{"title":"Activation of NRF2 by celastrol increases antioxidant functions and prevents the progression of osteoarthritis in mice","authors":"Mingming LIU , Jiatian GUO , Jing ZHAO , Hongye LI , Xiaoxiao FENG , Haojun LIU , Hao ZHANG , Xuejun JIA , Rushuai WEI , Fang LI , Chong CHEN , Mingzhuang HOU , Nanning LV , Haiyan XU","doi":"10.1016/S1875-5364(24)60586-8","DOIUrl":"https://doi.org/10.1016/S1875-5364(24)60586-8","url":null,"abstract":"<div><p>Excessive oxidative stress impairs cartilage matrix metabolism balance, significantly contributing to osteoarthritis (OA) development. Celastrol (CSL), a drug derived from <em>Tripterygium wilfordii</em>, has recognized applications in the treatment of cancer and immune system disorders, yet its antioxidative stress mechanisms in OA remain underexplored. This study aimed to substantiate CSL's chondroprotective effects and unravel its underlying mechanisms. We investigated CSL's impact on chondrocytes under both normal and inflammatory conditions. <em>In vitro</em>, CSL mitigated interleukin (IL)-1β-induced activation of proteinases and promoted cartilage extracellular matrix (ECM) synthesis. <em>In vivo</em>, intra-articular injection of CSL ameliorated cartilage degeneration and mitigated subchondral bone lesions in OA mice. Mechanistically, it was found that inhibiting nuclear factor erythroid 2-related factor 2 (NRF2) abrogated CSL-mediated antioxidative functions and exacerbated the progression of OA. This study is the first to elucidate the role of CSL in the treatment of OA through the activation of NRF2, offering a novel therapeutic avenue for arthritis therapy.</p></div>","PeriodicalId":10002,"journal":{"name":"Chinese Journal of Natural Medicines","volume":null,"pages":null},"PeriodicalIF":4.6,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139713682","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}
Xiaolei HUANG , Chengrun TANG , Xusheng HUANG , Yun YANG , Qirun LI , Mengdi MA , Lei ZHAO , Liumeng YANG , Yadong CUI , Zhenqing ZHANG , Yongtang ZHENG , Jian ZHANG
{"title":"Synthesis and anti-HIV activities of phorbol derivatives","authors":"Xiaolei HUANG , Chengrun TANG , Xusheng HUANG , Yun YANG , Qirun LI , Mengdi MA , Lei ZHAO , Liumeng YANG , Yadong CUI , Zhenqing ZHANG , Yongtang ZHENG , Jian ZHANG","doi":"10.1016/S1875-5364(24)60587-X","DOIUrl":"https://doi.org/10.1016/S1875-5364(24)60587-X","url":null,"abstract":"<div><p>In this study, 37 derivatives of phorbol esters were synthesized and their anti-HIV-1 activities evaluated, building upon our previous synthesis of 51 phorbol derivatives. 12-Para-electron-acceptor-<em>trans</em>-cinnamoyl-13-decanoyl phorbol derivatives stood out, demonstrating remarkable anti-HIV-1 activities and inhibitory effects on syncytia formation. These derivatives exhibited a higher safety index compared with the positive control drug. Among them, 12-(<em>trans</em>-4-fluorocinnamoyl)-13-decanoyl phorbol, designated as compound <strong>3c</strong>, exhibited the most potent anti-HIV-1 activity (EC<sub>50</sub> 2.9 nmol·L<sup>−1</sup>, CC<sub>50</sub>/EC<sub>50</sub> 11 117.24) and significantly inhibited the formation of syncytium (EC<sub>50</sub> 7.0 nmol·L<sup>−1</sup>, CC<sub>50</sub>/EC<sub>50</sub> 4891.43). Moreover, compound <strong>3c</strong> is hypothesized to act both as an HIV-1 entry inhibitor and as an HIV-1 reverse transcriptase inhibitor. Isothermal titration calorimetry and molecular docking studies indicated that compound <strong>3c</strong> may also function as a natural activator of protein kinase C (PKC). Therefore, compound <strong>3c</strong> emerges as a potential candidate for developing new anti-HIV drugs.</p></div>","PeriodicalId":10002,"journal":{"name":"Chinese Journal of Natural Medicines","volume":null,"pages":null},"PeriodicalIF":4.6,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139713687","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}
