摘要:ObjectiveTo observe the effects of Wendantang on the expression of inflammatory cytokines, autophagy markers, and key molecules of phosphatidylinositol-3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/Akt/mTOR) signaling pathway in the adipocytes of the rat model of obesity (syndrome of phlegm-dampness) and to explore the material basis of inflammation in obesity (syndrome of phlegm-dampness) and the underlying mechanism of Wendantang intervention.MethodA total of 126 SD rats were randomized into 2 groups: 16 rats in the blank group and 110 rats in the modeling group. The blank group was fed with a basic diet while the modeling group with a high-fat diet to establish the animal model of obesity (syndrome of phlegm-dampness) for 8 weeks. After successful modeling, 48 obese rats were selected according to their body mass and randomized into a model control group, an orlistat (ORLI, 32.40 mg·kg-1) group, a rapamycin (RAPA, 2 mg·kg-1) group, and low-, medium-, and high-dose (4.45, 8.90, 17.80 g·kg-1, respectively) Wendantang groups, with 8 rats in each group. In addition, 8 rats were randomly selected from the blank group to be set as the normal control group. The corresponding agents in each group were administrated by gavage and the model and control groups were administrated with equal amounts of distilled water once daily for 6 weeks. The body mass, Lee's index, body fat ratio, and obesity rate were measured or calculated. The expression of UNC51-like kinase-1 (ULK1), Beclin1, human autophagy-related protein 5 (Atg5), p62, and microtubule-associated protein 1 light chain 3 (LC3) Ⅰ/Ⅱ (markers of autophagy in adipocytes) was detected by the immunohistochemical two-step method. Enzyme-linked immunosorbent assay (ELISA) was employed to determine the expression of tumor necrosis factor (TNF)-α, interleukin-6 (IL-6), IL-1β, monocyte chemotactic protein-1 (MCP-1), IL-4, IL-10, IL-13, and transforming growth factor (TGF)-β in adipocytes. Western blot was employed to measure the protein levels of classⅠ-PI3K, phosphatidylinositol triphosphate (PIP3), Akt, mTORC1, ULK1, TSC1, and TSC2 in adipocytes.ResultCompared with the blank group, the modeling group showed increased body mass and Lee's index (P<0.01), the obesity rate >20%, and phlegm-dampness syndrome manifestations such as physical obesity, decreased mobility, decreased appetite, lusterless and tight fur, loose stools, decreased responsiveness to the outside world, and decreased water intake. Compared with the normal control group, the model control group showed increased body mass, Lee's index, body fat ratio, adipocyte autophagy marker expression, pro- and anti-inflammatory cytokine levels (P<0.05, P<0.01), down-regulated protein levels of classⅠ-PI3K, PIP3, Akt, mTORC1, TSC1, and TSC2 (P<0.01), and up-regulated protein level of ULK1 (P<0.01). The intervention groups showed lower body mass, body fat ratio, adipocyte autophagy marker protein expression, and protein levels of TNF-α, IL-6, IL-1β, MCP-1, IL-4, and IL-13 than the model control group (P<0.05, P<0.01). Moreover, the RAPA and Wendantang (medium and high dose) groups showed lowered levels of IL-10 and TGF-β (P<0.01), and the ORLI group showed down-regulated expression of TGF-β (P<0.01). The expression of key molecules of the signaling pathway was up-regulated (P<0.05, P<0.01) while that of ULK1 was down-regulated (P<0.01) in all the intervention groups. Compared with the RAPA group, the Wendantang groups showed up-regulated expression of all autophagy marker proteins in adipocytes (P<0.01). In addition, the low-dose Wendantang group showed elevated levels of inflammatory cytokines (except TNF-α) (P<0.05, P<0.01) and down-regulated expression of all key molecules of the signaling pathway (P<0.05, P<0.01). The levels of inflammatory cytokines (except IL-16, MCP-1, and IL-10) were elevated in the medium-dose Wendantang group (P<0.05, P<0.01). The expression of key molecules except PI3K of the signaling pathway was down-regulated in the medium- and high-dose Wendantang groups (P<0.05, P<0.01). Compared with the ORLI group, low- and medium-dose Wendantang groups showed up-regulated expression of autophagy markers in adipocytes (P<0.01), and the low-dose group showed elevated levels of inflammatory cytokines (IL-6, IL-4, and TGF-β) (P<0.01) and down-regulated expression of all key molecules of the signaling pathway (P<0.01). The medium-dose Wendantang group showed up-regulated expression of IL-4 (P<0.01) and down-regulated expression of key molecules except PI3K of the signaling pathway (P<0.05, P<0.01). The high-dose Wendantang group showed increased body mass, up-regulated expression levels of autophagy markers (ULK1, LC3 Ⅰ/Ⅱ) (P<0.05, P<0.01), down-regulated expression of PIP3, mTORC1, and TSC1 (P<0.05, P<0.01), and lowered levels of Beclin1, Atg5, TNF-α, and IL-13 (P<0.05, P<0.01).ConclusionThe inflammation in obesity (syndrome of phlegm-dampness) is closely associated with the PI3K/Akt/mTOR pathway-mediated adipocyte autophagy. Wendantang can treat the chronic inflammation in obese rats with the syndrome of phlegm-dampness by regulating this signaling pathway and thus improve adipocyte autophagy.
关键词:Wendantang;obesity (syndrome of phlegm-dampness);phosphatidylinositol-3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/Akt/mTOR) signaling pathway;autophagy;chronic inflammation;mechanism of action
摘要:ObjectiveTo investigate the effect of Jingui Shenqiwan on diabetic osteoporosis (DOP) in mice by regulating the advanced glycation end products (AGEs)/receptor activator of nuclear factor-κB ligand (RANKL)/nuclear factor-κB (NF-κB) signaling pathway based on the theory of "kidneys governing bones".MethodForty 6-week-old male and female skeletal-muscle-specific, dominant negative insulin-like growth factor-1 receptor (MKR) mice were selected and fed on a high-fat diet for eight weeks to establish the DOP model. The model mice were randomly divided into a model group, low- and high-dose Jingui Shenqiwan group (1.3, 2.6 g·kg-1), and an alendronate sodium group (0.01 g·kg-1), with 10 mice in each group. Additionally, 10 FVB/N mice of the same age were assigned to the normal group. The corresponding drugs were administered orally to each group once a day for four weeks. After the administration period, fasting blood glucose (FBG) measurement and oral glucose tolerance test (OGTT) were conducted. Kidney function and kidney index were measured. Renal tissue pathological changes were observed through hematoxylin-eosin (HE) and Masson staining. Immunohistochemistry was performed to assess the protein expression levels of AGEs, phosphorylated NF-κB (p-NF-κB), and RANKL in renal tissues. Western blot analysis was conducted to measure the expression of proteins related to the AGEs/RANKL/NF-κB signaling pathway, osteoprotegerin (OPG), and Runt-related transcription factor 2 (RUNX2) proteins in femoral bone tissues.ResultCompared with the normal group, mice in the model group exhibited significantly increased FBG (P<0.01), trabecular bone degeneration, abnormal bone morphological parameters, significantly increased area under the curve (AUC) of OGTT (P<0.01), enlarged kidney volume, significantly increased kidney function indicators and kidney index (P<0.01), disrupted renal glomeruli and renal tubule structures, significantly increased expression of AGEs, RANKL, and p-NF-κB/NF-κB in renal tissues (P<0.05), and significantly decreased expression of OPG and RUNX2 in femoral bone tissues (P<0.01). Compared with the model group, mice in the Jingui Shenqiwan groups showed a significant decrease in OGTT AUC (P<0.01). Histopathological analysis revealed alleviated structural lesions in renal glomeruli and renal tubules. Furthermore, the expression of AGEs, RANKL, and p-NF-κB/NF-κB in renal tissues was significantly reduced (P<0.05, P<0.01), and the expression of RUNX2 and OPG in femoral bone tissues was significantly increased (P<0.05, P<0.01).ConclusionJingui Shenqiwan can improve kidney function and downregulate the AGEs/RANKL/NF-κB signaling pathway to inhibit inflammatory reactions, thereby alleviating the symptoms of DOP in mice, demonstrating a therapeutic effect on DOP from the perspective of the kidney.
