Jiaotai Pill Research Articles

Molecular targets and mechanisms of Jiawei Jiaotai Pill on diabetic cardiomyopathy based on network pharmacology

The complication of diabetes, which is known as diabetic foot ulcer (DFU), is a significant concern due to its association with high rates of disability and mortality. It not only severely affects patients’ quality of life, but also imposes a substantial burden on the healthcare system. In spite of efforts made in clinical practice, treating DFU remains a challenging task. While mesenchymal stem cell (MSC) therapy has been extensively studied in treating DFU, the current efficacy of DFU healing using this method is still inadequate. However, in recent years, several MSCs-based drug delivery systems have emerged, which have shown to increase the efficacy of MSC therapy, especially in treating DFU. This review summarized the application of diverse MSCs-based drug delivery systems in treating DFU and suggested potential prospects for the future research.

Research progress in the prevention and treatment of insomnia with classical prescriptions.

Insomnia is a common disease and its impact on human health cannot be ignored. At present, there are 3 main clinical treatments for insomnia, including traditional Chinese medicine treatment, sedative hypnotic drug therapy, and cognitive behavioral therapy. Traditional Chinese medicine (TCM) treatment for insomnia is widely used due to its advantages of low side effects, good efficacy, and no drug dependence. This paper summarizes the pathogenesis of insomnia in the theories of traditional Chinese and Western medicine. Modern medical research generally believes that sleep-wake disorder is the main pathological mechanism of insomnia, involving many factors such as monoamine neurotransmitter disorder, cytokine imbalance and intestinal flora imbalance. TCM mainly divides the pathogenesis of insomnia into 9 kinds of syndrome types: Liver depression transforming into fire, hyperactivity of fire due to yin deficiency, phlegm-heat attacking internally, disharmony between heart and kidney, deficiency of both heart and spleen, qi deficiency of both heart and gallbaldder, stomach qi disharmony, exuberance of heart fire, and internal blockade of static blood. According to these 9 kinds of pathogenesis of insomnia, the corresponding classical prescriptions such as Longdanxiegan decoction, Suanzaoren decoction, Huanglian-Wendan decoction, Jiaotai pill and Guipi decoction were analyzed and summarized. There is evidence that traditional Chinese medicine could treat insomnia mainly by increasing the level of 5-hydroxytryptamine, reducing the levels of dopamine, noradrenaline, tumor necrosis factor α, and interlukin-6, decreasing the ratio of glutamic acid to γ-aminobutyric acid, and inhibiting the hypothalamic-pituitary-adrenal axis.

Fecal metabolomics combined with 16S rRNA gene sequencing to analyze the effect of Jiaotai pill intervention in type 2 diabetes mellitus rats.

The occurrence and development of type 2 diabetes mellitus (T2DM) are closely related to gut microbiota. Jiaotai pill (JTP) is used to treat type 2 diabetes mellitus, with definite efficacy in clinical practice. However, it is not clear whether the therapeutic effect is produced by regulating the changes in gut microbiota and its metabolism. In this study, T2DM rat models were established by a high-fat diet and low-dose streptozotocin (STZ). Based on the pharmacodynamic evaluation, the mechanism of JTP in the treatment of type 2 diabetes mellitus was investigated by fecal metabolism and 16S rRNA gene sequencing. The results showed that JTP decreased blood glucose (FBG, HbA1c) and blood lipid (TC, TG, and LDL) levels and alleviated insulin resistance (FINS, IL-10) in T2DM rats. 16S rRNA gene sequencing results revealed that JTP increased microbiota diversity and reversed the disorder of gut microbiota in T2DM rats, and therefore achieved the therapeutic effect in T2DM. JTP regulated 13 differential flora, which were Actinobacteria, Bacteroidetes, Firmicutes, Proteobacteria, Eubacteriaceae, Prevotellaceae, Ruminococcaceae, Clostridium_IV, Clostridium_XlVa, Eubacterium, Fusicatenibacter, Romboutsia, and Roseburia. Metabolomics analysis showed that JTP interfered with 13 biomarkers to play a therapeutic role in type 2 diabetes mellitus. They were L-Valine, Choline, L-Aspartic acid, Serotonin, L-Lysine, L-Histidine, 3-Hydroxybutyric acid, Pyruvic acid, N-Acetylornithine, Arachidonic acid, L-Tryptophan, L-Alanine, and L-Methionine. KEGG metabolic pathway analysis of the above differential metabolites and gut microbiota by using the MetaboAnalyst database and Picrust software. It was found that JTP treated type 2 diabetes mellitus by affecting metabolic pathways such as amino acid metabolism, carbohydrate metabolism, and lipid metabolism. Spearman correlation analysis revealed high correlations for 7 pharmacological indicators, 12 biomarkers, and 11 gut microbiota. In this study, the therapeutic effect and potential mechanism of JTP on type 2 diabetes mellitus were preliminarily demonstrated by gut microbiota and metabolomics, which could provide a theoretical basis for the treatment of T2DM with JTP.

