Abstract: Naringin is a naturally obtained chemical from plants that is formed as a secondary metabolite in them. It possesses significant properties that are useful to humans. The primary sources of naringin extract include fruits of the citrus family which are Citrus reticulata, Citrus bergamia, Citrus aurantium, and Citrus paradisi. It belongs to a class of alcohols primarily consisting of a fused ring system which is responsible for its different medicinal properties, as a consequence, it is widely used in the nutraceutical market nowadays. Nutraceuticals are a part of food that provides health benefits by giving supplements to the body; their final extract form is white in color having crystalline properties with a melting point of 83oC and solubility of 1 mg/ml at 40oC. The absorption of nutraceuticals occurs inside the stomach as it requires a specific pH range between 3.5-4.2. After absorption, it gets converted into naringenin in the liver via a cascade of reactions like dehydrogenation, acetylation, and hydrolysis. Several enzymes are responsible for its conversion into an active form which includes cytochrome P-450, and chalcone isomerase. Its bioavailability depends on a variety of factors including disease condition, gastric moiety, pH of absorption site, the presence of other drugs, and many more. It gets metabolized in the liver itself and finally excreted in the urine. It can be tolerated by the body at high doses, but other conditions can cause its toxicity inside the human body. Its primary properties include anti-inflammatory actions, anti-aging properties, antibacterial properties, anti-cancer properties, and obesity issues.
{"title":"An Overview of Biosynthetic Pathway and Therapeutic Potential of Naringin","authors":"Jugnu Goyal Goyal, Rishab Goyal Goyal, Prabhakar Kumar Verma","doi":"10.2174/012210299x244607231030095326","DOIUrl":"https://doi.org/10.2174/012210299x244607231030095326","url":null,"abstract":"Abstract: Naringin is a naturally obtained chemical from plants that is formed as a secondary metabolite in them. It possesses significant properties that are useful to humans. The primary sources of naringin extract include fruits of the citrus family which are Citrus reticulata, Citrus bergamia, Citrus aurantium, and Citrus paradisi. It belongs to a class of alcohols primarily consisting of a fused ring system which is responsible for its different medicinal properties, as a consequence, it is widely used in the nutraceutical market nowadays. Nutraceuticals are a part of food that provides health benefits by giving supplements to the body; their final extract form is white in color having crystalline properties with a melting point of 83oC and solubility of 1 mg/ml at 40oC. The absorption of nutraceuticals occurs inside the stomach as it requires a specific pH range between 3.5-4.2. After absorption, it gets converted into naringenin in the liver via a cascade of reactions like dehydrogenation, acetylation, and hydrolysis. Several enzymes are responsible for its conversion into an active form which includes cytochrome P-450, and chalcone isomerase. Its bioavailability depends on a variety of factors including disease condition, gastric moiety, pH of absorption site, the presence of other drugs, and many more. It gets metabolized in the liver itself and finally excreted in the urine. It can be tolerated by the body at high doses, but other conditions can cause its toxicity inside the human body. Its primary properties include anti-inflammatory actions, anti-aging properties, antibacterial properties, anti-cancer properties, and obesity issues.","PeriodicalId":479738,"journal":{"name":"Current Indian Science","volume":"23 2","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135430737","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}
Background:: Traditional approach to shelf-life prediction claims a substantial amount of product development time, leading to significant delays. Objective:: The capability of the unconventional Accelerated Stability Assessment Program (ASAP) to decode chemical stability and expedite shelf-life prediction is discussed in the manuscript. Methods:: As per the ASAP approach, shelf-life limiting attributes for two APIs’ and a formulation were identified based on the isoconversion ratio. Isoconversion times at varying accelerated conditions were obtained and the degradation kinetics were modeled using the humidity-modified Arrhenius equation. R2 and Q2 values were derived to assure model predictability. Temperature and humidity sensitivity of the attributes were determined from the activation energy; Ea, and humidity sensitivity factor, B, respectively. Degradation plots demonstrated the dynamics of degradation with time. The predicted values were verified by the available real-time data. Results:: The degradation rate was modeled for impurities that exhibited conversion substantiated by an isoconversion ratio between 0.25-2.0. The Ea and B data provided valuable details regarding the sensitivity of the products. Predicted shelf-life of less than a year for the finished product instigated redevelopment. In the case of the APIs’, the existing storage conditions were found unsuitable for shelf-life stability, and alternate conducive conditions were identified. Conclusion:: The study provided cognizance regarding the distinct degradation pattern of an API and its formulation and the contradictory storage requirement for APIs’ of two different molecules. While the traditional approach claims 3-6 months to predict shelf-life, the ASAP approach provides the same with enhanced accuracy in just 3-4 weeks.
