Natural products have long been used as drugs to treat a wide array of human diseases. The lead compounds discovered from natural sources are used as novel templates for developing more potent and safer drugs. Natural products produce biological activity by binding with biological macromolecules, since natural products complement the protein-binding sites and natural product–protein interactions are already optimized in nature. Sirtuin 6 (SIRT6) is an NAD+ dependent histone deacetylase enzyme and a unique Sirtuin family member. It plays a crucial role in different molecular pathways linked to DNA repair, tumorigenesis, glycolysis, gluconeogenesis, neurodegeneration, cardiac hypertrophic responses, etc. Thus, it has emerged as an exciting target of several diseases such as cancer, neurodegenerative diseases, aging, diabetes, metabolic disorder, and heart disease. Recent studies have shown that natural compounds can act as modulators of SIRT6. In the current review, a list of natural products, their sources, and their mechanisms of SIRT6 activity modulation has been compiled. The potential application of these naturally occurring SIRT6 modulators in the amelioration of major human diseases such as Alzheimer’s disease, aging, diabetes, inflammation, and cancer has also been delineated. Natural products such as isoquercetin, luteolin, and cyanidin act as SIRT6 activators, whereas vitexin, catechin, scutellarin, fucoidan, etc. work as SIRT6 inhibitors. It is noteworthy to mention that quercetin acts as both SIRT6 activator and inhibitor depending on its concentration used. Although none of them were found as highly selective and potent modulators of SIRT6, they could serve as the starting point for developing selective and highly potent scaffolds for SIRT6.
BackgroundBacopa monniera has been used as a cure for various ailments that include anxiety, epileptic disorders, dementia, blood purifier, cough and rheumatism, and some important local uses of the plant are in dermatitis, anemia, diabetes, promote fertility and prevent miscarriage for many years in Bangladesh. According to this background, the aim of the study was to evaluate the antidepressant-like effect of the methanolic extract of B. monniera (MEBM) in different behavioral models such as forced swimming test (FST), measurement of locomotor activity test (MLAT) and tail suspension test (TST) on mice after two weeks treatment.MethodsMice were divided into five groups (n = 5/group): control group (deionized water), standard group where Imipramine hydrochloride (30 mg/kg) was used as standard drug and three test groups where three doses of the methanolic extract of B. monniera (MEBM) (50, 100, and 200 mg/kg) was used for two weeks treatment. All the drug and test samples were administered via gavage through oral route. To assess the antidepressant-like effect of MEBM forced swimming test (FST), tail suspension test (TST) and measurement of locomotor activity test (MLAT) have been done in mice.ResultsThe results showed that a strong and dose-dependent antidepressant effects in different mice models. The main findings of the MEBM significantly reduced the duration of immobility times in the forced swimming test (p < 0.001). Likewise, the extract significantly decreased the immobility time in the tail suspension test (p < 0.001). Moreover, we employed an additional measurement of locomotor activity test to check the motor stimulating activity of the MEBM. The extract also significantly increased the locomotion, rearing and defecation effects in comparison to the control group (p < 0.001).ConclusionThe present results clearly demonstrate that the methanolic extract of B. monniera possesses antidepressant-like activity in the animal behavioral models. The current study warrants further investigation into identification of the active compounds in herbal medicines, in particular extract of B. monniera with antidepressant-like effects.
DiscussionThis review includes detailed description of antidepressant activity of 21 medicinal plants whose roots, leaves, fruits extracts were used to evaluate the activity from various research articles.The tests employed for antidepressant activity includes HBT, FST, TST, OFT, EPMT, and MACT using rotarod and THB. These tests are employed with slight modification from original method, keeping basic concept same. HBTExploratory behaviour of rodents such as mice is evaluated using hole board test. The floor of the apparatus has regularly arranged holes. The animal is placed in the arena. Both frequency and duration of spontaneous elicited hole-poking behavior are then measured during a short period of time. This test also provides a simple method for assessing anxious response of a rodent to an unfamiliar environment. The use of the hole-board in this perspective relies on the hypothesis that the behavior of animals exposed to a novel situation results from competition AbstractDepression refers to a state of low mood and aversion to activity characterized by depressed mood, loss of interest, reduced energy and concentration. The reasons for the disease include stimulation of MAO-A, inhibition of NA and 5-HT. Symptoms include the diminished interest of pleasure, feelings of worthlessness or inappropriate guilt, a decrease in appetite and libido, insomnia, and recurrent thoughts of death or suicide. There are plenty of synthetic drugs used to treat depression but not enough blissful for patients, moreover, these synthetic drugs have potential side effects. After decades of serious obsession with the modern medicinal system, people have started looking at the ancient healing systems like Ayurveda, Siddha, and Unani. Many scientists are researching plant material for treating this disorder and there are lots of publications on it. But this is not sufficient for treating depression; further outcome should come into light that's the purpose of our review.
