Pub Date : 2025-03-01DOI: 10.1016/j.jhip.2025.03.005
Hongyu Bi , Jun Zhu , Yuanxuan Cai , Xiaofang Shangguan , Zherui Chen , Maimoon Shihab Ahmed , Rui Huang
Adverse drug reactions (ADRs) are a significant public health issue, contributing substantially to patient morbidity and mortality. The growing accessibility of genomic technologies has greatly advanced our understanding of the genetics underlying ADRs. Pharmacogenomics, which investigates how genetic polymorphisms influence individual responses to drug therapy on a genome-wide scale, plays a pivotal role in this field. The article summarizes the relationship between ADRs and genes, outlines the current applications and advancements of pharmacogenomics in the prediction, diagnosis, prevention, regulation, and personalized treatment of ADRs, and reviews cutting-edge research methods and large-scale international studies. These insights aim to provide a reference for the future development of pharmacogenomics in ADR research.
{"title":"Review on application and development of pharmacogenomics of adverse drug reactions","authors":"Hongyu Bi , Jun Zhu , Yuanxuan Cai , Xiaofang Shangguan , Zherui Chen , Maimoon Shihab Ahmed , Rui Huang","doi":"10.1016/j.jhip.2025.03.005","DOIUrl":"10.1016/j.jhip.2025.03.005","url":null,"abstract":"<div><div>Adverse drug reactions (ADRs) are a significant public health issue, contributing substantially to patient morbidity and mortality. The growing accessibility of genomic technologies has greatly advanced our understanding of the genetics underlying ADRs. Pharmacogenomics, which investigates how genetic polymorphisms influence individual responses to drug therapy on a genome-wide scale, plays a pivotal role in this field. The article summarizes the relationship between ADRs and genes, outlines the current applications and advancements of pharmacogenomics in the prediction, diagnosis, prevention, regulation, and personalized treatment of ADRs, and reviews cutting-edge research methods and large-scale international studies. These insights aim to provide a reference for the future development of pharmacogenomics in ADR research.</div></div>","PeriodicalId":100787,"journal":{"name":"Journal of Holistic Integrative Pharmacy","volume":"6 1","pages":"Pages 105-116"},"PeriodicalIF":0.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143725795","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-03-01DOI: 10.1016/j.jhip.2025.03.004
Qiu Zhang , Mandong Huang , Xiaoxin Huang , Lu Gan , Yiling Li , Huiying Huang
Objective
This study aims to analyze factors affecting the competitiveness of China's biopharmaceutical industry cluster, offering insights for policymakers and stakeholders, while providing Chinese experience and theoretical support for sustainable development of global biopharmaceutical industry clusters.
Methods
Based on relevant data from Guangdong and Zhejiang Provinces in China, the entropy value method was used to evaluate the comprehensive competitiveness of biopharmaceutical industry clusters in Guangdong and Zhejiang provinces respectively, and the principal component regression method was applied to respectively examine factors affecting the competitiveness of biopharmaceutical industry clusters in Guangdong and Zhejiang provinces.
Results
The competitiveness study showed that the comprehensive competitiveness scores of biopharmaceutical industry clusters in Guangdong and Zhejiang both show an upward trend from 2010 to 2020. From 2010 to 2020, the average value of Zhejiang's competitiveness was 0.53 and Guangdong's was 0.41. The influencing factor study showed that the top five factors affecting the competitiveness of biopharmaceutical industry clusters in Guangdong and Zhejiang were the same, namely, the ratio of general public service expenditure to regional GDP, ratio of regional road freight turnover to regional road mileage, proportion of R&D expenditure to total industrial output, ratio of total healthcare expenditure to provincial consumption, and product sales rate.
Conclusion
The results suggested that core factors affecting the competitiveness of China's biopharmaceutical industry cluster center on four aspects: infrastructure, innovation resources, enterprise performance, and market environment. Therefore, the primary strategy is to strengthen infrastructure construction and investment in innovation resources, while balancing enterprise performance with market environment optimization. This study pioneered the research on factors influencing the competitiveness of China's biopharmaceutical industry cluster, providing a new perspective and reference framework for subsequent research in this field.
