Exposure to ephedrine attenuates Th1/Th2 imbalance underlying OVA-induced asthma through airway epithelial cell-derived exosomal lnc-TRPM2-AS.

Although various anti-inflammatory medications, such as ephedrine, are employed to manage cough-variant asthma, their underlying mechanisms are yet to be fully understood. Recent studies suggest that exosomes derived from airway epithelial cells (AECs) contain components like messenger RNAs (mRNAs), micro-RNAs (miRNAs), and long noncoding RNA (lncRNA), which play roles in the occurrence and progression of airway inflammation. This study investigates the influence of AEC-derived exosomes on the efficacy of ephedrine in treating cough-variant asthma. We established a mouse model of asthma and measured airway resistance and serum inflammatory cell levels. Real-time polymerase chain reaction (RT-qPCR), Western blotting, and enzyme-linked immunosorbent assay (ELISA) analyses were used to assess gene and protein expression levels. Exosomes were isolated and characterized. RNA immunoprecipitation (RIP) and RNA pull-down assays were conducted to examine the interaction between hnRNPA2B1 and lnc-TRPM2-AS1. In the ovalbumin (OVA)-challenged mouse model, ephedrine treatment reduced inflammatory responses, airway resistance, and Th1/Th2 cell imbalance. Exosomes from OVA-treated AECs showed elevated levels of lnc-TRPM2-AS1, which were diminished following ephedrine treatment. The exosomal lnc-TRPM2-AS1 mediated the Th1/Th2 imbalance in CD4+ T cells, with its packaging into exosomes being facilitated by hnRNPA2B1. This study unveils a novel mechanism by which ephedrine ameliorates OVA-induced CD4+ T cell imbalance by suppressing AEC-derived exosomal lnc-TRPM2-AS1. These findings could provide a theoretical framework for using ephedrine in asthma treatment.

Biochemical and immunohistochemical examination of the effects of ephedrine in rat ovary tissue.

PURPOSE: It was aimed to investigate the biochemical and immunohistochemical effects of ephedrine (EPH) in bilateral ovariectomized rats. METHODS: Twenty-four Sprague Dawley female rats were divided into three groups: control group: The abdomen was opened and closed without any treatment; ischemia-reperfusion (IR) group: 2 h of ischemia followed by 2 h of reperfusion were allowed to cause IR injury; IR+EPH group: oral EPH solution (5 mg/kg) was administered for 28 days. RESULTS: Biochemical parameters were statistically significant in group comparisons. Increased interleukin-6 (IL-6) expression, degenerative preantral and antral follicle cells and inflammatory cells around blood vessels were seen in IR group. Negative IL-6 expression was observed in seminal epithelial cells, preantral and antral follicle cells in IR+EPH group. While caspase-3 activity increased in granulosa cells and stromal cells in IR group, caspase-3 expression was negative in preantral and antral follicle cells in the germinal epithelium and cortex in IR+EPH group. CONCLUSIONS: The effect of apoptosis, which occurs with the signaling that starts in the cell nucleus, caused the cessation of the stimulating effect at the nuclear level after EPH administration, and a decrease in the antioxidative effect in IR damage and inflammation in the apoptotic process.

Ephedrae Herba: A Review of Its Phytochemistry, Pharmacology, Clinical Application, and Alkaloid Toxicity.

Ephedrae Herba (Ephedra), known as "MaHuang" in China, is the dried straw stem that is associated with the lung and urinary bladder meridians. At present, more than 60 species of Ephedra plants have been identified, which contain more than 100 compounds, including alkaloids, flavonoids, tannins, sugars, and organic phenolic acids. This herb has long been used to treat asthma, liver disease, skin disease, and other diseases, and has shown unique efficacy in the treatment of COVID-19 infection. Because alkaloids are the main components causing toxicity, the safety of Ephedra must be considered. However, the nonalkaloid components of Ephedra can be effectively used to replace ephedrine extracts to treat some diseases, and reasonable use can ensure the safety of Ephedra. We reviewed the phytochemistry, pharmacology, clinical application, and alkaloid toxicity of Ephedra, and describe prospects for its future development to facilitate the development of Ephedra.

Correlation Between Cerebral Tissue Oxygen Saturation and Oxygen Extraction Fraction During Anesthesia: Monitoring Cerebral Metabolic Demand-supply Balance During Vasopressor Administration.

