Aceclofenac-induced hepatotoxicity:An ameliorative effect of Terminalia bellirica fruit and ellagic acid

BACKGROUND Aceclofenac(ACF),a widely used nonsteroidal anti-inflammatory drug,has been associated with a number of severe cases of clinical hepatotoxicity.Terminalia bellirica,an evergreen tree,is known to have several ethnomedicinal uses including antioxidant and hepatoprotective effects.Hence T.bellirica fruit extracts and its phytoconstituent ellagic acid(EA)are expected to provide protection against oxidative stress and liver damage produced by long-term use of ACF.AIM To evaluate the antioxidant and hepatoprotective activities of T.bellirica fruit extracts and EA against ACF-induced toxicity in albino Wistar rats.METHODS The in vitro antioxidant activities of T.bellirica fruit ethyl acetate and aqueous extracts were measured by metal ion chelation and nitric oxide radical scavenging assays.The in vivo antioxidant and hepatoprotective effects of T.bellirica extracts(200 mg/kg)and EA(40 mg/kg)in ACF-induced hepatotoxic rats were assessed in serum and liver tissue after oral administration for 21 d.Silymarin(40 mg/kg)was used as a standard control.Oxidative stress markers in the blood(ferric reducing ability of plasma and lipid peroxidation inhibition)and liver tissues(superoxide dismutase,catalase and malondialdehyde)were analyzed using standard protocols.Liver function markers such as alkaline phosphatase,glutamic pyruvic transaminase,glutamic oxaloacetic transaminase,lactate dehydrogenase,γ-glutamyl transferase,creatinine,total protein,and uric acid were evaluated in rat serum.RESULTS The T.bellirica fruit ethyl acetate extract exhibited superior metal ion chelating and nitric oxide radical scavenging abilities during in vitro antioxidant assays as compared to aqueous extracts.Oral administration of ACF in rats(15 mg/kg)for 21 d produced oxidative stress and adversely affected liver function suggesting liver injury.Treatment with extracts(ethyl acetate and aqueous),EA and silymarin accounted for a significant reduction in the adverse effects of ACF on oxidative stress and liver function markers in serum and hepatic tissue in rats.Histopathological evaluation of the liver indicated that the extracts and EA significantly decreased the degree of liver damage.The in vivo efficacy of EA was higher than T.bellirica fruit extracts.Of these extracts,ethyl acetate extract revealed comparatively better antioxidant and hepatoprotective activity.CONCLUSION Ellagic acid and T.bellirica fruit extracts exhibited considerable hepatoprotective and antioxidant activities in long-term ACF-treated rats.

Role of baicalin as a potential therapeutic agent in hepatobiliary and gastrointestinal disorders:A review

Baicalin is a natural bioactive compound derived from Scutellaria baicalensis,which is extensively used in traditional Chinese medicine.A literature survey demonstrated the broad spectrum of health benefits of baicalin such as antioxidant,anticancer,anti-inflammatory,antimicrobial,cardio-protective,hepatoprotective,renal protective,and neuroprotective properties.Baicalin is hydrolyzed to its metabolite baicalein by the action of gut microbiota,which is further reconverted to baicalin via phase 2 metabolism in the liver.Many studies have suggested that baicalin exhibits therapeutic potential against several types of hepatic disorders including hepatic fibrosis,xenobiotic-induced liver injury,fatty liver disease,viral hepatitis,cholestasis,ulcerative colitis,hepatocellular and colorectal cancer.During in vitro and in vivo examinations,it has been observed that baicalin showed a protective role against liver and gut-associated abnormalities by modifying several signaling pathways such as nuclear factor-kappa B,transforming growth factor beta 1/SMAD3,sirtuin 1,p38/mitogen-activated protein kinase/Janus kinase,and calcium/calmodulin-dependent protein kinase kinaseβ/adenosine monophosphate-activated protein kinase/acetyl-coenzyme A carboxylase pathways.Furthermore,baicalin also regulates the expression of fibrotic genes such as smooth muscle actin,connective tissue growth factor,β-catenin,and inflammatory cytokines such as interferon gamma,interleukin-6(IL-6),tumor necrosis factor-alpha,and IL-1β,and attenuates the production of apoptotic proteins such as caspase-3,caspase-9 and B-cell lymphoma 2.However,due to its low solubility and poor bioavailability,widespread therapeutic applications of baicalin still remain a challenge.This review summarized the hepatic and gastrointestinal protective attributes of baicalin with an emphasis on the molecular mechanisms that regulate the interaction of baicalin with the gut microbiota.

A novel approach for part family formation using K-means algorithm

The reconfigurable manufacturing system （RMS） is the next step in manufacturing, allowing the production of any quantity of highly customized and complex parts together with the benefits of mass production. In RMSs, parts are grouped into families, each of which requires a specific system configuration. Initially system is configured to produce the first family of parts. Once it is finished, the system will be reconfigured in order to produce the second family, and so forth. The effectiveness of a RMS depends on the formation of the optimum set of part families addressing various recon figurability issues. The aim of this work is to establish a methodology for grouping parts into families for effective working of RMS. The methodology carried out in two phases. In the first phase, the correlation matrix is used as similarity coefficient matrix. In the second phase, agglomerative hier archical Kmeans algorithm is used for the parts family for mation resulting in an optimum set of part families for reconfigurable manufacturing system.