Publications by authors named "Wenxiang Fan"

19 Publications

  • Page 1 of 1

Quality assessment of Fritillariae cirrhosae using portable NIR spectrometer.

Spectrochim Acta A Mol Biomol Spectrosc 2021 Aug 28;265:120325. Epub 2021 Aug 28.

Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu 610072, PR China. Electronic address:

This paper mainly focuses on the feasibility of rapidly identifying Fritillariae cirrhosae varieties, distinguishing its authenticity and detecting its components by using a portable near infrared (NIR) spectrometer. Five different varieties of Fritillariae cirrhosae, five common counterfeits and two main components (ethanol-soluble extractives and total alkaloids) were studied. The reference values of ethanol-soluble extractives were determined by hot dip method and the reference value of total alkaloid was determined by ultraviolet-visible spectrophotometry (UV-Vis). Linear discriminant analysis (LDA) algorithm was used to identify the sources of different varieties of Fritillariae cirrhosae and the common counterfeits of Fritillariae cirrhosae, respectively. As a result, the best models seemed to be effective, with accuracy of the two models' prediction sets reaches 83.33% and 90.91%, respectively. The partial least squares regression (PLSR) algorithm was used to relate the sample spectra with the reference values of ethanol-soluble extractives and total alkaloid content. Coefficient of determination of prediction (Rp) and root mean square errors of prediction (RMSEP) obtained were 0.8562 and 0.3911; 0.6917 and 0.0117, for ethanol-soluble extractives and total alkaloid content, respectively. The results showed that the portable NIR spectrometer could evaluate the quality of Fritillariae cirrhosae with high efficiency and practicability.
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http://dx.doi.org/10.1016/j.saa.2021.120325DOI Listing
August 2021

S-oxiracetam Facilitates Cognitive Restoration after Ischemic Stroke by Activating α7nAChR and the PI3K-Mediated Pathway.

Neurochem Res 2021 Apr 22;46(4):888-904. Epub 2021 Jan 22.

Department of Neurobiology and Acupuncture Research, The Third Clinical Medical College, Zhejiang Chinese Medical University, Key Laboratory of Acupuncture and Neurology of Zhejiang Province, Hangzhou, 310053, China.

S-oxiracetam (S-ORC), a nootropic drug, was used to protect against ischemic stroke by lessening the blood brain barrier dysfunction and inhibiting neuronal apoptosis. However, the potential effects of S-ORC in the recovery of cognitive functions after ischemic stroke and the underlying mechanisms remains unclear. In this study, middle cerebral artery occlusion/reperfusion (MCAO/R) in rats was used as the animal model. By using Y-maze test, Morris water maze, triphenyl tetrazolium chloride (TTC) staining, terminal deoxynucleotidyl transferase-mediated 2'-deoxyuridine 5'-triphosphate (dUTp) nick end labeling (TUNEL) assay, hematoxylin and eosin, immunohistochemical staining and western blot to evaluate the protective effect of S-ORC on cognitive recovery, we were able to confirm that S-ORC ameliorated spatial learning impairment, tissue loss, and hippocampal neuronal apoptosis and injury induced by MCAO/R in rats. These cognitive effects were achieved by restoring the normal function of synaptophysin and increasing PSD95 expression in the hippocampus. Furthermore, we found that methyllycaconitine, the antagonist of α7 nicotinic acetylcholine receptor (α7nAChR), and LY294002, the inhibitor of phosphoinositide 3-kinase (PI3K), were able to block the cognitive effects of S-ORC after MCAO/R in rats. In conclusion, α7nAChR and PI3K are key molecules that mediated the signaling pathway leading to S-ORC-induced cognitive restoration after MCAO/R.
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http://dx.doi.org/10.1007/s11064-021-03233-0DOI Listing
April 2021

Kappa opioid receptor controls neural stem cell differentiation via a miR-7a/Pax6 dependent pathway.

Stem Cells 2021 05 15;39(5):600-616. Epub 2021 Jan 15.

Department of Pharmacology, University of Minnesota Medical School, Minneapolis, Minnesota, USA.

Although the roles of opioid receptors in neurogenesis have been implicated in previous studies, the mechanism by which κ-opioid receptor (OPRK1) regulates adult neurogenesis remains elusive. We now demonstrate that two agonists of OPRK1, U50,488H and dynorphin A, inhibit adult neurogenesis by hindering neuronal differentiation of mouse hippocampal neural stem cells (NSCs), both in vitro and in vivo. This effect was blocked by nor-binaltorphimine (nor-BNI), a specific antagonist of OPRK1. By examining neurogenesis-related genes, we found that OPRK1 agonists were able to downregulate the expression of Pax6, Neurog2, and NeuroD1 in mouse hippocampal NSCs, in a way that Pax6 regulates the transcription of Neurog2 and Neurod1 by directly interacting with their promoters. Moreover, this effect of OPRK1 was accomplished by inducing expression of miR-7a, a miRNA that specifically targeted Pax6 by direct interaction with its 3'-UTR sequence, and thereby decreased the levels of Pax6, Neurog2, and NeuroD1, thus resulted in hindrance of neuronal differentiation of NSCs. Thus, by modulating Pax6/Neurog2/NeuroD1 activities via upregulation of miR-7a expression, OPRK1 agonists hinder the neuronal differentiation of NSCs and hence inhibit adult neurogenesis in mouse hippocampus.
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http://dx.doi.org/10.1002/stem.3334DOI Listing
May 2021

