A Review on Therapeutic Potential of Natural Phytocompounds for Stroke.

Stroke is a serious condition that results from an occlusion of blood vessels that leads to brain damage. Globally, it is the second highest cause of death, and deaths from strokes are higher in older people than in the young. There is a higher rate of cases in urban areas compared to rural due to lifestyle, food, and pollution. There is no effective single medicine for the treatment of stroke due to the multiple causes of strokes. Thrombolytic agents, such as alteplase, are the main treatment for thrombolysis, while multiple types of surgeries, such ascraniotomy, thrombectomy, carotid endarterectomy, and hydrocephalus, can be performed for various forms of stroke. In this review, we discuss some promising phytocompounds, such as flavone C-glycoside (apigenin-8-C-ß-D-glucopyranoside), eriodictyol, rosamirinic acid, 6″-O-succinylapigenin, and allicin, that show effectiveness against stroke. Future study paths are given, as well as suggestions for expanding the use of medicinal plants and their formulations for stroke prevention.

Investigation into the Antihypertensive Effects of Diosmetin and Its Underlying Vascular Mechanisms Using Rat Model.

OBJECTIVE: Diosmetin is a flavonoid that is found in many important medicinal plants that have antihypertensive therapeutic potential. Diosmetin has been shown to have antiplatelet, anti-inflammatory and antioxidant properties, which suggests that it could be a potential candidate for use in antihypertensive therapy. METHODS: In vivo and in vitro methods were used for our investigation into the antihypertensive effects of diosmetin. RESULTS: Diosmetin significantly decreased the mean arterial pressure (MAP). The effects of diosmetin on the MAP and heart rate were more pronounced in hypertensive rats. To explore the involvement of the muscarinic receptors-linked NO pathway, Nω-nitro-L-arginine methyl ester (L-NAME) and atropine were pre-administered in vivo. The pretreatment with L-NAME did not significantly change the effects of diosmetin on the MAP by excluding the involvement of NO. Unlike L-NAME, the atropine pretreatment reduced the effects of diosmetin on the MAP, which demonstrated the role of the muscarinic receptors. In the in vitro study, diosmetin at lower concentrations produced endothelium-dependent and -independent (at higher concentrations) vasorelaxation, which was attenuated significantly by the presence of atropine and indomethacin but not L-NAME. Diosmetin was also tested for high K+-induced contractions. Diosmetin induced significant relaxation (similar to verapamil), which indicated its Ca2+ antagonistic effects. This was further confirmed by diosmetin shifting the CaCl2 CRCs toward the right due to its suppression of the maximum response. Diosmetin also suppressed phenylephrine peak formation, which indicated its antagonist effects on the release of Ca2+. Moreover, BaCl2 significantly inhibited the effects of diosmetin, followed by 4-AP and TEA, which suggested that the K+ channels had a role as well. CONCLUSIONS: The obtained data showed the Ca2+ channel antagonism, potassium channel activation and antimuscarinic receptor-linked vasodilatory effects of diosmetin, which demonstrated its antihypertensive potential.

Spore exines increase vitamin D clinical bioavailability by mucoadhesion and bile triggered release.

Sporopollenin exine capsules (SpECs) are microcapsules derived from the outer shells (exines) of plant spore and pollen grains. This work reports the first clinical study on healthy volunteers to show enhanced bioavailability of vitamin D encapsulated in SpECs from Lycopodium clavatum L. spore grains vs vitamin D alone, and the first evidence (in vitro, ex vivo and in vivo) of mechanisms to account for the enhancement and release of the active in the small intestine. Evidence for mucoadhesion of the SpECs contributing to the mechanism of the enhancement is based on: (i) release profile over time of vitamin D in a double blind cross-over human study showing significant release in the small intestine; (ii) in vivo particle counting data in rat showing preferred retention of SpECs vs synthetic beads; (iii) ex vivo99mTc labelling and counting data using rat small intestine sections showing preferred retention of SpECs vs synthetic beads; (iv) in vitro mucoadhesion data. Triggered release by bile in the small intestine was shown in vitro using solid state NMR and HPLC.

Noscapine hydrochloride (benzyl-isoquinoline alkaloid) effectively prevents protein denaturation through reduction of IL-6, NF-kB, COX-2, Prostaglandin-E2 in rheumatic rats.

