Pub Date : 2025-07-12DOI: 10.1007/s11418-025-01932-4
Tamami Shimazaki, Tomoki Iguchi, Aki Kanda, Ami Shirakawa, Yoshihiro Mimaki
A saponin fraction from Allium chinense G. Don. bulbs has previously been reported to exhibit cytotoxicity against melanoma and carcinoma cell lines; however, the active compounds responsible for this cytotoxicity have not been identified. A phytochemical investigation was conducted on A. chinense bulbs to identify novel anticancer seeds from natural products. Seven steroidal glycosides (1–7), comprising three spirostan-type (1–3) and four furostan-type (4–7), were obtained. This is the first report of the isolation of 6 and 7 from A. chinese. The cytotoxicity of 1–7 was evaluated in SBC-3 human small-cell lung cancer cells using the MTT assay. Compounds 2, 3, and 5 demonstrated moderate cytotoxicity against SBC-3 cells, with IC50 values ranging from 15 to 42 μM dose-dependently. Compound 3, (25R)-3β-[(O-α-L-arabinopyranosyl-(1 → 6)-O-[β-D-xylopyranosyl-(1 → 4)]-β-D-glucopyranosyl)oxy]-5α-spirostan-6-one, which exhibited the most potent cytotoxicity among the isolated compounds, induced caspase-dependent apoptotic cell death via both mitochondrial dysfunction leading to reactive oxygen species (ROS) release and endoplasmic reticulum stress caused by ROS. Furthermore, since calreticulin exposure on the outer leaflet of the plasma membrane and extracellular ATP release were observed in SBC-3 cells treated with 3, it may elicit immunogenic cell death in SBC-3 cells.
{"title":"Apoptosis-inducing activity of a steroidal glycoside from Allium chinense G. Don. bulbs in human small-cell lung cancer cells via mitochondrial dysfunction and ER stress","authors":"Tamami Shimazaki, Tomoki Iguchi, Aki Kanda, Ami Shirakawa, Yoshihiro Mimaki","doi":"10.1007/s11418-025-01932-4","DOIUrl":"10.1007/s11418-025-01932-4","url":null,"abstract":"<div><p>A saponin fraction from <i>Allium chinense</i> G. Don. bulbs has previously been reported to exhibit cytotoxicity against melanoma and carcinoma cell lines; however, the active compounds responsible for this cytotoxicity have not been identified. A phytochemical investigation was conducted on <i>A. chinense</i> bulbs to identify novel anticancer seeds from natural products. Seven steroidal glycosides (<b>1–7</b>), comprising three spirostan-type (<b>1–3</b>) and four furostan-type (<b>4–7</b>), were obtained. This is the first report of the isolation of <b>6</b> and <b>7</b> from <i>A. chinese</i>. The cytotoxicity of <b>1–7</b> was evaluated in SBC-3 human small-cell lung cancer cells using the MTT assay. Compounds <b>2</b>, <b>3</b>, and <b>5</b> demonstrated moderate cytotoxicity against SBC-3 cells, with IC<sub>50</sub> values ranging from 15 to 42 μM dose-dependently. Compound <b>3</b>, (25<i>R</i>)-3β-[(<i>O</i>-α-L-arabinopyranosyl-(1 → 6)-<i>O</i>-[β-D-xylopyranosyl-(1 → 4)]-β-D-glucopyranosyl)oxy]-5α-spirostan-6-one, which exhibited the most potent cytotoxicity among the isolated compounds, induced caspase-dependent apoptotic cell death via both mitochondrial dysfunction leading to reactive oxygen species (ROS) release and endoplasmic reticulum stress caused by ROS. Furthermore, since calreticulin exposure on the outer leaflet of the plasma membrane and extracellular ATP release were observed in SBC-3 cells treated with <b>3</b>, it may elicit immunogenic cell death in SBC-3 cells.</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":"79 5","pages":"1200 - 1215"},"PeriodicalIF":2.5,"publicationDate":"2025-07-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144615754","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}
Pub Date : 2025-07-11DOI: 10.1007/s11418-025-01928-0
Dao Thi Anh Phan, Hien Phung Le, Tran Huyen Tran, Ut Van Le, Minh Van Le, Trieu Hai Ly
