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Aflatoxin B1 (AFB1) is recognized as the most toxic mycotoxin, widely present in nature and known to specifically target the liver, leading to severe consequences to animal and human health. The mechanisms underlying AFB1-induced hepatotoxicity involve oxidative stress and apoptosis. Radix Bupleuri (RB) and its extracts (RBE), traditional Chinese herbs with a rich history spanning over 2000 years, have been reported to possess hepatoprotective properties. Nevertheless, the impact of RBE on AFB1-induced liver injury remains to be fully elucidated. The current study utilized Pekin ducks as experimental models to explore the effects of RBE on AFB1-induced liver injury both in vitro and in vivo. In vitro findings indicated that RBE mitigated AFB1-induced cytotoxicity, improved primary duck hepatocytes (PDHs) morphology, and reduced intracellular reactive oxygen species (ROS) levels. In vivo experiments demonstrated that: I) RBE alleviated the growth inhibitory caused by AFB1, as evidenced by improved final body weight and weight gain. II) AFB1 led to significant alterations in serum biochemical parameters (AST, ALT, TP, and ALB) and liver lesions attenuated by RBE supplementation at 2.5 g/kg. III) RBE significantly mitigated oxidative stress induced by AFB1. IV) AFB1-induced changes in mRNA and protein levels associated with oxidative stress and apoptosis were counteracted by RBE. In conclusion, our results suggest that RBE offers protection against AFB1-induced liver injury in ducks, primarily through its antioxidative and anti-apoptotic properties. These findings indicate the potential of RBE in preventing and treating AFB1 poisoning., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Diethylnitrosamine (DEN) was applied to create the primary liver cancer (PLC) animal model. In the study, the normal group, model group, cyclophosphamide (CTX) group, Cortex Juglandis Mandshuricae (CJM) extract group, myricetin group and myricitrin group were divided. LC-MS/MS technology was applied to determine the metabolites of liver tissue samples from different locations (nodular and non-nodular parts of liver tissue) in each group of rats. Through metabolomics research, the connection and difference of anti-PLC induced by the CJM extract, myricetin and myricitrin was analyzed. The surface of the liver tissues of rats in the model group was rough, dimly colored, inelastic, on which there were scattered gray white cancer nodules and blood stasis points. The number of cancer nodules was significantly reduced, and the degree of cell malignancy was low, but there were some inflammatory cell infiltrations, necrosis area and karyokinesis in the CJM extract group, myricetin group, myricitrin group and CTX group. The result of metabolic research indicated that 45 potential biomarkers of the PLC were found, as gamma-aminoisobutyrate, taurochenodeoxycholate, xanthurenic acid, etc. There were 22 differential metabolites in the CTX group, 16 differential metabolites in the CJM extract group, 14 differential metabolites in the myricetin group, 14 differential metabolites in the myricitrin group., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Scuellaria Root (SR, root of Scutellaria baicalensis), which has potent anti-inflammatory effects, is a component of useful Kampo formulae. Albeit a low frequency, SR induces serious interstitial pneumonia and liver dysfunction. In this study, to control the adverse effects of SR, we investigated the causal constituent responsible for its hepatocytotoxicity and aimed to develop a method to control it. As a result, we revealed that the hepatocytotoxicity of SR was correlated with its baicalin content, a major constituent in SR. It was confirmed by preparing a baicalin-free SR extract, which exhibited reduced hepatocytotoxicity. The addition of baicalin to the baicalin-free SR extract restored the hepatocytotoxicity, indicating that the hepatocytotoxicity of SR is dependent on its baicalin content. Thus, SR extract-induced hepatocytotoxicity can be controlled by regulating its baicalin content., (© 2024. The Author(s) under exclusive licence to The Japanese Society of Pharmacognosy.)

Background: Polygonatum sibiricum polysaccharides protect against obesity and NAFLD. However, the potential effects of PS rhizome aqueous extracts (PSRwe) on adiposity and hepatic lipid accumulation remains unexplored., Purpose: Elucidating the impact and underlying mechanism of PSRwe on HFD-induced obesity and liver fat depostition., Study Design: 56 male mice, aged eight weeks, were divided into seven groups: Positive, four doses of PSRwe, Model, and Control. HFD was fed for eight weeks, followed by alternate-day gavage of orlistat and PSRwe for an additional eight-week period. Integrative analysis encompassing multiomics, physiological and histopathological, and biochemical indexes was employed., Methods: Body weight (BW); liver, fat and Lee's indexes; TC, TG, LDL-C, HDL-C, AST, ALT, FFA, leptin, and adiponectin in the liver and blood; TNFα, IL-6, and LPS in the colon, plasma, and liver; H&E, PAS and oil red O staining on adipose and liver samples were examined. OGTT and ITT were conducted The gut microbiome, microbial metabolome, colonic and liver transcriptome, plasma and liver metabolites were investigated., Results: PSRwe at the dosage of 7.5 mg/kg demonstrated significant and consistent reduction in BW and hepatic fat deposition than orlistat. PSRwe significantly decreased TC, TG, LDL-C, LEP, FFA levels in blood and liver. PSRwe significantly enhanced the relative abundance of probiotics including Akkermansia muciniphila, Bifidobacterium pseudolongum, Lactobacillus reuteri, and metabolic pathways including glycolysis and fatty acids β-oxidation. The 70 up-regulated microbial metabolites in PSRwe-treated mice mainly involved in nucleotides and amino acids metabolism, while 40 decreased metabolites primarily associated with lipid metabolism. The up-regulated colonic differentially expressed genes (DEGs) participate in JAK-STAT/PI3K-Akt/FoxO signaling pathway, serotonergic/cholinergic/glutamatergic synapses, while the down-regulated DEGs predominantly focused on fat absorption and transport. The up-regulated liver DEGs mainly concentrated on fatty acid oxidation and metabolism. Liver metabolisms revealed 131 differential metabolites, among which carnitine and oxidized lipids significantly increased in PSRwe-treated mice. In plasma, the 58 up-regulated metabolites mainly participate in co-factors/vitamins metabolism while 154 down-regulated ones in fatty acids biosynthesis. Comprehensive multiomics association analysis revealed significant associations between gut microbiota and colonic/liver gene expression, and suggested exogenous and endogenous betaine may be active compound in alleviating HFD-induced symptoms., Conclusion: PSRwe effectively mitigate HFD-induced obesity and hepatic steatosis by increasing beneficial bacteria, reducing colonic fat digestion/absorption, increasing hepatic lipid metabolism, and elevating betaine levels., Competing Interests: Declaration of competing interest The authors declare that there is no conflicts of interest., (Copyright © 2024 The Author(s). Published by Elsevier GmbH.. All rights reserved.)

Extracts of Salvia officinalis ( S. officinalis ) have been described to have many therapeutic properties. However, the effect of S. officinalis on copper sulfate toxicity has not been previously reported. The aim of this study was to investigate the toxicity of copper sulfate and the potential beneficial effects of S. officinalis aqueous infusion on proinflammatory response and antioxidant status. 56 male mice were used and equally divided into 6 groups: control group, copper sulfate treated group (40 mg/kg), S. officinalis aqueous infusion treated groups (200 mg/kg and 400 mg/kg) separately or in combination with copper. IL-6 (interleukine-6) and TNF-α (Tumor necrosis factor alpha) were assessed by Elisa. Catalase (CAT), superoxide dismutase (SOD) and acetylcholinesterase (AChE) activities, malondialdehyde (MDA) and oxygen peroxide levels were determined. Serum biochemical parameters were analyzed. Copper enhanced aspartate aminotransferase (AST), alanine aminotransferase (ALT) and Lactate dehydrogenase (LDH) (p < 0.05). Copper enhances significantly IL-6, TNF-α and MDA levels in liver and kidney and reduced CAT, SOD and AChE activities (p < 0.05). Aqueous infusion of S. officinalis at 400 mg/kg abolished copper-induced changes in AST and ALT activity. S. officinalis aqueous infusion at 200 mg/kg reversed copper-induced IL-6 in kidney and TNF-α in liver at both doses. S. officinalis aqueous infusion at 400 mg/kg restored SOD in kidney and CAT and AChE activities in both liver and kidney. S. officinalis aqueous infusion may be useful in partially ameliorating tissue disorders induced by copper exposure such as inflammatory response, oxidative stress imbalance and organ dysfunction through its phenolic compounds and higher antioxidant capacity.

Salvia officinalis L., commonly known as sage and belonging to the Lamiaceae family, is a medicinal herb indigenous to the Mediterranean region. It is celebrated for its diverse pharmacological properties and traditional uses in folk medicine, particularly in addressing hepatotoxicity. Cisplatin (Cis), a potent chemotherapeutic agent widely employed in cancer treatment, is recognized for its efficacy but often accompanied by adverse effects, including hepatotoxicity. The aim of this study was to assess whether an ethanolic S. officinalis extract (ESOE) could provide protection against Cis-induced hepatotoxicity in an experimental rat model. The ESOE was prepared using standard extraction techniques, and its chemical constituents were elucidated through UPLC-ESI-MS/MS analysis, revealing the presence of bioactive compounds such as alkaloids, phenolic compounds, and flavonoids, which are associated with various therapeutic effects, including hepatoprotection. Adult male albino rats were allocated into four groups: control, ESOE (250 mg/kg), Cis (7.5 mg/kg), and ESOE (250 mg/kg) + Cis (7.5 mg/kg). The treatment duration lasted 21 days, with Cis administration on the 22nd day. Twenty-four hours post-Cis administration, blood and liver samples were collected for analysis. Cis-induced hepatotoxicity was evidenced by alterations in hematological parameters, including erythrocyte, thrombocyte, leukocyte, and lymphocyte counts, alongside elevated serum levels of liver enzymes (ALT, LDH, AST, ALP, and GGT), indicative of liver damage. Furthermore, Cis exposure resulted in increased hepatic malondialdehyde (MDA) and Nitric oxide (NO) levels, oxidative stress markers, coupled with decreased levels of reduced glutathione (GSH), a non-enzymatic antioxidant, and histopathological changes in liver tissue, characterized by necrosis and inflammation. Additionally, Cis treatment led to elevated levels of 8-hydroxy-2'-deoxyguanosine (8-OH-dG), TNF-α, and IL-6, indicating oxidative stress and inflammation. Remarkably, pretreatment with ESOE ameliorated these Cis-induced hepatotoxic effects, as evidenced by improved hematological parameters, reduced liver enzyme activities, alleviated oxidative stress, and ameliorated histopathological alterations. The observed hepatoprotective effects of ESOE against Cis-induced liver injury may be attributed to its antioxidant and anti-inflammatory properties, highlighting its potential as a natural therapeutic agent in mitigating chemotherapy-associated hepatotoxicity., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Eleutherococcus senticosus (Rupr. et Maxim.) Maxim. (ES) has gained popularity for its adaptogenic, immunostimulant, and anti-inflammatory properties. Because of overexploitation of the roots, the species is considered to be endangered and has been put on the Red List in some countries (e.g., the Republic of Korea). Therefore, the fruits of E. senticosus might be explored as a new sustainable source of compounds with adaptogenic activity. This study aimed to assess the chemical composition and the safety profile (hepatotoxicity, blood morphology, biochemical parameters of blood plasma) of E. senticosus fruit intractum in Balb/c mice after oral administration of 750 and 1500 mg/kg b.w. UHPLC analysis coupled with DAD and MS detectors was used to quantify the metabolites. For the first time, oleanolic and ursolic acids were quantified in the intractum (16.01 ± 1.3 and 2.21 ± 0.17 µg/g of oleanolic and ursolic acids, respectively). Regarding polyphenols, chlorogenic acid (0.92 mg/g of dried extract), caffeic acid (0.43 mg/g), dicaffeoylquinic acids (in total: 1.27 mg/g), and an unidentified caffeic acid ester (0.81 mg/g) were identified. The results in Balb/c mice revealed that the intractum does not cause significant variations in red blood cells parameters. In turn, a significant decrease in the total number of leukocytes was observed (5.8 × 10 3 µL), with a percentage increase in lymphocytes among the groups (80.2, 81.8, and 82.6). The ability of the intractum to decrease alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels may indicate its anti-inflammatory activity. Our observations justify that the fruits of E. senticosus are safe in the doses used and do not cause significant changes in the activity of the liver enzymes or in blood parameters.

