JOURNAL OF ETHNOPHARMACOLOGY
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2023
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IF 5.4
Yudi Yao,Yang Chen,Huijian Chen,Xin Pan,Xiaojun Li,Wenqi Liu,Yerlan Bahetjan,Binan Lu,Kejian Pang,Xinzhou Yang,Zongran Pang
Ethnopharmacological relevance Black mulberry ( Morus nigra L.) is an ancient dual-use plant resource for medicine and food. It is widely used in Uyghur folklore for hypoglycemic treatment and is a folkloric plant medicine with regional characteristics. However, the mechanism of Morus nigra L. treatment in diabetes mellitus has not been fully understood, especially from the perspective of hepatic lipid accumulation is less reported. Objective of this study This study was to explore the potential of Morus nigra L. fruit ethyl acetate extract (MNF-EA) to reduce blood sugar levels by preventing the production of hepatic lipogenesis and to provide more evidence for the use of MNF-EA as an adjuvant therapy for type 2 diabetes mellitus (T2DM). Materials and methods In this study, the chemical composition of MNF-EA was first analyzed and characterized using UPLC-Q-TOF-MS technique. A series of in vitro studies were performed with HepG2-IR cells and oleic acid (OA)-induced HepG2 cells, including MTT assay, glucose uptake assay, oil red O staining and Western blot analysis . The STZ-HFD co-induced T2DM mice were employed for in vivo research, including physical indices, biochemical analysis, histopathological examination, and Western blot analysis. Results The 19 compounds in MNF-EA were identified by UPLC-Q-TOF-MS technique. Insulin resistance (IR) and lipid droplet accumulation in HepG2 cells were greatly improved by MNF-EA treatment, which had no appreciable side effects at the dosage used. In T2DM mice, MNF-EA decreased fasting blood glucose (FBG), saved body weight, and significantly improved oral glucose tolerance (OGTT) and IR status. In addition, MNF-EA treatment also improved lipid metabolism disorders and liver function in T2DM mice. Histopathological sections showed that MNF-EA treatment reduced hepatic steatosis . Mechanistic studies suggest that MNF-EA acted through the AMPK/mTOR pathway. Conclusions These results suggest that MNF-EA has great potential to reverse the metabolic abnormalities associated with T2DM by regulating the AMPK/mTOR signaling pathway. Therefore, we believe that MNF is a promising medicinal and food-homologous agent to improve T2DM.
研究领域:
药理学
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民族药理学
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糖尿病研究
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代谢紊乱
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植物化学
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细胞生物学
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动物模型
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PubMed
高影响因子
BIOMATERIALS
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2024
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IF 12.8
Xiudan Wang,Rui Tian,Chenghong Liang,Yifan Jia,Lingyun Zhao,Qinyuan Xie,Fenglian Huang,Huijuan Yuan
Insulin resistance and pancreatic β -cell dysfunction are the main pathogenesis of type 2 diabetes mellitus (T2DM). However, insulin therapy and diabetes medications do not effectively solve the two problems simultaneously. In this study, a biomimetic oral hydrogen nanogenerator that leverages the benefits of edible plant-derived exosomes and hydrogen therapy was constructed to overcome this dilemma by modulating gut microbiota and ameliorating oxidative stress and inflammatory responses. Hollow mesoporous silica (HMS) nanoparticles encapsulating ammonia borane (A) were used to overcome the inefficiency of H 2 delivery in traditional hydrogen therapy, and exosomes originating from ginger (GE) were employed to enhance biocompatibility and regulate intestinal flora. Our study showed that HMS/A@GE not only considerably ameliorated insulin resistance and liver steatosis, but inhibited the dedifferentiation of islet β -cell and enhanced pancreatic β -cell proportion in T2DM model mice. In addition to its antioxidant and anti-inflammatory effects, HMS/A@GE augmented the abundance of Lactobacilli spp. and tryptophan metabolites, such as indole and indole acetic acid, which further activated the AhR/IL-22 pathway to improve intestinal-barrier function and metabolic impairments. This study offers a potentially viable strategy for addressing the current limitations of diabetes treatment by integrating gut-microbiota remodelling with antioxidant therapies.