Ginsenosides for the treatment of metabolic syndrome and cardiovascular diseases: Pharmacology and mechanisms.

Biomed Pharmacother 2020 Dec 2;132:110915. Epub 2020 Nov 2.

Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, 610072, PR China. Electronic address:

Epidemiological studies showed that the metabolic syndromes (MetS) and cardiovascular diseases (CVDs) are responsible for a serious threat to human health worldwide. MetS is a syndromes characterized by fat metabolism disorder, obesity, diabetes, insulin resistance and other risk factors, which increases the risk of CVDs initiation and development. Although certain drugs play a role in lowering blood sugar and lipid, some side effects also occur. Considering the multiple pathogenesis, a great deal of natural products have been attempted to treat metabolic syndromes. Ginsenosides, as the active components isolated from Panax ginseng C.A.Mey, have been reported to have therapeutic effects on MetS and CVDs, of which pharmacological mechanisms were further studied as well. This review aims to systematically summarize current pharmacological effects of ginsenosides on MetS and CVDs, potential mechanisms and clinic trials, which will greatly contribute to the development of potential agents for related disease treatment.
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http://dx.doi.org/10.1016/j.biopha.2020.110915DOI Listing
December 2020

Efficacy and tolerability of decoction in gout patients: a systematic review and Meta-analysis.

Pharm Biol 2020 Dec;58(1):1023-1034

School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, China.

Context: decoction (GSZD), a famous ancient oriental Chinese prescription, has been widely used for thousands of years to treat 'arthromyodynia'.

Objective: The clinical studies of GSZD for the treatment of gout were systematically reviewed to evaluate its clinical efficacy and safety.

Methods: All randomized controlled trials (RCTs) related to GSZD and gout were collected starting from the database establishment until 29 February 2020, from the Embase, PubMed, Cochrane Library, Web of Knowledge, VIP and other databases. This systematic review and meta-analysis were performed in strict accordance with the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analysis) statement, and all analysis of the test was completed using Stata (SE12.0) and Revman (5.3).

Results: A total of 535 studies were searched, and 13 studies were included in our meta-analysis ( = 1056 participants). Compared with the conventional western medicine treatments, GSZD treatment yielded a significantly increase in the number of clinically effective patients (OR = 3.67, 95%CI = 2.39-5.64,  = 0.57), an improved mean reduction in the level of uric acid (MD = -54.06; 95% CI = -69.95 to -38.17). Meanwhile, the levels of erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) and interleukin-6 (IL-6) were also significantly decreased after the GSZD treatment with no increased relative risk of side-effects.

Conclusions: Our present works suggested that GSZD could be considered as an effective alternative remedy for clinical treatment of gout. In addition, it also provides a scientific basis for GSZD to be better applied in clinic in the future.
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http://dx.doi.org/10.1080/13880209.2020.1823426DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7737674PMC
December 2020

The Application of Fermentation Technology in Traditional Chinese Medicine: A Review.

Am J Chin Med 2020 20;48(4):899-921. Epub 2020 May 20.

School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, P. R. China.

In Chinese medicine, fermentation is a highly important processing technology whereby medicinal herbs are fermented under appropriate temperature, humidity, and moisture conditions by means of the action of microorganisms to enhance their original characteristics and/or produce new effects. This expands the scope of such medicines and helps them to meet the stringent demands of clinical application. Since ancient times, Chinese medicine has been made into Yaoqu to reduce its toxicity and increase its efficiency. Modern fermentation technologies have been developed on the basis of traditional fermentation techniques and modern biological technology, and they can be divided into solid fermentation, liquid fermentation, and two-way fermentation technologies according to the fermentation form employed. This review serves as an introduction to traditional fermentation technology and its related products, modern fermentation technologies, and the application of fermentation technology in the field of Chinese medicine. Several problems and challenges facing the field are also briefly discussed.
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http://dx.doi.org/10.1142/S0192415X20500433DOI Listing
September 2020

Traditional uses, botany, phytochemistry, pharmacology, separation and analysis technologies of Euonymus alatus (Thunb.) Siebold: A comprehensive review.