关键词:Jingui Shenqiwan;diabetic osteoporosis;advanced glycation end products (AGEs)/receptor activator of nuclear factor-κB ligand (RANKL)/nuclear factor-κB (NF-κB) signaling pathway;kidneys governing bones
摘要:ObjectiveTraditional Chinese medicine, namely Dahuang Zhechongwan (DHZCW) was used to treat myocardial fibrosis in model rats, observe its effect on myocardial fibrosis in rats, and explore its action mechanism.MethodThirty-six SPF male Kunming rats were divided into blank group, model group, low-, medium-, high-dose groups of DHZCW (0.056, 0.084, 0.168 g·kg-1), captopril group (10 mg·kg-1), with six rats in each group. Except for the blank group, the other groups were intraperitoneally injected isoproterenol solution of 5 mg·kg-1 for 15 consecutive days to replicate the myocardial fibrosis model. At the beginning of modeling, the rats in each group took drugs, and they were sacrificed 28 days after administration. Serum and heart tissue were collected for the corresponding detection. Hematoxylin-eosin (HE) staining and Masson staining were used to observe tissue inflammation, cellular degeneration, necrosis, and fibrosis. The contents of hydroxyproline (HYP), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6), hyaluronic acid (HA), laminin (LN), type-Ⅲ procollagen (PC Ⅲ) in serum of rats and rats were determined by enzyme-related immunosorbent assay (ELISA). The expression levels of key pathway proteins transforming growth factor-β1 (TGF-β1), α-smooth muscle actin (α-SMA), Smad2, Smad3, and Smad7 were detected by Western blot. The expression levels of key pathway genes TGF-β1, α-SMA, Smad2, Smad3, Smad7, miR-29a-5p, miR-29b-2-5p, and miR-29c-5p were detected by Real-time quantitative polymerase chain reaction (Real-time PCR).ResultCompared with the blank group, the pathological changes of fibrosis in the model group were obvious, the contents of serum HYP, TNF-α, IL-1β, IL-6, HA, LN, and PCⅢ were increased (P<0.01), the protein expression levels of TGF-β1, α-SMA, Smad2, and Smad3 were increased; the protein expression level of Smad7 was decreased (P<0.01). The mRNA expression levels of TGF-β1, α-SMA, Smad2, and Smad3 were increased (P<0.05, P<0.01), while those of Smad7, miR-29a-5p, miR-29b-2-5p, and miR-29c-5p were decreased (P<0.01). Compared with the model group, after 28 days of administration, serum HYP, TNF-α, IL-1β, IL-6, HA, LN, and PCⅢ in high-, medium-, and low-dose groups of DHZCW and captopril groups were decreased (P<0.01). Except for the low-dose group, the protein contents of TGF-β1, α-SMA, Smad2, and Smad3 were decreased, while the protein content of Smad7 was increased (P<0.01). The mRNA expression levels of TGF-β1, Smad2, α-SMA, and Smad3 in high-dose group of DHZCW were decreased (P<0.05,P<0.01), while those of Smad7, miR-29a-5p, miR-29b-2-5p, and miR-29c-5p were increased (P<0.05). The mRNA expressions of TGF-β1, Smad2, and Smad3 in the medium-dose group of DHZCW were decreased (P<0.05, P<0.01), while mRNA expression of Smad7 was increased (P<0.01). The mRNA levels of TGF-β1 and Smad2 in the low-dose group of DHZCW were decreased (P<0.01).ConclusionDHZCW can improve myocardial fibrosis in rats, and its action mechanism may be related to the regulation of the TGF-β1/Smads/miR-29 pathway. In addition, there is dose dependence in the range of 0.056-0.168 g·kg-1, and the effect of the high-dose group is more stable.
摘要:ObjectiveTo validate the alleviating effect of Gegen Qinliantang (GGQLT) on insulin resistance in db/db diabetic mice by regulating the silent information regulator 1 (SIRT1)/forkhead transcription factor O1 (FoxO1) autophagy pathway.MethodSeventy-five SPF-grade spontaneous type 2 diabetic db/db mice and 15 control db/m mice were selected and maintained on regular feed for one week before measuring blood glucose. They were randomly divided into six groups, with 15 mice in each group. The groups included a normal group (physiological saline, 0.2 g·kg-1), a metformin group (0.2 g·kg-1), high-, medium-, and low-dose GGQLT groups (31.9, 19.1, 6.9 g·kg-1), and a model group (physiological saline, 0.2 g·kg-1). They were orally treated with corresponding drugs for eight weeks, once daily. Fasting blood glucose (FBG) was measured using a Roche glucometer. Serum levels of high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), triglyceride (TG), and total cholesterol (TC) were measured using an automated biochemical analyzer. Fasting serum insulin (INS) levels were determined using enzyme-linked immunosorbent assay (ELISA), and the homeostasis model assessment of insulin resistance (HOMA-IR) was calculated. Western blot was used to detect the expression of Beclin-1, microtubule-associated protein 1 light chain 3 (LC3), and SIRT1/FoxO1 autophagy pathway-related proteins in liver tissues. Immunohistochemistry was performed to assess the expression of SIRT1, FoxO1, Beclin-1, and LC3B proteins in liver tissues. Transmission electron microscopy was used to observe the formation of autophagosomes in the liver.ResultCompared with the normal group, the model group showed significant increases in FBG, FINS, HOMA-IR, TC, TG, LDL-C, and HDL-C levels (P<0.01), and significant increases in the expression of SIRT1, Beclin-1, LC3, and FoxO1 proteins in liver tissues (P<0.01). Transmission electron microscopy revealed the highest number of autophagosomes in the model group. Compared with the model group, the metformin group and the low-, medium-, and high-dose GGQLT groups showed significant decreases in serum FBG, FINS, HOMA-IR, TC, TG, LDL-C, and HDL-C levels (P<0.05, P<0.01), significant decreases in the expression of SIRT1, Beclin-1, LC3 (P<0.05, P<0.01), and up-regulated FoxO1 protein (P<0.01). Transmission electron microscopy showed a reduction in the degree of autophagy in the treatment groups. Compared with the metformin group, the medium- and high-dose GGQLT groups showed significant decreases in FBG, FINS, and TG levels (P<0.01), significant decreases in the expression of SIRT1, Beclin-1, and LC3 in liver tissues (P<0.05, P<0.01), and reduced FoxO1 protein (P<0.01). The high-dose GGQLT group showed reduced HOMA-IR, TC, LDL-C, and HDL-C levels (P<0.05, P<0.01). Transmission electron microscopy revealed a significant reduction in autophagosomes in the medium- and high-dose GGQLT groups.ConclusionGGQLT can significantly improve glucose and lipid metabolism disorders, alleviate insulin resistance in db/db mice, and prevent and treat type 2 diabetes by activating the SIRT1/FoxO1 autophagy pathway.
摘要:ObjectiveTo observe the regulatory effects of Yiqi Wenyang Huwei decoction (YWHD) on autophagy and phosphatidylinositol 3-kinase (PI3K)/protein kinase B(Akt)/mammalian target of rapamycin (mTOR) signaling pathway in asthmatic rats and bronchial epithelial cells (16HBE) and further reveal the mechanism of YWHD in treating bronchial asthma (BA).MethodForty-eight rats were randomly assigned into normal group, model group, dexamethasone group, and low-, medium-, and high-dose YWHD groups, with 8 rats in each group. The rat model of BA was established by intraperitoneal injection with ovalbumin (OVA) + aluminum hydroxide suspension and atomizing inhalation with OVA for 2 weeks. The normal group was administrated with an equal dose of normal saline. The bronchial maximum airway resistance (Max Rrs) induced by methacholine chloride (Mch) was determined by an animal lung function evaluation system. Enzyme-linked immunosorbent assay (ELISA) was employed to measure the levels of interleukin (IL)-4, IL-13, IL-6, IL-33, IL-25, tumor necrosis factor-α (TNF-α), and immunoglobulin E (IgE) in the bronchial alveolar lavage fluid. Hematoxylin-eosin (HE) and Masson staining were used for observation of the pathological changes of bronchi in the lung tissue. The immunofluorescence assay was employed to measure the levels of the autophagy-associated proteins LC3B and Beclin1. The IL-13-induced autophagy of 16HBE cells exposed to the YWHD-containing serum was observed, and the autophagy level was traced by mRFP-GFP-LC3 adenovirus infection. The protein levels of LC3Ⅱ/Ⅰ, p-PI3K, p-Akt and p-mTOR were determined by Western blot.ResultCompared with the normal group, the model group showed increased Max Rrs (P<0.01) and elevated levels of IL-4, IL-13, IL-6, IL-33, IL-25, TNF-α, and IgE in the bronchial alveolar lavage fluid (P<0.05,P<0.01). The modeling caused focal infiltration of inflammatory cells and lymphocytes around bronchus and blood vessels, epithelial goblet cell metaplasia, and increased subepithelial collagen deposition. Furthermore, it up-regulated the protein levels of LC3B and Beclin1 (P<0.01), promoted the autophagy flux of GFP to mRFP in 16HBE cells induced by IL-13, down-regulated the protein levels of p-PI3K, p-Akt, and p-mTOR, and increased the LC3Ⅱ/Ⅰ ratio (P<0.01). Compared with the model group, medium- and high-dose YWHD decreased Max Rrs (P<0.01), lowered the levels of IL-4, IL-13, IL-6, IL-33, IL-25, TNF-α, and IgE in the bronchial alveolar lavage fluid (P<0.05, P<0.01), and reduced lymphocyte and granulocyte infiltration in bronchi of the lung tissue, epithelial goblet cell metaplasia, and subepithelial collagen deposition. Moreover, they down-regulated the protein levels of LC3B and Beclin1 (P<0.05, P<0.01), decreased the autophagy flux of GFP to mRFP, up-regulated the protein levels of p-PI3K, p-Ak, and p-mTOR, and decreased the LC3Ⅱ/Ⅰ ratio (P<0.05, P<0.01).ConclusionYWHD ameliorates airway hyperresponsiveness and airway inflammation and inhibits the autophagy of airway epithelial cells in the lung tissue of BA rats by activating the PI3K/Akt/mTOR signaling pathway.
