Hepatoprotective Potential Research Articles

Composition and hepatoprotective effect of geopropolis of Melipona subnitida

Background: Geopropolis produced by bees of the subfamily Meliponinae (Hymenoptera, Apidae) is used in Brazilian popular medicine for the treatment of different diseases. The aim of the present work was to evaluate the hepatoprotective potential of the hydroethanolic extract from geopropolis (HPE) produced by Melipona subnitida Ducke. Additionally, the chemical composition of HPE and antioxidant activity were also evaluated. Methods: The hepatoprotective potential of HPE was evaluated by serum biochemical profile and macroscopic and histological examination of the liver of 24 Wistar rats (Rattus norvegicus), distributed in four experimental groups: G1 (negative control), G2 (HPE), G3 (HPE plus acetaminophen), G4 (acetaminophen - positive control). The HPLC-DADESI-MS/MS method was used to evaluate the chemical composition of HPE and the 2,2-diphenyl-1-picrylhydrazyl (DPPH) method was used to measure the antioxidant activity of geopropolis. Results: While HPE alone (G2) caused no liver injury, the livers of G4 exhibited color and histological alterations, extensive hemorrhagic suffusions, friable consistence, yellowish-white multifocal areas, degeneration and diffuse hepatocyte necrosis, in addition to altered levels of urea and enzymes TGO (glutamic-oxaloacetic transaminase) and TGP (glutamic pyruvic transaminase). HPE was shown to exert hepatoprotective effect in G3 animals, only mild hemorrhage and focal areas of vacuolar degeneration and hepatocyte necrosis having been observed. The geopropolis analyzed contains a high diversity of phenolic compounds, including chalcones, flavones and flavonols. high antioxidant activity was determined (IC50=48 μg/mL). Conclusions: The hydroethanolic extract of the geopropolis produced by M. subnitida has a high diversity of phenolic compounds and a high antioxidant activity. It has hepatoprotective action, as evidenced by a reduction in the levels of enzymaraes and the severity of the macroscopic and histological changes in livers of Wistar rats subjected to acetaminophen induced liver changes.

Phytochemical Properties of Croton gratissimus Burch (Lavender Croton) Herbal Tea and Its Protective Effect against Iron-Induced Oxidative Hepatic Injury.

Oxidative stress plays a vital role in the pathogenesis and progression of various liver diseases. Traditional medicinal herbs have been used worldwide for the treatment of chronic liver diseases due to their high phytochemical constituents. The present study investigated the phytochemical properties of Croton gratissimus (lavender croton) leaf herbal tea and its hepatoprotective effect on oxidative injury in Chang liver cells, using an in vitro and in silico approach. C. gratissimus herbal infusion was screened for total phenolic and total flavonoid contents as well as in vitro antioxidant capacity using ferric reducing antioxidant power (FRAP) and 2,2-diphenyl-1-picryl-hydrazyl (DPPH) methods. Oxidative hepatic injury was induced by incubating 0.007 M FeSO4 with Chang liver cells which has been initially incubated with or without different concentrations (15-240 μg/mL) of C. gratissimus infusion or the standard antioxidants (Gallic acid and ascorbic acid). C. gratissimus displayed significantly high scavenging activity and ferric reducing capacity following DPPH and FRAP assays, respectively. It had no cytotoxic effect on Chang liver cells. C. gratissimus also significantly elevated the level of hepatic reduced glutathione (GSH), superoxide dismutase (SOD), and catalase activities as well as suppressed the malondialdehyde (MDA) level in oxidative hepatic injury. Liquid Chromatography-Mass Spectrometry (LC-MS) analysis of the herbal tea revealed the presence of 8-prenylnaringenin, flavonol 3-O-D-galactoside, caffeine, spirasine I, hypericin, pheophorbide-a, and 4-methylumbelliferone glucuronide. In silico oral toxicity prediction of the identified phytochemicals revealed no potential hepatotoxicity. Molecular docking revealed potent molecular interactions of the phytochemicals with SOD and catalase. The results suggest the hepatoprotective and antioxidative potentials of C. gratissimus herbal tea against oxidative hepatic injury.

