In Vitro Antioxidant and In Vivo Hepatoprotective Properties of Wissadula periplocifolia Extract.

Wissadula periplocifolia (L.) Thwaites is a traditional medicinal plant belonging to the family Malvaceae, used in folk medicine for inflamed snake bites and bee stings. The current study was designed to investigate the in vitro antioxidant and in vivo anti-inflammatory and hepatoprotective activities of 80% ethanol extract of W. periplocifolia and its different fractions. The crude ethanolic extract (CEE) was then serially fractionated with petroleum ether fraction (PEF), chloroform fraction (CHF), and aqueous fraction (AQF). The antioxidant activity was assessed using 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical assay, anti-inflammatory activity was determined in the xylene-induced ear edema model, and hepatoprotective activity was measured in the paracetamol-induced hepatic injury model. PEF showed a significant scavenging effect with an IC50 value of 33.5 µg/mL, followed by CEE (IC50 = 42.2 µg/mL), CHF (IC50 = 77 µg/mL), and AQF (IC50 = 80 µg/mL), compared to standard butylated hydroxytoluene (IC50 = 14.8 µg/mL). Both doses of CEE (250 and 500 mg/kg) could reduce ear edema by 41.3 and 50%, respectively, compared to standard diclofenac sodium (76.09%). Moreover, CEE significantly reduces the elevated liver enzymes (ALT, AST, and ALP), compared to control. Nevertheless, it elevated blood protein and reduced the blood bilirubin level (p < 0.01), compared to control. Histopathological studies also indicated significant protection of the liver from paracetamol-induced liver damage. In conclusion, W. periplocifolia could be a good source of antioxidant and hepatoprotective phytochemicals; meanwhile, toxicological and pharmacokinetic studies are recommended.

GC-MS analysis, and evaluation of protective effect of Piper chaba stem bark against paracetamol-induced liver damage in Sprague-Dawley rats: Possible defensive mechanism by targeting CYP2E1 enzyme through in silico study.

The present study attempted to scrutinize the protective effect of the methanolic extract of P. chaba stem bark against paracetamol-induced hepatotoxicity in Sprague-Dawley rats, along with the gas chromatography-mass spectrometry (GC-MS) analysis to identify phytochemicals, which were further docked in the catalytic site of CYP2E1 and the MD simulation for system that plays a major role in the bio-activation of toxic substances that produce reactive metabolites, leading to hepatotoxicity. P. chaba stem methanol extract (250 and 500 mg/kg) were treated orally with the negative control and the negative control silymarin (50 mg/kg) groups. Phytochemical profiling was conducted using GC-MS. In in-silico studies, PyRx software was used for docking analysis and the stability of the binding mode in the target active sites was evaluated through a set of standard MD-simulation protocols using the Charmm 27 force field and Swiss PARAM. Co-administration of P. chaba at both doses with APAP significantly reduced the APAP-augmented liver marker enzymes ALT, AST, ALP, and LDH, along with serum albumin, globulin, hepatic enzymes, histopathological architecture, lipid profiles, total protein, and total bilirubin, and elevated the levels of MDA. The GC-MS analysis indicated that P. chaba extract is enriched in fatty acid methyl esters (46.23 %) and alkaloids (10.91 %) and piperine is represented as a main phytochemical. Among all the identified phytochemicals, piperine (-8.0 kcal/mol) was found to be more interacting and stable with the binding site of CYP2E1. Therefore, all of our findings may conclude that the P. chaba stem extract and its main compound, piperine, are able to neutralize APAP-induced hepatic damage.

Subchronic Toxicity Study of Alternanthera philoxeroides in Swiss Albino Mice Having Antioxidant and Anticoagulant Activities.