{"title":"Early Prediction of the Chemical Stability of Drug Substances and Drug Products during the Development Phase","authors":"Trupti Tol, Swapnil Mhamunkar, Harshad Tawde, Gautam Samanta","doi":"10.2174/012210299x258686231026051150","DOIUrl":"https://doi.org/10.2174/012210299x258686231026051150","url":null,"abstract":"Background:: Traditional approach to shelf-life prediction claims a substantial amount of product development time, leading to significant delays. Objective:: The capability of the unconventional Accelerated Stability Assessment Program (ASAP) to decode chemical stability and expedite shelf-life prediction is discussed in the manuscript. Methods:: As per the ASAP approach, shelf-life limiting attributes for two APIs’ and a formulation were identified based on the isoconversion ratio. Isoconversion times at varying accelerated conditions were obtained and the degradation kinetics were modeled using the humidity-modified Arrhenius equation. R2 and Q2 values were derived to assure model predictability. Temperature and humidity sensitivity of the attributes were determined from the activation energy; Ea, and humidity sensitivity factor, B, respectively. Degradation plots demonstrated the dynamics of degradation with time. The predicted values were verified by the available real-time data. Results:: The degradation rate was modeled for impurities that exhibited conversion substantiated by an isoconversion ratio between 0.25-2.0. The Ea and B data provided valuable details regarding the sensitivity of the products. Predicted shelf-life of less than a year for the finished product instigated redevelopment. In the case of the APIs’, the existing storage conditions were found unsuitable for shelf-life stability, and alternate conducive conditions were identified. Conclusion:: The study provided cognizance regarding the distinct degradation pattern of an API and its formulation and the contradictory storage requirement for APIs’ of two different molecules. While the traditional approach claims 3-6 months to predict shelf-life, the ASAP approach provides the same with enhanced accuracy in just 3-4 weeks.","PeriodicalId":479738,"journal":{"name":"Current Indian Science","volume":"23 6","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135430735","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}
aims: We report herein the design of 2-(5-(substituted)-4H-1,2,4-triazole-2-ylthio)-N-(substituted) phenyl acetamide (5A-5E) derivatives using SAR studies as an inhibitor of Groel2 enzyme. These designed compounds were subjected to molecular docking, synthesis, ADME analysis, and biological evaluation against the H37Ra strain. background: Tuberculosis (TB) is one of the most contagious and deadly infectious diseases and contributes to an increase in fatalities. According to the WHO’s 2022 report, there is an increase in TB-related illnesses due to Covid-19. objective: We report herein the design of 2-(5-(substituted)-4H-1,2,4-triazole-2-ylthio)-N-(substituted) phenyl acetamide (5A-5E) derivatives using SAR studies as an inhibitor of Groel2 enzyme. These designed compounds were subjected to molecular docking, synthesis, ADME analysis, and biological evaluation against the H37Ra strain. method: On the basis of SAR and molecular docking using Autodock/vina the highest dock score compounds were synthesized using a conventional method. The synthesized compounds (5A-5E) were analyzed for the pharmacokinetic parameters to check their drug-likeness property using the molsoft program. The biological screening against Mycobacterium tuberculosis H37Rv strain was done using MABA assay to check its antimycobacterial activity. result: All the synthesized compounds have shown docking scores (-8.0 to -9.1Kcal/mol) that reflected their drug-binding affinities towards the Groel2 enzyme. ADME analysis predicts that compound 5B shows the highest drug-likeness score of 1.13 followed by compound 5C possesses a 0.8 score compared to other compounds. The minimum inhibitory concentrations of these compound 5D reached 0.8μM, which is superior to all the current first-line anti-tuberculosis drugs. Furthermore, almost all compounds possess excellent antimycobacterial activity compared to the standard drugs used. conclusion: All the compounds show excellent inhibitory activity against the Mycobacterium tuberculosis H37Rv strain. Compound 5D shows a promising activity as compared to standard and also shows the highest docking score towards the GroEl2 enzyme. The emphasis of this work is the development and synthesis of new antimycobacterial agents and their In-silico studies. other: No