Orthosiphon stamineus Benth. (OSB) is a popular plant used for making "Shen tea" or "Java tea". It has been demonstrated with antioxidant, anti-inflammatory, and hepatoprotective activities. However, its potential beneficial effects and bioactive material basis for nonalcoholic fatty liver disease (NAFLD) has not been convincingly studied. In the present work, we conducted dual phytochemical/activity-guided extraction optimization and component fractionation of OSB, and evaluated its beneficial effects on NAFLD. Flavonoids and polyphenols (caffeic acid/protocatechuic acid derivatives) were determined as the dominant phytochemicals in OSB. The extraction process for these phytochemicals was optimized by using response surface methodology. Noticeably, flavonoids showed a stronger correlation with the antioxidant activities of OSB than polyphenols. Likewise, the flavonoid-rich fraction of OSB exerted antioxidant activities stronger than those of other fractions. As expected, in vitro and in vivo studies demonstrated that the flavonoid-rich fraction effectively attenuated weight increase, improved lipid metabolism, alleviated hepatic steatosis, and reversed hepatic inflammation. Importantly, this fraction showed equivalent beneficial effects to the total extract of OSB, suggesting that flavonoids were the main bioactive constituents of OSB. The action mechanism was indicated as direct antioxidant effect through chemical interaction with free radicals and indirect mitochondria-mediated antioxidant defense. Our research offers bioactive substances for further exploitation and expands the potential application of OSB.

Background: Yellow leaf green tea (YLGT) is a new variety of Camellia sinensis (L.) O. Ktze, which has yellow leaves and the unique qualities of 'three green through three yellow'. The present study aimed to investigate the anti-obesity effect of YLGT in mice fed a high-fat diet (HFD) and to explore the potential mechanisms by regulating the AMPK/ACC/SREBP1c signaling pathways and gut microbiota., Results: The results showed that YLGT aqueous extract reduced body weight, hepatic inflammation, fat accumulation and hyperlipidemia in HFD-induced C57BL/6J mice, and also accelerated energy metabolism, reduced fat synthesis and suppressed obesity by activating the AMPK/CPT-1α signaling pathway and inhibiting the FAS/ACC/SREBP-1c signaling pathway. Fecal microbiota transplantation experiment further confirmed that the alteration of gut microbiota (e.g. increasing unclassified&#95;Muribaculaceae and decreasing Colidextribacter) might be an important cause of YLGT water extract inhibiting obesity., Conclusion: In conclusion, YLGT has a broad application prospect in the treatment of obesity and the development of anti-obesity function beverages. © 2024 Society of Chemical Industry., (© 2024 Society of Chemical Industry.)

Nonalcoholic fatty liver disease (NAFLD) is fatty liver mainly related to metabolic syndrome. NAFLD with inflammation and hepatocellular damage is defined as nonalcoholic steatohepatitis (NASH), which can progress to cirrhosis and hepatocellular carcinoma. We have previously reported that a hexane insoluble fraction from an anthocyanin-rich purple rice ethanolic extract (PRE-HIF) can suppress prostate carcinogenesis. However, the extract's effect on NASH has not yet been established. In the present study, we investigated the chemopreventive effect of a PRE-HIF on NASH and liver fibrosis using a connexin 32 (Cx32) dominant negative transgenic (Cx32ΔTg) rat NASH model. Seven-week-old male Cx32ΔTg rats were fed a control diet, a high-fat diet (HFD), or an HFD with 1% PRE-HIF and intraperitoneal administration of dimethylnitrosamine for 17 weeks. Histological findings of NASH such as fat deposition, lobular inflammation, hepatocyte ballooning injury, and bridging fibrosis were observed in the HFD group but not in the control group, and all histological parameters were significantly improved by PRE-HIF treatment. Corresponding to the histological changes, increased expression of inflammatory cytokine mRNAs (TNF-α, IL-6, IL-18, IFN-γ, IL-1β, TGF-β1, TIMP1, TIMP2, COL1A1), along with and activation of nuclear factor-κB (NF-κB) and c-Jun N-terminal kinase (JNK) signaling were observed in the HFD group, which was significantly decreased by PRE-HIF. The number and area of hepatic precancerous glutathione S -transferase placental form-positive foci tended to be decreased by PRE-HIF. These results indicate that intake of purple rice as a dietary supplement may reduce steatohepatitis, liver injury, and fibrosis in NASH by inactivation of NF-κB or JNK.

Chronic and continuous alcohol consumption increases the risk of cognitive decline and may lead to alcohol-related dementia. We investigated the potential of Heracleum moellendorffii Hance root extract (HME) for treating alcohol-related cognitive impairment. Behavioral tests evaluated the effects of HME on cognitive function and depression. Changes in hippocampus and liver tissues were evaluated by Western blotting and H&E staining. The group treated with HME 200 mg/kg showed a significant increase in spontaneous alternation in Y-maze and a decrease in immobility in a forced swimming test (FST) compared to the vehicle-treated group. These results suggest that HME can restore memory deficits and reverse depressive symptoms caused by chronic alcohol consumption. The HME-treated group also upregulated brain-derived neurotrophic factor (BDNF), phosphorylated extracellular signal-regulated kinase 1/2 (ERK1/2), and phosphorylated cAMP response element-binding protein (CREB) in the hippocampus. Additionally, it reduced lipid vacuolation in the liver and increased the expression of aldehyde dehydrogenase 1 (ADH1). The administration of HME improves cognitive impairment and reverses depressive symptoms due to alcohol consumption, restoring neural plasticity in the hippocampus and alcohol metabolism in the liver. These findings suggest that HME is a promising treatment for alcohol-related brain disorders. Molecular mechanisms underlying the therapeutic effects of HME and its active ingredients should be investigated further.

The study aimed to investigate the effect of the aqueous extract of the chamomile plant on oxidative stress induced by procyclidine in rats. 30 rats were randomly divided into five groups, with 6 rats in each group. The first group was given distilled water only, while the second group was administered procyclidine (1 mg/kg body weight) in three doses daily for a period of 60 days. The third group was given procyclidine in the same doses as the second group for 30 days. Afterward, they were administered an aqueous extract of chamomile (300 mg/kg) for another 30 days. The fourth group was administered the aqueous extract (300 mg/kg) for 30 days. Subsequently, they were given procyclidine in the same doses as the second group for another 30 days. On the other hand, the fifth group was administered the aqueous extract of chamomile (300 mg/kg) for a period of 60 days to investigate the potential effects of the extract. Afterward, blood samples were drawn to measure various biological parameters, including Total Oxidant Status (TOS), Malondialdehyde (MDA), Aspartate Aminotransferase (AST), Alanine Transaminase (ALT), and Acetylcholinesterase (AChE) activity. Finally, an anatomical study was conducted on the kidneys, brain, and liver to enhance the research. The results displayed a significant increase in the levels of TOS, MDA, AST, ALT enzymes, and Ach-E activity in the second group compared to the first group. Groups 3 and 4 significantly decreased compared to the second group based on the same standards. In regard to Group 5, there are no significant moral differences between it and Group 1. Finally, this study demonstrated the importance of using chamomile extract as an antioxidant and its potential in cancer prevention against the oxidative stress induced by excessive doses of procyclidine. (p ≤ 0.005).

Background: Many kinds of orchids have significant health benefits although adequate research on their biological functions is yet to be carried out. This study investigated the paracetamol-induced liver damage-protecting effect of epiphytic Aerides odorata methanol extract (AODE)., Methods: The protective effects of AODE were studied by analyzing its effect on liver function parameters, messenger RNA (mRNA) expression, and tissue histopathological architecture. The results were confirmed by ligand-receptor interaction of molecular docking and multitarget interaction of network pharmacological analyses., Results: AODE significantly (p < 0.05) minimized the dose-dependent increase in acid phosphatase, aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, γ-glutamyl transferase, lactate dehydrogenase, and total bilirubin compared to the reference drug silymarin. Malondialdehyde level decreased, and the antioxidant genes catalase (CAT), superoxide dismutase (SOD), β-actin, paraoxonase-1 (PON1), and phosphofructokinase-1 (PFK-1) were upregulated in AODE-treated paracetamol-intoxicated rats. A total of 376 compounds comprising phenols and flavonoids were identified using ultra-high-performance liquid chromatography-quadrupole time-of-flight-mass spectrometry (UPLC-qTOF-MS). The online toxicity assessment using SwissADME and admetSAR exhibited drug-like, nontoxic, and potential pharmacological properties. Additionally, in silico analysis showed that isoacteoside, one of the identified compounds, exhibited the best docking score (-11.42) with the liver protein human pituitary adenylate cyclase-1 (Protein Data Bank ID: 3N94). Furthermore, network pharmacology analysis identified the top 10 hub genes, namely AKT1 (protein kinase B), CTNNB1 (catenin beta-1), SRC (proto-oncogene c-Src), TNF (tumor necrosis factor), EGFR (epidermal growth factor receptor), HSP90AA1 (heat shock protein 90α), MAPK3 (mitogen-activated protein kinase 3), STAT3 (signal transducer and activator of transcription 3), CASP3 (caspase protein), and ESR1 (estrogen receptor 1), which are responsible for hepatoprotective activity., Conclusion: The findings demonstrate that AODE could be a novel hepatoprotective target in drug-induced liver damage with a further single compound-based animal study., (© 2024 The Author(s). Animal Models and Experimental Medicine published by John Wiley & Sons Australia, Ltd on behalf of The Chinese Association for Laboratory Animal Sciences.)

