Estimation of phytochemicals and antimicrobial activities of mentha spicata from southern districts of KPKNaseem Ullah, Muhammad Khurram, Farhat Ali Khan, Sahibzada Umar Khayyam, Muhammad Usman Amin, Saleem Ullah, Umberin Najeeb, Said Muhammad, Javid Hussain, M Asif Khan
1, 8‐naphthyridine‐3‐carboxylic acid analogs were synthesized and found to possess potential 5‐HT 3 receptor antagonism as well as antidepressant‐like activity. Initially, 5‐HT 3 receptor antagonism of all the compounds was determined in the form of p A 2 value against agonist 2‐methyl 5‐HT in longitudinal muscle–myenteric plexus preparation from guinea‐pig ileum. Among all the compounds tested, compound 7a demonstrated most promising pA 2 value of 7.6. Subsequently, all the compounds were evaluated for antidepressant activity using forced swim test and tail suspension test in mice. Compounds 7a , 7d , 7f , 7h , and 7i exhibited significant (p < 0.05) antidepressant‐like activity as compound to vehicle‐treated group. Importantly, none of the tested compound affected locomotor activity of mice at tested dose levels.
Alzheimer's disease (AD) is a progressive neurodegenerative disorder that causes structural as well as functional disturbance to neurons in discrete brain regions. Despite the extensive efforts to understand its pathophysiology, the exact mechanisms underlying AD remain unknown. There are various hypotheses on the causes of AD, including the cholinergic hypothesis, amyloid and tau protein hypothesis, neurovascular hypothesis, mitochondrial mitophagy hypothesis, metal ion hypothesis, and olfactory vector hypothesis (OVH). This article principally aims to provide a general idea of how olfaction is related to cognition and neurodegenerative diseases, particularly AD, and an overview of recent studies in this field. The olfactory system is very well connected to the central brain structure, such as the limbic system, which is associated with olfaction and can lead to evoke strong memories and emotions in human beings. Further, this review tries to reflect the central association of the olfactory system, detailing its anatomical peculiarities to support OVH with evidence on olfactory memory, altered olfactory functions, and memory induced by toxins, thereby culminating in its therapeutic utility through aromas as olfactory agonists. This hypothesis uplifts the role of olfaction and its system from a sensory modality to be an easily accessible point for toxins to reach the brain owing to its anatomical proximity, which eventually becomes a risk factor for neurodegenerative diseases like AD. The major focus of the current review is to specify the distinct involvement of the olfactory system compared to other senses in dementia, particularly AD, both in its pathogenesis and therapy.Funding Information: The authors thank DST-CSRI [New Delhi, India] for financial assistance to conduct the research work on this subject to SNM (Principal investigator) and AR is the recipient of the DST-INSPIRE fellowship.Declaration of Interests: The author’s report no conflict of interest relevant to this work.
Background: Metformin belongs to the antidiabetic drug but it has been shown some beneficial effects towards Central Nervous System (CNS) disorders and found to be neuroprotective by inhibiting apoptosis in neuronal cortical cells in various animal models apart from its anti-diabetic potential as per the available reports.
Lung cancer is a big challenge for current research because it increases in numbers, day by day with advancement (MDR type of cancer) due to the increase in environmental pollutants and daily life habitual practices of the people like smoking. Lung cancer classifies into non-small-cell lung cancer and small cell lung cancer. It is further subclassified into squamous-cell-carcinoma, large-cell-carcinoma, and lung adenocarcinoma. Day-by-day researchers try to develop new treatment strategy to manage the drug resistance, intracellular accumulation, metastasis, invasion, side effects, and toxicity and develop a more effective personalized novel treatment for the treatment of lung cancer. The current treatment regime depends upon the stage of progression of cancer, the health of the patients, and the affordability during the time of diagnosis. Different pathways can be utilized to treat the lung cancer. T-Cell activation is one of the pathways which can retard the growth of the cancer cells. PD-1 and CTLA-4 inhibitors can modify the signaling pathway and growth of the cancer cell by T-cell activation. PD-1 inhibitors can inhibit immune response and promote self-tolerance by-T-cell activation, antigen-specific T-cell-apoptosis, and regulatory T-cell-apoptosis-inhibition. Similarly, CTLA-4 inhibitors can also function as inhibitory signals by inducing the production of IL-2 and progression of the-cell cycle. CTLA-4 inhibitors stimulate the proliferation of T-cells, mainly in lymph nodes, whereas PD-1 inhibits the-proliferation-of T-cell afterward, primarily in peripheral tissues. The role and application of PD-1 and CTLA-4 inhibitors are explored in this chapter to inhibit the PD-1 and CTLA-4 signaling pathway to manage and treat the lung cancer.
