Pub Date : 2025-12-16DOI: 10.1016/j.fitote.2025.107039
Ludmilla Santana, Viviane de Oliveira Leal, Priscila Mansur Leal, Larissa de Mattos Manhães, Denise Mafra, Natália Alvarenga Borges
Advancements in immunosuppressive therapy have significantly improved long-term graft survival in kidney transplant recipients. Concurrently, the global use of medicinal plants and herbal medicines as complementary and alternative therapies has expanded, with many patients seeking to mitigate adverse effects and enhance their overall well-being. However, the simultaneous use of medicinal plants or herbal medicines alongside conventional immunosuppressive regimens presents significant clinical challenges due to the potential for pharmacokinetic and pharmacodynamic interactions. Many of these natural alternatives contain bioactive compounds that may modulate the metabolism and efficacy of immunosuppressants, either by enhancing or diminishing their therapeutic effects. This modulation often occurs through the induction or inhibition of hepatic cytochrome P450 enzymes and drug transporters, leading to fluctuations in immunosuppressant blood concentrations. Such variations can predispose transplant recipients to graft rejection due to subtherapeutic drug levels or, conversely, to toxicity from supratherapeutic exposure. Beyond pharmacological interactions, contamination of herbal preparations with heavy metals poses an additional risk. Exposure to nephrotoxic metals has been linked to graft dysfunction and an increased risk of graft loss. This narrative review critically examines the current scientific evidence regarding the interactions between medicinal plants and/or herbal medicines and immunosuppressive therapies, highlighting the potential implications for kidney transplant recipients. Also, it discusses the impact on graft survival, patient safety, and the need for greater regulatory oversight in the use of herbal medicines among this vulnerable population.
{"title":"Herb-immunosuppressive drug interactions: Implications for kidney transplant recipients.","authors":"Ludmilla Santana, Viviane de Oliveira Leal, Priscila Mansur Leal, Larissa de Mattos Manhães, Denise Mafra, Natália Alvarenga Borges","doi":"10.1016/j.fitote.2025.107039","DOIUrl":"https://doi.org/10.1016/j.fitote.2025.107039","url":null,"abstract":"<p><p>Advancements in immunosuppressive therapy have significantly improved long-term graft survival in kidney transplant recipients. Concurrently, the global use of medicinal plants and herbal medicines as complementary and alternative therapies has expanded, with many patients seeking to mitigate adverse effects and enhance their overall well-being. However, the simultaneous use of medicinal plants or herbal medicines alongside conventional immunosuppressive regimens presents significant clinical challenges due to the potential for pharmacokinetic and pharmacodynamic interactions. Many of these natural alternatives contain bioactive compounds that may modulate the metabolism and efficacy of immunosuppressants, either by enhancing or diminishing their therapeutic effects. This modulation often occurs through the induction or inhibition of hepatic cytochrome P450 enzymes and drug transporters, leading to fluctuations in immunosuppressant blood concentrations. Such variations can predispose transplant recipients to graft rejection due to subtherapeutic drug levels or, conversely, to toxicity from supratherapeutic exposure. Beyond pharmacological interactions, contamination of herbal preparations with heavy metals poses an additional risk. Exposure to nephrotoxic metals has been linked to graft dysfunction and an increased risk of graft loss. This narrative review critically examines the current scientific evidence regarding the interactions between medicinal plants and/or herbal medicines and immunosuppressive therapies, highlighting the potential implications for kidney transplant recipients. Also, it discusses the impact on graft survival, patient safety, and the need for greater regulatory oversight in the use of herbal medicines among this vulnerable population.</p>","PeriodicalId":12147,"journal":{"name":"Fitoterapia","volume":" ","pages":"107039"},"PeriodicalIF":2.6,"publicationDate":"2025-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145780586","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-15DOI: 10.1016/j.fitote.2025.107036
Gaohui Zhu, Yanhong Luo, Xuejiao Xu, Huijiao Zhang, Min Zhu
