Chenghao Lv

Oxidative stress-induced senescence is a key driver of aging-related diseases, particularly in the liver, yet effective and safe natural interventions remain limited. This study aimed to develop a green extraction method for lotus peel proanthocyanidins (LPPs) and evaluate their antioxidant activity, monomer release during digestion, and anti-aging mechanisms. Among eight natural deep eutectic solvents (NADESs), glycerol-betaine (GL-BET, 1:1) was optimal. Using response surface methodology, the optimal extraction conditions were: water content 35%, liquid-to-solid ratio 10 mL/g, sonication time 22 min, temperature 36 °C, yielding 10.97%, which was 5.23-fold higher than 70% ethanol. During simulated digestion, six monomers were identified; proanthocyanidin B2 (PB2) showed the highest content at all stages, proanthocyanidin B3 (PB3) peaked in gastric digestion, and proanthocyanidin B4 (PB4) exhibited the strongest stability (retaining 55.32% after 4 h intestinal digestion). GL-BET, PB3, and PB4 were non-cytotoxic to HepG2 cells at 0–150 μg/mL. Pretreatment with 150 μg/mL of each compound significantly restored viability in tert-butyl hydroperoxide (t-BHP)-damaged cells, with PB4 showing the highest recovery (88.98%). PB4 reduced senescence-associated β -galactosidase (SA-β-gal)-positive cells from 43.23 to 15.76%, decreased reactive oxygen species (ROS) and malondialdehyde (MDA), increased superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) activities. Western blotting confirmed that PB4 upregulated nuclear factor erythroid 2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), and NAD (P)H:quinone oxidoreductase 1 (NQO1), and downregulated Kelch-like ECH-associated protein 1 (Keap1), indicating modulation of the Nrf2/Keap1/antioxidant response element (ARE) pathway. Among the three compounds tested in cellular assays (GL-BET, PB3, and PB4), PB4 exhibited the most potent anti-senescence effects. Thus, ultrasound-assisted deep eutectic solvent (DES) extraction significantly improves LPPs yield and bioactivity, providing a basis for green extraction and application of LPPs.

Background/Objectives: Metabolic syndrome (MetS) is a pressing global health challenge comprising obesity, hyperglycemia, hypertension, and hyperlipidemia. Conventional polypharmacy often presents long-term compliance issues and side effects. Eucommia ulmoides Oliv., a traditional medicinal and edible plant rich in iridoids, lignans, flavonoids, and polysaccharides, has emerged as a promising natural intervention. This review aims to systematically summarize the bioavailability and multifaceted pharmacological mechanisms of E. ulmoides and its bioactive components in alleviating MetS. Methods: We comprehensively reviewed the recent in vitro and in vivo literature to map the functional evidence, specific signaling pathways, and gut microbiota–host interactions associated with E. ulmoides extracts and its key phytochemicals (e.g., asperuloside) against various metabolic dysfunctions. Results: Current evidence indicates that E. ulmoides operates through a “multi-component, multi-target, and multi-pathway” paradigm. For hyperlipidemia and obesity, it activates hepatic lipid metabolism (PPARα/CPT1A, FXR/CYP7A1) and mitigates oxidative stress (Nrf2/ARE). Furthermore, it dose-dependently reshapes the gut microbiota by enriching beneficial bacteria like Akkermansia and increasing butyrate production, exerting profound gut–liver axis regulation. It also ameliorates hypertension by activating the ACE2-Ang-(1–7)-Mas axis, improves insulin resistance via the AMPK/PI3K/Akt cascade, and manages hyperuricemia by modulating XOD and renal transporters. Notably, the low oral bioavailability of its glycosides highlights the crucial role of gut microbial hydrolysis in its efficacy. Conclusions: E. ulmoides holds substantial therapeutic potential as a multi-target natural supplement for MetS. However, future translational applications necessitate large-scale randomized clinical trials, multi-omics studies to further clarify host–microbiome interactions, and the development of standardized formulations to ensure clinical efficacy.

Procyanidin B2 (PB2), a dimer of oligomeric procyanidins, has been reported to ameliorate abnormal glucose metabolism; however, its efficacy in regulating redox-related insulin resistance (IR) and underlying mechanism has not yet been studied. Currently, antioxidant activity and digestive enzyme inhibitory tests were applied to screen the preliminary chemopreventive effect of PB2 on glucose metabolism dysfunction, further computational biology and molecular verification to elucidate its mechanism on improving IR. The results indicated that PB2 had limited antioxidant property against ROS and inhibitory property on digestive enzyme. Network pharmacology analysis implied that PI3K/AKT and FoxO pathways were the main targeted by PB2 to combating IR. Further molecular data demonstrated that PB2 promoted glycogen synthesis by activation of PI3K/AKT-Nrf2 signaling pathway via promoting posttranscriptional protein stability, nuclear translocation of Nrf2 and ARE binding ability, and inhibited gluconeogenesis by stimulating FoxO1 phosphorylation to reduce the expression of downstream G6Pase. Innovatively, molecular docking coupled with different Pull-Down assays revealed that PB2 could directly bind with AKT, Nrf2 and GSK3β, suggesting PB2 may improve IR via regulation of PI3K/AKT-Nrf2-GSK3β signaling, more than FoxO1 signaling pathway; subsequently, Nrf2 could directly bind with GSK3β, reinforcing evidence for PB2-Nrf2-GSK3β complex formation. Besides, co-treatment with PI3K/AKT and Nrf2 inhibitors or siRNAs highlighted the essential role of Nrf2 activation in PB2-contributed IR improvement. Moreover, PB2 has also been validated to exert its effect via regulation of PI3K/AKT-Nrf2-GSK3β signaling pathway in vivo. Therefore, these findings suggest that PB2 is a potent and promising compound to ameliorate glucose metabolism by targeting IR.

