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BackgroundThe use of multimodal pharmacological prophylactic regimes has decreased postoperative nausea and vomiting (PONV) in general but it still occurs in over 60% of female patients after bariatric surgery. This study aimed to evaluate the efficacy of ST36 acupoint injection with anisodamine in prevention of PONV among female patients after bariatric surgery.MethodsNinety patients undergoing laparoscopic sleeve gastrectomy were randomly allocated to anisodamine or control group at the ratio of 2:1. Anisodamine or normal saline was injected into Zusanli (ST36) bilaterally after induction of general anesthesia. The incidence and severity of PONV were assessed during the first 3 postoperative days and at 3 months. The quality of early recovery of anesthesia, gastrointestinal function, sleep quality, anxiety, depression, and complications were also evaluated.ResultsBaseline and perioperative characteristics were comparable between two groups. In the anisodamine group, 25 patients (42.4%) experienced vomiting within postoperative 24 h compared with 21 (72.4%) in the control group (relative risk 0.59; 95% confidence interval 0.40-0.85). Time to first rescue antiemetic was 6.5 h in anisodamine group, and 1.7 h in the control group (P = 0.011). Less rescue antiemetic was required during the first 24 h in the anisodamine group (P = 0.024). There were no differences in either postoperative nausea or other recovery characteristics.ConclusionsThe addition of ST36 acupoint injection with anisodamine significantly reduced postoperative vomiting without affecting nausea in female patients with obesity undergoing laparoscopic sleeve gastrectomy.

Purpose: To evaluate the influence of anisodamine injection at the Zusanli (ST36) on early postoperative recovery quality in patients who have undergone laparoscopic sleeve gastrectomy. Materials and Methods: 141 patients undergoing laparoscopic sleeve gastrectomy were randomly divided into the control group (group C), the normal saline group (group S) and the anisodamine group (group A). Acupuncture point injections were administered after induction of general anesthesia. The quality of recovery-40 questionnaire (QoR-40) scores were documented preoperatively (D0) and on the 1st (D1), 3rd (D3) and 7th (D7) days postoperatively. Additional metrics included: the numerical rating scale (NRS) for pain, postoperative nausea and vomiting (PONV), assessment and analgesic consumption 24-h post-extubation and the initial postoperative times for ambulation and anal exhaust. Substance P (SP), β-endorphin (β-EP), motilin (MTL) and gastrin (GAS) were quantified at 24-h post-surgery. Results: Compared with group C, group A demonstrated an elevation in QoR-40 scores and physical comfort dimensions during D1-3, and an increased pain scores during D1-7; group S exhibited an augmentation in QoR-40 scores and pain scores on D1 (p < 0.05). Compared with group S, group A improved QoR-40 scores on D1 and pain scores during D1-3 (p < 0.05). SP, β-EP, MTL and GAS presented significant variances among the groups 24-h post-surgery (p < 0.05). There were significant differences between the groups in NRS pain scores and PONV scores at 24-h postoperatively, dosage of dizocin on the first postoperative day, and time to first anal defecation (p < 0.05). Conclusion: The administration of anisodamine via ST36 acupoint injections has been demonstrated to facilitate the recuperation of gastrointestinal functionality, to alleviate postoperative pain and nausea, and substantially to enhance the quality of early postoperative recovery. [ABSTRACT FROM AUTHOR]

Sepsis-induced myocardial dysfunction presents significant challenges in clinical management and is associated with increased mortality. Anisodamine (654–1/−2) has potentials in alleviating cardiac and endothelial impairments associated with sepsis. Exosomes, small vesicles secreted by cells, carry various bioactive molecules, such as nucleic acids, proteins, and lipids. These vesicles can travel to target cells to influence their function and modulating biological processes. In the context of endothelial-cardiac crosstalk, exosomes derived from endothelial cells can transfer signals that either exacerbate or mitigate myocardial injury, playing a crucial role in the progression of cardiovascular diseases. However, the precise role of endothelial-cardiac crosstalk, particularly through exosomes, in mediating the cardioprotective effects of anisodamine remains unclear. This study evaluated the effects of anisodamine on myocardial and endothelial injuries induced by LPS. Mechanisms were analyzed through network pharmacology, molecular docking, Western blotting, and RT-qPCR. The interaction between endothelial and cardiomyocyte inflammatory responses to anisodamine was assessed using a co-culture assay. Furthermore, both in vivo and in vitro assays were conducted to evaluate the effects of anisodamine-/LPS- treated HUVECs exosomes on A16 cell and myocardial function in mice. Anisodamine effectively mitigated apoptosis, inflammation, mitochondrial and myocardial injury, glycocalyx degradation, and oxidative stress by regulating the PI3K-AKT, NLRP-3/Caspase-1/ASC, TNF-α/PKCα/eNOs/NO, and NF-κB/iNOs/NO pathways in A16 cells and HUVECs. Moreover, in vivo and in vitro assays confirmed the protective effects of anisodamine against myocardial injuries mediated by exosomes derived from LPS-treated HUVECs. In summary, anisodamine ameliorated inflammation-induced endothelial and cardiomyocyte dysfunction. The in vitro and in vivo assays demonstrated that anisodamine could alleviate myocardial dysfunction through exosome-mediated mechanisms, offering new therapeutic avenues for treating myocardial injury and highlighting the potential of targeted exosome therapy in clinical settings. [Display omitted] [ABSTRACT FROM AUTHOR]

Purpose: To study the effects of anisodamine (Ad) combined with lidocaine (Ldc) on myocardial ischemia-reperfusion injury (MIRI) in rats, and its correlation with PI3K/AKT signaling pathway. Methods: A total of 70 healthy rats were randomly divided into S group, M group, Ad group, Ldc group, Ad + Ldc group, Ad + Ldc + LY group, and LY group. The cardiac hemodynamic indices in each group were determined, and the area of myocardial infarction measured. Serum biochemical indices were also determined. Furthermore, the protein expressions of p-Akt, T-Akt, Bcl-2, and Bax in myocardial cells were determined by Western blotting. Results: Compared with those in M group, Ad group, Ldc group, Ad + Ldc + LY group, and LY group, cardiac hemodynamic indices significantly improved, while the area of myocardial infarction was significantly reduced (p < 0.01). Furthermore, serum malondialdehyde (MDA) concentration but the activities of CK, CK-MB, TNF-α, and IL-6 declined, while the activities of superoxide dismutase (SOD), CAT and GSH-Px rose in Ad + Ldc group (p < 0.01). In Ad + Ldc group, p-Akt, T-Akt, and Bcl-2 increased, while Bax significantly decreased. Through comparison LY294002 significantly inhibited the protective effect of Ad combined with Ldc against MIRI in rats (p < 0.01). Conclusion: Anisodamine combination with lidocaine has a protective effect against MIRI in rats via PI3K/Akt signaling pathway, thus indicating that it is a potential therapeutic strategy for the management of myocardial ischemia-reperfusion. [ABSTRACT FROM AUTHOR]

