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

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

Network Pharmacological Mechanism Research of Herba Drynariae Rhizoma-Epimedii Folium in Treating Osteoarthritis

Objective: To investigate the potential mechanism of Drynariae Rhizoma-Epimedii Folium in the treatment of osteoarthritis (OA) based on network pharmacology. Methods: The potential active constituents and targets of Drynariae Rhizoma-Epimedii Folium were screened through the traditional Chinese medicine (TCM) systems pharmacology database and analysis platform (TCMSP). Genecards database is used to find relevant targets of OA. The targets of “Drynariae Rhizoma-Epimedii Folium” were mapped to the targets of OA, and used Cytoscape software to build a “drug-ingredient-target-di- sease” regulatory network and protein protein interaction (PPI) network. R software was used to analyze the Gene ontology (GO) function and Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment of traditional Chinese medicine-disease targets. Results: Thirty-four effective ingredients and 130 traditional Chinese medicine-disease targets were screened out for the treatment of OA. The GO functions of traditional Chinese medicine-disease targets mainly included cytokine activity, cytokine receptor binding, nuclear receptor activity, transcription factor activity, proximal promoter DNA-binding transcription activator activity, DNA-binding transcription activator activity, phosphatase binding and so on. KEGG pathways involved in traditional Chinese medicine-disease targets mainly included TLR4 signaling pathway, TNF signaling pathway, IL-17 signaling pathway, MAPK signaling pathway, PI3K/AKT signaling pathway, apoptotic signaling pathway and so on. Conclusion: Network pharmacology may predict the multiple targets and multiple signaling pathways in Drynariae Rhizoma-Epimedii Folium treatment for OA, providing new ideas for future research.

Prediction of the mechanisms of liver injury of Epimedii Folium by network pharmacology and validation in HepaRG Cells

Objective:EpimediiFolium(EF),a traditional Chinese medicinal material,has the effect of tonifying kidney Yang,strengthening bones and treating rheumatism.However,its clinical applications are limited by its drug-induced liver injury(DILI)effects and the underlying mechanisms have not been elucidated.Methods:Active EF compounds were obtained from the TCMSP database and their targets predicted in Targetnet.Next,DILI-targets were obtained from CTD,Genecards and Digsee databases.Protein-protein interactions of EF DILI-targets were determined using STRING and hub targets identified via topological analyses.Then,hub targets were subjected to GO and KEGG pathway enrichment analyses.Finally,HepaRG cells were used for further validation of molecular mechanisms.Results:Fifty seven active compounds and 164 targets that interacted with these active compounds were identified with Sagittatoside A,icariside I,and Icariin being the best active compounds.Enrichment analysis revealed the PI3K/Akt and NF-kB signaling pathways to be markedly enriched.Molecular docking revealed that Sagittatoside A,icariside I and Icariin had good binding activities to RAC1,PTGS2,and NOS3.Validation analysis in HepaRG cells revealed that Epimedium flavonoids upregulated RAC1,PTGS2 and NOS3 levels.Conclusion:Our findings show that EF induces oxidative stress,inflammation,and apoptosis via PI3K/Akt and NF-kB signaling pathways,and provides a basis for more in-depth studies on EF-induced DILI.

Compatibility with Fructus Ligustri Lucidi Effectively Mitigates Idiosyncratic Liver Injury of Epimedii Folium by Modulating NOD-like Receptor Family Pyrin Domain Containing 3 Inflammasome Activation

Background: Idiosyncratic drug-induced liver injury(IDILI) is a serious side effect of drugs, Epimedii Folium(EF) is unequivocally implicated in idiosyncratic liver injury onset, potentially due to its ability to perturb the NOD-like receptor family pyrin domain containing 3(NLRP3) inflammasome. Fructus Ligustri Lucidi(FLL), a frequently used medicinal combination with EF, has not yet been investigated for its ability to ameliorate EF-associated hepatotoxicity. Aims and Objectives: Study on the mechanism of compatibility of FLL to alleviate liver injury caused by EF. Materials and Methods: Western blot was used to determine the expression of related proteins, ELISA was used to detect the secretion of related inflammatory factors IL-1β, IL-18, IL-6 and TNF-α, liver injury indexes were detected and liver pathological tissue staining was used to evaluate the liver injury. Results: Our results demonstrated that EF exerted a particular augmenting effect on the stimulation of the NLRP3 inflammasome mediated by nigericin or ATP, whereas FLL suppressed the NLRP3 inflammasome stimulation. Furthermore, an equal EF to FLL ratio significantly reduced the stimulatory effects of EF. Moreover, EF has the potential to induce hepatic injury and augment pro-inflammatory cytokine synthesis in rats subjected to LPS. However, when combined with FLL, the detrimental effects of EF were mitigated. Conclusions: FLL possesses the capacity to attenuate EF-associated hepatotoxicity by suppressing EF-triggered NLRP3 inflammasome activation. Thus, FLL holds promise for improving the clinical safety profile of EF, shedding light on the potential of compatibility and detoxification theories in traditional Chinese medicine.

