Anisodamine affects the pigmentation, mineral density, craniofacial area, and eye development in zebrafish embryos.

Anisodamine is one of the major components of the tropine alkaloid family and is widely used in the treatment of pain, motion sickness, pupil dilatation, and detoxification of organophosphorus poisoning. As a muscarinic receptor antagonist, the low toxicity and moderate drug effect of anisodamine often result in high doses for clinical use, making it important to fully investigate its toxicity. In this study, zebrafish embryos were exposed to 1.3-, 2.6-, and 5.2-mM anisodamine for 7 days to study the toxic effects of drug exposure on pigmentation, mineral density, craniofacial area, and eye development. The results showed that exposure to anisodamine at 1.3 mM resulted in cranial malformations and abnormal pigmentation in zebrafish embryos; 2.6- and 5.2-mM anisodamine resulted in significant eye development defects and reduced bone density in zebrafish embryos. The associated toxicities were correlated with functional development of neural crest cells through gene expression (col1a2, ddb1, dicer1, mab21l1, mab21l2, sox10, tyrp1b, and mitfa) in the dose of 5.2-mM exposed group. In conclusion, this study provides new evidence of the developmental toxicity of high doses of anisodamine in aqueous solutions to organisms and provides a warning for the safe use of this drug.

Effectiveness of anisodamine for the treatment of critically ill patients with septic shock: a multicentre randomized controlled trial.

BACKGROUND: Septic shock is characterized by an uncontrolled inflammatory response and microcirculatory dysfunction. There is currently no specific agent for treating septic shock. Anisodamine is an agent extracted from traditional Chinese medicine with potent anti-inflammatory effects. However, its clinical effectiveness remains largely unknown. METHODS: In a multicentre, open-label trial, we randomly assigned adults with septic shock to receive either usual care or anisodamine (0.1-0.5 mg per kilogram of body weight per hour), with the anisodamine doses adjusted by clinicians in accordance with the patients' shock status. The primary end point was death on hospital discharge. The secondary end points were ventilator-free days at 28 days, vasopressor-free days at 28 days, serum lactate and sequential organ failure assessment (SOFA) score from days 0 to 6. The differences in the primary and secondary outcomes were compared between the treatment and usual care groups with the χ2 test, Student's t test or rank-sum test, as appropriate. The false discovery rate was controlled for multiple testing. RESULTS: Of the 469 patients screened, 355 were assigned to receive the trial drug and were included in the analyses-181 patients received anisodamine, and 174 were in the usual care group. We found no difference between the usual care and anisodamine groups in hospital mortality (36% vs. 30%; p = 0.348), or ventilator-free days (median [Q1, Q3], 24.4 [5.9, 28] vs. 26.0 [8.5, 28]; p = 0.411). The serum lactate levels were significantly lower in the treated group than in the usual care group after day 3. Patients in the treated group were less likely to receive vasopressors than those in the usual care group (OR [95% CI] 0.84 [0.50, 0.93] for day 5 and 0.66 [0.37, 0.95] for day 6). CONCLUSIONS: There is no evidence that anisodamine can reduce hospital mortality among critically ill adults with septic shock treated in the intensive care unit. Trial registration ClinicalTrials.gov ( NCT02442440 ; Registered on 13 April 2015).

Protective effect of anisodamine in rats with glycerol-induced acute kidney injury.

BACKGROUND: Anisodamine is used for the treatment of reperfusion injury in various organs. In this study, we investigated the effectiveness and mechanisms of action of anisodamine in promoting recovery from glycerol-induced acute kidney injury (AKI). METHODS: We compared the protective effects of atropine and anisodamine in the rat model of glycerol-induced AKI. We examined signaling pathways involved in oxidative stress, inflammation and apoptosis, as well as expression of kidney injury molecule-1 (KIM-1). Renal injury was assessed by measuring serum creatinine and urea, and by histologic analysis. Rhabdomyolysis was evaluated by measuring creatine kinase levels, and oxidative stress was assessed by measuring malondialdehyde (MDA) and superoxide dismutase (SOD) levels in kidney tissues. Inflammation was assessed by quantifying interleukin 6 (IL-6) and CD45 expression. Apoptosis and necrosis were evaluated by measuring caspase-3 (including cleaved caspase 3) and RIP3 levels, respectively. RESULTS: Glycerol administration resulted in a higher mean histologic damage score, as well as increases in serum creatinine, urea, creatine kinase, reactive oxygen species (ROS), MDA, IL-6, caspase-3 and KIM-1 levels. Furthermore, glycerol reduced kidney tissue SOD activity. All of these markers were significantly improved by anisodamine and atropine. However, the mean histologic damage score and levels of urea, serum creatinine, creatine kinase, ROS and IL-6 were lower in the anisodamine treatment group compared with the atropine treatment group. CONCLUSION: Pretreatment with anisodamine ameliorates renal dysfunction in the rat model of glycerol-induced rhabdomyolytic kidney injury by reducing oxidative stress, the inflammatory response and cell death.

