Pub Date : 2026-01-15DOI: 10.1016/j.prenap.2026.100514
A. Ibeyaima , Anupriya Borah , Prasenjit Manna
Local people in India have traditionally used Brassica juncea to treat various permutations. This practice opens a pathway to drug discovery. Drug discovery is one of the major challenges faced during this era globally. In the pipeline of drug discovery, exploring bioactive compounds from the unutilized sources could be an immense contribution. This review is literature survey based compilation of B. juncea and its bioactive compounds in order to validate the bioactive compounds for biomedical applications. This review highlights the importance of bioactive compounds in B. juncea and its health benefits, as well as nutraceutical aspects of B. juncea of India. B. juncea is rich in vitamins, minerals, dietary fiber, chlorophylls, and glucosinolates. The nutraceutical properties of B. juncea have also been reported. Notably B. juncea can be used for plant biofortification. There is an urgent need to explore such unutilized resources for discovering the novel and potential bioactive compound(s) to combat the global issues of human health complications. The findings of this review serve as benchmarks for the development, investigation of active compounds, and utilization of B. juncea, a bio-resource of India, since very limited studies have been reported. The way of consuming B. juncea by different localities has been documented and reported its various health benefits. Further studies are needed for proper documentation through various literature surveys following extensive experimental work in order to validate the presence of potential bioactive compounds in B. juncea.
{"title":"Bioactive compounds in Brassica juncea: A systematic review on biomedical potential and drug discovery pathways","authors":"A. Ibeyaima , Anupriya Borah , Prasenjit Manna","doi":"10.1016/j.prenap.2026.100514","DOIUrl":"10.1016/j.prenap.2026.100514","url":null,"abstract":"<div><div>Local people in India have traditionally used <em>Brassica juncea</em> to treat various permutations. This practice opens a pathway to drug discovery. Drug discovery is one of the major challenges faced during this era globally. In the pipeline of drug discovery, exploring bioactive compounds from the unutilized sources could be an immense contribution. This review is literature survey based compilation of <em>B. juncea</em> and its bioactive compounds in order to validate the bioactive compounds for biomedical applications. This review highlights the importance of bioactive compounds in <em>B. juncea</em> and its health benefits, as well as nutraceutical aspects of <em>B. juncea</em> of India<em>. B. juncea</em> is rich in vitamins, minerals, dietary fiber, chlorophylls, and glucosinolates. The nutraceutical properties of <em>B. juncea</em> have also been reported. Notably <em>B. juncea</em> can be used for plant biofortification. There is an urgent need to explore such unutilized resources for discovering the novel and potential bioactive compound(s) to combat the global issues of human health complications. The findings of this review serve as benchmarks for the development, investigation of active compounds, and utilization of <em>B. juncea</em>, a bio-resource of India, since very limited studies have been reported. The way of consuming <em>B. juncea</em> by different localities has been documented and reported its various health benefits. Further studies are needed for proper documentation through various literature surveys following extensive experimental work in order to validate the presence of potential bioactive compounds in <em>B. juncea</em>.</div></div>","PeriodicalId":101014,"journal":{"name":"Pharmacological Research - Natural Products","volume":"10 ","pages":"Article 100514"},"PeriodicalIF":0.0,"publicationDate":"2026-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145977350","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 : 2026-01-13DOI: 10.1016/j.prenap.2026.100501
Alice König , Georg Sandner , Gerald Klanert , Lisa Pühringer , Tina Karimian , Jonas Schurr , Kostas Syriopoulos , Rolf Tona , Julian Weghuber
Evidence suggests that citrus flavonoids activate nuclear factor erythroid 2-related factor 2 (Nrf2) that regulates cellular defense against oxidative damage. The effects of citrus flavonoids on the homologous transcription factor skinhead-1 (SKN-1) in the nematode Caenorhabditis elegans are insufficiently studied. Here, we investigated the molecular mechanisms behind the biological activity of a biotransformed citrus extract (FermCAE) and related flavonoids in THP-1 macrophages and in C. elegans. FermCAE upregulated the expression of the Nrf2 target genes heme oxygenase 1 (HMOX1) and NAD(P)H-quinone oxidoreductase 1 (NQO1) in THP-1 macrophages. The formation of excessive reactive oxygen species (ROS) was reduced in stressed cells and nematodes. Transcriptome analysis further indicated that FermCAE modulates stress-response pathways in C. elegans, particularly mitochondrial energy metabolism, nucleotide biosynthesis and ribosome biosynthesis, correlating with improved worm motility and reduced ROS levels. Notably, FermCAE could counteract the paraquat-induced reduction in worm motility in wild-type worms but not in SKN-1 loss-of-function mutants. An elevated GCS-1P::GFP signal in transgenic nematodes further confirmed SKN-1 involvement. These findings suggest that FermCAE protects against oxidative stress by inducing Nrf2/SKN-1 and modulating energy and metabolic pathways to enhance stress resilience.
