[Study on protective effect of Chaihu Shugan Powder against liver injury in rats with intrahepatic cholestasis by regulating FXR/Nrf2/ARE pathway].

This study aims to investigate the effect of Chaihu Shugan Powder(CHSG) on liver injury in rats with intrahepatic cholestasis by regulating farnesoid X receptor(FXR)/nuclear factor erythroid-2-related factor(Nrf2)/antioxidant response element(ARE) pathway. Eighty-four SD rats were classified into normal group, model group, CHSG-L group(0.5 g·kg~(-1)), CHSG-H group(2.5 g·kg~(-1)), ursodeoxycholic acid group(UDCA group, 100 mg·kg~(-1)), CHSG-H+sh-NC group(2.5 g·kg~(-1) CHSG+subcutaneous injection of sh-NC lentivirus), CHSG-H+sh-FXR group(2.5 g·kg~(-1) CHSG+subcutaneous injection of sh-FXR lentivirus), with 12 rats in each group. Rats were treated with corresponding drugs except for the normal group and the model group, once a day, for 7 days. On 5 th day, rats, except the normal group, were given α-naphthalene isothiocyanate(ANIT) at a dose of 100 mg·kg~(-1), once a day for 3 days to induce intrahepatic cholestasis, and the normal group was given the same amount of normal saline. Rats were anesthetized 1 h after the last administration and the 2 h bile flow was measured. Aeroset chemistry analyzer was employed to detect the levels of alanine aminotransferase(ALT), aspartate aminotransferase(AST), total bilirubin(TBIL), and total bile acid(TBA) in rat serum. Based on hematoxylin and eosin(HE) staining, the pathological changes of rat liver tissue were observed. Glutathione peroxidase(GSH-Px), superoxide dismutase(SOD), and malondialdehyde(MDA) in rat liver tissue homogenate were monitored with corresponding kits. Western blot was used to detect the expression of FXR, Nrf2, and heme oxygenase-1(HO-1) proteins in rat liver tissue. Compared with the normal group, the model group showed many spots or concentrated necrotic areas in the liver tissue, infiltration of a large number of inflammatory cells, swelling liver cells with nuclear shrinkage. The 2 h bile flow, levels of GSH-Px and SOD, and relative expression of FXR, Nrf2, and HO-1 proteins were significantly lower, and the levels of ALT, AST, TBIL, TBA and MDA were significantly higher in the model group than in the normal group. Compared with the model group, CHSG-L group, CHSG-H group, and UDCA group demonstrated significant alleviation of pathological damage of the liver tissue, significantly high 2 h bile flow, levels of GSH-Px and SOD, and expression of FXR, Nrf2 and HO-1 proteins, and significantly low levels of ALT, AST, TBIL, TBA and MDA. Compared with the CHSG-H group, the CHSG-H+sh-FXR group had worse liver pathological damage, significantly low levels of 2 h bile flow, levels of GSH-Px and SOD, and expression of FXR, Nrf2, and HO-1 proteins, and significantly high levels of ALT, AST, TBIL, TBA, and MDA. CHSG may protect against liver injury in rats with intrahepatic cholestasis by activating the FXR/Nrf2/ARE pathway.

Advances in traditional Chinese medicine as adjuvant therapy for diabetic foot.

Diabetes mellitus (DM) is a complex disease that often causes multiple systemic complications that have become a major international public health problem. Diabetic foot (DF) is one of the severe and frequent chronic complications of DM due to vascular lesions and neuropathy. DF ulcers (DFU) affect approximately 15% of people with DM and are the leading cause of death and disability. The prevalence and recurrence of DF are worrisome, and morbidity and mortality are also on the rise, which poses a substantial socioeconomic burden. Treating DF is difficult for clinicians and requires multidisciplinary cooperation, combining local and systemic therapy to reduce amputation and case-fatality rates. Traditional Chinese Medicine (TCM) has received extensive attention due to noticeable therapeutic effects and few adverse reactions. In recent years, research on DF treatment by TCM has been increasing, and further progress has been made. TCM includes oral medication, injectable preparations, and adjuvant therapy. This article reviews the relevant research on TCM-related adjuvant therapy for DF. We describe current progress in TCM in terms of external application, acupuncture, massage, acupoint injection, foot bath, fumigation, and moxibustion, as well as the mechanisms involved.