Wei WANG , Lijuan LIU , Zhuo YANG , Chuanjian LU , Pengfei TU , Ruizhi ZHAO , Kewu ZENG
{"title":"Anti-psoriasis molecular targets and active components discovery of Optimized Yinxieling Formula via affinity-purified strategy","authors":"Wei WANG , Lijuan LIU , Zhuo YANG , Chuanjian LU , Pengfei TU , Ruizhi ZHAO , Kewu ZENG","doi":"10.1016/S1875-5364(24)60563-7","DOIUrl":"https://doi.org/10.1016/S1875-5364(24)60563-7","url":null,"abstract":"<div><p>Psoriasis, a prevalent inherited skin condition, involves an inflammatory response as a key pathogenic mechanism. The Optimized Yinxieling Formula (OYF), rooted in traditional Chinese medicine, is extensively utilized in clinical settings to treat psoriasis. Although previous studies have demonstrated OYF's significant anti-inflammatory effects in psoriasis, its potential molecular targets and active components remain unexplored. This study aimed to unveil the anti-psoriasis molecular targets and active components of OYF. Our findings indicated that OYF extract markedly reduced the production of several inflammatory mediators, including IL-23, nitric oxide, TNF-α, and IL-1β, in LPS-induced RAW264.7 cells. We synthesized OYF extract-crosslinked beads to isolate pharmacological targets from RAW264.7 lysates using an affinity purification strategy, known as Target Fishing. The enriched target proteins were subsequently identified <em>via</em> LC-MS/MS, followed by bioinformatics analysis to map the psoriasis-associated pathway-gene network. We identified a total of 76 potential target proteins, which were highly associated with mRNA transcription mechanisms. In particular, pathway-gene network analysis revealed that the IL-23 inflammatory pathway was involved in the anti-psoriasis effect of OYF extract. We further utilized a target protein-based affinity capture strategy, combined with LC-MS and SPR analysis, to globally screen OYF's active components, focusing on the mRNA transcription regulator, fused in sarcoma (FUS). This process led to the identification of umbelliferone, vanillic acid, protocatechuic acid, gentisic acid, and echinacoside as key compounds targeting FUS to inhibit IL-23 expression. Additionally, we formulated a compound cocktail (CpdC), which significantly reduced psoriasis area and severity index (PASI) scores and the expressions of IL-23 and Ki67 in an imiquimod (IMQ)-induced psoriasis mouse model. Collectively, our study elucidates the primary molecular targets and active components of OYF, offering novel insights for psoriasis treatment.</p></div>","PeriodicalId":10002,"journal":{"name":"Chinese Journal of Natural Medicines","volume":null,"pages":null},"PeriodicalIF":4.6,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139713679","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":"Recent advances in the culture-independent discovery of natural products using metagenomic approaches","authors":"Yiping SHEN, Nan LIU, Zongqiang WANG","doi":"10.1016/S1875-5364(24)60585-6","DOIUrl":"https://doi.org/10.1016/S1875-5364(24)60585-6","url":null,"abstract":"<div><p>Natural products derived from bacterial sources have long been pivotal in the discovery of drug leads. However, the cultivation of only about 1% of bacteria in laboratory settings has left a significant portion of biosynthetic diversity hidden within the genomes of uncultured bacteria. Advances in sequencing technologies now enable the exploration of genetic material from these metagenomes through culture-independent methods. This approach involves extracting genetic sequences from environmental DNA and applying a hybrid methodology that combines functional screening, sequence tag-based homology screening, and bioinformatic-assisted chemical synthesis. Through this process, numerous valuable natural products have been identified and synthesized from previously uncharted metagenomic territories. This paper provides an overview of the recent advancements in the utilization of culture-independent techniques for the discovery of novel biosynthetic gene clusters and bioactive small molecules within metagenomic libraries.