Black spotted frogs have rich nutrition and delicious meat, and its market consumption has increased year by year. However, outbreaks of the diseases have caused huge losses to the breeding industry. The crooked head disease caused by Elizabethkingia miricola (E. miricola) is highly contagious and lethal, and there is no effective treatment method. Vaccination is the most promising strategy to prevent infectious diseases. Immersion vaccination has attracted many researchers because of its simplicity of operation in preventing infectious diseases. In addition, immersion vaccines can be more effective when used with adjuvants. In this study, we prepared inactivated E. miricola with 0.3% formaldehyde, and the black spotted frogs were vaccinated by soaking in inactivated E. miricola vaccine, anisodamine + vaccine mixture, β-glucan + vaccine mixture, chitosan + vaccine mixture for 60 min. PBS was used as a control. After being challenged by E. miricola , the survival rate of anisodamine + vaccine (57%) and chitosan + vaccine group (63%) was significantly higher than that of the control group (17%). By analyzing pathological sections, we found that the chitosan + vaccine and anisodamine + vaccine groups protected the brain, eye, liver and kidney tissues of the black spotted frogs compared to the control group, which was consistent with the trend of survival rate. In addition, chitosan + vaccine and anisodamine + vaccine groups had better effects on LZM, TSOD and C3 in serum than control group. Meanwhile, the numbers of the percentage of leukocytes/haemocytes in the peripheral blood of immunized black spotted frogs increased. The anisodamine + vaccine group (5.3%) and chitosan + vaccine (5.38%) group were significantly higher than the blank control group (2.24%), which indicate that the two groups induced a more significant immune response and were more resistant to bacterial invasion. The tissue bacterial loads in liver, brain, kidney and eye were significantly lower in the anisodamine + vaccine and chitosan + vaccine groups than that of the control group. This study explored and demonstrated the good efficiency of chitosan and anisodamine as adjuvants for immunization by immersion and provided a reference for improving the efficiency of immunization by immersion. • Inactivated E. miricola vaccine prevents black spotted frogs crooked head disease. • Chitosan or anisodamine improves the protection rate after E. miricola infection. • Chitosan or anisodamine as adjuvant significantly enhances the immune responses. • Chitosan or anisodamine as adjuvant alleviates tissue damage. [ABSTRACT FROM AUTHOR]

Objectives: To study the effects of anisodamine-tirofiban combined therapy on cardiac function and serological expression of serum NGF and ESM-1 in patients with acute myocardial infarction treated with percutaneous coronary intervention (PCI). Methods: Eighty patients with myocardial infarction treated in Cangzhou Medical College, Hebei, China from February 2015 to April 2017 were selected and divided into the control group and the research group according to the principle of random draw, 40 patients per group. The patients in the control group received symptomatic routine treatment, while the patients in the research group received anisodaminetirofiban combined therapy on the top of symptomatic routine treatment. Differences between the two groups in TIMI flow grades, cardiac function, levels of NGF and ESM-1 and adverse response were observed. Results: The recovery of cardiac function in the research group was statistically significant with P value (p<0.05) and better than the control group in TIMI flow grades, myocardial perfusion capacity and cardiac function. The serological indicators in the research group had a higher level of NGF and a lower level of ESM-1 than the control group, and the differences were statistically significant (p<0.05). In terms of safety, neither group showed significant hepatorenal disorders. Conclusion: The combined treatment of anisodamine-tirofiban in patients with acute myocardial infarction after percutaneous coronary intervention (PCI) can recover NGF and ESM-1 related proteins, improve postoperative myocardial perfusion, and accelerate the recovery of cardiac function. It is worth promoting in clinic. [ABSTRACT FROM AUTHOR]

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) provoked a pandemic of acute respiratory disease, namely coronavirus disease 2019 (COVID-19). Currently, effective drugs for this disease are urgently warranted. Anisodamine is a traditional Chinese medicine that is predicted as a potential therapeutic drug for the treatment of COVID-19. Therefore, this study aimed to investigate its antiviral activity and crucial targets in SARS-CoV-2 infection. SARS-CoV-2 and anisodamine were co-cultured in Vero E6 cells, and the antiviral activity of anisodamine was assessed by immunofluorescence assay. The antiviral activity of anisodamine was further measured by pseudovirus entry assay in HEK293/hACE2 cells. Finally, the predictions of crucial targets of anisodamine on SARS-CoV-2 were analyzed by molecular docking studies. We discovered that anisodamine suppressed SARS-CoV-2 infection in Vero E6 cells, and reduced the SARS-CoV-2 pseudovirus entry to HEK293/hACE2 cells. Furthermore, molecular docking studies indicated that anisodamine may target SARS-CoV-2 main protease (Mpro) with the docking score of −6.63 kcal/mol and formed three H-bonds with Gly143, Cys145, and Cys44 amino acid residues at the predicted active site of Mpro. This study suggests that anisodamine is a potent antiviral agent for treating COVID-19. [Display omitted] • Anisodamine inhibits SARS-CoV-2 replication in Vero E6 cells. • Anisodamine inhibits SARS-CoV-2 pseudovirus entry to HEK293/hACE2 cells. • Anisodamine targets SARS-CoV-2 main protease (Mpro) by molecular docking. • Anisodamine is a potent antiviral agent for treating COVID-19. [ABSTRACT FROM AUTHOR]

Abstract 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 χ 2 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).

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. We studied the early developmental toxicity of anisodamine in zebrafish. The results showed that anisodamine exposure resulted in toxicity such as increased pigmentation, decreased mineral density, smaller craniofacial area, and smaller eyes. Alterations in related genes were associated with the functional development of neural crest cells. [ABSTRACT FROM AUTHOR]

Purpose: To analyze intravenous administration of anisodamine's impact on coronary microvascular dysfunction (CMD) in obstructive epicardial coronary artery disease (CAD) patients who had undergone percutaneous coronary intervention (PCI). Methods: Enrollment of 210 patients in Shanghai Chest Hospital, Shanghai Jiaotong University with CMD was done in a randomized-controlled study. They were divided randomly into groups, viz, anisodamine (A) group and nitrate (N) group. A 14-day course of treatment was carried out in each group. 99mTc-MIBI myocardial perfusion imaging (MPI), treadmill exercise test (TET) and twodimensional echocardiography (TDE) were performed, and the symptoms of angina pectoris were recorded before and after treatment according to the classification, frequency, and duration of angina, as defined by Canadian Cardiovascular Society (CCS). Results: After treatment, summed stress score (SSS) and summed rest score (SRS) of MPI in group A significantly decreased after treatment (p < 0.001, respectively) and were remarkably lower than those in group N (p < 0.001, respectively). The CCS class in group A improved after treatment (p < 0.001) and was also better than in group N (p < 0.001). The frequency and duration of angina attack in group A significantly reduced after treatment (p < 0.001, respectively) and were notably lower than in group N (p < 0.001, respectively). Left ventricular ejection fraction in group A after treatment was higher than that before treatment (p = 0.046) and than that in group N (p = 0.048). Furthermore, the side effects of anisodamine were slight and tolerable. Conclusion: Intravenous administration of anisodamine is a potentially suitable optional treatment for CMD in patients with obstructive epicardial CAD who have undergone PCI. [ABSTRACT FROM AUTHOR]

