{"title":"Vincazalidine A, a unique bisindole alkaloid from Catharanthus roseus","authors":"Yusuke Hirasawa, Ayaka Kase, Akie Okamoto, Keigo Suzuki, Mizuki Hiroki, Toshio Kaneda, Nahoko Uchiyama, Hiroshi Morita","doi":"10.1007/s11418-023-01775-x","DOIUrl":"10.1007/s11418-023-01775-x","url":null,"abstract":"<div><p>A new dimeric indole alkaloid, vincazalidine A consisting of an aspidosperma type and a modified iboga type with 1-azatricyclo ring system consisting of one azepane and two piperidine rings coupled with an oxazolidine ring was isolated from <i>Catharanthus roseus</i>, and the structure including absolute stereochemistry was elucidated on the basis of spectroscopic data as well as DP4 statistical analysis. Vincazalidine A induced G2 arrest and subsequent apoptosis in human lung carcinoma cell line, A549 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":"78 2","pages":"382 - 392"},"PeriodicalIF":2.5,"publicationDate":"2024-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139721122","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":"Angelica dahurica extract and its effective component bergapten alleviated hepatic fibrosis by activating FXR signaling pathway","authors":"Chong Gao, Zhong-He Hu, Zhen-Yu Cui, Yu-Chen Jiang, Jia-Yi Dou, Zhao-Xu Li, Li-Hua Lian, Ji-Xing Nan, Yan-Ling Wu","doi":"10.1007/s11418-024-01780-8","DOIUrl":"10.1007/s11418-024-01780-8","url":null,"abstract":"<div><p><i>Angelica dahurica (A. dahurica)</i> has a wide range of pharmacological effects, including analgesic, anti-inflammatory and hepatoprotective effects. In this study, we investigated the effect of <i>A. dahurica</i> extract (AD) and its effective component bergapten (BG) on hepatic fibrosis and potential mechanisms. Hepatic fibrosis was induced by intraperitoneal injection with carbon tetrachloride (CCl<sub>4</sub>) for 1 week, and mice were administrated with AD or BG by gavage for 1 week before CCl<sub>4</sub> injection. Hepatic stellate cells (HSCs) were stimulated by transforming growth factor-β (TGF-β) and cultured with AD, BG, GW4064 (FXR agonist) or Guggulsterone (FXR inhibitor). In CCl<sub>4</sub>-induced mice, AD significantly decreased serum aminotransferase, reduced excess accumulation of extracellular matrix (ECM), inhibited caspase-1 and IL-1β, and increased FXR expressions. In activated HSCs, AD suppressed the expressions of α-SMA, collagen I, and TIMP-1/MMP-13 ratio and inflammatory factors, functioning as FXR agonist. In CCl<sub>4</sub>-induced mice, BG significantly improved serum transaminase and histopathological changes, reduced ECM excessive deposition, inflammatory response, and activated FXR expression. BG increased FXR expression and inhibited α-SMA and IL-1β expressions in activated HSCs, functioning as GW4064. FXR deficiency significantly attenuated the decreasing effect of BG on α-SMA and IL-1β expressions in LX-2 cells. In conclusion, AD could regulate hepatic fibrosis by regulating ECM excessive deposition and inflammation. Activating FXR signaling by BG might be the potential mechanism of AD against hepatic fibrosis.</p></div>","PeriodicalId":654,"journal":{"name":"Journal of Natural Medicines","volume":"78 2","pages":"427 - 438"},"PeriodicalIF":2.5,"publicationDate":"2024-02-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139705744","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}
Xingxian Guo, Shiying Huang, Yonghong Zhang, Hong Wang, Lisha Li, Jianhua Ran, Dilong Chen, Xiaopeng Li, Jing Li
{"title":"Evodiamine inhibits growth of vemurafenib drug-resistant melanoma via suppressing IRS4/PI3K/AKT signaling pathway","authors":"Xingxian Guo, Shiying Huang, Yonghong Zhang, Hong Wang, Lisha Li, Jianhua Ran, Dilong Chen, Xiaopeng Li, Jing Li","doi":"10.1007/s11418-023-01769-9","DOIUrl":"10.1007/s11418-023-01769-9","url":null,"abstract":"<div><p>Evodiamine, a novel alkaloid, was isolated from the fruit of tetradium. It exerts a diversity of pharmacological effects and has been used to treat gastropathy, hypertension, and eczema. Several studies reported that evodiamine has various biological effects, including