Liver Ailments Research Articles

Herbal Components for the Treatment of Liver Disorders: Advances and Prospective

Abstract: The situation is made worse by the absence of detailed treatment plans for liver disease, a dangerous illness. The current liver disease treatments are insufficient, and their long-term usage is prevented by systemic toxicity. Since the toxicity factor seems to be on the lower end of the spectrum, herbal remedies have been utilized for ages to treat liver ailments. This article focuses on providing insight into liver diseases along with the herbal components that are used nowadays for efficiently treating them. The given herbal components glycyrrhizin, quercetin, curcumin, silymarin, and Phyllantus niruri have proven to be efficacious in treating liver diseases with no or bare minimum side effects. The liver diseases discussed in this review article include alcoholic liver disease, non-alcoholic fatty liver disease, hepatitis C, hepatitis B, hemochromatosis as well and auto-immune hepatitis. After summarization, it is concluded that these herbal components are proven to be effective in the treatment of liver diseases, and various research as well as studies have been conducted for the same.

Toxicological evaluation of LivLonga®, a polyherbal combination, in rodents

There has been keen interest on herbs and phytoconstituents with hepatoprotective property to help restore healthy liver function. Ayurveda, the ancient Indian traditional system of medicine mentions about Curcuma longa, Garcinia indica and Piper nigrum which are reported to have hepatoprotective activity. Apart from supporting metabolism, liver plays pivotal role in numerous bodily processes, immune functions to digestion, detoxification, and storage of nutrients. Factors such as sedentary lifestyle, viral infections, drugs/chemicals, high calorie diet, excess intake of alcohol etc have adverse impact on normal functioning of liver. Development of novel herbal combination with standards of safety and efficacy can help manage liver ailments and protect liver health. LivLonga® is a polyherbal combination of scientifically validated ingredients- curcuminoids, garcinol and piperine to support healthy liver function. The present work was conducted to evaluate toxicity of LivLonga® using in vivo models when administered orally. The acute, subacute, and subchronic toxicity studies were carried out in accordance with the test guidelines established by the Organization for Economic Cooperation and Development. A single-dose acute oral toxicity produced no toxic effects after 14 days of treatment. Four-week (subacute) and 3-months (subchronic) oral toxicity studies were conducted and observed no abnormal clinical signs, no alterations in the body weight, hematology and biochemical parameters or gross and histopathological changes. Thus, oral administration of LivLonga® showed no signs of toxicity when dosed orally to rats, with a no observed adverse effect level (NOAEL) of 600 mg/kg/day.

Hepatoprotective activity of medicinal plants, their phytochemistry, and safety concerns: a systematic review.

Medicinal plants and their derivatives represent a promising reservoir of remedies for various ailments. Especially secondary metabolites of these plants, including alkaloids, flavonoids, phenolic compounds, terpenoids, steroids, saponins, tannins, and anthraquinones, play crucial roles in hepatoprotection. Studies have identified several prominent phytoconstituents, such as silymarin, quercetin, luteolin, glycyrrhizin, curcumin, gallic acid, chebulic acid, catechin, aloin, emodin, liquiritin, liquiritigenin, cudraflavone B, and karaviloside, as effective agents for addressing hepatotoxicity. The mechanisms underlying their efficacy include antioxidant, anti-inflammatory, free radical scavenging, and the ability to block oxidative stress, cytokine production, and stabilize liver cell membranes. The application of natural products derived from medicinal plants in treating liver injuries is rooted in their efficacy, cost-effectiveness, and safety profile, contributing to their popularity. Many studies, encompassing invitro, invivo, preclinical, and clinical investigations, have demonstrated that the extracts of medicinal plants mitigate chemical-induced liver damage using animal models. However, intensive research efforts regarding the safety, regulatory standard, and quality control issues for using medicinal plants as hepatoprotective agents remain the strong task of scholars. The primary focus of this systematic review is to analyze the current state of the literature regarding treating liver ailments using extracts from medicinal plants, examining their phytochemical composition, and addressing associated safety considerations.

