Significant Hepatoprotective Activity Research Articles

New compounds with a dihydropyridine framework as promising hypolipidemic and hepatoprotective agents

Introduction: To solve the problem of complex and safe pharmacological correction of metabolic disorders, including hyperlipidemia, hyperglycemia, and liver lesions is currently very important. With this in mind, the new derivatives of cyanothioacetamide with a dihydropyridine framework, with a potential effect on lipid and carbohydrate metabolism and the functioning of the liver are of great interest. Materials and Methods: To conduct an experiment, three samples were selected from an extensive library of new cyanothioacetamide derivatives, which, according to in silico studies, proved promising towards the positive effect on lipid and carbohydrate metabolism, as well as towards the protective effect on the liver. To study the compounds in vivo, metabolic disorders were simulated in Wistar rats by long -term alimentary and subsequent dexamethasone loads. The pharmacological efficacy of new compounds AZ-383, AZ-257, AZ-020 (administered in a dose of 1 mg/kg for 14 days) was assessed in comparison with metformin (300 mg/kg for 14 days) and vildagliptin (8 mg/kg for 14 days) by determining the biochemical indicators of blood (ALT, AST, total bilirubin, total cholesterol, triglycerides, and glucose), morphological and morphometric studies of the liver sections, and the study of immunohistochemical indicators of hepatocyte proliferation. The experimental results were statistically processed using the recognized methods of mathematical statistics. When processing the experimental data, the average arithmetic (AA) was determined. The statistical significance of the compared options was determined on the basis of the Student’s t-test, with the critical value of the Student’s t-test equal to 2.101 and the significance level α = 0.05. Results: The study shows that all the new compounds studied in the experiment – AZ-383, AZ-257, AZ-020 – have hypolipidemic and hepatoprotective properties, which manifested in the reduced levels of liver biochemical markers of blood, which had increased after simulating metabolic disorders, in the reduced concentration of total cholesterol and triglycerides in blood, in the normalization of liver microarchitecture, as well as in the proliferative activity of hepatocytes. Discussion: The hepatoprotective and hypolypidemic properties of the new derivatives of cyanothioacetamide with a dihydropyridine framework, which were determined while conducting the experiment, can be accounted for by their effects on the biotargets, identified for AZ-383, AZ-257, and AZ-020 in silico. According to the results, the most pronounced hepatoprotective activity was found in AZ-383 (intragastrically, 1 mg/kg for 14 days). The Ki-67 proliferation index under the influence of this compound was registered at the level of 1.48±0.03%, which exceeds this indicator in the control animals and proves a significant hepatoprotective activity of AZ-383. Conclusion: The results show good prospects and high efficacy of the new studied cyanothioacetamide derivatives, such as AZ-383, AZ-257, AZ-020 (in a dose of 1 mg/kg), in terms of comprehensive correction of metabolic disorders. Further study is needed for this class of compounds.

Green synthesis of pectin-functionalized silver nanocomposites using Carpesium nepalense and evaluation its bactericidal kinetics and hepatoprotective mechanisms

The present study reports the green synthesis of pectin-fabricated silver nanocomposites (Pectin-AgNPs) using Carpesium nepalense leaves extract, evaluating their bactericidal kinetics, in vivo hepatoprotective, and cytotoxic potentials along with possible mechanisms. GC/MS and LC/MS analyses revealed novel phytochemicals in the plant extract. The Pectin-AgNPs were characterized using UV/Vis, AFM, SEM, TEM, DLS, FTIR, and EDX techniques, showing a spherical morphology with a uniform size range of 50–110 nm. Significant antibacterial activity (P < 0.005) was found against four bacterial strains with ZIs of 4.1 ± 0.15 to 27.2 ± 3.84 mm. AFM studies revealed significant bacterial cell membrane damage post-treatment. At 0.05 mg/kg, the nanocomposites showed significant (P < 0.005) hepatoprotective activity in biochemical and histopathology analyses compared to the CCl4 control group. Pectin-AgNPs significantly reduced (P < 0.005) LDH, AST, ALT, ALP, and DB levels. qPCR analysis showed ameliorative effects on PPARs and Nrf2 gene expression, restoring gene alterations caused by CCl4 intoxication. In vivo acute toxicity studies confirmed low toxicity of Pectin-AgNPs in major organs. Pectin-AgNPs exhibited cytotoxic activity against HeLa cell lines at higher doses with an LC50 of 223.7 μg/mL. These findings demonstrate the potential of Pectin-AgNPs as promising antibacterial, hepatoprotective, and cytotoxic agents.

