Lingqun Zhu

Panax notoginseng saponins provide neuroprotection by regulating NgR1/RhoA/ROCK2 pathway expression, in vitro and in vivo

ETHNOPHARMACOLOGICAL RELEVANCE Panax notoginseng saponins (PNS) extracted from a traditional Chinese herbal medicine, Panax notoginseng (Burkill) F.H. Chen (Araliaceae), which has been extensively used in treating coronary heart disease, ischemic cerebrovascular disease and hemorrhagic disorders in China over hundreds of years. AIMS OF THE STUDY This study explored whether panax notoginseng saponins (PNS) provided neuroprotective effects by inhibiting the expressions of NgR1, RhoA, and ROCK2 following middle cerebral artery occlusion in rats and oxygen-glucose deprivation/reoxygenation (OGD/R) injury in SH-SY5Y cells. MATERIALS AND METHODS 2,3,5-Triphenyltetrazolium chloride staining was used to determine successful middle cerebral artery occlusion establishment in sham-operated and operated Sprague-Dawley rats 1 day after injury. The rats were randomly separated into sham, model, NEP1-40, PNS, and NEP1-40 plus PNS (N+P) groups. After 7 days of treatment, body mass and neurological deficit scores were analyzed. Tissues were harvested and analyzed by hematoxylin-eosin staining and immunohistochemical analysis, western blotting, and quantitative real-time PCR (qRT-PCR). The optimal drug concentration of NEP1-40 and PNS on SH-SY5Y cells exposed to OGD/R injury was determined by CCK8 analysis. qRT-PCR was used to measure mRNA expression profiles of NgR1, RhoA, and ROCK2 in SH-SY5Y cells subjected to OGD/R. RESULTS The results showed that MCAO surgery successfully produced an infarct, and the PNS, NEP1-40, and N+P groups exhibited increased body mass and ameliorated neurological deficits compared with the model group. NEP1-40 treatment markedly reduced NgR1 and RhoA overexpression when compared to the model group, although there was no significant difference in ROCK2 expression. PNS and N+P treatment significantly decreased NgR1, RhoA, and ROCK2 overexpression compared with the model group. However, N+P treatment did not result in a synergistic effect, as assessed by immunohistochemistry, western blotting, and qRT-PCR. Following optimal administration of PNS (160μg/ml) and NEP1-40 (10ng/ml) on SH-SY5Y cells exposed to OGD/R injury, cell viability in the NEP1-40, PNS, and N+P groups significantly increased compared with the model group, as assessed by CCK8 analysis. Additionally, NgR1, RhoA, and ROCK2 mRNA expression profiles were significantly less in the NEP1-40, PNS, and N+P groups compared with the model group. CONCLUSION PNS provided neuroprotective effects in a rat model of cerebral ischemia and SH-SY5Y cells exposed to oxygen/glucose deprivation injury by inhibiting the overexpression of NgR1, RhoA, and ROCK2.

Effect of Wenxin Granule on Ventricular Remodeling and Myocardial Apoptosis in Rats with Myocardial Infarction

Aim. To determine the effect of a Chinese herbal compound named Wenxin Granule on ventricular remodeling and myocardial apoptosis in rats with myocardial infarction (MI). Methods. Male Sprague-Dawley (SD) rats were randomly divided into four groups: the control group, the model group, the metoprolol group, and the Wenxin Granule group (WXKL group) with sample size (n) of 7 rats in each group. An MI model was established in all rats by occlusion of the left anterior descending coronary artery (the control group was without occlusion). Wenxin Granule (1.35 g/kg/day), metoprolol (12 mg/kg/day), and distilled water (5 mL/kg/day for the control and model groups) were administered orally for 4 weeks. Ultrasonic echocardiography was used to examine cardiac structural and functional parameters. Myocardial histopathological changes were observed using haematoxylin and eosin (H&E) dyeing. Myocardial apoptosis was detected by terminal deoxynucleotidyl transferase mediated dUTP nick end labeling (TUNEL) staining. Serum angiotensin II (Ang II) concentration was measured using the enzyme-linked immunosorbent assay (ELISA). Results. It was found that Wenxin Granule could partially reverse ventricular remodeling, improve heart function, alleviate the histopathological damage, inhibit myocardial apoptosis, and reduce Ang II concentration in rats with MI. Conclusions. The results of the current study suggest that Wenxin Granule may be a potential alternative and complementary medicine for the treatment of MI.