BACKGROUND: The speculation that cerebral tissue oxygen saturation (SctO 2 ) measured using tissue near-infrared spectroscopy reflects the balance between cerebral metabolic rate of oxygen and cerebral oxygen delivery has not been validated. Our objective was to correlate SctO 2 with cerebral oxygen extraction fraction (OEF) measured using positron emission tomography; OEF is the ratio between cerebral metabolic rate of oxygen and cerebral oxygen delivery and reflects the balance between these 2 variables. MATERIALS AND METHODS: This cohort study was based on data collected in a previously published trial assessing phenylephrine versus ephedrine treatment in anesthetized patients undergoing brain tumor surgery. The variables of interest were measured twice over the healthy hemisphere before surgery: the first measurement performed after anesthesia induction and the second measurement performed after induction of a ∼20% increase in blood pressure using either phenylephrine or ephedrine. RESULTS: Data from 24 patients were analyzed. The overall vasopressor-induced relative changes in SctO 2 (ΔSctO 2 ) and OEF (ΔOEF) were 3.16% [interquartile range, -0.73% to 6.04%] and -12.5% [interquartile range, -24.0% to -6.19%], respectively. ΔSctO 2 negatively correlated with ΔOEF after phenylephrine treatment (Spearman rank correlation coefficient [ rs ]=-0.76; P =0.007), ephedrine treatment ( rs =-0.76; P =0.006), and any treatment ( rs =-0.79; P <0.001). ΔSctO 2 significantly associated with ΔOEF based on multivariable analysis with ΔOEF, relative changes in mean arterial pressure, arterial blood oxygen tension, and the bispectral index as covariates ( P =0.036). CONCLUSIONS: The negative correlation between changes in SctO 2 and OEF suggests that SctO 2 may reflect the cerebral metabolic demand-supply balance during vasopressor treatment. The generalizability of our findings in other clinical scenarios remains to be determined.

The Regional Cerebral Oxygen Saturation Effect of Inotropes/Vasopressors Administered to Treat Intraoperative Hypotension: A Bayesian Network Meta-analysis.

One of the main concerns of intraoperative hypotension is adequacy of cerebral perfusion, as cerebral blood flow decreases passively when mean arterial pressure falls below the lower limit of cerebral autoregulation. Treatment of intraoperative hypotension includes administration of drugs, such as inotropes and vasopressors, which have different pharmacological effects on cerebral hemodynamics; there is no consensus on the preferred drug to use. We performed a network meta-analysis (NMA) to pool and analyze data comparing the effect on cerebral oxygen saturation (ScO 2 ) measured by cerebral oximetry of various inotropes/vasopressors used to treat intraoperative hypotension. We searched randomized control trials in Embase, Ovid Medline, Scopus, Cochrane Central Register of Controlled Trials, and Web of Science. We included studies that enrolled adult patients undergoing surgery under general/spinal anesthesia that compared at least 2 inotropes/vasopressors to treat hypotension. We reviewed 51 full-text manuscripts and included 9 randomized controlled trials in our study. The primary outcome was change in ScO 2 . Our results showed the likelihood that dopamine, ephedrine, and norepinephrine had the lowest probability of decreasing ScO 2 . The suggested rank order to maintain ScO 2 , from higher to lower, was dopamine

Cardiac effects of ephedrine, norephedrine, mescaline, and 3,4-methylenedioxymethamphetamine (MDMA) in mouse and human atrial preparations.

The use of recreational drugs like ephedrine, norephedrine, 3,4-methylenedioxymethamphetamine (MDMA), and mescaline can lead to intoxication and, at worst, to death. One reason for a fatal course of intoxication with these drugs might lie in cardiac arrhythmias. To the best of our knowledge, their inotropic effects have not yet been studied in isolated human cardiac preparations. Therefore, we measured inotropic effects of the hallucinogenic drugs ephedrine, norephedrine, mescaline, and MDMA in isolated mouse left atrial (mLA) and right atrial (mRA) preparations as well as in human right atrial (hRA) preparations obtained during cardiac surgery. Under these experimental conditions, ephedrine, norephedrine, and MDMA increased force of contraction (mLA, hRA) and beating rate (mRA) in a time- and concentration-dependent way, starting at 1-3 µM but these drugs were less effective than isoprenaline. Mescaline alone or in the presence of phosphodiesterase inhibitors did not increase force in mLA or hRA. The positive inotropic effects of ephedrine, norephedrine, or MDMA were accompanied by increases in the rate of tension and relaxation and by shortening of time of relaxation and, moreover, by an augmented phosphorylation state of the inhibitory subunit of troponin in hRA. All effects were greatly attenuated by cocaine (10 µM) or propranolol (10 µM) treatment. In summary, the hallucinogenic drugs ephedrine, norephedrine, and MDMA, but not mescaline, increased force of contraction and increased protein phosphorylation presumably, in part, by a release of noradrenaline in isolated human atrial preparations and thus can be regarded as indirect sympathomimetic drugs in the human atrium.

