Journal of Holistic Integrative Pharmacy最新文献

Traditional Chinese medicine is the treasure of Chinese traditional culture. A series of questions should be answered on the base of systematic, comprehensive and in-depth research according to the TCM theory and its own characteristics. For example, how to construct a research framework with clear guidance and route, as well as reasonable plan for elucidating the effective material basis of Traditional Chinese medicine (TCM) formula? How to discover and excavate the effective material basis of TCM, clarify and interpret the related action mechanism? How to clarify the reasonableness of compatibility, the scientificity for usage of medication, as well as the scientific connotation of TCM in preventing and curing disease? Aforementioned questions had been considered as the important frontier scientific problems to be solved in the field of TCM. According to the practice progress and thinking on research of effective material basis and related mechanism in Naomaitong Granule and Dengzhan Shengmai Capsule, a systematic strategy from the perspective of interaction between drug system, intestinal microecosystem and host living system had been proposed and elucidated in three aspects: (1) Discovering the TCM regulated genes and proteins dated from functional metabolites, in order to characterize the biological response of host systematically. (2) Deciphering the effective material basis and related acting mechanism on the base of interaction between TCM formula and intestinal microecosystem. (3) The systematic characterization of material basis of TCM formula by Chemomics.

Objective

Triptriolide (T11) is isolated from the Chinese herb Tripterygium wilfordii Hook F (TwHF), which has been used as an immunosuppressive reagent for many years in China, while the role of this compound in TwHF is still unknown. In this study, we try to investigate the immune regulating effects of T11 on the proliferation and apoptosis of splenic lymphocyte in vivo and in vitro.

Methods

we pretreated the BALB/c mice with T11 (2.8, 14, 28 mg/kg) and prednisone acetate (PA, 1.3 mg/kg, positive control) for 7 days before lipopolysaccharides (LPS, 3 mg/kg) stimulation. Then the histopathologic change of spleen was examined by H&E method, and the apoptosis of splenic lymphocyte was assessed by flow cytometry method. In addition, we further studied the inhibition effect of T11 (50, 100, 150, 200 µg/mL) on the proliferation and activity of splenic lymphocyte, which was with or without the stimulation of concanavalin A (Con A, 5 µg/mL) and lipopolysaccharides (LPS, 5 µg/mL) in vitro, respectively.

Results

We found that T11 not only can restore the pathogenesis process in spleen, and boost the splenic lymphocyte apoptosis in vivo, but also can inhibit the splenic lymphocyte proliferation and affect its viability in vitro.

Conclusion

The results indicated that T11 might modulate the immune function of LPS-induced BALB/c mice by inhibiting the proliferation and inducing the apoptosis of splenic lymphocyte. Therefore, T11 could be a novel immunomodulator in autoimmune disease treatment in clinical.

Objective

Ligustilide (Lig), a major component of Radix Angelica Sinensis, exhibits a protective effect on many cardiovascular diseases. Our previous study showed that Lig inhibited the proliferation of vascular smooth muscle cells. In this study, we aimed to investigate the effect of Lig on the migration of vascular smooth muscle A7r5 cells induced by Angiotensin II (Ang II) and explore the mechanism underlying based on network pharmacology.

Methods

In this study, scratch-wound healing assay and transwell migration assay were used to assess the migration activity of Lig on Ang II-induced vascular smooth muscle A7r5 cells, and network pharmacology method was used to predict the possible target molecules. Western blot analysis, Gelatin zymography assay, and small interfering RNA (siRNA) were used to determine the underlying mechanism of Lig on the migration in Ang II-induced A7r5 cells.

Results

We found that Lig could prevented the migration induced by Ang II in A7r5 cells, which could be associated with c-Myc and MMPs from the results of network pharmacology. Our results revealed that Lig could significantly reduce the increase in the protein expression levels of c-Myc and MMP-2 in Ang II-induced A7r5 cells, but not affect the protein expression levels of MMP-9. Our data further showed that c-Myc siRNA, just as Lig, could obviously inhibit the cell migration accompanied by decreased MMP-2 expression.

Conclusion

These findings suggested the anti-migratory effect of Lig could be associated with the c-Myc/MMP-2 pathway, and Lig administration had a promising potential for preventing cardiovascular diseases.