Biochemical characterization and hypocholesterolemic properties of sesame yogurt made from deoiled edible quality sesame flour (DEQSF) supplemented with rice bran oil

Despite having a high polyphenol content, deoiled edible quality sesame flour (DEQSF), a byproduct of the sesame oil extraction process, is frequently thrown away. DEQSF contains antioxidants, amino acids, minerals, protein, and many non-nutrient-based health advantages. It could serve as an excellent material for the formulation of a value-added functional food product. The current study developed fortified sesame yogurts using rice bran oil (RBO) and DEQSF at percentages of 6, 7, and 8 in order to compare them to control sesame yogurts manufactured from whole sesame seeds and kept at 4 °C for 28 days. The other goal was to examine the in vivo cholesterol-lowering potential of sesame yogurt prepared from DEQSF and RBO. Evaluations were done on the physicochemical, microbiological, sensory, antioxidative, proteolytic, morphological, and nutritional properties. The proximate composition of RBO-fortified sesame yogurts differed considerably when compared to control yogurt in terms of protein, fat, ash, total solids, and carbohydrate content. After 28 days of storage, the addition of 8% DEQSF not only decreased syneresis but also maintained proper viscosity and penetration properties. The right quantity of probiotic bacteria was present in the RBO-fortified sesame yogurts that contained 8% DEQSF, and RBO-fortified sesame yogurt treated with 8% DEQSF (w/v) had a general overall acceptability score. During storage at 4 °C, all RBO-fortified sesame yogurts had nearly identical antioxidant activity to the control sesame yogurt. The addition of 8% DEQSF increased the amount of proteolysis by Lactobacillus spp. and Streptococcus spp., as evidenced by a significant increase in o-phthaldialdehyde levels. Microstructural studies confirmed the dense, compressed, homogeneous structure of the fortified sesame yogurt. To investigate the effects of RBO-supplemented, DEQSF-based yogurt on hypercholesterolemia, a hypercholesterolemic mice model was developed. Comparing animal groups that received fortified sesame yogurts to control groups, there was a significant effect on serum lipid profile as well as hepatoprotective potential. The implication was that RBO-fortified sesame yogurt could help cure hypercholesterolemia. In the end, it was discovered that 8% DEQSF (w/v) and RBO were the perfect combinations to produce sesame yogurt with an anti-obesity and hypocholesteremic impact.Graphical

BIOASSAY GUIDED HEPATOPROTECTIVE ACTIVITY OF POLYGONATUM CIRRHIFOLIUM AGAINST ISONIAZID AND RIFAMPICIN INDUCED HEPATOTOXICITY IN RATS

The present investigation was performed to examine the hepatoprotective effect of the aqueous ethanolic extract of Polygonatum cirrhifolium in antitubercular drug-induced liver damage. P. cirrhifolium rhizomes were crushed, dissolved in various solvents (in order of polarity), and then tested for phytochemicals. Based on their findings, mass extraction utilizing the ethanol-water mixture (50: 50) was carried out using the Soxhlet method. The doses for animal research were established through acute toxicity tests. The hepatoprotective potential of aqueous ethanolic extract (50:50) of rhizomes was determined in Wistar rats at doses of 200 mg kg-1 and 400 mg kg-1 p.o. per day. Blood samples were examined for the biochemical markers SGOT, SGPT, ALP, total bilirubin, and albumin. Histopathology of the liver was also conducted followed by in vitro anti-oxidant studies. Simultaneously, the extract was subjected to LCMS characterization. P. cirrhifolium extract at both the doses 200 mg kg-1 and 400 mg kg-1 has shown significant hepatoprotective activity against hepatotoxicity induced by INH+ RIF in a dose-dependent manner, as depicted by the significant changes in the values of blood biomarkers and in vitro anti-oxidant studies. Histopathological studies showed that the treatment with 200 mg kg-1 and 400 mg kg-1 of P. cirrhifolium exhibited regeneration of liver architecture and portal system by reducing the haemorrhage and inflammatory infiltrate. LC-MS characterization showed serpentine, 5-hydroxy methylfurfural and cephalotaxine as active constituents. It can be inferred that hydroethanolic extract of P. cirrhifolium protects the liver from anti-TB induced toxicity and this protection could be due to the active phytoconstituents.

Pleurospermum candollei Methanolic Extract Ameliorates CCl4-Induced Liver Injury by Modulating Oxidative Stress, Inflammatory, and Apoptotic Markers in Rats.

The main objective of this study was to investigate the hepatoprotective potency of the Pleurospermum candollei methanol extract against CCl4-induced liver damage in rats. HPLC technique was used to estimate the presence of polyphenols in the methanol extract of P. candollei (PCM), while proximate analysis revealed the presence of carbohydrates, lipids, and moisture in the extract. The antioxidant potential of PCM was evaluated by 2,2-diphenylpicrylhydrazyl (DPPH) and reducing power assay, which showed a high percentage of inhibition against free radicals. Hepatotoxicity was induced by carbon tetrachloride (CCl4). CCl4 administration reduced the activity of endogenous antioxidants, whereas it increased the production of nitrites and hydrogen peroxide (H2O2) in rats. Furthermore, the level of hepatic markers in serum was also elevated after CCl4 administration. Moreover, the expression of stress-related markers, proinflammatory mediators, and apoptotic genes was enhanced in CCl4-treated rats. Coadministration of PCM along with CCl4 in rats reduced the levels of free radicals and the above genes to normal levels. CCl4 administration caused histopathological alterations in liver tissues, while cotreatment with PCM mitigated liver injuries. These findings suggest that the methanol extract of P. candollei possesses antioxidant and anti-inflammatory properties and can prevent liver injury. Further pharmacological research will be helpful in determining the effectiveness of P. candollei in humans. Development of FDA-approved plant-based anti-inflammatory drugs can help treat patients and reduce the chances of toxicity.