摘要:ObjectiveTo explore the underlying mechanism of bran-fried Atractylodis Rhizoma (AR) in improving gastrointestinal function by comparing the effects of raw AR and bran-fried AR on the small intestine tissue structure and transport-related protein carriers in rats with spleen deficiency syndrome.MethodSeventy male SD rats were randomly divided into a normal group, a model group, high- and low-dose raw AR groups (10, 2.5 g·kg-1), high- and low-dose bran-fried AR groups (10, 2.5 g·kg-1), and a compound glutamine group (9 mg·kg-1), with 10 rats in each group. Except for the normal group, the other six groups were subjected to the spleen deficiency model induced by the method of bitter and cold breaking stagnated Qi and abnormal hunger and fullness for 21 days. After modeling, each treatment group was given medication orally according to the corresponding doses every day for a total of 14 days, and the normal group and the model group were given an equal volume of normal saline orally. During the treatment period, the general survival status, macroscopic syndrome score, daily increase in body weight and food intake, and rectal temperature of the spleen deficiency rats were evaluated, and after the treatment, the rats were sacrificed. The pathological changes in the small intestine tissues of each group were observed by hematoxylin-eosin (HE) staining. The content of serum 5-hydroxytryptamine (5-HT) was detected by enzyme-linked immunosorbent assay (ELISA), and the content of serum D-xylose, lactate, and amylase was detected by colorimetry. The levels of free fatty acid receptor 3 (FFA3) and peptide transporter 1 (PepT1) in small intestinal tissues were detected by the Bradford method, and the protein expression of sodium-dependent glucose transporter 1 (SGLT1) and glucose transporter 1 (GLUT1) in small intestinal tissue was detected by immunohistochemistry. Real-time fluorescence-based quantitative PCR was used to detect the mRNA expression of glucose transporter 2 (GLUT2), sodium/hydrogen exchanger 3 (NHE3), and 5-hydroxytryptamine receptor 4 (5-HT4R).ResultCompared with the normal group, the model group exhibited symptoms of spleen deficiency, such as sluggishness, squint, reduced food intake, and lethargy at the end of modelling, damaged basic structure of the small intestinal mucosal epithelium and lamina propria, increased serum lactate and 5-HT content, and decreased serum amylase and D-xylose (P<0.01). Compared with the model group, all treatment groups showed varying degrees of improvement, with the small intestinal microstructure repaired to different degrees. The daily weight gain, anal temperature, and macroscopic syndrome score of spleen deficiency improved to varying degrees (P<0.05, P<0.01). The serum lactate and 5-HT content decreased to varying degrees, while the serum amylase and D-xylose content increased to varying degrees (P<0.05, P<0.01). The PepT1 content in the small intestinal tissues increased, while the FFA3 content decreased to varying degrees. The protein expression of SGLT1 and GLUT1 increased, while the mRNA expression of GLUT2 and NHE3 increased to varying degrees. The mRNA expression of 5-HT4R decreased to varying degrees (P<0.05, P<0.01). Compared with the high- and low-dose raw AR groups, the high- and low-dose bran-fried AR groups showed significant improvement in general conditions and histopathological improvement of the small intestinal tissues. The daily weight gain, anal temperature, and macroscopic syndrome score of spleen deficiency also improved (P<0.05, P<0.01). The serum lactate and 5-HT content decreased, while the serum amylase and D-xylose content increased (P<0.05, P<0.01). The PepT1 content in the small intestinal tissues increased, while the FFA3 content decreased. The protein expression of SGLT1 and GLUT1 increased, while the mRNA expression of GLUT2 and NHE3 increased. The mRNA expression of 5-HT4R decreased significantly (P<0.05, P<0.01).ConclusionBran-fried AR can improve the spleen deficiency-related symptoms and histopathology of the small intestinal tissues in spleen deficiency model rats. Its mechanism may be related to the regulation of the expression of various transport-related protein carriers and the secretion of various digestive enzymes after stir-frying of AR, thus restoring the absorption and transport function of the small intestine.
摘要:ObjectiveTo investigate the effect of alcohol extract of Oroxylum indicum (MHD-80) on reducing uric acid (UA) and protecting the kidney in the hyperuricemia (HUA) model in vivo.MethodPotassium oxazine (350 mg·kg-1) and adenine (80 mg·kg-1) were used to construct an HUA model of mice in vivo to evaluate the mechanism related to UA reduction and the protective effect of renal function of MHD-80. Seventy male ICR mice were randomly divided into seven groups, including the normal group, model group, allopurinol group (5 mg·kg-1), febusotan group (5 mg·kg-1), and MHD-80 low-, medium-, and high-dose groups (3, 6, 12 mg·kg-1), with 10 in each group. Except for the normal group, the other groups were given intragastric administration of potassium oxazine and adenine for 14 consecutive days to establish the HUA model. On the 8th to 14th day after modeling, each group was given corresponding drugs by intragastric administration, once a day. 1 h after the last administration, blood was collected from the eyeballs, and kidney and liver tissues of mice were collected. Serum levels of UA, urea nitrogen (BUN), and creatinine (Cr) and liver activity of xanthine oxidase (XOD) were determined by enzyme colorimetry. Serum contents of tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) were determined by enzyme-linked immunosorbent assay (ELISA). Hematoxilin-eosin (HE) staining was used to observe the pathological changes in kidney tissues. The protein expression levels of ATP-binding box transporter G2 (ABCG2) and glucose-facilitating transporter 9 (GLUT9) in kidney tissues were detected by Western blot.ResultIn vivo experiment shows that compared with the normal group, the serum levels of UA, Cr, BUN, inflammatory factors TNF-α, IL-1β, and liver XOD activity in the serum of mice in the model group were significantly increased (P<0.05, P<0.01), and the expression of GLUT9 in kidney tissues was significantly up-regulated (P<0.05). ABCG2 protein expression was significantly down-regulated (P<0.05), and renal injury was obvious. Compared with the model group, the levels of UA, BUN, Cr, TNF-α, IL-1β, and liver XOD activity in the serum of mice in the high-dose group of MHD-80 were decreased to different degrees (P<0.05, P<0.01), GLUT9 protein expression was significantly down-regulated (P<0.01), ABCG2 protein expression was significantly up-regulated (P<0.05) in the high-dose group of MHD-80, and the degree of renal injury was reduced.ConclusionMHD-80 has certain uric acid reduction, anti-inflammatory, and anti-renal injury effects, which are related to inhibiting XOD activity and regulating the expression of ABCG2 and GLUT9 uric acid transporter.
关键词:alcohol extract of Oroxylum indicum;hyperuricemia;xanthine oxidase;renal injury;uric acid transporter
摘要:ObjectiveTo investigate the predictive indicators of early efficacy of Bushen Shengxue prescription combined with western medicine in the treatment of aplastic anemia, and provide prognosis indicators for the treatment of aplastic anemia (AA) with kidney-tonifying therapy in traditional Chinese medicine (TCM) combined with western medicine.MethodA total of 126 patients treated by Bushen Shengxue prescription combined with western medicine in 19 hospitals including Xiyuan Hospital of the China Academy of Chinese Medical Sciences from September 2018 to March 2021 were selected for a retrospective study. The therapy was proven to be effective after six months of treatment. According to the efficacy after 4 months of treatment, the patients were assigned into a 4-month effective group and a 4-month ineffective group. The age, sex, disease severity (including severe aplastic anemia and non-severe aplastic anemia), course of disease, degree of bone marrow nucleated cell proliferation, baseline hemogram levels [including white blood cell count (WBC), absolute neutrophil count (ANC), hemoglobin (HGB), platelets (PLT), and reticulocytes (RET)], T lymphocytes subsets, and the expression levels of T-box transcription factor (T-bet) and GATA-binding protein-3 (GATA-3) were compared between the two groups before treatment.ResultThe proportions of patients within the age ranges of [20, 40) and [60, 80) were higher in the 4-month effective group (P<0.05). The sex, disease severity, course of disease, and comorbidities had no significant differences between the two groups. The 4-month effective group had higher baseline levels of HGB, WBC, ANC, and PLT than the 4-month ineffective group (P<0.05), and there was no significant difference in the RET level between the two groups before treatment. Binary Logistic regression analysis showed that the PLT level before treatment was an independent factor affecting the onset time, while other indicators did not affect the onset time. The receiver operating characteristic (ROC) curve was established to analyze the value of PLT level before treatment for predicting the onset time, and the area under the curve was 0.691. With the critical value of 40.5×109/L, the sensitivity and specificity of the prediction that the therapy will take effect within 4 months were 0.569 and 0.893, respectively. The two groups of patients were graded according to age {(14, 20), [20, 40), [40, 60), and [60, 80)} and PLT level before treatment (PLT<40×109/L, PLT≥40×109/L). The proportion of the patients with PLT≥40×109/L before treatment in the 4-month effective group was significantly higher than that in the 4-month ineffective group (P<0.05). The degree of bone marrow nucleated cell proliferation before treatment had no significant difference between the two groups. The level of total T lymphocytes in the 4-month effective patients was lower than that in the 4-month ineffective patients before treatment (P<0.05). The levels of Th1 cells, Th2 cells, CD4+ T cells, and CD8+ T cells showed no significant differences between the two groups before treatment. The T-bet expression level in the 4-month effective group was higher than that in the 4-month ineffective group before treatment (P<0.05), while the expression level of GATA-3 showed no significant difference between the two groups before treatment.ConclusionBushen Shengxue prescription combined with western medicine will achieve faster effect for the patients within the age ranges of [20, 40) or [40, 60), with higher levels of HGB, WBC, ANC, and PLT (especially those with PLT≥40×109/L), lower level of total T lymphocytes, or higher T-bet expression level before treatment.