Shenqi Pill alleviates acetaminophen-induced liver injury: a comprehensive strategy of network pharmacology and spectrum-effect relationship reveals mechanisms and active components

BackgroundAcetaminophen (APAP), commonly used for its antipyretic and analgesic properties, can cause severe liver injury or even acute liver failure when overdosed. However, the options for treating APAP-induced liver toxicity are limited. Shenqi Pill (SQP), a traditional Chinese herbal formula, has shown effectiveness in treating various liver ailments. SQP consists of cinnamon, aconite, rehmannia, cornus, peony bark, Chinese yam, poria, and alisma in a ratio of 1:1:8:4:3:4:3:3. However, the mechanisms and active components of SQP that counteract drug-induced liver injury (DILI) are not well understood. PurposeThis study aimed to explore the protective effects of SQP against APAP-induced liver injury in both laboratory and animal settings. It seeks to identify the active components and potential mechanisms by which SQP targets mitochondria to alleviate liver damage. MethodsA mouse model with APAP-induced liver injury was established to assess SQP's therapeutic impact. This study then analyzed the components of SQP using UPLC-Q-TOF-MS in both in vivo and in vitro environments. Network pharmacology and the GEO database helped predict potential pathways and targets. Potential active components were identified through spectrum-effect relationship analysis and validated their efficacy using Seahorse assays and molecular docking. ResultsTreatment with SQP significantly reduced liver dysfunction, tissue damage, lipid metabolic disruptions, and inflammation caused by APAP in mice. In cellular tests, SQP-treated serum notably enhanced mitochondrial function, maintained membrane potential, decreased ROS levels, and prevented mitochondrial permeability transition pore opening. Biochemically, SQP reversed the suppression of p-AMPK, p-ACC, CPT1, and ACADM expression caused by APAP overdose. This study identified 97 in vitro and 24 in vivo components of SQP, with eight showing significant mitochondrial benefits. Molecular docking studies suggest that fuziline and paeoniflorin could activate AMPK. ConclusionSQP effectively mitigates APAP-induced liver injury by enhancing mitochondrial function via the AMPK-ACC-CPT1-ACADM pathway. Moreover, this study introduces a novel strategy for analyzing the relationship between the chemical and pharmacological properties of drug-containing serum, successfully identifying compounds with mitochondrial activity. Fuziline and paeoniflorin, in particular, emerge as promising mitochondrial protectants and warrant further investigation. This research underpins the development of innovative treatments for DILI using SQP and its components.

Ethnobotanical survey and scientific validation of liver-healing plants in northeastern Morocco.

Liver diseases represent a significant global health challenge, with primary causes including excessive alcohol consumption, infections, chemotherapy, and autoimmune disorders. Medicinal plants, due to their natural bioactive compounds, hold promise for developing effective treatments and preventive measures against liver ailments. This study aimed to document the use of herbal remedies in northeastern Morocco for liver diseases and correlate these uses with scientific evidence through a bibliometric analysis. An ethnobotanical survey was conducted in remote communities of northeastern Morocco from October 2020 to January 2022. A total of 189 informants were interviewed using semi-structured questionnaires to gather information on local medicinal plants used for liver ailments. The data were analyzed using four ethnobotanical quantitative indices: use value (UV), familial use value (FUV), informant consensus factor (ICF), and fidelity level (FL). Additionally, a bibliometric analysis was performed to evaluate the scientific support for the ethnopharmacological uses documented. The survey identified 45 plant species from 26 different families used in the treatment of liver diseases. The most frequently utilized species were Cuminum cyminum L. (UV = 0.1065), Allium sativum L. (UV = 0.1015), Salvia officinalis L. (UV = 0.0761), Asparagus officinalis L. (UV = 0.0558), and Ziziphus lotus (L.) Lam. (UV = 0.0457). The Apiaceae family showed the highest familial use value (FUV = 0.1066), followed by Alliaceae (FUV = 0.1015). Liver congestion had the highest informant consensus factor (ICF = 0.83), followed by hepatic colic (ICF = 0.80). Bibliometric analysis revealed that 61% of the plants identified had documented pharmacological effects related to liver health. The study demonstrates that traditional knowledge in northeastern Morocco encompasses a rich diversity of medicinal plants used to treat liver diseases. The high ICF values indicate a strong consensus among informants on the efficacy of these remedies. The correlation between ethnopharmacological use and scientific validation for a significant portion of these plants suggests their potential as reliable therapeutic agents for liver conditions. However, further scientific investigations are necessary to confirm their efficacy and safety in clinical settings. This research contributes valuable information for future studies on the therapeutic potential of these plants. This ethnobotanical survey provides a comprehensive database of medicinal plants used in northeastern Morocco for liver diseases. The findings highlight the potential of these plants in developing novel treatments for hepatic conditions, although further research is essential to substantiate their therapeutic claims.

