Pub Date : 2026-01-14DOI: 10.1016/j.phanu.2026.100472
Amol Patil, Durgacharan Bhagwat
Caffeic acid (CA) is a naturally occurring phenolic compound found in coffee, fruits, vegetables, and herbs. It exhibits significant anticancer potential via multiple biological mechanisms. In healthy cells, CA acts as an antioxidant, while in cancer cells it exerts pro-oxidant effects that promote cytotoxicity. CA induces apoptosis through Bcl-2 suppression, cytochrome c release, and caspase activation. Furthermore, it inhibits tumor metastasis by downregulating Snail and matrix metalloproteinases, and counters multidrug resistance by inhibiting efflux pump activity. CA’s derivative, caffeic acid phenethyl ester (CAPE), shares these properties and exhibits synergistic effects with chemotherapeutic agents such as tamoxifen and doxorubicin. Despite compelling preclinical evidence, clinical application is limited by CA’s low bioavailability and rapid metabolism. Innovative drug delivery strategies, including nanoparticles, liposomes, and targeted systems, are being explored to overcome these challenges. Early-phase clinical trials in cancers are underway, investigating CA as a potential adjuvant or chemosensitizer. While clinical data remain sparse, CA holds promise as an integrative component in cancer therapy, warranting further investigation in well-designed clinical studies.
{"title":"Caffeic acid and its derivatives as multifunctional anticancer agents: From mechanisms to clinical prospects","authors":"Amol Patil, Durgacharan Bhagwat","doi":"10.1016/j.phanu.2026.100472","DOIUrl":"10.1016/j.phanu.2026.100472","url":null,"abstract":"<div><div>Caffeic acid (CA) is a naturally occurring phenolic compound found in coffee, fruits, vegetables, and herbs. It exhibits significant anticancer potential via multiple biological mechanisms. In healthy cells, CA acts as an antioxidant, while in cancer cells it exerts pro-oxidant effects that promote cytotoxicity. CA induces apoptosis through Bcl-2 suppression, cytochrome c release, and caspase activation. Furthermore, it inhibits tumor metastasis by downregulating Snail and matrix metalloproteinases, and counters multidrug resistance by inhibiting efflux pump activity. CA’s derivative, caffeic acid phenethyl ester (CAPE), shares these properties and exhibits synergistic effects with chemotherapeutic agents such as tamoxifen and doxorubicin. Despite compelling preclinical evidence, clinical application is limited by CA’s low bioavailability and rapid metabolism. Innovative drug delivery strategies, including nanoparticles, liposomes, and targeted systems, are being explored to overcome these challenges. Early-phase clinical trials in cancers are underway, investigating CA as a potential adjuvant or chemosensitizer. While clinical data remain sparse, CA holds promise as an integrative component in cancer therapy, warranting further investigation in well-designed clinical studies.</div></div>","PeriodicalId":20049,"journal":{"name":"PharmaNutrition","volume":"35 ","pages":"Article 100472"},"PeriodicalIF":2.4,"publicationDate":"2026-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145978188","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-01DOI: 10.1016/j.phanu.2025.100471
Partha Pratim Sarma , Santanu Das , Swarnali Bhattacharjee , Mojibur R. Khan , Rajlakshmi Devi
Fruits and vegetables, including their derivatives or preparations, play a crucial role in maintaining overall human health due to their rich nutrient content, including vitamins, minerals, fibre, and antioxidants. Musa balbisiana (MB) and Garcinia pedunculata (GP) are two versatile medicinal plants, widely used by the ethnic people of the Indian subcontinent for their remarkable health benefits, without much scientific study. In this study, we investigated the beneficial effects of these fruit preparations on lowering lipid parameters and gut microbiota in aged albino Wistar rats. Our results indicate the potential of MB and GC (a candy prepared from GP) in managing blood lipid profiles such as HDL, LDL, cholesterol, triglycerides, liver enzymes, and kidney parameters. Additionally, microbiota study revealed higher bacterial diversity (alpha diversity) and a significant increase in beneficial gut bacteria such as Muribaculum, Phocaeicola, and Ruminococcus following the administration of GC and MB. Additionally, dominant taxa at the genus level showed a strong association with serum biochemical markers. GC-MS analysis identified important fecal metabolites with a significant role in managing gut microbial metabolism and systemic physiological responses. Overall, this study suggests the beneficial effects of MB and GC in managing healthy aging and gut microbial composition, thereby maintaining healthy gastrointestinal physiology.