Two new cucurbitane-type triterpenoid saponins from the fruit of Citrullus colocynthis

Two new cucurbitane-type triterpenoid saponins, 2,20β,22β-trihydroxy-16α,23(R)-epoxycucurbita-1,5,24-triene-3,11-dione 2-O-β-D-glucopyranoside (1), 2,20β,22α-trihydroxy-16α,23(S)-epoxycucurbita-1,5,11,24-tetraene-3-one 2-O-β-D-glucopyranoside (2) were isolated from the fruit of Citrullus colocynthis (L.) Schrad. Their structures were elucidated by mass spectrometry, IR, 1D, and 2D NMR spectroscopy, etc. Besides, both of the compounds showed significant hepatoprotective activities at 10 μM against paracetamol-induced HepG2 cell damage.

Symplosaponins A–D: New acylated oleanane-type triterpene saponins from Symplocos cochinchinensis and their hepatoprotective effect

Four new acylated oleanane-type triterpene saponins, symplosaponins A–D (1–4) were successfully isolated from the leaves of Symplocos cochinchinensis (Lour.) S. Moore, alongside with five known compounds (5–9), 2-methoxy-4-prop-1-enylphenyl-1-O-β-D-apiofuranosyl-(1 → 6)-β-D-glucopyranoside (5), and 1-[O-β-d-xylopyranosyl-(1 → 6)-O-β-d-glucopyranosyl]-2,6-dimethoxy-4-propenyl-phenol (6), 6-O-p-coumaroylsucrose (7), arillatose B (8), and (−)-secoisolariciresinol-O-β-D-glucopyranoside (9). The structures of these compounds were elucidated through spectroscopic methods, comparison with existing data, and chemical methods. Furthermore, all compounds were assessed for their impact on hepatocellular viability using the Resazurin reduction assay. These investigations aimed to explore the potential hepatoprotective properties of isolated compounds. As a result, 1-[O-β-d-xylopyranosyl-(1 → 6)-O-β-d-glucopyranosyl]-2,6-dimethoxy-4-propenyl-phenol (6) and (−)-secoisolariciresinol-O-β-D-glucopyranoside (9) demonstrated statistically significant hepatoprotective activity in a concentration-dependent manner.

Preliminary Pharmacognostical &amp; Pharmacological Studies on The Pisonia Grandis R. Br. on Rats

The plant Pisonia Grandis R.Br. belongs to the family Nyctaginaceae was taken up for the study by me to screening and gave a report on the possible Pharmacognostical and Pharmacological studies. The various ash values and extract values are determined. In Phytochemical screening showed the nature of the chemical constituents such as Alkaloids, Carbohydrates, Phenolic compounds, Protein and Amino acids, Saponins, Sterols, Flavonoids and Tanins present in the leaf extract of Pisonia Grandis R.Br. The LD50 of the aqueous and alcoholic extracts of Pisonia Grandis R.Br. leaves was found to be 2500 mg/kg. Therefore ED50 was calculated as 250 mg/kg. The Hepatoprotective activity was carried out by the Paracetamol induced model in rats. Administration of the aqueous and alcoholic extracts of Pisonia grandis R.Br. leaves showed significant hepatoprotective activity which was compared with the standared drug silymarin. The effect was more pronounced with the aqueous extracts Pisonia grandis R.Br., this may be probably due to the high contents of flavonoids. Keywords: Pisonia grandis R.Br , Hepatoprotective, Histopathology, Paracetamol.