Yinyanghuo(Herba Epimedii Brevicornus) and its components for chronic obstructive pulmonary disease:preclinical evidence and possible mechanisms

OBJECTIVE:To integrate Meta-analysis and bioinformatics strategies in the preliminary exploration of the potential mechanism of Yinyanghuo(Herba Epimedii Brevicornus) and its extract in treating chronic obstructive pulmonary disease(COPD).METHODS:First,Meta-analysis was carried out.The Chinese and English literature of Yinyanghuo(Herba Epimedii Brevicornus) in treating COPD was searched using the systematic strategy of combining subject words with free words.The included studies were evaluated by the SYRCLE risk bias assessment tool,after which the review manager software was used to combine the effect quantities for statistical analysis.Then,based on bioinformatics technology,the active ingredients and their targets of Yinyanghuo(Herba Epimedii Brevicornus) were screened,and the intersection genes were obtained by mapping and comparing with the targets of COPD.The "medicinal materials-compounds-targets model" was constructed,and the key pathways were annotated.Finally,the core target was docked with important compounds.RESULTS:A total of 8 studies were included in the Metaanalysis.The results showed that the Yinyanghuo(Herba Epimedii Brevicornus) group could significantly downregulate pro-inflammatory factors such as tumor necrosis factor-α(TNF-α) and interleukin(IL)-8 and increase the expression of anti-inflammatory factors and antioxidant factors such as IL-10 and phospho-protein kinase B(pAKT) in the COPD model(all P < 0.05).A total of 23 active components and 102 corresponding target genes of Yinyanghuo(Herba Epimedii Brevicornus) were obtained by bioinformatics technology,among which 17 compounds and 63 targets were closely related to COPD.The results of enrichment analysis mainly included TNF signaling pathway,phosphoinositide 3-kinase(PI3K)/Akt signaling pathway,cancer signaling pathway,and other inflammatory reactions,oxidative stress,and tumorrelated pathways.The molecular docking results showed that the binding energy fractions of the top five components of 24-epicampesterol with 10 core targets such as IL-6 were all less than ﹣5.0 kcal/mol,suggesting good binding ability.CONCLUSIONS:Meta-analysis and bioinformatics results indicated that the therapeutic effect of Yinyanghuo(Herba Epimedii Brevicornus) and its components on COPD might be related to antagonizing inflammation and oxidative stress.The above findings provide a preliminary basis for the development of Yinyanghuo(Herba Epimedii Brevicornus) as a natural drug for preventing and treating COPD.

Bibliometric analysis of 100 most-cited papers on Icariin

Icariin is the most prevalent component of the medicinal herb Herba Epimedii.Icariin exhibits many medicinal properties,including anti-cancer impact and osteoprotective and neuroprotective effects.The goal of this study was to use bibliometric analysis to find and describe the top 100 papers about Icariin that had received the most citations.The Science Citation Index-Expanded(SCI-E)of the Web of Science Core Collection was used to find publications on Icariin(WoSCC).Descriptive analysis was conducted using VOSviewer software.There were 1473 articles about Icariin in all.The top 100 papers were published between 1996 and 2024 and received citations in the range of 55 to 390.The country that has contributed the most to Icariin research is China(84).The most productive institution was Fudan University.The most published journal was Phytomedicine.The research hotspots of Icariin mainly focus on the following aspects:research on Icariin treatment of sex hormone-related osteoporosis and erectile function;The effect of Icariin on cells by regulating oxidative stress,apoptosis,and proliferation;the mechanism of Icariin in the treatment of cancer;the neuroprotective effect of Icariin in central nervous diseases,such as Alzheimer's disease,Parkinson's disease,and depression.Future research should focus on further elucidating Icariin's anti-tumor effects,its application in cartilage tissue engineering and orthopedic biomaterials,and developing novel drug delivery systems to enhance its bioavailability.This research contributed essential knowledge to the study of Icariin.These results may be used in new study areas and to direct drug development.