{"title":"Beneficial effects of Musa balbisiana fruit pulp and Garcinia candy on gut microbiota alterations of aged albino Wistar rats","authors":"Partha Pratim Sarma , Santanu Das , Swarnali Bhattacharjee , Mojibur R. Khan , Rajlakshmi Devi","doi":"10.1016/j.phanu.2025.100471","DOIUrl":"10.1016/j.phanu.2025.100471","url":null,"abstract":"<div><div>Fruits and vegetables, including their derivatives or preparations, play a crucial role in maintaining overall human health due to their rich nutrient content, including vitamins, minerals, fibre, and antioxidants. <em>Musa balbisiana</em> (MB) and <em>Garcinia pedunculata</em> (GP) are two versatile medicinal plants, widely used by the ethnic people of the Indian subcontinent for their remarkable health benefits, without much scientific study. In this study, we investigated the beneficial effects of these fruit preparations on lowering lipid parameters and gut microbiota in aged albino Wistar rats. Our results indicate the potential of MB and GC (a candy prepared from GP) in managing blood lipid profiles such as HDL, LDL, cholesterol, triglycerides, liver enzymes, and kidney parameters. Additionally, microbiota study revealed higher bacterial diversity (alpha diversity) and a significant increase in beneficial gut bacteria such as <em>Muribaculum</em>, <em>Phocaeicola</em>, and <em>Ruminococcus</em> following the administration of GC and MB. Additionally, dominant taxa at the genus level showed a strong association with serum biochemical markers. GC-MS analysis identified important fecal metabolites with a significant role in managing gut microbial metabolism and systemic physiological responses. Overall, this study suggests the beneficial effects of MB and GC in managing healthy aging and gut microbial composition, thereby maintaining healthy gastrointestinal physiology.</div></div>","PeriodicalId":20049,"journal":{"name":"PharmaNutrition","volume":"35 ","pages":"Article 100471"},"PeriodicalIF":2.4,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145926821","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-24DOI: 10.1016/j.phanu.2025.100470
Qiao Zhang , Yuqi Tang , Hao Nie , Xu Wang , Guangkui Wang , Chaoqiang Xiao
Calcium is essential for bone health and various physiological processes, but the poor water solubility of calcium supplements often leads to inadequate absorption and potential adverse reactions, such as gastrointestinal discomfort. This study aims to evaluate and compare the in vitro dissolution characteristics and pharmacological performance of five commonly used calcium supplement preparations, with the goal of identifying formulations that offer improved solubility and bioavailability. We examined physical properties, pH values, and calcium dissolution content in artificial gastric fluid. Dissolved drug solutions were analyzed using online Raman spectroscopy, providing real-time insights into chemical transformations during dissolution. The in vitro dissolution profiles ranging from clear to turbid and pH values from 4.52 ± 0.05–10.18 ± 0.01. Calcium dissolution rates ranged from 47.53 ± 2.91 % to 88.65 ± 0.90 %. Online Raman spectroscopy revealed that calcium in compound calcium carbonate effervescent granules was transformed into calcium citrate malate, which exhibited high calcium content, weak acidity, and good water solubility as the most notable differences among the supplements. These findings highlight the large performance differences among various calcium carbonate preparations, providing a foundation for studies of calcium formulations with weak acidity and high water solubility. This study reveals insights for the development of calcium supplements with improved solubility and absorption; offers targeted suggestions for enhancing current quality standards; and provides a basis for rational selection of calcium supplements for different populations, including children, pregnant women, and other special groups, potentially improving clinical outcomes and overall health benefits.
{"title":"Pharmacological characteristics and solubility profiles of calcium supplement preparations: A comparative study with clinical implications","authors":"Qiao Zhang , Yuqi Tang , Hao Nie , Xu Wang , Guangkui Wang , Chaoqiang Xiao","doi":"10.1016/j.phanu.2025.100470","DOIUrl":"10.1016/j.phanu.2025.100470","url":null,"abstract":"<div><div>Calcium is essential for bone health and various physiological processes, but the poor water solubility of calcium supplements often leads to inadequate absorption and potential adverse reactions, such as gastrointestinal discomfort. This study aims to evaluate and compare the in vitro dissolution characteristics and pharmacological performance of five commonly used calcium supplement preparations, with the goal of identifying formulations that offer improved solubility and bioavailability. We examined physical properties, pH values, and calcium dissolution content in artificial gastric fluid. Dissolved drug solutions were analyzed using online Raman spectroscopy, providing real-time insights into chemical transformations during dissolution. The <em>in vitro</em> dissolution profiles ranging from clear to turbid and pH values from 4.52 ± 0.05–10.18 ± 0.01. Calcium dissolution rates ranged from 47.53 ± 2.91 % to 88.65 ± 0.90 %. Online Raman spectroscopy revealed that calcium in compound calcium carbonate effervescent granules was transformed into calcium citrate malate, which exhibited high calcium content, weak acidity, and good water solubility as the most notable differences among the supplements. These findings highlight the large performance differences among various calcium carbonate preparations, providing a foundation for studies of calcium formulations with weak acidity and high water solubility. This study reveals insights for the development of calcium supplements with improved solubility and absorption; offers targeted suggestions for enhancing current quality standards; and provides a basis for rational selection of calcium supplements for different populations, including children, pregnant women, and other special groups, potentially improving clinical outcomes and overall health benefits.</div></div>","PeriodicalId":20049,"journal":{"name":"PharmaNutrition","volume":"35 ","pages":"Article 100470"},"PeriodicalIF":2.4,"publicationDate":"2025-12-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145842091","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","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.phanu.2025.100468
Luis E. Simental-Mendía , Paola Aguillón-Marín , Amirhossein Sahebkar
Background
Omega-3 fatty acids exhibit health benefits, including anti-inflammatory, cardioprotective, anti-cancer, and anti-arthritis properties. However, the effect of omega-3 polyunsaturated fatty acids (PUFA) on lipoprotein(a) [Lp(a)], which is causally associated with atherosclerotic cardiovascular disease, is inconsistent. While some studies have shown a significant decrease in Lp(a) levels, others have found no significant changes after omega-3 PUFA administration. Therefore, the goal of this meta-analysis of randomized controlled trials was to investigate the effect of omega-3 supplementation on plasma Lp(a) levels.
