Fenugreek extract improves diabetes-induced endothelial dysfunction via the arginase 1 pathway.

Endothelial dysfunction (ED) is an initiating trigger and key factor in vascular complications, leading to disability and mortality in individuals with diabetes. The research concerning therapeutic interventions for ED has gained considerable interest. Fenugreek, a commonly used edible plant in dietary consumption, has attracted significant attention due to its management of diabetes and its associated complications. The research presented in this study examines the potential therapeutic benefits of fenugreek in treating ED and investigates the underlying mechanism associated with its effects. The analysis on fenugreek was performed using 70% ethanol extract, and its chemical composition was analyzed using ultrahigh-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS). In total, we identified 49 compounds present in the fenugreek extract. These compounds encompass flavonoids, saponins, and phospholipids. Then, the models of ED in streptozotocin-induced diabetic mice and high glucose-induced isolated rat aortas were established for research. Through vascular function testing, it was observed that fenugreek extract effectively improved ED induced by diabetes or high glucose. By analyzing the protein expression of arginase 1 (Arg1), Arg activity, Arg1 immunohistochemistry, nitric oxide (NO) level, and the protein expression of endothelial nitric oxide synthase (eNOS), p38 mitogen-activated protein kinase (p38 MAPK), and p-p38 MAPK in aortas, this study revealed that the potential mechanism of fenugreek extract in anti-ED involves the downregulation of Arg1, leading to enhanced NO production. Furthermore, analysis of serum exosomes carrying Arg activity indicates that fenugreek may decrease the activity of Arg transported by serum exosomes, potentially preventing the increase in Arg levels triggered by the uptake of serum exosomes by vascular endothelial cells. In general, this investigation offers valuable observations regarding the curative impact of fenugreek extract on anti-ED in diabetes, revealing the involvement of the Arg1 pathway in its mechanism.

Serum metabonomics study on antidiabetic effects of fenugreek flavonoids in streptozotocin-induced rats.

Fenugreek is a well-known medicinal plant used for treatment of diabetes. In this study, the antidiabetic effect of fenugreek flavonoids was investigated by metabonomics based on ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS). Fenugreek flavonoids were purified using polyamide resin and D101 macroporous adsorption resin, characterized by UPLC-Q-TOF-MS, and administered to streptozotocin (STZ)-induced diabetic rats for 28 days. Pharmacological study results indicated that fenugreek flavonoids exerted a strong antidiabetic effect characterized by significant reduction of fasting blood glucose (P < 0.01), increase in serum insulin level (P < 0.01) and liver glycogen content (P < 0.01), attenuation of weight loss, and improvement of pancreatic islet and kidney conditions. The antidiabetic effect of fenugreek flavonoids was further analyzed by metabonomics. Serum samples of health and diabetic rats treated or not with fenugreek flavonoids were evaluated by UPLC-Q-TOF-MS, followed by principal component analysis (PCA) and orthogonal projection to latent structures squares-discriminant analysis (OPLS-DA). The PCA model revealed significant differences among the animal groups, and OPLS-DA identified fenugreek flavonoids-induced changes of 11 potential biomarkers involved in lipid metabolism (docosahexaenoic acid, arachidonic acid, sphinganine, sphingosine­1­phosphate, and lysophosphatidylcholines 20:4, 18:2, 16:0, and 20:2), amino acid metabolism (hippuric acid and tryptophan), and kidney function-related metabolism (2­phenylethanol glucuronide). Our study demonstrates that flavonoids are bioactive components of fenugreek with potent antidiabetic activity, which exert their therapeutic effects by multiple mechanisms, including reducing insulin resistance, improving gluconeogenesis, and protecting islet cells and kidneys from damage.

Metabonomics study of the therapeutic mechanism of fenugreek galactomannan on diabetic hyperglycemia in rats, by ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry.