Protective effects of Nogo-B deficiency in NAFLD mice and its multiomics analysis of gut microbiology and metabolism

BackgroundNonalcoholic fatty liver disease (NAFLD) is a prevalent chronic liver ailment that can lead to serious conditions such as cirrhosis and hepatocellular carcinoma. Hepatic Nogo-B regulates glucose and lipid metabolism, and its inhibition has been shown to be protective against metabolic syndrome. Increasing evidence suggests that imbalances in the gut microbiota (GM) and lipid metabolism disorders are significant contributors to NAFLD progression. Nevertheless, it is not yet known whether Nogo-B can affect NAFLD by influencing the gut microbiota and metabolites. Hence, the aim of the present study was to characterize this process and explore its possible underlying mechanisms.MethodsA NAFLD model was constructed by administering a high-fat diet (HFD) to Nogo-B−/− and WT mice from the same litter, and body weight was measured weekly in each group. The glucose tolerance test (GTT) and insulin tolerance test (ITT) were performed to assess blood glucose levels. At the end of the 12-week period, samples of serum, liver, and intestinal contents were collected and used for serum biochemical marker and inflammatory factor detection; pathology evaluation; and gut microbiome and metabolomics analysis. Spearman’s correlation analysis was performed to determine possible correlations between differential gut microbiota and differential serum metabolites between groups.ResultsNogo-B deficiency attenuated the effects of the HFD, including weight gain, liver weight gain, impaired glucose tolerance, hepatic steatosis, elevated serum lipid biochemicals levels, and liver function. Nogo-B deficiency suppressed M1 polarization and promoted M2 polarization, thus inhibiting inflammatory responses. Furthermore, Nogo-B−/−-HFD-fed mice presented increased gut microbiota richness and diversity, decreased Firmicutes/Bacteroidota (F/B) ratios, and altered serum metabolites compared with those of WT-HFD-fed mice. During analysis, several differential gut microbiota, including Lachnoclostridium, Harryflintia, Odoribacter, UCG-009, and unclassified_f_Butyricoccaceae, were screened between groups. These microbiota were found to be positively correlated with upregulated purine metabolism and bile acid metabolites in Nogo-B deficiency, while they were negatively correlated with downregulated corticosterone and tricarboxylic acid cyclic metabolites in Nogo-B deficiency.ConclusionNogo-B deficiency delayed NAFLD progression, as demonstrated by reduced hepatocellular lipid accumulation, attenuated inflammation and liver injury, and ameliorated gut microbiota dysbiosis and metabolic disorders. Importantly, Odoribacter was strongly positively correlated with ALB and taurodeoxycholic acid, suggesting that it played a considerable role in the influence of Nogo-B on the progression of NAFLD, a specific feature of NAFLD in Nogo-B−/− mice. The regulation of bile acid metabolism by the gut microbiota may be a potential target for Nogo-B deficiency to ameliorate NAFLD.

