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Integration of transcriptomics and metabolomics to study the mechanism of Siwei Huangqi powder in Tibetan medicine for protecting against high-altitude hypoxic brain injuries
IF 3 3区 医学 Q1 INTEGRATIVE & COMPLEMENTARY MEDICINE Pub Date : 2024-11-05 DOI: 10.1016/j.jtcme.2024.11.002
Wangjie Cao , Jiawang Guo , Nengxian Zhang , Xinjue Zhang , Congyi Li , Yong Huang , Jianzheng He , Yongqi Liu , Hongxia Gong , Yun Su

Background and aim

Siwei Huangqi powder (SWHQP) is a folk medicine that is extensively used in Tibetan medicine. It is widely employed at the medical institutions of various monasteries in the Tibetan region and is highly recommended by esteemed folk practitioners. It is mainly used in clinical practice for high-altitude diseases caused by an imbalance of the three bases of Tibetan medicine, namely, Long, Chiba, and Peigen, which leads to disorders of qi and blood circulation. This study aimed to investigate the potential molecular mechanism underlying the therapeutic and preventive effects of SWHQP in a high-altitude hypoxia brain injury (HHBI) rat model.

Methods

An HCP-III experimental animal low-pressure simulation chamber was used to simulate high-altitude hypoxic environmental exposure in rats to establish an HHBI model. The severity of brain injury, including the brain wet/dry (W/D) ratio and H&E staining, was evaluated through a series of assessments. Transcriptomic and metabolomic analyses were performed to identify gene expression changes and metabolite alterations in brain tissue. Western blotting and immunofluorescence were used to assess the relative expression of proteins involved in the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT)/nuclear factor-kappa B p65 (NF-kB p65) pathway. The expression levels of genes related to the PI3K/AKT/NF-κB p65 signaling pathway were detected via real-time PCR. Enzyme-linked immunosorbent assays (ELISAs) were conducted to measure the serum levels of proinflammatory cytokines such as tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-1β (IL-1β).

Results

SWHQP significantly improved brain function, reduced the wet/dry ratio, and alleviated brain tissue damage. Transcriptomic and metabolomic analyses revealed that the PI3K/AKT/NF-κB signaling pathway was significantly upregulated in the HHM group and that the expression of inflammatory factors related to amino acid metabolism and lipid metabolism was increased. A previous study also revealed that SWHQP inhibited the activation of the PI3K/AKT/NF-κB p65 signaling pathway in brain tissue, reducing the release of the downstream proinflammatory cytokines IL-6, IL-1β, and TNF-α.

Conclusion

The therapeutic effect of SWHQP on brain injury in HHBI rats is attributed to its ability to regulate inflammation-related amino acid synthesis and lipid metabolism and modulate inflammation-related pathways. These findings provide a robust research foundation for the potential clinical application of SWHQP in Tibetan medicine.
本研究旨在探讨SWHQP对高海拔缺氧脑损伤(HHBI)大鼠模型的治疗和预防作用的潜在分子机制。方法采用HCP-III型实验动物低压模拟室模拟大鼠高海拔缺氧环境暴露,建立HHBI模型。通过一系列评估评估脑损伤的严重程度,包括脑湿/干(W/D)比和H&;E染色。转录组学和代谢组学分析用于鉴定脑组织中基因表达的变化和代谢物的改变。采用Western blot和免疫荧光法检测磷脂酰肌醇3-激酶(PI3K)/蛋白激酶B (AKT)/核因子κ B p65 (NF-kB p65)通路相关蛋白的相对表达。real-time PCR检测PI3K/AKT/NF-κB p65信号通路相关基因的表达水平。采用酶联免疫吸附法(elisa)检测血清促炎因子如肿瘤坏死因子-α (TNF-α)、白细胞介素-6 (IL-6)和白细胞介素-1β (IL-1β)水平。结果sswhqp能显著改善大鼠脑功能,降低干湿比,减轻脑组织损伤。转录组学和代谢组学分析显示,HHM组PI3K/AKT/NF-κB信号通路显著上调,氨基酸代谢和脂质代谢相关炎症因子表达增加。先前的研究也发现,SWHQP抑制脑组织PI3K/AKT/NF-κB p65信号通路的激活,减少下游促炎细胞因子IL-6、IL-1β和TNF-α的释放。结论SWHQP对HHBI大鼠脑损伤的治疗作用可能与其调节炎症相关氨基酸合成和脂质代谢,调节炎症相关通路有关。
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引用次数: 0
Antiosteoporotic activity of nodakenetin, a coumarin compound from Angelica decursiva, by activation of the Wnt/β-catenin signaling pathway 从当归中提取的香豆素化合物nodakenetin通过激活Wnt/β-catenin信号通路的抗骨质疏松活性
IF 3 3区 医学 Q1 INTEGRATIVE & COMPLEMENTARY MEDICINE Pub Date : 2024-11-05 DOI: 10.1016/j.jtcme.2024.11.001
Eun Ju Jeong , Jayoung Song , Hyen Joo Park , Jae Sue Choi , Sang Kook Lee
Angelica decursiva (Umbelliferae) is a medicinal plant widely used to treat colds, coughs and fevers in Korea, Japan, and mainland China. The anti-inflammatory activity of nodakenetin, a furano-coumarin compound from A. decursiva, has been reported, although, the antiosteoporotic activity remains unknown. This study sought to investigate the antiosteoporotic activity and precise mechanism of action of nodakenetin in vitro cell culture and in vivo bone remodeling models. The transcriptional activity of nodakenetin on the Wnt signaling pathway was assessed using the TOPflash/FOPflash assay. The effect of nodakenetin on the osteoblast differentiation was measured using Alizarin red staining and alkaline phosphatase (ALP) activity. Western blotting and real-time RT-PCR were used to assess the effect of nodakenetin on the expression of markers related to Wnt/β-catenin pathway and osteoblast differentiation. The in vivo antiosteoporotic activity of nodakenetin was assessed using an ovariectomized (OVX)-induced bone loss mouse model. Nodakenetin activated the Wnt/β-catenin pathway through regulation of DKK1, β-catenin and other target proteins of the Wnt/β-catenin pathway in HEK293 and MC3T3-E1 cells. Nodakenetin induced the differentiation of MC3T3-E1 cells as shown by enhanced Alizarin red staining and ALP activity. Induction of osteoblast differentiation was related to upregulated expression of bone formation biomarkers such as bone morphogenic proteins and Runx2. Oral administration of nodakenetin in the OVX mouse model effectively protected the deterioration of bone microstructure in OVX mice. Nodakenetin exhibits antiosteoporotic activity in vitro and in vivo through the activation of the Wnt/β-catenin pathway and subsequent induction of osteoblast differentiation.
当归(伞科)是一种药用植物,在韩国、日本和中国大陆广泛用于治疗感冒、咳嗽和发烧。野檀叶素是一种呋喃-香豆素化合物,其抗炎活性已被报道,但其抗骨质疏松活性尚不清楚。本研究旨在探讨nodakenetin在体外细胞培养和体内骨重塑模型中的抗骨质疏松活性及其作用机制。采用TOPflash/FOPflash法评估nodakenetin在Wnt信号通路上的转录活性。采用茜素红染色法和碱性磷酸酶(ALP)活性法测定nodakenetin对成骨细胞分化的影响。Western blotting和real-time RT-PCR检测nodakenetin对Wnt/β-catenin通路相关标志物表达及成骨细胞分化的影响。采用卵巢切除(OVX)诱导的骨质流失小鼠模型,评估nodakenetin的体内抗骨质疏松活性。Nodakenetin通过调控HEK293和MC3T3-E1细胞中Wnt/β-catenin通路的DKK1、β-catenin等靶蛋白激活Wnt/β-catenin通路。从茜素红染色和ALP活性的增强可以看出,Nodakenetin诱导MC3T3-E1细胞分化。成骨细胞分化的诱导与骨形成生物标志物如骨形态发生蛋白和Runx2的表达上调有关。在OVX小鼠模型中口服nodakenetin可有效保护OVX小鼠骨微结构恶化。Nodakenetin通过激活Wnt/β-catenin通路并随后诱导成骨细胞分化,在体外和体内表现出抗骨质疏松活性。
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引用次数: 0
Electroacupuncture improves cardiac function in hyperlipidemic rats by enhancing efferocytosis in myocardial macrophages via the PPARγ-LXRα-MerTK pathway 电针通过PPARγ-LXRα-MerTK通路增强心肌巨噬细胞的胞浆功能,改善高脂血症大鼠心功能
IF 3.3 3区 医学 Q1 INTEGRATIVE & COMPLEMENTARY MEDICINE Pub Date : 2024-10-30 DOI: 10.1016/j.jtcme.2024.10.003
Yong-Li Han , Shu-Wen Jin , Xiao-Li Pan , Hong-Xing Zhang