Evaluation of Hepatoprotective Efficacy of a Polyherbal Unani Formulation Majoon-Najah against Cadmium Chloride-induced Liver Damage.

Majoon-Najah is a composite Unani formulation that consists of multiple medicinal plants and is advised for neurological illnesses. Several studies were carried out on Majoon-Najah (MN) and its ingredients to evaluate the protective effect against seizure and antidepressant activity in animals using a classical form as well as extract. Terminalia bellerica and Emblica officinalis are the major constituents of MN. Scientifically documented literature summarises the hepatoprotective potential of these constituents. The current study aimed to evaluate the possible hepatoprotective, antioxidant and antiinflammatory perspective of traditional Indian Unani formulation MN and Majoon-Najah hydroalcoholic extract (MNHE) in a Guinea pig model. Thirty adult male albino guinea pigs were randomly assigned into five groups for this study. MN and MNHE were given intragastrically for 15 days, followed by intraperitoneal Cadmium chloride (CdCl2, 3 mg/kg/day) from days 8 to 15, as per the schedule. Blood samples were taken from the heart on the 16th day, and the liver was operated on for biochemical analysis and histopathology under complete anesthesia. CdCl2 changed the levels of liver function markers, serum biochemical indicators like albumin, total protein, glucose, and cholesterol in the blood; lipid peroxidation (MDA), glutathione reductase (GSH), superoxide dismutase (SOD), and glutathione peroxidase (GPX) in hepatic tissue homogenate, pro-inflammatory cytokines level and liver cytoarchitecture. MN and MNHE were found to protect guinea pigs' liver from CdCl2-induced injury by lowering raised parameters and increasing enzymatic antioxidants. MN and MNHE did not significantly heal injured liver tissues caused by CdCl2 in histopathological examinations. CdCl2 induces hepatotoxicity that is likely to worsen with increasing dosage and duration of exposure. MN and MNHE exert their hepatoprotective action by scavenging free radicals, decreasing malondialdehyde levels, activating antioxidant enzymes, and down-regulating proinflammatory indicators.

Flavonoids of Chromolaena odorata (L.) R.M.King & H.Rob. as potential leads for treatment against tuberculosis

Tuberculosis (TB) is currently rated as the 13th leading cause of mortality and the second leading cause of death after COVID-19, and above AIDS. Existing challenges relating to the development of multidrug-resistant strains and dangerous side effects of currently used drugs add impetus to the search for additional TB treatments. Hence, interest has grown in the use of medicinal plants as a source of bioactive preparations with efficacy against TB-causing organisms, and also with the ability to ameliorate the negative effects of TB drugs. This study aimed to evaluate the antimycobacterial and hepatoprotective potentials of extracts and isolated flavonoid compounds from invasive Chromolaena odorata. Test organisms used were pathogenic Mycobacterium bovis and M. tuberculosis H37RV, and the fast-growing M. aurum, M. fortuitum and M. smegmatis. The selectivity index (SI) values of the test substances were determined through cytotoxicity assays to promote these extracts and compounds as leads for the development of effective and safe anti-tubercular drugs. The antimycobacterial activity was evaluated using a serial microdilution method, and the SI was calculated from the 50% lethal concentrations calculated from cytotoxicity tests. Hepatoprotective activity was determined using HepG2 liver cells treated with rifampicin as a toxin. The extracts and compounds had a range of antimycobacterial activity with minimum inhibitory concentration (MIC) values ranging from 0.031 to 2.5 mg/mL. Two flavonoid compounds, 5,7,4′-trimethoxy flavanone and 5‑hydroxy-3,7,4′-trimethoxyflavone showed promising antimycobacterial potential, and minimal toxicity was observed, as most SI values were higher than 1. The flavonoid compound 5,7,4′-trimethoxy flavanone had the highest SI (6.452), which was against M. tuberculosis H37RV. The HepG2 cells were reduced to 65% due to toxicity by rifampicin, however, the flavonoid compounds were able to improve cell viability to between 81 and 89% at different concentrations tested. Results obtained indicate that C. odorata may serve as a lead for the development of safe and effective antimycobacterial and hepatoprotective drugs.

