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Purpose Excessive proliferation, migration and anti-apoptosis of pulmonary artery smooth muscle cells (PASMCs) are the basis for the development of pulmonary vascular remodeling, and it is the driving force for pulmonary arterial hypertension (PAH). 18β-glycyrrhetinic acid (18β-GA) is the main active substance extracted from Chinese herbal medicine licorice, with outstanding anti-inflammatory, anti-oxidation and anti-proliferative effects. Our team found in previous studies that 18β-GA has protective effects on monocrotaline-induced PAH in rats. However, the anti-angiogenic effect of 18β-GA on PAH remains unclear. Therefore, in order to further investigate whether the beneficial effects of 18β-GA on PAH are related to its antiproliferative effect, we conducted experiments in vivo and in vitro. Methods and results In vivo, 18β-GA relieved mean pulmonary arterial pressure, right ventricular systolic pressure, and right ventricular hypertrophy index, improving pulmonary remodeling. In vitro, 18β-GA significantly inhibited PDGF-BB-induced proliferation and DNA synthesis of HPASMCs, blocking the progression of G0/G1 to S phase of the cell cycle. Furthermore, after treatment with 18β-GA, the expression of Rho A, ROCK1, ROCK2 was decreased and ROCK activity was inhibited in HPASMC. In addition, 18β-GA also attenuated PDGF-induced changes in p27kip1, Bax and Bcl-2. Conclusions In summary, these results indicate that 18β-GA regulates the activity of RhoA-ROCK signaling pathway, inhibits the proliferation of HPASMCs, and has potential value in the treatment of PAH.

Pulmonary arterial hypertension (PAH) is a destructive and rare disorder characterized by a progressive increase in pulmonary artery pressure and vasoconstriction, ultimately leading to right ventricular failure and death. 18β-Glycyrrhetinic acid (18β-GA) is an active ingredient in the commonly used Chinese herbal medicine radix glycyrrhizae, and it possesses antioxidant, anti-inflammatory, anti-tumor, and other pharmacological properties. This study aimed to determine whether 18β-GA has protective effects against monocrotaline (MCT)-induced PAH and whether it is associated with oxidative stress. The PAH of rats was induced by MCT (60 mg/kg) and oral administration of 18β-GA (100, 50, or 25 mg/kg/day), sildenafil (30 mg/kg), or saline for 21 consecutive days. The development of PAH was evaluated by hemodynamic parameters and right ventricular hypertrophy index. Hematoxylin and eosin staining, Masson trichrome staining, and electron microscopy were used to determine the degree of vascular remodeling and proliferation in lung tissue. Moreover, the antioxidant capacity and malondialdehyde levels in the lungs were measured according to the instructions provided by the test kits, and the expression levels of nicotinamide adenine dinucleotide phosphate oxidase-2 (Nox2) and Nox4 were detected through Western blot analysis. Results of our study indicated that 18β-GA treatment significantly improved the hemodynamic and pathomorphological data of the rats, reduced the changes in oxidative stress biomarkers, and inhibited Nox2 and Nox4 expression. Our research indicated that 18β-GA has a protective effect against MCT-induced PAH by inhibiting oxidative stress in rats.

Oxysophoridine (OSR) is a bioactive alkaloid extracted from the Sophora alopecuroides Linn. Our aim is to explore the potential anti-inflammation mechanism of OSR in cerebral ischemic injury. Mice were intraperitoneally pretreated with OSR (62.5, 125, and 250 mg/kg) or nimodipine (Nim) (6 mg/kg) for 7 days followed by cerebral ischemia. The inflammatory-related cytokines in cerebral ischemic hemisphere tissue were determined by immunohistochemistry staining, Western blot and enzyme-like immunosorbent assay (ELISA). OSR-treated groups observably suppressed the nuclear factor kappa B (NF-κB), intercellular adhesion molecule-1 (ICAM-1), inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2). OSR-treated group (250 mg/kg) markedly reduced the inflammatory-related protein prostaglandin E2 (PGE2), tumor necrosis factor alpha (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6), and interleukin-8 (IL-8). Meanwhile, it dramatically increased the interleukin-10 (IL-10). Our study revealed that OSR protected neurons from ischemia-induced injury in mice by downregulating the proinflammatory cytokines and blocking the NF-κB pathway.

