Editorial: preventing and treating liver diseases: medicinal and food plants, their metabolites as potential options

Rongrui Wei ^1,2 Wenmin Liu ³ Chunsu Yuan ⁴ Chunlei Zhang ⁵ Zhipei Sang ^6,7 Qinge Ma ^2*

• ¹ Jiangxi University of Traditional Chinese Medicine, Nanchang, China
• ² Wuhan Polytechnic University, Wuhan, Hubei Province, China
• ³ Nanyang Normal University, Nanyang, Henan Province, China
• ⁴ The University of Chicago, Chicago, Illinois, United States
• ⁵ China Pharmaceutical University, Nanjing, Jiangsu Province, China
• ⁶ Hannan University, Matsubara, Ōsaka, Japan
• ⁷ Hainan University, Haikou, Hainan Province, China

Liver disease is seriously endangering human health in the world. It has become the leading cause of death in the word (Israelsen et al., 2024). The presence and progression of liver fibrosis led by hepatic inflammation is the main predictor of liver-related death across the entire spectrum of steatotic liver diseases (Taru et al., 2024). A combination of recent advancements of widely available biomarkers for early detection of liver fibrosis together with considerable advancements in therapeutic interventions offer the possibility to reduce morbidity and mortality in patients with liver disease (Dabrowska et al., 2024). Thus, it is urgent to find safe and effective drugs to treat liver diseases. The medicinal and food plants have unique advantages in terms of safety and compliance, which have always been an important source for finding new hepatoprotective drugs (Xu et al., 2024). Consequently, the discovery of new hepatoprotective natural products from medicinal and food plants is of great practical significance for the development of new hepatoprotective drugs, which has the advantages of safety, multi-targets, and multi-pathways. We are deeply privileged to compile this research topic of Frontiers in Pharmacology dedicated to "preventing and treating liver diseases: medicinal and food plants, their metabolites as potential options".The study by Han et al. discussed about the effects of a low-dose (0.6 g/kg) and high-dose (1.2 g/kg) of zhuyu pill on a cholestasis rat model induced by naphthyl isothiocyanate (50 mg/kg). In this study, serum biochemistry and histopathology results were used to evaluate the therapeutic effect of zhuyu pill, and mRNA-Seq analysis was performed and verified using real-time uorescence quantitative PCR.The GO, KEGG, and GSEA analyses were integrated to identify the mechanism by which Zhuyu pill impacted cholestatic rats.It was found that zhuyu pill significantly improved abnormal changes in the biochemical blood indexes and liver histopathology of cholestasis rats, regulated pathways related to bile and lipid metabolism, including fatty acid metabolism, retinol metabolism, and steroid hormone biosynthesis, and alleviated inflammation, cholestasis, and lipid metabolism disorders.Relative expression of the essential genes Cyp2a1, Ephx2, Acox2, Cyp1a2, Cyp2c11, and Sult2a1 was verified by qRT-PCR and showed the same trend as mRNA-seq analysis (Han et al., 2023). Therefore, zhuyu pill has a significant anti-cholestatic effect by regulating bile metabolism and lipid metabolism related pathways. These findings indicate that zhuyu pill is a novel and promising prospect for treating cholestasis.Rutaecarpine is a natural pentacyclic indolopyridoquinazolinone alkaloid, which is isolated from Evodia rutaecarpa for the first time. It is used for treating a variety of ailments, including headaches, gastrointestinal disorders, postpartum hemorrhage, amenorrhea, difficult menstruation, and other diseases. Li et al. made a comprehensive description of Rutaecarpine derivatives by focusing on their diverse biological activities. In this review, the modification of Rutaecarpine aimed at seeking its derivatives with better physicochemical properties and more potency had been extensively studied. These derivatives exhibited diverse pharmacological activities, including anti-inflammatory, anti-atherogenic, anti-Alzheimer's disease, anti-tumor, and anti-fungal activities via a variety of mechanisms, such as inhibiting cyclooxygenase-2, acetylcholine, phosphodiesterase 4B, phosphodiesterase 5, or topoisomerases (Li et al., 2023). This review gave an insight into the biological activities of Rutaecarpine derivatives and encourage further exploration of Rutaecarpine.Nawaz et al. reviewed therapeutic approaches for chronic hepatitis C. In this review, he critically assesseed the landscape of hepatitis C virus treatment, drawing parallels between traditional interferon/ribavirin therapy historically pivotal in hepatitis C virus management and herbal approaches rooted in traditional and complementary medicine. This review made a comprehensive understanding of the diverse hepatitis C virus genome, its natural variations, pathogenesis, and the impact of dietary, social, environmental, and economic factors (Nawaz et al., 2024). This review primarily focused on the intricate nature of hepatitis C virus genomes and explored the