不同基原淫羊藿综合品质研究

目的对不同基原淫羊藿综合品质进行研究,为其质量评价及开发利用提供依据。方法分析采用Agilent ZORBAX SB-C _(18)色谱柱(4.6 mm×250 mm,5μm);流动相乙腈-0.1%磷酸,梯度洗脱;体积流量1 mL/min;柱温30℃;检测波长270 nm。建立29批样品HPLC指纹图谱。采用聚类分析、主成分分析、正交偏最小二乘法-判别分析进行化学模式识别。结果29批样品指纹图谱中有12个共有峰,指认出其中5个,相似度0.235~0.999。不同基原淫羊藿中朝藿定A、朝藿定B、朝藿定C、淫羊藿苷、宝藿苷Ⅰ含量有明显差异。各批样品聚为4类,3号峰、朝藿定B、朝藿定C、淫羊藿苷为主要成分。结论该方法专属性强,稳定可靠,可快速鉴别不同基原淫羊藿,并能对其进行质量评价。

基于BMSCs淫羊藿-仙茅-巴戟天角药抗骨质疏松药效物质提取工艺研究

目的筛选淫羊藿-仙茅-巴戟天角药抗骨质疏松药效物质的最佳提取工艺。方法采用正交设计,选取提取时间、料液比、乙醇浓度为考察因素,以BMSCs细胞增殖率结合淫羊藿苷、总黄酮含量为考察指标,筛选淫羊藿-仙茅-巴戟天角药抗骨质疏松药效物质的最佳提取工艺,并对最佳提取条件进行验证。结果兼顾生产效率和节约能源,优选出淫羊藿-仙茅-巴戟天角药药效物质的最佳提取条件为提取时间1.5 h,乙醇浓度55%,溶剂用量10倍。验证实验结果BMSCs细胞增殖率、淫羊藿苷及总黄酮含量与工艺考察结果非常接近。结论该方法在保证淫羊藿-仙茅-巴戟天角药治疗骨质疏松的药效基础上,结合淫羊藿苷及总黄酮含量进行综合评价,优化提取工艺,使得实验结果更科学合理。

New incompatible pair of TCM:Epimedii Folium combined with Psoraleae Fructus induces idiosyncratic hepatotoxicity under immunological stress conditions

Epimedii Folium(EF)combined with Psoraleae Fructus(PF)is a common modern preparation,but liver injury caused by Chinese patent medicine preparations containing EF and PF has been frequently reported in recent years.Zhuangguguanjiewan pills(ZGW),which contain EF and PF,could induce immune idiosyncratic liver injury according to clinical case reports and a nonhepatotoxic dose of lipopolysaccharide(LPS)model.This present study evaluated the liver injury induced by EF or PF alone or in combination and investigated the related mechanism by using the LPS model.Liver function indexes and pathological results showed that either EF or PF alone or in combination led to liver injury in normal rats;however,EF or PF alone could lead to liver injury in LPS-treated rats.Moreover,EF combined with PF could induce a greater degree of injury than that caused by EF or PF alone in LPS-treated rats.Furthermore,EF or PF alone or in combination enhanced the LPS-stimulated inflammatory cytokine production,implying that IL-1β,which is processed and released by activating the NLRP3 inflammasome,is a specific indicator of EF-induced immune idiosyncratic hepatotoxicity.Thus,EF may induce liver injury through enhancing the LPS-mediated proinflammatory cytokine production and activating the NLRP3 inflammasome.In addition,the metabolomics analysis results showed that PF affected more metabolites in glycerophospholipid and sphingolipid metabolic pathways compared with EF in LPS model,suggesting that PF increased the responsiveness of the liver to LPS or other inflammatory mediators via modulation of multiple metabolic pathways.Therefore,EF and PF combination indicates traditional Chinese medicine incompatibility,considering that it induces idiosyncratic hepatotoxicity under immunological stress conditions.

