Herb pair of Huangqi-Danggui exerts anti-tumor immunity to breast cancer by upregulating PIK3R1

Background:According to traditional Chinese medicine(TCM),drugs supplementing the vital energy,Qi,can eliminate tumors by restoring host immunity.The objective of this study is to investigate the underlying immune mechanisms of anti-tumor activity associated with Qi-supplementing herbs,specifically the paired use of Huangqi and Danggui.Methods:Analysis of compatibility regularity was conducted to screen the combination of Qi-supplementing TCMs.Using the MTT assay and a transplanted tumor mice model,the anti-tumor effects of combination TCMs were investigated in vitro and in vivo.High content analysis and flow cytometry were then used to evaluate cellular immunity,followed by network pharmacology and molecular docking to dissect the significant active compounds and potential mechanisms.Finally,the anti-tumor activity and the mechanism of the active ingredients were verified by molecular experiments.Results:There is an optimal combination of Huangqi and Danggui that,administered as an aqueous extract,can activate immunity to suppress tumor and is more effective than each drug on its own in vitro and in vivo.Based on network pharmacology analysis,PIK3R1 is the core target for the anti-tumor immunity activity of combined Huangqi and Danggui.Molecular docking analysis shows 6 components of the combined Danggui and Huangqi extract(quercetin,jaranol,isorhamnetin,kaempferol,calycosin,and suchilactone)that bind to PIK3R1.Jaranol is the most important component against breast cancer.The suchilactone/jaranol combination and,especially,the suchilactone/kaempferol combination are key for immunity enhancement and the anti-tumor effects of the extract.Conclusions:The combination of Huangqi and Danggui can activate immunity to suppress breast cancer and is more effective than the individual drugs alone.

Spatiotemporal transformable nano-assembly for on-demand drug delivery to enhance anti-tumor immunotherapy

Induction of tumor cell senescence has become a promising strategy for anti-tumor immunotherapy,but fibrotic matrix severely blocks senescence inducers penetration and immune cells infiltration.Herein,we designed a cancer-associated fibroblasts(CAFs)triggered structure-transformable nano-assembly(HSD-P@V),which can directionally deliver valsartan(Val,CAFs regulator)and doxorubicin(DOX,senescence inducer)to the specific targets.In detail,DOX is conjugated with hyaluronic acid(HA)via diselenide bonds(Se-Se)to form HSD micelles,while CAFs-sensitive peptide is grafted onto the HSD to form a hydrophilic polymer,which is coated on Val nanocrystals(VNs)surface for improving the stability and achieving responsive release.Once arriving at tumor microenvironment and touching CAFs,HSD-P@V disintegrates into VNs and HSD micelles due to sensitive peptide detachment.VNs can degrade the extracellularmatrix,leading to the enhanced penetration of HSD.HSD targets tumor cells,releases DOX to induce senescence,and recruits effector immune cells.Furthermore,senescent cells are cleared by the recruited immune cells to finish the integrated anti-tumor therapy.In vitro and in vivo results show that the nanoassembly remarkably inhibits tumor growth as well as lungmetastasis,and extends tumorbearing mice survival.This work provides a promising paradigm of programmed delivering multi-site nanomedicine for cancer immunotherapy.

Anti-Tumor and Anti-Diabetic Effects of Sarsasapogenin

In this paper,the pharmacological effects and molecular mechanisms of sarsasapogenin,such as anti-oxidant,anti-inflammatory and anti-diabetic effects,are reviewed in order to provide a theoretical basis for the subsequent development and clinical application of sarsasapogenin.

Mechanism of Anti-tumor Effects of Viola Medicinal Materials Based on Network Pharmacology and Molecular Docking

[Objectives]To explore the relationship between anti-tumor components,targets,and pathways involved in Viola medicinal materials,study its main active components,and evaluate its inhibitory activity.[Methods]Through network pharmacological analysis,molecular docking simulation experiments and in vitro experiments,the main components and corresponding targets of Viola were screened out,and their anti-tumor signaling pathways were confirmed.MTT colorimetric assay was used to investigate the inhibitory effect of different extraction layers of Viola on the growth of tumor cells.[Results]18 anti-tumor active components such as 2α,19α-Dihydroxyursolic acid,Corlumine,Madolin U,Trifolirhizin and etc.,and 52 action targets such as PTGS2,PTGS1,P2RX7,MMP1,and GABRB3,and anti-tumor signaling pathways were confirmed.The results of molecular docking showed that all the selected Viola compounds had good binding activity.The results of MTT colorimetric assay showed that the petroleum ether layer and n-butanol layer had a good inhibitory effect on the growth of tumor cell lines.[Conclusions]Viola medicinal materials have the potential of anti-tumor,triterpenoids and flavonoids may be the main active components,and the petroleum ether layer and n-butanol layer have better inhibitory effect on the growth of tumor cells.