关键词:aplastic anemia;Bushen Shengxue prescription;integrated traditional Chinese and western medicine treatment;early efficacy;predictive indicators
摘要:ObjectiveTo explore the clinical effect of kidney-tonifying and blood-generating method and qi-promoting and blood-nourishing method combined with western medicine on the treatment of aplastic anemia and the characteristics of blood routine recovery, and to explore a new phased treatment model for aplastic anemia.MethodThis study was based on a prospective, multicenter, double-blind, and randomized controlled clinical trial. Patients with aplastic anemia from 19 centers were analyzed and divided into a kidney-tonifying and blood-generating group and a Qi-promoting and blood-nourishing group, which were treated with traditional Chinese medicine (TCM) combined with western medicine. The clinical effect and the changes in blood routine in each group during treatment were evaluated.ResultDuring the observation period, 375 cases of aplastic anemia were included in two groups, and TCM syndrome differentiation conformed these cases as Qi-deficiency type and both Qi and blood-deficiency type. These cases were randomly divided into two groups, including 184 in the kidney-tonifying and blood-generating group and 191 in the Qi-promoting and blood-nourishing group, being treated by kidney-tonifying and blood-generating granules and Qi-promoting and blood-nourishing granules, respectively, and combined oral androgen and ciclosporin soft capsules. The treatment lasted for six months and was divided into three stages. Visits were conducted from the beginning of the treatment to the end of the first, fourth, and sixth months. The curative effect was evaluated six months later. The total effective rate of the kidney-tonifying and blood-generating group was 86.4% (159/184), which was significantly better than that of the Qi-promoting and blood-nourishing group [68.6% (131/191), P<0.01)]. The results of the percentage quartile of blood cell growth in each stage of the 2 groups were analyzed. The hemoglobin concentration and platelet count of the patients in the kidney-invigorating blood group continued to increase after treatment, and significantly increased in the second and third stages compared with the first stage (P<0.05). The increase of reticulocyte count was most significant in the first stage of treatment (P<0.05). The reticulocyte count in supplementing Qi and nourishing blood group increased significantly in the first and second stages of treatment (P<0.05). The other observation indicators increased at each stage, but there was no statistical difference in the growth rate. The effects of the two groups were compared by stages. In the second stage of treatment, the increase of hemoglobin concentration in the kidney-invigorating blood group was better than that in the supplementing Qi-nourishing blood group (P<0.05). The increase of platelet count and red blood cell count in supplementing Qi and nourishing blood group was greater (P<0.05). In the third stage of treatment, the increase of hemoglobin concentration in the bushen Shengxue group was more significant (P<0.05).ConclusionThe overall effective rate of the kidney-tonifying and blood-generating method in the treatment of aplastic anemia is better than that of the Qi-promoting and blood-nourishing method, with significant effects and safety. This study has proposed a three-stage early treatment mode for aplastic anemia. The first and third stages (0-1, 5-6 months) were mainly treated by invigorating kidney and generating blood. In the second stage of treatment (2-4 months), invigorating kidney and generating blood combined with invigorating Qi and nourishing blood were adopted. It may be closer to the actual clinical treatment response and objective rule changes of aplastic anemia.
关键词:aplastic anemia;kidney-tonifying and blood-generating method;Qi-promoting and blood-nourishing method;clinical effect;stage;blood routine
摘要:ObjectiveTo explore the effects of Bushen Jianpi prescription on the autophagy and phosphatidylinositol-3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/Akt/mTOR) signaling pathway in the patients with aplastic anemia (AA).MethodA total of 30 AA patients admitted to Xiyuan Hospital and 6 healthy donors who were prepared to undergo peripheral blood hematopoietic stem cell transplantation in 304 Hospital from September 2020 to August 2021 were enrolled and assigned into an AA group and a control group. The AA group was treated with Bushen Jianpi prescription combined with cyclosporin A (CsA) and androgen for 3 months. The mononuclear cells from bone marrow in the AA group before and after treatment and the peripheral blood of the control group were collected. Transmission electron microscopy was then employed to detect autophagosomes. Western blotting was employed to determine the protein levels of microtuble-associated protein 1 light chain 3 (LC3)Ⅰ, LC3Ⅱ, mTOR, phosphorylated (p)-mTOR, Akt, p-Akt, PI3K, and p-PI3K, and real-time polymerase chain reaction (PCR) to determine the mRNA levels of LC3, mTOR, Akt, and PI3K.ResultIn the AA group, the treatment was completed in 29 patients, and the total response rate was 51.72% (15/29). ① The AA group showed lower levels of white blood cell (WBC), hemoglobin (HGB), platelet (PLT), and absolute neutrophil count (ANC) in the peripheral blood (P<0.01) and lower number of intracellular autophagosomes than the control group before treatment. Moreover, the AA group showed lower mRNA level of LC3 (P<0.01) and protein levels of LC3Ⅰ and LC3Ⅱ (P<0.01) and higher mRNA levels of mTOR, Akt, and PI3Kα (P<0.01) and protein levels of Akt, p-Akt, PI3K, p-PI3K, mTOR, and p-mTOR (P<0.01) than the control group. ② In AA group, the levels of HGB and PLT elevated (P<0.05) and the number of intracellular autophagosomes increased after treatment compared with those before treatment. Moreover, the mRNA level of LC3 and the protein levels of LC3Ⅰ and LC3Ⅱ were up-regulated (P<0.01), the mRNA levels of mTOR, Akt, and PI3Kα (P<0.01) and the protein levels of Akt, p-PI3K (P<0.01), p-Akt, PI3K, mTOR, p-mTOR (P<0.05) were down-regulated after treatment.ConclusionAA patients show lower autophagy levels, while Bushen Jianpi prescription can effectively improve the autophagy level and down-regulated the expression of PI3K/Akt/mTOR signaling pathway in AA patients.
关键词:aplastic anemia;Bushen Jianpi prescription;autophagy;phosphatidylinositol-3-kinases/protein kinase B/mammalian target of rapamycin (PI3K/Akt/mTOR) signaling pathway;clinical research
摘要:ObjectiveTo reveal the clinical efficacy of Yunpi Huatan Tongqiao prescription in relieving inflammation, hypoxia, and adenoidal hypertrophy (AH), and improving the quality of sleep-disordered breathing in children with AH by promoting M2-type polarization of macrophages through a randomized double-blind clinical trial.MethodSeventy-one AH children who met the research criteria and were treated in the Department of Pediatrics of Longhua Hospital Affiliated to Shanghai University of Traditional Chinese Medicine from March 2022 to February 2023 were divided into an observation group (36 cases) and a control group (35 cases). A randomized double-blind method was adopted. The patients in the observation group were given Yunpi Huatan Tongqiao prescription combined with placebo of montelukast sodium chewable tablets, while those in the control group were given montelukast sodium chewable tablets combined with placebo of Yunpi Huatan Tongqiao prescription. The treatment course was 84 days. After treatment, the therapeutic effect and sleep monitoring indicators were compared. Before and after treatment, venous blood was collected to compare the levels of macrophage polarization-related inflammatory factors between the two groups.ResultThe adenoidal/nasopharyngeal space (A/N) integral in the nasal and pharyngeal lateral radiographs, After treatment, the AH therapeutic effect score, and the traditional Chinese medicine (TCM) syndrome therapeutic effect score in both groups were lower than those before treatment (P<0.01). Compared with the control group after treatment, the observation group showed a more significant reduction in various integral levels (P<0.05, P<0.01). The improvement degree of A/N in the nasal and pharyngeal lateral radiographs in the observation group was better than that in the control group (Z=-2.970, P<0.01), and the total effective rate of the therapeutic effect of AH (χ2=7.715, P<0.01) and the TCM syndrome therapeutic effect (χ2=13.239, P<0.01) were superior to those in the control group. The levels of interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) in both groups after treatment were lower, and the level of interleukin-10 (IL-10) was higher than those before treatment (P<0.01). The level of transforming growth factor-beta (TGF-β) showed an increasing trend, but the difference was not statistically significant. Compared with the control group after treatment, the observation group showed more significant improvement in IL-10 and TNF-α levels (P<0.01), a decreasing trend in IL-6, and an increasing trend in TGF-β, but the difference was not statistically significant. Compared with the results before treatment, the apnea-hypopnea index (AHI) and oxygen desaturation index (ODI) in both groups decreased significantly (P<0.01). The observation group showed a significant reduction in the duration of the longest apnea and the longest hypopnea, as well as a significant increase in the mean and lowest oxygen saturation (P<0.01). The control group also showed improvements in the above indicators, but the difference was not statistically significant. Compared with the control group after treatment, the observation group showed a more significant improvement in AHI, ODI, the duration of the longest hypopnea, and mean and lowest oxygen saturation (P<0.05, P<0.01). There was a decreasing trend in the longest duration of apnea, but the difference was not statistically significant.ConclusionYunpi Huatan Tongqiao prescription can reduce the size of adenoids, alleviate clinical symptoms and signs in AH children, improve the constitution characterized by "spleen deficiency and phlegm obstruction", reduce the occurrence of sleep-disordered breathing events, alleviate the degree of hypoxia in the child's body during sleep at night, and has satisfactory clinical efficacy. The improvement of clinical symptoms and sleep quality in AH children by Yunpi Huatan Tongqiao prescription may be achieved by promoting macrophage polarization from M1 to M2.
