Preparation and Characterisation of Liposomes of Bergenia Ciliata Extract and Evaluation of their Hepatoprotective Activity.

Acute liver damage (ALD) can cause biochemical and pathological changes, which can lead to major complications and even death. The goal of the study was to examine the therapeutic efficacy of liposomes of Bergenia ciliata extract against thioacetamide-induced liver damage in rats. Liposomal batches of B. ciliata extract were prepared by altering the kind and amount of phospholipids and characterized through various physiochemical properties such as laser diffraction, TEM, encapsulation efficiency, stability and in-vitro release studies. In-vivo hepatoprotective studies were performed on TAA-induced acute hepatic damage model. Further, in-silico studies of bergenin against the three hepatic damage markers viz. TGF-ß1, TNF-α and interleukin-6 were also performed. Laser diffraction and TEM showed that most stable liposome batch of B. ciliata extract were in the range of 678-1170 nm with encapsulation efficiency of 84.3±3.5. Extract was found to be rapidly dissociated from B. ciliata liposomes in HCl than PBS, according to in-vitro release data. In-vivo data revealed a significant decline in LFT indicators, amelioration of pathological changes and high bergenin bioavailability in the liposomal group. Protective activity of bergenin against ALD targets like TGF-ß1, TNF-α and interleukin-6 was anticipated via molecular docking research. As a result, the current findings of the study indicate that B. ciliata liposomes and bergenin have promising ameliorative potential in the management of ALD.

Myopia, its prevalence, current therapeutic strategy and recent developments: A Review.

Myopia is a widespread and complex refractive error in which a person's ability to see distant objects clearly is impaired. Its prevalence rate is increasing worldwide, and as per WHO, it is projected to increase from 22% in 2000 to 52% by 2050. It is more prevalent in developed, industrial areas and affects individuals of all ages. There are a number of treatments available for the control of myopia, such as glasses, contact lenses, laser surgery, and pharmaceuticals agents. However, these treatments are less beneficial and have significant side effects. A novel molecule, 7-methylxanthine (7-MX), has been found to be a highly beneficial alternate in the treatment of myopia and excessive eye elongation. Many preclinical and clinical studies showed that 7-MX is effective for the treatment of myopia and is presently under phase II of clinical investigation. We have also investigated preclinical toxicity studies such as acute, sub-acute, sub-chronic, and chronic on rats. In these studies, 7-MX was found to be non-toxic as compared to other reported anti-myopic agents. Moreover, as an ideal drug, 7-MX is observed to have no or low toxicity, brain permeability, non-allergic, higher oral administration efficacy, and low treatment costs and thus qualifies for the long-term treatment of myopia. This review article on 7-MX as an alternative to myopia treatment will highlight recent findings from well-designed preclinical and clinical trials and propose a potential future therapy.

Micro RNAs as Emerging Therapeutic Targets in Liver Diseases.

MicroRNAs (MiRNAs) are endogenous non-coding small RNA molecules that regulate gene expression in plants, animals and some viruses. Both normal and pathological liver processes are regulated by miRNAs. Recent research indicated that miRNAs have been implicated in liver diseases caused by viral hepatitis (Hepatitis B and Hepatitis C), metabolic problems, alcohol and drug abuse. Because altered miRNA expression is linked to liver metabolic dysregulation, liver damage, liver fibrosis, and tumour growth, miRNAs are promising therapeutic targets for the detection and treatment of liver diseases. In this review, we summarise the current knowledge about the role of microRNAs in acute and chronic liver diseases, including hepatocellular carcinoma. We cover the miRNA-based therapy for liver disorders as well as the use of miRNAs as biomarkers for early diagnosis, prognosis and assessment of liver diseases. The investigation of miRNAs in liver diseases will provide a better understanding of the pathogeneses, identification of biomarkers and therapeutic targets for liver diseases in the future.

ß-Carotene inhibits NF-κB and restrains diethylnitrosamine-induced hepatic inflammation in Wistar rats.

ß-Carotene exhibits antioxidant and hepatoprotective activities via a multitude of biochemical mechanisms. However, the action mechanism involved in antioxidant and anti-inflammatory effects of this carotene in chronic liver diseases is not fully understood. In the present investigation, we have attempted to outline a plausible mechanism of ß-carotene action against liver fibrosis in albino Wistar rats. To induce hepatic fibrosis, diethylnitrosamine (DEN) was administered in experimental rats for two weeks. DEN treated rats were divided into four groups, wherein each group comprised of five rats. ß-Carotene supplement attenuated DEN-induced elevation in LFT markers (P < 0.05); averted depletion of glycogen (24%, P < 0.05) and, increased nitrite (P < 0.05), hydroxyproline (~67%, P < 0.05) and collagen levels (~65%, P < 0.05). Confocal microscopy of tissue sections stained with picrosirius red revealed accrued collagen in DEN-administered group, which was found to be reduced by ß-carotene supplementation. Furthermore, ß-carotene decreased the expression of iNOS/NOS-2 and NF-κB, as revealed by immunohistochemistry and Western immunoblotting. Collectively, these results demonstrate that ß-carotene mitigates experimental liver fibrosis via inhibition of iNOS and NF-κB in-vivo. Thus, ß-carotene may be suggested as a possible nutraceutical to curb experimental liver fibrosis.