The cholinergic system is involved in neurodegenerative diseases, and visualization of cholinergic innervations with positron emission tomography (PET) would be a useful tool in understanding these diseases. A ligand for the vesicular acetylcholine transporter (VAChT), acknowledged as a marker for cholinergic neurons, could serve as such a PET tracer. The aim was to find a VAChT PET tracer using a library concept to create a small but diverse library of labeled compounds. From the same precursor and commercially available aryl iodides 6a-f, six potential VAChT PET tracers, [(11)C]-(±)5a-f, were (11)C-labeled by a palladium (0)-mediated aminocarbonylation, utilizing a standard protocol. The labeled compounds [(11)C]-(±)5a-f were obtained in radiochemical purities >95% with decay-corrected radiochemical yields and specific radioactivities between 4-25% and 124-597 GBq/µmol, respectively. Autoradiography studies were then conducted to assess the compounds binding selectivity for VAChT. Labeled compounds [(11)C]-(±)5d and [(11)C]-(±)5e showed specific binding but not enough to permit further preclinical studies. To conclude, a general method for a facile synthesis and labeling of a small piperazine-based library of potential PET tracers for imaging of VAChT was shown, and in upcoming work, another scaffold will be explored using this approach.
Streblus asper Lour., traditionally used for antidiarrheal effects as like dysentery and diarrhea. The present study aims to prove the anti-diarrheal activities of methanolic extract of leaves of S. asper in animal models. The anti-diarrheal activity was evaluated using castor oilinduced diarrhea and magnesium sulphate-induced diarrhea models whereas anti-motility activities were investigated using gastrointestinal transit test examined in animal models. In castor oil-induced diarrhea model, methanolic extract of S. asper (MESA) at the doses of 100, 200, and 400 mg/kg produced statistically significant (P \ 0.001) decreased the number of diarrheal feces of rats against castor oil-induced diarrhea as well as magnesium sulphate-induced diarrhea model also showed the same manner. In gastrointestinal transit test, delayed gastric emptying time decreased significantly (P \ 0.001), the propulsion of charcoal meal in the gastrointestinal tract which also showed a dose-dependent manner in rats. The recent study indicates that MESA possesses anti-diarrheal property. The findings represent a rational explanation for its use in traditional medicine for the management of diarrhea management.
Alzheimer’s disease (AD) is a complex neurological disorder with economic, social, and medical burdens which is acknowledged as leading cause of dementia marked by the accumulation and aggregation of amyloid-β peptide and phosphorylated tau (p-tau) protein and concomitant dementia, neuron loss and brain atrophy. AD is the most prevalent neurodegenerative brain disorder with sporadic etiology, except for a small fraction of cases with familial inheritance where familial forms of AD are correlated to mutations in three functionally related genes: the amyloid-β protein precursor and presenilins 1 and 2, two key γ-secretase components. The common clinical features of AD are memory impairment that interrupts daily life, difficulty in accomplishing usual tasks, confusion with time or place, trouble understanding visual images and spatial relationships. Age is the most significant risk factor for AD, whereas other risk factors correlated with AD are hypercholesterolemia, hypertension, atherosclerosis, coronary heart disease, smoking, obesity, and diabetes. Despite decades of research, there is no satisfying therapy which will terminate the advancement of AD by acting on the origin of the disease process, whereas currently available therapeutics only provide symptomatic relief but fail to attain a definite cure and prevention. This review also represents the current status of AD in Bangladesh.
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