作者机构：
[Xie, Qing-ling; Li, Bin; Wang, Wei; Peng, Cai-yun; Yang, Yu-pei; Yu, Huang-he; Liu, Yong-bei; Jian, Yu-qing; Wang, Bin] Hunan Univ Chinese Med, Innovat Mat Med Res Inst, TCM & Ethnomed Innovat & Amp Dev Int Lab, Sch Pharm, Changsha 410208, Hunan, Peoples R China.
通讯机构：
[Wei Wang] T;TCM and Ethnomedicine Innovation & Development International Laboratory, Innovative Materia Medica Research Institute, School of Pharmacy, Hunan University of Chinese Medicine, Changsha, People's Republic of China
摘要：
Heilaohu, the roots of Kadsura coccinea, has been used in Tujia ethnomedicine to treat rheumatic arthritis (RA). Heilaohuacid G (1), a new 3,4-seco-lanostane type triterpenoid isolated from the ethanol extract of Heilaohu, whose structure was determined using HR-ESI-MS data, NMR spectroscopic analyses, and ECD calculations. In this study, our purpose is to elucidate the mechanisms of Heilaohuacid G in the treatment of RA by inhibited proliferation of rheumatoid arthritis-fibroblastoid synovial (RA-FLS) cells and inhibited the inflammatory reactions in LPS-induced RA-FLS and RAW 264.7 cell lines via inhibiting NF-κB pathway. The biological activity screening experiments indicated that Heilaohuacid G significantly inhibited proliferation of RA-FLS cells with IC(50) value of 8.16 ± 0.47μM. CCK-8 assay, ELISA, flow cytometry assay, and Western blot were used to measure the changes of cell viability, apoptosis, and the release of inflammatory cytokines. Heilaohuacid G was found not only induced RA-FLS cell apoptosis, but also inhibited the inflammatory reactions in LPS-induced RA-FLS and RAW 264.7 cell lines via inhibiting NF-κB pathway. Furthermore, Heilaohuacid G (p.o.) at doses of 3.0, 6.0, and 12.0 mg/kg and the ethanol extracts of Heilaohu (p.o.) at doses of 200, 400, and 800 mg/kg both were confirmed antiinflammatory effects on xylene-induced ear mice edema model.
作者：
Nie, Duorui;Liu, Siyu;Cai, Si;Xing, Xiaoqi;Xu, Fei
期刊：
Advances in Therapy,2022年39(11):5043-5057 ISSN：0741-238X
通讯作者：
Fei Xu
作者机构：
[Nie, Duorui; Liu, Siyu] Hunan Univ Chinese Med, Grad Sch, Changsha, Peoples R China.;[Cai, Si] China Pharmaceut Univ, Inst Technol, Nanjing, Peoples R China.;[Xing, Xiaoqi; Xu, Fei] Hunan Univ Chinese Med, Coll Pharm, Changsha 410208, Peoples R China.;[Xu, Fei] Hunan Engn Technol Res Ctr Bioact Subst Discovery, Changsha, Peoples R China.;[Xu, Fei] Hunan Prov Sino US Int Joint Res Ctr Therapeut Dr, Changsha, Peoples R China.
通讯机构：
[Fei Xu] C;College of Pharmacy, Hunan University of Chinese Medicine, Changsha, China<&wdkj&>Hunan Engineering Technology Research Center for Bioactive Substance Discovery of Chinese Medicine, Changsha, China<&wdkj&>Hunan Province Sino-US International Joint Research Center for Therapeutic Drugs of Senile Degenerative Diseases, Changsha, China
摘要：
INTRODUCTION: Chemotherapy (CT) is the main treatment for patients with unresected pancreatic cancer (PC). Whether the addition of radiotherapy to chemotherapy improves the prognosis of elderly patients with unresected PC is unclear. The aim of our study was to compare the efficacy of chemoradiotherapy (CRT) with chemotherapy alone in elderly patients with unresected PC. METHODS: The clinical data of elderly patients with unresected PC who received chemotherapy between 2004 and 2017 were determined from the Surveillance, Epidemiology, and End Results (SEER) database, and the patients were divided into CT and CRT groups. The primary outcome was overall survival (OS), and secondary endpoints were cancer-specific survival (CSS) and cancer-specific mortality (CSM). Propensity matching analysis (PSM) was used to balance the differences between the two groups. OS and CSS were assessed using Kaplan-Meier analysis, while CSM was assessed using a competing risk model. Subgroup analyses were also performed, and Cox regression was used to adjust for confounding factors. RESULTS: A total of 17,814 patients were diagnosed with PC including 14,222 who received CT alone and 3592 who received CRT. The 1-year OS of the CT and CRT groups after PSM was 30.1% and 40.8%, and the 1-year CSS was 31.4% and 42.1%, respectively. Overall, the CRT group had better OS, CSS, and CSM rates than the CT group before and after PSM (P < 0.05). After adjustment for age, sex, race, histological grade, stage, and other factors, the CRT group still had a lower risk of death than the CT group, and subgroup analysis further revealed the survival benefit of CRT in each population. CONCLUSIONS: CRT improves the outcome of patients with non-surgical PC over 65years of age. But prospective studies are needed to validate our results.