Ephedra herb reduces adriamycin-induced testicular toxicity by upregulating the gonadotropin-releasing hormone signalling pathway.

OBJECTIVE: We investigated the protective effects of ephedra herb (HEPH) on adriamycin-induced testicular toxicity in rats and explored the potential mechanisms underlying these effects. METHODS: A rat model of adriamycin injury was established, and sperm motility-related indicator and oxidative stress levels in the testis were evaluated. Serum levels of sex hormones and levels of testicular cell apoptosis were detected by enzyme-linked immunosorbent assay and flow cytometry, respectively. Western blotting (WB), immunofluorescence analyses, and reverse transcription-polymerase chain reaction (RT-PCR) were performed to evaluate the gonadotropin-releasing hormone (GnRH) signalling pathway- and meiosis-related genes and proteins. In subsequent in vitro experiments, adriamycin was used to stimulate GC-1 cells, which were treated with HEPH, ephedrine, or pseudoephedrine. Cell viability was assessed using flow cytometry to detect apoptosis and reactive oxygen species, whereas the GnRH signalling pathway and levels of meiosis-related genes and proteins were evaluated by InCell WB, a high-content imaging system, and RT-PCR. RESULTS: Per in vivo experiments, HEPH restored testicular weight and function, sperm characteristics, serum and tissue hormonal levels, and antioxidant defences and significantly activated the GnRH signalling pathway- and meiosis-related protein levels. All protective effects of HEPH against adriamycin-induced injury were antagonised by the GnRH antagonist cetrorelix. In vitro, HEPH, ephedrine, and pseudoephedrine significantly reduced adriamycin-induced GC-1 cell apoptosis and reactive oxygen species levels and increased the expression of GnRH signalling pathway- and meiosis-related proteins. The effect of pseudoephedrine was greater than that of ephedrine, and these findings may be an important basis for understanding the effects of HEPH.

A randomized comparison of hemodynamic changes in response to a heart rate-dependent phenylephrine/ephedrine protocol versus ephedrine-only for spinal hypotension during elective cesarean section.

AIM: To compare incidences of abnormal heart rate (HR) between the phenylephrine/ephedrine protocol (P/E protocol) against the ephedrine-only (C) protocol, conventionally used for treating predelivery hypotension following spinal anesthesia for cesarean section. METHODS: Two hundred and sixty-eight parturients with pre-delivery hypotension after spinal anesthesia were equally randomized to (1) Group P/E (n = 134), phenylephrine 100 mcg in 10 mL intravenously if HR ≥ 60 beats/min (bpm), or ephedrine 6 mg intravenously if HR < 60 bpm, and 2) Group C (n = 134). The primary outcome was the incidence of the parturients with abnormal HR after vasopressor administration. The secondary outcome was the mean differences of HR and hypotensive periods during the pre-delivery period. RESULTS: There was no significant difference of between-group incidences of bradycardia (12.0% in Group P/E vs 6.7% in Group C, p = 0.136) and tachycardia (26.9% vs 35.8%, p = 0.114). Mean HR was 81.9 bpm (95% confidence interval [CI] 79.9, 84.3) in Group P/E, and 88.8 bpm (86.8, 90.6) in Group C (p < 0.001). The duration of hypotension in relation to the time interval from spinal anesthesia to delivery was 20.9% (95% CI 18.4-23.2) in Group P/E, and 26.5% (23.9-29.3) in Group C (p < 0.01). The calculated area under the curve (AUC) of abnormal HR in relation to time was significantly reduced only in Group P/E (p < 0.010). CONCLUSIONS: The incidences of out-of-range HR were comparable, but the P/E protocol resulted in a lower mean HR and better control of systolic blood pressure than the ephedrine-only protocol.