Methods
A systematic literature search was performed in PubMed, Scopus, Web of Science, ClinicalTrials.gov, and Google Scholar databases from inception to February 14, 2025. A fixed-effects model and the generic inverse variance weighting method were employed for meta-analysis.
Results
A total of 12 randomized controlled trials, comprising 9722 participants, were included in the meta-analysis. The results showed no significant effect of omega-3 supplementation on plasma Lp(a) concentrations (WMD: −0.54 mg/dL, 95 % CI: −1.52, 0.44, p = 0.28, I2 = 4 %). This finding was robust in the leave-one-out sensitivity analysis. Additionally, there were no significant changes in Lp(a) values after omega-3 administration in the subset of clinical trials with baseline Lp(a) < 30 mg/dL (WMD: −0.48 mg/dL, 95 % CI: −1.47, 0.51, p = 0.35, I2 = 0 %) and ≥ 30 mg/dL (WMD: −5.03 mg/dL, 95 % CI: −13.42, 3.37, p = 0.24, I2 = 22 %).
Conclusion
The findings of our study suggest that omega-3 supplementation does not affect plasma Lp(a) levels.
{"title":"Effect of omega-3 supplementation on plasma lipoprotein(a) levels: A systematic review and meta-analysis of randomized controlled trials","authors":"Luis E. Simental-Mendía , Paola Aguillón-Marín , Amirhossein Sahebkar","doi":"10.1016/j.phanu.2025.100468","DOIUrl":"10.1016/j.phanu.2025.100468","url":null,"abstract":"<div><h3>Background</h3><div>Omega-3 fatty acids exhibit health benefits, including anti-inflammatory, cardioprotective, anti-cancer, and anti-arthritis properties. However, the effect of omega-3 polyunsaturated fatty acids (PUFA) on lipoprotein(a) [Lp(a)], which is causally associated with atherosclerotic cardiovascular disease, is inconsistent. While some studies have shown a significant decrease in Lp(a) levels, others have found no significant changes after omega-3 PUFA administration. Therefore, the goal of this meta-analysis of randomized controlled trials was to investigate the effect of omega-3 supplementation on plasma Lp(a) levels.</div></div><div><h3>Methods</h3><div>A systematic literature search was performed in PubMed, Scopus, Web of Science, ClinicalTrials.gov, and Google Scholar databases from inception to February 14, 2025. A fixed-effects model and the generic inverse variance weighting method were employed for meta-analysis.</div></div><div><h3>Results</h3><div>A total of 12 randomized controlled trials, comprising 9722 participants, were included in the meta-analysis. The results showed no significant effect of omega-3 supplementation on plasma Lp(a) concentrations (WMD: −0.54 mg/dL, 95 % CI: −1.52, 0.44, <em>p</em> = 0.28, <em>I</em><sup><em>2</em></sup> = 4 %). This finding was robust in the leave-one-out sensitivity analysis. Additionally, there were no significant changes in Lp(a) values after omega-3 administration in the subset of clinical trials with baseline Lp(a) < 30 mg/dL (WMD: −0.48 mg/dL, 95 % CI: −1.47, 0.51, <em>p</em> = 0.35, <em>I</em><sup><em>2</em></sup> = 0 %) and ≥ 30 mg/dL (WMD: −5.03 mg/dL, 95 % CI: −13.42, 3.37, <em>p</em> = 0.24, <em>I</em><sup><em>2</em></sup> = 22 %).</div></div><div><h3>Conclusion</h3><div>The findings of our study suggest that omega-3 supplementation does not affect plasma Lp(a) levels.</div></div>","PeriodicalId":20049,"journal":{"name":"PharmaNutrition","volume":"35 ","pages":"Article 100468"},"PeriodicalIF":2.4,"publicationDate":"2025-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145789330","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
