期刊：
Frontiers in Microbiology,2024年15:1354823 ISSN：1664-302X
通讯作者：
Tan, ZJ;He, WZ
作者机构：
[Guo, Mingmin] Hunan Univ Chinese Med, Sch Pharm, Changsha, Peoples R China.;[Shen, Junxi; Tan, Zhoujin; Fang, Leyao] Hunan Univ Chinese Med, Sch Tradit Chinese Med, Changsha, Peoples R China.;[Chen, Meili] Changsha Hosp Tradit Chinese Med, Changsha, Peoples R China.;[He, Wenzhi] Hunan Univ Chinese Med, Sch Stomatol, Changsha, Peoples R China.
通讯机构：
[He, WZ ; Tan, ZJ ] H;Hunan Univ Chinese Med, Sch Tradit Chinese Med, Changsha, Peoples R China.;Hunan Univ Chinese Med, Sch Stomatol, Changsha, Peoples R China.
关键词：
CutC;TMAO;adenine;cecal microbiota;diarrhea with kidney-yang deficiency syndrome;folium sennae;inflammatory factors
摘要：
OBJECTIVE: Previous studies have indicated that diarrhea with kidney-yang deficiency syndrome leads to a disorder of small intestine contents and mucosal microbiota. However, the relationship of TMA-lyase (CutC) activity and TMAO with diarrhea with kidney-yang deficiency syndrome remains unexplored. Therefore, this study explores the relationship between cecal microbiota and choline TMA-lyase (CutC) activity, as well as the correlation between trimethylamine oxide (TMAO), inflammatory index, and CutC activity. METHOD: Twenty SPF-grade male KM mice were randomly divided into the normal group (CN) and the diarrhea model group (CD). Diarrhea mouse models were established by adenine combined with Folium sennae administration. CutC activity, TMAO, interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) levels were detected, and the cecal content microbiota was sequenced. RESULT: After 14 days, diarrhea occurred in the CD group. Compared with the CN group, there was no significant change in the activity of CutC in the small intestine of the CD group, while the activity of CutC in the cecum was significantly increased, and the levels of TMAO, IL-6, and TNF-α showed a significant increase. The Chao1 index, Observed_species index, Shannon index, and Simpson index all exhibited a decreasing trend. The main changes at the bacterial genus level were Alistipes, Enterorhabdus, Desulfovibrio, Bacteroides, Candidatus_Saccharimonas, and [Ruminococcus]_torques_group. The results of LEfSe analysis, random forest analysis and ROC curve analysis revealed Paludicola, Blautia, Negativibacillus, Paraprevotella, Harryflintia, Candidatus_Soleaferrea, Anaerotruncus, Oscillibacter, Colidextribacter, [Ruminococcus]_torques_group, and Bacteroides as characteristic bacteria in the CD group. Correlation analysis showed a significant negative correlation between cecal CutC activity and Ligilactobacillus, and a significant positive correlation with Negativibacillus and Paludicola. The level of TMAO was significantly positively correlated with CutC activity and IL-6. CONCLUSION: Diarrhea with kidney-yang deficiency syndrome significantly affects the physiological status, digestive enzyme activity, CutC activity, TMAO levels, and inflammatory response in mice. Additionally, there are changes in the composition and function of cecal microbiota, indicating an important impact of diarrhea with kidney-yang deficiency syndrome on the host intestinal microbiota balance. The occurrence of diarrhea with kidney-yang deficiency syndrome may be associated with dysbiosis of intestinal microbiota, increased CutC activity, elevated TMAO levels, and heightened inflammatory factor levels.
通讯机构：
[Wu, P; Lin, LM ] H;Hunan Univ Chinese Med, Coll Pharm, 300 Xueshi Rd, Changsha 410208, Peoples R China.