Polyscias fruticosa leaves have been used in traditional medicine to aid in the therapy of brain and nerve-related disorders, including dementia. However, the evidences for the effects and mechanisms of P. fruticosa leaf extract (PFLE) and its constituents in improving dementia remain unclear. This study aims to evaluate the ameliorative effect of PFLE in aluminum chloride-induced neurotoxicity Drosophila melanogaster model. Simultaneously, the dementia-improving mechanisms of PFLE’s compounds were explored by computational pharmacological analysis. Results showed that D. melanogaster exposed to 1.0, 2.0, and 4.0 mg/mL PFLE or 0.1 mg/mL donepezil hydrochloride had significant improvements in lifespan, memory, motor behavior, and oxidative stress markers, including decreased malondialdehyde level and increased glutathione level in flies’ homogenates. Also, PFLE had acetylcholinesterase inhibitory ability with an IC50 value of 266.10 µg/mL. Applying the UHPLC-Q-TOF-MS/MS technique, 36 compounds were identified in the PFLE. Among these, 25 compounds, including acid amines, flavonoids, saponins, choline, piperine, and vitamin B1, have been demonstrated potential for supporting the treatment of Alzheimer’s disease (AD). Interestingly, molecular docking study indicated that many of the compounds are agents of prominent targets in dementia treatment including N-methyl-d-aspartate (NMDA) receptor and cholinesterase, in which polyscioside A–E are the main components of the PFLE that may be responsible for the NMDA receptor antagonistic and anticholinesterase activities. These compounds have favorable physiochemical properties and drug-likeliness. This study suggested the potential of the PFLE and its compounds in the prophylactic and treatment of neurodegenerative pathologies, including AD, and laid the foundation for further studies.
Graphical abstract
枸杞的叶子在传统医学中被用来帮助治疗大脑和神经相关疾病，包括痴呆症。然而，关于金果叶提取物（PFLE）及其成分改善痴呆的作用和机制的证据尚不清楚。本研究旨在评价PFLE对氯化铝诱导的黑腹果蝇神经毒性模型的改善作用。同时，通过计算药理学分析探讨PFLE化合物对痴呆的改善机制。结果表明，暴露于1.0、2.0和4.0 mg/mL PFLE或0.1 mg/mL盐酸多奈哌酮的黑腹大蠊在果蝇的寿命、记忆、运动行为和氧化应激指标方面均有显著改善，包括果蝇匀浆中丙二醛水平降低和谷胱甘肽水平升高。PFLE对乙酰胆碱酯酶具有抑制作用，IC50值为266.10µg/mL。采用UHPLC-Q-TOF-MS/MS技术，在PFLE中鉴定出36个化合物。其中，包括酸胺、类黄酮、皂苷、胆碱、胡椒碱和维生素B1在内的25种化合物已被证明具有支持治疗阿尔茨海默病（AD）的潜力。有趣的是，分子对接研究表明，许多化合物是痴呆治疗的重要靶点，包括n -甲基- d -天冬氨酸（NMDA）受体和胆碱酯酶，其中多糖A-E是PFLE的主要成分，可能负责NMDA受体拮抗和抗胆碱酯酶活性。这些化合物具有良好的理化性质和药效。本研究提示PFLE及其化合物在预防和治疗AD等神经退行性病变方面的潜力，为进一步的研究奠定了基础。
{"title":"Ameliorative role of Polyscias fruticosa leaf extract in aluminum chloride-induced neurotoxicity flies possibly mediated by N-methyl-d-aspartate receptor antagonistic and anticholinesterase active compounds","authors":"Dao Thi Anh Phan, Hien Phung Le, Tran Huyen Tran, Ut Van Le, Minh Van Le, Trieu Hai Ly","doi":"10.1007/s11418-025-01928-0","DOIUrl":"10.1007/s11418-025-01928-0","url":null,"abstract":"<div><p><i>Polyscias fruticosa</i> leaves have been used in traditional medicine to aid in the therapy of brain and nerve-related disorders, including dementia. However, the evidences for the effects and mechanisms of <i>P. fruticosa</i> leaf extract (PFLE) and its constituents in improving dementia remain unclear. This study aims to evaluate the ameliorative effect of PFLE in aluminum chloride-induced neurotoxicity <i>Drosophila melanogaster</i> model. Simultaneously, the dementia-improving mechanisms of PFLE’s compounds were explored by computational pharmacological analysis. Results showed that <i>D. melanogaster</i> exposed to 1.0, 2.0, and 4.0 mg/mL PFLE or 0.1 mg/mL donepezil hydrochloride had significant improvements in lifespan, memory, motor behavior, and oxidative stress markers, including decreased malondialdehyde level and increased glutathione level in flies’ homogenates. Also, PFLE had acetylcholinesterase inhibitory ability with an IC<sub>50</sub> value of 266.10 µg/mL. Applying the UHPLC-Q-TOF-MS/MS technique, 36 compounds were identified in the PFLE. Among these, 25 compounds, including acid amines, flavonoids, saponins, choline, piperine, and vitamin B1, have been demonstrated