Background and aim

Electroacupuncture (EA) is an effective treatment for hyperlipidemia because it decreases the protein expression of peroxisome proliferator-activated receptor γ (PPARγ) and liver X receptor alpha (LXRα). Lowering blood lipids can reverse cardiac insufficiency, but the underlying mechanisms remain unclear. We aimed to explore whether EA reduces blood lipid levels and restores cardiac function in hyperlipidemic rats and to elucidate the underlying mechanism involved.

Procedures

A hyperlipidemic rat model was established by providing the animals with a high-fat diet (HFD). Animals were divided into normal control diet (NC), HFD, PPARγ siRNA, EA, and EA + PPARγ siRNA groups. H&E staining was used to observe the histopathology of the heart and liver. Transmission electron microscopy and oil red O staining were used to detect the distribution of myocardial lipid droplets and the efferocytosis of macrophages. Double immunofluorescence was used to detect the expression of ATP binding cassette transport A1 (ABCA1), ATP binding cassette transport G1 (ABCG1), PPARγ, LXR, and MER proto-oncogene tyrosine kinase (MerTK) in cardiac macrophages. The MerTK−/− rats and littermate wild-type rats were divided into NC, HFD, and EA groups. The efferocytosis rate of myocardial macrophages in different groups was detected using TUNEL and Annexin V-FITC/PI double staining.

Results and conclusion

EA had positive effects on the blood lipid profile, cardiac function, and heart and liver weights; reduced fat deposition in cardiomyocytes and hepatocytes; promoted reverse cholesterol transport; and enhanced macrophage efferocytosis in HFD-fed rats. This effect was blocked by PPARγ siRNA. The protein expression of the PPARγ-LXRα-MerTK pathway was also increased by EA treatment. However, under MerTK−/− conditions, the beneficial effects of EA on efferocytosis in myocardial macrophages were blocked. EA reversed ectopic lipid deposition in the liver and heart, increased efferocytosis in myocardial macrophages, improved hyperlipidemia, and ameliorated cardiac dysfunction in HFD-fed rats through the PPARγ-LXRα-MerTK pathway.
背景和目的电针(EA)可降低过氧化物酶体增殖物激活受体γ (PPARγ)和肝脏X受体α (LXRα)的蛋白表达,是治疗高脂血症的有效方法。降低血脂可以逆转心功能不全,但其潜在机制尚不清楚。我们的目的是探讨EA是否能降低高脂血症大鼠的血脂水平和恢复心脏功能,并阐明其潜在的机制。方法采用高脂饮食法建立高脂血症大鼠模型。将动物分为正常对照组(NC)、HFD组、PPARγ siRNA组、EA组和EA + PPARγ siRNA组。H&;E染色观察大鼠心、肝组织病理学变化。透射电镜及油红O染色检测心肌脂滴分布及巨噬细胞的efferocylosis。采用双免疫荧光法检测心肌巨噬细胞中ATP结合盒转运A1 (ABCA1)、ATP结合盒转运G1 (ABCG1)、PPARγ、LXR、MER原癌基因酪氨酸激酶(MerTK)的表达。将MerTK - / -大鼠和同窝野生型大鼠分为NC组、HFD组和EA组。TUNEL和Annexin V-FITC/PI双染色检测各组心肌巨噬细胞的efferocytic率。结果与结论ea对血脂、心功能、心肝质量均有积极影响;心肌细胞和肝细胞脂肪沉积减少;促进逆向胆固醇运输;并增强了hfd喂养大鼠的巨噬细胞efferocytosis。这种作用被PPARγ siRNA阻断。EA处理后PPARγ-LXRα-MerTK通路的蛋白表达也增加。然而,在MerTK−/−条件下,EA对心肌巨噬细胞efferocytosis的有益作用被阻断。EA通过PPARγ-LXRα-MerTK通路逆转hfd喂养大鼠肝脏和心脏的异位脂质沉积,增加心肌巨噬细胞的efferocytosis,改善高脂血症,改善心功能障碍。
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引用次数: 0
Parthenolide alleviates doxorubicin-induced cardiotoxicity via regulation of Cyp1a1 and Nppa and suppression of NLRP3 inflammasome Parthenolide通过调节Cyp1a1和Nppa以及抑制NLRP3炎性体减轻阿霉素诱导的心脏毒性
IF 3 3区 医学 Q1 INTEGRATIVE & COMPLEMENTARY MEDICINE Pub Date : 2024-10-28 DOI: 10.1016/j.jtcme.2024.10.004
Yuanying Yang , Shanshan Wei , Sa Liu , Suifen Xie , Wei Xiao , Jian Liu , Ning Xie , Wenqun Li , Bikui Zhang

Background and aim

Doxorubicin (Dox) has limited clinical use due to its multiple adverse reactions, typically severe cardiotoxicity. Parthenolide (PTL) is the main active ingredient extracted from the buds of Tanacetum balsamita and exhibits diverse pharmacological properties. However, the cardioprotective effects and underlying mechanisms of PTL against Dox-induced cardiotoxicity (DIC) need to be fully investigated. Herein, this study was designed to explore the protective mechanism of PTL against DIC.