Evaluation of VGF peptides as potential anti-obesity candidates in pre-clinical animal models.

VGF is a peptide precursor expressed in neuroendocrine cells that is suggested to play a role in the regulation of energy homeostasis. VGF is proteolytically cleaved to yield multiple bioactive peptides. However, the specific actions of VGF-derived peptides on energy homeostasis remain unclear. The aim of the present work was to investigate the role of VGF-derived peptides in energy homeostasis and explore the pharmacological actions of VGF-derived peptides on body weight in preclinical animal models. VGF-derived peptides (NERP-1, NERP-2, PGH-NH2, PGH-OH, NERP-4, TLQP-21, TLQP-30, TLQP-62, HHPD-41, AQEE-30, and LQEQ-19) were synthesized and screened for their ability to affect neuronal activity in vitro on hypothalamic brain slices and modulate food intake and energy expenditure after acute central administration in vivo. In addition, the effects of NERP-1, NERP-2, PGH-NH2, TLQP-21, TLQP-62, and HHPD-41 on energy homeostasis were studied after chronic central infusion. NERP-1, PGH-NH2, HHPD-41, and TLQP-62 increased the functional activity of hypothalamic neuronal networks. However, none of the peptides altered energy homeostasis after either acute or chronic ICV administration. The present data do not support the potential use of the tested VGF-derived peptides as novel anti-obesity drug candidates.

[Synthesis and anti-tumor activity of ginsenoside Rh_2 caprylic acid monoester].

Ginsenoside Rh_2,firstly isolated from red ginseng,is protopanaxadiol type of steroidal saponin. Rh_2 possessed variety of activities,but bioavailability of oral administration Rh_2 was extremely low due to poor absorption. Moreover,ginsenoside Rh_2 exhibited toxicity on human normal cells. Therefore,to improve stronger anti-tumor activity and attenuate toxicity,it was essential to design and optimize chemical structure of ginsenoside Rh_2. Through n-octanoylchloride modifications,a novel ester derivative of ginsenoside Rh_2 named caprylic acid monoester of Rh_2( C-Rh_2) was designed and synthesized. Structure of novel ginsenoside derivative was identified by1 D and 2 D NMR,as well as ESI-MS analyses. Anti-tumor effect of C-Rh_2 was tested on H22 tumor bearing mice. C-Rh_2 displayed certain anti-tumor activities and exhibited less toxicity than Rh_2. In the present study,C-Rh_2 as ester form of ginsenoside Rh_2 showed better anti-tumor activity and less toxicity,but the specific mechanism needs further investigation.

Effect of Chaishao Shugan Lidan Paishitang on Inflammation, Stress Response and Gastrointestinal Function in Gallstones Patients with Chronic Cholecystitis / 中国实验方剂学杂志

Objective: To explore the effect of Chaishao Shugan Lidan Paishitang on inflammation, stress response and gastrointestinal function in gallstones patients with chronic cholecystitis. Method: Gallstones patients with chronic cholecystitis treated in our hospital from March 2017 to May 2018 were randomly divided into two groups, with 65 cases in each group. The control group was orally given ursodeoxycholic acid combined with metronidazole. In addition to the therapy of the control group, the Observation group was also given Chaishao Shugan Lidan Paishitang. Traditional Chinese medicine symptom scores, interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), hypersensitive C-reactive protein (hs-CRP), superoxide disproportionation alcohol (SOD), propylene glycol (MDA) and carbohydrate antigen 19-9 (CA19-9), carcinoembryonic antigen (CEA), gastric dynamic element (MOT), gastrin-releasing (GAS) and somatostatin (SS), alanine aminotransferase (ALT), aspertate aminotransferase (AST), total bilirubin (TBIL) and total bile acid (associates), and total cholesterol (TC) levels before and after treatment were observed in two groups, and the curative effect, reactions and relapse were also observed. Result: The inflammatory effect, stone ablation effect and clinical effect of observation group were significantly better than those of control group (Z=2.329, PZ=2.686, PZ=2.940, PPα, hs-CRP, IL-6, CEA, CA19-9, SS and MDA in observation group were lower than those in control group (PPχ2=5.140, PConclusion: The treatment of gallstones patients with chronic cholecystitis by Chaishao Shugan Lidan Paishitang has a good curative effect, and can alleviate clinical symptoms, inhibit oxidative stress and inflammation, improve liver and bile functions and gastrointestinal function, and reduce the recurrence rate.

