Mechanisms of Chinese Medicine in Gastroesophageal Reflux Disease Treatment: Data Mining and Systematic Pharmacology Study.

OBJECTIVE: To identify specific Chinese medicines (CMs) that may benefit patients with gastroesophageal reflux disease (GERD), and explore the action mechanism. METHODS: Domestic and foreign literature on the treatment of GERD with CMs was searched and selected from China National Knowledge Infrastructure, China Science and Technology Journal Database, Wanfang Database, and PubMed from October 1, 2011 to October 1, 2021. Data from all eligible articles were extracted to establish the database of CMs for GERD. Apriori algorithm of data mining techniques was used to analyze the rules of herbs selection and core Chinese medicine formulas were identified. A system pharmacology approach was used to explore the action mechanism of these medicines. RESULTS: A total of 278 prescriptions for GERD were analyzed, including 192 CMs. Results of Apriori algorithm indicated that Evodiae Fructus and Coptidis Rhizoma were the highest confidence combination. A total of 32 active ingredients and 66 targets were screened for the treatment of GERD. Enrichment analysis showed that the mechanisms of action mainly involved pathways in cancer, fluid shear stress and atherosclerosis, advanced glycation end product (AGE), the receptor for AGE signaling pathway in diabetic complications, bladder cancer, and rheumatoid arthritis. CONCLUSION: Evodiae Fructus and Coptidis Rhizoma are the core drugs in the treatment of GERD and the potential mechanism of action of these medicines includes potential target and pathways.

Progress in Treatment of Gout Using Chinese and Western Medicine.

Gout is a crystal-related arthropathy resulting from the deposition of monosodium urate. Identifying appropriate treatments and novel drugs to decrease serum uric acid (SUA) levels and gout risk has been a major focus. By performing extensive literature review on the pathogenesis and Chinese and Western medicine treatment of gout, this paper aimed to identify novel targets for effective control of acute gout attacks and long-term reduction of SUA. In addition, we aimed to provide new directions for the improvement of therapeutic measures and the development of drugs. Although Western medicine can significantly contribute to the treatment of gout, Chinese herbal medicine has unique advantages, including reduced adverse reactions and higher patient compliance. It may also fill in the shortcomings of Western medicine in the intermittent period treatment of gout. In addition to constantly exploring pathogenesis and drug targets, research on Chinese herbal medicine is equally important. The combination of Chinese and Western medicine has proven to become an important direction for gout treatment.

[Effect of Huazhuo Jiedu formula on HIF-1α, VEGF, and PTEN in chronic erosive gastritis patients with syndrome of accumulation of turbidity and toxicity].

To observe the clinical efficacy of Huazhuo Jiedu formula in treating chronic erosive gastritis (CEG) patients with syndrome of accumulation of turbidity and toxicity, explore its mechanism by observing the changes in expression levels of hypoxia inducible factor (HIF-1α), vascular endothelial growth factor (VEGF) in serum and gastric mucosa tissues after treatment, and provide theoretical basis for the clinical application of Huazhuo Jiedu formula in treating chronic erosive gastritis. All 70 patient of CEG were randomly divided into control group and treatment group, 35 cases in each group. The patients in control group received Alatan Wuwei Wan, bid, 1 bag/time; while the patients in treatment group were given with Huazhuo Jiedu formula, 1 dose/day. The course of the treatment was 6 months in both groups. The changes in clinical symptoms, gastroscopic signs, pathology and the expression levels of HIF-1α, VEGF, and phosphatase and tensin homolog deleted on chromosome ten (PTEN) in serum and gastric mucosa tissues were observed in both groups. The results showed that treatment group was better than control group in clinical efficacy, gastroscopic efficacy and pathological effect after treatment (P<0.05); the levels of HIF-1α and VEGF in serum of treatment group were lower than those in the control group after treatment (P<0.05), while the level of PTEN in serum of treatment group was higher than that in the control group after treatment (P<0.05); the levels of HIF-1α and VEGF in gastric mucosa tissues in the treatment group were lower than those in the control group after treatment, while the level of PTEN in gastric mucosa tissues in treatment group was higher than that in the control group after treatment (P<0.05), with statistically significant differences between these two groups (P<0.05). Huazhuo Jiedu formula can improve the clinical symptoms, gastroscopic signs and pathological conditions in CEG patients with syndrome of accumulation of turbidity and toxicity, and the mechanism may be associated with decreasing the expression level of HIF-1α, VEGF and increasing the expression level of PTEN.

[Correlation Research on HGF and c-Met of Chronic Erosive Gastritis Patients].