Matrine, an active constituent of the Chinese herb, Sophora flavescens Ait., and it is known for its antioxidant, anti-inflammatory and antitumor activities. It has been demonstrated that matrine exerts protective effects against heart failure by decreasing the expression of caspase-3 and Bax, and increasing Bcl-2 levels. In this study, we aimed to determine whether these protective effects of matrine can be applied to cerebral ischemia. Following 7 successive days of treatment with matrine (7.5, 15 and 30 mg/kg) and nimodipine (1 mg/kg) by intraperitoneal injection, male Institute of Cancer Research (ICR) mice were subjected to middle cerebral artery occlusion (MCAO). Following reperfusion, the neurobehavioral score and brain infarct volume were estimated, and morphological changes were analyzed by hematoxylin and eosin (H&E) staining and electron microscopy. The percentage of apoptotic neurons was determined by flow cytometry. The levels of oxidative stress were assessed by measuring the levels of malondialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and catalase (CAT), and the total antioxidant capacity (T-AOC). Western blot analysis and immunofluorescence staining were used to examine the expression of the apoptosis-related proteins, caspase-3, Bax and Bcl-2. Our results revealed that pre-treatment with matrine significantly decreased the infarct volume and improved the neurological scores. Matrine also reduced the percentage of apoptotic neurons and relieved neuronal morphological damage. Furthermore, matrine markedly decreased the MDA levels, and increased SOD, GSH-Px and CAT activity, and T-AOC. Western blot analysis and immunofluorescence staining revealed a marked decrease in caspase-3 expression and an increase in the Bcl-2/Bax ratio in the group pre-treated with matrine (30 mg/kg) as compared with the vehicle-treated group. The findings of the present study demonstrate that matrine exerts neuroprotective effects against cerebral ischemic injury and that these effects are associated with its antioxidant and anti-apoptotic properties.

Pulmonary hypertension (PH) is fatal disease which closely involves Rho A/ Rho kinsase (ROCK) pathway. Aloperine is a main active alkaloid extracted from Sophora alopecuroides, which is a traditional Chinese herbal medicine that has been used widely. However, the effects of this alkaloid on pulmonary hypertension and its mechanisms remain unclear. Therefore, this study is designed to investigate whether aloperine has protective effects on PH induced by monocrotaline, whether these effects may be related to regulation of RhoA/ROCK pathway in rats. Pulmonary hypertension was induced by monocrotaline (60mg/kg), and subsequently oral administration of aloperine (25, 50, 100mg/kg/day) for 21 days. At the end of the experiment, rats were underwent hemodynamic and morphologic assessments. At same time, the expression of Rho A, ROCK1, ROCK2, as well as activities of ROCK in the lung of rat has been detected. Afterwards, the expression of p27kip1, Bax, Bcl-2, which was the downstream proliferation and apoptosis factors of ROCK, were tested. The result indicted that aloperine treatment showed significantly improvement in hemodynamic and pathomorphologic data. Moreover, the reduction in expression of Rho A, ROCK1, ROCK2, and suppression in activities of ROCK were found in rat lungs after aloperine treatment. Furthermore, aloperine also alleviated the MCT-induced changes of p27kip1, Bax and Bcl-2. In summary, this study indicates that aloperine have protective effects on monocrotaline-induced PH. And these effects may be partially related to RhoA/ROCK pathway. Thus, aloperine could be considered a possible therapeutic strategy for PH.

