Advances of traditional Chinese medicine preclinical mechanisms and clinical studies on diabetic peripheral neuropathy.

CONTEXT: Diabetic peripheral neuropathy (DPN) results in an enormous burden and reduces the quality of life for patients. Considering there is no specific drug for the management of DPN, traditional Chinese medicine (TCM) has increasingly drawn attention of clinicians and researchers around the world due to its characteristics of multiple targets, active components, and exemplary safety. OBJECTIVE: To summarize the current status of TCM in the treatment of DPN and provide directions for novel drug development, the clinical effects and potential mechanisms of TCM used in treating DPN were comprehensively reviewed. METHODS: Existing evidence on TCM interventions for DPN was screened from databases such as PubMed, the Cochrane Neuromuscular Disease Group Specialized Register (CENTRAL), and the Chinese National Knowledge Infrastructure Database (CNKI). The focus was on summarizing and analyzing representative preclinical and clinical TCM studies published before 2023. RESULTS: This review identified the ameliorative effects of about 22 single herbal extracts, more than 30 herbal compound prescriptions, and four Chinese patent medicines on DPN in preclinical and clinical research. The latest advances in the mechanism highlight that TCM exerts its beneficial effects on DPN by inhibiting inflammation, oxidative stress and apoptosis, endoplasmic reticulum stress and improving mitochondrial function. CONCLUSIONS: TCM has shown the power latent capacity in treating DPN. It is proposed that more large-scale and multi-center randomized controlled clinical trials and fundamental experiments should be conducted to further verify these findings.

Silk fibroin microspheres loaded Rehmannia Liuwei extract for the protection of endothelial cells from the inhibitory effects.

Liuwei Dihuang (LWDH) is a multi-component and multi-target Chinese herbal compound widely used for treating chronic conditions such as diabetes, diabetic nephropathy, hypertension, osteoporosis, and chronic kidney disease. However, traditional Chinese medicine (TCM) preparations like decoction and pill face limitations, including low active component concentration, limited bioavailability, short half-life, and the need for high dosage, which may increase the burden on liver and kidney functions and reduce clinical efficacy. In this study, LWDH was further purified using D101 macroporous adsorption resin, resulting in a soluble extract with an active component content 53.6 times higher than that of LWDH itself. The freeze-dried LWDH extract was then encapsulated within silk fibroin (SF) microspheres to significantly enhance the sustained release performance of the drug. In a human umbilical vein endothelial cell (HUVEC) model cultured under high glucose conditions, methanol vapor-treated SF/LWDH microspheres demonstrated a decrease in the 24-hour drug release rate from 61.88 % to 34.81 %, augmenting their protective effect on endothelial cells.

Efficacy of Huoxue Qianyang Qutan Recipe on essential hypertension: A randomized, double-blind, placebo-controlled trial.

BACKGROUND: Hypertension, a prevalent disease, is a significant risk factor for coronary heart disease. Huoxue Qianyang Qutan Recipe (HQQR), a traditional Chinese herbal remedy, has been used for treating hypertension over several years. OBJECTIVE: This study assesses HQQR's efficacy for controlling blood pressure among patients with hypertension related to blood stasis, yang hyperactivity and phlegm. DESIGN, SETTING, PARTICIPANTS AND INTERVENTIONS: A randomized controlled trial was conducted at the Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, China, from July 2020 to June 2022. Major components of HQQR were identified using thin-layer chromatography and high-performance liquid chromatography. Participants aged 18-80 years, exhibiting traditional Chinese medicine syndromes of blood stasis, yang hyperactivity or phlegm, along with grades 1 or 2 hypertension, were randomly categorized into two groups. The intervention group was given HQQR granules alongside conventional hypertension treatment, while the control group was given placebo granules in addition to conventional treatment for 12 weeks. MAIN OUTCOME MEASURES: The primary outcome was clinic blood pressure, whereas secondary outcomes included metabolic indices (e.g., homeostasis model assessment of insulin resistance [HOMA-IR], total cholesterol [TC], low-density lipoprotein cholesterol and triglyceride), target organ damage indices (left ventricular mass index and urinary albumin creatinine ratio [UACR]) and inflammation indices (interleukin-6 [IL-6] and high-sensitivity C-reactive protein [hs-CRP]). RESULTS: HQQR's primary components were identified as salvianolic acid B, emodin and ferulic acid. Of the 216 participants (108 in each group), compared to the control, the intervention group exhibited significant improvements (P < 0.001) in clinic systolic blood pressure ([136.24 ± 7.63] vs [130.06 ± 8.50] mmHg), clinic diastolic blood pressure ([84.34 ± 8.72] vs [80.46 ± 6.05] mmHg), home systolic blood pressure ([131.64 ± 8.74] vs [122.36 ± 8.45] mmHg) and home diastolic blood pressure ([78.47 ± 9.53] vs [71.79 ± 6.82] mmHg). HQQR demonstrated a reduction in ambulatory blood pressure (24-hour systolic blood pressure: [133.75 ± 10.49] vs [132.46 ± 8.84] mmHg and 24-hour diastolic blood pressure: [84.12 ± 8.01] vs [82.11 ± 7.45] mmHg) and an improvement in HOMA-IR ([4.09 ± 1.72] vs [3.98 ± 1.44]), TC ([4.66 ± 1.47] vs [3.75 ± 1.81] mmol/L) and UACR (75.94 [5.12, 401.12] vs 45.61 [4.26, 234.26]). Moreover, HQQR demonstrated a decrease in hs-CRP (1.46 [0.10, 10.53] vs 0.57 [0.12, 3.99] mg/L) and IL-6 (6.69 [2.00, 29.74] vs 5.27 [2.00, 9.73] pg/mL), with no reported side effects (P < 0.001). CONCLUSION: This study highlights the therapeutic potential of HQQR use in ameliorating blood pressure, glycolipid metabolism, and inflammation in patients with hypertension. TRIAL REGISTRATION: ChiCTR2000035092 (https://www.chictr.org.cn/). Please cite this article as: Xie J, Ma YL, Gui MT, Yao L, Li JH, Wang MZ, Zhou XJ, Wang YF, Zhao MY, Cao H, Lu B, Fu DY. Efficacy of Huoxue Qianyang Qutan Recipe on essential hypertension: A randomized, double-blind, placebo-controlled trial. J Integr Med. 2024; Epub ahead of print.

