Effects Of Icariin Research Articles

An auxiliary diagnostic technology and clinical efficacy evaluation in knee osteoarthritis based on serum surface-enhanced Raman spectroscopy

Knee osteoarthritis (KOA), a progressive joint disease, is a leading source of chronic pain and disability, and its diagnosis mainly depends on medical imaging findings and clinical symptoms. This study aimed to explore an auxiliary diagnostic technology and clinical efficacy evaluation in KOA based on surface-enhanced Raman scattering (SERS). Three sequential experiments were performed: 1) preliminary observation of the therapeutic effects of icariin (ICA); 2) using serum SERS spectra obtained from rat models belonging to sham group, KOA group and icariin treatment group, respectively, to analyze the KOA-related expression profiles; 3) employing partial least squares (PLS) and support vector machines (SVM) algorithms to establish KOA diagnosis model. Pathological changes verified the efficacy of icariin in KOA. Raman peak assignment combined with spectral difference analysis reflected the biochemical changes associated with KOA, including amino acid, carbohydrates and collagen. ICA intervention significantly reversed these changes, although full recovery could not be achieved. Based on PLS-SVM approach, the sensitivity, specificity and accuracy of 100%, 98.33% and 98.89%, respectively, were obtained for screening KOA. This work proves that SERS has great potential to be used as an auxiliary diagnostic technology for KOA, and is also helpful for the exploration of novel KOA treatment agent.

Pharmacology-Based Prediction of the Targets and Mechanisms for Icariin against Myocardial Infarction.

Background and Objectives: This study aims to illustrate the mechanisms underlying the therapeutic effect of Icariin after myocardial infarction (MI). Materials and Methods: Based on the network pharmacology strategy, we predict the therapeutic targets of Icariin against MI and investigate the pharmacological molecular mechanisms. A topological network was created. Biological process and Kyoto Encyclopedia of Genes and Genomes pathway enrichment were also performed. We also conducted the molecular docking analysis to stimulate the component-target interaction further and validate the direct bind effect. Results: Network pharmacology analysis identified 61 candidate genes related to the therapeutic effect of Icariin against MI. EGFR, AKT1, TP53, JUN, ESR1, PTGS2, TNF, RELA, HSP90AA1, and BCL2L1 were identified as hub genes. The biological processes of the candidate targets were significantly involved in the reactive oxygen species metabolic process, response to hypoxia, response to decreased oxygen levels, response to oxidative stress, regulation of reactive oxygen species metabolic process, and so forth. Overall, biological process enrichment analysis indicated that the protective effect of Icariin against MI might be associated with oxidative stress. Moreover, the pathway analysis showed that the candidate targets were closely associated with lipid and atherosclerosis, AGE-RAGE signaling pathway in diabetic complications, HIF-1 signaling pathway, etc. We identified the conformation with the lowest affinity score as the docking conformation. The simulated molecular docking was displayed to illustrate the topical details of the binding sites between Icariin and TNF protein. Conclusions: This study provides an overview of the mechanisms underlying the protective effect of Icariin against MI.

Inhibition of ferroptosis by icariin treatment attenuates excessive ethanol consumption-induced atrial remodeling and susceptibility to atrial fibrillation, role of SIRT1.

Ferroptosis contributes to the pathogenesis of atrial fibrillation (AF), although the mechanisms are still largely uncovered. The current study was designed to explore the pharmacological effects of icariin against ethanol-induced atrial remodeling, if any, and the mechanisms involved with a focus on SIRT1 signaling. Excessive ethanol-treated animals were administered with Ferrostatin-1, Erastin or icariin to evaluate the potential effects of icariin or ferroptosis. Then, the underling mechanisms was further explored in the in vitro experiments using HL-1 atrial myocytes. Excessive ethanol administration caused significant atrial damage as evidenced by increased susceptibility to AF, altered atrial conduction pattern, atrial enlargement, and enhanced fibrotic markers. These detrimental effects were reversed by Ferrostatin-1 or icariin treatment, while Erastin co-administration markedly abolished the beneficial actions conferred by icariin. Mechanistically, ethanol-treated atria exhibited markedly up-regulated pro-ferroptotic protein (PTGS2, ACSL4, P53) and suppressed anti-ferroptotic molecules (GPX4, FTH1). Icariin treatment inhibited ethanol-induced atrial ferroptosis by reducing atrial mitochondrial damage, ROS accumulation and iron overload. Interestingly, the in vivo and in vitro data showed that icariin activated atrial SIRT1-Nrf-2-HO-1 signaling pathway, while EX527 not only reversed these effects, but also abolished the therapeutic effects of icariin. Moreover, the stimulatory effects on GPX4, SLC7A11 and the suppressive effects on ACSL4, P53 conferred by icariin were blunted by EX527 treatment. These data demonstrate that ferroptosis plays a causative role in the pathogenesis of ethanol-induced atrial remodeling and susceptibility to AF. Icariin protects against atrial damage by inhibiting ferroptosis via SIRT1 signaling. Its role as a prophylactic/therapeutic drug deserves further clinical study.

