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Zishenwan， also known as Tongguanwan， is composed of three herbs：Anemarrhenae Rhizoma， Phellodendri Chinensis Cortex， and Cinnamomi Cortex， which thus is thought to be the representative formula to clear heat， purge fire， nourish Yin， and tonify Qi， and it is often used for treating anuresis and renal arthralgia. In recent years， this formula has become a commonly used combination of herbs and is used to treat diabetes （consumptive thirst disease） diagnosed with "lower consumption" syndrome. This article systematically reviewed the development of traditional Chinese medicine （TCM） theory for Zishenwan. Moreover， based on modern pharmacological research， the previous studies on the components of Zishenwan， the improvement of diabetes-related diseases by Zishenwan， and the relationship between the single herd of Zishenwan and the treatment of diabetes were summarized， and the chemical components and the mechanisms for treating diabetes by the three herbs were discussed. It is found that Zishenwan can alleviate diabetes and diabetic nephropathy by performing anti-inflammation， enhancing insulin sensitivity， and inhibiting pyroptosis of renal tubular epithelial cells. Three herbs in Zishenwan and several components of them， including mangiferin， timosaponins， berberine， jatrorrhizine， cinnamaldehyde， and cinnamic acid can ameliorate diabetes and maintain stable glycometabolism by a variety of mechanisms such as improving insulin resistance in insulin target tissues， suppressing inflammation， anti-oxidation， regulating lipid metabolism， enhancing insulin secretion， and regulating gut microbiota. This review provides a theoretical foundation and reference for subsequent studies on the mechanisms of the anti-diabetic effect of Zishenwan.
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ObjectiveTo explore the effect of Zishenwan on glucose and lipid metabolism in spontaneous type 2 diabetes （db/db） mice and investigate the underlying mechanism for improving diabetes based on intestinal barrier function and skeletal muscle transcriptome sequencing results. MethodLiquid chromatography-tandem mass spectrometry （LC-MS/MS） was used to analyze the components of Zishenwan. Sixteen 6-week-old db/db mice were divided into a model group and a Zishenwan group， while eight wild-type mice were assigned to the normal group. The Zishenwan group received oral administration of drugs for six weeks， during which fasting blood glucose， body weight， and food intake were measured. Serum total cholesterol （TC） and triglyceride （TG） levels were determined， and fasting insulin levels were measured to calculate the homeostatic model assessment of insulin resistance （HOMA-IR）. After the treatment， skeletal muscle and ileum tissues were collected， followed by hematoxylin-eosin （HE） staining. Immunohistochemistry was used to detect the expression of tight junction proteins occludin and zonula occludens-1 （ZO-1） in the ileum. Transcriptome sequencing was performed to detect the skeletal muscle transcriptome， and enrichment analysis was conducted for differentially expressed genes. ResultMultiple active components were identified in Zishenwan. Compared with the normal group， the model group showed increased fasting blood glucose， body weight， TC， TG， and HOMA-IR （P<0.01）. Compared with the model group， Zishenwan significantly reduced fasting blood glucose， body weight， TC， TG， and HOMA-IR in db/db mice （P<0.01）， while there was no statistically significant difference in food intake. Compared with the normal group， the model group exhibited lipid deposition in skeletal muscle， as well as structural changes in the ileum， with significant decreases in the protein expression levels of intestinal occludin and ZO-1 （P<0.01）. Compared with the model group， Zishenwan improved the pathological changes in skeletal muscle and ileum， and increased the protein expression of occludin and ZO-1 in the ileum （P<0.01）. Transcriptome analysis suggested that Zishenwan might improve skeletal muscle metabolism and increase insulin sensitivity in mice. ConclusionZishenwan can improve glucose and lipid metabolism in db/db mice， and this effect may be related to its protection of intestinal barrier function and transcriptional regulation of skeletal muscle metabolism-related genes.
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Diabetic nephropathy （DN） is a serious complication of diabetes， a major risk factor for chronic renal failure and end-stage renal disease， a major cause of deaths of diabetic patients， and a major cause of noncommunicable disease-associated deaths in the world. Pyroptosis and inflammasome activation are closely associated with the occurrence and development of DN. They can mediate a variety of pathological changes such as the loss and fusion of podocytes， up-regulated expression of inflammatory cytokines， macrophage infiltration， glomerular mesangial matrix expansion， and increased urinary albumin-to-creatinine ratio， eventually leading to nephron loss and kidney injury. The available studies have reported that the active ingredients in Chinese medicinal herbs or classical prescriptions play a role in the treatment of DN by lowering blood glucose and lipid levels， mitigating insulin resistance， reducing inflammation， alleviating oxidative stress， and regulating immunity. Moreover， the active ingredients can inhibit the activation of inflammasomes and the pyroptosis of renal cells， repair the inflammation-induced damage， improve renal function， and slow the progression of DN， demonstrating definite therapeutic effect. Chinese medicines can treat DN in a multi-target， multi-pathway， and multi-system manner， possessing broad prospects in the prevention and treatment of DN. Despite the extensive studies about the traditional Chinese medicine （TCM） intervention of DN in vivo and in vitro， a comprehensive summary of experimental studies on the TCM intervention of DN model remains to be carried out. This paper reviews the research progress in pyroptosis， inflammasomes， roles of pyroptosis and inflammasomes in DN， and TCM intervention of DN， aiming to provide ideas and reference for the research and development of drugs for this disease.