{"title":"Corrigendum to \"Anti-diabetic compounds from the seeds of Psoralea corylifolia\" [Fitoterapia 139 (2019) 104373].","authors":"Gaohui Zhu, Yanhong Luo, Xuejiao Xu, Huijiao Zhang, Min Zhu","doi":"10.1016/j.fitote.2025.107036","DOIUrl":"https://doi.org/10.1016/j.fitote.2025.107036","url":null,"abstract":"","PeriodicalId":12147,"journal":{"name":"Fitoterapia","volume":" ","pages":"107036"},"PeriodicalIF":2.6,"publicationDate":"2025-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145767568","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-15DOI: 10.1016/j.fitote.2025.107038
Muhammad Zulqarnain, Sidra Abbas, Muhammad Arfan Zaman, Muhammad Zahid Sarfaraz, Aziz-Ur-Rehman, Tariq Hussain, Abdul Basit, Kasim Sakran Abass
Fasciola spp. is a significant parasitic threat to both humans and livestock, causing estimated economic losses of US$3.2 billion annually, including treatment expenses and reduced on-farm productivity. The study was aimed at performing the phytochemical profiling, evaluation of the anthelmintic activity of Artemisia absinthium against different life stages of Fasciola gigantica, and in silico identification of hit compounds from the extract. The ESI-MS/MS analysis was performed to identify the phytochemicals in the extract. Ovicidal and adulticidal assays were used for in vitro anthelmintic evaluation. Subsequently, in silico molecular docking of identified phytochemicals was conducted against proteins, thioredoxin, glutathione S-transferase, and cathepsin L. Phytochemical analysis identified 22 compounds, including terpenoids, flavonoids, and phenols, and revealed Parishin C and Parishin B as the distinct compounds in the extract. The extract exhibited concentration-dependent ovicidal efficacy, at 50 μg/mL, the percentage of undeveloped ova was 84.33 % for A. absinthium and 88 % for albendazole. In the adulticidal assay, a concentration- and time-dependent response was observed, with comparable efficacy to that of albendazole. In silico results showed the strong inhibitory potential of Parishin C and Parishin B against all protein, and unveiled them as potential hit compounds. These findings validated the anthelmintic activity of A. absinthium and underscore its potential as a natural source of antifasciolic agents. Moreover, the inhibitory activity of parishins across all proteins positions them as promising candidates for the development of novel anthelmintic therapies against drug-resistant Fasciola species.
{"title":"Integrated in vitro and in silico analysis of Artemisia absinthium identifies Parishin C and Parishin B as promising multitarget antifasciolic agents.","authors":"Muhammad Zulqarnain, Sidra Abbas, Muhammad Arfan Zaman, Muhammad Zahid Sarfaraz, Aziz-Ur-Rehman, Tariq Hussain, Abdul Basit, Kasim Sakran Abass","doi":"10.1016/j.fitote.2025.107038","DOIUrl":"https://doi.org/10.1016/j.fitote.2025.107038","url":null,"abstract":"<p><p>Fasciola spp. is a significant parasitic threat to both humans and livestock, causing estimated economic losses of US$3.2 billion annually, including treatment expenses and reduced on-farm productivity. The study was aimed at performing the phytochemical profiling, evaluation of the anthelmintic activity of Artemisia absinthium against different life stages of Fasciola gigantica, and in silico identification of hit compounds from the extract. The ESI-MS/MS analysis was performed to identify the phytochemicals in the extract. Ovicidal and adulticidal assays were used for in vitro anthelmintic evaluation. Subsequently, in silico molecular docking of identified phytochemicals was conducted against proteins, thioredoxin, glutathione S-transferase, and cathepsin L. Phytochemical analysis identified 22 compounds, including terpenoids, flavonoids, and phenols, and revealed Parishin C and Parishin B as the distinct compounds in the extract. The extract exhibited concentration-dependent ovicidal efficacy, at 50 μg/mL, the percentage of undeveloped ova was 84.33 % for A. absinthium and 88 % for albendazole. In the adulticidal assay, a concentration- and time-dependent response was observed, with comparable efficacy to that of albendazole. In silico results showed the strong inhibitory potential of Parishin C and Parishin B against all protein, and unveiled them as potential hit compounds. These findings validated the anthelmintic activity of A. absinthium and underscore its potential as a natural source of antifasciolic agents. Moreover, the inhibitory activity of parishins across all proteins positions them as promising candidates for the development of novel anthelmintic therapies against drug-resistant Fasciola species.