Advances in Research of Anti-tumor Effect of Aconiti Radix

In this paper,the anti-tumor effects of Aconiti Radix were reviewed and summarized,and the clinical feasibility of Aconiti Radix as a potential anti-tumor drug was analyzed,in order to provide a useful reference for the future research and development of new anti-cancer drugs of Aconiti Radix.

Screening for Anti-tumor Activity of Fractions from Buddleja officinalis Maxim

[Objectives]The anti-tumor activity of fractions from Buddleja officinalis Maxim.by petroleum ether,ethyl acetate,n-butanol and water solvent was studied.[Methods]The ethanol extract from B.officinalis Maxim.was extracted and then concentrated with petroleum ether,ethyl acetate,n-butanol and water,respectively,and the extracts were obtained.The inhibitory effects of the four different fractions on the growth of three tumor cell lines in vitro were detected by CCK-8 method,and the median inhibitory concentration(IC 50 value)was calculated.[Results]The four fractions inhibited the growth of the three tumor cell lines in vitro,among which the n-butanol fraction had the best anti-tumor activity.The IC 50 values of the n-butanol fraction on human gastric cancer(SGC-7901),human breast cancer(MCF-7)and human liver cancer(BEL-7404)cell lines were 0.08,1.58 and 0.12 mg/mL,respectively.[Conclusions]Petroleum ether,ethyl acetate,n-butanol and water fractions from the ethanol extract of B.officinalis Maxim.had certain anti-tumor effects,and the n-butanol fraction had the best anti-tumor activity.

Treatment of primary nasal tuberculosis with anti-tumor necrosis factor immunotherapy:A case report

BACKGROUND Primary nasal tuberculosis(TB)is a rare form of extrapulmonary TB,particularly in patients receiving anti-tumor necrosis factor(TNF)immunotherapy.As a result,its diagnosis remains challenging.CASE SUMMARY A 58-year-old male patient presented to the ear,nose,and throat department with right-sided nasal obstruction and bloody discharge for 1 month.He was diagnosed with psoriatic arthritis and received anti-TNF immunotherapy for 3 years prior to presentation.Biopsy findings revealed chronic granulomatous inammation and a few acid-fast bacilli,suggestive of primary nasal TB.He was referred to our TB management department for treatment with oral anti-TB agents.After 9 months,the nasal lesions had disappeared.No recurrence was noted during follow-up.CONCLUSION The diagnosis of primary nasal TB should be considered in patients receiving TNF antagonists who exhibit thickening and crusting of the nasal septum mucosa or inferior turbinate,particularly when pathological findings suggest granulomatous inflammation.

Emodin attenuates inflammation and demyelination in experimental autoimmune encephalomyelitis

Emodin,a substance extracted from herbs such as rhubarb,has a protective effect on the central nervous system.However,the potential therapeutic effect of emodin in the context of multiple sclerosis remains unknown.In this study,a rat model of experimental autoimmune encephalomyelitis was established by immune induction to simulate multiple sclerosis,and the rats were intraperitoneally injected with emodin(20 mg/kg/d)from the day of immune induction until they were sacrificed.In this model,the nucleotide-binding domain-like receptor family pyrin domain containing 3(NLRP3)inflammasome and the microglia exacerbated neuroinflammation,playing an important role in the development of multiple sclerosis.In addition,silent information regulator of transcription 1(SIRT1)/peroxisome proliferator-activated receptor-alpha coactivator(PGC-1α)was found to inhibit activation of the NLRP3 inflammasome,and SIRT1 activation reduced disease severity in experimental autoimmune encephalomyelitis.Furthermore,treatment with emodin decreased body weight loss and neurobehavioral deficits,alleviated inflammatory cell infiltration and demyelination,reduced the expression of inflammatory cytokines,inhibited microglial aggregation and activation,decreased the levels of NLRP3 signaling pathway molecules,and increased the expression of SIRT1 and PGC-1α.These findings suggest that emodin improves the symptoms of experimental autoimmune encephalomyelitis,possibly through regulating the SIRT1/PGC-1α/NLRP3 signaling pathway and inhibiting microglial inflammation.These findings provide experimental evidence for treatment of multiple sclerosis with emodin,enlarging the scope of clinical application for emodin.

