摘要:ObjectiveTo investigate the effects of Linggui Zhugantang (LGZGT)-containing serum on primary astrocytes (AS) induced by β amyloid 1-42 (Aβ1-42) in a rat model of Alzheimer's disease (AD) and explore the phagocytic and degradative effects of LGZGT on Aβ.MethodAn AD model was established by inducing AS with Aβ1-42. The cells were divided into normal group, model group, LGZGT low-, medium-, and high-dose (LGZGT-L, LGZGT-M, and LGZGT-H) groups, and donepezil hydrochloride group. The model group was treated with Aβ1-42 at a final concentration of 10 μmol∙L-1. The LGZGT-L, LGZGT-M, and LGZGT-H groups were treated with 10% serum containing LGZGT on the basis of the model group. Cell viability was assessed using a cell counting kit-8 (CCK-8), lactate dehydrogenase (LDH) activity was measured using an LDH assay kit, and cell morphology was observed using an inverted microscope. The expression of Aβ-related degradation enzymes insulin-degrading enzyme (IDE) and cathepsin D (CTSD) was detected using Western blot, and the fluorescence intensity of cathepsin B (CTSB) was measured using immunofluorescence. The content of Aβ1-42 in cells was determined using an enzyme-linked immunosorbent assay (ELISA).ResultCompared with the normal group, the viability of AS in all groups decreased, and Aβ1-42 at different concentrations had inhibitory effects on AS proliferation. After administration, compared with the normal group, the cell survival rate of the model group decreased significantly (P<0.05). Compared with the model group, the cell survival rates of the LGZGT-H group and donepezil hydrochloride group increased significantly (P<0.05). The LDH activity of cells in the model group was significantly increased compared with that in the normal group (P<0.05), and cell bodies were swollen and enlarged with increased protrusions and elongation, suggesting more obvious cell damage. Compared with the model group, the LDH activity of cells in the donepezil hydrochloride, LGZGT-L, LGZGT-M, and LGZGT-H groups decreased significantly (P<0.05). After administration, the cell swelling in the LGZGT-M, LGZGT-H, and donepezil hydrochloride groups improved, cell protrusions shortened, and cell clustering decreased. Compared with the normal group, the expression of IDE and CTSD in the model group decreased significantly (P<0.05). Compared with the model group, the expression of IDE increased significantly in the LGZGT-M and LGZGT-H groups (P<0.05). Compared with the model group, the expression of CTSD increased significantly in the LGZGT-L, LGZGT-M, LGZGT-H, and donepezil hydrochloride groups (P<0.05). The average fluorescence intensity of CTSB in the model group was significantly lower than that in the normal group (P<0.05). Compared with the model group, the average fluorescence intensity of CTSD in the LGZGT-L, LGZGT-M, LGZGT-H, and donepezil hydrochloride groups increased significantly (P<0.05). The intracellular content of Aβ1-42 in cells in the model group was significantly higher than that in the normal group (P<0.05). After administration, compared with the model group, the intracellular content of Aβ1-42 in cells in the LGZGT-L, LGZGT-M, LGZGT-H, and donepezil hydrochloride groups decreased significantly (P<0.05), and LGZGT-containing serum reduced Aβ1-42 in a dose-dependent manner (P<0.05).ConclusionLGZGT has a protective effect on Aβ1-42-induced AS and can promote the degradation of Aβ. Its mechanism may be related to reducing Aβ toxicity, enhancing cell viability, promoting the expression of IDE, CTSD, and CTSB, and restoring lysosomal function.
摘要:ObjectiveThis study aims to explore the potential mechanism of Danggui Niantongtang in treating knee osteoarthritis (KOA) by regulating the intestinal flora through 16S rDNA analysis.MethodThirty-six C57BL/6J mice were subjected to anterior cruciate ligament transection (ACLT) to establish a KOA model and were randomly divided into the sham surgery group, model group, low-dose Danggui Niantongtang group (0.819 g·kg-1), medium-dose Danggui Niantongtang group (1.638 g·kg-1), high-dose Danggui Niantongtang group (3.276 g·kg-1), and Meloxicam group (0.975 mg·kg-1), with 6 mice in each group. Except for the treatment groups, the sham surgery group and model group were given normal saline by gavage. After 4 weeks of continuous intervention, feces and intact knee joints of the mice were collected. Hematoxylin-eosin (HE) staining and Safranin O-Fast Green staining were performed to observe the pathological changes in knee joint tissue morphology. The 16S rDNA sequencing was used to analyze changes in the abundance and diversity of intestinal microorganisms before and after treatment, along with corresponding functional predictions.ResultHigh-dose Danggui Niantongtang and Meloxicam significantly relieved pain symptoms in KOA mice, improved the disorder of joint structure, maintained the integrity of knee articular cartilage, increased the expression of type Ⅱ collagen alpha 1 (Col2a1) in articular cartilage, and decreased the expression of matrix metalloproteinase-13 (MMP-13). The results of 16S rDNA sequencing showed that high-dose Danggui Niantongtang could adjust the abundance and structure of intestinal microbial species. Compared with the sham surgery group, the abundance of Proteobacteria, Actinobacteria, Ruminococcus, and Bacteroides was significantly increased in the model group (P<0.05), while in the Danggui Niantongtang group, the abundance of these four flora was significantly reduced compared with the model group. Compared with the sham surgery group, the abundance of Verrucomicrobia, Oscillospira, and Akkermansia was significantly decreased in the model group (P<0.05), while in the Danggui Niantongtang groups, the abundance of these three flora was significantly increased compared with the model group (P<0.05). Functional pathway prediction of differential genera revealed that species differences among groups mainly involved metabolic pathways with high abundance associated with biosynthesis and precursors, as well as energy production, including amino acid biosynthesis, nucleotide and nucleoside biosynthesis, cofactors, prosthetic groups, electron carriers, and vitamin biosynthesis.ConclusionDanggui Niantongtang can effectively protect articular cartilage and delay the progression of KOA, possibly by regulating the structure of the intestinal flora, promoting probiotics, and inhibiting the growth of harmful pathogenic bacteria.
摘要:ObjectiveTo explore the effect and mechanism of Sishenjian on synovial lesions induced by monosodium iodoacetate (MIA) in rats with knee osteoarthritis (KOA).MethodSixty female Sprague-Dawley (SD) rats were randomly divided into the following six groups: normal group, model group, celecoxib group, and high-, medium-, and low-dose Sishenjian group. The KOA rat model was established by intra-articular injection of MIA. Celecoxib (18 mg·kg-1) and Sishenjian (14.4, 7.2, 3.6 g·kg-1) were administered by gavage according to the groups. All rats were euthanized after four weeks of continuous administration. The transverse diameter of the bilateral knee joints of rats was measured, and gross observation of the knee joint was performed. Pathological changes in knee joint synovial tissue were observed by hematoxylin-eosin (HE) staining and picrosirius red staining. Immunohistochemistry (IHC) was used to detect the expression of vascular endothelial growth factor A (VEGFA) in synovial tissue. The levels of inflammatory cytokines in the joint synovial fluid were detected by enzyme-linked immunosorbent assay (ELISA). Real-time quantitative polymerase chain reaction (Real-time PCR) and Western blot were used to detect the expression of mRNA and proteins related to the transforming growth factor-β1 (TGF-β1)/Smad2/3 pathway in knee joint synovium.ResultCompared with the normal group, the transverse diameter of the knee joint in the model group significantly increased (P<0.01). Compared with the model group, the transverse diameter of the knee joint in rats of each Sishenjian group significantly decreased (P<0.01). Compared with the normal group, the expression levels of interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) in the knee joint synovial fluid of model group significantly increased (P<0.01). Compared with the model group, the expression levels of IL-1β and TNF-α in the knee joint synovial fluid of rats in each Sishenjian group significantly decreased (P<0.01). Compared with the normal group, the expression levels of TGF-β1, Smad2/3, phosphorylation(p)-Smad2/3, type Ⅰ collagen α1 (ColⅠα1), type Ⅲ collagen α1 (ColⅢα1), VEGFA proteins and TGF-β1, Smad2/3, ColⅠα1, ColⅢα1 mRNA in knee joint synovium of model group significantly increased (P<0.01). Compared with the model group, the expression levels of TGF-β1, Smad2/3, phosphorylation (p)-Smad2/3, ColⅠα1, ColⅢα1, VEGFA proteins and TGF-β1, Smad2/3, ColⅠα1, ColⅢα1 mRNA in knee joint synovium of rats in each Sishenjian group significantly decreased (P<0.05, P<0.01).ConclusionSishenjian can inhibit synovial inflammation and angiogenesis, and may become a potential drug for treating synovial lesions in KOA by regulating the TGF-β1/Smad2/3 pathway.
摘要:ObjectiveTo investigate the effect of modified Weijingtang on the pyroptosis of RAW264.7 macrophages via the cysteinyl aspartate-specific protease-1 (Caspase-1)/gasdermin D (GSDMD) pathway.MethodLipopolysaccharide (LPS) was used to induce pyroptosis of RAW264.7 cells. The blank group was treated with the blank serum, and the intervention groups were treated with the sera containing different doses of modified Weijingtang. After 24 h, the viability of cells in different groups was examined by the cell counting kit-8 (CCK-8). The pyroptosis and morphology of cells in each group were observed by a scanning electron microscope and a phase-contrast microscope, respectively. The mRNA and protein levels of nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3), Caspase-1, and GSDMD in each group were determined by real-time fluorescence quantitative polymerase chain reaction (Real-time PCR) and Western blot, respectively. The levels of interleukin (IL)-18 and IL-1β in each group were measured by enzyme-linked immunosorbent assay.ResultUnder the electron microscope, RAW264.7 cells presented the best morphology and structure in the blank group and obvious pyroptosis and leakage of cell contents in the model (LPS) group. Compared with the model group, the intervention groups showed reduced pyroptosis to varying degrees, and the high-dose group had the closest cell morphology and structure to the blank group. Under the optical microscope, RAW264.7 cells were spherical in the blank group and irregular with protrusions in the model group. Compared with the model group, the intervention groups showed improved cell morphology, and the cell morphology in the group with the dose of 20% was the closest to that in the blank group. The mRNA and protein levels of NLRP3, Caspase-1, and GSDMD in the model group were higher than those in the blank group (P<0.05). Compared with the model group, each intervention group showed down-regulated expression of the above indicators (P<0.05). Compared with the blank group, the model group presented elevated levels of IL-18 and IL-1β (P<0.05), which were lowered in the intervention (10%, 20%) groups (P<0.01).ConclusionModified Weijingtang inhibits the pyroptosis of macrophages by down-regulating the Caspase-1/GSDMD pathway and reducing the release of proinflammatory cytokines.
