Horny Goat Weed (Epimedium)

Alzheimer's disease (AD) is a neurodegenerative condition that predominantly affects elderly individuals, characterised by progressive cognitive dysfunction, memory impairment and behavioural changes. Icariin (ICA), the primary active ingredient of the traditional Chinese medicine Epimedium spp., has demonstrated significant potential in the treatment of neurological disorders. Nevertheless, the precise mechanisms through which it exerts its anti-AD effects remain to be elucidated. And this meta-analysis aimed to discuss the mechanisms by which ICA exerts its anti-AD effects and the differences in the efficacy of different doses of ICA by evaluating behavioral indicators and biochemical characteristics. A total of 31 pre-clinical studies were included, and the results showed that ICA treatment significantly improved cognitive dysfunction in animal models of AD in terms of resistance to neurotoxic substances, inhibition of oxidative stress, anti-inflammation, inhibition of apoptosis, modulation of neuronal autophagy, and protection of nerves to promote regeneration. Furthermore, 68 mg/kg of ICA was identified as the most effective doses in terms of improving cognition. However, further research is required, incorporating studies of higher quality and larger sample sizes, in addition to clinical trials, in order to verify the efficacy and safety of this approach in neurological disorders.

Icariin, a major bioactive flavonoid extracted from Epimedium species, has demonstrated promising neuroprotective and antidepressant-like effects in preclinical research. However, the magnitude and consistency of these effects remain unclear due to substantial methodological heterogeneity across studies. Therefore, we conducted a systematic review and meta-analysis to evaluate the antidepressant efficacy of icariin in rodent models of depression. Literature searches were performed in Scopus, PubMed and Embase up to May 2025, following PRISMA 2020 guidelines. Twenty-three studies were included in the qualitative synthesis, and thirteen provided sufficient data for quantitative analysis. icariin administration significantly improved anhedonia-like behavior in the sucrose preference test (SPT), with a pooled Hedges’ g of 2.26 (95% CI: 1.56–2.96), and markedly reduced immobility in the forced swim test (FST), with a pooled Hedges’ g of 3.64 (95% CI: 2.65–4.64), indicating strong and robust antidepressant-like effects. Both findings were comparable in magnitude to conventional antidepressants. Meta-regression revealed that longer duration of depression model induction was associated with stronger behavioral improvement, whereas dose did not significantly predict efficacy. Mechanistic evidence suggests that icariin acts through multi-target neuroprotective pathways, including enhancement of BDNF-mediated neuroplasticity, inhibition of neuroinflammation, and regulation of HPA-axis dysfunction. Although methodological variability, male-biased animal selection, and pharmacokinetic limitations were identified, the overall evidence supports icariin as a promising antidepressant candidate for further translational investigation.

BACKGROUND: Primary Osteoporosis (POP) is a global public health issue, and traditional medications have long-term safety concerns. Epimedium, a kidney-tonifying traditional Chinese medicine (TCM), has the potential to regulate bone metabolism through multiple targets, but clinical evidence is scattered and inconclusive. OBJECTIVE: This systematic review and meta-analysis aim to evaluate the efficacy and safety of Epimedium and its active components in treating POP. METHOD: Computer searches were conducted in multiple domestic and international databases, including PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure (CNKI), and Wanfang Database, to collect randomized controlled trials (RCTs) comparing the use of Epimedium as an adjunct or alternative therapy with traditional drug treatments for POP. Literature was screened according to predefined inclusion and exclusion criteria, quality assessments were performed on eligible articles, relevant data were extracted, and statistical analysis was conducted using RevMan 5.4 software. RESULTS: A total of 10 RCTs were included, with a final inclusion of 890 cases, 448 in the experimental group and 442 in the control group. Meta-analysis suggests that the overall efficacy rate of the Epimedium group was significantly higher than that of the control group (OR = 3.80; 95% CI: 2.27,6.37; p = 0.0001). Compared with the control group, Epimedium group's Lumbar vertebra bone mineral density (BMD) (SMD = 1.15; 95% CI: 0.61,1.70; p < 0.0001), Femoral neck BMD (SMD = 1.11; 95% CI: 0.58,1.65; p < 0.0001), Distal radius BMD (SMD = 1.27; 95% CI: 0.57,1.98; p = 0.0004), and Metacarpal BMD (MD = 0.04; 95% CI: 0.04,0.12; p < 0.0001) all showed significant improvement, with a shorter time to relief of lower back pain (MD = -11.38; 95% CI: -12.63, -10.12; p < 0.00001). Serum alkaline phosphatase (ALP) was significantly reduced (MD = -8.78; 95% CI: -12.80, -4.77; <0.0001), while bone-specific alkaline phosphatase (BALP) increased (MD = 6.73; 95% CI: 3.32,10.14; p = 0.0001). Adverse reactions were low, mainly mild gastrointestinal reactions or skin allergies. CONCLUSION: Epimedium can effectively improve bone density

OBJECTIVES: Icariside II (ICS-II), a flavone containing 3-rhamnopyranosyl and 8-prenyl groups, is one of the main natural compounds found in Epimedum species (the family Berberidaceae). The current study aims to provide a systematic review of its natural occurrence, pharmacological value, synthetic modification, pharmacokinetics, and bioavailability. KEY FINDINGS: Sources such as Google Scholar, Web of Science, PubMed, and journal websites were used to gather references about ICS-II. 'Icariside II' is the most meaningful keyword to seek references, and references have been updated till now. SUMMARY: ICS-II is a characteristic metabolite of various Epimedum plants, and it can be obtained by enzymatic hydrolysis of other flavonoids. It is a promising compound with multiple in vitro and in vivo pharmacological potentials. The studied flavone showed cancer-related biological activity via cell cycle arrest, proliferation inhibition, autophagy, and apoptosis and inhibited cytokines in anti-inflammatory actions. Significantly, the health benefits were accompanied by its role in antidiabetics, sexual reproduction, and protection against harmful effects on the heart, brain, bones, lungs, kidneys, livers, and eyes. Molecular mechanisms of action were deduced from various signaling pathways, such as Akt/NOS/NF-κB, JAK/STAT3/MAPK, and PI3K/Akt/mTOR. Pharmacokinetic evidence involved sugar and methyl removals, hydroxylation, glucuronidation, and glycosylation. © The Author(s) 2025. Published by Oxford University Press on behalf of the Royal Pharmaceutical Society. All rights reserved. For commercial re-use, please contact [email protected] for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact [email protected].