potential of botanical drugs in both preventing and treating hepatitis C virus infections.Feng et al. used meta-analysis to search relevant preclinical references from multiple databases. Statistical analysis was conducted using STATA, which included the use of 3D maps and radar charts to display the effects of matrine dosage and frequency on hepatoprotection and hepatotoxicity. The results demonstrated that matrine had bidirectional effects on ALT and AST levels, and it also regulated SOD, MDA, TG, TC, IL-6, TNF-α, and CAT levels. Based on comprehensive three-dimensional analysis, the optimal bidirectional effective dosage of matrine ranged from 10 to 69.1 mg/kg. However, it demonstrated high liver protection and low toxicity at a dose of 20-30 mg/kg/d for 0.02-0.86 weeks. The molecular docking analysis revealed the interaction between MT and SERCA as well as SREBP-SCAP complexes. Matrine could alter Ca 2+ homeostasis in liver injury via multiple pathways, including the SREBP1c/SCAP, Notch/RBP-J/HES1, IκK/NF-κB, and Cul3/Rbx1/Keap1/Nrf2 (Feng et al., 2024).The pericarp of Herpetospermum pedunculosum has traditionally been used for treating jaundice and hepatitis. Liu et al. characterized the total cucurbitacins extracted from H. pedunculosum and evaluated their hepatoprotective potential.Molecular networking based on UHPLC-MS/MS identified cucurbitacin B, isocucurbitacin B, and cucurbitacin E as the major components in total cucurbitacins, comprising 70.3%, 26.1%, and 3.6% as determined by RP-HPLC, respectively. Total cucurbitacins treatment significantly reversed CCl4-induced metabolic changes associated with liver damage in a dose-dependent manner, impacting pathways including energy metabolism, oxidative stress and phenylalanine metabolism, and showed superior efficacy to HLSP. Safety evaluation also showed that total cucurbitacins were safe, with higher LD50 and NOAEL values than HLSP. The LD50 and NOAEL values of total cucurbitacins were 36.21 and 15 mg/kg body weight, respectively, while the LD50 of HLSP was 14 mg/kg body weight (Liu et al., 2024). In summary, total cucurbitacins extracted from H. pedunculosum demonstrated promising potential as the natural hepatoprotective agent, warranting further investigation into synergistic effects of individual cucurbitacin components. Kim et al. applied meta-analysis to evaluate the additive effects of herbal medicines on lifestyle modification in the treatment of non-alcoholic fatty liver disease. In this review, eight randomized controlled trials with a total of 603 participants were included for this review study. Participants were administered with multi-herbal formulas or single-herbal extracts along with lifestyle modification for 12 weeks. The results showed a significant improvement in ultrasoundbased liver steatosis measured by odds ratio in the herbal medicine group than those with lifestyle modification alone (OR = 7.9, 95% CI 0.7 to 95.2, p < 0.1). In addition, herbal medicines decreased the levels of aspartate transferase (MD-7.5, 95% CI-13.4 to -1.7, p = 0.01) and total cholesterol (MD-16.0, 95% CI-32.7 to 0.7, p = 0.06) more than lifestyle modification alone (Kim et al., 2024).To evaluate the efficacy of the fruit of the medicinal plant Forsythia suspensa (Thunb.) Vahl in treating inflammation-associated diseases, Zhou et al. used a meta-analysis of animal models to study and probe deeply into the signaling pathways underlying the progression of inflammation. In this study, all data analyses were performed using Review Manager 5.3 and the results were presented as flow diagrams, risk-of-bias summaries, forest plots, and funnel plots. As a result, 11 records were selected for the final meta-analysis from the 710 records identified in the initial search. It was found that that F. suspensa (Thunb.) Vahl alleviated the inflammatory cytokine levels in serum and improved the antioxidant enzyme superoxide dismutase. Therefore, F. suspensa (Thunb.) Vahl effectively reversed the change in acute or chronic inflammation indicators in animal models, and the regulation of multiple channel proteins in inflammatory signaling pathways suggested that F. suspensa (Thunb.) Vahl was a good potential drug for inflammatory disease drug therapy (Zhou et al., 2024).Tiao Zhi decoction on alcohol-associated liver disease. The results revealed Xie Zhuo Tiao Zhi significantly alleviated alcohol-induced liver dysfunction, based on histological examinations and biochemical parameters after 4-week administration.Mechanically, alcohol-stimulated hepatic oxidative stress was ameliorated by Xie Zhuo Tiao Zhi, accompanied by the improvement of Nrf2/Keap1 expression and alcohol-activated phosphorylation of pro-inflammatory transcription factors, including JNK, P38, P65, and IκBα, were rescued by Xie Zhuo Tiao Zhi (Chang et al., 2024). Thus, Xie Zhuo Tiao Zhi demonstrated potential in alleviating alcohol-induced liver injury, oxidative stress, and inflammation possibly through modulation of Nrf2/Keap1 and MAPKs/NF-κB signaling