Hepatoprotective efficacy of Argemone mexicana L. root in paracetamol-induced hepatotoxicity in a rat model.

Argemone mexicana L. (Papaveraceae), a weed that thrives in the tropical and subtropical areas of South and Central America, Mexico, Caribbean Islands and India. In India, it has been used traditionally to treat vesicular calculus, inflammatory conditions, and hepatobiliary disorders. The present study was aimed to investigate the hepatoprotective efficacy of A. Mexicana roots in paracetamol (PCM)-induced toxicity rat. The methanol extract of A. mexicana (MEAM) root was analyzed using Gas Chromatography-Mass Spectrometry (GC-MS) analysis to identify its compounds. Molecular docking analysis of the compounds was conducted against TGF-β and PPAR-α. The hepatoprotective activity of MEAM (200, 400 mg/kg) was evaluated in PCM (3000 mg/kg) intoxicated rats by measuring serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), gamma-glutamyl transferase (GGT), lactate dehydrogenase (LDH), total bilirubin (TB), total protein (TP), albumin (ALB), globulin (GLB), total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C). Silymarin (100 mg/kg) was used as reference drug. Oxidative stress biomarkers such as superoxide dismutase (SOD), catalase (CAT), reduced glutathione (GSH), and lipid peroxidation (LPO) were investigated using liver homogenate. Additionally, the levels of pro-inflammatory cytokines including tumor necrosis factor-alpha (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6), and anti-inflammatory cytokines interleukin-4 (IL-4) and interleukin-10 (IL-10) were studied. The results of the study were supported by histopathological examination. GC-MS analysis revealed 163 compounds, from which eleven compounds were selected based on their docking scores against TGF-β and PPAR-α. MEAM (400 mg/kg) demonstrated a remarkable reduction in ALT, AST, ALP, GGT, and LDH in contrast to the PCM intoxicated group. A remarkable decline in TB and GLB, along with an increase in TP and ALB, was observed in the MEAM (400 mg/kg) group compared to the untreated PCM group. Rats receiving MEAM (400 mg/kg) exhibited a noticeable decrease in TC, TG, and LDL-C, along with an increase in HDL-C levels compared to PCM-induced untreated rats. The higher dose of MEAM also resulted in a significant decrease in TNF-α, IL-1β, and IL-6, and an increase in IL-4 and IL-10. Similarly, a notable elevation in SOD, CAT, and GSH, along with a decrease in MDA content, was observed in the group receiving MEAM (400 mg/kg). The histopathological result showed reduction of sinusoidal space and vesicular nuclei, with improvement of hepatocytes at the dose of MEAM (400 mg/kg). In molecular docking study, Eupatilin exhibited the highest docking scores of -10.4 kcal/mol and -9.1 kcal/mol against TGF-β and PPAR-α, respectively. MEAM root at dose of 400 mg/kg exhibited hepatoprotective effect against PCM-induced toxicity rat. Eupatilin might be considered as a potential candidate for the hepatoprotective effect of A. mexicana root.

Bagchi A ，Raha A ，Das C ，Dash P ，Pradhan D ，Rai VK ，Rajwar TK ，Halder J ，Das D ，Manoharadas S ，Kar B ，Ghosh G ，Rath G ... -  《-》

Protective Effects of a Brassica nigra Sprout Hydroalcoholic Extract on Lipid Homeostasis, Hepatotoxicity, and Nephrotoxicity in Cyclophosphamide-Induced Toxicity in Rats.

Barakat H ，Aljutaily T ，Alkhurayji RI ，Aljumayi H ，Alhejji KS ，Almutairi SO ... -  《Metabolites》

Hepatoprotective effects of olive leaf extract against carbon tetrachloride-induced oxidative stress: in vivo and in-silico insights into the Nrf2-NFκB pathway.