[HPLC fingerprint study for the quality evaluation of atractylodis macrocephalae rhizoma].

OBJECTIVE: To establish an HPLC fingerprint analysis method for Atractylodis Macrocephalae Rhizoma (warm dried). METHODS: Took methanol extract of Atractylodis Macrocephalae Rhizoma as sample by ultrasonic processing, HPLC analysis was carried out on Sinochrom ODS-BP (4.6 mm x 250 mm, 5 microm) chromatographic column with mobile phase of acetonitrile (A)-water (B), gradient elution with a flow at 1.0 mL/min, ultraviolet detection wavelength at 242 nm and column temperature at 30 degrees C. RESULTS: An HPLC fingerprint analysis method for Atractylodis Macrocephalae Rhizoma was developed. Eight common peaks were obtained and three peaks were identified. CONCLUSION: The method is accurate and credible which can be used for quality control of Atractylodis Macrocephalae Rhizoma (warm dried).

CCL19-induced chemokine receptor 7 activates the phosphoinositide-3 kinase-mediated invasive pathway through Cdc42 in metastatic squamous cell carcinoma of the head and neck.

Metastatic squamous cell carcinoma of the head and neck (SCCHN) has been shown to express chemokine receptor 7 (CCR7), which activates phosphoinositide-3 kinase (PI3K) to promote invasion and survival of SCCHN cells. We hypothesized that Cdc42 might be involved in the CCR7-PI3K pathway. Adhesion assays, migration assays, immunofluorescence staining, Western blotting and immunohistochemical analysis were used to find whether Cdc42 can be activated by CCL19 (the CCR7 ligand) and its role in SCCHN. Results showed that CCL19 induced polarized localization of Cdc42 and actin polymerization in the leading edge of migrating cells. The level of activated membrane-bound Cdc42 was elevated, as measured by the GTPase activity pull-down assay. The increased membrane localization and membrane-bound activity of Cdc42 were abolished by CCR7 and PI3K inhibition, indicating the involvement of Cdc42 in the CCR7-PI3K cascade. Knockdown of Cdc42 by small interfering RNA (siRNA) led to significant reduction in the activation of Rac, filamentous actin (F-actin) accumulation as well as in the migration and invasion induced by CCL19. Taken together, our data indicate the important role played by Cdc42 in CCL19-induced migration and invasion of SCCHN cells.

Clinical experience in treatment of Amanita mushroom poisoning with Glossy Ganoderma Decoction and routine Western medicines.

OBJECTIVE: To assess the effects of treatment of Amanita mushroom poisoning with Glossy anoderma Decoction (, GGD). METHODS: Twelve patients with acute Amanita mushroom poisoning received conventional treatment (penicillin and reduced glutathione) combined with oral administration of GGD (treated group), which was prepared out of 200 g Glossy ganoderma decocted in water to 600 mL, and 200 ml was given once, three times a day for 7 successive days; while conventional treatment alone was given to the other 11 patients assigned to the control group. The therapeutic efficacy and changes in serum levels of total bilirubin (TBil), bile acids (BA), alanine transaminase (ALT), and aspartate transaminase (AST) activities in the two groups were compared. RESULTS: The cured-markedly effective rate in the treated group was more significant than that in the control group (P<0.01). Elevation in TBil, BA, ALT, and AST activities were observed in both groups 3 days after poisoning, which progressively increased thereafter in the control group. In the treated group, they reached their peak on the 3rd day and then declined gradually. The differences between pre-treatment and post-treatment in both groups were obviously significant (P<0.01), so were the differences between the two groups at corresponding time points (P<0.01). CONCLUSION: GGD shows excellent clinical efficacy in the treatment of acute Amanita mushroom poisoning and can reduce mortality significantly.