Icariside Ⅱ, a main compound in Epimedii Folium, induces idiosyncratic hepatotoxicity by enhancing NLRP3 inflammasome activation

Idiosyncratic drus-induced liver injury(IDILI)is an intrequent but potentially serious disease that develops the main reason for post-marketing safety warnings and withdrawals of drugs.Epimedii Folium(EF),the widely used herbal medicine,has shown to cause idiosyncratic liver injury,but the underlying mechanisms are poorly understood.Increasing evidence has indicated that most cases of IDILI are immune mediated.Here,we report that icarisideⅡ(ICSⅡ),the major active and metabolic constituent of EF,causes idiosyncratic liver injury by promoting NLRP3 inflammasome activation.ICSⅡexacerbates NLRP3 inflammasome activation triggered by adenosine triphosphate(ATP)and nigericin,but not silicon dioxide(SiO2),monosodium urate(MSU)crystal or cytosolic lipopolysaccharide(LPS).Additionally,the activation of NLRC4 and AIM2 inflammasomes is not affected by ICSⅡ.Mechanistically,synergistic induction of mitochondrial reactive oxygen species(mtROS)is a crucial contributor to the enhancing effect of ICSⅡon ATP-or nigericin-induced NLRP3 inflammasome activation.Importantly,in vivo data show that a combination of non-hepatotoxic doses of LPS and ICSⅡcauses the increase of aminotransferase activity,hepatic inflammation and pyroptosis,which is attenuated by Nlrp3 deficiency or pretreatment with MCC950(a specific NLRP3 inflammasome inhibitor).In conclusion,these findings demonstrate that ICSⅡcauses idiosyncratic liver injury through enhancing NLRP3 inflammasome activation and suggest that ICSⅡmay be a risk factor and responsible for EF-induced liver injury.

Effects of Herba Epimedii and Fructus Ligustri lucidi on the Transcription Factors in Hypothalamus of Aged Rats

Objective： To comparatively analyze the difference in the expression of 54 transcription factors in the hypothalamus using protein chips following the medication of Chinese drugs for Shen （肾）-tonification, Herba Epimedii, and Fructus Ligustri lucidi （FL） to aged rats. Methods： Wistar rats, aged 15 months of SPF grade, were randomized into three groups, three males and three females in each group. They were medicated with Herba Epimedii decoction （HED, 0.14 g/kg）, Fructus Ligustri lucidi decoction （FLD, 0.12 g/kg）, and distilled water, respectively, twice a day for 15 days. The rats were sacrificed at the morning of the 16th day 1 h after medication, and their hypothalamus was taken and made into homogenate under an ice-bath for detecting the expression of transcription factors with chip technique. Results： The expressions of signal transduction and transcription activation factor-6 （Stat-6） and androgen receptor （AR） were up-regulated, and those of pre-B transcription factor1 （Pbx-1）, stat-1 and AP-2 were down-regulated in both HED and FLD treated groups, but these changes occurred mainly in female rats in the former while mainly in males in the latter. Conclusions： Chinese drugs for Shen-tonification could impact the expression of transcription factors in the hypothalamus of aged rats, dominantly on the neuro-endocrine factors responsible for the growth and development. The effects of drugs for tonifying Shen-yang and for tonifying Shen-yin are different, which is probably one of the pharmacological mechanisms of the Shen-tonifying drugs.

The antidepressive effect of the complex consisting of Radix Pseudostellariae,Radix Pueraria and Herba Epimedii:the involvement of NRSF/NRSE-TPH2 signaling

Depression is a psychological disease with no particularly effective therapy currently available.In the present study,we aimed to examine the antidepressive activity of a pharmaceutical Chinese medicine called TaiZi(TZ)capsule,consisting of total polysaccharides of Radix Pseudostellariae and total flavonoids of both Radix Pueraria and Herba Epimedii.A tail suspension test and forced swimming test were performed to assess the effect of TZ in vivo.A plasmid of TPH2(tryptophan hydroxylase-2)was constructed to determine the exact target of TZ in vitro.In addition,mRNA expression was detected using a real-time PCR assay,and the protein expression was investigated using a Western blotting analysis.The results showed that TZ had an anti-depression effect in mouse and rat models with increased serotonin in the brain,and in the upregulation of mRNA and protein expression of TPH2 in the brain simultaneously by inhibition of NRSF(neuron restrictive silencer factor)expression because NRSF could bind to NRSE(neuron restrictive silencer element)to repress TPH2 transcription during the depression conditions.Icariin could bind to NRSE directly and block NRSF protein toward to NRSE for TPH2 inhibition.Therefore,we concluded that TZ had potential antidepressive effects because it could ameliorat the depression-like behavior in the animals,and the underlying mechanism of the effect was involved in NRSF/NRSE-TPH2 signaling.Icariin was identified as the active component of TZ.This study provided a new perspective for the development of antidepression drugs(Chinese medicines)based on NRSF/NRSE-TPH2 signaling.