有证据表明，柑橘类黄酮激活核因子红系2相关因子2 (Nrf2)，调节细胞防御氧化损伤。柑橘类黄酮对秀丽隐杆线虫同源转录因子skinhead-1 （SKN-1）的影响研究尚不充分。在这里，我们研究了生物转化柑橘提取物（FermCAE）和相关黄酮类化合物在THP-1巨噬细胞和秀丽隐杆线虫中生物活性的分子机制。FermCAE上调THP-1巨噬细胞中Nrf2靶基因血红素加氧酶1 （HMOX1）和NAD(P) h -醌氧化还原酶1 （NQO1）的表达。过度活性氧（ROS）的形成在应激细胞和线虫中减少。转录组分析进一步表明，FermCAE调节秀丽隐杆线虫的应激反应途径，特别是线粒体能量代谢、核苷酸生物合成和核糖体生物合成，与蠕虫运动能力改善和ROS水平降低相关。值得注意的是，FermCAE可以抵消百草枯引起的野生型蠕虫运动减少，但在SKN-1功能丧失突变体中不起作用。转基因线虫中GCS-1P::GFP信号的升高进一步证实了SKN-1的参与。这些研究结果表明，FermCAE通过诱导Nrf2/SKN-1和调节能量和代谢途径来增强应激恢复能力，从而防止氧化应激。
{"title":"Biotransformed citrus extract counteracts oxidative stress in THP-1 macrophages and Caenorhabditis elegans via Nrf2/SKN-1 dependent mechanisms","authors":"Alice König , Georg Sandner , Gerald Klanert , Lisa Pühringer , Tina Karimian , Jonas Schurr , Kostas Syriopoulos , Rolf Tona , Julian Weghuber","doi":"10.1016/j.prenap.2026.100501","DOIUrl":"10.1016/j.prenap.2026.100501","url":null,"abstract":"<div><div>Evidence suggests that citrus flavonoids activate nuclear factor erythroid 2-related factor 2 (Nrf2) that regulates cellular defense against oxidative damage. The effects of citrus flavonoids on the homologous transcription factor skinhead-1 (SKN-1) in the nematode <em>Caenorhabditis elegans</em> are insufficiently studied. Here, we investigated the molecular mechanisms behind the biological activity of a biotransformed citrus extract (FermCAE) and related flavonoids in THP-1 macrophages and in <em>C. elegans</em>. FermCAE upregulated the expression of the Nrf2 target genes heme oxygenase 1 (<em>HMOX1</em>) and NAD(P)H-quinone oxidoreductase 1 (<em>NQO1</em>) in THP-1 macrophages. The formation of excessive reactive oxygen species (ROS) was reduced in stressed cells and nematodes. Transcriptome analysis further indicated that FermCAE modulates stress-response pathways in <em>C. elegans</em>, particularly mitochondrial energy metabolism, nucleotide biosynthesis and ribosome biosynthesis, correlating with improved worm motility and reduced ROS levels. Notably, FermCAE could counteract the paraquat-induced reduction in worm motility in wild-type worms but not in SKN-1 loss-of-function mutants. An elevated GCS-1P::GFP signal in transgenic nematodes further confirmed SKN-1 involvement. These findings suggest that FermCAE protects against oxidative stress by inducing Nrf2/SKN-1 and modulating energy and metabolic pathways to enhance stress resilience.</div></div>","PeriodicalId":101014,"journal":{"name":"Pharmacological Research - Natural Products","volume":"10 ","pages":"Article 100501"},"PeriodicalIF":0.0,"publicationDate":"2026-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145977477","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 : 2026-01-13DOI: 10.1016/j.prenap.2026.100508
Arupjyoti Konwar, Rajesh Kumar Shah
Assam, a biodiversity hotspot in Northeast India, harbors a rich tradition of medicinal plant use among its tribal communities. These plants are widely employed to treat helminth infections, yet scientific validation remains limited. Bridging traditional knowledge with modern pharmacology can provide effective, affordable and sustainable plant-based anthelmintics. The main objective of this review is to compile ethnobotanical knowledge of medicinal plants used against helminth infections in Assam and to critically evaluate available pharmacological evidence for identifying promising candidates for drug development. A comprehensive review was conducted using Google Scholar, PubMed, ResearchGate, NISCAIR and Scopus with keywords including “Indigenous medicinal plants of Assam,” “Worm infection,” “Anthelmintic,” “Ethnobotany,” “Ethnomedicine” and “Pharmacological activity”. In this study, 42 manuscripts between May 2006 and June 2025 have been reviewed and analyzed. Data on plant species, tribal use, parts used, preparation, administration and pharmacological validation were extracted. Ethnobotanical and pharmacological data were also categorized to compare traditional knowledge with scientific validation. A total of 149 plant species from 115 genera and 63 families were documented with Fabaceae, Rutaceae, Solanaceae and Lamiaceae being the most represented. Leaves were the most frequently used plant part, followed by fruits, roots and seeds. Traditional preparations primarily involved raw consumption, decoctions and juices, predominantly administered orally. Among documented species, only a small fraction has been pharmacologically validated, with 87.29 % evaluated in vitro, 5.93 % in vivo and 6.78 % using both approaches. Bioactive principles such as azadirachtin, embelin andrographolide, mimosine and eugenol exhibited significant anthelmintic activity. Assam’s ethnomedicinal flora presents a valuable, yet underexplored, resource for developing plant-based anthelmintics. Some of the key target species were Azadirachta indica A. Juss., Cassia fistula L. and Clerodendrum infortunatum L. and these species had an encouraging anthelmintic activity. Assam’s ethnomedicinal flora has tremendous potential for developing new anthelmintics and future studies must focus on pharmacological validation, isolation of active compounds, toxicity assessment to translate traditional knowledge to develop effective clinical therapies.