目的:本文报道了利用SAR研究作为Groel2酶抑制剂的2-(5-(取代)- 4h -1,2,4-三唑-2-基硫)- n -(取代)苯乙酰胺(5A-5E)衍生物的设计。这些设计的化合物进行了分子对接、合成、ADME分析和对H37Ra菌株的生物学评价。背景:结核病(TB)是传染性最强和最致命的传染病之一，导致死亡人数增加。根据世卫组织2022年的报告，Covid-19导致的结核病相关疾病有所增加。目的:本文报道了利用SAR研究设计2-(5-(取代)- 4h -1,2,4-三唑-2-基硫)- n -(取代)苯乙酰胺(5A-5E)衍生物作为Groel2酶抑制剂。这些设计的化合物进行了分子对接、合成、ADME分析和对H37Ra菌株的生物学评价。方法:在SAR和Autodock/vina分子对接的基础上，采用常规方法合成对接分数最高的化合物。采用molsoft程序对合成的化合物(5A-5E)进行药代动力学参数分析，验证其药物相似性。采用MABA法对结核分枝杆菌H37Rv进行生物筛选，检测其抑菌活性。结果:所有合成的化合物都显示出对接分数(-8.0 ~ -9.1Kcal/mol)，反映了它们与Groel2酶的药物结合亲和力。ADME分析预测化合物5B与其他化合物的药物相似度评分最高，为1.13分，其次是化合物5C，为0.8分。这些化合物5D的最低抑菌浓度达到0.8μM，优于目前所有一线抗结核药物。此外，与使用的标准药物相比，几乎所有化合物都具有出色的抗细菌活性。结论:所有化合物对结核分枝杆菌H37Rv株均有良好的抑菌活性。与标准化合物相比，化合物5D显示出很好的活性，并且与GroEl2酶的对接得分最高。本工作的重点是新型抗菌药物的开发和合成及其在计算机上的研究。其他:不
{"title":"ADME, Synthesis and Antimycobacterial Activity of 1,2,4-Triazol-3-thiol Linked Phenylacetamide Derivatives","authors":"Trupti Chitre, Shivani Jadhav, Kalyani Asgaonkar, Kunal Pradhan, Kalash Shelke, Shubhangi Thorat, Aniket Bhatambrekar","doi":"10.2174/012210299x239429231026060353","DOIUrl":"https://doi.org/10.2174/012210299x239429231026060353","url":null,"abstract":"aims: We report herein the design of 2-(5-(substituted)-4H-1,2,4-triazole-2-ylthio)-N-(substituted) phenyl acetamide (5A-5E) derivatives using SAR studies as an inhibitor of Groel2 enzyme. These designed compounds were subjected to molecular docking, synthesis, ADME analysis, and biological evaluation against the H37Ra strain. background: Tuberculosis (TB) is one of the most contagious and deadly infectious diseases and contributes to an increase in fatalities. According to the WHO’s 2022 report, there is an increase in TB-related illnesses due to Covid-19. objective: We report herein the design of 2-(5-(substituted)-4H-1,2,4-triazole-2-ylthio)-N-(substituted) phenyl acetamide (5A-5E) derivatives using SAR studies as an inhibitor of Groel2 enzyme. These designed compounds were subjected to molecular docking, synthesis, ADME analysis, and biological evaluation against the H37Ra strain. method: On the basis of SAR and molecular docking using Autodock/vina the highest dock score compounds were synthesized using a conventional method. The synthesized compounds (5A-5E) were analyzed for the pharmacokinetic parameters to check their drug-likeness property using the molsoft program. The biological screening against Mycobacterium tuberculosis H37Rv strain was done using MABA assay to check its antimycobacterial activity. result: All the synthesized compounds have shown docking scores (-8.0 to -9.1Kcal/mol) that reflected their drug-binding affinities towards the Groel2 enzyme. ADME analysis predicts that compound 5B shows the highest drug-likeness score of 1.13 followed by compound 5C possesses a 0.8 score compared to other compounds. The minimum inhibitory concentrations of these compound 5D reached 0.8μM, which is superior to all the current first-line anti-tuberculosis drugs. Furthermore, almost all compounds possess excellent antimycobacterial activity compared to the standard drugs used. conclusion: All the compounds show excellent inhibitory activity against the Mycobacterium tuberculosis H37Rv strain. Compound 5D shows a promising activity as compared to standard and also shows the highest docking score towards the GroEl2 enzyme. The emphasis of this work is the development and synthesis of new antimycobacterial agents and their In-silico studies. other: No","PeriodicalId":479738,"journal":{"name":"Current Indian Science","volume":"23 11","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135430871","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}
Background:: Glucose regulation and energy homeostasis mitigate energy crises milieu in reperfusion injury. We investigated Banaba for its outcomes on cerebral ischemia reperfusion (IR) injury using artery occlusion in rats. The pleiotropic activity of Banaba on various debilitating mechanisms inducing reperfusion injury was evaluated. Aim:: This study aimedto evaluate the pharmacological activity of Banaba (Lagerstroemia speciosa) extract on reperfusion injury and investigate the effect of Banaba on vascular permeability, oxidative stress and cellular damage in ischemia reperfusion injury in rats. Methods:: Transient ischemia and reperfusion through occlusion of the middle cerebral artery (MCAO) lead to Cerebral IR injury in Wistar rats; it was treated with oral administration of Banaba extract (100mg/kg and 200mg/kg). The injury outcomes were evaluated after 22 hours of reperfusion by determining cellular injury, its impact on musculoskeletal coordination, multiple free radical scavenging measures (SOD, GSH, LPO) and vascular permeability of the blood-brain barrier. Result:: Banaba treatment led to a marked improvement in neurological outcomes by enhanced coordination and reduced cerebral infarct in comparison to vehicle control ischemic group. Free radical scavenging activity (SOD and GSH) was