Biofabricated Palladium Nanoparticle-Decorated Reduced Graphene Oxide Nanocomposite Using the Punica granatum (Pomegranate) Peel Extract: Investigation of Potent In Vivo Hepatoprotective Activity against Acetaminophen-Induced Liver Injury in Wistar Albino Rats.

Acute acetaminophen (APAP) toxicity is a predominant clinical problem, which causes serious liver injury in both humans and experimental animals. This study presents the histological and biochemical factor and antioxidant enzyme level changes induced by an acute acetaminophen overdose in Wistar albino rat livers to elucidate the effective hepatoprotective potential of biofabricated palladium nanoparticle-decorated reduced graphene oxide nanocomposites (rGO/PdNPs-NC) compared to silymarin. After detailed characterization of the hepatoprotective potential of the synthesized rGO/PdNPs-NC, the rats were divided into eight groups (n = 6): control group (normal saline, 1 mL/kg b.w.), silymarin, Punica granatum (pomegranate) peel extract, PdNPs, reduced graphene oxide (rGO-PG), and reduced graphene oxide palladium nanocomposites (rGO/PdNPs-NC, low and high doses) for 7 successive days. The acetaminophen (APAP)-treated group was administered a single dose of acetaminophen (2 g/kg b.w.) on the 8th day. The histopathological results showed that the acetaminophen overdose group exhibited massive intrahepatic hemorrhagic necrosis around the centrilobular region with hepatocytes with vacuolization and swollen cytoplasm found in the liver architecture. This hepatopotential was further assessed by various biochemical parameters such as SGOT, SGPT, ALB, ALP, LDH, direct bilirubin, total bilirubin, and total protein. Also, the antioxidant parameters such as SOD, CAT, MDA, GSH, GRD, and GST were assayed. Rats of groups 7 and 8 showed a significant decrease in SGOT, SGPT, ALP, LDH, direct bilirubin, and total bilirubin (p < 0.001), while a significant increase in the final total protein and ALB as compared to group 2 rats (p < 0.001) was observed. The antioxidant parameters exhibited that rats of groups 7 and 8 showed a significant (p < 0.001) increase in the level of SOD, CAT, GSH, GRD, and GST without affecting the MDA as compared to group 2 rats. Also, the hepatoprotective potential of rGO/PdNPs-NC (low and high doses) was comparable to that of the standard reference drug silymarin. The present study reveals that the rGO/PdNPs-NC possesses significant hepatoprotective activity and acts as an effective and promising curative agent against acetaminophen-induced hepatotoxicity.

Hepatoprotective potentials of aqueous leaf and seed extracts of Artocarpus heterophyllus on testosterone propionate induced prostatitis in Wistar rats.

This study evaluated the hepatoprotective potentials of aqueous leaf and seed extracts of Artocarpus heterophyllus on testosterone propionate induced prostatitis in Wistar Rat. Male Wistar rats of 100- 125g and 100 in number were obtained from the Department of Pharmacology, University of Port Harcourt animal house and was grouped into 10 of 10 rats each. The various groups were fed and administered with various concentrations (100mg/kg, 200mg/kg, 300mg/kg and 200mg/kg combined extract) of the leaves and seeds extracts of A. heterophyllus. The hepatoprotective potentials was studied by evaluating the liver function parameters on the male Wistar rats by day 21, 42 and 63 of the experiment using standard laboratory methods. The results obtained showed significantly (p&lt; 0.05) increased ALP levels (401.57±0.85) on administration of testosterone propionate in group 2 (induced not treated group) day 21, as against the normal control group (294.57±0.06), while group 5 (Rats induced with TP (4 mg/kg) and administered 200 mg/kg of aqueous extract of A. heterophyllus leaves) revealed minimal level of ALP 293.47±0.006 by day 63. Minimum values for AST 23.00±0.51 was seen in group 8 day 21) with maximum activity 76.82±0.09 seen in group 1 day 21, ALT minimum level 7.67±0.33 was observed in group 4 day 21, while maximum levels 38.41±0.51 was seen in group 2 day 21, Albumin minimum level 17.87±0.09 was seen in group 2 day 63, with maximum level 31.13±0.18 observed in group 8 day 63, while minimum Total Protein 26.31±0.84 was shown in group 2 day 63 and maximum 64.63±0.49 in group 8 day 42. Obtained values from groups 5, 6, 9 and 10 were shown to be significantly different when compared with the negative control in group 2 but not significantly different with control group 1 and 3, hence depicting a more stabilized and hepatoprotective system in the plant extract treated groups compared to the negative control (group 2) at day 21. However, group 5 was shown to have higher hepatoprotective potentials by day 42 followed by group 10.