Up-regulation of PPAR-γ involved in the therapeutic effect of icariin on cigarette smoke-induced inflammation

Icariin (ICA) might be a potential anti-inflammatory medication in a variety of diseases including COPD, and previous studies showed that ICA could attenuate cigarette smoke (CS)-induced inflammation by inhibiting nuclear factor (NF)-κB. Peroxisome proliferator-activated receptor (PPAR) γ, a nuclear hormone receptor, has been reported to play a critical role in the inflammatory process in COPD. Whether PPAR-γ is involved in the anti-inflammatory effect of icariin on COPD has scarcely been explored. This study aimed at investigating the role of ICA in PPAR-γ expression in the CS-induced model, and then elucidating the therapeutic effects of ICA on COPD based on the PPARγ–NF–κB signaling pathway. The Beas-2B cells and H292 cells were induced with cigarette smoke extract (CSE) for 8 h after treatment with ICA for 16 h. The PPARγ expression and NF-κB pathway-related indicators were detected by western blotting, cellular immunofluorescence, and Real-time PCR. The PPARγ knock down or T0070907-treated Beas-2B cells were constructed to further investigate the relationship between the inhibition of NF-κB by ICA and PPARγ. A COPD model was established by CS exposure for 6 months, and ICA (40 mg/kg) was administrated by gastric perfusion. Then, the pulmonary function, lung histology, inflammatory cytokine levels, and protein expressions were detected. We found ICA up-regulated PPARγ protein expression in both Beas-2B cells and H292 cells, and it improved CSE-induced PPARγ down regulation and NF-κB activation. Furthermore, the inhibition of NF-κB pathway by ICA was partially dependent on PPARγ in the PPARγ knock down or T0070907-treated Beas-2B cells, suggesting that ICA attenuated CSE-induced inflammatory responses were associated with modulating the PPARγ–NF–κB pathway. Moreover, ICA showed similar effects on PPARγ and NF-κB expressions in the COPD model, and it effectively ameliorated the pulmonary function and lung inflammatory infiltration in the COPD rat model. Conclusively, the therapeutic effect of ICA on COPD was indirectly achieved by reducing airway inflammation, which was partially associated with modulating the PPARγ–NF–κB signaling pathway.

Icariin Alleviates Nonalcoholic Fatty Liver Disease in Polycystic Ovary Syndrome by Improving Liver Fatty Acid Oxidation and Inhibiting Lipid Accumulation.

