Pharmaceutical Biology最新文献

Context: Silver fir (Abies alba) contains polyphenols and lignans with antioxidant and therapeutic properties. Efficient extraction methods are essential to preserve these compounds and maximize bioactivity.

Objective: To compare extraction techniques and identify the optimal method for obtaining high-quality silver fir extracts with strong antioxidant activity and minimal cytotoxicity.

Materials & methods: Extracts from bark and branches were prepared using subcritical water extraction (SWE, 70-200 °C), supercritical CO₂ extraction, and high-pressure ethanol extraction. Extracts were analyzed for total polyphenol content (TPC), lignan concentration (HPLC), antioxidant activity (DPPH and ABTS assays), and volatile profile (GC-MS). Cytotoxicity and cell migration were evaluated in HaCaT and Caco-2 cell lines via MTS and gap closure assays.

Results: The SWE bark extract at 100 °C (SWE-BA-100) showed the highest TPC (73.8 mg GAE/g), lignan content (secoisolariciresinol 204.7 µg/mL), and antioxidant activity (DPPH: 24.2, ABTS: 32.0 mg GAE/g). Bark extracts had superior bioactive profiles compared to branches, though branch extractions gave higher yields. All extracts were non-cytotoxic. SWE-BA-100 inhibited cell migration, indicating a complex interaction between composition and cellular response.

Discussion and conclusion: SWE at 100 °C is a promising green method for producing potent antioxidant extracts from A. alba. Bark extracts offer strong antioxidant potential and safety for pharmaceutical, cosmetic, and nutritional uses. However, high lignan content may influence cellular behavior. Further studies should address the role of non-phenolic antioxidants and refine extraction strategies to balance efficacy and bioactivity.

Context: Benzofuran derivatives are important structural motifs found in natural products, often exhibiting significant biological activities. Ruta graveolens L. is a plant source known for containing diverse bioactive compounds.

Objective: This study aimed to isolate and characterize compounds from the aerial parts of R. graveolens, confirm their structures through synthesis, develop a novel synthetic methodology, and evaluate their potential anti-inflammatory effects and monoamine oxidase inhibitory activity.

Materials and methods: The structures of benzofuran enantiomers were elucidated using integrated NMR, HRMS, and ECD analyses. (±)-Rutacycoumarins A and B were synthesized via a novel direct C3 alkylation of coumarin bearing phenolic hydroxyl groups. Biological evaluation assessed the anti-inflammatory effects of (±)-Rutacycoumarins A and B in LPS-stimulated HepG2 cells by measuring liver biomarkers and pro-inflammatory cytokines, and their inhibitory activity against monoamine oxidase B (MAO-B).

Results: Two novel Z/E pairs of benzofuran enantiomers, (±)-Rutacycoumarins A and B, featuring fused cyclopropane motifs, were isolated and structurally confirmed. Their synthesis employed a novel catalytic EDA complex (DIPEA/potassium ethyl xanthate donor, NHPI ester acceptor). (±)-Rutacycoumarins A and B reduced liver biomarkers and pro-inflammatory cytokines in LPS-treated HepG2 cells, and all four enantiomers inhibited MAO-B.

Conclusions: This study isolated two novel benzofuran enantiomer pairs with fused cyclopropane motifs from R. graveolens Their structures were confirmed via a new catalytic EDA complex synthesis. Racemic mixtures reduced LPS-induced liver/cellular damage and cytokines in HepG2 cells, while all enantiomers inhibited MAO-B.

Context: Turmeric (Curcuma longa) is widely used as a spice and in dietary/food supplements and herbal medicines. Reports assessing the authenticity of commercial products have shown that the ingredient is subject to adulteration with, among others, artificial dyes, undeclared diluents, and synthetic curcumin.

Objective: This scoping review summarizes published data on adulteration of turmeric products sold as spice and dietary or food supplements to estimate the prevalence of non-authentic turmeric on the market.

Methods: This scoping review was based on a literature analysis from Google Scholar, PubMed, ScienceDirect, Scopus, and Web of Science databases, covering publications from 2000 to 2025. Article selection was performed according to PRISMA-ScR guidelines. After the initial search, specific countries were added to refine the search. Of the 375 publications retrieved, 347 were eliminated as duplicates or because they lacked information on turmeric adulteration, adulteration of commercial products, or did not provide the number of adulterated samples. An additional 19 papers were found searching the citations, or by using Google Search with the keywords "Curcuma longa", "turmeric", "government report", and "adulteration". One more report from the CVUA Stuttgart was found using the keywords "Kurkuma", "Verfälschung", and "Report". In total, 48 papers were included in the review.

Results: A total of 48 publications representing 2235 commercial turmeric samples were included in the study. The overall adulteration rate was 20.0%, with spice samples having a slightly lower percentage of adulterated samples (20.4%) than dietary and food supplements (22.0%).

Conclusion: Adulteration of turmeric remains a concern on markets worldwide.