Experimental procedure

A stable cardiotoxicity model was established in H9c2 cells (1 μM for 24 h) and C57BL/6 J mice (15 mg/kg). RNA sequencing was used to identify key genes mediating the protection of PTL against DIC. The key genes and mechanism of PTL against DIC were comprehensively examined by transcriptomic technologies and experimental validation.

Results and conclusion

A combination administration of PTL effectively inhibited Dox-induced cytotoxicity as well as cardiomyocyte apoptosis in H9c2 cells. PTL also exerts a protective effect on Dox-induced cardiac injury by improving myocardial function, histological morphological changes, and myocardial apoptosis in Dox-treated mice. Subsequently, we utilized the transcriptomic approach and validated the results by RT-qPCR, confirming that Cyp1a1 and Nppa were the key genes in PTL against DIC. PTL could also protect from DIC via the suppression of the NLRP3 inflammasome activation and subsequent secretion of IL-1β and Caspase1. Our study confirmed that PTL treatment attenuated DIC in mice and H9c2 cells via regulation of Nppa and Cyp1a1 and the suppression of the NLRP3 inflammasome activation and subsequent secretion of pro-inflammatory cytokines.
背景和目的多柔比星(Dox)由于其多重不良反应,特别是严重的心脏毒性,临床应用有限。Parthenolide (PTL)是从香醋草(Tanacetum balsamita)芽中提取的主要活性成分,具有多种药理特性。然而,PTL对dox诱导的心脏毒性(DIC)的心脏保护作用和潜在机制需要充分研究。本研究旨在探讨PTL对DIC的保护机制。实验方法H9c2细胞(1 μM)和C57BL/6 J小鼠(15 mg/kg)分别建立稳定的心脏毒性模型。利用RNA测序技术鉴定PTL对DIC保护的关键基因。通过转录组学技术和实验验证,全面研究了PTL抗DIC的关键基因和机制。结果与结论PTL联合用药可有效抑制dox诱导的H9c2细胞毒性及心肌细胞凋亡。PTL还通过改善dox处理小鼠心肌功能、组织学形态学改变和心肌凋亡,对dox诱导的心脏损伤具有保护作用。随后,我们利用转录组学方法并通过RT-qPCR验证结果,证实Cyp1a1和Nppa是PTL抗DIC的关键基因。PTL还可以通过抑制NLRP3炎性小体的激活和随后IL-1β和Caspase1的分泌来保护DIC。我们的研究证实,PTL通过调节Nppa和Cyp1a1以及抑制NLRP3炎性小体的激活和随后的促炎细胞因子的分泌来减轻小鼠和H9c2细胞的DIC。
{"title":"Parthenolide alleviates doxorubicin-induced cardiotoxicity via regulation of Cyp1a1 and Nppa and suppression of NLRP3 inflammasome","authors":"Yuanying Yang ,&nbsp;Shanshan Wei ,&nbsp;Sa Liu ,&nbsp;Suifen Xie ,&nbsp;Wei Xiao ,&nbsp;Jian Liu ,&nbsp;Ning Xie ,&nbsp;Wenqun Li ,&nbsp;Bikui Zhang","doi":"10.1016/j.jtcme.2024.10.004","DOIUrl":"10.1016/j.jtcme.2024.10.004","url":null,"abstract":"<div><h3>Background and aim</h3><div>Doxorubicin (Dox) has limited clinical use due to its multiple adverse reactions, typically severe cardiotoxicity. Parthenolide (PTL) is the main active ingredient extracted from the buds of <em>Tanacetum balsamita</em> and exhibits diverse pharmacological properties. However, the cardioprotective effects and underlying mechanisms of PTL against Dox-induced cardiotoxicity (DIC) need to be fully investigated. Herein, this study was designed to explore the protective mechanism of PTL against DIC.</div></div><div><h3>Experimental procedure</h3><div>A stable cardiotoxicity model was established in H9c2 cells (1 μM for 24 h) and C57BL/6 J mice (15 mg/kg). RNA sequencing was used to identify key genes mediating the protection of PTL against DIC. The key genes and mechanism of PTL against DIC were comprehensively examined by transcriptomic technologies and experimental validation.</div></div><div><h3>Results and conclusion</h3><div>A combination administration of PTL effectively inhibited Dox-induced cytotoxicity as well as cardiomyocyte apoptosis in H9c2 cells. PTL also exerts a protective effect on Dox-induced cardiac injury by improving myocardial function, histological morphological changes, and myocardial apoptosis in Dox-treated mice. Subsequently, we utilized the transcriptomic approach and validated the results by RT-qPCR, confirming that <em>Cyp1a1</em> and <em>Nppa</em> were the key genes in PTL against DIC. PTL could also protect from DIC via the suppression of the NLRP3 inflammasome activation and subsequent secretion of IL-1β and Caspase1. Our study confirmed that PTL treatment attenuated DIC in mice and H9c2 cells via regulation of <em>Nppa</em> and <em>Cyp1a1</em> and the suppression of the NLRP3 inflammasome activation and subsequent secretion of pro-inflammatory cytokines.</div></div>","PeriodicalId":17449,"journal":{"name":"Journal of Traditional and Complementary Medicine","volume":"15 7","pages":"Pages 726-735"},"PeriodicalIF":3.0,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145384178","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Anti-inflammatory and antinociceptive effects of Aloysia gratissima leaves essential oil: An in vivo study 荆芥叶精油的抗炎和抗伤作用:体内研究
IF 3 3区 医学 Q1 INTEGRATIVE & COMPLEMENTARY MEDICINE Pub Date : 2024-10-09 DOI: 10.1016/j.jtcme.2024.10.002
Maryelen A. Souza , Ketelin Kunh , Otávio Sanaiotto , Ana C. Provinelli , Mayara Barufke , Monica S.Z. Schindler , Samara Cristina Mazon , J. Vladimir Oliveira , Indiara Brusco , Jaqueline Scapinello , Jacir Dal Magro , Liz G. Müller

Background and aim

Aloysia gratissima is used in popular medicine as an analgesic and sedative. However, studies on its biological activities are still scarce. Therefore, this work aimed to evaluate the antinociceptive and anti-inflammatory effect of A. gratissima leaves essential oil (OAG) in mice.

