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。
{"title":"Mechanisms underlying the dynamic changes in tannins associated with food processing and plant growth","authors":"Takashi Tanaka","doi":"10.1007/s11418-025-01925-3","DOIUrl":"10.1007/s11418-025-01925-3","url":null,"abstract":"<div><p>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-<i>O</i>-gallate (EGCg) by autoxidation have been explained via the addition of catechin A-rings to B-ring<i> o</i>-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 <i>Triadica sebifera</i> is reduced to the corresponding HHDP ester as the leaves grow. Additionally, CuCl<sub>2</sub> oxidation of gallic acid esters and 1,2,3,4,6-pentagalloyl-<i>β</i>-<span>d</span>-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.</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":"967 - 985"},"PeriodicalIF":2.5,"publicationDate":"2025-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s11418-025-01925-3.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144493360","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 : 2025-06-25DOI: 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}
{"title":"Correction: Ellagic acid prevents ovariectomy-induced bone loss and attenuates oxidative damage of osteoblasts by activating SIRT1","authors":"Liwei Guo, Pengcheng Wei, Shijie Li, Lulu Zhou, Yunjie Yan, Duan Li","doi":"10.1007/s11418-025-01915-5","DOIUrl":"10.1007/s11418-025-01915-5","url":null,"abstract":"","PeriodicalId":654,"journal":{"name":"Journal of Natural Medicines","volume":"79 5","pages":"1262 - 1263"},"PeriodicalIF":2.5,"publicationDate":"2025-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144482807","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 : 2025-06-19DOI: 10.1007/s11418-025-01924-4
Debina Bhattacharyya, Jayasri Das Sarma
The miraculous golden tree of the century, neem or Azadirachta indica, has been used in ancient ayurvedic and traditional medicine since the inception of medicinal practices. The phytochemicals present in each part of this tree are known to possess the ability to cure a variety of diseases, from viral, bacterial, and fungal infections and associated pathogenesis to inflammatory diseases, different metabolic disorders, and cancers. Predominant phytochemicals from neem, azadirachtin, nimbin, nimbolide, quercetin, etc., are known to be potent anti-inflammatory, antiviral, and anti-cancer agents. These and many other bio-active compounds from neem restrict the viral spread and replication of β-coronaviruses, Human Immunodeficiency Virus, Herpes Simplex Virus, etc. Likewise, neem extracts and bio-active compounds from neem have been targeting cancer cells by restricting their proliferation, survival, and migration and inducing apoptosis, leading to the establishment of neem as a potent anti-cancer agent. Multiple studies have reported neem's efficiency in intervening with inflammatory pathways and oxidative stress pathways, which are known to be linked to viral infections and cancers. In this review, we discuss the role of methanolic neem bark extracts and their bio-active compounds in preventing β-coronavirus mouse hepatitis virus and SARS-CoV-2 replication and spread, and simultaneously the anti-cancer effects exerted by MNBE via activating pro-apoptotic markers, restricting the proliferation and migration of cervical cancer cells, inducing cell cycle arrest.
{"title":"The pleiotropic anti-cancer, antiviral, and anti-neuro-immunomodulatory role of methanolic neem bark extract","authors":"Debina Bhattacharyya, Jayasri Das Sarma","doi":"10.1007/s11418-025-01924-4","DOIUrl":"10.1007/s11418-025-01924-4","url":null,"abstract":"<div><p>The miraculous golden tree of the century, neem or <i>Azadirachta indica,</i> has been used in ancient ayurvedic and traditional medicine since the inception of medicinal practices. The phytochemicals present in each part of this tree are known to possess the ability to cure a variety of diseases, from viral, bacterial, and fungal infections and associated pathogenesis to inflammatory diseases, different metabolic disorders, and cancers. Predominant phytochemicals from neem, azadirachtin, nimbin, nimbolide, quercetin, etc., are known to be potent anti-inflammatory, antiviral, and anti-cancer agents. These and many other bio-active compounds from neem restrict the viral spread and replication of β-coronaviruses, Human Immunodeficiency Virus, Herpes Simplex Virus, etc. Likewise, neem extracts and bio-active compounds from neem have been targeting cancer cells by restricting their proliferation, survival, and migration and inducing apoptosis, leading to the establishment of neem as a potent anti-cancer agent. Multiple studies have reported neem's efficiency in intervening with inflammatory pathways and oxidative stress pathways, which are known to be linked to viral infections and cancers. In this review, we discuss the role of methanolic neem bark extracts and their bio-active compounds in preventing β-coronavirus mouse hepatitis virus and SARS-CoV-2 replication and spread, and simultaneously the anti-cancer effects exerted by MNBE via activating pro-apoptotic markers, restricting the proliferation and migration of cervical cancer cells, inducing cell cycle arrest.</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":"951 - 966"},"PeriodicalIF":2.5,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144324107","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}