{"title":"Medicinal plants for helminth treatment in Assam: Bridging indigenous knowledge with pharmacological research","authors":"Arupjyoti Konwar, Rajesh Kumar Shah","doi":"10.1016/j.prenap.2026.100508","DOIUrl":"10.1016/j.prenap.2026.100508","url":null,"abstract":"<div><div>Assam, a biodiversity hotspot in Northeast India, harbors a rich tradition of medicinal plant use among its tribal communities. These plants are widely employed to treat helminth infections, yet scientific validation remains limited. Bridging traditional knowledge with modern pharmacology can provide effective, affordable and sustainable plant-based anthelmintics. The main objective of this review is to compile ethnobotanical knowledge of medicinal plants used against helminth infections in Assam and to critically evaluate available pharmacological evidence for identifying promising candidates for drug development. A comprehensive review was conducted using Google Scholar, PubMed, ResearchGate, NISCAIR and Scopus with keywords including “Indigenous medicinal plants of Assam,” “Worm infection,” “Anthelmintic,” “Ethnobotany,” “Ethnomedicine” and “Pharmacological activity”. In this study, 42 manuscripts between May 2006 and June 2025 have been reviewed and analyzed. Data on plant species, tribal use, parts used, preparation, administration and pharmacological validation were extracted. Ethnobotanical and pharmacological data were also categorized to compare traditional knowledge with scientific validation. A total of 149 plant species from 115 genera and 63 families were documented with Fabaceae, Rutaceae, Solanaceae and Lamiaceae being the most represented. Leaves were the most frequently used plant part, followed by fruits, roots and seeds. Traditional preparations primarily involved raw consumption, decoctions and juices, predominantly administered orally. Among documented species, only a small fraction has been pharmacologically validated, with 87.29 % evaluated in vitro, 5.93 % in vivo and 6.78 % using both approaches. Bioactive principles such as azadirachtin, embelin andrographolide, mimosine and eugenol exhibited significant anthelmintic activity. Assam’s ethnomedicinal flora presents a valuable, yet underexplored, resource for developing plant-based anthelmintics. Some of the key target species were <em>Azadirachta indica</em> A. Juss<em>., Cassia fistula</em> L. and <em>Clerodendrum infortunatum</em> L. and these species had an encouraging anthelmintic activity. Assam’s ethnomedicinal flora has tremendous potential for developing new anthelmintics and future studies must focus on pharmacological validation, isolation of active compounds, toxicity assessment to translate traditional knowledge to develop effective clinical therapies.</div></div>","PeriodicalId":101014,"journal":{"name":"Pharmacological Research - Natural Products","volume":"10 ","pages":"Article 100508"},"PeriodicalIF":0.0,"publicationDate":"2026-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145977351","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 : 2026-01-13DOI: 10.1016/j.prenap.2026.100509
Md. Jahirul Islam Mamun , Sifatul Islam Mizan , Mahathir Mohammad , Md. Hossain Rasel , Mohi Uddin
Syzygium grande (Wight) Walp., a member of the Myrtaceae family, has been traditionally used to address various health conditions. This research aimed to assess the phytochemical composition and the potential antioxidant, anti-inflammatory, antidiabetic, and thrombolytic properties of the methanolic leaf extract of S. grande (MESG). MESG exhibited mild antioxidant activity in the DPPH assay, with an IC50 value of 238 µg/mL, compared to the standard ascorbic acid (IC50 = 95.85 µg/mL). However, it was less potent than the reference ascorbic acid, which had an IC50 value of 95.85 µg/mL. MESG at 200 mg/kg significantly (p < 0.001) reduced ear edema in mice compared to the control in the xylene-induced ear edema test (78.89 % inhibition). The extract also exhibited notable anti-inflammatory effects, with 73.12 ± 0.98 % protection at 1000 µg/mL in the HRBC test and an IC50 value of 246.67 µg/mL in the protein denaturation assay. MESG showed a strong antidiabetic effect in the alpha-amylase inhibitory test, with an IC50 value of 51.22 µg/mL, compared to the reference acarbose (IC50 = 36.95 µg/mL). Furthermore, the extract displayed considerable thrombolytic activity, achieving 65.2 ± 4.66 % clot lysis in the human blood clot lysis test. Molecular docking studies provided further support for our findings, confirming the predicted interactions and binding affinities of the identified compounds with their respective target proteins. These results indicate that MESG may have potential applications in addressing oxidative stress, inflammation, diabetes, and thrombosis-related conditions. However, further research is necessary to confirm these outcomes and explore their therapeutic potential.