This study aimed to determine the effect of pumpkin (Cucurbita maxima) enriched with calcium carbonate on the PCSK9 gene relative expression level in an animal model of postmenopausal osteoporosis. The study was conducted in forty female Wistar rats, which were divided into five groups: a group fed a standard diet (C) and four ovariectomized groups fed a standard diet (OVX_C): a group receiving a calcium-free diet (OVX_DEF), a group receiving a calcium-deficient diet with the addition of unenriched C.maxima (OVX_P), and the OVX_PCaC group that was fed a diet with the addition of C. maxima enriched with calcium carbonate. After 12 weeks of the dietary intervention, the rats were sacrificed, and their tissues and blood were collected. Serum levels of inflammatory markers, antioxidants, and lipids were measured using enzyme-linked immunosorbent assay method. The PCSK9 gene relative expression level was assessed using quantitative PCR. It was found that ovariectomy decreased PCSK9 gene expression. Enriched C. maxima, particularly with calcium carbonate, increased PCSK9 expression above control levels. LDL and HDL cholesterol concentrations were affected by ovariectomy but not by diet modifications. A significant increase in serum C-reactive protein was observed after consuming unenriched C. maxima, as opposed to C. maxima enriched with calcium. However, after consuming both types of C. maxima, the concentration of cyclooxygenase 2 and lipoxygenase 1 in the serum decreased. These findings indicate that calcium-enriched C. maxima modulates PCSK9 expression, inflammation, and lipid metabolism, offering potential benefits in managing estrogen deficiency-related metabolic disturbances.
{"title":"Calcium carbonate-enriched Cucurbita maxima increases the relative expression level of the PCSK9 gene in the liver of ovariectomized rats","authors":"Natalia Wawrzyniak , Joanna Stecyna , Anna Gramza-Michałowska , Joanna Suliburska","doi":"10.1016/j.phanu.2025.100467","DOIUrl":"10.1016/j.phanu.2025.100467","url":null,"abstract":"<div><div>This study aimed to determine the effect of pumpkin (<em>Cucurbita maxima</em>) enriched with calcium carbonate on the PCSK9 gene relative expression level in an animal model of postmenopausal osteoporosis. The study was conducted in forty female Wistar rats, which were divided into five groups: a group fed a standard diet (C) and four ovariectomized groups fed a standard diet (OVX_C): a group receiving a calcium-free diet (OVX_DEF), a group receiving a calcium-deficient diet with the addition of unenriched <em>C.maxima</em> (OVX_P), and the OVX_PCaC group that was fed a diet with the addition of <em>C. maxima</em> enriched with calcium carbonate. After 12 weeks of the dietary intervention, the rats were sacrificed, and their tissues and blood were collected. Serum levels of inflammatory markers, antioxidants, and lipids were measured using enzyme-linked immunosorbent assay method. The PCSK9 gene relative expression level was assessed using quantitative PCR. It was found that ovariectomy decreased PCSK9 gene expression. Enriched <em>C. maxima</em>, particularly with calcium carbonate, increased PCSK9 expression above control levels. LDL and HDL cholesterol concentrations were affected by ovariectomy but not by diet modifications. A significant increase in serum C-reactive protein was observed after consuming unenriched <em>C. maxima</em>, as opposed to <em>C. maxima</em> enriched with calcium. However, after consuming both types of <em>C. maxima</em>, the concentration of cyclooxygenase 2 and lipoxygenase 1 in the serum decreased. These findings indicate that calcium-enriched <em>C. maxima</em> modulates PCSK9 expression, inflammation, and lipid metabolism, offering potential benefits in managing estrogen deficiency-related metabolic disturbances.</div></div>","PeriodicalId":20049,"journal":{"name":"PharmaNutrition","volume":"35 ","pages":"Article 100467"},"PeriodicalIF":2.4,"publicationDate":"2025-12-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145789238","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-07DOI: 10.1016/j.phanu.2025.100463
Jung Hyun Kwak , Jean Kyung Paik
Background and aims
Selenium consumption influences the association between obesity and hypertension (HTN) in elderly individuals. This study aimed to evaluate the association between obesity and HTN prevalence based on selenium intake in elderly individuals.
