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Natural Product Communications
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  This is an Open Access Journal Open Access journal
ISSN (Print) 1934-578X - ISSN (Online) 1555-9475
Published by Sage Publications Homepage  [1176 journals]
  • Raspberry Ketone Protects Kidney Damage in Diabetic Nephropathy by
           Improving Kidney Mitochondrial Dysfunction

    • Authors: Jiawang Ma, Xin Wang, Meng Xu, Ying Chang, Mingxin Dong, Chengbiao Sun, Yan Wang, Jianxu Zhang, Na Xu, Wensen Liu
      Abstract: Natural Product Communications, Volume 18, Issue 1, January 2023.
      Mitochondrial dysfunction and oxidative stress play essential roles in the pathogenesis of diabetic nephropathy (DN). The respiratory oxygen consumption and oxidative stress status of kidney mitochondria are closely associated with the development of DN. In this study, raspberry ketone (RK), the predominant bioactive component extracted from raspberry, was applied to treat the established DN mice model. This study investigated whether RK protects the kidneys of high-fat and high-sugar/streptozotocin (STZ)-induced diabetic rats by inhibiting oxidative stress and ameliorating mitochondrial dysfunction. Besides, the DN mice models were established by injecting high-fat and high-sugar/STZ (130 mg/kg, intraperitoneal injection). The animals were randomly divided into the control group (normal saline, ig), DN group (normal saline, ig), DN + RK group (200 mg/kg RK + normal saline, ig), DN + RK group (400 mg/kg RK + normal saline, ig), and DN + Metformin (Met) (200 mg/kg Met + normal saline, ig). Regular monitoring of fasting blood glucose (FBG) levels was observed in mice. After 10 weeks of drug treatment, the kidneys of mice in each group were analyzed using ultrasound, and the mice were euthanized humanely. Kidney weight (KW)/body weight (BW) and kidney injury, mitochondrial function, and oxidative stress indicators were determined. The histopathological changes in renal tissue were observed after hematoxylin and eosin (H&E) staining. The results recommended that RK has a renoprotective function on DN mice by improving mitochondrial dysfunction and inhibiting oxidative stress.
      Citation: Natural Product Communications
      PubDate: 2023-01-31T11:40:37Z
      DOI: 10.1177/1934578X221148619
      Issue No: Vol. 18, No. 1 (2023)
  • Distinguish the Characteristic Mechanism of 3 Drug Pairs of Corydalis
           Rhizome in Ameliorating Angina Pectoris: Network Pharmacology and

    • Authors: Zhenwei Zhai, Zhishan Zhu, Fanjing Kong, Danni Xie, Jie Cai, Jingyi Dai, Yanmei Zhong, Yanxiong Gan, Shichao Zheng, Ying Xu, Tao Sun
      Abstract: Natural Product Communications, Volume 18, Issue 1, January 2023.
      Objective: Angina pectoris (AP), affecting over 523 million people, can be alleviated by corydalis rhizome (CR), usually combined with chuanxiong rhizome (CXR), angelica dahuricae radix (ADR), or astragali radix (AR) to enhance the effect. This study aims to distinguish the different mechanisms among 3 drug pairs to treat AP. Methods: The drug pair-disease intersection targets, compound targets, protein–protein interaction (PPI), and herb-compound-target-pathway network were obtained by Cytoscape, STRING, Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses (http://www.kegg.jp/ or http://www.genome.jp/kegg/). Importantly, with principal component analysis (PCA), the key point of KEGG and GO were explored and supported, while by meta-analysis, the different mechanisms of the drug pairs on AP were discovered. Results: JUN, SRC, PIK3CA, and MAPK1 as PPI core network of CR-AP, (CR-CXR)-AP, (CR-ADR)-AP, and (CR-AR)-AP. (highest confidence> 0.9). 10, 45, 35, and 21 key compounds, and 68, 123, 117, and 97 core targets were obtained from CR-AP, (CR-CXR)-AP, (CR-ADR)-AP, and (CR-AR)-AP based on more than 2-fold median value for degree and betweenness centrality, more than the median of closeness centrality. The core pathways of (CR-CXR)-AP and (CR-AR)-AP cover “fluid shear stress and atherosclerosis” and the “pathways in cancer”, while (CR-ADR)-AP was found as the “pathways in cancer” by PCA and KEGG (P < .01). The core biological processes of (BP) (CR-CXR)-AP, (CR-ADR)-AP, and (CR-AR)-AP were all enriched in the “circulatory system process” by PCA and GO (P < .01). Moreover, meta-analysis indicated the significant differences (P < .05) of the 3 drug pairs. Conclusion: CR-CXR, CR-ADR, or CR-AR outperformed CR-AP in AP mitigation. Furthermore, meta-analysis revealed, CR-CXR was superior to alleviating AP by affecting “circulatory system process” and “fluid shear stress and atherosclerosis”, particularly the targets PTGS1, PTGS2, ADRB2, ADRA2C, and NOS, when compared with the drug pair of CR-ADR and the CR-AR.
      Citation: Natural Product Communications
      PubDate: 2023-01-27T11:24:08Z
      DOI: 10.1177/1934578X231152309
      Issue No: Vol. 18, No. 1 (2023)
  • Farrerol Inhibits Vascular Smooth Muscle Cell Proliferation and Protects
           Them From Oxidative Injury via Bidirectional Modulation of the
           PI3K/Akt/mTOR Signaling Pathway