Maoto, a traditional Japanese medicine, controls acute systemic inflammation induced by polyI:C administration through noradrenergic function.

Maoto, a traditional Japanese medicine (Kampo), is widely used to treat upper respiratory tract infections, including influenza virus infection. Although maoto is known to inhibit pro-inflammatory responses in a rodent model of acute inflammation, its underlying mechanism remains to be determined. In this study, we investigated the involvement of immune responses and noradrenergic function in the inhibitory action of maoto. In a mouse model of polyI:C-induced acute inflammation, maoto was administered orally in conjunction with intraperitoneal injection of PolyI:C (6 mg/kg), and blood was collected after 2 h for measurement of plasma cytokines by ELISA. Maoto significantly decreased PolyI:C-induced TNF-α levels and increased IL-10 production. Neither pretreatment with IL-10 neutralizing antibodies nor T-cell deficiency using nude mice modified the inhibitory effect of maoto, indicating that the anti-inflammatory effects of maoto are independent of IL-10 and T cells. Furthermore, the inhibitory effects of maoto on PolyI:C-induced TNF-α production were not observed in ex vivo splenocytes, suggesting that maoto does not act directly on inflammatory cells. Lastly, pretreatment with a ß-adrenergic receptor antagonist partially cancelled the anti-inflammatory effects of maoto. Collectively, these results suggest that maoto mediates its anti-inflammatory effects via ß-adrenergic receptors in vivo.

Ephedrine ameliorates chronic obstructive pulmonary disease (COPD) through restraining endoplasmic reticulum (ER) stress in vitro and in vivo.

Chronic obstructive pulmonary disease (COPD) is a chronic lung disease with limited therapeutic options. Ephedrine (Eph) isolated from Ephedra exerts regulatory role in inflammatory response. However, its effects on COPD development still remain unknown. In the present study, we found that Eph significantly ameliorated apoptosis, oxidative stress and inflammatory response in cigarette smoke extract (CSE)-stimulated human bronchial epithelial cells (HBECs). Moreover, all these cellular events attenuated by Eph were closely associated with reactive oxygen species (ROS) decreasing. Furthermore, we found that the expression of endoplasmic reticulum (ER) stress-associated signaling could be down-regulated by Eph in HBECs without any stimuli. Meanwhile, ER stress was strongly induced by CSE, which was, however, effectively mitigated by Eph exposure in HBECs. Intriguingly, we found that Eph-alleviated cell death, ROS generation and inflammation were almost eliminated by the promotion of ER stress via over-expressing Bip in HBECs upon CSE stimulation. Moreover, Eph administration significantly ameliorated pulmonary indexes and histological impairments in mice with long-term CS exposure, which were largely through the suppression of inflammation, apoptosis and oxidative stress via blocking ER stress as detected in vitro. Collectively, all these findings indicated that Eph exhibited protective effects against CS-caused COPD by hindering ER stress.

Ephedrine ameliorates cerebral ischemia injury via inhibiting NOD-like receptor pyrin domain 3 inflammasome activation through the Akt/GSK3ß/NRF2 pathway.

Ischemic stroke is a leading cause of death and long-term disability worldwide. The aim of this study is to explore the potential function of ephedrine in ischemic stroke and the underlying molecular mechanism. A middle cerebral artery occlusion (MCAO) rat model was established. The potential effects of ephedrine on MCAO rats and LPS-stimulated BV2 microglial cells were evaluated. Ephedrine reduced the infarct volume, cell apoptosis, brain water content, neurological score, and proinflammatory cytokines (TNF-α and IL-1ß) production in MCAO rats. Ephedrine treatment also suppressed TNF-α and IL-1ß production and NOD-like receptor pyrin domain 3 (NLRP3) inflammasome activation in BV2 microglial cells. The expression of NLRP3, caspase-1, and IL-1ß was suppressed by ephedrine. Moreover, ephedrine treatment increased the phosphorylation of Akt and GSK3ß and nuclear NRF2 levels in LPS-treated BV2 microglial cells. Meanwhile, LY294002 attenuated the inhibitory effects of ephedrine on NLRP3 inflammasome activation and TNF-α and IL-1ß production. In addition, the level of pAkt was increased, while NLRP3, caspase-1, and IL-1ß were decreased by ephedrine treatment in MCAO rats. In conclusion, ephedrine ameliorated cerebral ischemia injury via inhibiting NLRP3 inflammasome activation through the Akt/GSK3ß/NRF2 pathway. Our results revealed a potential role of ephedrine in ischemic stroke treatment.