Exploring the Pharmacological Potential of Acacia auriculiformis: A Comprehensive Review of Medicinal Properties and Therapeutic Applications

This review explores the pharmacological potential of Acacia auriculiformis, highlighting its diverse medicinal properties and therapeutic applications. Through a detailed analysis of experimental evidence, the study showcases the plant's efficacy in various health concerns. The plant exhibits significant wound healing, antifungal, antibacterial, antifilarial, antioxidant, antimalarial, hepatoprotective, chemoprotective, antimutagenic, CNS depressant, spermicidal, and cestocidal activities. The global interest in herbal medicine and the increasing utilization of A. auriculiformis underscore its importance in alternative healthcare approaches. The review emphasizes the need for further research to elucidate the mechanisms of action underlying the plant's pharmacological activities and to explore its potential clinical benefits. The findings suggest that A. auriculiformis holds promise as a source of therapeutic agents for a wide range of health conditions. Continued investigation into the bioactive compounds derived from the plant, along with clinical trials to assess efficacy and safety, could pave the way for the development of novel treatments. Overall, this review sheds light on the multifaceted medicinal properties of A. auriculiformis and its potential contribution to the field of herbal medicine and drug discovery.

Effects of Garnoderma lucidum on Acetaminophen-Induced Liver Injury in Wistar Rats

Introduction: Ganoderma lucidum is considered to be a medicinal mushroom, widely used to prevent or treat different types of diseases including cancer, cardiovascular disease and hepatic dysfunction. This study aimed to evaluate the effect of Ganoderma lucidum on acetaminophen-induced liver injury in wistar rats. Methods: Forty (40) male wistar rats were used for this study. Hepatoxicity was induced by oral administration of acetaminophenn (3000 mg/kg of body weight) for the last 21 consecutive days of the dietary of regimen Ganoderma lucidum. These rats were divided into eight cages each containing Five rats. Control Group 1 fed on feed and water only throughout the study, Group 2 received acetaminophen only, Group 3 received Acetaminophen + Standard drug (silymarin), Group 4 received Acetaminophen +100 mg/kg body weight of Ganoderma lucium extract, Group 5 received Acetaminophen + 200 mg/kg body weight of Ganoderma lucidum extract, Group 6 received Acetaminophen + 300 mg/kg body weight of Ganoderma lucidum extract , Group 7 received 100 mg/kg of Ganoderma lucidum extract, Group 8 received Acetaminophen+Standard Drug (silymarin) + 300 mg/kg body weight of Ganderma lucidum extract. Blood samples was collected via cardiac puncture within 24 hours of Sacrifice. The extent of the liver injury was determined by assessing the plasma levels of Tumor Necrosis Factor Alpha (TNF-α), Alpha Feto protein, Alanine aminotransferase (ALT), Aspartate aminotransferase (AST), Alkaline phosphatase (ALP), Total bilirubin (TB), Conjugated bilirubin (CB), Unconjugated Bilirubin (UB), Albumin, Gamma Glutamyl Transaminase (GGT) and total protein (TP) using spectrophotometric method and ELISA as appropriate. Results: Oral administration of Acetaminophen significantly increased the plasma levels of the parameters accessed, suggesting severe liver damage in the rats. However, the treatment of Ganoderma lucidum decreased these hepatotoxic indices at a significant level of P &lt;0.01 for TNF-α, AFP, ALT, AST, UB, TB, GGT and ALP, while Albumin and Conjugated Bilirubin were significantly decreased at a level of (P&lt;0.05) in the Ganoderma lucidum + Acetaminophen-administered group compared to those of the control group. Conclusion: Thus, the results of the present investigation demonstrates that the Ganoderma lucidum provides significant hepatoprotective activity against acetaminophen-induced liver injury in wistar rats.

&lt;i&gt;In Vivo&lt;/i&gt; Hepatoprotective Activity of Hydroalcohol Extract of &lt;i&gt;Gyrocarpus asiaticus&lt;/i&gt; Willd and &lt;i&gt;Lactuca runcinata&lt;/i&gt; DC

