{"title":"Ephedplics E-I: three lignans and two benzofuran-type compounds from the roots of Ephedra sinica Stapf and their neuroprotective activity.","authors":"Yunlong Dou, Bowen Zhang, Meng Li, Xiaolan Wang, Shuyan Liu, Yanjun Sun, Xiaoke Zheng, Weisheng Feng","doi":"10.1007/s11418-026-02036-3","DOIUrl":"10.1007/s11418-026-02036-3","url":null,"abstract":"<p><p>Five new compounds Ephedplics E-I were isolated from the roots of Ephedra sinica Stapf, including three lignans (1-3) and two benzofuran-type compounds (4-5). Their structures were elucidated by spectroscopic methods, involving UV, IR, NMR spectra and HRESIMS analyses. The absolute configuration of compounds 1-5 was determined by comparing their experimental and calculated ECD spectra. All compounds were assessed for their neuroprotective activities against damage induced by corticosterone (CORT) in PC-12 cells. Compounds 1 and 2 were capable of significantly ameliorating CORT-induced PC-12 injury.</p>","PeriodicalId":654,"journal":{"name":"Journal of Natural Medicines","volume":" ","pages":"1357-1366"},"PeriodicalIF":2.6,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148468149","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Tinosporide promotes melanogenesis via activation of cAMP/PKA/CREB-MITF signaling in B16F10 and SK-MEL-2 cells.","authors":"Sukhamoy Dhabal, Anirban Kr Chakrabarty, Rajiva Kumar Rai, Satyabrata Mohapatra, Rahul Singh, Chandra Kant Katiyar, Sunil Kumar Dubey","doi":"10.1007/s11418-026-02054-1","DOIUrl":"10.1007/s11418-026-02054-1","url":null,"abstract":"<p><p>Hypopigmentation disorders are characterized by impaired melanogenesis and remain challenging to manage due to limited efficacy of current interventions and insufficient mechanistic insights. Natural products represent a valuable source of bioactive phytoconstituents capable of regulating key pathways involved in melanin synthesis. Despite its extensive traditional use and diverse pharmacological activities, Tinospora cordifolia and its major bioactive constituent tinosporide remain unexplored for their role in melanogenesis. The present study aimed to evaluate the melanogenesis-promoting potential of bioactive phytoconstituents isolated from Tinospora cordifolia, and to elucidate their underlying molecular mechanisms. Four phytoconstituents-columbin, tinosporide, 8-hydroxy tinosporide and ecdysterone-were isolated and structurally characterized from T. cordifolia. Their melanogenic potential was evaluated in murine (B16F10) and human (SK-MEL-2) melanoma cells by assessing melanin content, tyrosinase activity, and expression of melanogenesis-associated genes. Intracellular cAMP levels and associated signalling pathways were further analysed to investigate the mechanism of action. Among the isolated compounds, tinosporide exhibited the most pronounced melanogenic activity, significantly increasing melanin synthesis and tyrosinase activity. Tinosporide promotes nuclear localization of the microphthalmia-associated transcription factor (MITF), leading to upregulation of MITF-target genes, including Trp1, Tyr, Dct, Pmel, and Mlana. Furthermore, mechanistic studies revealed that tinosporide elevated intracellular cAMP levels and induced the phosphorylation of PKA and CREB, thereby activating cAMP/PKA/CREB signalling pathway. Pharmacological inhibition of PKA and CREB markedly attenuated tinosporide-induced melanogenesis, confirming the essential role of the cAMP/PKA/CREB-MITF axis. Collectively, these findings identify tinosporide as a promising natural melanogenic agent derived from Tinospora cordifolia and highlight its potential relevance in the development of plant-based interventions for hypopigmentation disorders.</p>","PeriodicalId":654,"journal":{"name":"Journal of Natural Medicines","volume":" ","pages":"1403-1416"},"PeriodicalIF":2.6,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148358906","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Fufangteng Yixin Formula alleviates myocardial ischemia-reperfusion injury by modulating gut microbiota and resultant metabolites in rats.","authors":"Fengyi Li, Haitao Zhao, Yilu Lei, Jinwei Luo, Boling Chen, Chenglin Li, Xuan Zhao, Huizhen Jiang","doi":"10.1007/s11418-026-02065-y","DOIUrl":"10.1007/s11418-026-02065-y","url":null,"abstract":"<p><p>This study aimed to explore whether Fufangteng Yixin Formula (FFTYXF) can ameliorate myocardial ischemia-reperfusion injury (MIRI) by regulating the gut microbiota and resultant metabolites. Wistar rats were given FFTYXF by gavage for 7 days, and MIRI rat model was established. Serum level of inflammatory markers was determined by ELISA, and heart function was evaluated by echocardiography. Myocardial histological changes and infarct size were examined by hematoxylin-eosin and triphenyltetrazolium chloride staining, respectively. 