    • Authors: Jiacheng Fang, Huanhuan Jiang, Enli Liu, Rui Ge, Qingshan Li
      Abstract: Natural Product Communications, Volume 18, Issue 1, January 2023.
      The inhibition of intimal hyperplasia (IH) is an effective strategy to improve the long-term outcome of endovascular therapy and prevent restenosis. Farrerol, a naturally occurring dihydroflavone with a variety of bioactivities, exerts inhibitory effects against balloon injury-induced IH in rats. In the present study, bioinformatics analysis, in combination with in vitro experimental validation, was performed to elucidate the underlying inhibitory mechanisms. The protein–protein interaction (PPI) network was assessed to identify farrerol-related protein targets in the context of IH, based on which biological functions and pathway enrichment were analyzed. The proliferation and cell cycle distribution of vascular smooth muscle cells (VSMCs) were investigated using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide and 5-ethynyl-2-deoxyuridine incorporation assays and flow cytometric analysis, respectively. The level of pro-inflammatory cytokines in the cell culture medium was estimated using an enzyme-linked immunosorbent assay (ELISA). Protein expression in A7r5 cells was determined by western blotting. Forty-six IH-related targets of farrerol were identified, and the PI3K/Akt/mTOR pathway was highly enriched among the 43 predicted pathways (P 
      Citation: Natural Product Communications
      PubDate: 2023-01-27T10:33:31Z
      DOI: 10.1177/1934578X221117414
      Issue No: Vol. 18, No. 1 (2023)
  • New Marine Diterpenoid from the Okinawan Soft Coral, Lobophytum sp.

    • Authors: Kosuke Sato, Shinnosuke Ishigami, Masaki Koike, Haruto Takegahara, Ayumi Yamamoto, Kensuke Kaneko, Kazuki Tani, Takahiro Ishii, Takashi Kamada
      Abstract: Natural Product Communications, Volume 18, Issue 1, January 2023.
      A new lobane-type diterpenoid, loba-8,10,13(15)-triene-14,17,18-triol 17-acetate (1), and 5 known compounds, lobatriene (2), (17R)-loba-8,10,13(15)-triene-17,18-diol (3), loba-8,10,13(15)-triene-14,17,18-triol 14,17-diacetate (4), loba-8,10,13(15)-triene-14,17,18-triol 14-acetate (5), and lobatrienetriol (6), were isolated from a population of Okinawan soft coral Lobophytum sp. The structures of these compounds were elucidated by spectroscopy, including nuclear magnetic resonance and high-resolution mass spectrometry. The cytotoxicity and genotoxicity of these compounds were tested using human lymphoblastoid TK6 cells.
      Citation: Natural Product Communications
      PubDate: 2023-01-23T08:58:59Z
      DOI: 10.1177/1934578X221075978
      Issue No: Vol. 18, No. 1 (2023)
  • Correction to “Alizarin as a New Activator of the Aryl Hydrocarbon
           Receptor Signaling Pathway”

    • Abstract: Natural Product Communications, Volume 18, Issue 1, January 2023.