Pien Tze Huang, a 500-Year-Old Traditional Composite Medicine in China for Liver Ailments Alleviates Some Effects of the Alcoholic Liver in a Mouse Model

Pien Tze Huang, a 500-Year-Old Traditional Composite Medicine in China for Liver Ailments Alleviates Some Effects of the Alcoholic Liver in a Mouse Model

Withania coagulans Dunal.: A Narrative Review of an Anti-diabetic Shrub of the Desert Biome

Abstract: Diabetes mellitus is a chronic disease affecting more than 300 million people worldwide. Even after advances in medicine, we are still away from a permanent solution to this problem. Longterm use of currently available treatments are associated with adverse effects ranging from cardiovascular conditions, renal disorders, liver ailments, and weight gain. Subsequently, a significant diabetic population seeks herbal medicines that are said to control blood sugar levels. Several plants have been explored in this context; one such plant is Withania coagulans Dunal., which is known for the hypoglycemic property due to its fruits. Different plant parts and bioactive components like withanolides exhibited anti-diabetic activity in type 2 diabetes models in vivo and in vitro. However, clinical studies are limited and more research is warranted. Bioactive composition of W. coagulans include Withanolide J, F; Coagulin C, E, L; Ajugin E, Withaperuvin C and others. Bioavailability of Withaferin A from W. coagulans was enhanced by co-administration of Piperine. Herbal quality control and commercialization aspects are also highlighted. W. coagulans can be employed in managing type 2 diabetes mellitus after detailed follow-up studies.

Exploring the ethnopharmacological significance of Cynara scolymus bracts: Integrating metabolomics, in-Vitro cytotoxic studies and network pharmacology for liver and breast anticancer activity assessment

Ethnopharmacological relevanceLiver and breast cancers are the most dominant cancer types with high occurrence rates. Artichoke (Cynara scolymus L.) has been reputed for its traditional use in alleviating many liver and gallbladder ailments beside its anticancer activity against various types of cancer cells. Aim of the studyTo demonstrate detailed chemical matrices of the different plant parts and evaluate their cytotoxic activities aiming to unveil the relationship between these activities and the intrinsic metabolites using metabolomic studies, in-vitro experiments and network pharmacology. Materials and methodsChemical profiling of extracts from the different plant parts (stems, leaves, bracts and receptacles) was performed using HPLC/QqQ/MS followed by unsupervised chemometric studies. In-vitro cytotoxic potentials of the extracts were evaluated on breast and liver cancer cell line then an OPLS study using linear regression was conducted. Consequently, a network pharmacology analysis on the most bioactive plant organ was applied. ResultsUnsupervised chemometric analysis revealed that kaempferol-3-O-α-L-rhamnopyranoside-7-O-β-D-galacturonopyranoside, chrysoeriol-7-rutinoside and 1-caffeoylquinic acid were responsible for the segregation of the bract (CSB) segregated from the rest of the plant organs. Interestingly, CSB extract possessed the highest potential in-vitro cytotoxic activity against both liver and breast cancer cells (IC50 = 1.65 and 1.77 μg/mL). As expected, the aforementioned biomarkers were observed to be the discriminatory cytotoxic metabolites in the constructed supervised chemometric model. Network pharmacology analysis on CSB revealed 27 liver cancer-related metabolites of which, 1-caffeoylquinic acid was the most enriched one contributing to 13% of the total interactions. Furthermore, 38 target genes were involved, the most enriched of which were Aldo-keto reductase family 1 member B1 (AKR1B10) and interleukin-2 (IL-2). KEGG pathway analysis unveiled 23 significantly related pathways including metabolic pathways that possessed the lowest p-value (1.6E-5). ConclusionThe findings demonstrated that CSB is a significant source of cytotoxic metabolites against breast cancer and liver cancer cell lines, hence, drawing attention to the pharmaceutical and medicinal value of this negligible plant organ and paving the route for insightful research into its exact pharmacological cytotoxic mechanisms.

