01800nas a2200265 4500008004100000022001400041245007700055210006900132260000800201300001100209490000800220520092900228653002201157653001401179653002501193653002901218653002401247653001601271100002901287700002801316700002001344700002601364700003601390856010801426 2019 eng d a0003-986100aBaicalein suppresses repeat tau fibrillization by sequestering oligomers0 aBaicalein suppresses repeat tau fibrillization by sequestering o cOCT a1081190 v6753 a

Alzheimer's disease (AD) is a neurodegenerative disorder caused by protein misfolding, aggregation and accumulation in the brain. A large number of molecules are being screened against these pathogenic proteins but the focus for therapeutics is shifting towards the natural compounds as aggregation inhibitors, mainly due to their minimum adverse effects. Baicalein is a natural compound belonging to the class of flavonoids isolated from the Chinese herb Scutellaria baicalensis. Here we applied fluorescence, absorbance, microscopy, MALDI-TOF spectrophotometry and other biochemical techniques to investigate the interaction between Tau and Baicalein in vitro. We found the aggregation inhibitory properties of Baicalein for the repeat Tau. Overall, the potential of Baicalein in dissolving the preformed Tau oligomers as well as mature fibrils can be of utmost importance in therapeutics for Alzheimer's disease.

10aAlzheimer disease10aBaicalein10aMicrotubule assembly10aPaired helical filaments10aProtein aggregation10atau protein1 aSonawane, Shweta, Kishor1 aBalmik, Abhishek, Ankur1 aBoral, Debjyoti1 aRamasamy, Sureshkumar1 aChinnathambi, Subashchandrabose uhttp://library.ncl.res.in/content/baicalein-suppresses-repeat-tau-fibrillization-sequestering-oligomers02929nas a2200217 4500008004100000245010400041210006900145260000900214300000700223490000700230520216300237653002402400653001402424653002002438653001902458653001802477100002902495700002602524700003602550856012502586 2021 eng d00aBaicalein inhibits heparin-induced Tau aggregation by initializing non-toxic Tau oligomer formation0 aBaicalein inhibits heparininduced Tau aggregation by initializin cFEB  a160 v193 a

Background: Amyloid aggregate deposition is the key feature of Alzheimer's disease. The proteinaceous aggregates found in the afflicted brain are the intra-neuronal neurofibrillary tangles formed by the microtubule-associated protein Tau and extracellular deposits, senile plaques, of amyloid beta (A beta) peptide proteolytically derived from the amyloid precursor protein. Accumulation of these aggregates has manifestations in the later stages of the disease, such as memory loss and cognitive inabilities originating from the neuronal dysfunction, neurodegeneration, and brain atrophy. Treatment of this disease at the late stages is difficult, and many clinical trials have failed. Hence, the goal is to find means capable of preventing the aggregation of these intrinsically disordered proteins by inhibiting the early stages of their pathological transformations. Polyphenols are known to be neuroprotective agents with the noticeable potential against many neurodegenerative diseases, such as Alzheimer's, Parkinson's, and Prion diseases. Methods: We analyzed the capability of Baicalein to inhibit aggregation of human Tau protein by a multifactorial analysis that included several biophysical and biochemical techniques. Results: The potency of Baicalein, a polyphenol from the Scutellaria baicalensis Georgi, against in vitro Tau aggregation and PHF dissolution has been screened and validated. ThS fluorescence assay revealed the potent inhibitory activity of Baicalein, whereas ANS revealed its mechanism of Tau inhibition viz. by oligomer capture and dissociation. In addition, Baicalein dissolved the preformed mature fibrils of Tau thereby possessing a dual target action. Tau oligomers formed by Baicalein were non-toxic to neuronal cells, highlighting its role as a potent molecule to be screened against AD. Conclusion: In conclusion, Baicalein inhibits aggregation of hTau40 by enhancing the formation of SDS-stable oligomers and preventing fibril formation. Baicalein-induced oligomers do not affect the viability of the neuroblastoma cells. Therefore, Baicalein can be considered as a lead molecule against Tau pathology in AD.

10aAlzheimer's disease10aBaicalein10aTau dissolution10aTau inhibition10aTau Oligomers1 aSonawane, Shweta, Kishor1 aUversky, Vladimir, N.1 aChinnathambi, Subashchandrabose uhttp://library.ncl.res.in/content/baicalein-inhibits-heparin-induced-tau-aggregation-initializing-non-toxic-tau-oligomer02072nas a2200253 4500008004100000022001400041245007300055210006900128260000800197300001400205490000700219520130800226653001401534653001301548653002201561653002601583653001501609100002001624700001901644700001801663700001701681700001901698856010101717 2022 eng d a0739-110200aMolecular elucidation of pancreatic elastase inhibition by baicalein0 aMolecular elucidation of pancreatic elastase inhibition by baica cJUL a5759-57680 v403 a

The serine protease, elastase exists in various forms and plays diverse roles in the human body. Pharmacological inhibition of elastase has been investigated for its therapeutic role in managing conditions such as diabetes, pneumonia and arthritis. Sivelestat, a synthetic molecule, is the only elastase inhibitor to have been approved by any major drug regulatory authority (PMDA, in this case) - but still has failed to attain widespread clinical usage owing to its high price, cumbersome administration and obscure long-term safety profile. In order to find a relatively better-suited alternative, screening was conducted using plant flavonoids, which yielded baicalein, a molecule that showed robust inhibition against Pancreatic Elastase inhibition (IC50: 3.53 mu M). Other than having a considerably lower IC(50)than sivelestat, baicalein is also cheaper, safer and easier to administer. While MicroScale Thermophoresis validated baicalein-elastase interaction, enzyme-kinetic studies, molecular docking and molecular dynamic simulation revealed the mode of inhibition to be non-competitive. Baicalein exhibited binding to a distinct allosteric site on the enzyme. The current study demonstrates the elastase inhibition properties of baicalein in an in-vitro and in-silico environment.

10aBaicalein10aelastase10aEnzyme inhibition10amolecular interaction10asivelestat1 aGhosh, Debajeet1 aBansode, Sneha1 aJoshi, Rakesh1 aKolte, Baban1 aGacche, Rajesh uhttp://library.ncl.res.in/content/molecular-elucidation-pancreatic-elastase-inhibition-baicalein