Haoyu Wu,1 Yiwei Cao,2 Fengjun Chang,1 Chunyan Zhang,3 Yanchao Hu,3 Lei Liang1 1Department of Cardiology, Shaanxi Provincial People’s Hospital, Xi’an 710068, People’s Republic of China; 2Department of Electrocardiology, Shaanxi Provincial People’s Hospital, Xi’an 710068, People’s Republic of China; 3Department of Cardiology, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710004, People’s Republic of ChinaCorrespondence: Haoyu WuDepartment of Cardiology, Shaanxi Provincial People’s Hospital, No. 256 West Youyi Road, Xi’an 710068, People’s Republic of ChinaTel +86-29-85251331-3201Fax +86-29-85236987Email wxs5132006@163.comAbstract: Kounis syndrome is a rare type of acute coronary syndrome caused by coronary spasm with or without atherosclerotic plaque erosion or rupture due to inflammatory factors released by allergic reactions. Due to a lack of awareness, Kounis syndrome is often underdiagnosed. Here, we for the first time report a case of Kounis syndrome induced by anisodamine. A 48-year-old woman presented with upper abdominal pain and vomiting after eating. She was diagnosed with gastrointestinal spasm and intramuscularly injected with 10 mg anisodamine. The patient subsequently developed chest pain and hypotension with erythematous rash. A systemic allergic reaction was diagnosed. Saline solution, promethazine and dexamethasone were administered immediately. A 12-lead electrocardiogram indicated ST-segment elevation in II, III and aVF leads. Emergent coronary angiography was recommended. According to a preoperative electrocardiogram, the ST-segment elevation in the II, III and aVF leads had disappeared. Coronary angiograph revealed no significant coronary stenosis. The patient was diagnosed with Kounis syndrome induced by anisodamine, showing acute ST-segment elevation myocardial infarction due to allergic coronary vasospasm. During the 9-month follow-up, the patient did not receive further anisodamine injections and remained free of chest pain. In conclusion, it is essential for clinicians to be aware of Kounis syndrome because of the wide range of triggers and its potentially fatal evolution if not identified in time.Keywords: Kounis syndrome, allergic injury, coronary artery vasospasm, anisodamine

Ping Li, Yu Liu, Qiang He Department of Hepatobiliary Surgery, Beijing Chaoyang Hospital, Capital Medical University, Beijing 100020, People’s Republic of ChinaCorrespondence: Qiang HeDepartment of Hepatobiliary Surgery, Beijing Chaoyang Hospital, Capital Medical University, No. 8, Gongti South Road, Chaoyang District, Beijing 100020, People’s Republic of ChinaTel + 86-010-85231504Email heqiang349@sina.comIntroduction: Hepatocellular carcinoma (HCC) is a primary liver cancer with a 5-year incidence of over 70%. Anisodamine (ANI), an alkaloid extracted from Anisodus, has a good therapeutic effect in septic shock and morphine addiction. Our study designed to investigate the anticancer effect of anisodamine (ANI) on HCC.Materials and Methods: HepG2 cells were subcutaneously injected into BALB/C nude mice and the tumor tissue was subcutaneously inoculated to construct the transplanted tumor. Mice were randomly divided into 10 groups (n = 5): control group, ANI-10 group, ANI-50 group, ANI-200 group, ANI-200+pcDNA-NLRP3 group, ANI-200+EV group, sh-NLRP3 group, ANI-200 + sh-NLRP3 group, normal group and normal+ANI-200 group.Results: Studies indicated that ANI inhibited the growth of HCC xenografts and reduced liver damage in a dose-dependent manner. Besides, ANI increased the survival rate of tumor-bearing mice and suppressed the expression of NLRP3 in a dose-dependent manner. It is worth noting that NLRP3 overexpression reversed the inhibitory effect of ANI on HCC xenografts. In addition, TUNEL analysis showed that ANI-induced apoptosis of tumor cells, and NLRP3 overexpression reversed the inhibitory effect of ANI on HCC. Moreover, ANI further regulated the levels of IFN-γ, TNF-α, IL-4 and IL-27. Notably, low expression of NLRP3 enhanced the inhibitory effect of ANI on the development of HCC xenografts in mice.Discussion: These findings indicate that ANI suppressed the growth of HCC cells, induced apoptosis and regulated the levels of inflammatory factors by inhibiting NLRP3 inflammasome activation.Keywords: hepatocellular carcinoma, anisodamine, NOD-like receptor family pyrin domain containing 3, NLRP3, inflammatory factors, anticancer

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). [ABSTRACT FROM AUTHOR]

Background: The present study aimed to explore the potential effect of combining anisodamine with neostigmine on local scar formation following Roux-en-Y choledochojejunostomy (RCJS) in a novel rat model.Methods: The biliary obstruction model of Sprague Dawley (SD) rats was established in advance, and 54 rats were divided into nine groups randomly (sham operation group, anisodamine group, neostigmine group, combination group, and control group). Anisodamine (25 mg/kg) and neostigmine (50 μg/kg) were injected to the abdominal cavity separately or simultaneously for 1 week since the first day after surgery according to their allocated intervention, while the same amount of saline (0.5 ml) was injected intraperitoneally in the control group. Indexes including body weight, the diameter of the common bile duct, liver function, inflammatory indexes, and the condition of scar formation in different groups at certain time were evaluated in our study.Results: Recovery of liver function (ALT, AST, TB, DB, and GGT) and systematic inflammation indexes (CRP, TNF-α, and IL-1β) in the combination group was prior to that in the control group (p < 0.05), while no statistical difference in the serum level of IL-10 was observed among groups. Rats in the combination group represented a wider anastomotic diameter and lower expression of α-SMA and TGF-β1 at anastomotic stoma compared to the control group (p < 0.05). Histopathological staining showed slighter proliferation of collagen and smooth muscle fibers in rats’ bile duct wall and less local scar formation at anastomotic stoma compared to the control group.Conclusion: The combination of anisodamine and neostigmine can alleviate local and systemic inflammatory response, promote the recovery of liver function, and reduce scar formation in rats after the RCJS procedure.

