Alpha stone decoction, a polyherbal formulation induces liver mitochondrial-mediated apoptosis in a monosodium glutamate model of hyperplasia
Studies have shown that reduced apoptosis is a recurrent theme of most tumorigenic cells. The mitochondrial Permeability Transition (mPT) pore is therefore an important target in the regulation of cell death because the release of apoptogenic proteins from the organelle causes cell suicide. Evidence of health hazards associated with MonoSodium Glutamate (MSG) is well documented. Our initial findings revealed that Alpha Stone Decoction (ASD), a polyherbal formulation used in the traditional treatment of uterine fibroids, reduced fibroblast cell count and deposits of collagen in the uteri of MSG-treated female Wistar rats. This study therefore investigated the effects of ASD on liver mitochondrial-mediated apoptosis in a model of MSG-induced hyperplasia. Twenty-four male Wistar rats were randomly divided into four groups with six animals in each group; A (Control), B (MSG only: 200mg/kgbw), C (MSG: 200mg/kgbw & ASD: 100 mg/kgbw) and D (ASD only: 100mg/kgbw). The administration was carried out by as a single daily dose via intra-peritoneal route for 14 days, after which the animals were sacrificed. Mitochondrial swelling, mitochondrial ATPase activity, Caspase-9 and 3 activities were measured spectrophotometrically. Our data revealed that administration of ASD in a model of MSG-induced hyperplasia induced opening of the mPT pore in rat liver by 4.6 folds while the inductive effect was potentiated in animals administered both MSG and ASD by 5 folds. Similarly, ASD significantly enhanced (p < 0.05) mitochondrial ATPase activity, elevated levels of malondialdehyde and activated caspase-9 & 3 by 3.1, 2, 6 and 7 -folds, respectively relative to levels observed in untreated animals. These effects were higher in animals co-administered ASD and MSG. Hence, Alpha Stone Decoction contains bioactive components that induce opening of the pore via generation of free radicals, depletion of ATP levels and activation of caspases 9 and 3. Therefore, ASD may mediate its anti-fibrotic effect in part via induction of mitochondrial-mediated apoptosis.
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