Objective To observe the correlation of hepatocyte growth factor (HGF) and Hepato- cyte growth factor receptor (c-Met ) in serum and gastric mucosa tissues of chronic erosive gastritis pa- tients. Methods Totally 70 patients with chronic erosive gastritis were selected and assigned to turbidity toxin intrinsic syndrome group and Gan-wei disharmony syndrome group, HGF expression level of ser- um,and HGF,c-Met expression level of gastric mucosa tissues were measured;the correlation of HGF and c-Met in gastric mucosa tissues, and the correlation of HGF in serum and gastric mucosa tissues were analyzed. Results The expression level of HGF and c-Met in turbidity toxin intrinsic syndrome group was higher than that in Gan-wei disharmony syndrome group (P <0. 05) ; the expression level of HGF in gastric mucosa tissues was positively correlated with c-Met(r =0. 831 , P <0. 05) ; the expression level of HGF in serum was positively correlated with that of gastric mucosa tissues(r =0. 656, P <0. 05). Conclusions There was correlation between turbidity toxin intrinsic syndrome of Chronic Erosive Gastri- tis patients and the expression level of HGF and c-Met.

Combined chromium and magnesium decreases insulin resistance more effectively than either alone.

BACKGROUND AND OBJECTIVES: Peroral supplementation with trivalent-chromium (Cr) or magnesium (Mg) has been shown to improve insulin resistance (IR). The objective of this study was to determine whether combined peroral supplementation with Cr and Mg improves IR more effectively than Cr or Mg alone. METHODS AND STUDY DESIGN: Subjects (n=120, age range 45-59 years old) and diagnosed with IR were randomly divided into four groups and monitored for a period of 3 months: group 1 (the placebo control group), group 2 (160 µg/d Cr), group 3 (200 mg/d Mg), and group 4 (160 µg/d Cr plus 200 mg/d Mg). Fasting blood glucose (FBG), fasting insulin (FIns), erythrocyte Cr and Mg content, and glucose-transporter-4 (GLUT4) and glycogen-synthase-kinase-3ß (GSK3ß) mRNA levels in activated T-lymphocytes were measured, and insulin resistant index (IRI) was calculated. RESULTS: Significant decreases between the baseline and study conclusion values of FBG (0.37 mmol/L, p<0.01), FIns (2.91 µIU/mL, p<0.01) and IRI (0.60, p<0.01) were observed in group 4, but not groups 1-3. Similarly, compared with baseline, significant changes in GLUT4 (2.9-fold increase, p<0.05) and GSK3ß (2.2-fold decrease, p<0.05) mRNA levels in activated T-lymphocyte were observed at the study's conclusion in group 4, but not in groups 1-3. CONCLUSIONS: Our results indicate that combining peroral supplementation with Cr and Mg improves IR more effectively than Cr or Mg alone, and this may be attributable to increased induction and repression, respectively, of GLUT4 and GSK3ß expression.

Effect of sodium alginate addition to resveratrol on acute gouty arthritis.

OBJECTIVE: Resveratrol has been shown to exert anti-inflammatory and antioxidant effects, while sodium alginate is a common pharmaceutic adjuvant with antioxidative and immunomodulatory properties. We performed an animal study to investigate the effect of sodium alginate addition to resveratrol on acute gouty arthritis. METHODS: Twenty-four SPF Wistar mice were randomized to four groups receiving the combination of sodium alginate and resveratrol, resveratrol alone, colchicine, and placebo, respectively. Acute gouty arthritis was induced by injection of 0.05 ml monosodium urate (MSU) solution (25g/mL) into ankle joint cavity. IL-1ß, CCR5, and CXCL10 levels in both serum and synovial fluid were measured using ELISA. NLRP3 expression in the synovial tissues was measured using western plot. RESULTS: The combination of sodium alginate and resveratrol significantly reduced synovial levels of IL-1ß, CCR5, and CXCL10 when compared with colchicines, and all P values were less than 0.0001. The combination of sodium alginate and resveratrol was also superior to resveratrol in terms of both serum levels and synovial levels of IL-1ß, CCR5, and CXCL10. In addition, resveratrol, with or without sodium alginate, could reduce NLRP3 expression obviously in the synovial tissues. CONCLUSION: The combination of sodium alginate and resveratrol has better effect over colchicines in treating MSU-induced acute gouty arthritis.

[Study on correlation of glucagons, type 2 diabetes and impaired glucose regulation].