      Citation: Natural Product Communications
      PubDate: 2023-01-20T06:14:48Z
      DOI: 10.1177/1934578X231152543
      Issue No: Vol. 18, No. 1 (2023)
  • Antifungal Efficacy of Gallic Acid Extracted From Pomegranate Peel Against
           Trichophyton rubrum: In Vitro Case Study

    • Authors: GaoFu Fan, ZhenGuo Xu, XiuShu Liu, Wei Yin, LiHua Sun, Dan Wu, MengQiang Wei, Wei Wang, YuHua Cai
      Abstract: Natural Product Communications, Volume 18, Issue 1, January 2023.
      Objectives: Trichophyton rubrum is one of the main pathogens causing superficial dermatophytosis, producing symptoms such as skin itching and pain, which seriously affects the quality of life of patients. Pomegranate peel extract is rich in gallic acid (GA), which has been reported to have biological effects including antifungal activity. However, the morphological and molecular mechanisms underlying the effects of GA on T rubrum are not well understood. The objectives of this study were to determine the antifungal efficacy of GA extracted from pomegranate peel against T rubrum in vitro, and to explore the underlying molecular mechanisms. Methods: The effects of 0-, 0.5-, and 1 mg/mL GA in pomegranate peel extract on T rubrum was investigated by detecting cell viability using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays. Transmission electron microscopy (TEM) was used to analyze the ultrastructure of T. rubrum, and transcriptome sequencing was used to analyze the enrichment pathway of differentially expressed genes. The identification of biosynthesis-related and key genes in the pathways involved using real-time quantitative reverse transcription polymerase chain reaction (RT-qPCR) technology. Terbinafine hydrochloride (TERB) as a positive control group. Results: Pomegranate peel extract has a GA content of 1.0 mg/mL. Compared with untreated group, following treatment with 1.0 mg/mL GA content is rich in pomegranate peel extract, and the microstructure of T rubrum is destroyed. TEM results show that the number of lipid droplets in T rubrum was significantly increased, mitochondrial vacuoles degenerated, the serosa were damaged, and the boundary of thallus was unclear. In addition, 1 mg/mL GA can significantly inhibit T rubrum proliferation, and its inhibition ability is better than TERB. Transcriptomics results show that GA can change the gene expression profile of T rubrum, specifically: The biosynthesis was blocked, drug resistance was weakened, the transport of ATP-binding cassette (ABC) drugs transporter was increased, and the mitogen-activated protein kinase (MAPK) pathway was significantly inhibited. Conclusions: Pomegranate peel extract is rich in GA, which strongly inhibited the growth of T rubrum and reduced its drug resistance. This extract is a promising natural antifungal agent for clinical use.
      Citation: Natural Product Communications
      PubDate: 2023-01-17T01:15:56Z
      DOI: 10.1177/1934578X221148607
      Issue No: Vol. 18, No. 1 (2023)
  • Two New Nitrogen-Containing Glycosides From Stixis scandens

    • Authors: Tran Thi Yen, Nguyen Thanh Tam, Nguyen Thanh Thi Kim, Vo Ngoc Binh, Nguyen Thao Kim Nu, Ngo Quoc Anh
      Abstract: Natural Product Communications, Volume 18, Issue 1, January 2023.
      Phytochemical investigation of a methanol extract of Stixis scandens stems and leaves led to the isolation of 3 nitrogen-containing compounds (1-3) and 6 phenolics (4-9), which included 2 new glycosides, one a phenolic amide glucoside, scandemide (1), and the other an indole alkaloid glycoside, stixilenin (2). Their structures were elucidated by spectroscopic (1D- and 2D-NMR) and spectrometric (HR-ESI-MS) analyses, and acid hydrolysis. The isolated compounds were evaluated for their inhibitory effects on nitric oxide production in lipopolysaccharide-induced RAW264.7 cells.
      Citation: Natural Product Communications
      PubDate: 2023-01-13T06:43:55Z
      DOI: 10.1177/1934578X221148621
      Issue No: Vol. 18, No. 1 (2023)
  • Piperlongosides A–C, Three New Phenolic Constituents From Piper
           longum L.