anti-nociceptive, anti-bacterial, anti-obesity, and anti-cancer activities. However, there is no research regarding its effects on drug-resistant cancer. This study aimed to investigate the effect of evodiamine on human vemurafenib-resistant melanoma cells (A375/R cells) proliferation ability and its mechanism. Cell activity was assessed using the cell counting kit-8 (CCK-8) method. Flow cytometry assay was used to assess cell apoptosis and cell cycle. A xenograft model was used to analyze the inhibitory effects of evodiamine on tumor growth. Bioinformatics analyses, network pharmacology, and molecular docking were used to explore the potential mechanism of evodiamine in vemurafenib-resistant melanoma. RT-qPCR and Western blotting were performed to reveal the molecular mechanism. The alkaloid extract of the fruit of tetradium, evodiamine showed the strongest tumor inhibitory effect on vemurafenib-resistant melanoma cells compared to treatment with vemurafenib alone. Evodiamine inhibited vemurafenib-resistant melanoma cell growth, proliferation, and induced apoptosis, conforming to a dose–effect relationship and time–effect relationship. Results from network pharmacology and molecular docking suggested that evodiamine might interact with IRS4 to suppress growth of human vemurafenib-resistant melanoma cells. Interestingly, evodiamine suppressed IRS4 expression and then inhibited PI3K/AKT signaling pathway, and thus had the therapeutic action on vemurafenib-resistant melanoma.</p></div>","PeriodicalId":654,"journal":{"name":"Journal of Natural Medicines","volume":"78 2","pages":"342 - 354"},"PeriodicalIF":2.5,"publicationDate":"2024-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139696634","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":"Phytohemagglutinin from Phaseolus vulgaris enhances the lung cancer cell chemotherapy sensitivity by changing cell membrane permeability","authors":"Peipei Wang, Shitong Min, Congliang Chen, Junmei Hu, Dapeng Wei, Xia Wang","doi":"10.1007/s11418-023-01772-0","DOIUrl":"10.1007/s11418-023-01772-0","url":null,"abstract":"<div><p>Chemotherapy is still a prevalent strategy for clinical lung cancer treatment. However, the inevitable emerged drug resistance has become a great hurdle to therapeutic effect. Studies have demonstrated that the primary cause of drug resistance is a decrease in the chemotherapeutic medicine concentration. Several lectins have been confirmed to be effective as chemotherapy adjuvants, enhancing the anti-tumor effects of chemotherapy drugs. Here, we combined phytohemagglutinin (PHA), which has been reported possess anti-tumor effects, with chemotherapy drugs Cisplatin (DDP) and Adriamycin (ADM) on lung cancer cells to detect the sensitivities of PHA as a chemotherapy adjuvant. Our results demonstrated that the PHA significantly enhanced the sensitivity of lung cancer cells to DDP and ADM, and Western blot showed that PHA combined with DDP or ADM enhance cytotoxic effects by inhibiting autophagy and promoting apoptosis. More importantly, we found PHA enhanced the chemotherapeutic drugs cytotoxicity by changing the cell membrane to increase the intracellular chemotherapeutic drugs concentration. Besides, the combination of PHA and ADM increased the ADM concentration in the multidrug-resistant strain A549-R cells and achieved the drug sensitization effect. Our results suggest that PHA combined with chemotherapy can be applied in the treatment of lung cancer cells and lung cancer multidrug-resistant strains, and provide a novel strategy for clinical tumor chemotherapy and a new idea to solve the problem of drug resistance in clinical lung cancer.