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ObjectiveTo investigate the effect of Loulianwan on the gut microbiota of db/db mice with type 2 diabetes mellitus （T2DM）. MethodMale db/m+ mice aged 4-5 weeks were assigned to the normal group， and male db/db model mice of the same age were randomly divided into model group， metformin group （0.25 g·kg-1·d-1）， and Loulianwan group （13 g·kg-1·d-1）， with six mice in each group. Drug intervention lasted five weeks. The body weight， water intake， and fasting blood glucose （FBG） of the mice were recorded every week. After five weeks， the FBG， liver triglyceride （TG）， liver total cholesterol （TC）， glycated serum protein （GSP）， and fasting serum insulin （FINS） were detected， and the insulin resistance index （HOMA-IR） was calculated. The feces in the mouse intestines were collected， and the 16S rRNA sequencing technology was used to detect the structural changes in the fecal gut microbiota of mice in each group. ResultCompared with the normal group， the model group showed increased body weight， water intake， FBG， liver TG， liver TC， GSP， FINS， and HOMA-IR （P<0.01）. Compared with the model group， the Loulianwan group showed reduced water intake， FBG， liver TG， liver TC， GSP， FINS， and HOMA-IR （P<0.01）. The gut microbiota in the Loulian Lills group changed from phylum to genus level. The relative abundance of beneficial bacteria increased and the relative abundance of harmful bacteria decreased. Among them， the abundance of Akkermansia muciniphila， Blautia， Ruminococcus， and Parabacteroides increased （P<0.01）. ConclusionLoulianwan can significantly improve glucose and lipid metabolism in db/db mice with T2DM， and its mechanism may be related to the increase in the abundance of Akkermansia muciniphila， Blautia， Ruminococcus， and Parabacteroides in the intestine.
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Type 2 diabetes mellitus （T2DM） is a chronic metabolic disease characterized by insulin resistance， hyperinsulinemia， and disturbance of glucose and lipid metabolism， with elevated blood glucose as the main clinical manifestation. Due to its complex etiology and pathogenesis， there is no effective treatment， which critically threatens human health and places a heavy burden on society and families. Saponins are a class of glycosides with complex structures that have the advantage of a wide range of sources， elevated safety， and low adverse effects. As an essential active ingredient in Chinese medicine， Chinese medicine saponins have a variety of biological activities such as hypoglycemia， hypoglycaemia， anti-inflammation， antioxidation， anti-tumor， and immune modulation. In recent years， numerous studies have shown that Chinese medicine saponins are effective in preventing and treating T2DM. Although there have been numerous studies on the hypoglycemic effects and mechanisms of Chinese medicine saponins， there has been no systematic review of the mechanisms of Chinese medicine saponins in the treatment of T2DM. Therefore， to provide a theoretical basis for an in-depth study of the hypoglycemic effects of Chinese medicine saponins and a scientific basis for the development and clinical application of drugs， this paper systematically summarized the hypoglycemic mechanisms of Chinese medicine saponins， such as improving islet β-cell function， improving insulin resistance， inhibiting glycosidase activity， reducing the inflammatory response， anti-oxidative stress， and regulating intestinal flora， and analyzed the current research problems and development trends.
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Diabetic kidney disease （DKD）， a major microvascular complication of diabetes mellitus， serves as the most common cause of end-stage renal disease worldwide. The progression of DKD is closely related to oxidative stress， inflammatory response， apoptosis， and fibrosis in renal tissues activated by high glucose. Numerous studies have shown that the transduction of the p38 mitogen-activated protein kinase （p38 MAPK） signaling pathway is involved in the pathological process of DKD in renal tissues， activating various pathological mechanisms， such as oxidation， inflammation， apoptosis， and fibrosis. Therefore， blocking the transduction of the p38 MAPK signaling pathway is beneficial to alleviating DKD. At present， the main treatment principles of western medicine are glucose lowering， lipid lowering， and blood pressure lowering， as well as medications with new drugs renal sodium-glucose co-transporter 2 （SGLT2）， mineralocorticoid receptor， and endothelin receptor， but the progression of DKD still cannot be stopped. The treatment of DKD by traditional Chinese medicine （TCM） has the advantages of simplicity， low cost， and convenience， and the symptoms and root causes can be both treated. In recent years， the basic research on Chinese medicine intervention in DKD has greatly advanced， and p38 MAPK is the key factor of Chinese medicine intervention in DKD. The present study searched and reviewed the literature on the Chinese medicine intervention in the p38 MAPK signaling pathway in DKD treatment in the past decade. The results showed that p38 MAPK interacted with transforming growth factor-β1 （TGF-β1）， cysteinyl aspartate-specific protease-3 （Caspase-3）， nuclear factor-κB （NF-κB）， and other factors to activate fibrosis， inflammation， oxidative stress， and apoptosis. By acting on p38 MAPK and its upstream and downstream factors， Chinese medicine blocked the pathological processes of DKD and inhibited the pathological injury of DKD and the deterioration of renal function. This study is expected to provide new ideas and directions for the prevention and treatment of DKD with Chinese medicine.