研究领域:
纳米技术
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糖尿病研究
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胃肠病学
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药理学
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分子生物学
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免疫学
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PubMed
高影响因子
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
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2025
·Vol. 26
·期 10
·4578
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IF 4.9
Yaping Chen,Qiuqi Wen,Bing Yang,Liang Feng,Xiaobin Jia
Traditional Chinese Medicine (TCM) is recognized for its complex composition and multiple therapeutic targets. Current pharmacological research often concentrates on extracts or individual components. The former approach faces numerous challenges, whereas the latter oversimplifies and disregards the synergistic effects of TCM components. This study aimed to address this limitation by evaluating the therapeutic efficacy and mechanisms of Huang-Qi San (HQS) active constituent (AC) against type 2 diabetes (T2DM). Active components of HQS were identified using network pharmacology and spectrum–effect correlation analysis. The reconstituted AC group was assessed both in vitro (for glucose consumption and glycogen synthesis) and in vivo (in T2DM mice), with metabolomics and molecular docking techniques used to elucidate the underlying mechanisms. Eight components exhibiting a correlation degree greater than 0.85 were identified as the representative components of HQS intervention for T2DM. These eight components were then mixed in equal proportions to produce AC. The AC group demonstrated increased glucose uptake and glycogen synthesis in vitro, surpassing both the HQS extract and individual components. In diabetic mice, AC significantly increased the insulin sensitivity, outperforming the HQS extract and matching the efficacy of metformin. Metabolomics analysis identified pentose and glucuronic acid interconversion as a critical metabolic pathway, with strong binding affinity (less than −15 kJ/mol) between AC and key enzymes. This research further substantiates the scientific validity and feasibility of emphasizing active constituents in the evaluation of TCM efficacy. Additionally, it provides a scientific foundation for the clinical application of HQS. Most importantly, this study serves as a demonstration of the development of new TCM drugs characterized by clear ingredients, safety, and effectiveness.
研究领域:
中药学
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药理学
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代谢生物学
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DOI
PubMed
高影响因子
FOOD SCIENCE AND BIOTECHNOLOGY
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2025
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IF 3.1
Liu Ye,Fan Minxia,Xu Yongbing,Muema Felix Wambua,Chen Guilin,Guo Mingquan
Moringa oleifera have been widely consumed in China and African countries to treat DM. This study investigated the arresting hypoglycemic effects of Moringa oleifera leaves extracts (MOLE) on T2DM via the gut microbiota pathway. The results displayed that MOLE treatment for 30 days significantly improved the plasma FBG and lipids (TC, TG, LDL-C and HDL-C) levels in T2DM rats in a dose-dependent manner ( p < 0.05, p < 0.01), respectively. Also, MOLE treatment increased the abundance of Bacteroidetes and Firmicutes/Bacteroidetes ratio and decreased the abundance of Firmicutes, and dramatically increased the contents of the acetic acid, propionic acid, and total SCFAs in the feces of T2DM rats ( p < 0.05, p < 0.01), respectively. KEGG signaling pathway further suggested that MOLE strongly participated in the carbohydrate metabolism in T2DM rats. This work indicates the noteworthy improvement of MOLE on metabolic disorders in T2DM rats via the regulation of gut microbiota and SCFAs.