</p></div>","PeriodicalId":654,"journal":{"name":"Journal of Natural Medicines","volume":"78 2","pages":"355 - 369"},"PeriodicalIF":2.5,"publicationDate":"2024-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139540981","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":"Linderapyrone analogue LPD-01 as a cancer treatment agent by targeting importin7","authors":"Takahiro Kitagawa, Takahiro Matsumoto, Tomoe Ohta, Tatsusada Yoshida, Youhei Saito, Yuji Nakayama, Yuki Hadate, Eishi Ashihara, Tetsushi Watanabe","doi":"10.1007/s11418-023-01774-y","DOIUrl":"10.1007/s11418-023-01774-y","url":null,"abstract":"<div><p>The Wnt/<i>β</i>-catenin signaling pathway plays important roles in several cancer cells, including cell proliferation and development. We previously succeeded in synthesizing a small molecule compound inhibiting the Wnt/<i>β</i>-catenin signaling pathway, named LPD-01 (<b>1</b>), and <b>1</b> inhibited the growth of human colorectal cancer (HT-29) cells. In this study, we revealed that <b>1</b> inhibits the growth of HT-29 cells stronger than that of another human colorectal cancer (SW480) cells. Therefore, we have attempted to identify the target proteins of <b>1</b> in HT-29 cells. Firstly, we investigated the effect on the expression levels of the Wnt/<i>β</i>-catenin signaling pathway<b>-</b>related proteins. As a result, <b>1</b> inhibited the expression of target proteins of Wnt/<i>β</i>-catenin signaling pathway (c-Myc and Survivin) and their genes, whereas the amount of transcriptional co-activator (<i>β</i>-catenin) was not decreased, suggesting that <b>1</b> inhibited the Wnt/<i>β</i>-catenin signaling pathway without affecting β-catenin. Next, we investigated the target proteins of <b>1</b> using magnetic FG beads. Chemical pull-down assay combined with mass spectrometry suggested that <b>1</b> directly binds to importin7. As expected, <b>1</b> inhibited the nuclear translocation of importin7 cargoes such as Smad2 and Smad3 in TGF-<i>β</i>-stimulated HT-29 cells. In addition, the knockdown of importin7 by siRNA reduced the expression of target genes of Wnt/<i>β</i>-catenin signaling pathway. These results suggest that importin7 is one of the target proteins of <b>1</b> for inhibition of the Wnt/<i>β</i>-catenin signaling pathway.</p><h3>Graphical abstract</h3>\u0000<div><figure><div><div><picture><img></picture></div></div></figure></div></div>","PeriodicalId":654,"journal":{"name":"Journal of Natural Medicines","volume":"78 2","pages":"370 - 381"},"PeriodicalIF":2.5,"publicationDate":"2024-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139540932","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}
Rui Zeng, Yuefan Zhang, Shengtong Shi, Xianqin Long, Haixia Zhang, Min Wang, Jianfeng Shi, Ye Jiang, Bin Chen
{"title":"Study on the mechanism of Panax notoginseng–Salvia miltiorrhiza herb pair on invigorating blood circulation and eliminating blood stasis by blocking the conversion of arachidonic acid to prostaglandin","authors":"Rui Zeng, Yuefan Zhang, Shengtong Shi, Xianqin Long, Haixia Zhang, Min Wang, Jianfeng Shi, Ye Jiang, Bin Chen","doi":"10.1007/s11418-023-01773-z","DOIUrl":"10.1007/s11418-023-01773-z","url":null,"abstract":"<div><p>We combined untargeted and targeted metabolomics to explore the mechanism of blood circulation and blood stasis activation in the traditional Chinese herb pair <i>Panax notoginseng</i>–<i>Salvia miltiorrhiza</i> (PS). In this study, the right hind limb of SD rats was struck by a 1 kg weight, causing traumatic blood stasis (TBS) model, then the rats were gavaged with PS (at ratios of 1:0, 0:1, 3:1, 1:1, and 1:3) for 5 consecutive days. At the end of treatment, blood samples were collected for blood rheology and metabolomics analysis, and muscle tissues of injured limbs were used for HE staining and q-PCR analysis. The results showed that different ratios of PS reduced swelling and improved stasis and blood viscosity in the injured limbs of rats, and intervened in metabolism by modulating 11, 11, 17, 15, and 13 differential metabolites, respectively. The PS (3:1) shows the best treatment effect and the most differential metabolites regression. Targeted metabolomics shows that PS (3:1) can increase the content of AA, and reduce the content of PGF<sub>2</sub>-α by down-regulating the expression of enzymes Ptgs1 and Cbrl12 and up-regulating the expression of enzyme Hpgd. These results suggested that the PS herb pair exerts its blood stasis activating effects by blocking the conversion of arachidonic acid to prostaglandins.</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":"78 2","pages":"411 - 426"},"PeriodicalIF":2.5,"publicationDate":"2024-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139519110","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}
