Haifang Wang

Guided by an integrated GNPS molecular networking strategy, the chemical investigation of endophytic fungus Aspergillus sp. FH-1 (isolated from Valeriana officinalis L.) led to the discovery of four butenolides (1-4). Their structures were elucidated through comprehensive spectroscopic data analysis, including HRESIMS, 1D/2D NMR and ECD, revealing two new congeners, asperianas A (1) and B (2), along with the known analogues 3 and 4. Notably, compounds 1 and 3 exhibited significant antifungal activity against Colletotrichum gloeosporioides, with EC50 values of 19.23 ± 1.14 and 43.36 ± 1.12 μg/mL, respectively.

Nerium oleander L. is part of the Apocynaceae family and Nerium genus. Primarily found in subtropical areas, this plant is indigenous to the Mediterranean coast. It is also widely cultivated in China. To date, more than 146 compounds have been obtained from the plant, chiefly including cardiac glycosides, triterpenoids, phytosterols and other chemical constituents, of which cardiac glycosides are the main type of compounds with good pharmacological activity. Pharmacological studies have shown that N. oleander has anti-tumor, anti-diabetic, cardiotonic, hepatoprotective, anti-inflammatory, anti-viral, and other activities. This article provides important insights for future research, development, and use of this plant by summarizing the chemical contents, pharmacological properties, toxicity, and structure-activity connections of N. oleander over the previous 50 years.

Epimedium genus is a traditional Chinese medicine, which has functions of tonifying kidney and yang, strengthening tendons and bones, dispelling wind and emoving dampness. It is mainly used for the treatment of impotence and spermatorrhea, osteoporosis, Parkinson's, Alzheimer's, and cardiovascular diseases. The aim of this review is to provide a systematic summary of the phytochemistry, pharmacology, and clinical applications of the Epimedium Linn. In this paper, the relevant literature on Epimedium Linn. was collected from 1987 to the present day, and more than 274 chemical constituents, including flavonoids, phenylpropanoids, lignans, phenanthrenes, and others, were isolated from this genus. Modern pharmacological studies have shown that Epimedium Linn. has osteoprotective, neuroprotective, cardiovascular protective, and immune enhancing pharmacological effects. In addition, Epimedium Linn. has been commonly used to treat osteoporosis, erectile dysfunction, hypertension and cardiovascular disease. In this paper, the distribution of resources, chemical compositions, pharmacological effects, clinical applications and quality control of Epimedium Linn. are progressed to provide a reference for further research and development of the resources of this genus.

To observe the effects of pre-electroacupuncture at "Taichong"(LR3), "Neiguan"(PC6) and "Waiguan"(TE5) on blood pressure and cardiac function of high-salt-induced hypertension rats, so as to explore the possible mechanism of pre-electroacupuncture in improving hypertension. Twenty-four SD rats were randomly divided into control group, high-salt group and pre-electroacupuncture group, with 8 rats in each group. The hypertension model was established by feeding high-salt diet for 7 weeks. In the pre-electroacupuncture group, rats received electroacupuncture intervention at bilate-ral LR3, PC6 and TE5 (2 Hz/15 Hz, 2 mA) for 30 min, once a day, from the first day of modeling, for a total of 7 weeks. The blood pressure of rats was monitored by caudal artery noninvasive blood pressure measurement technique before and at the 1^st, 3^rd, 5^th and 7^th week of modeling. At the 8^th week of the experiment, left ventricular catheterization was performed and biological signal acquisition system was used to detect left ventricular hemodynamics indexes and analyze left ventricular function, the car-diac mass ratio was measured to evaluate the degree of myocardial hypertrophy. The mRNA expressions of atrial natriuretic peptide(ANP), myosin heavy chain 7(MYH7), α-smooth muscle actin(α-SMA), interleukin(IL)-1β, and IL-6 of myocardial tissues were detected by quantitative real-time PCR. Sirius red staining was used to observe the degree of myocardial fibrosis. Compared with the control group, systolic blood pressure, diastolic blood pressure, mean arterial pressure, left ventricular end-diastolic pressure (LVEDP), cardiac mass ratio，and the mRNA expressions of ANP, MYH7, α-SMA, IL-1β, and IL-6, and sirius red staining area of myocardium were all significantly increased(PPmax) were decreased (PPmax,down-regulated mRNA expressions of ANP, MYH7, α-SMA, IL-1β, IL-6, and smaller area of sirius red staining(PP<0.01). Pre-electroacupuncture tends to lower blood pressure, improve cardiac function and reduce myocardial fibrosis in high-salt-induced hypertension rats, which may be associated with inhibiting inflammatory response.