</p></div>","PeriodicalId":10002,"journal":{"name":"Chinese Journal of Natural Medicines","volume":null,"pages":null},"PeriodicalIF":4.6,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139713685","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}
Haiyan ZHANG , Qiuyue WANG , Jianan WANG , Sichao ZHANG , Weiwei JIA , Ning HE , Xiaoyan XIA , Ting WANG , Liyu LAI , Jiaying LI , Jing DU , Olajide E. OLALEYE , Xiangmei CHEN , Junling YANG , Chuan LI
{"title":"Composition analysis of Compound Shenhua Tablet, a seven-herb Chinese medicine for IgA nephropathy: evaluation of analyte-capacity of the assays","authors":"Haiyan ZHANG , Qiuyue WANG , Jianan WANG , Sichao ZHANG , Weiwei JIA , Ning HE , Xiaoyan XIA , Ting WANG , Liyu LAI , Jiaying LI , Jing DU , Olajide E. OLALEYE , Xiangmei CHEN , Junling YANG , Chuan LI","doi":"10.1016/S1875-5364(24)60553-4","DOIUrl":"https://doi.org/10.1016/S1875-5364(24)60553-4","url":null,"abstract":"<div><p>Compound Shenhua Tablet, a medicine comprising seven herbs, is employed in treating IgA nephropathy. This study aimed to meticulously analyze its chemical composition. Based on a list of candidate compounds, identified through extensive literature review pertinent to the tablet's herbal components, the composition analysis entailed the systematic identification, characterization, and quantification of the constituents. The analyte-capacity of LC/ESI-MS-based and GC/EI-MS-based assays was evaluated. The identified and characterized constituents were quantified to determine their content levels and were ranked based on the constituents' daily doses. A total of 283 constituents, classified into 12 distinct categories, were identified and characterized in the Compound Shenhua Tablet. These constituents exhibited content levels of 1–10 982 μg·g<sup>−1</sup>, with daily doses of 0.01–395 μmol·d<sup>−1</sup>. The predominant constituents, with daily doses of ≥ 10 μmol·d<sup>−1</sup>, include nine organic acids (citric acid, quinic acid, chlorogenic acid, cryptochlorogenic acid, gallic acid, neochlorogenic acid, isochlorogenic acid C, isochlorogenic acid B, and linoleic acid), five iridoids (specnuezhenide, nuezhenoside G13, nuezhenidic acid, secoxyloganin, and secologanoside), two monoterpene glycosides (paeoniflorin and albiflorin), a sesquiterpenoid (curzerenone), a triterpenoid (oleanolic acid), and a phenylethanoid (salidroside). Additionally, there were 83, 126, and 55 constituents detected in the medicine with daily doses of 1–10, 0.1–1, and 0.01–0.1 μmol·d<sup>−1</sup>, respectively. The combination of the LC/ESI-MS-based and GC/EI-MS-based assays demonstrated a complementary relationship in their analyte-capacity for detecting the constituents present in the medicine. This comprehensive composition analysis establishes a solid foundation for further pharmacological research on Compound Shenhua Tablet and facilitates the quality evaluation of this complex herbal medicine.</p></div>","PeriodicalId":10002,"journal":{"name":"Chinese Journal of Natural Medicines","volume":null,"pages":null},"PeriodicalIF":4.6,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139713689","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}
Shengge LI , Qin ZHANG , Yuetong WANG , Bin LIN , Dahong LI , Huiming HUA , Xu HU