{"title":"Study on the factors affecting the competitiveness of biopharmaceutical industry cluster: Evidence from Guangdong and Zhejiang of China","authors":"Qiu Zhang , Mandong Huang , Xiaoxin Huang , Lu Gan , Yiling Li , Huiying Huang","doi":"10.1016/j.jhip.2025.03.004","DOIUrl":"10.1016/j.jhip.2025.03.004","url":null,"abstract":"<div><h3>Objective</h3><div>This study aims to analyze factors affecting the competitiveness of China's biopharmaceutical industry cluster, offering insights for policymakers and stakeholders, while providing Chinese experience and theoretical support for sustainable development of global biopharmaceutical industry clusters.</div></div><div><h3>Methods</h3><div>Based on relevant data from Guangdong and Zhejiang Provinces in China, the entropy value method was used to evaluate the comprehensive competitiveness of biopharmaceutical industry clusters in Guangdong and Zhejiang provinces respectively, and the principal component regression method was applied to respectively examine factors affecting the competitiveness of biopharmaceutical industry clusters in Guangdong and Zhejiang provinces.</div></div><div><h3>Results</h3><div>The competitiveness study showed that the comprehensive competitiveness scores of biopharmaceutical industry clusters in Guangdong and Zhejiang both show an upward trend from 2010 to 2020. From 2010 to 2020, the average value of Zhejiang's competitiveness was 0.53 and Guangdong's was 0.41. The influencing factor study showed that the top five factors affecting the competitiveness of biopharmaceutical industry clusters in Guangdong and Zhejiang were the same, namely, the ratio of general public service expenditure to regional GDP, ratio of regional road freight turnover to regional road mileage, proportion of R&D expenditure to total industrial output, ratio of total healthcare expenditure to provincial consumption, and product sales rate.</div></div><div><h3>Conclusion</h3><div>The results suggested that core factors affecting the competitiveness of China's biopharmaceutical industry cluster center on four aspects: infrastructure, innovation resources, enterprise performance, and market environment. Therefore, the primary strategy is to strengthen infrastructure construction and investment in innovation resources, while balancing enterprise performance with market environment optimization. This study pioneered the research on factors influencing the competitiveness of China's biopharmaceutical industry cluster, providing a new perspective and reference framework for subsequent research in this field.</div></div>","PeriodicalId":100787,"journal":{"name":"Journal of Holistic Integrative Pharmacy","volume":"6 1","pages":"Pages 117-123"},"PeriodicalIF":0.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143760001","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-03-01DOI: 10.1016/j.jhip.2025.02.004
Quanwei Xie , Feirong Zhou , Runan He , Lianbao Ye , Zonghao Lin , Xiangyu Nie , Yuanzheng Wei , Chuqin Yu
Objective
The insoluble compound 1,1′-(2,4,6-trihydroxy-1,3-phenylene)bis(3-methylbutan-1-one) (TPM) is used in preparing a TPM nanocrystals gel (TPM–NCs–gel), and its in vitro antibacterial activity and therapeutic effect on subcutaneous abscesses caused by Staphylococcus aureus were evaluated.
Methods
The effect of a prescription technology on the particle size of a TPM–NCs suspension was investigated using a single factor, and the TPM–NCs prescription was optimized using a Box–Behnken design. A TPM–NCs–gel was prepared using hydroxyethyl cellulose–HHX (HEC–HHX) as a gel matrix and characterized. The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of TPM–NCs–gel were determined with the microdilution method. The susceptibility of Staphylococcus aureus to mupirocin ointment, TPM–NCs–gel, and TPM–gel was evaluated by the disk diffusion method. The efficacy of the TPM–NCs–gel for subcutaneous abscess caused by Staphylococcus aureus was evaluated using a mouse model.
Results
The optimized TPM–NCs prescription consisted of Tween 80 and TPGS (2.47%), TPM (1.24%) and mannitol (2.32%). The size of the TPM–NCs was 98.2 ± 3.9 nm, and the polydispersion coefficient (PDI) was 0.235 ± 0.023. The particle size and PDI of the TPM–NCs–gel were 112.4 ± 7.3 nm and 0.148 ± 0.068, respectively. The MIC and MBC were both 2.98 μg/mL. After 12 days of administration, the bacteria in the abscess site of 2% TPM–NCs–gel experimental group were cleared, the inflammatory cells were reduced, and the skin structure was remodeled.
Conclusion
After TPM was prepared into TPM–NCs–gel, the antibacterial activity was enhanced, Staphylococcus aureus at the site of abscess was effectively removed, and wound healing was promoted.