Alternanthera philoxeroides, a tropical herb and edible vegetable, has been popular as a medicinal plant. Applying in vitro approach, we initially attempted to assess the phytochemicals, bioactive chemicals, as well as antioxidant and anticoagulant activities of this plant. Following that, the in vivo toxicological effects of methanolic extracts of A. philoxeroides using different doses on the kidney, heart, lung, liver, stomach, brain, and blood of female Swiss Albino mice were investigated. We estimated phytochemicals content as well as antioxidant activity through DPPH, NO, CUPRAC, and reducing power assays, followed by the anticoagulant activities of PT and aPTT and bioactive compounds using HPLC. To confirm the biocompatibility of A. philoxeroides extracts, histopathological and hematological parameters were examined in a mice model. Total phenol, flavonoid, and tannin content in A. philoxeroides was 181.75 ± 2.47 mg/g, 101.5 ± 3 .53 mg/g, and 68.58 ± 0.80 mg/g, respectively. Furthermore, the HPLC study confirmed the presence of four phenolic compounds: catechin, tannic acid, gallic acid, and vanillic acid. The methanolic extract of A. philoxeroides showed considerable antioxidant activity in all four antioxidant assay methods when compared to the standard. In comparison to ascorbic acid, A. philoxeroides also demonstrated a minor concentration-dependent ferric and cupric reduction activity. In vivo evaluation indicated that A. philoxeroides extracts (doses: 250, 500, and 1000 mg/kg) had no negative effects on the relative organ or body weight, or hematological indicators. Our study concluded that A. philoxeroides had significant antioxidant and anticoagulant activities and demonstrated no negative effects on the body or relative organ weight, histopathological, and hematological indices in the mouse model.

Redox Activity of Flavonoids: Impact on Human Health, Therapeutics, and Chemical Safety.

The cost-effectiveness of presently used therapies is a problem in overall redox-based management, which is posing a significant financial burden on communities across the world. As a result, sophisticated treatment models that provide notions of predictive diagnoses followed by targeted preventive therapies adapted to individual patient profiles are gaining global acclaim as being beneficial to patients, the healthcare sector, and society as a whole. In this context, natural flavonoids were considered due to their multifaceted antioxidant, anti-inflammatory, and anticancer effects as well as their low toxicity and ease of availability. The aim of this review is to focus on the capacity of flavonoids to modulate the responsiveness of various diseases and ailments associated with redox toxicity. The review will also focus on the flavonoids' pathway-based redox activity and the advancement of redox-based therapies as well as flavonoids' antioxidant characteristics and their influence on human health, therapeutics, and chemical safety. Research findings indicated that flavonoids significantly exhibit various redox-based therapeutic responses against several diseases such as inflammatory, neurodegenerative, cardiovascular, and hepatic diseases and various types of cancer by activating the Nrf2/Keap1 transcription system, suppressing the nuclear factor κB (NF-κB)/IκB kinase inflammatory pathway, abrogating the function of the Hsp90/Hsf1 complex, inhibiting the PTEN/PI3K/Akt pathway, and preventing mitochondrial dysfunction. Some flavonoids, especially genistein, apigenin, amentoflavone, baicalein, quercetin, licochalcone A, and biochanin A, play a potential role in redox regulation. Conclusions of this review on the antioxidant aspects of flavonoids highlight the medicinal and folk values of these compounds against oxidative stress and various diseases and ailments. In short, treatment with flavonoids could be a novel therapeutic invention in clinical trials, as we hope.

Role of Citrus medica L. Fruits Extract in Combatting the Hematological and Hepatic Toxic Effects of Carbofuran.

Citrus medica L. is rich in numerous vital bioactive constituents, though it is an underutilized among the citrus genus. Therefore, the aim of the present investigation was to evaluate the protective role of the C. medica fruit (CMF) methanol extract against carbofuran (CF)-induced toxicity in experimental rats. In addition, this work aims at detecting and measuring polyphenolic compounds by means of high-performance liquid chromatography (HPLC) and evaluation of the antioxidant activity of this extract. For this, studies dealing with serum hematological and biochemical parameters, liver endogenous antioxidants, as well as hepatic histo-architectural features have been carried out to assess the protective ability of CMF against CF-induced toxicity. Additionally, total phenol, flavonoid, and antioxidant capability were measured and the antioxidant action was investigated using DPPH and nitric oxide radical scavenging assays as well as reducing power assessments. HPLC results revealed the presence of benzoic acid, cinnamic acid, gallic acid, quercetin, and salicylic acid in CMF extract. Furthermore, results showed that CMF has considerable total phenol, flavonoid, and antioxidant capability and exhibits significant free radical scavenging and reducing potentialities. On the other hand, CF intoxication of rats significantly altered the hematological and serum biochemical parameters with hepatocytes disruption. Carbofuran also caused an upsurge in malondialdehyde (MDA) level and a decline in hepatic cellular antioxidant enzymes levels in rats compared to the control group. Co-administration of CMF amended the anomalies and improved the histo-architectural arrangement of hepatocytes in treated groups. CMF also inhibited the alteration of endogenous antioxidant enzymes and MDA levels as compared to the carbofuran treated group and returned them to their normal state. Taken all together, results from this investigation highlight the protective role of CMF against CF-induced toxicity which might be attributed to the polyphenolic constituents of the extract.