Solasodine reverses stemness and epithelial-mesenchymal transition in human colorectal cancer.

Adverse side effects of conventional chemotherapy, acquired resistance and fatal tumor metastasis of human colorectal cancer (CRC) are propelling the exploration for novel selective anticarcinogens. Solasodine is a main active component isolated from Solanum incanum L that exhibited a potent stemness and invasion inhibitory effect on human colorectal cancer HCT116 cells. Colony Spheroid formation assay showed that solasodine dose-dependently prohibited HCT116 cell stemness. CD133, CD44, Nanog, Oct-4 and Sox-2 were inhibited by solasodine to reverse stemness and similar mechanism was stimulated in vivo. Transwell and scratch wound assays revealed that solasodine impeded HCT116 cell invasion and migration potential strengthened by TGF-ß1. Moreover, solasodine attenuated TGF-ß1-induced EMT and decreased MMPs while in vivo study showed the same trend. The results of this study implied that solasodine may be a novel therapeutic drug for CRC treatment.

Targeting EP4 downstream c-Jun through ERK1/2-mediated reduction of DNMT1 reveals novel mechanism of solamargine-inhibited growth of lung cancer cells.

Lung cancer is the most common cancer and the leading cause of cancer deaths worldwide. We previously showed that solamargine, one natural phytochemicals from traditional plants, inhibited the growth of lung cancer cells through inhibition of prostaglandin E2 (PGE2 ) receptor EP4. However, the potential downstream effectors of EP4 involving in the anti-lung cancer effects of solamargine still remained to be determined. In this study, we further verified that solamargine inhibited growth of non-small-cell lung cancer (NSCLC) cells in multiple cell lines. Mechanistically, solamargine increased phosphorylation of ERK1/2. Moreover, solamargine inhibited the protein expression of DNA methyltransferase 1 (DNMT1) and c-Jun, which were abrogated in cells treated with MEK/ERK1/2 inhibitor (PD98059) and transfected with exogenously expressed DNMT1 gene, respectively. Interestingly, overexpressed DNMT1 gene antagonized the effect of solamargine on c-Jun protein expression. Intriguingly, overexpressed c-Jun blocked solamargine-inhibited lung cancer cell growth, and feedback resisted the solamargine-induced phosphorylation of ERK1/2. A nude mouse xenograft model implanted with lung cancer cells in vivo confirmed the results in vitro. Collectively, our results show that solamargine inhibits the growth of human lung cancer cells through reduction of EP4 protein expression, followed by increasing ERK1/2 phosphorylation. This results in decrease in DNMT1 and c-Jun protein expressions. The inter-correlations between EP4, DNMT1 and c-Jun and feedback regulation of ERK1/2 by c-Jun contribute to the overall responses of solamargine in this process. This study uncovers an additional novel mechanism by which solamargine inhibits growth of human lung cancer cells.

Combination of Solamargine and Metformin Strengthens IGFBP1 Gene Expression Through Inactivation of Stat3 and Reciprocal Interaction Between FOXO3a and SP1.