Mechanism deconvolution of Qing Fei Pai Du decoction for treatment of Coronavirus Disease 2019 (COVID-19) by label-free integrative pharmacology assays.

ETHNOPHARMACOLOGICAL RELEVANCE: Traditional Chinese medicine (TCM) has a long history in the prevention and treatment of pandemics. The TCM formula Lung Cleansing and Detoxifying Decoction (LCDD), also known as Qing Fei Pai Du Decoction, has been demonstrated effective against Coronavirus Disease 2019 (COVID-19). AIM OF THE STUDY: This work aimed to elucidate the active ingredients, targets and pathway mechanism of LCDD related to suppression of inflammatory, immunity regulation and relaxation of airway smooth muscle for the treatment of COVID-19. MATERIALS AND METHODS: Mining chemical ingredients reported in LCDD, 144 compounds covering all herbs were selected and screened against inflammatory-, immunity- and respiratory-related GPCRs including GPR35, H1, CB2, B2, M3 and ß2-adrenoceptor receptor using a label-free integrative pharmacology method. Further, all active compounds were detected using liquid chromatography-tandem mass spectrometry, and an herb-compound-target network based on potency and content of compounds was constructed to elucidate the multi-target and synergistic effect. RESULTS: Thirteen compounds were identified as GPR35 agonists, including licochalcone B, isoliquiritigenin, etc. Licochalcone B, isoliquiritigenin and alisol A exhibited bradykinin receptor B2 antagonism activities. Atractyline and shogaol showed as a cannabinoid receptor CB2 agonist and a histamine receptor H1 antagonist, respectively. Tectorigenin and aristofone acted as muscarinic receptor M3 antagonists, while synephrine, ephedrine and pseudoephedrine were ß2-adrenoceptor agonists. Pathway deconvolution assays suggested activation of GPR35 triggered PI3K, MEK, JNK pathways and EGFR transactivation, and the activation of ß2-adrenoceptor mediated MEK and Ca2+. The herb-compound-target network analysis found that some compounds such as licochalcone B acted on multiple targets, and multiple components interacted with the same target such as GPR35, reflecting the synergistic mechanism of Chinese medicine. At the same time, some low-abundance compounds displayed high target activity, meaning its important role in LCDD for anti-COVID-19. CONCLUSIONS: This study elucidates the active ingredients, targets and pathways of LCDD. This is useful for elucidating multitarget synergistic action for its clinical therapeutic efficacy.

Cerebral Macro- and Microcirculation during Ephedrine versus Phenylephrine Treatment in Anesthetized Brain Tumor Patients: A Randomized Clinical Trial Using Magnetic Resonance Imaging.

BACKGROUND: This study compared ephedrine versus phenylephrine treatment on cerebral macro- and microcirculation, measured by cerebral blood flow, and capillary transit time heterogeneity, in anesthetized brain tumor patients. The hypothesis was that capillary transit time heterogeneity in selected brain regions is greater during phenylephrine than during ephedrine, thus reducing cerebral oxygen tension. METHODS: In this single-center, double-blinded, randomized clinical trial, 24 anesthetized brain tumor patients were randomly assigned to ephedrine or phenylephrine. Magnetic resonance imaging of peritumoral and contralateral hemispheres was performed before and during vasopressor infusion. The primary endpoint was between-group difference in capillary transit time heterogeneity. Secondary endpoints included changes in cerebral blood flow, estimated oxygen extraction fraction, and brain tissue oxygen tension. RESULTS: Data from 20 patients showed that mean (± SD) capillary transit time heterogeneity in the contralateral hemisphere increased during phenylephrine from 3.0 ± 0.5 to 3.2 ± 0.7 s and decreased during ephedrine from 3.1 ± 0.8 to 2.7 ± 0.7 s (difference phenylephrine versus difference ephedrine [95% CI], -0.6 [-0.9 to -0.2] s; P = 0.004). In the peritumoral region, the mean capillary transit time heterogeneity increased during phenylephrine from 4.1 ± 0.7 to 4.3 ± 0.8 s and decreased during ephedrine from 3.5 ± 0.9 to 3.3 ± 0.9 s (difference phenylephrine versus difference ephedrine [95%CI], -0.4[-0.9 to 0.1] s; P = 0.130). Cerebral blood flow (contralateral hemisphere ratio difference [95% CI], 0.3 [0.06 to 0.54]; P = 0.018; and peritumoral ratio difference [95% CI], 0.3 [0.06 to 0.54; P = 0.018) and estimated brain tissue oxygen tension (contralateral hemisphere ratio difference [95% CI], 0.34 [0.09 to 0.59]; P = 0.001; and peritumoral ratio difference [95% CI], 0.33 [0.09 to 0.57]; P = 0.010) were greater during ephedrine than phenylephrine in both regions. CONCLUSIONS: Phenylephrine caused microcirculation in contralateral tissue, measured by the change in capillary transit time heterogeneity, to deteriorate compared with ephedrine, despite reaching similar mean arterial pressure endpoints. Ephedrine improved cerebral blood flow and tissue oxygenation in both brain regions and may be superior to phenylephrine in improving cerebral macro- and microscopic hemodynamics and oxygenation.