{"title":"Preparation of TPM–NCs–gel and its effect on subcutaneous abscess caused by Staphylococcus aureus","authors":"Quanwei Xie , Feirong Zhou , Runan He , Lianbao Ye , Zonghao Lin , Xiangyu Nie , Yuanzheng Wei , Chuqin Yu","doi":"10.1016/j.jhip.2025.02.004","DOIUrl":"10.1016/j.jhip.2025.02.004","url":null,"abstract":"<div><h3>Objective</h3><div>The insoluble compound 1,1′-(2,4,6-trihydroxy-1,3-phenylene)bis(3-methylbutan-1-one) (TPM) is used in preparing a TPM nanocrystals gel (TPM–NCs–gel), and its <em>in vitro</em> antibacterial activity and therapeutic effect on subcutaneous abscesses caused by <em>Staphylococcus aureus</em> were evaluated.</div></div><div><h3>Methods</h3><div>The effect of a prescription technology on the particle size of a TPM–NCs suspension was investigated using a single factor, and the TPM–NCs prescription was optimized using a Box–Behnken design. A TPM–NCs–gel was prepared using hydroxyethyl cellulose–HHX (HEC–HHX) as a gel matrix and characterized. The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of TPM–NCs–gel were determined with the microdilution method. The susceptibility of <em>Staphylococcus aureus</em> to mupirocin ointment, TPM–NCs–gel, and TPM–gel was evaluated by the disk diffusion method. The efficacy of the TPM–NCs–gel for subcutaneous abscess caused by <em>Staphylococcus aureus</em> was evaluated using a mouse model.</div></div><div><h3>Results</h3><div>The optimized TPM–NCs prescription consisted of Tween 80 and TPGS (2.47%), TPM (1.24%) and mannitol (2.32%). The size of the TPM–NCs was 98.2 ± 3.9 nm, and the polydispersion coefficient (PDI) was 0.235 ± 0.023. The particle size and PDI of the TPM–NCs–gel were 112.4 ± 7.3 nm and 0.148 ± 0.068, respectively. The MIC and MBC were both 2.98 μg/mL. After 12 days of administration, the bacteria in the abscess site of 2% TPM–NCs–gel experimental group were cleared, the inflammatory cells were reduced, and the skin structure was remodeled.</div></div><div><h3>Conclusion</h3><div>After TPM was prepared into TPM–NCs–gel, the antibacterial activity was enhanced, <em>Staphylococcus aureus</em> at the site of abscess was effectively removed, and wound healing was promoted.</div></div>","PeriodicalId":100787,"journal":{"name":"Journal of Holistic Integrative Pharmacy","volume":"6 1","pages":"Pages 41-49"},"PeriodicalIF":0.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143686159","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-03-01DOI: 10.1016/j.jhip.2025.03.002
Arjun Bilapatte , Anjali More , Kranti Satpute , Shoaeb Mohammad Syed
Objective
This study aimed to develop a novel intranasal drug delivery system for carbamazepine, an antiepileptic drug, to enhance its therapeutic efficacy through targeted and sustained delivery. The goal was to evaluate the suitability of various polymers and excipients for formulating an effective and mucoadhesive nasal gel.
Methods
Ethosomes were prepared using the cold method and evaluated for particle size, zeta potential, entrapment efficiency, and drug release. Gels were formulated using poloxamer 407 and carbopol 934 and characterized for their physicochemical properties. The optimized ethosomal gel was further assessed for mucoadhesive properties and in vitro drug release. Nasal in-situ gels were also prepared using carbopol and HPMC k 100, and their spreadability and drug release profiles were compared.
Results
The optimized ethosomal batch (ET3) exhibited a particle size of 200.7 nm, a zeta potential of −54.8 mV, and a high drug entrapment efficiency of 93%. The in vitro drug release from ET3 was 88.64%. Among the nasal in-situ gels, the carbopol-based batches demonstrated better spreadability compared to HPMC k 100. The optimized in-situ gel batch (G2) showed a gelation temperature of 33.7 °C and an in vitro drug release of 94.05%.
Conclusion
The developed ethosomal gel and in-situ gel formulations demonstrated sustained drug release, enhanced mucoadhesion, and targeted delivery, making them promising alternatives for the treatment of epilepsy. This intranasal delivery system could improve patient compliance and therapeutic outcomes by providing a non-invasive and effective route for carbamazepine administration.
{"title":"Formulation and evaluation of carbamazepine loaded ethosomal nasal in-situ gel for brain targeted drug delivery","authors":"Arjun Bilapatte , Anjali More , Kranti Satpute , Shoaeb Mohammad Syed","doi":"10.1016/j.jhip.2025.03.002","DOIUrl":"10.1016/j.jhip.2025.03.002","url":null,"abstract":"<div><h3>Objective</h3><div>This study aimed to develop a novel intranasal drug delivery system for carbamazepine, an antiepileptic drug, to enhance its therapeutic efficacy through targeted and sustained delivery. The goal was to evaluate the suitability of various polymers and excipients for formulating an effective and mucoadhesive nasal gel.</div></div><div><h3>Methods</h3><div>Ethosomes were prepared using the cold method and evaluated for particle size, zeta potential, entrapment efficiency, and drug release. Gels were formulated using poloxamer 407 and carbopol 934 and characterized for their physicochemical properties. The optimized ethosomal gel was further assessed for mucoadhesive properties and <em>in vitro</em> drug release. Nasal in-situ gels were also prepared using carbopol and HPMC k 100, and their spreadability and drug release profiles were compared.</div></div><div><h3>Results</h3><div>The optimized ethosomal batch (ET3) exhibited a particle size of 200.7 nm, a zeta potential of −54.8 mV, and a high drug entrapment efficiency of 93%. The <em>in vitro</em> drug release from ET3 was 88.64%. Among the nasal in-situ gels, the carbopol-based batches demonstrated better spreadability compared to HPMC k 100. The optimized in-situ gel batch (G2) showed a gelation temperature of 33.7 °C and an <em>in vitro</em> drug release of 94.05%.</div></div><div><h3>Conclusion</h3><div>The developed ethosomal gel and in-situ gel formulations demonstrated sustained drug release, enhanced mucoadhesion, and targeted delivery, making them promising alternatives for the treatment of epilepsy. This intranasal delivery system could improve patient compliance and therapeutic outcomes by providing a non-invasive and effective route for carbamazepine administration.</div></div>","PeriodicalId":100787,"journal":{"name":"Journal of Holistic Integrative Pharmacy","volume":"6 1","pages":"Pages 57-63"},"PeriodicalIF":0.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143686161","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-03-01DOI: 10.1016/j.jhip.2025.02.005
Saili Paul , Anisur Rahman Khuda-Bukhsh
Objective
In homeopathy, ethanolic extract of Carduus marianus (EECM), is used against various liver disorders including cancer. This investigation aims at evaluating hepatoprotective potential of EECM, if any, against p-dimethylaminoazobenzene (pDAB)-induced hepatocarcinogenesis in mouse models in vivo and elucidating its possible underlying mechanism(s).