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Diabetic peripheral neuropathy （DPN） is a symptom and/or sign of peripheral nerve dysfunction that occurs in patients with diabetes mellitus when other causes are excluded. DPN， one of the most common complications of diabetes mellitus， can lead to disability， foot ulcers， and amputation at a later stage. Its pathogenesis is closely related to high glucose-induced inflammatory damage， oxidative stress， mitochondrial disorders， and apoptosis in neural tissues. The p38 mitogen-activated protein kinase （p38 MAPK） signaling pathway is a key mechanism mediating the expression of inflammatory factors， oxidative factors， and apoptotic factors of neural tissues in DPN. The inflammatory response， oxidative stress damage， and apoptosis， induced by the activation of p38 MAPK phosphorylation by factors such as high glucose， can cause cell lipid peroxidation， protein modification， and nucleic acid damage， which results in axonal degeneration and demyelination changes. The current treatment of DPN with western medicine has obvious shortcomings such as adverse effects and addictive tendencies. In recent years， the research on traditional Chinese medicine （TCM） in the prevention and treatment of DPN has gradually increased， and the exploration of Chinese medicine intervention in the p38 MAPK pathway transduction to improve DPN has advanced. The present study reviewed the relations of the p38 MAPK pathway with insulin resistance and peripheral neuropathy and summarized the molecular biological mechanisms involved in the pathological process of DPN， such as inflammation regulation， oxidative stress， polyol pathway regulation， and Schwann cell apoptosis in the past 10 years. In addition， the literature on Chinese medicine monomers， Chinese patent medicines， and Chinese medicine compounds in inhibiting inflammatory reactions， oxidative injury， and apoptosis of DPN peripheral nerves based on the p38 MAPK pathway， resisting axonal degeneration and demyelination changes， improving sensory and motor abnormalities， relieving peripheral pain sensitization， and facilitating nerve conduction mechanism to provide references for the development of new drugs for clinical prevention and treatment of DPN.
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ObjectiveTo explore the effect of Tangbikang granules （TBK） on sciatic nerve inflammation in diabetic rats through modulation of adenosine monophosphate-activated protein kinase （AMPK）/nuclear factor （NF）-κB pathway. MethodSD rats were fed with high-fat and high-sugar diet for 8 weeks and then treated with streptozotocin （STZ， ip） at 35 mg·kg-1 for modeling. Then the rats were randomized into diabetes group， low-dose （0.625 g·kg-1）， medium-dose （1.25 g·kg-1）， and high-dose （2.5 g·kg-1） TBK groups， and lipoic acid group （0.026 8 g·kg-1） according to body weight and blood glucose level， and a normal group was designed. After modeling， administration began and lasted 12 weeks. The body mass， blood glucose level， and thermal withdrawal latency （TWL） of the rats were detected before treatment and at the 4th， 8th， and 12th week of administration. At the 12th week， the sciatic nerve was collected for hematoxylin-eosin （HE） and Luxol fast blue （LFB） staining， and the structural changes of sciatic nerve were observed under scanning electron microscope. The levels of interleukin-1β （IL-1β） and tumor necrosis factor-α （TNF-α） in sciatic nerve were measured by enzyme-linked immunosorbent assay （ELISA）， and the levels of AMPK， phosphorylated （p）-AMPK， and NF-κB proteins in the sciatic nerve were measured by Western blot. ResultThe blood glucose concentration and TWL in the model group were higher than those in the normal group at each time point （P<0.01）. The levels of IL-1β， TNF-α， and NF-κB protein in sciatic nerve in the model group were higher than those in the normal group （P<0.01）， and the p-AMPK/AMPK ratio was smaller than that in the normal group （P<0.01）. Compared with the model group， TBK of the three doses lowered the TWL （P<0.05， P<0.01） and the levels of IL-1β， TNF-α， and NF-κB protein in sciatic nerve of rats （P<0.05， P<0.01）， and high-dose and medium-dose TBK raised p-AMPK/AMPK （P<0.05， P<0.01）. The sciatic nerve fibers were orderly and compact with alleviation of demyelination in rats treated with TBK compared with those in the model group. ConclusionTBK improves the function of sciatic nerve and alleviates neuroinflammation in diabetic rats. The mechanism is the likelihood that it up-regulates the expression of AMPK in the AMPK/NF-κB pathway and inhibits the expression of downstream NF-κB， thereby alleviating the neuroinflammation caused by high levels of inflammatory factors such as IL-1β and TNF-α due to NF-κB activation.