Effects of Lantana camara leaf extract on the activity of superoxide dismutase and accumulation of H2O2 in water hyacinth leaf.

Water hyacinth (Eichhornia crassipes) is one of the most productive plants, but is also a troublesome weed in the world. In order to protect the public water system from chemical herbicides pollution, biological method has been suggested to control the growth and the reproduction of this weed. Lantana (Lantana camara L.) is an important weed of the family Verbenaceae and its leaf extract is highly toxic to water hyacinth. The results of this study showed that the extract of lantana leaves suppressed the emergence of leaf buds of water hyacinth plant, and caused the decay of its leaves by foliar spraying. In addition, the increase of SOD activity in water hyacinth leaves was in accordance with the accumulation of H(2)O(2) and the increase in degree of membrane peroxidation, while the activity of catalase, which might remove the excessive H(2)O(2) in water hyacinth leaves, was inhibited by treatment with lantana extract. At tissue level, high H(2)O(2) histochemical labeling was detected in guard cells after treatment with lantana extract. This overproduction of H(2)O(2) could kill the leaf cells and cause leaf necrosis in the treated plant. Therefore, the high toxicity of lantana leaf extract to water hyacinth might be due to oxidative stress.

[Studies on chemical constituents from herb of Dracocephalum moldavica].

OBJECTIVE: To study the chemical constituents from the whole plant of Dracocephalum moldavica. METHOD: The compounds were isolated by using column chromatography with RA polystyrene resin, polyamide and silica gel as packing materials, and the structures of the compounds were identified by means of spectral data. RESULT: eight compounds were identified as apigenin(I), luteolin(II), kaempferol(III), isorhamnetin(IV), tilianin(V), agastachoside(VI), acacetin-7-O-(6-O-Malonyl-beta-D-glucopyranoside) (VII) and syringaresinol(VIII). CONCLUSION: Compounds I, II and III were isolated from genus Dracocephalum for the first time and compounds IV, VII and VIII were isolated from Dracocephalum moldavuca for the first time.

[Clinical observation on treatment of Russula subnigricans poisoning patients by Ganoderma lucidum decoction].

OBJECTIVE: To observe the effect of Ganoderma lucidum decoction in treating Russula subnigricans poisoning (RSP) patients. METHODS: The 14 patients of RSP in the treated group were treated with GLD (GLD, one dose was prepared by 100 g of Ganoderma lucidum decocted with water to 600 ml), on the base of conventional treatment, and 11 patients received conventional therapy in the previous year were taken as control. The clinical efficacy and parameters in them were compared, including the urine N-acetyl-D-glucosaminidase (NAG, which reflects the injury of kidney), the red blood cell and protein in urine, the alanine transaminase (ALT, which reflects the injury of liver), and the aspartate aminotransferase (AST, which reflects the injury of heart). RESULTS: A better clinical cure-markedly improving rate was showed in the treated group as compared with the control group, P < 0.01. In the treated group, red blood cell in urine disappeared after 24 hrs treatment in the majority of patients, urinary protein reduced obviously and the other three parameters reached the peak at the 3rd day then lowered gradually. In the control group, all the parameters increased continuously. Comparison between the parameters at corresponding time in the two groups showed significant difference (P < 0.01), those in the treated group were markedly lower than those in the control group respectively. CONCLUSION: GLD has good effect in treating RSP, could obviously lower the fatat rate of RSP.