Objective

Aging is typically characterized by imbalanced gut microbiota and bile acid (BA) dyshomeostasis. However, features of the gut microbiota-regulated BA metabolism in the aging process remain unclear.

Aim

To establish a direct link between gut microbiota and BA profile changes in the liver, plasma, and intestinal contents and to further understand aging and aging-related diseases from the liver-gut axis.

Methods

The BA content in the liver, plasma, and intestine were determined using ultra-performance liquid chromatography-tandem mass spectrometry. Gut microbiota were sequenced by 16S rDNA, and the expression of the liver-gut axis-related proteins was detected.

Results

The plasma content of total cholesterol, triglycerides, and low-density lipoprotein cholesterol gradually increased during aging, and Lactobacillus, Bacteroides, Bacillus, Ruminococcus, Blautia, and Streptococcus, which can produce bile salt hydrolase, were increased. The concentration of total BAs was increased, especially that of unconjugated BAs, and the ratio of unconjugated BAs to conjugated BAs was also increased. The expression of bile acid transporter receptors and intestinal tight junction proteins was significantly decreased.

Conclusion

The presented data show that the changes in BA profile mediated by gut microbiota were closely related to aging and highlights that more attention should be paid to targeting gut microbiota-regulated BA metabolism to prevent and treat aging-related diseases, especially lipid metabolism disorders.

Aims

Qi-yin deficiency (QYD) and Yang-deficiency (YD) syndrome are two common syndromes with contrasting clinical manifestations of low fever and cold phobia. Different syndrome phenotypes must have distinct biological underpinnings in vivo. Based on serum metabolomics, this study aims to reveal the biological characteristics of the two diabetic coronary heart disease syndromes mentioned above.

Methods

A total of 33 diabetic coronary heart disease (DCHD) patients were included in the study, with 13 cases of QYD, 11 cases of YD syndrome, and 9 cases of Pinghe constitution (PH). Based on UPLC-Q/TOF MS, metabolomics was used to detect and analyze serum samples from the three groups mentioned above. To find differentiating metabolites, PLS-DA (Partial least squares discrimination analysis) and database searching were used. Meanwhile, the metabolic pathways of various metabolites were investigated.

Results

There were 17 different metabolites between QYD syndrome and YD syndrome of DCHD. Cyclic GMP, LysoPE (20:3), proline, isoleucine, N-lactoyl-tyrosine, 3-oxohexadecanoyl-CoA, and oxalosuccinic acid were lower in the (YD) group than those in the PH group, while galactitol, N-lactoyl-tyrosine, and oxalosuccinic acid were higher in the QYD group than in the PH group. The 17 differential metabolites mentioned above were linked to a variety of pathways, including amino acid metabolism, purine metabolism, fatty acid elongation in mitochondria, the tricarboxylic acid cycle, lipid metabolism, energy metabolism, etc.

Conclusion

Different DCHD syndromes, such as liver-kidney Yin deficiency and YD syndrome, have different biological bases for the same disease. To some extent, the findings of this study provide a scientific foundation for different approaches to treating the same disease in Traditional Chinese Medicine. It is also important for guiding the clinical use of herbal medicine.

Cardiovascular disease (CVD) is the leading cause of death worldwide. It has been recognized that specific regulatory factors from peripheral tissues can influence the pathological progression of atherosclerosis, myocardial infarction (MI) and heart failure (HF). Drugs targeting the regulation of pathways related to hepatic lipid metabolism, intestinal flora, renal sodium excretion and hypoglycemia, bone marrow clonal hematopoiesis and immune inflammation, such as Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, Sodium-glucose Cotransporter-2 (SGLT2) inhibitors, IL-1β monoclonal antibodies and Chimeric antigen receptor (CAR) -T therapy, have been shown to have significant protective effects in the prevention and treatment of cardiovascular disease, especially ischemic heart disease and HF. Various forms of interaction between cardiovascular system diseases and cerebrovascular, liver and intestinal metabolism, kidney and other functional disorders have been widely reported. In this review, we focus on the interactions between the cardiovascular system and other organs in ischemic heart disease and HF, highlight novel therapeutic strategies that modulate cardiometabolic and inflammatory processes.

Objective

This study aimed to investigate the anti-obesity effects of the combination of metformin and epigallocatechin-3-gallate (EGCG) in a diet-induced obese (DIO) model.