Context: Diabetic nephropathy (DN) is a major complication of diabetes. Moringa oleifera seeds are recognized as a source of bioactive compounds with potential health benefits, prompting investigation into their specific components and effects on DN.

Objective: This study aimed to isolate bioactive compounds from M. oleifera seeds and evaluate their renoprotective effects and underlying mechanisms of action against high-glucose-induced diabetic nephropathy.

Materials and methods: Four cyanoglycosides and one cyanoaglycone were isolated from M. oleifera seeds using chromatographic techniques. The renoprotective effects of these compounds were then evaluated using an in vitro model of high-glucose-induced diabetic nephropathy in HBZY-1 mesangial cells. Mechanistic studies further investigated the compounds' effects on oxidative stress, inflammation, mitochondrial function, expression of the glycolysis-related protein PFKFB3, and the TGF-β1/Smad signaling pathway.

Results: Two previously undescribed cyanoglycosides were isolated alongside three known compounds. All five compounds demonstrated significant renoprotective effects in the high-glucose-induced HBZY-1 cell model. Mechanistically, these effects were achieved by suppressing oxidative stress and inflammation, protecting mitochondrial function, modulating the expression of the glycolysis-related protein PFKFB3, and inhibiting the TGF-β1/Smad signaling pathway, collectively contributing to beneficial metabolic reprogramming.

Conclusions: This study isolated two novel cyanoglycosides from M. oleifera seeds. These compounds, alongside known ones, protect against high-glucose-induced renal injury. Their renoprotection involves metabolic reprogramming via suppressing oxidative stress/inflammation, preserving mitochondrial function, modulating PFKFB3, and inhibiting TGF-β1/Smad signaling. These findings offer insights for utilizing M. oleifera seeds and suggest these cyanoglycosides as potential diabetic nephropathy therapeutics.

Context: Proprotein convertase subtilisin/kexin type 9 (PCSK9) regulates plasma low-density lipoprotein cholesterol (LDL-C) metabolism and is a key target for cardiovascular therapies. It also plays roles in inflammation, cancer, and metabolic disorders, prompting interest in repurposing PCSK9-targeting drugs for non-lipid conditions.

Objective: This review comprehensively summarizes PCSK9-regulating medications, delves into their mechanisms of action, and explores their increasingly expanding therapeutic potential across multiple organ systems, such as the liver, immune system, small intestine, heart, brain, and pancreas.

Methods: A comprehensive literature search was carried out in databases such as PubMed, with keywords like 'PCSK9 inhibitors', 'lipid metabolism', 'liver', 'immune system', 'neoplasms' and 'PCSK9-related diseases'. The search was meticulously designed to cover relevant research extensively. Only those studies that delved into the molecular mechanisms underlying PCSK9 regulation and the practical clinical applications of PCSK9-targeting therapies were selected for inclusion.

Results: PCSK9-regulating drugs, encompassing monoclonal antibodies, small peptides, antisense oligonucleotides, small interfering RNAs, and vaccines, modulate PCSK9 expression or activity at different levels. These drugs are effective in lowering LDL-C levels and demonstrate potential benefits in the treatment of inflammation, non-alcoholic fatty liver disease, renal lipotoxicity, and various metabolic disorders. They mainly exert their effects by controlling PCSK9 gene transcription, influencing mRNA translation, and blocking the interaction between PCSK9 and LDL-R.

Conclusions: PCSK9-regulating drugs hold great promise for treating a diverse array of diseases. Future research should focus on optimizing their application in personalized therapies that target multiple pathways.

Context: The use of herbal products in Malawi remains widespread and culturally significant, often occurring alongside pharmaceutical medicine treatments. As the burden of non-communicable diseases such as diabetes and hypertension continues to rise, the potential for herbal-drug interactions (HDIs) represents an underexamined public health concern.

Objective: Evaluate the concurrent use of herbal products and pharmaceutical medicines among patients with diabetes or hypertension in a large health care facility in Malawi and identify potential adverse HDIs.

Materials & methods: An exploratory mixed-methods, cross-sectional study was conducted with 301 patients attending a diabetes or hypertension clinic at Queen Elizabeth Central Hospital in Blantyre, Malawi. Participants self-reported herbal and pharmaceutical use, and a targeted literature review was undertaken to assess potential pharmacokinetic and pharmacodynamic interactions between commonly reported herbal products and prescribed medications.

Results: Participants reported concurrent use of a wide variety of herbal products (e.g., garlic, ginger, okra, lemon, mango, moringa) with prescription medicines (e.g., metformin, insulin, glibenclamide, hydrochlorothiazide, enalapril, amlodipine). While clinical outcomes were not independently verified, literature review findings, in some cases, indicated meaningful potential for HDIs.

Discussion and conclusion: This study provides foundational data on herbal-pharmaceutical co-use in Malawi and highlights the need for expanded research, improved documentation of herbal use in healthcare settings, and improved education for patients and providers. Integrating awareness of herbal product use into clinical care is essential, and the methodology and findings may inform future hypothesis-driven studies across Africa and other regions where traditional and modern medicine use overlaps.