BACKGROUND/AIMS: Solamargine, one natural photochemical component from traditional plants, has been shown to have anti-cancers properties. We previously showed that solamargine inhibited the growth of non-small-cell lung cancer (NSCLC) cells through suppression of prostaglandin E2 (PGE2) receptor EP4 gene and regulation of downstream signaling pathways. However, the detailed mechanism underlying this, especially in combination of metformin, a known AMPK activator, still remained to be determined. METHODS: Cell viability was measured using a 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) and colorimetric 5-bromo-2-deoxyuridine (BrdU) ELISA methods, respectively. Western blot analysis and immunohistochemistry were performed to examine the phosphorylation and protein expressions of signal transducer and activator of transcription 3 (Stat3), SP1, forkhead box O3a (FOXO3a), and insulin-like growth factor (IGF)-IGF binding protein 1 (IGFBP1). The expression of IGFBP1 mRNA was measured by quantitative real time PCR (qRT-PCR). Silencing of FOXO3a and IGFBP1 were examined by siRNA procedures. Exogenously expression of SP1, FOXO3a, and IGFBP1 were carried out by transient transfection assays. The promoter activity of IGFBP1 was tested using Secrete-PairTM Dual Luminescence Assay Kit. A xenografted tumor model was used to further test the effect of solamargine in combining with metformin in vivo. RESULTS: We further demonstrated that solamargine inhibited growth and induced cell cycle arrest in other NSCLC cell lines. Through mechanism-based approaches, we showed that solamargine decreased the phosphorylation of Stat3; In addition, solamargine induced FOXO3a, whereas reduced SP1 protein levels; all of which were abrogated in cells with overexpressed Stat3 gene. Interestingly, there is interaction between FOXO3a and SP1. Moreover, solamargine increased mRNA, protein expression and promoter activity of IGFBP1, which was not observed in cells with overexpressed SP1 or with silenced FOXO3a genes. Finally, ablation of IGFBP1 expression by siRNA blocked the effect of solamargine on cell growth inhibition. More importantly, there was a synergy of combination of solamargine and metformin. Similar findings were also observed in vivo. CONCLUSION: Our results show that solamargine increases IGFBP1 gene expression through inactivation of Stat3, followed by regulation and reciprocal interaction of FOXO3a and SP1 in vitro and in vivo. This ultimately leads to suppression of human lung cancer cell growth. Moreover, this is a synergy of solamargine in combination with metformin in this process. This study unravels a novel mechanism underlying the anti-lung cancer effects of solamargine in combination of metformin, and suggests a potential new lung cancer associated therapy.

A New Antileishmanial Preparation of Combined Solamargine and Solasonine Heals Cutaneous Leishmaniasis through Different Immunochemical Pathways.

Little has been done during the past 100 years to develop new antileishmanial drugs. Most infected individuals live in poor countries and have a low cash income to be attractive targets to pharmaceutical corporations. Two heterosidic steroids, solamargine and solasonine, initially identified as major components of the Brazilian plant Solanum lycocarpum, were tested for leishmanicidal activity. Both alkaloids killed intracellular and extracellular Leishmania mexicana parasites more efficiently than the reference drug sodium stibogluconate. A total of 10 µM each individual alkaloid significantly reduced parasite counts in infected macrophages and dendritic cells. In vivo treatment of C57BL/6 mice with a standardized topical preparation containing solamargine (45.1%) and solasonine (44.4%) gave significant reductions in lesion sizes and parasite counts recovered from lesions. Alkaloids present different immunochemical pathways in macrophages and dendritic cells. We conclude that this topical preparation is effective and a potential new and inexpensive treatment for cutaneous leishmaniasis.

Study on the synthesis and biological activities of α-substituted arylacetates derivatives.

Anisodamine was isolated from the medicinal herb, it was used in the treatment of gastrointestinal smooth muscle spasm, infective toxic shock and organophosphorus intoxication. But there is no report about anisodamine with α-glucosidase inhibitory activity. In order to find novel α-glucosidase inhibitors, a series of α-substituted arylacetates derivatives have been synthesized based on the active unit of anisodamine. In α-glucosidase assay, compound 9 in Schiff base form and compound 22 in ester form show strong inhibition against α-glucosidase with IC50 value of 46.81µM and 83.76µM, respectively. Compounds 9 and 22 exhibit comparable good antidiabetic activities as commercial drug Glimepiride. In addition, Schiff bases of α-substituted arylacetates show antitumor activities against human cancer cell lines, where compound 9 with thiourea moiety performs the best antitumor activity. We anticipate that our research will provide potential candidate scaffolds for antidiabetic drug design.

Retinal Branch Artery Embolization Following Hyaluronic Acid Injection: A Case Report.