RETRACTED: Potential of ephedrine to suppress the gene expression of TNF-α, IL-1ß, IL-6 and PGE2: A novel approach towards management of rheumatoid arthritis.

This article has been retracted: please see Elsevier Policy on Article Withdrawal (https://www.elsevier.com/about/our-business/policies/article-withdrawal). This article has been retracted at the request of the Editor-in-Chief. A reader reported that Figure 9 of the above paper contains similar section with Figure 4 of another article authored by the same group in Inflammopharmacology, 29, (2021) 1119-1129, https://doi.org/10.1007/s10787-021-00840-9, and part of the Figure 9 of the above paper is used in Figure 9 of another article authored by the same group in Inflammopharmacology, 29, (2021) 673­682, https://doi.org/10.1007/s10787-021-00804-z. The journal requested the authors to explain the repeated use of the image and provide the raw data. However, the authors were not able to fulfill this request and therefore the Editor-in-Chief has decided to retract the article.

Ephedrine alleviates middle cerebral artery occlusion-induced neurological deficits and hippocampal neuronal damage in rats by activating PI3K/AKT signaling pathway.

Inflammation and oxidative stress are crucial in ischemic stroke. Ephedrine (EPH) has been proven to have anti-inflammatory and anti-oxidative stress effects. The present study analyzes whether EPH possessed neuroprotective effects and explored the underlying mechanisms of EPH based on an experimental model of middle cerebral artery occlusion (MCAO). We found that intraperitoneal injection with EPH attenuated the neurological deficit, cerebral infarction, and cerebral edema induced by MCAO in rats. Besides, EPH treatment alleviated MCAO-induced brain tissue damage and morphological abnormality, as well as neuronal loss. Moreover, EPH treatment upregulated GPx and CAT activity and downregulated MDA and NO content. EPH also evidently decreased the levels of IL-6 and TNF-α but increased IL-4 and IL-10 levels. Of note, EPH treatment promoted the phosphorylation of PI3K and AKT proteins in MCAO rats. Furthermore, administration of PI3K/AKT pathway inhibitor LY294002 abolished the beneficial effects of EPH. These results confirmed that EPH alleviated brain injury induced by MCAO via activating PI3K/AKT signaling pathway.

Therapeutic effects of Gambi-jung for the treatment of obesity.

Obesity is known as metabolic syndrome and it affects many tissues including adipose tissue, liver, and central nervous system (CVS). Gambi-jung (GBJ) is a modified prescription of Taeumjowi-tang (TJT), which has been used to treat obesity in Korea. GBJ is composed of 90% Ephedra sinica Stapf (ES). Therefore, the present study was designed to assess the antiobesity effects of GBJ and to compare the effects of GBJ and ES on obesity. GBJ administration remarkably reduced the body weight, Body mass index (BMI), and body fat percentage compared to the ES administration in human subjects. GBJ-treated mice had lower white adipose tissue (WAT) amounts than ES-treated mice. GBJ and ES administration enhanced adenosine monophosphate-activated protein kinase (AMPK) expression in 3T3-L1 adipocytes, epididymal WAT and liver of HFD-induced obese mice. Moreover, GBJ and ES reduced food intake by suppressing the mRNA levels of orexigenic peptides, agouti-related protein (AgRP) and neuropeptide-Y (NPY), as well as AMPK in the brain of HFD-induced obese mice. Furthermore, GBJ-treated mice had dramatically lower expression of macrophage marker F4/80 in epididymal WAT than those of ES-treated mice. Based on these results, we suggest the use of GBJ as a natural drug to control weight gain.