Anti-inflammatory and anti-angiogenic effects of Withania somnifera extract on liver toxicity induced by silver nanoparticles in vivo.

The liver is a critical organ in the human body and is frequently exposed to numerous exogenous toxic substances, including silver nanoparticles (AgNPs). This study aimed to examine the anti-inflammatory, anti-angiogenic, and hepatoprotective effects of Withania somnifera (W. somnifera) extract on AgNP-induced liver toxicity in Swiss mice. Fifty mice were divided into five groups. Group I (negative control) consisted of ten mice. Group II received oral W. somnifera extracts (80 mg/kg/bw) for 14 days. Group III was injected intraperitoneally (i.p.) with AgNPs at a daily dose of 35 mg/kg/bw for 3 days. Group IV received i.p. AgNPs for 3 days, followed by saline for 14 days. Group V received i.p. AgNPs for 3 days, followed by oral W. somnifera (80 mg/kg/bw) for 14 days. Liver function tests, pro and anti-inflammatory cytokines, antioxidant activities, protein carbonyl (PC) levels, liver histopathological analysis, immunohistochemical expressions of transcription factor (NF-κB), and vascular endothelial growth factor (VEGF) were examined. Group III had elevated levels of liver function, a significant increase of pro and anti-inflammatory cytokines, antioxidant activity, and PC levels. Histological observations revealed congested sinusoids filled with red blood cells (RBCs) and hepatocyte necrosis. Also, positive expressions of NF-κB and VEGF were detected compared with Group I. However, the administration of W. somnifera to Group V revealed significant changes with evident improvements in liver function biomarkers, pro and anti-inflammatory cytokines, antioxidant activities, oxidative stress markers (PC), and histopathological and immunohistochemical parameters compared to Group III. The results revealed that W. somnifera has promising and potential hepatoprotective, anti-inflammatory, and anti-angiogenic effects against liver toxicity. Further detailed studies are recommended to explore the potential of W. somnifera as a treatment for human liver ailments.

Hepatoprotective effects of Juglans regia on carbon tetrachloride‐induced hepatotoxicity: In silico/in vivo approach

AbstractJuglans regia L. is a well‐known therapeutic plant in Nepal, employed in traditional medicine for treating liver ailments. This study aimed to evaluate the in vivo and in silico liver‐protective effects of J. regia extract using a carbon tetrachloride (CCl4)‐induced hepatic damage rat model. Healthy male rats were randomly divided into six groups: normal control (distilled water 10 mL/kg), toxic control (distilled water 10 mL/kg), standard test (silymarin 100 mg/kg), and three groups receiving oral J. regia extracts (125, 250, and 500 mg/kg/day) for seven days. On the eighth day, carbon tetrachloride (CCl4) was administered intraperitoneally (i.p.) (1.5 mL/kg in 1:1 olive oil ratio for all groups, except the normal control). Rats were sacrificed on the ninth day, and blood was collected retro‐orbitally for liver blood injury tests and histopathological studies. Molecular docking was performed against cytochrome P450 2E1 (CYP450 2E1) enzyme for 16 selected phytoconstituents. J. regia, at doses of 125, 250, and 500 mg/kg, significantly reduced liver enzyme levels (alanine aminotransferase, alkaline phosphatase, direct bilirubin, and total bilirubin), while increasing serum albumin. Histological analysis revealed mitigation of carbon tetrachloride (CCl4)‐induced liver injury, reducing fatty degeneration and necrosis. Molecular docking supported the findings, with Beta‐sitosterol and Betulinic acid exhibiting the best binding affinity of −9.2 and −9.1 kcal/mol, respectively. In conclusion, result suggests that J. regia showed dose‐dependent hepatoprotective activity in CCl4‐induced hepatotoxicity and it could be utilized as a promising hepatoprotective agent. This study suggests the hepatoprotective potential of J. regia bark extracts, emphasizing the need for further clinical validation.