Background: The present study aimed to explore the potential effect of combining anisodamine with neostigmine on local scar formation following Roux-en-Y choledochojejunostomy (RCJS) in a novel rat model. Methods: The biliary obstruction model of Sprague Dawley (SD) rats was established in advance, and 54 rats were divided into nine groups randomly (sham operation group, anisodamine group, neostigmine group, combination group, and control group). Anisodamine (25 mg/kg) and neostigmine (50 μg/kg) were injected to the abdominal cavity separately or simultaneously for 1 week since the first day after surgery according to their allocated intervention, while the same amount of saline (0.5 ml) was injected intraperitoneally in the control group. Indexes including body weight, the diameter of the common bile duct, liver function, inflammatory indexes, and the condition of scar formation in different groups at certain time were evaluated in our study. Results: Recovery of liver function (ALT, AST, TB, DB, and GGT) and systematic inflammation indexes (CRP, TNF-α, and IL-1β) in the combination group was prior to that in the control group (p < 0.05), while no statistical difference in the serum level of IL-10 was observed among groups. Rats in the combination group represented a wider anastomotic diameter and lower expression of α-SMA and TGF-β1 at anastomotic stoma compared to the control group (p < 0.05). Histopathological staining showed slighter proliferation of collagen and smooth muscle fibers in rats' bile duct wall and less local scar formation at anastomotic stoma compared to the control group. Conclusion: The combination of anisodamine and neostigmine can alleviate local and systemic inflammatory response, promote the recovery of liver function, and reduce scar formation in rats after the RCJS procedure. [ABSTRACT FROM AUTHOR]

• Exploring the role of the JAK2/STAT3 signaling pathway in sepsis-associated diaphragm dysfunction. • Revealing the antioxidant role of Anisodamine in septic diaphragmatic dysfunction. • Anisodamine relieves sepsis-related diaphragmatic dysfunction. 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. [ABSTRACT FROM AUTHOR]

Abstract 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.

Purpose: To investigate the therapeutic effect of anisodamine on hypoxic injury of brain microvascular endothelial cells, and the underlying mechanism of action. Methods: A hypoxic injury model of rat primary brain microvascular endothelial cells was established. Cell viability, proliferation, percent survival and apoptosis were assessed using MTT, EdU staining, trypan blue staining and TUNEL staining assays, respectively. The activities of lactate dehydrogenase (LDH) and matrix metalloproteinase-9 (MMP-9) were measured using colorimetry and enzyme-linked immunosorbent assay (ELISA), respectively. Expression levels of key proteins in the PI3K/Akt signal route were determined by Western blotting. Results: Anisodamine treatment significantly reduced apoptosis and LDH leakage in the rat cerebral vascular endothelial cell hypoxia injury model group (p < 0.001). At doses of 3 and 10 mM, anisodamine markedly reduced the cellular level of MMP-9 in rat cerebral vascular endothelial cell hypoxia injury model group (p < 0.001). Treatment of rat brain microvascular endothelial cells with anisodamine significantly reduced levels of caspase-3 and Bax, but up-regulated the expression levels of Bcl2, p-Akt and PI3K (p < 0.001). Conclusion: Anisodamine exerts significant protective effect against hypoxic injury in rat brain microvascular endothelial cells by modulating PI3K/Akt signaling pathway. This finding provides a scientific basis for the clinical application of anisodamine in the treatment and prevention of ischemic cerebrovascular disease. [ABSTRACT FROM AUTHOR]

[Display omitted] • Scopolamine ratio in shoots is 3-fold higher than that in the roots of D. innoxia seedlings. • D. innoxia roots synthesize tropane alkaloids from 2H 5 -Phenylalanine. • 2H 5 -Scopolamine is preferentially transported to shoots. • D. innoxia roots express all biosynthetic genes in the scopolamine pathway. Pharmacologically important tropane alkaloids such as hyoscyamine, and scopolamine, are synthesized in the roots of several Solanaceae and also accumulate in their shoots. The tropane alkaloids content in roots of D. innoxia seedlings was almost 3-fold higher than in their shoots. Moreover, scopolamine accounted for 77 % of the total tropane alkaloid content in shoots as compared to only 20 % in roots. All candidate genes in the scopolamine biosynthetic pathway were significantly expressed in D. innoxia mature roots with limited expression in mature leaves. Using exogenous isotopically labeled 2H 5 L-phenylalanine, we show here that root tissues, but not detached shoots, readily biosynthesize scopolamine. Tropane alkaloids newly synthesized by roots, and preferentially scopolamine, were further transported to shoots. Our evidence indicates that D. innoxia seedlings have the ability to synthesize tropane alkaloids in their roots and differentially transport them to the shoots. [ABSTRACT FROM AUTHOR]

Endotoxemia is characterized by initial uncontrollable inflammation, terminal immune paralysis, significant cell apoptosis and tissue injury, which can aggravate or induce multiple diseases and become one of the complications of many diseases. Therefore, anti-inflammatory and anti-apoptotic therapy is a valuable strategy for the treatment of endotoxemia-induced tissue injury. Traditional Chinese medicine exhibits great advantages in the treatment of endotoxemia. In this review, we have analyzed and summarized the active ingredients and their metabolites of Sanhuang Xiexin Decoction, a famous formula in endotoxemia therapy. We then have summarized the mechanisms of Sanhuang Xiexin Decoction against endotoxemia and its mediated tissue injury. Furthermore, silico strategy was used to evaluate the anti-apoptotic mechanism of anisodamine, a well-known natural product that widely used to improve survival in patients with septic shock. Finally, we also have summarized other anti-apoptotic natural products as well as their therapeutic effects on endotoxemia and its mediated tissue injury.

Purpose: Anisodamine hydrobromide (Ani HBr) has been used to improve the microcirculation during cardiovascular disorders and sepsis. Glycocalyx plays an important role in preserving the endothelial cell (EC) barrier permeability and nitric oxide (NO) production. We aimed to test the hypothesis that Ani HBr could protect the EC against permeability and NO production via preventing glycocalyx shedding. Methods: A human cerebral microvascular EC hCMEC/D3 injury model induced by lipopolysaccharide (LPS) was established. Ani HBr was administrated to ECs with the LPS challenge. Cell viability was performed by Cell Counting Kit-8 assay. Cell proliferation and apoptosis were detected by EdU and Hoechst 33342 staining. Apoptosis and cell cycle were also assessed by flow cytometry with annexin V staining and propidium iodide staining, respectively. Then, adherens junction integrity was evaluated basing on the immunofluorescence staining of vascular endothelial cadherin (VE-cadherin). The glycocalyx component heparan sulfate (HS) was stained in ECs. The cell permeability was evaluated by leakage of fluorescein isothiocyanate (FITC)-dextran. Cellular NO production was measured by the method of nitric acid reductase. Results: Ani HBr at 20 μg/mL significantly increased the viability of ECs with LPS challenge, but significantly inhibited the cell viability at 80 μg/mL, showing a bidirectional regulation of cell viability by Ani HBr. Ani HBr had not significantly change the LPS-induced EC proliferation. Ani HBr significantly reversed the induction of LPS on EC apoptosis. Ani HBr reinstated the LPS-induced glycocalyx and VE-cadherin shedding and adherens junction disruption. Ani HBr significantly alleviated LPS-induced EC layer permeability and NO production. Conclusion: Ani HBr protects ECs against LPS-induced increase in cell barrier permeability and nitric oxide production via preserving the integrity of glycocalyx. Ani HBr is a promising drug to rescue or protect the glycocalyx. [ABSTRACT FROM AUTHOR]

Alkaloids are natural products that occur widely in many herbal plants. Anisodamine, widely present in the Solanaceae family, is an alkaloid extracted from the roots of the Anisodus tanguticus Maxim. It is an antagonist to M-choline receptors and exhibits diverse pharmacological effects, such as cholinolytic effect, calcium antagonist effect, anti-oxygenation effect. Anisodamine, a prominent constituent of the tropine alkaloid family, exhibits a range of pharmacological effects akin to those of atropine and scopolamine. owing to its low toxicity and moderate efficacy in clinical to wide applications, especially for varieties of shock treatment. However, there remains a dearth of research regarding the in vivo pharmacokinetics, mechanism of action, and toxicity of anisodamine. Consequently, this paper provides a comprehensive review of the anti-shock effects, toxicity, and pharmacokinetic characteristics of anisodamine to increase the understanding of its medicinal value, and provide reference and inspiration for the clinical application and further in-depth research of anisodamine., (© 2024 Wiley-VHCA AG, Zurich, Switzerland.)