Objective: Investigation of hepatoprotective activity of Gyrocarpus asiaticus Willd (GA) and Lactuca runcinata DC (LR) prepared by hydroalcohol extraction. Methodology: Albino rats were used for the in vivo experiments for the determination of oral acute toxicity study. For these experiments, 6 groups were created of which 5 groups were for each plant extract and 1 group for control. A total of 11 groups were made for the toxicity study. Each group required 2 albino mice. Different doses of 0.025, 0.2, 0.5, 2, and 5 gm/kg body weight were administered orally for each plant extract. For the control group, these were administered with distilled water. For hepatoprotective activity, albino rats were randomly divided into 5 (control, toxic, standard, 2 samples) groups, and 4 animals were randomly divided into each group. For 2 plants, a total of 7 groups were made. 5% gum acacia was used as the vehicle. For induced hepatotoxicity CCl4 and as a standard drug silymarin was used. Result and Discussion: Plant extracts did not show any toxicity, and no histopathological changes were seen in the liver, kidney, or lungs due to toxicity. In the study of GA Willd and LR DC extract prepared by hydroalcohol solution, there was evidence of protection against CCl4-induced hepatotoxicity in the Histopathological study of the liver of albino rats. Conclusion: Hydroalcohol extract of LR DC and GA Willd shows no oral acute toxicity and LR DC shows no significant hepatoprotective activity but GA Willd shows significant hepatoprotective activity

Identification of Quality Markers in Schisandra chinensis (Turcz.) Baill. Using UPLC-Q-Extractive Orbitrap/MS, Chemometric Analysis, and Network Pharmacology

Chemical composition is a critical factor for determining the efficacy of any traditional Chinese medicine (TCM) and can be used as an indicator of commercial quality. To develop a new strategy for discovering potential quality markers (Q-markers) of TCM by integrating ultra-performance liquid chromatography-Q-extractive orbitrap/mass spectrometry (UPLC-Q-Extractive Orbitrap/MS), chemometric analysis, and network pharmacology, using Schisandra chinensis (Turcz.) Baill. (S. chinensis) as an example. The chemical profiling of S. chinensis was performed using UPLC-Q-Extractive Orbitrap/MS, followed by identification of hepatoprotective Q-markers through a comprehensive understanding of chemometric analysis and virtual target prediction of network pharmacology. Six compounds were considered potent candidates for Q-markers, which were identified as schisandrol A (6), angeloylgomisin H (10), schisantherin A (17), schisantherin B (18), schisandrin A (23), and schisandrin C (26). All Q-markers exhibited significant hepatoprotective activity, as evidenced by in vitro experiments. Subsequently, a method for simultaneous quantification was established and employed to analyse seven batches of S. chinensis. Therefore, the integrated approach of UPLC-Q-Extractive Orbitrap/MS, chemometrics, and network pharmacology proved to be an effective strategy for the discovery of Q-markers that can assist in assessing the overall chemical consistency of samples and provide a basis for quality evaluation of the material basis of S. chinensis.

Hepatoprotective effect of the ethanol extract of Detarium senegalense stem bark in albino Wistar

Aim: The hepatoprotective effect of Detarium senegalense ethanol stem bark extract was evaluated against paracetamol induced hepatic damage in albino rats. Material and methods: The ethanol stem bark extract of D. senegalense at doses of 100 mg/kg, 200 mg/kg and 400 mg/kg were orally administered once daily for 3 days.The liver function tests and biochemical investigation such as asparte transaminase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP), total bilirubin (TB) and direct bilirubin were carried out against paracetamol induced hepatotoxicity in rats. Phytochemical investigation was performed to find active constituents of the plant extracts by the different phytochemical tests. Results: Pre-treatment with the ethanol stem bark extract significantly prevented the biochemical, histological, and changes induced by paracetamol in the liver. The extract showed significant hepatoprotective effects as evidenced by decreased serum enzyme activities such as AST, ALT,, ALP, TB and DB which was supported by histopatological assessment of the liver.The ethanol stem bark extract exhibited significant hepatoprotective activity comparable with silymarin, the standard drug as well as hepatotoxin agent, paracetamol. The phytochemical screening of the extract revealed the presence of alkaloids, saponins, tannins, flavonoids, terpenoids, steroids, cardiac glycosides, resins and balsam. Conclusion: The results of this study strongly show that ethanol stem bark extract of Detarium senegalense possess a potent hepatotoxicity activity against paracetamol induced hepatic damage in rats.