Methods and results
The participants were 198 individuals aged ≥ 65 years who visited the Seongnam Elderly Friendly Experience Center and belonged to the active senior group (those with no activity restrictions). Nutritional status was evaluated using a 24-h recall survey conducted by a professional nutritionist. The participants were classified as having HTN if they were diagnosed by a physician. The body mass index was classified as normal (< 23 kg/m2), overweight (23–24.9 kg/m2), or obese (≥ 25 kg/m2). Selenium intake was classified as high or low according to the cutoff average value (50.9 μg/day). Among participants with low selenium intake, analysis adjusted for age, sex, smoking status, alcohol consumption, exercise status, current medication, and dietary factors (intake of carbohydrates, proteins, fat, and fiber) showed that higher body mass index categories had significant dose-dependent trends with a higher risk of HTN (p = 0.004). The odds ratio for HTN in the obese vs. normal weight groups was 8.30 (95 % confidence interval; 1.92–32.91, p < 0.05). However, there was no significant difference between obesity status and HTN in participants with high selenium intake.
Conclusion
Among obese older adults, low selenium intake was significantly associated with an increased prevalence of HTN, whereas this association was not observed in those with higher selenium intake (≥50.9 μg/day).
{"title":"Obesity status, hypertension, and selenium intake in the elderly","authors":"Jung Hyun Kwak , Jean Kyung Paik","doi":"10.1016/j.phanu.2025.100463","DOIUrl":"10.1016/j.phanu.2025.100463","url":null,"abstract":"<div><h3>Background and aims</h3><div>Selenium consumption influences the association between obesity and hypertension (HTN) in elderly individuals. This study aimed to evaluate the association between obesity and HTN prevalence based on selenium intake in elderly individuals.</div></div><div><h3>Methods and results</h3><div>The participants were 198 individuals aged ≥ 65 years who visited the Seongnam Elderly Friendly Experience Center and belonged to the active senior group (those with no activity restrictions). Nutritional status was evaluated using a 24-h recall survey conducted by a professional nutritionist. The participants were classified as having HTN if they were diagnosed by a physician. The body mass index was classified as normal (< 23 kg/m<sup>2</sup>), overweight (23–24.9 kg/m<sup>2</sup>), or obese (≥ 25 kg/m<sup>2</sup>). Selenium intake was classified as high or low according to the cutoff average value (50.9 μg/day). Among participants with low selenium intake, analysis adjusted for age, sex, smoking status, alcohol consumption, exercise status, current medication, and dietary factors (intake of carbohydrates, proteins, fat, and fiber) showed that higher body mass index categories had significant dose-dependent trends with a higher risk of HTN (<em>p</em> = 0.004). The odds ratio for HTN in the obese vs. normal weight groups was 8.30 (95 % confidence interval; 1.92–32.91, p < 0.05). However, there was no significant difference between obesity status and HTN in participants with high selenium intake.</div></div><div><h3>Conclusion</h3><div>Among obese older adults, low selenium intake was significantly associated with an increased prevalence of HTN, whereas this association was not observed in those with higher selenium intake (≥50.9 μg/day).</div></div>","PeriodicalId":20049,"journal":{"name":"PharmaNutrition","volume":"35 ","pages":"Article 100463"},"PeriodicalIF":2.4,"publicationDate":"2025-12-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145753858","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-01DOI: 10.1016/j.phanu.2025.100462
Idrisa Kiryowa , Aya Darwish , Denis Baranenko , Tamer M. El-Messery , Mohamed Said Boulkrane
Leptospermum scoparium, or Manuka honey, contains active elements such as methylglyoxal, methylsyringate, and leptosin that have been identified to possess anti-cancer property. These molecules eradicate cancer cells by a reduction of the AKT/mTOR pathway, the damping of the stress caused by oxidation, and the induction of apoptosis. Studies on animals have proved that those substances have capacities to inhibit the growth of tumors in breast, colorectal, and liver cancers, both in vitro and in vivo. Manuka honey not only protects the body from side effects of chemotherapeutics but also increases the efficiency of the drugs. The usage of this method in clinical practice still holds back due to the bioavailability, variations in the compounds, and the standardization of the dose. Manuka honey has become a potential adjunct therapy that not only enhances the treatment outcomes but also maintains the minimal side effects. This meta-analysis paper pinpoints not only limited potential but, in fact, multi-targeted therapeutic ability the honey possesses. However, despite the growing evidence supporting its biological activity, there are still several challenges to be addressed before its clinical application. These include issues related to bioavailability, standardization of formulations based on UMF classification, and the lack of well-controlled human clinical trials. Additionally, future research should focus on developing advanced delivery systems, such as nanoparticle formulations, to enhance the stability and targeted delivery of the bioactive components in manuka honey. In conclusion, manuka honey holds great promise as a complementary therapy in oncology. With its multi-target mechanisms and robust safety profile, it offers a valuable opportunity for incorporation into cancer treatment protocols. Addressing current application barriers will be essential to fully realize its therapeutic potential in clinical settings.