Effect of Chinese herbal compound dressings in treating patients with diabetic foot ulcers: A meta-analysis.

This meta-analysis aims to systematically investigate the clinical efficacy of Chinese herbal compound dressings in treating patients with diabetic foot ulcers (DFUs). A comprehensive computerised search was conducted in databases including PubMed, Embase, Google Scholar, Cochrane Library, China National Knowledge Infrastructure, and Wanfang databases, from database inception to November 2023, to identify randomised controlled trials (RCTs) concerning the use of Chinese herbal compound dressings in patients with DFU. Two researchers independently screened the literature, extracted data, and assessed the quality based on inclusion and exclusion criteria. Data analysis was performed using Stata 17.0 software. Overall, 18 RCTs involving 1405 DFU patients were included. The analysis indicated that compared to the control group, the group treated with Chinese herbal compound dressings had significantly shorter ulcer healing time (standardised mean difference [SMD] = -2.49, 95% confidence interval [CI]: -3.53 to -1.46, p < 0.001), reduced ulcer surface area (SMD = -3.38, 95% CI: -4.67 to -2.09, p < 0.001), and higher healing rates (odds ratio [OR] = 2.24, 95% CI: 1.72-2.92, p < 0.001) as well as overall effectiveness rates (OR = 4.56, 95% CI: 3.10-6.71, p < 0.001). This study demonstrates that the external application of Chinese herbal compound dressings in patients with DFU can significantly shorten the ulcer healing time and improve wound healing rates.

An exploration of the effect of Chinese herbal compound on the occurrence and development of large intestine cancer and intestinal flora.

This study was conducted to observe the effect of Chinese herbal compound on the treatment of colon cancer using AOM/DSS-induced C57BL/6J colon cancer mice and to validate potential influence on intestinal flora of mice. A colorectal cancer (CRC) mouse model was built with a total of 50 C57BL/6J mice that were induced by administrating AOM/DSS. These experimental animals were split up into 5 groups, a control group, a model group, and low-, medium- and high-dose Chinese herbal compound groups. All mice were given Chinese herbal compound treatment, and the colon tissues of each group were harvested with the length measured and the number of colon polyps accounted. The Ki-67 expression in the colon tissues was detected via immuno-histochemistry. Relative quantification of the expression of genes and proteins was determined through qPCR and WB assays. Contents of IL-6, TNF-α, IFN-γ, and IL-10 in serum and colon tissues of mice were determined by ELISA. An additional 16S rRNA sequencing analysis was implemented for the identification of mouse intestinal flora. The results suggested that all low-, medium- or high-dose Chinese herbal compound could markedly inhibit the shortening of colon length and significant number reduction of colon polyps in the model group. The relative expression of genes and proteins (PCNA, Muc16, and MMP-9) associated with proliferation in mouse colon tissues were inhibited. In addition, compared with the model group, the contents of IL-6, TNF-α, and IFN-γ in serum and colon tissues were substantially decreased in the high-dose Chinese herbal compound group, thereby reducing the structure damage in colon tissues and the infiltration degree of inflammatory cells. Besides, the expression of TLR4/MyD88/NF-κB protein was markedly decreased. The 16S rRNA sequencing analysis demonstrated that mice in the model group had decreased intestinal flora diversity, and there were significant changes in flora abundance and amino acid metabolism between the control group and the model group. Taken together, the treatment of Chinese herbal compound against CRC in this study might be regulated by the TLR4/MyD88/NF-κB signaling pathway, and the imbalance in intestinal flora was also closely related to CRC occurrence.