Progress on the Study of the Anti-Tumor Effect of Emodin

Cancer is a disease caused by the loss of normal cell regulation and excessive proliferation. At present, there are a lot of anticancer drugs, but most of them are not ideal, with sereve side effects. Besides, during the treatment, the patients feel very bad, and they are always in great pain. Emodin is a natural anthraquinone derivative found in a variety of herbal preparations. Many studies have shown that emodin has a significant therapeutic effect on lung cancer, liver cancer, breast cancer, and so on. After reviewing a large amount of literatures, this paper summarizes the research progresses of emodin anticancer in the past five years, in order to provide theoretical basis for further development and utilization of emodin and its metabolites.

In vitro study of emodin-induced nephrotoxicity in human renal glomerular endothelial cells on a microfluidic chip

Emodin is an effective component of rhubarb with positive pharmacological effects on human health.However,it is also toxic to different cells or tissues to varying degrees.The effects of emodin on glomerular endothelial cells(GECs)remain to be tested,and the documented works were always performed in vitro and hardly reflect the real physiological situation.To study the effects of emodin on GECs in a biomimetic environment,we utilized a microfluidic chip to assess the physiological reaction of human renal glomerular endothelial cells to various concentrations of emodin in this work.The results showed that emodin caused cytotoxicity,impaired glomerular filtration barrier integrity to macromolecules,and increased barrier permeability in a dose-dependent manner.With the increase in emodin concentration,the concentration of the pro-inflammatory cytokine tumor necrosis factor-α,interleukin(IL)-6,transforming growth factor-β1,and monocyte chemoattractant protein(MCP-1)increased while the production of inflammatory cytokine IL-6 first increased and then decreased with the increase in emodin concentration.Our findings shed new light on emodin-induced nephrotoxicity and provide insights for the application of microfluidic chip devices to reveal drug-cell interactions.

Anti-tumor,Anti-allergy,Anti-angiogenesis and Hepatoprotective Effects of Deoxypodophyllotoxin and Its Molecular Mechanism

Deoxypodophyllotoxin not only has pharmacological effects such as anti-allergy,anti-angiogenesis and liver protection,but also has good anti-tumor activity.It can play an anti-tumor role by inhibiting cell viability,inducing apoptosis,blocking cell cycle and inhibiting cell migration.In this paper,the related research on pharmacological effect and mechanism of deoxypodophyllotoxin is reviewed,to lay a foundation for the follow-up study of deoxypodophyllotoxin and drug development.

Anti-tumor Activity of Isovanillin and Its Molecular Mechanism

Taking isovanillin and the important products synthesized from raw materials of isovanillin as objects,this paper reviews its pharmacological effects and molecular mechanisms,including inhibiting tumor angiogenesis,blocking cancer cell self-repair,inducing cancer cell DNA fragmentation,cytotoxicity,inhibiting tumor growth,regulating brain nerves,inhibiting renin and other pharmacological effects,etc.,which provide new ideas for the in-depth research and development of isovanillin.

Research Progress in Anti-tumor Effects of Traditional Chinese Medicine and Its Extracts

Traditional Chinese medicine and its extracts have received widespread attention due to their significant anti-tumor effects and low adverse reactions.Many traditional Chinese medicine and its extracts have been applied in clinical tumor treatment.In this paper,the research progress in anti-tumor effects of plant-based traditional Chinese medicine and its extracts,animal-based traditional Chinese medicine and its extracts,and traditional Chinese medicine compound is reviewed.

Activity Screening Study on the Anti-tumor Effects of Extracts from Mahoniae caulis

[Objectives]To explore the anti-tumor activity of the extracts of petroleum ether,ethyl acetate,n-butanol and aqueous solution from Mahoniae caulis.[Methods]The extracts were extracted with petroleum ether,ethyl acetate,n-butanol and aqueous solution respectively,and then concentrated.The inhibitory effects of these extracts on the growth of three tumor cell lines in vitro were detected by CCK-8 method,and the IC 50 value was calculated.[Results]The four extracts inhibited the growth of the three tumor cell lines in vitro,among which the n-butanol extract had the best anti-tumor activity.The IC 50 values of the n-butanol extract on human gastric cancer(SGC-7901),human breast cancer(MCF-7)and human liver cancer(BEL-7404)cell lines were 0.23,0.25 and 0.58 mg/mL,respectively.[Conclusions]The ethanol extract of Mahoniae caulis under petroleum ether,ethyl acetate,n-butanol and aqueous solution had certain anti-tumor effect,and n-butanol extract had the best anti-tumor activity.