Excessive glutamate in the central nervous system is a key pathogenic mechanism in neurodegenerative disorder. This study investigated the neuroprotective effect of acrovestone (AVT), an acetophenone dimer from Acronychia pedunculata, and its underlying mechanism in glutamate-induced neuroblastoma SH-SY5Y cells. The protective effect of AVT was evaluted through cell viability assay and analysis of apoptosis-related protein expression via Western blot analysis. Our finding revealed that AVT significantly improved cell viability under glutamate induced excitotoxicity conditions. Mechanistic investigations demonstrated that AVT attenuated the activation of pro-apoptotic proteins including ERK1/2, Bim, BAX, caspase-3, caspase-7, and caspase-9. Concurrently, AVT upregulated the expression of anti-apoptotic proteins Bcl-2 and Bcl-xL. Furthermore, AVT modulated the Akt/FoxO3a signaling pathway, alleviating acute oxidative stress caused by glutamate exposure in SH-SY5Y cells. These results suggest that AVT inhibits glutamate-induced neurotoxicity by modulating apoptosis signaling pathway, highlighting its potential as a therapeutic candidate for preventing neurodegenerative diseases.
{"title":"Neuroprotective effects of acetophenone dimers from Acronychia pedunculata on human neuroblastoma SH-SY5Y cells in glutamate-induced apoptosis","authors":"Panuwat Worasrihirun, Ardiansah Ardiansah, Kiminori Matsubara, Khanitha Pudhom","doi":"10.1007/s11418-025-01920-8","DOIUrl":"10.1007/s11418-025-01920-8","url":null,"abstract":"<div><p>Excessive glutamate in the central nervous system is a key pathogenic mechanism in neurodegenerative disorder. This study investigated the neuroprotective effect of acrovestone (AVT), an acetophenone dimer from <i>Acronychia pedunculata,</i> and its underlying mechanism in glutamate-induced neuroblastoma SH-SY5Y cells. The protective effect of AVT was evaluted through cell viability assay and analysis of apoptosis-related protein expression via Western blot analysis. Our finding revealed that AVT significantly improved cell viability under glutamate induced excitotoxicity conditions. Mechanistic investigations demonstrated that AVT attenuated the activation of pro-apoptotic proteins including ERK1/2, Bim, BAX, caspase-3, caspase-7, and caspase-9. Concurrently, AVT upregulated the expression of anti-apoptotic proteins Bcl-2 and Bcl-xL. Furthermore, AVT modulated the Akt/FoxO3a signaling pathway, alleviating acute oxidative stress caused by glutamate exposure in SH-SY5Y cells. These results suggest that AVT inhibits glutamate-induced neurotoxicity by modulating apoptosis signaling pathway, highlighting its potential as a therapeutic candidate for preventing neurodegenerative diseases.</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 4","pages":"938 - 949"},"PeriodicalIF":2.5,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144197986","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}
Eight new resin glycosides, named calyhedins XXIV (1)–XXXI (8), were isolated from the rhizomes of Calystegia hederacea Wall. (Convolvulaceae), along with six known calyhedins: calyhedins II (9), III (10), IV (11), V (12), VIII (13), and XII (14). Their structures were determined from the spectroscopic data. Compounds 1–7 were hexa- or hepta-glycosides with macrolactone structures (jalapins), and their sugar moieties were partially acylated by five organic acids, including 2S-methylbutyric, (E)-2-methylbut-2-enoic, and 2R-methyl-3R-hydroxybutyric acids. Compounds 1–7 were macrolactones with 22- (1, 7), 23- (2), 27- (3–5), or 28- (6) membered rings. Compound 8 was identified as an acylated glycosidic acid methyl ester, corresponding to the compound in which the lactone ring of 1 was cleaved and subsequently methylated. In addition, the cytotoxic activities of 1–8, 11, 12, and 14 against HL-60 human promyelocytic leukemia cells and the antiviral activities of 1–14 and 11 previously isolated calyhedins against herpes simplex virus type 1 (HSV-1) were evaluated. Except for 1, the other ten tested compounds exhibited cytotoxicity against HL-60 cells, with the IC50 values of 3, 4, 6, 7, 11, and 12 being closer to or rather lower than that of the positive control cisplatin. Additionally, all tested compounds demonstrated anti-HSV-1 activity, with seven compounds, i.e., 3, 6, 9, 10, 22, 23, and 24, having EC50 values lower than or comparable to that of the positive control acyclovir.