Study on the Mechanism of Jiaotai Pill Intervention on Insomnia Animal Model Based on Gut Microbiome and Metabolomics.

With the continuous advancement of clinical application and experimental research of JTP, the application prospect of JTP in nervous system diseases and metabolic diseases is becoming increasingly clear. Jiaotai Pill (JTP) is a traditional Chinese medicine formula for insomnia, consisting of Coptidis rhizoma and Cinnamomi cortex, which dates back to Han Shi Yi Tong in the Ming Dynasty of China. Based on the brain-gut axis theory, this paper aims to explore the potential mechanism of JTP in the intervention of insomnia by using intestinal microbiome and metabolomics technology, taking the animal model of insomnia as the research object, so as to provide experimental basis for its further application and research. The insomnia mouse model was induced by intraperitoneal injection of para-chlorophenylalanine (PCPA). The clinical equivalent dose of JTP was administered by gavage for one week. The efficacy of JTP was evaluated by behavioral tests, serum biochemical detection, and brain histomorphological observation. The contents of cecum were analyzed by microbiomics and metabolomics. The results show that insomnia caused by PCPA led to daytime dysfunction, higher HPA axis hormone levels, and morphologically impaired hippocampus. JTP reversed these anomalies. Omics research indicates that JTP significantly reduced gut α diversity; at the phylum level, JTP reduced the relative abundance of Firmicutes, Deferribacterota, Cyanobacteria, and Actinobacteriota and increased the relative abundance of Verrucomicrobiota, Proteobacteria, and Desulfobacterota. At the genus level, JTP reduced the relative abundance of Muribaculaceae, Lachnospiraceae_NK4A136_group, Alistipes, Colidextribacter, Muribaculum, and Mucispirillum and increased the relative abundance of Bacteroides and Akkermansia. JTP also reversed the activation of the linoleic acid metabolism pathway induced by insomnia. The combined analysis of omics suggests that JTP may play a role by regulating the inflammatory state of the body. Further gene expression analysis of brain tissue confirmed this. We hypothesize that JTP may achieve insomnia relief by eliminating inflammation-causing bacteria in the gut and reducing inflammation levels through the brain-gut axis, pointing to potential targets and pathways for future research on JTP.

Jiaotai Pill () Alleviates Insomnia through Regulating Monoamine and Organic Cation Transporters in Rats.