Correlation Between Expression of HIF-1α and Prognosis of Arsenic-containing Chinese Herbal Compound in Treatment of Myelodysplastic Syndrome / 中国实验方剂学杂志

ObjectiveMyelodysplastic syndromes （MDS） is a group of clonal hematopoietic stem cell disorders，and this study aims to investigate the expression of hypoxia-inducible factor-1α（HIF-1α） in the bone marrow cells of patients with MDS and its correlation with the clinical features of MDS，the therapeutic efficacy of arsenic-containing Chineseherbal compound，and the survival prognosis. MethodAccording to the inclusion and exclusion criteria，27 MDS patients treated with arsenic-containing Chinese herbal compound in the Department of Hematology，Xiyuan Hospital，China Academy of Chinese Medical Sciences from January 2022 to September 2022 were included，and their bone marrow samples were collected by myelotomy. HIF-1α expression level in bone marrow cells was detected by real-time polymerase chain reaction （PCR） to analyze its correlation with clinical features，and logistic and Cox regression was used to analyze the risk factors affecting the efficacy and prognostic survival of MDS patients. ResultThe HIF-1α mRNA expression level was lower in bone marrow cells of MDS patients than in healthy subjects. HIF-1α was positively correlated with the degree of myelodysplasia（r=0.384，P<0.05） and bone marrow granulocytic system%（G%）（r=0.560，P<0.01）. Logistic regression showed that HIF-1α was a risk factor for the prognosis in the follow-up of the efficacy of treatment（P<0.05）and Cox regression showed that HIF-1α was an independent factor affecting the survival prognosis of MDS patients ［odds ratio（OR）=398.968，95% confidence interval（CI）（1.281，116 858.743），P<0.05］. ConclusionThe level of HIF-1α expression in bone marrow cells of MDS patients was closely related to the degree of clinical myelodysplasia and G%，and HIF-1α was a risk factor for the efficacy for and survival prognosis of MDS patients.

[Medication rules of Chinese herbal compound prescriptions for treating angina in national patent database based on multiple data mining].

This study explored the medication rules of Chinese herbal compound prescriptions for the treatment of angina based on the Chinese herbal compound patents in the patent database of the China National Intellectual Property Administration. The data of eligible Chinese herbal compound patents for the treatment of angina were collected from the patent database of the China National Intellectual Property Administration from database inception to November 10, 2022, and subjected to data modeling, analysis of main syndromes, medication frequency analysis, cluster analysis, association rule analysis, and data visualization by using Excel 2021, IBM SPSS Statistics 26.0, IBM SPSS Modeler 18.0, Cytoscape 3.9.1, and Rstudio R 4.2.2.2 to explore the medication rules for angina. The study included 636 pieces of patent data for angina that met the inclusion criteria, involving 815 drugs, with a total frequency of 6 586. The most common main syndromes were blood stasis obstructing the heart syndrome(222, 34.91%) and Qi deficiency and blood stasis syndrome(112, 17.61%). The top 10 most frequently used drugs were Salviae Miltiorrhizae Radix et Rhizoma, Chuanxiong Rhizoma, Notoginseng Radix et Rhizoma, Astragali Radix, Angelicae Sinensis Radix, Carthami Flos, Glycyrrhizae Radix et Rhizoma, Ginseng Radix et Rhizoma, Borneolum Syntheticum, and Corydalis Rhizoma. High-frequency drugs included blood-activating and stasis-resolving drugs(1 197, 18.17%) and deficiency-tonifying drugs(809, 12.28%). Cluster analysis identified eight drug combinations, including five new prescriptions suitable for clinical use and new drug development, and three drug pairs. The core drug combination of Salviae Miltiorrhizae Radix et Rhizoma-Chuanxiong Rhizoma-Carthami Flos was identified through the complex co-occurrence network analysis of Chinese medicines. Association rule analysis yielded a total of 17 rules, including 13 drug pairs and 4 tripartite combinations. Common drug pairs included Salviae Miltiorrhizae Radix et Rhizoma-Chuanxiong Rhizoma(support degree 25.79%, confidence coefficient 69.49%, lift 1.30) and Salviae Miltiorrhizae Radix et Rhizoma-Notoginseng Radix et Rhizoma(support degree 22.01%, confidence coefficient 61.95%, lift 1.16). Common tripartite combinations included Salviae Miltiorrhizae Radix et Rhizoma-Chuanxiong Rhizoma-Astragali Radix(support degree 10.85%, confidence coefficient 73.40%, lift 1.37) and Salviae Miltiorrhizae Radix et Rhizoma-Chuanxiong Rhizoma-Notoginseng Radix et Rhizoma(support degree 10.69%, confidence coefficient 79.07%, lift 1.48). The results showed that the underlying pathogenesis of angina involved blood stasis obstructing the heart and Qi deficiency and blood stasis. The overall nature of the disease was characterized as asthenia in origin and sthenia in superficiality. In the prescription formulation, blood-activating and stasis-resolving drugs, such as Salviae Miltiorrhizae Radix et Rhizoma, Chuanxiong Rhizoma, and Carthami Flos were often used to resolve the excess manifestation, which were combined with tonifying drugs such as Astragali Radix, Angelicae Sinensis Radix, Glycyrrhizae Radix et Rhizoma, and Ginseng Radix et Rhizoma to reinforce the deficiency. The syndrome, pathogenesis, disease nature, and medication were consistent with clinical practice. Additionally, the new compound prescriptions and drug combinations derived from the multiple data mining in this study could provide references and insights for the clinical diagnosis and treatment of angina and the development of new drugs.

Chinese herbal compound SanHuang decoction reverses axitinib resistance in ccRCC through regulating immune cell infiltration by affecting ADAMTS18 expression.