关键词：
AMPK;Diabetes mellitus;Medicinal and edible homologous;PI3K/Akt;Plant polysaccharides
摘要：
Medicinal and edible homologs (MEHs) can be used in medicine and food. The National Health Commission announced that a total of 103 kinds of medicinal and edible homologous plants (MEHPs) would be available by were available in 2023. Diabetes mellitus (DM) has become the third most common chronic metabolic disease that seriously threatens human health worldwide. Polysaccharides, the main component isolated from MEHPs, have significant antidiabetic effects with few side effects. Based on a literature search, this paper summarizes the preparation methods, structural characterization, and antidiabetic functions and mechanisms of MEHPs polysaccharides (MEHPPs). Specifically, MEHPPs mainly regulate PI3K/Akt, AMPK, cAMP/PKA, Nrf2/Keap1, NF-κB, MAPK and other signaling pathways to promote insulin secretion and release, improve glycolipid metabolism, inhibit the inflammatory response, decrease oxidative stress and regulate intestinal flora. Among them, 16 kinds of MEHPPs were found to have obvious anti-diabetic effects. This article reviews the prevention and treatment of diabetes and its complications by MEHPPs and provides a basis for the development of safe and effective MEHPP-derived health products and new drugs to prevent and treat diabetes.
通讯机构：
[Lin, LM ] H;Hunan Univ Chinese Med, Coll Pharm, Changsha 410208, Peoples R China.
关键词：
Acute mastitis;Blood-milk barrier;Lipopolysaccharides;Prunella vulgaris L.
摘要：
ETHNOPHARMACOLOGICAL RELEVANCE: According to ancient literature, Prunella vulgaris L. (P vulgaris) alleviates mastitis and has been used in China for many years; however, there are no relevant reports that confirm this or the mechanism of its efficacy. AIM OF THE STUDY: To explore the anti-acute mastitis effect and potential mechanism of P vulgaris extract. MATERIALS AND METHODS: First, the active ingredients and targets of P vulgaris against mastitis were predicted using network pharmacology. Next, the relevant active ingredients were enriched using macroporous resins and verified using UV and UPLC-Q-TOF-MS/MS. Lastly, a mouse model of acute mastitis was established by injecting lipopolysaccharides into the mammary gland and administering P vulgaris extract by oral gavage. The pathological changes in mammary tissue were observed by HE staining. Serum and tissue inflammatory factors were measured by ELISA method. MPO activity in mammary tissue was measured using colorimetry and MPO expression was detected by immunohistochemistry. The expression of tight junction proteins (ZO-1, claudin-3, and occludin) in mammary tissue was detected by immunofluorescence and Western blot. iNOS and COX-2 in mammary tissue were detected by Western blot. MAPK pathway and NF-κB pathway related proteins were also detected by Western blot. RESULTS: Network pharmacology predicted that phenolic acids and flavonoids in P vulgaris had anti-mastitis effects. The contents of total flavonoids and total phenolic acids in P vulgaris extract were 64.5% and 29.4%, respectively. UPLC-Q-TOF-MS/MS confirmed that P vulgaris extract contained phenolic acids and flavonoids. The results of animal experiments showed that P vulgaris extract reduced lipopolysaccharide-induced inflammatory edema, inflammatory cell infiltration, and interstitial congestion of mammary tissue. It also reduced the levels of serum and tissue inflammatory factors TNF-α, IL-6, and IL-1β, and inhibited the activation of MPO. Furthermore, it downregulated the expression of MAPK and NF-κB pathway-related proteins. The expressions of ZO-1, occludin, and claudin-3 in mammary gland tissues were upregulated. CONCLUSIONS: P vulgaris extract can maintain the integrity of mammary connective tissue and reduce its inflammatory response to prevent acute mastitis. Its mechanism probably involves regulating NF-κB and MAPK pathways.