potential for supporting the treatment of Alzheimer’s disease (AD). Interestingly, molecular docking study indicated that many of the compounds are agents of prominent targets in dementia treatment including <i>N</i>-methyl-<span>d</span>-aspartate (NMDA) receptor and cholinesterase, in which polyscioside A–E are the main components of the PFLE that may be responsible for the NMDA receptor antagonistic and anticholinesterase activities. These compounds have favorable physiochemical properties and drug-likeliness. This study suggested the potential of the PFLE and its compounds in the prophylactic and treatment of neurodegenerative pathologies, including AD, and laid the foundation for further studies.</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":"79 5","pages":"1167 - 1187"},"PeriodicalIF":2.5,"publicationDate":"2025-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144615710","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}
Nine previously undescribed drimane sesquiterpenoids, ganoresinosins A–I (1–9), were isolated from cultures of basidiomycete Ganoderma subresinosum. The absolute configuration of ganoresinosin H (8) was determined using the modified Mosher’s method. Ganoresinosin A (1) showed antimalarial activity against Plasmodium falciparum K1 (IC50 34 μM), whereas ganoresinosin E (5) exhibited antitubercular activity against Mycobacterium tuberculosis H37Ra (MIC 12.5 μg/mL).
{"title":"Drimane sesquiterpenoids from cultures of basidiomycete Ganoderma subresinosum","authors":"Arunrat Yangchum, Malipan Sappan, Wilunda Choowong, Tuksaporn Thummarukcharoen, Thitiya Boonpratuang, Masahiko Isaka, Prapairat Seephonkai","doi":"10.1007/s11418-025-01931-5","DOIUrl":"10.1007/s11418-025-01931-5","url":null,"abstract":"<div><p>Nine previously undescribed drimane sesquiterpenoids, ganoresinosins A–I (<b>1</b>–<b>9</b>), were isolated from cultures of basidiomycete <i>Ganoderma subresinosum</i>. The absolute configuration of ganoresinosin H (<b>8</b>) was determined using the modified Mosher’s method. Ganoresinosin A (<b>1</b>) showed antimalarial activity against <i>Plasmodium falciparum</i> K1 (IC<sub>50</sub> 34 μM), whereas ganoresinosin E (<b>5</b>) exhibited antitubercular activity against <i>Mycobacterium tuberculosis</i> H37Ra (MIC 12.5 μg/mL).</p><h3>Graphical abstract</h3>\u0000<div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":654,"journal":{"name":"Journal of Natural Medicines","volume":"79 5","pages":"1081 - 1090"},"PeriodicalIF":2.5,"publicationDate":"2025-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144574640","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}
The immune system plays a crucial role in protecting the body from harmful bacterial, viral infections and vital for cancer suppression. Dendritic cells (DCs) are indispensable mediators that facilitate the connection between innate and acquired immunity via antigen presentation and cytokine production. One of the major intestinal microbial metabolites of green tea polyphenols, 5-(3′,5′-dihydroxyphenyl)-γ-valerolactone (EGC-M5), enhances T cell activity. However, the detailed underlying mechanisms remain unknown. Here, we revealed that the oral administration of EGC-M5 increases and activates plasma cytoid dendritic cells (pDCs) in the spleen without causing changes in body weight. Consistent with these findings, administration of EGC-M5 increased the gene expression of interleukin-12 in the spleen. Oral administration of EGC-M5 significantly increased type I Interferon (IFN) and IL-6 levels, which are involved in vaccine-induced antibody production. Ex vivo experiments showed that EGC-M5 treatment did not directly enhance pDC differentiation. In conclusion, EGC-M5 indirectly increased pDC levels in vivo, accompanied by an increase in the expression of pDC activation markers and the gene expression of interleukin-12, type I IFN and IL-6 in the spleen.