    • Authors: Le Thi Huyen, Nguyen Thi Thu Hau, Phan Van Kiem
      Abstract: Natural Product Communications, Volume 18, Issue 1, January 2023.
      Phytochemical study on the methanolic extract of the aerial parts of this plant led to the isolation of 7 phenolic compounds (1-7), including 3 new ones (1-3). Their chemical structures were determined to be (7,8-threo)-1-O-β-D-[6′-O-syringoylglucopyranosyl]-2-methoxy-7,8,9-trihydroxyphenylpropane (1), (7,8-threo)-8-O-(2′′-methoxyacetophenone-1′′-yl)-1-O-β-D-glucopyranosyl-2-methoxy-7,9-dihydroxyphenylpropane (2), 1-O-β-D-glucopyranosyl-2-O-(2′′-methoxy-4′′-acetylphenyl)-3-hydroxypropane (3), (−)-isolariciresinol 4-O-β-D-glucopyranoside (4), (−)-isolarisiresinol 9′-O-β-D-glucopyranoside (5), (+ )-lyoniresinol 9′-O-β-D-glucopyranoside (6), (+ )-isolarisiresinol 9′-O-β-D-glucopyranoside (7) by the spectroscopic data and in comparison with those reported in the literature. Compounds 3 to 7 significantly inhibited NO production in LPS-activated RAW264.7 cells with IC50 values ranging from 32.09 ± 3.34 to 38.16 ± 1.35 µM, similar to those of the positive control, NG-monomethyl-L-arginine acetate (IC50 32.51 ± 3.70 µM).
      Citation: Natural Product Communications
      PubDate: 2023-01-12T07:43:41Z
      DOI: 10.1177/1934578X221150367
      Issue No: Vol. 18, No. 1 (2023)
  • Indirubin Inhibits TRAIL-Induced Activation of Death Receptor 5 in Jurkat

    • Authors: Malaney C. Young, Nagamani Vunnam, Robyn T. Rebbeck, Samantha L. Yuen, David D. Thomas, Jonathan N. Sachs
      Abstract: Natural Product Communications, Volume 18, Issue 1, January 2023.
      Death receptor 5 (DR5) is an apoptosis-inducing membrane receptor that mediates cell death in several life-threatening conditions. There is a crucial need for the discovery of DR5 antagonists for the therapeutic intervention of conditions in which the overactivation of DR5 underlies the pathophysiology. DR5 activation mediates cell death in non-alcoholic fatty liver disease (NAFLD) and neurodegenerative processes including amyloid-beta (Aβ) accumulation, spinal cord injury (SCI), and brain ischemia. In the current work, we used fluorescence resonance energy transfer (FRET) to monitor the conformational dynamics of DR5 that mediate death signaling. We used a time-resolved FRET screening platform to screen the Selleck library of 2863 U.S. Food and Drug Administration (FDA)-approved compounds. The high-throughput screen (HTS) identified 13 compounds that modulated the FRET between DR5 monomers beyond 5 median absolute deviations (MADs) from the DMSO controls. Of these 13 compounds, indirubin was identified to specifically inhibit tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced caspase-8 activity without modulating DR5 surface expression or TRAIL binding. Indirubin inhibited Fas-associated death domain (FADD) oligomerization and increased cellular FLICE-inhibitory protein (c-FLIP) expression; both are molecular mechanisms involved in inhibiting the DR5 signaling cascade. This study has elucidated previously unknown properties of indirubin that make it a promising candidate for therapeutic investigation of diseases in which overactivation of DR5 underlies pathology.
      Citation: Natural Product Communications
      PubDate: 2023-01-12T07:42:21Z
      DOI: 10.1177/1934578X221144580
      Issue No: Vol. 18, No. 1 (2023)
  • Antimycic Acid and its Acetyl Derivative from Deep-sea-derived Alcanivorax
           sp. SHA4 with Neuroprotective Properties

    • Authors: Shuang Chen, Da-shan Zhang, Jin-hui Wang
      Abstract: Natural Product Communications, Volume 18, Issue 1, January 2023.
      Chemical investigation of secondary metabolites of the deep-sea-derived Alcanivorax sp. SHA4 identified a new compound 1 which was antimycic acid (2)'s acetyl derivative, and 11 known compounds (2-12). Their structures were elucidated by extensive nuclear magnetic resonance and mass spectrometry spectroscopic analyses, and the absolute configuration of compound 1 was determined by Marfey's method. Bioactivity assays indicated that compounds 1 and 2 exhibited significant neuroprotective properties against glutamate-induced PC12 cell death in 0.02-0.31 μM.
      Citation: Natural Product Communications
      PubDate: 2023-01-12T07:41:22Z
      DOI: 10.1177/1934578X221110661
      Issue No: Vol. 18, No. 1 (2023)
  • Vanillic Acid Alleviates Right Ventricular Function in Rats With
           MCT-Induced Pulmonary Arterial Hypertension