J Ethnopharmacol 2020 Sep 11;259:112942. Epub 2020 May 11.

Hospital of Chengdu University of Traditional Chinese Medicine, No.37 Shierqiao Road, Chengdu, 610072, China. Electronic address:

Ethnopharmacological Relevance: Euonymus alatus (Thunb.) Siebold (E. alatus), a well-known medicinal plant, has been widely used thousands of years in China for the treatment of various diseases such as urticaria, dysmenorrhea, wound, dysentery, blood stasis, rheumatism and arthritis. Due to the extensive application of E. alatus in the fields of ethnopharmacological usage, the pharmaceutical researches of E. alatus keeps deepening.

Aim Of The Study: This paper reviewed and summarized the integrated research progress of this medicinal plant. A comprehensive summary and comparison of traditional usages, botany, phytochemistry, pharmacology, toxicology, separation and analysis technologies of the E. alatus highlight recent scientific advances, which provides new insights into the research and development of this medicinal plant and would be helpful to promote the research situation of underlying pharmacological mechanisms and further utilizations of E. alatus.

Material And Methods: Literature survey was carried out via classic books of herbal medicine, PhD. and MSc. Dissertations. Online scientific databases including Pubmed, SciFinder, Science Direct, Scopus, the Web of Science, Google Scholar, China National Knowledge Infrastructure (CNKI) and others were searched up to February 2020 to identify eligible studies. All literatures of the research subject are analyzed and summarized in this review.

Results: The E. alatus has been widely used in traditional practice in China, Korea and other Asian Countries. In the study of phytochemistry, more than 230 chemical constituents have been isolated and identified from E. alatus, including sesquiterpenoids, diterpenoids, triterpenoids, flavonoids, phenylpropanoids, lignans, steroids, alkaloids and other compounds. Among them, literature reports show that flavonoids and steroids are the most important bioactive substances found in this plant. A number of researches also have shown that extracts and compounds from E. alatus exert a wide spectrum of pharmacological effects, including antidiabetic effect, anti-tumor effects, anti-inflammatory effects, hepatoprotective effects, antioxidant effects, antibacterial effects, as well as other effects. However, most of the studies without clinical research. Research into plant's toxicological effects has also been limited. In addition, this review also summarizes and compares the separation and analysis technologies of E. alatus.

Conclusions: E. alatus has potential for the treatment of many diseases, especially tumors and diabetes. But many traditional uses of E. alatus have not been validated by current investigations. Additionally, modern studies haven't gone far enough into its pharmacological effects and the corresponding chemical constituents, more efforts should be made to illuminate the underlying mechanisms of E. alatus for treatment of tumors and diabetes. Moreover, the toxicological effects of this plant can be further studied. Currently, there are limited studies on its side effects and toxicological effects, which should provide further guidance for the safety of clinical use.
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http://dx.doi.org/10.1016/j.jep.2020.112942DOI Listing
September 2020

A Retrospective Study on Risk Factors for Urinary Tract Infection in Patients with Intracranial Cerebral Hemorrhage.

Biomed Res Int 2020 28;2020:1396705. Epub 2020 Jan 28.

Department of Rehabilitation Medicine, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui 230001, China.

Objective: This study aimed to explore the risk factors of urinary tract infection (UTI) in patients with intracranial cerebral hemorrhage (ICH).

Design: This is a retrospective study, and a total of 77 patients with ICH consecutively admitted to the First Affiliated Hospital of USTC (Anhui Provincial Hospital, Hefei, China) during the period of August 2015 to August 2017 were included. The patients were divided into an UTI group (24 cases) and a non-UTI group (53 cases); patients with UTI were diagnosed according to clinical manifestations, recent urinary routines, and urine culture results. The following information in these two groups was recorded: age, sex, course of disease, side of paralysis, location and type of cerebral hemorrhage, disturbance of consciousness or not, the Brunnstrom stage of paralysed lower limbs, number of basic diseases, whether there were complications (tracheotomy, retention catheterization, pulmonary infection, pressure sore, deep venous thrombosis, etc.), whether rehabilitation interventions were conducted, blood routine, biochemistry index, DIC complete set, urine routine, and urine culture data. Univariate analysis and multivariate logistic regression analysis were used to examine the risk factors of UTI in patients with ICH.

Results: Univariate analysis showed that age, side of paralysis, disturbance of consciousness, the Brunnstrom stage of lower limbs, tracheotomies, retention catheterization, pulmonary infection, leukocyte count, neutrophil proportion, sodium, uric acid, D-dimer, and fibrinogen may be related to UTI in patients with ICH ( < 0.05). Regression analysis showed that age (OR (95% CI) = 1.207 (1.022-1.424), < 0.05). Regression analysis showed that age (OR (95% CI) = 1.207 (1.022-1.424), < 0.05). Regression analysis showed that age (OR (95% CI) = 1.207 (1.022-1.424), < 0.05). Regression analysis showed that age (OR (95% CI) = 1.207 (1.022-1.424).