Chinese Herbal Formula, Modified Danggui Buxue Tang, Attenuates Apoptosis of Hematopoietic Stem Cells in Immune-Mediated Aplastic Anemia Mouse Model

A derivative formula, DGBX, which is composed of three herbs (Radix astragali, Radix Angelicae sinensis, and Coptis chinensis Franch), is derived from a famous Chinese herbal formula, Danggui Buxue Tang (DBT) (Radix astragali and Radix Angelicae sinensis). We aimed to investigate the effects of DGBX on the regulation of the balance between proliferation and apoptosis of hematopoietic stem cells (HSCs) due to the aberrant immune response in a mouse model of aplastic anemia (AA). Cyclosporine (CsA), an immunosuppressor, was used as the positive control. Our results indicated that DGBX could downregulate the production of IFNγ in bone marrow cells by interfering with the binding between SLAM and SAP and the expressions of Fyn and T-bet. This herbal formula can also inhibit the activation of Fas-mediated apoptosis, interferon regulatory factor-1-induced JAK/Stat, and eukaryotic initiation factor 2 signaling pathways and thereby induce proliferation and attenuate apoptosis of HSCs. In conclusion, DGBX can relieve the immune-mediated destruction of HSCs, repair hematopoietic failure, and recover the hematopoietic function of HSCs in hematogenesis. Therefore, DGBX can be used in traditional medicine against AA as a complementary and alternative immunosuppressive therapeutic formula.

Meta-Analysis of the Effects of Xingnaojing Injection on Consciousness Disturbance.

AbstractXingnaojing (XNJ) is commonly extracted from Angongniuhuang, a classic Chinese emergency prescription, and widely used in the treatment of nervous system disorders including consciousness disturbance in China.To evaluate the beneficial and adverse effects of XNJ injection, on consciousness disturbance.Seven major electronic databases were searched to retrieve randomized controlled trials designed to evaluate the clinical efficacy of XNJ alone or combined with Western medicine in treating consciousness disturbance caused by conditions such as high fever, poisoning, and stroke. The methodological quality of the included studies was assessed using criteria from the Cochrane Handbook for Systematic Review of Interventions, and analyzed using the RevMan 5.3.0 software.Seventeen randomized controlled trials on XNJ were included in this study and the trials generally showed low methodological quality. The results revealed that XNJ alone or in combination with other medicines and adjuvant methods had a positive effect on patients with fever-, poisoning-, and stroke-induced coma.XNJ effectively treated consciousness disturbances that were caused by high fever, poisoning, or stroke.

Herbal formula Xian-Fang-Huo-Ming-Yin regulates differentiation of lymphocytes and production of pro-inflammatory cytokines in collagen-induced arthritis mice

BackgroundXian-Fang-Huo-Ming-Yin (XFHM), a traditional herbal formula, has been used to treat sores and carbuncles for hundreds of years in Asia. Nowadays, its clinical effects in treatment of rheumatoid arthritis (RA) have been validated. In this study, we want to study its possible molecular mechanisms of regulating the differentiation of lymphocytes and production of pro-inflammatory cytokines in collagen-induced arthritis (CIA) mice for RA treatment.MethodsA high performance liquid chromatography-electrospray ionization/mass spectrometer (HPLC-ESI/MSn) system was used to analyze the constituents of XFHM granules. An arthritics mouse model was induced by collagen and leflunomide (LEF) was used as a positive control medicine. Pathological changes at the metatarsophalangeal joint were studied through Safranin O and immunohistochemical staining. The differentiation of T, B and NK cells was examined by flow cytometry and pro-inflammatory cytokines were assayed using an Inflammation Antibody Array assay. The expression of key molecules of the nuclear factor κB (NF-κB) and Janus kinase/signal transducers and activators of transcription (JAK/STAT) signaling pathways in spleen were studied by western-blot analysis.ResultsIn our study. 21 different dominant chemical constituents were identified in XFHM. Treatment with XFHM suppressed the pathological changes in arthrosis of CIA. Additionally, XFHM down-regulated the proliferation and differentiation of CD3+ T cells and CD3−CD19+ B cells significantly. However, XFHM had no significant effect on CD3−NK1.1+ NK cells. Further study showed that the production of pro-inflammatory cytokines had been suppressed by inhibiting the activation of NF-κB and JAK/STAT signaling.ConclusionsXFHM can regulate and maintain the immunologic balance of lymphocytic immunity and inhibit the production of pro-inflammatory cytokines, thus suppressing the pathological changes of RA. Therefore, XFHM may be used as an application of traditional medicine against RA in modern complementary and alternative therapeutics.

The Correlation between High-Sensitivity C-Reactive Protein, Matrix Metallopeptidase 9, and Traditional Chinese Medicine Syndrome in Patients with Hypertension

Hypertension is a common disease affecting millions of people throughout the world. Currently, there is a growing interest in the traditional Chinese medicine (TCM) for patients with hypertension mainly due to the personalized therapy of TCM in many countries. Clinical treatment of patients relies on the successful differentiation of a specific TCM syndrome for hypertension. However, it is difficult to understand that TCM syndrome classifications depend on the clinical experience of a TCM practitioner. Therefore, discovering an objective biomarker associated with TCM syndrome may be beneficial for TCM syndrome classifications. This paper focused on high sensitivity C-reactive protein (HCRP), matrix metallopeptidase 9 (MMP9), and TCM syndrome, and aimed to investigate the relationships between TCM syndrome and the two inflammatory biomarkers in patients with essential hypertension. The result showed that both HCRP and MMP9 are positively correlated with syndrome of wind and phlegm turbidity. Detection of the serum levels of HCRP and MMP9 is beneficial for TCM syndrome classification and prediction of cardiovascular and cerebrovascular risk events in hypertensive patients.