摘要：
Hyperlipidemia, the most common form of dyslipidemia, is the main source of cardiovascular disorders, characterized by elevated level of total cholesterol (TC), triglycerides (TG) and low-density lipoprotein cholesterol (LDL-C) with high-density lipoprotein cholesterol (HDL-C) in peripheral blood. It is caused by a defect in lipid metabolism in the surface of Apoprotein C-II or a defect in lipoprotein lipase activity as well as reported in genetic, dietary and environmental factors. Several electronic databases were investigated as information sources, including Google Scholar, PubMed, Web of Science, Scopus, ScienceDirect, SpringerLink, Semantic Scholar, MEDLINE and CNKI Scholar. The current review focused on the risk factors of dyslipidemia, synthetic medication with their side effects and different types of medicinal plants having significant potential for the management of hyperlipidemia. The management of hyperlipidemia mostly involves a constant decrease in lipid level using different remedial drugs like statin, fibrate, bile acid sequestrates and niacin. However, this extensive review suggested that the consequences of these drugs are arguable, due to their numerous adverse effects. The selected parts of herb plants are used intact or their extracts containing active phytoconstituents to regulate the lipids in blood level. It was also noted that the Chinese herbal medicine and combination therapy is promising for the lowering of hyperlipidemia. This review intends to provide a scientific base for future endeavors, such as in-depth biological and chemical investigations into previously researched topics.
期刊：
Journal of Applied Microbiology,2022年132(3):2280-2292 ISSN：1364-5072
通讯作者：
Shunxiang Li
作者机构：
[Pan, Yu] Guangxi Botanical Garden of Medical Plants, Nanning, Guangxi, China;[Xu, Fei; Li, Hanyin; Zeng, Yangli; Li, Juan; Li, Shunxiang] School of Pharmacy, Hunan University of Chinese Medicine, Changsha, Hunan, China
通讯机构：
[Shunxiang Li] S;School of Pharmacy, Hunan University of Chinese Medicine, Changsha, Hunan, China
作者机构：
[Xu Dehong; Hong Siqin; Zeng Peng; Wu Wenmei] Hunan Univ Chinese Med, Coll Pharm, Lab Biol Engn, Changsha 410208, Hunan, Peoples R China.;[Xu Dehong; Zeng Xiongzhi; Wang Xianchun] Hunan Normal Univ, Coll Life Sci, Key Lab Prot Chem & Dev Biol, Minist Educ, Changsha 410081, Hunan, Peoples R China.
通讯机构：
[Wang Xianchun; Zeng Xiongzhi] K;Key Laboratory of Protein Chemistry and Developmental Biology of Ministry of Education, College of Life Sciences, Hunan Normal University, Changsha, Hunan 410081, P. R. China<&wdkj&>Key Laboratory of Protein Chemistry and Developmental Biology of Ministry of Education, College of Life Sciences, Hunan Normal University, Changsha, Hunan 410081, P. R. China
摘要：
JZTX-V is a toxin isolated from the venom of the Chinese spider Chilobrachys jingzhao. Previous studies had shown that JZTX-V could inhibit the transient outward potassium current of Kv4.2 and Kv4.3 expressed in Xenopus oocytes but had no effects on Kv1.2-1.4. However, the underlying action mechanism of JZTX-V on Kv4.3 remains unclear. In our study, JZTX-V could inhibit not only transient outward potassium currents evoked in small-sized DRG neurons but also Kv4.3-encoded currents expressed in HEK293T cells in the concentration and voltage dependence. The half maximal inhibitory concentration of JZTX-V on Kv4.3 was 9.6±1.2nM. In addition, the time course for JZTX-V inhibition and release of inhibition after washout were 15.8±1.54 s and 58.8±4.35 s. Electrophysiological assays indicated that 25nM JZTX-V could shift significantly the voltage dependence of steady-state activation and steady-state inactivation to depolarization. Meanwhile, 25nM JZTX-V decreased markedly the time constant of activation and inactivation but had no effect on the time constant of recovery from inactivation. To study the molecular determinants of Kv4.3, we performed alanine scanning on a conserved motif of Kv4.3 and assayed the affinity between mutants and JZTX-V. The results not only showed that I273, L275, V283, and F287 were molecular determinants in the conserved motif of Kv4.3 for interacting with JZTX-V but also speculated the underlying action mechanism that the hydrophobic interaction and steric effects played key roles in the binding of JZTX-V with Kv4.3. In summary, our studies have laid a scientific theoretical foundation for further research on the interaction mechanism between JZTX-V and Kv4.3.