</p>","PeriodicalId":12147,"journal":{"name":"Fitoterapia","volume":" ","pages":"107038"},"PeriodicalIF":2.6,"publicationDate":"2025-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145774123","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Harpagoside, a pharmacologically active iridoid glycoside from Harpagophytum procumbens (Devil's Claw), exhibits broad therapeutic properties including anti-inflammatory, antioxidant, analgesic, anticancer, and bone-protective effects. Preclinical studies demonstrate pathway modulation at concentrations of 10-50 μM, targeting NF-κB, AP-1, Nrf2/HO-1, PI3K/Akt, and MAPKs, with in vivo evidence for bone preservation, metabolic regulation, and neuroprotection. Clinical trials using standardized extracts (50-100 mg/day harpagoside or 2.6 g/day powdered root) have reported significant improvements in osteoarthritis and chronic low back pain, with fewer gastrointestinal adverse effects compared to NSAIDs. Unlike previous reviews, this article emphasizes the multi-pathway and systems pharmacology mechanisms of harpagoside, its prodrug-like behavior through biotransformation into active metabolites, and formulation strategies, such as nanoparticles, phospholipid complexes, and semi-synthetic derivatives, to overcome poor oral bioavailability. Current challenges include variability in phytochemical content, limited pharmacokinetic and safety data, and insufficient GLP-compliant long-term toxicity studies. By integrating molecular targets, preclinical and clinical evidence, and advances in delivery technologies, this review positions harpagoside as a prototype multi-target phytochemical with significant translational promise in inflammatory, metabolic, and degenerative disorders.
{"title":"Decoding the mechanistic landscape of harpagoside: From molecular targets to translational pharmacology.","authors":"Harpreet Kaur, Dinesh Kumar, Vinod Gauttam, Ashish Suttee, Romanpreet Kaur, Rajni Tanwar, Suresh Babu Kondaveeti, Neeraj Choudhary","doi":"10.1016/j.fitote.2025.107029","DOIUrl":"https://doi.org/10.1016/j.fitote.2025.107029","url":null,"abstract":"<p><p>Harpagoside, a pharmacologically active iridoid glycoside from Harpagophytum procumbens (Devil's Claw), exhibits broad therapeutic properties including anti-inflammatory, antioxidant, analgesic, anticancer, and bone-protective effects. Preclinical studies demonstrate pathway modulation at concentrations of 10-50 μM, targeting NF-κB, AP-1, Nrf2/HO-1, PI3K/Akt, and MAPKs, with in vivo evidence for bone preservation, metabolic regulation, and neuroprotection. Clinical trials using standardized extracts (50-100 mg/day harpagoside or 2.6 g/day powdered root) have reported significant improvements in osteoarthritis and chronic low back pain, with fewer gastrointestinal adverse effects compared to NSAIDs. Unlike previous reviews, this article emphasizes the multi-pathway and systems pharmacology mechanisms of harpagoside, its prodrug-like behavior through biotransformation into active metabolites, and formulation strategies, such as nanoparticles, phospholipid complexes, and semi-synthetic derivatives, to overcome poor oral bioavailability. Current challenges include variability in phytochemical content, limited pharmacokinetic and safety data, and insufficient GLP-compliant long-term toxicity studies. By integrating molecular targets, preclinical and clinical evidence, and advances in delivery technologies, this review positions harpagoside as a prototype multi-target phytochemical with significant translational promise in inflammatory, metabolic, and degenerative disorders.</p>","PeriodicalId":12147,"journal":{"name":"Fitoterapia","volume":" ","pages":"107029"},"PeriodicalIF":2.6,"publicationDate":"2025-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145755541","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Cordyceps cicadae and Ophiocordyceps sobolifera are entomopathogenic fungi often misidentified due to taxonomic ambiguity, leading to confusion in research and applications. This study compared their metabolite compositions and immunomodulatory activities using molecular identification, chemical profiling, and in vitro assays. High-performance liquid chromatography and LC-MS/MS revealed distinct signatures: C. cicadae lacked myriocin but accumulated N6-(2-hydroxyethyl)adenosine (HEA), while O. sobolifera produced abundant myriocin but no HEA. Beauvericin was enriched in wild C. cicadae, whereas adenosine was consistently present in both species, with higher levels in O. sobolifera. Cordycepin was detected only in artificially cultivated C. cicadae. Functional assays showed that C. cicadae extracts, HEA, and adenosine significantly suppressed C48/80-induced histamine release from mast cells, and ethanol extracts of C. cicadae reduced interleukin-33 (IL-33) activation. In contrast, O. sobolifera water extracts enhanced glucagon-like peptide-1 (GLP-1) secretion, while myriocin, beauvericin, and oosporein were inactive in these pathways. These findings clarify the compositional and functional divergence between the two fungi. The absence of toxic myriocin in C. cicadae supports its safer use in food and medicinal applications, with HEA emerging as a key bioactive marker. Liquid fermentation further enhances HEA levels while reducing beauvericin, suggesting its suitability for controlled production. Meanwhile, O. sobolifera may be explored for GLP-1-related benefits. Overall, this study provides a molecular and functional basis to differentiate the two species and highlights their distinct potential in health applications.
{"title":"Comparative chemical profiles of fruiting bodies and mycelia of Cordyceps cicadae and Ophiocordyceps sobolifera, and Immunometabolic modulation by liquid-fermented mycelia.","authors":"Jui-Hsia Hsu, Ying-Yu Chen, Ting-Wei Lin, I-Tsang Chiang, Lynn-Huey Chiang, Chin-Chu Chen","doi":"10.1016/j.fitote.2025.107028","DOIUrl":"https://doi.org/10.1016/j.fitote.2025.107028","url":null,"abstract":"<p><p>Cordyceps cicadae and Ophiocordyceps sobolifera are entomopathogenic fungi often misidentified due to taxonomic ambiguity, leading to confusion in research and applications. This study compared their metabolite compositions and immunomodulatory activities using molecular identification, chemical profiling, and in vitro assays. High-performance liquid chromatography and LC-MS/MS revealed distinct signatures: C. cicadae lacked myriocin but accumulated N<sup>6</sup>-(2-hydroxyethyl)adenosine (HEA), while O. sobolifera produced abundant myriocin but no HEA. Beauvericin was enriched in wild C. cicadae, whereas adenosine was consistently present in both species, with higher levels in O. sobolifera. Cordycepin was detected only in artificially cultivated C. cicadae. Functional assays showed that C. cicadae extracts, HEA, and adenosine significantly suppressed C48/80-induced histamine release from mast cells, and ethanol extracts of C. cicadae reduced interleukin-33 (IL-33) activation. In contrast, O. sobolifera water extracts enhanced glucagon-like peptide-1 (GLP-1) secretion, while myriocin, beauvericin, and oosporein were inactive in these pathways. These findings clarify the compositional and functional divergence between the two fungi. The absence of toxic myriocin in C. cicadae supports its safer use in food and medicinal applications, with HEA emerging as a key bioactive marker. Liquid fermentation further enhances HEA levels while reducing beauvericin, suggesting its suitability for controlled production. Meanwhile, O. sobolifera may be explored for GLP-1-related benefits. Overall, this study provides a molecular and functional basis to differentiate the two species and highlights their distinct potential in health applications.</p>","PeriodicalId":12147,"journal":{"name":"Fitoterapia","volume":" ","pages":"107028"},"PeriodicalIF":2.6,"publicationDate":"2025-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145755549","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-11DOI: 10.1016/j.fitote.2025.107032
Xiao-Ning Liu, Bo-Tao Lu, Mei Wang, Yue-Tong Zhu, Yong-Xian Cheng, Yan-Zhi Wang
Six new sesquiterpenoids, including two cadinane sesquiterpenoids (1 and 2), four eudesmane sesquiterpenoids (3-6), together with seven known analogues (7-13) and two diphenylheptanes (14 and 15) were isolated from the fruits of Alpinia oxyphylla. The structures of these new compounds were elucidated by analysis of spectroscopic data (NMR) and electronic circular dichroism (ECD) calculations. The cell viability and anti-renal fibrotic activity of compounds 1-6 were analyzed by CCK-8 and Western blot, and compounds 2 and 6 exhibited inhibitory renal fibrosis activity in TGF-β1-induced renal proximal renal tubular cells, and dose-effect relationships were observed in compounds 2 and 6.