This investigation aims to study the reversal effect of the Chinese herbal compound SanHuang decoction on axitinib resistance in clear cell renal cell carcinoma (ccRCC) cells and its mechanistic role by employing cellular and mouse models. Axitinib-resistant ccRCC cell lines (A498-DR and 786-O-DR) were cultured and treated with SanHuang decoction. The apoptosis and migration of tumor cells were observed by flow cytometry and wound healing assays, respectively, and the expression of a disintegrin-like and metalloprotease with thrombospondin type 1 motif 18 (ADAMTS18) was evaluated by reverse transcription-polymerase chain reaction (RT-PCR) and Western blotting (WB). In addition, A498-DR cells were inoculated into mice to establish tumorigenic models, and the models were treated with normal saline, axitinib, or different concentrations of SanHuang decoction plus axitinib. Then, the tumor diameter in each group was measured, and the expression of ADAMTS18 was evaluated by RT-PCR, WB and immunohistochemistry. In addition, the distribution of T cells (CD45+, CD4+, CD8+) and PD-L1 expression was analyzed by flow cytometry to evaluate the level of immune cell infiltration. SanHuang decoction significantly reduced the proliferative activity of axitinib-resistant tumor cells and enhanced the sensitivity of tumors to axitinib in vitro (cell lines) and in mice. In the SanHuang decoction group, the expression level of ADAMTS18 was increased to some extent, and several phenomena were observed, including (1) subcutaneous transplanted tumors grew slower, (2) the CD45+/PD-L1 ratio was decreased and (3) the proportions of CD8+ and CD4+ T cells were increased. Overexpression of ADAMTS18 was synergistic with SanHuang decoction treatment to jointly improve tumor immune infiltration and inhibit immune escape. Pearson correlation analysis of sample data showed that there was a negative correlation between the expression of ADAMTS18 and PD-L1 in tumor tissues. In conclusion, the Chinese herbal compound SanHuang decoction can reverse axitinib resistance in ccRCC cells by regulating immune cell infiltration and affecting ADAMTS18 expression.

San Huang Xiao Yan recipe modulates the HMGB1-mediated abnormal inflammatory microenvironment and ameliorates diabetic foot by activating the AMPK/Nrf2 signalling pathway.

BACKGROUND: Diabetic foot (DF) is one of the serious complications of diabetes and lacks of therapeutic drugs. Abnormal and chronic inflammation promoting foot infection and wound healing delay are the main pathogenesis of DF. The traditional prescription San Huang Xiao Yan Recipe (SHXY) has been used in the clinical treatment of DF for several decades as approved hospital experience prescription and showed remarkable therapeutic effect, but the mechanisms by which SHXY treats DF are still unclear. PURPOSE: Objectives of this study were to investigate SHXY anti-inflammatory effect on DF and explore the molecular mechanism for SHXY. METHODS: We detected the effects of SHXY on DF in C57 mouse and SD rat DF models. Animal blood glucose, weight and wound area were detected every week. Serum inflammatory factors were detected by ELISA. H&E and Masson's trichrome were used to observe tissue pathology. Single-cell sequencing data reanalysis revealed the role of M1 macrophages in DF. Venn analysis showed the co-target genes between DF M1 macrophages and compound-disease network pharmacology. Western blotting was used to explored target protein expression. Meanwhile, RAW264.7 cells were treated with drug-containing serum of SHXY to further unravel the roles of target proteins during high glucose-induced inflammation in vitro. The Nrf2 inhibitor ML385 was used on RAW 264.7 cells to further explore the relationship between Nrf2, AMPK and HMGB1. The main components of SHXY were analysed by HPLC. Finally, the treatment effect of SHXY on DF were detected on rat DF model. RESULTS: In vivo, SHXY can ameliorate inflammatory, accelerate wound healing and upregulate expression of Nrf2, AMPK and downregulate of HMGB1. Bioinformatic analysis showed that M1 macrophages were the main inflammatory cell population in DF. Moreover, the Nrf2 downstream proteins HO-1 and HMGB1 were potential DF therapeutic targets for SHXY. In vitro, we also found that SHXY increased AMPK and Nrf2 protein levels and downregulated HMGB1 expression in RAW264.7 cells. Inhibiting the expression of Nrf2 impaired the inhibition effect of SHXY on HMGB1. SHXY promoted Nrf2 translocation into the nucleus and increased the phosphorylation of Nrf2. SHXY also inhibited HMGB1 extracelluar release under high glucose. In rat DF models, SHXY also exhibited significant anti-inflammatory effect. CONCLUSION: The SHXY activated AMPK/Nrf2 pathway to suppress abnormal inflammation on DF via inhibiting HMGB1 expression. These findings provide novel insight into the mechanisms by which SHXY treats DF.

Topical Chinese herbal compound in the treatment of oral candidiasis: A systematic review and meta-analysis of randomized controlled trials.

