Phyllanthin inhibits CCl4-mediated oxidative stress and hepatic fibrosis by down-regulating TNF-α/NF-κB, and pro-fibrotic factor TGF-ß1 mediating inflammatory signaling.

Hepatic fibrosis is an important outcome of chronic liver injury and results in excess synthesis and accumulation of extracellular matrix (ECM) components. Phyllanthin (PLN) isolated from Phyllanthus amarus exhibits strong antioxidative property and protects HepG2 cells from carbon tetrachloride (CCl4)-induced experimental toxicity. The present study reports the antifibrotic potential of PLN. The in vivo inhibitory effect of PLN on CCl4-mediated lipid peroxidation and important profibrotic mediator transforming growth factor ß1 and on predominant ECM components collagen and fibronectin were also studied. The results show that PLN acts by suppressing the expression of inflammatory cytokine tumor necrosis factor-α and prevents activation of nuclear factor-κB in hepatic tissue. Our study highlights the molecular mechanism responsible for the antifibrotic efficacy of PLN.

Mechanism of protective effect of phyllanthin against carbon tetrachloride-induced hepatotoxicity and experimental liver fibrosis in mice.

Chronic injury to liver triggers synthesis of extracellular matrix components resulting in progressive fibrosis and eventually cirrhosis. Transforming growth factor-ß1 (TGF-ß1) transduces its signal by binding to TGF-ß type 1 receptor kinase or activin like kinase (ALK5) receptor and mediates hepatic fibrosis by increasing the transcription of downstream entities such as collagen via Smad2 and Smad3. The present study was carried out to investigate the mechanism by which phyllanthin, a hepatoprotective lignin isolated from the plant Phyllanthus amarus (P. amarus) exerts its anti-fibrotic effect. The inhibitory role of phyllanthin on ALK5 was first analyzed using molecular docking experiments. Phyllanthin was found to effectively bind to serine (Ser) 280 at the active site of ALK5 by forming hydrogen bonds. The in vivo protective effect of phyllanthin against carbon tetrachloride (CCl4)-induced hepatic fibrosis was established by studying the protein expressions of TGF-ß1, ALK5 and Smad2 and 3 and by determining various biochemical and histopathological parameters. Phyllanthin was found to exert its anti-fibrotic effect by down-regulating TGF signaling pathway via ALK5 and Smad2 and 3 inhibition.

Beneficial antioxidative effect of the homeopathic preparation of Berberis vulgaris in alleviating oxidative stress in experimental urolithiasis.

BACKGROUND: Oxidative stress is a major mediator in the pathophysiology of several kidney diseases. The cellular damage is mediated by an alteration in the antioxidant status, which increases the concentration of reactive oxygen species (ROS) in the stationary state (oxidative stress). Therefore, interventions favoring the scavenging and/or depuration of ROS should attenuate or prevent the oxidative stress, thereby safeguarding the kidneys against damage. In this sense, this study attempts to evaluate the extent of oxidative stress in experimental urolithiasis by measuring some parameters of oxidant stress and antioxidant defenses in rat kidneys, before and after Berberis vulgaris homeopathic preparation supplementation, and to assess the role, if any, of homeopathic treatment in mitigating free radical toxicity in kidney stone disease. METHODS: Rat model of urolithiasis was established by administering 0.75% ethylene glycol (EG) in drinking water, and the effects of a homeopathic preparation of B. vulgaris root bark (HPBV) on the renal antioxidative defense system as well as on potent markers of free radical activities were investigated. RESULTS: HPBV brought about an augmentation in the activities of enzymatic antioxidants such as superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, and glucose-6-phosphate dehydrogenase and improved the nonenzymatic antioxidants, e.g., tocopherol, ascorbic acid, and glutathione. HPBV ameliorated the malondialdehyde and protein carbonyl levels and restored renal thiols almost completely. CONCLUSION: Thus, it is shown that HPBV acts as a renoprotective remedy in alleviating the renal calculi-associated oxidative damage by upregulating the antioxidant status.

Preliminary investigation on ultra high diluted B. vulgaris in experimental urolithiasis.

PURPOSE: The study focuses on the anti-urolithiasis potential of ultra-diluted homeopathic potency of Berberis vulgaris (B. vulgaris) root bark, commonly used in homeopathic system to treat renal calculi. METHODOLOGY: B. vulgaris root bark (200c, 20 µl/100 g body weight/day, p.o, for 28 days) was tested in an animal model of urolithiasis. Urolithiasis was induced in male Wistar rats by adding 0.75% ethylene glycol (EG) to drinking water. Urine and serum samples were analyzed for calcium, magnesium, phosphorus, uric acid and creatinine. Enzymic makers of renal damage (alkaline phosphatase, lactate dehydrogenase, leucine aminopeptidase and γ-glutamyl transpeptidase) were assessed in kidney and urine. Renal tissues were analyzed for oxalate content. RESULTS: Administration of EG to rats increased the levels of the stone-forming constituents calcium, phosphorus and uric acid, in urine. Levels were normalized by B. vulgaris treatment. The decrease in the urolithiasis inhibitor magnesium in urine was prevented by treatment with B. vulgaris. Serum creatinine levels were largely normalized by B. vulgaris treatment. Hyperoxaluria induced renal damage was evident from the decreased activities of tissue marker enzymes and an apparent escalation in their activity in the urine in control animals; this was prevented by B. vulgaris treatment. CONCLUSION: Homeopathic B. vulgaris root bark has strong anti-urolithiasis potential at ultra-diluted dose.

Attenuation of senescence-induced oxidative exacerbations in aged rat brain by (-)-epigallocatechin-3-gallate.

Aging is a complex biological phenomenon which involves free radicals and oxidative stress. Brain is more susceptible and vulnerable to oxidative damage due to its high-polyunsaturated fatty acid content and high rate of aerobic metabolism. Since the antioxidant defense system is diminished during aging, antioxidant supplementation might be a protective strategy against age-associated oxidative damage. The present study evaluates the antioxidant potential of (-)-epigallocatechin-3-gallate (EGCG), a major polyphenol present in green tea against age-associated oxidative damage in rat brain. Male albino rats of Wistar strain were used in the study. Group I (young) and Group II (aged) rats received saline alone orally for 30 days. Group III (young) and Group IV (aged) rats received EGCG (2mg/kg body weight/day) orally for 30 days. Antioxidant status and oxidative damage were assessed. EGCG brought about an augmentation in the activities of enzymic antioxidants like superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, glucose-6-phosphate dehydrogenase and improved the non-enzymic antioxidants like tocopherol, ascorbic acid and glutathione. EGCG ameliorated the malondialdehyde and protein carbonyl levels. Thus, EGCG has emerged out as a good antioxidant neutraceutical and a neuroprotective agent in alleviating the age-associated oxidative damage in aged rat brain.