significantly better, and lipid peroxidation was reduced by Banaba treatment; it also reduced the vascular permeability of the blood-brain barrier. We observed that a lower dose of Banaba (100 mg/kg) was more effective than the higher (200 mg/kg) in ischemic rats. The anti-inflammatory and anti-oxidant activity could drive the neuroprotective outcomes of Banaba in cerebral IR injury. The critical factor of the beneficial effect of Banaba in cerebral injury is the optimization of dose in this experimental setup of reperfusion injury using rats. Conclusion:: The recovery of injury could be attributed to Banaba’s multi-factorial effect targeting free radicals, inflammation, and necrosis during ischemiareperfusion injury.
{"title":"Banaba Restricts Brain Damage: Neuroprotective Role in Cerebral Ischemiareperfusion Injury","authors":"Maneesh Soni, Avinash Singh Mandloi, Kapil Baraskar, Manisha Kawadkar, Vipin Dhote","doi":"10.2174/012210299x261536231025093606","DOIUrl":"https://doi.org/10.2174/012210299x261536231025093606","url":null,"abstract":"Background:: Glucose regulation and energy homeostasis mitigate energy crises milieu in reperfusion injury. We investigated Banaba for its outcomes on cerebral ischemia reperfusion (IR) injury using artery occlusion in rats. The pleiotropic activity of Banaba on various debilitating mechanisms inducing reperfusion injury was evaluated. Aim:: This study aimedto evaluate the pharmacological activity of Banaba (Lagerstroemia speciosa) extract on reperfusion injury and investigate the effect of Banaba on vascular permeability, oxidative stress and cellular damage in ischemia reperfusion injury in rats. Methods:: Transient ischemia and reperfusion through occlusion of the middle cerebral artery (MCAO) lead to Cerebral IR injury in Wistar rats; it was treated with oral administration of Banaba extract (100mg/kg and 200mg/kg). The injury outcomes were evaluated after 22 hours of reperfusion by determining cellular injury, its impact on musculoskeletal coordination, multiple free radical scavenging measures (SOD, GSH, LPO) and vascular permeability of the blood-brain barrier. Result:: Banaba treatment led to a marked improvement in neurological outcomes by enhanced coordination and reduced cerebral infarct in comparison to vehicle control ischemic group. Free radical scavenging activity (SOD and GSH) was significantly better, and lipid peroxidation was reduced by Banaba treatment; it also reduced the vascular permeability of the blood-brain barrier. We observed that a lower dose of Banaba (100 mg/kg) was more effective than the higher (200 mg/kg) in ischemic rats. The anti-inflammatory and anti-oxidant activity could drive the neuroprotective outcomes of Banaba in cerebral IR injury. The critical factor of the beneficial effect of Banaba in cerebral injury is the optimization of dose in this experimental setup of reperfusion injury using rats. Conclusion:: The recovery of injury could be attributed to Banaba’s multi-factorial effect targeting free radicals, inflammation, and necrosis during ischemiareperfusion injury.","PeriodicalId":479738,"journal":{"name":"Current Indian Science","volume":"73 3","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135545174","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}
Abstract: Arthritis is one of the major inflammatory diseases and is a global issue. Arthritis is currently an utmost public health problem and it will further impact the life of the geriatric population. There are several types of arthritis such as Rheumatoid arthritis, Osteoarthritis, Gout, and Fibromyalgia, which limit the mobility of the patient. In most cases, the reason for the disease is not known clearly and available treatment can reduce the symptoms but cannot cure it completely. Though Non-Steroidal Anti-Inflammatory Drugs (NSAIDs), glucocorticoids, and Disease Modifying Anti Rheumatic Drugs (DMADRS) are the first-line treatments available in arthritis, gastrointestinal discomfort, low solubility, strong first-pass metabolism, low bioavailability, and systemic adverse reactions are the main drawbacks related to these drugs when used in long-term. Based on the evidence related to side effects of the current treatment methodology, several recent studies and developments have been designed and summarized in this field. From these studies, it has been observed that the transdermal drug delivery system can minimize the side effects associated with the oral dosage forms and can deliver the drug directly to the target site along with controlled and prolonged drug release. Hence, novel approaches in transdermal drug delivery systems like transdermal patches and microneedle therapy could be an alternative approach in the treatment and management of arthritis.