{"title":"Eight new resin glycosides, calyhedins XXIV–XXXI, from the rhizomes of Calystegia hederacea","authors":"Masateru Ono, Yosuke Matsuoka, Ryota Arakawa, Hiroyuki Shimadzu, Takumi Nagasawa, Hirotaka Nishikawa, Shin Yasuda, Hiroyuki Miyashita, Kazumi Yokomizo, Hitoshi Yoshimitsu, Ryota Tsuchihasi, Masafumi Okawa, Junei Kinjo","doi":"10.1007/s11418-025-01919-1","DOIUrl":"10.1007/s11418-025-01919-1","url":null,"abstract":"<p>Eight new resin glycosides, named calyhedins XXIV (<b>1</b>)–XXXI (<b>8</b>), were isolated from the rhizomes of <i>Calystegia hederacea</i> Wall. (Convolvulaceae), along with six known calyhedins: calyhedins II (<b>9</b>), III (<b>10</b>), IV (<b>11</b>), V (<b>12</b>), VIII (<b>13</b>), and XII (<b>14</b>). Their structures were determined from the spectroscopic data. Compounds <b>1</b>–<b>7</b> were hexa- or hepta-glycosides with macrolactone structures (jalapins), and their sugar moieties were partially acylated by five organic acids, including 2<i>S</i>-methylbutyric, (<i>E</i>)-2-methylbut-2-enoic, and 2<i>R</i>-methyl-3<i>R</i>-hydroxybutyric acids. Compounds <b>1</b>–<b>7</b> were macrolactones with 22- (<b>1</b>, <b>7</b>), 23- (<b>2</b>), 27- (<b>3</b>–<b>5</b>), or 28- (<b>6</b>) membered rings. Compound <b>8</b> was identified as an acylated glycosidic acid methyl ester, corresponding to the compound in which the lactone ring of <b>1</b> was cleaved and subsequently methylated. In addition, the cytotoxic activities of <b>1</b>–<b>8</b>, <b>11</b>, <b>12</b>, and <b>14</b> against HL-60 human promyelocytic leukemia cells and the antiviral activities of <b>1</b>–<b>14</b> and 11 previously isolated calyhedins against herpes simplex virus type 1 (HSV-1) were evaluated. Except for <b>1</b>, the other ten tested compounds exhibited cytotoxicity against HL-60 cells, with the IC<sub>50</sub> values of <b>3</b>, <b>4</b>, <b>6</b>, <b>7</b>, <b>11</b>, and <b>12</b> being closer to or rather lower than that of the positive control cisplatin. Additionally, all tested compounds demonstrated anti-HSV-1 activity, with seven compounds, i.e., <b>3</b>, <b>6</b>, <b>9</b>, <b>10</b>, <b>22</b>, <b>23</b>, and <b>24</b>, having EC<sub>50</sub> values lower than or comparable to that of the positive control acyclovir.</p>","PeriodicalId":654,"journal":{"name":"Journal of Natural Medicines","volume":"79 4","pages":"845 - 862"},"PeriodicalIF":2.5,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12228659/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144197985","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 : 2025-05-30DOI: 10.1007/s11418-025-01914-6
Tarik A. Mohamed, Ahmed Zayed, Emad A. AlSherif, Mohamed A. Farag, Hossam M. Abdallah
Commiphora species, valued for their resinous cell saps rich in terpenoids and other compounds, are known for their therapeutic benefits. This study aimed to be the first NMR-based metabolome profiling of oleo-gum resin derived from endemic rare Commiphora species. Insights into taxonomic variation and tree sex differences were targeted for future correlation with bioactivities-related assays. Oleo-gum resins and cell sap were collected and extracted by methanol from four naturally growing Commiphora species, including C. gileadensis, C. quadricincta, C. kataf female, and C. kataf male. Afterward, NMR acquisition and spectra interpretation were carried out, including various 1D and 2D-techniques. A total of 36 metabolites were identified, including 3 cycloartane derivatives, 12 amino acids and their derivatives, 7 organic acids, 1 phenolic acid, 6 sugars and sugar alcohols, 6 terpenoids, and 1 nitrogenous compound. Multivariate analysis, employing both unsupervised and supervised modeling, facilitated classification of samples and provided a foundation for future authentication and quality control of these taxa. Notably, C. gileadensis cell sap and C. quadricincta oleo-gum resin were metabolically distinct, enriched in terpenoids such as cycloartane 24-en-1,2,3-triol (1) and 1-acetoxycycloartan-24-ene-2,3-diol (2), while trehalose (24) was more abundant in other species. Further, quantitative NMR (qNMR) quantified 9 metabolite markers detected at high levels in Commiphora accessions. In conclusion, terpenoids were found to be abundant and discriminant compounds in Commiphora products. The results shall aid in the future standardization of Commiphora oleo-gum resins to be included in nutraceuticals and for future correlation with bioactivities-related assays.