Objective: This study compared the ability of Liquorice roots aqueous extract (LRE) and its ingredient, isoliquiritigenin (ISL), in alleviating high-fat diet (HFD)-induced hepatic steatosis and examined if this effect involves activation of AMPK. Materials and methods: Control or HFD-fed rats were treated with the vehicle, LRE (200 mg/kg), or ISL (30 mg/kg) for 8 weeks orally. Results: ISL and LRE reduced HFD-induced hyperglycaemia, improved liver structure, lowered serum and hepatic lipids, and attenuated hepatic oxidative stress and inflammation. In the control and HFD-fed rats, ISL and LRE significantly stimulated the muscular and hepatic mRNA and protein levels of AMPK, improved oral glucose tolerance, reduced hepatic mRNA levels of SREBP1/2, and upregulated hepatic levels of PPARα and Bcl2. These effects were comparable for ISL and LRE and were prevented by co-administration of compound C, an AMPK inhibitor. Discussion and conclusion: ISL and LRE provide an effective theory to alleviate hepatic steatosis through activating AMPK.

Amiodarone (AMD) is an effective antiarrhythmic drug, but its long-term usage strongly forms liver toxicity due to its accumulation tendency. The chard (Beta vulgaris L. var. cicla) is a unique plant which has a blood sugar-lowering effect and powerful antioxidant activity. The aim of the current study was to investigate the possible protective effects of chard on AMD-induced liver injury. Male Sprague-Dawley rats were divided into four groups. Control group, aqueous chard extract given group 500 mg/kg/day for one week, AMD given group 100 mg/kg/day for one week, AMD+Chard given group (at the same doses and times). They were sacrificed on the 8th day. The blood and liver samples were taken. The serum and liver biochemical parameters were found to be changed in AMD treated group. Chard administration reversed these parameters in serum and liver. In histological experiments, necrotic areas, mononuclear cell infiltration, the endothelial rupture in central vein, sinusoidal dilatation, hyperemia, dark eosinophilic cells and picnotic nucleus were observed in liver tissues of AMD treated group. Chard treatment reduced liver tissue damage. Considering results, we can suggest that chard prevented AMD induced liver injury biochemically and histologically., (© 2024 Wiley-VHCA AG, Zurich, Switzerland.)

This study aimed to assess the effectiveness of aflatoxin B 1 (AFB 1 ) and Thunbergia laurifolia extract (TLE) in the diets of Cherry Valley ducklings. Our investigation covered growth indicators, blood biochemical indices, meat quality, intestinal morphology, immune response, and CP450 enzyme-related gene expression. We conducted the study with 180 seven-day-old Cherry Valley ducks, randomly divided into five dietary treatments. These treatments included a basal diet without AFB 1 (T1 group), TLE, or a commercial binder; the basal diet containing 0.1 mg AFB 1 /kg (T2 group), 0.1 mg AFB 1 /kg and 100 mg TLE/kg (T3 group), 0.1 mg AFB 1 /kg and 200 mg TLE/kg (T4 group), and 0.1 mg AFB 1 /kg and 0.5 g/kg of a commercial binder (T5 group), respectively. Ducklings fed with the T2 diet exhibited lower final body weight (BW), average body weight gain (ADG), and poor feed conversion ratio (FCR) during the 42-day trials. However, all ducklings in the T3, T4, and T5 groups showed significant improvements in final BW, ADG, and FCR compared to the T2 group. Increased alanine transaminase (ALT) concentration and increased expression of CYP1A1 and CYP1A2 indicated hepatotoxicity in ducklings fed the T2 diet. In contrast, ducklings fed T3, T4, and T5 diets all showed a decrease in the expression of CYP1A1 and CYP1A2, but only the T4 treatment group showed improvement in ALT concentration. AFB 1 toxicity considerably raised the crypt depth (CD) in both the duodenum and jejunum of the T2 group, while the administration of 200 mg TLE/kg (T4) or a commercial binder (T5) effectively reduced this toxicity. Additionally, the villus width of the jejunum in the T2 treatment group decreased significantly, while all T3, T4, and T5 groups showed improvement in this regard. In summary, T. laurifolia extract can detoxify aflatoxicosis, leading to growth reduction and hepatic toxicosis in Cherry Valley ducklings.

Abrus cantoniensis Hance is a vegetative food and can be used as a folk beverage or soup to clear liver toxins and prevent liver damage. However, the components and effects of A. cantoniensis Hance in alcohol-induced liver injury were unknown. This study aimed to obtain abundant phytochemicals from A. cantoniensis Hance and identify the potency of the isolates in preventing alcohol-induced liver injury. Alcohol-stimulated AML12 cells and Lieber-DeCarli diet-fed mice were used to establish in vitro and in vivo models, respectively. Our findings indicated that flavonoid glycosides, especially AH-15 , could significantly alleviate alcohol-induced liver injury by inhibiting oxidative stress. Furthermore, we demonstrated that AH-15 inhibited ferroptosis induced by lipid peroxidation. Mechanically, we found that AH-15 regulated nuclear factor erythroid 2-related factor 2 (NRF2) expression via activation of AMP-activated protein kinase (AMPK) signaling. These results indicate that A. cantoniensis Hance is a great potential functional food for alleviating alcohol-induced liver injury.

This work investigated the antioxidant and hepatoprotective activities of lemongrass extract and its effects on rat hepatotoxicity. The lemongrass extract (LGE) contains bioactive components such as phenolic acids, flavonoid components, vitamin C, fibers, and tannins. The LGE had high phenolic content (397 mg/100g) and flavonoids (164 mg/100g), influencing its antioxidant activity of 91.25%. Additionally, it inhibited 81% of breast cancer, also, inhibited the growth of pathogenic bacteria and Candida at a concentration of 20-40 µg/mL. Additionally, it inhibited SARS-Cov-2 by 75%; however, increasing the activity of Cas-3. Quercetin-3-rhamnoside was the main phenolic compound in the HPLC profile; the phenolic compounds may be attributable to the beneficial effects of LGE. In this study, the CCl4-challenged rats delivered two levels of LGE (100 and 300 mg/kg BW). LGE reduced ALT, AST, creatinine and urea by 50 and 37%, respectively. Generally, LGE mitigated the oxidative stress induced by CCl4, which is evident in the histology of liver and kidney tissues, where significant improvement, with no cytoplasmic degradation in undamaged liver hepatocytes, improved kidney performance and shape. It can be concluded that polyphenolic-rich LGE can mitigate the oxidative stress induced by CCl4 and other parameters while enhancing kidney and liver performance.

Acrocomia aculeata pulp (ACP) is a source of oleic acid, phenolic compounds, and flavonoids that protect against diseases and improve antioxidant capacity. We evaluated whether regular intake of ACP, in combination with a standard diet, improves the antioxidant system and physiological parameters. Male Wistar rats were divided into: control (C), 250 mg/kg ACP, and 500 mg/kg ACP groups. Rats received either water or the respective A. aculeata solution doses for 28 days. We observed increased food intake, lower carcass protein levels, and higher carcass lipid levels in the 500 mg/kg ACP group than in the other groups. Postprandial glucose, oral glucose tolerance test results, and the area under the curve were greater, while urea was lower in the 500 mg/kg ACP group. Total liver lipids were increased, and PPAR-α, PPARγ, and carbonylated protein levels were reduced in the 500 mg/kg ACP group. NRF2 contents and glutathione reductase, superoxide dismutase, and catalase activities were increased in the 500 mg/kg ACP group. In the 250 mg/kg ACP group, only glutathione system activity increased. Thus, ACP intake improved the enzymatic antioxidant system in the liver at the evaluated doses, although the 500 mg/kg dose induced alterations in lipid, protein, and carbohydrate metabolism.

Recently, the incidence of NAFLD has exploded globally, but there are currently no officially approved medications for treating the condition. The regulation of NAFLD through plant-derived active substances has become a new area of interest. Quinoa ( Chenopodium quinoa Willd.) has been discovered to contain a large quantity of bioactive compounds. In this study, we established a free fatty acid (FFA)-induced steatosis model and explored the effects of quinoa polyphenol extract (QPE) on the major hallmarks of NAFLD. The results indicated that QPE significantly reduced intracellular triglyceride (TG) and total cholesterol (TC) levels. Additionally, QPE remarkably elevated the levels of superoxide dismutase (SOD), catalase (CAT) and glutathione (GSH) and lowered levels of malondialdehyde (MDA). Further examination revealed that QPE attenuated intracellular inflammation, which was verified by the reduced levels of pro-inflammatory cytokines. Mechanistically, QPE inhibited fatty acid biosynthesis mainly by targeting de novo lipogenesis (DNL) via the AMPK/SREBP-1c signaling pathway. Moreover, network pharmacology was used to analyze key targets for NAFLD mitigation by ferulic acid (FA), a major component of QPE. Taken together, this study suggests that QPE could ameliorate NAFLD by modulating hepatic lipid metabolism and alleviating oxidative stress and inflammation.

Our previous study demonstrated that thyme polyphenol-rich extract (TPE) mitigated hepatic injury induced by a high-fat diet (HFD) through the regulation of lipid metabolism, promotion of short-chain fatty acid production, enhancement of intestinal barrier function, and attenuation of inflammation. In this study, we aimed to further elucidate additional mechanisms underlying TPE-mediated preventive effects on hepatic steatosis, with a specific focus on its impact on the gut microbiota and bile acid (BA) metabolism in HFD-fed mice. TPE treatment resulted in a significant reduction in serum total BA levels and a notable increase in fecal total BA levels. In particular, elevations in fecal conjugated BA levels, in turn, impede intestinal farnesoid X receptor (FXR) signaling, thereby enhancing hepatic synthesis and fecal excretion of BAs. The downregulated mRNA expression levels of intestinal Fxr and Fgf15 , and hepatic Fgfr4 , along with the upregulated mRNA expression levels of Cyp7a1 and Cyp27a1 after TPE treatment also prove the above inference. Meanwhile, TPE appeared to promote BA efflux and enterohepatic circulation, as evidenced by changes in the mRNA levels of Bsep , Ntpc , Shp , Asbt , Ibabp , and Ostα / β . TPE also modulated the gut microbiota and was characterized by an increased relative abundance of Lactobacillus . Furthermore, antibiotic treatment depleted the intestinal flora in mice, also abrogating the hepatoprotective effect of TPE against NAFLD. These findings collectively indicate that TPE effectively mitigates HFD-induced NAFLD by modulating the gut-liver axis, specifically targeting the gut microbiota and bile acid metabolism.