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ObjectiveTo explore the mechanism of Tangbikang granules （TBK） against diabetic peripheral neuropathy （DPN） based on network pharmacology and in-vivo experiment. MethodThe active components in medicinals of TBK and their target genes were searched from Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform （TCMSP）. The active components of the medicinals which are not included in TCMSP were searched from previous research. After the analysis of drug-likeness by SwissADME， the target genes of them were predicted with SwissTargetPrediction. DPN-related target genes were retrieved from GeneCards. The common targets of the disease and the prescription were the hub genes of TBK against DPN， which were uploaded to Metascape for Gene Ontology （GO） term enrichment and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment analysis. High-sugar and high-fat diet and low-dose streptozotocin （STZ， ip） were employed to induce diabetes in rats， and then the model rats were respectively treated with low-dose （0.625 g·kg-1）， medium-dose （1.25 g·kg-1）， and high-dose （2.5 g·kg-1） TBK for 12 weeks. Sensory nerve conduction velocity （SNCV） was evaluated. After hematoxylin and eosin （HE） staining， the sciatic nerve was observed under light microscope to examine the nerve damage. Real-time PCR was performed to detect the gene expression of adenosine monophosphate-activated protein kinase （AMPK） pathway-related targets in rat sciatic nerve， and Western blot to measure the protein expression of AMPK and phosphorylated （p）-AMPK in rat sciatic nerve. ResultThe main active components of TBK， such as quercetin， kaempferol， β-sitosterol， leech pteridine A， stigmasterol， and baicalein were screened out， mainly acting on interleukin-6 （IL-6）， tumor necrosis factor （TNF）， protein kinase B （Akt）， JUN， and HSP90AA1 and signaling pathways such as AMPK， nuclear factor-κB （NF-κB）， and Janus kinase/signal transducer and activator of transcription （JAK/STAT）. Molecular docking results showed that β-sitosterol and stigmasterol had high binding affinity with IL-6， TNF， JUN， and HSP90AA1. As for the animal experiment， compared with the normal group， model group had low SNCV of sciatic nerve （P<0.01）， disordered and loose myelinated nerve fibers with axonotmesis and demyelinization， low mRNA expression of AMPKα， AMPKβ， peroxisome proliferator-activated receptor γ coactivator-1α （PGC-1α）， Sirtuin 3 （SirT3）， mitochondrial transcription factor A （TFAM）， and low p-AMPK/AMPK ratio in sciatic nerve （P<0.05， P<0.01）. Compared with the model group， TBK of the three doses raised the SNCV （P<0.01）， restored nerve morphology and nerve compactness， and increased the mRNA expression of AMPKα， AMPKβ， PGC-1α， SirT3， and TFAM （P<0.05， P<0.01）. The ratio of p-AMPK/AMPK in the high-dose and medium-dose TBK groups was higher than that in the model group （P<0.01）， while the protein expression in the low-dose TBK group was insignificantly different from that in the model group. ConclusionTBK exerts therapeutic effect on DPN through multiple pathways and targets. The mechanism is that it activates and regulates AMPK/PGC-1α/SirT3 signaling， which lays a basis for further study of TBK in the treatment of DPN.
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ObjectiveThis study aims to investigate the therapeutic effect of Tangbikang granules（TBK） on type 2 diabetes mellitus （T2DM） complicated with non-alcoholic fatty liver disease （NAFLD） and to elucidate the underlying mechanism. MethodT2DM and NAFLD were induced in ZDF rats， which were then respectively treated （ig） with low-dose （0.625 g·kg-1）， medium-dose （1.25 g·kg-1）， and high-dose （2.5 g·kg-1） TBK for 12 weeks. Fasting blood glucose （FBG） and body mass were recorded every 4 weeks during the treatment. One week before sampling， the feed intake of rats was detected， and after 12 h night fasting， oral glucose tolerance test （OGTT） was performed. The area under the curve （AUC） was used to evaluate glucose tolerance， and the homeostatic model assessment for insulin resistance （HOMA-IR） was calculated. Blood in abdominal aorta and liver were collected for determination of blood glucose and lipid metabolism indexes： Fasting serum insulin （FINS）， serum total cholesterol （TC）， triglyceride （TG）， low density lipoprotein cholesterol （LDL-C）， high density lipoprotein cholesterol （HDL-C）， and nonesterified fatty acids （NEFA）. The liver was weighed to calculate the liver index， and the liver tissue morphology was observed and analyzed based on hematoxylin-eosin （HE） staining and periodic acid-Schiff （PAS） staining. The protein levels of insulin receptor substrate （IRS）， phosphatidylinositol 3-kinase （PI3K）， protein kinase B （Akt） and phosphorylated IRS and Akt were detected by Western blotting. All data were analyzed by SPSS 20.0. ResultThe feed intake of the model group was higher than that in the normal group （P<0.01）， and the feed intake the administration groups was lower than that in the model group （P<0.05， P<0.01）. At the 8th and 12th week， the body mass in the model group was lower than that in the normal group （P<0.01）. Compared with the model group， TBK reduced FBG in a concentration-dependent manner. The blood glucose level in OGTT and AUC in the model group were higher/larger than those in the normal group （P<0.01）. The blood glucose value in OGTT was decreased in TBK groups and the metformin group compared with that in the model group， and AUC in the administration groups was significantly different from that in the model group （P<0.01）. The serum level of FINS and HOMA-IR in the model group were higher than those in the normal group （P<0.01）， and they were lower in the TBK groups than in the model group （P<0.01）. Serum levels of TG， TC， HDL-C， NEFA （P<0.05， P<0.01）， and LDL-C were higher in the model group than in the normal group. Serum levels of TG， TC， LDL-C， and NEFA in the TBK groups were lower than those in the model group， and the levels