Olive Leaves Extract (OLE) holds therapeutic potential, traditionally used to treat hepatic ailments, though its molecular mechanisms remain unclear. This study evaluated the efficacy of ethanolic OLE against Carbon Tetrachloride (CCl4)-induced oxidative stress in a rat model. Phytochemical analysis was performed using High Performance Liquid Chromatography (HPLC). For this porous, thirty rats were divided into six groups (n = 5): Group 1 (negative control) received a standard diet, while Groups 2-6 were subjected to CCl4-induced toxicity. Group 2 served as the disease control, and Group 3 was treated with silymarin (100 mg/kg). Groups 4, 5, and 6 received OLE at 100 mg/kg, 200 mg/kg, and 300 mg/kg, respectively, for 21 days. OLE significantly modulated hepatic biomarkers (ALT, AST, ALP), increased Total Antioxidant Capacity (TAC), decreased Total Oxidation Capacity (TOC), and restored levels of SOD, GSH, and CAT compared to the CCl4 group. Malondialdehyde (MDA) levels, elevated in the disease group, however downregulated by OLE, particularly at 300 mg/kg. Histological examination revealed normal liver integrity in the OLE-treated groups. Additionally, OLE modulated the mRNA expression of IL-1β, IL-6, TNF-α, NF-kB, Bcl2, and p-53. Apoptotic markers such as Nrf2, HO-1, Cytochrome c, caspase 3, caspase 7, and Bax were normalized with OLE treatment. The inhibition of KEAP1-NRF2 protein-protein interaction showed OLE's superior efficacy compared to silymarin, with a better docking score. These findings suggest that OLE exerts significant hepatoprotective effects against CCl4-induced oxidative stress and inflammation via the Nrf2-NFκB pathway.

Buzdar JA ，Shah QA ，Khan MZ ，Zaheer A ，Shah T ，Ataya FS ，Fouad D ... -  《-》

Erratum: Eyestalk Ablation to Increase Ovarian Maturation in Mud Crabs.

《Jove-Journal of Visualized Experiments》

Nephroprotective and diuretic effect of Alternanthera brasiliana (L.) Kuntze leaf extract; acute and sub-acute toxicity assessment.

Alternanthera brasiliana (L.) Kuntze of the family Amaranthaceae has been extensively used in traditional medicinal practices in Brazil and India for its reputed efficacy in promoting diuresis, as well as treating wounds, inflammation, postnatal symptoms, diarrhea, and cough. Its selection for this study was driven not only by its ethnomedicinal significance but also by its rich phytochemical composition, including bioactive compounds such as flavonoids, saponins, and alkaloids, which are known to exhibit nephroprotective and diuretic effects. Additionally, while many species from the Amaranthaceae family have demonstrated similar therapeutic properties, A. brasiliana remains underexplored in this context. Therefore, this research aimed to scientifically evaluate its potential nephroprotective and diuretic activities, providing a pharmacological basis for its traditional uses. This experiment was designed to determine nephroprotective effect against cisplatin-induced kidney injury and diuretic effect of Alternanthera brasiliana (L.) in rats. This study also aimed to evaluate the toxicity of plant's extract by performing acute and sub-acute toxicity trials. In current study, the nephroprotective effect of aqueous-ethanol extract of A. brasiliana was evaluated after induction of kidney injury with cisplatin. Extract was given in three doses as 75 mg/kg, 150 mg/kg and 300 mg/kg. A diuretic activity was also performed by comparing results with control and standard (furosemide). Extract was given in three doses as 75 mg/kg, 150 mg/kg and 300 mg/kg. A 14 day trial for acute toxicity assessment was performed at doses 2000 mg/kg and 3000 mg/kg, whereas a 28 day trial for sub-acute toxicity assessment was performed at doses 250 mg/kg, 500 mg/kg and 1000 mg/kg. The biological active ingredients were identified and determined using HPLC technique. The aqueous-ethanol extract of A. brasiliana (ABAE) safeguarded the rats from toxic effects of cisplatin. This extract also enhanced urine output. The protective effect of ABAE increased with increasing dose and produced maximum nephroprotective effect and diuresis at a dose 300 mg/kg. The outcomes from acute toxicity trials suggested that LD50 lied beyond 3000 mg/kg, and no antagonizing effects occurred in sub-acute toxicity trials at doses 250 mg/kg, 500 mg/kg and 1000 mg/kg. ABAE posed no toxicities on kidney, liver, and heart tissues as evident from histopathological, hematological, and serum biochemical analysis. HPLC-DAD analysis of ABAE indicated the presence of betanin, kaempherol, gallic acid, p-coumaric acid and oxalic acid. These results demonstrate an abundant supply of bioactive chemicals found in A. brasiliana (L.) extracts, which should be taken into account to improve renal functions with fewer negative effects.

Bilal MH ，Bibi I 《-》