摘要:ObjectiveTo observe the microbial changes in Wistar rats with liver injury caused by the Dictamni Cortex-Flavescens Sophora by high-throughput sequencing technology and investigate the potential mechanism of liver injury caused by the Dictamni Cortex-Flavescens Sophora.MethodFemale Wistar rats were randomly divided into four groups: normal group, as well as low-dose, medium-dose, and high-dose groups of traditional Chinese medicine (TCM). The rats were gavaged with the Dictamni Cortex-Flavescens Sophora in different doses (4.125, 8.25, 16.5 g·kg-1 of raw drug respectively) for 28 days, and the general condition was recorded. The liver-body weight ratio was calculated, and the biochemical indexes of serum were observed. The Hematoxylin-eosin (HE) staining was used to observe pathological changes in the liver, and 16S rDNA high-throughput sequencing was utilized to detect fecal microbial changes in rats.ResultCompared with the normal group, Dictamni Cortex-Flavescens Sophora increased the liver weights and liver-body weight ratios of Wistar rats. The difference in liver weight between the medium-dose and high-dose groups of TCM was statistically significant (P<0.05), and the liver-body weight ratios of the low-dose, medium-dose, and high-dose groups of TCM were all statistically significant (P<0.05). Compared with the normal group, serum albumin and cholesterol levels increased in the medium-dose and high-dose groups of TCM (P<0.05). The histopathology of the liver in the medium-dose and high-dose groups of TCM showed tiny vacuole-like changes. Compared with the normal group, there were obvious intestinal flora disorders after administration of Dictamni Cortex-Flavescens Sophora, and alpha diversity increased in the medium-dose and high-dose groups of TCM. The principal coordinates analysis showed that species increasingly deviated from the normal group as the administered dose increased. Compared with the normal group, the proportion of Firmicutes and Bacteroidota decreased after the drug administration, and the genus level of Parasutterella, Romboutsia, Turicibacter, Allobaculum, and Dubosiella increased. The genus level of Lachnospiraceae_NK4A136_group, Blautia, Erysipelatoclostridium, Muribaculum, and Ruminococcus_gnavus_group decreased. The correlation analysis showed that Parasutterella, Romboutsia, Turicibacter, Allobaculum, and Dubosiella were positively correlated with serum cholesterol and liver-body weight ratio, and lanchnospiraceae_NK4A136_group, Blautia, Muribaculum, Erysipelatoclostridium, and Ruminococcus_gnavus_group were negatively associated with serum cholesterol and liver-body weight ratio.ConclusionThe liver injury caused by Dictamni Cortex-Flavescens Sophora is manifested as a lipid metabolism disorder, and the mechanism is related to the increase in lipid metabolism-related microorganisms.
关键词:lipid metabolism disorder;intestinal microorganisms;16S rDNA sequencing;correlation analysis;liver injury caused by traditional Chinese medicine (TCM);Dictamni Cortex-Flavescens Sophora
摘要:ObjectiveTo observe the effect of water extract of Mori Folium (MLE) on oxidative stress in adipose tissue of type 2 diabetes mellitus (T2DM) mice and explore its mechanism.MethodTwenty-four male db/db mice were randomly divided into model group, metformin group, low-dose MLE (MLE-L) group, and high-dose MLE (MLE-H) group according to their body weight and blood glucose, with six mice in each group, and other six C57BLKS/JGpt wild littermate mice were selected as normal group. The mice in the metformin group were given 200 mg·kg-1 metformin suspension, and the mice in the MLE-L and MLE-H groups were respectively given 2 g·kg-1 and 4 g·kg-1 MLE, while the mice in the normal group and model group were given the same dose of deionized water by daily gavage for eight weeks. Body weight, subcutaneous fat index, fasting blood glucose (FBG), and oral glucose tolerance level (OGTT) of the mice were detected, and serum superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and malondialdehyde (MDA) were measured. The expression levels of silent information regulator 1 (SIRT1) and NADPH oxidase type 4 (NOX4) protein in subcutaneous adipose tissue of the mice were detected by Western blot.ResultThe FBG level, OGTT, and subcutaneous fat index of T2DM mice were significantly decreased (P<0.05, P<0.01) after administration of MLE compared with the blank group. The contents of serum SOD and GSH were significantly increased, while the level of oxidative stress damage marker MDA was significantly decreased (P<0.05, P<0.01). The expression of SIRT1 protein in adipose tissue was significantly increased, while the expression of NOX4 protein was significantly decreased (P<0.05, P<0.01).ConclusionMLE can ameliorate T2DM by alleviating oxidative stress in adipose tissue of T2DM mice and reducing blood glucose.
关键词:water extract of Mori Folium;type 2 diabetes mellitus;oxidative stress;adipose tissue
摘要:ObjectiveTo investigate the protective effects of Mori Folium extract (MLE) on the kidney of db/db diabetic mice and its mechanism.MethodTwenty-four male C57BLKS/JGpt-Leprdb/Leprdb (db/db) mice were randomly divided into model group, metformin group, low-dose group of MLE (MLE-L), and high-dose group of MLE (MLE-H) according to their fasting blood glucose (FBG), with six mice in each group, and other six C57BLKS/JGpt wild littermate (m/m) mice were selected as normal group. The mice in the drug administration groups were given corresponding drugs by gavage, and the mice in the normal group and model group were given the same dose of deionized water by gavage once a day for continuous eight weeks. Body weight, bilateral kidney weight, and FBG were measured, and an oral glucose tolerance test (OGTT) was performed. The pathological changes in the kidney tissue of mice were observed by hematoxylin-eosin (HE) and periodic acid-silver (PAS) staining, and serum creatinine (SCr) and blood urea nitrogen (BUN) levels were detected. Enzyme-linked immunosorbent assay (ELISA) was used to detect the levels of tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) in serum and urinary microalbumin (U-mAlb) of mice. The expression levels of toll-like receptor 4 (TLR4), myeloid differentiation factor 88 (MyD88), and nuclear factor-kappa B p65 (NF-κB p65) protein in kidney tissue of mice were tested by Western blot.ResultCompared with the normal group, the body weight, absolute renal weight, FBG, and the area under the curve (AUC) of OGTT of mice in the model group were significantly increased (P<0.01), and the levels of SCr, BUN, and U-mAlb, as well as TNF-α and IL-6 in serum were significantly increased (P<0.01). The glomerular basement membrane in the kidney tissue of mice was thicker, with obvious inflammatory cell infiltration. The protein expression levels of TLR4, MyD88, and NF-κB p65 in the kidney tissue of mice were increased significantly (P<0.01). Compared with the model group, there was no statistical difference in the body weight of mice in each drug administration group. The absolute renal weight of mice in the MLE-H and metformin groups was significantly reduced (P<0.05, P<0.01). The FBG levels of mice in the metformin, MLE-L, and MLE-H groups started to decrease after treatment for four to eight weeks (P<0.05, P<0.01). The AUC of mice in the MLE-H and metformin groups was significantly decreased (P<0.01). The levels of SCr, BUN, and U-mAlb of mice in the MLE-H and metformin groups were significantly decreased (P<0.01), and those of SCr and U-mAlb of mice in the MLE-L group were significantly decreased (P<0.01). The levels of TNF-α and IL-6 in the serum of mice in the MLE-H and metformin groups were significantly decreased (P<0.01). The renal tissue pathology of mice in each drug administration group was improved to varying degrees, and the protein expression levels of TLR4, MyD88, and NF-κB p65 in the MLE-H group were decreased significantly (P<0.05, P<0.01).ConclusionMLE can improve the renal structure and function of db/db diabetic mice, and its mechanism may be related to the inhibition of the TLR4/MyD88/NF-κB signaling pathway.
“科技新闻播报:桑叶,这一古老的中药材,如今在糖尿病研究领域展现出新的活力。桑叶具有疏散风热、清肺润燥、平肝明目、凉血止血等多种功效,尤其是其调节血糖的作用备受关注。通过检索中国知网、Web of Science及PubMed等数据库,相关研究发现,桑叶中的黄酮、生物碱、多糖、酚类等成分在降糖方面表现出显著效果。桑叶降糖机制涉及多成分、多通路、多靶点,主要通过改善糖脂代谢、保护胰腺β细胞、减轻胰岛素抵抗等方式减轻高血糖对机体的损害。为了更好地提取桑叶中的降糖活性成分,研究者们不断探索新的提取工艺,包括传统的溶剂提取法、超声辅助、微波辅助等,以及新兴的CO2超临界流体萃取法、酶解法、浊点萃取法等。通过对桑叶降糖有效部位的研究,分析各类降糖成分适用的提取方法,对比传统与新兴提取工艺的优缺点,有望为桑叶降糖有效部位提取工艺的优化、降糖化学成分及其作用机制研究、新药开发和临床应用提供有效的理论支撑。这一研究成果不仅为糖尿病治疗提供了新的思路,也为中药材的现代化应用开辟了新的方向。”
摘要:Mori Folium, the dried leaves of Morus alba, is widely used in clinical practice for dispersing wind and heat, clearing the lung and moistening dryness, soothing the liver and improving vision, and cooling blood and stopping bleeding. It has been used to regulate blood glucose since ancient times, and modern studies have shown that the active components of Mori Folium for lowering blood glucose mainly include flavonoids, alkaloids, polysaccharides, and phenols. These components are mainly extracted by solvents such as water and alcohols with the assistance of ultrasound and microwave. In addition, new extraction methods are emerging, such as CO2 supercritical fluid extraction, enzymatic hydrolysis, and cloud point extraction. Mori Folium lowers blood glucose via multiple components, pathways, and targets. Specifically, it can improve glucose and lipid metabolism, protect pancreatic β cells, and alleviate insulin resistance to reduce the damage caused by hyperglycemia and restore normal physiological functions. Although a large number of studies have been carried out on diabetes, the causes and radical treatment methods remain to be explored, and diabetes is still a major disease that endangers human health and needs to be solved urgently. The articles about extraction process and mechanism of active components in Mori Folium for lowering blood glucose were retrieved from the China National Knowledge Infrastructure (CNKI), Web of Science, and PubMed. We analyzed the applicable extraction methods for the blood glucose-lowering components such as flavonoids, polysaccharides, and alkaloids in Mori Folium, and compared the conventional and emerging methods. Furthermore, we summarized our research achievements in the extraction of active components from Mori Folium and the blood glucose-lowering effect and mechanisms. This review aims to provide theoretical support for the optimization of the extraction process, the research on the blood glucose-lowering components and mechanism, and the development of new drugs and clinical application of Mori Folium.