Graphical Abstract
由于其富含萜类化合物和其他化合物的树脂细胞汁液而受到重视，以其治疗益处而闻名。本研究旨在成为第一个基于核磁共振成像的来自特有稀有物种的油胶树脂代谢组分析。对分类变异和树木性别差异的见解是未来与生物活性相关分析的目标。从自然生长的四种木芋属植物（C. gileadensis， C. quadricincta， C. kataf雌株和C. kataf雄株）中收集油胶树脂和细胞液，并用甲醇提取。随后进行核磁共振采集和光谱解释，包括各种一维和二维技术。共鉴定出36种代谢物，包括3种环artane衍生物、12种氨基酸及其衍生物、7种有机酸、1种酚酸、6种糖和糖醇、6种萜类和1种氮化合物。多变量分析采用无监督和有监督两种建模方法，为样本分类提供了便利，为今后对这些类群的鉴定和质量控制提供了基础。值得注意的是，C. gileadensis细胞汁液和C. quadricincta油胶树脂代谢差异明显，富含环artane -24-en -1,2,3-三醇(1)和1-acetoxycycloartan-24-ene-2,3-二醇(2)等萜类化合物，而海藻糖（24）在其他物种中含量更高。此外，定量核磁共振（qNMR）量化了9个在Commiphora材料中检测到的高水平代谢物标记。综上所述，萜类化合物在康菲乐产品中含量丰富且具有鉴别性。该结果将有助于将来将香茅油胶树脂纳入营养药品的标准化，并有助于将来与生物活性相关的分析相关联。
{"title":"NMR-based metabolomics for unraveling oleo-gum resin metabolome of rare Commiphora species: insights into taxonomic variation and tree sex differences","authors":"Tarik A. Mohamed, Ahmed Zayed, Emad A. AlSherif, Mohamed A. Farag, Hossam M. Abdallah","doi":"10.1007/s11418-025-01914-6","DOIUrl":"10.1007/s11418-025-01914-6","url":null,"abstract":"<div><p><i>Commiphora</i> species, valued for their resinous cell saps rich in terpenoids and other compounds, are known for their therapeutic benefits. This study aimed to be the first NMR-based metabolome profiling of oleo-gum resin derived from endemic rare <i>Commiphora</i> species. Insights into taxonomic variation and tree sex differences were targeted for future correlation with bioactivities-related assays. Oleo-gum resins and cell sap were collected and extracted by methanol from four naturally growing <i>Commiphora</i> species, including <i>C. gileadensis</i>, <i>C. quadricincta</i>, <i>C. kataf</i> female, and <i>C. kataf</i> male. Afterward, NMR acquisition and spectra interpretation were carried out, including various 1D and 2D-techniques. A total of 36 metabolites were identified, including 3 cycloartane derivatives, 12 amino acids and their derivatives, 7 organic acids, 1 phenolic acid, 6 sugars and sugar alcohols, 6 terpenoids, and 1 nitrogenous compound. Multivariate analysis, employing both unsupervised and supervised modeling, facilitated classification of samples and provided a foundation for future authentication and quality control of these taxa. Notably, <i>C. gileadensis</i> cell sap and <i>C. quadricincta</i> oleo-gum resin were metabolically distinct, enriched in terpenoids such as cycloartane 24-en-1,2,3-triol (<b>1</b>) and 1-acetoxycycloartan-24-ene-2,3-diol (<b>2</b>), while trehalose (<b>24</b>) was more abundant in other species. Further, quantitative NMR (qNMR) quantified 9 metabolite markers detected at high levels in <i>Commiphora</i> accessions. In conclusion, terpenoids were found to be abundant and discriminant compounds in <i>Commiphora</i> products. The results shall aid in the future standardization of <i>Commiphora</i> oleo-gum resins to be included in nutraceuticals and for future correlation with bioactivities-related assays.</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 4","pages":"807 - 820"},"PeriodicalIF":2.5,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144186210","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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