Methods
Randomized sets of inbred mice were chronically fed with different food regimens for varying periods of time and divided accordingly, 6 mice in each group, into control (Normal I and Alcohol II) and treated groups (III-V); group I: fed Normal diet, group II: Normal diet + Alcohol, group III: pDAB + Phenobarbital (PB), group IV: pDAB + PB + Alcohol, group V: pDAB + PB + EECM. They were sacrificed at day 30, 60, 90 and 120. All routine protocols were deployed for cytogenetical, enzymatic, and histopathological studies. Expressions of B-cell lymphoma 2 (Bcl-2), B-cell lymphoma-extra large (Bcl-xl), Bcl-2 associated X protein (Bax), Cysteine aspartic acid protease-3 (Caspase-3), and Matrix metalloproteinase 9 (MMP-9) were evaluated at day 90 and 120 only. The DPPH free-radical scavenging activity of EECM was estimated to determine the antioxidant properties.
Results
No mice of groups I and II developed tumors in liver at any fixation intervals while all mice of groups (III-IV) developed liver tumors at three fixation intervals. But in group V mice, 4 each of 6 mice at 90 and 120 days, did not show tumor nodules in their livers, signifying that feeding of EECM could combat carcinogenesis. EECM reduced genotoxic effects and favorably modulated expression of Caspase 3 and MMP-9 as compared to control.
Conclusion
The treatment of EECM clearly demonstrated protective action against pDAB induced hepatocarcinogenesis in mice for delaying tumor progression, decreasing total tumor load and genotoxic effects, and also evidenced by favourable modulations of the apoptotic signal proteins like Bcl2, Bcl-xl. Bax, Caspase 3 and other marker enzymes AST (Aspartate amino transferase), ALT (Alanine amino transferase) etc. However, the molecular mechanism of this protective action still needs to be further elucidated.
{"title":"Protective potential of Carduus marianus extract against p-dimethylaminoazobenzene (pDAB) induced hepatocarcinogenesis in mice through apoptosis induction and antioxidant pathway","authors":"Saili Paul , Anisur Rahman Khuda-Bukhsh","doi":"10.1016/j.jhip.2025.02.005","DOIUrl":"10.1016/j.jhip.2025.02.005","url":null,"abstract":"<div><h3>Objective</h3><div>In homeopathy, ethanolic extract of <em>Carduus marianus</em> (EECM)<em>,</em> is used against various liver disorders including cancer. This investigation aims at evaluating hepatoprotective potential of EECM, if any, against p-dimethylaminoazobenzene (pDAB)-induced hepatocarcinogenesis in mouse models <em>in vivo</em> and elucidating its possible underlying mechanism(s).</div></div><div><h3>Methods</h3><div>Randomized sets of inbred mice were chronically fed with different food regimens for varying periods of time and divided accordingly, 6 mice in each group, into control (Normal I and Alcohol II) and treated groups (III-V); group I: fed Normal diet, group II: Normal diet + Alcohol, group III: pDAB + Phenobarbital (PB), group IV: pDAB + PB + Alcohol, group V: pDAB + PB + EECM. They were sacrificed at day 30, 60, 90 and 120. All routine protocols were deployed for cytogenetical, enzymatic, and histopathological studies. Expressions of B-cell lymphoma 2 (Bcl-2), B-cell lymphoma-extra large (Bcl-xl), Bcl-2 associated X protein (Bax), Cysteine aspartic acid protease-3 (Caspase-3), and Matrix metalloproteinase 9 (MMP-9) were evaluated at day 90 and 120 only. The DPPH free-radical scavenging activity of EECM was estimated to determine the antioxidant properties.</div></div><div><h3>Results</h3><div>No mice of groups I and II developed tumors in liver at any fixation intervals while all mice of groups (III-IV) developed liver tumors at three fixation intervals. But in group V mice, 4 each of 6 mice at 90 and 120 days, did not show tumor nodules in their livers, signifying that feeding of EECM could combat carcinogenesis. EECM reduced genotoxic effects and favorably modulated expression of Caspase 3 and MMP-9 as compared to control.</div></div><div><h3>Conclusion</h3><div>The treatment of EECM clearly demonstrated protective action against pDAB induced hepatocarcinogenesis in mice for delaying tumor progression, decreasing total tumor load and genotoxic effects, and also evidenced by favourable modulations of the apoptotic signal proteins like Bcl2, Bcl-xl. Bax, Caspase 3 and other marker enzymes AST (Aspartate amino transferase), ALT (Alanine amino transferase) etc. However, the molecular mechanism of this protective action still needs to be further elucidated.</div></div>","PeriodicalId":100787,"journal":{"name":"Journal of Holistic Integrative Pharmacy","volume":"6 1","pages":"Pages 64-73"},"PeriodicalIF":0.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143686151","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
To evaluate the effectiveness of oral pH-triggered colon-specific ketoprofen-loaded microspheres (C-SKLMs) in managing early morning symptoms of rheumatoid arthritis (RA) through pharmacokinetic and pharmacodynamic assessments.
