Cortical spreading depression: culprits and mechanisms.

Cortical spreading depression or CSD is an electrophysiological phenomenon affecting various perspectives of brain physiology such as ionic balance, neurotransmitter level, and blood flow in the brain. This phenomenon has greater impact on the brain function and results in the pathological contribution of many diseases in humans such as migraine with aura, stroke, and traumatic brain injury. Various factors such as nutrition, stress, sleep, age, alcohol, inflammation and oxidative stress worsen the condition and affect CSD susceptibility. The underlying mechanisms such as ionic imbalance and neurotransmitters' alteration are interconnected and may worsen the condition of CSD. Thus, correction of these main culprits might ameliorate the cumbersome effect of CSD, thereby providing benefits in diseases associated with CSD. This review collates most of the triggering factors that makes one prone to the CSD condition along with its underlying mechanisms.

'Magnesium'-the master cation-as a drug-possibilities and evidences.

Magnesium (Mg2+) is the 2nd most abundant intracellular cation, which participates in various enzymatic reactions; there by regulating vital biological functions. Magnesium (Mg2+) can regulate several cations, including sodium, potassium, and calcium; it consequently maintains physiological functions like impulse conduction, blood pressure, heart rhythm, and muscle contraction. But, it doesn't get much attention in account with its functions, making it a "Forgotten cation". Like other cations, maintenance of the normal physiological level of Mg2+ is important. Its deficiency is associated with various diseases, which point out to the importance of Mg2+ as a drug. The roles of Mg2+ such as natural calcium antagonist, glutamate NMDA receptor blocker, vasodilator, antioxidant and anti-inflammatory agent are responsible for its therapeutic benefits. Various salts of Mg2+ are currently in clinical use, but their application is limited. This review collates all the possible mechanisms behind the behavior of magnesium as a drug at different disease conditions with clinical shreds of evidence.

Unveiling the therapeutic potential of plant steroid peimine: A study on apoptotic induction in MRMT-1 cell line-induced breast cancer in rats.

BACKGROUND: Breast cancer stands as a leading contributor to global cancer-related mortality. Progressing Research and Medical Innovations Elevate Treatment Choices and Results for Breast Cancer. Among these, Peimine, a natural steroid inherent in plants, notably within the Fritillaria species, demonstrates the capability to trigger apoptosis in breast cancer cells through the mitochondrial membrane permeation pathway. Nevertheless, its impact within an appropriate cancer model remains an area necessitating further exploration. AIM: This study explored the in vivo anticancer effects of peimine on MRMT-1 Cell-line induced breast cancer in rats. METHOD: Cancer was induced by the administration of MRMT-1 (6 x 106 cells) cells in the mammary pads of SD rats. The daily drug treatmentcommenced on day 14 and continued till 39 days. Peimine was administered in two doses (0.24 mg/kg and 0.48 mg/kg p.o) to examine its efficacy in curing breast cancer while tamoxifen was used as standard. RESULTS: A reduction in tumour size was observed in the peimine-treated groups. Peimine can correct the changed blood cell count in addition to its anti-tumour activity. In peimine-treated rats, imbalanced immune marker IgE, serum oxidative marker, and tissue apoptotic markers like cytochrome c and calcium level were shown to be restored significantly. CONCLUSION: Our findings imply that quinine has beneficial effects as an anti-neoplastic medication for breast cancer, most likely through its apoptotic activity. More research is necessary to thoroughly understand their mechanisms of action, ideal dose, and potential side effects.

Exploring the effects of vasoactive constituents in large cardamom: implications for the anti-hypertensive effect via eNOS coupling pathway - an in-vitro study in rat endothelial cells.

Endothelial dysfunction, linked to reduced eNOS expression and nitric oxide (NO) availability, contributes to cardiovascular diseases (CVDs). Large cardamom exhibits antihypertensive effects by augmenting NO levels and antioxidant activity. To decipher its mechanisms, selected constituents were docked with eNOS-associated target genes such as GTP cyclohydrolase I (GTPCH-1) and (dihydrofolate reductase [DHFR]). Endothelial damage induced by L-NAME and fructose was countered by assessing nitric oxide metabolites (NOx), tetrahydrobipterin (BH4 levels), GCH-I expression and super oxide dismutase (SOD) activity after constituent incubation. Cyanidin-3-O-glucoside and petunidin-3-O-glucoside notably restored impaired vascular markers in both models. These phytoconstituents are likely to activate GCH-BH4-eNOS pathways, upregulating SOD and NO expression, maintaining endothelial integrity. Large cardamom's antihypertensive effects may stem from these components, synergistically enhancing endothelial NO release via the eNOS pathway.

A Mini Review on the Various Facets Effecting Brain Delivery of Magnesium and Its Role in Neurological Disorders.