大黄素对骨关节炎软骨细胞增殖、凋亡和氧化应激的影响

背景:既往研究显示,沉默交配型信息调节因子2同源蛋白1(silent mating-type information regulator 2 homolog 1,SIRT1)-雷帕霉素机械靶蛋白(mechanistic target of rapamycin,mTOR)信号在骨关节炎进展中起重要作用,大黄素对骨关节炎软骨细胞有一定的保护作用。目的:基于SIRT1-mTOR探究大黄素对骨关节炎软骨细胞增殖、凋亡和氧化应激的影响。方法:体外分离培养大鼠软骨细胞,采用10 ng/mL的白细胞介素1β诱导构建体外骨关节炎细胞模型,以CCK-8法测定经0,20,40,80,120,160μmol/L的大黄素处理后的大鼠软骨细胞活力,选出合适大黄素作用浓度。将软骨细胞随机分为对照组、模型组、大黄素低剂量组、大黄素高剂量组、SIRT1抑制剂EX527组、大黄素高剂量+EX527组,除对照组外其余各组以10 ng/mL的白细胞介素1β诱导构建体外骨关节炎模型,同时以大黄素和EX527分组处理细胞后,用CCK-8法、Edu染色法及流式细胞术分别检测各组细胞增殖与凋亡情况;用试剂盒检测各组细胞活性氧相对含量、丙二醛与抗氧化酶超氧化物歧化酶、过氧化氢酶、谷胱甘肽过氧化物酶水平;免疫印迹检测各组细胞基质降解、凋亡与SIRT1-mTOR通路相关蛋白表达。结果与结论:①与对照组相比,模型组大鼠软骨细胞活力、Edu阳性率、超氧化物歧化酶与过氧化氢酶、谷胱甘肽过氧化物酶水平、Bcl-2与SIRT1蛋白表达降低,凋亡率、活性氧相对含量、丙二醛水平、Bax与基质金属蛋白酶3、基质金属蛋白酶9蛋白表达及p-mTOR/mTOR升高(P<0.05)。与模型组相比,大黄素低、高剂量组上述各项指标呈相反变化(P<0.05);EX527组各指标水平与大黄素各组呈相反趋势(P<0.05)。②与大黄素高剂量组相比,大黄素高剂量+EX527组细胞活力、Edu阳性率、超氧化物歧化酶与过氧化氢酶、谷胱甘肽过氧化物酶水平、Bcl-2与SIRT1蛋白表达降低,凋亡率、活性氧相对含量、丙二醛水平、Bax与基质金属蛋白酶3、基质金属蛋白酶9蛋白表达及p-mTOR/mTOR升高(P<0.05)。③结论:大黄素可通过激活SIRT1-mTOR信号而抑制骨关节炎软骨细胞氧化应激,从而促进软骨细胞增殖并减轻其凋亡。

Research Progress on Anti-tumor Mechanism of Clearing Heat-Toxin Intervention of Apoptosis-related Proteins

Apoptosis is a spontaneous programmed cell death process,which is closely related to the occurrence and development of tumors.Inducing apoptosis of tumor cells has become an important way of anti-tumor therapy.Studies have found that clearing heat-toxin Chinese medicine has a significant effect on inducing apoptosis,which may be the key mechanism of anti-tumor of Chinese medicine.By reviewing the theoretical origin of anti-tumor TCM of clearing heat-toxin Chinese herbs and the pharmacological research progress of intervening apoptosis-related proteins to promote apoptosis of tumor cells,this paper provides a basis for TCM to induce apoptosis of tumor cells to prevent and treat malignant tumors.

Research on Incentive Policies for Chinese Innovative Drug R&D - Taking Innovative Anti-tumor Drugs as an Example

Objective To provide reference for improving Chinese innovative drug research and development incentive policies.Methods Based on investigating the incentive policies for innovative drug research and development in clinical research,evaluation and approval in China,anti-tumor drugs were taken as the research object to discuss relevant policies from the perspective of clinical trials and registration approval based on data statistics and current situation analysis.Results and Conclusion Driven by a series of incentive policies for innovative drug R&D,great achievements have been made on anti-tumor drugs.However,there are problems such as concentration of drug targets,homogenization of clinical trials,and gaps in some drugs with large clinical needs.To improve incentive policies for innovative drug R&D,China should adhere to the orientation of clinical value,focusing on basic research and translational research,improving evaluation and approval capabilities,and establishing a sound ecosystem for innovative drugs.