Muhammad Fitrah, Syatirah Djalaluddin, Zhichao Wang, Kana Nishida, Hideaki Otsuka, Katsuyoshi Matsunami
{"title":"Revision of NMR assignment for Morin-3-O-glucoside and microbial production of Morin-2’-O-glucoside","authors":"Muhammad Fitrah, Syatirah Djalaluddin, Zhichao Wang, Kana Nishida, Hideaki Otsuka, Katsuyoshi Matsunami","doi":"10.1007/s11418-023-01771-1","DOIUrl":"10.1007/s11418-023-01771-1","url":null,"abstract":"<div><p>Morin is a flavonol having 2’,4’-dihydroxy group on B-ring identified especially in <i>Moraceae</i> plants. While morin is widely known, its glycosides are relatively rare. To the best of our knowledge, morin-3-<i>O</i>-glucoside (<b>1</b>) was first reported in 2008. However, the reported chemical shift values of <b>1</b> were unsatisfactory with those of the aglycone, morin, which is rather similar to quercetin-3-<i>O</i>-glucoside (<b>2</b>). Therefore, we prepared morin-3-<i>O</i>-glucoside (<b>1</b>) by microbial transformation of morin with <i>Cunninghamella</i> sp., and the NMR assignment was reinvestigated. The microbial culture also produced another compound (<b>3</b>). The NMR and MS analyses of <b>3</b> revealed it as a novel compound, morin-2’-<i>O</i>-glucoside (<b>3</b>).</p><p>In this study, the revision of the NMR assignment of morin-3-<i>O</i>-glucoside (<b>1</b>), and the preparation and structural elucidation of a novel compound, morin-2’-<i>O</i>-glucoside (<b>3</b>), were described.</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":"78 2","pages":"403 - 410"},"PeriodicalIF":2.5,"publicationDate":"2024-01-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139490487","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":"Improved quantitative analysis of tenuifolin using hydrolytic continuous-flow system to build prediction models for its content based on near-infrared spectroscopy","authors":"Tatsuki Kitazoe, Chisato Usui, Eiichi Kodaira, Takuro Maruyama, Noriaki Kawano, Hiroyuki Fuchino, Kazuhiko Yamamoto, Yasushi Kitano, Nobuo Kawahara, Kayo Yoshimatsu, Tatsuya Shirahata, Yoshinori Kobayashi","doi":"10.1007/s11418-023-01764-0","DOIUrl":"10.1007/s11418-023-01764-0","url":null,"abstract":"<div><p>This study used two types of analyses and statistical calculations on powdered samples of Polygala root (PR) and Senega root (SR): (1) determination of saponin content by an independently developed quantitative analysis of tenuifolin content using a flow reactor, and (2) near-infrared spectroscopy (NIR) using crude drug powders as direct samples for metabolic profiling. Furthermore, a prediction model for tenuifolin content was developed and validated using multivariate analysis based on the results of (1) and (2). The goal of this study was to develop a rapid analytical method utilizing the saponin content and explore the possibility of quality control through a wide-area survey of crude drugs using NIR spectroscopy. Consequently, various parameters and appropriate wavelengths were examined in the regression analysis, and a model with a reasonable contribution rate and prediction accuracy was successfully developed. In this case, the wavenumber contributing to the model was consistent with that of tenuifolin, confirming that this model was based on saponin content. In this series of analyses, we have succeeded in developing a model that can quickly estimate saponin content without post-processing and have demonstrated a brief way to perform quality control of crude drugs in the clinical field and on the market.</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":"78 2","pages":"296 - 311"},"PeriodicalIF":2.5,"publicationDate":"2024-01-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139085433","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}
Lingling Xuan, Song Yang, Lulu Ren, He Liu, Wen Zhang, Yuan Sun, Benshan Xu, Lili Gong, Lihong Liu