of TG， LDL-C， and NEFA in TBK groups were concentration-dependent （lowest levels in high-dose TBK group）. Compared with the model group， high-dose TBK significantly increased the level of HDL-C （P<0.05）. Liver index of the model group was higher than that in the normal group （P<0.01）. The liver index of the administration groups showed a decreasing trend with no significant difference from that in the model group. As for the HE staining result of liver， the model group had unclear structure of liver lobule， enlarged cells of different sizes， and obvious steatosis of hepatocytes. TBK of all doses alleviated liver injury， particularly the high dose. For the PAS staining， compared with the normal group， the model group demonstrated significant fat vacuoles and significant reduction in purplish red glycogen granules in the cytoplasm. The staining results of high- and medium-dose groups of TBK were more similar to the normal group. Western blot was used to detect the protein expression of liver tissue. The expression of PI3K protein， p-IRS1/IRS1， and p-Akt/Akt in the model group were lower than those in the normal group （P<0.01）， and they were higher in the high-dose TBK group than in the model group （P<0.01）. ConclusionTBK exerts therapeutic effect on T2DM combined with NAFLD in ZDF rats by activating the typical PI3K signaling pathway.
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Diabetic nephropathy （DN）， the most feared microvascular complication of diabetes and one of the most common and serious complications of diabetes， is the major cause of end-stage renal disease worldwide， leading cause of morbidity and mortality in patients with diabetes， and the main non-communicable cause of death worldwide. There are many types of saponins， which are the main bioactive components of various Chinese medicinals. They have various pharmacological activities such as lowering blood glucose and blood lipids， improving insulin resistance， anti-inflammation， anti-oxidative stress， anti-tumor， and immune modulation. In recent years， it has been frequently verified that the saponins in Chinese medicinals have definite effect in regulating DN， showing multi-target， multi-pathway， multi-system， multi-effect characteristics. Thus， they have broad prospects in the prevention and treatment of this disease. There has been an explosion of research on the treatment of DN with saponins in Chinese medicinals in vivo and in vitro， but there is a lack of systematic and comprehensive summary. Therefore， this study summed up the studies of saponins in Chinese medicinals in the intervention of DN and summarized the mechanisms such as improving glucolipid metabolism， inhibiting oxidative stress， anti-inflammation， anti-apoptosis， regulating autophagy， anti-fibrosis， and protecting podocytes， with a view to providing ideas and references for the development of drugs related to DN.
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ObjectiveTo observe the effects of the water extracts of Trichosanthis Radix-Polygonati Rhizoma at different ratios on glucose and lipid metabolism in KKAy mice with spontaneous type 2 diabetes and explore the mechanism of the extract in alleviating insulin resistance based on phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt）/forkhead box O1 （FoxO1） signaling pathway. MethodThe 8-week-old C57BL/6J male mice were taken as the normal control group， and KKAy male mice of the same age were randomly assigned into a model group， a metformin group， Trichosanthis Radix-Polygonati Rhizoma groups at the ratios of 1∶1 （Trichosanthis Radix 30 g， Polygonati Rhizoma 30 g）， 1∶3 （Trichosanthis Radix 15 g， Polygonati Rhizoma 45 g）， and 1∶5 （Trichosanthis Radix 10 g， Polygonati Rhizoma 50 g） according to blood glucose level and body weight， with 6 mice in each group. The administration lasted for 8 weeks， and the body weight （BW） and fasting blood glucose （FBG） of mice were recorded at the same time points of the 2nd， 4th， 6th， and 8th weeks， respectively. Oral glucose tolerance test （OGTT） was performed at the 7th week. After drug administration， the serum levels of total cholesterol （TC）， triglyceride （TG）， low-density lipoprotein cholesterol （LDL-C）， high-density lipoprotein cholesterol （HDL-C）， and fasting insulin （FINS） were measured， and homeostasis model assessment-insulin resistance （HOMA-IR） index was calculated. The liver tissue samples were stained with hematylin-eosin （HE） and periodic acid-Schiff （PAS） for observation of the fat distribution and glycogen content. The protein levels of PI3K， Akt， p-Akt， FoxO1， and p-FoxO1 in the liver were determined by Western blot. ResultCompared with the normal group， the model group showed increased food intake， FBG， glucose tolerance， FINS， HOMA-IR， TC， TG， and LDL-C （P<0.01）， and down-regulated protein levels of PI3K， Akt， phosphorylaison （p）-Akt， FoxO1， and p-FoxO1 in the liver （P<0.01）. Compared with the model group， Trichosanthis Radix-Polygonati Rhizoma lowered FBG and HOMA-IR （P<0.05， P<0.01）. In particular， the combination at the ratio of 1∶3 showed the best performance （P<0.01） comparable to metformin. Furthermore， Trichosanthis Radix-Polygonati Rhizoma at different ratios lowered blood glucose at different time points of OGTT （P<0.05） and TC and LDL-C （P<0.01）. Additionally， the combination at the ratio of 1∶3 reduced TG （P<0.01）. The liver of mice in the drug administration groups showed regular morphology， with few lipid droplets and rich glycogen. Western blot showed that Trichosanthis Radix-Polygonati Rhizoma up-regulated the protein levels of PI3K and p-Akt， down-regulated the protein level of FoxO1， and up-regulated the protein level of p-FoxO1 （P<0.05）. ConclusionTrichosanthis Radix-Polygonati Rhizoma， especially at the ratio of 1∶3， lowered the FBG， TC， LDL-C， and HOMA-IR index， promoted liver glycogen synthesis， and reduced steatosis in KKAy mice， which may be related to the regulation of PI3K/Akt/FoxO1 signaling pathway in the liver.