{"title":"Sesquiterpenoids from the fruits of Alpinia oxyphylla and their anti-renal fibrosis activities.","authors":"Xiao-Ning Liu, Bo-Tao Lu, Mei Wang, Yue-Tong Zhu, Yong-Xian Cheng, Yan-Zhi Wang","doi":"10.1016/j.fitote.2025.107032","DOIUrl":"10.1016/j.fitote.2025.107032","url":null,"abstract":"<p><p>Six new sesquiterpenoids, including two cadinane sesquiterpenoids (1 and 2), four eudesmane sesquiterpenoids (3-6), together with seven known analogues (7-13) and two diphenylheptanes (14 and 15) were isolated from the fruits of Alpinia oxyphylla. The structures of these new compounds were elucidated by analysis of spectroscopic data (NMR) and electronic circular dichroism (ECD) calculations. The cell viability and anti-renal fibrotic activity of compounds 1-6 were analyzed by CCK-8 and Western blot, and compounds 2 and 6 exhibited inhibitory renal fibrosis activity in TGF-β1-induced renal proximal renal tubular cells, and dose-effect relationships were observed in compounds 2 and 6.</p>","PeriodicalId":12147,"journal":{"name":"Fitoterapia","volume":" ","pages":"107032"},"PeriodicalIF":2.6,"publicationDate":"2025-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145741757","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background and aim: Recent epidemiological studies have highlighted a significant increase in the global prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD). This study explores the hepatoprotective mechanisms of Maren-Tiaogan Decoction (MRTGD), a traditional Chinese medicine (TCM) formulation, using a high-fat diet (HFD) murine model of MASLD. The findings may provide a safer and more effective TCM-based therapeutic option for patients with MASLD.
Experimental procedure: A 12-week HFD-induced mouse model of MASLD was established. MRTGD was administered at high, medium and low doses via oral gavage twice daily as the therapeutic intervention. The chemical constituents of MRTGD were identified using UPLC-MS/MS. Hepatic steatosis and changes in adipocyte area were assessed using hematoxylin and eosin (H&E) staining and Oil Red O staining. Biochemical analyses were conducted to measure serum aminotransferase levels, serum lipid profiles, hepatic lipid content and oxidative stress. Furthermore, mRNA expression and protein abundance of critical regulators governing lipid homeostasis and autophagic flux were quantitatively analyzed through real-time reverse transcription quantitative polymerase chain reaction (RT-qPCR) and Western blot.
Results: MRTGD, containing 467 constituents, exhibits significant protective effects against HFD-induced MASLD/MASH by suppressing elevated serum transaminases and hyperlipidemia, reducing hepatic lipid accumulation and steatosis, ameliorating histopathological alterations and adipocyte hypertrophy, while alleviating hepatocyte apoptosis and hepatic oxidative stress. MRTGD not only effectively restores the abnormal up-regulation of lipogenic proteins (such as SREBP-1c and ACC) and the down-regulation of lipid-catabolizing proteins (including PPARα), but also normalizes the expression levels of the PI3K/AKT/mTOR signaling pathway.
Conclusion: The experimental results demonstrate that MRTGD effectively prevents HFD-induced MASLD, partially through modulation of lipid metabolism and autophagy pathways.