{"title":"Akebia saponin D attenuates allergic airway inflammation through AMPK activation","authors":"Lingling Xuan, Song Yang, Lulu Ren, He Liu, Wen Zhang, Yuan Sun, Benshan Xu, Lili Gong, Lihong Liu","doi":"10.1007/s11418-023-01762-2","DOIUrl":"10.1007/s11418-023-01762-2","url":null,"abstract":"<div><p>Akebia saponin D (ASD) is a bioactive triterpenoid saponin extracted from <i>Dipsacus asper</i> Wall. ex DC.. This study aimed to investigate the effects of ASD on allergic airway inflammation. Human lung epithelial BEAS-2B cells and bone marrow-derived mast cells (BMMCs) were pretreated with ASD (50, 100 and 200 μΜ) and AMPK activator 5-aminoimidazole-4-carboxamide-1-β-D-ribofuranoside (AICAR) (1 mM), and then stimulated with lipopolysaccharide (LPS) or IL-33. Pretreatment with ASD and AICAR significantly inhibited TNF-α and IL-6 production from BEAS-2B cells, and IL-13 production from BMMCs. Moreover, pretreatment with ASD and AICAR significantly increased p-AMPK expression in BEAS-2B cells. Inhibition of AMPK by siRNA and compound C partly abrogated the suppression effect of ASD on TNF-α, IL-6, and IL-13 production. Asthma murine model was induced by ovalbumin (OVA) challenge and treated with ASD (150 and 300 mg/kg) or AICAR (100 mg/kg). Infiltration of eosinophils, neutrophils, monocytes, and lymphocytes, and production of TNF-α, IL-6, IL-4, and IL-13 were attenuated in ASD and AICAR treated mice. Lung histopathological changes were also ameliorated after ASD and AICAR treatment. Additionally, it showed that treatment with ASD and AICAR increased p-AMPK expression in the lung tissues. In conclusion, ASD exhibited protective effects on allergic airway inflammation through the induction of AMPK activation.</p></div>","PeriodicalId":654,"journal":{"name":"Journal of Natural Medicines","volume":"78 2","pages":"393 - 402"},"PeriodicalIF":2.5,"publicationDate":"2024-01-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139085432","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}
Seung-U Son, Hee Won Lee, Ju-Hyeon Park, Kwang-Soon Shin
{"title":"Identification of intracellular activation mechanism of rhamnogalacturonan-I type polysaccharide purified from Panax ginseng leaves in macrophages and roles of component sugar chains on activity","authors":"Seung-U Son, Hee Won Lee, Ju-Hyeon Park, Kwang-Soon Shin","doi":"10.1007/s11418-023-01768-w","DOIUrl":"10.1007/s11418-023-01768-w","url":null,"abstract":"<div><p>This study aimed to investigate the mechanisms underlying intracellular signaling pathways in macrophages in relation to the structural features of rhamnogalacturonan (RG) I-type polysaccharide (PGEP-I) purified from <i>Panax ginseng</i> leaves. For this investigation, we used several specific inhibitors and antibodies against mitogen-activated protein kinase (MAPK), nuclear factor-kappa B (NF-κB), and pattern recognition receptors (PRRs). Furthermore, we investigated the roles of component sugar chains on immunostimulating activity through a sequential enzymatic and chemical degradation steps. We found that PGEP-I effectively induced the phosphorylation of several MAPK- and NF-κB-related proteins, such as p38, cJun N-terminal kinase (JNK), extracellular signal-regulated kinase (ERK), and p65. Particularly, immunocytochemistry analysis confirmed the PGEP-I-induced translocation of p65 into the nucleus. Furthermore, the breakdown of PGEP-I side chains and main chain during sequential enzymatic and chemical degradation reduced the PGEP-I-induced macrophage cytokine secretion activity. IL-6, TNF-α, and NO secreted by macrophages are associated with several signaling pathway proteins such as ERK, JNK, and NF-κB and several PRRs such as dectin-1, CD11b, CD14, TLR2, TLR4, and SR. Thus, these findings suggest that PGEP-I exerts potent macrophage-activating effects, which can be attributed to its typical RG-I structure comprising arabinan, type II arabinogalactan, and rhamnose-galacturonic acid repeating units in the main chain.</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":"78 2","pages":"328 - 341"},"PeriodicalIF":2.5,"publicationDate":"2023-12-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139047964","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}