摘要:ObjectiveTo observe the effect of gastrodin on the steroid regulatory element-binding protein 1c (SREBP1c) signaling pathway in high-fat high-cholesterol diet (HFHC)-induced mice and explore the mechanism of gastrodin in the treatment of non-alcoholic fatty liver disease (NAFLD).MethodEight-week-old male C57BL/6J mice were used in vivo and divided into the following four groups, with six mice in each group: normal group, gastrodin group (50 mg·kg-1), model group, and model + gastrodin group (50 mg·kg-1). NAFLD model was established by feeding mice with HFHC for four weeks, and the mice were euthanized and the liver tissues were collected after four weeks. In vitro experiments were performed using Huh7 cells which were divided into five groups, and induced with free fatty acids (FFA, 200 μmol·L-1, oleic acid-palmitic acid 2∶1) to establish an NAFLD cell model. After 24 h, different concentrations of gastrodin (0, 5, 10, 20, and 40 μmol·L-1) were added to each group and cultured for another 24 h. Oil red O staining was used to detect lipid accumulation in mouse liver and Huh7 cells. Hematoxylin-eosin (HE) staining was used to observe pathological changes in liver tissue. Levels of serum total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and triglycerides (TG) were measured using an automatic biochemical analyzer. Relevant assay kits were used to detect liver TC, TG, and FFA levels. Real-time quantitative polymerase chain reaction (Real-time PCR) and Western blot were used to detect the expression of lipid synthesis-related proteins fatty acid synthase (FASN), acetyl-CoA carboxylase 1 (ACC1), and stearoyl-CoA desaturase 1 (SCD1).ResultCompared with the normal group, the model group showed significantly increased serum TC, LDL-C, and TG levels (P<0.01), liver TC, TG, and FFA levels (P<0.01), increased lipid accumulation in Huh7 cells (P<0.01), and significantly increased expression levels of lipid synthesis-related genes SREBP1c, FASN, ACC1, and SCD1 in mice and Huh7 cells (P<0.01). Compared with the model group, after gastrodin treatment, the serum TC, LDL-C, and TG levels in mice significantly decreased (P<0.05, P<0.01), the severity of fatty liver disease improved significantly, liver TC, TG, and FFA levels decreased significantly (P<0.05, P<0.01), lipid accumulation in Huh7 cells decreased significantly (P<0.05, P<0.01), the expression levels of lipid synthesis-related genes SREBP1c, FASN, ACC1, and SCD1 in mice and Huh7 cells decreased significantly (P<0.05, P<0.01).ConclusionGastrodin can reduce hepatic lipid accumulation and blood lipid levels, improve HFHC-induced NAFLD, and its mechanism of action may be related to the regulation of the SREBP1c lipid synthesis-related signaling pathway.
关键词:gastrodin;nonalcoholic fatty liver disease;steroid regulatory element-binding protein 1c (SREBP1c);dyslipidemia;steatosis
摘要:ObjectiveTo observe the intervention effect of Huaiqihuang granules (HQH) on immunoglobulin A vasculitis nephritis (IgAVN) mice and explore the underlying therapeutic mechanism.MethodFifty SPF-grade male Kunming mice were randomly divided into a normal group, an IgAVN model group, a dexamethasone group (2.5 mg·kg-1·d-1), a low-dose HQH group (4 g·kg-1·d-1), and a high-dose HQH group (8 g·kg-1·d-1). The mouse model was established using oral administration of gliadin combined with intravenous injection of India ink. After successful modeling, the mice were euthanized after 4 weeks of gastric gavage according to groups. The 24 h urinary total protein (24 h UTP), urine β2-microglobulin (β2-MG), serum total protein, albumin, IgA, etc. were detected in each group. Flow cytometry was used to determine the proportion of T helper 17 (Th17) cells in spleen cell suspension. Western blot was employed to detect the expression of adenosine 5'-monophosphate-activated protein kinase α (AMPKα), phosphorylated AMPKα (p-AMPKα), acetyl-CoA carboxylase 1 (ACC1), and phosphorylated ACC1 (p-ACC1) in Th17 cells. Pathological changes in the spleen and kidneys were observed.ResultCompared with the normal group, the IgAVN model group showed significant increases in 24 h UTP, urine β2-MG, total cholesterol (P<0.05), serum interleukin-17 (IL-17), IgA, Th17 proportion in the spleen cell suspension, and IL-17 expression in the spleen tissue (P<0.01), and significantly decreased serum total protein, albumin, p-AMPKα/AMPKα, and p-ACC1/ACC1 expression of Th17 cells (P<0.01). Compared with the IgAVN model group, in the 4th week, the 24 h UTP, urine β2-MG, serum IL-17, IgA levels, and renal IgA deposition were significantly reduced in each treatment group (P<0.01), and the Th17 proportion and IL-17 expression in spleen tissue were significantly decreased (P<0.05, P<0.01). Serum albumin levels significantly increased (P<0.05). Compared with the IgAVN model group, the dexamethasone group and the high-dose HQH group showed increases in serum total protein (P<0.01), p-AMPKα/AMPKα, and p-ACC1/ACC1 expression of Th17 cells (P<0.05, P<0.01). The high-dose HQH group showed a significant decrease in total cholesterol level (P<0.05). Various treatment groups showed different degrees of improvement in spleen and kidney pathological changes.ConclusionHQH may affect Th17 cell differentiation by regulating the AMPK/ACC pathway, correcting immune inflammatory disorders, and exerting therapeutic effects on IgAVN.
关键词:Huaiqihuang granules;immunoglobulin A vasculitis nephritis (IgAVN);adenosine 5'-monophosphate-activated protein kinase (AMPK);acetyl CoA carboxylase (ACC);T helper 17 (Th17) cell
摘要:ObjectiveTo prepare a rat model of heart failure after myocardial infarction by ligation of the anterior descending branch of the left coronary artery, and to observe the effect of Shenfu Yixin granules on the mitochondrial dynamics of rats with heart failure.MethodFifty SD male rats were randomly taken ten as the sham operation group and the rest as modeling group. The rat model of heart failure after myocardial infarction was prepared by ligation of anterior descending branch of left coronary artery. According to the left ventricular ejection fraction(LVEF) on the 28th day after operation, the model rats were randomly divided into the model group, Shenfu Yixin granule low-dose and high-dose groups(3.011, 15.055 g·kg-1) and sacubitril valsartan sodium group(20.83 mg·kg-1). Each administration group was gavaged daily with the corresponding dose of drug solution, while the sham operation group and model group were given the same amount of normal saline once a day for 28 days, with 6 rats in each group. Ultrasound was used to detect the cardiac function parameters, rat heart mass and body mass were weighed to calculate the cardiac mass index, enzyme linked immunosorbent assay(ELISA) was used to detect serum brain natriuretic peptide(BNP) and soluble growth stimulation expressed gene 2 protein(sST2) levels. Hematoxylin-eosin(HE) staining was used to observe the pathological morphology of the myocardium. Real-time fluorescence quantitative polymerase chain reaction(Real-time PCR) and Western blot were used to detect the mRNA and protein expression of mitochondrial fusion protein 1/2(Mfn1/2), optic atrophy protein 1(Opa1), dynamin-related protein 1(Drp1) and fission protein 1(Fis1).ResultCompared with the sham operation group, the mRNA and protein expression of LVEF, Mfn1, Mfn2, Opal in the model group decreased(P<0.05), while BNP, sST2, cardiac mass index, Drp1, Fis1 mRNA and protein levels increased(P<0.05). Compared with the model group, the expression of LVEF, Mfn1, Mfn2, Opal mRNA and protein increased in Shenfu Yixin granule high-dose and sacubitril valsartan sodium groups(P<0.05), while BNP, sST2, cardiac mass index, Drp1, Fis1 mRNA and protein levels decreased(P<0.05). Pathological observation showed that compared with the sham operation group, the model group had disordered arrangement of myocardial cells, inflammatory cell infiltration and myocardial fibrosis. Compared with the model group, the degree of inflammatory cell infiltration, myocardial or interstitial fibrosis was improved and alleviated in all administered groups.ConclusionShenfu Yixin granules can resist heart failure, reduce cardiac mass index, decrease BNP and sST2 contents, and improve cardiac function. Its mechanism may be related to the adjustment of mitochondrial dynamics.
摘要:ObjectiveTo investigate the intervention effect of Jiedu Tongluo Tiaogan prescription (JTTP) in protecting pancreatic β cells by targeting the bile acid Takeda G protein-coupled receptor 5 (TGR5)/cyclic adenosine monophosphate (cAMP) signaling pathway against NOD-like receptor protein 3 (NLRP3) inflammasome.MethodThirty-two male SPF-grade db/db mice were randomly divided into the model group, low-dose JTTP group (3.6 g·kg-1), high-dose JTTP group (7.2 g·kg-1), and metformin group (0.2 g·kg-1). Eight db/m mice were assigned to the blank control group. The mice were treated with drugs for 8 weeks, and fasting blood glucose (FBG) was measured every 2 weeks. Oral glucose tolerance tests (OGTT) were conducted after the last administration. Enzyme-linked immunosorbent assay (ELISA) was performed to detect fasting insulin (FINS), and the homeostasis model assessment of β-cell function (HOMA-β), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and IL-1β levels were calculated. Hematoxylin-eosin (HE) staining was used to observe pathological changes in mouse pancreatic tissue. Immunofluorescence was performed to detect insulin expression in mouse pancreatic tissue. Western blot and real-time quantitative polymerase chain reaction (Real-time PCR) were used to detect the expression of proteins and mRNAs of key targets in the TGR5/cAMP signaling pathway and NLRP3 inflammasome.ResultCompared with blank group, FBG, OGTT, FINS, IL-6, TNF-α and IL-1β in model group were significantly increased (P<0.01). Compared with model group, after 6 weeks of drug treatment, FBG level in JTTP group and metformin group decreased significantly (P<0.01). The results of OGTT experiment showed that compared with model group, the blood glucose levels of mice in each administration group were decreased at all time points (P<0.05, P<0.01), and the levels of FINS, TNF-α and IL-6 in JTTP dose groups and metformin group were significantly decreased. The level of IL-1β in JTTP high-dose group and metformin group was significantly decreased (P<0.01). Pancreatic pathology showed that the islets in the model group were irregular in shape, uneven in distribution, and showed signs of atrophy. The prognosis of JTTP was that the cell count increased and the boundary was clearer. Immunofluorescence results showed that the islet cells in the blank group were arranged in an orderly and full shape with appropriate insulin secretion, while the islet cells in model group were distorted in shape, atrophy in structure and less insulin secretion. The insulin content of mice in JTTP and metformin group was significantly increased. Compared with blank group, mRNA expressions of NLRP3, apoptosis-related spot-like protein (ASC) and Caspase-1 in pancreatic tissues of model group were significantly increased (P<0.01). Compared with model group, JTTP high-dose group and metformin group promoted the up-regulation of TGR5 and cAMP mRNA, and down-regulated the mRNA expressions of NLRP3, ASC and Caspase-1 (P<0.05, P<0.01). Compared with blank group, the expression of TGR5 protein in model group was significantly decreased (P<0.01). Compared with model group, TGR5 protein in JTTP high-dose group and metformin group was significantly increased (P<0.01).