作者机构：
[Liao, Duan-fang; Choudhary, M. Iqbal; Shehla, Nuzhat; Li, Bin; Wang, Wei; Atta-ur-Rahman; Cao, Liang; Jian, Yuqing] Hunan Univ Chinese Med, TCM & Ethnomed Innovat & Dev Int Lab, Acad Atta Ur Rahman Belt & Rd Tradit Med Res Ctr, Sch Pharm, Changsha, Peoples R China.;[Choudhary, M. Iqbal; Shehla, Nuzhat; Wang, Wei; Atta-ur-Rahman] Univ Karachi, HEJ Res Inst Chem, Int Ctr Chem & Biol Sci, Karachi, Pakistan.;[Zhao, Jianping; Khan, Ikhlas A.] Univ Mississippi, Natl Ctr Nat Prod Res, Pharmaceut Sci Res Inst, University, MS 38677 USA.
通讯机构：
[Choudhary, M. Iqbal] H;[Choudhary, M. Iqbal] U;Hunan Univ Chinese Med, TCM & Ethnomed Innovat & Dev Int Lab, Acad Atta Ur Rahman Belt & Rd Tradit Med Res Ctr, Sch Pharm, Changsha, Peoples R China.;Univ Karachi, HEJ Res Inst Chem, Int Ctr Chem & Biol Sci, Karachi, Pakistan.
摘要：
Kadsura heteroclita Roxb. Craib. (Schisandraceae), is a vine plant mainly distributed in southwest part of China. A new dibenzocyclooctadiene lignan, kadsulignan W (1), along with eleven known lignans (2–12) were isolated from chloroform soluble fraction of stems of Kadsura heteroclita. The structure of new lignan was elucidated by extensive spectroscopic techniques, namely one- and two-dimensional NMR spectroscopy, and HRESI-MS analysis. The absolute configuration of the biphenyl ring in the new dibenzocyclooctadiene lignan was discerned by circular dichroism (CD) spectroscopy. Antioxidative effects of these compounds were evaluated on human isolated neutrophils, and compounds 5, 8, 9, and 10 were found to be strongly active with the IC50 of 36.68, 34.41, 35.97, and 33.65 µM, respectively. Furthermore, compound 8 was also found to be cytotoxic against human gastric cancer cells (BGC 823), and human cervical cancer cell lines (HeLa) with the IC50 values of 11.0, and 23.8 µM, respectively.
通讯机构：
[Weihua Wu; Kai He] H;Hunan Provincial Key Laboratory of Dong Medicine, Hunan Provincial Key Laboratory for Synthetic Biology of Traditional Chinese Medicine, School of Pharmaceutical Science, Hunan University of Medicine, Huaihua, 418000, Hunan, China<&wdkj&>Hunan Provincial Key Laboratory of Dong Medicine, Hunan Provincial Key Laboratory for Synthetic Biology of Traditional Chinese Medicine, School of Pharmaceutical Science, Hunan University of Medicine, Huaihua, 418000, Hunan, China
关键词：
Bidirectional effects;Blood circulation;Central nervous system;Gastrointestinal motility;Immune function;Traditional Chinese medicine
摘要：
ETHNOPHARMACOLOGICAL RELEVANCE: The bidirectional property of traditional Chinese medicines (TCMs) was recorded in the classic work Medicine Origin (Yi Xue Qi Yuan) as early as the Jin and Yuan dynasties of ancient China. Since then, this imperative theory has been applied to guide the clinical application of TCMs. Studies have been performed to investigate this phenomenon only over the last three decades. A limited number of reviews on the bidirectional role of TCMs have been published, and almost all current studies are published in the Chinese language. AIM OF THE REVIEW: The aim of this review is to provide the first comprehensive evidence regarding the bidirectional effects and the underlying mechanisms of TCMs and their active compounds. MATERIALS AND METHODS: Information relevant to opposing pharmacological activities or opposing properties exerted by TCM prescriptions, herbal medicines, and their active compound, as well as their mechanisms was summarized by searching Chinese and English databases, including the Chinese National Knowledge Infrastructure (CNKI), Wan Fang Data, Chinese Scientific Journal Database (VIP), Google Scholar, PubMed, Web of Science, Science Direct, and Wiley Online Library. RESULTS: Although the bidirectional regulation of TCMs has been applied in the clinic since ancient times in China, only limited reviews have been published in Chinese. The existing data showed that bidirectional effects can be found in TCM prescriptions, herbal medicines, and pure active compounds. Additionally, the bidirectional role of TCMs was primarily reported in the modulation of immune function, blood circulation and hemostasis, gastrointestinal motility, the central nervous system and blood pressure. This may because the therapeutic outcomes of these disorders are more obvious than those of other complicated diseases. Intriguingly, some herbal medicines have multiple bidirectional activities; for instance, Panax ginseng C. A. Meyer showed bidirectional regulation of immune function and the central nervous system; Astragalus membranaceus can bidirectionally regulate blood pressure and immune function; and Rheum officinale Baill exerts bidirectional effects on blood circulation and hemostasis, gastrointestinal motility and immune function. The mechanisms underlying the bidirectional effects of TCMs are largely attributed to the complexity of herbal constituents, dosage differences, the processing of herbal medicine, and compatibility of medicines, the physiological conditions of patients and adaptogenic effects. CONCLUSION: Uncovering the bidirectional effects and mechanisms of TCMs is of great importance for both scientific research and clinical applications. This review may help to facilitate the recognition of the bidirectional role of TCMs, to explain some seemingly-opposite phenomena in the pharmacological study of herbal medicines and to provide guidance for TCM practitioners.