Objective: To explore the target and mechanism of Astragalus membranaceus, poria, salvia miltiorrhiza and semen leiocarpa in the treatment of heart failure by network pharmacology. Methods: The active components of traditional Chinese medicine and the target of heart failure were screened by multi-platform, and the standard gene was transformed by Uniprot. CytoCasp 3.6.1 was used to draw the network diagram of traditional Chinese medicine - component - target. Go and KEGG analysis were performed by Metascape. Results: A total of 36 predictive target sites of Radix Astragalus, Fuling poria, Salvia miltiorrhiza and Draba nemorosa were screened for treatment of heart failure, mainly involving nerve and factor pathways: ADRB2, ADRA1B and AChE. Cancer pathway: TP53, TNF; Pathways of inflammation: IL1B, PTSG2, PTSG1; Sex hormone pathway: ESR1, AR, PGR; Others: SCN5A, HIF1A, etc. The results of GO and KEGG enrichment suggested that the treatment of heart failure with the top four drugs involved cancer pathway, calcium signaling pathway, HIF-1 signaling pathway, and involved in blood circulation, cell proliferation and other processes. Conclusion: This study combines the pharmacological studies of Chinese medicine and western medicine to reveal the mechanism of multi-target and multi-channel regulation of body balance in Chinese medicine treatment.

Background: We aimed to conduct a retrospective analysis of the epidemiological changes and prevention effects for malaria in Weifang, Shandong Peninsula, China from 1957 to 2017. Methods: The malaria data from a web-based reporting system were analyzed to explore malaria epidemiological characteristics and prevention effects in Weifang. Results: Overall, 1, 704, 890 malaria cases were reported in Weifang from 1957 to 2017, of which two major malaria epidemics occurred in 1961 (827.28/10, 000) and 1971 (366.14/10, 000). Prior to 1997, all malaria patients (1, 704, 829) were infected with Plasmodium vivax (P. vivax). After 2007, the cases of Plasmodium falciparum (P. falciparum) showed an upward trend (76.8%). The reported cases after the 21st century were mainly imported cases, and the last indigenous case was a patient that infected with P. vivax in 2006. Overall, 36 imported cases were reported from 2010 to 2017, of which 88.9% were acquired in Africa. Except for one 32-year-old woman, the rest were male (97.2%), in which laborers and farmers represented the vast majority (66.6%). From 1987 to 2017, there were 1, 224, 474 cases of fever with blood tests, and the average blood test rate was 4.9%. From 1957 to 2017, a total of 1, 704, 890 malaria patients were treated, 96 cases were treated during resting phase from 1987 to 2017. Conclusion: Weifang should continue to strengthen the management of the migrant population, making blood tests for fever patients and patient treatment as important means of malaria control and monitoring.

Astragaloside III (AS‐III) is a triterpenoid saponin contained in Astragali Radix and has potent anti‐inflammatory effects on vascular endothelial cells; however, underlying mechanisms are unclear. In this study, we provided the first piece of evidence that AS‐III induced phosphorylation of TNF‐α converting enzyme (TACE) at Thr735 and enhanced its sheddase activity. As a result, AS‐III reduced surface TNFR1 level and increased content of sTNFR1 in the culture media, leading to the inhibition of NF‐κB signaling pathway and attenuation of downstream cytokine gene expression. Furthermore, AS‐III induced TACE‐dependent epidermal growth factor receptor (EGFR) transactivation and activation of downstream ERK1/2 and AKT pathways. Finally, AS‐III induced activation of p38. Both TACE activation and EGFR transactivation induced by AS‐III were significantly inhibited by p38 inhibitor SB203580. Taken together, we concluded that AS‐III activates TACE‐dependent anti‐inflammatory and growth factor signaling in vascular endothelial cells in a p38‐dependent fashion, which may contribute to its cardiovascular protective effect.

Paeoniflorin (PF), the most abundant active ingredient of traditional Chinese herbal medicine Paeoniae Radix, has been recognized as a potential neuroprotectant due to its remarkable efficacy on mitigating cerebral infarction and preventing the neurodegenerative diseases. However, the precise mechanisms of PF remain incompletely understood. In this study, we first provided evidence for the protective effect of PF on hydrogen peroxide‐induced injury on mouse brain microvascular endothelial bEnd.3 cells, and for transactivation of the epidermal growth factor receptor (EGFR) signal induced by PF, suggesting that EGFR transactivation might be involved in the beneficial role of PF. Next, by detecting the phosphorylation of a disintegrin and metalloprotease 17 (ADAM17) at Thr 735 and performing loss‐of‐function experiments with the ADAM17 inhibitor and ADAM 17‐siRNA, we showed that PF‐induced transactivation of EGFR and downstream ERKs and AKT signaling pathways were dependent on ADAM17. Furthermore, PF‐induced phosphorylation of ADAM17 and the EGFR transactivation were inhibited by the inhibitors of adenosine A1 receptor (A1R) or Src kinase that were applied to cells prior to PF treatment, implying the involvement of A1R, and Src in the activation of ADAM17. Finally, PF reduced the cell surface level of TNF‐receptor 1 (TNFR1) and increased the content of soluble TNFR1 (sTNFR1) in the culture media, indicating that PF might enhance the shedding of sTNFR1. Taken together, we conclude that A1R and Src‐dependent activation of ADAM17 participates in PF‐induced EGFR transactivation and TNFR1 shedding on mouse brain microvascular endothelial cells, which may contributes to the neuroprotective effects of PF.