Ethnopharmacological Relevance: Epimedium sagittatum (Sieb. et Zucc.) Maxim. has been used traditionally in Asia. It can dispel wind and cold, tonify the kidney, and strengthen bones and tendons. However, adverse effects of E. sagittatum have been reported, and the underlying mechanisms remain unclear., Aim of the Study: This study aimed to investigate liver injury caused by an aqueous extract of E. sagittatum in Institute of Cancer Research (ICR) mice and explore its potential mechanisms., Materials and Methods: Dried E. sagittatum leaves were decocted in water to prepare aqueous extracts for ultra-high performance liquid chromatography analysis. Mice were administered an aqueous extract of E. sagittatum equivalent to either 3 g raw E. sagittatum/kg or 10 g raw E. sagittatum/kg once daily via intragastric injection for three months. The liver weights and levels of the serum biochemical parameters including alanine transaminase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase (LDH), total bilirubin (TBIL), and alkaline phosphatase were measured. Hematoxylin-eosin staining was performed for histopathology. Apoptosis was detected using the TUNEL apoptosis assay kit. IL-1β was detected using ELISA kits. Proteomics was used to identify the differentially expressed proteins. Western blot analysis was performed to determine the levels of proteins significantly affected by the aqueous extract of E. sagittatum., Results: E. sagittatum treatment increased the liver weights and liver coefficients, and ALT and AST levels significantly increased (p < 0.05). A high dose of E. sagittatum significantly increased LDH and TBIL levels (p < 0.05). Ruptured cell membranes and multiple sites of inflammatory cell infiltration were also observed. No evidence of apoptosis was observed. IL-1β levels were significantly increased (p < 0.05). The expressions of PIK3R1, p-MAP2K4, p-Jun N-terminal kinase (JNK)/JNK, p-c-Jun, VDAC2, Bax, and CYC were upregulated, whereas that of Bcl-2 was inhibited by E. sagittatum. The expression of cleaved caspase-1 was significantly increased; however, its effects on GSDMD and GSDMD-N were significantly decreased. The expression levels of cleaved caspase-3 and its effector proteins GSDME and GSDME-N significantly increased., Conclusions: Our results suggest that the aqueous extract of E. sagittatum induces liver injury in ICR mice after three months of intragastric injection via inflammatory pyroptosis., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Iron is a vital trace element for our bodies and its imbalance can lead to various diseases. The progression of metabolic-associated fatty liver disease (MAFLD) is often accompanied by disturbances in iron metabolism. Alisma orientale extract (AOE) has been reported to alleviate MAFLD. However, research on its specific lipid metabolism targets and its potential impact on iron metabolism during the progression of MAFLD remains limited. To establish a model of MAFLD, mice were fed either a standard diet (CON) or a high-fat diet (HFD) for 9 weeks. The mice nourished on the HFD were then randomly assigned to the HF group and the HFA group, with the HFA group receiving AOE by gavage on a daily basis for 13 weeks. Supplementation with AOE remarkably reduced overabundant lipid accumulation in the liver and restored the iron content of the liver. AOE partially but significantly reversed dysregulated lipid metabolizing genes (SCD1, PPAR γ, and CD36) and iron metabolism genes (TFR1, FPN, and HAMP) induced by HFD. Chromatin immunoprecipitation assays indicated that the reduced enrichment of FXR on the promoters of SCD1 and FPN genes induced by HFD was significantly reversed by AOE. These findings suggest that AOE may alleviate HFD-induced disturbances in liver lipid and iron metabolism through FXR-mediated gene repression.

This study aimed to investigate the therapeutic potential of Citrullus mucosospermus extract (CME) in counteracting adipogenesis and its associated metabolic disturbances in murine models. In vitro experiments utilizing 3T3-L1 preadipocytes revealed that CME potently inhibited adipocyte differentiation, as evidenced by a dose-dependent reduction in lipid droplet formation. Remarkably, CME also attenuated glucose uptake and intracellular triglyceride accumulation in fully differentiated adipocytes, suggesting its ability to modulate metabolic pathways in mature adipose cells. Translating these findings to an in vivo setting, we evaluated the effects of CME in C57BL/6N mice fed a high-fat diet (HFD) for 10 weeks. CME administration, concomitantly with the HFD, resulted in a significant attenuation of body weight gain compared to the HFD control group. Furthermore, CME treatment led to substantial reductions in liver weight, total fat mass, and deposits of visceral and retroperitoneal adipose tissue, underscoring its targeted impact on adipose expansion. Histological analyses revealed the remarkable effects of CME on hepatic steatosis. While the HFD group exhibited severe lipid accumulation within liver lobules, CME dose-dependently mitigated this pathology, with the highest dose virtually abolishing hepatic fat deposition. An examination of adipose tissue revealed a progressive reduction in adipocyte hypertrophy upon CME treatment, culminating in a near-normalization of adipocyte morphology at the highest dose. Notably, CME exhibited potent anti-inflammatory properties, significantly attenuating the upregulation of pro-inflammatory cytokines' mRNA levels (TNF-α, IL-1β and IL-6) in the livers of HFD-fed mice. This suggests a potential mechanism through which CME may exert protective effects against inflammation associated with obesity and fatty liver disease.

Solanum nigrum L. (SN) berry is an edible berry containing abundant polyphenols and bioactive compounds, which possess antioxidant and antiinflammatory properties. However, the effects of SN on alcohol-induced biochemical changes in the enterohepatic axis remain unclear. In the current study, a chronic ethanol-fed mice ALD model was used to test the protective mechanisms of SN berries. Microbiota composition was determined via 16S rRNA sequencing, we found that SN berries extract (SNE) improved intestinal imbalance by reducing the Firmicutes to Bacteroides ratio, restoring the abundance of Akkermansia microbiota, and reducing the abundance of Allobaculum and Shigella. SNE restored the intestinal short-chain fatty acids content. In addition, liver transcriptome data analysis revealed that SNE primarily affected the genes involved in lipid metabolism and inflammatory responses. Furthermore, SNE ameliorated hepatic steatosis in alcohol-fed mice by activating AMP-activated protein kinase (AMPK), acetyl-CoA carboxylase (ACC), peroxisome proliferator-activated receptor α (PPAR-α). SNE reduced the expression of toll-like receptor 4 (TLR4), myeloid differentiation factor-88 (MyD88) nuclear factor kappa-B (NF-κB), which can indicate that SNE mainly adjusted LPS/TLR4/MyD88/NF-κB pathway to reduce liver inflammation. SNE enhanced hepatic antioxidant capacity by regulating NRF2-related protein expression. SNE alleviates alcoholic liver injury by regulating of gut microbiota, lipid metabolism, inflammation, and oxidative stress. This study may provide a reference for the development and utilization of SN resources., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

Safe chemicals for drug withdrawal can be extracted from natural sources. This study investigates the effects of clonidine and Thymbra spicata extract (TSE) on mice suffering from morphine withdrawal syndrome. Thymol, which is the active constituent in TSE, was also tested. A total of 90 mice were divided into nine groups. Group 1 was the control group, while Group 2 was given only morphine, and Group 3 received morphine and 0.2 mg/kg of clonidine. Groups 4-6 were given morphine along with 100, 200, and 300 mg/kg of TSE, respectively. Groups 7-9 received morphine plus 30, 60, and 90 mg/kg of Thymol, respectively, for 7 days. An oral naloxone challenge of 3 mg/kg was used to induce withdrawal syndrome in all groups. Improvement of liver enzyme levels (aspartate aminotransferase, alkaline phosphatase, and alanine transaminase) (p < .01) and behavioral responses (frequencies of jumping, frequencies of two-legged standing, Straub tail reaction) (p < .01) were significantly observed in the groups receiving TSE and Thymol (Groups 4-9) compared to Group 2. Additionally, antioxidant activity in these groups was improved compared to Group 2. Nitric oxide significantly decreased in Groups 4 and 6 compared to Groups 2 and 3 (p < .01). Superoxide dismutase increased dramatically in Groups 5, 8, and 9 compared to Groups 2 and 3 (p < .01). Groups 5-9 were significantly different from Group 2 in terms of malondialdehyde levels (p < .01). Certain doses of TSE and Thymol were found to alleviate the narcotics withdrawal symptoms. This similar effect to clonidine can pave the way for their administration in humans., (© 2024 John Wiley & Sons Ltd.)

Citrus flavanones are recognized as promising bioactives within the concept of healthy aging. Thus, the present study investigated the effects of a nutritionally relevant dose of lemon extract (LE) on liver redox regulation and persulfidation levels in 24-month-old Wistar rats. LE (40 mg/kg b.m.) was administered orally once daily for 4 weeks. Control groups received either vehicle (sunflower oil) or remained intact. The applied methodology considered qPCR, Western blot, protein persulfidation levels evaluation, histochemistry in line with immunofluorescence, liver biochemical assays (glutathione, total -SH groups and malonaldehyde; MDA), liver enzymes in serum and in silico analysis to explore the potential interaction/binding between the proteins studied in the paper. Our results showed that LE increased glutathione peroxidase (GPx), reductase (GR), glutamate-cysteine ligase catalytic and modifier subunit, respectively, as well as Nrf2 gene expressions, but decreased the expression of superoxide dismutase 2 (SOD2). Upon LE application, protein expression showed upregulation of NRF2, SOD2, GPx, GR, and thioredoxin 1 (Trx1). LE significantly decreased the protein persulfidation levels and concentration of MDA, a marker of oxidative damage in the cell. Histological analysis showed a normal liver histoarchitecture without pathological changes, aligning with the normal serum level of hepatic enzymes. Obtained results showed that LE, by modulating hepatic redox regulators Nrf2 and Trx1, diminishes oxidative stress and alters the persulfidation levels, suggesting a considerable beneficial antioxidant potential of lemon flavanones in the old-aged liver., (© 2024 International Union of Biochemistry and Molecular Biology.)

Study on the hypolipidemic effect of turmeric combined with hawthorn on C57BL/6 obese mice and its possible mechanism. C57 mice were fed with 60% high-fat diet for 8 weeks to establish an obesity model, and 4 mice were slaughtered to verify whether the modeling was successful. The successful mice were divided into model group (HFD), positive group (high fat feed group [HFD] + simvastatin group [SIM]), turmeric group (HFD + TUR), hawthorn group (HFD + HAW), and para-medicine group (HFD + para-drug group [DOU]) for 4 weeks by gavage intervention. Different intervention groups had certain lipid-lowering effects, and the para-medicine group showed significant differences (p < 0.05, p < 0.01, p < 0.001) in reducing serum total cholesterol, triglycerides, low-density lipoprotein cholesterol, glutamic acid transaminase (ALT), glutamic acid transaminase (AST), and increasing high-density lipoprotein cholesterol. In the para-medicine group, the protein expression of peroxisome proliferator-activated receptor γ, fatty acid synthase, platelet-reactive protein receptor 36, and CCAAT/enhancer binding protein α were significantly downregulated, and the protein expression of carnitine palmitoyl transferase1 and peroxisome proliferator-activated receptor α protein expression (p < 0.01, p < 0.001), thus suggesting that turmeric and hawthorn are superior to turmeric and hawthorn alone in enhancing lipid metabolism-related mechanisms. Combined effects of turmeric and hawthorn improve lipid metabolism in mice, protect the liver, and improve the protein expression of liver-related genes. This study can lay the theoretical basis for the future association of medicinal food products and the development of related weight loss products., (© 2024 Institute of Food Technologists.)

