Hepatoprotective Effects of Bioflavonoid Luteolin Using Self-Nanoemulsifying Drug Delivery System

Luteolin (LUT) is a natural pharmaceutical compound that is weakly water soluble and has low bioavailability when taken orally. As a result, the goal of this research was to create self-nanoemulsifying drug delivery systems (SNEDDS) for LUT in an attempt to improve its in vitro dissolution and hepatoprotective effects, resulting in increased oral bioavailability. Using the aqueous phase titration approach and the creation of pseudo-ternary phase diagrams with Capryol-PGMC (oil phase), Tween-80 (surfactant), and Transcutol-HP (co-emulsifier), various SNEDDS of LUT were generated. SNEDDS were assessed for droplet size, polydispersity index (PDI), zeta potential (ZP), refractive index (RI), and percent of transmittance (percent T) after undergoing several thermodynamic stability and self-nanoemulsification experiments. When compared to LUT suspension, the developed SNEDDS revealed considerable LUT release from all SNEDDS. Droplet size was 40 nm, PDI was <0.3, ZP was −30.58 mV, RI was 1.40, percent T was >98 percent, and drug release profile was >96 percent in optimized SNEDDS of LUT. For in vivo hepatoprotective testing in rats, optimized SNEDDS was chosen. When compared to LUT suspension, hepatoprotective tests showed that optimized LUT SNEDDS had a substantial hepatoprotective impact. The findings of this investigation suggested that SNEDDS could improve bioflavonoid LUT dissolution rate and therapeutic efficacy.

Antioxidative Role of Azadirachta Indica Vit. E in Restoration of Histopathological changes in Acetaminophen induced liver

Aim: To study the comparative effect of Acetaminophen induced liver toxicity with aqueous extract of Azadirachta Indica (Neem) and vitamin E on the basis of liver Histopathology. Methods: Sixty Wistar Rats of both sexes were split into four groups. Each group contained 15 animals. The control group was group A, Group B was treated orally with single dose of Paracetamol 2 mg / kg by weight, Group C was administrated orally with aqueous Neem extract 500 mg/kg +2 mg/Kg by weight oral Paracetamol, and Group D was given orally paracetamol+Neem extract+Vitamin E with 100mg/Kg/body weight for 15 days. Rats from all groups were decapitated, the liver was sliced, and liver tissues were taken for histological examination. Tissue samples were fixed in 10% formaldehyde, embedding in paraffin followed by Hematoxylin and Eosin dye (H&E) and observed under 400x magnification with a digital microscope. Results: On Histopathological examination of the rat`s liver in we found that the control group had a normal appearance, colour, and uniform surface without any necrosis. Group B showed severe necrosis and haemorrhagic patches. In comparison, Group C revealed normal appearance, colour, and smooth surface with no necrotic alterations. Livers from the group D looked virtually normal in terms of colour, undersurfaces, and organ weight. However, hepatoprotective effects were observed in the Group C and D. Therefore, we can conclude that Azadirachta indica and Vitamin E could serve as a good medication for defence against liver injury. Conclusion: Our findings showed thatextract of Azadirachta Indica and Vitamin E exhibited hepatoprotective effects on the Wistar rats that were subjected to Acetaminophen. Key words: Azadirachta Indica leaf extract, Vitamin E, hepatoprotective Paracetamol, Wistar rats.

Evaluation of Hypolipidemic and Hepatoprotective Effects of Linum usitatissimum L. Seeds on Hypercholesterolemic Rats

Background: Hyperlipidaemia is a chronic progressive disease, which encompasses various genetic and acquired conditions resulting in inappropriately elevated lipid levels in humans. Several preclinical and clinical studies have demonstrated that dietary supplementation with Linum Usitatissimum have beneficial cardiovascular effects like antihypertensive action, antiatherogenic effects, lowering of cholesterol, anti-inflammatory action and inhibition of arrhythmia. There are few studies on hepatoprotective effects of flax seeds in hyperlipidemic animal models. Aim and objectives: Hence, this study was undertaken to evaluate the hypolipidemic and hepatoprotective effect of Linum seeds. Methods: The study was conducted for the period of two months in Department of Pharmacology KIMS, Bhubaneswar. Total 36 Albino wistar rats were taken and divided into 6 groups containing 6 rats each. Group II was hypercholesterolemic (HC) control, Group III was treatment control and Group IV to VI rats were given different doses of extract. Blood samples were taken at the end of two months. Results: All the values are expressed as Mean±SD (standard deviation). Significant decrease in lipid parameters and liver enzymes is seen at the end of two months in all 3 groups receiving the extract, where the highest dose of extract used, is near to the standard drug. Conclusion: From this study, it can be concluded that the addition of the flaxseeds to the diet may alleviate the rise in circulating cholesterol levels induced by the high cholesterol diet through its content of alfa-linolenic acid (ALA) and lignins. The hepatoprotective role of flaxseed in hypercholesterolaemia has also been demonstrated in this this study.