OBJECTIVE: This study aimed to evaluate the therapeutic efficacy of Invigorating Spleen and Replenishing Kidney and Resolving Phlegm Prescription (ISRKRPP) in treating obesity-type polycystic ovary syndrome (PCOS) and to analyze the prescription regularity through data mining technology. METHODS: Databases were retrieved up to September 30, 2024. RCTs on obesity-type PCOS treated with ISRKRPP and Western medicine (WM) were included. The Risk of Bias 2 tool was used for quality assessment. Network meta-analysis was performed using Stata 14.0. After standardizing herb names, a corresponding herbal database was built in Excel. Based on Excel and R language, the core drugs and prescription rules used in the treatment of obese PCOS were analyzed and visualized. RESULTS: A total of 14 articles, involving 1,163 patients and 7 prescriptions, were included. Network meta-analysis indicated the following: Qihuang Zengmin Decoction + WM may be optimal for overall efficacy (Confidence in Network Meta-Analysis [CINeMA]: moderate confidence); Cangfu Daotan Decoction + WM showed superiority in reducing BMI (CINeMA: moderate confidence); Method of Regulating and Supplementing Spleen and Kidney + WM most effectively improved HOMA-IR (CINeMA: moderate confidence); Cangfu Daotan Decoction + WM best regulated LH (CINeMA: moderate confidence); Heshi Powder + WM medicine most effectively reduced testosterone (CINeMA: moderate confidence). Herbal Regularity analysis revealed core herbs for the treatment included Rhizoma atractylodis, Poria cocos, Angelica sinensis, Pinellia ternata, and Epimedium. The herbal cluster, including Epimedium, Poria cocos, Angelica sinensis, Citrus, Spina gleditsiae, Salviae miltiorrhizae, Rhizoma atractylodis, Pinellia ternata, and Rhizoma cyperi may be the core prescription for the treatment of obesity-type PCOS. CONCLUSION: Based on the results of the present studies, ISRKRPP combined with WM can improve the effect of obesity-type PCOS. Due to the limitations of the present studies, more clinical studies are needed for further validation. SYSTEMATIC REVIEW REGISTRATION: https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42024594257.

OBJECTIVE: To evaluate the effectiveness of various nutritional supplements as interventions for patients with Chronic Obstructive Pulmonary Disease (COPD) using network meta-analysis. METHODS: We searched PubMed, Embase, Cochrane Library, and Web of Science databases for randomized controlled trials on nutritional supplements for COPD patients, with the search updated to March 24, 2025. The risk of bias for each included study was assessed using appropriate tools, and the certainty of evidence was evaluated according to the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. Data synthesis was performed using R software, employing network meta-analysis methods to compare the relative efficacy of different nutritional interventions. RESULTS: Thirty-seven studies involving 1975 COPD patients and 21 different nutritional supplements were analyzed. Butyrate [MD = 2.7, 95% CrI (1.0, 4.4)], Nanocurcumin [MD = 13, 95% CrI (5.4, 21)], and probiotics [MD = 7.1, 95% CrI (5.2, 9.1)] significantly improved Forced Expiratory Volume in One Second (FEV1). Nanocurcumin also slowed the decline in the ratio of Forced Expiratory Volume in One Second to Forced Vital Capacity (FEV1/FVC) [MD = 12, 95% CrI (5.5, 18)]. For exercise endurance, coenzyme Q10 combined with creatine [MD = 63, 95% CrI (36, 90)], Melatonin (MLT) [MD = 46, 95% CrI (1.3, 92)], Nitrate [MD = 30, 95% CrI (19, 41)], and whey proteins [MD = 11, 95% CrI (9.2, 13)] significantly improved 6-minute walk distance (6MWD). Regarding dyspnea reduction, MLT [MD = -0.90, 95% CrI (-1.6, -0.21)] and Yam-Epimedium [MD = -1.3, 95% CrI (-1.9, -0.67)] significantly lowered modified Medical Research Council (mMRC) scores. In terms of quality of life, MLT [MD = -8, 95% CrI (-12, -4.2)], Vitamin D (VD) [MD = -2.5, 95% CrI (-3.1, -1.9)], and whey proteins [MD = -0.70, 95% CrI (-0.99, -0.41)] reduced COPD Assessment Test (CAT) scores. Additionally, AKL1 [MD = -9.2, 95% CrI (-18, -0.41)], creatine [MD = -9.6, 95% CrI (-17, -2.8)], and Yam-Epimedium [MD = -24, 95% CrI (-34, -13)] lowered St. George's Respiratory Questionnaire (SGRQ) scores. The Surface Under the Cumulative Ranking Curve (SUCRA) analysis

BACKGROUND: Epimedium total flavonoids (EF) have been recommended to be one of the effective components in Traditional Chinese Medicine (TCM) for the treatment of primary osteoporosis (POP) in China. Due to the lack of evidence-based medical evidence on the efficacy and safety of EF for the treatment of POP, the current systematic review and meta-analysis was carried out aimed at evaluating the curative effects and safety profile of EF treatment for POP in order to provide decision making references for clinical research. METHODS: The PubMed, Cochrane Library, EMBASE, Web of Science, CNKI, Wanfang, and VIP databases were searched from the date of inception to 11 August 2024. The outcomes of effectiveness and safety of included studies were collected to conduct meta-analysis or systematic review. RESULTS: A total of 6 RCTs were included in this study, involving 838 participants. Overall, our results revealed that the experimental group (EG) had comparable results of efficacy to the control group (CG). The lumbar vertebra bone mineral density (BMD) was statistically different compared to the CG (MD = 0.03; 95% CI: 0.01, 0.04; p = 0.0003), but the clinical significance deserved consideration because the 95% CI nearly crossed the invalid line. The femoral neck BMD was neither statistically different nor clinically different between two groups (MD = 0.00; 95% CI: 0.01, 0.02; p = 0.67). The total complication rates were comparable among the two groups (RR = 0.68; 95% CI: 0.39, 1,19; p = 0.18). The quality of the evidence of the present study was judged as moderate and low based on the GRADE analysis. CONCLUSION: EF treatment exhibited good curative effects and safety. The result was comparable to the CG, including other Chinese patent medicines and calcium and vitamin D supplements. The EF treatment was proved to be a reliable alternative option for POP.