pathways, suggesting its potential as a therapeutic option for patients with alcoholic liver disease.Elshaer et al. evaluated the deterioration effects of NaNO2 additives on hematology, metabolic profile, liver function, and kidney function of male Wistar rats, and explored the therapeutic potential of supplementation with Saussurea costus root ethanolic extract to improve NaNO2-induced hepatorenal toxicity. The results revealed that the NaNO2-treated group showed a significant change in deterioration in body and organ weights, hematological parameters, lipid profile, and hepatorenal dysfunction, as well as immunohistochemical and histopathological alterations.Furthermore, the NaNO2-treated group demonstrated a considerable increase in the expression of TNF-α cytokine and tumor suppressor gene P53 in the kidney and liver, while a significant reduction was detected in the anti-inflammatory cytokine IL-4 and the apoptosis suppressor gene BCL-2, compared to the control group. Interestingly, S. costus root ethanolic extract demonstrated the ability to significantly alleviate the toxic effects of NaNO2 and improve liver function in a dose-dependent manner, including hematological parameters, lipid profile, and modulation of histopathological architecture. Additionally, S. costus root ethanolic extract exhibited the ability to modulate the expression levels of inflammatory cytokines and apoptotic genes in the liver and kidney (Elshaer et al., 2024). In a word, this study established the potential of S. costus root ethanolic extract in mitigating the toxic effects of NaNO2 by modulating metabolic, inflammatory, and apoptosis, underscored the promise of S. costus root ethanolic extract as a potential natural food detoxifying additive to counteract the harmful impacts of sodium nitrite.Libreville. Various quantitative indexes were calculated from the collected data and One-way ANOVA and independent samples t-test were used for statistical analyses.The survey identified 63 plant species belonging to 35 families. Prevalent symptoms treated included fever (18%), cough (16%), fatigue (13%), and cold (12%). The demographic data highlighted that 52.58% of male subjects (p > 0.94) aged 31-44 years were enrolled in the survey, of which 48.45% (p < 0.0001) and 74.73% (p < 0.99) of informants had university-level education. The results indicated that a total of 66% of the informants used medicinal plants for prophylaxis (34%), for both prevention and treatment (26%), exclusively for treatment (3%), and only for prevention (3%) while suffering from COVID-19, against 34% of the participants who did not use plants for prevention or treatment. Annickia chlorantha, Citrus sp., Alstonia congensis, Zingiber officinale, and Carica papaya emerged as the most commonly cited plants with the highest RFC (0.15-0.26), ) values (Mounanga et al., 2024). Therefore, this survey reinforced the use of traditional medicine as a method to alleviate COVID-19 symptoms, thereby advocating for the utilization of medicinal plants in managing coronavirus infections.NASH and its underlying mechanisms on C57BL/6J mice subjected to a methionineand choline-deficient diet. The study revealed that salidroside showed both promising preventive and therapeutic effects on NASH in vivo, salidroside could upregulate autophagy, downregulate apoptosis, rebalance immunity, and alleviate inflammation to exert anti-NASH properties. Finally, the results of transcript-proteome sequencing, molecular docking evaluation, and experimental validation showed that salidroside might exert its multiple effects through targeting PPARα. In a word, the research findings revealed that salidroside could regulate liver autophagy and apoptosis, regulating both innate immunity and adaptive immunity and alleviating inflammation in NASH prevention and therapy via the PPAR pathway, suggesting that SDS could be a potential anti-NASH drug in the future (Chu et al., 2024).Chen et al. established the NASH C57BL/6J mouse model via high-fat diet feeding for 12 weeks, and mice were gavaged with Polygonatum cyrtonema ethanol extract (100, 300, and 900 mg/kg/day), simvastatin (4 mg/kg). As a result, 211 metabolites were identified through UHPLC-MS/MS analysis. P. cyrtonema ethanol extract ameliorated high-fat diet induced liver injury and improved hepatocellular degeneration and steatosis in a dose-dependent way. P. cyrtonema ethanol extract restored the expression of AMPK, SIRT1, SREBP1, and PPAR-α both in mRNA and protein levels. RNAseq identified unique gene expression profiles in response to high-fat diet compared to the P. cyrtonema ethanol extract treatments. Ingenuity pathway analysis of RNA-seq data revealed key canonical pathways and upstream molecules regulated by P. cyrtonema ethanol extract (Chen et al., 2025). Thus, the study confirmed the ability of P. cyrtonema ethanol extract in alleviating NASH and underscores AMPK/SIRT1 pathway as a potential theraputic target for NASH treatment.To evaluate both the hepatoprotective and hepatotoxic effects of