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Objective:To observe the clinical effects of Traditional Chinese Medicine (TCM) Tangnaikang granules, supplementing to conventional treatment methods, on type 2 diabetic foot ulcer.Methods:A total of 67 patients, from Beijing University of Chinese Medicine subsidiary Dongfang Hospital, Tuanjie Lake Community Health Service Center, Qingta Community Health Service Center between August, 2019 and November, 2020 were assigned to treatment group (37 patients) and control group (30 patients) using sealed envelope randomization method. The control group underwent conventional treatment methods that manage blood sugar and treat infections. The treatment group received, in addition to the conventional treatment methods administered to the control group, Tangnaikang granules. Both groups were continuously treated for 90 days. The TCM symptom scores, granulation tissue scores, visual analogue scale (VAS), itching scores and Generic Quality of Life Inventory-74 (GQOL-74) score, wound area were observed pre- and post-treatment. The ELISA kits were used to detect the Vascular Endothelial Growth Factor (VEGF), Epidermal Growth Factor (EGF), Basic Fibroblast Growth Factor (bFGF), fasting blood glucose level, glycated hemoglobin test (HbA1c), fasting insulin level, postprandial 2 hour insulin level, insulin resistance index. And all possible adverse events were noted. The overall clinical treatment effects and TCM symptom treatment effects were assessed.Results:Total effective rate for the treatment group 89.2% (33/37), was significantly different from that of the control group 70.0% (21/30) with χ2=3.90 and P<0.01. The TCM symptom effective rate was 86.5% (32/37) for the treatment group and 63.3% (19/30) for the control group. The difference was statistically different with χ2=4.88 and P<0.01. After treatment, whole blood viscosity, plasma viscosity, fibrinogen and erythrocyte sedimentation rate (ESR) of the treatment group were significantly improved than those of the control group ( t=-23.38, -8.01, 18.10, -18.93,all Ps<0.01). The ulcer closure area (5.43±1.65 cm 2vs. 4.65±1.14 cm 2, t=2.20) and ulcer closure area percentage (59.14%±3.37% vs. 42.42%±3.21%， t=20.63) were statistically different of both groups ( P<0.05 or P<0.01). The VEGF, EGF, and bFGF at 90 day of the treatment group were significantly higher than those of the control group ( t=3.19, 40.59, 28.53, all Ps<0.01). The post-treatment fasting blood glucose level, insulin resistance index of the treatment group were significantly lower than those of the control group ( t=-8.55, -21.38, all Ps<0.01). TCM symptoms of thirsty, feverish sensation in chest, palms and soles in the treatment group were significantly improved than the control group ( χ2=4.38, 4.48, all Ps<0.01). Conclusion:TCM compound Tangnaikang granules can relieve diabetic foot ulcer, reduce wound healing time and improve overall treatment outcome, when it was combined of the conventional treatment.