摘要:ObjectiveTo investigate the mechanism of modified Shenhong Tongluo prescription on cell apoptosis in rats with myocardial ischemia-reperfusion injury (MIRI).MethodSixty Sprague-Dawley (SD) rats were randomly divided into a blank group, a model group, low-, medium-, and high-dose groups of modified Shenhong Tongluo prescription, and a simvastatin group. Except for the blank group, a rat model of MIRI was prepared by ligating the left anterior descending coronary artery. Starting from the first day after successful modeling, the blank group (1.0 mL·kg-1 physiological saline), model group (1.0 mL·kg-1 physiological saline), low-, medium-, and high-dose groups of modified Shenhong Tongluo prescription (1.031, 2.063, and 4.126 g·kg-1 Shenhong Tongluo prescriptiona standard concentrate), and simvastatin group (0.71 mg·kg-1 simvastatin) were orally administered once daily for 2 weeks. Hematoxylin-eosin (HE) staining was used to observe the pathological changes of cardiomyocytes. Enzyme-linked immunosorbent assay (ELISA) was used to detect the levels of serum creatine kinase isoenzyme (CK-MB), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α). TdT-mediated dUTP nick-end labeling(TUNEL) staining was used to detect the apoptosis rate of rat cardiomyocytes. Western blot was used to detect the expression levels of apoptosis-related proteins B-cell lymphoma-2 (Bcl-2), Bcl-2-associated X protein (Bax), and caspase-3.ResultCompared with the blank group, in the model group, HE staining showed disturbed arrangement of cardiomyocytes, incomplete fibers, focal necrosis of cardiomyocytes, and inflammatory cell infiltration; serum CK-MB, IL-6, and TNF-α levels were significantly increased (P<0.05); apoptosis rate of cardiomyocytes was significantly increased (P<0.01), with significantly increased expression levels of Bax and Caspase-3 proteins, and significantly decreased Bcl-2 expression (P<0.05). Compared with the model group, the low-, medium-, and high-dose groups of modified Shenhong Tongluo prescription significantly reduced CK-MB, IL-6, and TNF-α levels (P<0.05), significantly downregulated cardiomyocyte apoptosis rate (P<0.05), significantly decreased Bax and Caspase-3 proteins, and significantly increased Bcl-2 expression levels (P<0.01). In the modified Shenhong Tongluo prescription groups, the expression levels of Bax and Caspase-3 proteins significantly decreased with increasing dosage, while the expression level of Bcl-2 significantly increased with increasing dosage of modified Shenhong Tongluo prescription (P<0.05).ConclusionShenhong Tongluo prescription can alleviate myocardial tissue pathological damage and reduce myocardial cell apoptosis, possibly by inhibiting Caspase-3 and Bax expression and promoting Bcl-2 expression.
关键词:Shenhong Tongluo prescription;myocardial ischemia-reperfusion injury;apoptosis;B-cell lymphoma-2 (Bcl-2);Bcl-2-associated X protein (Bax);cysteine aspartic acid specific protease(Caspase)-3
摘要:ObjectiveTo observe the effects of Xibining (XBN) and adipose stem cell exosome (ADSC-Exos) in the cases of separate or joint application on cartilage degeneration and mitochondrial autophagy and explore its mechanism of action to improve knee osteoarthritis (KOA).MethodSD rats were divided into a sham operation group (sham group), a model group, an ADSC-Exos group (Exos group), an XBN group, and an ADSC-Exos+XBN group (Exos+XBN group). KOA model was established by using anterior cruciate ligament transection (ACLT). The pain sensitivity status of rats was evaluated, and the degeneration degree of the knee joint and cartilage tissue was detected by Micro-CT and pathological staining. The expression of p62 and LC3B was observed by immunofluorescence, and the serum levels of TNF-α, IL-1β, IL-6, and IL-15 in rats were detected by ELISA. The Western blot was used to detect the protein expression levels of MMP-3, MMP-13, ADAMTS5, ColⅡ, TIMP, ACAN, PINK1, Parkin, p62, and LC3A/B.ResultCompared with the sham group, rats in the model group showed decreased cold-stimulated foot-shrinkage thresholds and mechanical pain sensitivity thresholds, varying degrees of abrasion and loss of cartilage tissue, degeneration of cartilage tissue, elevated serum IL-1β, IL-6, IL-15, and TNF-α levels (P<0.01), and increased protein expression of MMP-3, MMP-13, and ADAMTS5 in cartilage tissue. In addition, the protein expression of ColⅡ, TIMP1, and ACAN was decreased (P<0.01). Compared with the model group, rats in each treatment group showed higher cold-stimulated foot-shrinkage thresholds and mechanical pain sensitivity thresholds, reduced cartilage tissue degeneration, lower serum levels of IL-1β, IL-6, IL-15, and TNF-α (P<0.05,P<0.01), decreased protein expression of MMP-3, MMP-13, and ADAMTS5, and higher protein expression of Cold, TIMP1, and ACAN in cartilage tissue (P<0.05,P<0.01). Moreover, the changes were the most obvious in the Exos+XBN group.ConclusionBoth ADSCs-Exos and XBN can increase the level of mitochondrial autophagy in chondrocytes and delay cartilage tissue degeneration by promoting the expression of the PINK1/Parkin signaling pathway, and the combination of the two can enhance the therapeutic effect.
摘要:ObjectiveTo observe the effect of modified Tianwang Buxindan (MTBD) on the skin of sleep-deprived (SD) mice and investigate its mechanism.MethodSixty 2-month-old female Kunming mice were randomly divided into a blank group, a model group, a vitamin C (VC, 0.08 g·kg-1), and MTBD low-, medium-, and high-dose groups (6.5, 12.5, 25 g·kg-1). Except for the blank group, the other groups were subjected to SD mouse model induction (using multiple platform water environment method for 18 hours of sleep deprivation daily from 15:00 to next day 9:00), continuously for 14 days, and caffeine (CAF, 7.5 mg·kg-1) was injected intraperitoneally from the 2nd week onwards, continuously for 7 days. While modeling, the blank group and the model group were administered with normal saline (0.01 mL·g-1), and the other groups received corresponding drugs for treatment. On the day of the experiment, general observations were recorded (such as body weight, spirit, fur, and skin). After sampling, skin tissue pathological changes were observed under an optical microscope using hematoxylin-eosin (HE) and Masson staining methods. Skin thickness and skin moisture content were measured. Biochemical assay kits were used to detect skin hydroxyproline (HYP) content, skin and serum superoxide dismutase (SOD) activity, and malondialdehyde (MDA) content. Enzyme-linked immunosorbent assay (ELISA) was used to detect serum interleukin (IL)-6, tumor necrosis factor (TNF)-α, and IL-1β levels in mice. Western blot was used to detect skin tissue type Ⅰ collagen (ColⅠ), type Ⅲ collagen (ColⅢ), phosphatidylinositol 3-kinase (PI3K), phosphorylated (p)-PI3K, protein kinase B (Akt), p-Akt, nuclear factor E2-related factor 2 (Nrf2), heme oxygenase (HO)-1, and nuclear factor (NF)-κB protein expression.ResultCompared with the blank group, the model group showed varying degrees of changes. In general, signs of aging such as reduced body weight (P<0.01), listlessness, dull fur color, and formation of wrinkles on the skin appeared. Tissue specimen testing revealed skin thinning, flattening of the dermoepidermal junction (DEJ), and reduced collagen fibers under the optical microscope. Skin thickness and moisture content decreased, skin tissue HYP content significantly decreased (P<0.01), skin and serum SOD activity significantly decreased (P<0.01), and MDA content significantly increased (P<0.01). Serum IL-6, TNF-α, and IL-1β levels significantly increased (P<0.01). Skin ColⅠ, ColⅢ, p-PI3K/PI3K, p-Akt/Akt, Nrf2, and HO-1 protein expression significantly decreased (P<0.05, P<0.01), and NF-κB expression increased (P<0.01). Compared with the model group, the VC group and the MTBD low-dose group showed increased skin moisture content, HYP content, SOD activity, and ColⅠ, ColⅢ, p-PI3K/PI3K protein expression (P<0.05, P<0.01), and decreased serum MDA content (P<0.05). In addition, a decrease in serum IL-6 and IL-1β levels was detected in the MTBD low-dose group (P<0.05), while the above indicators in the MTBD medium- and high-dose groups improved (P<0.05, P<0.01).ConclusionSleep deprivation accelerates the aging process of the skin in SD model mice. MTBD can improve this phenomenon, exerting anti-inflammatory and antioxidant effects, and its mechanism of action may be related to the activation of the PI3K/Akt/Nrf2 signaling pathway.