Antioxidant mediated protective effect of Bridelia tomentosa leaf extract against carbofuran induced oxidative hepatic toxicity.

Bridelia tomentosa (B. tomentosa) is a traditional medicinal plant for treating diverse ailments. Hence, we designed our study to scrutinize the protective effect of the methanol extract of B. tomentosa leaf (BTL) against carbofuran-induced oxidative stress-mediated hepato-toxicity in Sprague-Dawley rats for the first time, along with the identification and quantification of phenolic acids and flavonoids by high-performance liquid chromatography (HPLC) and evaluation of antioxidant and antiradical activities of this extract. HPLC analysis confirmed the existence of tannic acid, gallic acid, salicylic acid, and naringin in B. tomentosa leaf extract which showed in-vitro antioxidant potentialities with DPPH, nitric oxide, hydrogen peroxide, and hydroxyl radical scavenging properties. Co-administration of B. tomentosa leaf extract with carbofuran showed dose-dependent significant protective effects of hepatic toxicity on serum markers such as alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, γ-glutamyl-transferase, lactate dehydrogenase, total bilirubin, total protein, albumin, globulin, lipid profile, urea, uric acid, and creatinine. Carbofuran intoxication also revealed an upsurge in malondialdehyde (MDA) and a decline in cellular endogenous antioxidant enzyme levels in rats compared with the control group. However, B. tomentosa leaf extract co-treatment increased the levels of hepatic antioxidant enzymes, such as superoxide dismutase, catalase, and glutathione peroxidase, and amended the MDA level. Similarly, histopathological evaluation further assured that BTL could keep the hepatocyte from carbofuran-induced damage. Therefore, all of our findings may conclude that the phenolic acids and flavonoids of B. tomentosa leaf extract are responsible to neutralize the toxic free radical-mediated oxidative hepatic damages.

Heliotropium indicum L.: From Farm to a Source of Bioactive Compounds with Therapeutic Activity.

This study aimed to summarize the available data on the ethnomedicinal and phytopharmacological activities of Heliotropium indicum L. based on database reports. For this purpose, an up-to-date literature search was carried out in the Google Scholar, Scopus, Springer Link, Web of Science, ScienceDirect, ResearchGate, PubMed, Chem Spider, Elsevier, BioMed Central, and patent offices (e.g., USPTO, CIPO, NPI, Google patents, and Espacenet) for the published materials. The findings suggest that the plant contains many important phytochemicals, including pyrrolizidine alkaloids, indicine, echinitine, supinine, heleurine, heliotrine, lasiocarpine, acetyl indicine, indicinine, indicine N-oxide, cynoglossine, europine N-oxide, heleurine N-oxide, heliotridine N-oxide, heliotrine N-oxide, heliotrine, volatile oils, triterpenes, amines, and sterols. Scientific reports revealed that the herb showed antioxidant, analgesic, antimicrobial, anticancer, antituberculosis, antiplasmodial, anticataract, antifertility, wound healing, antiinflammatory, antinociceptive, antihyperglycemic, anthelmintic, diuretic, antitussive, antiglaucoma, antiallergic, and larvicidal activity. In conclusion, in vitro studies with animal models seem to show the potential beneficial effects of H. indicum against a wide variety of disorders and as a source of phytotherapeutic compounds. However, clinical studies are necessary to confirm the effects observed in animal models, determine the toxicity of the therapeutic dose and isolate the truly bioactive components.

Effects of nerol on paracetamol-induced liver damage in Wistar albino rats.