Injection of hyaluronic acid (HA) filler is a common aesthetic procedure. Impairment of vision, although rare, is a devastating complication of this procedure, which may not be reversible. We report on a patient who experienced visual acuity impairment and ischemic oculomotor nerve palsy after injection of HA into the nasal dorsum. In this case, clinical signs improved within 14 days of treatment. We also provide a review of the mechanism, clinical features, risk factors, and prevention and treatment strategies relating to embolization of ocular circulation after injection of HA. Vision loss is a rare but devastating complication of injection of hyaluronic acid (HA) in the face. Visual acuity seldom recovers completely. We report on a 22-year-old Asian woman who experienced obstruction of a branch of the retinal artery after injection of HA to augment her nose. The patient's visual acuity declined shortly after the procedure, and ophthalmoplegia occurred. Combination treatment was administered to restore the perfusion and oxygen supply to the retina and optic nerve. Within 14 days of rigorous treatment, the patient experienced improvement in visual acuity, extraocular movement, and visual field defects. LEVEL OF EVIDENCE 5: Risk.

Expression of IL-17A and IL-17F in lipopolysaccharide-induced acute lung injury and the counteraction of anisodamine or methylprednisolone.

Th17 cytokines IL-17A and IL-17F as pro-inflammatory cytokines played an important role in triggering inflammatory responses. However, little was known about the expression of IL-17A and IL-17F in acute lung injury (ALI). Therefore, the present study investigated the expression of IL-17A and IL-17F in lipopolysaccharide (LPS)-induced ALI in rats and rat pulmonary microvascular endothelial cells (PMVEC) by enzyme-linked immunosorbant assay or reverse transcription-polymerase chains reaction. Anisodamine and methylprednisolone were also investigated as anti-inflammatory strategy in the process of LPS-induced ALI. Lung injury was evaluated by histological changes, right lung wet weight:body weight (LW/BW) ratios, and protein education and total leukocyte count of bronchoalveolar lavage fluid (BALF). Our findings showed that LPS exposure elevated the levels of leukocyte number, protein education in BALF and the ratios of LW/BW, increased the expression of IL-17A and IL-17F in the lung tissues homogenate, BALF and serum of ALI rats. Up-regulation of IL-17F expression was also observed after LPS challenge in rat PMVEC. Treatment with anisodamine or methylprednisolone significantly inhibited the increases of parameters of ALI induced by LPS, and markedly reduced the expression of IL-17A and IL-17F in rats and the IL-17F expression in PMVEC. These data suggested that IL-17A and IL-17F maybe play an important role in LPS-induced ALI via autocrine and paracrine mechanisms, and anisodamine is similar in extent to methylprednisolone that contributes to relieve LPS-induced ALI.

Protective role of pretreatment with Anisodamine against sepsis-induced diaphragm atrophy via inhibiting JAK2/STAT3 pathway.

There is an increasing tendency for sepsis patients to suffer from diaphragm atrophy as well as mortality. Therefore, reducing diaphragm atrophy could benefit sepsis patients' prognoses. Studies have shown that Anisodamine (Anis) can exert antioxidant effects when blows occur. However, the role of Anisodamine in diaphragm atrophy in sepsis patients has not been reported. Therefore, this study investigated the antioxidant effect of Anisodamine in sepsis-induced diaphragm atrophy and its mechanism. We used cecal ligation aspiration (CLP) to establish a mouse septic mode and stimulated the C2C12 myotube model with lipopolysaccharide (LPS). After treatment with Anisodamine, we measured the mice's bodyweight, diaphragm weight, fiber cross-sectional area and the diameter of C2C12 myotubes. The malondialdehyde (MDA) levels in the diaphragm were detected using the oxidative stress kit. The expression of MuRF1, Atrogin1 and JAK2/STAT3 signaling pathway components in the diaphragm and C2C12 myotubes was measured by RT-qPCR and Western blot. The mean fluorescence intensity of ROS in C2C12 myotubes was measured by flow cytometry. Meanwhile, we also measured the levels of Drp1 and Cytochrome C (Cyt-C) in vivo and in vitro by Western blot. Our study revealed that Anisodamine alleviated the reduction in diaphragmatic mass and the loss of diaphragmatic fiber cross-sectional area and attenuated the atrophy of the C2C12 myotubes by inhibiting the expression of E3 ubiquitin ligases. In addition, we observed that Anisodamine inhibited the JAK2/STAT3 signaling pathway and protects mitochondrial function. In conclusion, Anisodamine alleviates sepsis-induced diaphragm atrophy, and the mechanism may be related to inhibiting the JAK2/STAT3 signaling pathway.

Immunomodulatory effect of the alkaloidic extract of Solanum lycocarpum fruits in mice infected with Schistosoma mansoni.