关键词:Yunpi Huatan Tongqiao prescription;adenoidal hypertrophy;macrophage polarization;clinical research
摘要:ObjectiveTo comprehensively evaluate the clinical application value of four types of Jinsang Kaiyin preparation(JSKYs) and the other two Chinese patent medicines(CPMs) in the treatment of acute pharyngitis/laryngitis,so as to provide evidence for their rational clinical use and regulatory decision-making.MethodAccording to the guideline for clinical comprehensive evaluation of CPM,the effectiveness,safety,economy,innovation,suitability and accessibility of four JSKYs and the other two CPM in the treatment of acute pharyngitis/laryngitis were comprehensively evaluated,which were ranked based on the quantitative scoring tool.Result① Effectiveness:Compared with the control group,JSKYs can improve the total effectiveness rate of acute pharyngitis/laryngitis and improve the symptoms. Network meta-analysis showed that the probability of JSKY ranked the first in terms of total effectiveness rate.② Safety:JSKYs did not show acute toxicity and long-term toxicity. The main adverse reactions were skin rash,abdominal pain,diarrhea,nausea and vomiting,etc,which were similar with the other two CPM.③ Economy:For patients with acute laryngitis(wind heat syndrome),compared with drug A,JinsangKaiyin capsule has the comparable cost-effectiveness. For patients with acute pharyngitis(wind heat syndrome),compared with drug B,JinsangKaiyin capsul has low cost and better effectiveness.④ Innovation:Compared with the other two CPM,the indications of JSKYs have their own unique population. JSKYs have six patent approval certifications and has been approved for sale in the Philippines.⑤ Suitability:Compared with the other two CPM,the investigated doctors,pharmacists and patients all believed that the instruction of JSKY was clearer and easier to understand,the use and storage conditions were more convenient,etc.⑥ Accessibility:JSKYs are included in the category B of the National Basic Medical Insurance(2022 edition),which has good cost-effectiveness and affordability for medical insurance and self paid patients. JSKYs do not contain endangered animals and plants. The supply of raw materials can meet the demand of production at present.ConclusionAs for the drug value calculation,JSKY obtained the highest score. Based on all dimensions of evidence,expert consensus on JSKY is class A,which can be directly converted into decision making.
关键词:clinical comprehensive evaluation of Chinese patent medicine;health technology assessment;JinsangKaiyin preparation;acute pharyngitis;acute laryngitis
摘要:ObjectiveHenoch-Schönlein purpura(HSP) is one of the dominant diseases in Mongolian medicine. Qishun Baolier(QSBLE), as the main prescription for the treatment of HSP, has significant clinical effect, but its mechanism is not yet clear. Baed on this, this study is intended to screen the differentially expressed proteins before and after treatment, and preliminarily explore the molecular mechanism of QSBLE in the treatment of HSP.MethodTaking oneself as the control, 30 HSP patients aged 6-45 years were collected, and QSBLE was taken orally at 12:00 and 24:00, respectively. The dose was adjusted according to age and the course of treatment was one week. The distribution of proteinuria, hematuria and skin purpura of all patients were determined before and after treatment. The serum samples of 10 patients with clinically significant remission after QSBLE treatment were randomly selected for proteomics. Isobaric tags for relative and absolute quantification(iTRAQ) combined with liquid chromatography tandem mass spectrometry(LC-MS/MS) was used to analyze the proteins in serum of HSP patients before and after treatment, and differential proteins were analyzed bioinformatically and the protein-protein interaction(PPI) networks were constructed.ResultA total of 378 proteins were identified from serum, including 18 differentially expressed proteins, of which 15 proteins were up-regulated and 3 proteins were down regulated. Bioinformatics showed that the differential proteins were mainly involved in biological processes such as immune response, immunoglobulin production, phagocytosis, adaptive immune response before and after treatment. Biological processes, pathways and proteins were used to construct the PPI network, the proteins represented by immunoglobulin heavy constant γ1(IGHG1), immunoglobulin λ-chain 7-43(IGLV7-43), gelsolin(GSN) and 60 kDa heat shock protein(HSPD1) were involved in biological processes and related pathways such as adaptive immune response, immunoglobulin production, leukocyte-mediated immunity, regulation of stress response, regulation of immune system processes, regulation of trauma response, and these proteins were at the center of the PPI network.ConclusionQSBLE may play a role in the treatment of HSP by regulating the expression of IGHG1, IGLV7-43, GSN, HSPD1 and other key proteins to affect immune-related biological processes.
关键词:Henoch-Schönlein purpura(HSP);immune response;Qishun Baolier;isobaric tags for relative and absolute quantification(iTRAQ);proteomics;biomarkers;serum proteins
摘要:ObjectiveTo achieve high-dimensional prediction of class imbalanced of adverse drug reaction(ADR) of traditional Chinese medicine(TCM) and to classify and identify risk factors affecting the occurrence of ADR based on the post-marketing safety data of TCM monitored centrally in real world hospitals.MethodThe ensemble clustering resampling combined with regularized Group Lasso regression was used to perform high-dimensional balancing of ADR class-imbalanced data, and then to integrate the balanced datasets to achieve ADR prediction and the risk factor identification by category.ResultA practical example study of the proposed method on a monitoring data of TCM injection performed that the accuracy of the ADR prediction, the prediction sensitivity, the prediction specificity and the area under receiver operating characteristic curve(AUC) were all above 0.8 on the test set. Meanwhile, 40 risk factors affecting the occurrence of ADR were screened out from total 600 high-dimensional variables. And the effect of risk factors on the occurrence of ADR was identified by classification weighting. The important risk factors were classified as follows:past history, medication information, name of combined drugs, disease status, number of combined drugs and personal data.ConclusionIn the real world data of rare ADR with a large amount of clinical variables, this paper realized accurate ADR prediction on high-dimensional and class imbalanced condition, and classified and identified the key risk factors and their clinical significance of categories, so as to provide risk early warning for clinical rational drug use and combined drug use, as well as scientific basis for reevaluation of safety of post-marketing TCM.
关键词:hospital centralized monitoring;adverse drug reaction(ADR);cluster resampling;Danhong injection;group structure regularization;class-imbalance high-dimensional prediction;risk factor identification by category
摘要:ObjectiveTo obtain high-quality chloroplast genome information on Stemona tuberosa and clarify its structure, sequence features, and phylogenetic status.MethodThe Illumina NovaSeq 6000 and PacBio RS Ⅱ platforms were used for library construction and sequencing of S. tuberosa, respectively. The data from both sequencing platforms were combined and subjected to bioinformatics analysis for genome assembly and base correction, resulting in a high-quality chloroplast genome. Subsequently, sequence features, repetitive sequences, gene diversity, and phylogeny were analyzed.ResultThe chloroplast genome size of S. tuberosa was determined to be 154 379 bp. The structure of the chloroplast genome followed the typical quadripartite circular form, consisting of a pair of inverted repeat regions (IRs) with a length of 27 074 bp, a small single-copy region (SSC) of 17 924 bp, and a large single-copy region (LSC) of 82 307 bp. The average GC content was 37.86%. A total of 121 genes were annotated, including 30 tRNA genes, four rRNA genes, and 87 protein-coding genes. Among them, six tRNA genes and 12 protein-coding genes contained introns. In the chloroplast genome of S. tuberosa, 49 long repetitive sequences and 59 single-nucleotide simple sequence repeats (SSRs) were identified. Comparative analysis of chloroplast genomes among four Stemona species revealed high diversity in the ycf1 and ndhF genes. The phylogenetic tree constructed based on the chloroplast genome showed consistent classification with the current taxonomic status of S. tuberosa.ConclusionThe high-quality chloroplast genome of S. tuberosa was successfully assembled, providing valuable information on the structure and sequence features of chloroplast genomes in four Stemona species, including S. tuberosa. These findings lay a foundation for the identification, evolution, and phylogenetic studies of medicinal plants in the genus Stemona.
摘要:Chinese herbal piece is an important component of the traditional Chinese medicine (TCM) system, and identifying their quality and grading can promote the development and utilization of Chinese herbal pieces. Utilizing deep learning for intelligent identification of Chinese herbal pieces can save time, effort, and cost, while also reasonably avoiding the constraints of human subjectivity, providing a guarantee for efficient identification of Chinese herbal pieces. In this study, a dataset containing 108 kinds of Chinese herbal pieces (14 058 images) was constructed,the basic YOLOv4 algorithm was employed to identify the 108 kinds of Chinese herbal pieces of our database The mean average precision (mAP) of the developed basic YOLOv4 model reached 85.3%. In addition, the receptive field block was introduced into the neck network of YOLOv4 algorithm, and the improved YOLOv4 algorithm was used to identify Chinese herbal pieces. The mAPof the improved YOLOv4 model achieved 88.7%, the average precision of 80 kinds of decoction pieces exceeded 80%, the average precision of 48 kinds of decoction pieces exceeded 90%. These results indicate that adding the receptive field module can help to some extent in the identification of Chinese herbal medicine pieces with different sizes and small volumes. Finally, the average precision of each kind of Chinese herbal medicine piece by the improved YOLOv4 model was further analyzed. Through in-depth analysis of the original images of Chinese herbal medicine pieces with low prediction average precision, it was clarified that the quantity and quality of original images of Chinese herbal medicine pieces are key to performing intelligent object detection. The improved YOLOv4 model constructed in this study can be used for the rapid identification of Chinese herbal pieces, and also provide reference guidance for the manual authentication of Chinese herbal medicine decoction pieces.