Gemfibrozil is a well-known potent antihyperlipidemic drug with the capacity to lower triglyceride and cholesterol levels, which are responsible for most cardiovascular and cerebrovascular diseases. In addition, gemfibrozil has a potent activity at elevating the high density lipoprotein levels. However, this drug has a very short half-life of about 2 h and toxicity is observed in the liver as the dose increases. The drug piperine has the capacity to enhance the bioavailability of other drugs without altering their basic properties as well as improving their activity. In this study, we aimed to enhance the bioavailability of gemfibrozil as well as making it more potent and less toxic by applying piperine as a bio-enhancer. Thus, piperine was co-administered to rats with gemfibrozil and the antihyperlipidemic activity was tested when fed on a high fat diet. The results showed that co-administration of gemfibrozil with piperine decreased the elevated triglyceride and cholesterol levels to normal, and they performed significantly better than the individual drugs. Weight gain was controlled effectively by drug administration together with piperine compared with other groups. Hepatic function analyses demonstrated that the potentiation of gemfibrozil did not alter the hepatic function but instead it improved significantly by normalizing the elevated serum glutamic oxaloacetic transaminase, serum glutamic pyruvic transaminase, and alkaline phosphatase levels. The plasma drug concentration of gemfibrozil was studied over time, where the enhanced activity of the drug reached its Cmax within 1 h of administration and the activated drug level was observed in the blood for 4 h.
A series of novel 1,8-naphthyridine-3-carboxamides as 5-HT3 receptor antagonists were synthesized with an intention to explore the antidepressant activity of these compounds. The title carboxamides were designed using ligand-based approach keeping in consideration the structural requirement of the pharmacophore of 5-HT3 receptor antagonists. The compounds were synthesized using appropriate synthetic route from the starting material nicotinamide. 5-HT3 receptor antagonism of all the compounds, which was denoted in the form of pA2 value, was determined in longitudinal muscle myenteric plexus preparation from guinea-pig ileum against 5-HT3 agonist, 2-methyl-5-HT. Compound 8g (2-methoxy-1, 8-naphthyridin-3-yl) (2-methoxy phenyl piperazine-1-yl) methanone was identified as the most active compound, which expressed a pA2 value of 7.67. The antidepressant activity of all the compounds was examined in mice model of forced swim test (FST); importantly, none of the compounds was found to cause any significant changes in the locomotor activity of mice at the tested dose levels. In FST, the compounds with considerably higher pA2 value exhibited promising antidepressant-like activity, whereas compounds with lower pA2 value did not show antidepressant-like activity as compared to the control group.
'%3e%3ccircle r='20' fill='%23008'/%3e%3ccircle r='17.5' fill='%23fff'/%3e%3ccircle r='3.5' fill='%23008'/%3e%3cg id='d'%3e%3cg id='c'%3e%3cg id='b'%3e%3cg id='a' fill='%23008'%3e%3ccircle r='.875' transform='rotate(7.5 -8.75 133.5)'/%3e%3cpath d='M0 17.5.6 7 0 2l-.6 5L0 17.5z'/%3e%3c/g%3e%3cuse xlink:href='%23a' transform='rotate(15)'/%3e%3c/g%3e%3cuse xlink:href='%23b' transform='rotate(30)'/%3e%3c/g%3e%3cuse xlink:href='%23c' transform='rotate(60)'/%3e%3c/g%3e%3cuse xlink:href='%23d' transform='rotate(120)'/%3e%3cuse xlink:href='%23d' transform='rotate(-120)'/%3e%3c/g%3e%3c/svg%3e)
'/%3e%3c/defs%3e%3cpath fill='%23012169' d='M0 0h10080v5040H0z'/%3e%3cpath stroke='%23fff' stroke-width='.6' d='m0 0 6 3m0-3L0 3' clip-path='url(%23b)' transform='scale(840)'/%3e%3cpath stroke='%23e4002b' stroke-width='.4' d='m0 0 6 3m0-3L0 3' clip-path='url(%23c)' transform='scale(840)'/%3e%3cpath stroke='%23fff' stroke-width='840' d='M2520 0v2520M0 1260h5040'/%3e%3cpath stroke='%23e4002b' stroke-width='504' d='M2520 0v2520M0 1260h5040'/%3e%3cg fill='%23fff'%3e%3cuse xlink:href='%23d' x='2520' y='3780'/%3e%3cuse xlink:href='%23a' x='7560' y='4200'/%3e%3cuse xlink:href='%23a' x='6300' y='2205'/%3e%3cuse xlink:href='%23a' x='7560' y='840'/%3e%3cuse xlink:href='%23a' x='8680' y='1869'/%3e%3cuse xlink:href='%23e' x='8064' y='2730'/%3e%3c/g%3e%3c/svg%3e)