研究领域:
药理学
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微生物学
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内分泌学
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营养科学
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代谢研究
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PubMed
高影响因子
BIOMEDICINE & PHARMACOTHERAPY
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2024
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IF 6.9
Hong-Bo Yang,Jie-Yu Song,Chan Xu,Jin Li,Chan Zhang,Sun Xie,Chun-li Teng
Pueraria lobata, commonly known as kudzu, is a medicinal and food plant widely used in the food, health food, and pharmaceutical industries. It has clinical pharmacological effects, including hypoglycemic, antiinflammatory, and antioxidant effects. However, its mechanism of hypoglycemic effect on type 2 diabetes mellitus (T2DM) has not yet been elucidated. In this study, we prepared a Pueraria lobata oral liquid (POL) and conducted a comparative study in a T2DM rat model to evaluate the hypoglycemic effect of different doses of Pueraria lobata oral liquid. Our objective was to investigate the hypoglycemic effect of Puerarin on T2DM rats and understand its mechanism from the perspective of metabolomics. In this study, we assessed the hypoglycemic effect of POL through measurements of FBG, fasting glucose tolerance test, plasma lipids, and liver injury levels. Furthermore, we examined the mechanism of action of POL using hepatic metabolomics. The study's findings demonstrated that POL intervention led to improvements in weight loss, blood glucose, insulin, and lipid levels in T2DM rats, while also providing a protective effect on the liver. Finally, POL significantly affected the types and amounts of hepatic metabolites enriched in metabolic pathways, providing an important basis for revealing the molecular mechanism of Pueraria lobata intervention in T2DM rats. These findings indicate that POL may regulate insulin levels, reduce liver damage, and improve metabolic uptake in the liver. This provides direction for new applications and research on Pueraria lobata to prevent or improve T2DM.
研究领域:
药理学
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代谢组学
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内分泌学
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天然产物研究
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中医药
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DOI
高影响因子
Food Frontiers
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2023
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IF 9.9
Guilin Chen,Yongbing Xu,Hui Zhang,Felix Wambua Muema,Mingquan Guo
Gymnema sylvestre (GS) has been traditionally used to treat diabetes mellitus (DM) and consumed as both food and medicine. The present work aimed to reveal the arresting hypoglycemic properties of GS leaves on type 2 DM (T2DM) rats meditated by gut microbiota pathway. After administration for 30 days, GS treatment observably improved the abnormal fasting blood glucose (FBG) levels, lipid profiles, and the glucose tolerance of the T2DM rats in a dose-dependent manner. Furthermore, GS treatment reversibly restored the gut microbiota diversities in the T2DM rats based on the decreased Firmicute abundance and boosted Bacteroidetes abundance and Firmicutes/Bacteroidetes ratio. Particularly, the KEGG pathway suggested that GS treatment strongly interfered with the glucose metabolism processes, such as the glycolysis from glucose 6-phosphate and glucose, along with the changes in the relative abundances of the beneficial bacteria of Clostridium , Lactobacillus , and Bacteroides . In addition, the GS treatment dramatically promoted the contents of the acetic acid, the total short-chain fatty acids in the T2DM rat feces. This study showcased the remarkable amelioration of GS on the metabolic disorders of blood glucose and lipids via the regulation of gut microbiota in T2DM rats, which could offer a new mechanism of GS as a potential natural antidiabetic food supplement for T2DM.