To reveal the effect and mechanism of Jiaotai Pill (, JTP) on insomniac rats. The insomniac model was established by intraperitoneal injection of p-chlorophenylalanine (PCPA). In behavioral experiments, rats were divided into control, insomniac model, JTP [3.3 g/(kg•d)], and diazepam [4 mg/(kg•d)] groups. The treatment effect of JTP was evaluated by weight measurement (increasement of body weight), open field test (number of crossings) and forced swimming test (immobility time). A high performance liquid chromatography-electrochemical detection (HPLC-ECD) method was built to determine the concentration of monoamine transmitters in hypothalamus and peripheral organs from normal, model, JTP, citalopram [30 mg/(kg•d)], maprotiline [40 mg/(kg•d)] and bupropion [40 mg/(kg•d)] groups. Expressions of serotonin transporter (SERT), dopamine transporter (DAT), and norepinephrine transporter (NET) were analyzed by quantitative polymerase chain reaction (qPCR) and Western blot in normal, model and JTP groups. A high performance liquid chromatography-electrospray ionization mass spectrometry (HPLC-ESI-MS/MS) method was established to determine the pharmacokinetics, urine cumulative excretion of metformin in vivo, and tissue slice uptake in vitro, which were applied to assess the activity of organic cation transporters (OCTs) in hypothalamus and peripheral organs. Compared with the insomniac model group, the body weight and spontaneous locomotor were increased, and the immobility time was decreased after treatment with JTP (P<0.01). Both serotonin and dopamine contents in hypothalamus and peripheral organs were increased (P<0.01). The norepinephrine content was increased in peripheral organs and decreased in hypothalamus (P<0.05 or P<0.01). At the same time, SERT, DAT, OCT1, OCT2, and OCT3 were down-regulated in hypothalamus and peripheral organs (P<0.05). NET was down-regulated in peripheral organs and up-regulated in hypothalamus (P<0.05 or P<0.01). Moreover, the activity of OCTs in hypothalamus and peripheral organs was inhibited (P<0.05). JTP alleviates insomnia through regulation of monoaminergic system and OCTs in hypothalamus and peripheral organs.

Hong Kong Chinese medicine clinical practice guideline for insomnia

IntroductionInsomnia in Chinese Medicine can be defined as inability to sleep or inability to relax when lying down. Insomnia is common among people in Hong Kong and requires appropriate management. Approximately 39.4% of adults are thought to suffer from insomnia in Hong Kong, a significant proportion of whom seek Chinese Medicine (CM) therapies as supportive care. This article provides a CM clinical practice guideline (CPG) for insomnia to guide local licensed CM practitioners which can be beneficial by providing a reference point for medical decision makers as well as patients. MethodsA systematic search of clinical research regarding CM treatments for insomnia was conducted. After data retrieval and evaluation, the guideline was drafted on the basis of clinical evidence, data mining, consensus of experts in Hong Kong and overseas, and synthesizing information by the process of assessment and consultation. ResultsBased on the results of data mining and consensus by experts, common patterns of insomnia included: transformation of liver depression into fire, harassment of interior phlegm-heat, yin deficiency with internal fire, dual deficiency of the heart and spleen and lack of interaction between the heart and kidney. The recommended CM herbal prescriptions were: Longdanxiegan decoction, Modified Wendan decoction, Huanglianejiao decoction, Renshenguipi decoction and Jiaotai pill respectively. Appropriate acupuncture points were also identified ConclusionsThis article provides the first CM CPG for insomnia for Hong Kong local use which will provide a milestone in the development of CM in Hong Kong. It may help standardize and secure CM clinical practice thus improving efficacy and safety of CM.

Coptidis Rhizoma-Contained Traditional Formulae for Insomnia: A Potential to Prevent Diabetes?

It has been well known that insomnia and sleep deprivation can lead to many metabolic diseases such as type 2 diabete mellitus (T2DM). Chinese medicine (CM) has been used to improve insomnia and showed many good therapeutic effects. Some Coptidis Rhizoma-contained traditional formulae have been found to exert obvious effects on insomnia, such as Jiaotai Pill (), Huanglian Ejiao Decoction (), Huanglian Wendan Decoction (), Niuhuang Qingxin Pill (), and Zhusha Anshen Pill (). Coptidis Rhizoma, a traditional herbal medicine which can purge Xin (Heart) fire, is the most important component of these formulas. Studies have found that these formulae could improve T2DM symptoms. We hypothesized that treating insomnia theoretically may help to prevent diabetes and organized many experimental studies in this review and concluded that Coptidis Rhizoma-contained traditional formulae for insomnia might be a potential to prevent diabetes.

Effect of Jiaotai Pill () on intestinal damage in partially sleep deprived rats.

