[Evidence mapping analysis of traditional Chinese medicine intervention in pulmonary fibrosis].

This study utilized evidence mapping methodology to systematically identify, describe, and evaluate the evidence from relevant research on traditional Chinese medicine(TCM) interventions in patients with pulmonary fibrosis. CNKI, Wanfang, VIP, SinoMed, PubMed, Web of Science, EMbase, and Cochrane Library were searched from database inception to March 2023 for systematic reviews/Meta-analysis/network Meta-analysis on TCM interventions in pulmonary fibrosis. The quality of included studies was assessed using the AMSTAR 2 scale, and the evidence mapping approach was employed to present comprehensive information on populations, intervention methods, the sample size in systematic reviews/Meta-analysis, and conclusion classifications. Ultimately, 44 systematic reviews/Meta-analysis/network Meta-analysis were included. Apart from syndrome differentiation and treatment, TCM injections accounted for a significant proportion of the observed interventions. The treatment methods were mainly focused on nourishing Qi and Yin, promoting blood circulation, resolving stasis, and dredging collaterals. The results from the included studies demonstrated that TCM treatment for pulmonary fibrosis could improve efficacy, increase lung function, improve PaO_(2 )levels, increase the 6-minute walk distance(6MWD), alleviate clinical symptoms, and enhance patients' quality of life. Based on the assessment using the AMSTAR 2 scale, methodological issues were identified, including the lack of protocol registration, failure to provide a list of excluded literature, and incomplete explanations regarding the impact of heterogeneity and bias on the results. The evidence mapping revealed that 42 conclusions were beneficial, while two conclusions were potentially beneficial. Overall, the quality of evidence was relatively low, primarily due to methodological imprecision and publication bias. Although TCM showed certain efficacy in the treatment of pulmonary fibrosis, the quality of reported literature, methodological quality, and overall evidence quality need improvement. It is recommended to conduct high-quality and standardized studies in the future to provide better evidence-based guidance.

[Mechanism of Gardeniae Fructus in ameliorating rheumatoid arthritis based on metabolomics and intestinal microbiota].

Rheumatoid arthritis(RA), a chronic autoimmune disease, is featured by persistent joint inflammation. The development of RA is associated with the disturbance of endogenous metabolites and intestinal microbiota. Gardeniae Fructus(GF), one of the commonly used medicinal food in China, is usually prescribed for the prevention and treatment of jaundice, inflammation, ache, fever, and skin ulcers. GF exerts an effect on ameliorating RA, the mechanism of which remains to be studied. In this study, ultra-perfor-mance liquid chromatography-tandem mass spectrometry(UPLC-MS/MS)-based serum non-target metabolomics and 16S rDNA high-throughput sequencing were employed to elucidate the mechanism of GF in ameliorating RA induced by complete Freund's adjuvant in rats. The results showed that GF alleviated the pathological conditions in adjuvant arthritis(AA) rats. The low-and high-dose GF lo-wered the serum levels of interleukin(IL)-6, tumor necrosis factor-α(TNF-α), IL-1ß, and prostaglandin E2 in the rats(P<0.05, P<0.01). Pathways involved in metabolomics were mainly α-linolenic acid metabolism and glycerophospholipid metabolism. The results of 16S rDNA sequencing showed that the Streptococcus, Facklamia, Klebsiella, Enterococcus, and Kosakonia were the critical gut microorganisms for GF to treat AA in rats. Spearman correlation analysis showed that the three differential metabolites PE-NMe[18:1(9Z)/20:0], PC[20:1(11Z)/18:3(6Z,9Z,12Z)], and PC[20:0/18:4(6Z,9Z,12Z,15Z)] were correlated with the differential bacteria. In conclusion, GF may ameliorate RA by regulating the composition of intestinal microbiota, α-linolenic acid metabolism, and glycerophospholipid metabolism. The findings provide new ideas and data for elucidating the mechanism of GF in relieving RA.

Integration of transcriptomics and proteomics to elucidate inhibitory effect and mechanism of rosmarinic acid from Perilla frutescens (L.) Britt. in treating Trichophyton mentagrophytes.