    • Authors: Ju Chen, Meiduo Huayu, Shanshan Su, Shan Wang, Zhanting Yang, Xingmei Nan, Dianxiang Lu, Zhanqiang Li
      Abstract: Natural Product Communications, Volume 18, Issue 1, January 2023.
      This study examined the molecular processes behind the effects of vanillic acid (VA) on right ventricular (RV) hypertrophy and function in rats with monocrotaline (MCT)-induced pulmonary arterial hypertension (PAH). There were 40 male Sprague‒Dawley (SD) rats that were separated into 4 groups: Control, PAH, MCT + VA (50 mg/kg/d), and MCT + VA (100 mg/kg/d). Male SD rats were injected with MCT once under the skin to create the PAH model (40 mg/kg). RV morphological properties were evaluated using Masson and hematoxylin and eosin (H&E) staining. Echocardiography was used to evaluate RV functioning and right ventricle–pulmonary artery (RV-PA) coupling. In addition, Rho-associated protein kinase (ROCK) pathway-related factors were evaluated using Western blotting. Enzyme-linked immunosorbent assay (ELISA) was used to detect inflammatory markers as well as atrial natriuretic peptide (ANP) and brain-type natriuretic peptide (BNP) in the blood of PAH rats. As a result, VA effectively reduced the development of RV cardiomyocyte hypertrophy and fibrosis in PAH rats; levels of ANP, BNP, and inflammatory markers in the blood of PAH rats were also significantly decreased by VA intervention. Additionally, VA enhanced RV functioning and RV-PA coupling in PAH rats. In response to VA, the expression of proteins related to the ROCK pathway (ROCK1, ROCK2, NFATc3, P-STAT3, and Bax) was downregulated, whereas Bcl-2 expression was elevated. This study found that VA could attenuate RV remodeling and improve RV-PA coupling in PAH rats. RV remodeling and dysfunction may be linked to the dysregulation of the ROCK pathway, and the protective action of VA on RV function may be due to a block in the ROCK signaling pathway or its downstream signaling molecules.
      Citation: Natural Product Communications
      PubDate: 2023-01-09T06:54:08Z
      DOI: 10.1177/1934578X221148896
      Issue No: Vol. 18, No. 1 (2023)
  • Tetrastigma hemsleyanum Ethanolic Extract Inhibited the Growth of Nonsmall
           Cell Lung Cancer Cells by Suppressing Hypoxia-Inducible
           Factor-1α-Dependent Glycolysis and Angiogenesis

    • Authors: Zhiqiang Wu, Bin Xu, Qin He, Zhuyuan Hu, Zhiyi Yu
      Abstract: Natural Product Communications, Volume 18, Issue 1, January 2023.
      Background:The ethanolic extract of Tetrastigma hemsleyanum Diels et Gilg (T hemsleyanum ethanolic extract [Te-EtOH]) showed positive effects against various tumors. However, there are few studies on the effects of Te-EtOH on nonsmall cell lung cancer (NSCLC). We attempted to examine the inhibiting effect of Te-EtOH on NSCLC cells and to elucidate the relevant mechanisms. Methods: A549 and H1299 cells were pretreated with Te-EtOH at different concentrations. Cell viability was analyzed by Cell Counting Kit-8, flow cytometry, and the 3-dimensional spheroid model; RNA-sequencing was also performed. Moreover, enzyme-linked immunosorbent assay and Western blot tests were performed to determine the metabolic capability, the expressions of energy metabolism-related proteins, and the phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT)/hypoxia-inducible factor-1α (HIF-1α) pathway. Additionally, under hypoxic conditions, the ability of Te-EtOH to inhibit HIF-1α expression and the metabolic capability of NSCLC cells was tested. Results: Te-EtOH considerably repressed cell viability in a dose-dependent manner. RNA-sequencing revealed that Te-EtOH's inhibition of NSCLC cells activity was related to metabolism. In addition, Te-EtOH significantly inhibited glycolysis, and adenosine triphosphate and lactate accumulation in NSCLC cells. Furthermore, we found that Te-EtOH could block PI3K/AKT/HIF-1α pathway activation. Moreover, Te-EtOH significantly inhibited hypoxia-induced expression of HIF-1α, vascular endothelial growth factor, and metabolic capability. Conclusions: Our results suggested that Te-EtOH inhibited the growth of NSCLC cells by suppressing HIF-1α-dependent glycolysis and angiogenesis.
      Citation: Natural Product Communications
      PubDate: 2022-12-30T01:50:56Z
      DOI: 10.1177/1934578X221142796
      Issue No: Vol. 18, No. 1 (2022)
  • Study on Anti-Inflammatory Mechanism of Angelica pubescens Based on
           Network Pharmacology and Molecular Docking