摘要:ObjectiveTo draft the Metadata of Evidence from Traditional Chinese Medicine Randomized Controlled Trials for standardizing thedata collection, storage, transmission, exchange, analysis, and evaluation of traditional Chinese medicine (TCM) studies. In addition to the application of conventional systematic review and meta-analysis, this draft will provide strong support for the development of automated systematic review, facilitate the efficient utilization of TCM clinical evidence, and underpin the evidence-based rapid decision-making in TCM.MethodThis study was structured into three stages. During the first stage (pre-research), suggestions for formulating new standards were proposed based on comprehensive research and demonstration of views obtained from literature investigation and expert interviews. The second stage concentrated on drafting the standard by assembling a working group and crafting a draft solicitation document for metadata standards. At the third stage, feedback was sought from relevant institutions, organizations, and experts and scholars outside the research group via mail or other means to finalize the draft standard.ResultDuring the pre-research stage, a preliminary examination was conducted to assess the characteristics and current status of clinical research metadata standards, and the information was identified regarding the significance of formulating the standard, principles guiding metadata formulation, reference materials, and suggestions for metadata subset establishment. After establishing a working group and drafting the initial version of the standard, opinions from external experts were sought via email. Based on the comments, a third round of revisions was conducted, resulting in the finalization of a draft for the standard. The finalized version of the standard draft comprised 12 sections: preface, introduction, scope, normative reference documents, terms and abbreviations, principles and composition, metadata description method, metadata summary representation, metadata dictionary description, Extensible Markup Language (XML) markup example, JavaScript Object Notation (JSON) markup example, and references. Of these, the section of metadata summary representation/metadata dictionary description contained 6 metadata subsets, involving 20 metadata entities and 141 metadata elements.ConclusionThrough literature research, expert interviews, questionnaire surveys, standard drafting, and opinion solicitation, this study drafts the Metadata of Evidence from Traditional Chinese Medicine Randomized Controlled Trials. This draft plays a crucial role in standardizing TCM clinical research and advancing objective scientific evaluation and effective utilization of TCM.
关键词:clinical evidence of traditional Chinese medicine;randomized controlled trial;metadata standard;formulation of a standard
摘要:ObjectiveTo systematically review the existing evidence of Tongxiening(TXN) Granules in the treatment of diarrhea-predominant irritable bowel syndrome (IBS-D) with liver Qi invading spleen syndrome,and evaluate the clinical comprehensive value from the 6+1 dimension,providing references for national medical decision-making,drug clinical application promotion,pharmaceutical services,etc.MethodFollowing the relevant standards of the "Guidelines for the Management of Clinical Evidence and Value Evaluation of Drugs", a combination of qualitative and quantitative approaches based on evidence-based medicine,questionnaire surveys,pharmacoeconomic evaluation,etc.,was employed. Multi-criteria decision analysis (MCDA) model was employed to comprehensively evaluate the clinical evidence and value of TXN Granules in the treatment of IBS-D with liver Qi invading spleen syndrome from the "6+1" dimensions of effectiveness,safety,economy,innovation,suitability,accessibility, and traditional Chinese medicine (TCM) characteristicsResult① Safety: Based on the evaluation of known risks and adequacy of safety evidence, TXN granules were considered to have controllable risks with sufficient safety evidence. ② Effectiveness: Meta-analysis showed that TXN granules combined with probiotics could reduce the intestinal symptom score level of IBS-D patients [mean difference (MD)=-2.29, 95% confidence interval (CI) (-3.20, -1.38), P<0.01], and TXN granules combined with conventional treatments (such as Bifidobacterium triple viable capsules,pinaverium bromide tablets,or trimebutine maleate tablets)effectively improved the comprehensive improvement rate of IBS-D patients [relative risk (RR)=1.19, 95%CI (1.14,1.25), P<0.01]. TXN granules significantly improved abdominal pain [RR=1.99, 95%CI (1.62,2.44), P < 0.01] and diarrhea efficacy rate [RR = 1.56, 95% CI (1.07,2.25), P<0.05] in IBS-D patients. TXN granules were comparable to pinaverium bromide tablets in reducing HAMA score [MD = 0.29, 95% CI (-0.30, 0.88), P=0.34], HAMD score [MD=0.35, 95%CI (-0.31,1.00),P=0.30], and improving IBS-QOL score [MD = 0.28, 95%CI (-1.70,2.26), P=0.78]. Based on the quality of evidence and evidence value assessment of effectiveness, it was considered that there was sufficient evidence of effectiveness for this product. ③ Economy: TXN granules are a national medical insurance category B product. After 5 years of simulation with three kinds of Markov models, it was considered that TXN granules were the advantageous treatment option with stable results and good economy. ④ Innovation: TXN granules adhered to original innovation, conducting research and development from clinical application, product components, and production processes. They have obtained national TCM new drug certificates, first prizes from the China Association of Chinese Medicine for Science and Technology, and excellent awards for Chinese patents, providing sufficient innovative evidence in clinical, corporate, and industrial aspects. ⑤ Suitability: The information service of this drug is comprehensive. The questionnaire survey results showed that this drug was suitable for clinical doctors, nurses, pharmacists, and patients in terms of individual compliance, system, and management across multiple dimensions. The overall assessment showed sufficient evidence of suitability for this product. ⑥ Accessibility: The daily cost of TXN granules accounts for 2.43% of the median disposable daily income of urban residents and 9.26% of rural residents, which is moderate and reasonable compared to similar drugs. There is sufficient evidence of affordability, and it is sold nationwide covering all 31 provinces, municipalities, and autonomous regions, with full accessibility evidence and clear results. TCM characteristics: TXN granules originate from the prescription for treating diarrhea in Danxi's Experiential Therapy. They are derived from classical formulas and have undergone multiple clinical trials involving 5 000 cases since their launch, accumulating a certain amount of human use experience. Based on the principles of evaluating TCM characteristics, TXN granules highlight TCM characteristics. The comprehensive value measured using CSC V2.0 software is 0.83 points based on the results of “6+1” dimensions.ConclusionBased on the evaluation results of TXN granules in various dimensions and the comprehensive evaluation score, it is considered that there is sufficient clinical value evidence for TXN granules in treating IBS-D with liver Qi invading spleen syndrome, which can provide references for clinical decision-making and pharmaceutical management. It is suggested for future research to conduct network Meta-analysis, conduct horizontal comparisons of similar TCM treatments for IBS-D, improve the quality of evidence-based evidence, and fully leverage the clinical value advantages of TXN granules.
摘要:ObjectiveTo observe the clinical efficacy of modified Yigongsan combined with multi-enzyme tablets and bifidobacterium triple live powder on infantile anorexia with spleen-stomach Qi deficiency syndrome.MethodA total of 112 infantile patients anorexia with spleen-stomach Qi deficiency syndrome treated at Hebei Provincial Hospital of Traditional Chinese Medicine from January 2022 to June 2023 were enrolled and divided into a control group and an observation group, with 56 cases in each group, according to a random number table. Children in the control group were treated with multi-enzyme tablets and Bifidobacterium triple live powder, while those in the observation group were treated with modified Yigongsan in addition to the treatment in the control group. During the study, one case dropped out in the control group and two cases dropped out in the observation group. The clinical efficacy of the two groups of children was compared, including changes in traditional Chinese medicine (TCM) syndrome scores (main symptoms, secondary symptoms, tongue, and pulse), time to restore normal food intake, and increase in body weight. Changes in calcium, iron, zinc levels, hemoglobin, and albumin levels before and after treatment, as well as changes in gastrointestinal hormones such as gastrin and motilin, vasoactive intestinal peptide, somatostatin, neuropeptide Y, orexin, and leptin, were observed. The occurrence of adverse reactions in the two groups of children during the study was also recorded.ResultThe total effective rate of children in the control group after treatment was 85.19% (46/54), while that in the observation group was 98.15% (53/54) (χ2 =5.939, P<0.05). Compared with the control group, the time for food intake to return to normal in the observation group was shorter, and the increase in body weight was greater (P<0.05). Compared with the results before treatment, the TCM syndrome scores (main symptoms, secondary symptoms, tongue, and pulse) in both groups of children significantly decreased, while the levels of calcium, iron, zinc, hemoglobin, albumin, gastrin, motilin, neuropeptide Y, and orexin increased, and the levels of vasoactive intestinal peptide, somatostatin, and leptin decreased (P< 0.01). Compared with the control group after treatment, the improvement in the above indicators in the observation group was more significant (P<0.01). The incidence of adverse reactions in the two groups of children during the treatment period was similar, and the difference was not statistically significant.ConclusionModified Yigongsan combined with multi-enzyme tablets and Bifidobacterium triple live powder is highly effective in treating infantile anorexia (spleen-stomach Qi deficiency syndrome). After treatment, symptoms of the children were improved,appetite and food intake increased, gastrointestinal function was improved, body weight increased, and adverse reactions were few, indicating that the treatment was safe and reliable.
摘要:ObjectiveKey microRNAs (miRNAs) of colorectal adenoma (CRA) were identified and analyzed by bioinformatics methods, and differentially expressed genes (DEGs) were screened to construct regulatory relationships. The mechanism of Xiezhuo Jiedu recipe in preventing CRA was speculated and verified by animal experiments.MethodThe miRNAs dataset GSE50194 was obtained from the Gene Expression Omnibus (GEO) database of intestinal mucosal tissue of CRA patients, and the differentially expressed miRNAs were screened by GEO2R and Excel. TargetScan, miRTarbase, and miRDB databases were used to predict the target genes of the differentially expressed miRNAs, and an intersection was obtained. Key DEGs were screened through the STRING database and Cytoscape software, and the TRRUST database was used to predict downstream binding transcription factors (TFs). The mRNA intersection was enriched by gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) in the Metascape database. DIANA TOOLS were applied to perform KEGG enrichment analysis of key miRNAs, and the key signaling pathways were selected for animal experiments. In animal experiments, the CRA mice model was established by using sodium glycan sulfate (DSS) drinking combined with intraperitoneal injection of azomethane oxide (AOM), and Xiezhuo Jiedu recipe and aspirin were given by intragastric administration at the same time. The experiment lasted for nine weeks. The pathological changes in intestinal tissue were observed by hematoxylin-eosin (HE) staining. Real-time fluorescence quantitative polymerase chain reaction (Real-time PCR) was used to detect the mRNA expression of miR-34a-5p in adenoma tissue. Protein expression levels of phosphatidylinositol 3-kinase (PI3K), protein kinase B (Akt), phosphoryl-PI3K (p-PI3K), phosphoryl-Akt (p-Akt), and B cell lymphoma (Bcl)-2 were detected by Western blot. The expression of Cyclin D1 (CCND1) was detected by immunohistochemistry (IHC). In situ terminal transferase labeling (TUNEL) was used to detect apoptosis of adenoma tissue cells.ResultThe GEO database screened the GSE50194 dataset, and miR-34a-5p was selected as the research object from CRA and normal tissue. A total of 93 DEGs were selected. Among them, GO and KEGG enrichment analyses were closely related to biological processes such as transcriptional regulatory complex, RNA polymerase Ⅱ transcriptional regulatory complex, enzyme-linked receptor protein signaling pathway, and DNA-binding transcriptional activator activity, cancer pathway, PI3K/Akt pathway, etc. miR-34a-5p is mainly enriched in PI3K/Akt, cell cycle, and colorectal cancer pathways. Five key DEGs were screened out through the Matescape database, among which Bcl-2 and CCND1 were the key DEGs of miR-34a-5p. Further screening of the TFs of key DEGs revealed that E2F transcription factor 1 (E2F1) and tumor protein P53 (TP53) were the main TFs of Bcl-2 and CCND1. Animal experiments showed that Xiezhuo Jiedu recipe could effectively up-regulate mRNA level of miR-34a-5p, down-regulate the expression of PI3K, Akt, Bcl-2, p-PI3K, and p-Akt proteins in the intestinal tissue of CRA mice, down-regulate the positive expression rate of CCND1, and increase the apoptosis rate of intestinal epithelial cells.ConclusionIt is speculated that Xiezhuo Jiedu recipe may inhibit the abnormal proliferation and promote the apoptosis of intestinal epithelial cells in CRA mice by regulating the miR-34a-5p/PI3K/Akt signaling pathway, thus playing a role in the prevention of CRA.