摘要：
Objective Based on the theory of supramolecular"imprinting template",the fingerprint of Liuwei Dihuang Concentrated Pills(六味地黄丸浓缩丸,LDCP)was divided and integrated,and it was characterized as a material unit,and the spectralquality control and evaluation reaearch were conducted.Methods The matching frequency statistical moment method was used to divide,integrate and characterize the material units of 50 batches of LDCP fingerprints.According to Lambert-Beer's law,the total peak area of each material unit and the paste yield were subjected to multiple linear regression to establish a spectral equation for spectral research.Results The UPLC fingerprints of 50 batches of LDCP were divided into 35 material units(A1-A35).The spectral equations of the total peak area and the paste yield of the 35 material units(A1-A35)were obtained by multiple linear regression:PT=23.390+0.041 06 A1-9.100 × 10-3 A2+0.014 68 A3+0.027 98 A4-0.033 61 A5-0.042 25 A6-6.608 × 10-3 A7-0.025 90 A8-0.145 60 A9+0.165 00 A10-0.027 50 A11+3.408 × 10-3 A12-0.021 03 A13-1.070 × 10-3 A14+2.833 × 10-5 A15-8.774 × 10-3 A16+0.018 52 A17-1.882 9 × 10-3 A18+0.023 61 A19+8.566 × 10-3 A20+0.013 94 A21-5.894 × 10-3 A22-0.012 27 A23-0.014 91 A24+1.792 × 10-3 A25-1.571 × 10-4 A26-3.942 × 10-3A27-0.054 80 A28+0.083 15 A29+0.119 30 A30-0.060 71 A31-0.083 42 A32+0.014 96 A33-2.989 × 10-3 A34+0.063 17 A35(r=0.915).Conclusion This method can divide,integrate and characterize the LDCP fingerprint material units with high accuracy,and retain the total statistical moment characteristics of the original fingerprint.Its spectral equation can better predict the paste rate of LDCP and the average paste rate,which can provide new ideas and methods for the quality control of LDCP.
通讯机构：
[Tan, Y; Pei, G ] H;Hunan Univ Chinese Med, Coll Pharm, Changsha 410000, Peoples R China.;Educ Dept Hunan Prov, Key Lab Modern Res TCM, Changsha 410000, Peoples R China.
关键词：
H3K18la;LDHA;histone lactylation;liver injury;macrophages;salvianolic acid B
摘要：
Salvianolic acid B (Sal B) is the primary water-soluble bioactive constituent derived from the roots of Salvia miltiorrhiza Bunge. This research was designed to reveal the potential mechanism of Sal B anti-liver injury from the perspective of macrophages. In our lipopolysaccharide-induced M1 macrophage model, Sal B showed a clear dose-dependent gradient of inhibition of the macrophage trend of the M1 type. Moreover, Sal B downregulated the expression of lactate dehydrogenase A (LDHA), while the overexpression of LDHA impaired Sal B's effect of inhibiting the trend of macrophage M1 polarization. Additionally, this study revealed that Sal B exhibited inhibitory effects on the lactylation process of histone H3 lysine 18 (H3K18la). In a ChIP-qPCR analysis, Sal B was observed to drive a reduction in H3K18la levels in the promoter region of the LDHA, NLRP3, and IL-1β genes. Furthermore, our in vivo experiments showed that Sal B has a good effect on alleviating CCl(4)-induced liver injury. An examination of liver tissues and the Kupffer cells isolated from those tissues proved that Sal B affects the M1 polarization of macrophages and the level of histone lactylation. Together, our data reveal that Sal B has a potential mechanism of inhibiting the histone lactylation of macrophages by downregulating the level of LDHA in the treatment of liver injury.
作者：
Shah, Muhammad Raza;Fatima, Samreen;Khan, Sehrosh Naz;Azam, Zahid;Shaikh, Hafeezullah;...
期刊：
Frontiers in Pharmacology,2024年15:1293272 ISSN：1663-9812
通讯作者：
Shah, MR
作者机构：
[Shah, MR; Fatima, Samreen; Shah, Muhammad Raza; Khan, Sehrosh Naz] Univ Karachi, Ctr Bioequivalence Studies & Clin Res, Dr Panjwani Ctr Mol Med & Drug Res, Int Ctr Chem & Biol Sci, Karachi, Pakistan.;[Shaikh, Hafeezullah; Azam, Zahid] Dow Univ Hlth Sci, Natl Inst Liver & GI Dis NILGID, Karachi, Sindh, Pakistan.;[Majid, Shahid] Indus Hosp Karachi, Karachi, Sindh, Pakistan.;[Zhou, Daijun; He, Chengdong] Hunan Xinhui Pharmaceut Co Ltd, Changsha, Hunan, Peoples R China.;[Wang, Wei] Hunan Univ Chinese Med, Sch Pharm, TCM & Ethnomed Innovat & Dev Int Lab, Changsha, Peoples R China.