Nerol, a monoterpene is evident to possess diverse biological activities, including antioxidant, anti-microbial, anti-spasmodic, anthelmintic, and anti-arrhythmias. This study aims to evaluate its hepatoprotective effect against paracetamol-induced liver toxicity in a rat model. Five groups of rats (n = 7) were orally treated (once daily) with 0.05% tween 80 dissolved in 0.9% NaCl solution (vehicle), paracetamol 640 mg/kg (negative control), 50 mg/kg silymarin (positive control), or nerol (50 and 100 mg/kg) for 14 days, followed by the hepatotoxicity induction using paracetamol (PCM). The blood samples and livers of the animals were collected and subjected to biochemical and microscopical analysis. The histological findings suggest that paracetamol caused lymphocyte infiltration and marked necrosis, whereas maintenance of the normal hepatic structural was observed in group pre-treated with silymarin and nerol. The rats pre-treated with nerol significantly and dose-dependently reduced the hepatotoxic markers in animals. Nerol at 100 mg/kg significantly reversed the paracetamol-induced altered situations, including the liver enzymes, plasma proteins, antioxidant enzymes and serum bilirubin, lipid peroxidation (LPO) and cholesterol [e.g., total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-c), low-density lipoprotein cholesterol (LDL-c)] levels in animals. Taken together, nerol exerted significant hepatoprotective activity in rats in a dose-dependent manner. PCM-induced toxicity and nerol induced hepatoprotective effects based on expression of inflammatory and apoptosis factors will be future line of work for establishing the precise mechanism of action of nerol in Wistar albino rats.

Therapeutic perspectives of the black cumin component thymoquinone: A review.

The dietary phytochemical thymoquinone (TQ), belonging to the family of quinones, mainly obtained from the black and angular seeds of Nigella sativa, is one of the promising monoterpenoid hydrocarbons, which has been receiving massive attention for its therapeutic potential and pharmacological properties. It plays an important role as a chemopreventive and therapeutic agent in the treatment of various diseases and illnesses. The aim of this review is to present a summary of the most recent literature pertaining to the use of TQ for the prevention and treatment of various diseases along with possible mechanisms of action, and the potential use of this natural product as a complementary or alternative medicine. Research findings indicated that TQ exhibits numerous pharmacological activities including antioxidant, anti-inflammatory, cardioprotective, hepatoprotective, antidiabetic, neuroprotective, and anticancer, among others. Conclusions of this review on the therapeutic aspects of TQ highlight the medicinal and folk values of this compound against various diseases and ailments. In short, TQ could be a novel drug in clinical trials, as we hope.

Anti-diarrheal activities of phytol along with its possible mechanism of action through in-vivo and in-silico models.

Phytol (PHY), a chlorophyll-derived diterpenoid, exhibits numerous pharmacological properties, including antioxidant, antimicrobial, and anticancer activities. This study evaluates the anti-diarrheal effect of phytol (PHY) along with its possible mechanism of action through in-vivo and in-silico models. The effect of PHY was investigated on castor oil-induced diarrhea in Swiss mice by using prazosin, propranolol, loperamide, and nifedipine as standards with or without PHY. PHY at 50 mg/kg (p.o.) and all other standards exhibit significant (p < 0.05) anti-diarrheal effect in mice. The effect was prominent in the loperamide and propranolol groups. PHY co-treated with prazosin and propranolol was found to increase in latent periods along with a significant reduction in diarrheal section during the observation period than other individual or combined groups. Furthermore, molecular docking studies also suggested that PHY showed better interactions with the α- and ß-adrenergic receptors, especially with α-ADR1a and ß-ADR1. In the former case, PHY showed interaction with hydroxyl group of Ser192 at a distance of 2.91Å, while in the latter it showed hydrogen bond interactions with Thr170 and Lys297 with a distance of 2.65 and 2.72Å, respectively. PHY exerted significant anti-diarrheal effect in Swiss mice, possibly through blocking α- and ß-adrenergic receptors.

Hepatoprotective and Antioxidant Activities of Justicia gendarussa Leaf Extract in Carbofuran-Induced Hepatic Damage in Rats.