BACKGROUND: Neurovascular glial unit (NVGU) dysfunction has been reported to be an early and critical event in the pathophysiology of Alzheimer's disease (AD) and vascular dementia (VD). Although herbal medicines, with their favorable safety profiles and low adverse effects, have been suggested to be useful for the treatment of cognitive impairment, the potential role of the NVGU as the target of the effects of herbal medicines is still unclear. PURPOSE: This review aimed to retrieve evidence from experimental studies of phytopharmaceuticals targeting the NVGU for the treatment of cognitive impairment in AD and VD, and discussed the potential of phytopharmaceuticals to improve cognitive impairment from the perspective of the NVGU. STUDY DESIGN AND METHODS: We systematically searched PubMed, Google Scholar, Web of Science, and CNKI. The keywords used for searching information on the NVGU in the treatment of cognitive impairments included "Alzheimer's disease," "Vascular dementia," "Herbal medicines," "Natural products," "Neurovascular," "Adverse reaction," and "Toxicity, etc." We selected studies on the basis of predefined eligibility criteria. RESULTS: NVGU mainly consists of endothelial cells, pericytes, astrocytes, microglia, oligodendrocytes, and neurons, and damage to these cells can induce cognitive impairment by impairing the blood-brain barrier (BBB) and cerebral blood flow (CBF) as well as neuronal function. The active components of herbal medicines, including Ginkgo biloba L., Ginseng Radix et Rhizoma, Epimedium Folium, Chuanxiong Rhizoma, Carthami flos, and Acorus tatarinowii Schott, as well as traditional Chinese medicine prescriptions have shown the potential to improve BBB function and increase CBF to prevent cognitive impairment by inhibiting astrocyte and microglia activation, protecting oligodendrocyte myelin function, reducing neuronal apoptosis, and promoting angiogenesis. CONCLUSIONS: Herbal medicines demonstrate great potential to prevent cognitive impairment. Multiple components from herbal medicines may function through different signaling pathways to target the NVGU. Future studies using novel drug-carrier or delivery systems targeting the

ETHNOPHARMACOLOGICAL RELEVANCE: Epimedium koreanum Nakai (E. koreanum), a member of the genus Epimedium in the family Berberidaceae, is a well-known and well-liked traditional herb used as a "kidney tonic". For thousands of years, it has been utilized for renal yang deficiency, impotence, spermatorrhea, impotence, weakness of tendons and bones, rheumatic paralysis and discomfort, numbness, and constriction. AIM OF THE STUDY: The paper aims to comprehensively in-depth, and methodically review the most recent research on the traditional uses, phytochemistry, pharmacology, and toxicity of E. koreanum. MATERIALS AND METHODS: Scientific databases including Web of Science, PubMed, Google Scholar, Elsevier, Springer, ScienceDirect, Baidu Scholar, and CNKI and medicine books in China were searched for relevant information on E. koreanum. RESULTS: In traditional uses, E. koreanum is frequently used to treat various diseases like erectile dysfunction, infertility, rheumatoid arthritis, osteoporosis, asthma, kidney-yang deficiency syndrome, etc. To date, more than 379 compounds have been discovered from various parts of E. koreanum, including flavonoids, lignans, organic acids, terpenoids, hydrocarbons, dihydrophenanthrene derivatives, alkaloids, and others. Research has revealed that the compounds and crude extracts have a wide range of pharmacological effects on the reproductive, cardiovascular, and nervous systems, as well as anti-osteoporosis, anti-tumor, antioxidant, anti-inflammatory, immunomodulatory, hepatoprotective, and antiviral properties. Besides, the crude extracts show potential hepatotoxicity. CONCLUSION: Based on recent domestic and international research investigations, E. koreanum contains a wealth of chemical components with pronounced pharmacological activities. Its traditional uses are numerous, and the majority of these traditional uses have been supported by contemporary pharmacological investigations. Crude extracts, on the other hand, can result in hepatotoxicity. Therefore, additional in vivo and in vitro experimental research on the pharmacology and toxicology of E. koreanum are required in the future to assess its safety and efficacy. This will

Background: The efficacy of conventional pharmacotherapy on osteoporosis was limited and accompanied with serious side effects. Epimedium might have the potential to be developed as agents to treat osteoporosis. The present systematic review and meta-analysis integrating Western medicine and Eastern medicine ("WE" medicine) was to evaluate the efficacy of Epimedium on osteoporosis. Methods: Eleven electronic databases were searched to identify the randomized controlled trials (RCTs) comparing Epimedium as an adjunctive or alternative versus conventional pharmacotherapy during osteoporosis. Bone mineral density (BMD), effective rate, and Visual Analog Scale (VAS) were measured as primary outcomes. The secondary outcomes were pain relief time, bone metabolic markers, and adverse events. Research quality evaluation was conducted according to the modified Jadad scale. Review Manager 5.4 was utilized to perform analyses, and the data were pooled using a random-effect or fixed-effect model to calculate the weighted mean difference (WMD), standardized mean difference (SMD), risk ratio (RR), and 95% confidence intervals (CI). Results: Twelve RCTs recruiting 1,017 patients were eligible. Overall, it was possible to verify that, in the Epimedium plus conventional pharmacotherapy group, BMD was significantly improved (p = 0.03), effective rate was significantly improved (p = 0.0001), and VAS was significantly decreased (p = 0.01) over those in control group. When compared to conventional pharmacotherapy, Epimedium used alone improved BMD (p = 0.009) and effective rate (p < 0.0001). VAS was lower (p < 0.00001), and the level of alkaline phosphatase (ALP) was significantly decreased (p = 0.01) in patients taking Epimedium alone compared with those given conventional pharmacotherapy. Results of subgroup analyses yielded that the recommended duration of Epimedium as an adjuvant was >3 months (p = 0.03), the recommended duration of Epimedium as an alternative was ≤3 months (p = 0.002), and Epimedium decoction brought more benefits (SMD = 2.33 [1.92, 2.75]) compared with other dosage forms. No significant publication bias was identified based on statistical tests (t = 0.81, p =