摘要:ObjectiveTo investigate the mechanism of Magnolia officinalis cortex for constipation-type irritable bowel syndrome(IBS-C) rats before and after sweating.MethodIBS-C rat model was established by gavage of ice water, and rats were randomly divided into the blank group, model group, mosapride group(1 mg·kg-1), M. officinalis cortex group(10 g·kg-1) and sweated M. officinalis cortex group(10 g·kg-1). The changes of body weight, fecal number and fecal water content of rats were observed, 16S rRNA sequencing was used to detect the structural changes of fecal intestinal flora in rats, the levels of 5-hydroxytryptamine(5-HT) and substance P(SP) in colonic tissues of rats were determined by enzyme-linked immunosorbent assay(ELISA).ResultCompared with the model group, the fecal water content and fecal number of mosapride group, M. officinalis cortex group and sweated M. officinalis cortex group were significantly increased(P<0.05). At the phylum level, the top four species of flora abundance were Firmicutes, Bacteroidetes, Spirochaetes and Proteobacteria. Compared with the blank group, the proportion of Firmicutes in the model group was significantly reduced(P<0.05), while the proportion of Spirochaetes was significantly increased(P<0.05). Compared with the model group, the proportion of Firmicutes and Spirochaetes in M. officinalis cortex group and sweated M. officinalis cortex group tended to be similar to that in the blank group, and the proportion of Spirochaetes in sweated M. officinalis cortex group was lower than that of M. officinalis cortex group. At the family level, the top four species of flora abundance were Lactobacillaceae, S24_7, Ruminococcaceae, Bacteroidaceae, compared with the blank group, the proportion of Lactobacillaceae in the model group decreased significantly(P<0.05), and its proportion in the M. officinalis cortex group and sweated M. officinalis cortex group increased significantly after administration(P<0.05), and the flora structure of the two groups tended to be similar to that of the blank group. At the genus level, the top four species of flora abundance were Lactobacillus, Unspecified_S24_7, Bacteroides and Treponema. Compared with the blank group, the proportion of Lactobacillus in the model group decreased significantly(P<0.05), while the proportion of Treponema increased significantly(P<0.05). Compared with the model group, ratio of bacterial structure of Lactobacillus and Treponema in the M. officinalis cortex group and sweated M. officinalis cortex group tended to be similar to those in the blank group, indicating that M. officinalis cortex could restore the intestinal microbial structure of IBS-C rats before and after sweating. Compared with the model group, the 5-HT content in mosapride group was significantly reduced(P<0.05), the contents of 5-HT and SP in the M. officinalis cortex group and sweated M. officinalis cortex group were significantly increased(P<0.01), and the sweated M. officinalis cortex group was higher than the M. officinalis cortex group.ConclusionM. officinalis cortex can play a therapeutic role on IBS-C rats by regulating 5-HT pathway and intestinal flora structure before and after sweating.
摘要:ObjectiveTo analyze the migrating components absorbed into blood of the aqueous extract of Euphorbia helioscopia, and to explore the pharmacodynamic material basis of the aqueous extract of E. helioscopia against chronic obstructive pulmonary disease(COPD).MethodUltra-performance liquid chromatography-quadrupole-time-of-flight mass spectrometry(UPLC-Q-TOF-MS/MS) was used to detecte the migrating components absorbed into blood of rats after intragastric administration of aqueous extract of E. helioscopia. An Agilent RRHD SB-C18 column(3 mm×100 mm, 1.8 μm) was used with 0.1% formic acid aqueous solution(A)-acetonitrile(B) as the mobile phase for gradient elution(0-15 min, 5%-30%B; 15-20 min, 30%-50%B; 20-30 min, 50%-95%B; 30-35 min, 95%-5%B), and the detection wavelength of 190-800 nm, column temperature of 40 ℃, flow rate of 0.3 mL∙min-1 and injection volume of 4 μL. The electrospray ionization(ESI) was used in positive and negative ion modes, and the detection range was m/z 50-1 250. Network pharmacology was used to screen out the key components and the key targets of COPD through the interaction analysis. Metascape database was used to predict the molecular function, biological process, cellular composition and signal pathways mainly involved in the anti-COPD effect of E. helioscopia. Molecular docking technique was used to determine the affinity of key targets with key components.ResultA total of 29 migrating components absorbed into blood of rats were identified after intragastric administration of aqueous extract of E. helioscopia, 9 of which were prototype components and 20 were metabolites. Network pharmacological analysis showed that luteolin, quercetin, apigenin, naringenin and helioscopinolide C were the key components of E. helioscopia against COPD, and vascular endothelial growth factor A(VEGFA), albumin(ALB), protein kinase B1(Akt1), tumor necrosis factor(TNF) and interleukin-6(IL-6) were the key targets. Molecular docking results showed that one diterpene lactone(helioscopinolide C) and three flavonoids(naringenin, luteolin, apigenin) in the migrating components absorbed into blood all had strong binding activity to the key targets of E. helioscopia against COPD.ConclusionNaringenin, helioscopinolide C, luteolin and apigenin may be the main anti-COPD active substances of E. helioscopia.
摘要:In order to standardize the quality control of traditional Chinese medicine(TCM) dispensing granules, the Chinese Pharmacopoeia Commission has promulgated and implemented 200 national drug standards for TCM dispensing granules, but there are still varieties of TCM dispensing granules without unified standards. Many provinces have actively invested in the formulation of provincial standards for TCM dispensing granules to make up for the gaps in standards for varieties of traditional Chinese medicine dispensing granules other than the national standards. By the end of July 2022, 29 provincial-level administrative regions have successively promulgated and implemented a total of 5 602 provincial standards for TCM dispensing granules, involving more than 400 varieties. In order to better understand the formulation and characteristics of provincial standards, this study took 105 provincial standards that have been promulgated and implemented in Henan province as an example, and comprehensively analyzed the formulation and characteristics through quality control indicators such as dry extract rate of raw materials, contents of index components and their transfer rates, specifications and so on. The formulation and characteristics of the same TCM dispensing granules in the provincial standards of different provinces were further analyzed, in order to provide reference for the formulation of provincial standards of TCM dispensing granules and the implementation of national standards.
关键词:traditional Chinese medicine dispensing granules;provincial standards;national pharmaceutical standards;dry extract rate;index components;specifications;equivalence ratio
摘要:Lamiophlomis Herba, one of the medicinal herbs commonly used by the Tibetan ethnic minority, has the effect of activating blood, stopping bleeding, dispelling wind, and relieving pain and is frequently used to treat trauma, traumatic bleeding, rheumatic arthralgia, and dampness and dampness-heat. By a review of ancient Tibetan medicine classics, materia medica classics, and modern literature, this paper systematically analyzed the name, nature, taste, original plant, medicinal part, harvest, processing, efficacy, and indications of Lamiophlomis Herba. The textual research showed that Lamiophlomis Herba was first recorded in the Somaratsa (《月王药诊》) in the middle of the eighth century. This medicinal herb was mainly recorded with a plain and warm nature and a sweet, bitter, and astringent taste. The herb was recorded as non-toxic in other books except the Tibetan Medicinal Plants in Gannan of Qinghai-Tibet Plateau (《青藏高原甘南藏药植物志》). In the books of the past dynasties, the aboveground part of Lomiophlomis rotatd was used as medicine. In addition, there were also records of using the whole herbs of Ajuga ovalifolia, A. ovalifolia var. calantha, and Oreosolen wattii as the medicine. In ancient times, the herb was mainly harvested before Frost's Descent in the 8th-9th months of the lunar calendar, while it was mainly harvested during the flowering-fruiting stage in autumn in modern times. Due to the decreased reserve of Lamiophlomis Herba, the medicinal part evolved from whole herb or fresh leaves to the aboveground part. According to the ancient and modern records, this herb mainly has the functions of nourishing bone and marrow, eliminating dampness and dampness-heat, stopping bleeding, and relieving pain. In ancient times, it was used for treating parasitic diseases, menostaxis, spermatorrhea, diarrhea, and nourishing the body. This paper aims to provide a basis for further development and study of Lamiophlomis Herba through the textual research.
关键词:Lamiophlomis rotata;herbal textual research;original plants;Tibetan medicinal herb
摘要:ObjectiveTo analyze the functions, formulae, dosage forms, and methods of administration of the menstruation-regulating Chinese patent medicines included in the 2020 edition of the Chinese Pharmacopoeia, so as to provide reference for rational clinical use.MethodThe relevant Chinese patent medicines were recorded one by one, and the efficacy, dosage forms, methods of administration, and contraindications were counted, classified, and summarized. Further, we analyzed the Chinese medicines used in these Chinese patent medicines, identified the high-frequency Chinese medicines for menstrual regulation, and analyzed their natures, tastes, meridian tropism, and functions, aiming to guide the clinical use.ResultA total of 142 Chinese patient medicines for menstrual disorders were included in this study. They were classified into 12 categories according to their efficacy, mainly for regulating menstruation and blood, tonifying, activating blood, and eliminating mass. The representative Chinese patent medicines were Bazhen Yimu pills, Shaofu Zhuyu pills, Lyujiao Buxue granules, and Guizhi Fuling pills, which are in line with the principles of moving Qi and blood and regulating liver and spleen. Menstruation-regulating Chinese patents medicines are mostly in pills and capsules and are mainly taken with yellow wine or ginger decoction. Pregnancy was the contraindication with the highest frequency, followed by menstruation and dietary precautions. The high-frequency Chinese medicines mainly had the functions of tonifying, activating blood, resolving stasis, and clearing heat, with the top three being Angelicae Sinensis Radix, Paeoniae Radix Alba, and Chuanxiong Rhizoma. These medicines mainly had warm nature, sweet, bitter, and pungent tastes, and tropism to liver and spleen meridians.ConclusionThe treatment of menstrual disorders should focus on nourishing and activating blood, regulating Qi, tonifying kidney, supporting spleen, nourishing liver, and harmonizing stomach. The appropriate dosage form should be selected according to the patient's specific conditions. The medicinal guide and the method of administration should be selected on the basis of syndrome differentiation with attention to the contraindications. In summary, the Chinese patient medicines for menstrual regulation should be chosen based on the patient’s syndrome under guidance of the theory of traditional Chinese medicine.