作者机构：
[Li, Bin; Wang, Wei; Sheng, Wen-Bing; Xie, Qing-Ling; Liu, Xin-Yi; Zhou, Xu-Dong; Cui, Pei-Wu; Gong, Li-Min; Tang, Hong-Xia] Hunan Univ Chinese Med, Sch Pharm, Innovat Mat Med Res Inst, TCM & Ethnomed Innovat & Dev Int Lab, Changsha, Peoples R China.;[Wang, Wen-Mao] Hunan Qiankun Biotechnol Co Ltd, Meicha Technol Res Ctr, Zhangjiajie, Hunan, Peoples R China.
通讯机构：
[Wei Wang; Xu-Dong Zhou] T;TCM and Ethnomedicine Innovation & Development International Laboratory, Innovative Materia Medica Research Institute, School of Pharmacy, Hunan University of Chinese Medicine, Changsha, P.R. China<&wdkj&>TCM and Ethnomedicine Innovation & Development International Laboratory, Innovative Materia Medica Research Institute, School of Pharmacy, Hunan University of Chinese Medicine, Changsha, P.R. China
摘要：
Journal of Empirical Research on Human Research Ethics, Volume 17, Issue 3, Page 362-372, July 2022. <br/>This study aims to investigate the knowledge and attitudes of participants and potential participants in clinical trials toward electronic informed consent. We conducted a survey-based cross-sectional study in Hunan Province, China in March 2021. A total of 547 respondents were included in this study. All questions in an 8-item survey section assessing participants’ knowledge of electronic informed consent received correct answers from at least 70% of participants. In terms of attitude scores, most participants (86.3%) believed that electronic informed consent is more convenient than the paper-based version, and more than half (51.2%) believed that electronic informed consent could completely replace the paper-based version. Responses indicated that common concerns about electronic informed consent were its security and confidentiality, legal benefits, and implications for rights protection.
摘要：
Curcumin nicotinate (Curtn) is a synthesized ester derivative of curcumin and niacin. Our previous study has shown that Curtn lowers serum low-density lipoprotein cholesterol (LDL-C) levels in apoE(-/-) mice and promotes LDL-C uptake into HepG2 cells in vitro. The present study was to test the hypothesis that Curtn decreases serum LDL-C levels through decreased expression of pro-protein convertase subtilisin/kexin type 9 (PCSK9) and subsequent increase in LDL receptor expression. Male Wistar rats on high-fat diet (HFD) were treated with Curtn or rosuvastatin. Curtn or rosuvastatin treatment significantly decreased serum levels of total cholesterol (TC) and LDL-C in rats on HFD with increased liver LDL receptor expression. LDL-C-lowering effect of Curtn was not observed in LDL receptor deficient (LDLR(-/-)) mice on HFD, while rosuvastatin still decreased serum lipid levels in LDLR(-/-) mice, indicating that the reduction of serum LDL-C levels by Curtn treatment was LDL receptor-dependent. Curtn treatment also significantly decreased the protein expression of PCSK9 in Wistar rats and LDLR(-/-) mice. In HepG2 cells with overexpression of human PCSK9, Curtn treatment significantly increased LDL-C uptakes into hepatocytes, and increased LDL receptor distribution on cell surface in association with decreased PCSK9 protein expression. RNAi-LDLR significantly attenuated the effect of Curtn on LDLR distribution on cell surface. These data indicates that Curtn would decrease serum LDL-C level at least partially through inhibition of PCSK9 expression, and subsequent increase in LDL receptor expression and distribution in hepatocytes, serving as a potential novel compound to treat hyperlipidemia.
摘要：
Klebsiella pneumoniae (K. pneumoniae) is a common bacterium whose drug-resistant can cause surgical failures and incurable infections in hospital patients. Thus, how to reverse or delay the resistance induction has become a great challenge for development antiresistant drug. Recently, the combination of nanomaterial-loaded antibiotics with photothermal therapy showed the efficient antibacteria ability under a low dosage of antibiotics. In this study, a nanocomposite of HMPB NPs with inherent photothermal therapy capability was used to eradicate K. pneumoniae after loading with Ofloxacin, an antibiotic against K. pneumoniae in vitro and in vivo. The nanocomplexes named as Ofloxacin@HMPB@HA NPs showed a higher effect against K. pneumoniae by destroying cell integrity and inducing ATP leakage with the assistance of laser irradiation, compared with sole Ofloxacin@HMPB@HA NPs or laser irradiation. Surgical wound infection assay further demonstrated the efficient killing K. pneumoniae and promoting the formation of new tissues, as well, which was reflected by the rapid healing of surgical wound. In summary, these results indicate the great potential of this combinational tactic based on Ofloxacin@HMPB@HA NPs for preventing the failure caused by K. pneumoniae infection.