Experimental procedure

The OAG was obtained by hydrodistillation and its composition was determined by gas chromatography-mass spectrometry. The sesquiterpenes pinocamphone, β-pinene, and guaiol were the major constituents of OAG. The effect of OAG (1, 10, and 30 mg/kg, p.o.) was assessed by pre-treating male mice 1h before the formalin assay, carrageenan-induced peritonitis test, or the paw edema induced by arachidonic acid (AA). The acute toxicity of OAG (2000 mg/kg, p.o.) was also investigated.

Results and conclusion

The minimum effective dose of OAG in the formalin test was 1 mg/kg. This dose did not affect the locomotor activity of mice. The OAG decreased the number of leukocytes/mm³ in the peritoneal exudate of mice and reduced paw edema 45 min after the arachidonic acid injection. OAG treatment elicited a reduction in NPSH levels in the paw tissue and increased NPSH levels in mice blood plasma and did not cause mice mortality. The OAG is devoid of acute toxicity and shows anti-inflammatory activity, which can be related to the presence of pinocamphone, guaiol, and β-pinene and is mediated, at least in part, by mechanisms that involve the participation of NPSH.
背景和目的马来蓟是一种常用的镇痛和镇静药。然而,对其生物活性的研究仍然很少。因此,本研究旨在评价黄菖蒲叶精油(OAG)对小鼠的抗伤性和抗炎作用。实验方法:采用加氢蒸馏法得到OAG,采用气相色谱-质谱联用法测定OAG的组成。倍半萜皮诺酮、β-蒎烯和愈创油酚是其主要成分。通过在福尔马林实验、卡拉胶性腹膜炎实验或花生四烯酸(AA)诱导的足跖水肿前1h预处理雄性小鼠,评估OAG(1、10和30 mg/kg, p.o.)的作用。研究了OAG (200mg /kg, p.o.)的急性毒性。结果与结论OAG在福尔马林试验中的最小有效剂量为1 mg/kg。该剂量不影响小鼠的运动活动。注射花生四烯酸45 min后,OAG可降低小鼠腹膜渗出液中白细胞/mm³的数量,减轻足跖水肿。OAG治疗引起小鼠爪组织中NPSH水平的降低和血浆中NPSH水平的增加,并且没有引起小鼠死亡。OAG没有急性毒性,并具有抗炎活性,这可能与皮诺酚、愈创木酚和β-蒎烯的存在有关,至少部分是由NPSH参与的机制介导的。
{"title":"Anti-inflammatory and antinociceptive effects of Aloysia gratissima leaves essential oil: An in vivo study","authors":"Maryelen A. Souza ,&nbsp;Ketelin Kunh ,&nbsp;Otávio Sanaiotto ,&nbsp;Ana C. Provinelli ,&nbsp;Mayara Barufke ,&nbsp;Monica S.Z. Schindler ,&nbsp;Samara Cristina Mazon ,&nbsp;J. Vladimir Oliveira ,&nbsp;Indiara Brusco ,&nbsp;Jaqueline Scapinello ,&nbsp;Jacir Dal Magro ,&nbsp;Liz G. Müller","doi":"10.1016/j.jtcme.2024.10.002","DOIUrl":"10.1016/j.jtcme.2024.10.002","url":null,"abstract":"<div><h3>Background and aim</h3><div><em>Aloysia gratissima</em> is used in popular medicine as an analgesic and sedative. However, studies on its biological activities are still scarce. Therefore, this work aimed to evaluate the antinociceptive and anti-inflammatory effect of <em>A. gratissima</em> leaves essential oil (OAG) in mice.</div></div><div><h3>Experimental procedure</h3><div>The OAG was obtained by hydrodistillation and its composition was determined by gas chromatography-mass spectrometry. The sesquiterpenes pinocamphone, <em>β-</em>pinene, and guaiol were the major constituents of OAG. The effect of OAG (1, 10, and 30 mg/kg, p.o.) was assessed by pre-treating male mice 1h before the formalin assay, carrageenan-induced peritonitis test, or the paw edema induced by arachidonic acid (AA). The acute toxicity of OAG (2000 mg/kg, p.o.) was also investigated.</div></div><div><h3>Results and conclusion</h3><div>The minimum effective dose of OAG in the formalin test was 1 mg/kg. This dose did not affect the locomotor activity of mice. The OAG decreased the number of leukocytes/mm³ in the peritoneal exudate of mice and reduced paw edema 45 min after the arachidonic acid injection. OAG treatment elicited a reduction in NPSH levels in the paw tissue and increased NPSH levels in mice blood plasma and did not cause mice mortality. The OAG is devoid of acute toxicity and shows anti-inflammatory activity, which can be related to the presence of pinocamphone, guaiol, and <em>β-</em>pinene and is mediated, at least in part, by mechanisms that involve the participation of NPSH.</div></div>","PeriodicalId":17449,"journal":{"name":"Journal of Traditional and Complementary Medicine","volume":"15 7","pages":"Pages 714-725"},"PeriodicalIF":3.0,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145384169","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Isoliquiritigenin: A natural compound with a promising role in inhibiting breast cancer lung metastasis 异硫基黄素:一种具有抑制乳腺癌肺转移作用的天然化合物
IF 3 3区 医学 Q1 INTEGRATIVE & COMPLEMENTARY MEDICINE Pub Date : 2024-10-05 DOI: 10.1016/j.jtcme.2024.10.001
Kumar Ganesan , Cong Xu , Bing Du , Jianhua Che , Fei Gao , Chuan Zheng , Jianping Chen

Background and aim

Isoliquiritigenin (ISL) is a dietary bioactive compound that is derived from the roots of licorice and various other plants. Accumulating evidence suggests that ISL has noteworthy anticancer activity in a variety of cancer cells, but it is currently unknown how ISL affects the invasion and migration of breast cancer (BC) cells. Hence, the purpose of this study to determine the inhibitory effect of ISL on cell invasion, migration, and metastasis of BC cells in 4T1-treated lung metastatic animal models.

Experimental procedure

ISL was found to inhibit BC lung metastasis, as confirmed by MTT assay, clonogenic assay, wound healing assay, transwell assay, histological analysis, Western blot and bioluminescence assay in the xenograft model.