Schistosomiasis is a chronic disease caused by trematode flatworms of the genus Schistosoma; it accounts for more than 280,000 deaths annually. In this work we investigated the effect of the alkaloidic extract obtained by acid-base extraction of the dried fruits of Solanum lycocarpum on schistosomiasis. We used this extract at concentrations of 10, 20, and 40 mg/kg to treat mice infected with Schistosoma mansoni in different phases of the parasite cycle, and we compared its effect with that of the positive control praziquantel (60 mg/kg). We evaluated the results on the basis of the number of macrophages, eggs, and granulomas; we also assessed nitric oxide (NO) and interferon-gamma (IFN-γ) production. Animals treated with a daily dose of 10 or 20 mg/kg alkaloidic extract between the 37th and 41st day of infection showed increased number of macrophages, elevated NO and IFN-γ concentrations, and reduced number of eggs and granulomas in the liver. The alkaloidic extract of S. lycocarpum fruits displayed an immunomodulatory effect on mice infected with S. mansoni, so its potential to treat schistosomiasis deserves further studies.

Update on the sources, pharmacokinetics, pharmacological action, and clinical application of anisodamine.

Anisodamine is an anticholinergic drug extracted and isolated from the Anisodus tanguticus (Maxim.) Pascher of the Solanaceae family which is also a muscarinic receptor antagonist. Owing to the lack of natural sources of anisodamine, synthetic products are now used. Using ornithine and arginine as precursor compounds, putrescine is catalyzed by different enzymes and then undergoes a series of reactions to produce anisodamine. It has been used clinically to protect cardiac function and treat septic shock, acute pancreatitis, calculous renal colic, bronchial asthma, blood circulation disturbances, jaundice, analgesia, vertigo, acute poisoning, and other conditions.This review describes the relevant pharmacokinetic parameters. Anisodamine is poorly absorbed in the gastrointestinal tract, and it is not as effective as intravenous administration. For clinical medication, intravenous infusion should be used rather than rapid intravenous injection. With the advancement of research in recent years, the application scope of anisodamine has expanded, with significant developments and application values surging.This review systematically describes the sources, pharmacokinetics, pharmacological effects and clinical application of anisodamine, in order to provide a basis for clinical use.

Combined administration of anisodamine and neostigmine produces anti-shock effects: involvement of α7 nicotinic acetylcholine receptors.

AIM: To evaluate the anti-effects of anisodamine and neostigmine in animal models of endotoxic and hemorrhagic shock. METHODS: Kunming mice were injected with lipopolysaccharide (LPS 30 mg/kg, ip) to induce endotoxic shock. Anisodamine (12.5, 25, and 50 mg/kg, ip) and neostigmine (12.5, 25, and 50 µg/kg, ip) were administered immediately after LPS injection. Survival rate was monitored, and the serum levels of TNF-α and IL-1ß were analyzed using ELISA assays. The effects of anisodamine and neostigmine were also examined in α7 nicotinic acetylcholine receptor (α7 nAChR) knockout mice with endotoxic shock and in Beagle dogs with hemorrhagic shock. RESULTS: In mice with experimental endotoxemia, combined administration of anisodamine and neostigmine significantly increased the survival rate and decreased the serum levels of inflammatory cytokines, as compared to those produced by either drug alone. The anti-shock effect of combined anisodamine and neostigmine was abolished in α7 nAChR knockout mice. On the other hand, intravenous injection of the combined anisodamine and neostigmine, or the selective α7 nAChR agonist PNU282987 exerted similar anti-shock effects in dogs with hemorrhagic shock. CONCLUSION: The results demonstrate that combined administration of anisodamine and neostigmine produces significant anti-shock effects, which involves activation of α7 nAChRs.

The endoplasmic reticulum in cardiovascular health and disease.

The endoplasmic reticulum has an intricate network of pathways built to deal with the secretory and integral membrane protein synthesis demands of the cell, as well as adaptive responses set up for the endoplasmic reticulum to rely on when stressed. These pathways are both essential and complex, and because of these 2 factors, several situations can lead to a dysfunctional endoplasmic reticulum and result in a dysfunctional cell with the potential to contribute to the progression of disease. The endoplasmic reticulum has been implicated in several metabolic, neurodegenerative, inflammatory, autoimmune, and renal diseases and disorders, and in particular, cardiovascular diseases. The role of the endoplasmic reticulum in cardiovascular disease shows how the change in function of a particular microscopic organelle can lead to macroscopic changes in the form of disease.