关键词:Chinese Pharmacopoeia;menstrual disorders;Chinese patent medicine;clinical application;analysis of characteristics
摘要:ObjectiveTo explore the role of efficacy evaluation methods in providing evidence for traditional Chinese medicine (TCM) clinical practice guidelines based on a demonstration study of clinical efficacy evaluation of TCM for allergic rhinitis (AR),aiming to enrich the sources of evidence for guideline development.MethodReal-world data of TCM medication for AR were collected and efficacy evaluation was carried out. SPSS 16.0 software was used to calculate the conformity of clinical syndromes,main prescriptions, and medications to the guidelines. Correlation analysis of efficacy and medications was performed according to guideline conformity to compare the differences in medications between real-world clinical applications and current guidelines.ResultA total of 198 cases were collected and the clinical medications were compared with the relevant guidelines for AR. It was found that the clinical syndrome conformity was above 70%,and in addition to the guideline syndrome,there were also syndromes in six meridians and other mixed syndromes in clinical practice. The guideline conformity of the main prescriptions used in clinical practice showed a positive correlation trend with efficacy. There were some differences between the commonly used drugs in clinical practice and those recommended by the guidelines. For example,for lung Qi deficiency and cold syndrome,drugs such as Angelicae Dahuricae Radix, Magnoliae Flos, and Schisandrae Chinensis Fructus were often used. For kidney Yang deficiency syndrome,drugs such as Atractylodis Macrocephalae Rhizoma and Ostreae Concha were often used. For spleen Qi deficiency and weakness syndrome,drugs such as Poria, Cinnamomi Ramulus, and Magnoliae Flos were used. For lung Qi deficiency and cold syndrome in children,drugs such as Chebulae Fructus, Cicadae Periostracum, Zingiberis Rhizoma, and Ginseng Radix et Rhizoma were used. For lung and spleen Qi deficiency syndrome,drugs such as Dioscoreae Rhizoma, Menthae Haplocalycis Herba, Amomi Fructus, and Zingiberis Rhizoma were used. There were also some differences in the commonly used drugs for adults and children. For example,for lung Qi deficiency and cold syndrome,adults often used Angelicae Dahuricae Radix, Magnoliae Flos, and Tribuli Fructus,while children often used Ginseng Radix et Rhizoma, Paeoniae Radix Alba, and Poria. For lung meridian hidden heat syndrome, adults often used Bupleuri Radix, Asari Radix et Rhizoma, Pinelliae Rhizoma, and Xanthii Fructus, while children often used Houttuyniae Herba, Menthae Haplocalycis Herba, Citri Reticulatae Pericarpium, and Massa Medicata Fermentata.ConclusionEffective medication regimens can be screened out based on efficacy evaluation methods,which can help supplement immediate, objective, and clinically relevant evidence of medication for the development of clinical practice guidelines in TCM from the perspective of clinical effectiveness.
关键词:efficacy evaluation;clinical diagnosis and treatment evidence;allergic rhinitis;medication analysis
摘要:The incidence of spontaneous abortion (SAB) has been increasing year by year, and its etiology is complex, with limited treatment options, which poses a serious threat to social stability. The "disease-syndrome-therapy" research model can significantly improve the clinical efficacy of traditional Chinese medicine (TCM) for preventing miscarriage, but there has always been a lack of key and recognized diagnostic and treatment evaluation markers, which need to be further explored to establish a scientific and unified evaluation standard system. It is proposed to collect existing "disease-syndrome-therapy" SAB animal models, transplant and improve the model evaluation indicators, evaluate the degree of match between SAB animal models and the clinical characteristics of TCM and Western medicine diseases and syndromes, and compare the advantages and disadvantages of different SAB animal models in terms of construction methods, target selection, and evaluation indicators. In addition, the frontiers of TCM experimental research will be explored. In view of the current status and related bottlenecks of molecular biomarkers research on SAB TCM animal models, a single-cell multimodal omics research strategy will be proposed to break through the related evaluation defects of the "disease-syndrome-therapy" SAB and analyze the differences in various cell types, cell subpopulations, spatiotemporal trajectories, and gene expression in the mother-fetal interface tissue at the single-cell level. This will provide accurate guidance and model animal platform support for the in-depth study of disease-syndrome models, Zang-fu biology, and novel targeted drugs. It will also provide a basis for establishing a stable and repeatable "disease-syndrome-therapy" SAB animal model and evaluation indicator system, which is beneficial for the long-term development of TCM reproductive animal model research.
关键词:spontaneous abortion;combination of diseases and syndromes;animal models;research progress;development trend
摘要:Since LIU Hejian proposed the concept of sweat pore, the theory of sweat pore has experienced accelerated development. Especially with the advances in modern human anatomy and physiology, the microscopic anatomy of sweat pore begins to focus on the intercellular space, ion channels and other membranous space with channels, pores, doors, etc., which exert the functions of exchanging fluid, information, and energy inside and outside blood vessels and discharging metabolic wastes so as to maintain the normal operation of organs. Therefore, sweat pore is the structural basis for the movement of Qi and the central link of Qi-fluid exchange in the body. The brain, as the house of original spirit, is in charge of the spirit of five Zang-organs. The brain sweat pore is pivotal for the circulation of Qi, blood, and fluid in the brain, and it is the structural basis for the normal physiological functions of the brain. The dysfunction of the brain sweat pore will cause the stagnation of Qi and the abnormal transport of blood and fluid. It will cause the abnormal exchange of Qi, liquid and other material and information, which fail to nourish the original spirt and cause the loss of vital activity, eventually leading to consciousness and emotion disorders. The treatment should focus on opening the brain sweat pore, smoothing the exchange of Qi and fluid inside and outside the pore, and restoring the Qi movement, so as to cure encephalopathy. At present, western medicine treatment of encephalopathy needs to solve the problem of drug efflux from the blood-brain barrier and improve the effective concentration of drugs into the brain. The structure and function of brain sweat pore is similar to those of the blood-brain barrier. The aromatic resuscitative medicines and wind-extinguishing medicines can open the brain sweat pore. When being combined with other medicines, they can lead the medicine to enter the brain to restore the Qi movement of the brain sweat pore and enhance the therapeutic effect. Liver-pacifying wind-extinguishing medicines, insect medicines, tonifying medicines, heat-clearing toxin-removing medicines, and damp-draining medicines can treat pathological factors such as wind, phlegm, stasis, deficiency, toxin, and dampness, respectively. These medicines, combined with the medicines with the tropism to brain meridians, can open the brain sweat pore and guide the medicine into the brain to enhance the effective concentration of the medicine, thereby enhancing the efficacy against encephalopathy.
摘要:Zhuye Shigaotang, first recorded in ZHANG Zhongjing's Synopsis of the Golden Chamber (《金匮要略》), is a commonly used prescription for treating heat syndrome in modern times. However, physicians of the past dynasties have different opinions on the mechanism of Zhuye Shigaotang in disease treatment. Based on HUANG Yuanyu's theory of Qi circulation, this paper holds that the root cause of the diseases treated by Zhuye Shigaotang is the deficiency of spleen and stomach in the middle energizer and the dysfunction of ascending and descending. The failure of Yin ascending leads to the failure of Yang transformation, and the failure of Yang descending causes the failure of Yin generation. As a result, heat and fire become predominant in the heart, lung, and stomach, which causes Qi counterflow and fluid consumption. Based on this pathogenesis, Zhuye Shigaotang is mainly composed of pungent, warm, sweet, and cold herbs. The combination of these herbs can protect the spleen and stomach and recover the Qi movement in the middle energizer, thereby clearing heat and fire, descending Qi, and promoting the generation of Qi and fluid. In clinical practice, this prescription can be applied to treating the syndromes of deficiency in spleen and stomach, dysfunction of middle energizer in transportation, dysfunction of ascending and descending, excessive heat and fire, and Qi counterflow and fluid consumption. The interpretation of Zhuye Shigaotang from the theory of Qi circulation can provide a new idea for differentiating syndromes, seeking causes, and developing prescriptions, which broadens the scope of clinical application of this prescription and provides a reference for interpreting ZHANG Zhongjing's method of compatibility.
关键词:Qi circulation;Zhuye Shigaotang;pathogenesis;compatibility idea
摘要:With the acceleration of social rhythm, the progress of science and technology, and the increase of the number of phubbers, the incidence of cervical degenerative diseases is also increasing year by year. Cervical spondylotic radiculopathy(CSR), as one of the diseases induced by cervical degeneration, has seriously affected people's quality of life and physical and mental health. Traditional Chinese medicine(TCM) is effective in the treatment of CSR, but the theoretical and basic experimental evidence is not sufficient, and the current formulation standard of animal model is not unified. Therefore, based on the clinical guidelines of Chinese and Western medicine for CSR and the characteristics of the disease and syndrome, the author systematically summarized and analyzed the existing animal models, and found that the existing models of microvascular clamp nerve root compression method had a poor agreement with the the Chinese and Western medical guidelines, while the modeling methods of spinal canal insertion, autologous bone insertion compression, stainless steel column compression, and fixed frame cervical degeneration reflected a high degree of agreement in the Western medical guidelines. However, the Chinese medical diagnostic criteria were poorly matched. This indicates that the existing animal models of this disease show few TCM syndrome elements, and lack information collection and evaluation in animal behavioral evaluation similar to the four diagnoses of TCM. In conclusion, this paper aims to systematically evaluate the current status of animal model establishment of CSR based on the concept of combination of disease and syndrome, so as to provide a theoretical basis for the model establishment of CSR that is more consistent with clinical characteristics and symptoms of Chinese and Western medicine.