BACKGROUND: Dermatophyte caused by Trichophyton mentagrophytes is a global disease with a growing prevalence that is difficult to cure. Perilla frutescens (L.) Britt. is an edible and medicinal plant. Ancient books of Traditional Chinese Medicine and modern pharmacological studies have shown that it has potential anti-fungi activity. This is the first study to explore the inhibitory effects of compounds from P. frutescens on Trichophyton mentagrophytes and its mechanism of action coupled with the antifungal activity in vitro from network pharmacology, transcriptomics and proteomics. METHODS: Five most potential inhibitory compounds against fungi in P. frutescens was screened with network pharmacology. The antifungal activity of the candidates was detected by a broth microdilution method. Through in vitro antifungal assays screening the compound with efficacy, transcriptomics and proteomics were performed to investigate the pharmacological mechanisms of the effective compound against Trichophyton mentagrophytes. Furthermore, the real-time polymerase chain reaction (PCR) was applied to verify the expression of genes. RESULTS: The top five potential antifungal compounds in P. frutescens screened by network pharmacology are: progesterone, luteolin, apigenin, ursolic acid and rosmarinic acid. In vitro antifungal assays showed that rosmarinic acid had a favorable inhibitory effect on fungi. The transcriptomic findings exhibited that the differentially expressed genes of fungus after rosmarinic acid intervention were mainly enriched in the carbon metabolism pathway, while the proteomic findings suggested that rosmarinic acid could inhibit the average growth of Trichophyton mentagrophytes by interfering with the expression of enolase in the glycolysis pathway. Comparison of real-time PCR and transcriptomics results showed that the trends of gene expression in glycolytic, carbon metabolism and glutathione metabolic pathways were identical. The binding modes and interactions between rosmarinic acid and enolase were preliminary explored by molecular docking analysis. CONCLUSION: The key findings of the present study manifested that rosmarinic acid, a medicinal compound extracted from P. frutescens, had pharmacological activity in inhibiting the growth of Trichophyton mentagrophytes by affecting its enolase expression to reduce metabolism. Rosmarinic acid is expected to be an efficacious product for prevention and treatment of dermatophytes.

Mechanism of salidroside against coronary artery disease by network pharmacology analysis.

BACKGROUND: Rosenroot (Rhodiola rosea) is a traditional Chinese herbal medicine. It has been used to treat patients with coronary artery disease (CAD). Salidroside is the main active constituent of rosenroot. This study was designed to explore the mechanism of salidroside in treating CAD and its role in angiogenesis in CAD systematically. METHODS: In this study, potential targets related to salidroside and CAD were obtained from public databases. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), Disease Ontology (DO) and CellMarker enrichment analyses were performed. The binding of salidroside to angiogenesis-related targets was assessed by PyMOL and Ligplot. Furthermore, the effects of salidroside on collateral circulation were evaluated by correlation analysis of these angiogenesis-related targets with the coronary flow index (CFI), and the influence of salidroside on human umbilical vein endothelial cell (HUVEC) proliferation and migration was assessed. RESULTS: Eighty-three targets intersected between targets of salidroside and CAD. GO and KEGG analyses indicated that salidroside mainly treated CAD through angiogenesis and anti-inflammatory action. There were 12 angiogenesis-related targets of salidroside in coronary heart disease, among which FGF1 (r = 0.237, P = 2.597E-3), KDR (r = 0.172, P = 3.007E-2) and HIF1A (r = -0.211, P = 7.437E-3) were correlated with the coronary flow index (CFI), and salidroside docked well with them. Finally, cell experiments confirmed that salidroside promoted the proliferation and migration of HUVECs. CONCLUSIONS: This study revealed the potential molecular mechanism of salidroside on angiogenesis in CAD and provided new ideas for the clinical application of salidroside in the treatment of CAD.

[Active fractions of Camellia nitidissima inhibit non-small cell lung cancer via suppressing epidermal growth factor receptor].