{"title":"The healing power of Manuka honey: A comprehensive review of its anti-cancer properties","authors":"Idrisa Kiryowa , Aya Darwish , Denis Baranenko , Tamer M. El-Messery , Mohamed Said Boulkrane","doi":"10.1016/j.phanu.2025.100462","DOIUrl":"10.1016/j.phanu.2025.100462","url":null,"abstract":"<div><div>Leptospermum scoparium, or Manuka honey, contains active elements such as methylglyoxal, methylsyringate, and leptosin that have been identified to possess anti-cancer property. These molecules eradicate cancer cells by a reduction of the AKT/mTOR pathway, the damping of the stress caused by oxidation, and the induction of apoptosis. Studies on animals have proved that those substances have capacities to inhibit the growth of tumors in breast, colorectal, and liver cancers, both in vitro and in vivo. Manuka honey not only protects the body from side effects of chemotherapeutics but also increases the efficiency of the drugs. The usage of this method in clinical practice still holds back due to the bioavailability, variations in the compounds, and the standardization of the dose. Manuka honey has become a potential adjunct therapy that not only enhances the treatment outcomes but also maintains the minimal side effects. This meta-analysis paper pinpoints not only limited potential but, in fact, multi-targeted therapeutic ability the honey possesses. However, despite the growing evidence supporting its biological activity, there are still several challenges to be addressed before its clinical application. These include issues related to bioavailability, standardization of formulations based on UMF classification, and the lack of well-controlled human clinical trials. Additionally, future research should focus on developing advanced delivery systems, such as nanoparticle formulations, to enhance the stability and targeted delivery of the bioactive components in manuka honey. In conclusion, manuka honey holds great promise as a complementary therapy in oncology. With its multi-target mechanisms and robust safety profile, it offers a valuable opportunity for incorporation into cancer treatment protocols. Addressing current application barriers will be essential to fully realize its therapeutic potential in clinical settings.</div></div>","PeriodicalId":20049,"journal":{"name":"PharmaNutrition","volume":"34 ","pages":"Article 100462"},"PeriodicalIF":2.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145620253","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-13DOI: 10.1016/j.phanu.2025.100458
Tushar Mishra, Ravinder K. Kaundal
Hepatocellular carcinoma (HCC) is a leading cause of cancer-related mortality worldwide, characterized by limited therapeutic options and poor prognosis. The multifaceted nature of HCC pathogenesis, encompassing oxidative stress, immune dysregulation, angiogenesis, and metabolic reprogramming, underscores the need for multi-targeted treatment strategies. In this study, we employed an integrative network pharmacology approach to elucidate the molecular mechanisms through which Silybum marianum (Milk Thistle) constituents, particularly silymarin, exert anti-HCC effects. A total of 208 overlapping targets between Milk Thistle phytoconstituents and HCC-related genes were identified, with silymarin emerging as the most connected compound. Topological and co-expression analyses revealed 20 hub genes, including TP53, STAT3, MYC, AKT1, ESR1, and BCL2, which regulate apoptosis, proliferation, angiogenesis, and metabolism. Functional classification of these targets showed silymarin's potential to restore apoptosis via BCL2 and Caspase-3 interaction, inhibit hypoxia-induced angiogenesis through HIF-1α disruption, suppress cell cycle progression via CCND1, and impair glycolytic metabolism by targeting AKT1. Molecular docking confirmed strong interactions of silymarin with key oncogenic proteins, suggesting plausible in vivo target engagement. GO and KEGG enrichment analyses highlighted involvement in apoptosis, cytokine signaling, oxidative stress, and immune regulation. Nonetheless, this study provides a systems-level perspective of silymarin’s polypharmacological potential, positioning it as a promising multi-targeted candidate for HCC therapy, especially in overcoming resistance associated with monotherapies.
