated rats. Significant (p<0.05) increase in serum testosterone level was also found in rats treated with testosterone and Mucuna seeds extract. Serious damage to liver cells (hepatocytes) and testicular histology in the CCl₄ intoxicated rats was observed, while an improvement was found in testosterone and extract treated rats.   

Conclusion & Significance: The study concluded that MP seeds extract have therapeutic potential to revert the toxic effect of CCl₄ bringing the biochemical and histological alterations toward normal. MP seeds extract may provide potential therapeutic agents to be used as medicines for various ailments.    

Background: Obsessive-compulsive disorder (OCD) is a common mental illness which usually starts in the second decade of life. Onset after age of 50 is relatively rare and may be more likely to have an organic aetiology.

Method: To report a case presents symptoms of OCD in a previously healthy 66 year-old man, who was found to have a dilated perivascular space in the left lentiform nucleus.

Finding: A 66-year-old Malay gentleman who presented with repetitive, intrusive and distressing thoughts that ‘God is evil’ and compulsions of excessively praying or talking to himself to counteract the thoughts for two months. He does not have any past psychiatric history or family history of mental illness; he has never taken any psychiatric medications before and he does not abuse alcohol or illicit drugs. He was diagnosed with OCD according to DSM-V criteria. Physical and neurological examinations were unremarkable. A brain computed tomography (CT) scan revealed a non-specific hypodense focus in left lentiform nucleus, and the configuration suggested dilated perivascular space and chronic in nature. He was treated with fluoxetine and the medication was titrated up to 80 mg a day. He achieved a partial remission of his OCD after 3 months of treatment. But because of his religious belief, it is hard to involve him in psychological treatments as he finds it distressing even to elaborate on his obsessive thoughts.

Conclusion: This report adds to a body of evidence suggesting organic brain lesions can induce obsessive-compulsive symptomatology and shares our experience in managing such a case. However, more large scale research is needed to study the pathology and treatment of brain lesion induced OCD.