Fenugreek is a traditional plant for the treatment of diabetes. Galactomannan, an active major component in fenugreek seeds, has shown hypoglycemic activity. The present study was performed to investigate the therapeutic mechanism underlying fenugreek galactomannan (F-GAL) in treating diabetes, using a metabonomics approach based on ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-QTOF/MS). The F-GAL used for study was highly purified, and its yield, purity, and galactose/mannose ratio were characterized by capillary zone electrophoresis (CZE) and a modified phenol-sulfuric acid method. After treatment of streptozotocin (STZ)-induced diabetic rats with F-GAL for 28days, urine and serum samples were analyzed by UPLC-QTOF/MS. Multivariate statistical approaches such as principal component analysis (PCA) and orthogonal projection to latent structures squares-discriminant analysis (OPLS-DA) were applied to distinguish the non-diabetic/untreated, diabetic/untreated, and diabetic/F-GAL-treated groups. Then, potential biomarkers were identified that may help elucidate the underlying therapeutic mechanism of F-GAL in diabetes. The results demonstrated that there was a clear separation among the three groups in the PCA model. Fourteen potential biomarkers were identified by OPLS-DA, and they were determined to be produced in response to the therapeutic effects of F-GAL. These biomarkers were involved in histidine metabolism, tryptophan metabolism, energy metabolism, phenylalanine metabolism, sphingolipid metabolism, glycerophospholipid metabolism, and arachidonic acid metabolism. In conclusion, our study demonstrates that a metabonomics approach is a powerful, novel tool that can be used to evaluate the underlying therapeutic mechanisms of herb extracts.

[Research ontherapeutics effect of extract of Ornithogalum caudatum on liver fibrosis].

Rat models of liver fibrosis were made by carbon tetrachloride, and the serum levels of AST, ALT, γ-GT, MDA, GSH-px, SOD were detected, serum markers of PCⅢ, IV-C, LN, HA were detected by ELISA method. HE and Masson staining were conducted in hepatic tissues to observe pathological variations. Collagen Ⅲ, TGF-ß, α-SMA, E-cadherin were detected by Western blot. The curative effect of the extract of Ornithogalum caudatum on rat liver fibrosis induced by CCl4was observed and the mechanism was discussed. The experiment results showed that the extract of O. caudatum (50, 150, 500 mg•kg⁻¹) obviously decreased the serum levels of AST, ALT, γ-GT, MDA, increased the serum levels of GSH-px, SOD, decreased the expression of serum markers of PCⅢ, IV-C, LN, HA, and improved the liver pathological variations of fibrotic rats. The experiment proved that the extract of O. caudatum could treat the liver fibrogenesis induced by CCl4 in rats. The positive medicine may inhibit accumulation of extracellular and activate hepatic stellate cell and epithelial-mesenchymal transition.

[Separation of 1-phenyl-3-methyl-5-pyrazolone derivatives of traditional Chinese medicine oligosaccharides by capillary zone electrophoresis].

A simple and practical capillary zone electrophoretic (CZE) method has been developed for the separation of traditional Chinese medicine oligosaccharides according to their relative molecular masses (M(r)). To optimize the conditions of the method, the concentration and pH value of the running buffer, and the applied voltage were evaluated. The optimized conditions were as follows: 1-phenyl-3-methyl-5-pyrazolone (PMP) derivatives of the oligosaccharides were separated with 50 mmol/L phosphate buffer (pH 2.5) as running buffer and the voltage was 15 kV. The detection was performed with an ultraviolet detector at 245 nm. An uncoated fused-silica capillary of 50 microm i. d. and 38/48 cm length (effective length/total length) was employed, and a hydrodynamic pressure injection (10 cm x 2 s) was applied. In order to examine the practicability of the method for the analysis of actual traditional Chinese medicine oligosaccharide samples, a complex sample consisting of some usual monosaccharides and oligosaccharides degraded from beta-cyclodextrin was separated under the electrophoretic conditions. And then, the method was applied to the analysis of the controlled degradation products of Indigowoad Root polysaccharide. The results indicated that the oligosaccharide sample could fully be separated from low to high M(r). This method is efficient and practical. In addition, the separation hypothesis of PMP derivatives of monosaccharides and oligosaccharides in pH 2.5 running buffer is also discussed, which would be helpful for us to understand the unusual migration of the PMP derivatives of rhamnose and mannose.

[A neglected master on integrative medicine: Wei-Ju ZHU].

