Non-alcoholic fatty liver disease (NAFLD) is one of the major global health issues, strongly correlated with insulin resistance, obesity and oxidative stress. The current study aimed to evaluate anti-NAFLD effects of three different extracts of Phyllanthus niruri (P. niruri). NAFLD was induced in male Sprague–Dawley rats using a special high-fat diet (HFD). A 50% methanolic extract (50% ME) exhibited the highest inhibitory effect against NAFLD progression. It significantly reduced hepatomegaly (16%) and visceral fat weight (22%), decreased NAFLD score, prevented fibrosis, and reduced serum total cholesterol (TC) (48%), low-density lipoprotein (LDL) (65%), free fatty acids (FFAs) (25%), alanine aminotransferase (ALT) (45%), alkaline phosphatase (ALP) (38%), insulin concentration (67%), homeostatic model assessment of insulin resistance (HOMA-IR) (73%), serum atherogenic ratios TC/high-density lipoprotein (HDL) (29%), LDL/HDL (66%) and (TC–HDL)/HDL (64%), hepatic content of cholesterol (43%), triglyceride (29%) and malondialdehyde (MDA) (40%) compared to a non-treated HFD group. In vitro, 50% ME of P. niruri inhibited α-glucosidase, pancreatic lipase enzymes and cholesterol micellization. It also had higher total phenolic and total flavonoid contents compared to other extracts. Ellagic acid and phyllanthin were identified as major compounds. These results suggest that P. niruri could be further developed as a novel natural hepatoprotective agent against NAFLD and atherosclerosis.

The growth of adipose tissues is considered angiogenesis-dependent during non-alcoholic fatty liver disease (NAFLD). We have recently reported that our standardized 50% methanolic extract (ME) of Phyllanthus niruri (50% ME of P. niruri) has alleviated NAFLD in Sprague–Dawley rats. This study aimed to assess the molecular mechanisms of action, and to further evaluate the antiangiogenic effect of this extract. NAFLD was induced by eight weeks of high-fat diet, and treatment was applied for four weeks. Antiangiogenic activity was assessed by aortic ring assay and by in vitro tests. Our findings demonstrated that the therapeutic effects of 50% ME among NAFLD rats, were associated with a significant increase in serum adiponectin, reduction in the serum levels of RBP4, vaspin, progranulin, TNF-α, IL-6, and significant downregulation of the hepatic gene expression of PPARγ, SLC10A2, and Collα1. Concomitantly, 50% ME of P. niruri has exhibited a potent antiangiogenic activity on ring assay, cell migration, vascular endothelial growth factor (VEGF), and tube formation, without any cytotoxic effect. Together, our findings revealed that the protective effects of P. niruri against NAFLD might be attributed to its antiangiogenic effect, as well as to the regulation of adipocytokines and reducing the expression of adipogenic genes.

Background: Raphanus sativus is traditionally used as an anti-inflammatory agent. Objectives: The current study was designed to explore the in vivo anti-inflammatory and antiangiogenic properties of Raphanus sativus seeds oil. Methods: Cold press method was used for the extraction of oil (RsSO) and was characterised by using GC-MS techniques. Three in vitro antioxidant assays (DPPH, ABTS and FRAP) were performed to explore the antioxidant potential of RsSO. Disc diffusion methods were used to study in vitro antimicrobial properties. In vivo anti-inflammatory properties were studied in both acute and chronic inflammation models. In vivo chicken chorioallantoic membrane assay was performed to study antiangiogenic effects. Molecular mechanisms were identified using TNF-α ELISA kit and docking tools. Results: GC-MS analysis of RsSO revealed the presence of hexadecanoic and octadecanoic acid. Findings of DPPH, ABTS, and FRAP models indicated relatively moderate radical scavenging properties of RsSO. Oil showed antimicrobial activity against a variety of bacterial and fungal strains tested. Data of inflammation models showed significant (p < 0.05) anti-inflammatory effects of RsSO in both acute and chronic models. 500 mg/kg RsSO halted inflammation development significantly better (p < 0.05) as compared with lower doses. Histopathological evaluations of paws showed minimal infiltration of inflammatory cells in RsSO-treated animals. Findings of TNF-α ELSIA and docking studies showed that RsSO has the potential to down-regulate the expression of TNF-α, iNOS, ROS, and NF-κB respectively. Moreover, RsSO showed in vivo antiangiogenic effects. Conclusion: Data of the current study highlight that Raphanus sativus seeds oil has anti-inflammatory, and antiangiogenic properties and can be used as an adjunct to standard NSAIDs therapy which may reduce the dose and related side effects.