16S rRNA gene and metagenomics analyses were employed to explore gut microbiota, while untargeted metabolomics analysis was used to explore serum metabolites. FFTYXF pretreatment could significantly improve cardiac function, reduce infarct size, decrease level of inflammatory factors (TNF-α and IL-6) and inflammatory cells infiltration. At genus level, g__Oscillibacter and g__Rikenellaceae_RC9_gut_group were identified as key microbial bacteria in MIRI rat response to FFTYXF pretreatment. After FFTYXF pretreatment, the functional categories of gut microbiota were participated in fatty acid (FA) biosynthesis/metabolism, glycolysis _ gluconeogenesis and sphingolipid metabolism. Genes response to FFTYXF pretreatment in MIRI rats included K00023 (phbB), K00281 (GLDC, gcvP), K03879 (ND2), K07827 (KRAS) and K15192 (BTAF1), and they were mainly participated in carbon, butanoate, glyoxylate and dicarboxylate metabolism. Differential metabolites were also mainly participated in FA biosynthesis/metabolism, such as alpha-Linolenic acid, omega-3/omega-6 FA, and flavan-3-ol metabolic pathway. Abundance of g__Rikenellaceae_RC9_gut_group positively correlated with differential metabolites FAHFA 34:0, FAHFA 16:1/18:3, and FA 24:5. FFTYXF could alleviate MIRI by modulating gut microbial bacteria alteration and resultant metabolites, particularly short-chain FAs.</p>","PeriodicalId":654,"journal":{"name":"Journal of Natural Medicines","volume":" ","pages":"1521-1537"},"PeriodicalIF":2.6,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148597443","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Supporting exploration and sustainable utilization of the medicinal plant Uncaria rhynchophylla in Kyushu, Japan through potential distribution modeling using MaxEnt and GIS.","authors":"Toshiyuki Atsumi, Suzuka Hokazono, Kaito Kikuchi, Taichi Fujii, Kiyoshi Takejima, Mikiyo Wada, Katsunori Miyake, Tadahiro Yahagi, Kenichi Nakamura, Akihito Takano, Motoyasu Minami","doi":"10.1007/s11418-026-02058-x","DOIUrl":"10.1007/s11418-026-02058-x","url":null,"abstract":"<p><p>Sustainable utilization of wild medicinal plant resources requires reproducible approaches for locating and managing natural populations. In Japan, exploration and resource planning for wild medicinal plants rely heavily on expert knowledge, and reproducible approaches remain scarce. We developed a species distribution model (SDM) for Uncaria rhynchophylla (Rubiaceae), a botanical source of the crude drug Uncaria Hook used in Kampo medicine, to estimate its potential distribution and identify major environmental correlates in the Kyushu region, southern Japan. Using 122 occurrence records collected from 2021 to 2023 and nine environmental predictors, MaxEnt models were trained with background points and bootstrap replicates. Because mean minimum winter temperature in January and mean maximum summer temperature in August were highly correlated, three candidate models were compared using the small-sample corrected Akaike information criterion (AICc), test omission rates, and test area under the receiver operating characteristic curve (AUC). The model including winter minimum temperature was best supported (test AUC = 0.82; test omission rate = 24%), whereas adding summer maximum temperature provided limited improvement (ΔAICc = + 75.75). Variable importance and jackknife tests ranked winter minimum temperature as the most influential predictor, followed by slope angle and distance to the nearest rivers. The suitable area, defined using the maximum training sensitivity plus specificity (MTSS) threshold, covered 10,595 km² (25.9% of the terrestrial area) and formed continuous zones across hilly and low-montane regions. Targeted surveys in high-suitability areas confirmed three additional sites in the Kirishima Mountains. Overall, integrating SDM and geographic information systems provides a reproducible, data-driven, decision-support framework for the exploration, planning of sustainable harvesting, and resource management of wild medicinal plants.</p>","PeriodicalId":654,"journal":{"name":"Journal of Natural Medicines","volume":" ","pages":"1417-1432"},"PeriodicalIF":2.6,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148358873","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Lu-Lu Zhang, Xiao-Wei Wang, Yi-Dan Cheng, Ya Liu, Hesham R El-Seedi, Peng-Cheng Sun, Wen-Bin He, Jian-Jun Zhang, Zhi-Guang Zhai