Background: Current treatments for osteoarthritis (OA) pain and stiffness have limitations, including adverse effects. Therefore, effective and safe complementary or alternative therapies are needed. Dietary supplement GJ 191, comprising Epimedium, Dioscorea, and Salvia miltiorrhiza extracts, may address this need. Methods: This randomized, double-blind, placebo-controlled study investigated GJ 191 supplementation on knee OA symptoms. Seventy-two adults (40-75 years) with mild to moderate knee OA and mild to moderate knee pain were enrolled. The Knee Injury and Osteoarthritis Outcome Score (KOOS), Pain Visual Analog Scale (VAS), Quality of Life questionnaire, knee joint range of motion, serum C-reactive protein, and rescue medication use were assessed. The Western Ontario McMaster Universities Osteoarthritis Index (WOMAC) pain and stiffness scores were computed using KOOS scores. Results: Decreases in WOMAC pain scores were reported by both GJ 191 and placebo groups after 6 (-1.78 ± 2.71 and -1.34 ± 1.93, respectively; p < 0.01) and 12 (-2.31 ± 2.83 and -1.59 ± 2.69, respectively; p < 0.01) weeks, with no significant difference between groups. There were decreases in WOMAC stiffness scores for participants supplemented with GJ 191 by 0.53 ± 1.22 and 0.72 ± 1.46 (p ≤0.02) after 6 and 12 weeks, respectively, with respective decreases of 0.81 ± 1.51 and 0.75 ± 1.85 (p ≤0.03) for those on placebo. Significant improvements in current pain, as assessed by the Pain VAS, and bodily pain were reported by the GJ 191 group after 6 and 12 weeks, while the placebo group only reported significant improvements in these measures after 12 weeks. GJ 191 supplementation was safe and well tolerated. Conclusion: There was no significant difference in pain and stiffness scores between GJ 191 and placebo over the 12 weeks. While both groups reported improvements in WOMAC pain from baseline, improvements in current and bodily pain were experienced sooner with GJ 191 than placebo and were sustained over the study period. GJ 191 supplementation was safe and well tolerated. (CTR#: NCT04395547).

BACKGROUND: Fragility fractures due to menopausal osteoporosis are a major cause of morbidity and mortality. Osteoporotic medications have substantial side effects that limit long term use. HYPOTHESES: Ingestion of a purified extract of Epimedium spp. (EP) is safe, can increase serum levels of prenylflavonoid metabolites, exert positive changes in bone specific alkaline phosphatase (BSAP), suppress of tumor necrosis factor receptor associated factor 6 (TRAF6) protein in osteoclast-precursor monocytes in peripheral blood and therefore have the potential to reduce post-menopausal bone loss. STUDY DESIGN & METHODS: Healthy postmenopausal women were randomized in a double-blind fashion to consume either EP prenylflavonoid extract (740 mg daily) or placebo daily for 6 weeks. The main outcome measures were safety and pharmacokinetics of EP flavonoids. Fasting blood was collected at 3- and 6-weeks, and two weeks after stopping medication for safety evaluations and measurement of BSAP. Peripheral blood monocytes were harvested for measurement of TRAF6 levels. Serum levels of the EP metabolites icariin, icariside I & II, icaritin and desmethylicaritin were measured using tandem mass spectrometry, and non-compartmental pharmacokinetic analyses performed using WinNonlin software. RESULTS: Between October 2018 and Jun 2020, 58 postmenopausal women, aged 57.9 ± 8.9 years, were randomized and completed the study. Consumption of EP prenylflavonoids was not associated with any significant adverse symptoms, with no changes in hepatic, hematological, and renal parameters observed. The main metabolites detected in sera after ingestion of EP prenylflavonoid capsules were desmethylicaritin, icaritin and icariside II. Icariin and icariside I were below detection levels. Ingestion of EP prenylflavonoids induced a median Cmax and AUC0→∞ for desmethylicaritin of 60.9 nM, and 157.9 nM ×day, respectively; and were associated with higher levels of BSAP (p < 0.05) and a trend (p = 0.068) towards lower levels of TRAF6 in peripheral blood monocytes eight weeks after commencing prenylflavonoid ingestion. Prenylflavonoid metabolites were not detected in the sera of placebo participants. CONCLUS

This report is third in a three-part clinical trial series screening potential treatments for Gulf War Illness (GWI). The goal of the project was to rapidly identify agents to prioritize for further efficacy research. We used a placebo-controlled, pseudo-randomized, crossover design to test the effects of reishi mushroom (Ganoderma lucidum), stinging nettle (Uritca dioica), and epimedium (Epimedium sagittatum) in 29 men with GWI. Participants completed 30 days of symptom reports for baseline, then a botanical line consisting of 30 days of placebo, followed by 30 days each of lower-dose and higher-dose botanical. After completing a botanical line, participants were randomized to complete the protocol with another botanical, until they completed three botanical trials. GWI symptom severity, pain, and fatigue were contrasted between the four conditions (baseline, placebo, lower-dose, higher dose) using linear mixed models. GWI symptom severity was unchanged from placebo in the reishi lower-dose condition (p = 0.603), and was higher in the higher-dose condition (p = 0.012). Symptom severity was not decreased from placebo with lower-dose stinging nettle (p = 0.604), but was significantly decreased with higher-dose stinging nettle (p = 0.048). Epimedium showed no significant decreases of GWI symptoms in the lower (p = 0.936) or higher (p = 0.183) dose conditions. Stinging nettle, especially at higher daily dosages, may help reduce the symptoms of GWI. Epimedium does not appear to beneficially affect GWI symptom severity, and reishi may exaggerate symptoms in some GWI sufferers. These results are in a small sample and are preliminary. Further research is required to determine if stinging nettle is indeed helpful for the treatment of GWI, and what dosage is optimal. This trial was registered on ClinicalTrials.gov (NCT02909686).

Leaves of the Epimedium plant are traditionally consumed for bone health and other indications. The aim of this study was to establish the safety and pharmacokinetics of the metabolites of prenylflavonoids (icariin, icariside I, icariside II, icaritin, and desmethylicaritin) following single doses of a defined Epimedium prenylflavonoid extract in humans. A single oral dose of 370, 740, or 1110 mg of a standardized Epimedium prenylflavonoid extract was administered to 30 healthy male subjects in a randomized, placebo-controlled trial. Serum samples were collected over a 48-h period and analyzed by liquid chromatography-tandem mass spectrometry and non-compartmental pharmacokinetic modelling. Epimedium prenylflavonoid extracts were well tolerated and no adverse effects were observed. The principle metabolites detected in the serum were icariside II and desmethylicaritin. Icariside II had a T max of between 4.1 - 4.3 h, reaching a maximum AUC0→∞ of 23.0 (17.5, 29.9) h×ng/mL (median [IQR: interquartile range]) with the highest dose of the Epimedium prenylflavonoid. On the other hand, desmethylicaritin had a delayed T max of 24.1 - 24.4 h and reached a maximum AUC0→∞ of 126.1 (62.4, 202.9) h×ng/mL. The median maximum plasma concentration and AUC0→∞ of desmethyliciaritin showed an increase with higher doses of the Epimedium prenylflavonoid (p < 0.05). Icariin, icariside I, and icaritin levels were below detection limits. Levels of Epimedium prenylflavonoid metabolites observed in this study were consistent with levels demonstrated to have anti-osteoporotic effects in cellular and animal studies. Coupled with the favorable safety profile of the extract observed, further studies are required to explore the utility of Epimedium prenylflavonoid extracts to prevent osteoporosis in postmenopausal women. Georg Thieme Verlag KG Stuttgart · New York.