Antioxidant and Hepatoprotective Potential of Echinops ritro L. Extracts on Induced Oxidative Stress In Vitro/In Vivo.

Echinops ritro L. (Asteraceae) is traditionally used in the treatment of bacterial/fungal infections and respiratory and heart ailments. The aim of this study was to evaluate the potential of extracts from E. ritro leaves (ERLE) and flowering heads (ERFE) as antioxidant and hepatoprotective agents on diclofenac-induced lipid peroxidation and oxidative stress under in vitro and in vivo conditions. In isolated rat microsomes and hepatocytes, the extracts significantly alleviated oxidative stress by increasing cell viability and GSH levels and reducing LDH efflux and MDA production. During in vivo experiments, the administration of the ERFE alone or in combination with diclofenac resulted in a significant increase in cellular antioxidant protection and a decrease in lipid peroxidation witnessed by key markers and enzymes. A beneficial influence on the activity of the drug-metabolizing enzymes ethylmorphine-N-demetylase and aniline hydroxylase in liver tissue was found. In the acute toxicity test evaluation, the ERFE showed no toxicity. In the ultrahigh-performance liquid chromatography-high-resolution mass spectrometry analysis, 95 secondary metabolites were reported for the first time, including acylquinic acids, flavonoids, and coumarins. Protocatechuic acid O-hexoside, quinic, chlorogenic and 3, 5-dicaffeoylquinic acid, apigenin; apigenin 7-O-glucoside, hyperoside, jaceosidene, and cirsiliol dominated the profiles. The results suggest that both extracts should be designed for functional applications with antioxidant and hepatoprotective capacity.

Hepatoprotective Effect of Myricetin following Lipopolysaccharide/DGalactosamine: Involvement of Autophagy and Sirtuin 1.

Acute liver injury (ALI) is a critical and fatal disorder associated with excessive oxidative stress and inflammation, ultimately leading to the death of hepatocytes. Myricetin is a bioflavonoid in some berries, including blueberries and strawberries, with anti-inflammatory, antioxidant and anti-apoptotic properties. In the current research, the hepatoprotective potential of myricetin was studied in the LPS/D-GalN model of ALI in C57BL/6 mice. For inducing liver injury, D-GalN (400 mg/kg) and LPS (50 µg/kg) were injected via intraperitoneal route and myricetin was orally administered (25 or 100 mg/kg/day) for two days before inducing injury. Functional indices of liver dysfunction along with hepatic apoptotic, autophagic, oxidative stress and inflammatory factors were measured. Myricetin (100 mg/kg) reduced the fatality rate of animals and pathological liver changes and suitably lowered serum levels of total bilirubin, 8-OH-dG, ALT, AST and ALP in addition to decreasing apoptotic, oxidative and inflammatory factors, NOX, NLRP3, caspase 3, MPO and enhancing some antioxidants. Besides, myricetin improved the hepatic level and activity of sirtuin 1 and reversed inappropriate alterations of autophagic parameters, including LC3 II, Beclin 1, and P62. The beneficial effects of myricetin were attenuated after co-treatment with the autophagy inhibitor 3- methyladenine. This study indicates the hepatoprotective potential of myricetin that can be ascribed to its down-regulation of oxidative, apoptotic, and inflammatory factors and upregulation of antioxidants besides its partial regulation of sirtuin 1 and autophagic pathway.

Hepatoprotective Potential of Phytoconstituents and Vitamins against Antitubercular Drugs Induced Hepatotoxicity in Albino Rats

Background: This study aims to develop a new hepatoprotective drug from common plants and vitamins that are potent, nontoxic, and cost-effective. The literature search found that Curcuma longa, Zingiber officinale, Terminalia, chebula, and Vitamin A (Vitamin C + Vitamin E) provide hepatoprotective action against drugs-induced hepatotoxicity. A major side effect of antitubercular drugs (ATD) is liver toxicity, which reduces their effectiveness. Aim: In this study, Vitamins and Phytoconstituents (Combined extract) were evaluated for their potential hepatoprotective effects against hepatotoxicity induced by antitubercular drugs in Wistar albino rats of either sex. Materials and Methods: In the study, ethanolic extract of rhizomes of Curcuma longa and Zingiber officinale, fruits of Terminalia chebula, and vitamins C and E were used. As a standard drug, silymarin was also used. For 30 days, albino rats received 7.5 mg/kg isoniazid, 10 mg/kg rifampicin, and 35 mg/kg pyrazinamide orally as a suspension in distilled water. Result: A combined extract plus vitamins (500mg/kg) treatment significantly reduced the hepatic toxicity caused by antitubercular drugs (P&lt;0.05-P&lt;0.001). A combination of extracts + vitamins (500mg/kg) eliminates hepatotoxicity, and the results are close to those of Silymarin, a standard drug. Conclusion: As a result of this study, extracts+vitamins provide protection against liver injury attributed to their hepatoprotective activity, which supports their traditional use.