    • Authors: Jianwei Ren, Minghui Ren, Zhiting Mo, Ming Lei
      Abstract: Natural Product Communications, Volume 18, Issue 1, January 2023.
      References and data show that AP has a certain effect on alleviating inflammation. Based on the methods of network pharmacology and molecular docking, this paper predicts the potential mechanism of anti-inflammatory effect of the effective components. Methods: Active components and target genes of AP were screened out by SymMap, an associated database of TCM syndromes. First, screen out the active components according to the setting conditions, and its molecular structure file was obtained from the PubChem database. The target genes of anti-inflammatory effect were obtained from GeneCards database with “anti-inflammation effect” as the keyword, and then the common gene targets between AP and anti-inflammatory effect were screened. The PPI network diagram was constructed with Cytoscape 3.80 software to screen the core genes. The GO function and KEGG pathway of the core genes were enriched and analyzed by David database; 3D view of proteins encoded by the core gene from the PDB database, conduct molecular docking between the active components and the core proteins in Auto Dock Vina software, and made a heat map with binding free energy. Results: The main anti-inflammatory components were O-Acetylcolumbianetin, isoindigo, Nodakenetin, Marmesin, Diphencyprone; The core targets are TNF, VEGFA, IL6, TP53, IL1B, ESR1, MMP9, PPARG, Jun, CASP3, PTGS2. AP participated in cytokine-mediated signaling pathway, response to drug, positive regulation of gene expression, and other processes by regulating the combination of extracellular space, cell surface with protein and enzyme, and then exert anti-inflammatory activity. The signal pathways mainly involved IL-17 signaling pathway, hepatitis B, TNF signaling pathway, inflammatory bowel disease, rheumatoid arthritis, etc.; Through molecular docking, it was found that the key targets were MMP9, TNF, PTGS2, ESR1, JUN, and PPARG, while the active components which ha,d a strong effect on these genes were O-Acetylcolumbianetin, isoindigo, Nodakenetin, Marmesin, Diphencyprone. Conclusion: This study used network pharmacology and molecular docking methods to predict the potential active components, target genes, and signal pathways of the anti-inflammatory effect of AP, so as to provide a theoretical reference for the follow-up experimental research and clinical treatment of AP.
      Citation: Natural Product Communications
      PubDate: 2022-12-30T01:03:54Z
      DOI: 10.1177/1934578X221146616
      Issue No: Vol. 18, No. 1 (2022)
  • Phillyrin Inhibits Isoproterenol-Induced Cardiac Hypertrophy Via P38 and
           NF-κB Pathways

    • Authors: Juanjuan Liu, Jiahang Li, Shengqian Yang, Yuanting She, Xiaohui Li, Yi Jia
      Abstract: Natural Product Communications, Volume 18, Issue 1, January 2023.
      Cardiac hypertrophy (CH) is the main compensatory response to chronic heart stress and often progresses to a decompensation state potentially leading to heart failure. Phillyrin (PHI) is a novel compound derived from Forsythia, which has shown anti-inflammatory and anti-virus activities as well as renal protective effects on diabetic nephropathy. Therefore, we investigated the effects of PHI on CH induced by isoproterenol (ISO). Cardiac hypertrophy was induced by ISO in vivo, and the H9C2 cells were treated with ISO. PHI treatment alleviated CH in isoproterenol-induced mice in 7 and 14 days. Echocardiography showed that the PHI improved ISO-induced CH heart function and structure. PHI significantly decreased heart weight/body weight (HW/BW) and heart weight/tibia length (HW/TL) ratios and improved left ventricular (LV) function in ISO-treated mice. Hematoxylin and eosin staining revealed cardiomyocyte areas of the ISO group were significantly increased, and PHI was significantly reduced at 7 and 14 days, PHI-100 groups showed significantly better improvements than PHI-50. Sirius red staining indicated PHI significantly decreased collagen deposition in heart cross-sections induced by ISO, and PHI repressed ISO-induced cTn-I and NT-proBNP expression in mouse serum. In vitro data from H9C2 cells showed that PHI decreased cell areas and total cell protein levels in cells induced by ISO, whereas ANP, BNP, IL-6, and IL-1β expression was significantly inhibited by PHI. Also, PHI simultaneously inhibited P65 and P38 phosphorylation in vivo and in vitro. In conclusion, this study demonstrated the protective effect of PHI on CH in in vivo and in vitro, and this effect was related to the suppression of inflammation through the activation of the P38/NF-κB pathway.
      Citation: Natural Product Communications
      PubDate: 2022-12-30T01:03:25Z
      DOI: 10.1177/1934578X221144581
      Issue No: Vol. 18, No. 1 (2022)
  • Mechanism Underlying the Action of Berberine in the Treatment of Gouty
           Arthritis Based on Network Pharmacology