Exploring the Potential Hepatoprotective Properties of Cactus (Cactaceae) in Liver Health and Disease Management: A Brief Review

Cacti are renowned for their resilience in arid environments and have been utilized as a valuable food source in various cultures for centuries. The potential effects of cactus (Cactaceae) consumption on liver health have garnered significant scientific interest in recent years. This review aimed to consolidate and analyze existing research findings regarding the relationship between cactus-derived compounds and their influence on liver function and health. Various cactus species, particularly Opuntia spp., are rich reservoirs of antioxidants, polyphenols, flavonoids, and betalains. In vitro and in vivo studies with animal models have shown that bioactive constituents of cactus exhibit anti-inflammatory, antioxidative, and antifibrotic properties, which potentially mitigate liver damage induced by oxidative stress, inflammation, and hepatotoxic agents. Understanding their mechanisms of action and conducting rigorous clinical studies with administration of cactus will ascertain their role in preventing and treating liver ailments, offering novel avenues in nutrition, hepatology, and natural medicine.

Ethanol Extract of the Microalga Phaeodactylum tricornutum Shows Hepatoprotective Effects against Acetaminophen-Induced Acute Liver Injury in Mice.

Acute liver failure is an infrequent yet fatal condition marked by rapid liver function decline, leading to abnormalities in blood clotting and cognitive impairment among individuals without prior liver ailments. The primary reasons for liver failure are infection with hepatitis virus or overdose of certain medicines, such as acetaminophen. Phaeodactylum tricornutum (PT), a type of microalgae known as a diatom species, has been reported to contain an active ingredient with anti-inflammatory and anti-obesity effects. In this study, we evaluated the preventive and therapeutic activities of PT extract in acute liver failure. To achieve our purpose, we used two different acute liver failure models: acetaminophen- and D-GalN/LPS-induced acute liver failure. PT extract showed protective activity against acetaminophen-induced acute liver failure through attenuation of the inflammatory response. However, we failed to demonstrate the protective effects of PT against acute liver injury in the D-GalN/LPS model. Although the PT extract did not show protective activity against two different acute liver failure animal models, this study clearly demonstrates the importance of considering the differences among animal models when selecting an acute liver failure model for evaluation.

PSTPIP2 protects against alcoholic liver injury and invokes STAT3-mediated suppression of apoptosis

Alcoholic liver injury (ALI) stands as a prevalent affliction within the spectrum of complex liver diseases. Prolonged and excessive alcohol consumption can pave the way for liver fibrosis, cirrhosis, and even hepatocellular carcinoma. Recent findings have unveiled the protective role of proline serine-threonine phosphatase interacting protein 2 (PSTPIP2) in combating liver ailments. However, the role of PSTPIP2 in ALI remains mostly unknown. This study aimed to determine the expression profile of PSTPIP2 in ALI and to uncover the mechanism through which PSTPIP2 affects the survival and apoptosis of hepatocytes in ALI, using both ethyl alcohol (EtOH)-fed mice and an EtOH-induced AML-12 cell model. We observed a consistent decrease in PSTPIP2 expression both in vivo and in vitro. Functionally, we assessed the impact of PSTPIP2 overexpression on ALI by administering adeno-associated virus 9 (AAV9)-PSTPIP2 into mice. The results demonstrated that augmenting PSTPIP2 expression significantly shielded against liver parenchymal distortion and curbed caspase-dependent hepatocyte apoptosis in EtOH-induced ALI mice. Furthermore, enforcing PSTPIP2 expression reduced hepatocyte apoptosis in a stable PSTPIP2-overexpressing AML-12 cell line established through lentivirus-PSTPIP2 transfection in vitro. Mechanistically, this study also identified signal transducer and activator of transcription 3 (STAT3) as a direct signaling pathway regulated by PSTPIP2 in ALI. In conclusion, our findings provide compelling evidence that PSTPIP2 has a regulatory role in hepatocyte apoptosis via the STAT3 pathway in ALI, suggesting PSTPIP2 as a promising therapeutic target for ALI.

Turning points in the practice of liver surgery: A historical review.