The growing prevalence of obesity is being increasingly acknowledged as a major public health issue. This mainly stems from the excessive intake of dietary fats. Dendrobium officinale (DO), recognized as an herb with dual roles of food and medicine, is renowned for its diverse health-promoting effects. Nevertheless, the specifics of its antiobesity and anti-inflammatory properties and the underlying mechanisms are still obscure. The present study shows that treatment with Dendrobium officinale extract (DOE) alleviates obesity, liver steatosis, inflammation, and oxidative stress in rats that are obese due to a high-fat diet (HFD). Firstly, with respect to HFD obese rats, higher doses of DOE significantly reduced TG, TC, LDL-C, blood glucose, and liver AST and ALT, along with lipid droplets. Meanwhile, DOE supplementation significantly reduced oxidative stress induced by ROS and MDA and increased the levels of GSH-Px and SOD in liver tissues. Furthermore, integrated analysis of transcriptomic and microbiomic data revealed that DOE modulated inflammatory responses through the NF-κB/IκB pathway. This regulatory mechanism was evidenced by corresponding changes in the protein expression levels of both NF-κB and IκB. Additionally, DOE was found to modulate gut microbiota composition in obese rats, specifically reducing the relative abundance of Bilophila while increasing beneficial bacterial populations, particularly the genera Akkermansia and Roseburia. These findings suggest that DOE may help retain the homeostasis of the gut microbiota and improve metabolic health by regulating inflammation in the liver and intestine, thereby providing protection against obesity and related metabolic syndromes. Our study demonstrates that DOE, as a natural botanical extract, can effectively facilitate the prevention or treatment of metabolic syndrome through precision dietary interventions.

The primary active compound in vine tea is dihydromyricetin (DMY), which has a longstanding history as a dietary supplement and traditional ethnic medicine. However, the precise molecular mechanism by which vine tea dihydromyricetin extract (VDMY) regulates glucolipid metabolic disorder remains unclear. In this study, we first assessed the effect of VDMY on various physiological parameters in db/db mice, followed by RNA sequencing (RNA-seq) to identify key signaling pathways affected by VDMY in liver tissues. We also examined the impact of VDMY on the liver’s TLR4/MyD88/NF-κB and FOXO1 pathways using Western blotting. Our results showed that VDMY significantly reduced fasting blood glucose (FBG), total cholesterol (TC), triglycerides (TGs), and low-density lipoprotein cholesterol (LDL-C), while increasing high-density lipoprotein cholesterol (HDL-C) levels. Additionally, VDMY enhanced the liver’s antioxidant capacity by upregulating superoxide dismutase (SOD), catalase (CAT), and glutathione (GSH), while lowering malondialdehyde (MDA), alanine aminotransferase (ALT), and aspartate aminotransferase (AST), thus alleviating liver damage. RNA-seq analysis further revealed that VDMY influenced multiple biological processes, including transcription, glycolysis, gluconeogenesis, and redox reactions, suggesting that its effects may be mediated through the TLR4/MyD88/NF-κB and FOXO1 pathways. Additionally, Western blot analysis revealed that VDMY effectively downregulated the expressions of TLR4, MyD88, NF-κB, and FOXO1 proteins in the liver of db/db mice, indicating that VDMY could target these pathways to intervene glucolipid metabolism dysfunction.

Lotus seed skin extract is rich in flavonoids, making it a promising candidate for developing health products. In a previous study, we found that proanthocyanidins from lotus seed skin, particularly proanthocyanidin B1 (PB1), can indirectly activate the Nrf2 signaling pathway, exerting an antioxidant effect. In this study, we isolate proanthocyanidins from lotus seed skin (PLS) using ethanol extraction and RP-HPLC identification, and investigate its effects on glycolipid metabolism both in vivo and in vitro. Our results demonstrate that PLS reduces body weight in high-fat diet (HFD) mice by decreasing food efficiency. PLS also normalizes serum glucose, insulin secretion, glycosylated hemoglobin (HbA1c), and intraperitoneal glucose tolerance (IPGTT). Furthermore, PLS significantly improves blood lipid parameters and inhibits the expression of six proinflammatory factors, including IL-1α, IL-1β, IL-3, IL-6, IFN-γ, and TNF-α in HFD mice. Additionally, analysis of fresh liver tissues reveals that PLS and PB1 induce the expression of antioxidant proteins such as HO-1 and NQO1 by activating the p38-Nrf2 signaling pathway and inhibiting the NF-κB signaling pathway. In conclusion, proanthocyanidins from lotus seed skin regulate glycolipid metabolism disorders by targeting the p38/Nrf2/NF-κB signaling pathway. Our study offers a new approach for the high-value comprehensive utilization of lotus seed skin by-products and precise dietary intervention for metabolic syndrome.