Results and conclusion

The in vitro studies revealed that ISL treatment significantly prevented BC cell invasion and migration for 24 h. ISL decreased the protein expressions of PI3K, Akt, p-Akt, mTOR, p-mTOR, matrix metalloproteinase (MMP)-2, MMP-9, and N-cadherin, thereby inhibiting BC cell invasion. In addition, ISL decreased MMP-2/9 and N-cadherin expression in lung tissues and reduced mouse 4T1 BC cell lung metastasis. Based on these findings, it suggests that ISL inhibits cell migration and invasion in BC cells by inhibiting the PI3K/Akt signaling pathway and decreasing the activation of MMP-2 and MMP-9 expression. Therefore, ISL may be useful in managing BC invasion and metastasis.
背景和目的低脂甘草素(ISL)是从甘草和其他植物的根中提取的一种膳食生物活性化合物。越来越多的证据表明,ISL对多种癌细胞具有显著的抗癌活性,但目前尚不清楚ISL如何影响乳腺癌(BC)细胞的侵袭和迁移。因此,本研究的目的是在4t1处理的肺转移动物模型中,确定ISL对BC细胞侵袭、迁移和转移的抑制作用。通过MTT实验、克隆实验、创面愈合实验、transwell实验、组织学分析、Western blot和生物发光实验证实,isl对BC肺转移有抑制作用。结果与结论体外实验表明,ISL可显著抑制BC细胞侵袭和迁移24 h,降低PI3K、Akt、p-Akt、mTOR、p-mTOR、基质金属蛋白酶(MMP)-2、MMP-9和N-cadherin的蛋白表达,从而抑制BC细胞侵袭。此外,ISL可降低肺组织中MMP-2/9和N-cadherin的表达,减少小鼠4T1 BC细胞的肺转移。综上所述,ISL通过抑制PI3K/Akt信号通路,降低MMP-2和MMP-9的表达激活,从而抑制BC细胞的迁移和侵袭。因此,ISL可能有助于控制BC的侵袭和转移。
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引用次数: 0
Integrated lipidomics and network pharmacology analysis to determine how Gu Fu Sheng Capsule improves lipid metabolism in rats with steroid-induced osteonecrosis of the femoral head 综合脂质组学和网络药理学分析,探讨骨复生胶囊对激素性股骨头坏死大鼠脂质代谢的改善作用
IF 3 3区 医学 Q1 INTEGRATIVE & COMPLEMENTARY MEDICINE Pub Date : 2024-09-26 DOI: 10.1016/j.jtcme.2024.09.005
Yue Li , Ying Liu , Yingchun Li , Yang Cao , Hui Zhang , Puwei Yuan , Bo Dong , Li Shen

Background

Steroid-induced osteonecrosis of the femoral head (SONFH) is a prevalent refractory condition in orthopedics, often causing high disability rates. Gu Fu Sheng Capsule (GFSC) is commonly used to treat SONFH during the early and intermediate stages. However, the precise underlying mechanism of action of GFSC remains elusive.

Objective

To elucidate the mechanism through which GFSC improves lipid metabolism in rats with SONFH.

Methods

A rat model of SONFH was established by administering methylprednisolone and lipopolysaccharide. Micro-computed tomography assessed femoral head effects, while hematoxylin–eosin staining examined femoral head tissues. Pathological changes were evaluated using an automated biochemical analyzer to measure changes in serum lipid levels. Besides, quantitative lipidomics and network pharmacology were used to determine how GFSC impacts SONFH. qRT-PCR and Western blotting were performed to assess mRNA and protein expression levels of key targets.

Results

GFSC can enhance bone density and prevents surface collapse of the femoral head, improve hollow bone lacuna density, reduce adipocyte infiltration, minimize osteocyte cavities, regulate the serum lipid levels and enhance lipid metabolism in SONFH rats. Moreover, integrated lipidomics and network pharmacology suggested that GFSC affects lipid metabolism-related genes by regulating nine targets, thereby influencing four metabolites and two metabolic pathways, which may mainly be due to components in GFSC such as quercetin, tanshinone iia, berberine. Western blotting and qRT-PCR data highlighted that GFSC improves lipid metabolism by regulating TP53, HSP90AA1, and ESR1.

Conclusion

GFSC effectively retards SONFH progression, potentially attributed to its ability to regulate lipid metabolism.
背景:类固醇性股骨头坏死(SONFH)是骨科中一种常见的顽固性疾病,通常导致高致残率。谷复生胶囊(GFSC)通常用于治疗SONFH的早期和中期。然而,GFSC的确切作用机制仍不清楚。目的探讨GFSC改善SONFH大鼠脂质代谢的作用机制。方法采用甲基强的松龙加脂多糖建立大鼠SONFH模型。显微计算机断层扫描评估股骨头的影响,而苏木精-伊红染色检查股骨头组织。采用自动生化分析仪测量血脂水平的变化来评估病理变化。此外,定量脂质组学和网络药理学研究了GFSC对SONFH的影响。采用qRT-PCR和Western blotting检测关键靶点mRNA和蛋白的表达水平。结果gfsc能提高SONFH大鼠的骨密度,防止股骨头表面塌陷,改善空心骨陷窝密度,减少脂肪细胞浸润,减少骨细胞空洞,调节血脂水平,促进脂质代谢。此外,综合脂质组学和网络药理学表明,GFSC通过调节9个靶点影响脂质代谢相关基因,从而影响4种代谢产物和2种代谢途径,这可能主要与GFSC中槲皮素、丹参酮、小檗碱等成分有关。Western blotting和qRT-PCR数据显示,GFSC通过调节TP53、HSP90AA1和ESR1来改善脂质代谢。结论fsc有效延缓了SONFH的进展,可能与其调节脂质代谢的能力有关。
{"title":"Integrated lipidomics and network pharmacology analysis to determine how Gu Fu Sheng Capsule improves lipid metabolism in rats with steroid-induced osteonecrosis of the femoral head","authors":"Yue Li ,&nbsp;Ying Liu ,&nbsp;Yingchun Li ,&nbsp;Yang Cao ,&nbsp;Hui Zhang ,&nbsp;Puwei Yuan ,&nbsp;Bo Dong ,&nbsp;Li Shen","doi":"10.1016/j.jtcme.2024.09.005","DOIUrl":"10.1016/j.jtcme.2024.09.005","url":null,"abstract":"<div><h3>Background</h3><div>Steroid-induced osteonecrosis of the femoral head (SONFH) is a prevalent refractory condition in orthopedics, often causing high disability rates. Gu Fu Sheng Capsule (GFSC) is commonly used to treat SONFH during the early and intermediate stages. However, the precise underlying mechanism of action of GFSC remains elusive.</div></div><div><h3>Objective</h3><div>To elucidate the mechanism through which GFSC improves lipid metabolism in rats with SONFH.</div></div><div><h3>Methods</h3><div>A rat model of SONFH was established by administering methylprednisolone and lipopolysaccharide. Micro-computed tomography assessed femoral head effects, while hematoxylin–eosin staining examined femoral head tissues. Pathological changes were evaluated using an automated biochemical analyzer to measure changes in serum lipid levels. Besides, quantitative lipidomics and network pharmacology were used to determine how GFSC impacts SONFH. qRT-PCR and Western blotting were performed to assess mRNA and protein expression levels of key targets.</div></div><div><h3>Results</h3><div>GFSC can enhance bone density and prevents surface collapse of the femoral head, improve hollow bone lacuna density, reduce adipocyte infiltration, minimize osteocyte cavities, regulate the serum lipid levels and enhance lipid metabolism in SONFH rats. Moreover, integrated lipidomics and network pharmacology suggested that GFSC affects lipid metabolism-related genes by regulating nine targets, thereby influencing four metabolites and two metabolic pathways, which may mainly be due to components in GFSC such as quercetin, tanshinone iia, berberine. Western blotting and qRT-PCR data highlighted that GFSC improves lipid metabolism by regulating TP53, HSP90AA1, and ESR1.</div></div><div><h3>Conclusion</h3><div>GFSC effectively retards SONFH progression, potentially attributed to its ability to regulate lipid metabolism.</div></div>","PeriodicalId":17449,"journal":{"name":"Journal of Traditional and Complementary Medicine","volume":"15 7","pages":"Pages 687-701"},"PeriodicalIF":3.0,"publicationDate":"2024-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145384253","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Curcumol promotes ferroptosis of colon cancer by targeting the ubiquitination and degradation of GPX4 姜黄醇通过靶向 GPX4 的泛素化和降解促进结肠癌的铁变态反应
IF 3.3 3区 医学 Q1 INTEGRATIVE & COMPLEMENTARY MEDICINE Pub Date : 2024-08-21 DOI: 10.1016/j.jtcme.2024.08.006
Wuxia Zhao , Qiuying Yan , Lianfang Liu , Dahai Hou , Dongyang Xiang , Dongxin Tang , Liu Li , Weixing Shen , Weiwei Tao , Haibo Cheng , Dongdong Sun