Ephedrine versus Phenylephrine Effect on Cerebral Blood Flow and Oxygen Consumption in Anesthetized Brain Tumor Patients: A Randomized Clinical Trial.

BACKGROUND: Studies in anesthetized patients suggest that phenylephrine reduces regional cerebral oxygen saturation compared with ephedrine. The present study aimed to quantify the effects of phenylephrine and ephedrine on cerebral blood flow and cerebral metabolic rate of oxygen in brain tumor patients. The authors hypothesized that phenylephrine reduces cerebral metabolic rate of oxygen in selected brain regions compared with ephedrine. METHODS: In this double-blinded, randomized clinical trial, 24 anesthetized patients with brain tumors were randomly assigned to ephedrine or phenylephrine treatment. Positron emission tomography measurements of cerebral blood flow and cerebral metabolic rate of oxygen in peritumoral and normal contralateral regions were performed before and during vasopressor infusion. The primary endpoint was between-group difference in cerebral metabolic rate of oxygen. Secondary endpoints included changes in cerebral blood flow, oxygen extraction fraction, and regional cerebral oxygen saturation. RESULTS: Peritumoral mean ± SD cerebral metabolic rate of oxygen values before and after vasopressor (ephedrine, 67.0 ± 11.3 and 67.8 ± 25.7 µmol · 100 g · min; phenylephrine, 68.2 ± 15.2 and 67.6 ± 18.0 µmol · 100 g · min) showed no intergroup difference (difference [95% CI], 1.5 [-13.3 to 16.3] µmol · 100 g · min [P = 0.839]). Corresponding contralateral hemisphere cerebral metabolic rate of oxygen values (ephedrine, 90.8 ± 15.9 and 94.6 ± 16.9 µmol · 100 g · min; phenylephrine, 100.8 ± 20.7 and 96.4 ± 17.7 µmol · 100 g · min) showed no intergroup difference (difference [95% CI], 8.2 [-2.0 to 18.5] µmol · 100 g · min [P = 0.118]). Ephedrine significantly increased cerebral blood flow (difference [95% CI], 3.9 [0.7 to 7.0] ml · 100 g · min [P = 0.019]) and regional cerebral oxygen saturation (difference [95% CI], 4 [1 to 8]% [P = 0.024]) in the contralateral hemisphere compared to phenylephrine. The change in oxygen extraction fraction in both regions (peritumoral difference [95% CI], -0.6 [-14.7 to 13.6]% [P = 0.934]; contralateral hemisphere difference [95% CI], -0.1 [- 12.1 to 12.0]% [P = 0.989]) were comparable between groups. CONCLUSIONS: The cerebral metabolic rate of oxygen changes in peritumoral and normal contralateral regions were similar between ephedrine- and phenylephrine-treated patients. In the normal contralateral region, ephedrine was associated with an increase in cerebral blood flow and regional cerebral oxygen saturation compared with phenylephrine.

Quality Evaluation and Characterization of Fractions with Biological Activity from Ephedra Herb Extract and Ephedrine Alkaloids-Free Ephedra Herb Extract.

Previously, we reported that the c-Met inhibitory effect of Ephedra Herb extract (EHE) is derived from ingredients besides ephedrine alkaloids. Moreover, analgesic and anti-influenza activities of EHE and ephedrine alkaloids-free Ephedra Herb extract (EFE) have been reported recently. In this study, we examined the fractions containing c-Met kinase inhibitory activity from EHE and the fractions with analgesic and anti-influenza activities from EFE, and elucidated the structural characteristics of the active fractions. Significant c-Met kinase activity was observed in 30, 40, and 50% methanol (MeOH) eluate fractions obtained from water extract of EHE using Diaion HP-20 column chromatography. Similarly, 20 and 40% MeOH, and MeOH eluate fractions obtained from water extract of EFE were found to display analgesic and anti-influenza activities. Reversed phase-HPLC analysis of the active fractions commonly showed broad peaks characteristic of high-molecular mass condensed tannin. The active fractions were analyzed using 13C-NMR and decomposition reactions; the deduced structures of active components were high-molecular mass condensed tannins, which were mainly procyanidin B-type and partly procyanidin A-type, including pyrogallol- and catechol-type flavan 3-ols as extension and terminal units. HPLC and gel permeation chromatography (GPC) analyses estimated that the ratio of pyrogallol- and catechol-type was approximately 9 : 2, and the weight-average molecular weight based on the polystyrene standard was >45000. Furthermore, GPC-based analysis was proposed as the quality evaluation method for high-molecular mass condensed tannin in EHE and EFE.