    • Authors: Shan Fang, Yan Gao, Yuan Fang, Jing Sun, Zhijun Xie
      Abstract: Natural Product Communications, Volume 18, Issue 1, January 2023.
      Introduction: Gouty arthritis (GA) is induced by a purine metabolism disorder and monosodium urate (MSU) crystal-related inflammation. Berberine (BBR), extracted from Coptis chinensis, ameliorates MSU-induced GA. However, the mechanisms of BBR against GA remain to be fully elucidated. This study aimed to identify the key targets and pathways mediating the effects of BBR against GA using network pharmacology. Methods: BBR and GA targets were obtained from several databases, and the network of BBR-GA common targets was visualized using Cytoscape software. Protein–protein interaction (PPI), Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed using the STRING and Database for Annotation, Visualization, and Integrated Discovery databases, respectively. Animal experiments were performed to determine the outcomes of the BBB intervention. The serum levels of IL-1β, IL-8, and IL-6 were detected using enzyme-linked immunosorbent assay. Results: Thirty-three common targets (including NF-κB, RelA, MAPK1, IL-6, and IL-1β) of BBR and GA were identified, and a network of common targets between BBR and GA was constructed. PPI analysis demonstrated that IL-1β, IL-6, TNF, MAPK, and RelA are key targets with high degree values. GO and KEGG pathway analyses revealed the involvement of inflammation-related biological processes and signaling pathways, such as the NF-κB, MAPK, and TNF signaling pathways. Animal experiments demonstrated that the uric acid, IL-1β, IL-6, and IL-8 serum levels were significantly lower in the BBR group compared with those in hyperuricemic rats. Conclusions: Using systematic network analysis, potential targets mediating the effects of BBR on GA were detected. The pathways and inflammatory factors involved were identified using in vivo experiments, thus providing a reference for further basic research and clinical applications of BBR in the treatment of GA.
      Citation: Natural Product Communications
      PubDate: 2022-12-30T01:02:54Z
      DOI: 10.1177/1934578X221143627
      Issue No: Vol. 18, No. 1 (2022)
  • Phenolic Glycosides Citrulluside H and Citrulluside T Isolated From Young
           Watermelon (Citrullus lanatus) Fruit Have Beneficial Effects Against
           Cutibacterium acnes-Induced Skin Inflammation