Rhizophora Mucronata Lam. (Mangrove) Bark Extract Prevents Ethanol-induced Liver Injury, Oxidative Stress and Apoptosis in Swiss Albino Mice

The bark extract of Rhizophora mucronata (BERM) was recently reported for its prominent in vitro protective effects against liver cell line toxicity caused by various toxicants, including ethanol. Here, we aimed to verify the in vivo hepatoprotective effects of BERM against ethanol intoxication. An oral administration of different concentrations (100, 200, and 400 mg/kg) of BERM prior to high-dose ethanol via intraperitoneal injection was performed in mice. On the 7th day, liver and kidney sections were dissected out for histopathological examination. The ethanol intoxication caused large areas of liver necrosis while the kidneys were not affected. Pre-BERM administration decreased ethanol-induced liver injury, as compared to the mice treated with ethanol alone. In addition, the pre-BERM administration resulted in a decrement in the level of ethanol-induced oxidative stress, revealed by a concomitant increase of GSH and a decrease of MDA hepatic levels. The BERM extract also reversed the ethanol-induced liver injury and hepatotoxicity, characterized by the low detection of TNF-α gene expression level and fragmented DNA, respectively. Altogether, BERM extract exerts antioxidative activities and present promising hepatoprotective effects against ethanol intoxication. The identification of the related bioactive compounds will be of interest for future use at physiological concentrations in ethanol-intoxicated individuals.

Hypoglycemic and Hepatoprotective Effects of Dried and Rice-Fried Psidium guajava Leaves in Diabetic Rats

Psidium guajava leaves (PGL) have been long used as an adjuvant therapy for diabetics. The present study evaluated the in vivo hypoglycemic and hepatoprotective effects of dried and the rice-fried PGL decoctions (PGLD and RPGLD). Our results indicated that both PGLD and RPGLD could significantly decrease the contents of fasting blood glucose (FBG) and haemoglobin A1c (HbA1c) in diabetic rats. Compared with the HFD/STZ (high-fat diet with streptozotocin) group, the PGLD and RPGLD-treated diabetic rats showed different degrees of recovery against the liver pathological changes. The upregulated expressions of glucokinase (GK), glucose transporter 2 (GLUT2), insulin growth factor-1 (IGF-1), insulin receptor substrate-1 (IRS-1), and insulin receptor substrate-2 (IRS-2) in PGLD and RPGLD-treated groups were observed. In general, RPGLD exhibited a much better antidiabetic effect than PGLD, which was further verified by the comprehensive evaluation with the TOPSIS method. Besides, HPLC (high-performance liquid chromatography) and UPLC-MS/MS (ultra-performance liquid chromatography-tandem mass spectrometry) analyses revealed that the contents of the primary constituents (ellagic acid, hyperoside, isoquercitroside, reynoutrin, guaijaverin, auicularin, and quercetin) in RPGLD increased obviously compared with PGLD. These results shed new light on the antidiabetic potential and mechanism of PGL, as well as the “higher efficacy” of the rice-fried processing method in traditional Chinese medicine.

Mechanism of drug-induced liver injury and hepatoprotective effects of natural drugs

Drug-induced liver injury (DILI) is a common adverse drug reaction (ADR) and a serious threat to health that affects disease treatments. At present, no targeted clinical drugs are available for DILI. Traditional natural medicines have been widely used as health products. Some natural medicines exert specific hepatoprotective effects, with few side effects and significant clinical efficacy. Thus, natural medicines may be a promising direction for DILI treatment. In this review, we summarize the current knowledge, common drugs and mechanisms of DILI, as well as the clinical trials of natural drugs and their bioactive components in anticipation of the future development of potential hepatoprotective drugs.

Hepatoprotective effects of Cassiae Semen on mice with non-alcoholic fatty liver disease based on gut microbiota

Cassiae Semen (CS), the seeds of Cassia obtusifolia L. and C. tora L, have a long medicinal history in China, with suggestions for it to relieve constipation and exert hepatoprotective effects. However, the underlying mechanisms are still unclear. In this study, mice with high-fat diet (HFD)-induced non-alcoholic fatty liver disease (NAFLD) were used to study the hepatoprotective effects of CS. The relationship between gut microbiota and hepatoprotective effect mechanisms mediated by CS extracts, the total aglycone extracts of CS, rubrofusarin-6-β-gentiobioside, and aurantio-obtusin were examined. Our data indicate that CS extracts and components confer a protective effect by ameliorating lipid accumulation, intestinal barrier damage, liver damage, and inflammation on HFD-induced liver injury. Meanwhile, fecal microbe transplantation exerted the pharmacological effect of CS on HFD-fed mice; however, the efficacy of CS was inhibited or eliminated by antibiotic-induced dysbiosis. In conclusion, the therapeutic effects of CS on NAFLD were closely related to the gut microbiota, suggesting a role for TCM in treating disease.