Objective: A meta-analysis was performed to systematically review the clinical efficacy of external traditional Chinese medicine compounds in the treatment of oral candidiasis to provide a reference for the clinical treatment of this disease. Methods: We systematically searched relevant Chinese and English databases, including the Chinese Biomedical Literature Database, China National Knowledge Infrastructure, Chinese Scientific Journal Database, Wanfang Database, PubMed, Web of Science, the Cochrane Library and Scopus, from inception to September 2022 to identify all clinical randomized controlled studies of oral candidiasis treated with external Chinese medicine compounds. The inclusion criteria were a randomized controlled study of an experimental group with the intervention of an external traditional Chinese medicine compound, and the results of the literature were clear. Duplicate publications, literature on single or proprietary Chinese medicine treatment, literature from which relevant data could not be extracted and studies without rigorous experimental designs were excluded. Two researchers independently screened relevant studies that met the inclusion and exclusion criteria and conducted quality evaluation and data extraction for the included studies. The total effective rate, Candida negative conversion rate and recurrence rate were statistically analysed by RevMan 5.3 software. Results: This study included 29 studies and 30 studies, involving 2553 patients with oral candidiasis, with 1320 in the experimental group and 1233 in the control group. The total effective rate of the experimental group was better than that of the control group (RR = 1.21 [1.15, 1.27], P < 0.000). The negative rate of Candida in the experimental group was better than that in the control group (RR = 1.25 [1.05, 1.50], P=0.01). The recurrence rate of the experimental group was lower than that of the control group (RR = 0.34 [0.18, 0.63], P=0.0007). The difference was statistically significant. Conclusion: Compared with Western medicine alone, external traditional Chinese medicine in the treatment of oral candidiasis has certain advantages in improving the total effective rate, increasing the negative conversion rate of Candida and reducing the recurrence rate. However, larger samples and high-quality clinical studies are needed to obtain further support and verification.

Exploration of the Potential Mechanisms of Lingqihuangban Granule for Treating Diabetic Retinopathy Based on Network Pharmacology.

BACKGROUND: The Lingqihuangban Granule (LQHBG), a remarkable Chinese herbal compound, has been used for decades to treat diabetic retinopathy (DR) in the Department of Ophthalmology, Shanghai General Hospital (National Clinical Research Center for Eye Diseases) with obvious effects. Through the method of network pharmacology, the present study constructed bioactive component-relative targets and protein-protein interaction network of the LQHBG and implemented gene function analysis and pathway enrichment of targets, discussing the mechanisms of traditional Chinese medicine LQHBG in treating DR. MATERIALS AND METHODS: The bioactive ingredients of LQHBG were screened and obtained using TCMSP and ETCM databases, while the potential targets of bioactive ingredients were predicted by SwissTargetPrediction and ETCM databases. Compared with the disease target databases of TTD, Drugbank, OMIM and DisGeNET, the therapeutic targets of LQHBG for DR were extracted. Based on the DAVID platform, GO annotation and KEGG pathway analyses of key targets were explored, combined with the screening of core pathways on the Omicshare database and pathway annotation on the Reactome database. RESULTS: A total of 357 bioactive components were screened from LQHBG, involving 86 possible targets of LQHBG treating DR. In the PPI network, INS and ALB were identified as key genes. The effective targets were enriched in multiple signaling pathways, such as PI3K/Akt and MAPK pathways. CONCLUSION: This study revealed the possible targets and pathways of LQHBG treating DR, reflecting the characteristics of multicomponent, multitarget and multipathway treatment of a Chinese herbal compound, and provided new ideas for further discussion.

Application of Natural Ingredients of Traditional Chinese Medicine in Pain Management： A Review / 中国实验方剂学杂志

Pain is one of the most prevalent health problems. Current medications for pain are mainly anticonvulsants， tricyclic antidepressants， and opioidergic drugs. However， their therapeutic effectiveness is limited during application， and some even have severe side effects. In recent years， research on natural ingredients from Chinese herbal medicine has been extensively conducted for their analgesic activities. A series of natural ingredients represented by alkaloids， coumarins， flavonoids， and terpenoids have shown great analgesic activity， and further studies on their analgesic mechanism have found that most natural products have multi-target analgesic mechanisms. It can exert analgesic effects by blocking ion channels， regulating related receptors， or inducing anti-inflammatory or antioxidant effects. In addition， many traditional Chinese medicine （TCM） formulas have shown great analgesic ability after clinical application and have multiple complex analgesic mechanisms. The drug cloud （dCloud） theory can better describe the mechanisms， and it can represent the complete therapeutic spectrum of multi-target analgesics from two dimensions， namely the "direct efficacy" that directly inhibits pain signals and the "background efficacy" that targets the root causes of pain. The authors summarized the research progress of natural ingredients with analgesic effects found in Chinese herbal medicine so far， as well as the analgesic efficacy and potential mechanisms of TCM formulas with great analgesic effects in clinical applications， so as to provide a new basis for searching for new analgesic drugs from TCM.

Effect and Mechanism of Baoshen Prescription in Alleviating Renal Fibrosis in UUO Mice by Regulating ERK/p38 MAPK Signaling Pathway / 中国实验方剂学杂志

