{"title":"Activation of LONP1 by 84-B10 alleviates aristolochic acid nephropathy via re-establishing mitochondrial and peroxisomal homeostasis","authors":"","doi":"10.1016/S1875-5364(24)60608-4","DOIUrl":"10.1016/S1875-5364(24)60608-4","url":null,"abstract":"<div><div>Pharmaceutical formulations derived from Aristolochiaceae herbs, which contain aristolochic acids (AAs), are widely used for medicinal purposes. However, exposure to these plants and isolated AAs is linked to renal toxicity, known as AA nephropathy (AAN). Currently, the mechanisms underlying AAN are not fully understood, leading to unsatisfactory treatment strategies. In this study, we explored the protective role of 84-B10 (5-[[2-(4-methoxyphenoxy)-5-(trifluoromethyl) phenyl] amino]-5-oxo-3-phenylpentanoic acid) against AAN. RNA-seq analysis revealed that the mitochondrion and peroxisome were the most affected cellular components following 84-B10 treatment in AAN mice. Consistently, 84-B10 treatment preserved mitochondrial ultrastructure, restored mitochondrial respiration, enhanced the expression of key transporters (carnitine palmitoyltransferase 2) and enzymes (acyl-Coenzyme A dehydrogenase, medium chain) involved in mitochondrial fatty acid <em>β</em>-oxidation, and reduced mitochondrial ROS generation in both aristolochic acid I (AAI)-challenged mice kidneys and cultured proximal tubular epithelial cells. Additionally, 84-B10 treatment increased the expression of key transporters (ATP binding cassette subfamily D) and rate-limiting enzymes (acyl-CoA oxidase 1) involved in peroxisomal fatty acid <em>β</em>-oxidation and restored peroxisomal redox balance. Knocking down LONP1 expression diminished the protective effects of 84-B10 against AAN, suggesting LONP1-dependent protection. In conclusion, our study provides evidence that AAN is associated with significant disturbances in both mitochondrial and peroxisomal functions. The LONP1 activator 84-B10 demonstrates therapeutic potential against AAN, likely by maintaining homeostasis in both mitochondria and peroxisomes.</div></div>","PeriodicalId":10002,"journal":{"name":"Chinese Journal of Natural Medicines","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142315292","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Antibacterial and cytotoxic metabolites produced by Streptomyces tanashiensis BYF-112 isolated from Odontotermes formosanus","authors":"","doi":"10.1016/S1875-5364(24)60720-X","DOIUrl":"10.1016/S1875-5364(24)60720-X","url":null,"abstract":"<div><div>Chemical investigations of the termite-associated <em>Streptomyces tanashiensis</em> BYF-112 resulted in the discovery of four novel alkaloid derivatives: vegfrecines A and B (<strong>1</strong> and <strong>2</strong>), exfoliazone A (<strong>3</strong>), and venezueline H (<strong>7</strong>), in addition to nine known metabolites (<strong>4</strong>−<strong>6</strong>, <strong>8</strong>−<strong>13</strong>). The structures of these compounds were elucidated through comprehensive spectroscopic analysis and comparison with existing literature data. Antibacterial assays revealed that viridomycin A (<strong>11</strong>) exhibited potent antibacterial activity against <em>Staphylococcus aureus</em>, with a zone of inhibition (ZOI) of 12.67 mm, in comparison to a ZOI of 17.67 mm for the positive control gentamicin sulfate. Viridomycin A (<strong>11</strong>) showed moderate activity against <em>Micrococcus tetragenus</em> and <em>Pseudomonas syringae</em> pv. <em>actinidae</em>, with ZOI values of 15.50 and 14.33 mm, respectively, which were inferior to those of gentamicin sulfate (34.67 and 24.00 mm). Viridomycin F (<strong>12</strong>) also exhibited moderate antibacterial effects against <em>S. aureus</em>, <em>M. tetragenus</em>, and <em>P. syringae</em> pv. <em>actinidae</em>, with ZOI values of 8.33, 16.50, and 10.83 mm, respectively. Cytotoxicity assays demonstrated that viridobruunine A (<strong>5</strong>), exfoliazone (<strong>6</strong>), viridomycin A (<strong>11</strong>), and X-14881E (<strong>13</strong>) exhibited significant cytotoxicity against human malignant melanoma (A375), ovarian cancer (SKOV-3), and gastric cancer (MGC-803) cell lines, with IC<sub>50</sub> values ranging from 4.61 to 19.28 μmol·L<sup>−1</sup>. Furthermore, bioinformatic analysis of the complete genome of <em>S. tanashiensis</em> suggested a putative biosynthetic gene cluster (BGC) responsible for the production of compounds <strong>1−12</strong>. These findings indicate that the secondary metabolites of insect-associated <em>S. tanashiensis</em> BYF-112 hold promise as potential sources of novel antibacterial and anticancer agents.