{"title":"Metabolite derived from green tea polyphenol increases and activates plasmacytoid dendritic cells","authors":"Motofumi Kumazoe, Misato Nakajima, Reno Kawamoto, Yoshinori Fujimura, Reno Tomioka, Moeto Suzuki, Yuko Tanaka, Hirofumi Tachibana","doi":"10.1007/s11418-025-01929-z","DOIUrl":"10.1007/s11418-025-01929-z","url":null,"abstract":"<p>The immune system plays a crucial role in protecting the body from harmful bacterial, viral infections and vital for cancer suppression. Dendritic cells (DCs) are indispensable mediators that facilitate the connection between innate and acquired immunity via antigen presentation and cytokine production. One of the major intestinal microbial metabolites of green tea polyphenols, 5-(3′,5′-dihydroxyphenyl)-γ-valerolactone (EGC-M5), enhances T cell activity. However, the detailed underlying mechanisms remain unknown. Here, we revealed that the oral administration of EGC-M5 increases and activates plasma cytoid dendritic cells (pDCs) in the spleen without causing changes in body weight. Consistent with these findings, administration of EGC-M5 increased the gene expression of interleukin-12 in the spleen. Oral administration of EGC-M5 significantly increased type I Interferon (IFN) and IL-6 levels, which are involved in vaccine-induced antibody production. Ex vivo experiments showed that EGC-M5 treatment did not directly enhance pDC differentiation. In conclusion, EGC-M5 indirectly increased pDC levels in vivo<i>,</i> accompanied by an increase in the expression of pDC activation markers and the gene expression of interleukin-12, type I IFN and IL-6 in the spleen.</p>","PeriodicalId":654,"journal":{"name":"Journal of Natural Medicines","volume":"79 5","pages":"1057 - 1066"},"PeriodicalIF":2.5,"publicationDate":"2025-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s11418-025-01929-z.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144566952","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-07-04DOI: 10.1007/s11418-025-01930-6
Shengchuan Bao, Mei Feng, XiZhen Zhang, Mingjun Xie, Jing Teng
Atractylodin (ATR) is a natural sesquiterpene compound primarily isolated from the rhizomes of Atractylodes, a plant of the Asteraceae family. It is the core bioactive component of the traditional Chinese medicine Atractylodes and has been confirmed to possess anti-inflammatory, antioxidant, and neuroregulatory functions in various disease models. Recent studies have highlighted ATR's significant roles in anti-tumor, anti-inflammatory, and immune-regulatory activities. However, it remains unclear whether ATR can alleviate depression and its potential pharmacological mechanisms. Our study demonstrates that ATR treatment alleviated depression-like behaviors and improved neuronal changes in the hippocampus of rats. Transcriptomic and proteomic analyses revealed that ATR exerted its antidepressant effects primarily through the regulation of ferroptosis and synaptic plasticity. ATR increased the expression of IL-10, SOD, and GSH, while reducing IL-1β, TNF-α, MDA, and ROS levels, thereby improving inflammation and oxidative stress. Immunohistochemical results indicated that ATR treatment significantly increased the expression of GPX4, SLC7A11, BDNF and NRF2 proteins. This study demonstrates that ATR significantly alleviates depressive symptoms in CUMS rats, with its mechanism primarily involving the regulation of ferroptosis and improvement of synaptic plasticity. ATR may be a potential candidate as an antidepressant.
{"title":"Multi-omics analysis reveals the mechanism of action of Atractylodin against depression","authors":"Shengchuan Bao, Mei Feng, XiZhen Zhang, Mingjun Xie, Jing Teng","doi":"10.1007/s11418-025-01930-6","DOIUrl":"10.1007/s11418-025-01930-6","url":null,"abstract":"<div><p>Atractylodin (ATR) is a natural sesquiterpene compound primarily isolated from the rhizomes of Atractylodes, a plant of the Asteraceae family. It is the core bioactive component of the traditional Chinese medicine Atractylodes and has been confirmed to possess anti-inflammatory, antioxidant, and neuroregulatory functions in various disease models. Recent studies have highlighted ATR's significant roles in anti-tumor, anti-inflammatory, and immune-regulatory activities. However, it remains unclear whether ATR can alleviate depression and its potential pharmacological mechanisms. Our study demonstrates that ATR treatment alleviated depression-like behaviors and improved neuronal changes in the hippocampus of rats. Transcriptomic and proteomic analyses revealed that ATR exerted its antidepressant effects primarily through the regulation of ferroptosis and synaptic plasticity. ATR increased the expression of IL-10, SOD, and GSH, while reducing IL-1β, TNF-α, MDA, and ROS levels, thereby improving inflammation and oxidative stress. Immunohistochemical results indicated that ATR treatment significantly increased the expression of GPX4, SLC7A11, BDNF and NRF2 proteins. This study demonstrates that ATR significantly alleviates depressive symptoms in CUMS rats, with its mechanism primarily involving the regulation of ferroptosis and improvement of synaptic plasticity. ATR may be a potential candidate as an antidepressant.</p><h3>Graphical abstract</h3>\u0000<div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":654,"journal":{"name":"Journal of Natural Medicines","volume":"79 5","pages":"1067 - 1080"},"PeriodicalIF":2.5,"publicationDate":"2025-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144558761","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}