The history of liver surgery is a tale of progressive resolution of issues presenting one after another from ancient times to the present days when dealing with liver ailments. The perfect knowledge of human liver anatomy and physiology and the development of a proper liver resective surgery require time and huge efforts and, mostly, the study and research of giants of their own times, whose names are forever associated with anatomical landmarks, thorough descriptions, and surgical approaches. The control of parenchymal bleeding after trauma and during resection is the second issue that surgeons have to resolve. A good knowledge of intra and extrahepatic vascular anatomy is a necessary condition to develop techniques of vascular control, paving the way to liver transplantation. Last but not least, the issue of residual liver function after resection requires advanced techniques of volume redistribution through redirection of blood inflow. These are the same problems any young surgeon would face when approaching liver surgery for the first time. Therefore, obtaining a wide picture of historical evolution of liver surgery could be a great starting point to serve as an example and a guide.

Genetic-driven biomarkers for liver fibrosis through bioinformatic approach

BackgroundLiver fibrosis is a widespread chronic liver ailment linked to substantial mortality and limited therapeutic options. An in-depth comprehension of the genetic underpinnings of liver fibrogenesis is crucial for the development of effective management and treatment approaches.ResultsUsing bioinformatics tools and the DisGeNET database, we pinpointed 105 genes significantly linked to liver fibrosis. Subsequently, we conducted functional assessments, incorporating gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis, and the STRING database, to construct protein–protein interaction networks (PPI) for these 105 liver fibrosis-associated genes. These analyses were executed via the WebGestalt 2019 online platform. We employed Cytoscape plugins, MCODE, and CytoHubba, to identify potential biomarker genes from these functional networks. Noteworthy hub genes encompassed TGF-β1, MMP2, CTNNB1, FGF2, IL6, LOX, CTGF, SMAD3, ALB, and VEGFA. TGF-β1 and MMP-2 exhibited substantial promise as liver fibrosis biomarkers, as denoted by their high systemic scores determined through the MCC algorithm in the CytoHubba methodology.ConclusionsIn summary, this study presents a robust genetic biomarker strategy that may prove invaluable in the identification of potential liver fibrosis biomarkers.

In vitro study on anti-proliferative and anti-cancer activity of picrosides in triple-negative breast cancer.

Picrorhiza kurroa, an "Indian gentian," a known Himalayan medicinal herb with rich source of phytochemicals like picrosides I, II, and other glycosides, has been traditionally used for the treatment of liver and respiratory ailments. Picrosides anti-proliferative, anti-oxidant, anti-inflammatory and other pharmacological properties were evaluated in treating triple-negative breast cancer (TNBC). Picroside I and II were procured from Sigma-Aldrich and were analyzed for anti-cancer activity in triple-negative breast cancer (MDA-MB-231) cells. Cell viability was analyzed using MTT and trypan blue assays. Apoptosis was analyzed through DNA fragmentation and Annexin V/PI flow cytometric analysis. Wound healing and cell survival assays were employed to determine the inhibition of invasion capacity and anti-proliferative activity of picrosides in MDA-MB-231 cells. Measurement of intracellular ROS was studied through mitochondrial membrane potential assessment using DiOC6 staining for anti-oxidant activity of picrosides in MDA-MB-231 cells. Both Picroside I and II have shown decreased cell viability of MDA-MB-231 cells with increasing concentrations. IC50 values of 95.3µM and 130.8µM have been obtained for Picroside I and II in MDA-MB-231 cells. Early apoptotic phase have shown an increase of 20% (p < 0.05) with increasing concentrations (0, 50, 75, and 100µM) of Picroside I and 15% (p < 0.05) increase with Picroside II. Decrease in mitochondrial membrane potential of 2-2.5-fold (p < 0.05) was observed which indicated decreased reactive oxygen species (ROS) generation with increasing concentrations of Picroside I and II. An increasing percentage of 70-80% (p < 0.05) cell population was arrested in G0/G1 phase of cell cycle after Picroside I and II treatment in cancer cells. Our results suggest that Picroside I and II possess significant anti-proliferative and anti-cancer activity which is mediated by inhibition of cell growth, decreased mitochondrial membrane potential, DNA damage, apoptosis, and cell cycle arrest. Therefore, Picroside I and II can be developed as a potential anti-cancer drug of future and further mechanistic studies are underway to identify the mechanism of anti-cancer potential.