</div></div>","PeriodicalId":10002,"journal":{"name":"Chinese Journal of Natural Medicines","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142315293","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Macrocyclic trichothecenes from Myrothecium verrucaria PA 57 and their cytotoxic activity","authors":"","doi":"10.1016/S1875-5364(24)60573-X","DOIUrl":"10.1016/S1875-5364(24)60573-X","url":null,"abstract":"<div><div>Four novel macrocyclic trichothecenes, termed mytoxins D−G (<strong>1</strong>−<strong>4</strong>), along with four known analogs (<strong>5</strong>−<strong>8</strong>), were isolated from the ethyl acetate extract of fermented rice inoculated with the fungus <em>Myrothecium verrucaria</em> PA57. Each compound features a tricyclic 12,13-epoxytrichothec-9-ene (EPT) core. Notably, mytoxin G (<strong>4</strong>) represents the first instance of a macrocyclic trichothecene incorporating a glucosyl unit within the trichothecene structure. The structures of the newly identified compounds were elucidated through comprehensive spectroscopic analysis combined with quantum chemical calculations. All isolated compounds demonstrated cytotoxic activity against the CAL27 and HCT116 cell lines, which are models for human oral squamous cell carcinoma and colorectal cancer, respectively. Specifically, mytoxin D (<strong>1</strong>) and mytoxin F (<strong>3</strong>) exhibited pronounced cytotoxic effects against both cancer cell lines, with IC<sub>50</sub> values ranging from 3 to 6 nmol·L<sup>−1</sup>. Moreover, compounds <strong>1</strong> and <strong>3</strong> were found to induce apoptosis in HCT116 cells by activating caspase-3.</div></div>","PeriodicalId":10002,"journal":{"name":"Chinese Journal of Natural Medicines","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142315296","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Natural medicine can substitute antibiotics in animal husbandry: protective effects and mechanisms of rosewood essential oil against Salmonella infection","authors":"","doi":"10.1016/S1875-5364(24)60576-5","DOIUrl":"10.1016/S1875-5364(24)60576-5","url":null,"abstract":"<div><div><em>Aniba rosaeodora</em> essential oil (RO) has been traditionally used in natural medicine as a substitute for antibiotics due to its notable antidepressant and antibacterial properties. <em>Salmonella</em>, a prevalent pathogen in foodborne illnesses, presents a major challenge to current antibiotic treatments. However, the antibacterial efficacy and mechanisms of action of RO against <em>Salmonella</em> spp. remain underexplored. This study aims to elucidate the chemical composition of RO, evaluate its antibacterial activity and mechanisms against <em>Salmonella in vitro</em>, and further delineate its anti-inflammatory mechanisms <em>in vivo</em> during <em>Salmonella</em> infection. Gas chromatography-mass spectrometry (GC-MS) was utilized to characterize the chemical constituents of RO. The antibacterial activity of RO was assessed using minimal inhibitory concentration (MIC) and time-kill assays<em>.</em> Various biochemical assays were employed to uncover the potential bactericidal mechanisms. Additionally, mouse and chick models of <em>Salmonella</em> infection were established to investigate the prophylactic effects of RO treatment. RO exhibited significant antibacterial activity against both Gram-positive and Gram-negative bacteria, with an MIC of 4 mg·mL<sup>−1</sup> for <em>Salmonella</em> spp. RO treatment resulted in bacterial damage through the disruption of lipid and purine metabolism. Moreover, RO reduced injury and microbial colonization in infected mice and chicks. RO treatment also modulated the host inflammatory response by inhibiting proinflammatory pathways. In conclusion, our findings demonstrate that RO is effective against <em>Salmonella</em> infection, highlighting its potential as an alternative to antibiotics for antibacterial therapy.