研究领域:
药理学
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微生物学
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内分泌学
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营养学
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产品关联
DOI
高影响因子
Journal of Diabetes Investigation
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2026
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IF 3.6
An-Jun Tan,Tian-Rong Li,Jing-Jing Yang,Xiao-Lu Li,Wen-Qin Li,Jin-Wen Yu
Background Diabetic cardiomyopathy (DCM) and endothelial dysfunction are major drivers of cardiovascular morbidity in type 2 diabetes (T2DM). The present study investigates whether combined therapy with liraglutide (LIRA) and dapagliflozin (DAPA) provides synergistic cardioprotection and vascular improvement in a murine model of T2DM. Methods A murine model of T2DM was established by high-fat diet feeding followed by low-dose streptozotocin injection. Diabetic mice were treated for 4 weeks with LIRA, DAPA, or their combination. Echocardiographic analysis was performed to assess cardiac systolic function and structural parameters. Systemic metabolic parameters, cardiac injury biomarkers, histopathology, oxidative stress markers, and inflammation were assessed. Key signaling pathways were evaluated by Western blot and qPCR. Results Compared with monotherapies, combined LIRA and DAPA treatment produced superior metabolic improvements, including attenuated weight loss and enhanced glucose tolerance. The combination also more effectively reduced markers of myocardial injury (CK-MB, LDH), diminished cardiac fibrosis, and preserved aortic architecture while inhibiting endothelial apoptosis. Mechanistically, co-administration synergistically activated both the antioxidative NRF2/HO-1 pathway and the vasoprotective AMPK/PKA-eNOS axis, leading to a more comprehensive suppression of oxidative stress, inflammation, and apoptosis in cardiac and vascular tissues. Conclusion The combined use of LIRA and DAPA exerts synergistic cardioprotective and vasoprotective effects in a preclinical model of T2DM-induced DCM. This synergistic effect may be mediated by the coordinated activation of the NRF2/HO-1 and AMPK/PKA-eNOS signaling pathways, leading to the attenuation of the key pathological drivers of diabetic cardiovascular injury. These findings provide a mechanistic rationale for the clinical exploration of GLP-1RA and SGLT2i combination therapy in DCM.
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高影响因子
JOURNAL OF PERIODONTAL RESEARCH
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2024
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IF 3.4
Siying Xia,Rui Jing,Mingyan Shi,Yanan Yang,Meiting Feng,Li Deng,Lijun Luo
Background and Objective Periodontitis is intimately associated with the development of various systemic diseases, among which type 2 diabetes mellitus (T2DM) has a bidirectional relationship with the pathogenesis of periodontitis. The objective of the present work was to investigate the role of berberine (BBR) in periodontitis with T2DM and related mechanisms. Methods The mRNA expression of macrophage polarization-related factors in the microenvironment of periodontal inflammation was detected using real-time quantitative PCR (RT-qPCR). The experimental periodontitis model was constructed in wild-type (WT) and T2DM ( db/db ) mice, which were administered BBR after 7 days of modeling. Alveolar bone loss (ABL) in each group of mice was measured utilizing micro-computed tomography images. RT-qPCR was performed to analyze the levels of macrophage polarization-related factors in mouse gingiva. Lastly, using western blotting and RT-qPCR, the signaling pathway of BBR affecting macrophage polarization in the microenvironment of periodontitis was explored. Results BBR inhibited M1 polarization and stimulated M2 polarization in the periodontitis microenvironment. BBR decreased ABL in the WT and T2DM periodontitis models. And BBR reduced the production of proinflammatory cytokines and increased anti-inflammatory cytokine expression in the gingiva of WT and T2DM model mice. Ultimately, BBR mediates its anti-inflammatory effects on periodontitis through inhibition of the NF-κB pathway. Conclusions BBR had a therapeutic effect on T2DM-associated periodontitis via inhibiting the NF-κB pathway to affect macrophage polarization, which may have implications for the new pharmacological treatment of T2DM-associated periodontitis.