{"title":"Protective effect of Maren-Tiaogan Decoction on high-fat diet-induced MASLD in mice.","authors":"Qianru Zhu, Yujie Ren, Xujie Tang, Shu Jia, Jingyi Wu, Xiaomin Yao, Junling Zhu","doi":"10.1016/j.fitote.2025.107023","DOIUrl":"10.1016/j.fitote.2025.107023","url":null,"abstract":"<p><strong>Background and aim: </strong>Recent epidemiological studies have highlighted a significant increase in the global prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD). This study explores the hepatoprotective mechanisms of Maren-Tiaogan Decoction (MRTGD), a traditional Chinese medicine (TCM) formulation, using a high-fat diet (HFD) murine model of MASLD. The findings may provide a safer and more effective TCM-based therapeutic option for patients with MASLD.</p><p><strong>Experimental procedure: </strong>A 12-week HFD-induced mouse model of MASLD was established. MRTGD was administered at high, medium and low doses via oral gavage twice daily as the therapeutic intervention. The chemical constituents of MRTGD were identified using UPLC-MS/MS. Hepatic steatosis and changes in adipocyte area were assessed using hematoxylin and eosin (H&E) staining and Oil Red O staining. Biochemical analyses were conducted to measure serum aminotransferase levels, serum lipid profiles, hepatic lipid content and oxidative stress. Furthermore, mRNA expression and protein abundance of critical regulators governing lipid homeostasis and autophagic flux were quantitatively analyzed through real-time reverse transcription quantitative polymerase chain reaction (RT-qPCR) and Western blot.</p><p><strong>Results: </strong>MRTGD, containing 467 constituents, exhibits significant protective effects against HFD-induced MASLD/MASH by suppressing elevated serum transaminases and hyperlipidemia, reducing hepatic lipid accumulation and steatosis, ameliorating histopathological alterations and adipocyte hypertrophy, while alleviating hepatocyte apoptosis and hepatic oxidative stress. MRTGD not only effectively restores the abnormal up-regulation of lipogenic proteins (such as SREBP-1c and ACC) and the down-regulation of lipid-catabolizing proteins (including PPARα), but also normalizes the expression levels of the PI3K/AKT/mTOR signaling pathway.</p><p><strong>Conclusion: </strong>The experimental results demonstrate that MRTGD effectively prevents HFD-induced MASLD, partially through modulation of lipid metabolism and autophagy pathways.</p>","PeriodicalId":12147,"journal":{"name":"Fitoterapia","volume":" ","pages":"107023"},"PeriodicalIF":2.6,"publicationDate":"2025-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145741754","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-10DOI: 10.1016/j.fitote.2025.107024
Guanghui Gou, Wenli Bao, Liu Liu, Nannan Xu, Jun Li
Eight previously undescribed amide alkaloids [1-5], including three pairs of enantiomers [(±)-3, (±)-4, and (±)-5], along with 17 known compounds (6-22), were isolated from the fruits of Piper longum L with chromatographic techniques and chiral separation. The planar structures and relative configurations of these compounds were elucidated using HRESIMS and NMR analyses, while the absolute configurations were determined by electronic circular dichroism (ECD) calculations. Compounds 1-22 were assessed for their in vitro NO inhibition, cytotoxic, and anti-diabetic activities. Compounds (+)-5, 7, and 8 showed moderate NO inhibitory activity (10 μM < IC50 < 30 μM). Compounds 1, 9, and 13 exhibited significant cytotoxic effects against HeLa cells, with IC50 values of 9.99 ± 0.62, 6.25 ± 0.32, and 9.61 ± 0.48 μM, respectively. Compounds (+)-4, 7, 8, 9, 11, 12, 13, 15, and 16 showed potent cytotoxicity against HT-29 cells with IC50 values ranging from 2.65 to 7.78 μM. Compounds (+)-4, 6, and 16 exhibited weak cytotoxicity against MCF-7 cells (IC50 > 30 μM). Additionally, compound 6 showed moderate inhibitory activity against α-glucosidase with an IC50 of 112.03 ± 3.69 μM, whereas compound 8 significantly inhibited PTP1B, with an IC50 of 9.06 ± 0.68 μM. These findings offer valuable insights into the potential application of amide alkaloids from P. longum in developing functional foods and pharmaceuticals, highlighting their promise in health promotion.