Introduction: Contrast-induced nephropathy (CIN) is a common post-procedural complication of percutaneous coronary intervention for acute myocardial infarction (AMI). Anisodamine hydrobromide is an alkaloid that has demonstrated efficacy in improving microcirculation. This meta-analysis aims to evaluate the reno-protective effects of Anisodamine in patients undergoing percutaneous coronary intervention (PCI) for AMI., Methods: PubMed, Embase, Cochrane Library, Scopus, and clinicaltrials.gov were searched from inception to January 2024 for randomized controlled trials (RCTs) comparing the efficacy of Anisodamine in preventing the development of CIN. Outcomes of interest included the incidence of CIN, serum creatinine levels, and estimated glomerular filtration rate (eGFR). A random-effects model was used for pooling standard mean differences (SMDs) and odds ratios (ORs) with a 95% CI. Statistical significance was considered at a P less than 0.05., Results: Three RCTs involving 563 patients were included. Anisodamine was associated with a reduction in the incidence of CIN [OR: 0.44; 95% CI: 0.28, 0.69; P =0.0003], a reduction in serum creatinine levels at 48 [SMD: -6.78; 95% CI: -10.54,-3.02; P =0.0004] and 72 h [SMD: -6.74; 95% CI: -13.33,-0.15; P =0.03], and a higher eGFR at 24 [SMD: 5.77; 95% CI: 0.39, 11.14; P =0.03], and 48 h [SMD: 4.70; 95% CI: 2.03,7.38; P =0.0006]. The levels of serum creatinine at 24 h and eGFR value at 72 h were comparable between both groups., Conclusions: Anisodamine has demonstrated clinical efficacy in ameliorating the development of CIN post-PCI in AMI patients. Large, multi-centric RCTs are warranted to evaluate the robustness of these findings., Competing Interests: The authors declare no conflicts of interest.Sponsorships or competing interests that may be relevant to content are disclosed at the end of this article., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Objectives: Anisodamine (ANI) has been used to treat a variety of diseases. However, the study of ANI in intervertebral disc degeneration (IVDD) is unclear. This study investigated the effects of ANI on degenerative nucleus pulposus cells (NPCs) and IVDD rats, and its possible mechanisms.Methods: Human nucleus pulposus cells (HNPCs) were treated with IL-1β (20 ng/ml) to simulate IVDD, and an IVDD rat model was constructed. IL-1β-induced HNPCs were treated with different concentrations (10, 20, or 40 μM) of ANI, and IVDD rats were also treated with ANI (1 mg/kg).Results: ANI treatment significantly reduced the apoptosis, caspase-3 and SA-β-gal activities, and p53 and p21 proteins expression, while promoted telomerase activity and aggrecan and collagen II synthesis in IL-1β-induced HNPCs. Moreover, the introduction of ANI inhibited the expression of IL-6, phosphorylation of JAK and STAT3, and nuclear translocation of p-STAT3 in Degenerated HNPCs. Additionally, the application of ANI abolished the effects of IL-6 on apoptosis, SA-β-gal and telomerase activity, and the expression of p53, p21, aggrecan and collagen II proteins in degenerated HNPCs. Simultaneously, ANI treatment enhanced the effects of AG490 (inhibitor of JAK/STAT3 pathway) on IL-1β-induced apoptosis, senescence and ECM degradation in HNPCs. Furthermore, ANI treatment markedly inhibited the apoptosis and senescence in the nucleus pulposus of IVDD rats, while promoted the synthesis of aggrecan and collagen II. ANI treatment obviously inhibited JAK and STAT3 phosphorylation and inhibited nuclear translocation of p-STAT3 in IVDD rats.Conclusion: ANI inhibited the senescence and ECM degradation of NPCs by regulating the IL-6/JAK/STAT3 pathway to improve the function of NPCs in IVDD, which may provide new ideas for the treatment of IVDD.

As one of the most important fish in freshwater aquaculture, gibel carp (Carassius auratus gibelio) is easily susceptible to Cyprinid herpesvirus 2 (CyHV-2). Immersion vaccination has attracted many researchers due to its simple operation in preventing infectious diseases. However, the unavoidable disadvantage is that the immersion vaccine must be used with adjuvants to get a better performance. In this study, gibel carps were vaccinated by a 60 min bath in a β-propiolactone-inactivated Cyprinid herpesvirus 2, mixed with DTT, β-glucan, anisodamine and scopolamine, respectively. After immunization, the fishs were challenged by CyHV-2 in 2 weeks. By analyzing pathological section, we found that β-glucan, anisodamine and scopolamine groups protected the gibel carp compared to the control group, which was consistent with the trend of survival rate. Specifically, β-glucan group in serum appeared best on lysozyme, TSOD and complement C3. Real time quantitative RT-PCR results demonstrated that in both spleen and head kidney tissues, mRNA expressions of typical Th1 immune response cytokines IL-2 and IFN-γ2 in β-glucan group and anisodamine group were significantly higher than other groups and the level of immunoglobulins related to systemic immunity (IgM) and mucosal immunity (IgZ) were also enhanced in the immune period. DTT group slightly affected immune gene and serum enzyme activity, while did not show an adjuvant effect on survival rate. In addition, four adjuvant groups could obviously inhibit CyHV-2 replication. This study explored and proved the good efficiency of β-glucan or anisodamine as immersion immune adjuvant and also provided reference for improving the efficiency of immersion immunity. • The vaccine can enter the fish and stimulate the immune response through the hypertonic immersion immune pathway. • β-glucan and anisodamine as immersion immune adjuvant improves the survival rate of gibel carp against CyHV-2. • β-glucan as adjuvant reinforces inflammatory response, Th1 type immune response and the expression level of IgM and IgZ. • DTT, β-glucan, anisodamine and scopolamine strengthen the vaccine inhibiting CyHV-2 replication. [ABSTRACT FROM AUTHOR]