OBJECTIVE: To explore the clinical efficacy and partial mechanism of medicinal-cake-separated moxibustion for senile osteoporosis. METHODS: Sixty cases of senile osteoporosis were randomly divided into an observation group and a control group according to the random digits table, 30 cases in each one. The two groups were both treated with basic treatment of western medicine. The acupoints included four groups:① Dazhui (GV 14), Dazhu (BL 11) and Ganshu (BL 18); ② Zhongwan (CV 12), Danzhong (CV 17) and Zusanli (ST 36); ③ Pishu (BL 20), Shenshu (BL 23) and Mingmen (GV 4); ④ Shenque (CV 8) and Guanyuan (CV 4). Each group of acupoints was selected for one treatment. The observation group was treated with medicinal-cake-separated moxibustion, and the medicinal cake was consisted of fructus psoraleae (30 g), prepared rehmannia root (30 g), atractylodes (30 g), codonopsis pilosula (30 g), epimedium herb (20 g), rhizoma curculiginis (20 g), syzygium aromaticum (5 g) and cinnamon (5 g). The control group was treated with wheat-flour-cake moxibustion. Each acupoint was treated with 5 moxa cones in the two groups. The treatment was given once every other day for six months. The symptom score, lumbar and hip bone mineral density (BMD), serum type Ⅰ procollagen amino-terminal propeptide (PINP) and serum β-type Ⅰ collagen carboxy-terminal peptide (β-CTX) were observed before and after treatment. RESULTS: After treatment, the symptom score and serum β-CTX were significantly lowered (all P<0.05), while the lumbar and hip BMD and serum PINP were significantly increased (all P<0.05) of the two groups. After treatment, the symptom score and serum β-CTX in the observation group were significantly lower than those in the control group (both P<0.05), while the lumbar and hip BMD and serum PINP in the observation group were significantly higher than those in the control group (all P<0.05). CONCLUSIONS: The medicinal-cake-separated moxibustion has significant efficacy for senile osteoporosis, which is superior to wheat-cake-se-parated moxibustion.

"LEOPIN ROYAL®" (LER), a non-prescription health-promoting medication in Japan, is a preparation containing six natural medicines, namely, aged garlic extract, ginseng, oriental bezoar, velvet antler, cuscuta seed and epimedium herb. To determine the effect of LER on symptoms of aging in males, we conducted an open-labeled, randomized clinical trial using Kampo (mainly kamishoyosan) as a control. Forty-nine male patients (age, 62.7 (SD 11.8) years) with mild or more pronounced symptoms of aging were enrolled and randomly assigned to the LER (n = 24) or Kampo group (n = 25) for 6 months. The Aging Males' Symptoms (AMS) scale and the International Index of Erectile Function with 5 questions (IIEF-5) were tested at baseline, and after 3 and 6 months of administration of the medications. In the AMS scale, the somatic and psychological sub-scores and total score decreased depending on the time course in both groups. However, the decrease in the slope of the LER group was greater than that of the Kampo group. There was a significant difference between the groups and the group and month interaction (G × M), as revealed by a linear mixed model analysis (p < 0.05). The IIEF-5 score increased in the LER group (p = 0.02 with regard to G × M). In conclusion, the present results indicate that LER is possibly superior to mainly kamishoyosan on the rate of improvement of symptoms of aging, including erectile dysfunction, in males.

OBJECTIVE: To examine the clinical effects of a mixture of Chinese Yam and epimedium in patients with stable moderate or severe chronic obstructive pulmonary disease (COPD). METHODS: Forty-nine patients with COPD were randomly allocated to a group whose usual treatment was supplemented with oral Chinese yam-epimedium mixture, or a control group given placebo. For each patient, body mass index, airflow obstruction, dyspnea, and exercise capacity were measured and converted into the BODE index before treatment and at one and three months after initiation of treatment. Participants also completed the St. George's respiratory questionnaire (SGRQ) at the same intervals. RESULTS: After one month, improvements were seen in the BODE index and SGRQ of participants taking Chinese yam-epimedium mixture compared to controls. There were statistically significant differences in the SGRQ: three of its components and the total SGRQ scores were significantly decreased (P < 0.05), respiratory symptom scores had improved (P < 0.01), and the dyspnea component of the BODE index had significantly decreased (P < 0.05). Similar improvements were observed after three months of treatment, but exercise tolerance had also improved: the six-minute walking distance had significantly increased (P < 0.05) in the treatment group when compared with controls. CONCLUSION: Chinese yam-epimedium mixture can significantly improve dyspnea, exercise capacity, and the quality of life of patients with stable moderate or severe COPD.

To observe the kidney-tonifying herbal Fufangs with phytoestrogenic epimedium for prevention of postmenopausal osteoporosis with both bone mineral density (BMD) and fracture as study endpoints, a 5-year multicenter follow-up study in 194 postmenopausal women (47-70 years old) was conducted in which the subjects were given oral administration of herbal Fufang (10 g/day, twice per day, n = 101) or placebo (n = 93). Both groups were supplemented daily with calcium (600 mg) and vitamin D (400 IU). BMD at distal radius, potential adverse events, and fracture incidence were evaluated at baseline and at 6, 12, 24, 36, 48, and 60 months. At the end of 5 years, 155 subjects had completed the study, with better adherence in the treatment group (13% dropouts, n = 88 at year 5) as compared with the control group (28% dropouts, n = 67 at year 5) (P < 0.05). No notable adverse events were observed in either group. In the treatment group BMD increased significantly from baseline (0.211 ± 0.022 g/cm(2)) to the end of the study (0.284 ± 0.015 g/cm(2)), whereas the control group decreased significantly from baseline (0.212 ± 0.023 g/cm(2)) to 5 years later (0.187 ± 0.022 g/cm(2)) (P < 0.05). The fracture incidence was 2.4 fold lower in the treatment group than in the control group, with a relative risk of 0.57 for the treatment group (95% CI, 0.43-0.70, P < 0.05). In conclusion, in addition to the beneficial effects of oral herbal Fufang on prevention of postmenopausal bone loss, this 5-year multi-center clinical study demonstrated for the first time its potential for reduction in fragility fracture incidence.