Liver-boosting potential: chicory compound-mediated silver nanoparticles for hepatoprotection-biochemical and histopathological insights.

Background: Liver disease is a serious health concern in today's world, posing a challenge to both healthcare providers and pharmaceutical companies. Most synthetic drugs and chemicals cause liver damage accounting for approximately 10% of acute hepatitis and 50% of acute liver failure. Purpose: The present study aimed to evaluate the hepato-protective activity of an extract of chicory formulation assisted by silver nanoparticles against carbon tetra chloride (CCl4)-induced hepatic damage in rat's liver. Methods: Rats of the Wistar strain (Rattus norvegicus) were used to test the in vivo hepato-protective efficacy at various doses. Rats were randomly divided into nine groups, each containing six rats. The groups were as follows: first group (control), second group (CCl4), third group, silymarin (20mg/kg of body weight), fourth group (CCl4+chicory) (1.75mg/kg of b. wt), fifth group (CCl4 + chicory at the dose of 2.35mg/kg), sixth group (CCl4 + chicory of 3.25mg/kg), seventh group (CCl4 +AgNPs 1.75mg/kg of b. wt.), eighth group (CCl4 + AgNPs 2.35mg/kg of body weight), and ninth group (CCl4 + AgNPs 3.25mg/kg of b. wt.). Blood samples were taken 24h after the last administration (i.e., 30th day). The blood samples were analyzed for different serum enzymes such as ALP (alkaline phosphatase), ALT (alanine transaminase), bilirubin (Blr), triglyceride, and cholesterol. Histology liver sections were performed. Results: Treatment with AgNPs and chicory extract showed significant hepato-protective activity in a dose-dependent manner. In three doses, the chicory extract at a rate of 3.25mg/kg of body weight significantly reduced elevated levels of biochemical markers in comparison to CCl4-intoxicated rats. Histology of the liver sections from CCl4-treated rats revealed inflammation of hepatocytes, necrosis, cytoplasmic degeneration, vacuolization, and a deformed central vein. The chicory formulation extract exhibited a remarkable recovery percentage in the liver architecture that was higher than the drug (i.e., silymarin). While treatment with AgNPs also repaired the degenerative changes and restored the normal form of the liver, chicory formulation extract possessed more hepato-protective potential as compared to AgNPs by regulating biochemical and histo-pathological parameters. Conclusion: This study can be used as confirmation of the hepato-protective potential of chicory compounds for possible use in the development programs of drugs to treat liver diseases.

Chromatographical fingerprint analysis, in silico investigation, and identification of hepatoprotective active compounds from Capparis decidua Edgwe (Forssk.)

Liver disorders are globally distributed with a high burden of disease costs. The methanolic extract of Capparis decidua stem part and its dichloromethane (DCM) and ethylacetate fractions showed significant hepatoprotective activity, so this study aimed to develop gas chromatography/mass spectrometry (GC/MS), high-performance thin layer chromatography (HPTLC) fingerprint profile and in silico docking of identified compounds from both fractions responsible for hepatoprotective activity. Hexadecanoic acid, 9-octadecenoic acid, 9,12,15-octadecatrienoic acid, and dihydrolinalool are known hepatoprotective and antioxidant agents that were identified from both fractions by GC/MS, they have various degrees of hepatoprotective and antioxidant properties, this is the first time to identify hexadecanoic acid in C. decidua stem. Both fractions were chromatogramed with known hepatoprotective standard compounds, they were rutin, quercetin, kaempferol, ferulic acid, oleanolic acid, and β-sitosterol; β-sitosterol and oleanolic were isolated and identified in the DCM fraction by HPTLC, but nothing of these standard compounds were identified in the ethylacetate fraction. According to International Council for Harmonization guidelines, the HPTLC fingerprint profile method was validated to confirm our isolation and identification process of β-sitosterol and oleanolic acid in the DCM fraction, also their contents were quantified and they were 9.21 and 7.73 μg/mg, respectively, in the total dry fraction weight, this was the first time to isolate and identify oleanolic acid from C. decidua stem part. In silico docking was carried and was found that hexadecanoic acid showed significant predicted binding properties on Nrf2, p38 mitogen-activated protein kinase, and IL-1 receptor proteins. 9-octadecenoic acid (elaidic acid) showed significant predicted interactions with IL-1 receptor, Nrf2, and peroxisome proliferator-activated receptor-α (PPAR-α) proteins. Oleanolic acid showed significant predicted bindings with p65, JNK, and NF-kb. β-sitosterol showed significant predicted interaction with IL-6α protein, while 9,12,15-octadecatrienoic acid revealed significant binding with PPAR-α protein. Therefore, we recommend considering our active compounds in the field of drug development (structure-activity relationship) and the possibility of the presence of synergism if they are combined and administered together. Moreover, we recommend liquid chromatography-mass spectrometry and nuclear magnetic resonance on both fractions to search for the possibility of the presence of other hepatoprotective compounds.