Methods
Pharmacokinetic parameters, including Tmax, Cmax, and mean residence time (MRT), were analyzed in animals treated with C-SKLMs and compared with pure ketoprofen. Pharmacodynamic evaluations assessed the ability of C-SKLMs to address early morning RA symptoms effectively by aligning drug release with the body's circadian rhythm.
Results
The Tmax for the C-SKLMs group (9.33 ± 1.63 h) was significantly prolonged compared to pure ketoprofen (2 h), indicating delayed drug release tailored to circadian needs. The Cmax for C-SKLMs (5.94 ± 1.20 μg/mL) was lower than that of pure ketoprofen (12.4 ± 3.00 μg/mL), demonstrating a controlled-release profile. Additionally, the MRT for C-SKLMs (12.96 ± 1.42 h) was approximately 1.4 times longer than for pure ketoprofen (9.44 ± 0.69 h), emphasizing extended drug release. Pharmacodynamic evaluations supported the superior effectiveness of C-SKLMs in managing early morning RA symptoms compared to pure ketoprofen.
Conclusion
C-SKLMs demonstrated significant potential to improve the management of early morning symptoms associated with RA through controlled, extended, and circadian-tailored drug release, making them a promising therapeutic approach.
{"title":"Oral pH-triggered colon-specific ketoprofen loaded microspheres for the better management of early morning symptoms associated with rheumatoid arthritis. Part II: Pharmacokinetic and pharmacodynamic assessment in rats","authors":"Krishna Sanka , Prabhakar Reddy Veerareddy , Rajeswara Rao Pragada","doi":"10.1016/j.jhip.2025.03.001","DOIUrl":"10.1016/j.jhip.2025.03.001","url":null,"abstract":"<div><h3>Objective</h3><div>To evaluate the effectiveness of oral pH-triggered colon-specific ketoprofen-loaded microspheres (C-SKLMs) in managing early morning symptoms of rheumatoid arthritis (RA) through pharmacokinetic and pharmacodynamic assessments.</div></div><div><h3>Methods</h3><div>Pharmacokinetic parameters, including T<sub>max</sub>, C<sub>max</sub>, and mean residence time (MRT), were analyzed in animals treated with C-SKLMs and compared with pure ketoprofen. Pharmacodynamic evaluations assessed the ability of C-SKLMs to address early morning RA symptoms effectively by aligning drug release with the body's circadian rhythm.</div></div><div><h3>Results</h3><div>The T<sub>max</sub> for the C-SKLMs group (9.33 ± 1.63 h) was significantly prolonged compared to pure ketoprofen (2 h), indicating delayed drug release tailored to circadian needs. The C<sub>max</sub> for C-SKLMs (5.94 ± 1.20 μg/mL) was lower than that of pure ketoprofen (12.4 ± 3.00 μg/mL), demonstrating a controlled-release profile. Additionally, the MRT for C-SKLMs (12.96 ± 1.42 h) was approximately 1.4 times longer than for pure ketoprofen (9.44 ± 0.69 h), emphasizing extended drug release. Pharmacodynamic evaluations supported the superior effectiveness of C-SKLMs in managing early morning RA symptoms compared to pure ketoprofen.</div></div><div><h3>Conclusion</h3><div>C-SKLMs demonstrated significant potential to improve the management of early morning symptoms associated with RA through controlled, extended, and circadian-tailored drug release, making them a promising therapeutic approach.</div></div>","PeriodicalId":100787,"journal":{"name":"Journal of Holistic Integrative Pharmacy","volume":"6 1","pages":"Pages 83-90"},"PeriodicalIF":0.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143725790","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-03-01DOI: 10.1016/j.jhip.2025.03.003
Lin Yang , Liang Wang , Baofeng Yang , Yue Zhang
Mitochondria play a central role in cardiovascular diseases, primarily by providing cellular energy and facilitating various cardiac functions. Excessive fat accumulation, circadian rhythm disturbances, viral infections, and persistent inflammation can lead to myocarditis, fibrosis, and infarction, thereby exacerbating the progression of cardiovascular diseases. As essential organelles for energy production, mitochondria exhibit remarkable dynamic adaptability and can integrate diverse cellular signaling pathways, endowing myocardial cells with both bioenergetic and biosynthetic versatility. Consequently, targeting mitochondria for cardiovascular disease therapy has gained increasing attention and is applicable to various cardiovascular conditions. Numerous mitochondrial adaptive mechanisms, including dynamics, metabolic processes, and apoptosis regulation, have emerged as promising therapeutic targets. Nevertheless, contemporary investigations into mitochondrial biology have unveiled their intricate structural and functional characteristics, as well as their complex roles within cellular systems, which present obstacles to the clinical implementation of mitochondria-focused cardiovascular therapies. Recent studies have found that traditional Chinese medicine (TCM) possesses the potential to effectively address cardiovascular diseases while enhancing the structural integrity and functional capacity of mitochondria. This review aims to offer a comprehensive analysis of the modulatory effects of TCM on cardiac mitochondria and its therapeutic ramifications for cardiovascular conditions.