The present study explored the effects and its underlying mechanisms of four active fractions of Camellia nitidissima(leaf polyphenols, leaf saponins, flower polyphenols, and flower saponins in C. nitidissima) in inhibiting the proliferation and migration of non-small cell lung cancer(NSCLC) by suppressing the epidermal growth factor receptor(EGFR). MTT assay was used to detect the effect of four active fractions on the proliferation of NCI-H1975 and HCC827 cells. Wound healing assay and Transwell assay were adopted to evaluate the effect of four active fractions on the migration of NSCLC. The effect of four active fractions on the enzyme activity of EGFR was detected. Molecular docking was carried out to explore the direct action capacity and action sites between representative components of the four active fractions and EGPR. Western blot assay was employed to investigate the effect of four active fractions on the protein expression in EGFR downstream signaling pathways. The results of the MTT assay indicated that the cell viability of NCI-H1975 and HCC827 cells was significantly inhibited by four active fractions at 50, 100, 150, and 200 µg·mL~(-1) in a dose-dependent manner. Wound healing assay and Transwell assay revealed that the migration of NCI-H1975 and HCC827 cells was significantly suppressed by four active fractions. In addition, the results of the protein activity assay showed that the enzyme activity of EGFR was significantly inhibited by four active fractions. The molecular docking results confirmed that various components in four active fractions possessed strong binding activity to EGFR enzymes. Western blot assay revealed that four active fractions down-regulated the protein expression of EGFR and its downstream signaling pathways. It is concluded that the four active fractions of C. nitidissima can inhibit NSCLC. The mechanism may be related to EGFR and its downstream signaling pathways. This study provides a new scientific basis for the clinical treatment of NSCLC with active fractions of C. nitidissima, which is of reference significance for further research on the anti-tumor mechanism of C. nitidissima.

Reverse tracing anti-thrombotic active ingredients from dried Rehmannia Radix based on multidimensional spectrum-effect relationship analysis of steaming and drying for nine cycles.

ETHNOPHARMACOLOGICAL RELEVANCE: In traditional Chinese medicine (TCM) and modern pharmacodynamics, dried Rehmannia Radix (DRR) possesses prominent anti-thrombotic activity that decreases after processing by nine steaming and drying cycles to develop processed Rehmannia Radix (PRR). Due to the complexity of the DRR components, the chemical mechanism leading to efficacy changes of DRR caused by processing is still unclear. AIM OF STUDY: This study aimed to trace the anti-thrombotic active compounds of DRR and different degrees of processed RR (PRR) and to evaluate the synergistic effects among different active components. MATERIALS AND METHODS: The anti-thrombotic active chemical fraction of DRR extracts was evaluated. Targeted fractions of the processed products of RR were prepared at different processing stages. The changes in monosaccharides, oligosaccharides and secondary metabolites during processing were characterized by multidimensional high-performance liquid chromatography (HPLC). The anti-thrombotic effects of targeted fractions of different RR samples were evaluated by analyzing the length of tail thrombus (LT) and serum biochemical indicators in carrageenan-induced tail-thrombus mice. The spectrum-effect relationships were investigated by partial least squares regression (PLSR) analysis and gray correlation analysis (GRA). Finally, the active compounds were screened by spectrum-effect relationship analysis and validated in vivo, and their synergistic effects were determined by Webb's fraction multiplication method. RESULTS: Six ingredients highly associated with anti-thrombotic activities were screened out by the spectrum-effect relationship analysis, of which oligosaccharides (stachyose, sucrose and raffinose) and iridoid glycosides (catalpol, leonuride and melitoside) possessed a synergistic effect on tumor necrosis factors (TNF-α), interleukin 1ß (IL-1ß) and plasminogen activator inhibitor 1 (PAI-1)/tissue-type plasminogen activator (t-PA) ratio in vivo with synergistic coefficient (SC) > 1. CONCLUSION: The main material basis of the anti-thrombotic activities of DRR is oligosaccharide components of stachyose, raffinose and sucrose, iridoid glycosides components of catalpol, leonuride and melittoside. The two kinds of components exert synergistic anti-thrombotic effects by inhibiting the expression of inflammatory factors and regulating the balance of the fibrinolysis system.

Comparisons of antithrombosis, hematopoietic effects and chemical profiles of dried and rice wine-processed Rehmanniae Radix extracts.