Hepatoprotective and nephroprotective effects of Sedum adenotrichum in paracetamol-induced hepatotoxicity in rabbits.

Sedum adenotrichum (SA) has been traditionally used against various ailments due to the presence of several important phenolic compounds. This study provides a scientific basis for the hepatoprotective and nephroprotective potentials of Sedum adenotrichum in paracetamol-induced toxicity in rabbits. Methanolic extract of Sedum adenotrichum along with paracetamol was administered orally to rabbits alone or in combination with paracetamol for 2weeks. Results showed that paracetamol-induced toxicity was correlated with a significant change in biochemical, hematological parameters, and loss in body weight of rabbits, and the curative effect of SA methanolic extract was found. Liver and kidney histological studies showed significant induced toxicity of paracetamol and correspondence restoration power of SA methanolic extract. The levels of reduced glutathione, radical scavenging activity, and lipid peroxidation in the liver were restored to normal by the methanolic extract of SA. This study confirmed the protective effect of SA methanolic extract against hepatotoxicity and nephrotoxicity caused by paracetamol. Biochemical analysis of the methanolic extract of SA confirmed the presence of bioactive phenolic compounds which have hepatic and nephroprotective potentials.

Hepatoprotective potential of gabapentin in cecal ligation and puncture-induced sepsis; targeting oxidative stress, apoptosis, and NF-kB/MAPK signaling pathways.

Sepsis is a severe inflammatory response to infection with an incidence rate exceeding 48 million cases and 11 million sepsis-related deaths yearly. Furthermore, sepsis remains the fifth most common cause of death worldwide. The present study aimed to examine, for the first time, the potential hepatoprotective activity of gabapentin on cecal ligation and puncture (CLP)-induced sepsis in rats at the molecular level. CLP was used as a model of sepsis in male Wistar rats. Histological examination and liver functions were evaluated. Levels of MDA, GSH, SOD, IL-6, IL-1β, and TNF-α were investigated using ELISA. mRNA levels of Bax, Bcl-2, and NF-kB were assessed by qRT-PCR. Western blotting investigated the expression of ERK1/2, JNK1/2, and cleaved caspase 3 proteins. CLP resulted in liver damage, elevated serum levels of ALT, AST, ALP, MDA, TNF-α, IL-6, and IL-1β, increased expression of ERK1/2, JNK1/2, and cleaved caspase 3 proteins, and upregulated Bax and NF-κB genes expression while it down-regulated Bcl-2 gene expression. However, gabapentin treatment significantly reduced the severity of CLP-induced biochemical, molecular, and histopathological changes. Gabapentin attenuated the levels of the proinflammatory mediators, decreased the expression of JNK1/2, ERK1/2, and cleaved caspase 3 proteins, suppressed Bax and NF-κB genes expression and increased the expression of the Bcl-2 gene. Consequently, Gabapentin reduced hepatic injury resulting from CLP-induced sepsis by reducing proinflammatory mediators, attenuating apoptosis, and inhibiting the intracellular MAPK (ERK1/2, JNK1/2)-NF-kB signaling pathway.

Pharmacognostic Evaluation and Hepatoprotective Property of Crude and Fractions of Triumfetta cordifolia A. Rich. (Tiliaceae)

Background: The role of phytochemicals in modern medicine is abundant with more evidence being published. Triumfetta cordifolia is a local plant known for its vast medicinal applications in traditional medicine with limited documented evidence. This study thus aims to evaluate the leaves of Triumfetta cordifolia to determine its Pharmacognostic parameters and hepatoprotective potential.&#x0D; Methodology: The leaves were collected, identified, dried and subsequently pulverized before maceration in methanol. This was followed by fractionation using different solvent with increasing polarities (n-hexane, n-butanol, ethyl acetate and aqueous methanol). Physicochemical evaluations such as macroscopy, organoleptic tests, qualitative phytochemical analysis and total phenolic content was subsequently conducted on the extracts. Finally, an acute toxicity test and hepatoprotective evaluation was performed, the latter using carbon tetrachloride.&#x0D; Results: The leaves Triumfetta cordifolia on macroscopic evaluation shown a simple, alternate, stipules triangular, densely stellate hairy leaves. The organoleptic evaluation indicated a pungent aromatic smell and a slightly bitter taste. Several phytochemicals such as tannins, saponins, glycosides, steroids and flavonoids were identified qualitatively.The extracts was safe at a dose less than 5,000mg/kg. The ethyl acetate fraction showed consistent hepatoprotective activity at a concentration of 400 mg/kg when compared to Gallic acid (positive control). This was possibly due to its high composition of phenolic compounds which was recorded during the study.&#x0D; Conclusion: The ethyl acetate fraction of Triumfetta cordifolia leaves exhibited a hepatoprotective effect thus showcasing the potential benefits of the plant in mitigating liver damage. More research is however needed to identify specific compounds being extracted that may be responsible for the activity recorded in this study.