摘要:ObjectiveThe bioinformatics method was used to screen ferroptosis differential genes (FRGs) closely related to ulcerative colitis (UC), and animal experiments were conducted to verify whether the mechanism of Xiezhuo Jiedu recipe in treating UC is related to the regulation of ferroptosis.MethodThe differentially expressed genes (DEGs) of colonic mucosa tissue of UC patients were obtained from the GEO database, and the intersection of the genes with ferroptosis genes was used to obtain FRGs. The core FRGs were obtained by cluster analysis, minimum absolute contraction and selection operator (LASSO) regression, and receiver operating characteristic curve (ROC) curve analysis. In animal experiments, the UC mouse model was prepared by making the mouse freely drink 2.5% dextran sodium sulfate (DSS). Xiezhuo Jiedu recipe and mesalazine were given by gavage for seven days, and the inflammatory infiltration of colonic mucosa was observed by hematoxylin-eosin (HE) staining. Real-time fluorescence quantitative polymerase chain reaction (Real-time PCR) was used to detect the mRNA expression levels of E3 ubiquitin ligase (FBXW7), zinc finger protein (ZFP36), solute carrier family 7 member 11 (SLC7A11), and Toll-like receptor 4 (TLR4) in colon tissue. The protein expression levels of FBXW7, ZFP36, SLC7A11, and TLR4 in colon tissue were detected by Western blot.ResultDataset GSE87466 was screened from the GEO database, and its intersections with the ferroptosis gene were analyzed to obtain 21 FRGs. After cluster analysis, LASSO regression, and ROC analysis, core FRGs (FBXW7, ZFP36, SLC7A11, and TLR4) were obtained. Immunoinfiltration analysis showed significant differences in the expression of initial B cells, M1 macrophages, plasma cells, and M2 macrophages in the colonic mucosa tissue of UC mice, and there was a significant correlation between core FRGs and these immune cells. Further animal experiments showed that the colonic mucosa tissue of mice in the model group was disorganized and infiltrated by a large number of inflammatory cells. The inflammation of the colonic mucosa tissue of mice in each group was relieved to varying degrees after treatment with Xiezhuo Jiedu recipe and mesalazine, while the colonic mucosa tissue of mice in the high-dose group of Xiezhuo Jiedu recipe showed almost no inflammatory changes. Compared with the normal group, the protein and mRNA expressions of FBXW7, ZFP36, SLC7A11, and TLR4 in the model group were significantly increased, and the expression of core FRGs in colonic mucosa tissue of mice in all groups was significantly down-regulated after treatment with Xiezhuo Jiedu recipe and mesalazine.ConclusionFBXW7, ZFP36, SLC7A11, and TLR4 are ferroptosis genes closely related to the pathogenesis of UC, and Xiezhuo Jiedu recipe can significantly alleviate colonic mucosa inflammation in mice by down-regulating core ferroptosis genes.
摘要:ObjectiveThe differential expression of microRNAs (miRNAs) between the active stage and the remission stage of ulcerative colitis (UC) was analyzed by bioinformatics method, and the regulatory relationship was constructed by screening the differentially expressed genes (DEGs). The mechanism of Xizhuo Jiedu recipe in the treatment of UC was speculated and verified by animal experiments.MethodThe miRNAs data set of colonic mucosa tissue of UC patients was obtained from the gene expression database (GEO), and the most differentially expressed miRNAs were screened by GEO2R, Excel, and other tools as research objects. TargetScan, miRTarbase, miRDB, STRING, TRRUST, and Matescape databases were used to screen key DEGs, predict downstream transcription factors (TFs), gene ontology (GO), and conduct Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. The key signaling pathways were selected for animal experiments. In animal experiments, the UC mouse model was prepared by making the mouse freely drink 2.5% dextran sodium sulfate (DSS). Xiezhu Jiedu recipe and mesalazine were given by gavage for seven days, and the inflammatory infiltration of colonic mucosa was observed by hematoxylin-eosin (HE) staining. Real-time fluorescence quantitative polymerase chain reaction (Real-time PCR) was used to detect the mRNA expression of miR-155-5p in colon tissue. Immunohistochemistry and Western blot were used to detect the protein expression levels of cytokine signal transduction inhibitor (SOCS1), phosphorylated transcriptional signal transductor and activator 3 (p-STAT3), phosphorylated Janus kinase 2 (p-JAK2), and retinoic acid-associated orphan receptor-γt (ROR-γt). The expression levels of transforming growth factor-β (TGF-β), interleukin-17 (IL-17), interleukin-6 (IL-6), and interleukin-10 (IL-10) in serum were detected by enzyme linked immunosorbent assay (ELISA).ResultThe GSE48957 dataset was screened from the GEO database, and miR-155-5p was selected as the research object from the samples in the active and remission stages. 131 DEGs were screened. The GO/KEGG enrichment analysis was closely related to biological processes such as positive regulation of miRNA transcription and protein phosphorylation, as well as signaling pathways such as stem cell signaling pathway, IL-17 signaling pathway, and helper T cell 17 (Th17) cell differentiation. The Matescape database was used to screen out 10 key DEGs, among which SOCS1 was one of the key DEGs of miR-155-5p. Further screening of the TFS of key DEGs revealed that STAT3 was one of the main TFs of SOCS1. The results of animal experiments showed that Xiezhu Jiedu Recipe could effectively down-regulate the mRNA expression of miR-155-5p and protein expression of p-STAT3, p-JAK2, and ROR-γt in colon tissue of UC mice and the expression of IL-17 and IL-6 in serum of UC mice, up-regulate the protein expression of SOCS1 and the expression of TGF-β and IL-10, increase the level of anti-inflammatory factors, and reduce inflammatory cell infiltration.ConclusionIt is speculated that Xizhuo Jiedu recipe may interfere with SOCS1 by regulating the expression of miR-155-5p in UC mice, inhibit the phosphorylation of STAT3, inhibit the differentiation of CD4+ T cells into Th17 cells, reduce the levels of pro-inflammatory factors (IL-17 and IL-6), and increase the levels of anti-inflammatory factors (TGF-β and IL-10). As a result, the inflammation of colon mucosa in UC mice was alleviated.
关键词:bioinformatics;ulcerative colitis;Xiezhu Jiedu recipe;miRNA-155-Janus kinase 2 (p-JAK2)/signal transduction and activator of transcription 3 (STAT3) signaling pathway
摘要:ObjectiveTo realize the automatic recognition of the slicing angles of Fritillariae Thunbergii Bulbus (FTB) based on the improved YOLOv7-tiny algorithm.MethodFirstly, a diverse dataset of FTB images, totaling 16 000 pictures, with various angles was constructed. Furthermore, improvements were made to YOLOv7-tiny by replacing standard convolutions with ghost convolution (GhostConv), incorporating the coordinate attention (CA) mechanism as a preferred addition, substituting some activation functions with HardSwish function for decreasing the floating point operations. Additionally, a penalty term for angle recognition error was integrated into the loss function, and modifications were made to the non-maximum suppression (NMS) strategy to address cases where multiple detection results were associated with the same target. In order to verify the effectiveness of different improvement points on the optimization of the algorithm model, ablation experiments were carried out on all the improvement points, and the effectiveness of the improvement points was proved by comparing the prediction results before and after the addition of a certain improvement point on the basis of the original model or the model with the addition of an improvement point that has been verified to be effective, in order to evaluate the improvement of the indexes.ResultThe number of parameters required for the improved slicing angle recognition algorithm of FTB was about 55.4% of the original algorithm, and the amount of computation was about 59.4% of the original algorithm. The mAP@0.5[mean average precision at an intersection over union(IoU) of 0.5] increased by 12.2%, the mean absolute error(MAE) of the recognized angle was 5.02°, representing a reduction of 4.58° compared to the original algorithm. In the experimental environment of this paper, the average recognition time per image was as low as 8.7 ms, significantly faster than the average human reaction time.ConclusionThis study, by utilizing the improved YOLOv7-tiny algorithm, achieves effective slicing angle recognition of FTB with high accuracy and more lightweight, which provides a novel approach for stable and precise automated slicing of FTB, thereby providing valuable insights into the automation of processing other traditional Chinese medicines.