Type 2 diabetes (T2D) is a serious health problem, and its prevalence is expected to increase worldwide in the years ahead. Cruciferous vegetables such as Brassica oleracea var. capitata L. (green cabbage) and Raphanus sativus L. (radish) have therapeutic properties that can be used to support the treatment of T2D. This study evaluated the effect of B. oleracea (BAE) and R. sativus (RAE) aqueous extracts on zoometric parameters, glycemic profiles, and pancreas and liver in prediabetic rats induced by a high-sucrose diet (HSD). BAE and RAE were administered to male HSD-induced Wistar rats ( n = 35) at 5 and 10 mg/kg doses for 5 weeks. Zoometric and biochemical changes were measured, and then the pancreas and liver histological preparations were analyzed to observe the protective effect. BAE decreased feed intake and weight gain. Both extracts decreased fasting glucose and insulin levels compared with control (not treated), although not significantly ( P > .05). The extracts significantly ( P < .05) reduced homeostatic model assessment for insulin resistance, homeostasis model assessment of β-cell function, and glucose intolerance, similar to metformin control. In addition, minor damage occurred in the pancreas and liver. The results indicated that BAE and RAE decreased weight gain, improved glucose regulation, and protected the pancreas and liver in HSD rats. Therefore, they have multiple therapeutical properties and may be helpful in the prevention of T2D.

Obesity is an ongoing global health problem, and Cichorium glandulosum (CG, chicory) is traditionally used as a hepatoprotective and lipid-lowering drug. However, there is still a lack of research on the role of CG in the treatment of obesity. In the present study, we found that CG significantly delayed weight gain and positively affected glucolipid metabolism disorders, serum metabolism levels, and the degree of liver and kidney oxidative stress in high-fat diet (HFD) mice. Further examination of the effects of CG on intestinal microenvironmental dysregulation and its metabolites in HFD mice revealed that the CG ethanol extract high-dose group (CGH) did not have a significant regulatory effect on short-chain fatty acids. Still, CGH significantly decreased the levels of 12α-OH/non-12α-OH bile acids and also found significant upregulation of proteobacteria and downregulation of cyanobacteria at the phylum level. CG may have ameliorated obesity and metabolic abnormalities in mice by repairing gut microbiota dysbiosis and modulating bile acid biosynthesis.

Background: Obesity has become a prevalent issue worldwide, leading to various complications such as hyperlipidemia, diabetes, and cardiovascular problems. Statins, as FDA approved anti-hyperlipidemic drugs, still pose some concerns upon their administration. Recently, researchers have looked for natural products as an alternative to manage hyperlipidemia and obesity., Aim: This work aimed to study the hypolipidemic effect of Lepidium sativum garden cress (GC) from different preparations; orally administered seeds, and hydrogel, in comparison to atorvastatin., Methods: GC hydrogel was prepared from the GC aqueous extract and pharmaceutically evaluated for its pH, spreadability, seeds content, homogeneity, rheology, and in vitro release. The rat's body weight, blood glucose levels, total lipid profile, and liver biomarkers were evaluated on obese rats for one month. In addition, the histopathology study was also performed., Results: GC hydrogel had acceptable pharmaceutical properties and showed a sustained release performance over 24 h. Oral and topical GC significantly reduced the lipid profiles, blood sugar and ALT, AST levels more than the negative control group and comparable to atorvastatin. It was found that oral GC showed a significant effect on the percentage decrease in the rat's body weight than the applied hydrogel. Histopathology study revealed a better outcome in the histological structure of pancreas and liver compared with rats feed on high fat diet post-treatment for one month., Conclusion: GC orally administered, or topically applied hydrogel could be a promising, safe alternative formulation to atorvastatin in managing hyperlipidemia and normalizing body weight of obese rats.

Bamboo shoots are nutritionally rich source of antioxidants and bioactive compounds with immense therapeutic potentials. The fresh shoot is acrid and needs to be processed to make it palatable. Fermentation is one the best processing methods for long term storage and make the shoot palatable and enhance taste. This study aims to assess the prophylactic hepatoprotective effects of fresh and fermented B. nutans shoot aqueous extract (200 mg/kg b.w.) in STZ induced diabetic LACA mice. Both extracts effectively improved body weight loss, hyperglycemia, and hepatomegaly. Fresh shoot reduced LDH activity and LPO level by 26.1% and 46.6%, while fermented shoot reduced them by 51.5% and 55.8%, respectively. The fermented shoot extract group demonstrated a noteworthy decrease in liver enzymes (SGPT, SGOT, ALP, and bilirubin levels) and an increase in albumin and A/G ratio, with more substantial improvements compared to the group treated with fresh extract. Additionally, the extracts enhanced antioxidant activities and showed histological improvements in hepatocytes and central vein structure. The findings indicate that both fresh and fermented B. nutans extracts are non-toxic and possess hepatoprotective potential in hyperglycaemic liver dysfunction, with fermented shoot extract exhibiting superior efficacy suggesting its potential as a therapeutic agent for hyperglycemic liver conditions., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The study explored the hepatoprotective activity and metabolic profile of Verbena bonariensis L. methanol extract (VBM) and fractions using isoniazid as well as rifampicin-triggered liver toxicity in Wistar albino rats. Metabolite profiling of VBM using HPLC-PDA-ESI-MS identified 12 compounds, mainly iridoids, phenylpropanoids, and flavonoids, where verbascoside represents the major compound. Different biochemical parameters such as aspartate transaminase (AST), alanine transaminase (ALT), and alkaline phosphatase (ALP), bilirubin, and total protein levels were used to assess liver functions. All the evaluated samples exhibited hepatoprotective potential, but VBM exhibited maximum activity and a notable decline in ALP (p < 0.05, significant), even better than the standard drug (silymarin). VBM significantly reduced the elevated ALT, AST, ALP, and total bilirubin. It also triggered a significant elevation in total proteins compared with diseased animals. This was further consolidated by histopathological studies. Verbena bonariensis L. could serve as a potent hepatoprotective agent and may alleviate liver ailments., (© 2024 Deutsche Pharmazeutische Gesellschaft.)

Non-alcoholic fatty liver disease (NAFLD), particularly advanced non-alcoholic steatohepatitis (NASH), leads to irreversible liver damage. This study investigated the therapeutic effects and potential mechanism of a novel extract from traditional Chinese medicine Alisma orientale (Sam.) Juzep (AE) on free fatty acid (FFA)-induced HepG2 cell model and high-fat diet (HFD) + carbon tetrachloride (CCl 4 )-induced mouse model of NASH. C57BL/6 J mice were fed a HFD for 10 weeks. Subsequently, the mice were injected with CCl 4 to induce NASH and simultaneously treated with AE at daily doses of 50, 100, and 200 mg/kg for 4 weeks. At the end of the treatment, animals were fasted for 12 h and then sacrificed. Blood samples and liver tissues were collected for analysis. Lipid profiles, oxidative stress, and histopathology were examined. Additionally, a polymerase chain reaction (PCR) array was used to predict the molecular targets and potential mechanisms involved, which were further validated in vivo and in vitro. The results demonstrated that AE reversed liver damage (plasma levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), hepatocyte ballooning, hepatic steatosis, and NAS score), the accumulation of hepatic lipids (TG and TC), and oxidative stress (MDA and GSH). PCR array analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis revealed that AE protects against NASH by regulating the adipocytokine signaling pathway and influencing nuclear receptors such as PPARα. Furthermore, AE increased the expression of peroxisome proliferator-activated receptor gamma coactivator-1α (PPARGC1α) and reversed the decreased expression of PPARα in NASH mice. Moreover, in HepG2 cells, AE reduced FFA-induced lipid accumulation and oxidative stress, which was dependent on PPARα up-regulation. Overall, our findings suggest that AE may serve as a potential therapeutic approach for NASH by inhibiting lipid accumulation and reducing oxidative stress specifically through the PPARα pathway., Competing Interests: Declaration of Competing Interest No conflict of interest exits in the submission of this manuscript, and manuscript is approved by all authors for publication. I would like to declare on behalf of my co-authors that the work described was original research that has not been published previously, and not under consideration for publication elsewhere, in whole or in part. All the authors listed have approved the manuscript that is enclosed., (Copyright © 2024. Published by Elsevier Masson SAS.)