通讯机构：
[Shah, MR ] U;Univ Karachi, Ctr Bioequivalence Studies & Clin Res, Dr Panjwani Ctr Mol Med & Drug Res, Int Ctr Chem & Biol Sci, Karachi, Pakistan.
关键词：
Houtou Jianweiling tablet (HTJWT);clinical trial;omeperazole;randomization;traditional Chinese medicine (TCM)
摘要：
Background: Common symptoms of Chronic Non-atrophic Gastritis (CNAG) include nausea, stomach distension, and abdominal pain. The Houtou Jianweiling Tablet (HTJWT) is a chinese patent medicine (CN1368229A) and it has been used clinically for more than 20years with proven clinical efficacy in treating CNAG, prompted us to establish the clinical efficacy and safety of HTJWT on patients with mild to moderate CNAG symptoms in Pakistani population. Methods: This phase II, double-blind, randomized, parallel-controlled trial was conducted in a single center between November 2022 and February 2023 in Pakistan. In a ratio of 1:1, total 240 CNAG patients with erosion identified by pathological biopsy and gastroscopy were randomly assigned to control (Omeprazole) group (n = 120) and the treatment (HTJWT) group (n = 120). Patients in the treatment group received orally four HTJWT (0.38g/tablet), three times a day and one placebo of Omeprazole enteric-coated tablet prior to breakfast, daily. On the other hand, patients in the control group received one Omeprazole enteric-coated tablet (20 mg/tablet) prior to breakfast and four placebo of HTJWT, thrice a day. The patients consumed the investigated drugs (i.e., treatment and control) treatment regimen was followed for a duration of 28days. The safety of the patients were evaluated through adverse events, serious adverse events and laboratory tests such as blood biochemistry, urine analysis, liver and renal function tests. Vital signs like; blood pressure, pulse rate, body temperature, respiratory rate for all the patients were recorded. The cardiac status of the patients were assessed through electrocardiogram (ECG). The primary efficacy indicators were the improvement rate of gastric distention and gastralgia as the main clinical symptoms. Secondary indicators were visual analogue score (VAS); improvement rate of secondary clinical symptoms and signs; improvement rate of total clinical signs and symptoms; the disappearance/remission rate of Gastric pain and, remission/disappearance time of gastric distension; and the negative conversion rate of Helicobacter pylori (H. pylori). The outcomes among each group were compared using the chi-square test. Results: Patients in both groups had good drug compliance (80%-120%), and there was no statistically significant difference in the patients' baseline characteristics. The clinical improvement rate was found to be 91.1% in the treatment group and 91.0% in the control group with negligible variation among the two groups (p = 0.9824; 95% confidence interval: -0.0781-0.0798). Similarly, hardly no difference was found in the negative conversion rate of H. pylori between the treatment group and the control group (i.e., 70.1% and 71.8% respectively, p = 0.8125). There were no significant differences in respiratory rate, vital signs, blood pressure, laboratory results for blood biochemistry, urine analysis, liver and renal function tests between the two groups. The ECG assessment carried out for the treatment and control group revealed no considerable difference. Margin variation in the disappearance time of gastric pain (p = 0.1860) and remission rate (p = 0.5784) between the two groups were observed. The control group exhibited a faster remission period for gastrointestinal discomfort indications as compared to treatment group (p = 0.0430). Only one patient in the control group experienced mild to moderate adverse events, namely,; epigastric pain and dyspepsia. The results were consistent with the intention-to-treat and per-protocol analysis that included patients who were 100% compliant to the assigned therapy. Conclusion: The lower limit of confidence interval (CI, 95%) for the differences in the effective rate between the treatment and the control groups was found to be -0.0781 which is greater than -0.15, hence the treatment group is non-inferior to the control group. The therapeutic dosage used in the trial and treatment period did not cause any significant adverse event, and there were no obvious changes in the ECG profile, vital signs and biochemistry of the patients. Based on the clinical efficacy evaluation and reported adverse events, it can be concluded that the HTJWT is a safe and effective traditional chinese medicine for the treatment of patients suffering from chronic non-atrophic gastritis with mild to moderate symptoms. Clinical Trial Registration: [www.clinicaltrials.gov], identifier [NCT04672018].