ETHNOPHARMACOLOGICAL RELEVANCE: In traditional Chinese medicine (TCM), Rehmanniae Radix (RR, derived from the root of Rehmannia glutinosa (Gaertn.) DC.) is commonly used as natural medicine for thousands of years, two types including the dried and rice-wine processed RR were used for different clinical purposes respectively, which were the typical case that pharmaceutical effect changed by processing in TCM. AIM OF STUDY: The goal of this study was to investigate the differences in the antithrombosis and hematopoietic effects of extracts of dried and processed RR (DRR and PRR) in vivo, and to explore the chemical basis underlying changes of medicinal properties caused by processing. MATERIALS AND METHODS: The aqueous extracts of DRR and PRR were prepared. Protective effect of varying doses of different extracts were investigated in type-I carrageenan induced mice tail thrombosis and cyclophosphamide induced myelosuppression model. The chemical composition of DRR and PRR extracts were determined by High Performance Liquid Chromatography coupled with tandem quadrupole time-of-flight Mass Spectrometry (HPLC/Q-TOF-MS). RESULTS: In antithrombosis activity tests, PRR possessed less ameliorated effects than DRR in the model mouse on body temperature, tail thrombus length and blood flow. Both DRR and PRR had no significant influence on prothrombin time (PT) and activated partial thromboplastin time (APTT), only high dose DRR could decrease the content of fibrinogen (FIB) in plasma. Histological examination of lung tissue suggested that thrombosis was significantly improved in DRR-H group. For myelosuppression model, only PRR could improve peripheral hemogram, both DRR and PRR had hematopoietic effects as demonstrated by their abilities to ameliorate the bone marrow nucleated cells (BMNC) and pathology of bone marrow tissue. The hematopoietic effects of PRR were significantly more potent than that of DRR at the concentration of 9 g/kg. By comparing the chemical composition, we found that iridoid glycosides were decreased and furfural derivatives increased in DRR after processing which may be the chemical mechanism contribute to the differences in efficacy. CONCLUSIONS: According to the results of this research, processing with rice wine for nine cycles significantly reduced antithrombotic effects and enhanced the hematopoietic effects of DRR as demonstrated in model mice. It can scientifically explain the different effect among two types of RR in clinical through the diverse method of processing and usage. Meanwhile, the predicted activity compounds from two types of RR can be potential candidates for the treatment of thrombosis and anemia.

An integrated antioxidant activity fingerprint for commercial teas based on their capacities to scavenge reactive oxygen species.

An integrated antioxidant activity fingerprint, based on on-line screening methods for three reactive oxygen species (ROS: superoxide anion radical, hydrogen peroxide, and hydroxyl radical) was developed to comprehensively evaluate the quality of 12 batches of commercial tea. High-performance liquid chromatography (HPLC) coupled with a chemiluminescent detector was used to determine the antioxidant characteristics of a selection of teas as bioactivity fingerprints. An HPLC-electrospray ionization-mass spectrometry analysis was used to determine the chemical profiles of the teas in the chromatographic fingerprints. All of the green teas (S01-S08) were better scavengers of the three ROS compared to the oolong teas (S09-S12). The main scavengers of the three ROS in green tea were 5-galloylquinic acid, (-)-epigallocatechin-3-O-gallate, and (-)-epicatechin-3-O-gallate, whereas in oolong tea, they were (-)-epigallocatechin-3-O-gallate and (-)-epigallocatechin. This study demonstrates that comprehensive fingerprinting is a potentially meaningful method for evaluating the quality of food products.

Jiangtang Xiaozhi Recipe () prevents diabetic retinopathy in streptozotocin-induced diabetic rats.