Conclusions: Increased age and high D-dimer are independent risk factors for UTI in patients with ICH, while right-sided paralysis is a protective factor for UTI in patients with ICH.
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http://dx.doi.org/10.1155/2020/1396705DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7008289PMC
November 2020

Ginkgo diterpene lactones inhibit cerebral ischemia/reperfusion induced inflammatory response in astrocytes via TLR4/NF-κB pathway in rats.

J Ethnopharmacol 2020 Mar 31;249:112365. Epub 2019 Oct 31.

State Key Laboratory of Natural Medicines, School of Basic Medical Sciences and Clinical Pharmacy, China Pharmaceutical University, Nanjing, 210009, China. Electronic address:

Ethnopharmacological Relevance: Ginkgo biloba L. (Ginkgoaceae) is a traditional Chinese medicine known to treating stroke and other cardio-cerebrovascular diseases for thousands of years in China. Ginkgo diterpene lactones (GDL) attracted much attention because of their neuroprotective properties.

Aim Of The Study: To uncover the effects of GDL, which consist of ginkgolide A (GA), ginkgolide B (GB), and ginkgolide K (GK), on ischemic stroke, as well as the underlying molecular mechanisms.

Materials And Methods: We used middle cerebral artery occlusion/reperfusion (MCAO/R) and oxygen-glucose deprivation/reoxygenation (OGD/R) models mimicking the process of ischemia/reperfusion in vivo and in vitro, respectively. Anticoagulant effects of GDL were investigated on platelet activating factor (PAF), arachidonic acid (AA) and adenosine diphosphate (ADP)-induced platelet aggregation both in vivo and in vitro. We also evaluated the effects of GDL on lipopolysaccharide (LPS)-induced inflammatory response in primary cultured rats' astrocytes. Infarct size, neurological deficit score, and brain edema were measured at 72 h after MCAO. Immunohistochemistry was utilized to analyze neurons necrosis and astrocytes activation. Expression of pro-inflammatory cytokines, including tumor necrotic factor-α (TNF-α) and interleukin-1β (IL-1β) were detected using enzyme-linked immunosorbent assay (ELISA) and real time PCR. The levels of toll-like receptor 4 (TLR4) and nuclear factor κB (NF-κB) were assessed by real time PCR or Western blot.

Results: Compared with MCAO/R rats, GDL significantly reduced infarct size and brain edema, improved neurological deficit score. Meanwhile, GDL suppressed platelet aggregation, astrocytes activation, pro-inflammatory cytokines releasing, TLR4 mRNA expression and transfer of NF-κB from cytoplasm to nucleus. Furthermore, GDL alleviated OGD/R injury and LPS-induced inflammatory response in primary astrocytes, characterized by promoting cell viability, decreasing lactate dehydrogenase (LDH) activity, and inhibiting IL-1β and TNF-α releasing.

Conclusions: In summary, GDL attenuate cerebral ischemic injury, inhibit platelet aggregation and astrocytes activation. The anti-inflammatory activity might be associated with the downregulation of TLR4/NF-κB signal pathway. Our present findings provide an innovative insight into the novel treatment of GDL in ischemic stroke therapy.
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http://dx.doi.org/10.1016/j.jep.2019.112365DOI Listing
March 2020

Antiobesity, Regulation of Lipid Metabolism, and Attenuation of Liver Oxidative Stress Effects of Hydroxy--sanshool Isolated from on High-Fat Diet-Induced Hyperlipidemic Rats.

Oxid Med Cell Longev 2019 27;2019:5852494. Epub 2019 Aug 27.

School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, China.