Erectile dysfunction (ED) is one of the major health concerns affects the quality of life among Thai male. The treatment of ED by the first-line drugs is limited to a certain group of patients due to their side effects and costs. Alternative medicine can be beneficial for the treatment of ED. This is a randomized, double-blind, placebo-controlled, crossover study aimed to assess the efficacy and safety of Cappra(®), a traditional herbal medicine which was used in Thailand for decades, for the treatment of mild and mild to moderate ED in Thai patients. A total of 63 patients with mild or mild to moderate ED were randomized to receive Cappra(®) or placebo for two weeks in the first period, followed by one week washout period. The patients were switched to the alternative treatment in the second period. The efficacy was assessed by the International Index of Erectile Function (IIEF) questionnaire and adverse events. Sixty one patients completed the study. There was an improvement of IIEF score for all domains in Cappra(®) group compared with placebo group. The mean change of IIEF score from baseline for erectile function domain of Cappra(®) was significantly higher than placebo (4.87 vs 3.44, p = 0.032). The most common adverse events were dizziness (13.3% Cappra(®), 9.6% placebo), face numbness (1.6% Cappra(®), 0% placebo), and tachycardia (1.6% Cappra(®), 0% placebo). The results from this study demonstrated that Cappra(®) is effective and well-tolerated and can be used as alternative therapy for mild and mild to moderate ED.

OBJECTIVE: To observe the therapeutic effect of Bushen Qiangdu Recipe (BSQDR) on osteoporosis and bone loss in patients with ankylosing spondylitis (AS). METHODS: Patients with AS were randomly assigned to two groups. The 288 patients in the treatment group received BSQDR (consisting of cibotii rhizoma, antler, prepared rehmannia root, epimedium herb, rhizoma drynariae, teasel root, eucommia bark, pangolin scales, etc., one dose daily, taken in two portions, once in the morning and once in the evening). The 72 patients in the control group received SIDSM and sulfasalazine. The therapeutic course for both was six months. Clinical symptoms, pillow distance from the wall, hand distance from the ground, jaw distance from the handle, chest mobility, Schober test, spinal mobility and other signs of disease activity indices (ESR and CRP) were observed in patients before and after treatment. The bone mineral density (BMD) testing was performed in the lumbar spine, the femur, the forearm, and the heels, etc. Osteocalcin (BGP), calcitonin, parathyroid hormone (PTH), etc. bone metabolic indices were detected. RESULTS: BASFI, BASDAI, the overall assessment, the spinal pain, pillow distance from the wall, hand distance from the ground, jaw distance from the handle, chest mobility, Schober test, spinal mobility, and so on were all improved to some extent when compared with before treatment in the treatment group (P<0.05). The ESR and CRP decreased to various degrees, showing statistical significance when compared with before treatment (P <0.01). BGP increased and PTH decreased, showing statistical difference when compared with before treatment (P<0.05). The BMD in patients' lumbar spine, femoral neck, Ward's triangle, femoral trochanter increased to various degrees. The calcaneal intensity index, blood uric acid (BUA) and SOS values also increased more than before treatment, showing statistical significance (P<0.05). Long-term oral administration of BSQDR was safe, with no obvious adverse reaction. CONCLUSIONS: BSQDR showed significant effect in treatment of AS. It could regulate the bone metabolic level in patients, attenuate the immune inflammatory response, improve the spi

AIM: Epimedium plants are used in traditional Chinese medicine due to their medicinal properties and can be clinically used for the treatment of liver cancer.Using network pharmacology and HPLC, we identified a key anti-HCC complex, CMPLX (containing icariin and kaempferol), from four Epimedium species. In vitro and in vivo studies demonstrated that CMPLX suppresses HCC proliferation by downregulating p-Akt, p-PI3K, and Bcl-2 expression. Untargeted metabolomics and gut microbiome analysis revealed significant negative correlations between serum levels of lignin/kaempferol derivatives and Escherichia coli abundance. These findings highlight CMPLX as a promising candidate for HCC drug development. PURPOSE: Investigate the pharmacodynamic material basis of the components of four Epimedium species with activities against hepatocellular carcinoma based on biological target networks and multi-omics analysis. MATERIALS AND METHODS: We first screened four Epimedium extracts for anti-HCC activity using HepG2 cells. Shared bioactive compounds were identified through network pharmacology and HPLC, defining core target AKT1 and key complex CMPLX (icariin and kaempferol). Molecular docking/dynamics simulations confirmed CMPLX-AKT1 binding. In vitro assays (CCK-8, wound healing, colony formation, Annexin V/PI, Western blot) demonstrated CMPLX inhibits proliferation, migration, and induces apoptosis via PI3K/AKT/Bcl-2 pathway. In vivo validation in H22 tumor-bearing mice showed tumor suppression, corroborated by histology, serum metabolomics and gut microbiota analysis. RESULTS: CMPLX suppressed hepatocellular carcinoma proliferation in vitro and in vivo. Mechanistically, it downregulated p-Akt, p-PI3K, and Bcl-2 expression, inhibiting growth and promoting apoptosis in HepG2 cells. Integrated multi-omics revealed CMPLX treatment elevated flavonoid/kaempferol derivatives while reducing Enterobacteriaceae_A/Escherichia abundance, with Marinifilaceae dominating the gut microbiota. Crucially, lignan/kaempferol derivatives showed significant negative correlation with Escherichia levels. CONCLUSION: CMPLX demonstrated synergistic anti-HCC efficacy in vitro and in vivo. Multi-omics a

The immune system is a pivotal regulator of reproductive physiology, maintaining tissue homeostasis essential for successful pregnancy while contributing to infertility and reproductive disorders when dysregulated. Natural products represent a valuable source of novel immunomodulatory agents. Icariin (ICA), a prenylated flavonoid glycoside isolated from Epimedium species (Horny Goat Weed), has a long-standing traditional use for "invigorating yang," which modern research attributes to its reproductive function-enhancing properties. This review synthesizes emerging evidence that the beneficial effects of ICA on female and male reproductive health are primarily mediated through its sophisticated immunomodulatory actions on the reproductive-immune axis. We systematically dissect the molecular mechanisms by which ICA reprograms the reproductive immune microenvironment, focusing on its regulation of macrophage polarization, T-helper cell (Th1/Th2/Th17) and regulatory T-cell (Treg) balance, and suppression of key pro-inflammatory signaling pathways (NF-κB, NLRP3 inflammasome, JAK-STAT) in ovarian, uterine, and testicular tissues. This review provides a detailed account of how ICA modulates reproductive disorders via regulating immune responses, with the aim of offering innovative strategies for the design of novel immunomodulatory therapies targeting reproductive diseases.