{"title":"Antidepressant effects of Gardeniae Fructus on chronic unpredictable mild stress model mice: involvement of DNMT3B-mediated epigenetic regulation of GR in the prefrontal cortex.","authors":"Lu-Lu Zhang, Xiao-Wei Wang, Yi-Dan Cheng, Ya Liu, Hesham R El-Seedi, Peng-Cheng Sun, Wen-Bin He, Jian-Jun Zhang, Zhi-Guang Zhai","doi":"10.1007/s11418-026-02067-w","DOIUrl":"10.1007/s11418-026-02067-w","url":null,"abstract":"<p><p>This study aimed to investigate the antidepressant effects of Gardeniae Fructus (ZZ) and its potential mechanisms related to DNA methylation regulation via network pharmacology, in vivo experiments, and targeted molecular assessments; a depressive mouse model was established with chronic unpredictable mild stress (CUMS), ZZ at low/medium/high doses and fluoxetine as positive control were administered for 4 weeks, depressive-like phenotypes were assessed via behavioral tests, and Western blot, qPCR, immunofluorescence and targeted bisulfite sequencing (TBS) were used to detect key molecules, mRNA expression and gene methylation in the prefrontal cortex (PFC) and hippocampus. The results showed that ZZ significantly ameliorated CUMS-induced depressive-like behaviors with 2 g/kg (equivalent to 10 g in adult humans) as the optimal dose, downregulated DNMT3B and 5-mC levels, upregulated GR and reduced FKBP5 expression in the PFC with no hippocampal alterations, and TBS confirmed GR as a hypermethylated PFC target in CUMS mice while low-dose ZZ reversed hypermethylation at four key GR CpG loci. In conclusion, ZZ exerts antidepressant effects by downregulating PFC DNMT3B, reversing GR hypermethylation and restoring GR/FKBP5 balance to regulate the HPA axis, thus providing a novel epigenetic target for depression therapy.</p>","PeriodicalId":654,"journal":{"name":"Journal of Natural Medicines","volume":" ","pages":"1476-1491"},"PeriodicalIF":2.6,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148786698","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Bui Huu Tai, Pham Hai Yen, Duong Thi Dung, Nguyen Huy Hoang, Phan Thi Thanh Huong, Duong Thi Hai Yen, Nguyen The Cuong, Phan Van Kiem
{"title":"Dracafoliasides A-D, four undescribed spirostanol glycosides from Dracaena angustifolia with nitric oxide production inhibitory activity.","authors":"Bui Huu Tai, Pham Hai Yen, Duong Thi Dung, Nguyen Huy Hoang, Phan Thi Thanh Huong, Duong Thi Hai Yen, Nguyen The Cuong, Phan Van Kiem","doi":"10.1007/s11418-026-02078-7","DOIUrl":"https://doi.org/10.1007/s11418-026-02078-7","url":null,"abstract":"<p><p>Four undescribed spirostanol glycosides (23S,24S)-spirosta-5,25(27)-dien-1β,3β,23,24-tetrol 1-O-{2,3,4-tri-O-acetyl-α-L-rhamnopyranosyl-(1→2)-[β-D-xylopyranosyl-(1→3)]-α-L-arabinopyranoside} 24-O-β-D-quinovopyranoside (1), spirosta-5,25(27)-dien-1β,3β,17α-triol 1-O-α-L-rhamnopyranosyl-(1→2)-O-β-D-xylopyranoside (2), spirosta-5,25(27)-diene-1β,3β,17α-triol 1-O-β-D-glucopyranosyl-(1→3)-O-β-D-xylopyranoside (3), (25R)-spirosta-5-ene-1β,3β,17α-triol 1-O-α-L-rhamnopyranosyl-(1→2)-O-β-D-xylopyranoside (4), together with six known compounds (5-10) were isolated from Dracaena angustifolia roots. Their chemical structures were determined based on extensive spectroscopic analysis, including IR, HR-ESI-MS, 1D and 2D NMR spectra. Compounds 1-3, 5, 7 and 10 significantly inhibited nitric oxide (NO) production in lipopolysaccharide activated RAW264.7 cells with IC<sub>50</sub> values ranging from 22.5 to 36.2 µM, while compounds 4 and 9 showed moderate effects with IC<sub>50</sub> values of 67.2 and 60.5 µM, respectively.</p>","PeriodicalId":654,"journal":{"name":"Journal of Natural Medicines","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148863288","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Nguyen Thi Mai, Bui Thi Mai Anh, Tran Thuy Nga, Le Thi Huyen, Nguyen Vu Minh Tam, Nguyen Huy Hoang, Nguyen Viet Dung, Nguyen Phuong Thao