作者机构：
[Zhu, Liangdi; Zhou, Yuxing; Cheng, Xunlong; Zhu, Xixi] College of Pharmacy, Hunan University of Chinese Medicine, Changsha, 410208, China;[Fei, Lingyun] Hunan Provincial Key Laboratory of Efficient and Clean Utilization of Manganese Resources, College of Chemistry and Chemical Engineering, Central South University, Changsha, 410083, China;[Deng, Lanqing] College of Pharmacy, Hunan University of Chinese Medicine, Changsha, 410208, China. Electronic address: denglq1111@126.com;[Ma, Xin] Hunan Provincial Key Laboratory of Efficient and Clean Utilization of Manganese Resources, College of Chemistry and Chemical Engineering, Central South University, Changsha, 410083, China. Electronic address: maxin2013@csu.edu.cn
通讯机构：
[Lanqing Deng] C;[Xin Ma] H;Hunan Provincial Key Laboratory of Efficient and Clean Utilization of Manganese Resources, College of Chemistry and Chemical Engineering, Central South University, Changsha, 410083, China<&wdkj&>College of Pharmacy, Hunan University of Chinese Medicine, Changsha, 410208, China
期刊：
World Journal of Microbiology and Biotechnology,2022年38(6):1-10 ISSN：0959-3993
通讯作者：
Zeng, JG;Huang, P
作者机构：
[Sun, Mengshan; Zeng, Jianguo; Xu, Zixuan] Hunan Agr Univ, Hunan Key Lab Tradit Chinese Vet Med, Changsha, Hunan, Peoples R China.;[Zhong, Xiaohong; Sun, Mengshan] Hunan Agr Univ, Coll Hort, Changsha, Hunan, Peoples R China.;[Zhou, Li] Hunan Acad Agr Sci, Hunan Inst Agr Environm & Ecol, Changsha, Hunan, Peoples R China.;[Xu, Zixuan] Hunan Univ Chinese Med, Sch Pharm, Changsha, Hunan, Peoples R China.;[Huang, P; Huang, Peng] Hunan Agr Univ, Coll Anim Sci & Technol, Changsha, Hunan, Peoples R China.
通讯机构：
[Zeng, JG ; Huang, P ] H;Hunan Agr Univ, Hunan Key Lab Tradit Chinese Vet Med, Changsha, Hunan, Peoples R China.;Hunan Agr Univ, Coll Anim Sci & Technol, Changsha, Hunan, Peoples R China.;Hunan Agr Univ, Coll Vet Med, Changsha, Hunan, Peoples R China.;Hunan Agr Univ, Natl & Local Union Engn Res Ctr Vet Herbal Med Re, Changsha, Hunan, Peoples R China.
期刊：
European Journal of Pharmacology,2022年930:175149 ISSN：0014-2999
通讯作者：
Sheng Xie<&wdkj&>Yu-Hong Wang
作者机构：
[Li, Zi-Rong] Guangxi Univ Chinese Med, Affiliated Hosp 1, Dept Neurol, Nanning 530022, Guangxi, Peoples R China.;[Liu, De-Guo] Guangxi Univ Chinese Med, Affiliated Hosp 1, Dept Breast Surg, Nanning 530022, Guangxi, Peoples R China.;[Xie, Sheng] Guangxi Univ Chinese Med, Affiliated Hosp 1, Prevent Dis Tradit Chinese Med Ctr, Nanning 530022, Guangxi, Peoples R China.;[Li, Chun-Yan; Wang, Yu-Hong; Zou, Man-Shu] Hunan Univ Chinese Med, State Key Lab Chinese Med Powder & Med Innovat Hun, Changsha 410208, Hunan, Peoples R China.;[Han, Yuan-Shan] Hunan Univ Chinese Med, Affiliated Hosp 1, Dept Expt, Ctr Med Innovat, Changsha 410021, Hunan, Peoples R China.