{"title":"A Comprehensive Review on Management and Treatment of Arthritis Specially Emphasizing Treatment with Transdermal Patch","authors":"Ranajan Kirtania, Rizwana Parvin, Sayan Barman, Shreyasi Chakraborty, Laboni Das, Kajal Ghosal","doi":"10.2174/012210299x276015231102052904","DOIUrl":"https://doi.org/10.2174/012210299x276015231102052904","url":null,"abstract":"Abstract: Arthritis is one of the major inflammatory diseases and is a global issue. Arthritis is currently an utmost public health problem and it will further impact the life of the geriatric population. There are several types of arthritis such as Rheumatoid arthritis, Osteoarthritis, Gout, and Fibromyalgia, which limit the mobility of the patient. In most cases, the reason for the disease is not known clearly and available treatment can reduce the symptoms but cannot cure it completely. Though Non-Steroidal Anti-Inflammatory Drugs (NSAIDs), glucocorticoids, and Disease Modifying Anti Rheumatic Drugs (DMADRS) are the first-line treatments available in arthritis, gastrointestinal discomfort, low solubility, strong first-pass metabolism, low bioavailability, and systemic adverse reactions are the main drawbacks related to these drugs when used in long-term. Based on the evidence related to side effects of the current treatment methodology, several recent studies and developments have been designed and summarized in this field. From these studies, it has been observed that the transdermal drug delivery system can minimize the side effects associated with the oral dosage forms and can deliver the drug directly to the target site along with controlled and prolonged drug release. Hence, novel approaches in transdermal drug delivery systems like transdermal patches and microneedle therapy could be an alternative approach in the treatment and management of arthritis.","PeriodicalId":479738,"journal":{"name":"Current Indian Science","volume":"72 11","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135545019","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}
Abstract: Convolvulus prostratus, also known as sankhapushpi, is a very adaptable plant frequently used as a nervine tonic, nootropic, and rejuvenator in cases of insanity and epilepsy and has a broad spectrum of beneficial properties. Several medicinal qualities, including anxiety, neuroprotective, antioxidant, analgesic, immunomodulatory, antibacterial, antidiabetic, and cardioprotective effects, have been related to this herb in ancient literature. Numerous bioactive phytoconstituents, including kaempferol(flavonoid), ceryl alcohol, scopolamine(phenolics), and convolamine (alkaloid), are associated with the therapeutic capabilities of this herb. The Whole herb or its juice is credited with alterative, antiphlogistic, and nervine tonic action. Additionally, the involvement of C. prostratus extracts in neurodegenerative was thoroughly established. Although this significant herb has comprehensive preclinical studies, thorough clinical research and mechanistic mode-of-action studies still need to be conducted. With a detailed analysis of the research gaps, the current review aims to highlight the phytonutrient constituents, beneficial characteristics, and therapeutic properties of C. prostratus. The creation of CNS phytopharmaceuticals, derived from C. prostratus, is hoped to flourish due to the scientific upgrade on the ethnomedicinal characteristics of this herb.