基于数据挖掘的中医药治疗绝经后骨质疏松症用药规律

目的探讨中医药治疗绝经后骨质疏松症(PMOP)处方用药规律。方法检索中国知识资源总库(CNKI)、中国学术期刊数据库(万方数据)、中文科技期刊数据库(VIP)、中国生物医学文献数据库(CBM)、PubMed建库至2023年10月28日收录的中医药治疗PMOP研究文献,使用Zotero6.0文献管理系统筛选文献,数据录入中医传承辅助平台2.5中,统计用药频率、性味归经,进行关联规则分析和聚类分析。结果共纳入文献88篇,包含处方88首,涉及药物143味,总频次为952次,使用频次≥10的药物共25味,频次前5位药物为淫羊藿(57次)、熟地黄(47次)、黄芪(42次)、骨碎补(38次)、杜仲(37次)。主要药性为温性、平性,主要药味为甘、苦、辛,归经以肝经、肾经、脾经为主。关联规则以淫羊藿和熟地黄为核心,置信度最高的组合为“熟地黄+黄芪→淫羊藿”。聚类共获得10个核心药物组合及5首新处方。结论中医药治疗PMOP以补益肝肾、强筋健骨、健脾活血为主,多从肝、肾、脾三脏论治,主要使用温性、平性、甘味、苦味、辛味药物;核心药物为淫羊藿、熟地黄、黄芪、骨碎补、杜仲,常用配伍组合为“熟地黄-淫羊藿”“黄芪-淫羊藿”。

Upregulation of the angiotensin-converting enzyme 2-angiotensin-(1-7)-Mas receptor axis by a combination of Yinyanghuo(Herba Epimedii Brevicornus) and Cheqianzi(Semen Plantaginis) improves erectile function in spontaneously hypertensive rats

OBJECTIVE:To evaluate the effects of a combination of Yinyanghuo(Herba Epimedii Brevicornus)(HEB)and Cheqianzi(Semen Plantaginis)(SP)on erectile dysfunction caused by essential hypertension in spontaneously hypertensive rats(SHRs),and to elucidate the role of the angiotensin-converting enzyme 2-angiotensin-(1-7)-Mas receptor(ACE2/Ang[1-7]/Mas receptor)axis in this process.METHODS:A total of 24 SHRs were randomly assigned to three groups:SHR-control,low-dose(12.5 g/kg)and high-dose(25 g/kg)HEB+SP(HEBSP).Eight Wistar-Kyoto rats were used as normal controls.HEBSP was administered by oral gavage for 28 d.Erectile function was measured once a week using the Heaton test.After 4 weeks of treatment,the corpus cavernosum was harvested from each rat to measure nitric oxide(NO),nitric oxide synthase(e NOS)and Ang(1-7)levels,as well as ACE2,Mas receptor and neuronal nitric oxide synthase(n NOS)protein expression.RESULTS:After 4 weeks of treatment,HEBSP significantly increased erectile function in the treated group compared with SHR-control group(P<0.01).Additionally,HEBSP treatment significantly increased cavernosal levels of Ang(1-7),e NOS and NO.Moreover,HEBSP significantly elevated the expression levels of ACE2,Mas receptor and n NOS.These beneficial effects were elevated in the high-dose HEBSP group.CONCLUSION:HEBSP improved erectile function in SHRs by upregulating the ACE2/Ang(1-7)/Mas receptor axis,e NOS and n NOS pathways.