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ObjectiveTo investigate the effect of Chuanshanlong granule on Toll-like receptor 4 （TLR4）/myeloid differentiation protein 88 （MyD88）/nuclear transcription factor -κB （NF-κB） signaling pathway， and to explore the mechanism of its treatment of autoimmune thyroiditis （AIT） in rats. MethodForty AIT models were established following excess iodine and injection of porcine thyroglobulin and Freund's adjuvant into Lewis rats for six weeks. Then the rats were randomly divided into the model group， Chuanshanlong granule low-， medium- and high-dose group （0.52， 1.03， 2.06 g·kg-1·d-1）， with ten in each group. Rats in the Chuanshanlong granule low-， medium- and high-dose groups were separately given 0.01 mL·g-1·d-1 Chuanshanlong granule， and those in the normal group and the model group were given the same volume of deionized water for eight weeks. Serum of rats was taken to measure thyroglobulin antibody （TgAb） and thyroid peroxidase antibody （TPOAb） by enzyme-linked immunosorbent assay （ELISA）， and the concentrations of free triiodothyronine （FT3）， free thyroxine （FT4） and thyroid stimulating hormone （TSH） were detected. The rat thyroid lobes were stained with hematoxylin and eosin （HE）， and the pathological changes were observed under light microscope. In addition， the relative expression of TLR4， MyD88， NF-κB protein and mRNA was determined by immunohistochemistry and real-time polymerase chain reaction （Real-time PCR）. ResultCompared with the conditions in the normal group， the serum concentrations of TPOAb and TgAb （P<0.01） and FT3 and FT4 （P<0.01） increased and TSH decreased （P<0.01） in the model group. Compared with the conditions in the model group， the concentrations of TPOAb and TgAb in the Chuanshanlong granule treatment groups reduced （P<0.01）， and the concentrations of FT3 and FT4 were lowered （P<0.01） while TSH increased （P<0.01） in the Chuanshanlong granule high-dose group. HE staining showed that there was lymphocyte infiltration in the thyroid follicular space， a large number of destroyed or diminished follicular cavities， decreased colloid content， and thinned or destroyed follicular wall in the model group， while the thyroid lymphocyte infiltration in the Chuanshanlong granule treatment groups was significantly less and the structure of thyroid follicles was more complete than those in the model group. Compared with the normal group， the model group had up-regulated relative expression of TLR4， MyD88 and NF-κB protein （P<0.01） and mRNA （P<0.01）. Compared with the model group， the Chuanshanlong granule high-dose group had down-regulated relative expression of TLR4 protein and mRNA （P<0.05）， MyD88 protein （P<0.01） and mRNA （P<0.05）， and NF-κB protein and mRNA （P<0.01）. ConclusionChuanshanlong granule may play a therapeutic role in AIT by inhibiting the activation of TLR4/MyD88/NF-κB signaling pathway.
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Objective To evaluate the safety limits of amygdalin in the Chinese patent medicines and Chinese herbal medi-cines,so as to provide reference for establishing the standard in the safety limits of endogenous cyanide glycosides as toxic ingredients. Methods The toxicity differences between D-amygdalin and L-amygdalin were explored by CCK-8 assay. The daily safe dose of amyg-dalin was deduced by the no-observed-adverse-effect level(NOAEL)of cyanide. Based on the deduced results,the safety limits of amygdalin in thirty-six Chinese patent medicines and three different kinds of Chinese herbal medicine were calculated. Results The half maximal inhibitory concentration of D-amygdalin and L-amygdalin was(3.5±2.0)and(6.6±0.4)mmol/L,respectively,and the daily safe dose of amygdalin was 104.30 mg. Conclusion The toxicity of D-amygdalin was approximately two times that of L-amygda-lin. To establish the safety limits of amygdalin,the sum content of the epimer could be regarded as the D-amygdalin itself to enlarge the safety scope. The content of amygdalin of three Chinese patent medicines was determined to exceed the maximum safety limit for all measured batches,indicating some kind of safety risk. Moreover,in the researches on safety limit establishment,the toxicity-alleviat-ed processing effect should be included.
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Diabetes is the general chronic metabolic disease,with chronic hyperglycemia as the main clinical characteristic.Proteomics discusses and explores the pathogenesis of diabetes more deeply from the overall level of proteins,which has been frequently applied in Chinese medicine research.This paper summarized proteomics application in the study of Chinese medicine intervening diabetes mellitus,including screening and verification of proteomics in Chinese medicine syndromes of diabetes and its complications,as well as proteomics analysis of pharmacological mechanism of related Chinese medicine.This paper also prospected its outlook,in hope toprovide new clues and basis for the pathogenesis theory of diabetes in traditional Chinese medicine (TCM) and functioning targets,and to deepen research on Chinese medicine intervening diabetes.
