Aims:
Arsenic has carcinogenic property. Reason behind this is the formation of Reactive
Oxygen Species (ROS). ROS damages different macromolecules, tissues and organs, and
severely exhausts cellular antioxidants.
Background:
Cytosolic and mitochondrial contribution
of ROS production by arsenic is not well reported. In regard to the issues of therapy against
arsenic or any other toxicity, natural product has gained its popularity due to its less side-effects
and non-invasive nature.
Objectives:
Here, as an ethno-medicine the flesh-extract (BBE;
100mg/100g bw) of Bellamya bengalensis (an aquatic mollusk, pila) was applied in arsenic
intoxicated (0.6 ppm/100g bw/for 28 days alone or in combination with BBE) experimental rats.
Our objective was to study the anti-oxidative and anti-apoptotic role of BBE in hepatogastrointestinal tissue damage by arsenic.
Methods:
DNA fragmentation assay, catalase activity
(gel-zymogram assay) suggests that BBE has a strong protective role against arsenic toxicity
which is decisively demonstrated in hepatic histoarchitechture study by HE (hematoxylin and
eosin) staining and by intestinal PAS (Periodic Acid Schiff) staining.
Results:
Measurement of
mitochondrial-membrane-potential by fluroscent microcopy clearly demonstrated less membrane
damage and lower release of redox-active inner-membrane product (cytochrome-C, ubiquinone
etc.) in BBE supplemented group compared to that of only arsenic fed group. Present study
clearly suggests that mitochondrial disintegrity is one of the major causes of ROS mediated
tissue damage by arsenic.
Conclusions:
This study also offers an option for prevention/treatment
against arsenic toxicity and its carcinogenicity by widely available low-cost noninvasive
bellamya extract by protecting cytoskeleton, DNA and mitochondria in the cell.
Background
Over-expression of acetylcholinesterase (AChE), a key enzyme-regulator of neurotransmitter acetylcholine leads to neurodegenerative-disorder, Alzheimer’s-disease/muscular-dysfunction.
Aims
Therefore, inhibition of AChE may restrict these diseases.
Objectives
Presently, black-tea was tested in-vitro/in-vivo on AChE activities.
Methods
Inhibitory-effects on purified-AChE was screened from ten pure tea-phytochemicals viz. epicatechin(EC), epigallocatechin(EGC), catechin-gallate(CG), epicatechin-gallate(ECG), Epigallocatechin-gallate(EGCG), gallocatechin-gallate(GCG), theaflavin(TF), theaflavin-monogallate(TFMG), theaflavin-digallate(TFDG), and gallic-acid.
Results
Among those, TFDG and TFMG showed promising dose-dependent (mixed-type manner.) inhibition of AChE (IC50 = 1.6µM and 3.3µM, respectively). The TF showed moderate inhibitory-effect (IC50 = 29µM). Tea galloyl-ester catechins, ECG/CG/EGCG/GCG inhibited AChE (IC50 = 41, 49, 67and 54 µM, respectively). In-vivo, arsenic-intoxicated (0.6 ppm/4-weeks) rat increase of cerebellum AChE was completely restored by black-tea-extract (TF-rich). Molecular-docking by AutoDock-PatchDock server (binding/stability/kinetic) of AchE (PDBid:4M0E) and the experimental-flavonoids (PubChem-3Dstructures) suggest, TFDG (lowest Atomic-Contact-Energy − 369.87, TFMG, -347.06 kcal/mol) hampers the enzyme catalytic-hydrolytic-action and nucleophilic-attack by SER203 supporting the in-vitro results. Conclusively, the finding is therapeutically beneficial for cholinergic neurodegenerative/muscular disorders.
Chronic arsenic-exposure causes gastro-intestinal/nephrotoxic/neurodegenerative disorders with keratosis/melanosis and cancers. The reactive-oxygen-species (ROS) cause intrinsic-antioxidant (thiols/uric-acid) depletion eventuating cytoskeletal-extracellular-matrix and DNA damage. Therapeutic chelating-agents have multiple side-effects. The protective potential of tea-extract against arsenic neurotoxicity was studied. Influence of uric-acid in arsenic-toxicity was verified. Camellia sinensis (CS dry-leaves) 10mg/ml aqueous), uric-acid (UA) or allopurinol (Allo- urate-depletor) was supplemented to arsenic-intoxicated (0.6 ppm/100g bw/day/4-weeks) female albino-rats and cytotoxicity/biochemistry/histo-architecture/matrix-integrity and DNA-stability were evaluated in their cerebrum-cerebellum. In-vitro purified theaflavin-derivatives were tested on purified-AchE (acetyl-cholinesterase). Higher malondialdehyde, lactate-dehydrogenase and lower uric-acid levels were observed in the arsenic/Allo groups. Degenerations of cerebrum/cerebellum by higher matrix-metalloprotease (MMP2/9)/DNA-damages (comets) are observed. The CS-group restored the adverse-markers, protected tissues/DNA integrity which is supported in the UA-group and opposed in the Allo-group. Impairment of the neural-signaling, evident from the arsenic-exposed animal with unstable-movement/vertigo/tremor accompanied with higher AchE in the cerebellum is significantly restored/protected in the CS-group. This suggests that the neural integrity is maintained by the cellular intrinsic antioxidative-capacity, shown in catalase-SOD1 activities. In-vitro and in silico studies suggest that the theaflavin derivatives (pure, SIGMA) i.e theaflavin-digallate (TFDG) showed the strongest inhibition on purified (SIGMA) AchE (IC50 = 2.19 µg/ml) followed by TFMG (IC50 = 3.86 µg/ml). The4 CS is protective in arsenic-toxicity. Theaflavin-gallate is a strong AchE inhibitor which can be used in arsenic-induced neuro-muscular depletion. Beside antioxidant/anti-inflammatory/anti-carcinogenic role CS restores intrinsic-antioxidants.
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