Lepidium pinn(lt~fidum remediate CCL4 induced oxidative damage in liver by regulating ER stress markers, inflammatory mediators and anti-apoptotic markers in rat.

Abstract

Medicinal plants comprised of several bioactive chemical constituents which are providing significant compounds directly or indirectly which has proved to be an effective source to face the current healthcare challenges including cancer, infectious disorders, cardiovascular diseases, neurodegenerative diseases and several other types of lethal ailments. Lepidium pinnatifidum one of significant therapeutic plant which is traditionally used as a medicine in treating diseases like pile, constipation, menstrual pain, diarrhea etc. The pertinacity of our research study is to examine the hepatoprotective potential of Lepidium pinnatifidum against CCk Whole plant of Lepidium pinnatifidum was dried with crude methanol and then its fraction were made in several solvents in ascending order of polar activity starting from n-hexane (LPH), then chloroform (LPC), then ethyl acetate (LPE), and then butanol (LPB) and in the last aqueous fraction (LPA). Qualitative analysis of L. pinnatifidum verifies the existence of phenolic and flavonoid content, also validates the occurrence of saponins, cumarins, alkaloids, tannins and glycosides. Terpenoids are absent in all fractions except in hexane fraction. Hepatoprotective potential of hexane fraction Lepidium pinnatifidum was evaluated against oxidative damage in liver of rats mediated by carbon tetrachloride. At three levels; biochemical, histological and molecular level; liver tissues were studied. Treatment with plant fraction (LPH) in comparison to oxidative stress mediated by CCl4 was provided to rats on alternate days for four weeks. Amount of glutathione (OSH) and antioxidant enzymes (CAT, SOD, POD) activity in liver were decreased in CCl4 group in comparison to group treated with plant extract. However, in the case of peroxidation (TBARS) reduced level were present in group with plant treatment while CCl4 group has relatively enhanced levels. Likewise, H202 and nitrite levels were markedly repressed in group receiving plant treatment in comparison to CCl4 group. Rats with plant extract treatment showed restorative effects against CCl4 toxicity in dose dependent manner. These results were additionally validated by the microanatomical study. Histopathological analysis revealed hepatoprotective potential of LPH with improved anatomical structures at high dose (400 mg/kg), which was more vii A bstract productive in reducing the intoxications caused by CCL4 as compared to low dose (200 mg/kg). At molecular level, hepatoprotection from CCL4 induced toxicity in liver tissues was also studied. As CCL4 is one of the potent hepatotoxin, it has caused prolonged Oxidative stress which leads to ER stress, inflammation and if given for longer period of time apoptosis can occur. In order to study the hepatoprotective effect of plant extract ER stress markers, Inflammatory mediators and anti-apoptotic markers were studied. In groups treated with CCL4 their expression level was elevated except ani-apoptotic gene whose level was depressed. But, in the rats with plant treatment the results were in opposite direction i.e. expression level of all the genes were reduced and in Bcl-2 it is increased close to the normal thereby elaborating the protective potential of plant extract. The results elucidate that Lepidium pinnatifidum is a medicinal plant consisting of both antioxidant and hepatoprotective nature. Besides being a prominent antioxidant plant, it also illustrate promising activities like anti-microbial, anti- inflammatory and also anti-depressant activity due to the presence oflarge numbers ofphytochemicals. Hence, the current study assures the therapeutic significance in Ayurvedic therapies, which could be the durable support to the advancement of new drugs.