Non-alcoholic fatty liver disease (NAFLD) is one of the most common complications of a metabolic syndrome caused by excessive accumulation of fat in the liver. Orthosiphon stamineus also known as Orthosiphon aristatus is a medicinal plant with possible potential beneficial effects on various metabolic disorders. This study aims to investigate the in vitro inhibitory effects of O. stamineus on hepatic fat accumulation and to further use the computational systems pharmacology approach to identify the pharmacokinetic properties of the bioactive compounds of O. stamineus and to predict their molecular mechanisms against NAFLD. Methods: The effects of an ethanolic extract of O. stamineus leaves on cytotoxicity, fat accumulation and antioxidant activity were assessed using HepG2 cells. The bioactive compounds of O. stamineus were identified using LC/MS and two bioinformatics databases, namely the Traditional Chinese Medicine Integrated Database (TCMID) and the Bioinformatics Analysis Tool for the Molecular Mechanism of Traditional Chinese Medicine (BATMAN-TCM). Pathway enrichment analysis was performed on the predicted targets of the bioactive compounds to provide a systematic overview of the molecular mechanism of action, while molecular docking was used to validate the predicted targets. Results: A total of 27 bioactive compounds corresponding to 50 potential NAFLD-related targets were identified. O. stamineus exerts its anti-NAFLD effects by modulating a variety of cellular processes, including oxidative stress, mitochondrial β-oxidation, inflammatory signalling pathways, insulin signalling, and fatty acid homeostasis pathways. O. stamineus is significantly targeting many oxidative stress regulators, including JNK, mammalian target of rapamycin (mTOR), NFKB1, PPAR, and AKT1. Molecular docking analysis confirmed the expected high affinity for the potential targets, while the in vitro assay indicates the ability of O. stamineus to inhibit hepatic fat accumulation. Conclusion: Using the computational systems pharmacology approach, the potentially beneficial effect of O. stamineus in NAFLD was indicated through the combination of multiple compounds, multiple targets, and multicellular components.

Metabolic dysfunction-associated fatty liver disease (MAFLD) affects up to 30% of the global population, yet effective pharmacological treatments remain limited. This systematic review and meta-analysis evaluated the efficacy of GLP-1 receptor agonists and dual GLP-1/glucose-dependent insulinotropic polypeptide (GIP) receptor agonists in managing MAFLD. We systematically searched PubMed/MEDLINE, Cochrane CENTRAL, Web of Science, and Scopus, through July 2025. Randomised controlled trials (RCTs) assessing GLP-1 receptor agonists or dual GLP-1/GIP GIP receptor Agonists in managing MAFLD patients were included. Primary outcomes included liver fat content, liver enzymes, and glycemic parameters. Meta-analyses were performed with subgroup analyses by receptor target, treatment duration, control type, and age. In addition, implementing a formal GRADE evaluation framework. Twenty-six trials involving 3,453 participants were included. GLP-1 receptor agonists significantly reduced liver fat content (MD: -3.37%, 95% CI: -4.98 to -1.76, p < 0.001), ALT levels (SMD: -0.47, 95% CI: -0.73 to -0.22, p < 0.001), and AST levels (SMD: -0.29, 95% CI: -0.53 to -0.05, p < 0.05). Significant improvements were observed in HbA1c (SMD: -0.67, 95% CI: -0.99 to -0.34, p < 0.001), fasting glucose (MD: -0.60 mmol/L, 95% CI: -0.92 to -0.27, p < 0.001), HOMA-IR (SMD: -0.34, 95% CI: -0.66 to -0.02, p < 0.05), and total cholesterol (MD: -0.23 mmol/L, 95% CI: -0.30 to -0.15, p < 0.001). Liver stiffness showed no significant improvement (MD: -0.12 kPa, 95% CI: -0.75 to 0.50, p = 0.70). Dual GLP-1/GIP agonists demonstrated superior efficacy compared to mono GLP-1 agonists for reducing liver fat (MD: -7.15, 95% CI: -10.23 to -4.07, p < 0.001 versus MD: -2.44, 95% CI: -4.18 to -0.71, p < 0.01), representing a 2.9-fold greater effect. Long-term treatment (lasting over 48 weeks) demonstrated enhanced benefits across all outcomes. Overall, changes in body weight were not significant (MD: -1.51 kg, 95% CI: -4.07 to 1.06, p = 0.25). This meta-analysis provides evidence for the effectiveness of GLP-1 receptor agonists in managing MAFLD, with dual GLP-1/GIP agonists demonstrating superior hepatic benefits. Long-term therapy (lasting more than 48 weeks) is necessary for optimal outcomes. These findings support clinical implementation, particularly for patients with concurrent diabetes or obesity, positioning dual agonists as promising advancements in treatment.

Extensive attention has been focused on herbal medicine for the treatment of different endocrine disorders. In fact, compelling scientific evidence indicates that natural compounds might act as endocrine modulators by mimicking, stimulating, or inhibiting the actions of different hormones, such as thyroid, sex, steroidal, and glucose regulating hormones. These potentials might be effectively employed for therapeutic purposes related to the endocrine system as novel complementary choices. Nevertheless, despite the remarkable therapeutic effects, inadequate targeting efficiency and low aqueous solubility of the bioactive components are still essential challenges in their clinical accreditation. On the other hand, nanotechnology has pushed the wheels of combining inorganic nanoparticles with biological structures of medicinal bioactive compounds as one of the utmost exciting fields of research. Nanoparticle conjugations create an inclusive array of applications that provide greater compliance, higher bioavailability, and lower dosage. This can safeguard the global availability of these wealthy natural sources, regardless of their biological occurrence. This review inspects future challenges of medicinal plants in various endocrine disorders for safe and alternative treatments with examples of their nanoparticle formulations.