is a traditional Chinese medicine (TCM) used to relieve pain, dispel dampness, stop diarrhea, and prevent itching. The aim of this study was to investigate the antiobesity and hypolipidemic effects of hydroxy--sanshool (HAS) isolated from on hyperlipidemic rats. Wistar rats ( = 48) were randomly divided into six groups: (1) normal diet rats (ND), (2) high-fat diet- (HFD-) treated rats, (3) HFD+fenofibrate-treated rats (HFD+FNB), (4) HFD+low dose of HAS-treated rats (HFD+LD, 9 mg/kg), (5) HFD+middle dose of HAS-treated rats (HFD+MD, 18 mg/kg), and (6) HFD+high dose of HAS-treated rats (HFD+HD, 36 mg/kg). The body weight and food intake of the rats were recorded during the treatment period. After 4 weeks of HAS treatment, abdominal adipose tissues were observed and total cholesterol (T-CHO), triglycerides (TG), high-density lipoprotein (HDL) cholesterol (HDL-C), and low-density lipoprotein (LDL) cholesterol (LDL-C) of serum and liver tissues were determined. Furthermore, histochemical examinations using oil red O and hematoxylin-eosin staining (H&E) were carried out and levels of malondialdehyde (MDA) and glutathione (GSH) and activities of superoxide dismutase (SOD) in the liver were determined. After HFD feeding, the body weight gain and food efficiency ratio of HFD rats were significantly enhanced ( < 0.05 ND rats) and HAS treatment (18 and 36 mg/kg) significantly decreased the body weight gain and food efficiency ratio ( < 0.05 HFD rats). In addition, HAS treatment could decrease the abdominal adipose tissues and liver adipocytes. Furthermore, HAS treatment significantly decreased the T-CHO, TG, and LDL-C, whereas it increased HDL-C ( < 0.05 HFD rats) in serum and the liver. HAS treatment increased the GSH level and SOD activity in the liver ( < 0.05 HFD rats), whereas it decreased the levels of MDA ( < 0.05 HFD rats). mRNA analyses suggested that HAS treatment increases the expression of (proliferator-activated receptor ) and (peroxisome apolipoprotein E). Immunohistochemistry and Western blotting indicated that HAS stimulation increased the levels of PPAR and APOE in the liver, as a stress response of the body defense system. These results revealed that HAS exerts antiobesity and hypolipidemic activities in HFD rats by reducing liver oxidative stress and thus could be considered as a potential candidate drug to cure or prevent obesity and hyperlipidemia.
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http://dx.doi.org/10.1155/2019/5852494DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6732614PMC
March 2020

Propagermanium, a CCR2 inhibitor, attenuates cerebral ischemia/reperfusion injury through inhibiting inflammatory response induced by microglia.

Neurochem Int 2019 05 19;125:99-110. Epub 2019 Feb 19.

State Key Laboratory of Natural Medicines, School of Basic Medical Sciences and Clinical Pharmacy, China Pharmaceutical University, Nanjing, Jiangsu, 210009, China. Electronic address:

CCR2 could recruit immune cells migrating into brain after ischemic stroke. It is unclear whether and why Propagermanium (PG, a CCR2 inhibitor) is able to protect against ischemic injury. Middle cerebral artery occlusion (MCAO) and reperfusion injury in C57BL/6 J male mice were performed in vivo to mimic ischemic stroke. Cultured BV2 microglia exposed to oxygen and glucose deprivation (OGD)/reoxygenation injury, LPS or IL-4 incubation were served in vitro. TTC staining, neurological score, brain water content, and MRI scan were performed to evaluate stroke outcome. Real time PCR, ELISA, and immunofluorescence were used to estimate inflammatory cytokines expression and releasing. Western blot was utilized to detect pSTAT1/STAT1 expression. Compared with MCAO mice, PG treatment significantly reduced infarction size and brain edema, improved neurological behavior at 72 h after MCAO. For inflammatory response, PG treatment inhibited inflammatory cytokines releasing, such as TNF-α, IFN-γ, IL-1β, IL-6, IL-12, IL-17, and IL-23. Further studies indicated that PG treatment downregulated mRNA expression of pro-inflammatory iNOS and CD86, and inhibited CD16 expressed in microglia. In vitro, PG incubation inhibited BV2 polarized to pro-inflammatory phenotype through STAT1 downregulation, while had no obvious effect on anti-inflammatory phenotype. Our observations suggest that CCR2 inhibitor PG downregulated pro-inflammatory microglia polarization for decreasing pro-inflammatory microglia phenotype marker, and thereafter inhibited inflammatory responses after MCAO in a STAT1-dependent manner.
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http://dx.doi.org/10.1016/j.neuint.2019.02.010DOI Listing
May 2019

Traditional Uses, Botany, Phytochemistry, Pharmacology, Pharmacokinetics and Toxicology of L.: A Review.

Molecules 2019 Jan 19;24(2). Epub 2019 Jan 19.

School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China.

L. (Asteraceae) is a common and well-known traditional Chinese herbal medicine usually named Cang-Er-Zi, and has been used for thousands of years in China. The purpose of this paper is to summarize the progress of modern research, and provide a systematic review on the traditional usages, botany, phytochemistry, pharmacology, pharmacokinetics, and toxicology of the . Moreover, an in-depth discussion of some valuable issues and possible development for future research on this plant is also given. , as a traditional herbal medicine, has been extensively applied to treat many diseases, such as rhinitis, nasal sinusitis, headache, gastric ulcer, urticaria, rheumatism bacterial, fungal infections and arthritis. Up to now, more than 170 chemical constituents have been isolated and identified from , including sesquiterpenoids, phenylpropenoids, lignanoids, coumarins, steroids, glycosides, flavonoids, thiazides, anthraquinones, naphthoquinones and other compounds. Modern research shows that the extracts and compounds from possess wide-ranging pharmacological effects, including anti- allergic rhinitis (AR) effects, anti-tumor effects, anti-inflammatory and analgesic effects, insecticide and antiparasitic effects, antioxidant effects, antibacterial and antifungal effects, antidiabetic effects, antilipidemic effects and antiviral effects. However, further research should focus on investigating bioactive compounds and demonstrate the mechanism of its detoxification, and more reasonable quality control standards for should also be established.
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http://dx.doi.org/10.3390/molecules24020359DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6359306PMC
January 2019

Morphine regulates adult neurogenesis and contextual memory extinction via the PKCε/Prox1 pathway.