{"title":"Unveiling the anticancer potential of milk thistle in hepatocellular carcinoma: A network pharmacology perspective","authors":"Tushar Mishra, Ravinder K. Kaundal","doi":"10.1016/j.phanu.2025.100458","DOIUrl":"10.1016/j.phanu.2025.100458","url":null,"abstract":"<div><div>Hepatocellular carcinoma (HCC) is a leading cause of cancer-related mortality worldwide, characterized by limited therapeutic options and poor prognosis. The multifaceted nature of HCC pathogenesis, encompassing oxidative stress, immune dysregulation, angiogenesis, and metabolic reprogramming, underscores the need for multi-targeted treatment strategies. In this study, we employed an integrative network pharmacology approach to elucidate the molecular mechanisms through which Silybum marianum (Milk Thistle) constituents, particularly silymarin, exert anti-HCC effects. A total of 208 overlapping targets between Milk Thistle phytoconstituents and HCC-related genes were identified, with silymarin emerging as the most connected compound. Topological and co-expression analyses revealed 20 hub genes, including TP53, STAT3, MYC, AKT1, ESR1, and BCL2, which regulate apoptosis, proliferation, angiogenesis, and metabolism. Functional classification of these targets showed silymarin's potential to restore apoptosis via BCL2 and Caspase-3 interaction, inhibit hypoxia-induced angiogenesis through HIF-1α disruption, suppress cell cycle progression via CCND1, and impair glycolytic metabolism by targeting AKT1. Molecular docking confirmed strong interactions of silymarin with key oncogenic proteins, suggesting plausible in vivo target engagement. GO and KEGG enrichment analyses highlighted involvement in apoptosis, cytokine signaling, oxidative stress, and immune regulation. Nonetheless, this study provides a systems-level perspective of silymarin’s polypharmacological potential, positioning it as a promising multi-targeted candidate for HCC therapy, especially in overcoming resistance associated with monotherapies.</div></div>","PeriodicalId":20049,"journal":{"name":"PharmaNutrition","volume":"34 ","pages":"Article 100458"},"PeriodicalIF":2.4,"publicationDate":"2025-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145576330","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Inflammatory diseases, including cancers and autoimmune disorders, demand therapeutic strategies that are both effective and associated with fewer side effects. Current treatment modalities, particularly immunosuppressive agents, often exhibit limited efficacy and undesirable outcomes, necessitating exploration into alternative solutions. Natural compounds have emerged as promising candidates for addressing this gap. This review focuses on peiminine, a bioactive alkaloid derived from the Fritillaria species, investigating its potential as a natural therapeutic agent. A comprehensive search was conducted across multiple databases, including MEDLINE, EMBASE, and Scopus, to collate evidence from preclinical studies assessing the anti-inflammatory and disease-modulating properties of peiminine. The findings reveal that peiminine exhibits significant potential in ameliorating a range of conditions, such as cancers, autoimmune diseases, and other inflammation-driven disorders like endometriosis and Parkinson's disease in preclinical stages. Mechanistically, peiminine exerts its effects by inhibiting critical signaling pathways, including NF-κB and ERK, and by regulating cell cycle progression and apoptosis. The preclinical literature highlights its promise as a natural therapeutic agent for future studies such as clinical trials. Harnessing the therapeutic potential of peiminine could pave the way for more effective and safer treatment strategies for inflammatory diseases.
{"title":"Peiminine as an anti-inflammatory agent: Mechanisms and therapeutic applications across diseases","authors":"Amin Azizan , Mohamadali Abyazi , Seyed Kiarash Aghayan , Majid Mirzaei Nodooshan , Akbar Ghorbani Alvanegh , Hadi Esmaeili Gouvarchin Ghaleh","doi":"10.1016/j.phanu.2025.100460","DOIUrl":"10.1016/j.phanu.2025.100460","url":null,"abstract":"<div><div>Inflammatory diseases, including cancers and autoimmune disorders, demand therapeutic strategies that are both effective and associated with fewer side effects. Current treatment modalities, particularly immunosuppressive agents, often exhibit limited efficacy and undesirable outcomes, necessitating exploration into alternative solutions. Natural compounds have emerged as promising candidates for addressing this gap. This review focuses on peiminine, a bioactive alkaloid derived from the Fritillaria species, investigating its potential as a natural therapeutic agent. A comprehensive search was conducted across multiple databases, including MEDLINE, EMBASE, and Scopus, to collate evidence from preclinical studies assessing the anti-inflammatory and disease-modulating properties of peiminine. The findings reveal that peiminine exhibits significant potential in ameliorating a range of conditions, such as cancers, autoimmune diseases, and other inflammation-driven disorders like endometriosis and Parkinson's disease in preclinical stages. Mechanistically, peiminine exerts its effects by inhibiting critical signaling pathways, including NF-κB and ERK, and by regulating cell cycle progression and apoptosis. The preclinical literature highlights its promise as a natural therapeutic agent for future studies such as clinical trials. Harnessing the therapeutic potential of peiminine could pave the way for more effective and safer treatment strategies for inflammatory diseases.</div></div>","PeriodicalId":20049,"journal":{"name":"PharmaNutrition","volume":"34 ","pages":"Article 100460"},"PeriodicalIF":2.4,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145474414","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-01DOI: 10.1016/j.phanu.2025.100461
Wenjie Zhao , Peng Sun , Jiaming Huan , Lei Zhang , Shijing Peng , Tong Jiang , Linghui Kong , Xinghao Zhu , Wenqing Yang , Dongmei Qi , Yunlun Li
Background
Atherosclerosis is the primary contributor to coronary artery disease, peripheral artery disease, and cerebrovascular disease, making it one of the most prevalent causes of mortality worldwide. Macrophages play crucial roles in all stages of atherosclerosis development, providing new avenues for therapeutic interventions due to their inherent plasticity. Consequently, therapies aimed at macrophages may be advantageous for both the prevention and treatment of atherosclerosis. Accumulating evidence strongly indicates that traditional Chinese medicine (TCM) and its derived natural products have remarkable efficacy in modulating macrophage polarization. In this work, we comprehensively summarize the therapeutic potential of diverse natural products, aiming to provide a comprehensive overview.