Pub Date : 2025-07-03DOI: 10.1007/s11418-025-01926-2
Jianrong Liu, Tianbo Wu, Wei Li, Quanyi Zhao, Dian He
The tumor inflammatory microenvironment plays an important role in tumor development, and the compounds which modulate tumor microenvironment can be able to accelerate tumor cell death. Here, compound 1 was screened and evaluated through both inhibiting cancer cell proliferation and alleviating the inflammation in microenvironment. In the anti-cancer cell proliferation assay, compound 1 displayed strong proliferative inhibition against all six cell lines, with IC50 values in the range 2–6 μM; among them, the HCT116 cell line was the most sensitive to compound 1. Second, compound 1 showed better inflammatory activities in RAW264.7 cell model than the control GA and 5-FU; it not only decreased the NO level in a concentration-dependent manner, but also reduced the TLR4, HMGB1, IL-1β, TNF-α, iNOS and COX-2 levels; moreover, compound 1 also strongly inhibited NO produce in A549, HEPG2, and HCT116 cells, and it displayed the best for HCT116 cells, with an IC50 value of 2.04 ± 0.68 μM. Third, compound 1 decreased the MMP and increased ROS levels in HCT116 cells; and it upregulated the expression levels of Bax and Cyt-C, and downregulated the Bcl-2 level, finally activating caspase-3 to promote the HCT116 cells apoptosis. This indicates compound 1 had an anti-HCT116 activity possibly by inhibiting the inflammatory factors in microenvironment, as well as by inducing HCT116 cells apoptosis. In animal tests, compound 1 reduced the volume and weight of tumor, indicating it has an obvious anti-tumor effect. Overall, compound 1 is a multi-target drug for the treatment of colon cancer, and it has the potential to be an anti-colon cancer drug candidate.
{"title":"Anti-cancer activity of the glycyrrhetinic acid derivatives with an inhibitory inflammatory microenvironment","authors":"Jianrong Liu, Tianbo Wu, Wei Li, Quanyi Zhao, Dian He","doi":"10.1007/s11418-025-01926-2","DOIUrl":"10.1007/s11418-025-01926-2","url":null,"abstract":"<div><p>The tumor inflammatory microenvironment plays an important role in tumor development, and the compounds which modulate tumor microenvironment can be able to accelerate tumor cell death. Here, compound <b>1</b> was screened and evaluated through both inhibiting cancer cell proliferation and alleviating the inflammation in microenvironment. In the anti-cancer cell proliferation assay, compound <b>1</b> displayed strong proliferative inhibition against all six cell lines, with IC<sub>50</sub> values in the range 2–6 μM; among them, the HCT116 cell line was the most sensitive to compound <b>1</b>. Second, compound <b>1</b> showed better inflammatory activities in RAW264.7 cell model than the control GA and 5-FU; it not only decreased the NO level in a concentration-dependent manner, but also reduced the TLR4, HMGB1, IL-1β, TNF-α, iNOS and COX-2 levels; moreover, compound <b>1</b> also strongly inhibited NO produce in A549, HEPG2, and HCT116 cells, and it displayed the best for HCT116 cells, with an IC<sub>50</sub> value of 2.04 ± 0.68 μM. Third, compound<b> 1</b> decreased the MMP and increased ROS levels in HCT116 cells; and it upregulated the expression levels of Bax and Cyt-C, and downregulated the Bcl-2 level, finally activating caspase-3 to promote the HCT116 cells apoptosis. This indicates compound <b>1</b> had an anti-HCT116 activity possibly by inhibiting the inflammatory factors in microenvironment, as well as by inducing HCT116 cells apoptosis. In animal tests, compound <b>1</b> reduced the volume and weight of tumor, indicating it has an obvious anti-tumor effect. Overall, compound <b>1</b> is a multi-target drug for the treatment of colon cancer, and it has the potential to be an anti-colon cancer drug candidate.</p><h3>Graphical abstract</h3>\u0000<div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":654,"journal":{"name":"Journal of Natural Medicines","volume":"79 5","pages":"986 - 1004"},"PeriodicalIF":2.5,"publicationDate":"2025-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144551621","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}
Pub Date : 2025-06-30DOI: 10.1007/s11418-025-01927-1
Juan Zhu, Shiyao Liu, Peipei Liu, Kefeng Zhai, Hao Liu
Dichroa febrifuga Lour., a traditional Chinese medicinal herb historically used for malaria treatment, contains the active compound Febrifugine. Through structural modification, Halofuginone was semi-synthesized, retaining antimalarial activity with reduced toxicity. Recent studies reveal Halofuginone’s broad biologic activities, including significant therapeutic potential in autoimmune diseases. By modulating abnormal immune responses, suppressing inflammation, and exerting antifibrotic effects, Halofuginone alleviates symptoms and prevents tissue damage in these conditions. This review comprehensively summarizes advances in Halofuginone research for autoimmune diseases and discusses key challenges in this field.