The herbal decoction modified Danggui Buxue Tang attenuates immune-mediated bone marrow failure by regulating the differentiation of T lymphocytes in an immune-induced aplastic anemia mouse model.

Angelicae Sinensis, Radix Astragali and Rhizoma Coptidis are all herbs of modified Danggui Buxue Tang (DGBX) and are extensively applied herbs in traditional Chinese medicine for the treatment of anemia and inflammation. In this study, immune-induced AA mice were used as an animal model, and the immunosuppressive agent, Ciclosporin A (CsA), was used as a positive control. Multiple pro-inflammatory cytokines were examined by bead-based multiplex flow cytometry. The T-cell subsets were assessed using a fluorescence-activated cell sorter (FACS). Western blot analysis was used to estimate the protein expression levels of specific transcription factors for T helper cells (Th1, Th2 and Th17) and key molecules of the Janus-activated kinase (Jak)/signal transducer and activator of transcription (Stat3) signaling pathway. DGBX treatment could significantly increase the production of whole blood cells in peripheral blood (PB); inhibit the expansion of Th1 and Th17 cells; increase the differentiation of Th2 and Tregs cells; regulate the expression levels of T-bet, GATA-3, RORγ and proinflammatory cytokines; and decrease the expression levels of key molecules in the Jak/Stat signaling pathway. These results indicate that DGBX can regulate the differentiation of T lymphocytes, resulting in immunosuppressive and hematogenic functions on AA mice. DGBX might be a good candidate for inclusion in a randomized study for AA with more data on the possible side effects and doses used in humans. Ultimately, it may be used for applications of traditional medicine against AA in modern complementary and alternative immunosuppressive therapeutics.

The Mechanism of Exosomes Function in Neurological Diseases: A Progressive Review

Exosomes are extracellular microparticles (≈30-100 nm in diameter) secreted from nearly all types of cells, containing a whole set of biological information including proteins, ribonucleic acid (RNA) and lipids. Latest studies show that exosomes contribute to cell-cell communication and are considered closely related with the modulation of angiogenesis and neurogenesis in many neurological diseases. In the past decade, numerous researchers were devoted to exosomes study, but the mechanism of exosomes function and delivery is uncertain. In this review, we summarized several potential mechanisms of exosomes function in angiogenesis, neurogenesis and Blood Brain Barrier (BBB) delivery, and differentiate various sources of exosomes in stroke, tumor, Traumatic Brain Injury (TBI) and Alzheimers Disease (AD) aimed to report the most advanced mechanical theories in related past three years to provide a new sight for this research area.

A Systematic Review and Meta-Analysis on the Treatment of Cerebral Hemorrhage with NaoXueShu Oral Liquid

NaoXueShu oral liquid invigorates Qi and promotes blood circulation, which is mainly used for treating the acute stage of the meridian of hemorrhagic apoplexy and acute blood stasis syndrome during early convalescence. Its main clinical manifestations include hemiplegia, mouth askew, hemianesthesia, and inarticulateness. It is used mainly in patients with lobar hemorrhage, basal ganglia, and thalamus of the small amount of bleeding without disturbing consciousness of hypertensive cerebral. The purpose of this study was to evaluate the efficacy and adverse effects of NaoXueShu oral liquid on the treatment of cerebral hemorrhage. In this study, literature on randomized controlled trials was collected from seven databases to evaluate the clinical efficiency of the treatment of cerebral hemorrhage alone or combined with Western medicine. The methodologic quality of the included studies was assessed using a standard Cochrane system review and analyzed using RevMan 5.3.0 software. The study included 14 eligible randomized controlled trials. The results showed that the use of NaoXueShu oral liquid alone or combined with other drugs or auxiliary methods can play a significant role in the treatment of cerebral hemorrhage, especially hypertensive intracerebral hemorrhage.

Xianfanghuomingyin, a Chinese Compound Medicine, Modulates the Proliferation and Differentiation of T Lymphocyte in a Collagen-Induced Arthritis Mouse Model

In traditional Chinese medicine (TCM), xianfanghuomingyin (XFHM) is used to treat autoimmune diseases, including rheumatoid arthritis (RA). Here, we studied the mechanisms underlying its treatment effects, especially its anti-inflammatory effects in a collagen-induced arthritis (CIA) mouse model. We found that cartilage destruction and pannus formation were alleviated by treatment with XFHM. The abnormal differentiation of Th1 and Th17 cells was downregulated significantly by XFHM, and Th2 and Treg cells were upregulated. Moreover, the expression levels of specific cytokines and transcription factors related to Th1 cells (interferon γ [IFNγ], T-bet) and Th17 cells (interleukin- [IL-] 17) and the nuclear receptor retinoic acid receptor-related orphan receptor-gamma (RORγ) were downregulated. Serum IL-4 and GATA-3, which contribute to Th2 cells differentiation, increased significantly after XFHM administration. These results indicate that XFHM can restore the balance of T lymphocytes and reestablish the immunological tolerance to inhibit autoinflammatory disorder of RA. Taken together, XFHM can be used as a complementary or alternative traditional medicine to treat RA.