INTRODUCTION: Skeletal fluorosis patients face a markedly elevated risk of cardiovascular metabolic abnormalities, including endothelial dysfunction, excessive oxidative stress, and impaired calcium-phosphate metabolism. Current clinical interventions for this condition are limited to symptomatic analgesia and conventional anti-osteoporotic treatments, and lack targeted therapeutic strategies for the "kidney deficiency and blood stasis" pathogenesis of skeletal fluorosis that can synergistically protect both the skeletal and cardiovascular systems. METHODS: This multicenter randomized controlled trial was conducted on 1,480 skeletal fluorosis patients from the China Fluorosis Cohort (CFC), to investigate the synergistic therapeutic effects of three traditional Chinese medicine (TCM) combinations-Ginkgo biloba combined with Epimedium (Drug 1), Xianling Gubao combined with Eucommia ulmoides (Drug 2), and Gusongbao combined with Rosa roxburghii (Drug 3)-in conjunction with lifestyle modifications on cardiovascular metabolic outcomes. RESULTS: Smoking and alcohol consumption were identified as independent risk factors for reduced therapeutic efficacy in skeletal fluorosis patients with comorbid cardiovascular metabolic abnormalities (OR = 2.755, 95% CI: 1.400 -5.421). Among the three TCM combinations, Drug 2 and Drug 3 significantly counteracted these adverse risk factors, reducing the risk of treatment failure by 53.9% (OR = 0.461) and 57.0% (OR = 0.430), respectively. Drug 3 exhibited superior efficacy in reducing diastolic blood pressure (β = -2.263, P = 0.010), while its systolic blood pressure-lowering effect diminished with increasing age. Drug 2 showed synergistic benefits with improved sleep quality (β = 1.596, P = 0.002) and healthy dietary habits (β = -1.180, P = 0.001), which enhanced its antihypertensive effects and led to a significant reduction in low-density lipoprotein cholesterol (LDL-C) levels (P < 0.05). Additionally, the interaction models outperformed the main-effect models, confirming the dynamic synergistic effect between lifestyle interventions and TCM pharmacotherapy. DISCUSSION: These findings highlight the clinical necessity of integrating

BACKGROUND: Ovarian cancer is a prevalent gynecologic malignancy. Despite multimodal treatment centered on surgery and supplemented by chemo and targeted therapy, challenges such as drug resistance and surgical trauma persist, underscoring the need for new approaches. Epimedium, a traditional Chinese medicine, has shown preliminary anti-ovarian cancer activity, warranting systematic investigation. This study applied network pharmacology and computational simulations to elucidate its molecular mechanisms and virtually screen for potential therapeutic compounds. METHODS: To identify potential therapeutic targets, ovarian cancer-associated genes were retrieved from the GeneCards, OMIM, and TTD databases. Concurrently, active components of Epimedium were filtered from TCMSP employing pharmacokinetic thresholds. The resulting intersection of targets was analyzed through functional enrichment and PPI network analysis. The interactions between the key components and core targets were further validated by molecular docking and molecular dynamics simulations. RESULTS: Network pharmacology identified that Epimedium treats ovarian cancer by modulating immunity, cellular stress, death, and proliferation via key targets such as EGFR, SRC, and PI3K subunits (PIK3CA, PIK3CB, PIK3R1). The compounds Yinyanghuo A and Magnograndiolide, which show strong binding to these targets, are predicted to function through EGFR inhibition, leading to suppression of the PI3K-AKT axis and consequent inhibition of tumor proliferation and metastasis. CONCLUSION: This study systematically elucidates the multi-component, multi-target, and multi-pathway mechanisms underlying Epimedium's anti-ovarian cancer effects, thereby providing a theoretical foundation for its potential clinical application. It should be noted, however, that these findings are computational predictions and thus require experimental validation.

Respiratory diseases pose a significant global health challenge due to their high morbidity and mortality rates. Traditional Chinese medicine (TCM), particularly the herb Epimedium, has demonstrated therapeutic potential in managing these diseases. This review systematically evaluates evidence from both in vitro and in vivo studies to assess the effects of Epimedium and its bioactive compounds, including icariin (ICA), icariside I (ICS I), icariside II (ICS II), icaritin (ICT), and others, on respiratory diseases. The synthesis of current literature reveals that these compounds exhibit anti-inflammatory, antioxidant, and immunomodulatory activities, as well as other effects crucial for the management of respiratory diseases. Further research is needed to fully understand and harness the therapeutic potential of Epimedium and its bioactive compounds in respiratory diseases. © 2025 Published by Elsevier B.V. on behalf of Xi’an Jiaotong University.

Cryptocaryon irritans Brown, 1951, a ciliated protozoan, is the pathogen of cryptocaryoniasis (white spot disease) in marine fish, causing substantial morbidity and mortality, particularly in tropical and subtropical regions. This is the first study to investigate the antiparasitic activity of baohuoside I, a natural flavonoid isolated from Epimedium brevicornu Maxim., against C. irritans. In vitro exposure to baohuoside I suppressed theront viability and tomont hatching in a dose- and time-dependent manner, inducing an apoptosis-like death in both stages, characterized by ciliary detachment, mitochondrial disruption, nuclear condensation, and extensive vacuolization, as evidenced by transmission electron microscopy and Annexin V-FITC/PI staining. Further studies demonstrated that baohuoside I elevated the intracellular Ca2+ and reactive oxygen species levels in tomonts, indicating Ca2+ overload and oxidative stress. Transcriptomic analysis of infected Larimichthys crocea skin revealed that baohuoside I upregulated immune-related genes while downregulating pro-inflammatory genes, concurrently enhancing host serum acid phosphatase activity and mitigating oxidative stress in enzyme activity assays. In vivo trials showed that oral administration of baohuoside I reduced trophont attachment and improved fish survival. It did not exhibit hemolytic activity at concentrations effective against the parasites. Collectively, these findings elucidate a multi-target mechanism of baohuoside I, highlighting its potential as an eco-friendly therapeutic agent for cryptocaryoniasis control in marine aquaculture.