Noscapine hydrochloride (benzyl-isoquinoline antitussive alkaloid) is an opium derivative and generally used as a cough suppressant. Numerous studies on noscapine hydrochloride have reported that it has potent anti-inflammatory activity. However, the mechanisms by which it exerts an anti-inflammatory function is not well understood. Protein denaturation is the primary step that leads to the organ destruction and permanent arthritic disability. The above-mentioned facts provided the ground to plan this study using different in-vitro and in-vivo approaches. RT-qPCR and ELISA assays were used to assess the inflammatory markers related to protein denaturation in complete adjuvant persuaded rheumatism in Sprague - Dawley rats. The results were collected as paw volume and body weight changes, arthritic scoring and serum antioxidant enzymes assays. These findings demonstrated that all doses of noscapine hydrochloride (10, 20 and 40 mg/kg) studied in this study, significantly (p < 0.001) decreased the protein denaturation by preventing the increase in levels of interleukin-1ß (IL-1ß), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), nuclear factor-kB (NF-kB), cyclooxygenase-2 (COX-2) and prostaglandin E2. Noscapine hydrochloride significantly reduced the paw volume (p < 0.001), arthritic scoring and reversed the body mass as compared to arthritic control diseased rats.

Involvement of the dopaminergic system in the reward-related behavior of pregabalin.

There has been an increase in cases of drug addiction and prescription drug abuse worldwide. Recently, pregabalin abuse has been a focus for many healthcare agencies, as highlighted by epidemiological studies. We previously evaluated the possibility of pregabalin abuse using the conditioned place preference (CPP) paradigm. We observed that a 60 mg/kg dose could induce CPP in mice and that pregabalin-rewarding properties were mediated through glutamate neurotransmission. Notably, the dopaminergic reward circuitry is also known to play a crucial role in medication-seeking behavior. Therefore, this study aimed to explore the possible involvement of dopaminergic receptor-1 in pregabalin-induced CPP. Mice were randomly allocated to receive saline or the dopamine-1 receptor antagonist SKF-83566 (0.03 mg/kg, intraperitoneal). After 30 min, the mice received either saline or pregabalin (60 mg/kg) during the conditioning phase. Among the control groups that received saline or SKF-83566, the time spent in the two conditioning chambers was not significantly altered. However, among the pregabalin-treated group, there was a marked increase in the time spent in the drug-paired chamber compared to the time spent in the vehicle-paired chamber. Notably, blocking dopamine-1 receptors with SKF-83566 completely prevented pregabalin-induced place preference, thus demonstrating the engagement of the dopaminergic system in pregabalin-induced reward-related behavior.

Short- and Long-Term Effects of Vitamin D Treatment on Bacillus Calmette-Guerin-Induced Depressive-Like Behavior in Mice.

PURPOSE: Depression is one of the most common psychological disorders. The nutritional etiology of the depression proposes that vitamin D may play a significant role in the pathogenesis of depression. Further, vitamin D deficiency has been found to aggravate depression in animals. Therefore, vitamin D treatment might be a potential therapeutic aid in depression management. This study aimed to explore the antidepressant effects of vitamin D in a Bacillus Calmette-Guerin (BCG)-induced depression model. METHODS: Thirty-six mice were randomly assigned to short-term and long-term experimental groups. In each group, mice were randomly subcategorized into three subgroups: 1. control (received vehicle), 2. BCG (received BCG [107 CFU/mouse]), and 3. BCG + vitamin D (received vitamin D [60.000 IU/kg] before BCG [107 CFU/mouse] inoculation). After completion of the two experimental periods (3 days for the short-term group and 2 weeks for the long-term group), the mice underwent three behavioral tests: locomotor activity, the forced swimming test (FST), and the tail suspension test (TST). RESULTS: Locomotor activity did not significantly differ among the subgroups in either the long-term or short-term groups. In the short-term group, the total immobility time on the FST was decreased in the vitamin D-treated group compared to the BCG group. However, in the TST, no significant difference was found between the vitamin D-treated group and the BCG group. In the long-term group, the immobility time on the FST was decreased in the vitamin D-treated group compared to the BCG group. Similarly, the total immobility time on the TST was also significantly lower in the vitamin D-treated mice than in the BCG-treated mice. CONCLUSION: Vitamin D is useful in the management of depressive behavior. The potential role of vitamin D in the etiology of depression should be investigated in future work.

Multivalency in CXCR4 chemokine receptor targeted iron oxide nanoparticles.

The CXCR4 chemokine receptor is an important biomolecular target in cancer diagnostics and therapeutics. In a new multivalent approach, iron oxide nanoparticles were conjugated with multiple binding units of a low affinity azamacrocylic CXCR4 antagonist. The silica coated nanostructure has good suspension stability, a mode size of 72 nm and high affinity for CXCR4, showing >98% inhibition of anti-CXCR4 mAb binding in a receptor binding competition assay on Jurkat cells.