Methods

Male C57BL/6J mice were fed with high-fat diet (HFD, 60% fat) to establish a DIO model. The DIO mice were administered intragastrically daily with vehicle, metformin (Met, 250 mg/kg), EGCG (200 mg/kg), or mixture of Met and EGCG (Met/EGCG; 250 and 200 mg/kg) for 32 days. Body weight was measured daily at a fixed time point. An intraperitoneal glucose tolerance test was performed on day 26 after treatments. Body composition was determined by using nuclear magnetic resonance technology. Adipose tissues and major organs were collected after culling. Gene expression in brown adipose tissue (BAT) and subcutaneous white adipose tissue (scWAT) were detected by quantitative polymerase chain reaction.

Results

Compared with the vehicle group, the body weight was significantly reduced in DIO mice in the Met and Met/EGCG groups. The weight loss rate in the Met and EGCG groups were 9.1% and 1.0%, respectively. However, Met/EGCG induced a 14.0% body weight loss, suggesting that the combination of Met and EGCG has a synergistic effect on reversing the body weight in DIO mice. Met/EGCG demonstrated beneficial effects on the subcutaneous fat, BAT, and glucose homeostasis in DIO mice. Furthermore, Met/EGCG did not significantly increase the thermogenic gene expression in BAT, whereas in scWAT, Met/EGCG showed moderate effects on the expression of specific markers of browning fat or beige fat.

Conclusion

Metformin and EGCG have combined treatment effect on the body weight of DIO mice. Their combination might be a promising treatment approach for obesity.

Objective

To observe the effects of Lingguizhugan decoction on obesity and investigate its preliminary mechanism in activating fat mobilization based on gut microbiota.

Methods

In this prospective one-armed clinical research, we analyzed the data of 32 obese patients with Yang deficiency and phlegm-dampness syndrome treated by Lingguizhugan decoction combined with lifestyle intervention for 2 months. The anthropometric data, body composition, metabolic data, traditional Chinese medicine (TCM) syndrome scores, fecal 16S rDNA, core temperature, and visceral fat fractions of patients were analyzed. Animal experiments were conducted for further verification: ob/ob mice and pseudo-germ-free ob/ob mice (ABX) were given Lingguizhugan decoction by gavage for 2 months. The body mass, core temperature (rectum), respiratory exchange ratio (RER), micro-positron emission tomography/computed tomography (micro-PET/CT) results, and uncoupling protein 1 (UCP1) expression (including gene, protein, and immunohistochemistry staining results) in inguinal adipose tissue of mice were evaluated.

Results

The clinical effective rates of TCM and Western medicine were 96.87% and 93.75%, respectively. Compared with those before treatment, the body mass index (BMI), body fat ratio (BFR), waist-to-hip ratio, TCM syndrome scores, low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC), triglyceride (TG), fasting plasma glucose (FPG), 2 h postprandial plasma glucose (2hPPG), glycosylated hemoglobin A1C (GHbA1c), and blood uric acid (UA) significantly decreased after treatment. Moreover, we randomly selected five patients to investigate their core temperature and visceral fat fractions. Compared with healthy volunteers, the five patients had higher core temperature. According to the 1.5 T magnetic resonance imaging (MRI) results, the fat fractions of the liver, pancreas, greater omentum, and subcutaneous abdominal wall were notably decreased after treatment. Fecal 16S rDNA principal component analysis and partial least squares discriminant analysis showed that the biodiversity and species abundance of gut microbiota were significantly different between pre- and post-treatment. The relative abundance of Bacteroidetes was remarkably elevated and that of Firmicutes was notably reduced by Lingguizhugan decoction. The animal experiments showed that the weight of ob/ob mice decreased significantly by gavage of Lingguizhugan decoction for 2 months. Compared with the model group, the Lingguizhugan group showed increased core temperature (rectum) and decreased RER. Micro-PET/CT showed that ¹⁸F-2-deoxyglucose-6-phosphate (¹⁸F-FDG) was enriched obviously and the SUV index was increased in the Lingguizhugan group. However, after eliminating the gut microbiota in the ABX group, the weight loss, core temperature, ¹⁸F-FDG enrichment, and SUV index decreased, and RER was similar to that