{"title":"β-Carboline alkaloids from the roots of Peganum harmala L.","authors":"Shengge LI , Qin ZHANG , Yuetong WANG , Bin LIN , Dahong LI , Huiming HUA , Xu HU","doi":"10.1016/S1875-5364(24)60583-2","DOIUrl":"https://doi.org/10.1016/S1875-5364(24)60583-2","url":null,"abstract":"<div><p>This study reports the isolation of four new <em>β</em>-carboline alkaloids (<strong>1</strong>−<strong>4</strong>) and six previously identified alkaloids (<strong>5</strong>−<strong>10</strong>) from the roots of <em>Peganum harmala</em> L. Among these compounds, <strong>1</strong> and <strong>2</strong> were characterized as rare <em>β</em>-carboline-quinazoline dimers exhibiting axial chirality. Compound <strong>3</strong> possessed a unique 6/5/6/7 tetracyclic ring system with an azepine ring, and compound <strong>4</strong> was a novel annomontine <em>β</em>-carboline. The structures of these compounds were elucidated by spectroscopic data and quantum mechanical calculations. The biosynthetic pathways of <strong>1</strong>−<strong>3</strong> were proposed. Additionally, the cytotoxicity of some isolates against four cancer cell lines (HL-60, A549, MDA-MB-231, and DU145) was evaluated. Notably, compound <strong>4</strong> exhibited significant cytotoxicity against HL-60, A549, and DU145 cells with IC<sub>50</sub> values of 12.39, 12.80, and 30.65 μmol·L<sup>−1</sup>, respectively. Furthermore, compound <strong>2</strong> demonstrated selective cytotoxicity against HL-60 cells with an IC<sub>50</sub> value of 17.32 μmol·L<sup>−1</sup>.</p></div>","PeriodicalId":10002,"journal":{"name":"Chinese Journal of Natural Medicines","volume":null,"pages":null},"PeriodicalIF":4.6,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139713688","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}
Boxue REN , Yang LI , Lei DI , Ranran CHENG , Lijuan LIU , Hongmei LI , Yi LI , Zhangrui TANG , Yongming YAN , Tao LU , Rong FU , Yongxian CHENG , Zhaoqiu WU
{"title":"A naturally derived small molecule compound suppresses tumor growth and metastasis in mice by relieving p53-dependent repression of CDK2/Rb signaling and the Snail-driven EMT","authors":"Boxue REN , Yang LI , Lei DI , Ranran CHENG , Lijuan LIU , Hongmei LI , Yi LI , Zhangrui TANG , Yongming YAN , Tao LU , Rong FU , Yongxian CHENG , Zhaoqiu WU","doi":"10.1016/S1875-5364(24)60550-9","DOIUrl":"https://doi.org/10.1016/S1875-5364(24)60550-9","url":null,"abstract":"<div><p>The tumor suppressor protein p53 is central to cancer biology, with its pathway reactivation emerging as a promising therapeutic strategy in oncology. This study introduced LZ22, a novel compound that selectively inhibits the growth, migration, and metastasis of tumor cells expressing wild-type p53, demonstrating ineffectiveness in cells devoid of p53 or those expressing mutant p53. LZ22's mechanism of action involves a high-affinity interaction with the histidine-96 pocket of the MDM2 protein. This interaction disrupted the MDM2-p53 binding, consequently stabilizing p53 by shielding it from proteasomal degradation. LZ22 impeded cell cycle progression and diminished cell proliferation by reinstating the p53-dependent suppression of the CDK2/Rb signaling pathway. Moreover, LZ22 alleviated the p53-dependent repression of Snail transcription factor expression and its consequent EMT, effectively reducing tumor cell migration and distal metastasis. Importantly, LZ22 administration in tumor-bearing mice did not manifest notable side effects. The findings position LZ22 as a structurally unique reactivator of p53, offering therapeutic promise for the management of human cancers with wild-type <em>TP53</em>.</p></div>","PeriodicalId":10002,"journal":{"name":"Chinese Journal of Natural Medicines","volume":null,"pages":null},"PeriodicalIF":4.6,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139713686","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}
Zeshi SUN , Shan LIN , Zhi-Li WU , Hong-Yuan DONG , Xi-Ke XU , Hui-Liang LI , Jinxin WANG