{"title":"Deciphering the phytochemical and pharmacological potential of Syzygium grande (Wight) Walp. through in vivo, in vitro, and computational approaches","authors":"Md. Jahirul Islam Mamun , Sifatul Islam Mizan , Mahathir Mohammad , Md. Hossain Rasel , Mohi Uddin","doi":"10.1016/j.prenap.2026.100509","DOIUrl":"10.1016/j.prenap.2026.100509","url":null,"abstract":"<div><div><em>Syzygium grande</em> (Wight) Walp., a member of the Myrtaceae family, has been traditionally used to address various health conditions. This research aimed to assess the phytochemical composition and the potential antioxidant, anti-inflammatory, antidiabetic, and thrombolytic properties of the methanolic leaf extract of <em>S. grande</em> (MESG). MESG exhibited mild antioxidant activity in the DPPH assay, with an IC<sub>50</sub> value of 238 µg/mL, compared to the standard ascorbic acid (IC<sub>50</sub> = 95.85 µg/mL). However, it was less potent than the reference ascorbic acid, which had an IC<sub>50</sub> value of 95.85 µg/mL. MESG at 200 mg/kg significantly (p < 0.001) reduced ear edema in mice compared to the control in the xylene-induced ear edema test (78.89 % inhibition). The extract also exhibited notable anti-inflammatory effects, with 73.12 ± 0.98 % protection at 1000 µg/mL in the HRBC test and an IC<sub>50</sub> value of 246.67 µg/mL in the protein denaturation assay. MESG showed a strong antidiabetic effect in the alpha-amylase inhibitory test, with an IC<sub>50</sub> value of 51.22 µg/mL, compared to the reference acarbose (IC<sub>50</sub> = 36.95 µg/mL). Furthermore, the extract displayed considerable thrombolytic activity, achieving 65.2 ± 4.66 % clot lysis in the human blood clot lysis test. Molecular docking studies provided further support for our findings, confirming the predicted interactions and binding affinities of the identified compounds with their respective target proteins. These results indicate that MESG may have potential applications in addressing oxidative stress, inflammation, diabetes, and thrombosis-related conditions. However, further research is necessary to confirm these outcomes and explore their therapeutic potential.</div></div>","PeriodicalId":101014,"journal":{"name":"Pharmacological Research - Natural Products","volume":"10 ","pages":"Article 100509"},"PeriodicalIF":0.0,"publicationDate":"2026-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145977485","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}
Phospholipids (PLs) are crucial membrane components and interact with membrane proteins and cellular receptors to mediate signal transduction and influence metabolic processes. Dietary phospholipids from natural origin, such as those from soybean, egg yolk, krill, squid, and others, are increasingly gaining scientific attention due to growing evidence of their health-enhancing potential. Notably, PLs having long-chain omega-3 polyunsaturated fatty acids (PUFA), especially docosahexaenoic acid (DHA)-containing PLs, have been shown to alleviate experimentally induced conditions such as neurological and metabolic disorders, including liver, kidney, and intestinal damage, heat/UV-radiation-induced stress, and aging. In elderly humans with depression and animal models of neurodegenerative disorders, PLs are reported to alleviate depression and anxiety and improve cognitive abilities. This review discusses the preparation and mechanisms of health promotion by PLs as reported in the scientific literature, mainly within the last two decades. Inhibition of inflammation, oxidative stress, apoptosis, and fat accumulation in tissues and prevention of gut mucosa dysbiosis were among the significant modes of action of PLs. Despite the interesting results reported from in vitro and in vivo studies, there is a lack of consensus on the quantity of PLs to be added to the diet or ingested for optimal health. More clinical studies are needed to clarify the benefits of dietary PLs in humans since most of the recent studies were conducted in rodents.
{"title":"Therapeutic potentials of dietary phospholipids against neurological and metabolic disorders: A review","authors":"Innocent Uzochukwu Okagu, Rita Ngozi Aguchem, Chidera Peace Ogbu, Andy Ugunna Omeje","doi":"10.1016/j.prenap.2026.100510","DOIUrl":"10.1016/j.prenap.2026.100510","url":null,"abstract":"<div><div>Phospholipids (PLs) are crucial membrane components and interact with membrane proteins and cellular receptors to mediate signal transduction and influence metabolic processes. Dietary phospholipids from natural origin, such as those from soybean, egg yolk, krill, squid, and others, are increasingly gaining scientific attention due to growing evidence of their health-enhancing potential. Notably, PLs having long-chain omega-3 polyunsaturated fatty acids (PUFA), especially docosahexaenoic acid (DHA)-containing PLs, have been shown to alleviate experimentally induced conditions such as neurological and metabolic disorders, including liver, kidney, and intestinal damage, heat/UV-radiation-induced stress, and aging. In elderly humans with depression and animal models of neurodegenerative disorders, PLs are reported to alleviate depression and anxiety and improve cognitive abilities. This review discusses the preparation and mechanisms of health promotion by PLs as reported in the scientific literature, mainly within the last two decades. Inhibition of inflammation, oxidative stress, apoptosis, and fat accumulation in tissues and prevention of gut mucosa dysbiosis were among the significant modes of action of PLs. Despite the interesting results reported from <em>in vitro</em> and <em>in vivo</em> studies, there is a lack of consensus on the quantity of PLs to be added to the diet or ingested for optimal health. More clinical studies are needed to clarify the benefits of dietary PLs in humans since most of the recent studies were conducted in rodents.</div></div>","PeriodicalId":101014,"journal":{"name":"Pharmacological Research - Natural Products","volume":"10 ","pages":"Article 100510"},"PeriodicalIF":0.0,"publicationDate":"2026-01-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145977353","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}
Breast cancer remains a major global health challenge requiring novel, safe, and effective therapeutic agents. Trigonelline (1-Methylpyridinium-3-carboxylate), a naturally occurring bioactive compound, has gained growing attention for its potential anticancer properties. In this study, we systematically investigated the molecular characteristics and pharmacological profile of trigonelline using a suite of integrated computational methods, including density functional theory (DFT), molecular docking, and pharmacokinetic (ADMET) assessments. Trigonelline’s geometry was optimized at the B3LYP/6–311 + +G (d, p) level, and quantum descriptors such as HOMO-LUMO gap, molecular electrostatic potential, and Mulliken charge distribution were evaluated to elucidate its stability and reactive behavior. Docking analyses against breast cancer-relevant targets (AKT1, BCL2, BRCA1, Caspase6, GSK3β, PARP1) demonstrated favorable binding, with the strongest affinity observed for BCL2 (-6.3 kcal/mol), highlighting its potential modulatory activity. Pharmacokinetic evaluation through ADMET profiling and BOILED-Egg modeling indicated good gastrointestinal absorption and oral bioavailability, alongside minimal toxicity concerns with no predicted hERG inhibition. Overall, these integrative computational findings underscore trigonelline’s potential as a multitarget anticancer candidate and support its advancement to experimental validation in breast cancer research.