In folk medicines, Justicia gendarussa (J. gendarussa) is used as a depurative herb for treating fever, pain, and cancer and as laxative for constipation. The aim of the present investigation was to evaluate the hepatoprotective effect of the leaf methanol extract of J. gendarussa leaf (J gMe) against carbofuran (CF)-intoxicated liver injuries in Sprague-Dawley rats, along with the antioxidant activity of this extract. For this purpose, levels of serum diagnostic markers, hepatic antioxidant enzymes, and liver histo-architecture were employed to justify the protective efficacy of J gMe. In addition, the phenolic and flavonoid contents of the extract were quantified, and antioxidant activity was investigated using the 1,1-diphenyl-2-picrylhydrazyl (DPPH), nitric oxide, hydrogen peroxide, and hydroxyl free radical scavenging assays. Results revealed that the leaf extract caused a significant (<0.05, <0.01) decrease of the level of hepatic enzymes, triglycerides, and bilirubin and an increase of the total protein. J gMe has also significantly (<0.05, <0.01) lowered the level of malonylaldehyde. Carbofuran markedly suppressed hepatic antioxidant enzymes, however, the leaf extract significantly augmented these enzymes. The hepatoprotective effect was demonstrated by the improvement in the histo-architectural features of liver sections of CF-intoxicated rats treated with J gMe at 500 mg/kg dose. In addition, J gMe showed moderate total phenolic and total flavonoid content, whereas the IC50 values of DPPH, nitric oxide, hydrogen peroxide, and hydroxyl free radical scavenging assays were 71.31 ± 0.42, 134.82 ± 0.14, 47.69 ± 0.38, and 118.44 ± 0.30 µg/mL, respectively. In conclusion, the present study suggests the protective role of J gMe against hepatic injury induced by CF, which may be attributed to its higher antioxidant properties and thereby scientifically justifies its traditional use.

Protective Role of Syzygium Cymosum Leaf Extract Against Carbofuran-Induced Hematological and Hepatic Toxicities.

The aim of the present study was to evaluate the protective effect of Syzygium cymosum leaf methanol extract (SCL) against carbofuran (CF)-induced hepatotoxicity in Sprague-Dawley rats, along with the identification and quantification of polyphenolic composition by high-performance liquid chromatography (HPLC). Results revealed the presence of alkaloids, tannins, and flavonoids in SCL. Similarly, HPLC analysis suggests that SCL contains some known important antioxidants, such as rutin, benzoic acid, and salicylic acid that could be responsible for the hepatoprotective activity of the extract. In CF-exposed rats, significant hematological alterations along with histological changes were marked by the presence of necrosis, congestion, and inflammation. CF-intoxication also showed an increase in lipid peroxidation and decrease in cellular antioxidant enzymes (e.g., superoxide dismutase, catalase, and glutathione peroxidase) levels in rats compared with the control group. Furthermore, coadministration of SCL significantly ameliorated the abnormalities and improved the cellular arrangement in experimental animals. SCL also reversed the alteration of hematological and biochemical parameters and brought them back to normal levels as compared to the control group. In conclusion, S. cymosum may be one of the best sources of natural antioxidant compounds that can be used in the treatment of oxidative stress and stress-related diseases and disorders.

Protective effect of chloroform extract of Stereospermum chelonoides bark against amyloid beta42 induced cell death in SH-SY5Y cells and against inflammation in Swiss albino mice.

Background This study was designed to evaluate the free radical scavenging property of chloroform extract of the bark of Stereospermum chelonoides (SCBC) and to investigate its potential in Alzheimer's disease and inflammation, two oxidative stress related disorders. Methods Preliminary phytochemical analysis and in vitro antioxidant potential of SCBC were evaluated using 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging assay, ferric reducing antioxidant power (FRAP) assay, cupric reducing antioxidant capacity (CUPRAC) and total antioxidant capacity determination assay. Total phenol and total flavonoid contents were also determined. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) based cytotoxicity and cyto-protective assays were performed on human neuroblastoma SH-SY5Y cells. Thioflavin-T assay and caspase activation measurement assay were carried out to elucidate the mechanism of cytoprotection of SCBC observed here. In vivo anti-inflammatory potential was measured using croton oil and xylene induced ear edema tests. Results Phytochemical screening of SCBC revealed the presence of various phytoconstituents. Dose-dependent in vitro antioxidant activity was observed. The extract was enriched in flavonoids and polyphenolic compounds too. SCBC was found to inhibit amyloid-ß peptide 1-42 (Aß42) induced cell death in a dose-dependent manner. Encouraged by the cyto-protective effect, its effects on Aß42 fibrillogenesis and caspase-3 activated apoptosis were observed. SCBC significantly slowed down the Aß42 fibrillogenesis and caspase-3 activation in a concentration-dependent manner indicating its probable mechanism of rendering cyto-protection. SCBC has been able to reduce inflammation significantly in croton oil induced ear edema in both doses. Conclusions Thus, this study could form the basis for further study for the potential use of SCBC in oxidative stress associated cell death and inflammation.