{"title":"Mitochondrial function: A new direction for the targeted treatment of cardiovascular diseases with Chinese herbal medicine","authors":"Lin Yang , Liang Wang , Baofeng Yang , Yue Zhang","doi":"10.1016/j.jhip.2025.03.003","DOIUrl":"10.1016/j.jhip.2025.03.003","url":null,"abstract":"<div><div>Mitochondria play a central role in cardiovascular diseases, primarily by providing cellular energy and facilitating various cardiac functions. Excessive fat accumulation, circadian rhythm disturbances, viral infections, and persistent inflammation can lead to myocarditis, fibrosis, and infarction, thereby exacerbating the progression of cardiovascular diseases. As essential organelles for energy production, mitochondria exhibit remarkable dynamic adaptability and can integrate diverse cellular signaling pathways, endowing myocardial cells with both bioenergetic and biosynthetic versatility. Consequently, targeting mitochondria for cardiovascular disease therapy has gained increasing attention and is applicable to various cardiovascular conditions. Numerous mitochondrial adaptive mechanisms, including dynamics, metabolic processes, and apoptosis regulation, have emerged as promising therapeutic targets. Nevertheless, contemporary investigations into mitochondrial biology have unveiled their intricate structural and functional characteristics, as well as their complex roles within cellular systems, which present obstacles to the clinical implementation of mitochondria-focused cardiovascular therapies. Recent studies have found that traditional Chinese medicine (TCM) possesses the potential to effectively address cardiovascular diseases while enhancing the structural integrity and functional capacity of mitochondria. This review aims to offer a comprehensive analysis of the modulatory effects of TCM on cardiac mitochondria and its therapeutic ramifications for cardiovascular conditions.</div></div>","PeriodicalId":100787,"journal":{"name":"Journal of Holistic Integrative Pharmacy","volume":"6 1","pages":"Pages 91-104"},"PeriodicalIF":0.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143725794","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-03-01DOI: 10.1016/j.jhip.2025.02.006
Ngakou Mukam Joseph , Mvongo Clémence , Mfopa Adamou , Kamgang Tchawou Armel Georges , Nkoubat Tchoundjwen Sandrine , Fankem Gaëtan Olivier , Noubissi Paul Aimé , Fokam Tagne Michel Archange , Kamgang René , Essame Oyono Jean-Louis
Objective
Kalanchoe crenata is a medicinal plant traditionally used in diabetes management. Type 2 diabetes is a metabolic disorder characterized by abnormally high glycemia and insulin resistance. We investigated the effects of Kalanchoe crenata aqueous extracts on diabetic rats.
Methods
Six-week-old normal rats were fed a high-fat diet for 16 weeks. Then, selected obese rats intravenously received a unique dose of streptozotocin (22.5 mg/kg b.w.). One week later, the obtained diabetic rats received K. crenata decoction (DKc) or infusion (IKc) once daily, respectively, at 37.5, 75.0, or 150.0 mg/kg b.w., or Metformin(70 mg/kg) once daily for 42 days, during which the fasting glycemia, urine volume, and water intake were recorded. At the end of the treatment, animals were subjected to oral glucose tolerance and insulin tolerance tests. They were then sacrificed; serum and pancreas were collected for insulinemia evaluation and histological analysis, respectively.