Background and aim

Colon cancer (CC) is one of the common malignant tumors in the digestive tract, the prognosis of CC patients has never been satisfying. A Ferrous-dependent form that regulates cell death, plays a key role in cancer development. As a core regulator of ferroptosis, GPX4 has become a potential molecular target for the development of antitumor drugs. Curcumol (Cur), a sesquiterpene natural product, it has significant anti-tumor effect. However, whether Cur mediates ferroptosis in colon cancer and its mechanism are still unclear. This study aimed to investigate the underlying mechanisms of Cur anti-tumor.

Experimental procedure

By investigating the Cancer Genome Atlas (TCGA) database and tissue immunofluorescence staining was also used to detect the levels of GPX4 protein in CC and matching paracancerous tissues. The anti-CC and pro-ferroptosis effects of Cur were detected in the vivo and vitro experiment. The interaction between Cur and GPX4 was predicted. In addition, the potential mechanism of Cur anti-CC was further discussed. Co-immunoprecipitation was used to confirm Cur-mediated GPX4 ubiquitination.

Results and conclusion

GPX4 was upregulated in CC tissue and was correlated with poor survival of patients. Cur inhibited the proliferation of CC cells, accompanied by regulating Fe2+ overload, reactive oxygen species (ROS) formation, malondialdehyde (MDA) production and superoxide dismutase (SOD) consumption. Furthermore, GPX4 was predicted and verified as the direct target of Cur by molecular docking and structure-based virtual prediction. Meanwhile, Cur could promote the ubiquitination-mediated degradation of GPX4, induce ferroptosis in CC cells and regulate the expression of ferroptosis-related protein FTH1 and TfR1. In addition, when GPX4 was overexpressed (GPX4-OE), the inhibitory effect of Cur on the expression of GPX4 and ferroptosis-related protein FTH1 and the promotion of TfR1 expression were abolished. Cur could inhibit CC by increasing the ubiquitination degradation level of GPX4 to induce ferroptosis in CC cells.
背景与目的结肠癌(colorectal cancer, CC)是消化道常见的恶性肿瘤之一,其预后一直不理想。一种调节细胞死亡的铁依赖形式在癌症发展中起着关键作用。GPX4作为铁下垂的核心调控因子,已成为开发抗肿瘤药物的潜在分子靶点。Curcumol (Cur)是一种倍半萜类天然产物,具有显著的抗肿瘤作用。然而,Cur是否介导结肠癌铁下垂及其机制尚不清楚。本研究旨在探讨其抗肿瘤作用机制。通过肿瘤基因组图谱(Cancer Genome Atlas, TCGA)数据库和组织免疫荧光法检测GPX4蛋白在CC及配对癌旁组织中的表达水平。在体内和体外实验中检测了Cur的抗cc和促铁下垂作用。预测了Cur与GPX4的相互作用。此外,还进一步探讨了氯化铜抗氯化铜的潜在机理。共免疫沉淀法证实了curr介导的GPX4泛素化。结果与结论ongpx4在CC组织中表达上调,与患者生存不良相关。Cur抑制CC细胞增殖,同时调节Fe2+过载、活性氧(ROS)形成、丙二醛(MDA)产生和超氧化物歧化酶(SOD)消耗。通过分子对接和基于结构的虚拟预测,预测并验证了GPX4是Cur的直接靶点。同时,Cur可促进泛素化介导的GPX4降解,诱导CC细胞铁沉,调节铁沉相关蛋白FTH1和TfR1的表达。此外,当GPX4过表达(GPX4- oe)时,Cur对GPX4和铁凋亡相关蛋白FTH1表达的抑制作用以及对TfR1表达的促进作用被取消。Cur可以通过提高GPX4的泛素化降解水平来抑制CC,诱导CC细胞铁凋亡。
{"title":"Curcumol promotes ferroptosis of colon cancer by targeting the ubiquitination and degradation of GPX4","authors":"Wuxia Zhao ,&nbsp;Qiuying Yan ,&nbsp;Lianfang Liu ,&nbsp;Dahai Hou ,&nbsp;Dongyang Xiang ,&nbsp;Dongxin Tang ,&nbsp;Liu Li ,&nbsp;Weixing Shen ,&nbsp;Weiwei Tao ,&nbsp;Haibo Cheng ,&nbsp;Dongdong Sun","doi":"10.1016/j.jtcme.2024.08.006","DOIUrl":"10.1016/j.jtcme.2024.08.006","url":null,"abstract":"<div><h3>Background and aim</h3><div>Colon cancer (CC) is one of the common malignant tumors in the digestive tract, the prognosis of CC patients has never been satisfying. A Ferrous-dependent form that regulates cell death, plays a key role in cancer development. As a core regulator of ferroptosis, GPX4 has become a potential molecular target for the development of antitumor drugs. Curcumol (Cur), a sesquiterpene natural product, it has significant anti-tumor effect. However, whether Cur mediates ferroptosis in colon cancer and its mechanism are still unclear. This study aimed to investigate the underlying mechanisms of Cur anti-tumor.</div></div><div><h3>Experimental procedure</h3><div>By investigating the Cancer Genome Atlas (TCGA) database and tissue immunofluorescence staining was also used to detect the levels of GPX4 protein in CC and matching paracancerous tissues. The anti-CC and pro-ferroptosis effects of Cur were detected in the <em>vivo</em> and <em>vitro</em> experiment. The interaction between Cur and GPX4 was predicted. In addition, the potential mechanism of Cur anti-CC was further discussed. Co-immunoprecipitation was used to confirm Cur-mediated GPX4 ubiquitination.</div></div><div><h3>Results and conclusion</h3><div>GPX4 was upregulated in CC tissue and was correlated with poor survival of patients. Cur inhibited the proliferation of CC cells, accompanied by regulating Fe<sup>2+</sup> overload, reactive oxygen species (ROS) formation, malondialdehyde (MDA) production and superoxide dismutase (SOD) consumption. Furthermore, GPX4 was predicted and verified as the direct target of Cur by molecular docking and structure-based virtual prediction. Meanwhile, Cur could promote the ubiquitination-mediated degradation of GPX4, induce ferroptosis in CC cells and regulate the expression of ferroptosis-related protein FTH1 and TfR1. In addition, when GPX4 was overexpressed (GPX4-OE), the inhibitory effect of Cur on the expression of GPX4 and ferroptosis-related protein FTH1 and the promotion of TfR1 expression were abolished. Cur could inhibit CC by increasing the ubiquitination degradation level of GPX4 to induce ferroptosis in CC cells.</div></div>","PeriodicalId":17449,"journal":{"name":"Journal of Traditional and Complementary Medicine","volume":"15 2","pages":"Pages 170-181"},"PeriodicalIF":3.3,"publicationDate":"2024-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142078010","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Raddeanin A promotes the apoptosis of gastric cancer in conjunction with autophagy inhibitor Hydroxychloroquine via MAPK signaling pathway Raddeanin A 与自噬抑制剂羟氯喹通过 MAPK 信号通路共同促进胃癌细胞凋亡
IF 3.3 3区 医学 Q1 INTEGRATIVE & COMPLEMENTARY MEDICINE Pub Date : 2024-07-20 DOI: 10.1016/j.jtcme.2024.07.004
Yuhao Teng , Ying Xing , Weiwei Xue , Yue Hu , Zirui Li , Jun Qian , Ruiping Wang