Ethnopharmacological Relevance: Rheum palmatum (RP) is a widely used traditional herb, which possesses antioxidant properties, inhibits ROS production and reduces fever., Aim of the Study: The aim of this study was to examine the antioxidative properties of the water extract of RP on oxidative-stressed mice., Materials & Methods: Forty mice were administered with DL-homocysteine (DL-Hcy) to induce oxidative stress and were divided into four groups: 1) CK: NaCl and water; 2) DL-Hcy: DL-Hcy and water; 3) DL-Hcy+50RP: DL-Hcy with 50 mg kg -1 body weight (BW) d -1 RP; and 4) DL-Hcy+150RP: DL-Hcy with 150 mg kg -1 BW d -1 RP. Rhein (0.3 mg g -1 dry matter) was the main active ingredient in RP., Results: When compared with Dl-Hcy mice, the mice with supplementary RP mitigated oxidative stress by reducing the liver concentrations of superoxide dismutase (SOD) by 27% and glutathione peroxidase (GSH-Px) by 32%, and the reactive oxygen species (ROS) in the kidney and spleen. These responses were more pronounced in DL-Hcy+150RP than DL-Hcy+50RP mice. RP also exhibited therapeutic effects on liver steatosis, chronic kidney nephritis and intestinal villus width shortening caused by oxidative stress, and concomitantly decreased the serum glucose concentration (RP vs. DL-HCY, 2.3 vs. 4.1 mmol L -1 )., Conclusion: It was concluded that RP possesses antioxidant and therapeutic properties that can mitigate lesions on organs and prevent diabetes in oxidative-stressed mice. This study highlights the potential of RP as a medicinal supplement for animals in the future., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Homalium tomentosum (Vent.) Benth, is a valuable agroforestry species and has industrial importance high-quality wood is used for malas, the manufacture of matches, and is suitable for making a wide range of articles. Nevertheless, leaves and bark are relatively rich in phenols and flavonoids, used for medicinal purposes. In this study, phenols and flavonoids rich in bio-privileged antioxidants in ethyl-acetate extracted fractions of bark (HTEB), and leaves (HTEL) at 300, and 400 mg/kg were examined in carbon tetrachloride (CCl 4 )-induced hepatotoxicity in experimental rats. HTEB and HTEL (400) showed improvement in liver structural integrity, but, HTEB400 significantly improved serum (total protein, TP; alkaline phosphatase, ALP; total bilirubin, TB; serum glutamate oxaloacetate transaminase, SGOT, and serum glutamate pyruvate transaminase, SGPT), and hepatic oxidative (catalase, CAT; thiobarbituric acid reactive species, TBARS; reduced glutathione, GSH; superoxide dismutase, SOD), and inflammatory (transforming growth factor, TGF-β; ineterleukin-6, IL-6) biomarkers accompanied by histopathological improvements of the liver. GC-MS analysis of HTEB and HTEL identified 14 and 18 compounds, but physicochemical properties of 3-major antioxidants of HTEB (levoglucosenone, (+)-borneol, α-N-normethadol), and HTEL (2-coumaranone, salicyl alcohol, D-allose) were satisfied for the parameters molecular weight, no. of H-acceptor and H-donor, partition co-efficient (clogP), and topological polar surface area (tPSA) of Lipinski's rule. ADME-Tox properties were directly related to the biological activities of HTEB and HTEL. Molecular docking investigation of α-N-normethadol showed the highest binding energy against TGF-β and IL-6 than other antioxidants. HTEB and HTEL were powerful antioxidant potential, but levoglucosenone, (+)-borneol, and α-N-normethadol of HTEB demonstrated better activities in neutralizing reactive oxygen species (ROS) to preserve cellular membrane integrity in liver cirrhosis as found evidence in restoring the liver inflammatory cytokines. This study confirmed the economic interest of H. tomentosum bark as crude material for the preparation of biobased materials for the pharmaceutical and food industries., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Ethnopharmacological Relevance: Rheum webbianum Royle (RW) holds significant ethnopharmacological importance owing to its 5000-year history of cultivation for medicinal and culinary purposes. Demonstrating therapeutic advantages in traditional and contemporary medical practices, RW exhibits key pharmacological effects including anticancer activity, gastrointestinal control, anti-inflammatory properties, and suppression of fibrosis. Despite its recognized vast bioactivities in ethnopharmacology, its efficacy against the colorectal cancer (CRC) remains incompletely understood., Aim of the Study: This study for the first time aims to investigate the chemo-preventive capabilities of various extracts derived from RW rhizomes against CRC development., Materials and Methods: Four types of RW extracts were prepared by using different solvents viz: Hexane, Ethy-acetate, Ethanol and Methanol. All the four extracts were evaluated for cytotoxicity on HCT-116 human CRC cells. Promising extracts were further investigated in-vivo at varying doses using 1,2-dimethylhydrazine (DMH) induced rat CRC model to assess the anti-oxidant and anticancer properties as well as their effects on the associated hepatic deterioration and hematological alterations., Results: Cell viability: In-vitro assessments demonstrated a dose and time-dependent reduction in HCT-116 cell viability following treatment with methanolic and ethanolic extracts of RW, reducing viability by up to 85% and 90%, respectively, at 200 μg/ml., Histopathology: Histopathological analyses revealed significant improvements in colon tissue morphology in RW extract-treated groups compared to DMH-only treated animals. RW-treated groups showed reduced structural abnormalities, congestion, inflammatory cell infiltration, crypt abscess formation, and dysplasia. In contrast, the DMH-only group exhibited irregular glandular structure, mucosal destruction, extensive inflammatory cell infiltration, crypt abscess formation, and dysplasia. These results highlight the potential of RW methanolic and ethanolic extracts in mitigating colon cancer-related histopathological alterations. Haematological, and hepatic parameters: In the DMH-induced colorectal cancer rat model, significant hematological imbalances were evident, including a 49.13% decrease in erythrocytes, 32.18% in hemoglobin, and 26.79% in hematocrit, along with a 79.62% increase in white blood cells and 68.96% rise in platelets. Administration of RW rhizome extracts effectively restored these hematological parameters to levels comparable to those in the control group. Furthermore, RW treatment significantly reduced serum ALT and AST levels, which had increased by 36.78% and 33.12%, respectively, due to DMH exposure. RW intervention also mitigated the onset of atherosclerosis, evidenced by notable reductions in serum total cholesterol and triglyceride levels. Comparative analysis indicated that RW-treated DMH groups effectively restored lipid profiles, contrasting with the DMH-only group which exhibited markers indicative of colon cancer. Oxidative stress: The DMH-treated group showed a significant increase in MDA levels by 195.59%, indicative of heightened free radical production, coupled with decreased levels of SOD (33%), CAT (48%), GSH (58%), and GR activity (49%), signifying oxidative stress. Treatment with RW extracts in DMH-treated rats markedly reduced MDA levels and enhanced SOD, CAT, GSH, and GR activities. These results underscore the antioxidant efficacy of RW extracts., Conclusion: This study underscores the significant potential of RW rhizome extracts in inhibiting colorectal cancer development. Further investigations are warranted to identify the active constituents responsible for these promising outcomes, positioning RW as a natural and potential agent in combating colon cancer., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Ethnopharmacological Relevance: Hepatic ischemia/reperfusion injury (HIRI) is a common occurrence during or after liver surgery, representing a major cause for postoperative complications or increased morbidity and mortality in liver diseases. Rehmanniae Radix Praeparata (RRP) is a traditional Chinese medicine frequently used and has garnered extensive attention for its therapeutic potential treating cardiovascular and hepatic ailments. Recent studies have indicated the possibility of RRP in regulating lipid accumulation and apoptosis in hepatocytes., Aim of the Study: This study aimed to investigate the specific mechanisms by which RRP may impede the progression of HIRI through the regulation of lipid metabolism., Materials and Methods: High-performance liquid chromatography (HPLC) was used to identify the major components of RRP water extract. C57BL/6J mice were orally given RRP at doses of 2.5 g/kg, 5 g/kg, and 10 g/kg for a duration of 7 days before undergoing HIRI surgery. Furthermore, we established a lipid-loaded in vitro model by exposing hepatocytes to oleic acid and palmitic acid (OAPA). The anti-HIRI effect of RRP was determined through transcriptomics and various molecular biology experiments., Results: After identifying active ingredients in RRP, we observed that RRP exerted lipid-lowering and hepatoprotective effects on HIRI mice and OAPA-treated hepatocytes. RRP activated AMP-activated protein kinase (AMPK) and inhibited mammalian target of rapamycin (mTOR), which further on the one hand, inhibited the cleavage and activation of sterol regulatory element binding protein 2 (SREBP2) by limiting the movement of SREBPs cleavage-activating protein (SCAP)-SREBP2 complex with the help of endoplasmic reticulum lipid raft-associated protein 1 (ERLIN1) and insulin-induced gene 1 (INSIG1), and on the other hand, promoted liver X receptor α (LXRα) nuclear transportation and subsequent cholesterol efflux. Meanwhile, the anti-lipotoxic effect of RRP can be partly reversed by an LXRα inhibitor but largely blocked by the application of compound C, an AMPK inhibitor., Conclusion: Our study elucidated that RRP served as a potential AMPK activator to alleviate HIRI by blocking SREBP2 activation and cholesterol synthesis, while also activating LXRα to facilitate cholesterol efflux. These findings shed new light on the potential therapeutic use of RRP for improving HIRI., Competing Interests: Declaration of competing interest The authors have declared no conflict of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Ethnopharmacological Relevance: Moringa oleifera (Moringaceae family), commonly known as horseradish or tree of life, is traditionally used for various diseases, such as diabetes, hypercholesterolemia, neurological disorders, among others., Aim of the Study: To evaluate the toxicological profile of the oral use of an aqueous extract of Moringa oleifera leaves for 13 weeks in mice., Materials and Methods: Initially, a factorial design (2 3 ) was carried out to optimize aqueous extraction using as variables; the extraction method and proportion of drug. The 13-week repeated-dose toxicity trial used female and male mice, with oral administration of aqueous extract of Moringa oleifera leaves at doses of 250, 500, and 1000 mg/kg. The animals were evaluated for body weight, water and feed intake, biochemical and hematological parameters, urinalysis, ophthalmology and histopathology of the liver, spleen and kidneys., Results: The extraction efficiency was evidenced by the extraction by maceration at 5%, obtaining the optimized extract of Moringa oleifera (OEMo). The oral administration of OEMo did not promote significant difference (p > 0.05) in the weight gain, food and water consumption of the control animals and those treated with 250 and 500 mg/kg. However, treatment with 1000 mg/kg promoted a reduction (p < 0.05) in food intake and body weight from the 7th week onwards in male and female mice. No alterations were detected in the hematological and histological parameters in the concentrations tested for both sexes. The highest concentration treatment (1000 mg/kg) promoted an increase in transaminases in males and females. All concentrations promoted a significant decrease (p < 0.05) in the serum lipid profile of mice., Conclusion: This study developed an optimized extract of Moringa oleifera leaves, which should be used with caution in preparations above 500 mg/kg for the long term because it leads to significant changes in liver enzymes. On the other hand, the extract proved to be a promising plant preparation for hyperlipidemia in mice., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Alcoholic liver injury (ALI) accounts for a major