Purpose: Anisodamine (An) has anti-inflammatory effects, but its role in acute pancreatitis is still unknown. This study aimed to explore the action mechanism of An pretreatment in lipopolysaccharide (LPS)-induced pancreatic acinar cells, hoping to provide a research basis for the disease treatment. Materials and methods: Pancreatic acinar cells were pretreated with An at different concentrations and then induced by LPS. The viability and apoptosis of the treated cells were measured by Cell Counting Kit-8 and flow cytometry. The releases of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and IL-18 were measured by enzyme-linked immunosorbent assay. The expressions of thioredoxin-interacting protein (TXNIP), apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC), NOD-like receptor protein 3 (NLRP3), Caspase-1, p65, and inhibitor of kappa B alpha (IκBα) in the treated cells were detected by Western blot and quantitative real-time polymerase chain reaction assay. Results: LPS promoted apoptosis of pancreatic acinar cells, suppressed cell viability, increased TNF-α, IL-1β, and IL-18 releases and the expression levels of TXNIP, ASC, NLRP3, Caspase-1, p-p65, and p-IκBα, however, such effects of LPS could be alleviated by An pretreatment with the strongest effect when the concentration of An was set at 100 μg/mL. Moreover, overexpressed NLRP3 aggravated the effects of LPS in pancreatic acinar cells, which could be reversed by pretreatment of 100 μg/mL An. Conclusion: An pretreatment attenuated LPS-induced apoptosis and inflammatory response of pancreatic acinar cells through suppressing NLRP3 and inactivating NF-κB signaling pathway, thus, it could be explored as a potential therapy for treating acute pancreatitis. [ABSTRACT FROM AUTHOR]

Hyperkalemia is a major cause of on-site death in crush syndrome (CS), which is more severe and common in male victims. Anisodamine is a belladonna alkaloid and widely used in China for treatment of shock through activation of α7 nicotinic acetylcholine receptor (α7nAChR). The present work was designed to study the protective effect of anisodamine in CS and the possible role of estradiol involved. Male and ovariectomized female CS mice exhibited lower serum estradiol and insulin sensitivity, and higher potassium compared to the relative female controls at 6 h after decompression. There was no gender difference in on-site mortality in CS mice within 24 h after decompression. Serum estradiol increased with similar values in CS mice of both gender compared to that in normal mice. Anisodamine decreased serum potassium and increased serum estradiol and insulin sensitivity in CS mice, and methyllycaconitine, selective antagonist of α7nAChR, counteracted such effects of anisodamine. Treatment with anisodamine or estradiol increased serum estradiol and insulin sensitivity, decreased serum potassium and on-site mortality, and eliminated the difference in these parameters between CS mice received ovariectomy or its sham operation. Anisodamine could also increase blood pressure in CS rats within 3.5 h after decompression, which could also be attenuated by methyllycaconitine, without influences on heart rate. These results suggest that activation of α7nAChR with anisodamine could decrease serum potassium and on-site mortality in CS through estradiol-induced enhancement of insulin sensitivity.

Huashanshen dripping pill (HSS), a commonly used traditional Chinese medicine, has been widely used in China due to its properties of antiasthma, expectorant, and antitussive. However, it was less in-depth understanding of the chemical composition, their absorption in plasma and potential biological mechanism. In this research, ultra performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry was developed to simultaneously identify the chemical constituents and absorption in rat plasma after oral administration of HSS. IgE-sensitized to ovalbumin was induced in BALB/c mice. ELISA and molecular docking analysis were carried out to identify their antiasthmatic mechanisms. As a result, 11 compounds were tentatively characterized by comparing the retention time, ion fragments, and the accurate mass measurement of [M + H]+ ions in the HSS. Two alkaloids including d-anisodamine and l-anisodamine were identified in the rat plasma after oral administration of HSS. The pills alleviated airway inflammation in lung tissues, and inhibited IgE, IL-4, and IL-5 in the serum. Furthermore, there were several amino acid residues involved in anisodamine-targeting receptors of hydrogen bonds and hydrophobic interactions via molecular docking indication. All in all, anisodamine would be the main component in the HSS whose antiasthmatic effects based on the inhibition of IgE, IL-4, and IL-5 production. [ABSTRACT FROM AUTHOR]

Hyperkalemia is a major cause of on-site death in crush syndrome (CS), which is more severe and common in male victims. Anisodamine is a belladonna alkaloid and widely used in China for treatment of shock through activation of α7 nicotinic acetylcholine receptor (α7nAChR). The present work was designed to study the protective effect of anisodamine in CS and the possible role of estradiol involved. Male and ovariectomized female CS mice exhibited lower serum estradiol and insulin sensitivity, and higher potassium compared to the relative female controls at 6 h after decompression. There was no gender difference in on-site mortality in CS mice within 24 h after decompression. Serum estradiol increased with similar values in CS mice of both gender compared to that in normal mice. Anisodamine decreased serum potassium and increased serum estradiol and insulin sensitivity in CS mice, and methyllycaconitine, selective antagonist of α7nAChR, counteracted such effects of anisodamine. Treatment with anisodamine or estradiol increased serum estradiol and insulin sensitivity, decreased serum potassium and on-site mortality, and eliminated the difference in these parameters between CS mice received ovariectomy or its sham operation. Anisodamine could also increase blood pressure in CS rats within 3.5 h after decompression, which could also be attenuated by methyllycaconitine, without influences on heart rate. These results suggest that activation of α7nAChR with anisodamine could decrease serum potassium and on-site mortality in CS through estradiol-induced enhancement of insulin sensitivity. [ABSTRACT FROM AUTHOR]

Siniperca chuatsi is an economically important fish in China, but infectious spleen and kidney necrosis virus (ISKNV) causes high mortality and significant economic losses. Currently, vaccination is the most promising strategy to prevent infectious diseases, while adjuvant can effectively enhance immune responses. In this study, inactivated ISKNV vaccine was prepared, then poly (I:C), chitosan, anisodamine and ims1312 were used as adjuvants to evaluate the effect on the immune responses and ISKNV replication. Chitosan could strongly boost the protection of liver and spleen tissues by pathological sections. In serum, poly (I:C) and chitosan group had protective effect on catalase, acid phosphatase, blood urea nitrogen. mRNA expressions showed these adjuvants induced the cytokines of early immune responses (TNF-α , Viperin) in both spleen and mesonephron by real time quantitative RT-PCR assays. Meanwhile, poly (I:C), chitosan and anisodamine were significantly improved the antiviral function and inhibited ISKNV replication. Chitosan and anisodamine played a significantly protective role in the immune protective rate test. The results indicated that all the four adjuvants are valid in the inactivated ISKNV vaccine, and chitosan is recommended preferentially. The present study provides reference for other animal vaccine adjuvants. • Chitosan and anisodamine as adjuvant enhance the survival rate. • Chitosan and poly (I:C) strongly improve the effects of the whole immune levels. • Chitosan and anisodamine strengthen the vaccine inhibiting ISKNV replication. [ABSTRACT FROM AUTHOR]