ObjectiveTo observe the protective effect of Baoshen prescription against renal fibrosis and explore its underlying mechanism through network pharmacology， molecular docking， and in vivo experiments. MethodAll mice were randomly divided into sham surgery group， model group， low-， medium-， and high-dose Baoshen prescription groups， and a benazepril hydrochloride group. Unilateral ureteral obstruction （UUO） was performed to establish a renal fibrosis model， and the administration of Baoshen prescription at low， medium， and high doses （0.455， 0.91， and 1.82 g·kg-1）， and benazepril hydrochloride （1.68 mg·kg-1） or distilled water began on the same day as model preparation. Mice in the model group and the sham surgery group were given an equal volume of distilled water. The intervention was carried out once daily for 14 days. Mouse serum levels of blood urea nitrogen （BUN） and creatinine （Cr） were measured. Hematoxylin-eosin （HE） staining and Masson staining were used to observe renal pathological changes. Western blot and immunohistochemistry were used to assess the expression of fibronectin （FN）， α-smooth muscle actin （α-SMA）， and E-cadherin， which are related to renal fibrosis. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） was used to measure the mRNA expression of transforming growth factor-β1 （TGF-β1）， tumor necrosis factor-α （TNF-α）， NOD-like receptor protein 3 （NLRP3）， and monocyte chemoattractant protein-1 （MCP-1） in renal tissues. The mechanism of Baoshen prescription in improving renal fibrosis was explored through network pharmacology， molecular docking， and Western blot experiments. ResultCompared with the sham surgery group， the model group showed significantly increased levels of BUN and Cr （P<0.01）. The model group exhibited abnormal renal glomerular morphology， loss of tubular brush borders， tubular dilation， and an enlarged area of blue collagen fibers. Mice in the model group showed significantly elevated levels of FN and α-SMA （P<0.01）， significantly decreased expression of E-cadherin （P<0.01）， and significantly increased expression of TGF-β1， TNF-α， NLRP3， and MCP-1 mRNA （P<0.05， P<0.01）. Compared with the model group， the Baoshen prescription groups showed significantly reduced BUN and Cr levels （P<0.01）， alleviated renal pathological damage， improved fibrosis， reduced expression of FN and α-SMA （P<0.01）， increased E-cadherin expression （P<0.01）， and downregulated mRNA expression of TGF-β1， TNF-α， NLRP3， and MCP-1 （P<0.05， P<0.01）. Network pharmacology and molecular docking predicted that Baoshen prescription could potentially improve renal fibrosis through the extracellular signal-regulated kinase （ERK）/p38 mitogen-activated protein kinase （MAPK） signaling pathway. Pharmacological research showed that compared with the sham surgery group， the model group exhibited significantly increased expression of phosphorylated （p）-ERK and p-p38 （P<0.05， P<0.01）. Compared with the model group， medium- and high-dose Baoshen prescription groups showed significantly downregulated expression of p-ERK and p-p38 proteins （P<0.05， P<0.01）. ConclusionBaoshen prescription can effectively improve renal fibrosis induced by UUO in mice， and its mechanism of action may be related to the ERK/p38 MAPK signaling pathway.

Pharmacodynamics and mechanism of Zhuling Jianpi capsule on 2,4,6-trinitrobenzenesulfonic acid-induced experimental colitis in rats / 中国药科大学学报

@#To investigate the pharmacodynamic effects and mechanism of Zhuling Jianpi capsule(Zhuling) on 2,4, 6-trinitrobenzene sulfonic acid (TNBS)-induced experimental colitis in rats.The experimental colitis model was established by enema with 2.5% TNBS.The rats were randomly divided into normal group,model group,Changyanning (180 mg/kg) group and Zhuling low-dose (40 mg/kg) group and Zhuling high-dose (120 mg/kg) group.After modeling,the rats were executed after 7 days of drug treatment.During this period,the disease activity status of the rats was observed,and the body weights of the rats were recorded daily.At the end of the experiment,the colonic tissues were obtained for the analysis of the expression of hematoxylin-eosin(HE) staining.The myeloperoxidase (MPO) enzyme activity,mRNA expression levels of inducible nitric oxide synthase (iNOS) and inflammatory cytokines (IL-6, IL-1β, IFN-γ, IL-10) were determined, and the levels of intestinal tight junction proteins and serum inflammatory factor levels were measured.The results showed that compared with model group, the administration of Zhuling significantly alleviated the weight loss and elevated the disease activity index (DAI) caused by TNBS, relieved the shortening, edema and pathological damage of colonic tissue, reduced inflammatory cell infiltration, destruction of crypt and loss of goblet cells, decreased the MPO enzyme activity of colonic tissue, iNOS and pro-inflammatory cytokines in colon, increased the levels of colonic tight junction protein (occludin, ZO-1), and decreased serum levels of inflammatory factors (IL-6,IL-1β).The results suggest that Zhuling administration ameliorates TNBS-induced experimental colitis in rats by decreasing the level of inflammatory factors and increasing the expression of intestinal tight junction proteins.This experiment could provide a theoretical basis for the clinical application of Zhuling.

Medication rules of Chinese herbal compound prescriptions for treating angina in national patent database based on multiple data mining / 中国中药杂志