Efficacy of an Yinyanghuo(Herba Epimedii Brevicornus)-Xianmao(Rhizoma Curculiginis)drug pair in a rat model of polycystic ovary syndrome

OBJECTIVE:To identify active compounds in an Yinyanghuo(Herba Epimedii Brevicornus)-Xianmao(Rhizoma Curculiginis)drug pair(ECD)and investigate its efficacy on polycystic ovary syndrome(PCOS),and its possible mechanism in a rat model of PCOS.METHODS:A network pharmacology approach involving a characteristic drug assessment,active compound and target prediction,PCOS gene collection as well as network analysis was employed.The ovary morphology after treatment was observed using an animal model and western blotting and real-time PCR were used to verify AKT1 as the molecular target.RESULTS:Six networks were constructed,an active compound-target network for the ECD(C-T network),a drug-target network(D-T network),a related genes network,a targets interaction network,a key genes interaction network,and a gene-pathway network.A total of 41 compounds and 261 targets were identified for the ECD,232 PCOS-related genes,31 cogenes,and 14 pathways.These pathways may be involved in the efficacy of ECD on PCOS.The proteins most involved in the signal pathways for all targets were AKT1,IL6,INSR,ESR,and GSK3B.The AKT1 target was selected for experimental verification.Based on the Western blot and real-time PCR results,the expression of AKT1 in the PCOS model varied after treatment with ECD.CONCLUSIONS:Our findings suggest that the ECD can reverse the negative morphological changes in ovarian tissue that occur in model rats of PCOS.AKT1 may be a key mediator of the observed ability of the ECD to protect against PCOS in the model rats.

淫羊藿的生物活性及现代临床应用研究进展

淫羊藿的生物活性包括免疫活性、抗衰老抗氧化、抗骨质疏松、抗肿瘤、抗心肌缺氧、降血糖、抗炎症、抗动脉粥样硬化、神经保护作用等;其现代应用包括淫羊藿相关产品开发(临床药物、保健食品、动物饲料补充剂)及淫羊藿培育等。目前,关于淫羊藿的药理研究仍处于初级阶段,许多实验研究集中在实验室环境中的动物模型上,缺乏相应的临床研究和全面的循证医学证据;淫羊藿市场应用较为局限,目前主要为保健食品和动物饲料补充剂,生物利用率低。今后,应在加大研究力度的基础上,采用循证医学和大数据技术,对中医药的临床路径进行评估分析处方集,识别药物模式,整合临床标记物来观察中药的变化;作为药食同源药物的典范,淫羊藿具有预防保健作用,可开发成多种形式的功能性产品,如养生茶包、保健药酒、抗衰老化妆品等;结合肠道菌群,可通过3D打印技术研制新型药物载体,采用中药纳米化、中药发酵等技术增加其活性含量,提高难溶性物质的溶解度。

仙茅-淫羊藿对药治疗老年肾阳虚型骨质疏松症临床研究

目的:观察仙茅-淫羊藿对药治疗肾阳虚型老年骨质疏松症(OP)的临床效果。方法:选取90例肾阳虚型老年OP患者为研究对象,随机分为A组、B组、C组,各30例。所有患者均按医嘱完成治疗,无剔除病例。A组给予基础治疗,B组在基础治疗上给予对药1号方(低剂量)治疗,C组在基础治疗上给予对药2号方(高剂量)治疗。治疗24周后,比较3组临床疗效、中医证候评分、疼痛视觉模拟评分法(VAS)评分、骨密度、骨代谢指标[Ⅰ型前胶原氨基末端前肽(PⅠNP)、β-胶原羧基端肽(β-CTX)、血清钙、血清磷]、炎症因子指标[血清白细胞介素-1β(IL-1β)、白细胞介素-6(IL-6)、肿瘤坏死因子-α(TNF-α)]水平、安全性及不良反应发生率。结果:治疗后,C组临床总有效率为96.67%,高于A组(66.67%)、B组(80.00%),差异均有统计学意义(P<0.05)。治疗12、24周,3组中医证候评分、VAS评分均较治疗前降低(P<0.05),且C组相同时间点的中医证候评分、VAS评分均低于A组、B组(P<0.05)。治疗24周,3组股骨颈、L_(2~4)骨密度T值均较治疗前提高(P<0.05),B组、C组股骨颈、L_(2~4)骨密度T值均高于A组(P<0.05),而B组、C组比较差异无统计学意义(P>0.05)。治疗12、24周,3组PⅠNP水平较治疗前均提高(P<0.05),且B组、C组PⅠNP水平高于A组(P<0.05);3组β-CTX水平较治疗前均降低(P<0.05),且B组、C组β-CTX水平低于A组(P<0.05);B组、C组相同时间点的PⅠNP、β-CTX水平比较,差异无统计学意义(P>0.05)。3组血清磷、钙水平治疗前后比较,差异均无统计学意义(P>0.05)。治疗12、24周,3组血清IL-1β、IL-6、TNF-α水平均较治疗前降低(P<0.05),且呈降低趋势(P<0.05);C组上述各项炎症指标水平在相同时间点均低于A组、B组(P<0.05)。治疗期间,A组、B组未见不良反应病例,C组出现口干5例、便秘4例,不良反应发生率为30.00%;3组不良反应发生率比较,差异有统计学意义(P<0.05)。结论:仙茅-淫羊藿对药治疗老年OP肾阳虚型疗效显著,其中对药2号方(高剂量)能进一步提高疗效,促进症状体征缓解,在改善骨密度、骨代谢指标及减轻机体炎症反应方面更有优势,且不影响机体血清磷钙代谢,但因药物剂量过大而易引发口干、便秘等不良反应。