摘要:ObjectiveThe glycosidic linkage structural characteristics of polysaccharides from Pinelliae Rhizoma(PR) and its processed products were analyzed by sugar spectrum, high performance thin layer chromatography(HPTLC), fluorescence-assisted carbohydrate gel electrophoresis(PACE) based on partial acid hydrolysis and specific glycosidase hydrolysis, and the antioxidant activities of polysaccharides before and after hydrolysis(enzymolysis) were compared.MethodPolysaccharides from PR and its processed products were extracted by ultrasound extraction, starch was hydrolyzed by α-amylase, and small molecules below 3 kDa were removed by ultrafiltration. The purified polysaccharides were prepared by hydrolysis of acid and five different specific glycosidases, and the hydrolysates were analyzed by HPTLC and PACE. The antioxidant capacity of polysaccharides was analyzed by 2,2′-azino-bis(3-ethylbenzthiazoline-6-sulfonic acid)(ABTS) and 2,2-diphenyl-1-picrylhydrazyl(DPPH) free radical scavenging experiment before and after different hydrolysis.ResultThrough HPTLC and PACE analysis, it was found that polysaccharides from PR and its processed products could be hydrolyzed by β-galactosidase, β-mannase, cellulase and pectinase, but hardly hydrolyzed by glucanase, indicating that the polysaccharides contained β-galactopyranoside bond, β-1,4-mannoside bond, β-1,4-glucoside bond and α-1,4-galacturonic acid glycosidic bond. In vitro antioxidant experiments showed that the ABTS radical scavenging capacity of the polysaccharides from PR and its processed products was weakened after acid hydrolysis and pectinase enzymatic hydrolysis, while the ABTS radical scavenging capacity was enhanced after enzymatic hydrolysis with cellulase, β-galactosidase, and β-mannase. And after different hydrolysis, the DPPH free radical scavenging capacity of polysaccharides from PR and its processed products was all significantly enhanced.ConclusionThe glycosidic linkage structural characteristics of polysaccharides from PR and its processed products was analyzed by sugar spectrum in this paper, and the relationship between glycosidic bond types and their antioxidant activity was clarified through in vitro antioxidant experiments, which is beneficial for further elucidating the material basis of the related efficacy of PR and its processed products, and providing new ideas and methods for analyzing the structural characteristics of polysaccharides in Chinese medicines.
摘要:ObjectiveUltra-performance liquid chromatography-quadrupole-time-of-flight mass spectrometry(UPLC-Q-TOF-MS) was used to identify the metabolites of harmine in rats, in order to explore the differences in distribution of metabolites in rats after single dose(40 mg·kg-1) intragastric administration of harmine, as well to speculate the metabolic pathways.MethodSD rats were given a single dose of harmine by intragastric administration. Plasma, bile, urine and feces samples were collected after administration, and the samples were processed for determination by UPLC-Q-TOF-MS. The separation was performed on an ACQUITY UPLC™ HSS T3 columu(2.1 mm×100 mm, 1.8 μm) with acetonitrile(A)-0.1% formic acid aqueous solution(B) as mobile phase for gradient elution(0-2 min, 5%A; 2-9 min, 5%-35%A; 9-9.5 min, 35%-100%A; 9.5-12 min, 100%A; 12-12.5 min, 100%-5%A; 12.5-14 min, 5%A), the mass spectra were obtained in positive ion mode with electrospray ionization(ESI), the scanning range was m/z 50-1 200. The metabolites of harmine were identified based on the information of the obtained compounds and the literature data, and the metabolic pathways were hypothesized.ResultA total of 42 compounds(harmine and its metabolites) were identified in rats, including 27 in plasma, 17 in bile, 26 in urine and 13 in feces. The metabolic pathways involved in these 42 metabolites included monohydroxylation, dihydroxylation, demethylation, glucuronidation and sulfation.ConclusionHarmine can undergo phase Ⅰ and phase Ⅱ metabolic reactions in rats, and the prototype drug is metabolized rapidly in vivo, and the metabolites are mainly excreted by the kidneys, which can provide a reference basis for the pharmacodynamics and material basis of harmine.
关键词:harmine;ultra performance liquid chromatography-quadrupole-time-of-flight mass spectrometry(UPLC-Q-TOF-MS);metabolites;metabolic pathways;plasma;bile;urine
摘要:This paper systematically combed and verified the name, origin, producing area, quality evaluation, harvesting, processing of Euryales Semen in famous classical formulas by consulting relevant ancient materia medica, medical books, prescription books and modern literature. The results showed that Euryales Semen was first collected by materia medica under the name of Jitoushi, and since the Ming dynasty, Qianshi has been used as a proper name and continues to this day, with other aliases such as Yanhuishi. Euryale ferox, a plant of the Nymphaeaceae family, is the same as that used in the past dynasties. However, due to long-term artificial domestication, the varieties vary with the origin, including Beiqian and Suqian. The medicinal part of Euryales Semen is mature seed kernel, its origin of ancient records mainly includes Shandong, Jiangsu, Henan and other places, since the Ming and Qing dynasties, Euryales Semen produced in Suzhou has been highly praised. Since modern times, it has gradually summarized and formed the best quality evaluation method of Euryales Semen with full grains, white cross-section, powdery enough and no broken powder. The harvesting time in the past dynasties was mainly August or in autumn. The main processing methods in the past dynasties included peeling for powder, pounding powder after steaming, drying and frying. Up to now, two mainstream processing methods of cleansing and stir-frying have been formed. Based on the research results, it is recommended that the mature seed kernel of E. ferox be used in famous classical formula Yihuangtang. Combined with the processing requirements of the original formula, it is suggested to refer to the stir-frying method in the general principles of processing of the current edition of Chinese Pharmacopoeia.
关键词:famous classical formulas;Euryales Semen;herbal textual research;origin;species;change of geographical origin;evolution of scientific name
摘要:Daochisan is a pediatric famous classical formula in traditional Chinese medicine(TCM) specializing in clearing the heart, disinhibiting water and enriching Yin, which has been inherited and developed by medical experts of successive generations. The formula can be traced back to Xiaoer Yaozheng Zhijue written by QIAN Yi from Song dynasty, and most of the later-developed Daochisan(Daochitang) is based on this formula with additions and subtractions. So as to promote the literature excavation of this formula, this paper conducts a thorough textual research and analysis of the composition, processing, preparation methods, clinical applications of Daochisan based on a systematic collation of relevant ancient and modern literature in the method of bibliometrics. A total of 127 pieces of data involving 86 antient TCM books were collected. Statistical analysis showed that the drug origin of Daochisan is basically clear, we suggest that Rehmanniae Radix is the root tuber of Rehmannia glutinosa of Scrophulariaceae, Akebiae Caulis is the dry stem of Akebia quinata of Lardizabalaceae, Glycyrrhizae Radix et Rhizoma is the dry root and stem of Glycyrrhiza uralensis of legume, bamboo leaf is the dry leaves of Phyllostachys nigra var. henonis of gramineous plants. Four herbs are recommended to use its raw products. The key information of the dosage and decocting method is supposed to be "4.13 g each of raw Rehmanniae Radix, raw Glycyrrhizae Radix et Rhizoma, Akebiae Caulis, adding 300 mL of water, and then adding 4.13 g of bamboo leaf, decocting together to 150 mL, taking warmly after meal". Daochisan has the effect of clearing the heart and enriching Yin, disinhibiting water and relieving stranguria, and is widely used in treating symptoms such as heart vexed hotness, hydrodipsia and reddish complexion. Modern studies have showed that Daochisan are frequently used in treating oral ulcer, herpetic stomatitis, urinary tract infection, herpes zoster and other diseases. The above research results can provide scientific reference for the future development and research of Daochisan.
关键词:Daochisan;historic origin;prescription analysis;efficacy;clinical application;pediatric famous classical formula;textual research
摘要:Lung cancer has the highest incidence and mortality rate among all cancers in China, with its complex and variable nature, long treatment duration, and often poor prognosis. Currently, the treatment of lung cancer mainly employs classical therapies such as surgery, radiotherapy, and chemotherapy, but some patients may experience a series of adverse reactions, which affect their quality of life, survival period, and treatment outcomes. As reported, oxidative stress is one of the important pathogenic factors of lung cancer, affecting its occurrence and development. Oxidative stress is a state of imbalance between oxidative products and antioxidant defense mechanisms in the body. The intervention of oxidative stress in the occurrence and development of lung cancer is related to multiple signaling pathways, including the Kelch-like ECH-associated protein 1 (Keap1)-nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway, phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR) signaling pathway, mitogen-activated protein kinase (MAPK) signaling pathway, and nuclear factor-κB (NF-κB) signaling pathway. Currently, researchers in China and abroad have conducted extensive studies on the occurrence and development of lung cancer and the pathophysiological mechanisms of drug intervention. The results have shown that oxidative stress plays an important role in the occurrence and development of lung cancer. Chinese medicine monomers and compounds can regulate oxidative stress levels and intervene in related signaling pathways, thereby inhibiting or delaying the occurrence and development of lung cancer. Based on this, this article mainly summarized the relevant signaling pathways regulating oxidative stress intervention in lung cancer in recent years, and also reviewed the latest research on Chinese medicine monomers and compounds in regulating oxidative stress to treat lung cancer, aiming to provide new ideas for research on drug treatment of lung cancer and clinical drug development, as well as to provide references and guidance for further in-depth mechanistic studies in the future.
关键词:oxidative stress;lung cancer;traditional Chinese medicine;signaling pathways
摘要:Idiopathic oligoasthenospermia (IO) has been increasingly emphasized in the diagnosis and treatment of male infertility. Oxidative stress damage directly affects sperm quality and spermatogenesis, constituting a major causative factor of IO. Firstly, due to its high content of polyunsaturated fatty acids, the sperm plasma membrane is highly sensitive to reactive oxygen species (ROS), leading to lipid peroxidation accumulation and even inducing ferroptosis. Secondly, deficient downstream key proteins in the base excision repair pathway render sperm unable to repair extensive DNA oxidative damage under oxidative stress. Simultaneously, under oxidative stress, the apoptotic pathway of sperm is cascade-activated, causing rapid loss of motility. ROS further disrupts the hypothalamic-pituitary-gonadal axis, inhibiting testosterone production and ultimately affecting spermatogenesis. Wuzi Yanzongwan,in line with traditional Chinese medicine theory of treating IO through "nourishing kidney essence and harmonizing Yin and Yang", clinically demonstrates its ability to improve sperm morphology, count, and motility, thereby enhancing male fertility. The research on the pharmacological constituents of Wuzi Yanzongwan primarily involves establishing a characteristic spectrum of Chinese medicine to achieve quality control and exploring the pharmacology of effective components. Studies have found that its main active ingredients consist of flavonoids and phenylpropanoids. Specifically, compounds such as hyperin, acteoside, kaempferol, and schisandrin A are identified as the primary active substances and quality control components. These compounds exhibit strong antioxidant activity and have been partly applied in research related to reproductive endocrine disorders. Tripterygium glycoside is primarily used for modeling of oxidative stress-induced IO. It leads to the accumulation of various lipid peroxides in testicular tissues and concurrently compromises the body's antioxidant capacity. Mechanistic studies have found that Wuzi Yanzongwan can inhibit elevated ROS levels in IO models and enhance the body's antioxidant capacity, thereby ameliorating inflammation, suppressing cell apoptosis, promoting testosterone production, and ultimately alleviating the decline in sperm quality and spermatogenesis caused by oxidative stress.
