Novel Findings regarding the Bioactivity of the Natural Blue Pigment Genipin in Human Diseases

Genipin is an important monoterpene iridoid compound isolated from Gardenia jasminoides J.Ellis fruits and from Genipa americana fruits, or genipap. It is a precursor of a blue pigment which may be attractive alternative to existing food dyes and it possesses various potential therapeutic properties such as anti-cancer, anti-diabetic and hepatoprotective activity. Biomedical studies also show that genipin may act as a neuroprotective drug. This review describes new aspects of the bioactivity of genipin against various diseases, as well as its toxicity and industrial applications, and presents its potential mechanism of action.

COMPARISON OF HEPATOPROTECTIVE ACTIVITY OF NISHA LAUHA (NL) AND NISHA LAUHA WITHOUT LAUHA BHASMA (NLWL) AGAINST CCL4 INDUCED HEPATOTOXICITY IN WISTAR RATS

Introduction: Many herbal drugs are used to treat liver diseases, but the dose of the herbal drug is high, and they have lesser palatability. An ideal medicine is a medicine that is effective, easy palatable and produces quick action in a low dose. It is possible by adding metals like Lauha (Iron) to the herbal drugs. Objective: To compare the hepatoprotective effect of Nisha Lauha (NL) and Nisha Lauha without Lauha Bhasma (NLWL) in experimental rats. Materials and methods: 40 rats were taken divided into five groups, and each group contained eight rats. Among these groups, four groups receive 0.2 ml of injection containing the 0.1 ml CCL4 plus 0.1 ml liquid paraffin given intraperitoneally for 28 days to induce Hepatotoxicity. Both Test groups received NL and NLWL at a dose of 45mg/kg bd. wt. and 450mg/kg bd. wt. respectively for 28 days. The standard group receives silymarin at a 100 mg/kg bd dose. wt. for 28 days by oral route. The hepatoprotective effect was analyzed using biochemical parameters and histopathological study of the liver. Results: Both the Test and standard groups do not show toxic effects against CCL4 induced hepatotoxicity and lower the dose of the herbal drug due to the addition of Lauha. Conclusion: The result suggests that both test group NL and NL without Lauha Bhasma shows the hepatoprotective activity as equivalent to standard drug silymarin. The addition of Lauha Bhasma to herbal drugs decreases the dose without affecting the drug’s efficacy against the hepatoprotective effect.

Hepatoprotective activity of the ethanolic extract of Morus indica roots from Indian Bodo tribes

The roots of Morus species are well described in the Pharmacopoeia of the People's Republic of China (ChP) for its traditional use in treating liver fibrosis due to its hepatoprotective property. However, little is known about the hepatoprotective effect of the roots of Morus indica L. (RoMi), and the pharmacological mechanism(s) are uncertain due to its intricacy. Therefore, this study evaluates the hepatoprotective activity of the ethanolic extract of RoMi (eRoMi) against the CCl4-induced in-vivo animal model at different dosages (100 and 200 mg/kg BW) in comparison with silymarin as a positive control. The hepatoprotective activity of eRoMi was evaluated by measuring the levels of serum biomarkers, hepatic antioxidant enzymes and was verified by histological studies. Interestingly, 1,2-bis(trimethylsilyl) benzene, 1,4-phenylenebis (trimethylsilane), 2,4,6-cycloheptatriene-1-one, 3,5-bis-trimethylsilyl and α-amyrin were the active components found in eRoMi as detected by GC–MS. Oral administration of eRoMi (200 mg/kg BW) to rats significantly protected serum biochemical parameters (increased ALT, AST, LDH, bilirubin and GGT as well as depletion of antioxidant enzymes and hepatic GSH) and elevation in hepatic lipid peroxidation as compared to CCl4-treated rats. The hematological indices such as erythrocytes, hemoglobin, monocytes and lymphocytes were also normal in eRoMi-treated rats. The histopathological evaluation indicated a significant restoration of liver structure as compared to silymarin. This study is the first scientific validation for the traditional use of eRoMi to understand its hepatoprotective activity.