To explore the effect and mechanism of Jiaotai Pill (, JTW) on intestinal mucosal damage in rats with chronic partial sleep deprivation (PSD). Obesity resistant (OR) rats were selected, and underwent 4 h PSD by being exposed to environmental noise for 4 weeks. During the whole PSD period, JTW and estazolam were orally given to the rats respectively in the treating groups. Plasma concentration of lipopolysaccharide (LPS) which is the marker of gut-origin endotoxemia was examined. Intestinal morphology changes were observed by optical microscopy. The protein expression of occludin (Ocln) in the intestine was measured by immunofluorescence technique and Western blot. The expressions of circadian proteins cryptochromes (Cry1 and Cry2) in the intestine were also determined. The treatment of JTW significantly decreased LPS level in OR rats with PSD (P<0.05). JTW also attenuated insomnia-induced intestinal injury like shorter, sparse and incomplete villus, wide gap between the villus, mucosal swelling and congesting (P<0.05). These changes were associated with the effect of JTW on up-regulating the expressions of Cry1 protein, Cry2 protein and Ocln protein in the intestine. JTW has the beneficial effect on improving intestinal mucosal damage caused by PSD. The mechanism appears to be related to the modulation of the expressions of circadian proteins and Ocln protein in the intestine, thereby attenuating inflammation and improving insulin resistance in insomnia rats.

Therapeutic effects of Jiaotai pill on rat insomnia via regulation of GABA signal pathway

Purpose: To investigate the therapeutic effects of Jiaotai pill (JTP) on rats with insomnia induced by pchlorophenylalanine (PCPA).Methods: Rats with PCPA-induced insomnia were divided into 5 groups (n = 10), made up of control group, positive treatment group (estazolam 0.1 mg/kg), and 3 JTP treatment groups (0.6, 1.2 and 2.4 g/kg). Another group of 10 rats were treated as normal group. Rats in normal and control groups were treated with normal saline (10 mL/kg). After 14 days of drug treatment, the rats were injected intraperitoneally with sodium pentobarbital (45 mg/kg) and thereafter, latent period and sleeping time were recorded, while contents of γ-aminobutyric acid (GABA) and glutamic acid (Glu) in hypothalamus were determined by high performance liquid chromatography (HPLC). Furthermore, the expressions of glutamate decarboxylase 65 (GAD-65), glutamate decarboxylase 67 (GAD-67), GABAaminotransferase (GABA)-T, anti-GABA transporter 1 (GAT)-1, anti-GABA transporter (GAT)-3, and GABA receptors (GABA-A and GABA-B) in the hypothalamus were analyzed by western blotting assay.Results: The results showed that JTP (0.6, 1.2 and 2.4 g/kg) significantly shortened latent period and prolonged sleeping time (p &lt; 0.01). JTP also increased GABA level (p &lt; 0.01), but decreased Glu contents of the rat hypothalamus (p &lt; 0.01). Western blotting data indicate that JTP significantly upregulated the levels of GAD-65 (p &lt; 0.01), GAD-67 (p &lt; 0.05), GAT-1 (p &lt; 0.01), GAT-3 (p &lt; 0.01), GABA-A (p &lt; 0.01) and GABA-B (p &lt; 0.01), while the level of GABA-T was down-regulated.Conclusion: The results demonstrate that JTP possesses significant sedative effects on insomnia in rats, most probably through a mechanism involving GABA signal pathway.Keywords: Jiaotai pill, Insomnia, GABA, Glutamate, Estazolam, GABA signal pathway

Effects of berberine and cinnamic acid on palmitic acid-induced intracellular triglyceride accumulation in NIT-1 pancreatic β cells.

