IN VITRO SCREENING FOR ACETYLCHOLINESTERASE ENZYME INHIBITION POTENTIAL OF MUTHU PARPAM – THERAPEUTIC LEAD FOR ALZHEIMER’S DISEASE

Objective: Siddha system is an ancient traditional system of medicine treats many chronic ailments and neurological disorders. Muthu parpam is one of the herbo marine Siddha drugs which have the indication for neurocognitive dysfunction. The main objective of this current study was to evaluate the acetylcholine esterase (AChE) inhibition of Muthu parpam. Methods: AChE activity was evaluated using a modified 96-well microplate assay based on Ellman’s method. Physostigmine (5, 10, 20, and 40 μg/ml) was used as the positive control. Results: The result of this study clearly indicates that the test drug Muthu Parpam was effective in inhibiting AChE enzyme at the specified concentration dose dependently. Maximum percentage inhibition of about 71.68% was observed at 500 μg/ml when compared to that of the Physostigmine, a known AChE inhibitor with the maximum inhibition 84.87% at the concentration of 40 μg/ml. Conclusion: Hence, this preliminary screening has proven the efficacy of Muthu parpam through AChE inhibition potential in the management of Alzheimer disease

ANGIOTENSIN CONVERTING ENZYME INHIBITION POTENTIAL OF ANNAPAVALA CHENDHURAM FOR THE TREATMENT OF HYPERTENSION - AN IN–VITRO ASSAY

Hypertension is that the most noteworthy risk factor for cardiovascular diseases and stroke. Dietary and lifestyle changes play the foremost part to decrease the hazard of hypertension and other related wellbeing complications. Angiotensin Converting Enzyme (ACE) inhibitors play a major role in treating hypertension. Annapavala chendhuram is a herbo – mineral Siddha formulation comes under the type of 32 internal medicines of Siddha. Hypolipidemic activity of Annapavala chendhuram has been proven by some research studies. Hence, the purpose of the present study was to evaluate the ACE inhibition activity on Annapavala chendhuram by using an in-vitro assay. The ACE inhibition assay was evaluated by UV Spectrophotometry technique based on the hydrolysis of histidyl-hippuryl-leucine (HHL) by ACE. About 50µL test sample with varying concentration (100- 500 µg/ml) along with standard captopril (100µg/ml) added with 50µL of ACE and some process had continued. The present study indicates that the test drug Annapavala chendhuram was effective in inhibiting the enzyme ACE dose-dependently. Maximum percentage inhibition of about 53.24±8.403% was observed at 500μg/ml when compared to that of the Captopril, a standard ACE enzyme inhibitor agent with the maximum inhibition 86.98 ± 6.375 at the concentration of 100μg/ml. It was concluded that the test drug Annapavala chendhuram possess significant anti-hypertensive property in protein denaturation assay. So, further in-vitro evaluation of ACE inhibitory activity on Siddha herbal preparations and clinical trials will be the need of the hour

Diethyl [(2-bromo­anilino)(1,3-diphenyl-1H-pyrazol-4-yl)meth­yl]phospho­nate

In the title compound, C26H27BrN3O3P, the central pyrazole ring forms a dihedral angle of 71.7 (2)° with the bromo­phenyl ring. In the crystal, mol­ecules are linked by pairs of N—H⋯O hydrogen bonds, forming inversion dimers with R 2 2(10) ring motifs. Four C atoms of the 3-phenyl ring are disordered over two sets of sites [site occupancies = 0.745 (6) and 0.225 (6)]

The inner centromere is a biomolecular condensate scaffolded by the chromosomal passenger complex.

The inner centromere is a region on every mitotic chromosome that enables specific biochemical reactions that underlie properties, such as the maintenance of cohesion, the regulation of kinetochores and the assembly of specialized chromatin, that can resist microtubule pulling forces. The chromosomal passenger complex (CPC) is abundantly localized to the inner centromeres and it is unclear whether it is involved in non-kinase activities that contribute to the generation of these unique chromatin properties. We find that the borealin subunit of the CPC drives phase separation of the CPC in vitro at concentrations that are below those found on the inner centromere. We also provide strong evidence that the CPC exists in a phase-separated state at the inner centromere. CPC phase separation is required for its inner-centromere localization and function during mitosis. We suggest that the CPC combines phase separation, kinase and histone code-reading activities to enable the formation of a chromatin body with unique biochemical activities at the inner centromere

Microbiota derived short chain fatty acids promote histone crotonylation in the colon through histone deacetylases

The recently discovered histone post-translational modification crotonylation connects cellular metabolism to gene regulation. Its regulation and tissue-specific functions are poorly understood. We characterize histone crotonylation in intestinal epithelia and find that histone H3 crotonylation at lysine 18 is a surprisingly abundant modification in the small intestine crypt and colon, and is linked to gene regulation. We show that this modification is highly dynamic and regulated during the cell cycle. We identify class I histone deacetylases, HDAC1, HDAC2, and HDAC3, as major executors of histone decrotonylation. We show that known HDAC inhibitors, including the gut microbiota-derived butyrate, affect histone decrotonylation. Consistent with this, we find that depletion of the gut microbiota leads to a global change in histone crotonylation in the colon. Our results suggest that histone crotonylation connects chromatin to the gut microbiota, at least in part, via short-chain fatty acids and HDACs

The integrin αvβ6 drives pancreatic cancer through diverse mechanisms and represents an effective target for therapy

Pancreatic ductal adenocarcinoma (PDAC) has a five‐year survival rate of <4% and desperately needs novel effective therapeutics. Integrin αvβ6 has been linked with poor prognosis in cancer but its potential as a target in PDAC remains unclear. We report that transcriptional expression analysis revealed high levels of β6 mRNA correlated strongly with significantly poorer survival (n=491 cases, p= 3.17x10‐8). In two separate cohorts we showed that over 80% of PDAC expressed αvβ6 protein and that paired metastases retained αvβ6 expression. In vitro, integrin αvβ6 promoted PDAC cell growth, survival, migration and invasion. Treatment of both αvβ6‐positive human PDAC xenografts and transgenic mice bearing αvβ6‐positive PDAC with the αvβ6 blocking antibody 264RAD, combined with gemcitabine, significantly reduced tumour growth (p<0.0001) and increased survival (Log‐rank test, p<0.05). Antibody therapy was associated with suppression of both tumour cell activity (suppression of pErk growth signals, increased apoptosis seen as activated Caspase 3) and suppression of the pro‐tumourigenic microenvironment (suppression of TGFβ signalling, fewer αSMA‐positive myofibroblasts, decreased blood vessel density). These data show that αvβ6 promotes PDAC growth through both tumour cell and tumour microenvironment mechanisms and represents a valuable target for PDAC therapy