Methods
A literature search was performed with the keywords “atherosclerosis” or “macrophage polarization” or “herbal medicine” or “natural extracts” or “natural compounds” or “traditional Chinese medicine” or “natural products”. Classic book-based herbal and scientific databases include PubMed, CNKI, SciFinder, Scopus, Web of Science, and Google Scholar.
Results
This review highlights the relationship between macrophage polarization and the progression of atherosclerotic disease and discusses the limitations and future prospects of the current clinical applications of TCM and natural products, as well as the potential for therapeutic strategies targeting macrophages.
Conclusion
A range of natural products, such as ginsenosides, alkaloids, polysaccharides, terpenoids, flavones and quinones, have been shown to affect the treatment of atherosclerosis by modulating macrophage polarization. This study meticulously summarizes their effective dosages both in vitro and in vivo, with the intention of providing valuable insights for further drug development.
背景：动脉硬化是冠状动脉疾病、外周动脉疾病和脑血管疾病的主要诱因，是全球最普遍的死亡原因之一。巨噬细胞在动脉粥样硬化发展的各个阶段起着至关重要的作用，由于其固有的可塑性，为治疗干预提供了新的途径。因此，针对巨噬细胞的治疗可能对预防和治疗动脉粥样硬化都是有利的。越来越多的证据表明，中药及其衍生天然产物在调节巨噬细胞极化方面具有显著的功效。在这项工作中，我们全面总结了各种天然产物的治疗潜力，旨在提供一个全面的概述。方法以“动脉粥样硬化”或“巨噬细胞极化”或“草药”或“天然提取物”或“天然化合物”或“中药”或“天然产物”为关键词进行文献检索。经典的基于书籍的草药和科学数据库包括PubMed， CNKI, SciFinder, Scopus， Web of Science和b谷歌Scholar。结果本文综述了巨噬细胞极化与动脉粥样硬化疾病进展的关系，讨论了目前中药和天然产物临床应用的局限性和未来前景，以及针对巨噬细胞的治疗策略的潜力。结论人参皂苷、生物碱、多糖、萜类、黄酮类和醌类等多种天然产物通过调节巨噬细胞极化而影响动脉粥样硬化的治疗。本研究精心总结了它们在体外和体内的有效剂量，旨在为进一步的药物开发提供有价值的见解。
{"title":"Potential strategies of natural products in the treatment of atherosclerosis: Focusing on modulating macrophage polarization","authors":"Wenjie Zhao , Peng Sun , Jiaming Huan , Lei Zhang , Shijing Peng , Tong Jiang , Linghui Kong , Xinghao Zhu , Wenqing Yang , Dongmei Qi , Yunlun Li","doi":"10.1016/j.phanu.2025.100461","DOIUrl":"10.1016/j.phanu.2025.100461","url":null,"abstract":"<div><h3>Background</h3><div>Atherosclerosis is the primary contributor to coronary artery disease, peripheral artery disease, and cerebrovascular disease, making it one of the most prevalent causes of mortality worldwide. Macrophages play crucial roles in all stages of atherosclerosis development, providing new avenues for therapeutic interventions due to their inherent plasticity. Consequently, therapies aimed at macrophages may be advantageous for both the prevention and treatment of atherosclerosis. Accumulating evidence strongly indicates that traditional Chinese medicine (TCM) and its derived natural products have remarkable efficacy in modulating macrophage polarization. In this work, we comprehensively summarize the therapeutic potential of diverse natural products, aiming to provide a comprehensive overview.</div></div><div><h3>Methods</h3><div>A literature search was performed with the keywords “atherosclerosis” or “macrophage polarization” or “herbal medicine” or “natural extracts” or “natural compounds” or “traditional Chinese medicine” or “natural products”. Classic book-based herbal and scientific databases include PubMed, CNKI, SciFinder, Scopus, Web of Science, and Google Scholar.</div></div><div><h3>Results</h3><div>This review highlights the relationship between macrophage polarization and the progression of atherosclerotic disease and discusses the limitations and future prospects of the current clinical applications of TCM and natural products, as well as the potential for therapeutic strategies targeting macrophages.</div></div><div><h3>Conclusion</h3><div>A range of natural products, such as ginsenosides, alkaloids, polysaccharides, terpenoids, flavones and quinones, have been shown to affect the treatment of atherosclerosis by modulating macrophage polarization. This study meticulously summarizes their effective dosages both <em>in vitro</em> and <em>in vivo</em>, with the intention of providing valuable insights for further drug development.</div></div>","PeriodicalId":20049,"journal":{"name":"PharmaNutrition","volume":"34 ","pages":"Article 100461"},"PeriodicalIF":2.4,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145474417","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
扫码关注我们
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号