Context: Tanshinone IIA (Tan IIA), a bioactive compound derived from the traditional Chinese herb Salvia miltiorrhiza (Family Lamiaceae, Authority Bunge), is well-known for its protective effects in various kidney diseases. However, its role in obstructive nephropathy has not been thoroughly investigated.

Objective: This study aimed to explore the protective effects of Tan IIA in a mouse model of unilateral ureteral obstruction (UUO) and to elucidate the cellular and molecular mechanisms underlying these effects.

Materials and methods: Gasdermin D (GSDMD) knockout mice and their wild-type (WT) littermates underwent UUO surgery, with Tan IIA treatment administered 24 h prior. Human proximal tubular cells (HK-2 cells) were treated with TGF-β1 to induce fibrosis (50 ng/mL for 24 h), followed by Tan IIA treatment (5 μM) for an additional 3 h.

Results: Tan IIA significantly reduced the expression of extracellular matrix (ECM) components, including collagen I, α-smooth muscle actin (α-SMA), vimentin and fibronectin, in UUO mice. Tan IIA attenuated GSDMD-mediated pyroptosis. However, in GSDMD knockout mice subjected to UUO, the protective effects of Tan IIA on ECM gene expression and collagen deposition in the tubular interstitium were reduced. In vitro studies showed that Tan IIA reduced GSDMD activation and fibronectin protein expression in HK-2 cells.

Discussion and conclusions: Tan IIA may mitigate GSDMD-mediated pyroptosis in renal tubular epithelial cells (RTECs) and reduce kidney fibrosis, highlighting its potential as a therapeutic strategy to prevent the progression of kidney disease after ureteral obstruction.

Context: Apigenin, a naturally flavonoid, is reported to have protective effects in chronic and metabolic diseases. But the therapeutic or ameliorative effects of apigenin on atherosclerosis are not known.

Objective: Our study aimed to elucidate the underlying mechanism of apigenin on preventing atherosclerosis by enhancing selective autophagy/lipophagy and promoting RCT process.

Materials and methods: ApoE^-/- mice fed with a high-fat diet (HFD) for 18 weeks were used to establish atherosclerosis model. Oil-Red-O staining of the plaques in the aorta and the heart was used to determine the severity of atherosclerosis. The autophagy flux was evaluated by western blot and reverse transcription quantitative PCR (RT-qPCR). Then triton WR-1339 (TWR) was injected into muscles of C57BL/6 mice, and the role of autophagy was assessed by autophagy inhibitor LY294002 intervention. The transmission electron microscopy (TEM) and immunofluorescence microscopy analysis (IFM) were used to elucidate the lipid-lowering mechanism of apigenin.

Results: In HFD-induced mice, apigenin inhibited the dangerous progression of atherosclerosis through decreasing lipid deposition in plaques, lowering serum and liver lipid contents, activating autophagy and promoting reverse cholesterol transport (RCT). In TWR-induced mice, apigenin reduced the serum and liver lipid levels, enhanced the autophagy flux and increased RCT, but the above effects of apigenin were weakened by LY294002. The TEM and IFM images revealed that apigenin promoted the formation of autophagosomes and the co-localization between autophagy proteins with lipid protein.

Discussion and conclusions: The lipid-lowering effects of apigenin were mediated through promoting RCT and enhancing selective lipophagy, meanwhile it provided a potential therapeutic option for atherosclerosis.

Context: Antibiotic resistance in bacteria is a growing global problem, with biofilm formation and efflux pumps playing crucial roles in this issue.

Objective: This study explores the effects of phenolic compounds of Origanum majorana against Escherichia coli and methicillin-resistant Staphylococcus aureus (MRSA) strains by inhibiting biofilm formation and efflux pumps.

Materials and methods: The methanolic extract of O. majorana was fractionated guided by an antibiofilm assay, and the active fractions were analyzed by multistep chromatographic separation to yield five pure compounds. Their structures were then determined using 1D and 2D nuclear magnetic resonance spectroscopy. The minimum inhibitory concentrations of the extracts, fractions, and isolated compounds were determined via the microdilution method in a 96-well plate. Antibiofilm activity was assessed using the crystal violet method, and the effect on efflux pumps was tested by a real-time ethidium bromide accumulation assay.

Results: Arbutin (1), apigenin 7-O-glucoside (2), 6'-caffeoylarbutin (3), rosmarinic acid (4), and 2-deoxy-d-1,4-ribonolactone (5) were isolated from the aqueous methanolic extract. Compounds 1, 2, and 4 reduced E. coli biofilm formation by 24.82%-42.98% at 100 µM, whereas only arbutin (1) moderately suppressed biofilm formation of MRSA (23.15 ± 1.56% at 50 µM). Arbutin also demonstrated efflux pump inhibitory activity against MRSA (relative fluorescence index of 0.49 at 100 µM).

Discussion and conclusions: The newly discovered natural antibiofilm agents show promise as candidates for treating biofilm-associated infections and combating antibiotic-resistant bacteria.