Results
Obese diabetic animals had fasting glycemia > 200 mg/dL. The DKc, IKc, and Metformin reduced (P < 0.05) glycemia with the maximum effect (P < 0.01) in the 6th week and improved glucose tolerance and insulin resistance. The extracts decreased 24-h urine volume as well as water intake and reduced insulinemia (P < 0.01): IKc75 (−66.4%) and IKc150 (−59.3%). This result was associated with decreased results of Homeostatic Model Assessment for Insulin Resistance (HOMA-IR). The extracts improved the size of Langerhans islets. Infusion improved diabetes parameters to a greater extent than decoction.
Conclusion
Kalanchoe crenata aqueous extracts improved glucose tolerance and insulin resistance in diabetic rats. This study contributed to justifying the empirical use of this plant for diabetes management.
{"title":"Kalanchoe crenata decoction and infusion improve insulin resistance and fasting glycemia of diabetic obese rats MACAPOS 2","authors":"Ngakou Mukam Joseph , Mvongo Clémence , Mfopa Adamou , Kamgang Tchawou Armel Georges , Nkoubat Tchoundjwen Sandrine , Fankem Gaëtan Olivier , Noubissi Paul Aimé , Fokam Tagne Michel Archange , Kamgang René , Essame Oyono Jean-Louis","doi":"10.1016/j.jhip.2025.02.006","DOIUrl":"10.1016/j.jhip.2025.02.006","url":null,"abstract":"<div><h3>Objective</h3><div><em>Kalanchoe crenata</em> is a medicinal plant traditionally used in diabetes management. Type 2 diabetes is a metabolic disorder characterized by abnormally high glycemia and insulin resistance. We investigated the effects of <em>Kalanchoe crenata</em> aqueous extracts on diabetic rats.</div></div><div><h3>Methods</h3><div>Six-week-old normal rats were fed a high-fat diet for 16 weeks. Then, selected obese rats intravenously received a unique dose of streptozotocin (22.5 mg/kg b.w.). One week later, the obtained diabetic rats received <em>K. crenata</em> decoction (DKc) or infusion (IKc) once daily, respectively, at 37.5, 75.0, or 150.0 mg/kg b.w., or Metformin(70 mg/kg) once daily for 42 days, during which the fasting glycemia, urine volume, and water intake were recorded. At the end of the treatment, animals were subjected to oral glucose tolerance and insulin tolerance tests. They were then sacrificed; serum and pancreas were collected for insulinemia evaluation and histological analysis, respectively.</div></div><div><h3>Results</h3><div>Obese diabetic animals had fasting glycemia > 200 mg/dL. The DKc, IKc, and Metformin reduced (<em>P</em> < 0.05) glycemia with the maximum effect (<em>P</em> < 0.01) in the 6th week and improved glucose tolerance and insulin resistance. The extracts decreased 24-h urine volume as well as water intake and reduced insulinemia (<em>P</em> < 0.01): IKc75 (−66.4%) and IKc150 (−59.3%). This result was associated with decreased results of Homeostatic Model Assessment for Insulin Resistance (HOMA-IR). The extracts improved the size of Langerhans islets. Infusion improved diabetes parameters to a greater extent than decoction.</div></div><div><h3>Conclusion</h3><div><em>Kalanchoe crenata</em> aqueous extracts improved glucose tolerance and insulin resistance in diabetic rats. This study contributed to justifying the empirical use of this plant for diabetes management.</div></div>","PeriodicalId":100787,"journal":{"name":"Journal of Holistic Integrative Pharmacy","volume":"6 1","pages":"Pages 50-56"},"PeriodicalIF":0.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143686160","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-03-01DOI: 10.1016/j.jhip.2025.02.001
Binzhi Zhang , Xia Luo , Song Lei , Wenbo Gao , Zhipeng Chen , Qing Zhu , Lizheng Huang , Qinqiang Long
Metabolic-associated fatty liver disease (MAFLD) has emerged as a prevalent chronic liver disease. Our review of the existing literature reveals that the interplay between gut microbiota, mitochondria, and the liver is a key mechanism in the development of MAFLD. This paper distills the pathogenic role of gut microbiota in MAFLD through its influence on mitochondria and outlines the therapeutic mitochondrial mechanisms of MAFLD that leverage gut microbiota. It also touches on the traditional Chinese medicine perspective on the liver-intestine connection and the concept of ''qi'' in relation to mitochondria, as well as its modern medical counterpart. We conclude that the gut microbiota and their metabolites can directly or indirectly affect the intestinal mitochondria, leading to structural and functional changes. These changes include shifts in mitochondrial membrane potential, changes in permeability, and dysregulation of signaling pathways. As a result, the permeability of intestinal epithelial cells may be increased, and the integrity of the intestinal barrier may be compromised. The gut microbiota and their metabolites can then influence hepatic mitochondria through the hepatic-intestinal axis, triggering liver pathology. When liver damage occurs, their metabolites can enter the intestine and affect intestinal mitochondria and microbiota, which in turn can lead to a disrupted intestinal barrier and microbiota and a dysregulated homeostatic balance. Our extensive literature review suggests that the gut microbiota may mediate the treatment of MAFLD through mitochondrial pathways. The therapeutic approach of modulating the gut microbiota to regulate mitochondrial function and restore liver health is promising. Traditional Chinese medicine diets are particularly well suited for this strategy. Further research is warranted to fully elucidate the underlying mechanisms. By protecting the body's own mitochondrial function through the gut microbiota, we can effectively combat liver injury, providing a novel therapeutic avenue for the treatment of liver disease.