期刊：
COMBINATORIAL CHEMISTRY & HIGH THROUGHPUT SCREENING,2024年 ISSN：1386-2073
作者机构：
[Li, Qing; Li, Xiao Ling; Hou, Chao Wen; Shi, Yuhe; Zhu, Jue; Tong, Qiao Zhen; Liu, Xiang Dan] Department of Hunan University of Chinese Medicine, School of Pharmacy, Changsha 410208, Hunan Province, P.R.China
摘要：
AIMS AND OBJECTIVE: This study aimed to identify the bioactive compounds and explore the multi-target mechanisms of Salvia miltiorrhiza Bunge (SMB) against coronary heart disease (CHD) using an integrated serum pharmacochemistry and network pharmacology approach. MATERIALS AND METHODS: The chemical constituents of SMB were characterized by UPLC-MS. The absorbed ingredients and metabolites after oral SMB administration were identified in rat serum. Therapeutic targets of SMB against CHD were predicted by intersecting the targets of absorbed compounds from databases and CHD-associated genes. Protein-protein interaction network, pathway analysis, molecular docking, and molecular dynamic simulation were performed. RESULTS: A total of 61 SMB-derived compounds were identified in rat serum. Network analysis revealed 111 candidate targets highly related to CHD pathways. Further topological analysis identified 10 hub targets and 20 key active compounds, constructing an informative compoundtarget- pathway network. PTGS2 and TNF were predicted as primary targets of SMB against CHD based on molecular dynamic simulation. CONCLUSION: This integrated approach identified bioactive compounds and multi-target mechanisms of SMB against CHD. The results provide scientific evidence supporting SMB's clinical efficacy and reveal potential anti-CHD targets.
期刊：
European journal of nutrition,2024年:1-15 ISSN：1436-6207
通讯作者：
Wuping Li
作者机构：
[Yinsheng Cao; Fuping Zhu; Hang Wu] Department of Foot and Ankle Orthopedics, The First Hospital of Hunan University of Chinese Medicine, Changsha, 410007, Hunan, China;[Hui Liu] Department of Orthopedic Surgery, The Second Xiangya Hospital of Central South University, Changsha, 410011, Hunan, China;[Bing Dai] Department of Pharmacy, The First Hospital of Hunan University of Chinese Medicine, Changsha, 410007, Hunan, China;[Wuping Li] Department of Foot and Ankle Orthopedics, The First Hospital of Hunan University of Chinese Medicine, Changsha, 410007, Hunan, China. 251475944@qq.com
通讯机构：
[Li, Wuping] D;Department of Foot and Ankle Orthopedics, The First Hospital of Hunan University of Chinese Medicine, Changsha, 410007, Hunan, China.