[Clinical re-evaluation of effects of two different "cocktail therapy" to prevent from phlebitis induced by Chansu injection].

OBJECTIVE: To re-evaluate the effects of different "cocktail therapy" to prevent from phlebitis induced by Chansu injection. METHOD: Patients treated with Chansu injection were divided randomLy into 4 groups with 90 per group, control group, phentolaminum group, the magnesium sulfate group-phentolaminum group, and anisodamine-phentolaminum group. Patients in the control group only received the routine nursing treatment, and patients in the various experiment group received different interventions. The comparison was made in the morbidity and the starting time of occurrence of phlebitis, the severity of pain, duration of pain. RESULT: The morbidity of phlebitis was 8%, 8%, 6%, respectively. The starting time of phlebitis occurrence was (22 +/- 4), (27 +/- 5), (28 +/- 7) h, respectively. The NRS of pain was (4.75 +/- 1.51), (3.27 +/- 1.02), (2.71 +/- 1.63), respectively. The duration time of pain was (4.25 +/- 1.36), (2.51 +/- 1.05), (2.19 +/- 1.13) d respectively. In control group, the morbidity of phlebitis, the starting time of occurrence of phlebitis, the severity of pain, duration of pain was 30%, (16 +/- 4) h, (6.34 +/- 1.21), (5.47 +/- 1.07) d, respectively. As compared with the control group, a significance difference was found between every group in three test groups and control group respectively (P<0.05). CONCLUSION: The morbidity and the starting time of occurrence of phlebitis, the severity of pain, duration of pain was significantly reduced respectively by two different "cocktail therapy".

Khasianine ameliorates psoriasis-like skin inflammation and represses TNF-α/NF-κB axis mediated transactivation of IL-17A and IL-33 in keratinocytes.

ETHNO-PHARMACOLOGICAL RELEVANCE: Khasianine is recently identified as a bioactive compound from Solanum nigrum L. (SNL) which is a traditional Chinese herb (named LongKui in China) and has been clinically applied for treating psoriasis in China but with limited knowledge about the active ingredients. AIM OF THE STUDY: This study tried to explore the bioactivity of Khasianine and showed that Khasianine possessed highly anti-inflammatory bioactivity which rapidly alleviated psoriasis-like mice skin inflammation. MATERIALS AND METHODS: Imiquimod induced psoriasis-like mouse model, and human keratinocytes were employed in this study. In vivo, immunohistochemistry and immunofluorescence were performed to evaluate the pathological improvement in psoriatic lesions after Khasianine treatment. In vitro, tumor necrosis factor α (TNF-α) treated HaCaT cells with or without Khasianine, were used to analyze the expression and cellular location of NF-κB p65, the expression of IL-17A and IL-33, and the binding intensity of NF-κB p65 on the promoter of IL-17A and IL-33 to understand the molecular mechanism of Khasianine mediated anti-inflammatory effect. RESULTS: Khasianine reduced infiltration of CD4+ T helper cells (Th cells) and macrophages in mice psoriatic lesions. Immunohistochemistry analysis revealed that Khasianine reduced TNF-α levels in lesions and suppressed NF-κB p65 activation as well as expression of IL-17A and IL-33 in mice epidermal keratinocytes. Further studies in human keratinocytes demonstrated that Khasianine inhibited TNF-α-induced transcriptional activation (transactivation) of NF-κB p65 such as evicting NF-κB p65 binding from the promoter regions of IL-17A and IL-33 and preventing NF-κB nuclear translocation. CONCLUSIONS: Our results suggested that Khasianine is a potent anti-inflammatory compound with the bioactivity of NF-κB inhibition and is a promising candidate for psoriasis topical therapy.

[Clinical re-evaluation of effects of different treatments to prevent from phlebitis induced by Chansu injection].