(1) Background: Icariin is the main component of the Chinese herb Epimedium. A number of studies have shown that it alleviates abnormal lipid metabolism. However, it is not clear whether and how icariin can ameliorate hepatic steatosis with polycystic ovary syndrome (PCOS). This study was designed to explore the anti-hepatosteatosis effect of icariin in rats with polycystic ovary syndrome. (2) Methods: Female Sprague Dawley(SD)rats were treated with a high-fat diet and letrozole for 21 days to make nonalcoholic fatty liver disease (NAFLD) in the polycystic ovary syndrome model. Then model rats were treated with icariin (by gavage, once daily) for 28 days. Serum hormones and biochemical variables were determined by ELISA or enzyme. RNA-sequence analysis was used to enrich related target pathways. Then, quantitative Real-time PCR (qRT-PCR) and Western blot were performed to verify target genes and proteins. (3) Results: Icariin treatment reduced excess serum levels of Testosterone (T), Estradiol (E2), Luteinizing hormone (LH), Follicle-stimulating hormone (FSH), LH/FSH ratio, insulin, triglycerides (TG), and aspartate aminotransferase (AST) in high-fat diet (HFD) and letrozole fed rats. Meanwhile, icariin ameliorated HFD and letrozole-induced fatty liver, as evidenced by a reduction in excess triglyceride accumulation, vacuolization, and Oil Red O staining area in the liver of model rats. Results of RNA-sequencing, western blotting, and qRT-PCR analyses indicated that icariin up-regulated fatty acid translocase (CD36), in mitochondria, and peroxisome proliferator-activated receptor α (PPARα) expression, which led to the enhancement of fatty acid oxidation molecules, such as cytochrome P450, family 4, subfamily a, polypeptide 3 (CYP4A3), carnitine palmitoyltransferase 1 α (CPT1α), acyl-CoA oxidase 1 (ACOX1), medium-chain acyl-CoA dehydrogenase (MCAD), and long-chain acyl-CoA dehydrogenase (LCAD). Besides, icariin reduced lipid synthesis, which elicited stearoyl-Coenzyme A desaturase 1 (SCD1), fatty acid synthase (FASN), and acetyl-CoA (ACC). (4) Conclusion: Icariin showed an ameliorative effect on hepatic steatosis induced by HFD and letrozole, which was associated with improved fatty acid oxidation and reduced lipid accumulation in the liver.

Effect of icariin on the H2O2-induced proliferation of mouse airway smooth muscle cells through miR-138-5p regulating SIRT1/AMPK/PGC-1α axis.

Icariin exerts antioxidative and anti-inflammatory effects and is used in the treatment of bronchial asthma. However, the specific modes of action are uncertain. In this study, we investigated whether icariin could modulate the silencing information regulator 2-related enzyme 1 (SIRT1)/adenosine monophosphate-activated protein kinase (AMPK)/peroxisome proliferator-activated receptor gamma co-activator 1α (PGC-1α) axis by regulating miR-138-5p during H2O2-induced proliferation of mouse airway smooth muscle cells (ASMCs). Primary BALB/c mouse ASMCs were cultured using the tissue block adherence method and were induced with hydrogen peroxide (H2O2; 200μmol/L) to establish a bronchial asthma ASMC proliferation model. With the aid of Western Blot and quantitative real-time polymerase chain reaction (qRT-PCR) in H2O2-induced ASMCs, the expression of miR-138-5p, SIRT1, AMPK, PGC-1α, α-smooth muscle actin (α-SMA), transforming growth factor-β1 (TGF-β1), collagen I, and collagen III protein and mRNA were investigated. The proliferation rate and activities of superoxide dismutase1 (SOD1), reduced glutathione (GSH), malonaldehyde (MDA), and reactive oxygen species (ROS) in ASMCs were determined. The results suggest Compared with the H2O2-induced group, icariin inhibited the miR-138-5p expression; enhanced SIRT1, p-AMPK, and PGC-1α expression; attenuated MDA activity and ROS level; lowered TGF-β1, collagen I, and collagen III expression levels; and decreased the proliferation of ASMCs induced by H2O2. The dual-luciferase reporter gene assay results showed that SIRT1 is a regulatory target of miR-138-5p.The results suggest that Icariin could improve the H2O2-induced proliferation of ASMCs. The mechanism may be related to the increase of activation of SIRT1/AMPK/PGC-1α axis by suppressing the expression of miR-138-5p. Thus, SIRT1 is the regulatory target of miR-138-5p.

Exploration on the Mechanism of the Effect of Icariin on Hepatocellular Carcinoma Based on Network Pharmacology

Exploration on the Mechanism of the Effect of Icariin on Hepatocellular Carcinoma Based on Network Pharmacology

Retracted: Exploration of the Effect of Icariin on Nude Mice with Lung Cancer Bone Metastasis via the OPG/RANKL/RANK System.

[This retracts the article DOI: 10.1155/2022/2011625.].

Effects of icariin and curcumol on autophagy, ferroptosis, and lipid metabolism based on miR-7/m-TOR/SREBP1 pathway on prostate cancer.