Purpose

Gastric cancer (GC) is among the malignant cancers with the highest incidence and mortality worldwide. As GC is not very sensitive to current chemotherapy drugs, there is an urgent need to develop new effective drugs. Raddeanin A (RA) is extracted from the traditional Chinese medicine Anemone raddeana Regel, which has an anti-cancer effect. The purpose of this study was to explore the effects of RA on GC in vitro and in vivo.

Methods

We explored the targets of RA in GC through network pharmacology. MTT assay, flow cytometry, Western blotting, and other methods were used to detect the effects of RA on the proliferation, apoptosis, and autophagy of GC cells. After preconditioning with hydroxychloroquine (HCQ) and rapamycin, we observed the effects of RA-induced autophagy on apoptosis. We further verified the antitumor effect and safety of RA in vivo. Using SNU-1 xenograft tumor model in nude mice, tumor volume was observed and liver toxicity was observed by immunohistochemistry.

Results

Many cancer-related signaling pathways were visualized using Cytoscape software. Among them, the MAPK signaling pathway was one of the highest-ranked pathways. The MTT assay results suggested that RA could inhibit the proliferation of HGC-27 and SNU-1 cells effectively. Flow cytometry and Western blotting confirmed that RA could significantly induce apoptosis of HGC-27 and SNU-1 cells. Electron microscopy and Western blotting demonstrated that RA could induce autophagy of HGC-27 and SNU-1 cells. Further experiments suggested that HCQ, an autophagy inhibitor, could enhance the capacity of RA to induce apoptosis. In animal studies, we found that intraperitoneal injection of RA could effectively and safely inhibit gastric tumors.

Conclusions

RA significantly inhibited the proliferation and induced autophagy and apoptosis of GC cells. In combination with HCQ, RA-induced apoptosis increased in vitro. The combined application of RA and autophagy inhibitors may serve as an added approach to the treatment of GC, but the underlying mechanism needs further exploration. In vivo, it was observed that RA has a good antitumor effect without increasing liver toxicity.
目的胃癌是世界上发病率和死亡率最高的恶性肿瘤之一。由于GC对现有化疗药物的敏感性不高,迫切需要开发新的有效药物。海葵素A (Raddeanin A, RA)是从中药海葵中提取的,具有抗癌作用。本研究的目的是探讨RA对体外和体内GC的影响。方法采用网络药理学方法,探索RA在GC中的作用靶点。采用MTT法、流式细胞术、Western blotting等方法检测RA对GC细胞增殖、凋亡和自噬的影响。在羟氯喹(HCQ)和雷帕霉素预处理后,观察ra诱导的自噬对细胞凋亡的影响。我们进一步在体内验证了RA的抗肿瘤作用和安全性。建立裸鼠移植瘤模型,采用免疫组化方法观察肿瘤体积和肝毒性。结果利用Cytoscape软件对多种肿瘤相关信号通路进行了可视化处理。其中,MAPK信号通路是排名最高的通路之一。MTT实验结果表明,RA能有效抑制HGC-27和SNU-1细胞的增殖。流式细胞术和Western blotting证实,RA能显著诱导HGC-27和SNU-1细胞凋亡。电镜和Western blot结果显示,RA可诱导HGC-27和SNU-1细胞自噬。进一步实验表明,自噬抑制剂HCQ可增强RA诱导细胞凋亡的能力。在动物实验中,我们发现腹腔注射RA能有效、安全地抑制胃肿瘤。结论ra能明显抑制胃癌细胞的增殖,诱导胃癌细胞自噬和凋亡。与HCQ联合,ra诱导的体外细胞凋亡增加。RA与自噬抑制剂联合应用可能是治疗胃癌的一种新途径,但其作用机制有待进一步探讨。在体内,观察到RA具有良好的抗肿瘤作用,且不增加肝毒性。
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引用次数: 0
The chemical composition of Diwu YangGan capsule and its potential inhibitory roles on hepatocellular carcinoma by microarray-based transcriptomics 基于芯片的转录组学研究地乌洋参胶囊的化学成分及其对肝细胞癌的潜在抑制作用
IF 3.3 3区 医学 Q1 INTEGRATIVE & COMPLEMENTARY MEDICINE Pub Date : 2024-07-01 DOI: 10.1016/j.jtcme.2023.12.002
Qingxin Shi , Jiangcheng He , Guangya Chen , Jinlin Xu , Zhaoxiang Zeng , Xueyan Zhao , Binbin Zhao , Xiang Gao , Zhihua Ye , Mingzhong Xiao , Hanmin Li