Gardenia jasminoides Ellis is abundant in crocin and has a longstanding historical usage both as a dietary and natural ethnic medicine. Enhanced studies have increasingly revealed the intricate interplay between glycolipid metabolism and gut microbiota, wherein their imbalance is regarded as a pivotal indicator of metabolic disorders. Currently, the precise molecular mechanism of the crude extract of crocin from Gardenia jasminoides Ellis (GC) targeting gut microbiota to regulate glycolipid metabolism disorder is still unclear. Firstly, we explored the effect of GC on digestive enzymes (α-amylase and α-glucosidase) in vitro. Secondly, we investigated the effect of GC on the physical and chemical parameters of high-fat diet (HFD) rats, such as body weight change, fasting blood glucose and lipid levels, and liver oxidative stress and injury. Then, 16S rDNA sequencing was used to analyze the effects of GC on the composition and structure of gut microbiota. Finally, the impact of GC on the TLR4/Myd88/NF-κB signaling pathway in the intestine was assessed by Western Blotting. In the present study, GC was found to exhibit a hypoglycemic effect in vitro, by inhibition of digestive enzymes. In animal experiments, we observed that GC significantly reduced fasting blood glucose, TC, and TG levels while increasing HDL-C levels. Additionally, GC demonstrated hepatoprotective properties by enhancing liver antioxidative capacity through the upregulation of SOD, CAT, and GSH-Px, while reducing ROS. 16S rDNA sequencing results showed that GC had a significant effect on the gut microbiota of HFD rats, mainly by reducing the ratio of Firmicutes/Bateroidota, and significantly affected the genera related to glycolipid metabolism, such as Akkermansia, Ligilactobacillus, Lactobacillus, Bacteroides, Prevotellaceae, etc. The Western Blotting results demonstrated that GC effectively downregulated the protein expressions of TLR4, Myd88, and NF-κB in the intestine of HFD rats, indicating that GC could target the TLR4/Myd88/NF-κB pathway to interfere with glycolipid metabolism disorder. Correlation analysis revealed that GC could target the Akkermansia-TLR4/Myd88/NF-κB pathway axis which attenuates glycolipid metabolism disorder. Therefore, this study establishes the foundation for GC as a novel therapeutic agent for glycolipid metabolism disorder chemoprevention, and it introduces a novel methodology for harnessing the potential of natural botanical extracts in the prevention and treatment of metabolic syndrome.

Type 2 diabetes mellitus (T2DM) is a chronic and complex disease, and traditional drugs have many side effects. The active compound dihydromyricetin (DHM), derived from natural plants, has been shown in our previous study to possess the potential for reducing blood glucose levels; however, its precise molecular mechanism remains unclear. In the present study, network pharmacology and transcriptomics were performed to screen the molecular targets and signaling pathways of DHM disturbed associated with T2DM, and the results were partially verified by molecular docking, RT-PCR, and Western blotting at in vivo levels. Firstly, the effect of DHM on blood glucose, lipid profile, and liver oxidative stress in db/db mice was explored and the results showed that DHM could reduce blood glucose and improve oxidative stress in the liver. Secondly, GO analysis based on network pharmacology and transcriptomics results showed that DHM mainly played a significant role in anti-inflammatory, antioxidant, and fatty acid metabolism in biological processes, on lipoprotein and respiratory chain on cell components, and on redox-related enzyme activity, iron ion binding, and glutathione transferase on molecular functional processes. KEGG system analysis results showed that the PI3K-Akt signaling pathway, IL17 signaling pathway, HIF signaling pathway, MAPK signaling pathway, AGE-RAGE signaling pathway in diabetic complications, and TNF signaling pathway were typical signaling pathways disturbed by DHM in T2DM. Thirdly, molecular docking results showed that VEGFA, SRC, HIF1A, ESR1, KDR, MMP9, PPARG, and MAPK14 are key target genes, five genes of which were verified by RT-PCR in a dose-dependent manner. Finally, Western blotting results revealed that DHM effectively upregulated the expression of AKT protein and downregulated the expression of MEK protein in the liver of db/db mice. Therefore, our study found that DHM played a therapeutic effect partially by activation of the PI3K/AKT/MAPK signaling pathway. This study establishes the foundation for DHM as a novel therapeutic agent for T2DM. Additionally, it presents a fresh approach to utilizing natural plant extracts for chemoprevention and treatment of T2DM.