This study explored the medication rules of Chinese herbal compound prescriptions for the treatment of angina based on the Chinese herbal compound patents in the patent database of the China National Intellectual Property Administration. The data of eligible Chinese herbal compound patents for the treatment of angina were collected from the patent database of the China National Intellectual Property Administration from database inception to November 10, 2022, and subjected to data modeling, analysis of main syndromes, medication frequency analysis, cluster analysis, association rule analysis, and data visualization by using Excel 2021, IBM SPSS Statistics 26.0, IBM SPSS Modeler 18.0, Cytoscape 3.9.1, and Rstudio R 4.2.2.2 to explore the medication rules for angina. The study included 636 pieces of patent data for angina that met the inclusion criteria, involving 815 drugs, with a total frequency of 6 586. The most common main syndromes were blood stasis obstructing the heart syndrome(222, 34.91%) and Qi deficiency and blood stasis syndrome(112, 17.61%). The top 10 most frequently used drugs were Salviae Miltiorrhizae Radix et Rhizoma, Chuanxiong Rhizoma, Notoginseng Radix et Rhizoma, Astragali Radix, Angelicae Sinensis Radix, Carthami Flos, Glycyrrhizae Radix et Rhizoma, Ginseng Radix et Rhizoma, Borneolum Syntheticum, and Corydalis Rhizoma. High-frequency drugs included blood-activating and stasis-resolving drugs(1 197, 18.17%) and deficiency-tonifying drugs(809, 12.28%). Cluster analysis identified eight drug combinations, including five new prescriptions suitable for clinical use and new drug development, and three drug pairs. The core drug combination of Salviae Miltiorrhizae Radix et Rhizoma-Chuanxiong Rhizoma-Carthami Flos was identified through the complex co-occurrence network analysis of Chinese medicines. Association rule analysis yielded a total of 17 rules, including 13 drug pairs and 4 tripartite combinations. Common drug pairs included Salviae Miltiorrhizae Radix et Rhizoma-Chuanxiong Rhizoma(support degree 25.79%, confidence coefficient 69.49%, lift 1.30) and Salviae Miltiorrhizae Radix et Rhizoma-Notoginseng Radix et Rhizoma(support degree 22.01%, confidence coefficient 61.95%, lift 1.16). Common tripartite combinations included Salviae Miltiorrhizae Radix et Rhizoma-Chuanxiong Rhizoma-Astragali Radix(support degree 10.85%, confidence coefficient 73.40%, lift 1.37) and Salviae Miltiorrhizae Radix et Rhizoma-Chuanxiong Rhizoma-Notoginseng Radix et Rhizoma(support degree 10.69%, confidence coefficient 79.07%, lift 1.48). The results showed that the underlying pathogenesis of angina involved blood stasis obstructing the heart and Qi deficiency and blood stasis. The overall nature of the disease was characterized as asthenia in origin and sthenia in superficiality. In the prescription formulation, blood-activating and stasis-resolving drugs, such as Salviae Miltiorrhizae Radix et Rhizoma, Chuanxiong Rhizoma, and Carthami Flos were often used to resolve the excess manifestation, which were combined with tonifying drugs such as Astragali Radix, Angelicae Sinensis Radix, Glycyrrhizae Radix et Rhizoma, and Ginseng Radix et Rhizoma to reinforce the deficiency. The syndrome, pathogenesis, disease nature, and medication were consistent with clinical practice. Additionally, the new compound prescriptions and drug combinations derived from the multiple data mining in this study could provide references and insights for the clinical diagnosis and treatment of angina and the development of new drugs.

Analysis of Outcome Indicators of Cancer-Related Fatigue Treated with Chinese Herbal Compounding.

Objective: In the direction of evaluating the current status of outcome indicators and control group selection in randomized controlled studies of Chinese herbal compounding (such as Sini plus Renshen Decoction, Jianpifuzhengfang, Bufei Jianzhong Decoction, etc) for cancer-caused fatigue and to provide a reference for clinical studies of Chinese herbal compounding for cancer-caused fatigue. Methods: Randomized controlled studies of Chinese herbal medicine for cancer-caused fatigue in the midst of 2012 and 2022 were searched in CNKI, PubMed, and EMBASE databases on the China Knowledge Network, and the literature was screened using NoteExpress. Two researchers independently conducted the literature review, and then the studies that met the criteria were grouped and analyzed adopting qualitative analysis of outcome indicators and control groups. Results: A total of 70 randomized controlled studies that met the requirements were included, and after doing statistical analysis, it can draw to the conclusion that the risk of bias in the included studies was high; at the same time, the TCM evidence score scale, objective indicators, and safety indicators were underutilized; additionally, there were no uniform standards for the fatigue scale, and the selection of control groups lacked balance and consistency. Conclusion: The outcome indicators of TCM compound treatment of cancer-caused fatigue should be on the basis of the principle of "diagnosis and treatment" in TCM, the proportion of objective indicators should be exaggerated, as well as the interventions in the control group should be unified.

Evaluation of the in vitro acaricidal activity of Chinese herbal compounds on the poultry red mite (Dermanyssus gallinae).

The poultry red mite Dermanyssus gallinae is an economically important pest in poultry farms worldwide, but an effective treatment option is lacking. The current study determined the effectiveness of six Chinese herbal medicines [Syzygium aromaticum (clove), Hibiscus syriacus (Hibiscus), Illicium verum (star anise), Leonurus artemisia (motherwort), Cinnamomum cassia (cinnamon), and Taraxacum sp. (dandelion)] against D. gallinae. Alcohol extracts were prepared via the solvent extraction method and the phenol, flavonoid, and tannin contents were determined. These active components were highest in S. aromaticum and lowest in H. syriacus, I. verum. No tannin content was detected in L. artemisia. All extracts showed contact toxicity against D. gallinae at a test concentration of 1 g/mL, with S. aromaticum and L. artemisia resulting in 100% mortality. S. aromaticum, L. artemisia, and I. verum showed the best efficacy (LC50 0.159, 0.200, and 0.292 g/mL, respectively). Different combinations of extracts showed an additive effect of I. verum LC90 + L. artemisia LC90. The acaricidal efficacy of this combination was tested against different developmental stages of D. gallinae, being most efficacious against nymphal and larval D. gallinae, with a corrected mortality rate of 100%. However, inhibition of egg hatching was only 53.69%. Taken together, these results highlight I. verum LC90 + L. artemisia LC90 as a promising compound with severe contact toxicity against D. gallinae. Given the wide cultivation of these species and their extensive use in foodstuffs and cosmetics as flavors and fragrances, they could be a cheap, readily available ecofriendly alternative to pesticides currently used in poultry farms.