{"title":"Traditional medicine meets modern science: Halofuginone’s role in combating autoimmune diseases","authors":"Juan Zhu, Shiyao Liu, Peipei Liu, Kefeng Zhai, Hao Liu","doi":"10.1007/s11418-025-01927-1","DOIUrl":"10.1007/s11418-025-01927-1","url":null,"abstract":"<div><p><i>Dichroa febrifuga</i> Lour., a traditional Chinese medicinal herb historically used for malaria treatment, contains the active compound Febrifugine. Through structural modification, Halofuginone was semi-synthesized, retaining antimalarial activity with reduced toxicity. Recent studies reveal Halofuginone’s broad biologic activities, including significant therapeutic potential in autoimmune diseases. By modulating abnormal immune responses, suppressing inflammation, and exerting antifibrotic effects, Halofuginone alleviates symptoms and prevents tissue damage in these conditions. This review comprehensively summarizes advances in Halofuginone research for autoimmune diseases and discusses key challenges in this field.</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":"79 5","pages":"1017 - 1029"},"PeriodicalIF":2.5,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144525908","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}
Pub Date : 2025-06-29DOI: 10.1007/s11418-025-01921-7
Qin Yin, Wanhong Peng, Jie Yang, Cunyu Fan, Qinru Wang, Hongyu Gan, Shiwei Zhang, Xiaohang Fan, Fajiu Li
Pulmonary hypertension is a disease characterized by complex diagnosis, challenging treatment, and a shortage of clinical medications. Among them, Group III pulmonary hypertension, which is caused by lung diseases and/or hypoxia, has the second-largest number of patients. Currently, there are extremely few clinically guided medications for Group III pulmonary hypertension, and their efficacy is limited. It is urgent to find new and effective drugs. To explore the potential efficacy of nobiletin in treating hypoxia-induced pulmonary hypertension and its underlying mechanism, the hypoxia-induced pulmonary hypertension rat model was copied by 6-week consecutive hypoxia. Nobiletin or sildenafil was administered daily via gavage for 2 weeks. Subsequently, hemodynamic parameters, HE staining and Masson staining, cytoplasmic calcium level of pulmonary arterial smooth muscle cells (PASMCs) were measured. In addition, cellular thermal shift assays, cell migration and proliferation assays, and immunoblotting were performed to explore the therapeutic effects and underlying mechanisms. Nobiletin effectively attenuated hypoxia-induced pulmonary hypertension in rat, leading to a decrease in mean pulmonary artery pressure, pulmonary vascular resistance, amelioration of vascular remodeling. Furthermore, nobiletin effectively inhibited the elevation of intracellular calcium level, the migration and proliferation of PASMCs induced by hypoxia. The mechanism underlying was attributed to the fact that nobiletin reduced calcium-sensing receptor (CaSR) activity by inhibiting the formation of CaSR dimers. Nobiletin effectively alleviated hypoxia-induced pulmonary hypertension by inhibiting CaSR activity. Nobiletin may be a potential candidate for the treatment of Group III pulmonary hypertension.