OBJECTIVE: To analyze the changes of patients with type 2 diabetes in different stages in glucagon (GC) and free fatty acid (FFA) in fasting, OGT and L-Arg experiments, and discusses the role of pancreatic alphabeta cells in diabetes pathogenesis by studying the relations among indexes such as glucagon (GC), free fatty acid (FFA) and blood glucose (BG), insulin, insulin homeostasis model (HOMA) and glucose metabolism hormone secretion curve, in order to provide theoretical basis for the treatment of diabetes. METHOD: Study objects were divided into the T2DM group (45 cases), the IGT group (28 cases) and the NGT group (30 cases) for an OGTT experiment and then an L-Arg experiment on the next day. Under the fasting state, their blood glucose (FBG), insulin (F), glucagon (FGC), free fatty acid (FFA) were detected to calculate HOMA-beta, insulin sensitivity index (ISI) and HOMA-IR of different groups. Meanwhile, efforts were made to calculate different time quantum detected in OGTT and L-Arg experiments and area under the curve AUC(BG), AUC(INS) and AUC(GC). RESULT: Obvious overall differences were observed in FFA and FGC of the three groups. FGC of each group was negatively correlated with HOMA-beta and ISI. Among all of the 103 study objects, FGC was positively correlated with FBG and HOMA-IR and negatively correlated with HOMA-beta and ISI, with no correlation with FINS; FFA was positively correlated with FBG, HOMA-IR and negatively correlated with FINS, HOMA-beta, ISI. FGC and FFA were positively correlated in the T2DM group and the IGT group, but with no statistical correlation in the NGT group. The sequence of the three study objects was T2DM > IGR > NGT in AUC(GC) in the OGTT experiment and T2DM > IGR > NGT in in AUC(GC) in the L-Arg experiment, with the significant positive correlation between AUC(GC) and AUC(BG) and significant negative correlation with AUC(INS). CONCLUSION: Glucagon and free fatty acid of T2DM and IGT patients increased, which was positively correlated with blood glucose and HOMA-IR and negatively correlated with INS, HOMA-beta and ISI. The increase in glucagons of T2DM and IGT patients indicated inappropriate secretion of pancreatic alphabeta cells among patients with type 2 diabetes.

[Effect of huazhuo jiedu hewei recipe on the mechanism of angiogenesis in precancerous lesions of gastric cancer rats].

OBJECTIVE: To explore the possible angiogenesis mechanism of Huazhuo Jiedu Hewei Recipe (HJHR) in preventing and treating precancerous lesions of gastric cancer (PLGC). METHODS: Totally 66 Wistar rats were randomly divided into 6 groups, i.e., the normal control group, the model group, the retinoic acid (RA) group, the high dose HJHR group, the middle dose HJHR group, the low dose HJHR group, 11 in each group. PLGC model was duplicated by inserting a spring with Helicobacter. Corresponding medicines were administered to rats in each medicated group once daily by gastrogavage, 2 mL each time for 12 successive weeks. The effect of HJHR on hypoxia induced factor (HIF-1alpha) and vascular endothelial growth factor (VEGF) of PLGC in chronic atrophic gastritis (CAG) rats' gastric mucosa was observed by immunohistochemical assay and Western blot method. RESULTS: Compared with the normal control group, the expression of VEGF and HIF-1alpha increased in the model group (P < 0.05). Compared with the model group, the expression of VEGF and HIF-1alpha decreased in each medicated group (P < 0.05). Besides, they were lower in the high and middle dose HJHR groups than in the RA group and the low dose HJHR group (P < 0. 05). There was no statistical difference between the low dose HJHR group and the RA group (P > 0.05). CONCLUSION: HJHR could prevent and treat PLGC of CAG rats possibly through decreasing the expression of HIF-1alpha and VEGF in a dose-dependent manner.

Acute neuroprotective effects of extremely low-frequency electromagnetic fields after traumatic brain injury in rats.

Traumatic brain injury commonly has a result of a short window of opportunity between the period of initial brain injury and secondary brain injury, which provides protective strategies and can reduce damages of brain due to secondary brain injury. Previous studies have reported neuroprotective effects of extremely low-frequency electromagnetic fields. However, the effects of extremely low-frequency electromagnetic fields on neural damage after traumatic brain injury have not been reported yet. The present study aims to investigate effects of extremely low-frequency electromagnetic fields on neuroprotection after traumatic brain injury. Male Sprague-Dawley rats were used for the model of lateral fluid percussion injury, which were placed in non-electromagnetic fields and 15 Hz (Hertz) electromagnetic fields with intensities of 1 G (Gauss), 3 G and 5 G. At various time points (ranging from 0.5 to 30 h) after lateral fluid percussion injury, rats were treated with kainic acid (administered by intraperitoneal injection) to induce apoptosis in hippocampal cells. The results were as follows: (1) the expression of hypoxia-inducible factor-1α was dramatically decreased during the neuroprotective time window. (2) The kainic acid-induced apoptosis in the hippocampus was significantly decreased in rats exposed to electromagnetic fields. (3) Electromagnetic fields exposure shortened the escape time in water maze test. (4) Electromagnetic fields exposure accelerated the recovery of the blood-brain barrier after brain injury. These findings revealed that extremely low-frequency electromagnetic fields significantly prolong the window of opportunity for brain protection and enhance the intensity of neuroprotection after traumatic brain injury.