摘要：
BACKGROUND: Postmenopausal osteoporosis (PMO) is a chronic condition characterized by decreased bone strength. This study aims to investigate the effects and mechanisms of the combination of Butyricicoccus pullicaecorum (Bp) and 3-hydroxyanthranilic acid (3-HAA) on PMO. METHODS: The effects of Bp and 3-HAA on PMO were evaluated in ovariectomized (OVX) rats by assessing stereological parameters, femur microstructure, and autophagy levels. The T helper (Th) 17/Regulatory T (Treg) cells of rats were detected using flow cytometric analysis. Furthermore, the impact of Bp and 3-HAA on the gut microbiota of rats was assessed using 16S rRNA gene sequencing. The correlation between the gut microbiota of rats and Th17/Treg immune factors, as well as femoral stereo parameters, was separately assessed using Spearman rank correlation analysis. RESULTS: Bp and 3-HAA treatments protected OVX rats by promoting osteogenesis and inhibiting autophagy. Compared to the Sham group, OVX rats showed an increase in Th17 cells and a decrease in Treg cells. Bp and 3-HAA reversed these changes. Enterorhabdus and Pseudomonas were significantly enriched in OVX rats. Bp and 3-HAA regulated the gut microbiota of OVX rats, enriching pathways related to nutrient metabolism and immune function. There was a correlation between the gut microbiota and the Th17/Treg, as well as femoral stereo parameters. The concurrent administration of Bp and 3-HAA medication facilitated the enrichment of gut microbiota associated with the improvement of PMO. CONCLUSION: The combination therapy of Bp and 3-HAA can prevent PMO by modulating the gut microbiota and restoring Th17/Treg immune homeostasis.
期刊：
CURRENT NEUROPHARMACOLOGY,2024年22(10):1672-1696 ISSN：1570-159X
作者机构：
Key Laboratory of Hunan Province for Integrated Traditional Chinese and Western Medicine on Prevention and
Treatment of Cardio-Cerebral Diseases, College of Integrated Traditional Chinese Medicine and Western Medicine,
Hunan University of Chinese Medicine, Changsha, Hunan 410208, China;Third-Grade
Pharmacological Laboratory on Chinese Medicine Approved by State Administration of Traditional Chinese Medicine,
College of Medicine and Health Sciences, China Three Gorges University, Yichang, Hubei 443002, China;Department of Neurosurgery, First Affiliated
Hospital of Hunan University of Traditional Chinese Medicine, Changsha, Hunan 410007, China;School
of Pharmacy, Hunan University of Chinese Medicine, Changsha, Hunan 410208, China;[Gong, Lipeng; Liang, Junjie; Xie, Letian] Key Laboratory of Hunan Province for Integrated Traditional Chinese and Western Medicine on Prevention and
Treatment of Cardio-Cerebral Diseases, College of Integrated Traditional Chinese Medicine and Western Medicine,
Hunan University of Chinese Medicine, Changsha, Hunan 410208, China
摘要：
Ischemic stroke is a leading cause of disability and death worldwide. However, the clinical efficacy of recanalization therapy as a preferred option is significantly hindered by reperfusion injury. The transformation between different phenotypes of gliocytes is closely associated with cerebral ischemia/ reperfusion injury (CI/RI). Moreover, gliocyte polarization induces metabolic reprogramming, which refers to the shift in gliocyte phenotype and the overall transformation of the metabolic network to compensate for energy demand and building block requirements during CI/RI caused by hypoxia, energy deficiency, and oxidative stress. Within microglia, the pro-inflammatory phenotype exhibits upregulated glycolysis, pentose phosphate pathway, fatty acid synthesis, and glutamine synthesis, whereas the anti-inflammatory phenotype demonstrates enhanced mitochondrial oxidative phosphorylation and fatty acid oxidation. Reactive astrocytes display increased glycolysis but impaired glycogenolysis and reduced glutamate uptake after CI/RI. There is mounting evidence suggesting that manipulation of energy metabolism homeostasis can induce microglial cells and astrocytes to switch from neurotoxic to neuroprotective phenotypes. A comprehensive understanding of underlying mechanisms and manipulation strategies targeting metabolic pathways could potentially enable gliocytes to be reprogrammed toward beneficial functions while opening new therapeutic avenues for CI/RI treatment. This review provides an overview of current insights into metabolic reprogramming mechanisms in microglia and astrocytes within the pathophysiological context of CI/RI, along with potential pharmacological targets. Herein, we emphasize the potential of metabolic reprogramming of gliocytes as a therapeutic target for CI/RI and aim to offer a novel perspective in the treatment of CI/RI.