Bolus administration of ephedrine and etilefrine induces transient vasodilation just after injection in combined epidural and general anesthesia patients: A randomized clinical study.

Hypotension commonly accompanies combined epidural and general anesthesia, and intravenous bolus ephedrine and etilefrine are widely used to correct hypotension. We have noticed that systemic vascular resistance (SVR) transiently decreases just after intravenous bolus administration of these drugs. The goal of the present study was to investigate whether bolus administration of these drugs decrease SVR just after intravenous administration in combined epidural and general anesthesia patients. We investigated 40 patients who were scheduled for elective abdominal surgery. Patients were chosen as subjects if their systolic arterial pressure decreased by 20% or to <100 mmHg at 30 min after the induction of general anesthesia. Baseline hemodynamic values were recorded, and after ephedrine 10 mg injection or etilefrine 2 mg injection (equipotent), the parameters were recorded again at 0.5 min and once each min for the next 5 min thereafter. The 40 patients were enrolled into the ephedrine (n = 20) or etilefrine (n = 20) treatment groups. Patient characteristics were comparable in both groups. After ephedrine injection, SVR decreased significantly at the 1-min time point, whereas after etilefrine injection, SVR decreased significantly at the 0.5- to 2-min time points compared with baseline values. SVR at the 0.5- to 1-min time points was lower in the etilefrine versus the ephedrine group. Both drugs transiently decreased SVR after intravenous injection, but etilefrine decreased SVR much more than ephedrine, indicating that more vasodilation occurred after the injection of etilefrine than after ephedrine. It is thus important to recognize the different characteristics of these drugs.

Effect of ephedrine on gastric conduit perfusion measured by laser speckle contrast imaging after esophagectomy: a prospective in vivo cohort study.

Compromised perfusion due to ligation of arteries and veins in esophagectomy with gastric tube reconstruction often (5-20%) results in necrosis and anastomotic leakage, which relate to high morbidity and mortality (3-4%). Ephedrine is used widely in anesthesia to treat intraoperative hypotension and may improve perfusion by the increase of cardiac output and mean arterial pressure (MAP). This study tests the effect of ephedrine on perfusion of the future anastomotic site of the gastric conduit, measured by laser speckle contrast imaging (LSCI). This prospective, observational, in vivo pilot study includes 26 patients undergoing esophagectomy with gastric tube reconstruction from October 2015 to June 2016 in the Academic Medical Center (Amsterdam). Perfusion of the gastric conduit was measured with LSCI directly after reconstruction and after an increase of MAP by ephedrine 5 mg. Perfusion was quantified in flux (laser speckle perfusion units, LSPU) in four perfusion locations, from good perfusion (base of the gastric tube) toward decreased perfusion (fundus). Intrapatient differences before and after ephedrine in terms flux were statistically tested for significance with a paired t-test. LSCI was feasible to image gastric microcirculation in all patients. Flux (LSPU) was significantly higher in the base of the gastric tube (791 ± 442) compared to the fundus (328 ± 187) (P < 0.001). After administration of ephedrine, flux increased significantly in the fundus (P < 0.05) measured intrapatients. Three patients developed anastomotic leakage. In these patients, the difference between measured flux in the fundus compared to the base of the gastric tube was high. This study presents the effect of ephedrine on perfusion of the gastric tissue measured with LSCI in terms of flux (LSPU) after esophagectomy with gastric tube reconstruction. We show a small but significant difference between flux measured before and after administration of ephedrine in the future anastomotic tissue (313 ± 178 vs. 397 ± 290). We also show a significant decrease of flux toward the fundus.