To study the inhibitory effect of paeoniflorin (PAE) on TNF-α-induced TNF receptor type I (TNFR1)-mediated signaling pathway in mouse renal arterial endothelial cells (AECs) and to explore its underlying molecular mechanisms. Mouse AECs were cultured in vitro and then they were treated by different concentrations PAE or TNF-α for various time periods. Expression levels of intercellular cell adhesion molecule-1 (ICAM-1) were detected in the normal group (cultured by serum-free culture media), the TNF-α group (cultured by 2-h serum-free culture media plus 6-h TNF-α 30 ng/mL), the low dose PAE group (cultured by 2-h PAE 0.8 μmo/L plus 6-h TNF-α 30 ng/mL), the middle dose PAE group (cultured by 2-h PAE 8 μmol/L plus 6-h TNF-α 30 ng/mL), the high dose PAE group (cultured by 2-h PAE 80 μmol/L plus 6-h TNF-α 30 ng/mL) with Western blot analysis. Nuclear translocation of transcription factor NF-κB (NE-κB) was detected in the normal group (cultured by serum-free culture media), the TNF-α group (cultured by 2-h serum-free culture media plus 45-mm TNF-α 30 ng/mL), and the high dose PAE group (cultured by 2-h PAE 80 μmol/L plus 45-min TNF-α 30 ng/mL) by immunofluorescent staining. Expression levels of the phosphorylation of extracellular signal-regulated (protein) kinase (ph-ERK) and p38 (ph- p38) were detected in the normal group (cultured by serum-free culture media) and the high dose PAE group (2-h PAE 80 μmol/L culture) by Western blot. NF-κB inhibitor-α (IκBα) protein expressions were detected in the normal group (cultured by serum-free culture media), the TNF-α group (cultured by 2-h serum-free culture media plus 30-min TNF-α 30 ng/mL), the high dose PAE group (cultured by 2-h PAE 80 μmol/L plus 30-min TNF-α 30 ng/mL), the p38 inhibitor group (SB group, pretreatment with SB238025 25 μmol/L for 30 min, then treated by PAE 80 μmol/L for 2 h, and finally treated by TNF-α 30 ng/mL for 30 min), the ERK inhibitor group (PD group, treated by PD98059 50 μmol/L for 30 min, then treated by PAE 80 μmol/L for 2 h, and finally treated by TNF-α 30 ng/mL for 30 min) by Western blot. Compared with the normal group, ICAM-1 protein expression levels obviously increased (P < 0.01). Compared with the TNFα group, ICAM-1 protein expression levels were obviously inhibited in the high dose PAE group (P < 0.05). Protein expression levels of ph-p38 and ph-ERK were obviously higher in the hIgh dose PAE group (P < 0.05). Compared with the normal group, IκBα protein expression levels obviously decreased in the TNF-α group (P < 0.01). Compared with the TNFα group, TNF-α-induced IκBα degradation could be significantly inhibited in the high dose PAE group (P < 0.01); the inhibition of PAE on IκBα degradation could be significantly inhibited in the SB group (P < 0.05). NF-κB/p65 signal was mainly located in cytoplasm in the normal group. NF-κB/p65 was translocated from cytoplasm to nucleus after stimulated by 45 min TNF-α in the TNF-α group, while it could be significantly inhibited in the high dose PAE group. PAE inhibited TNF-α-induced expression of lCAM-1. Its action might be associated with inhibiting TNFR1/NF-κB signaling pathway. p38 participated and mediated these actions.

Anopheles sinensis is a major vector of malaria and among the dominant species in Shandong province of China. Insecticide resistance is an important threat to vector-borne disease control. However, there are only few reports about insecticide resistance of An. sinensis populations from Shandong province. From 2003 to 2012, six districts in Shandong province were selected as the study areas. Insecticide susceptibility bioassay were tested on F1 progeny of An. sinensis to 4% DDT, 0.05% deltamethrin, 0.15% cyfluthrin, and 5% malathion, using the standard WHO resistance tube assay. The resistance status of An. sinensis showed a significant decrease in the mortality rates in DDT, deltamethrin and cyfluthrin during the past ten years. Whereas obvious increase of mortality to malathion was observed throughout the assay, ranging from 47.37% to 86.62%.