{"title":"Nobiletin alleviates hypoxia-induced pulmonary hypertension by inhibiting calcium-sensing receptor","authors":"Qin Yin, Wanhong Peng, Jie Yang, Cunyu Fan, Qinru Wang, Hongyu Gan, Shiwei Zhang, Xiaohang Fan, Fajiu Li","doi":"10.1007/s11418-025-01921-7","DOIUrl":"10.1007/s11418-025-01921-7","url":null,"abstract":"<div><p>Pulmonary hypertension is a disease characterized by complex diagnosis, challenging treatment, and a shortage of clinical medications. Among them, Group III pulmonary hypertension, which is caused by lung diseases and/or hypoxia, has the second-largest number of patients. Currently, there are extremely few clinically guided medications for Group III pulmonary hypertension, and their efficacy is limited. It is urgent to find new and effective drugs. To explore the potential efficacy of nobiletin in treating hypoxia-induced pulmonary hypertension and its underlying mechanism, the hypoxia-induced pulmonary hypertension rat model was copied by 6-week consecutive hypoxia. Nobiletin or sildenafil was administered daily via gavage for 2 weeks. Subsequently, hemodynamic parameters, HE staining and Masson staining, cytoplasmic calcium level of pulmonary arterial smooth muscle cells (PASMCs) were measured. In addition, cellular thermal shift assays, cell migration and proliferation assays, and immunoblotting were performed to explore the therapeutic effects and underlying mechanisms. Nobiletin effectively attenuated hypoxia-induced pulmonary hypertension in rat, leading to a decrease in mean pulmonary artery pressure, pulmonary vascular resistance, amelioration of vascular remodeling. Furthermore, nobiletin effectively inhibited the elevation of intracellular calcium level, the migration and proliferation of PASMCs induced by hypoxia. The mechanism underlying was attributed to the fact that nobiletin reduced calcium-sensing receptor (CaSR) activity by inhibiting the formation of CaSR dimers. Nobiletin effectively alleviated hypoxia-induced pulmonary hypertension by inhibiting CaSR activity. Nobiletin may be a potential candidate for the treatment of Group III pulmonary hypertension.</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":"79 5","pages":"1154 - 1166"},"PeriodicalIF":2.5,"publicationDate":"2025-06-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144525907","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}
Pub Date : 2025-06-25DOI: 10.1007/s11418-025-01925-3
Takashi Tanaka
This review describes the chemical mechanisms behind the structural changes in selected tannins associated with food processing and plant growth. Both the artificial removal of astringency from persimmon fruits and production of hydrophobic procyanidins in cinnamon bark occur via the condensation of proanthocyanidin A-rings with aldehydes. The production of black tea thearubigins from monomeric catechins and the oligomerization of epigallocatechin-3-O-gallate (EGCg) by autoxidation have been explained via the addition of catechin A-rings to B-ring o-quinones. These reactions can be ascribed to the nucleophilic properties of the A-ring methine carbons. Meanwhile, the oxidative B-B coupling of EGCg first produces a quinone dimer, dehydrotheasinensin A (DTSA), and subsequent reduction yields theasinensin A with a bis-pyrogallol structure. The structural similarity of DTSA to ellagitannin dehydrohexahydroxydiphenoyl (DHHDP) groups led us to propose a new hypothesis concerning ellagitannin biosynthesis, in which the oxidative coupling of two galloyl groups first produces a DHHDP group, and subsequent reduction yields a hexahydroxydiphenoyl (HHDP) group. In fact, the DHHDP-bearing ellagitannin in the young leaves of Triadica sebifera is reduced to the corresponding HHDP ester as the leaves grow. Additionally, CuCl2 oxidation of gallic acid esters and 1,2,3,4,6-pentagalloyl-β-d-glucose yields DHHDP esters rather than HHDP esters. In contrast, in the young leaves of a Japanese oak tree, ellagitannin vescalagin is oxidized regioselectively as the leaves grow; this oxidation reaction is related to the autoxidation of vescalagin in oak barrels during whisky aging. Furthermore, this review discusses the immobilization of vescalagin in heartwood.
Graphical abstract
本文综述了与食品加工和植物生长相关的鞣质结构变化背后的化学机制。人工去除柿子涩味和肉桂树皮中疏水原花青素的产生都是通过原花青素a环与醛的缩合而发生的。从单体儿茶素生产红茶茶红素和通过自氧化产生表没食子儿茶素-3- o-没食子酸酯（EGCg）的寡聚化已经通过在b环o-醌上添加儿茶素a环来解释。这些反应可归因于a环甲基碳的亲核性质。同时，EGCg的B-B氧化偶联首先产生醌二聚体脱氢酪氨酸酶a (DTSA)，随后还原生成具有双邻苯三酚结构的酪氨酸酶a。DTSA与鞣花单宁脱氢六羟基二酚（DHHDP）基团的结构相似性使我们提出了一种关于鞣花单宁生物合成的新假设，即两个没食子酰基的氧化偶联首先产生DHHDP基团，随后还原产生六羟基二酚（HHDP）基团。实际上，随着叶片的生长，三甘膦幼叶中含HHDP的鞣花单宁会被还原为相应的HHDP酯。此外，CuCl2氧化没食子酸酯和1,2,3,4,6-五没食子酰β- d -葡萄糖产生DHHDP酯而不是HHDP酯。相反，在日本橡树的嫩叶中，鞣花丹宁在叶子生长过程中被选择性氧化；这种氧化反应与威士忌陈酿过程中橡木桶内的自体氧化有关。此外，本文还对心材中血管再生蛋白的固定化进行了综述。
