Multidisciplinary strategies to enhance therapeutic effects of flavonoids from Epimedii Folium: Integration of herbal medicine, enzyme engineering, and nanotechnology

Journal of Pharmaceutical Analysis, Journal Year: 2022, Volume and Issue: 13(3), P. 239 - 254

Published: Dec. 30, 2022

Flavonoids such as baohuoside I and icaritin are the major active compounds in Epimedii Folium (EF) possess excellent therapeutic effects on various diseases. Encouragingly, 2022, soft capsules were approved to reach market for treatment of hepatocellular carcinoma (HCC) by National Medical Products Administration (NMPA) China. Moreover, recent studies demonstrate that can serve immune-modulating agent exert anti-tumor effects. Nonetheless, both production efficiency clinical applications epimedium flavonoids have been restrained because their low content, poor bioavailability, unfavorable vivo delivery efficiency. Recently, strategies, including enzyme engineering nanotechnology, developed increase productivity activity, improve efficiency, enhance flavonoids. In this review, structure-activity relationship is described. Then, enzymatic strategies increasing highly discussed. The nanomedicines overcoming barriers improving diseases summarized. Finally, challenges an outlook translation proposed.

Language: Английский

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Anti-Alzheimers molecular mechanism of icariin: insights from gut microbiota, metabolomics, and network pharmacology

Journal of Translational Medicine, Journal Year: 2023, Volume and Issue: 21(1)

Published: April 24, 2023

Abstract Background Icariin (ICA), an active ingredient extracted from Epimedium species, has shown promising results in the treatment of Alzheimer's disease (AD), although its potential therapeutic mechanism remains largely unknown. This study aimed to investigate effects and underlying mechanisms ICA on AD by integrated analysis gut microbiota, metabolomics, network pharmacology (NP). Methods The cognitive impairment mice was measured using Morris Water Maze test pathological changes were assessed hematoxylin eosin staining. 16S rRNA sequencing multi-metabolomics performed analyze alterations microbiota fecal/serum metabolism. Meanwhile, NP used determine putative molecular regulation treatment. Results Our revealed that intervention significantly improved dysfunction APP/PS1 typical pathologies hippocampus mice. Moreover, showed administration reversed AD-induced dysbiosis elevating abundance Akkermansia reducing Alistipe . Furthermore, metabolomic metabolic disorder via regulating glycerophospholipid sphingolipid metabolism, correlation closely related indicated might regulate signaling pathway PRKCA/TNF/TP53/AKT1/RELA/NFKB1 axis for AD. Conclusion These findings may serve as a approach ICA-mediated protective associated with amelioration disturbance disorder. Graphical

Language: Английский

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Advancements in the Biotransformation and Biosynthesis of the Primary Active Flavonoids Derived from Epimedium

Molecules, Journal Year: 2023, Volume and Issue: 28(20), P. 7173 - 7173

Published: Oct. 19, 2023

Epimedium is a classical Chinese herbal medicine, which has been used extensively to treat various diseases, such as sexual dysfunction, osteoporosis, cancer, rheumatoid arthritis, and brain diseases. Flavonoids, icariin, baohuoside I, icaritin, epimedin C, are the main active ingredients with diverse pharmacological activities. Currently, most flavonoids extracted from plants, but this method cannot meet increasing market demand. Biotransformation strategies promised huge potential for contents of high-value flavonoids, would promote full use herb. Complete biosynthesis major by microbial cell factories enable industrial-scale production flavonoids. This review summarizes structures, activities, pathways in plant, well extraction methods advancements biotransformation complete synthesis provide valuable insights future studies on herb usage

Language: Английский

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New insight into oxidative stress and inflammatory responses to kidney stones: Potential therapeutic strategies with natural active ingredients

Biomedicine & Pharmacotherapy, Journal Year: 2024, Volume and Issue: 179, P. 117333 - 117333

Published: Sept. 8, 2024

Language: Английский

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Activation of Sirt6 by icariside Ⅱ alleviates depressive behaviors in mice with poststroke depression by modulating microbiota-gut-brain axis

Journal of Advanced Research, Journal Year: 2025, Volume and Issue: unknown

Published: March 1, 2025

Sirt6-mediated gut microbiota plays a vital role in poststroke depression (PSD). Icariside Ⅱ (ICS Ⅱ) is naturally-occurring neuroprotectant with Sirt6 induction potency. However, it unknown whether ICS protects against PSD through modulation of microbiota. This study aimed to reveal the effect and potential mechanisms on PSD, microbiota-gut-brain axis was investigated. Using middle cerebral artery occlusion (MCAO) chronic unpredictable mild stress (CUMS) establish post-stroke (PSD) mice, we assessed anti-depressant effects via behavioral tests, immunohistochemistry, western blot. Transcriptome profiling, molecular docking, surface plasmon resonance were used identify key targets. 16S rDNA genomic-derived taxonomic profiling fecal transplantation (FMT) conducted figure out mechanistic short-chain fatty acids (SCFAs). ameliorated depressive-like behaviors mice as evidenced by sucrose preference test, forced swimming test tail suspension test. restored mitochondrial function, reduced oxidative damage pro-inflammatory cytokines both brain intestine regulation Sirt6/NF-κB pathway. significantly increased abundance (such asAkkermansia Ligilactobacillus), enhanced SCFAs concentrations, repaired intestinal barrier integrity upreglated tight junction protein expression. FMT from II-treated replicated these benefits, confirming microbiota's role. Mechanistically, directly bound its activity. Ⅱ-mediated neuroprotection neutralized or hydrogen peroxide-induced enteric glial cells when absent. Our findings expand pharmacological properties II demonstrating ability ameliorate axis. Ⅱ, novel activator, could be translated into an alternative microbiota-targeted avenue for coping PSD.