{"title":"The Pharmacological Significance of Convolvulus Prostratu:s Modern Perspectives of An Ancient Herb","authors":"Jeetendra Kumar Gupta, Jyoti Verma, Girdhar Khandelwal, Krishanveer Singh, Kuldeep Singh","doi":"10.2174/012210299x264928231020123247","DOIUrl":"https://doi.org/10.2174/012210299x264928231020123247","url":null,"abstract":"Abstract: Convolvulus prostratus, also known as sankhapushpi, is a very adaptable plant frequently used as a nervine tonic, nootropic, and rejuvenator in cases of insanity and epilepsy and has a broad spectrum of beneficial properties. Several medicinal qualities, including anxiety, neuroprotective, antioxidant, analgesic, immunomodulatory, antibacterial, antidiabetic, and cardioprotective effects, have been related to this herb in ancient literature. Numerous bioactive phytoconstituents, including kaempferol(flavonoid), ceryl alcohol, scopolamine(phenolics), and convolamine (alkaloid), are associated with the therapeutic capabilities of this herb. The Whole herb or its juice is credited with alterative, antiphlogistic, and nervine tonic action. Additionally, the involvement of C. prostratus extracts in neurodegenerative was thoroughly established. Although this significant herb has comprehensive preclinical studies, thorough clinical research and mechanistic mode-of-action studies still need to be conducted. With a detailed analysis of the research gaps, the current review aims to highlight the phytonutrient constituents, beneficial characteristics, and therapeutic properties of C. prostratus. The creation of CNS phytopharmaceuticals, derived from C. prostratus, is hoped to flourish due to the scientific upgrade on the ethnomedicinal characteristics of this herb.","PeriodicalId":479738,"journal":{"name":"Current Indian Science","volume":"72 9","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135545021","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 : 2023-11-07DOI: 10.2174/012210299x256054231020060356
Navneet Arora, Ranjeet Kumar
Abstract: The NLRP3 inflammasome holds a pivotal position in the pathophysiological landscape of cardiac disorders, presenting itself as a promising therapeutic target. Central to this role are the proinflammatory cytokines Interleukin (IL)-1 and IL-18, which emerge as major players orchestrated by the activation of the NLRP3 inflammasome. This activation culminates in pyroptosis, a programmed form of cell death. While controlled activation of NLRP3 supports tissue repair, its excessive activation yields adverse consequences. Within the spectrum of cardiovascular diseases, ranging from abdominal aortic aneurysm to calcific aortic valve disease, the NLRP3 inflammasome is notably implicated. Atherosclerosis, myocardial infarction, diabetic cardiomyopathy, heart failure, and dilated cardiomyopathy collectively contribute to the genesis of inflammatory conditions. Key to this process is the nucleotide oligomerization domain-containing leucine-rich repeat protein 3 (NLRP3) inflammation, necessitating both priming and activation signals to orchestrate inflammation. Extensive scientific evidence substantiates the critical role of the NLRP3 inflammasome in cardiac disorders. Experimental models and clinical studies converge, highlighting its contribution to the intricate web of inflammatory pathways that underlie cardiac pathologies. This deeper understanding has spurred interest in targeting the NLRP3 inflammasome as a therapeutic avenue. Efforts to modulate the NLRP3 inflammasome are underway, aiming to temper its hyperactivity without disrupting its beneficial functions. Strategies involve small molecule inhibitors and biological agents, targeting various points along the signaling cascade. By selectively intervening in the NLRP3 pathway, researchers aspire to mitigate inflammatory responses, potentially ameliorating the progression of cardiac disorders. In conclusion, the NLRP3 inflammasome is a central orchestrator in the pathophysiology of diverse cardiac disorders. Its dual nature, capable of both driving repair and provoking harm, accentuates its significance as a therapeutic target. Scientific endeavors are actively unraveling its complexities, fostering the development of innovative interventions that could potentially revolutionize the management of cardiac inflammatory conditions.
{"title":"NLRP3 Inflammasome: Key Role in the Pathophysiology of Cardiac Disorders and its Potential as a Therapeutic Target","authors":"Navneet Arora, Ranjeet Kumar","doi":"10.2174/012210299x256054231020060356","DOIUrl":"https://doi.org/10.2174/012210299x256054231020060356","url":null,"abstract":"Abstract: The NLRP3 inflammasome holds a pivotal position in the pathophysiological landscape of cardiac disorders, presenting itself as a promising therapeutic target. Central to this role are the proinflammatory cytokines Interleukin (IL)-1 and IL-18, which emerge as major players orchestrated by the activation of the NLRP3 inflammasome. This activation culminates in pyroptosis, a programmed form of cell death. While controlled activation of NLRP3 supports tissue repair, its excessive activation yields adverse consequences. Within the spectrum of cardiovascular diseases, ranging from abdominal aortic aneurysm to calcific aortic valve disease, the NLRP3 inflammasome is notably implicated. Atherosclerosis, myocardial infarction, diabetic