Pulmonary hypertension (PH) is serious, fatal disease which is promoted by oxidative stress. Aloperine have antioxidation effects, which effects on pulmonary arteries remain unclear. Therefore, this study is designed to investigate whether aloperine has protective effects on PH induced by monocrotaline and whether these effects are associated with oxidative stress. PH was induced by monocrotaline (60mg/kg), and subsequently oral administration of aloperine (25, 50, 100mg/kg/day). At the end of the experiment, hemodynamic, pathomorphologic, electrocardiographic and echocardiographic data from the rats were obtained. At same time, oxidative stress biomarkers (superoxide dismutase, malonyldialdehyde, catalase, glutathione peroxidase, total antioxidant capacity) and the protein expression of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX)-2, NOX-4 in the lung of rat has been detected. The result shows that aloperine treatment showed significantly improvement in hemodynamic, pathomorphologic, electrocardiographic and echocardiographic data. Moreover, aloperine treatment can alleviate the changes of oxidative stress biomarkers and suppress the expression levels of NOX-2, NOX-4. In summary, this study indicates that aloperine have protective effects on monocrotaline-induced PH. And these effects may be related to inhibit oxidative stress.

Neuropathic pain associated with peripheral nerve injury is characterized by the sensory abnormalities such as spontaneous pain, hyperalgesia, allodynia, and radiation of pain [1]. Pain after injury to the nervous system is a major chronic pain condition. The traditional analgesics like opioids or nonsteroidal antiinflammatory drugs (NSAIDs) are not very satisfactory because of their significant side effects and ineffectiveness [2]. Therefore, the treatment of neuropathic pain remains a challenge. Chronic constriction injury (CCI) of sciatic nerve induced neuropathy is a widely employed model for the induction of neuropathic pain in experimental animals [3]. CCI-induced neuropathy in experimental animals mimics complex regional pain syndrome in humans [4]. More recently, various studies have reported herbal medicine to produce the beneficial effect in the management of painful neuropathy. Sophora alopecuroides L. is a predominant herbal plant resource in Northwest China. Among various alkaloids from Sophora alopecuroids L., oxymatrine (OMT) has been identified as the major bioactive component contributing to a variety of pharmacological effects. In the recent years, a large number of pharmacological and clinical studies have found that oxymatrine itself has a wide spectrum of effect in antivirus, liver fibrosis, immunoinhibition [5]. Studies have shown that oxymatrine has analgesic effect [6], while there has been no published support that oxymatrine is beneficial for the treatment on neuropathic pain. In the present study, we tested the hypothesis that the analgesic effect of oxymatrine on neuropathic pain induced by CCI of sciatic nerve in mice. Male Institute of Cancer Research (ICR) mice (21–25 g) were injured using the CCI model, as previously described [3]. Shamoperated mice were subjected to all surgical procedures except

Aims of the Study To investigate the neuroprotective effect of Lycium barbarum polysaccharide (LBP) on focal cerebral ischemic injury in mice and to explore its possible mechanism. Materials and Methods Male ICR mice were used to make the model of middle cerebral artery occlusion (MCAO) after intragastric administration with LBP (10, 20 and 40 mg/kg) and Nimodipine (0.4 mg/kg) for seven successive days. After 24 h of reperfusion, neurological scores were estimated and infarct volumes were measured by 2, 3, 5-triphenyltetrazolium chloride (TTC) staining. Morphological changes in ischemic brains were performed for hematoxylin-eosin (HE) staining. The number of apoptotic neurons was detected by TUNEL staining. The Bax, Bcl-2 protein expression and CytC, Caspase-3, -9 and cleaved PARP-1 activation were investigated by immunofluorescence and western-blot analysis. Results LBP (10, 20 and 40 mg/kg) treatment groups significantly reduced infract volume and neurological deficit scores. LBP also relieved neuronal morphological damage and attenuated the neuronal apoptosis. LBP at the dose of 40 mg/kg significantly suppressed overexpression of Bax, CytC, Caspase-3, -9 and cleaved PARP-1, and inhibited the reduction of Bcl-2 expression. Conclusions Based on these findings we propose that LBP protects against focal cerebral ischemic injury by attenuating the mitochondrial apoptosis pathway.