通讯机构：
[Sheng Xie] P;[Yu-Hong Wang] S;Prevention of Diseases with Traditional Chinese Medicine Center, The First Affiliated Hospital of Guangxi University of Chinese Medicine, Guangxi, Nanning, 530022, China<&wdkj&>State Key Laboratory of Chinese Medicine Powder and Medicine Innovation in Hunan (incubation), Hunan University of Chinese Medicine, Hunan, Changsha, 410208, China
摘要：
There has been ample research showing that insomnia is a potential trigger of depression as well as a symptom of depression. These two factors contribute to behavioural problems and are closely related to the plasticity of hippocampal synapses. Although depression and insomnia impair hippocampal synaptic plasticity, the mechanism by which this happens remains a mystery. This study aimed to investigate the pathogenesis of insomnia comorbidity in depression and the regulatory effect of venlafaxine combined with melatonin on hippocampal synaptic plasticity in chronic unpredictable mild stress (CUMS) with sleep deprivation (SD) rats. Thus, rats were subjected to 14 days of chronic mild unpredictable stress, gradually acclimated to sleep deprivation on days 12-14. Followed by 21 consecutive days of sleep deprivation, 18h per day, with daily gavage of venlafaxine (13.5mg/kg)+melatonin (72mg/kg) on days 15-36. Venlafaxine+melatonin treatment improves depression-like behaviour, pentobarbital sodium experimental sleep latency, and sleep duration in CUMS+SD rats. In addition to improving depressive-like behaviors, sleep deprivation also upregulates the expression of caspase-specific cysteine protein 3 (Caspase 3) in the pineal glial cells of chronic mild rats, as well as in hippocampal microglia. Expression of ionic calcium-binding adaptor 1 (iba-1), downregulates the secretion of several synaptic plasticity-related proteins, notably cAMP response element binding protein (CREB), glial cell line-derived neurotrophic factor (GDNF), and the synaptic scaffolding protein Spinophiline (Spinophiline). Hematoxylin-eosin staining showed that the structure of the pineal gland and hippocampus was damaged, and Golgi staining showed that the dendrites and spines in the DG area of the hippocampus were destroyed, vaguely aggregated or even disappeared, and the connection network could not be established. Western blot analysis further revealed a positive correlation between low melatonin levels and reduced Spinophiline protein. Interestingly, venlafaxine+melatonin reversed these events by promoting hippocampal synaptic plasticity by regulating melatonin secretion from the pineal gland. Therefore, it exerted an antidepressant effect in sleep deprivation combined with CUMS model rats. Overall, the results of this study suggest that the pathophysiology of depressive insomnia comorbidity is mediated by impaired pineal melatonin secretion and impaired hippocampal synaptic plasticity. In addition, these responses are associated with melatonin secretion from the pineal gland.
作者机构：
[Li, Hongfang; Gong, Yongzhen; Shi, Yaning; Liao, Duanfang; Gu, Jia; Zhang, Chanjuan; Qin, Li] Hunan Univ Chinese Med, Sch Pharm, Lab Stem Cell Regulat Chinese Med & Its Applicat, Changsha 410208, Hunan, Peoples R China.;[Wang, Wei; Zhang, Chanjuan] Hunan Univ Chinese Med, Innovat Mat Med Res Inst, TCM & Ethnomed Innovat & Dev Int Lab, Changsha 410208, Hunan, Peoples R China.;[Zhu, Neng] Hunan Univ Chinese Med, Hosp 1, Changsha 410021, Hunan, Peoples R China.;[Dai, Aiguo; Qin, Li] Hunan Univ Chinese Med, Inst Key Lab Vasc Biol & Translat Med Hunan Prov, Changsha 410208, Hunan, Peoples R China.;[Qin, Li] Hunan Univ Chinese Med, Hunan Prov Engn Res Ctr Bioact Subst Discovery Tr, Changsha 410208, Hunan, Peoples R China.
通讯机构：
[Wei Wang] T;[Aiguo Dai] I;[Li Qin] L;TCM and Ethnomedicine Innovation & Development International Laboratory, Innovative Materia Medica Research Institute, Hunan University of Chinese Medicine, Changsha, Hunan, 410208, PR China<&wdkj&>Institutional Key Laboratory of Vascular Biology and Translational Medicine in Hunan Province, Hunan University of Chinese Medicine, Changsha, Hunan, 410208, PR China<&wdkj&>Laboratory of Stem Cell Regulation with Chinese Medicine and Its Application, School of Pharmacy, Hunan University of Chinese Medicine, Changsha, Hunan, 410208, PR China<&wdkj&>Institutional Key Laboratory of Vascular Biology and Translational Medicine in Hunan Province, Hunan University of Chinese Medicine, Changsha, Hunan, 410208, PR China<&wdkj&>Hunan Province Engineering Research Center of Bioactive Substance Discovery of Traditional Chinese Medicine, Hunan University of Chinese Medicine, Changsha, Hunan, 410208, PR China
摘要：
ETHNOPHARMACOLOGICAL RELEVANCE: With the spread of Coronavirus Disease (2019) (COVID-19), combination with traditional Chinese medicine (TCM) has been widely used as a prevention and therapy strategy in China. Xin guan No.1 (XG-1) prescription is a preventive formula recommended by the Hunan Provincial Administration of TCM to prevent the pandemic of COVID-19. AIM OF THE STUDY: To explore the potential preventive mechanisms of XG-1 against COVID-19 in the combination of network pharmacology approach, single-cell RNA expression profiling analysis, molecular docking and retrospective study. MATERIALS AND METHODS: Encyclopedia of Traditional Chinese Medicine (ETCM) database was used to determine the meridian tropism, active components and target genes of XG-1. Gene ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) functional enrichment analysis were conducted by R Cluster Profiler package (3.14.3). Single cell RNA sequencing (scRNA-seq) data of human lung (GSE122960) was downloaded from Gene Expression Omnibus (GEO) database and analyzed by R Seurat package (3.1.2). Cytoscape (3.7.2) was used to construct the interaction network. The main ingredients in XG-1 were identified by HPLC- Q-TOF- MS and used for molecular docking with COVID-19 3CL hydrolytic enzyme and angiotensin converting enzyme II (ACE2). A retrospective study of 47 close contact participants from Dongtang Community of Hunan Province was conducted to evaluated the preventive effect of XG-1. RESULTS: According to the network pharmacology analysis, XG-1 formula was closely related to lung-, spleen- and stomach-meridians and include a total of 206 active components and 853 target genes. GO and KEGG pathway enrichment revealed that XG-1 mainly regulated cellular amino acid metabolism process and neuroactive ligand-receptors interaction. The scRNA-seq profiling showed that angiotensin converting enzyme 2 (ACE2) was principally expressed in alveolar type 2 epithelial cells (AT2). 153 genes were up-regulated in AT2 cells expressing ACE2 and 12 genes were obtained by intersecting with XG-1 target genes, of which 3 were related to immunity. Five main chemical ingredients were detected in XG-1 sample by HPLC-Q-TOF-MS. The molecular docking showed that Rutin, Liquiritin and Astragaloside Ⅳ had a good affinity with COVID-19 3CL hydrolytic enzyme and ACE2. Compared with participants who didn't take XG-1, preventive treatment with XG-1gradules resulted in a significant lower rate of testing positive for SARS-CoV-2 nucleic acid (P<0.0001). CONCLUSION: The present study showed that XG-1 exerts a preventive effect in close contacts against COVID-19. The underlying mechanism may be related to modulate immunity response through multiple components, pathways, and several target genes co-expressed with ACE2. These findings provide preliminary evidences and methodological reference for the potential preventive mechanism of XG-1 against COVID-19.