Ameliorative effect of ethanolic extract of Limnophila rugosa (Scrophulariaceae) in paracetamol- and carbon tetrachloride-induced hepatotoxicity in rats

Background Limnophila rugosa (Scrophulariaceae) is a perennial aquatic plant used as a diuretic and digestive tonic as well as in the treatment of diarrhea, dysentery, dyspepsia and urinary ailments. Genus Limnophila has been reported as hepatoprotective. The present study was undertaken to evaluate the hepatoprotective activity of the ethanolic extract of L. rugosa aerial part in paracetamol- and carbon tetrachloride-induced (CCl4) hepatotoxicity in albino Wistar rats. Ethanolic extract was subjected to high-performance liquid chromatography (HPLC) analysis for the estimation of phenolic and flavonoid compounds and gas chromatography–mass spectrometry (GC–MS) analysis for phytochemical analysis. The in vitro antioxidant activity was carried out by 2,2-diphenyl-1-picrylhydrazyl, nitric oxide radical and hydrogen peroxide assay. Hepatoprotective potential of L. rugosa was studied in paracetamol (750 mg/mg)- and CCl4 (1.25 ml/kg)-induced liver damage in albino rats at dose 200 and 300 mg/kg using silymarin (100 mg/kg) as standard. Lipid peroxidation, superoxide dismutase (SOD), catalase (CAT) and glutathione (GSH) were determined in liver tissue homogenate. Serum biochemical and histopathological examination was performed. Molecular docking analysis was performed to understand the molecular mechanism of hepatoprotective activity. Results HPLC analysis revealed predominance of rutin. GC–MS analysis revealed camphor as principal component. Ethanolic extract exhibited significant concentration-dependent scavenging efficacy. The altered biochemical chemical parameters: aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, bilirubin, cholesterol, albumin, globulin and total protein, were significantly improved at 200 and 300 mg/kg in experimental rats. Extract signified hepatoprotective by decreasing lipid peroxidation and upregulating SOD, CAT and GSH. The findings were well supported by histological analysis. 2-Butyl-2, 7-octadien-1-ol (-5.8) and camphor (-4.8) gave the highest docking score on the transforming growth factor-β1. Conclusions The ameliorative effect of L. rugosa in the rat model of hepatotoxicity could be attributed to its antioxidant potential and bioactive principles such as betulin, 5-hydroxy-6,7,4′-trimethoxyflavone (salvigenin), betulinic acid, ursolic acid, 3-octanol, acetophenone, anisylacetone, caryophyllene, cis-anethole and the compounds camphor and 2-butyl-2,7-octadien-1-ol identified from GC–MS analysis.

The hematological and histological studies for the hepatoprotective-like effect of the hydromethanolic extract and the fractions of Viola serpens Wall.

Traditionally, Viola serpens has been used in the treatment of several human disorders including liver diseases without any scientific evidence. As the current therapies are not very effective and face challenges of unwanted effects and patient compliance, therefore more effective and safe agents are highly needed. The current study aimed to evaluate the hepatoprotective potential of the crude extract and subsequent fractions of the whole plant in the in-vivo model using various hematological and histopathological parameters followed by an HPLC study for the identification of phenolic compounds. Rabbits (1000-1200 g) were used in the study. Paracetamol (2g) was used to induce hepatotoxicity in experimental rabbits. The plant extract was used in two doses (150 and 300 mg/kg body weights) for eight days. The hematological parameters AST, ALT and ALP values were determined along with the histopathology of the liver. Phenolic compounds were identified by high-performance liquid chromatography (HPLC) Agilent-1260 infinity from their retention time, UV spectra and available standards while quantification was done taking the percent peak area. The doses 150 and 300 mg/kg body weight seemed to be more effective. The hematological values and the histopathological slides show the hepatoprotective effect of the plant. Regeneration indicated the presence of nuclei, nuclear cleaning, prominent nucleoli, RBC’s, central veins and plates of hepatocytes. The HPLC studies revealed the presence of a number of phenicol compounds. The crude extract and the subsequent fractions of the plant possess strong hepatoprotective activity, providing a scientific rationale for its uses in the treatment of liver toxicities.