{"title":"Amide alkaloids from the fruits of Piper longum L. and their bioactivities.","authors":"Guanghui Gou, Wenli Bao, Liu Liu, Nannan Xu, Jun Li","doi":"10.1016/j.fitote.2025.107024","DOIUrl":"10.1016/j.fitote.2025.107024","url":null,"abstract":"<p><p>Eight previously undescribed amide alkaloids [1-5], including three pairs of enantiomers [(±)-3, (±)-4, and (±)-5], along with 17 known compounds (6-22), were isolated from the fruits of Piper longum L with chromatographic techniques and chiral separation. The planar structures and relative configurations of these compounds were elucidated using HRESIMS and NMR analyses, while the absolute configurations were determined by electronic circular dichroism (ECD) calculations. Compounds 1-22 were assessed for their in vitro NO inhibition, cytotoxic, and anti-diabetic activities. Compounds (+)-5, 7, and 8 showed moderate NO inhibitory activity (10 μM < IC<sub>50</sub> < 30 μM). Compounds 1, 9, and 13 exhibited significant cytotoxic effects against HeLa cells, with IC<sub>50</sub> values of 9.99 ± 0.62, 6.25 ± 0.32, and 9.61 ± 0.48 μM, respectively. Compounds (+)-4, 7, 8, 9, 11, 12, 13, 15, and 16 showed potent cytotoxicity against HT-29 cells with IC<sub>50</sub> values ranging from 2.65 to 7.78 μM. Compounds (+)-4, 6, and 16 exhibited weak cytotoxicity against MCF-7 cells (IC<sub>50</sub> > 30 μM). Additionally, compound 6 showed moderate inhibitory activity against α-glucosidase with an IC<sub>50</sub> of 112.03 ± 3.69 μM, whereas compound 8 significantly inhibited PTP1B, with an IC<sub>50</sub> of 9.06 ± 0.68 μM. These findings offer valuable insights into the potential application of amide alkaloids from P. longum in developing functional foods and pharmaceuticals, highlighting their promise in health promotion.</p>","PeriodicalId":12147,"journal":{"name":"Fitoterapia","volume":" ","pages":"107024"},"PeriodicalIF":2.6,"publicationDate":"2025-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145741759","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-10DOI: 10.1016/j.fitote.2025.107033
Tang Chao, Xie Shuangnan, Jia Hongtao, Shen Qi, He Weizhong, Li Bin, Deng Shiyi, Tang Jing, Liu Zhi, Wang Cheng
Astragalus membranaceus (AM), a well-known traditional Chinese medicine (TCM), has been found to exhibit significant therapeutic effects on T2DM. The mechanism of AM (root) extract ameliorating diabetes and its medicinal components were deep inverstigated in this work. A mouse oral trial, LC-HRMS-based untargeted metabolomics, quantitative spectrum effect relationship analysis (QSERA), and network pharmacology was integrated for this studying. With the aid of data-mining by AntDAS (Automatic Data Analysis Strategy) platform, 59 bioactive compounds involved in the Leprdb/db mouse model of T2DM therapy were screened from LC-HRMS fingerprints of AM (root) extract even in the presence of heavily interfered background. The key bioactive AM (root) metabolites, astragaloside and i-arabinose, influence T2DM targets including IL2 and HSP90AA1. Molecular docking experiment revealed high-affinity binding between astragaloside and i-arabinose and these core targets. QSERA predicted the specific regulatory effects of bioactive compounds on T2DM in mice. This integrated approach provides a novel strategy for interpreting the pharmacodynamic effects of AM (root) extract in T2DM, which may facilitate the clinical application of traditional Chinese medicine.