Systematic screening of hepatoprotective components from traditional Chinese medicine: Zuojin Pill as an example

Ethnopharmacological relevanceZuojin Pill (ZJP), composed of Coptis chinensis Franch. and Euodia ruticarpa (A. Juss.) Benth. in a mass ratio of 6:1, is a famous traditional Chinese medicine (TCM) formula recorded in “Danxi's Experiential Therapy”, an ancient medical book from the Ming Dynasty of China. It is used to treat liver fire invading the stomach, which is caused by liver stagnation transforming into fire and disharmony between the liver and stomach. Aim of the studyTo develop a systematic strategy to screen hepatoprotective components from TCM using ZJP as a model sample. Materials and methodsA CCl4-induced mouse model of acute liver injury was used for the verification of the hepatoprotective effects of ZJP. UPLC-Q-Exactive Plus Orbitrap MS/MS was used for the identification of the components in mouse serum after intragastric administration of ZJP. The hepatoprotective activities of the components found in mouse serum were tested in primary cultured mouse hepatocytes induced by CCl4. ResultsNine components with significant hepatoprotective activity including berberine, epiberberine, coptisine, palmatine, jatrorrhizine, rutaecarpin, dehydroevodiamine, evocarpine and chlorogenic acid were successfully screened out. ConclusionsOur developed strategy has the advantages of high efficiency and low cost, and would provide a powerful tool for screening potential hepatoprotective components from TCM.

Hepatoprotective activities of polyherbal formulations: A systematic review

Background: Liver diseases pose a substantial global public health challenge, encompassing conditions such as liver failure, hepatitis, cirrhosis and associated complications Safeguarding the liver becomes important as these conditions impact human health. Hepatoprotective agents play a pivotal role in mitigating liver damage caused by chemicals, drugs and toxins. Polyherbal formulations, combining botanical components from traditional medicine, offer a promising approach to addressing liver disorders. Their popularity arises from a multi-targeted strategy in treating complex diseases, marking a shift in focus toward these formulations.Aim: The study aimed to conduct a thorough review of the existing literature on the hepatoprotective activity of polyherbal formulations and provide a comprehensive overview of their mechanisms of action. This review provides the overview of the use of polyherbal formulations in the management of liver disease.Method: A systematic search of electronic databases, including : Scopus, Academia, Elsevier, Science Direct, Wiley, BioMed Central, PubMed, and Google Scholar, was conducted using a combination of keywords such as ‘polyherbal formulations’, ‘hepatoprotective’ and ‘liver diseases’. Studies published between January 2010 and April 2023 were included in the review.Results: A total of 61 articles were reviewed, and the studies showed that polyherbal formulations possess significant hepatoprotective activity against various hepatotoxic agents. The mechanisms of action of these formulations include antioxidant, antiinflammatory, antifibrotic and antiapoptotic effects. Additionally, some polyherbal formulations were found to stimulate liver regeneration, enhance bile secretion and promote detoxification processes.Conclusion: Polyherbal formulations have shown promising hepatoprotective activity, and their multitargeted approach to treating complex diseases makes them a potential alternative to conventional medicines. However, identifying the active compounds responsible for the hepatoprotective effects of these formulations and their pharmacokinetics and pharmacodynamics could provide insights into the development of new and effective drugs for liver disorders.Contribution: This article contributes to the growing body of literature on the potential of polyherbal formulations as hepatoprotective agents.