OBJECTIVES: To screen key genes related to efferocytosis in osteoarthritis (OA) based on bioinformatics and machine learning methods, and explore their diagnostic value, immune microenvironment characteristics, and potential therapeutic targets of traditional Chinese medicines (TCM). METHODS: OA-related datasets GSE55235, GSE55457, and GSE117999 were obtained from the GEO database. An efferocytosis-related gene set was retrieved from GeneCards. Differential expression analysis was performed to identify OA-related differentially expressed genes (DEGs) and their intersection with efferocytosis-related genes, followed by GO and KEGG enrichment analyses. Three machine learning algorithms (Random Forest, LASSO regression, and SVM) were used to screen feature genes, and their diagnostic efficacy was evaluated using ROC curves. qRT-PCR was used to validate the feature gene expressions in a rat OA model. Immune cell infiltration was analyzed using CIBERSORT, GSEA was used to explore the related pathways, and the Coremine database was utilized to predict TCMs associated with the feature genes. RESULTS: A total of 959 OA-related DEGs were identified, including 15 efferocytosis-related genes, which were enriched in leukocyte migration, extracellular matrix, and inflammatory pathways. Machine learning identified 3 feature genes, namely UCP2, EGLN3, and IL1B, which showed good diagnostic performance in both the training (GSE55235) and validation sets (GSE55457 and GSE117999) and varying expression patterns in the mouse models. Immune infiltration analysis showed significant differences in resting mast cells, resting memory CD4⁺ T cells, and activated mast cells between OA patients and healthy controls. The feature genes were closely associated with the adipocytokine signaling pathway, sulfur metabolism, and spliceosome pathway. A total of 100 TCMs were predicted, which were primarily herbs for tonifying deficiency, clearing heat, and promoting blood circulation, such as Lycium barbarum, Epimedium brevicornu, Rehmannia glutinosa, Sophora flavescens, Ligusticum chuanxiong, and Achyranthes bidentata. CONCLUSIONS: Efferocytosis-related genes play important roles in OA pathogenes

Icaritin (ICT), a major prenylated flavone from Epimedium with anti-osteoporosis, anti-cancer, and anti-inflammatory properties, is limited clinically by poor water solubility and low bioavailability. In this study, ICT derivatives were prepared via multi-step chemical reactions and five ICT derivatives (ICTA, ICTB, ICTC, ICTD and ICTE) were successfully synthesized. Compared with ICT, most derivatives exhibited improved solubility and reduced cytotoxicity. Notably, ICTC showed a significant improvement in aqueous solubility (at least 12-fold higher), favorable lower cytotoxicity (at least 2-fold lower at 20 μM), and prominent neuroprotective effects. Mechanistically, in vitro studies revealed that ICTC targets the G protein-coupled estrogen receptor (GPER) to rescue defective mitophagy by restoring MPP+-suppressed expression of mitophagy-related proteins (PINK1, Parkin) and attenuating MPP+-induced accumulation of autophagic substrates (LC3-II, P62). In vivo, intraperitoneal injection of ICTC (0.3-3 mg/kg) effectively protected against MPTP-induced damage to dopaminergic neurons and attenuated neuroinflammation. Molecular docking, pharmacological blockade and studies in GPER knockout mouse models of Parkinson's disease (PD) confirmed that the effects of ICTC depend on GPER. Moreover, intravenous injection of ICTC also provided effective dopaminergic neuron protection, addressing the limitations of oral formulation. Overall, ICTC is a promising prodrug with enhanced solubility that exerts anti-inflammatory and neuroprotective effects in experimental PD by targeting GPER to ameliorate abnormal mitophagy.

BACKGROUND: Osteosarcopenia (OS) significantly elevates fracture risk in the elderly due to concurrent skeletal and muscular metabolic decline. Mitochondrial autophagy dysregulation is a significant mechanism driving myoskeletal metabolic imbalance, and myofibroblast-derived factor 5 (FNDC5)/irisin is a crucial mediator in the myoskeletal dialogue. It is unclear if the medicinal ingredient icariin (ICA) from the traditional Chinese herb Epimedium can work in concert to prevent and treat OS through this pathway, despite research suggesting that exercise may enhance muscular performance by modulating the FNDC5–PINK1/Parkin pathway. METHODS: With the use of dexamethasone (DEX) and ovariectomy (OVX), a female SD rat OS model was created. Low, medium, and high dosages (40, 80, and 120 mg/kg/d) of ICA were then administered. Micro-computed tomography (Micro-CT), forelimb grip strength tests, and dual-energy X-ray absorptiometry (DXA) were used to evaluate bone microarchitecture, muscle performance, and body composition, respectively. Using hematoxylin and eosin (HE) staining, the morphology of muscle tissue was investigated. In skeletal muscle, Western blotting revealed the expression of FNDC5 and mitochondrial autophagy-related proteins (PINK1, Parkin, LC3, p62). ELISA was used to evaluate the serum levels of FNDC5, muscle growth inhibitor (GDF-8), and inflammatory markers interleukin-6 (IL-6) and C-reactive protein (CRP). To directly verify the causal role of the PINK1/Parkin pathway in mediating ICA’s effects, an in vitro experiment using the mitochondrial autophagy inhibitor Mdivi-1 was performed alongside the CCCP-induced mitophagy model in C2C12 myoblasts. We used Bayesian co-localization, HEIDI heterogeneity testing, and summary-data-based Mendelian randomization (SMR) to further integrate expression quantitative trait locus (eQTL) data with genome-wide association study (GWAS) data from eQTLGen and IEU Consortium in order to genetically validate the causal relationship between FNDC5 and OS. RESULTS: DEX + OVX effectively produced a classic OS phenotype in rats, which was marked by a marked increase in fat percentage (FAT) (p < 0.01) and a significant decrease

Chronic atrophic gastritis is a precancerous condition in the gastric carcinogenesis cascade, in which persistent inflammation plays a central role. This study aimed to evaluate the protective effects of Icariside II, a bioactive flavonoid derived from Epimedium, against inflammation-associated gastric mucosal injury. A composite mouse model was established by oral inoculation with Helicobacter pylori, administration of N-methyl-N-nitrosourea in drinking water, and a high-salt diet. Mice were randomly assigned to a model control group, an Icariside II treatment group receiving 20 milligrams per kilogram per day by gavage, or an eradication therapy group. Icariside II alleviated gastric glandular atrophy and hyperplasia and significantly reduced interleukin-6, interleukin-1β, and tumor necrosis factor α levels in both serum and gastric tissue homogenates. In human gastric cancer cells exposed to an inflammatory stimulus with tumor necrosis factor α, Icariside II reduced cell proliferation and migration, promoted apoptosis, and decreased the release of pro-inflammatory cytokines. Mechanistic analyses showed that Icariside II suppressed inflammation-related signaling activity by reducing phosphorylation and nuclear translocation of key transcriptional regulators, leading to decreased expression of genes involved in inflammation, cell survival, and invasion. These findings indicate that Icariside II may represent a potential natural compound for preventing or delaying the progression of chronic atrophic gastritis.