To investigate the effects of berberine (BBR) and cinnamic acid (CA), the main active components in Jiaotai Pill (, JTP), on palmitic acid (PA)-induced intracellular triglyceride (TG) accumulation in NIT-1 pancreatic β cells. Cells were incubated in culture medium containing PA (0.25 mmol/L) for 24 h. Then treatments with BBR (10 μmol/L), CA (100 μmol/L) and the combination of BBR and CA (BBR+CA) were performed respectively. Intracellular lipid accumulation was assessed by Oil Red O staining and TG content was measured by colorimetric assay. The expression of adenosine monophosphate-activated protein kinase (AMPK) protein and its downstream lipogenic and fatty acid oxidation genes, including fatty acid synthase (FAS), acetyl-coA carboxylase (ACC), phosphorylation acetyl-coA carboxylase (pACC), carnitine acyl transferase 1 (CPT-1) and sterol regulating element binding protein 1c (SREBP-1c) were determined by Western blot or real time polymerase chain reaction. PA induced an obvious lipid accumulation and a significant increase in intracellular TG content in NIT-1 cells. PA also induced a remarkable decrease in AMPK protein expression and its downstream targets such as pACC and CPT-1. Meanwhile, AMPK downstream lipogenic genes including SREBP-1c mRNA, FAS and ACC protein expressions were increased. Treatments with BBR and BBR+CA, superior to CA, significantly reversed the above genes changes in NIT-1 pancreatic β cells. However, the synergistic effect of BBR and CA on intracellular TG content was not observed in the present study. It can be concluded that in vitro, BBR and BBR+CA could inhibit PA-induced lipid accumulation by decreasing lipogenesis and increasing lipid oxidation in NIT-1 pancreatic β cells.

Effect of Jiaotai pill on pancreatic fat accumulation and islet cell apoptosis in rats with type 2 diabetes

In this study, the rat type 2 diabetes mellitus (T2DM) model was established through tail vein injection with low dose of streptozotocin (STZ) and high fat diet for 8 weeks, and then treated with Jiaotai Pill. The oral glucose tolerance test (OGTT), fasting serum insulin (FINS), free fatty acid(FFA) levels and blood lipid were assayed. HOMA-IR was calculated. Pancreatic pathology was performed. And pancreatic triglyceride (TG) content was examined by the lipid extraction method. Pancreatic islet cell apoptosis were detected by terminal dexynucleotidyl transferase (TdT)-mediated dUTP nick end labeling (TUNEL). According to the results, the model group showed abnormal OGTT, increased FINS, HOMA-IR, FFA, lipid disorder, obvious fat accumulation and significantly increased TG content in pancreatic tissues, and enhanced pancreatic islet cell apoptosis. Compared with the model group, the Jiaotai Pill group displayed improved OGTT, reduced FINS, HOMA-IR, FFA, recovered lipid disorder, decreased fat accumulation and significantly declined TG content in pancreatic tissues, and lowered pancreatic islet cell apoptosis. In summary, Jiaotai pill could effectively treat type 2 diabetes in rats. Its mechanism may be related to the reduction in pancreatic fat accumulation and islet cell apoptosis.

Jiaotai pill (交泰丸) enhances insulin signaling through phosphatidylinositol 3-kinase pathway in skeletal muscle of diabetic rats

To investigate the effect of Jiaotai Pill (, JTP) at different constitutional proportions on insulin signaling through phosphatidylinositol 3-kinase (PI3K) pathway in the skeletal muscle of diabetic rats. The rat model of type 2 diabetes mellitus (T2DM) was established by intravenous injection of a small dose of streptozotoein plus high fat diet feeding. JTP at the same dosage of cinnamon and the increasing dosage of Coptis chinensis was administered to diabetic rats for nine weeks respectively. Plasma glucose and insulin levels were assayed. The expressions of proteins were determined by Western blot method. All the three formulations of JTP decreased plasma glucose and fasting insulin levels as well as increased the protein expressions of insulin receptor β (InsRβ) subunit, insulin receptor substrate-1 (IRS-1), PI3K p85 subunit and glucose transporter 4 (GLUT4) in skeletal muscle. Meanwhile, JTP increased the tyrosine phosphorylation of InsRβ subunit and IRS-1, and reduced the serine phosphorylation of IRS-1 in skeletal muscle. Interestingly, the effect of JTP on improving insulin sensitivity was not dose-dependent. In contrast, JTP containing the least amount of Coptis chinensis exhibited the best effect. JTP at different constitutional proportions attenuates the development of diabetes in a rat model of T2DM. The mechanism might be associated with enhancing insulin signaling through PI3K pathway in the skeletal muscle.