The Traditional Chinese Medicine compound preparation known as Diwu Yanggan capsule (DWYG) can effectively hinder the onset and progression of hepatocellular carcinoma (HCC), which is recognized worldwide as a significant contributor to fatalities associated with cancer. Nevertheless, the precise mechanisms implicated have remained ambiguous. In present study, the model of HCC was set up by the 2-acetylaminofluorene (2-AAF)/partial hepatectomy (PH) in rats. To confirm the differentially expressed genes (DEGs) identified in the microarray analysis, real-time quantitative reverse transcription PCR (qRT-PCR) was conducted. In the meantime, the liquid chromatography-quadrupole time of flight mass spectrometry (LC-QTOF-MS/MS) was employed to characterize the component profile of DWYG. Consequently, the DWYG treatment exhibited the ability to reverse 51 variation genes induced by 2-AAF/PH. Additionally, there was an overlap of 54 variation genes between the normal and model groups. Upon conducting RT-qPCR analysis, it was observed that the expression levels of all genes were increased by 2-AAF/PH and subsequently reversed after DWYG treatment. Notably, the fold change of expression levels for all genes was below 0.5, with 3 genes falling below 0.25. Moreover, an investigation was conducted to determine the signaling pathway that was activated/inhibited in the HCC group and subsequently reversed in the DWYG group. Moreover, the component profile of DWYG encompassed a comprehensive compilation of 206 compounds that were identified or characterized. The findings of this study elucidated the potential alleviative mechanisms of DWYG in the context of HCC, thereby holding significant implications for its future clinical utilization and widespread adoption.

地乌阳干胶囊(DWYG)是一种中药复方制剂,能有效阻止肝细胞癌(HCC)的发生和发展。然而,其确切的作用机制仍不明确。本研究以 2-乙酰氨基芴(2-AAF)/部分肝切除术(PH)为大鼠建立了 HCC 模型。为了确认芯片分析中发现的差异表达基因(DEGs),研究人员进行了实时定量反转录 PCR(qRT-PCR)分析。同时,采用液相色谱-四极杆飞行时间质谱(LC-QTOF-MS/MS)分析了DWYG的成分特征。结果表明,DWYG 能够逆转 2-AAF/PH 诱导的 51 个变异基因。此外,正常组和模型组之间有 54 个变异基因重叠。在进行 RT-qPCR 分析时,观察到所有基因的表达水平都因 2-AAF/PH 而增加,并在 DWYG 处理后逆转。值得注意的是,所有基因表达水平的折合变化均低于 0.5,其中 3 个基因低于 0.25。此外,研究还确定了在 HCC 组中被激活/抑制,随后在 DWYG 组中被逆转的信号通路。此外,DWYG 的成分概况包含了已鉴定或表征的 206 种化合物的综合汇编。本研究的结果阐明了 DWYG 对 HCC 的潜在缓解机制,从而对其未来的临床应用和广泛采用具有重要意义。
{"title":"The chemical composition of Diwu YangGan capsule and its potential inhibitory roles on hepatocellular carcinoma by microarray-based transcriptomics","authors":"Qingxin Shi ,&nbsp;Jiangcheng He ,&nbsp;Guangya Chen ,&nbsp;Jinlin Xu ,&nbsp;Zhaoxiang Zeng ,&nbsp;Xueyan Zhao ,&nbsp;Binbin Zhao ,&nbsp;Xiang Gao ,&nbsp;Zhihua Ye ,&nbsp;Mingzhong Xiao ,&nbsp;Hanmin Li","doi":"10.1016/j.jtcme.2023.12.002","DOIUrl":"10.1016/j.jtcme.2023.12.002","url":null,"abstract":"<div><p>The Traditional Chinese Medicine compound preparation known as Diwu Yanggan capsule (DWYG) can effectively hinder the onset and progression of hepatocellular carcinoma (HCC), which is recognized worldwide as a significant contributor to fatalities associated with cancer. Nevertheless, the precise mechanisms implicated have remained ambiguous. In present study, the model of HCC was set up by the 2-acetylaminofluorene (2-AAF)/partial hepatectomy (PH) in rats. To confirm the differentially expressed genes (DEGs) identified in the microarray analysis, real-time quantitative reverse transcription PCR (qRT-PCR) was conducted. In the meantime, the liquid chromatography-quadrupole time of flight mass spectrometry (LC-QTOF-MS/MS) was employed to characterize the component profile of DWYG. Consequently, the DWYG treatment exhibited the ability to reverse 51 variation genes induced by 2-AAF/PH. Additionally, there was an overlap of 54 variation genes between the normal and model groups. Upon conducting RT-qPCR analysis, it was observed that the expression levels of all genes were increased by 2-AAF/PH and subsequently reversed after DWYG treatment. Notably, the fold change of expression levels for all genes was below 0.5, with 3 genes falling below 0.25. Moreover, an investigation was conducted to determine the signaling pathway that was activated/inhibited in the HCC group and subsequently reversed in the DWYG group. Moreover, the component profile of DWYG encompassed a comprehensive compilation of 206 compounds that were identified or characterized. The findings of this study elucidated the potential alleviative mechanisms of DWYG in the context of HCC, thereby holding significant implications for its future clinical utilization and widespread adoption.</p></div>","PeriodicalId":17449,"journal":{"name":"Journal of Traditional and Complementary Medicine","volume":"14 4","pages":"Pages 381-390"},"PeriodicalIF":3.3,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2225411023001360/pdfft?md5=bfa76b9673e97a298fbe5a8c4cb54ab9&pid=1-s2.0-S2225411023001360-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139193418","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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Journal of Traditional and Complementary Medicine
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