Through analyzing the academic ideas in Shanghan Zhinan written by Wei-Ju ZHU, a modern famous physician, it is pointed out that ZHU's achievement on integrative medicine has been overlooked. Taking the theory of syndrome differentiation of six channels from Shanghan Lun as an example, ZHU presumed that the essence of therapeutic theory of traditional Chinese medicine was to conform to or strengthen human body's self-healing and self-regulating abilities. Since Yangqi is the major force in the body to help heal disease when it occurred, ZHU often took measures to strengthen Yang first in treating disease and also was good at using hot-natured herbs, such as Radix aconiti lateralis preparata. ZHU's thoughts on integrative medicine were concerned with etiology, pathology and therapeutics. In addition, ZHU generalized the syndrome differentiation into the theory of five phases and eight principles, and made important contributions to the history of integrative medicine. His thinking will provide valuable revelation for clinical practice and modern research on traditional Chinese medicine.

Therapeutic wisdom in traditional Chinese medicine: a perspective from modern science.

The reasons why the standards of evaluating Western medicine are not suitable for testing traditional Chinese medicine (TCM) are explicit in the therapeutic objective and principles of TCM. TCM aims to correct maladjustments and restore the self-regulatory ability of the body, and not to antagonize specific pathogenetic targets. Maladjustments in a disease can be classified into several 'patterns' according to TCM theory. Multiple diseases might share one 'pattern' and be treated by the same herbal formula whereas one disease might display several different 'patterns' and be treated by multiple formulae. These principles are supported by evidence that multi-system changes in one pattern can be modulated by a herbal formula. The approaches used in systems biology and pharmacogenetics are similar to the practices of TCM. I propose that a combined approach using specific parameters associated with modern medicine, the general condition of individuals, as outlined by TCM, and pattern stratification of diseases should be employed to re-evaluate herbal formulae.

Therapeutic wisdom in traditional Chinese medicine: A perspective from modern science.

Extract: Misunderstanding usually stems from ignorance. This is the case for comments directed at each other by western medicine and traditional Chinese medicine (TCM). Modern biomedical scientists insist that herbal remedies need quality control, rigorous clinical trials, and illumination of active ingredients and their action mechanisms. In fact, almost all ever-increasing number of research projects on herbal medicine are being conducted based on this belief. Researchers often disrespect those so-called unique, seemingly inaccessible and ridiculous theories in traditional medicine. While, in the eyes of TCM doctors, most published articles about TCM in Western medicine journals haven't felt TCM's "pulse" yet. They thought that such studies are also ridiculous to focus only on herbal drugs instead of the thinking which guides drug's usage. This is like studying Vincent van Gogh's paintbrush instead of his thoughts about art expression. TCM experts are disgruntled with the demand and rebuke from western medicine. They believe the real efficacy and toxicity of herbal agents will not be adequately demonstrated using the present evaluation paradigm for single chemical compounds, since TCM does not focus solely on the disease defined by specific pathological changes (e.g., the level of blood pressure or sugar, the identifying of tumor cells or microorganisms, etc.) but instead concentrates on the overall functional state of the patient. However, because of TCM's classic naming systems, they can not convey their notions effectively to the field of the mainstream medicine.

[Preliminary exploration on establishing a simulated model of acute and chronic after-qi-stagnation blood stasis by adrenaline injection].

OBJECTIVE: To testify the TCM theory on "qi-stagnation causes blood stasis" and explore the method of using adrenaline to establish an acute and chronic blood stasis animal model. METHODS: Wistar rats were divided into 5 groups, the blank group (un-modeled), the model group A (modeled with once subcutaneous injection of 0.1% adrenaline), the model group B (modeled with once a day of subcutaneous injection of 0.01% adrenalinei for consecutive seven days), the Salvia group (treated with salvia after modeling) and the Chuanxiong group (treated with Chuanxiong after modeling). The model was established by simulating the anger and anxious status to form acute and chronic blood stasis model respectively and the treatments of Salvia and Chuanxiong was used to testify the syndrome type. Hemorrheologic parameters of the rats were measured. RESULTS: Compared with that in the blank group, the low sheared rate of whole blood viscosity increased, and the RBC deformability and aggregation index raised in both model group A and B (P < 0.01 or P < 0.05). Compared with that in Group A, in the Salvia group, the in vitro thrombus lengthened (P < 0.01), with its dry weight, wet weight increased (P < 0.01) after treatment, but the above-mentioned parameters in the Chuanxiong group were not changed at all. CONCLUSION: One time large dosage and multiple times of small dosage adrenaline subcutaneous injection to simulate angry and anxious status could produce blood stasis animal model. This fact provides an experimental basis for "Qi stagnation causes blood stasis" theory in TCM.