{"title":"Computational investigation of Trigonelline (1-methylpyridinium-3-carboxylate) through DFT, docking and pharmacokinetic studies for Breast cancer treatment","authors":"Swetha Murugesan , Azar Zochedh , Kaliraj Chandran , Mohana Priya , Sureba Sukumaran , Thimma Mohan Viswanathan , Anbarasu Krishnan , Asath Bahadur Sultan , Thandavarayan Kathiresan","doi":"10.1016/j.prenap.2026.100507","DOIUrl":"10.1016/j.prenap.2026.100507","url":null,"abstract":"<div><div>Breast cancer remains a major global health challenge requiring novel, safe, and effective therapeutic agents. Trigonelline (1-Methylpyridinium-3-carboxylate), a naturally occurring bioactive compound, has gained growing attention for its potential anticancer properties. In this study, we systematically investigated the molecular characteristics and pharmacological profile of trigonelline using a suite of integrated computational methods, including density functional theory (DFT), molecular docking, and pharmacokinetic (ADMET) assessments. Trigonelline’s geometry was optimized at the B3LYP/6–311 + +G (d, p) level, and quantum descriptors such as HOMO-LUMO gap, molecular electrostatic potential, and Mulliken charge distribution were evaluated to elucidate its stability and reactive behavior. Docking analyses against breast cancer-relevant targets (AKT1, BCL2, BRCA1, Caspase6, GSK3β, PARP1) demonstrated favorable binding, with the strongest affinity observed for BCL2 (-6.3 kcal/mol), highlighting its potential modulatory activity. Pharmacokinetic evaluation through ADMET profiling and BOILED-Egg modeling indicated good gastrointestinal absorption and oral bioavailability, alongside minimal toxicity concerns with no predicted hERG inhibition. Overall, these integrative computational findings underscore trigonelline’s potential as a multitarget anticancer candidate and support its advancement to experimental validation in breast cancer research.</div></div>","PeriodicalId":101014,"journal":{"name":"Pharmacological Research - Natural Products","volume":"10 ","pages":"Article 100507"},"PeriodicalIF":0.0,"publicationDate":"2026-01-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145977356","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}
Pongamia pinnata (L.) Pierre (Fabacae) (P. pinnata), popularly known as “Karanja” (in Hindi) is traditionally used for many ailments due to the presence of diverse group of chemical constituents. The study aims to determine the chemical constituents of the leaves of P. pinnata, and to scientifically validate the plant for its anti-diabetic effect using in silico, in vitro, and in vivo studies.
Materials and Methods
n-hexane, ethyl acetate and ethanolic leaf extracts of P.pinnata were screened using spectroscopic and chromatographic analysis, followed by in silico molecular docking studies. The extracts were further evaluated for their in vitro antioxidant and antidiabetic activities, which were subsequently validated in a streptozotocin-induced diabetic rodent model
Results
The Gas chromatography-Mass Spectroscopy investigation revealed the presence of total 3, 7 and 48 peaks, respectively in chromatograms of n-hexane, ethyl acetate and ethanolic extracts respectively. The compound 2,7-diphenyl-1,6-dioxopyridazino [4,5:2’,3’] pyrrolo[ 4’,5’-d] pyridazine present in ethanolic extract, exhibited lowest binding energies for α-amylase and α-glucosidase enzyme targets suggesting antidiabetic potential comparable to acarbose. All the extracts demonstrated in vitro antidiabetic effect, with ethanolic extract having the most significant one. However, a weak antioxidant effect was seen with all the extracts. In streptozotocin induced diabetic rats, ethanolic and ethyl acetate extracts produced more significant antihyperglycemic effect than the standard drug metformin. The results correlated well with the findings of histopathological studies.
Conclusion
In a nutshell the antidiabetic effect of P. pinnata leaf extracts may be primarily attributed to mechanisms beyond antioxidant activity, such as the inhibition of enzymes involved in carbohydrate metabolism, warranting further extensive studies.