Metabolic profiling of Verbena bonariensis L. extract by LC/MS and evaluation of the hepatoprotective potential with isoniazid- and rifampicin-induced hepatotoxicity in rats.

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.

Unveiling the mitophagy puzzle in non-alcoholic fatty liver disease (NAFLD): Six hub genes for early diagnosis and immune modulatory roles

BackgroundNon-alcoholic fatty liver disease (NAFLD) stands as a predominant chronic liver ailment globally, yet its pathogenesis remains elusive. This study aims to identify Hub mitophagy-related genes (MRGs), and explore the underlying pathological mechanisms through which these hub genes regulate NAFLD. MethodsA total of 3 datasets were acquired from the GEO database and integrated to identify differentially expressed genes (DEGs) in NAFLD and perform Gene Set Enrichment Analysis (GSEA). By intersecting DEGs with MRGs, mitophagy-related differentially expressed genes (MRDEGs) were obtained. Then, hub MRGs with diagnostic biomarker capability for NAFLD were screened and a diagnostic prediction model was constructed and assessed using Nomogram, Decision Curve Analysis (DCA), and ROC curves. Functional enrichment analysis was conducted on the identified hub genes to explore their biological significance. Additionally, regulatory networks were constructed using databases. NAFLD was stratified into high and low-risk groups based on the Riskscore from the diagnostic prediction model. Furthermore, single-sample gene set enrichment analysis (ssGSEA) and CIBERSORT algorithms were employed to analyze immune cell infiltration patterns and the relationship between Hub MRGs and immune cells. ResultsThe integrated dataset comprised 122 NAFLD samples and 31 control samples. After screening, 18 MRDEGs were identified. Subsequently, six hub MRGs (NR4A1, PPP2R2A, P4HA1, TUBB6, DUSP1, NAMPT) with diagnostic potential were selected through WGCNA, logistic regression, SVM, RF, and LASSO models, all significantly downregulated in NAFLD samples compared to the control group. A diagnostic prediction model based on these six genes demonstrated robust predictive performance. Functional enrichment analysis of the six hub genes revealed involvement in processes such as protein phosphorylation or dephosphorylation. Correlation analysis demonstrated a significant association between hub MRGs and infiltrating immune cells. ConclusionWe identified six hub MRGs in NAFLD and constructed a diagnostic prediction model based on these six genes, applicable for early NAFLD diagnosis. These genes may participate in regulating NAFLD progression through the modulation of mitophagy and immune activation. Our findings may contribute to subsequent clinical and basic research on NAFLD.

Innovative pharmacotherapy for hepatic metabolic and chronic inflammatory diseases in China.

Liver disease constitutes a significant global health concern, particularly in China where it has distinctive characteristics. China grapples with a staggering 300 million cases, predominantly due to hepatitis B and metabolic non-alcoholic fatty liver disease. Additionally, hepatocellular carcinoma has become a prevalent which is a lethal type of cancer. Despite the scarcity of innovative treatment options, Chinese hepatologists and researchers have achieved notable breakthroughs in the prevention, diagnosis, management and treatment of liver diseases. Traditional Chinese medicines have found widespread application in the treatment of various liver ailments owing to their commendable pharmacological efficacy and minimal side effects. Furthermore, there is a growing body of research in extracellular vesicles, cell therapy and gene therapy, offering new hope in the fight against liver diseases. This paper provides a comprehensive overview of the epidemiological characteristics of liver diseases and the diverse array of treatments that Chinese scholars and scientists have pursued in critical field.