Nrf2 protein as a therapeutic target during diethylnitrosamine-induced liver injury ameliorated by ß-carotene-reduced graphene oxide (ßC-rGO) nanocomposite.

Oxidative stress plays a central role in the incidence of liver injury. Nuclear factor erythroid 2-related factor-2 (Nrf2) is a key protein regulator of antioxidant response elements (ARE)-mediated gene expression. Thus, Nrf2 can be regarded as a plausible therapeutic target during liver injury. ß-Carotene is implicated as one of the important antioxidant with diverse health benefits. The delivery of ß-carotene to the target tissue has been debatable due to its low bioavailability, poor water solubility and instability. Here, a nanocomposite of ß-carotene with reduced graphene oxide (ßC-rGO) has been developed to demonstrate its pronounced effect in regulating Nrf2 to trigger protection against diethylnitrosamine (DEN)-induced hepatic fibrosis in rats. The rGO and ßC-rGO samples were characterised by scanning electron microscopy (SEM), energy dispersive X-ray (EDX), transmission electron microscopy (TEM) and Fourier transform infrared (FTIR) spectroscopy. Progress of disease was monitored through ultrasonography, in vitro liver and serum biochemistry (alanine transaminase, aspartate transaminase, alkaline phosphatase, bilirubin, lipid peroxidation, protein carbonyls, superoxide dismutase, catalase, glutathione-S-transferase, Nrf2, vitamin-A, retinol dehydrogenase), histopathology, confocal and ultrastructural studies. In fibrotic animals liver biochemistry was significantly altered along with massive changes in liver anatomy. ßC-rGO ameliorates experimental fibrogenesis and restores liver functioning due to increased availability of ß-carotene in the liver. It is suggested that ßC-rGO nanocomposite promotes cellular antioxidant status via upregulation of Nrf2 protein factor and invigorate hepatic stellate cells (HSCs) through restoring vitamin-A.

Herbal remedies for liver fibrosis: A review on the mode of action of fifty herbs.

Liver fibrosis is a dynamic pathological condition which can be slowed down in its initial phases. Without proper clinical management of fibrosis, progressive liver damage may lead to cirrhosis and ultimately to liver failure or primary liver cancer, which are irreversible conditions. Therefore, in order to cure fibrotic damage to liver, its early stages should be the centre of attention. In this context, some supplements and 'complementary and alternative medicine (CAM)' deserve specific mention, because of their already recognized natural way of healing and long lasting curative effects. Moreover, CAM display negligible side effects and hence it is gaining worldwide importance in clinical practices. In particular, herbal medicines are now replacing synthetic pharmaceuticals and looked upon as the sources of novel bioactive substances. To develop satisfactory herbal combinations for treating liver fibrosis, phytoproducts need to be systematically evaluated for their potency as anti-fibrotic, anti-hepatotoxic and antioxidant agents. More importantly, the identified herb/agent should have the remarkable tendency to stimulate hepatocytes regeneration. The present review is a systematic account of at least fifty medicinal herbs and their products which in experimental models have demonstrated antifibrotic activity and thus, most likely candidates to offer therapeutic protection to liver. Nevertheless, much additional work is still needed to explore molecular pathways to discover potential applications of these medicines so as to open up new vistas in biomedical research.

Pomegranate action in curbing the incidence of liver injury triggered by Diethylnitrosamine by declining oxidative stress via Nrf2 and NFκB regulation.

Unearthing and employment of healthy substitutes is now in demand to tackle a number of diseases due to the excessive repercussions of synthetic drugs. In this frame of reference pomegranate juice (PGJ) is a boon comprising of anthocyanins and hydrolysable tannins, known for its anti-oxidant and anti-inflammatory properties. Despite various documented roles of PGJ, there are no studies on antifibrotic potential in NDEA-induced mammalian liver fibrotic model. Hepatic fibrosis in rats was induced by the intra-peritoneal injection of NDEA (10 mlkg-1b.wt. of 1% NDEA) in two weeks. Biochemical, histopathological and ultra-structural studies were carried out on control, fibrotic and treated rats. The liver function indices and LPO were increased significantly by intoxication of NDEA. The antioxidant status was disturbed with the decrease in SOD, GST and catalase in the liver and membrane-ATPases as well. Histopathological observations by H&E, M&T, picro-sirius and ultra-structural scrutiny by SEM and TEM indicated liver damage and increase in COX2 and α-SMA by NDEA which was successfully rectified by the supplementation of PGJ. PGJ abrogates liver fibrosis instigated by NDEA in Wistar rats by declining oxidative stress via regulation of Nrf2 and NFκB. These findings point towards pomegranate as a potential and efficacious therapeutic agent against liver fibrosis.