cardiomyopathy, heart failure, and dilated cardiomyopathy collectively contribute to the genesis of inflammatory conditions. Key to this process is the nucleotide oligomerization domain-containing leucine-rich repeat protein 3 (NLRP3) inflammation, necessitating both priming and activation signals to orchestrate inflammation. Extensive scientific evidence substantiates the critical role of the NLRP3 inflammasome in cardiac disorders. Experimental models and clinical studies converge, highlighting its contribution to the intricate web of inflammatory pathways that underlie cardiac pathologies. This deeper understanding has spurred interest in targeting the NLRP3 inflammasome as a therapeutic avenue. Efforts to modulate the NLRP3 inflammasome are underway, aiming to temper its hyperactivity without disrupting its beneficial functions. Strategies involve small molecule inhibitors and biological agents, targeting various points along the signaling cascade. By selectively intervening in the NLRP3 pathway, researchers aspire to mitigate inflammatory responses, potentially ameliorating the progression of cardiac disorders. In conclusion, the NLRP3 inflammasome is a central orchestrator in the pathophysiology of diverse cardiac disorders. Its dual nature, capable of both driving repair and provoking harm, accentuates its significance as a therapeutic target. Scientific endeavors are actively unraveling its complexities, fostering the development of innovative interventions that could potentially revolutionize the management of cardiac inflammatory conditions.","PeriodicalId":479738,"journal":{"name":"Current Indian Science","volume":"73 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135545175","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}
Background:: Cancer is caused by dysregulation of the cell cycle, which results in abnormal proliferation and the inability of cells to differentiate or die. Cyclins and cyclin-dependent kinases (CDK4) inhibitors are drugs that target a specific enzyme, CDK4 that controls cell cycle progression in cancer. Aim & Objective:: The aim of this study is to obtain an optimized pharmacophore of pyrrolo[2,3-d] pyrimidine as a CDK4 inhibitor using QSAR studies. This aids in determining the link between structure and activity in newly developed chemical entities (NCE’s). To perform molecular docking and ADMET analysis to determine the binding affinity and drug-likeness of NCE’s. Materials and Methods:: The Multiple linear regression approach (MLR) method was utilised to generate the QSAR Model using the programme QSARINS v.2.2.4. For molecular docking, the Autodock vina software was employed. While the Swiss ADME and ToxiM online tools were used to predict toxicity. Results and Discussion:: The best models generated for 2D QSAR had correlation coefficients of R2= 0.9247 & Q2= 0.924 and for 3D QSAR, coefficients were R2 = 0.9297 and Q2 = 0.876. A novel series of 68 derivatives was designed based on QSAR investigations. Molecule C-58 has shown maximum binding affinity in molecular docking as compared to the standard Ribociclib. result: For 2D QSAR, the best models produced has correlation coefficients of R2= 0.9247 and Q2= 0.924. The 3D-QSAR model obtained with R2= 0.9297 and Q2 = 0.876. Based on QSAR studies, a new series of 68 derivatives was generated Conclusion:: Fifteen compounds have shown potential as CDK4 inhibitors based on docking studies, pharmacokinetic behavior and toxicity profile. The maximum binding affinity was demonstrated by molecule C-58. other: N/A
{"title":"QSAR, Molecular Docking & ADMET Studies of Pyrrolo[2,3-d] Pyrimidine Derivatives as CDK4 Inhibitors for the Treatment of Cancer","authors":"Shital Patil, Varsha A. Patil, Kalyani Asgonkar, Vrushali Randive, Indrani Mahadik","doi":"10.2174/012210299x258569231006094309","DOIUrl":"https://doi.org/10.2174/012210299x258569231006094309","url":null,"abstract":"Background:: Cancer is caused by dysregulation of the cell cycle, which results in abnormal proliferation and the inability of cells to differentiate or die. Cyclins and cyclin-dependent kinases (CDK4) inhibitors are drugs that target a specific enzyme, CDK4 that controls cell cycle progression in cancer. Aim & Objective:: The aim of this study is to obtain an optimized pharmacophore of pyrrolo[2,3-d] pyrimidine as a CDK4 inhibitor using QSAR studies. This aids in determining the link between structure and activity in newly developed chemical entities (NCE’s). To perform molecular docking and ADMET analysis to determine the binding affinity and drug-likeness of NCE’s. Materials and Methods:: The Multiple linear regression approach (MLR) method was utilised to generate the QSAR Model using the programme QSARINS v.2.2.4. For molecular docking, the Autodock vina software was employed. While the Swiss ADME and ToxiM online tools were used to predict toxicity. Results and Discussion:: The best models generated for 2D QSAR had correlation coefficients of R2= 0.9247 & Q2= 0.924 and for 3D QSAR, coefficients were R2 = 0.9297 and Q2 = 0.876. A novel series of 68 derivatives was designed based on QSAR investigations. Molecule C-58 has shown maximum binding affinity in molecular docking as compared to the standard Ribociclib. result: For 2D QSAR, the best models produced has correlation coefficients of R2= 0.9247 and Q2= 0.924. The 3D-QSAR model obtained with R2= 0.9297 and Q2 = 0.876. Based on QSAR studies, a new series of 68 derivatives was generated Conclusion:: Fifteen compounds have shown potential as CDK4 inhibitors based on docking studies, pharmacokinetic behavior and toxicity profile. The maximum binding affinity was demonstrated by molecule C-58. other: N/A","PeriodicalId":479738,"journal":{"name":"Current Indian Science","volume":"32 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135322659","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 : 2023-10-24DOI: 10.2174/012210299x253718231006043520