• Mandragora spp. accessions show significant alkaloid chemodiversity. • M. officinarum and M. turcomanica lack anisodamine and scopolamine. • M. autumnalis accumulates hysocyamine, anisodamine and scopolamine. • H6H is conserved among scopolamine-producing species but mutated in M. officinarum. • H6H from M. autumnalis is functionally active but H6H from M. officinarum is not. Mandrakes (Mandragora spp., Solanaceae) are known to contain tropane alkaloids and have been used since antiquity in traditional medicine. Tropane alkaloids such as scopolamine and hyoscyamine are used in modern medicine to treat pain, motion sickness, as eye pupil dilators and antidotes against organo-phosphate poisoning. Hyoscyamine is converted to 6β-hydroxyhyoscyamine (anisodamine) and scopolamine by hyoscyamine 6β-hydroxylase (H6H), a 2-oxoglutarate dependent dioxygenase. We describe here a marked chemo-diversity in the tropane alkaloid content in Mandragora spp. M. officinarum and M. turcomanica lack anisodamine and scopolamine but display up to 10 fold higher hyoscyamine levels as compared with M. autumnalis. Transcriptomic analyses revealed that H6H is highly conserved among scopolamine-producing Solanaceae. MoH6H present in M. officinarum differs in several amino acid residues including a homozygotic mutation in the substrate binding region of the protein and its prevalence among accessions was confirmed by Cleaved-Amplified-Polymorphic-Sequence analyses. Functional expression revealed that MaH6H , a gene isolated from M. autumnalis encodes an active H6H enzyme while the MoH6H sequence isolated from M. officinarum was functionally inactive. A single G to T mutation in nucleotide 663 of MoH6H is associated with the lack of anisodamine and scopolamine in M. officinalis. [ABSTRACT FROM AUTHOR]

Septic shock is a common acute and critical disease in the emergency department. It refers to the persistent hypotension caused by severe infection, and the acute circulatory failure that is difficult to correct after adequate fluid resuscitation, which can quickly lead to severe damage of tissues and organs. The main cause of death is multi-organ failure, with a higher fatality rate. Anisodamine, an anticholinergic drug extracted from Chinese Solanaceae, can dilate the blood vessels, improve the microcirculation, improve the cardiovascular function, protect cells and reduce the blood lactic acid concentration, and decrease the mortality of septic shock. It is an important auxiliary means for the treatment of septic shock and is worthy of clinical application. This study systematically collected and reviewed the related literature on the treatment of septic shock with anisodamine by searching the databases of CNKI, Wanfang database and VIP database. The results showed that anisodamine was effective in the treatment of septic shock, and its main anti-shock mechanisms included relieving vasospasm, improving microcirculation, inhibiting platelet aggregation, blocking M-cholinergic receptor, stimulating the respiratory center of the body, regulating the vagus nerve and inhibiting the gland secretion. It is hoped that this review can provide a reference for the clinical application of anisodamine in the treatment of septic shock. [ABSTRACT FROM AUTHOR]

Anisodamine is an anticholinergic drug isolated from the Chinese Solanaceae. It is an M choline receptor blocker and is mainly used in the treatment of septic shock, smooth muscle spasm, peripheral vascular disease(thromboangiitis obliterans, diabetic peripheral vascular disease, etc.), various neuralgia, vertigo and fundus diseases(central retinitis, retinal arterial thrombosis). In this study, the clinical application literature of anisodamine was reviewed and analyzed by systematically searching databases such as CNKI, Wanfang database and VIP database. The results showed that anisodamine was mainly used for septic shock, smooth muscle spasm, vertigo, acute pancreatitis, calculous renal colic and bronchial asthma; in the meantime, anisodamine was also used in diabetic foot, gestational hypertension, anesthesia and endoscopy. It is hoped that this study can provide reference for the clinical application and further study of anisodamine. [ABSTRACT FROM AUTHOR]

[Display omitted] • The study investigated the protective effect of 654-2, a potential therapeutic compound, on radiation-induced lung injury. • Treatment with 654-2 resulted in reduced DNA damage and cellular senescence in lung tissue and alveolar epithelial cells. • 654-2 activated the Nrf2/ARE pathway, leading to increased expression of antioxidant genes such as NQO1 and HO-1. Radiation-induced lung injury (RILI) is a common side effect of thoracic tumor radiotherapy, including early-stage radiation-induced lung injury (RP) and late-stage radiation-induced pulmonary fibrosis (RIPF). Currently, it is urgently needed to clarify the pathogenesis of RILI and find safe and effective RILI treatment methods. Irradiation causes DNA damage and oxidative stress in tissues and cells, induces cellular senescence, and promotes the occurrence and development of RILI. In recent years, Anisodamine (654-2) has shown potential therapeutic value in acute lung injury, acute kidney injury, chlamydial pneumonia, and COVID-19. However, there is currently no research on the mechanism of 654-2-mediated cellular senescence and its preventive and therapeutic effects on RILI. This study aimed to investigate the protective effect and mechanism of 654-2 on X-ray-induced RILI. In vivo experiments involved a mouse RILI model with 18 Gy X-ray irradiation. Mice were divided into control, model, medication (control + 654-2), and treatment (model + 654-2) groups. And mice in medication and treatment groups were intraperitoneal injection of 5 mg/kg 654-2 every other day until being sacrificed at week 6. In vitro experiments used MLE-12 cells irradiated with 16 Gy and divided into control, model, and model + 654-2（2 μM and 10 μM） groups. Various assays were performed to evaluate lung tissue morphology, fibrosis, apoptosis, cytokine expression, cellular senescence, protein expression, and antioxidant capacity. 654-2 mitigated pulmonary pathological damage, inflammation, DNA damage, cellular senescence, and apoptosis in RILI mice and MLE-12 cells. It restored epithelial cell proliferation ability and enhanced antioxidant capacity. Additionally, 654-2 activated the Nrf2/ARE pathway, increased Nrf2 phosphorylation, and upregulated antioxidant gene expression. Inhibition of Nrf2 reversed the effects of 654-2 on ROS production, antioxidant capacity, and cell senescence. 654-2 can activate the Nrf2/ARE pathway, enhance cellular antioxidant capacity, and inhibit cellular senescence, thereby exerting a protective effect against RILI. [ABSTRACT FROM AUTHOR]