摘要:Inflammatory bowel disease (IBD), mainly including ulcerative colitis (UC) and Crohn's disease (CD), is a common chronic inflammatory disease of the gastrointestinal tract, with its incidence increasing year by year. Due to its long treatment duration, difficulty in treatment, prolonged remission, and high costs, it has attracted global attention. Exploring safe, effective, and sustainable treatment regimens has become an urgent global issue. The pathogenesis of IBD is complex, involving intestinal mucosal injury,disturbances in the internal environment, and inflammatory responses. In recent years, research has found that ferroptosis is also one of the important pathogenic factors of IBD. Ferroptosis, as a new form of non-apoptotic cell death, is characterized by iron dependence, lipid peroxidation, and imbalance in the redox system. Studies have shown that inhibiting ferroptosis in intestinal epithelial cells can protect the intestinal mucosa. Targeted intervention in ferroptosis may be a new direction for the treatment of IBD. IBD is mainly treated with drugs, including corticosteroids, aminosalicylates, biologics, and immunomodulators, but drug resistance and adverse reactions are common. Traditional Chinese medicine (TCM) has unique advantages such as low cost, low drug resistance, and fewer side effects, and has accumulated rich experience in the treatment of IBD. Scholars have confirmed that TCM can inhibit ferroptosis, and recent studies have shown that TCM can not only inhibit iron-dependent lipid peroxidation in intestinal cells but also enhance the antioxidant and anti-inflammatory abilities of intestinal mucosa, thus playing a role in the treatment of IBD. Increasing evidence suggests that TCM may treat IBD by interfering with ferroptosis. This article explores the relevance of TCM intervention in ferroptosis and the treatment of IBD, discusses the possible mechanisms of ferroptosis in IBD, and aims to provide a basis for the diagnosis and treatment of IBD.
关键词:inflammatory bowel disease;ulcerative colitis;Crohn's disease;ferroptosis;traditional Chinese medicine;research progress
摘要:Neurological diseases are common and frequent in clinical practices, which are the main reasons that affect the quality of life and physical and mental health of patients seriously. Tianma Goutengyin (TGY) is from the New Significance of Patterns and Treatment in Miscellaneous Diseases, which was compiled by a famous doctor, HU Guangci. TGY is widely used in clinical practice and has the effects of calming the liver and calming the wind, clearing heat and activating the blood, tranquilization, and nourishing the liver and kidneys. Clinical studies have confirmed that modified TGY can be used either alone or in combination with acupuncture or western medicine to treat dementia, headache, vertigo, hypertension, insomnia, Parkinson's disease, stroke, epilepsy, and other common neurological diseases, with significant curative effect, few side effects, and high safety. The main active constituents of single flavor drugs in the composition of TGY mainly include gastrodin, gastrodia elata blume polysaccharides, p-hydroxybenzyl alcohol, rhynchophylline, baicalein, leonurine, stachydrine, geniposide, 2,3,5,4,-tetrahydroxystilbene-2-Ο-β-D-glucoside, pinoresinol diglucoside, pachymic acid, β-ecdysteroid, avicularin, etc. It has been found that TGY and these constituents have the effects of ferroptosis inhibition, anti-apoptosis, anti-inflammation, and oxidation resistance, and they can regulate neurotransmitters and autophagy, reduce cerebral edema reduction, lower blood lipid and blood pressure, and improve blood circulation through multiple targets and pathways. This paper reviewed the clinical application of and the mechanism of the whole prescription and single flavor drugs of TGY in the treatment of neurological diseases, so as to provide a theoretical basis for the clinical application of TGY and offer ideas for the follow-up mechanism research of this prescription.
摘要:Ischemic stroke (IS) is a serious cerebrovascular disease common in clinical practice. Targeting the pathogenesis of IS, intravenous thrombolysis for restoring blood flow is still the most effective therapy. However, intravenous thrombolysis has shortcomings such as increased bleeding risk, narrow therapeutic window, and contraindications, which limited its clinical application. Protection of the ischemic brain tissue before full recovery of blood flow is associated with the prognosis of IS. Studies have identified multiple pathways in the alleviation of the brain injury caused by IS, such as the mammalian target of rapamycin (mTOR) signaling pathway. Traditional Chinese medicine (TCM) has abundant therapies and unique advantages in the treatment of IS, especially in alleviating symptoms and improving the quality of life of patients. After the onset of IS, TCM can be integrated with Western medicine to play a role in the whole process of treatment, rehabilitation, and recurrence prevention as soon as possible, thus maximizing patient benefits. TCM has clinical significance for the recovery of neurological and motor functions after IS. Studies have shown that TCM can reduce the cerebral injury caused by IS by regulating and activating the mTOR signaling pathway, thereby regulating autophagy, inhibiting apoptosis of nerve cells, and reducing oxidative stress and inflammation. TCM exerts a positive effect for achieving cerebral protection and improving the prognosis of IS and provides new ideas for the prevention and treatment of IS. This article introduces the role of the mTOR signaling pathway in the pathogenesis of IS and reviews the research progress in the TCM regulation of this pathway in the treatment of IS, aiming to provide new therapeutic ideas and systematic scientific reference for the treatment of IS with TCM.
关键词:ischemic stroke;mammalian target of rapamycin (mTOR);signaling pathway;autophagy;Chinese medicine;research progress
摘要:Inflammation is involved in the development of various acute and chronic diseases in the body. Sustained inflammatory responses are key driving factors for diseases such as cancer, neurodegenerative diseases, cardiovascular diseases, metabolic syndrome, inflammatory bowel disease, and arthritis. Therefore, finding anti-inflammatory drugs is crucial for the prevention and treatment of various diseases. In recent years, there has been increasing attention to finding natural drugs with minimal toxic side effects. Lonicerae Japonicae Flos and Lonicerae Flos, as traditional Chinese medicines potent in clearing heat and removing toxins, have strong biological activity and multiple pharmacological effects. They are widely distributed in the plant world and have significant medicinal value. With the continuous advancement of the research on Lonicerae Japonicae Flos and Lonicerae Flos, they have been widely used in the medical field and possess great development potential. Currently, research mainly focuses on the anti-inflammatory mechanisms of Lonicerae Japonicae Flos and Lonicerae Flos, while systematic summaries of their anti-inflammatory active ingredients are rare. Therefore, this paper focuses on the differential analysis of the anti-inflammatory active components of Lonicerae Japonicae Flos and Lonicerae Flos. In addition, it reviewed the possible mechanisms by which extracts and active ingredients of Lonicerae Japonicae Flos and Lonicerae Flos may exert anti-inflammatory effects through various pathways, such as influencing the release of cellular inflammatory factors, regulating inflammatory signaling pathways such as nuclear factor-κB (NF-κB), mitogen-activated protein kinase (MAPK), signal transducer and activator of transcription 3 (STAT3), MAPK/extracellular signal-regulated kinase (ERK)/c-Jun N-terminal kinase (JNK), phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt)/NF-κB, and Janus kinase (JAK)/signal transducer and activator of transcription (STAT) signaling pathways, increasing antioxidant stress capacity, enhancing immune defense capabilities, and improving intestinal microbiota, aiming to provide a theoretical basis for the rational clinical application of Lonicerae Japonicae Flos and Lonicerae Flos.
摘要:Osteoarthritis (OA) is a common degenerative joint disease with a rising incidence rate year by year. Treatment often relies on analgesics and non-steroidal anti-inflammatory drugs (NSAIDs), which can lead to gastrointestinal damage with long-term use and the recurrence of symptoms. Chinese medicine has a long history of preventing and treating OA, with widespread application and fewer side effects. It offers unique advantages such as a broad treatment scope, multiple targets, and pathways. The effective components of Chinese medicine can reduce the content of reactive oxygen species (ROS), relieve oxidative stress (OS) damage, and increase the antioxidant capacity of the body by interfering with the expression of biomarkers of OS response such as malondialdehyde (MDA) and superoxide dismutase (SOD). Through the modulation of signaling pathways such as nuclear factor E2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1), phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt), nuclear factor kappa B (NF-κB), c-Jun N-terminal kinase (JNK), NOD-like receptor protein 3 (NLRP3), and osteoprotegerin (OPG), they downregulated the expression of inflammatory factors such as interleukin-6 (IL-6), interleukin-1β (IL-1β), and tumor necrosis factor-α (TNF-α), thereby effectively relieving local joint inflammation, protecting chondrocytes and bone tissue, inhibiting chondrocyte apoptosis, and further alleviating the progression of OA. Currently, there are still certain limitations in the medical research status and development trends of OA, necessitating the continued advancement of traditional Chinese medicine. This paper reviewed the literature on the regulation of OS response by effective components of Chinese medicine for the prevention and treatment of OA, providing new directions and ideas for future research.
关键词:active ingredients of Chinese medicine;oxidative stress;anti-oxidation;osteoarthritis
摘要:Hippophae rhamnoides is a traditional Chinese medicine with homology of medicine and food, which has the effects of relieving cough and resolving phlegm, strengthening the stomach and digestion, and promoting blood circulation and resolving blood stasis. H. rhamnoides contains not only flavonoids, phenols, proteins, vitamins, and amino acids but also abundant polysaccharides. In order to explore the functional value and current research status of H. rhamnoides polysaccharides, this study systematically summarized the extraction process, structural characteristics, pharmacological effects, and mechanism of action of H. rhamnoides polysaccharides by reviewing Chinese and foreign literature. The results showed that H. rhamnoides polysaccharides have anti-tumor, hypoglycemic, antioxidant, immune regulation, anti-inflammatory, and anti-hyperlipidemia functions and could improve intestinal microbiota. There were various extraction processes for polysaccharides, including hot water extraction, microwave extraction, ultrasonic extraction, enzymatic extraction, flash extraction, ultrasonic-microwave synergistic extraction, emerald hot water extraction, enzymatic-ultrasonic synergistic extraction, etc. Based on comprehensive analysis, hot water extraction is suitable for industrial development and application. However, multiple homogeneous polysaccharides have been isolated and purified from H. rhamnoides polysaccharides, but their efficacy, structure, and structure-activity relationship still need to be further explored and studied. This study can provide a reference for the research and development of H. rhamnoides polysaccharides.
关键词:Hippophae rhamnoides polysaccharides;extraction process;chemical structure;anti-tumor;hypoglycemic;antioxidant;immune regulation;improvement of intestinal microbiota;anti-inflammatory