Our previous studies have demonstrated that oxysophoridine (OSR) has protective effects on cerebral neurons damage in vitro induced by oxygen and glucose deprivation. In this study, we further investigated whether OSR could reduce ischemic cerebral injury in vivo and its possible mechanism. Male Institute of cancer research mice were intraperitoneally injected with OSR (62.5, 125 and 250 mg/kg) for seven successive days, then subjected to brain ischemia induced by the model of middle cerebral artery occlusion. After reperfusion, neurological scores and infarct volume were estimated. Morphological examination of tissues was performed. Apoptotic neurons were detected by terminal deoxynucleotidyl transferase mediated dUTP nick end labeling staining. Oxidative stress levels were assessed by measurement of malondialdehyde (MDA), superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) levels. The expression of various apoptotic markers as Caspase-3, Bax and Bcl-2 were investigated by immunohistochemistry and Western-blot analysis. OSR pretreatment groups significantly reduced infract volume and neurological deficit scores. OSR decreased the percentage of apoptotic neurons, relieved neuronal morphological damage. Moreover, OSR markedly decreased MDA content, and increased SOD, GSH-Px activities. Administration of OSR (250 mg/kg) significantly suppressed overexpression of Caspase-3 and Bax, and increased Bcl-2 expression. These findings indicate that OSR has a protective effect on focal cerebral ischemic injury through antioxidant and anti-apoptotic mechanisms.

Primary dysmenorrhea is one of the most frequent gynecological disorders in young women. Chinese herbal medicine has the advantage in terms of multi-targeting efficacy, lower toxicity, as well as lower cost. Core licorice is the hard and atropurpureus heart part in root and rootstock of Glycyrrhiza uralensis Fisch (Leguminosae), having a therapeutic effect on dysmenorrhea.This experiment indicated the spasmolytic effect of core licorice aqueous extract (CLE) on spontaneous rhythmic contractions and spasmogen-provoked contractions of stilbestrol primed, estrogen-dominated, non-pregnant mouse isolated uterine horns and its spasmolytic mechanism.We investigated the spasmolytic effect of CLE (0.025-0.1 mg/mL) on spontaneous contractions and potassium chloride (KCl, 40 mM), acetylcholine (ACh, 5 μg/mL), carbachol (CCh, 5 μg/mL), oxytocin (OT, 2 U/L) or bradykinin (5 ng/mL)-provoked contractions of mouse isolated uterine horns. Contractions were recorded by tension force transducers using Biolap 420F software on a PC.Our present study showed that graded, escalated concentrations of CLE (0.025-0.1 mg/mL) significantly inhibited the amplitude of spontaneous phasic contractions (15.03-55.10%), as well as the contractions produced by KCl (40 mM; 20.16-53.99%), ACh (5 μg/mL; 14.65-48.32%), CCh (5 μg/mL; 38.40-76.70%), OT (2 U/L; 21.53-58.49%) or bradykinin (5 ng/mL; 58.01-79.44%) of the estrogen-dominated isolated mice uterine horn preparations in a concentration-related manner.The spasmolytic effect of CLE observed in the present study lends pharmacological support to the traditional use of core licorice in the management, control and treatment of primary dysmenorrhea.

Background: Our previous studies demonstrated that oxysophoridine (OSR) had neuroprotective effects on mice through antioxidant and anti-apoptotic mechanisms. In this study, we investigated whether OSR could influence the release of amino acids in ischemic mice brains. Materials and Methods: Male ICR mice were scheduled to undergo 2 h middle cerebral artery occlusion (MCAO) and 24 h reperfusion. Before MCAO, mice in corresponding groups were intraperitoneally injected with OSR (62.5, 125 and 250 mg/kg) for seven successive days. After reperfusion, neurological scores were estimated, infarct volume and the brain water content were assessed. The levels of glutamate (Glu), aspartate (Asp), γ-aminobutyric acid (GABA) and Glycine (Gly) were measured by amino acid analyzer. Results: OSR significantly decreased neurological scores, reduced infarct volume and the brain water content. After treatment with OSR of 250 mg/kg, the contents of Glu, Asp, GABA and Gly in mice brains could maintain at a normal level compared with MCAO group mice. The Glu/GABA ratio was significantly decreased in OSR group mice. Conclusion: These findings indicate that OSR has a protective effect on cerebral ischemic injury and helps to maintain the amino acids homeostasis after reperfusion for a long time.