Neuropharmacology 2018 10 28;141:126-138. Epub 2018 Aug 28.

State Key Laboratory of Natural Medicines, School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing, Jiangsu, 210009, People's Republic of China. Electronic address:

We have previously reported that the miR-181a/Prox1/Notch1 pathway mediates the effect of morphine on modulating lineage-specific differentiation of adult neural stem/progenitor cells (NSPCs) via a PKCε-dependent pathway, whereas fentanyl shows no such effect. However, the role of the PKCε/Prox1 pathway in mediating drug-associated contextual memory remains unknown. The current study investigated the effect of PKCε/Prox1 on morphine-induced inhibition of adult neurogenesis and drug-associated contextual memory in mice, while the effect of fentanyl was tested simultaneously. By using BrdU labeling, we were able to examine the lineages of differentiated NSPCs in adult DG. PKCε knockout blocked morphine's effects on inducing in vivo astrocyte-preferential differentiation of NSPCs, but did not alter NSPC lineages upon fentanyl treatment. Inhibited adult neurogenesis further resulted in prolonged extinction and enhanced reinstatement of morphine-induced CPP, as well as prolonged extinction of space reference memory indicated by the Morris water maze paradigm. However, after fentanyl administration, no significant changes were found between wild-type and PKCε knockout mice, during either CPP or water maze tasks. When the lentivirus encoding Nestin-promoter-controlled Prox1 cDNA was injected into hippocampi of wildtype and PKCε knockout adult mice to modulate PKCε/Prox1 activity, similar effects were discovered in adult mice injected with lentivirus encoding Prox1, and more dramatic effects were found in PKCε knockout mice with concurrent Prox1 overexpression. In conclusion, morphine mediates lineage-specific NSPC differentiation, inhibits adult neurogenesis and regulates contextual memory retention via the PKCε/Prox1 pathway, which are implicated in the eventual context-associated relapse.
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http://dx.doi.org/10.1016/j.neuropharm.2018.08.031DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6338672PMC
October 2018

S-oxiracetam ameliorates ischemic stroke induced neuronal apoptosis through up-regulating α7 nAChR and PI3K / Akt / GSK3β signal pathway in rats.

Neurochem Int 2018 05 19;115:50-60. Epub 2018 Jan 19.

State Key Laboratory of Natural Medicines, Department of Physiology, School of Basic Medical Sciences and Clinical Pharmacy, China Pharmaceutical University, Nanjing 210009, PR China. Electronic address:

Ischemic stroke, the main reason for severe disabilities in the world, is associated with a high incidence of sensorimotor and cognitive dysfunction. In this study, we use the middle cerebral artery occlusion/reperfusion (MCAO/R) model in rats and oxygen glucose deprivation/reoxygenation (OGD/R) model in fetal rat primary cortical neurons to investigate whether and how S-oxiracetam (S-ORC) protect brain injury from ischemic stroke. The results revealed that S-ORC reduced brain infarct size and lessened neurological dysfunction after stroke. Further study demonstrated that S-ORC diminished TUNEL positive cells, increased cell viability, decreased LDH activity, and inhibited cell apoptotic rate. Furthermore, S-ORC inhibited neuronal apoptosis by activating the PI3K/Akt/GSK3β signaling pathway via α7 nAChR, which was evidenced by α7 nAChR siRNA. In conclusion, our findings strongly suggest that S-ORC could be used as an effective neuroprotective agent for ischemic stroke due to its effect in preventing neuronal apoptosis.
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http://dx.doi.org/10.1016/j.neuint.2018.01.008DOI Listing
May 2018

Traditional Uses, Origins, Chemistry and Pharmacology of Bombyx batryticatus: A Review.

Molecules 2017 Oct 20;22(10). Epub 2017 Oct 20.

College of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China.