    • Authors: Tomohiro Itoh, Mai Muramatsu, Daiki Miyazono, Mamoru Koketsu, Shingo Fujita, Toshiharu Hashizume
      Abstract: Natural Product Communications, Volume 18, Issue 1, January 2023.
      Acne vulgaris, typically caused by Cutibacterium acnes (C. acnes) involves chronic inflammation of the sebaceous follicles and is the most common skin disease, afflicting 85% of adolescents. We previously isolated 2 novel phenolic glycosides, 2-caffeoyl-3-hydroxy-3-methylbutyric 4′-β-D-glucopyranosyloxy-3′-hydroxybenzyl ester (citrulluside H [CH]) and 2-caffeoyl-3-hydroxy-3-methylbutyric 4′-β-d-glucopyranosyloxybenzyl ester (citrulluside T [CT]), from young fruits of watermelon (Citrullus lanatus). Both compounds suppressed UVB-induced photoaging in human fibroblasts by scavenging intracellular reactive oxygen species (ROS) and thus might be useful as natural skin care ingredients. In this study, we examined the inhibitory effects of these phenolic glycosides on C. acnes growth and C.acnes-induced inflammation. Neither phenolic glycoside inhibited the growth of C. acnes. However, they both significantly suppressed toll-like receptor (TLR) 1/2 or TLR2/6/nuclear factor κB (NF-κB) signaling in heat-killed C. acnes (hk-C. acnes)-stimulated RAW264.7 cells. Additionally, both phenolic glycosides decreased the expression of M1 macrophage biomarkers (cluster of differentiation [CD] 80, CD86, and inducible NO synthase [iNOS]), suggesting that they attenuate M1 macrophage activation. These results indicated that both CH and CT are potential therapeutic substances against C. acnes-induced skin inflammation.
      Citation: Natural Product Communications
      PubDate: 2022-12-30T01:01:55Z
      DOI: 10.1177/1934578X221143202
      Issue No: Vol. 18, No. 1 (2022)
  • Biomimetic Total Synthesis of ( + )-Ranuncoside, a Unique Tricyclic
           Spiroacetal Glycoside of Christmas Rose (Helleborus niger L.)

    • Authors: Eckehard Cuny, Jörg Fohrer, Franz-Dietrich Klingler
      Abstract: Natural Product Communications, Volume 18, Issue 1, January 2023.
      Christmas Rose (Helleborus niger L.) is an alpine plant belonging to the Ranunculaceae family. Typical for this popular ornamental plant are white flowers that appear during winter. Root extracts contain numerous medicinally active ingredients and potent cardiac glycosides. Recent findings indicate that Helleborus root extracts possess the potential for cancer treatment and inhibit the proliferation of tumor cells. In 2022, we published a practical extraction method of ( + )-ranucoside 1 from the dried leaves of H niger L. Here, we describe for the first time the total synthesis of 1. Starting from 5-hydroxylevulinic acid methyl ester 8 and acetobromo-α-D-glucose 13, the β-glycoside 14 is formed stereoselectively on the application of Koenigs-Knorr conditions. Subsequent cleavage of the acetyl-protecting groups and saponification of the ester function yields the pyrano dioxane derivative 17. Its lactonization gives ( + )-ranuncoside 1. The presented synthesis is practical and very efficient, consisting of 6 steps from D-glucose and giving 22% overall yield. Furthermore, it is biomimetic due to its concordance with the biosynthesis of ( + )-ranuncoside 1 in H foetidus.
      Citation: Natural Product Communications
      PubDate: 2022-12-28T08:13:16Z
      DOI: 10.1177/1934578X221145919
      Issue No: Vol. 18, No. 1 (2022)
  • Resveratrol Ameliorates Hyperglycemic Cultured Cells and Inhibits the
           Rheb/mTOR Interaction

    • Authors: Tzu-Yung Lin, Ann-Chang Cheng, Hsiang-Chieh Chuang, Jeng-Yuan Yao
      Abstract: Natural Product Communications, Volume 18, Issue 1, January 2023.
      Resveratrol (RSV) is a natural polyphenol with anti-diabetic effects and has been reported to ameliorate diabetes-induced metabolic disorders through regulating activities of the mTOR signaling pathway. To delineate the effects of RSV treatment on the mTOR signaling pathway, hyperglycemic HepG2 cells were used for the following experiments. Cellular glucose uptake assays showed that high-glucose levels in the culture medium decelerate the glucose uptake of cultured cells. Co-immunoprecipitation showed that high-glucose culture promotes the interaction between mTOR and Rheb-GTP, which is the active form of Rheb. RSV treatment of the cells suppressed this interaction and accelerated the glucose uptake. Western blotting revealed that RSV down-regulated members of the mTOR signaling pathway, namely SREBP1, p70, and S6. Additionally, RSV ameliorated the metabolic disorders, including the decreased levels of AMPK, glycogen synthase, and glucose-6-phosphatase, in hyperglycemic HepG2 cells. These results indicate that RSV inhibits the Rheb/mTOR interaction and ameliorates metabolic disorders associated with high-glucose levels.
      Citation: Natural Product Communications
      PubDate: 2022-12-28T08:04:46Z
      DOI: 10.1177/1934578X221147376
      Issue No: Vol. 18, No. 1 (2022)
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