期刊：
Journal of Ethnopharmacology,2021年267:113496- ISSN：0378-8741
通讯作者：
Zeng, Rong;Wang, Wei
作者机构：
Hunan Univ Chinese Med, TCM & Ethnomed Innovat & Dev Int Lab, Sch Pharm, Changsha 410208, Hunan, Peoples R China.;Hunan Univ Chinese Med, Innovat Mat Med Res Inst, Sch Pharm, Changsha 410208, Hunan, Peoples R China.;[Zeng, Rong; Wang, Wei] Hunan Univ Chinese Med, Sch Pharm, Changsha 410208, Peoples R China.
通讯机构：
[Zeng, R; Wang, W] H;Hunan Univ Chinese Med, Sch Pharm, Changsha 410208, Peoples R China.
摘要：
ETHNOPHARMACOLOGICAL RELEVANCE: Kadsura heteroclita stem (KHS) is a well-known hepatoprotective Tujia ethnomedicine (folk named Xuetong), has long been used for the prevention and treatment of hepatitis and liver diseases. AIM OF THE STUDY: To explore the protective effects of KHS against carbon tetrachloride (CCl(4))-induced liver injury and the underlying mechanism, particularly antioxidative, anti-inflammatory, and anti-apoptotic potentials. MATERIALS AND METHODS: The acute toxicity of KHS was measured by the method of maximum tolerated dose (MTD). Liver injury in mice was induced by intraperitoneal injection of 25% carbon tetrachloride (olive oil solubilization) 2 times every week. After modeling, mice in KHS groups were treated with KHS at 100, 200, 400mg/kg/d, mice in positive control group were treated with bifendate (30mg/kg/d), and mice in normal and model groups were given ultrapure water. After 4 weeks of treatment, blood of mice was taken from the orbital venous plexus before mice euthanized, the liver, spleen, and thymus of mice were weighed by dissecting the abdominal cavity after mice euthanized. Moreover, the liver of mice was selected for histological examination. The alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities in mice serum were measured using the automatic biochemical analyzer. The levels of superoxide dismutase (SOD), myeloperoxidase (MPO), malondialdehyde (MDA), glutathione peroxidase (GPX-2), tumor necrosis factor (TNF-α), interleukin-6 (IL-6), interleukin-10 (IL-10), Bcl-2-associated X (Bax), B-cell lymphoma-2 (Bcl-2), Caspase-3, and Caspase-8 in mice liver were measured by Elisa kits. Furthermore, the protein expression of Bcl-2 and Bax in mice liver tissue was detected by Western blot. RESULTS: The MTD of KHS was determined to be 26g/kg in both sexes of mice. Treatment with KHS dose-dependently protected the liver and other main organs against CCl(4)-induced liver injury in mice. The ALT and AST levels in mice liver were significantly reduced after treatment with KHS at the dose of 100, 200, and 400mg/kg. In addition, the liver histopathological analyses revealed that KHS markedly alleviated inflammatory cell infiltration, hepatic fibrosis, hepatocyte ballooning, necrosis and severe apoptosis of hepatocytes induced by CCl(4). Further assay indicated that KHS significantly suppressed the production of MDA and MPO, while markedly increased the level of SOD and GPx-2. The TNF-α and IL-6 level in mice liver tissue were decreased by KHS, whereas the IL-10 level was increased. KHS also inhibited hepatocyte apoptosis by significantly reducing the expression of Bax, Caspase-3, Caspase-8, as well as increasing the expression of Bcl-2. Besides, the Western blot results strongly demonstrated that KHS inhibited hepatocyte apoptosis, as evidenced by reducing the expression of Bax protein and increasing the expression of Bcl-2 protein in liver injury tissues. CONCLUSIONS: This research firstly clarified that KHS has a significant protective effect against CCl(4)-induced liver injury, which might be closely related to alleviating oxidative stress, reducing inflammatory response, and inhibiting hepatocyte apoptosis.