This study aimed to investigate the effects and underlying molecular mechanisms of icariin (ICA) and curcumol on autophagy, ferroptosis, and lipid metabolism in prostate cancer (PCa), in vitro and in vivo. Normal prostate epithelial cells RWPE-1 and PCa cell lines DU145 and PC-3 were treated with ICA and curcumol. Ferrostatin-1 (Fer-1) or 3-MA was added to treat DU145 and PC-3 cells. In addition, we knocked down miR-7. The mechanism of ICA and curcumol in PCa cells after the knockdown of miR-7 was verified by in vitro nude mice tumorigenesis experiments. ICA and curcumol had no significant effect on the viability of RWPE-1 cells, but there was a significant difference between DU145 and PC-3 cells. After treatment with ICA and curcumol, the proliferation of PCa cells was inhibited, apoptosis, reactive oxygen species (ROS) levels, and miR-7 expression were increased. The combined treatment of ICA and curcumol had a more significant effect. ICA and curcumol treatment induced autophagy and ferroptosis in PCa cells, and si-miR-7 reversed the effects of ICA and curcumol on autophagy and ferroptosis. MiR-7 targeted mTOR and regulated the expression of the mTOR/SREBP1 pathway in PCa cells. ICA and curcumol may affect the lipid metabolism of PCa cells by affecting SREBP1. In addition, the effects and mechanisms of ICA and curcumol on autophagy, ferroptosis, and lipid metabolism in PCa cells were verified in vivo. ICA and curcumol synergistically regulated the miR-7/mTOR/SREBP1 pathway to induce autophagy and ferroptosis in PCa cells and affected lipid metabolism.

Effect of icariin in a rat model of colchicine-induced cognitive deficit: role of β-amyloid proteolytic enzymes

ABSTRACT The deposition of β-amyloid plaques, either due to their over-production or insufficient clearance, is an important pathological process in cognitive impairment and dementia. Icariin (ICA), a flavonoid compound extracted from Epimedium, has recently gained attention for numerous age-related diseases, such as neurodegenerative diseases. We aimed to explore the possible neuro-protective effect of ICA supplementation in colchicine-induced cognitive deficit rat model and exploring its effect on the β-amyloid proteolytic enzymes. The study included four groups (10 rats each): normal control, untreated colchicine, colchicine + 10 mg/kg ICA, and colchicine + 30 mg/ kg ICA. Results revealed that intra-cerebro-ventricular colchicine injection produced neuronal morphological damage, β amyloid deposition, and evident cognitive impairment in the behavioral assessment. Icariin supplementation in the two doses for 21 days attenuated neuronal death, reduced the β amyloid levels, and improved memory consolidation. This was associated with modulation of the proteolytic enzymes (Neprilysin, Matrix Metalloproteinase-2, and insulin-degrading enzyme) concluding that β-amyloid enzymatic degradation may be the possible therapeutic target for ICA.

Icariin inhibits thioacetamide-induced osteoclast differentiation through RANKL-p38/ERK-NFAT pathway

This study aims to investigate the therapeutic effect of icariin(ICA) on thioacetamide(TAA)-induced femoral osteolysis in rats. RAW264.7 cells were treated with TAA and ICA. Cell counting kit-8(CCK-8) assay was used to detect cell proliferation, and tartrate-resistant acid phosphatase(TRAP) staining to examine the formation of osteoclasts. The expression of TRAP, cathepsin K, c-FOS, and NFATc1 in RAW264.7 cells was determined by Western blot and immunofluorescence method. Thirty-two SD rats were randomized into the control group, TAA group(intraperitoneal injection of TAA at 300 mg·kg~(-1)), ICA group(gavage of ICA at 600 mg·kg~(-1)) and TAA + ICA group(intraperitoneal injection of TAA at 300 mg·kg~(-1) and gavage of ICA at 600 mg·kg~(-1)). Administration was performed every other day for 6 weeks. Body weight and length of femur were recorded at execution. Pathological injury and osteoclast differentiation of femur were observed based on hematoxylin-eosin(HE) staining and TRAP staining, and the changes of bone metabolism-related indexes alkaline phosphatase(ALP), calcium(Ca), phosphorus(P), magnesium(Mg), and cross-linked N-telopeptide of type Ⅰ collagen(NTX-Ⅰ) in serum were detected. Three-point bending test and micro-CT were applied to evaluate the quality of femur, and Western blot to detect the levels of osteoclast-related proteins TRAP, cathepsin K, RANK, RANKL, p38, p-p38, ERK, p-ERK, JNK, p-JNK, c-Fos, and NFATc1. The results showed ICA could inhibit TAA-induced production of TRAP-positive cells, the expression of osteoclast-related proteins, and nuclear translocation of NFATc1. ICA alleviated the weight loss, reduction of femur length, and growth inhibition induced by TAA in SD rats. ICA ameliorated the decline of femur elastic modulus caused by TAA and significantly restored trabecular bone mineral density(BMD), trabecular pattern factor(Tb.Pf), trabecular number(Tb.N), trabecular thickness(Tb.Th), and structure model index(SMI), thus improving bone structure. Western blot results showed ICA suppressed femoral osteoclast differentiation induced by TAA through RANKL-p38/ERK-NFATc1 signaling pathway. ICA inhibits osteoclast differentiation and prevents TAA-induced osteolysis by down-regulating RANKL-p38/ERK-NFAT signaling pathway.