{"title":"Alpikwangsides A-C, three previously undescribed compounds isolated from the rhizomes of Alpinia kwangsiensis and their NO inhibitory activity.","authors":"Nguyen Thi Mai, Bui Thi Mai Anh, Tran Thuy Nga, Le Thi Huyen, Nguyen Vu Minh Tam, Nguyen Huy Hoang, Nguyen Viet Dung, Nguyen Phuong Thao","doi":"10.1007/s11418-026-02079-6","DOIUrl":"https://doi.org/10.1007/s11418-026-02079-6","url":null,"abstract":"<p><p>Three previously undescribed compounds, alpikwangsides A-C (1-3), together with 10 known compounds (4-13), were isolated from the rhizomes of Alpinia kwangsiensis (Zingiberaceae). Their structures were elucidated by 1D and 2D NMR spectroscopy and HRESIMS data, and the absolute configuration of compound 3 was assigned based on ECD analysis. Coronarin G (6) is reported from the genus Alpinia for the first time, whereas pahangensin B (7) is identified for the first time from this species. Biological evaluation showed that compounds 1-3, 7, and 8 inhibited LPS-induced NO production in RAW264.7 cells, with IC<sub>50</sub> values ranging from 22.17 to 46.31 µM, compared with the positive control dexamethasone (IC<sub>50</sub> = 12.64 µM).</p>","PeriodicalId":654,"journal":{"name":"Journal of Natural Medicines","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148863274","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Phan Van Kiem, Nguyen Thi Viet Ai, Bui Huu Tai, Nguyen Huy Hoang, Phan Thi Thanh Huong, Duong Thi Hai Yen, Do Thi Thao, Nguyen Phuong Thao, Nguyen The Cuong, Bui Van Thanh, Duong Thi Dung, Pham Hai Yen
{"title":"Discovery of four new malabaricane saponins, malabarosides A-D, from the aerial parts of Dysphania ambrosioides with nitric oxide production inhibitory activity.","authors":"Phan Van Kiem, Nguyen Thi Viet Ai, Bui Huu Tai, Nguyen Huy Hoang, Phan Thi Thanh Huong, Duong Thi Hai Yen, Do Thi Thao, Nguyen Phuong Thao, Nguyen The Cuong, Bui Van Thanh, Duong Thi Dung, Pham Hai Yen","doi":"10.1007/s11418-026-02074-x","DOIUrl":"https://doi.org/10.1007/s11418-026-02074-x","url":null,"abstract":"<p><p>The plant Dysphania ambrosioides has long been best known for its traditional use as a medicine to treat worms and other intestinal parasites, as well as for treating wounds. Phytochemical study of the methanol extract of the aerial parts of D. ambrosioides led to the isolation of four undescribed 13α-malabaricane saponins named malabarosides A-D (1-4). Their chemical structures were determined based on extensive spectroscopic analysis, including HR-ESI-MS, 1D and 2D NMR spectra. These compounds moderately inhibited nitric oxide (NO) production in lipopolysaccharide activated RAW264.7 cells with IC<sub>50</sub> values ranging from 52.6 to 61.0 µM. This is the first malabaricane-type triterpenoid reported from the family Amaranthaceae.</p>","PeriodicalId":654,"journal":{"name":"Journal of Natural Medicines","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148849631","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Kouharu Otsuki, Mi Zhang, Kakeru Hirose, Takashi Kikuchi, Wei Li
{"title":"Liquid chromatography–mass spectrometry-based automated annotation program-assisted structural characterization of daphnane diterpenoids from Daphne genkwa","authors":"Kouharu Otsuki, Mi Zhang, Kakeru Hirose, Takashi Kikuchi, Wei Li","doi":"10.1007/s11418-026-02056-z","DOIUrl":"10.1007/s11418-026-02056-z","url":null,"abstract":"<div><p><i>Daphne genkwa</i> is a deciduous shrub distributed throughout East Asia and has long been used in traditional medicine. Previous phytochemical investigations have shown that <i>D. genkwa</i> is a rich source of bioactive daphnane diterpenoids. In the present study, a comprehensive structural characterization of daphnane diterpenoids in the flowers of <i>D. genkwa</i> was carried out using an LC–MS/MS-based approach. This approach integrated automated annotation program, manual inspection of MS/MS fragmentation pathways, and phytochemical investigation. It led to the structural characterization of 37 daphnane diterpenoids, including nine previously undescribed compounds. These findings demonstrated that <i>D. genkwa</i> flowers contain structurally diverse daphnane diterpenoids, mainly daphnane orthoesters and polyhydroxy daphnanes. Moreover, the diagnostic MS/MS fragmentation and retention time features established in this study provide reliable LC–MS/MS-based criteria for discriminating closely related structural isomers of polyhydroxy daphnanes that differ in their B-ring structures and acylation patterns.</p><h3>Graphical abstract</h3><div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":654,"journal":{"name":"Journal of Natural Medicines","volume":"80 4","pages":"1188 - 1198"},"PeriodicalIF":2.6,"publicationDate":"2026-06-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148292896","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}