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Objective To investigate the portal vein embolization (PVE) and portal vein ligation (PVL) in liver regeneration of rats with hepatic fibrosis.Methods Fifty rats with liver fibrosis were prepared,including 10 rats were randomly chosen as pre-operative control group.The other 40 rats were divided into two groups:PVE group (A1,n =20) and PVL group (A2,n =20).We chose to embolize and ligate the right portal vein,respectively.The blood samples were obtained at different end points for measuring ALT and AST levels.Each liver lobes and whole liver were weighed,and non-embolized liver lobe/whole liver weight ratio,non-ligated liver lobe/whole liver weight were caculated at different end points.The samples from liver with/without embolization or ligation were were stained with hematoxylin-eosin,and the changes of microstructure of liver were observed.Immunostained for PCNA and Ki-67 were performed.Results Transient elevation of postoperative ALT and AST levels were noted in each group.Serum ALT and AST reached the peak on the first day in both of PVE and PVL groups [ALT,A1 (66.5 ±6.3) U/L vs(491.5 ± 48.0) U/L,A2 group(62.8 ±5.7) U/L vs(433.7 ±41.0) U/L;AST,A1group (113.4 ± 12.5) U/L vs (685.2 ±65.7) U/L,A2 group (110.4 ± 11.1) U/L vs(623.9 ±75.2) U/L,P＜0.05),and started to decrease on the third day,recovered to the pre-operative level on the fourteenth day (P ＞ 0.05).The weight percentage of non-embolized and non-ligated liver lobes/whole liver after PVE and PVL increased.There was no significant difference between the first day and pre-operative levels (P ＞ 0.05).Nevertheless,there were significant differences observed from the third,seventh,fourteenth days (A1 group,50.2 ± 5.0,57.7 ±5.7,61.8 ±6.6;A2group,49.6 ±3.5,55.7 ±6.9,63.0±5.1,respectively)compared with preoperative groups (A1 group,34.4 ± 4.0;A2 group,34.4 ± 4.0) (P ＜ 0.05).There was no significant difference between group A1 and A2 in each time point (P ＞0.05).The PCNA and Ki-67 were positive in hepatocytes and increased after operation,reached the peak in the third day (P ＜ 0.05),decreased slowly and restored to the normal level in the fourteenth day after operation,meanwhile,there was no significant difference between group A1 and A2 (P ＞ 0.05).Conclusions Fibrosis rats had the ability of regeneration in the contralateral part of the liver after selective PVE and PVL and there was no significant difference on the proliferative degree.Therefore,the safety and reliability of PVE and PVL in inducing liver regeneration in rats with liver fibrosis were confirmed.
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This study was aimed to observe the effects of gymnema sylvestre total saponins (GA) on insulin resistance (IR) in adipose tissues of KKay mice,in order to discuss the action mechanism from the PI3K/AKT signal transduction pathway.A total of 27 KKay mice were randomly divided into the model group (DM),Pioglitazone group (BG) and GA group.Nine normal C57BL/6J mice were used as the normal control group (NC).Intragastric administration of drugs was given for eight weeks.The bodyweight and food intake of all mice were tested each week.After the experiment was completed,fasting plasma insulin (Fins) and fasting plasma glucose (FPG) were detected and the insulin sensitive index (ISI) was calculated.Expressions of PDK-1,AKT,P-AKT (Ser473),P-AKT (Thr308) in adipose tissues of epididymis in mice were detected.And expressions of PI3K-p85 mRNA,PTEN mRNA,APN mRNA were also measured.The results showed that compared with DM group,bodyweight of BG and GA groups were decreased (P＜0.05,P＜0.05);FPG and Fins level of BG and GA groups were decreased (P＜0.05,P＜0.05,P＜0.05,P＜0.05),ISI increased (P＜0.05,P＜0.05);APN mRNA increased in BG and GA group (P＜0.01,P＜0.01);PI3K-p85 mRNA increased in GA group (P＜0.05);P-AKT (Thr308) protein expression increased in BG and GA group (P＜0.05,P＜0.01);P-AKT (Ser473) protein expression increased in GA group (P＜0.05);the phosphorylation of AKT (Thr 308) was enhanced in BG and GA group (/9＜0.01,P＜ 0.01);the phosphorylation of AKT (Ser473) was enhanced in GA group (P＜0.01,P＜0.01).PDK-1 protein expression was decreased in BG and GA group (P＜0.05);PTEN mRNA decreased in BG and GA group (P＜0.05,P＜0.01).It was concluded that GA can ameliorate IR by sensitizing PI3κ/AKT signal pathway in adipose tissues of KKAy mice.
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Sibiraea angustata belongs to the Rosaceae family and it is widely disturbed in Qinghai,Sichuan,Gansu,Yunnan and Tibet.It is one of the commonly used Tibetan medicines.Sibiraea angustata is rich in triterpenes,organic acids,organic esters,alkanes,and etc.And studies showed that Sibiraea angustata has various medicinal effects,such as regulating the metabolism of glucose and lipid,reducing body weight,anti-oxidation,modulating the immune system,liver-protection,anti-tumor,anti-aging,antibacterial activities,and promoting digestion.
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Objective To establish the HPLC fingerprints of Tangbikang Granules; To scientifically evaluate and effectively control the quality of Tangbikang Granules; To ensure its production stability. Methods HPLC was performed on the column of Germany Merck RP-18 endcapped (250 mm × 4.6 mm, 5 μm) with mobile phase of acetonitrile-0.1% formic acid water; column temperature was 40 ℃; flow rate was 1.0 mL/min; detection wavelength was 240 nm; volume injection was 20 μL. Fingerprint Similarity Evaluation Software (edition 2004A) of Chinese Pharmacopoeia Commission was used to evaluate the similarity of the 10 batches of Tangbikang Granules, and to analyze the correlations of 9 ingredients in Tangbikang Granules. Results Wogonoside was used as the reference peak, and the common mode for the HPLC fingerprints was set up. The similarities of the 10 batches of Tangbikang Granules were above 0.930, and altogether 25 common peaks in the chromatograms were found, of which 18 peaks were assigned to Chinese materia medica in Tangbikang Granules. Conclusion The method has good separability and is accurate and simple, which can provide references for the quality control of Tangbikang Granules.