OBJECTIVE: To evaluate the prevention effect of diabetic retinopathy of Jiangtang Xiaozhi Recipe (, JXR) in streptozotocin (STZ)-induced diabetic rats. METHODS: Sprague-Dawley rats were randomly divided into normal control group and diabetic group. Rats in the diabetic group were induced by intraperitoneal administration of STZ (50 mg/kg), and subdivided into 5 groups. Rats in the diabetic control group were given saline; four treatment groups were given metformin (300 mg/kg), JXR (2, 4 and 8 g/kg) respectively for 8 weeks, while rats in the normal control group were injected with citrate buffer and given the same volume of vehicle. Body weight and food intake were measured every week. The hypoglycaemic effects were determined by testing fasting blood glucose (FBG) every other week, and hemoglobin A1c (HbA1c), insulin, and glucagon at the end of the treatment. The preventive effects of JXR on STZ-induced diabetic rats were determined by histopathological examination with hematoxylin and eosin staining, and periodic acid-schiff staining. The effects were further evaluated by serum superoxide dismutase (SOD) activity and malondialdehyde (MDA). RESULTS: High-dose JXR significantly reduced FBG and HbA1c level at the 8th week of administration (P<0.01, P<0.05). JXR significantly increased insulin level (P<0.05), and decreased glucagon level (P<0.05). JXR showed the antioxidant defense with increased SOD activity and decreased MDA contents in diabetic rats. Histopathological studies revealed that there were no basement membrane thickening and mild destruction in the treated groups. Morphometric measurements of retina microvascular showed that acellular capillary and capillary density decreased in treated rats while pericyte and endothelial cell increasing after the treatment. CONCLUSION: JXR have protective effect of diabetic retinopathy and its mechanism may be associated with the obvious hypoglycemic and antioxidant effect.

[Effect of Jiangtang Xiaozhi Tablet on Insulin Resistance KK-AY Transgenic Mice Model of Diabetes Mellitus].

Objective To observe effects of Jiangtang Xiaozhi Tablet (JTXZT) on homeostasis model of assessment for insulin resistance index (HOMA-IR) , insulin sensitivity index ( ISI) , expres- sions of insulin (INS) and insulin receptor (InsR) in pancreas tissues of KK-A(y) transgenic mice model of diabetes mellitus (DM). Methods KK-A(y) transgenic mice were fed with high fat forage to induce hyper- glycemic obese DM model. The C,7ice at same age were used as a normal control group (fed with e- qual volume of sterile water, n =11). Successful modeled 55 mice with DM obesity were divided into 5 groups by random digit table (11 in each group) , including the model group (fed with equal volume of ster- ile water, with no treatment) , the Pioglitazone Hydrochloride Tablet treatment group (8 mg/kg; as a posi- tive control group) , and JTXZT groups [high (10. 0 g crude drugs/kg) , middle (5. 0 g crude drugs/kg) and low dose (2. 5 g crude drugs/kg) ]. All medications were fed by gastrogavage, once per day for 8 succes- sive weeks. All mice were weighed and levels of random blood glucose (RBG) determined after 8 weeks of treatment. Blood was collected from ophthalmic vein. Levels of insulin (INS) , serum total cholesterol (TC) and triglyceride (TG) were detected. HOMA-IR and ISI were calculated. The morphological changes of pancreas tissues were extracted for performed pathological examinations. The expressions of INS and insulin receptor (InsR ) were measured by immunohistochemistry ( IHC ). Expressions of insulin receptorp ßInsRP) and insulin receptor substrate-1 (IRS-1) in pancreas tissues were detected using Western blot. Results Compared with the normal control group, obesity, obviously increased blood glu- cose and blood lipids occurred in each group after modeling (P <0. 01). After 8 weeks of medication mice in the model group had put up body weight (P <0. 01) , blood glucose and blood lipids were kept on quite higher levels. Compared with the model group, body weight, serum levels of TG, INS, and HOMA-IR obvi- ously decreased in each JTXZT group (P <0. 05, P <0. 01). Besides, RBG decreased obviously lower in the high dose JTXZT group (P <0. 01). ISI obviously increased in low and high dose JTXZT groups (P < 0. 05, P <0. 01). Pathological results of HE staining in pancreas showed that atrophied islets with obvious- ly reduced numbers in the model group. They were sparsely distributed with reduced islet density.-Islet cells were compensatively hypertrophy, with degenerated vacuoles. Apoptosis of islet cells could also be seen in the model group, manifested as swollen cytoplasm and paryopyknosis. Islet number was obvious- ly increased in high and middle dose JTXZT groups, with reduced apoptosis and degenerated cells. Re- sults of IHC assay showed, as compared with the normal control group, the grey values of INS and InsR were significantly decreased in the model group (P <0. 01). Compared with the model group, IOD values of INS and InsR (IOD) were significantly increased in each JTXZT group (P <0. 05, P <0. 01). Results from Western blot showed that protein expressions of InsRP ßnd IRS-1 were obviously decreased in the model group, as compared with the normal control group (P <0. 01). Compared with the model group, protein expressions of InsRP ßnd IRS-1 were obviously increased in each JTXZT group (P <0. 01) , but with no statistical difference as compared with the Pioglitazone Hydrochloride Tablet treatment group (P > 0. 05). Conclusions JTXZT had obvious roles in decreasing levels of blood glucose, serum lipids, and improving insulin resistance in KK-Ayt(r) ansgenic mice model with diabetic obesity. Its mechanism might involve in increasing expressions of lnsRp and IRS-1 in pancreas cells, promoting the integration of INS to its receptors, and thereby improving glucose metabolism , lipid metabolism , and IR state.