{"title":"Anti-diabetic effect of leaf extracts of Pongamia pinnata pierre: An in silico, in vitro and in vivo study","authors":"Jayshri Swarnkar , Saloni Rahi , Khushboo Pathania , Devendra Mishra , Mukesh Lal Sah , Sandip V. Pawar , Sangeeta Pilkhwal Sah","doi":"10.1016/j.prenap.2026.100504","DOIUrl":"10.1016/j.prenap.2026.100504","url":null,"abstract":"<div><h3>Aim</h3><div><em>Pongamia pinnata</em> (L.) Pierre (Fabacae) (P. pinnata), popularly known as “Karanja” (in Hindi) is traditionally used for many ailments due to the presence of diverse group of chemical constituents. The study aims to determine the chemical constituents of the leaves of <em>P. pinnata</em>, and to scientifically validate the plant for its anti-diabetic effect using <em>in silico</em>, <em>in vitro</em>, and <em>in vivo</em> studies.</div></div><div><h3>Materials and Methods</h3><div>n-hexane, ethyl acetate and ethanolic leaf extracts of <em>P.pinnata</em> were screened using spectroscopic and chromatographic analysis, followed by <em>in silico</em> molecular docking studies. The extracts were further evaluated for their <em>in vitro</em> antioxidant and antidiabetic activities, which were subsequently validated in a streptozotocin-induced diabetic rodent model</div></div><div><h3>Results</h3><div>The Gas chromatography-Mass Spectroscopy investigation revealed the presence of total 3, 7 and 48 peaks, respectively in chromatograms of n-hexane, ethyl acetate and ethanolic extracts respectively. The compound 2,7-diphenyl-1,6-dioxopyridazino [4,5:2’,3’] pyrrolo[ 4’,5’-d] pyridazine present in ethanolic extract, exhibited lowest binding energies for α-amylase and α-glucosidase enzyme targets suggesting antidiabetic potential comparable to acarbose. All the extracts demonstrated <em>in vitro</em> antidiabetic effect, with ethanolic extract having the most significant one. However, a weak antioxidant effect was seen with all the extracts. In streptozotocin induced diabetic rats, ethanolic and ethyl acetate extracts produced more significant antihyperglycemic effect than the standard drug metformin. The results correlated well with the findings of histopathological studies.</div></div><div><h3>Conclusion</h3><div>In a nutshell the antidiabetic effect of <em>P. pinnata</em> leaf extracts may be primarily attributed to mechanisms beyond antioxidant activity, such as the inhibition of enzymes involved in carbohydrate metabolism, warranting further extensive studies.</div></div>","PeriodicalId":101014,"journal":{"name":"Pharmacological Research - Natural Products","volume":"10 ","pages":"Article 100504"},"PeriodicalIF":0.0,"publicationDate":"2026-01-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145977482","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 : 2026-01-12DOI: 10.1016/j.prenap.2026.100511
Anshul Ram , Umashankar Nirmalkar , Jaya Shree , Swarnali Das Paul , Shekhar Verma , Rajesh Choudhary
Backgrounds
Cataract is the leading cause of ocular blindness, which is mainly associated with oxidative stress. The study evaluated and elucidated the molecular mechanism of phloretin, a potent antioxidant flavonoid, against cataract using network pharmacology, molecular docking, and in vivo experimental studies.
Methods
The Molecular mechanism of phloretin against cataract was elucidated using computational tools and a database. Further, therapeutic and pathophysiological insights of phloretin were evaluated against the naphthalene-induced cataract model in Sprague Dawley albino rats (either sex, 12–15 weeks, 150–180 g). The anticataract activity of Phloretin at a dose of 50 and 100 mg/kg/day, p.o., was assessed against the naphthalene (1 g/kg/day, p.o., for four weeks) induced model. The progression of lens opacity was assessed weekly, and pathophysiological markers were assessed after completion of experiments.
Results
In-silico studies revealed that NFKB1 is the most favorable key target for phloretin to manage cataract by modulating PI3K-Akt, MAPK, Ras, and cellular senescence signaling pathways. The in-vivo study showed that phloretin treatments at doses of 50 and 100 mg/kg considerably retained the lens transparency and mitigated the progression of cataract formation. Phloretin treatments significantly (P < 0.05) restored the worsened pathophysiological markers indicated by increasing antioxidants (CAT, SOD, and GSH), protein contents, and Ca2 +ATPase activity and decreasing lipid peroxidant (MDA), nitrite contents, and Ca2+ ion.
Conclusion
On the basis of the findings, phloretin shows potential beneficial effects in the management of cataract. These effects might be associated with the mitigation of oxidative stress and modulation of NFKB1 and PTPN11 action, which needs to be validated in future studies.