Language: Английский

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Promoting osteogenesis and bone regeneration employing icariin-loaded nanoplatforms

Journal of Biological Engineering, Journal Year: 2024, Volume and Issue: 18(1)

Published: April 22, 2024

Abstract There is an increasing demand for innovative strategies that effectively promote osteogenesis and enhance bone regeneration. The critical process of regeneration involves the transformation mesenchymal stromal cells into osteoblasts subsequent mineralization extracellular matrix, making up complex mechanism osteogenesis. Icariin’s diverse pharmacological properties, such as anti-inflammatory, anti-oxidant, osteogenic effects, have attracted considerable attention in biomedical research. Icariin, known its ability to stimulate formation, has been found encourage improve mineralization. Several studies demonstrated effects icariin, which can be attributed hormone-like function. It induce expression BMP-2 BMP-4 mRNAs significantly upregulate Osx at low doses. Additionally, icariin promotes formation by stimulating pre-osteoblastic genes like Osx, RUNX2, collagen type I. However, needs delivered perform promising functions. Encapsulating within nanoplatforms holds significant promise promoting through a range intricate biological effects. When encapsulated nanofibers or nanoparticles, exerts directly cellular level. Recalling inflammation factor influencing regeneration, icariin's anti-inflammatory harnessed amplified when nanoplatforms. Also, while cell adhesion migration are pivotal stages tissue icariin-loaded contribute these processes providing supportive matrix attachment movement. This review comprehensively discusses used osteogenesis, further presenting where field go before clinically.

Language: Английский

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Icariin as an emerging candidate drug for anticancer treatment: Current status and perspective

Biomedicine & Pharmacotherapy, Journal Year: 2022, Volume and Issue: 157, P. 113991 - 113991

Published: Nov. 9, 2022

Icariin (ICA) is a kind of natural flavonoid compound monomer, which derived from the extract dried stems and leaves Epimedium. Modern pharmacological studies have found that ICA has broad bioactive function in affecting biological processes variety cancers, including breast cancer, colorectal hepatocellular carcinoma, esophageal cancer other indicates promising application value treatment patients future. Nevertheless, targets molecular mechanisms not been elucidated detail. Therefore, this review, we systematically summarizes current research progress series cancers. In particular, an emphasis placed on mechanism its future development direction, aiming at providing relevant theoretical basis for strategies.

Language: Английский

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The protective effects of icariin against testicular dysfunction in type 1 diabetic mice Via AMPK-mediated Nrf2 activation and NF-κB p65 inhibition

Phytomedicine, Journal Year: 2023, Volume and Issue: 123, P. 155217 - 155217

Published: Nov. 14, 2023

Language: Английский

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Improvement of solubility and pharmacokinetic profile of hepatoprotector icariin through complexation with HP-γ-cyclodextrin

Frontiers in Pharmacology, Journal Year: 2023, Volume and Issue: 14

Published: March 22, 2023

Icariin as a hepatoprotector from Herba epimedii can expand the cardiovascular and cerebral blood vessels, promote hematopoietic functions, enhance immune system show anti-liver tumor activities. However, its low solubility (0.02 mg/mL) limits clinical applications food medical supplements. Through complexation with HP-γ-cyclodextrin by using trace amount of water-soluble polymer, water icariin was increased 654 times, which is best result to date for study icariin. In an in vitro pharmacokinetic study, dissolution rate 80 complex be 100% released first few minutes. complexation, vivo dog Cmax about 5 AUC0-120 20 times clearance changed 11.17 L/h/kg 0.65 L/h/kg. The half-life time 0.68 h 6.38 relative bioavailability nearly indicating that less drug needed same therapeutic effect complex, used potential potent or cancer drug.

Language: Английский

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New insights into the anticancer therapeutic potential of icaritin and its synthetic derivatives

Drug Development Research, Journal Year: 2024, Volume and Issue: 85(2)

Published: April 1, 2024

Abstract Icaritin is a natural prenylated flavonoid derived from the Chinese herb Epimedium. The compound has shown antitumor effects in various cancers, especially hepatocellular carcinoma (HCC). exerts its anticancer activity by modulating multiple signaling pathways, such as IL‐6/JAK/STAT3, ER‐α36, and NF‐κB, affecting tumor microenvironment immune system. Several clinical trials have evaluated safety efficacy of icaritin advanced HCC patients with poor prognoses, who are unsuitable for conventional therapies. results demonstrated that can improve survival, delay progression, produce benefits these patients, favorable profile minimal adverse events. Moreover, enhance response regulating function phenotype cells, CD8+ T MDSCs, neutrophils, macrophages. These findings suggest promising candidate immunotherapy other cancers. However, further studies needed to elucidate molecular mechanisms optimal dosing regimens potential synergistic agents. Therefore, this comprehensive review scientific literature aims summarize advances knowledge preclinical well pharmacokinetic, metabolism, toxicity, action recognize main challenge, gaps, opportunities develop medication cancer use. Thus, our objective was clarify current state use an drug.

Language: Английский

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