{"title":"Integrating mouse oral trial, LC-HRMS-based untargeted metabolomics and network pharmacology for screening bioactive components of Astragalus membranaceus curing type-II diabetes mellitus (T2DM).","authors":"Tang Chao, Xie Shuangnan, Jia Hongtao, Shen Qi, He Weizhong, Li Bin, Deng Shiyi, Tang Jing, Liu Zhi, Wang Cheng","doi":"10.1016/j.fitote.2025.107033","DOIUrl":"https://doi.org/10.1016/j.fitote.2025.107033","url":null,"abstract":"<p><p>Astragalus membranaceus (AM), a well-known traditional Chinese medicine (TCM), has been found to exhibit significant therapeutic effects on T2DM. The mechanism of AM (root) extract ameliorating diabetes and its medicinal components were deep inverstigated in this work. A mouse oral trial, LC-HRMS-based untargeted metabolomics, quantitative spectrum effect relationship analysis (QSERA), and network pharmacology was integrated for this studying. With the aid of data-mining by AntDAS (Automatic Data Analysis Strategy) platform, 59 bioactive compounds involved in the Leprdb/db mouse model of T2DM therapy were screened from LC-HRMS fingerprints of AM (root) extract even in the presence of heavily interfered background. The key bioactive AM (root) metabolites, astragaloside and i-arabinose, influence T2DM targets including IL2 and HSP90AA1. Molecular docking experiment revealed high-affinity binding between astragaloside and i-arabinose and these core targets. QSERA predicted the specific regulatory effects of bioactive compounds on T2DM in mice. This integrated approach provides a novel strategy for interpreting the pharmacodynamic effects of AM (root) extract in T2DM, which may facilitate the clinical application of traditional Chinese medicine.</p>","PeriodicalId":12147,"journal":{"name":"Fitoterapia","volume":" ","pages":"107033"},"PeriodicalIF":2.6,"publicationDate":"2025-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145741822","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-09DOI: 10.1016/j.fitote.2025.107035
Yuan Gao, Jia-Hui Wang, Ming-Qian Han, Rong Huang, Shao-Hua Wu
Three racemic pairs of new dimeric phthalides, (±)-phomophthalides A-C ((±)-1-3), together with eight known compounds (4-11), were obtained from the culture broth of the endophytic fungus Phomopsis sp. YM 355364 isolated from the medicinal plant Aconitum carmichaeli. The chemical structures of the new compounds were established by extensive NMR spectroscopic and HRESI-MS analysis and DP4+ calculations. The new compounds were tested for their antimicrobial activities by broth microdilution method. Compound 1 showed moderate inhibitory activity toward three pathogenic fungal strains Fusarium solani, Candida albicans, and Botrytis cinerea with MIC values of 16, 32, and 32 μg/mL, respectively. Compound 2 exhibited antifungal activity against B. cinerea and C. albicans with MIC values of 16 and 32 μg/mL, respectively.
从药用植物乌头内生真菌Phomopsis sp. YM 355364的培养液中分离得到3对新的二聚体苯酞(±)-phomophthalides A-C(±)-1-3)和8个已知化合物(4-11)。通过NMR、HRESI-MS分析和DP4+计算确定了新化合物的化学结构。用微量肉汤稀释法测定了新化合物的抑菌活性。化合物1对茄灰镰刀菌、白色念珠菌和灰霉病菌具有中等抑制活性,MIC值分别为16、32和32 μg/mL。化合物2对灰绿芽孢杆菌和白色念珠菌的MIC值分别为16和32 μg/mL。
{"title":"Dimeric Phthalides from an endophytic fungus Phomopsis sp. of Aconitum carmichaeli.","authors":"Yuan Gao, Jia-Hui Wang, Ming-Qian Han, Rong Huang, Shao-Hua Wu","doi":"10.1016/j.fitote.2025.107035","DOIUrl":"10.1016/j.fitote.2025.107035","url":null,"abstract":"<p><p>Three racemic pairs of new dimeric phthalides, (±)-phomophthalides A-C ((±)-1-3), together with eight known compounds (4-11), were obtained from the culture broth of the endophytic fungus Phomopsis sp. YM 355364 isolated from the medicinal plant Aconitum carmichaeli. The chemical structures of the new compounds were established by extensive NMR spectroscopic and HRESI-MS analysis and DP4+ calculations. The new compounds were tested for their antimicrobial activities by broth microdilution method. Compound 1 showed moderate inhibitory activity toward three pathogenic fungal strains Fusarium solani, Candida albicans, and Botrytis cinerea with MIC values of 16, 32, and 32 μg/mL, respectively. Compound 2 exhibited antifungal activity against B. cinerea and C. albicans with MIC values of 16 and 32 μg/mL, respectively.</p>","PeriodicalId":12147,"journal":{"name":"Fitoterapia","volume":" ","pages":"107035"},"PeriodicalIF":2.6,"publicationDate":"2025-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145741789","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}