share of the global burden of non-viral liver disease. In the absence of specialized medications, research on using fruit flavonoids as a treatment is gaining momentum. This study investigated the hepatoprotective effects of four fruits rich in structurally diverse flavonoids: ougan (Citrus reticulata cv. Suavissima, OG), mulberry (Morus alba L., MB), apple (Malus × domestica Borkh., AP), and turnjujube (Hovenia dulcis Thunnb., TJ). A total of one flavanone glycoside, three polymethoxyflavones, two anthocyanins, one flavonol glycoside, and one dihydroflavonol were identified through UPLC analysis. In an acute ethanol-induced ALI mouse model, C57BL/6J mice were supplemented with 200 mg/kg·BW/day of different fruit extracts for three weeks. Our results showed that the four extracts exhibited promising benefits in improving lipid metabolism disorders, iron overload, and oxidative stress. RT-PCR and Western blot tests suggested that the potential mechanism may partially be attributed to the activation of the NRF2-mediated antioxidant response and the inhibition of ferroptosis pathways. Furthermore, fruit extracts administration demonstrated a specific regulatory role in intestinal microecology, with increases in beneficial bacteria such as Dubosiella, Lactobacillus, and Bifidobacterium. Spearman correlation analysis revealed strong links between intestinal flora, lipid metabolism, and iron homeostasis, implying that the fruit extracts mitigated ALI via the gut microbiota-liver axis. In vitro experiments reaffirmed the activity against ethanol-induced oxidative damage and highlighted the positive effects of flavonoid components. These findings endorse the prospective application of OG, MB, AP, and TJ as dietary supplements or novel treatments for ALI., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Ethnopharmacological Relevance: Gynostemma pentaphyllum (Thunb.) Makino (G. pentaphyllum) is an oriental herb documented to treat many diseases, including obesity, hyperlipidemia, metabolic syndromes and aging. However, the anti-obesity mechanism of G. pentaphyllum remains poorly understood., Aim of the Study: To reveal the anti-obesity mechanism of G. pentaphyllum Extract (GPE) in High-Fat Diet (HFD)-induced obese mice through untargeted metabolomics, Real-Time Quantitative PCR (RT-qPCR), and immunohistochemical experiments. Additionally, to tentatively identify the active constituents through LC-MS/MS and molecular docking approaches., Materials and Methods: GPE was prepared using ethanol reflux and purified by HP-20 macroporous resins. The components of GPE were identified by Liquid Chromatography- Mass Spectrometry (LC-MS) system. Forty-two C57BL/6 J mice were randomly and evenly divided into six groups, with seven mice in each group: the control group, obese model group, Beinaglutide group (positive control), and GPE low, medium, and high-dose groups (50 mg/kg, 100 mg/kg, and 200 mg/kg of 80% ethanol extract). Body weight, liver weight, blood glucose, blood lipids, and liver histopathological changes were assessed. Untargeted metabolomics was employed to characterize metabolic changes in obese mice after GPE treatment. The expression of genes related to differential metabolites was verified using Real-Time Quantitative PCR (RT-qPCR) and immunohistochemical experiments. The constituents with anti-obesity effects from GPE were tentatively identified through molecular docking approaches., Results: A total of 17 compounds were identified in GPE. GPE significantly lowered body weight, total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) in obese mice and reduced liver weight and hepatic steatosis. Serum metabolomics identified 20 potential biomarkers associated with GPE treatment in obese mice, primarily related to tryptophan metabolism. GPE treatment downregulated the expression of Slc6a19 and Tph1 and upregulated Ucp1 expression. Molecular docking illustrated that compounds such as 20(R)-ginsenoside Rg3, Araliasaponin I, Damulin B, Gypenoside L, Oleifolioside B, and Tricin7-neohesperidoside identified in GPE exhibited favorable interaction with Tph1., Conclusion: The extract of G. pentaphyllum can inhibit the absorption of tryptophan and its conversion to 5-HT through the Slc6a19/Tph1 pathway, upregulating the expression of Ucp1, thereby promoting thermogenesis in brown adipose tissue, facilitating weight loss, and mitigating symptoms of fatty liver. Triterpenoids such as Araliasaponin I, identified in GPE, could be the potential inhibitor of Tph1 and responsible for the anti-obesity activities., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Ethnopharmacological Relevance: Artemisia stechmanniana Besser, one of the most prevalent botanical medicines in Chinese, has been traditionally used for hepatitis treatment. However, the bioactive components and pharmacological mechanism on alcohol-induced liver injury remains unclear., Aim of the Study: To investigate the effect of A. stechmanniana on alcohol-induced liver damage, and further explore its mechanism., Materials and Methods: Phytochemical isolation and structural identification were used to determine the chemical constituents of A. stechmanniana. Then, the alcohol-induced liver damage animal and cell model were established to evaluate its hepato-protective potential. Network pharmacology, molecular docking and bioinformatics were integrated to explore the mechanism and then the prediction was further supported by experiments. Moreover, both compounds were subjected to ADMET prediction through relevant databases., Results: 28 compounds were isolated from the most bioactive fraction, ethyl acetate extract A. stechmanniana, in which five compounds (abietic acid, oplopanone, oplodiol, hydroxydavanone, linoleic acid) could attenuate mice livers damage caused by alcohol intragastration, reduce the degree of oxidative stress, and serum AST and ALT, respectively. Furthermore, abietic acid and hydroxydavanone exhibited best protective effect against alcohol-stimulated L-O2 cells injury among five bioactive compounds. Network pharmacology and bioinformatics analysis suggested that abietic acid and hydroxydavanone exhibiting drug likeliness characteristics, were the principal active compounds acting on liver injury treatment, primarily impacting to cell proliferation, oxidative stress and inflammation-related PI3K-AKT signaling pathways. Both of them displayed strong binding energies with five target proteins (HRAS, HSP90AA1, AKT1, CDK2, NF-κB p65) via molecular docking. Western blotting results further supported the predication with up-regulation of protein expressions of CDK2, and down-regulation of HRAS, HSP90AA1, AKT1, NF-κB p65 by abietic acid and hydroxydavanone., Conclusion: Alcohol-induced liver injury protection by A. stechmanniana was verified in vivo and in vitro expanded its traditional use, and its two major bioactive compounds, abietic acid and hydroxydavanone exerted hepatoprotective effect through the regulation of PI3K-AKT signaling pathway., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Ethnopharmacological Relevance: Calotropis gigantea (L.) Dryand. (C. gigantea) is a traditional medicinal plant, recognized for its effectiveness in managing diabetes, along with its notable antioxidant, anti-inflammatory, and anticancer properties. Type II diabetes mellitus (T2DM) is characterized by chronic metabolic disorders associated with an elevated risk of hepatocellular carcinoma (HCC) due to hyperglycemia and impaired insulin response. The scientific validation of C. gigantea's ethnopharmacological efficacy offers advantages in alleviating cancer progression in T2DM complications, enriching existing knowledge and potentially aiding future clinical cancer treatments., Aim: This study aimed to investigate the preventive potential of the dichloromethane fraction of C. gigantea stem bark extract (CGDCM) against diethylnitrosamine (DEN)-induced HCC in T2DM rats, aiming to reduce cancer incidence associated with diabetes while validating C. gigantea's ethnopharmacological efficacy., Materials and Methods: Spontaneously Diabetic Torii (SDT) rats were administered DEN to induce HCC (SDT-DEN-VEH), followed by treatment with CGDCM. Metformin was used as a positive control (SDT-DEN-MET). All the treatments were administered for 10 weeks after the initial DEN injection. Diabetes-related parameters, including serum levels of glucose, insulin, and glycosylated hemoglobin (HbA1c), as well as liver function enzymes (aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, and gamma-glutamyl transferase), were quantified. Serum inflammation biomarkers interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) were evaluated. Liver tissue samples were analyzed for inflammation protein expression (IL-6, TNF-α, transforming growth factor-β1 (TGF-β1), and α-smooth muscle actin (α-SMA)). Histopathological evaluation was performed to assess hepatic necrosis, inflammation, and fibrosis. Liver cell proliferation was determined using immunohistochemistry for Ki-67 expression., Results: Rats with SDT-DEN-induced HCC treated with CGDCM exhibited reduced serum glucose levels, elevated insulin levels, and decreased HbA1c levels. CGDCM treatment also reduced elevated hepatic IL-6, TNF-α, TGF-β1, and α-SMA levels in SDT-DEN-VEH rats. Additionally, CGDCM treatment prevented hepatocyte damage, fibrosis, and cell proliferation. No adverse effects on normal organs were observed with CGDCM treatment, suggesting its safety for the treatment of HCC complications associated with diabetes. Additionally, the absence of adverse effects in SD rats treated with CGDCM at 2.5 mg/kg further supports the notion of its safe usage., Conclusions: These findings suggest that C. gigantea stem bark extract exerts preventive effects against the development of HCC complications in patients with T2DM, expanding the potential benefits of its ethnopharmacological advantages., Competing Interests: Declaration of competing interest The authors have no potential conflicts of interest to disclose. All authors have approved of the final article., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Ethnopharmacological Relevance: Artemisia argyi (AA), a herbal medicine traditionally used in Asian countries, to treat inflammatory conditions such as eczema, dermatitis, arthritis, allergic asthma and colitis. However, the mechanism of action of this plant with regard to hepatitis and other liver-related diseases is still unclear., Aim: This study aimed to investigate the effects of AA ethanol extract on NASH-related fibrosis and gut microbiota in a choline-deficient, L-amino acid-defined, high-fat diet (CDAHFD)-induced mouse model., Methods: Male C57BL/6J mice were fed CDAHFD, with or without AA ethanol extract treatment. Biochemical markers, lipid profiles, hepatic mRNA expression levels of key genes, and the fibrosis area were assessed. In vitro, TGF-β-stimulated human hepatic stellate LX-2 cells and mouse primary hepatic stellate cells (mHSCs) were used to elucidate the effects of AA ethanol extract on fibrosis and steatosis. 