研究领域:
药理学
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牙医学
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免疫学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
Annals of Translational Medicine
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2022
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IF 3.616
Weidong Li,Lisha Li,Fujie Yang,Qiongying Hu,Daqian Xiong
Background The relationship between gut microbiota and metabolites play an important role in the occurrence and development of type 2 diabetes mellitus (T2DM). However, the interaction between intestinal flora abundance and metabolites is still unclear. The purpose of this study was to investigate the correlation of the interaction network between intestinal flora and fecal metabolites in regulating the occurrence of T2DM. Methods This a case-control study. T2DM patients with different glucose levels and healthy people were divided into case group and normal controls (NC) group. Fasting plasma and fecal samples were collected from the subjects. Ultra-performance liquid chromatography-tandem mass spectrometry (LC-MS) untargeted fecal metabolomics was used to detect small molecular metabolites within 1,500 Da in two groups. The diversity and richness of intestinal flora were analyzed by the 16SrRNA third-generation full-length sequencing technique and the correlation between intestinal microflora and different metabolites was evaluated. Results A total of 30 patients with T2DM and 21 NC were included for analysis, glycated hemoglobin (HbAlc) (P<0.001), fasting blood glucose (FBG) (P<0.001), total triglycerides (TG) (P=0.002), and fasting serum insulin (FINS) (P=0.026) were significantly higher in the T2DM group compared with the NC group. The fecal metabolomics profiles of the T2DM group and NC group were significantly different, and 355 different metabolites were identified among the two. Compared with the NC group, the levels of ornithine (P=0.04), L-lysine (P=0.03), glutamate (P=0.01), alpha-linolenic acid (P=0.004), traumatin (P=0.05), and erucic acid (P=0.004) in the T2DM group decreased significantly, while PC[18:3(6Z,9Z,12Z)/24:1(15Z)] (P<0.001) levels increased. Compared with the NC group, the richness of Megamonas and Escherichia increased in T2DM patients, while that of Bacteroidota and Phascolarctobacterium were lower. Pearson correlation analysis revealed associations between gut microbiota and faecal metabolites, and Phascolarctobacterium was positively correlated with alpha-linolenic acid (r=0.72, P<0.001). Conclusions There may be a mutual regulatory network between intestinal bacteria and fecal metabolites in T2DM. The increased abundance of Phascolarctobacterium may increase alpha-linolenic acid uptake, and alpha-linolenic acid may also increase the abundance of intestinal Phascolarctobacterium in vivo after metabolic transformation. The combination of the two may play an important role in the treatment of diabetes.
研究领域:
医学
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微生物学
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代谢组学
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DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
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2025
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IF 8.5
Nuan Dong,Xue Lu,Dongmei Qin
Type 2 diabetes (T2DM) is a chronic metabolic disease with a high incidence, which seriously affects the physical and mental health of patients. The current treatment methods can only alleviate the disease and are accompanied by unavoidable toxic side effects. Cichorium pumilum Jacq (CG) is a kind of plant medicine with Xinjiang characteristics, which is often used to reduce blood sugar and protect the liver. CG polysaccharide (CGP) is the main active component of CG, but the hypoglycemic effect and mechanism of CGP on T2DM are still unclear. In vitro hypoglycemic and antioxidant experiments showed that CGP had effective hypoglycemic and antioxidant activities, and a series of characterizations of CGP was carried out. In vivo tests on T2DM mice showed that CGP improved liver glycogen metabolism, reduced oxidative stress and colonic damage. AKT and PI3K phosphorylation decreased, mTOR phosphorylation increased in T2DM mice liver; CGP reversed these changes, protected colonic mucosa, and increased Occludin and ZO-1 protein expression. CGP is a good antioxidant and hypoglycemic agent. It improves liver glycogen metabolism and repairs intestinal mucosal damage in T2DM mice via the PI3K/AKT/mTOR pathway, providing a research basis for its treatment.