期刊：
Current Microbiology,2021年78(11):3980-3988 ISSN：0343-8651
通讯作者：
Ok-Hwa Kang<&wdkj&>Dong-Yeul Kwon
作者机构：
[Li, Qian-Qian; Kang, Ok-Hwa; Kwon, Dong-Yeul] Wonkwang Univ, Coll Pharm, Dept Oriental Pharm, Iksan 54538, Jeonbuk, South Korea.;[Li, Qian-Qian; Kang, Ok-Hwa; Kwon, Dong-Yeul] Wonkwang Univ, Wonkwang Oriental Med Res Inst, Iksan 54538, Jeonbuk, South Korea.;[Liu, Xiang-Qian; Luo, Jiao] Hunan Univ Chinese Med, Sch Pharm, Changsha 410208, Hunan, Peoples R China.
通讯机构：
[Ok-Hwa Kang; Dong-Yeul Kwon] D;Department of Oriental Pharmacy, College of Pharmacy and Wonkwang Oriental Medicines Research Institute, Wonkwang University, Iksan, Republic of Korea<&wdkj&>Department of Oriental Pharmacy, College of Pharmacy and Wonkwang Oriental Medicines Research Institute, Wonkwang University, Iksan, Republic of Korea
摘要：
Methicillin-resistant Staphylococcus (S.) aureus (MRSA) is a representative pathogen that produces numerous virulence factors involving manifold cytotoxins and exotoxins. The present study was designed to investigate the influence of Eleutheroside K (ETSK), a single compound isolated from the leaves of Acanthopanax (A.) henryi (Oliv.) Harms, on the exotoxins secreted by MRSA. The transcription and translation of the exotoxins (α-hemolysin and staphylococcal enterotoxins) related to virulence in S. aureus were determined via quantitative RT-PCR and western blot analysis. The effect of ETSK on the production of tumor necrosis factor (TNF)-α was evaluated using enzyme-linked immunosorbent assay. As a result, ETSK at sub-MIC concentrations could reduce the protein expression of α-hemolysin and enterotoxin, and the expression of genes that regulate virulence factors was also inhibited. In addition, the TNF-inducing activity of S. aureus was attenuated by ETSK in a dose-dependent manner. These results revealed that ETSK not only reduced the protein and gene expression levels of related exotoxins but also suppressed the ability of S. aureus to induce macrophages to release cytokines. This study indicated that the inhibition of MRSA infection by ETSK may be achieved by reducing the virulence of S. aureus and highlighted the potential of ETSK as an innovative strategy for the prevention and treatment of MRSA infections.
作者机构：
[Tao, Xueqing; Liu, Bin; Tong, Chunyi; Hu, Yalei] Hunan Univ, Coll Biol, Hunan Prov Key Lab Plant Funct Genom & Dev Regula, Changsha 410082, Hunan, Peoples R China.;[Wang, Wei; Xie, Qian] Hunan Univ Chinese Med, Sch Pharm, Innovat Mat Med Res Inst, TCM & Ethnomed Innovat & Dev Int Lab, Changsha 410208, Peoples R China.;[Chang, Li] Chinese Acad Agr Sci, Inst Bast Fiber Crops, Changsha 410008, Peoples R China.
摘要：
Ribonuclease H is essential for the research and development of complex pathema. The high rigidity and versatility of DNA tetrahedrons means they are often used in biosensing systems. Inspired by "radar" technology, we proposed a radar-like monitor to detect RNase H activity in vitro and in situ by integrating DNA tetrahedral elements. The structure of a radar-like monitor was self-assembled from five customized single nucleic acid strands. Four DNA strands were assembled as DNA tetrahedrons with a long strand labeled by Dabcyl (quencher) at one of the apexes, while the fifth strand (DNA-RNA heterozygous strand) was labeled with a FAM (Fluorophore) hybrid with a long strand. The fluorescence was quenched because the fluorophore and the quencher were very close. In the presence of RNase H, the RNA chain was hydrolyzed and the fluorophore released, resulting in fluorescence recovery. The radar-like monitor was used to detect the RNase H activity in vitro with a detection limit of 0.01 U mL(-1). Based on the RNase H activity detection and the inhibitory effect of natural-compounds-targeting RNase H, three inhibitors were obtained among 35 compounds extracted from Panax japonicus. Therefore, the radar-like monitor was successfully used to detect RNase H activity in situ due to the long-term anti-DNase I effect of the RNA/DNA hybrid structure and DNA tetrahedrons structure. Overall, this radar-like monitor can effectively avoid false-positive signals and significantly improve the accuracy, precision, and reliability of detection. It is expected that the development of such an intelligent nano-platform will open the door to cancer diagnosis and treatment in clinical systems.