酪蛋白胶束-果胶复合物微胶囊对大黄素的负载作用

大黄素(emodin,E)是大黄中的主要活性成分,是一种疏水性分子。酪蛋白胶束(micellar casein,MC)是乳中酪蛋白的天然存在形态。该文采用荧光分析法研究了不同果胶(pectin,P)添加量下酪蛋白胶束与大黄素的结合作用,解析了果胶-酪蛋白胶束@大黄素(P-MC@E)复合物粒径及结构,评价了复合物的DPPH自由基和ABTS阳离子自由基清除活性,并通过模拟胃肠消化实验分析了复合物中大黄素的释放状况。结果显示,P-MC复合体系中,当果胶与酪蛋白胶束比例为0∶10~5∶5时,酪蛋白胶束与大黄素的结合作用均为疏水作用,二者结合常数大于103。随着果胶添加量的增加,P-MC@E复合物粒径逐渐增大,但其红外谱图没有显著变化。另外,复合物的DPPH自由基和ABTS阳离子自由基清除活性较游离大黄素显著提升,且随果胶添加量的增加而显著增大。与P-MC形成复合物后,大黄素的胃肠模拟消化释放率降低。研究结果可为大黄素的负载和递送提供参考依据。

不同来源芦荟药材品质评价研究

目的:对不同来源的24份芦荟药材品质进行分析及评价,为芦荟后期开发利用提供参考。方法:参照2020年版《中华人民共和国药典》的检测方法和含量要求及相关文献,测定不同来源的24份芦荟药材的性状、杂质、水分、总灰分、浸出物以及芦荟苷、芦荟大黄素含量。结果:进口芦荟药材性状主要是不规则块状,少部分粉末状;表面棕褐色,较粗糙,较有光泽;断面棕褐色,较光滑,较有光泽。国产芦荟药材性状主要是圆饼状,表面较粗糙,呈黑褐色,略有光泽,断面粗糙,呈黑褐色,略有光泽。杂质含量在0.00%~0.05%之间。水分含量均符合规定,达标率为100.00%。总灰分含量只有9份符合规定,达标率为37.50%(9/24)。浸出物含量范围在2.82%~93.57%之间。大部分芦荟苷含量测定未达到2020年版《中华人民共和国药典》中的标准(芦荟苷含量库拉索芦荟不得少于16.00%,好望角芦荟不得少于6.00%),仅有7份芦荟苷含量符合规定,达标率为29.17%(7/24)。13份无法检出芦荟大黄素,11份芦荟大黄素含量范围为0.07%~0.63%。结论:当前药材市场上芦荟主要为进口芦荟和国产芦荟,质量参差不齐,进口芦荟药材品质较为优良,在以后的生产、销售过程中应注意加强产地初加工监督管理,进一步提高药材品质。

基于动物实验系统评价大黄素治疗糖尿病肾病的可行性

目的:系统评价大黄素对糖尿病肾病动物肾脏的保护作用。方法:计算机检索中国知网、维普、万方、中国生物医学文献及PubMed等数据库,检索从建库至2023年2月25日关于大黄素治疗糖尿病肾病的动物实验。采用RevMan 5.4.1软件进行分析。结果:共纳入14个研究,结果显示,相比于对照组,大黄素组更能降低糖尿病动物血糖[SMD=-2.51,95%CI(-3.77,-1.24),I^(2)=89%]、肌酐[SMD=-3.05,95%CI(-4.75,-1.34),I^(2)=91%]、尿素氮[SMD=-2.69,95%CI(-3.88,-1.50),I^(2)=82%]、24 h尿蛋白定量[SMD=-3.35,95%CI(-4.85,-1.85),I^(2)=87%]、相对肾重[SMD=-7.72,95%CI(-12.55,-2.88),I^(2)=90%]、三酰甘油[SMD=-1.24,95%CI-1.94,-0.54),I^(2)=0%]等指标。而大黄素与对照组在胆固醇[SMD=-1.19,95%CI(-2.29,-0.55),I^(2)=77%]等方面的差异无统计学意义。同时Meta分析提示大黄素保护肾脏与nephrin的表达、相关信号通路等有关。此类研究相关的严重不良反应鲜有报道。结论:大黄素对糖尿病肾病动物肾脏有保护作用,但有待于更高质量、严谨规范的大样本临床试验进一步证实。