Effects of icariin on alleviating schizophrenia-like symptoms by regulating the miR-144-3p/ATP1B2/mTOR signalling pathway

Schizophrenia is a group of severe mental disorders. Icariin is a main active component of Epimedium, possessing therapeutic effects on various neurodegenerative diseases. The present study investigated whether icariin is effective in alleviating schizophrenia-like symptoms and explored its underlying molecular mechanism. A developmental schizophrenia rat model employing 2-week repeated MK-801 administration was established. Icariin was orally administrated 3 time per day for 2 weeks after the MK-801 administration. Open-field test (OFT), novel object recognition (NOR), rotarod, and Morris water maze (MWM) were performed to examine the therapeutic effects of icariin on behavioural abnormalities. Hematoxylin-eosin (HE) staining on hippocampus slices, and MTT assay and Calcein/PI staining on the SK-N-SH cells treated with MK-801 were carried out to assess the neuroprotective effects of icariin. Furthermore, the regulation of icariin on the miR-144-3p/ATP1B2/mTOR signalling pathway was examined by RT-PCR and Western blots. The results showed that icariin alleviated MK-801-induced anxiety and recognition memory deficits in the OFT and NOR, respectively. Additionally, weakened motor coordination caused by MK-801 was restored by icariin. The MWM test also showed that icariin can improve MK-801-induced impaired spatial memory and swimming ability. Furthermore, brain grey matter atrophy, cytotoxicity, and cell apoptosis caused by MK-801 can be eliminated by icariin. Lastly, icariin can regulate the expression of miR-144-3p and ATP1B2, and enhance the phosphorylation of PI3K, Akt, and mTOR. In conclusion, this study revealed that icariin may have therapeutic effects on schizophrenia-like disorders via regulating the miR-144-3p/ATP1B2/mTOR signalling, suggesting that icariin has potential to become an antipsychotic drug.

Icariin alleviates osteoarthritis through PI3K/Akt/mTOR/ULK1 signaling pathway

ObjectivesThis study aims to investigate the effects of Icariin (ICA) on interleukin-1β (IL-1β)-induced osteoarthritis (OA) and its potential mechanism of action.MethodsSW1353 chondrocytes were pretreated with ICA for 2 h, followed by stimulation with IL-1β to mimic OA. Expression levels of matrix metalloproteinases (MMP-3) and collagen II were determined using real-time PCR and Western blot assays. Autophagy activation (by ICA) or inhibition (by shRNA) was determined based on the expression levels of ULK1, Beclin-1, LC3-II/I, and p62, using Western blot analysis. The phosphorylation levels of PI3K, Akt, mTOR, and ULK1 were also detected using Western blot analysis.ResultsIL-1β increased MMP-3 overproduction, induced collagen II degradation, and reduced the level of autophagy-associated proteins, including ULK1, Beclin-1, and LC3-II/I. In contrast, ICA pretreatment attenuated IL-1β-induced MMP-3 overproduction, increased collagen II expression, and induced expression of autophagy-related proteins. ICA also decreased PI3K, Akt, and mTOR phosphorylation, increased the production of ULK1, and induced autophagy. Short hairpin RNA-mediated knockdown of ULK1 led to activation of the PI3K/Akt/mTOR pathway, which reversed the protective effects of ICA.ConclusionsOur findings indicate that ICA can induce autophagy by regulating the PI3K/AKT/mTOR/ULK1 signaling pathway. This study suggests that ICA may be effective for treating OA.