研究领域:
药理学
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生物化学
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分子生物学
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内分泌学
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天然产物研究
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
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2021
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IF 4.36
Tao He,Mingshuang Wang,Jiao Kong,Qiang Wang,Yue Tian,Chaofeng Li,Qian Wang,Chuanxin Liu,Jianmei Huang
Ethnopharmacological relevance Coptis Categorized Formula (CCF) is one of the core prescriptions in Treatise on Febrile Diseases . Its efficacy can be available not only in exogenous diseases but widely in various internal injuries and miscellaneous diseases. CCF (i.e., Huanglian Jiedu Decoction, Huanglian Ejiao Decoction, Dahuang Huanglian Xiexin Decoction, Gegen Qinlian Decoction) is different in composition, but they all play a favorable role in curative effect on type 2 diabetes mellitus (T2DM). Therefore, it is of great significance to reveal the common mechanism of CCF in treating T2DM. Aim of the study Based on network pharmacology and non-targeted metabolomics research strategy, the common mechanism of the CCF treating T2DM was discussed. Materials and methods Firstly, Ultra-high performance liquid chromatography-quadrupole-time of flight/mass spectrometry was used to identify the chemical constituents of the CCF. Then, the targets of these chemical components were used for network pharmacology analysis associated with therapeutic effect. Finally, the diabetic zebrafish model was constructed to further verify the common mechanism of the CCF in treating T2DM. Results A total of 160 chemical compositions were identified and 16 of them were common chemical compositions of the four CCF, including berberine , baicalin , coptisine and so forth. Network pharmacology results showed that Dipeptidyl peptidase (DPP)-4, cysteinyl aspartate specific proteinase (CASP)3, nitric oxide synthase (NOS)2, NOS3, and other 37 targets were common targets of CCF, and advanced glycation end products (AGE)-receptor of advanced glycation end products (RAGE) signaling pathway in diabetic complications , mitogen-activated protein kinase (MAPK) signaling pathway and hypoxia inducible factor (HIF)-1 signaling pathway were critical pathways of four CCF in the treatment of T2DM. CCF can lessen the blood glucose of diabetic zebrafish. The contents of 25 differential metabolites in diabetic zebrafish were altered. These metabolites were mainly related to phenylalanine , tyrosine and tryptophan biosynthesis, phenylalanine metabolism, arachidonic acid metabolism, sphingolipid metabolism, and tyrosine metabolism. Conclusion Our research shows that the common mechanism of CCF in improving T2DM is as follows: berberine, baicalin, coptisine and other chemical components can directionally regulate DPP-4, CASP3, NOS2, NOS3 and other targets, which are mediated by AGE-RAGE signaling pathway in diabetic complications, MAPK signaling pathway and HIF-1 signaling pathway. The content of endogenous metabolites such as L-valine and L-sorbitose changes, and further regulates the metabolism of amino acid metabolism, lipid metabolism, purine metabolism, sphingosine metabolism and arachidonic acid metabolism, so as to play a significant role in regulating glycolipid metabolism, improving insulin resistance, inhibiting cell apoptosis, anti-oxidation and anti-inflammation, and finally ameliorating T2DM.
研究领域:
民族药理学
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网络药理学
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代谢组学
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生物医学
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DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF PHARMACEUTICS
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2023
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IF 5.8
Yihui Yang,Mingchao Yu,Liwen Ren,Qi An,Wan Li,Hong Yang,Yizhi Zhang,Sen Zhang,Yue Hao,Guanhua Du,Dezhi Yang,Yang Lu,Jinhua Wang
Psoriasis is a common systemic inflammatory skin disorder affecting over 60 million people globally. Some patients with psoriasis are associated with a higher risk of type 2 diabetes mellitus (T2DM). Psoriasis and T2DM occur concurrently in some patients; however, there is no effective drug for the treatment of psoriasis with T2DM. Bexarotene (BEX) is a specific RXR agonist and an antineoplastic agent indicated by the FDA for cutaneous T-cell lymphoma (CTLA). Metformin (MET) is the first-line treatment for T2DM. To develop novel effective drugs for the treatment of psoriasis with T2DM, multicomponent salts containing MET and BEX were designed and synthesized based on the drug–drug combination strategy. MET-BEX (1:1) and MET-BEX-H 2 O (1:1:1) were obtained and structurally characterized. The in vitro evaluation results showed that the hygroscopicity of MET was significantly optimized by the salt formation strategy, while the solubility of BEX was improved, which laid the foundation for improving the bioavailability of BEX in vivo . In a mouse model of imiquimod-induced psoriasis with T2DM, MET-BEX ameliorated imiquimod-induced psoriasis morphological features and systematic inflammation and improved glucolipid metabolism. These results showed that the multicomponent drug combination strategy in this study optimized the physicochemical properties of MET and BEX simultaneously, providing a promising candidate therapy for psoriasis with T2DM.
研究领域:
药学
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药理学
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皮肤科
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内分泌学
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药物设计与开发
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DOI
PubMed
高影响因子
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