Network Pharmacology-Based Investigation of the Molecular Mechanisms of the Chinese Herbal Formula Shenyi in the Treatment of Diabetic Nephropathy.

Background: The Chinese herbal formula Shenyi (SY) is a prescription that was developed by the Department of Nephrology, Chinese People's Liberation Army General Hospital. This preparation is mainly used to treat chronic kidney disease (CKD) caused by Diabetic nephropathy (DN) and is effective. However, the active ingredients of SY, DN treatment-related molecular targets and the effector mechanisms are still unclear. Methods: The Traditional Chinese Medicine Systems Pharmacology (TCMSP) database and the Traditional Chinese Medicine and Chemical Component Database of Shanghai Institute of Organic Chemistry were used to screen the active ingredients in SY, the TCMSP database and Swiss Target Prediction database were used to collect the targets of the active ingredients of SY, and the Gene Cards and Online Mendelian Inheritance in Man (OMIM) databases were used to screen for DN pathogenesis targets. The intersections of the component targets and disease targets were mapped to obtain the therapeutic targets. The METASCAPE database was used to perform Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses of the therapeutic targets. Cytoscape 3.7.2 was used to analyze topological parameters and construct a network of SY for the treatment of DN. Results: Sixty-two active ingredients and 497 active ingredient effector targets in SY, 3260 DN-related targets, and 271 SY treatments for DN targets were identified. Among these targets, 17 were core targets, including AKT1, tumor necrosis factor (TNF), interleukin-6 (IL6), and TP53. The GO and KEGG enrichment analyses show that SY's therapeutic effects for DN occur mainly through pathways such as advanced glycation end product (AGE)-RAGE, PI3K-Akt, and IL-17. Conclusion: Multiple active ingredients in SY exhibit treatment effects on DN by affecting metabolism, inhibiting inflammation, and affecting cell structure growth.

Recent evidence in support of traditional chinese medicine to restore normal leptin function in simple obesity.

Reducing the incidence of obesity is the focus of global attention, and traditional Chinese medicine (TCM) may play an important role in achieving this goal. Numerous studies have shown that most individuals with obesity have leptin resistance, exogenous leptin is ineffective in individuals with obesity, and the effect of leptin decreases with increased serum leptin levels in individuals with obesity. At present, there are many hypotheses regarding the mechanism of leptin resistance, but there is no definite conclusion. TCM has a long history of treating obesity, and single and compound TCM is an effective obesity treatment method. However, TCM's mechanism of action is complex and resists further weight loss drug development. In the last decade, network pharmacology has become an important tool for exploring the mechanism of compound TCMs. In this study, we reviewed the interrelation between TCM obesity treatment and leptin resistance, and network pharmacology studies of TCM intervention in simple obesity revealed that their targets overlap with the leptin pathway. We also summarized TCM pairs that effectively interfere with leptin resistance and their related intervention mechanisms, providing targets for anti-obesity drug development.

[Yishen Tonglong Decoction inhibits the epithelial-mesenchymal transition and Ras/ERK signaling pathway in human prostate cancer DU-145 cells].

Objective: To observe the effect of Yishen Tonglong Decoction (YTD) on the epithelial-mesenchymal transition (EMT) and Ras/ERK signaling pathway in human PCa DU-145 cells and explore its action mechanism. METHODS: We treated human PCa DU-145 cells with normal plasma (the blank control) or plasma containing 5% (low-dose), 10% (medium-dose) and 15% (high-dose) YTD. After intervention, we examined the proliferation of the DU-145 cells in different groups with CCK-8 and their apoptosis by Annexin V/PI double staining. We detected the cell cycle by PI assay, the invasion and migration of the cells using the Transwell chamber and scratch test, and the expressions of the proteins and genes related to the EMT and Ras/ERK signaling pathways in the cells by Western blot and RT-PCR. RESULTS: Compared with the blank control group, high-, medium- and low-dose YTD significantly inhibited the proliferation of the PCa DU-145 cells, decreased their adherence and growth (P < 0.05, P < 0.01), promoted their apoptosis (P < 0.01), regulated their cell cycles (P < 0.05, P < 0.01), and reduced their in vitro invasion and migration abilities (P < 0.05), all in a dose-dependent manner. The results of Western blot and RT-PCR revealed down-regulated protein and mRNA expressions of N-cadherin, zinc finger transcription factor (Snail), Ras, p-ERK1/2 and ERK1/2, but up-regulated protein and mRNA expressions of E-cadherin in the PCa DU-145 cells treated with YTD (P < 0.05, P < 0.01). CONCLUSIONS: Yishen Tonglong Decoction can effectively inhibit the proliferation, promote the apoptosis, regulate the cell cycle and suppress the invasion and migration abilities and EMT process of human PCa DU-145 cells. The mechanism of Yishen Tonglong Decoction acting on PCa may be associated with its inhibitory effect on the EMT process and expression of the Ras/ERK signaling pathway in PCa cells./.