Progress in Composite Hydrogels and Scaffolds Enriched with Icariin for Osteochondral Defect Healing.

Osteochondral structure reconstruction by tissue engineering, a challenge in regenerative medicine, requires a scaffold that ensures both articular cartilage and subchondral bone remodeling. Functional hydrogels and scaffolds present a strategy for the controlled delivery of signaling molecules (growth factors and therapeutic drugs) and are considered a promising therapeutic approach. Icariin is a pharmacologically-active small molecule of prenylated flavonol glycoside and the main bioactive flavonoid isolated from Epimedium spp. The in vitro and in vivo testing of icariin showed chondrogenic and ostseoinductive effects, comparable to bone morphogenetic proteins, and suggested its use as an alternative to growth factors, representing a low-cost, promising approach for osteochondral regeneration. This paper reviews the complex structure of the osteochondral tissue, underlining the main aspects of osteochondral defects and those specifically occurring in osteoarthritis. The significance of icariin’s structure and the extraction methods were emphasized. Studies revealing the valuable chondrogenic and osteogenic effects of icariin for osteochondral restoration were also reviewed. The review highlighted th recent state-of-the-art related to hydrogels and scaffolds enriched with icariin developed as biocompatible materials for osteochondral regeneration strategies.

Icariin protects myocardial cells in spontaneously hypertensive rats by inhibiting mitochondrial and endopla smic reticulum stress related pathways

Purpose: To investigate the protective effect of icariin (ICA) on myocardial cells in spontaneously hypertensive rats (SHRs), and the mechanism involved.
 Methods: Twenty-four SPF-grade, 12-week-old SHRs were randomly assigned to model group and ICA group, with 12 rats/group. There were 12 Wistar-Kyoto (WKY) rats (aged 12 weeks) in the control group. Rats in ICA group were given ICA suspension (40 mg/kg) through gavage, daily for 3 months, while model rats were given equivalent volume of double distilled water (in place of ICA suspension) via gavage for 12 weeks. Blood pressure, cardiac function, left ventricular (LV) mass index, myocardial morphology and apoptosis-related protein levels were determined and compared among the four groups.
 Results: The myocardial cells were hypertrophic and disorderly arranged, with widened intercellular spaces. Besides, there were increases in protein expression levels of p53, caspase 3, Bok, Bax, GRP78, p-PERK, ATF-4, CHOP and DR5, while Bcl-2 protein was down-regulated. In contrast, the levels of these indicators in the ICA group were significantly better than those in the model group (p < 0.05).
 Conclusion: ICA reduces blood pressure in rats, but improves cardiac function and cardiomyocyte morphology by decreasing apoptosis in cardiomyocytes through down-regulation of mitochondrial and endoplasmic reticulum (ER) stress-related apoptosis pathways. Thus, icariin may be suitable for the treatment of hypertension; however, clinical trials need to be undertaken first.

Icariin attenuates the tumor growth by targeting miR-1-3p/TNKS2/Wnt/β-catenin signaling axis in ovarian cancer.

PurposeDespite various therapy advances, ovarian cancer remains an incurable disease for which survival rates have only modestly improved. Natural products are important sources of anti-cancer lead compounds. Icariin exhibited broad anti-cancer efficacy. However, the mechanism of icariin against ovarian cancer is poorly elucidated.MethodsCell viability was detected to evaluate the effect of icariin on SKOV-3 cells. The cell cycle and apoptosis were analyzed. The transcript of SKOV-3 cells was profiled by RNA-seq. GSEA and DEGs analyses were performed to interpret gene expression data. Western blot and TOP/FOP flash assay were applied to detect Wnt/β-catenin signaling. MiRDB database and dual-luciferase reporter assay was applied to study the regulation of miR-1-3p on TNKS2. Anti-tumor efficacy of icariin was evaluated by xenograft mouse model. Immunohistochemistry was performed with antibodies against Ki67.ResultsIcariin significantly suppressed the proliferation of SKOV-3 cells. Furthermore, icariin stalled cell cycle and induced apoptosis by blocking TNKS2/Wnt/β-catenin pathway through upregulating the level of miR-1-3p. Finally, icariin dramatically suppressed tumor growth in vivo.ConclusionsIn this study, we demonstrated for the first time that icariin significantly attenuated the growth of ovarian tumor in xenograft mouse model. Furthermore, we systematically revealed that icariin attenuates the tumor progression by suppressing TNKS2/Wnt/β-catenin signaling via upregulating the level of miR-1-3p in ovarian cancer with transcriptome analysis.