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Pub Date : 2025-06-25DOI: 10.1007/s11418-025-01917-3
Kosuke Nakamichi, Tetsuhiro Yoshino, Masahiro Akiyama, Aya Jibiki, Yuta Yokoyama, Hitoshi Kawazoe, Sayo Suzuki, Kenji Watanabe, Yun-Gi Kim, Tomonori Nakamura
Inhibiting body fat accumulation is important for the prevention of obesity. In Japan, three Kampo medicines are commonly used to treat obesity: bofutsushosan, boiogito, and daisaikoto. To compare the influences of these Kampo medicines on the intestinal microbiota, it is necessary to conduct a simultaneous investigation using the same mouse model under the same experimental conditions. C57BL/6J mice were divided into five groups: normal chow (NC), high-fat diet (HFD), HFD + 3% bofutsushosan extract (BTS), HFD + 3% boiogito extract (BOT), and HFD + 3% daisaikoto extract (DST). Epididymal white adipose tissue (WAT) weight, mesenteric WAT weight, serum triglyceride levels, and serum total cholesterol levels were measured. Additionally, total bacteria, alpha diversity, beta diversity, and bacterial composition in stool samples were measured. Body weight and epididymal WAT weight gain were significantly inhibited in the BTS-treated group and DST-treated group, but not in the BOT-treated group, compared with the HFD control group. Additionally, serum total cholesterol levels were significantly lower in the DST-treated group than in the HFD group. Specific intestinal bacteria, Clostridium sensu stricto 1, Erysipelatoclostridium, Roseburia, and the Lachnospiraceae NK4A136 group, were significantly changed in the Kampo-treated groups compared with the HFD group, and each of them was correlated with body weight gain, body fat rate, epididymal WAT weight, or mesenteric WAT weight. Our simultaneous investigation of BTS, BOT, and DST under the same conditions clearly demonstrated different changes in the intestinal microbiota and different effects on fat accumulation as well as their association among the three Kampo medicines.
{"title":"Three Kampo medicines—bofutsushosan, boiogito, and daisaikoto—have different effects on host fat accumulation and the intestinal microbiota in a high-fat-diet–induced mouse model of obesity","authors":"Kosuke Nakamichi, Tetsuhiro Yoshino, Masahiro Akiyama, Aya Jibiki, Yuta Yokoyama, Hitoshi Kawazoe, Sayo Suzuki, Kenji Watanabe, Yun-Gi Kim, Tomonori Nakamura","doi":"10.1007/s11418-025-01917-3","DOIUrl":"10.1007/s11418-025-01917-3","url":null,"abstract":"<div><p>Inhibiting body fat accumulation is important for the prevention of obesity. In Japan, three Kampo medicines are commonly used to treat obesity: bofutsushosan, boiogito, and daisaikoto. To compare the influences of these Kampo medicines on the intestinal microbiota, it is necessary to conduct a simultaneous investigation using the same mouse model under the same experimental conditions. C57BL/6J mice were divided into five groups: normal chow (NC), high-fat diet (HFD), HFD + 3% bofutsushosan extract (BTS), HFD + 3% boiogito extract (BOT), and HFD + 3% daisaikoto extract (DST). Epididymal white adipose tissue (WAT) weight, mesenteric WAT weight, serum triglyceride levels, and serum total cholesterol levels were measured. Additionally, total bacteria, alpha diversity, beta diversity, and bacterial composition in stool samples were measured. Body weight and epididymal WAT weight gain were significantly inhibited in the BTS-treated group and DST-treated group, but not in the BOT-treated group, compared with the HFD control group. Additionally, serum total cholesterol levels were significantly lower in the DST-treated group than in the HFD group. Specific intestinal bacteria, <i>Clostridium </i><i>sensu stricto</i><i> 1</i>, <i>Erysipelatoclostridium</i>, <i>Roseburia</i>, and the Lachnospiraceae NK4A136 group, were significantly changed in the Kampo-treated groups compared with the HFD group, and each of them was correlated with body weight gain, body fat rate, epididymal WAT weight, or mesenteric WAT weight. Our simultaneous investigation of BTS, BOT, and DST under the same conditions clearly demonstrated different changes in the intestinal microbiota and different effects on fat accumulation as well as their association among the three Kampo medicines.</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":"79 5","pages":"1044 - 1056"},"PeriodicalIF":2.5,"publicationDate":"2025-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144493340","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}
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