Discussion on concepts of ‘interaction between the heart and the kidney' and‘ non-interaction between the heart and the kidney' in the teaching material of traditional Chinese medicine

There are some problems in the definitions of 'interaction between the heart and the kidney' and 'non-interaction between the heart and the kidney' made in the teaching material of traditional Chinese medicine used by western medicine institutes,colleges and universities.In the teaching material,it explains 'interaction between the heart and the kidney' as the relation between heart fire and kidney water,and 'non-interaction between the beart and the kidney' as the relation between heart-yin and kidney-yin.If we cannot correctly understand the pathogenesis of 'non-interaction between the heart and the kidney',we will fail to determine the concrete treatment method for ' coordinating the heart and the kidney'.Through the analysis and discussion on the theory,clinical syndrome,therapeutic principles and prescriptions for the syndrome of disharmony between the heart and the kidney,the authors draw the conclusion that the therapy for this disease should be determined according to the excess and deficiency of the heat fire and kidney water.For instance,if the deficient kidney water cant ascend to coordinate with the heart and results in exuberance of heart fire,Huanglian Ejiao decoction should be used; in the other situation,if the exuberant heart-fire can't descend to coordinate with the kidney and results in deficiency of kidney yang,Jiaotai Pill should be used.The theoretical results could standardize textbook and give better service to the clinical education. Key words: Interaction between the heart and the kidney; Non-interaction between the heart and the kidney; Coordinating the heart and the kidney

Effects of different compatibility proportion of Jiaotai pills on treating type 2 diabetes mellitus in rats

To study the effects of different compatibility proportion of Jiaotai pills on treating type 2 diabetes mellitus (T2DM) in rats. The model of type 2 diabetes mellitus in rats was established by injecting streptozotocin from tail vein and feeding with high fat and high caloric diet. Diabetic rats were randomly divided into model group, Jiaotai pill 1 group (Coptidis Rhizoma-cinnamon 2: 1), Jiaotai pill 2 group (Coptidis Rhizoma-cinnamon 4: 1), Jiaotai pill 3 group (Coptidis Rhizoma-cinnamon 10: 1) and metformin group. Rats in different treatment groups were given by corresponding therapy from gastric tube. Meanwhile normal control group was another set. Body weight, oral glucose tolerance test (OGTT), blood lipid level including total cholesterol (TC), triglyceride (TG), high density lipoprotein-cholesterol (HDL-C) and low density lipoprotein-cholesterol (LDL-C), plasma levels of free fatty acid (FFA) and adiponectin, plasma liver enzymes activity(ALT, AST, AKP, gamma-GT) and pathological results of liver tissue were determined after eight weeks. Body weight, fasting plasma glucose (FPG), postpradial plasma glucose at one hour (PG-1 h), postpradial blood glucose at two hour (PG-2 h), plasma levels of TC, TG, LDL-C, FFA and liver enzymes activity were all increased in rats of model group compared with those in normal control group. Plasma levels of HDL-C and adiponectin were decreased in model group (P < 0.01). Fatty degeneration of hepatocytes was apparent in liver tissues in rats of model group. Compared with model group results of OGTT, blood lipid levels and liver enzymes activity were improved while levels of HDL-C and adiponectin were increased in rats of different treatment groups (P < 0.05 or P < 0.01). Meanwhile fatty degeneration of hepatocytes was improved in liver tissues in rats of different treatment groups. Compared with metformin group, plasma level of HDL-C was elevated while AKP and gamma-GT were decreased significantly in rats of Jiaotai pill 1 group (P < 0.05), gamma-GT level was decreased significantly in rats of Jiaotai pill 2 group (P < 0.05), AST, AKP and gamma-GT levels were decreased significantly in rats of Jiaotai pill 3 group (P < 0.05). Compared with Jiaotai Pill 1 group, plasma levels of HDL-C was decreased while AKP levels was elevated significantly in rats of Jiaotai pill 2 group, but HDL-C was decreased in rats of Jiaotai pill 3 group (P < 0.05). It is suggested that different compatibility proportion of Jiaotai pills are effective on treating type 2 diabetes mellitus in rats. The effect of Jiaotai pill 1 group is better than that of other therapy groups.

Clinical observation on application of Jiao Tai Pill on Shenque (CV 8) in treating insomnia

Objective To observe the clinical efficacy of application of Jiao Tai Pill on acupoint Shenque (CV 8) in the treatment of insomnia.