{"title":"Mechanistic elucidation of phloretin in the management of cataract based on network pharmacology, molecular docking, and in-vivo experimental studies","authors":"Anshul Ram , Umashankar Nirmalkar , Jaya Shree , Swarnali Das Paul , Shekhar Verma , Rajesh Choudhary","doi":"10.1016/j.prenap.2026.100511","DOIUrl":"10.1016/j.prenap.2026.100511","url":null,"abstract":"<div><h3>Backgrounds</h3><div>Cataract is the leading cause of ocular blindness, which is mainly associated with oxidative stress. The study evaluated and elucidated the molecular mechanism of phloretin, a potent antioxidant flavonoid, against cataract using network pharmacology, molecular docking, and in vivo experimental studies.</div></div><div><h3>Methods</h3><div>The Molecular mechanism of phloretin against cataract was elucidated using computational tools and a database. Further, therapeutic and pathophysiological insights of phloretin were evaluated against the naphthalene-induced cataract model in Sprague Dawley albino rats (either sex, 12–15 weeks, 150–180 g). The anticataract activity of Phloretin at a dose of 50 and 100 mg/kg/day, p.o., was assessed against the naphthalene (1 g/kg/day, p.o., for four weeks) induced model. The progression of lens opacity was assessed weekly, and pathophysiological markers were assessed after completion of experiments.</div></div><div><h3>Results</h3><div><em>In-silico</em> studies revealed that NFKB1 is the most favorable key target for phloretin to manage cataract by modulating PI3K-Akt, MAPK, Ras, and cellular senescence signaling pathways. The <em>in-vivo</em> study showed that phloretin treatments at doses of 50 and 100 mg/kg considerably retained the lens transparency and mitigated the progression of cataract formation. Phloretin treatments significantly (<em>P < 0.05</em>) restored the worsened pathophysiological markers indicated by increasing antioxidants (CAT, SOD, and GSH), protein contents, and Ca<sup>2 +</sup>ATPase activity and decreasing lipid peroxidant (MDA), nitrite contents, and Ca<sup>2+</sup> ion.</div></div><div><h3>Conclusion</h3><div>On the basis of the findings, phloretin shows potential beneficial effects in the management of cataract. These effects might be associated with the mitigation of oxidative stress and modulation of NFKB1 and PTPN11 action, which needs to be validated in future studies.</div></div>","PeriodicalId":101014,"journal":{"name":"Pharmacological Research - Natural Products","volume":"10 ","pages":"Article 100511"},"PeriodicalIF":0.0,"publicationDate":"2026-01-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145977352","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 review examines the therapeutic potential of Atropa belladonna for neurological disorders by analyzing its chemical composition, extraction methods, clinical applications, and mechanisms of action. It highlights essential alkaloids, such as atropine and scopolamine, and their neuropharmacological effects, especially in Parkinson’s disease. Furthermore, it identifies research gaps related to toxicity, standardization, and clinical validation.
Methods
A systematic literature review was conducted utilizing electronic databases such as PubMed, Scopus, Web of Science, and Google Scholar. This search aimed to explore studies regarding the chemical constituents, therapeutic applications, extraction techniques, and mechanisms of action of Atropa belladonna alkaloids in neurological disorders. Articles that did not provide details on bioactive compound extraction methods or used synthesized compounds were excluded to ensure a focus on naturally derived compounds.
Results
Findings suggest that Atropa belladonna possesses neuroprotective and anticholinergic properties, potentially benefiting conditions like Parkinson’s disease and epilepsy. However, toxicity concerns, a lack of extraction standardization, and limited clinical evidence present significant challenges. Case studies report both therapeutic and toxic effects, highlighting the need for caution.
Conclusion
Despite its promising neuropharmacological potential, Atropa belladonna remains under-researched in clinical settings. Further studies are needed to optimize extraction methods, minimize toxicity risks, and standardize dosages for safe therapeutic use. Tackling these challenges could position Atropa belladonna as a viable source for novel neurological applications and treatments.
目的从颠茄的化学成分、提取方法、临床应用及作用机制等方面综述颠茄对神经系统疾病的治疗潜力。它强调了必需的生物碱，如阿托品和东莨菪碱，以及它们的神经药理作用，特别是在帕金森病中。此外，它还确定了与毒性、标准化和临床验证相关的研究差距。方法利用PubMed、Scopus、Web of Science、b谷歌Scholar等电子数据库进行系统的文献综述。本研究旨在探讨颠茄生物碱在神经系统疾病中的化学成分、治疗应用、提取技术和作用机制。没有提供生物活性化合物提取方法或使用的合成化合物的详细信息的文章被排除在外，以确保关注天然衍生化合物。研究结果表明颠茄具有神经保护和抗胆碱能特性，可能对帕金森病和癫痫等疾病有益。然而，毒性问题、缺乏提取标准化和有限的临床证据提出了重大挑战。案例研究报告了治疗和毒性作用，强调了谨慎的必要性。结论尽管颠茄具有良好的神经药理潜力，但其临床研究仍不足。需要进一步的研究来优化提取方法，最大限度地降低毒性风险，并规范剂量以安全治疗。解决这些挑战可以使颠茄成为新的神经应用和治疗的可行来源。
{"title":"Exploring the potential of Atropa belladonna as a source of novel therapeutic agents for neurological disorders: A comprehensive review","authors":"Manka Marycleopha , Bachir Yaou Balarabe , Satish Kumar","doi":"10.1016/j.prenap.2026.100499","DOIUrl":"10.1016/j.prenap.2026.100499","url":null,"abstract":"<div><h3>Objectives</h3><div>This review examines the therapeutic potential of <em>Atropa belladonna</em> for neurological disorders by analyzing its chemical composition, extraction methods, clinical applications, and mechanisms of action. It highlights essential alkaloids, such as atropine and scopolamine, and their neuropharmacological effects, especially in Parkinson’s disease. Furthermore, it identifies research gaps related to toxicity, standardization, and clinical validation.