Magnesium is an essential cation present in the body that participates in the regulation of various vital body functions. Maintaining normal level of magnesium is essential for proper brain functions by regulating the activities of numerous neurotransmitters and their receptors. Various studies have been reported that magnesium level is found to be declined in both neurological and psychiatric diseases. Declined magnesium level in the brain initiates various cumbersome effects like excitotoxicity, altered blood-brain permeability, oxidative stress, and inflammation, which may further worsen the disease condition. Shreds of evidence from the experimental and clinical studies proved that exogenous administration of magnesium is useful for correcting disease-induced alterations in the brain. But one of the major limiting factors in the use of magnesium for treatment purposes is its poor blood-brain barrier permeability. Various approaches like the administration of its organic salts as pidolate and threonate forms, and the combination with polyethylene glycol or mannitol have been tried to improve its permeability to make magnesium as a suitable drug for different neurological disorders. These results have shown their experimental efficacy in diseased animal models, but studies regarding the safety and efficacy in human subjects are currently underway. We present a comprehensive review on the role of magnesium in the maintenance of normal functioning of the brain and various approaches for improving its BBB permeability.

Formulation and evaluation of magnesium sulphate nanoparticles for improved CNS penetrability.

Magnesium (Mg2+) is the fourth most abundant cation in the human body and is involved in maintaining varieties of cellular and neurological functions. Magnesium deficiency has been associated with numerous diseases, particularly neurological disorders, and its supplementation has proven beneficial. However, magnesium therapy in neurological diseases is limited because of the inability of magnesium to cross the blood-brain barrier (BBB). The present study focuses on developing magnesium sulphate nanoparticles (MGSN) to improve blood-brain barrier permeability. MGSN was prepared by precipitation technique with probe sonication. The developed formulation was characterized by DLS, EDAX, FT-IR and quantitative and qualitative estimation of magnesium. According to the DLS report, the average size of the prepared MGSN is found to be 247 nm. The haemocompatibility assay studies revealed that the prepared MGSN are biocompatible at different concentrations. The in vitro BBB permeability assay conducted by Parallel Artificial Membrane Permeability Assay (PAMPA) using rat brain tissue revealed that the prepared MGSN exhibited enhanced BBB permeability as compared to the marketed i.v. MgSO4 injection. The reversal effect of MGSN to digoxin-induced Na+/K+ ATPase enzyme inhibition using brain microslices confirmed that MGSN could attenuate the altered levels of Na+ and K+ and is useful in treating neurological diseases with altered expression of Na+/K+ ATPase activity.

Targeting Viral ORF3a Protein: A New Approach to Mitigate COVID-19 Induced Immune Cell Apoptosis and Associated Respiratory Complications.

Infection with SARS-CoV-2 is a growing concern to the global well-being of the public at present. Different amino acid mutations alter the biological and epidemiological characteristics, as well as immune resistance of SARS-CoV-2. The virus-induced pulmonary impairment and inflammatory cytokine storm are directly related to its clinical manifestations. But, the fundamental mechanisms of inflammatory responses are found to be the reason for the death of immune cells which render the host immune system failure. Apoptosis of immune cells is one of the most common forms of programmed cell death induced by the virus for its survival and virulence property. ORF3a, a SARS-CoV-2 accessory viral protein, induces apoptosis in host cells and suppress the defense mechanism. This suggests, inhibiting SARS-CoV-2 ORF3a protein is a good therapeutic strategy for the treatment in COVID-19 infection by promoting the host immune defense mechanism.

Cardioprotective Effect of Marsdenia tenacissima and Sansevieria roxburghiana in Doxorubicin-induced Cardiotoxicity in Rats in vivo: The Role of Dresgenin and Lupeol

Objectives: The major adverse effect of doxorubicin (DOX) in cancer treatment is cardiac toxicity. Murva is a controversial plant used in the Ayurvedic system, which consist of more than 12 medicinal plant roots found in different parts of India. Marsdenia tenacissima (MT) is an acceptable source in Murva, whereas Sansevieria roxburghiana (SR) Schult & Schult.f. (S. zeylanica Roxb.) are also considered as Murva in West Bengal, India. The present study focused on the evaluation of the cardioprotective mechanism as well as the in vivo cardioprotective potential of methanol extracts of MT and SR on rats by using in silico methods. Materials and Methods: A total of 48 rats were divided into 8 groups with 6 in each group. DOX 20 mg/kg, intraperitoneally (i.p.) was administered to all rats on the 13th day, with the exception of group 1. Group 2 was the disease control, group 3 was the treated with the standard drug propronolol, and groups 4 to 5 were treated with two lower doses of methanol extract of MT (MEMT) and methanol extract of SR (MESR), whereas group 7 received higher dose combinations of both extracts for 14 continuous days. Blood and tissue antioxidant levels as well as cardiac enzymes were measured at the end of the study. Damage to cellular functional units was analyzed by histopathological study. Dresgenin from MT similarly lupeol from SR were taken as ligands for the target peroxisome proliferator activated receptors (PPARα) protein to find out the mechanism of action. High-performance thin layer chromatography (HPTLC) fingerprinting was performed to determine the number of phytoconstituents present in both extracts. Results: The combination that showed the most significant (p<0.001) effect on altered cardiac enzymes and antioxidant enzyme levels in both blood and tissues also corrected the extreme damage in cellular functional units. Dresgenin and lupeol showed binding scores of -8.2 (kcal/mol) and -9 (kcal/mol), respectively, with PPARα. HPTLC reports revealed that 17 and 12 peaks were found at 254 nm for dresgenin and lupeol, respectively. Conclusion: The study results concluded that the combination of MESR and MEMT and that of MESR and MEMT exerted cardioprotective activity via binding of dresgenin and lupeol to PPARα. The order of efficacy was the extract combination > MESR > MEMT.