[Effects of Shengqi Jiangtang Granule on rat model of insulin resistance and its mechanism].

OBJECTIVE: To study the effect of Shengqi Jiangtang Granule (SJG) on rat model of insulin resistance (IR) and explore the mechanism. METHODS: IR model was induced by high fat diet and peritoneal injection of streptozotocin in Wistar rats. Model rats were randomly divided into the model group, the low, medium and high dose SJG groups treated with corresponding dose of SJG, and thc RGL group with rosiglitazone (RGL). A normal control group was also set up. Blood glucose (BG), protein expression of endothelin-1 (ET-1) and protein kinase C (PKC) in aortic tissue were detected. RESULTS: BG decreased in the high and medium dose SJG groups and the RGL group after treatment, and the lowest level was shown in the high dose SJG group. Compared with that in the normal group, the expressions of ET-1 and PKC obviously increased in the model group (P<0.05), which was lowered in the RGL group and the high and medium dose SJG groups after treatment in a dosage-depending manner, showing significant difference to those in the model group (P < 0.05). CONCLUSION: SJG can lower blood glucose and inhibit ET-1 and PKC expressions to improve vascular endothelial function, thus to promote insulin sensitiveness and alleviate IR.

[Study on effects of low frequency pulse plus auricular point magnetic therapy on electrogastrogram and clinical therapeutic effect in the patient of functional dyspepsia].

OBJECTIVE: To compare therapeutic effects of low frequency pulse plus auricular point magnetic therapy and prepulsid on functional dyspepsia (FD). METHODS: Fifty cases of FD were randomly divided into a treatment group and a control group. The treatment group were treated with low frequency pulse stimulation on Zhongwan (CV 12), Weishu (BL 21), Neiguan (PC 6), Zusanli (ST 36), with Fenglong (ST 40) and Sanyinjiao (SP 6) selected according to syndrome differentiation, once a day, 30 min each session. The control group were treated with oral administration of prepulsid. Five days constituted one course. The scores of symptoms and parameters of electrogastrogram (EGG) before and after treatment and the therapeutic effect were investigated. RESULTS: After treatment, the symptom scores significantly decreased (P < 0.01), with a significant difference in the decrease of symptom scores between the two groups (P < 0.05); and EGG parameters were improved (P < 0.05). The total effective rate of 93.3% in the treatment group was better than 75.0% in the control group with a significant difference between the two groups (P < 0.05). CONCLUSION: Low frequency pulse plus auricular point magnetic therapy can significantly improve the clinical symptoms and gastric activities in the patient of FD, with a better therapeutic effect than prepulsid.

[Effects of tonifying shen recipe on advanced glycation end products, amyloid-beta peptide in telencephalon and hippocampus of ovariectomized rats].

OBJECTIVE: To explore the effect of Tonifying Shen recipe (TSR) on advanced glycation end products (AGEPs), amyloid-beta peptide (A beta P) in telencephalon and hippocampus of ovariectomized rats. METHODS: Female SD rats, 9 months old, were randomly divided into 3 groups: the sham operation (Sh) group, the ovariectomized (OV) group and the TSR group. Medication via gastrogavage 4 weeks was given after ovariectomy consecutively for 16 weeks. Competitive ELISA and radioimmunoassay (RIA) was used to detect AGEPs and A beta P level in rats' telencephalon and hippocampus; florescent assay was used to determine the serum and urinary soluble AGE-peptide level; and also the rats' behavioral alteration and hippocampal morphological change were observed. RESULTS: Compared with those in the Sh group, the correct escape rate in the OV group was significantly lower (P < 0.05), content of A beta P in telencephalon and serum soluble AGE-peptide levels significantly higher (P < 0.05), contents of AGEPs in telencephalon and hippocampal tissue showed an increased tendency, but without significance (P > 0.05), argyrophil stain showed that nerve fiber thickened, senile plaques appeared in temporal cortex. In the TSR group after treatment, contents of AGEPs in telencephalon, A beta P in telencephalon and hippocampus significantly decreased (P < 0.05), the urinary soluble AGE-peptide level significantly increased (P < 0.05) and with markedly improvement of learning memory capability and above-mentioned pathological changes. CONCLUSION: TSR could reduce the accumulation of AGEPs in telencephalon and the contents of A beta P in telencephalon and hippocampal tissue, and improve the impaired ability of learning and memory caused by lack of estrogen. Its mechanism might be based on the elevation in excretion of AGE-peptide via kidney.