{"title":"New phenylbutenoids and terpene glycosides from Ginkgo biloba leaves","authors":"Zeshi SUN , Shan LIN , Zhi-Li WU , Hong-Yuan DONG , Xi-Ke XU , Hui-Liang LI , Jinxin WANG","doi":"10.1016/S1875-5364(24)60588-1","DOIUrl":"https://doi.org/10.1016/S1875-5364(24)60588-1","url":null,"abstract":"<div><p>Our continued works on the chemical constituents of <em>Ginkgo biloba</em> (<em>G. biloba</em>) leaves has led to the isolation of two novel phenylbutenoids (<strong>1, 2</strong>), along with five previously unidentified terpene glycosides (<strong>3–7</strong>). Among them, compounds <strong>1</strong> and <strong>2</strong> represent unique (<em>Z</em>)-phenylbutenoids, <strong>3–6</strong> are megastigmane glycosides, and <strong>7</strong> is identified as a rare bilobanone glycoside (Fig. 1). This study marks the first reported isolation of phenylbutenoid and bilobanone glycoside from <em>G. biloba</em>. The chemical structures of these compounds were elucidated through extensive spectroscopic analysis, including HR-ESI-MS and various 1D and 2D NMR experiments. Furthermore, the absolute configurations of these molecules were determined using Mosher's method, ECD experiments, and Cu-Kα X-ray crystallographic analyses.</p></div>","PeriodicalId":10002,"journal":{"name":"Chinese Journal of Natural Medicines","volume":null,"pages":null},"PeriodicalIF":4.6,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139713683","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}
Yongjiu XIAO , Binbin LI , Chang LIU , Xiuyu HUANG , Ling MA , Zhirong QIAN , Xiaopeng ZHANG , Qian ZHANG , Dunqing LI , Xiaoqing CAI , Xiangyong YAN , Shuping LUO , Dawei XIANG , Kun XIAO
{"title":"Effects of traditional Chinese medicine on treatment outcomes in severe COVID-19 patients: a single-centre study","authors":"Yongjiu XIAO , Binbin LI , Chang LIU , Xiuyu HUANG , Ling MA , Zhirong QIAN , Xiaopeng ZHANG , Qian ZHANG , Dunqing LI , Xiaoqing CAI , Xiangyong YAN , Shuping LUO , Dawei XIANG , Kun XIAO","doi":"10.1016/S1875-5364(24)60565-0","DOIUrl":"https://doi.org/10.1016/S1875-5364(24)60565-0","url":null,"abstract":"<div><p>As the search for effective treatments for COVID-19 continues, the high mortality rate among critically ill patients in Intensive Care Units (ICU) presents a profound challenge. This study explores the potential benefits of traditional Chinese medicine (TCM) as a supplementary treatment for severe COVID-19. A total of 110 critically ill COVID-19 patients at the Intensive Care Unit (ICU) of Vulcan Hill Hospital between Feb., 2020, and April, 2020 (Wuhan, China) participated in this observational study. All patients received standard supportive care protocols, with a subset of 81 also receiving TCM as an adjunct treatment. Clinical characteristics during the treatment period and the clinical outcome of each patient were closely monitored and analysed. Our findings indicated that the TCM group exhibited a significantly lower mortality rate compared with the non-TCM group (16 of 81 <em>vs</em> 24 of 29; 0.3 <em>vs</em> 2.3 person/month). In the adjusted Cox proportional hazards models, TCM treatment was associated with improved survival odds (<em>P</em> < 0.001). Furthermore, the analysis also revealed that TCM treatment could partially mitigate inflammatory responses, as evidenced by the reduced levels of proinflammatory cytokines, and contribute to the recovery of multiple organic functions, thereby potentially increasing the survival rate of critically ill COVID-19 patients.</p></div>","PeriodicalId":10002,"journal":{"name":"Chinese Journal of Natural Medicines","volume":null,"pages":null},"PeriodicalIF":4.6,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139549162","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}