Objective: To investigate the effect of anisodamine combining with conventional therapy on the degree of lung injury and inflammatory reaction of patients with acute pulmonary contusion. Methods: A total of 48 patients with acute pulmonary contusion treated in our hospital emergency department from April 2011 to October 2015 were enrolled as the research object and were divided into experimental group and control group by using a method of random number table. Experimental group received anisodamine combining with conventional therapy and control group received conventional therapy. In the process of the treatment, the mechanical ventilation time, hospital stays in intensive care unit and the number of cases developed into acute respiratory distress syndrome and multiple organ dysfunction syndromes of patients in two groups were observed. Oxygenation indexes of patients were respectively calculated on Days 1, 2 and 3 after treatment. The contents of inflammatory mediators in serum were detected on Day 3 after treatment. Results: The mechanical ventilation time and hospital stays in intensive care unit [(9.52 ± 1.41) vs. (14.57 ± 2.51) days] of patients in experimental group were signifi- cantly shorter than those in control group, and the number of cases developed into acute respiratory distress syndrome [1 (4.17%) vs. 9 (37.50%)] and multiple organ dysfunction syndrome [1 (4.17%) vs. 7 (29.17%)] was significantly less than those in control group. Oxygenation indexes (294.52 ± 41.26 vs. 257.63 ± 38.52; 357.74 ± 47.74 vs. 279.87 ± 31.46; 396.71 ± 55.12 vs. 279.87 ± 31.46) of patients were respectively calculated on Days 1, 2 and 3 after treatment, which were significantly higher than those in the control group. On Day 3 after treatment, the contents of serum C-reactive protein [(7.94 ± 1.05) vs. (14.49 ± 2.97) mg/L], tumor necrosis factor a [(264.69 ± 41.58) vs. (417.87 ± 64.51) ng/L], interleukin-6 (IL-6) [(147.72 ± 21.36) vs. (257.68 ± 41.54) ng/L], IL-8 [(93.68 ± 12.52) vs. (145.62 ± 22.65) ng/L], IL-10 [(205.64 ± 31.56) vs. (336.62 ± 51.38) ng/L] and myeloid cells-1 (73.32 ± 10.39 vs. 114.45 ± 18.51) of patients in experimental group were significantly lower than those in the control group. Conclusions: The anisodamine combining with conventional therapy can relieve the degree of lung injury caused by acute pulmonary contusion, improve ventilatory function, lower the incidence of acute respiratory distress syndrome and multiple organ dysfunction syndrome and inhibit the activation of inflammatory reaction and the release of inflammatory mediators.

Objective To examine whether no anisodamine injection before CTE was feasible without impairing image quality and diagnostic performance. Materials The change of mural thickness and luminal diameter were compared between using and no using anisodamine. The diagnostic performance of small-bowel disease was analyzed and compared. Results No motion artifact was detected in two groups. There was no significant difference regarding the change of luminal diameter and mural thickness (all P > 0.05). The diagnostic accuracy of small-bowel disease was no significant difference ( P = 0.63). Conclusion Lack of anisodamine injection before CTE did not impair image quality and diagnostic performance compared with CTEs performed with anisodamine injection. [ABSTRACT FROM AUTHOR]

Tibetan ethnomedicine is famous worldwide, both for its high effectiveness and unique cultural background. Many poisonous plants have been widely used to treat disorders in the Tibetan medicinal system. In the present review article, some representative poisonous plant species are introduced in terms of their significance in traditional Tibetan medicinal practices. They are Aconitum pendulum, Strychnos nux-vomica, Datura stramonium and Anisodus tanguticus, for which the toxic chemical constituents, bioactivities and pharmacological functions are reviewed herein. The most important toxins include aconitine, strychnine, scopolamine, and anisodamine. These toxic plants are still currently in use for pain-reduction and other purposes by Tibetan healers after processing.

The aim of the present study was to investigate the cardioprotective effects of anisodamine against myocardial ischemia/reperfusion (I/R) injury and the molecular mechanisms involved. The present results demonstrated that anisodamine attenuated myocardial infarct sizes, decreased the levels of creatine kinase and lactate dehydrogenase, whereas it increased the left ventricular (LV) systolic pressure, the LV end-diastolic pressure, and the LV pressure maximum rising and falling rates in a myocardial I/R rat model. In addition, anisodamine was revealed to suppress oxidative stress, inflammatory factor production and myocardial cell apoptosis, as demonstrated by the downregulation of caspase-3 and apoptosis regulator BAX protein expression. The production of reactive oxygen species was decreased and the protein expression of inducible nitric oxide synthase (iNOS) was downregulated, whereas the expression of endothelial NOS was enhanced. In addition, the activity of nicotinamide-adenine dinucleotide phosphate oxidase (Nox) was suppressed and the expression of Nox4 was downregulated in rats with myocardial I/R injury. In conclusion, the results of the present study suggested that anisodamine exerted a cardioprotective effect against myocardial I/R injury in rats, through the inhibition of oxidative stress, the suppression of inflammatory processes and the inhibition of myocardial cell apoptosis. [ABSTRACT FROM AUTHOR]

Objective To explore the synergistic effect of probucol combined with anisodamine on contrast-induced nephropathy (CIN) in diabetic rats. Methods Totally 130 rats were selected to make the models of diabetic rats. The diabetic rat models were randomly divided into the model group, probucol group, anisodamine group, and the combination group (probucol combined with anisodamine) , with 21 rats in each group. In addition, 10 normal rats were selected as the control group. After 9-week feeding, the diabetic rats in the probucol group and the combination group received intragastric administration of probucol (500 mg/kg) for 6 cl. On the eighth day, rats in the anisodamine group and combination group were injected with anisodamine 100μg/100g intraperitoneally before the preparation of CIN model. After 15 min, all diabetic rats were injected with urografin 0. 8 mL/100 g intravenously to prepare the CIN models. One hour later, rats in the anisodamine group and combination group were given anisodamine 100 μg/100 g intraperitoneally for 7 times. The coomassie brilliant blue (CBB) was used to determine the urinary protein before and after injection with contrast medium 24 h. Blood samples were taken from the inner canthus vein for measuring the serum BUN and Scr levels. After weighed, the left and right kidneys of all rats were also weighed for calculating the renal index. Pathological changes of kidneys were observed by HE staining. The renal tissues were homogenized for testing nitric oxide ( NO) , nitric oxide synthase (NOS), superoxide dismutase (SOD) , malondialdehyde (MDA) and total antioxidant capacity (T-AOC). The expression levels of B cell lymphoma/leukemia-2 gene (Bcl-2) and Bcl-2-relatecl X protein (Bax) mRNA were detected by fluorescent quantitative PCR. Results (l)The levels of BUN, Scr, and UAE in the model group were higher than those in the control group. The levels of BUN, Scr and UAE in the probucol group and combination group were lower than those in the model group, and the levels of BUN, Scr, and UAE in the combination group were lower than those of the anisodamine group ( all P < 0. 05 ). (2)The renal index in the model group was higher than that of the control group, and the renal index in the probucol group and the combination group was lower than that in the model group (all P < 0. 05 ).③ Compared with the model group, the NOS level increased and MDA decreased in the probucol group and anisodamine group (both P <0. 05). The levels of SOD and T-AOC in the combination group were higher than those in the probucol group and anisodamine group (both P <0. 05). (4)Compared with the model group, the Bax expression decreased, the levels of Bcl-2 and the ratio of Bcl-2/Bax increased in the probucol group and combination group ( all P <0. 05) , and the ratio of Bcl-2/Bax in the aniso-damine group increased (P < 0. 05 ). The ratio of Bcl-2/Bax in the combination group was higher than that in the aniso-damine group (P < 0. 05). Conclusion The probucol combined with anisodamine can alleviate the renal injury of diabetic CIN rats. The mechanism may be related to the inhibition of oxidative stress and up-regulation of Bcl-2/Bax ratio, and the effect is superior to single drug application. [ABSTRACT FROM AUTHOR]