(), a well-known traditional animal Chinese medicine, has been commonly used in China for thousands of years. The present paper reviewed advances in traditional uses, origin, chemical constituents, pharmacology and toxicity studies of . The aim of the paper is to provide more comprehensive references for modern study and application. In Traditional Chinese Medicine (TCM) culture, drugs containing have been used to treat convulsions, headaches, skin prurigo, scrofula, tonsillitis and fever. Many studies indicate contains various compounds, including protein and peptides, fatty acids, flavonoids, nucleosides, steroids, coumarin, polysaccharide and others. Numerous investigations also have shown that extracts and compounds from exert a wide spectrum of pharmacological effects both in vivo and in vitro, including effects on the nervous system, anticoagulant effects, antitumor effects, antibacterial and antifungal effects, antioxidant effects, hypoglycemic effects, as well as other effects. However, further studies should be undertaken to investigate bioactive compounds (especially proteins and peptides), toxic constituents, using forms and the quality evaluation and control of . Furthermore, it will be interesting to study the mechanism of biological activities and structure-function relationships of bioactive constituents in .
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http://dx.doi.org/10.3390/molecules22101779DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6151799PMC
October 2017

S-oxiracetam protect against ischemic stroke via alleviating blood brain barrier dysfunction in rats.

Eur J Pharm Sci 2017 Nov 29;109:40-47. Epub 2017 Jul 29.

State Key Laboratory of Natural Medicines, School of Basic Medical Sciences and Clinical Pharmacy, China Pharmaceutical University, Nanjing 210009, China. Electronic address:

The blood brain barrier (BBB) maintains the basic stability of the brain tissue under physiological conditions, while destroys and exaggerates brain edema and inflammatory response after ischemic stroke. In this study, we researched S-oxiracetam (S-ORC), a nootropic drug, alleviates BBB dysfunction and protects against ischemic stroke in rats. Middle cerebral artery occlusion(MCAO)/reperfusion in rats is applied to mimic ischemic stroke. One hour after reperfusion, rats are administered intravenously with different dose (0.12, 0.24, or 0.48g/kg) of S-ORC for continuative three days. Seventy-two hours after MCAO, TTC staining, hematoxylin and eosin (H&E) staining, brain water content, immunohistochemical staining, EB extravasation, western blot are provided to evaluate the protective effect and possible mechanism of S-ORC on BBB dysfunction. Furthermore, brain concentration of verapamil (P-glycoprotein substrate) and atenolol (paracellular transport marker) were assayed by UPLC-MS/MS co administration with or without S-ORC. The results show that post-treatment of S-ORC decreases cerebral infarct size, lessens brain edema, inhibits neutrophil infiltration and cytokines releasing. Furthermore, S-ORC treatment decreases EB leakage, downregulates MMP-9, upregulates occludin and claudin-5, and decreases brain concentration of verapamil and atenolol after MCAO surgery. In conclusion, the present study demonstrates that post-treatment of S-ORC alleviates BBB dysfunction by regulating tight junction proteins (TJPs), upregulating P-glycoprotein function, and protects against ischemic stroke as result.
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http://dx.doi.org/10.1016/j.ejps.2017.07.029DOI Listing
November 2017

Effects of modified sit-to-stand training on balance control in hemiplegic stroke patients: a randomized controlled trial.

Clin Rehabil 2016 Jul 27;30(7):627-36. Epub 2015 Aug 27.

Department of Rehabilitation Medicine, The Affiliated Provincial Hospital of Anhui Medical University, Anhui, Peoples' Republic of China

Objective: To explore the effectiveness of modified sit-to-stand training on balance function in hemiplegic stroke patients.

Design: Randomized controlled trial.

Setting: Rehabilitation medical centre.

Participants: A total of 50 hemiplegic patients with stroke were randomly assigned to the control and experimental groups (n = 25 for each group).

Interventions: Patients in the control group received the sit-to-stand training with symmetrical foot position, while patients in the experimental group were given the modified sit-to-stand training in which the paretic foot placed posterior. Subjects in both groups received 30 minutes of sit-to-stand training, five times a week, for four weeks.

Main Outcome Measures: The time and weight-bearing distribution during sit-to-stand movement, the centre of pressure sway length during quiet standing, the centre of pressure sway areas during dynamic standing and Berg Balance Scale were assessed before and after completing the four-week sit-to-stand training.

Results: Our data showed significant improvements in standing balance and the sit-to-stand movement for two groups in the post-training compared with the pre-training. After training, the rise time shortened more significantly in the experimental group (mean change, 0.90 ±0.25 seconds) than the control group (mean change, 0.42 ±0.18 seconds). Weight-bearing asymmetry showed significantly greater improvement in the experimental group (mean change, 0.17 ±0.10) than in the control group (mean change, 0.06 ±0.05). Centre of pressure sway length was significantly smaller in the experimental group (mean change, 27.85 ±10.58 cm) than in the control group (mean change, 21.95 ±8.19 cm). Centre of pressure sway areas was significantly larger in the experimental group (mean change, 84.24 ±26.48 cm(2)) than in the control group (mean change, 67.74 ±22.84 cm(2)) (P = 0.027). The Berg Balance Scale was significantly higher in the experiment group (mean change, 8.4 ±3.1) than the control group (mean change, 5.8±2.8).