16S rRNA sequencing, QIIME2, and PICRUST2 were employed to analyze gut microbial diversity, composition, and functional pathways., Results: Treatment with the AA ethanol extract improved plasma and liver lipid profiles, modulated hepatic mRNA expression levels of antioxidant, lipolytic, and fibrosis-related genes, and significantly reduced CDAHFD-induced hepatic fibrosis. Gut microbiota analysis revealed a marked decrease in Acetivibrio ethanolgignens abundance upon treatment with the AA ethanol extract, and its functional pathways were significantly correlated with NASH/fibrosis markers. The AA ethanol extract and its active components (jaceosidin, eupatilin, and chlorogenic acid) inhibited fibrosis-related markers in LX-2 and mHSC., Conclusion: The AA ethanol extract exerted therapeutic effects on CDAHFD-induced liver disease by modulating NASH/fibrosis-related factors and gut microbiota composition. Notably, AA treatment reduced the abundance of the potentially profibrotic bacterium (A. ethanolgignens). These findings suggest that AA is a promising candidate for treating NASH-induced fibrosis., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Ethnopharmacological Relevance: Artemisia rupestris L. (AR) is a traditional medicinal herb commonly used in the Uyghurs and Kazakhs; it was first documented in the Supplement to Compendium of Materia Medica written by Zhao Xuemin in the Qing Dynasty of China and is used clinically to treat colds, hepatitis, and allergic diseases., Aim of the Study: The material basis and mechanisms of AR in acute liver injury (ALI) remain unclear. The purpose of this study was to reveal the possible active components involved in liver protection in AR and to preliminarily explore their pharmacological mechanisms., Materials and Methods: The chemical composition of the ethanolic extract (ARA) was identified by UPLC-Q-Exactive-MS/MS and confirmed by 32 reference standards. The pharmacodynamic results were utilized to screen the active part within the ARA that contribute to the amelioration of CCl 4 /ConA-induced ALI. The main active components and core targets were predicted by network pharmacology and verified by molecular docking combined with qPCR and Western blotting., Results: A total of 131 chemical components were identified in the ARA. The extraction parts of ARA had different therapeutic effects on ALI, among which the dichloromethane extract (ARA-D), which might constitute the main effective fraction of ARA, had significant anti-ALI effects. The network pharmacology results showed that targets including PIK3R1, AKT1, and EGFR, as well as 7 compounds, such as artemetin, vitexicarpin and rupestonic acid may play pivotal roles in treating CCl 4 /ConA-induced ALI. GO and KEGG pathway enrichment analyses revealed that the PI3K-AKT signaling pathway was the main pathway involved. In each model, ARA-D dose-dependently reduced the increase in ALT levels. High-dose ARA-D markedly decreased ALT activity from 196.79 ± 24.82 to 66.37 ± 16.19 U/L in the CCl 4 model group and from 178.00 ± 28.39 to 50.67 ± 7.39 U/L in the ConA model group. Further studies revealed that ARA-D significantly inhibited TNF-α, IL-1β, and IL-6 expression and inhibited the protein expression of PI3K, p-PI3K, and p-AKT in CCl 4 /ConA-induced ALI., Conclusion: ARA-D exhibits protective effects against ALI induced by CCl 4 /ConA, potentially through inhibition of the PI3K-AKT signaling pathway. These findings may help to determine the material basis and mechanisms of action of ARA-D for liver protection and provide ideas for future comprehensive studies., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Ethnopharmacological Relevance: Pueraria lobata is essential medicinal and edible homologous plants widely cultivated in Asian countries. Therefore, P. lobata is widely used in the food, health products and pharmaceutical industries and have significant domestic and international market potential and research value. P. lobata has remarkable biological activities in protecting liver, relieving alcoholism, antioxidation, anti-tumor and anti-inflammation in clinic. However, the potential mechanism of ethyl acetate extract of Pueraria lobata after 70% alcohol extraction (APL) ameliorating nonalcoholic fatty liver disease (NAFLD) has not been clarified., Aim of the Study: This study aimed to investigate the ameliorative effect of P. lobata extract on human hepatoma cells and injury in rats, and to evaluate its therapeutic potential for ameliorating NAFLD., Methods: Firstly, the effective part of P. lobata extract was determined as APL by measuring its total substances and antioxidant activity. And then the in vitro and in vivo models of NAFLD were adopted., HepG2 cells were incubated with palmitic acid (PA) and hydrogen peroxide (H 2 O 2 ). In order to evaluate the effect of APL, Simvastatin and Vitamin C (VC) were used as positive control. Various parameters related to lipogenesis and fatty acid β-oxidation were studied, such as intracellular lipid accumulation, reactive oxygen species (ROS), Western Blot, mitochondrial membrane potential, apoptosis, and the mechanism of APL improving NAFLD. The chemical components of APL were further determined by HPLC and UPLC-MS, and molecular docking was carried out with Keap1/Nrf2/HO-1 pathway related proteins., Results: APL significantly reduced lipid accumulation and levels of oxidative stress-related factors in vitro and in vivo. Immunohistochemical、Western Blot and PCR analysis showed that the expressions of Nrf2 and HO-1 were up-regulated in APL treatment. The Nrf2 inhibitor ML385 can block the rescue by APL of cellular oxidative stress and lipid accumulation induced by H 2 O 2 and PA, demonstrating its dependence on Nrf2. UPLC/MS analysis showed that there were 3'-hydroxyl puerarin, puerarin, 3'-methoxy puerarin, daidzein, genistin, ononin, daidzin and genistein., Conclusion: This study further clarified the mechanism of P. lobata extract in improving NAFLD, which provided a scientific basis for developing new drugs to protect liver injury and laid a solid foundation for developing P. lobata Chinese herbal medicine resources., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Ethnopharmacological Relevance: The extracellular regulated protein kinase (ERK) plays a crucial role in the mitogen-activated protein kinase (MAPK) family, influencing apoptosis, proliferation, and differentiation. It connection to the insulin (INS) signaling cascade and the development of type 2 diabetes mellitus (T2DM) has been established. Rubus irritans Focke, an indispensable herb in Chinese Tibetan medicine for diabetes mellitus treatment, lacks a comprehensive understanding of its effects and pharmacological mechanisms in T2DM., Aim of the Study: This study aimed to elucidate the effects of Rubus irritans Focke extract (Rife) on a T2DM rat model, exploring its impact on glycemic and lipid metabolism, histopathological changes, and its potential targeting of the extracellular regulated protein kinase/insulin receptor substrate-1 (ERK/IRS-1) signaling pathway., Materials and Methods: A T2DM rat model was induced by streptozotocin (STZ) injection (40 mg/kg) in high-fat diet-fed (HFD) male Wistar rats. Rife and metformin (Met) were administered for 4 weeks, and glycemic, lipid metabolism indices, and histopathological changes were assessed. Protein expression of ERK, IRS-1 in rat liver tissues was examined to evaluate the impact on the ERK/IRS-1 pathway., Results: Rife reducing hepatic ERK and IRS-1 protein expression in T2DM rats. Untargeted metabolomics identified 13 potential biomarkers and 4 differential metabolic pathways related to glycolipid metabolism disorders., Conclusions: Rife demonstrated improved glycolipid metabolism in T2DM rats by inhibiting the ERK/IRS-1 related signaling pathway and influencing multiple metabolic pathways. This study provides valuable insights into the potential therapeutic mechanisms of Rife in the context of T2DM., Competing Interests: Declaration of competing interest The authors have declared that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Cannabidiol (CBD) has gained widespread popularity; however, its pharmacological and toxicological profiles in the context of human genetic diversity remain largely unexplored. Here, we investigated the variability in metabolism and toxicity of CBD-rich cannabis extract (CRCE) in genetically diverse mouse models: C57BL/6J, B6C3F 1 /J, and NZO/HlLtJ strains. Mice received a single dose of CRCE containing 57.9% CBD at dosages of 0, 246, 738, and 2460 mg/kg of CBD. At 24 h after treatment, no appreciable histomorphological changes were detected in the liver. Plasma bilirubin levels increased markedly in all strains at the highest CBD dose. Mice in all treatment groups displayed significant but distinct increases in ALT and AST levels. While B6C3F 1 /J and NZO/HlLtJ mice had negligible plasma CBD levels at 738 mg/kg, C57BL/6J mice exhibited levels exceeding 7000 ng/mL. At 2460 mg/kg, high CBD concentrations were found in B6C3F 1 /J and C57BL/6J mice, but markedly lower levels were seen in NZO/HlLtJ mice. Gene expression profiling showed significant increases in Cyp2b10 across all strains but varying responses in Cyp1a1 expression, indicating strain-specific CYP dysregulation. Genetically diverse mice exhibited differential pharmacological and toxicological responses to CRCE, suggesting a high potential for inter-individual variability in the pharmacology and toxicology of CBD in humans., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Spilanthes filicaulis (Schumach. & Thonn.) C. D Adam is a shrubby plant of the Asteraceae family that has medicinal benefits for the pharmaceutical and cosmetic industries., Purpose: The purpose of this study was to assess the effectiveness of Spilanthes filicaulis leaf extract in a streptozotocin (STZ)-induced rat model and the associated signaling pathways., Methods: A sample of 25 male Wistar rats was randomly assigned to groups I, II, III, IV, and V. Each group included five animals, i.e., control rats, diabetic control rats, diabetic rats treated with metformin, and diabetic rats treated with 150 mg/kg/bw and 300 mg/kg/bw of the methanolic extract of S. filicaulis leaves (MESFL). Treatment was administered for 15 successive days via oral gavage. After 15 days, the rats were evaluated for fasting blood glucose (FBG), glycated hemoglobin (HbA1c), alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), triglyceride (TG), total cholesterol (TC), low-density lipoprotein (LDL), high-density lipoprotein (HDL), reduced glutathione (GSH), glutathione-S-transferase (GST), superoxide dismutase (SOD), catalase (CAT), lipid peroxidation (MDA), hexokinase, and glucose-6-phosphatase activities. Gene expression levels of nuclear factor erythroid 2-related factor 2 (Nrf2), peroxisome proliferator-activated receptor gamma (PPAR-γ), kelch-like ECH-associated protein 1 (Keap1), protein tyrosine phosphatase 1B (PTP1B) and the antiapoptotic protein caspase-3 were examined., Results: MESFL was administered to diabetic rats, and changes in body weight, fasting blood glucose (FBG) and HbA1c were restored. Furthermore, in diabetic rats, S. filicaulis significantly reduced the levels of triglycerides (TGs), total cholesterol (TC), low-density lipoprotein (LDL), and very low-density lipoprotein (VLDL) and significantly increased HDL. S. filicaulis improved ALT, AST, and ALP enzyme activity in diabetic rats. MDA levels decreased considerably with increasing activity of antioxidant enzymes, such as GST, SOD, CAT and GSH, in diabetic liver rats treated with S. filicaulis. Diabetic rats treated with MESFL and metformin exhibited upregulated mRNA expression levels of nuclear factor erythroid 2-related factor 2 (Nrf2) and peroxisome proliferator-activated receptor gamma (PPAR-γ). Kelch-like ECH-associated protein 1 (Keap1) and protein tyrosine phosphatase 1B (PTP1B) mRNA expression in the liver was downregulated in diabetic rats treated with MESFL and metformin. In addition, MESFL downregulated the mRNA expression of caspase-3 in diabetic rats., Conclusion: It can be concluded from the data presented in this study that MESFL exerts a protective effect on diabetic rats due to its antidiabetic, antioxidant, antihyperlipidemic and antiapoptotic effects and may be considered a treatment for T2DM., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Ojo et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Accumulating evidence shows a strong correlation between type 2 diabetes mellitus, mitochondrial dysfunction, and oxidative stress. We evaluated the effects of dietary peanut shell extract (PSE) supplementation on mitochondrial function and antioxidative stress/inflammation markers in diabetic mice. Fourteen db/db mice were randomly assigned to a diabetic group (DM in AIN-93G diet) and a PSE group (1% wt/wt PSE in AIN-93G diet) for 5 weeks. Six C57BL/6J mice were fed with an AIN-93G diet for 5 weeks (control group). Gene and protein expression in the liver, brain, and white adipose tissue (WAT) were determined using qRT-PCR and Immunoblot, respectively. Compared to the control group, the DM group had (i) increased gene and protein expression levels of DRP1 (fission), PINK1 (mitophagy), and TNFα (inflammation) and (ii) decreased gene and protein expression levels of MFN1, MFN2, OPA1 (fusion), TFAM, PGC-1α (biogenesis), NRF2 (antioxidative stress) and IBA1 (microglial activation) in the liver, brain, and WAT of db/db mice. Supplementation of PSE into the diet restored the DM-induced changes in the gene and protein expression of DRP1, PINK1, TNFα, MFN1, MFN2, OPA1, TFAM, PGC-1α, NRF2, and IBA1 in the liver, brain, and WAT of db/db mice. This study demonstrates that PSE supplementation improved mitochondrial function in the brain, liver, and WAT of db/db mice, in part due to suppression of oxidative stress and inflammation.