关键词:cervical spondylotic radiculopathy;animal model;combination of Chinese and Western medicine;combination of disease and syndrome;clinical guidelines;anastomosis;cervical degenerative diseases
摘要:Pyroptosis, an atypical new cell death mode other than apoptosis and necrosis, has been discovered in recent years. Pyroptosis depends on the cleavage of gasdermins (GSDMs) by Caspases. The activated GSDMs act on the plasma membrane to form a perforation, which results in cell lysis and triggers inflammation and immune response. Pyroptosis can be induced by four distinct signaling pathways, including canonical and non-canonical inflammasome pathways, apoptosis-associated Caspases-mediated pathway, and granzyme pathway. In these signaling pathways, GSDMs are the executors of pyroptosis. Pyroptosis is associated with the death of tumor cells and the inflammatory damage of normal tissues. Recent studies have demonstrated that moderate pyroptosis can lead to tumor cell death to exert an anti-tumor effect, and meanwhile stimulate the tumor immune microenvironment, while it can promote tumor development. Despite the good performance, drug-based anti-tumor therapies such as tumor immunotherapy, chemotherapy, and targeted therapy have some shortcomings such as drug resistance, recurrence, and damage to normal tissues. The latest research shows that a variety of natural compounds have anti-tumor effects in the auxiliary treatment of tumors by mediating the pyroptosis pathways in a multi-target and multi-pathway manner, which provide new ideas for the study of anti-tumor therapy. We reviewed the molecular mechanism of pyroptosis and the regulatory role of pyroptosis in tumors and tumor immune microenvironment, and summarized the recent research progress in the natural medicinal components regulating pyroptosis in anti-tumor therapy, with a view to providing ideas for the research on the anti-tumor therapy based on pyroptosis.
关键词:pyroptosis;gasdermins (GSDMs);gasdermin E (GSDME);gasdermin D (GSDMD);natural medicine;anti-tumor therapy;progress
摘要:Depression is a mental disorder characterized by persistent low mood and belongs to the category of "stagnation syndrome" in traditional Chinese medicine (TCM), with the characteristics of high prevalence, high disability rate, high suicide rate, and high recurrence rate. The pathogenesis of depression is extremely complex and involves factors such as genetics, psychology, and social environment. Currently, clinical antidepressant drugs such as tricyclic and tetracyclic antidepressants, and selective serotonin reuptake inhibitors, have slow onset of action and significant adverse effects with long-term application. Furthermore, clinical statistics show that about one-third of patients do not respond to these types of medications. Enhancing the effectiveness of depression treatment has become a major challenge in the medical field. TCM, based on the holistic view and treatment based on syndrome differentiation, has unique advantages in the prevention and treatment of depression, including stable therapeutic effects, low recurrence rate, minimal side effects, and good patient compliance. As one of the heat-clearing drugs, Gardeniae Fructus has the effects of clearing heat, purging fire, cooling blood, and relieving restlessness, which makes it effective in treating patients with "stagnation syndrome". Literature studies have found that active components of Gardeniae Fructus, such as geniposide, genipin, and crocin, as well as drug pairs such as Gardeniae Fructus-Chuanxiong Rhizoma, Gardeniae Fructus-Acanthopanacis Senticosi Radix et Rhizoma Seu Caulis, and Gardeniae Fructus-Lycii Fructus, and prescriptions such as Zhizichi Tang, Yuejuwan, Zhizi Houpotang, Danzhi Xiaoyaosan, and Jieyu Anshen Granules, have shown significant antidepressant effects. The mechanism of action may be related to regulating the hypothalamic-pituitary-adrenal (HPA) axis, modulating neurotransmitters such as serotonin (5-HT) and dopamine (DA), increasing brain-derived neurotrophic factor (BDNF) in the hippocampus, enhancing neurogenesis in the hippocampus, and regulating the nuclear factor-kappa B (NF-κB) signaling pathway to inhibit neuroinflammation. This article summarized the research progress on the active components of Gardeniae Fructus, drug pairs, and Chinse medicinal prescriptions containing Gardeniae Fructus, providing references for further promoting the clinical application of Gardeniae Fructus and its prescriptions in the treatment of depression.
摘要:Myocardial infarction (MI) is a common cardiovascular disease in clinical practice and one of the main causes of cardiovascular mortality. Its pathogenesis is complex and associated with oxidative stress reactions. Nuclear factor E2-related factor 2 (Nrf2) is a key factor in regulating oxidative stress reactions. It can regulate the expression of heme oxygenase-1 (HO-1), playing a role in maintaining the oxidative-reductive homeostasis in the body. During the course of MI, the biological activity and levels of Nrf2 and HO-1 decrease, leading to weakened tissue antioxidant and anti-inflammatory capabilities, endothelial damage in myocardial blood vessels, release of vascular cell adhesion factors, and impaired endothelial function. In recent years, many basic research studies have explored the role and mechanisms of traditional Chinese medicine (TCM) in treating MI by modulating the Nrf2/HO-1 signaling pathway. The results have indicated that the Nrf2/HO-1 signaling pathway is an important potential target for TCM in the treatment of MI. This article reviewed the mechanism of the Nrf2/HO-1 signaling pathway in MI and the research progress of TCM in targeting and regulating this pathway, aiming to provide a theoretical basis for the prevention and treatment of MI and further drug development.
关键词:myocardial infarction;nuclear factor E2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) signaling pathway;traditional Chinese medicine;mechanism of action
摘要:Gastric cancer (GC) is one of the most common malignant tumors in the digestive system, with high morbidity and mortality. Early clinical symptoms of GC are not obvious, and most of them have entered the advanced stage after discovery, which greatly reduces the clinical cure rate and affects the quality of life of patients, and the prognosis is very poor. In recent years, with the continuous exploration in the field of bioinformatics, it has been found that micro-RNA (miRNA) and long non-coding RNA (lncRNA) exist as non-coding RNA (ncRNA) without translation ability, and regulate the expression levels of related signal proteins by acting on a certain target, thereby activating or inhibiting a certain signaling pathway, which plays an important role in assisting diagnosis, guiding clinical medication, and judging prognosis in the progress of GC. Chinese medicine is easily accepted by patients because of its good curative effect and less side effects. In the present basic studies, with the interaction mechanism between miRNA, lncRNA and signaling pathways as the breakthrough point, various studies on the regulation of related signaling molecules and signaling pathways by Chinese medicine have been carried out. A large number of experimental data have proved that the development of GC is closely related to the interaction of miRNA, lncRNA, and related signaling pathways, and Chinese medicine, with multi-target, multi-mechanism, and multi-pathway characteristics, affects various signaling molecules and signaling pathways and intervenes in the progress of GC cells. This paper reviewed the basic research on lncRNA, miRNA molecules, and main signaling pathways involved in the occurrence and development of GC, and summarized specific molecular mechanisms of Chinese medicine in the regulation of each signaling pathway, hoping to provide references for modern research of Chinese medicine in the intervention of GC progress at the molecular level.
摘要:Terpine-4-ol is abundant in nature. As a cyclic monoterpenoid compound, terpine-4-ol is distributed in a variety of natural plants. It is the main component and the key active substance in many traditional Chinese essential oils, such as Melaleuca alba essential oil and coral ginger essential oil. Terpine-4-ol has anti-microbial, anti-tumor, insecticidal, anti-inflammatory, and other effects. It can treat cancer, as well as oral and cardiovascular diseases with great safety. In terms of antibacterial activity, terpine-4-ol can destroy bacterial cell walls, improve membrane permeability, and regulate bacterial migration, reproduction, and other related genes to inhibit bacterial activity. In terms of antifungal activity, terpine-4-ol can bind with ergosterol in fungal cell walls to cause fungal death. In terms of insecticidal activity, terpine-4-ol can inhibit Na+ and K+-ATPase activity and cause the death of the insect. In terms of anticancer activity, terpine-4-ol can regulate the expression of apoptosis-related proteins in cancer cells, so as to control the apoptosis of cancer cells. In this paper, the pharmacological activity and action mechanism of terpine-4-ol were reviewed to provide a reference for further research and utilization of terpine-4-ol.
摘要:Microfluidic liver and kidney chips have become preferred model carriers in recent years for new drug development, pharmacological and toxicological research, mechanism exploration, and disease model construction. In the context of the USA. Food and Drug Administration allowing the use of in vitro model data as a substitute for animal model data in new drug applications when animal disease models are difficult to construct, microfluidic chips have received widespread attention due to their high throughput, ability to highly mimic biological characteristics of living organisms, convenient evaluation of drug toxicity in normal or pathological states with repeated dosing, real-time induction and monitoring of culture processes, and real-time data acquisition and analysis. In toxicology research, liver and kidney chips can construct in vitro models suitable for the pharmacological and toxicological detection of different substances by combining 2D monocultures and co-cultures from different species sources, 3D cultures, spheroids/organoid cells, precision-cut liver and kidney slices, immortalized cell lines, or sandwich-cultured cell lines. This model maximally simulates or retains the organ function and in vivo microenvironment of the liver and kidney, including specific physiological tissue structures, multicellular interactions/crosstalk, and multi-organ coordination/feedback, to obtain results similar to or the same as in vivo experimental data, reducing interspecies differences. At the same time, it greatly reduces the use of experimental animals and lowers costs. Microfluidic technology provides necessary shear force microenvironments for the cultivation of contents and solves problems encountered in the cultivation process of liver and kidney chips, such as insufficient tissue oxygen supply, nutrient deficiencies, and accumulation of metabolites, leading to cell apoptosis and even tissue necrosis fibrosis, which make it difficult to maintain long-term structure and function. This article reviewed the application of microfluidic technology combined with liver and kidney chips in Chinese medicine toxicology research. By summarizing the development of microfluidic technology, liver chips, kidney chips, and providing application examples of microfluidic liver and kidney chips in Chinese medicine toxicology research, combined with the characteristics of Chinese medicine administration, the article explored the advantages and future development directions of their application in the field of Chinese medicine toxicology research.
关键词:microfluidic liver chip;microfluidic kidney chip;toxicology of Chinese medicine;precision-cut organ slice;3D culture;organoids