In vivo anti-inflammatory effects of anti-toxic principles from Moringa oleifera(MO11) and Musa sapientum (MS06) via NF-KB/IL-4/IL-10- mediated pathway in Cadmium Chloride-induced hepato-toxicity.

Cadmium-induction of hepato-toxicity and inflammation in animal models have been reported. The mechanism underlying hepatic inflammation is poorly understood. This study evaluated antiinflammatory potentials of MO11 (isolated from Moringa oleifera leaves) and MS06 (isolated from Musa sapientum suckers) in Cadmium Chloride (CdCl)-induced hepato-toxicity and inflammation in rats.Twenty-eight adult male wistar rats (average weight of 155 g) were randomly divided into 7 groups (n = 4). Group 1 was control. Groups 2 - 4 and 7 received single intraperitoneal administration of 1.5 mg/Kg bodyweight of CdCl on Day 1. Thereafter, Groups 3, 4 and 7 were post-treated with 15 mg/Kg bodyweight of MO11, 15 mg/Kg bodyweight of MO11 + 7 mg/Kg bodyweight of MS06 and single-dose of 3.35 mg/Kg bodyweight of Doxorubicin respectively (Days 1 - 17). Groups 5 and 6 received only MO11-dose and Olive Oil (vehicle) respectively (Days 1 - 17). Liver histopathology (Heamatoxyline and Eosin technique) and ELISA concentrations of proinflammatory biomarkers (IL-1β, IL-6, IL-8 and NF-kB) and anti-inflammatory biomarkers (IL-4 and IL-10) in liver homogenates of rats of Groups 1 - 7 were evaluated. Computed data were statistically analysed using Mann-Whitney-U test at P ≤ 0.05. Histo-pathological analyses showed normal liver histology in Groups 1 - 7. Post-treatments of CdCl-induced hepato-toxicity and hepatic inflammation with MO11 and MO11+MS06 resulted in downregulations of IL-1β, IL-6, IL- 8 and NF-kB, but upregulations of IL-4 and IL-10 in Groups 3, 4 and 7, compared with Group 2. MO11 and MS06 possess hepato-protective and anti-inflammatory potentials.

Recent insights into the hepatoprotective potential of medicinal plants and plant‐derived compounds

Liver problems are a worldwide concern, and conventional medicinal therapies are ineffective. Hence, safeguarding the healthy liver is vital for good health and well-being. Infections due to virus, immune problems, cancer, alcohol abuse, and an overdose of drugs are some of the causes of liver diseases. Antioxidants derived from medicinal plants and conventional dietary sources can protect the liver from damages caused by oxidative stress system and various chemicals. Plants and plant-derived phytochemicals are appealing hepatoprotective agents since they have less side effects and still there is a lot of interest shown in using herbal tonics for treating liver disorders. This review therefore primarily focuses on newly discovered medicinal plants and compounds produced from plants that fall under the classifications of flavonoids, alkaloids, terpenoids, polyphenolics, sterols, anthocyanins, and saponin glycosides, all of which have the potential to be hepatoprotective. Hosta plantaginea, Ligusticum chuanxiong, Daniella oliveri, Garcinia mangostana, Solanum melongena, Vaccinium myrtillus, Picrorhiza kurroa, and Citrus medica are some potential plants having hepatoprotective effects. We conclude that these phytochemicals and the plant extracts listed above are used in the future to treat a variety of liver diseases, additional research is still needed to develop safer and more potent phytochemical drugs.

γ-Mangostin abrogates AINT-induced cholestatic liver injury: Impact on Nrf2/NF-κB/NLRP3/Caspase-1/IL-1β/GSDMD signalling