Hepatoprotective effects of bioactive compounds from traditional herb Tulsi (Ocimum sanctum Linn) against galactosamine-induced hepatotoxicity in rats.

Ocimum sanctum L. (Tulsi; Family: libiaceae), also known as "The Queen of herbs" or "Holy Basil," is an omnipresent, multipurpose plant that has been used in folk medicine of many countries as a remedy against several pathological conditions, including anticancer, antidiabetic, cardio-protective, antispasmodic, diaphoretic, and adaptogenic actions. This study aims to assess O. sanctum L.'s hepatoprotective potential against galactosamine-induced toxicity, as well as investigate bioactive compounds in each extract and identify serum metabolites. The extraction of O. sanctum L as per Ayurveda was simultaneously standardized and quantified for biochemical markers: rutin, ellagic acid, kaempferol, caffeic acid, quercetin, and epicatechin by HPTLC. Hepatotoxicity was induced albino adult rats by intra-peritoneal injection of galactosamine (400mg/kg). The quantified hydroalcoholic and alcoholic extract of O. sanctum L (100 and 200mg/kg body weight/day) were compared for evaluation of hepatoprotective potential, which were assessed in terms of reduction in histological damage, change in serum enzymes such as AST, ALT, ALP and increase TBARS. Twenty chemical constituents of serum metabolites of O. sanctum were identified and characterized based on matching recorded mass spectra by GC-MS with those obtained from the library-Wiley/NIST. We evaluated the hepatoprotective activity of various fractions of hydroalcoholic extracts based on the polarity and investigated the activity at each phase (hexane, chloroform, and ethyl acetate) in vitro to determine how they affected the toxicity of CCL4 (40mM) toward Chang liver cells. The ethyl acetate fraction of the selected plants had a higher hepatoprotective activity than the other fractions, so it was used in vacuum liquid chromatography (VLC). The ethyl acetate fraction contains high amounts of rutin (0.34% w/w), ellagic acid (2.32% w/w), kaempferol (0.017% w/w), caffeic acid (0.005% w/w), quercetin (0.038% w/w), and epicatechin (0.057% w/w) which are responsible for hepatoprotection. In comparison to standard silymarin, isolated bioactive molecules displayed the most significant hepatoprotective activity in Chang liver cells treated to CCl4 toxicity. The significant high hepatoprotection provided by standard silymarin ranged from 77.6% at 100μg/ml to 83.95% at 200μg/ml, purified ellagic acid ranged from 70% at 100μg/ml to 81.33% at 200μg/ml, purified rutin ranged from 63.4% at 100μg/ml to 76.34% at 200μg/ml purified quercetin ranged from 54.33% at 100μg/ml to 60.64% at 200μg/ml, purified epicatechin ranged from 53.22% at 100μg/ml to 65.6% at 200μg/ml, and purified kaempferol ranged from 52.17% at 100μg/ml to 60.34% at 200μg/ml. These findings suggest that the bioactive compounds in O. sanctum L. have significant protective effects against galactosamine-induced hepatotoxicity.

HEPATOPROTECTIVE EFFECT OF ZINC COMPLEX OF BETULINIC ACID ON PYRAZINAMIDE INDUCED HEPATOTOXICITY IN MICE

Background: Hepatotoxicity is a common side effect of pyrazinamide, a first line anti-tuberculous drug. Objective of this study was to determine the hepatoprotective effect of zinc complex of Betulinic acid (BA) on pyrazinamide induced hepatotoxicity in mice. Methods: This experimental, randomized control study was conducted at Islamic International Medical College, Rawalpindi, and National Institute of Health Islamabad from 1 Sep 2020 to 31 Aug 2021. Thirty male Balb/c albino mice were divided into three groups each having 10 mice. Group 1 received normal diet with no medication. Group 2 (NC) received pyrazinamide 500 mg/Kg daily for 28 days. Group 3 (DC) received Zinc complex of Betulinic acid 1 mg/Kg/day per oral once daily along with pyrazinamide. Final sampling was done on day 28 by intracardiac puncture for estimation of serum ALT and bilirubin level. Data was analysed on SPSS-21. Comparisons between the groups were analyzed using one way ANOVA (Post Hoc Tuckey test), and p&lt;0.05 was considered significant. Results: Zinc complex of Betulinic acid treated group had significantly decreased serum ALT (58.00±5.639) and bilirubin (0.617±0.601) in comparison with pyrazinamide treated group. Conclusion: Zinc complex of Betulinic acid exerted significant hepatoprotective activity in pyrazinamide induced hepatotoxicity. Pak J Physiol 2023;19(3):36–8