[Effect of shuangshen ningxin formula on energy metabolism of myocardial ischemia/reperfusion rats].

OBJECTIVE: To investigate the effect of Shuangshen Ningxin (SSNX) formula on energy metabolism of myocardial ischemia/reperfusion rats. METHOD: The myocardial ischemia/reperfusion model of Wistar rats was established through the ligation of left anterior descending branch of coronary artery of for 40 min and the reperfusion for 2 h. The Wistar rats were randomly divided into six groups: the sham operation group, the model group, the Trimetazidine group (10 mg x kg(-1)) and SSNX groups (22.5, 45, 90 mg x kg(-1)). Preventive administration was conducted for 5 d. The operation was performed at 1 h on the day of the last administration. CK-MB assay kit was adopted to detect the activity of serum CK-MB. HPLC was used to determine ATP, ADP and AMP contents in myocardial tissues and calculate TAN and EC. RESULT: The preventive administration with SSNX could reduce the activity of serum CK-MB and increase ATP content and EC level in myocardial tissues (P < 0.01 or P < 0.05 vs. the model group). CONCLUSION: SSNX formula can maintain energy charge in cardiomyocytes and relieve ischemia/reperfusion injury by preserving ischemic myocardium ATP.

[Experimental study of jiangtang xiaozhi tablet on decreasing the levels of blood glucose and serum lipids in transgenic mice with diabetes mellitus].

OBJECTIVE: To observe the effects of Jiangtang Xiaozhi Tablet (JTXZT) on decreasing the levels of blood glucose and serum lipids in KK-Ay transgenic model mice with diabetes mellitus (DM). METHODS: KK-Ay transgenic mice were fed with high fat diet to induce DM obesity model. The C57 mice of the same age were recruited as the control group. Then the modeled KK-Ay mice were divided into 5 groups, i.e., the model group, the Pioglitazone Hydrochloride Tablet treatment group (8 mg/kg, as the positive control group), and the high dose JTXZT group (10 g/kg), the middle dose JTXZT group (5 g/kg), and the low dose JTXZT group (2.5 g/kg), 11 in each group. Eight weeks was taken as one therapeutic course. All medicines were given by gastrogavage. The food intake and body weight were measured every week. The blood glucose level was determined once every 2 weeks. The levels of fasting blood glucose (FBG), serum lipids (TC and TG), insulin (INS), and leptin (Lep) were assayed 8 weeks after medication. The weight of liver and fat were weighed to calculate their indices. Then the adipose denaturalization of the liver was classified. The numbers of the pancreatic islet and adipocytes were respectively counted. RESULTS: Compared with the model group, the food intake and the body weight obviously decreased in the 3 JTXZT groups (P < 0.05, P < 0.01). From the 6th week, the FBG level obviously decreased in the high dose JTXZT group (P < 0.01). After eight successive weeks of intragastric administration, the levels of TG and INS obviously decreased in the 3 JTXZT groups (P < 0.05, P < 0.01). The Lep level somewhat decreased in the high dose JTXZT group (P < 0.05). The indices of the liver and fat obviously decreased and the number of the pancreatic islet obviously increased in the 3 JTXZT groups (P < 0.05, P < 0.01). The number of adipocytes obviously decreased in the high and middle dose JTXZT groups (P < 0.05, P < 0.01). The liver fatty degeneration was obviously improved in the high dose JTXZT group (P < 0.05). CONCLUSION: JTXZT had obvious effects on decreasing the levels of blood glucose and serum lipids in KK-Ay transgenic model mice with DM obesity.