汉中产淫羊藿不同部位黄酮含量比较分析

【目的】对陕西省汉中市所产淫羊藿不同部位的黄酮含量进行检测比较,为该地区淫羊藿的质量控制提供理论依据。【方法】采集汉中市九县二区,共17批(个)淫羊藿植株地上、地下部分,按照根、茎、叶柄、叶片4个部位,使用高效液相色谱(HPLC)测定朝藿定A1、朝藿定A、朝藿定B、朝藿定C、淫羊藿苷、宝藿苷Ⅰ共6种黄酮类成分,对淫羊藿4个部位的含量差异进行检测分析;并通过HPLC对所有样品构建淫羊藿特征指纹图谱,利用中药指纹图谱相似度评价系统判定和指认共有峰,最后绘制17批(个)样品的HPLC指纹图谱。【结果】淫羊藿叶片中6种成分含量均明显高于叶柄和茎;根中6种成分差异较大,其中朝藿定C含量为0.536%~4.712%。根、茎、叶柄和叶片的6种成分总含量分别为0.616%~5.141%、0.006%~0.136%、0.007%~0.271%和0.588%~5.100%;通过中药指纹图谱确定了17批(个)样品中朝藿定A1、朝藿定A、朝藿定B、朝藿定C、淫羊藿苷、宝藿苷Ⅰ6个共有峰,其根、茎、叶柄和叶片的相似度分别为0.962~1.000、0.791~0.990、0.728~0.996和0.629~0.995。【结论】基于多成分含量测定,明确了汉中产淫羊藿根、茎、叶柄和叶片的质量差异;构建了汉中产淫羊藿HPLC指纹图谱。

淫羊藿药材中黄酮类成分提取工艺优选

目的优选淫羊藿药材中黄酮类成分提取工艺。方法采用高效液相色谱法测定淫羊藿药材中朝藿定A1、朝藿定A、朝藿定B、朝藿定C、淫羊藿苷、宝藿苷Ⅰ含量。在单因素试验基础上,以提取溶剂、液料比、提取时间、提取次数为考察因素,待测成分提取总量为考察指标,采用响应面法优选淫羊藿药材中黄酮类成分的提取工艺。结果最佳提取工艺为液料比100(mL/g)时,以50%乙醇提取2次,每次40 min。验证试验结果显示,待测成分提取总量分别为3.16%,3.08%,3.03%,与预测值(3.12%)相当。结论该提取工艺合理可行,可为淫羊藿药材的进一步研发提供参考。

淫羊藿苷药理作用及应用研究进展

淫羊藿(Epimedium brevicornum Maxim)是一种中药材,广泛用于各种现代中成药产品和传统中药制剂。淫羊藿属植物中化学成分丰富,现已发现黄酮、多糖、植物甾醇等260多种化学成分,其中淫羊藿苷(Icariin,ICA)含量最丰富。淫羊藿苷不仅具有广泛的药理作用,如生殖功能、骨保护作用、神经保护作用、心血管保护作用,还有一定的抗病效果,如抗肿瘤作用、抗炎作用、提高免疫力等,并能用于治疗多种疾病。结合近年来国内外研究现状,对淫羊藿苷的药理作用及在相关疾病预防治疗的应用进行综述,以期为其未来的产品开发和相关疾病的预防治疗提供参考依据。