Optimization and Evaluation of Piperine Loaded Herbosomes for their Antioxidant and Hepatoprotective Potential

Piperine is classified as a class II drug in the biopharmaceutical classification system due to its low aqueous solubility. As a result, piperine herbosomes were created to improve the dissolution rate and in vivo liver protecting activity of piperine and physico-chemical characteristics were used to confirm herbosome formation. The piperine-herbosome formulation revealed spherical particle size of all formulations from P1-P10 and found142.4 ± 0.98 nm for best piperine-herbosome formulation (P2) and a PDI value of 0.237, indicating a homogeneous population of piperine loaded vesicles. In vitro drug release rate and percent entrapment efficiency were determined for all formulations P1-P25 and found to be 95.306 ± 0.21 and 97.306 ± 0.65 in 12 h, respectively for best piperine-herbosome formulation (P2). It exemplifies the complex’s long-term releasing capability. This information suggests that it may have a longer retention time inside the body, extending the duration of effect. The antioxidant potential of pure piperine was determined using the DPPH scavenging method, with an IC50 value of 107.59 ± 0.11 g/mL compared to a formulation with an IC50 value of 93.926 ± 0.03 g/mL. Swiss albino mice of either sex were utilized for the evaluation of hepatoprotective activity. On the 8th day, the hepatotoxicity was caused by giving a single oral dosage of CCl4 (0.5 mL) and the parameters were evaluated on the 9th day. This formulation has the best optimized based on drug content and drug entrapment. Serum glutamic oxaloacetic transaminase (SGOT), serum glutamic-pyruvic transaminase (SGPT), alkaline phosphatase (ALP) and total bilirubin were among the biochemical markers measured. In comparison to normal control (161 ± 0.31 IU/L, 52.78 ± 0.28 IU/L, 121.12 ± 0.14 IU/L and 0.633 ± 1.44 IU/L) and P2 formulation (163.23 ± 0.49 IU/L, 66.9 ± 0.05 IU/L, 128.3 ± 1.15 IU/L and 0.645 ± 0.67 IU/L respectively).

EVALUATION OF IN VITRO ANTIOXIDANT AND IN VIVO HEPATOPROTECTIVE ACTIVITY OF BAUHINIA VARIEGATA ROOT ETHANOLIC EXTRACT AGAINST CCL4 INDUCED LIVER INJURY IN RATS

Plant derived herbal formulations and remedies provide an effective means for the treatment of various types of disease that are dogmatic and incurable in other types of systems of medicines, but it is essential to explore and establish the scientific basis for therapeutic action of herbal plant medicines. Bauhinia variegata root ethanolic extract was studied for the hepatoprotective activity against CCl4 induced liver injury in rats. For estimation of hepatoprotective role of B. variegata, total bilirubin count, serum enzymes level and finally histopathological study of liver were performed. This extract’s DPPH radical scavenging potential was also studied. The ethanolic extract of B. variegata root administered orally to animal showed significant depletion in CCL4 induced increased level of SGPT, SGOT, ALP and total bilirubin concentration. Significantly (p<0.05), hepatotoxicity is reversed by treatment with Liv 52 syrup also. For initiation of biochemical analysis, the histopathological studies are provided supportive evidence. This extract also showed better activity in quenching DPPH radical. The ethanolic extract of B. variegata root shows antioxidant property by preventing the formation of trichloromethyl peroxy radicals, and thus reduce tissue damage, which is examined and confirmed by the histopathological studies. Therefore, the hepatoprotective activity of ethanolic extract of B. variegata root may be due to its antioxidant potential. Previously studies have reported that plants containing flavonoids possess antioxidant properties. The antioxidant and hepatoprotective properties of the test plant may be attributed to the presence flavonoids. B. variegata root ethanolic extract is shown to have hepatoprotective and antioxidant action.