OBJECTIVE: To re-evaluate the effects of different treatments to prevent from phlebitis induced by Chansu injection. METHOD: Patients treated with Chansu injection were divided randomly into 4 groups with 50 per group, control group, the magnesium sulfate group, phentolaminum group, and anisodamine group. Patients in the control group only received the routine nursing treatment, and patients in the various experiment group received different interventions. The comparison was made in the morbidity and the starting time of occurrence of phlebitis, the severity of pain, duration of pain. RESULT: The morbidity of phlebitis was 8%, 8%, 6% respectively. The starting time of phlebitis occurrence was (21 +/- 9.31) , (22.34 +/- 10.15), (20.19 +/- 11.23) h, respectively. The NRS of pain was (4. 15 +/- 1.03), (3.26 +/- 1.17), (4.32 +/- 1.36), respectively. The duration time of pain was (4.05 +/- 1.21), (3.37 +/- 1.17), (3.19 +/- 1.67) d, respectively. In control group, the morbidity of phlebitis, the starting time of occurrence of phlebitis, the severity of pain, duration of pain was 24%, (17 +/- 6.32) h, (6.58 +/- 1.29), (5.32 +/- 1.12) d, respectively. As compared with the control group, a significance difference was found between every group in three test groups and control group respectively (P<0.05). CONCLUSION: The morbidity and the starting time of occurrence of phlebitis, the severity of pain, duration of pain was significantly reduced respectively by external appication of magnesium sulfate, anisodamine, and intravenous drip infusion of phentolaminum.

Cardioprotective effect of anisodamine against ischemia/reperfusion injury through the mitochondrial ATP-sensitive potassium channel.

Previous clinical studies have shown that anisodamine could improve no-reflow phenomenon and prevent reperfusion arrhythmias, but whether this protective effect is related to the antagonism of the M-type cholinergic receptor or other potential mechanisms is uncertain. The aim of the present study was to investigate the role of the mitochondrial ATP-sensitive potassium channel (mitoK ATP ) in cardioprotective effect of anisodamine against ischemia/reperfusion injury. Anisodamine and 5- hydroxydecanoic acid were used to explore the relationship between anisodamine and mitoK ATP . Using a Langendorff isolated heart ischemia/reperfusion injury model, hemodynamic parameters and reperfusion ventricular arrhythmia were evaluated; in addition, changes in myocardial infarct size, cTnI from coronary effluent and myocardial ultrastructure, as well as ATP, MDA and SOD in myocardial tissues, were detected. In the hypoxia/reoxygenation injury model of neonatal rat cardiomyocyte, cTnI release in the culture medium and levels of ATP, MDA and SOD in cardiomyocytes and mitochondrial membrane potential, were analyzed. Overall, anisodamine could significantly improve the hemodynamic indexes of isolated rat heart injured by ischemia/reperfusion, reduce the occurrence of ventricular reperfusion arrhythmia and myocardial infarction area, and improve the ultrastructural damage of myocardium and mitochondria. The in vitro results demonstrated that anisodamine could improve mitochondrial energy metabolism, reduce oxidative stress and stabilize mitochondrial membrane potential. The cardioprotective effects were significantly inhibited by 5-hydroxydecanoic acid. In conclusion, this study suggests that the opening of mitoK ATP could play an important role in the protective effect of anisodamine against myocardial ischemia/reperfusion injury.

Randomized clinical trial of Chinese herbal medications to reduce wound complications after mastectomy for breast carcinoma.

BACKGROUND: Ischaemia and necrosis of skin flaps is a common complication after mastectomy. This study evaluated the influence of anisodamine and Salvia miltiorrhiza on wound complications after mastectomy for breast cancer. METHODS: Ninety patients undergoing mastectomy for breast carcinoma were divided into three groups. Group 1 received routine wound care, group 2 received intravenous Salvia miltiorrhiza after surgery for 3 days and group 3 similarly received intravenous anisodamine. Skin flaps were observed on postoperative days 4 and 8; areas of wound ischaemia and necrosis were graded and adverse events recorded. RESULTS: There was no difference in demographic characteristics between the groups. At 4 days after surgery the rate of ischaemia and necrosis in groups 2 and 3 was significantly reduced compared with that in control group 1 (median wound score 6·80 versus 23·38, P = 0·002, and 3·76 versus 23·38, P < 0·001, respectively). This improvement in groups 2 and 3 continued to postoperative day 8 (both P < 0·001), but wound scores at this stage were better in group 3 than in group 2 (1·82 versus 6·92 respectively; P = 0·022). The volume of wound drainage was lower in group 3 than in group 1 (P = 0·004). The incidence of adverse effects was highest in group 3, and two patients in this group discontinued treatment. No significant complications were noted in group 2. CONCLUSION: Anisodamine and S. miltiorrhiza were both effective in reducing skin flap ischaemia and necrosis after mastectomy, although anisodamine was associated with a higher rate of adverse effects.