</div></div>","PeriodicalId":10002,"journal":{"name":"Chinese Journal of Natural Medicines","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142315290","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Discovery of antitumor diterpenoids from Casearia graveolens targeting VEGFR-2 to inhibit angiogenesis","authors":"","doi":"10.1016/S1875-5364(24)60566-2","DOIUrl":"10.1016/S1875-5364(24)60566-2","url":null,"abstract":"<div><div>Eight novel clerodane diterpenoids (<strong>1</strong>−<strong>8</strong>) were isolated from the twigs of <em>Casearia graveolens</em>. Their structures were elucidated through comprehensive nuclear magnetic resonance (NMR), high-resolution electrospray ionization mass spectrometry (HR-ESI-MS), and electronic circular dichroism (ECD) analyses. In addition to structural determination, surface plasmon resonance (SPR) assays were conducted to investigate molecular interactions, revealing that compound <strong>8</strong> exhibited high affinity for vascular endothelial growth factor receptor 2 (VEGFR2), a key regulator of tumor angiogenesis. Subsequent <em>in vivo</em> experiments demonstrated that compound <strong>8</strong> effectively inhibited angiogenesis and displayed significant antitumor activity by suppressing tumor proliferation and metastasis in zebrafish xenograft models. These findings suggest that compound <strong>8</strong> holds promise as an anticancer lead compound targeting VEGFR-2 to obstruct tumor angiogenesis.</div></div>","PeriodicalId":10002,"journal":{"name":"Chinese Journal of Natural Medicines","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142315295","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Discovery and characterization of naturally occurring covalent inhibitors of SARS-CoV-2 Mpro from the antiviral herb Ephedra","authors":"","doi":"10.1016/S1875-5364(24)60577-7","DOIUrl":"10.1016/S1875-5364(24)60577-7","url":null,"abstract":"<div><div>The Chinese herb Ephedra (also known as Mahuang) has been extensively utilized for the prevention and treatment of coronavirus-induced diseases, including coronavirus disease 2019 (COVID-19). However, the specific anti-SARS-CoV-2 compounds and mechanisms have not been fully elucidated. The main protease (M<sup>pro</sup>) of SARS-CoV-2 is a highly conserved enzyme responsible for proteolytic processing during the viral life cycle, making it a critical target for the development of antiviral therapies. This study aimed to identify naturally occurring covalent inhibitors of SARS-CoV-2 M<sup>pro</sup> from Ephedra and to investigate their covalent binding sites. The results demonstrated that the non-alkaloid fraction of Ephedra (ENA) exhibited a potent inhibitory effect against the SARS-CoV-2 M<sup>pro</sup> effect, whereas the alkaloid fraction did not. Subsequently, the chemical constituents in ENA were identified, and the major constituents’ anti-SARS-CoV-2 M<sup>pro</sup> effects were evaluated. Among the tested constituents, herbacetin (HE) and gallic acid (GA) were found to inhibit SARS-CoV-2 M<sup>pro</sup> in a time- and dose-dependent manner. Their combination displayed a significant synergistic effect on this key enzyme. Additionally, various techniques, including inhibition kinetic assays, chemoproteomic methods, and molecular dynamics simulations, were employed to further elucidate the synergistic anti-M<sup>pro</sup> mechanisms of the combination of HE and GA. Overall, this study deciphers the naturally occurring covalent inhibitors of SARS-CoV-2 M<sup>pro</sup> from Ephedra and characterizes their synergistic anti-M<sup>pro</sup> synergistic effect, providing robust evidence to support the anti-coronavirus efficacy of Ephedra.</div></div>","PeriodicalId":10002,"journal":{"name":"Chinese Journal of Natural Medicines","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142315291","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Cytotoxic lignans from the roots and rhizomes of Diphylleia sinensis, a China’s endemic plant species","authors":"","doi":"10.1016/S1875-5364(24)60721-1","DOIUrl":"10.1016/S1875-5364(24)60721-1","url":null,"abstract":"<div><div>Eight novel arylnaphthalide lactone lignans, designated as diphylignan A−H (<strong>1</strong>−<strong>8</strong>), and a new dibenzyltyrolactone lignan, designated as diphylignan I (<strong>9</strong>), were isolated from the roots and rhizomes of <em>Diphylleia sinensis</em>, along with two additional novel natural products (<strong>11</strong> and <strong>14</strong>) and four known metabolites (<strong>10</strong>, <strong>12</strong>, <strong>13</strong>, <strong>15</strong>). The structural and stereochemical characterization of these compounds was accomplished using NMR spectroscopy and electronic circular dichroism (ECD) analysis. The cytotoxic activities of all isolated compounds were assessed against A-549 and SMMC-7721 cell lines. Notably, compound <strong>2</strong> demonstrated the most significant cytotoxicity, with IC<sub>50</sub> values of 10.27 and 11.58 µmol·L<sup>−1</sup> against A-549 and SMMC-7721 cell lines, respectively, exhibiting greater potency than the positive control, cisplatin.</div></div>","PeriodicalId":10002,"journal":{"name":"Chinese Journal of Natural Medicines","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142315294","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Approved drugs and natural products at clinical stages for treating Alzheimer’s disease","authors":"","doi":"10.1016/S1875-5364(24)60606-0","DOIUrl":"10.1016/S1875-5364(24)60606-0","url":null,"abstract":"<div><p>Alzheimer’s disease (AD) remains the foremost cause of dementia and represents a significant unmet healthcare need globally. The complex pathogenesis of AD, characterized by various pathological and physiological events, has historically challenged the development of anti-AD drugs. However, recent breakthroughs in AD drug development, including the approvals of aducanumab, lecanemab, and sodium oligomannate (GV-971), have ended a nearly two-decade hiatus in the introduction of new AD drugs. These developments have addressed long-standing challenges in AD drug development, marking a substantial shift in the therapeutic landscape of AD. Moreover, natural products (NPs) have shown promise in AD drug research, with several currently under clinical investigation. Their distinct properties and mechanisms of action offer new avenues to complement and enhance existing AD treatment approaches. This review article aims to provide an overview of the recent advancements and prospects in AD therapeutics, focusing on both NPs and approved drugs.</p></div>","PeriodicalId":10002,"journal":{"name":"Chinese Journal of Natural Medicines","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142077175","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Cancer statistics and trends in China: the potential of natural product application","authors":"","doi":"10.1016/S1875-5364(24)60649-7","DOIUrl":"10.1016/S1875-5364(24)60649-7","url":null,"abstract":"","PeriodicalId":10002,"journal":{"name":"Chinese Journal of Natural Medicines","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142077173","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Taohong Siwu Decoction: a classical Chinese prescription for treatment of orthopedic diseases","authors":"","doi":"10.1016/S1875-5364(24)60581-9","DOIUrl":"10.1016/S1875-5364(24)60581-9","url":null,"abstract":"<div><p>The pathogenesis of orthopedic diseases is intimately linked to blood stasis, frequently arising from damage to primary and secondary blood channels. This disruption can lead to “blood leaving the meridians” or Qi stagnation, resulting in blood stasis syndrome. Taohong Siwu Decoction (THSWD) is a renowned classical Chinese medicinal formula extensively used to promote blood circulation and mitigate blood stasis. Clinical studies have demonstrated its significant therapeutic effects on various orthopedic conditions, particularly its anti-inflammatory and analgesic properties, as well as its efficacy in preventing deep vein thrombosis post-surgery. Despite these findings, research on THSWD remains fragmented, and its interdisciplinary impact is limited. This review aims to provide a comprehensive evaluation of the efficacy and pharmacological mechanisms of THSWD in treating common orthopedic diseases. Additionally, we employ bibliometric analysis to explore research trends and hotspots related to THSWD. We hope this review will enhance the recognition and application of THSWD in orthopedic treatments and guide future research into its pharmacological mechanisms.</p></div>","PeriodicalId":10002,"journal":{"name":"Chinese Journal of Natural Medicines","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142075929","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}