</div></div><div><h3>Methods</h3><div>A systematic literature review was conducted utilizing electronic databases such as PubMed, Scopus, Web of Science, and Google Scholar. This search aimed to explore studies regarding the chemical constituents, therapeutic applications, extraction techniques, and mechanisms of action of <em>Atropa belladonna</em> alkaloids in neurological disorders. Articles that did not provide details on bioactive compound extraction methods or used synthesized compounds were excluded to ensure a focus on naturally derived compounds.</div></div><div><h3>Results</h3><div>Findings suggest that <em>Atropa belladonna</em> possesses neuroprotective and anticholinergic properties, potentially benefiting conditions like Parkinson’s disease and epilepsy. However, toxicity concerns, a lack of extraction standardization, and limited clinical evidence present significant challenges. Case studies report both therapeutic and toxic effects, highlighting the need for caution.</div></div><div><h3>Conclusion</h3><div>Despite its promising neuropharmacological potential, <em>Atropa belladonna</em> remains under-researched in clinical settings. Further studies are needed to optimize extraction methods, minimize toxicity risks, and standardize dosages for safe therapeutic use. Tackling these challenges could position <em>Atropa belladonna</em> as a viable source for novel neurological applications and treatments.</div></div>","PeriodicalId":101014,"journal":{"name":"Pharmacological Research - Natural Products","volume":"10 ","pages":"Article 100499"},"PeriodicalIF":0.0,"publicationDate":"2026-01-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145977355","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 : 2026-01-11DOI: 10.1016/j.prenap.2026.100502
P. Roshan Ali , Gottimukkala Rakshitha , V.V. Rajesham , Kavirayani Naga Lakshmi Shivani , Rajinikanth Sagapola , S. Sravanthi
Diabetic nephropathy (DN), a major contributor to end-stage renal disease, demands therapeutic approaches that can address its complex and multi-pathway progression. This study evaluates the synergistic renoprotective potential of Gallic Acid and berberine hydrochloride using a multi-target in-silico strategy aimed at providing a more comprehensive intervention against DN. Molecular docking revealed strong interactions of both compounds with several DN-related proteins, including human pancreatic alpha-amylase (1B2Y), GSK-3β (1UV5), RXR-α/PPAR-γ (1FM6), DPP-IV (3BJM), ERK2 (4IZ5), PPAR-γ (5U5L), maltase-glucoamylase (2QMJ), GFPT1 (2V4M), insulin receptor kinase (1GAG), 11β-HSD1 (3CH6), and AKT1 (3O96). Berberine HCl showed strong affinity for TGF-β (-11.4 kcal/mol) and PPAR-γ (-8.5 kcal/mol), suggesting effects on fibrotic modulation and improved insulin response. Gallic Acid demonstrated considerable binding to NF-κB (-9.0 kcal/mol) and aldose reductase (-6.6 kcal/mol), indicating its potential to reduce inflammatory activity and oxidative stress. Together, these findings highlight the ability of the two compounds to influence multiple pathological mechanisms, including inflammation, oxidative injury, fibrotic processes, and glucose dysregulation. Pharmacokinetic evaluation indicated favourable drug-likeness, minimal predicted hepatotoxicity, and compatibility for combined oral delivery. Comparative analysis further suggested that this dual-compound approach may offer greater predicted therapeutic benefit than standard DN therapies such as ACE inhibitors. These results support the development of this combination as a promising multi-mechanistic strategy for DN and provide a foundation for future in-vitro and in-vivo validation.
{"title":"In-silico molecular docking of berberine HCl and gallic acid: A multi-targeted approach for diabetic nephropathy","authors":"P. Roshan Ali , Gottimukkala Rakshitha , V.V. Rajesham , Kavirayani Naga Lakshmi Shivani , Rajinikanth Sagapola , S. Sravanthi","doi":"10.1016/j.prenap.2026.100502","DOIUrl":"10.1016/j.prenap.2026.100502","url":null,"abstract":"<div><div>Diabetic nephropathy (DN), a major contributor to end-stage renal disease, demands therapeutic approaches that can address its complex and multi-pathway progression. This study evaluates the synergistic renoprotective potential of Gallic Acid and berberine hydrochloride using a multi-target <em>in-silico</em> strategy aimed at providing a more comprehensive intervention against DN. Molecular docking revealed strong interactions of both compounds with several DN-related proteins, including human pancreatic alpha-amylase (1B2Y), GSK-3β (1UV5), RXR-α/PPAR-γ (1FM6), DPP-IV (3BJM), ERK2 (4IZ5), PPAR-γ (5U5L), maltase-glucoamylase (2QMJ), GFPT1 (2V4M), insulin receptor kinase (1GAG), 11β-HSD1 (3CH6), and AKT1 (3O96). Berberine HCl showed strong affinity for TGF-β (-11.4 kcal/mol) and PPAR-γ (-8.5 kcal/mol), suggesting effects on fibrotic modulation and improved insulin response. Gallic Acid demonstrated considerable binding to NF-κB (-9.0 kcal/mol) and aldose reductase (-6.6 kcal/mol), indicating its potential to reduce inflammatory activity and oxidative stress. Together, these findings highlight the ability of the two compounds to influence multiple pathological mechanisms, including inflammation, oxidative injury, fibrotic processes, and glucose dysregulation. Pharmacokinetic evaluation indicated favourable drug-likeness, minimal predicted hepatotoxicity, and compatibility for combined oral delivery. Comparative analysis further suggested that this dual-compound approach may offer greater predicted therapeutic benefit than standard DN therapies such as ACE inhibitors. These results support the development of this combination as a promising multi-mechanistic strategy for DN and provide a foundation for future <em>in-vitro</em> and <em>in-vivo</em> validation.</div></div>","PeriodicalId":101014,"journal":{"name":"Pharmacological Research - Natural Products","volume":"10 ","pages":"Article 100502"},"PeriodicalIF":0.0,"publicationDate":"2026-01-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145977484","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}
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