Conclusions: A modified sit-to-stand training improves the balance function in hemiplegic stroke patients.
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http://dx.doi.org/10.1177/0269215515600505DOI Listing
July 2016

The neuroprotective effect of a novel agent N2 on rat cerebral ischemia associated with the activation of PI3K/Akt signaling pathway.

Neuropharmacology 2015 Aug 25;95:12-21. Epub 2015 Feb 25.

State Key Laboratory of Natural Medicines, Department of Physiology, China Pharmaceutical University, Nanjing 210009, PR China. Electronic address:

Ischemic stroke is the third leading cause of death and the main reason for severe disabilities in the world today. N2, 4 - (2 - (1H - imidazol - 1 - yl) ethoxy) - 3 - methoxybenzoic acid is considered as a novel potent agent for cerebral ischemia due to its effect in preventing neuronal cell death after ischemic stroke. In the present study, we investigated the post-ischemic neuroprotective effect of N2 and its underlying mechanisms. Using a MCAO rat model, we found that N2 reversed brain infarct size, reduced cerebral edema and decreased the neurological deficit score significantly. Moreover, N2 diminished TUNEL positive cells, down-regulated bax expression and up-regulated bcl-2 expression notably. In addition, we evaluated the oxygen glucose deprivation/reoxygenation (OGD/R) injury induced neuron cell death in rat primary cortical neuron and assessed the neuroprotective effect of our drug. N2 increased cell viability, ameliorated neuron cell injury by decreasing LDH activity, and inhibited cell apoptotic rate while suppressed apoptotic signaling via inhibiting the bax expression, and elevating the bcl-2 expression. Furthermore, the neuroprotective effect of N2 was associated with the PI3K/Akt pathway which was proved by the use of PI3K inhibitor LY294002. The combination of our findings disclosed that N2 can be used as an effective neuroprotective agent for ischemic stroke due to its significant effect on preventing neuronal cell death after cerebral ischemia both in vivo and in vitro and the effectiveness was dose dependent.
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http://dx.doi.org/10.1016/j.neuropharm.2015.02.022DOI Listing
August 2015

N2 ameliorates neural injury during experimental ischemic stroke via the regulation of thromboxane A2 production.

Pharmacol Biochem Behav 2014 Sep 20;124:458-65. Epub 2014 Jun 20.

State Key Laboratory of Natural Medicines, Department of Physiology, China Pharmaceutical University, Nanjing 210009, PR China. Electronic address:

Thromboxane A2 (TXA2) promotes ischemic stroke injury and has strong effects in vascular contraction and vascular endothelial cell dysfunction. Agents that reduce TXA2 production have potential for ameliorating neural injury in ischemic stroke. Thromboxane synthetase (TXS) is essential for TXA2 production, and TXS inhibitors have been developed as drugs for the prevention and treatment of stroke. However, ozagrel, a typical TXS inhibitor currently in clinical use, must be delivered via intravenous injection (I.V.). N2, 4-(2-(1H-imidazol-1-yl) ethoxy)-3-methoxybenzoate, is a potential thromboxane synthetase (TXS) inhibitor, which is being developed as an orally available formulation. The aim of this study was to investigate the effects of N2 on focal cerebral ischemia-reperfusion injury and related mechanisms. Neurological deficits, a Y-maze test and infarct volume were measured to evaluate the effects of N2 post-treatment on middle cerebral artery occlusion (MCAO)-induced ischemia/reperfusion (I/R) injury in rats. Furthermore, the influence of N2 on U46619-induced rat aorta contraction was investigated ex vivo. Moreover, we investigated the protective effects of N2 on rat brain microvessel endothelial cells (RBMECs) in hypoxia/deoxygenating (H/R) induced by Na2S2O4 in vitro. Cell viability and TXA2 biosynthesis were measured by 3-(4, 5-dimethylthiazol-2-yl)- 195 2, 5-diphenyltetrazolium bromide (MTT) and enzyme-linked immunosorbent assay (ELISA) assays, respectively. The results showed that N2 treatment effectively improves performance in neurological deficit and the Y-maze test and reduces the infarct volume in I/R rats. U46619-induced rat aorta contraction was inhibited by N2 ex vivo. Furthermore, N2 incubation improved the morphology of RBMECs, increased cell viability, and suppressed TXA2 production by inhibiting TXS during H/R damage. In summary, this study demonstrated that N2 was neural protective in focal cerebral I/R injury, which might be associated with the effects of N2 on endothelium protection and vascular contraction inhibition. In depth, the mechanisms underlying this phenomenon might be the influence of N2 on TXA2 production targeting TXS.
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http://dx.doi.org/10.1016/j.pbb.2014.06.009DOI Listing
September 2014
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