A comprehensive review on traditional therapeutic uses, bioactive principles and pharmacological activities of Kantakari (Solanum virginianum L.): An important Ayurvedic herb

Solanum virginianum L., a perennial wild plant, belongs to the 'Dashamoola' group in Ayurveda. 'Kantkari Ghrita' in Charaka Samhita is used for cough, cold, fever, asthma, and cardiac diseases. 'Dasmul Asava' and 'Dashmularishta' are tonics for lactating mothers. Inflammatory disorders, rheumatism, and diabetes are traditionally treated using leaf juice and fruits. Various plant parts contain bioactive compounds like solamargine, solasonine, campesterol, ?-sitosterol, cycloartenol, chlorogenic acid, vanillic acid, etc. Roots, flowers, stems, and fruits are used for their medicinal properties such as carminative, febrifuge, expectorant, diuretic, and bitter tonic effects. They are employed to treat cough, asthma, fever, toothache, tuberculosis, rheumatism, sore throat, kidney disorders, gonorrhea, vesicular eruptions, and burning sensation in the feet. Different extracts from various plant parts exhibit significant anti-inflammatory, nephroprotective, anti-asthmatic, hepatoprotective, immunomodulatory, antimicrobial, larvicidal, antinociceptive, antispermatogenic, antioxidant, and antidiabetic activities. This study reviews 37 relevant research articles to comprehensively explore the plant's traditional uses, bioactive compounds, and pharmacological properties in both in-vitro and in-vivo settings, along with their mechanisms of action.

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.

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.

Amelioration of CCl4-induced oxidative stress and hepatotoxicity by Ganoderma lucidum in Long Evans rats

Liver disease is a serious health problem affecting people worldwide at an alarming rate. The present study aimed to investigate the protective effects of Ganoderma lucidum against CCl4-induced liver toxicity in rats. The experimental Long Evans rats were divided into five groups, of which four groups were treated with carbon tetrachloride (CCl4). Among the CCl4 treated groups, one of the groups was treated with silymarin and two of them with ethanolic extract of G. lucidum at 100 and 200 mg/Kg body weight. The oxidative stress parameters and endogenous antioxidant enzyme concentrations were assessed by biochemical tests. Liver enzymes ALT, AST, and ALP were determined spectrophotometrically. Histopathological examinations were carried out to assess hepatic tissue damage and fibrosis. Reverse transcription PCR (RT-PCR) was performed to determine the expression of IL-1β, IL-6, IL-10, TNF-α, and TGF-β genes. Gas Chromatography-Mass Spectroscopy (GC–MS) analysis revealed that G. lucidum is rich in several phytochemicals including 6-Octadecanoic acid (55.81%), l-( +)-Ascorbic acid 2,6-dihexadecanoate (18.72%), Cis-11-Eicosenamide (5.76%), and Octadecanoic acid (5.26%). Treatment with the G. lucidum extract reduced the elevated ALT, AST, ALP levels, and cellular oxidative stress markers and increased the endogenous antioxidant levels. Histopathology observations revealed that the inflammation, infiltration of immune cells, and aberration of collagen fibers in the hepatocytes were altered by the G. lucidum treatment. The increased expression of inflammatory cytokines TNF-α, TGF-β, IL-1 β, and IL-6 were markedly suppressed by G. lucidum extract treatment. G. lucidum also prevented the suppression of protective IL-10 expression by CCl4. This study strongly suggests that G. lucidum extract possesses significant hepatoprotective activity as evidenced by reduced oxidative stress and inflammation mediated by suppression in inflammatory cytokine expression and increased protective IL-10 cytokine expression.