{"title":"Unravelling the gut-liver axis: The role of gut microbiota-mitochondria interactions in the pathogenesis and management of metabolic-associated fatty liver disease (MAFLD)","authors":"Binzhi Zhang , Xia Luo , Song Lei , Wenbo Gao , Zhipeng Chen , Qing Zhu , Lizheng Huang , Qinqiang Long","doi":"10.1016/j.jhip.2025.02.001","DOIUrl":"10.1016/j.jhip.2025.02.001","url":null,"abstract":"<div><div>Metabolic-associated fatty liver disease (MAFLD) has emerged as a prevalent chronic liver disease. Our review of the existing literature reveals that the interplay between gut microbiota, mitochondria, and the liver is a key mechanism in the development of MAFLD. This paper distills the pathogenic role of gut microbiota in MAFLD through its influence on mitochondria and outlines the therapeutic mitochondrial mechanisms of MAFLD that leverage gut microbiota. It also touches on the traditional Chinese medicine perspective on the liver-intestine connection and the concept of ''<em>qi</em>'' in relation to mitochondria, as well as its modern medical counterpart. We conclude that the gut microbiota and their metabolites can directly or indirectly affect the intestinal mitochondria, leading to structural and functional changes. These changes include shifts in mitochondrial membrane potential, changes in permeability, and dysregulation of signaling pathways. As a result, the permeability of intestinal epithelial cells may be increased, and the integrity of the intestinal barrier may be compromised. The gut microbiota and their metabolites can then influence hepatic mitochondria through the hepatic-intestinal axis, triggering liver pathology. When liver damage occurs, their metabolites can enter the intestine and affect intestinal mitochondria and microbiota, which in turn can lead to a disrupted intestinal barrier and microbiota and a dysregulated homeostatic balance. Our extensive literature review suggests that the gut microbiota may mediate the treatment of MAFLD through mitochondrial pathways. The therapeutic approach of modulating the gut microbiota to regulate mitochondrial function and restore liver health is promising. Traditional Chinese medicine diets are particularly well suited for this strategy. Further research is warranted to fully elucidate the underlying mechanisms. By protecting the body's own mitochondrial function through the gut microbiota, we can effectively combat liver injury, providing a novel therapeutic avenue for the treatment of liver disease.</div></div>","PeriodicalId":100787,"journal":{"name":"Journal of Holistic Integrative Pharmacy","volume":"6 1","pages":"Pages 23-40"},"PeriodicalIF":0.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143686152","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-12-01DOI: 10.1016/j.jhip.2024.11.002
Kirti G. Sahu , Deepak S. Khobragade , Shriniwas P. Patil
Plants living in different environments inhabit endophytic microbes. The relationship between plants and endophytic microbes may be symbiotic or parasitic. Transmission of endophytes varies when they are obtained through roots or cracks on bark or airborne spores from soil or originated from seeds or pollens. Endophytes could be bacteria or fungi. So far, actual flavonoids have been detected from endophytic fungi only. Several flavonoids like rutin, quercetin, kaempferol, naringenin, vitexin, apigenin, luteolin, chrysin, and silymarin are isolated from endophytic fungi. These flavonoids are tested for their anticancer activity on different cell lines and their mechanisms were determined. This review focuses on endophytic fungi from which anticancer flavonoids have been reported.
{"title":"Anticancer flavonoids producing endophytic fungi: A review","authors":"Kirti G. Sahu , Deepak S. Khobragade , Shriniwas P. Patil","doi":"10.1016/j.jhip.2024.11.002","DOIUrl":"10.1016/j.jhip.2024.11.002","url":null,"abstract":"<div><div>Plants living in different environments inhabit endophytic microbes. The relationship between plants and endophytic microbes may be symbiotic or parasitic. Transmission of endophytes varies when they are obtained through roots or cracks on bark or airborne spores from soil or originated from seeds or pollens. Endophytes could be bacteria or fungi. So far, actual flavonoids have been detected from endophytic fungi only. Several flavonoids like rutin, quercetin, kaempferol, naringenin, vitexin, apigenin, luteolin, chrysin, and silymarin are isolated from endophytic fungi. These flavonoids are tested for their anticancer activity on different cell lines and their mechanisms were determined. This review focuses on endophytic fungi from which anticancer flavonoids have been reported.</div></div>","PeriodicalId":100787,"journal":{"name":"Journal of Holistic Integrative Pharmacy","volume":"5 4","pages":"Pages 305-313"},"PeriodicalIF":0.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143174791","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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