A Phytomolecule Icariin Protects from Sarcopenia Partially by Suppressing Myosin Heavy Chain Degradation in Orchiectomized Rats.

Treatments are lacking for sarcopenia, which is an age-related disease characterized by loss of skeletal muscle mass, strength, and/or physical performance. Icariin is a phytomolecule fromherbal Epimedium, a traditional Chinese medicine widely used to treat musculoskeletal disorders for thousands of years. Here the effects of icariin against sarcopenia are investigated and the underlying mechanism is elucidated. A classic rat model of bilaterally orchiectomized (ORX) is used to induce sarcopenia. After administration for 8 weeks, compared to the control group, the forelimb grip strength, the specific tetanic forces of the soleus (SOL) and extensor digitorum longus muscle (EDL) are higher, and the fiber cross-sectional areas (CSAs) of the gastrocnemius and tibialis anterior muscle are larger in the icariin group. In addition, icariin promotes mRNA and protein expressions of myosin heavy chain (MyHC) both in SOL and EDL. Mechanistically, icariin significantly suppresses the mRNA and protein expressions of FOXO3a, atrogin-1, and MuRF-1, which are related to the degradation of myosin heavy chain. Collectively, icariin protects from sarcopenia in ORX rats characterized by enhancing grip strength and skeletal muscle contraction, as well as increasing skeletal muscle CSA by inhibiting the ubiquitination degradation of the MyHC in skeletal muscle fibers.

Molecular mechanisms regulating the pharmacological actions of icariin with special focus on PI3K-AKT and Nrf-2 signaling pathways.

Icariin is a primary active component of the traditional Chinese medicinal plant Epimedium grandiflorum. A range of pharmacological effects of icariin has been researched by modern science to explain its traditional medicinal uses. Attributing to the wide range of pharmacological properties like anti-osteoporosis, anti-inflammation, anti-oxidative stress, anti-depression, and anti-tumor property possessed by icariin, it is now being considered a potential therapeutic agent for a wide variety of disorders ranging from neoplasm, neurodegenerative disorders, osteoporosis, and cardiovascular diseases. Various signaling pathways including NFκB/NALP3, IGF-1, MiR-223-3p/ NALP3, TLR4/ NFκB, and WNT1/β-catenin are involved in the different biological actions exerted by icariin. Apart from these pathways, PI3K-AKT (Phosphoinositide 3 kinase-Protein kinase B) and Nrf-2 (nuclear erythroid 2-related factor 2) signaling pathways are two important pathways that form the fundamental basis for the pharmaceutical efficacy of icariin. This review gives an overview of previous in vitro and in vivo studies that investigated the potential role of icariin via PI3K-AKT and Nrf-2 signaling pathways to provide greater insights into its potential clinical use in a variety of disorders.

Inhibitory Effect of Icariin on Agonist-Induced Modulation of Vascular Contractility via Calcium Desensitization-Related Pathways

Inhibitory Effect of Icariin on Agonist-Induced Modulation of Vascular Contractility via Calcium Desensitization-Related Pathways

Icariin: A Potential Neuroprotective Agent in Alzheimer's Disease and Parkinson's Disease.

Alzheimer's disease (AD) and Parkinson's disease (PD) are the most common neurodegenerative diseases worldwide. They are characterized by the loss of neurons and synapses in special parts of the central nervous system (CNS). There is no definitive treatment for AD and PD, but extensive studies are underway to identify the effective drugs which can slow the progression of these diseases by affecting the factors involved in their pathophysiology (i.e., aggregated proteins, neuroinflammation, and oxidative stress). Icariin, a natural compound isolated from Epimedii herba, is known because of its anti-inflammatory and anti-oxidant properties. In this regard, there are numerous studies indicating its potential as a natural compound against the progression of CNS disorders, such as neurodegenerative diseases. Therefore, this review aims to re-examine findings on the pharmacologic effects of icariin on factors involved in the pathophysiology of AD and PD.