γ-Mangostin (γ-MN) is one of the abundant xanthones separated from Garcinia mangostana (Clusiaceae) pericarps that has been reported to have varied bioactivities such as neuroprotective, cytotoxic, antihyperglycemic, antioxidant, and anti-inflammation. Yet, its effect on cholestatic liver damage (CLI) has not been investigated. This study explored the protective activity of γ-MN against alpha-naphthyl isothiocyanate (ANIT)-induced CLI in mice. The results showed that γ-MN protected against ANIT-induced CLI as indicated by reduced serum levels of hepatic injury parameters (e.g., ALT, AST, γ-GT, ALP, LDH, bilirubin, and total bile acids). ANIT-induced pathological lesions were improved in γ-MN pre-treated groups. γ-MN exerted potent antioxidant effects as it lowered the parameters of lipid peroxidation (4-HNE, PC, and MDA) and intensified the content and activity of antioxidants (TAC, GSH, GSH-Px, GST, and SOD) in the hepatic tissue. Furthermore, γ-MN enhanced the signalling of Nrf2/HO-1 as it augmented the mRNA expression of Nrf2/downstream genes (HO-1/GCLc/NQO1/SOD). The binding capacity and the immuno-expression of Nrf2 were also increased. γ-MN showed anti-inflammatory capacity as it suppressed the activation of NF-κB signalling, it decreased mRNA expression and levels of NF-κB/TNF-α/IL-6 and the immuno-expression of NF-κB/TNF-α. In addition, γ-MN inhibited the activation of NLRP3 inflammasome as it lowered the mRNA expression of NLRP3/caspase-1/IL-1β along with their levels as well as the immuno-expression of caspase-1/IL-1β. γ-MN also reduced the level of the pyroptotic parameter GSDMD. Collectively, this study demonstrated the potent hepatoprotective potential of γ-MN against CLI which was linked to its ability to potentiate Nrf2/HO-1 and to offset NF-κB/NLRP3/Caspase-1/IL-1β/GSDMD. Hence, γ-MN may be suggested as a new candidate for cholestatic patients.

Narirutin. A flavonoid found in citrus fruits modulates cell cycle phases and inhibits the proliferation of hormone-refractory prostate cancer cells by targeting hyaluronidase.

Narirutin is a dietary flavanone found in lemons, oranges, passion fruit, bergamot and grapefruit. It possesses anti-allergic, cardioprotective, neuroprotective, hepatoprotective potential, and its enriched fraction suppresses the growth of prostate cancer cells; however, there is currently no information on the chemopreventive potential of narirutin alone against hormone-refractory prostate cancer cells (PC-3) and its mode of action. Thus, the chemopreventive possibility of narirutin was investigated in PC-3cells by utilising cytotoxicity assays. Further, a mechanism was deduced targeting hyaluronidase, an early-stage diagnosis marker, by cell-free, cell-based and in silico studies. The results indicate that narirutin reduced the viability of PC-3cells with the inhibitory concentration range of 66.87-59.80μM. It induced G0/G1 phase arrest with a fold change of 1.12. Besides, it increased the generation of reactive oxygen species (ROS) with a fold change of 1.34at 100μM. Narirutin inhibited hyaluronidase's activity in cell-free (11.17μM) and cell-based assays (67.23μM) and showed a strong binding interaction with hyaluronidase. Finally, the MD simulation analysis supported the idea that narirutin binding enhanced compactness and stability and created a stable complex with hyaluronidase. In addition, ADMET prediction indicates that it is a non-toxic, non-CYPs inhibitor and thus didn't alter the metabolism. The results reveal that narirutin may be a potential chemopreventive agent for hormone-resistant prostate cancer cells in addition to offering data for supporting diet-based nutraceutical agents to prevent prostate cancer.

Biostatistical Analysis on Synergetic Therapy of the Three Plants

The liver is an important metabolic organ consisting of four different sized lobes in our bodies. The important function of liver includes the elimination of toxic material, detoxication and regulation of the blood, blood clotting, and manufacture of vital hormones. It also plays a crucial role in other activities, such as pathogen protection, synthesis of bile salts, food supply, and blood collecting. There is currently no obvious mechanism that includes direct hepatotoxicity and unfavorable immune response for several study reports on hepatic damage mechanisms. Pharmaceutical bioactivation creates reactive chemical metabolites that interact with lipids, nucleic acid, and proteins in the cell, producing DNA damage, protein malfunction, lipid peroxidation, and oxidative stress. Many illnesses also affect the liver due to its strategic position. Hepatotoxins, due to the overdose of drugs, xenobiotics, alcohol and industrial toxins, can harm the liver. However, Natural and synthetic chemicals are used to treat liver diseases as hepatoprotective agents. This study was conducted to evaluate the hepatoprotective potential of Geranium wallichianum, Elaeagnus parvifolia and Taraxacum officinale against Carbon Tetrachloride (CCl4) induced hepatotoxicity in experimental rats. Extract of all three plants was induced (200 mg/kg) and combination of all three plants were given in (100 mg/kg). Liver enzymes including Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST), Alkaline Phosphatase (ALP) and total bilirubin as well as liver histopathology were evaluated to see the effect of herbal treatments. Results of this study suggest that all three plants have hepatoprotective effect and highest effect was noted in synergetic therapy.