Navneet Arora, Ranjeet Kumar
Abstract: Rosacea, a prevalent dermatological condition, is characterized by the clinical manifestations of erythema, papules, and pustules. This paper delves into the emerging role of the gut-skin axis in Rosacea's pathophysiology. Convincing evidence supports the involvement of gut microbiota in orchestrating the inflammatory cutaneous response. Its multifaceted etiology is thought to be influenced by genetic susceptibility, alterations in the neurovascular and immune systems, and altered interactions with the microbiota. Strong connections broaden our understanding of Rosacea, linking it to neurological conditions like Parkinson's disease and gastrointestinal issues such as Helicobacter pylori infection and small intestinal bacterial overgrowth (SIBO), supporting the existence of an intricate brain-gut-skin connection. The interplay between these organs' homeostatic and regulatory systems is increasingly evident. While we have not fully grasped the details of immunological, neuroendocrine, and metabolic pathways, it is clear they play a part in chronic inflammatory skin conditions like Rosacea. Delving into these intricate pathways promises a nuanced comprehension of the disease's etiopathogenesis. An in-depth investigation into the roles of dysbiotic microbiota and dysregulated innate immune responses is imperative to comprehensively fathom Rosacea's pathophysiological landscape. A refined grasp of this condition and the gutskin axis holds the potential for optimizing therapeutic trajectories. The purpose of this review is to explore potential bacterial indicators of the disease and to assess whether the gut microbiome makeup of individuals with inflammatory Rosacea differs from that of healthy controls. Furthermore, it critically assesses and consolidates previously documented alterations in peripheral blood, skin, and gastrointestinal tract microbiomes within rosacea patients. This review illuminates the intricate dance of microbiota in the context of Rosacea, forging a bridge between cutting-edge insights and its implications. By synthesizing current knowledge, this review advances our understanding of microbiota-driven mechanisms in inflammatory Rosacea, paving the way for innovative therapeutic strategies.
{"title":"Gut–Skin Axis: Gut Microbiota as a Link Between Rosacea and Gastrointestinal Comorbidities","authors":"Navneet Arora, Ranjeet Kumar","doi":"10.2174/012210299x253718231006043520","DOIUrl":"https://doi.org/10.2174/012210299x253718231006043520","url":null,"abstract":"Abstract: Rosacea, a prevalent dermatological condition, is characterized by the clinical manifestations of erythema, papules, and pustules. This paper delves into the emerging role of the gut-skin axis in Rosacea's pathophysiology. Convincing evidence supports the involvement of gut microbiota in orchestrating the inflammatory cutaneous response. Its multifaceted etiology is thought to be influenced by genetic susceptibility, alterations in the neurovascular and immune systems, and altered interactions with the microbiota. Strong connections broaden our understanding of Rosacea, linking it to neurological conditions like Parkinson's disease and gastrointestinal issues such as Helicobacter pylori infection and small intestinal bacterial overgrowth (SIBO), supporting the existence of an intricate brain-gut-skin connection. The interplay between these organs' homeostatic and regulatory systems is increasingly evident. While we have not fully grasped the details of immunological, neuroendocrine, and metabolic pathways, it is clear they play a part in chronic inflammatory skin conditions like Rosacea. Delving into these intricate pathways promises a nuanced comprehension of the disease's etiopathogenesis. An in-depth investigation into the roles of dysbiotic microbiota and dysregulated innate immune responses is imperative to comprehensively fathom Rosacea's pathophysiological landscape. A refined grasp of this condition and the gutskin axis holds the potential for optimizing therapeutic trajectories. The purpose of this review is to explore potential bacterial indicators of the disease and to assess whether the gut microbiome makeup of individuals with inflammatory Rosacea differs from that of healthy controls. Furthermore, it critically assesses and consolidates previously documented alterations in peripheral blood, skin, and gastrointestinal tract microbiomes within rosacea patients. This review illuminates the intricate dance of microbiota in the context of Rosacea, forging a bridge between cutting-edge insights and its implications. By synthesizing current knowledge, this review advances our understanding of microbiota-driven mechanisms in inflammatory Rosacea, paving the way for innovative therapeutic strategies.","PeriodicalId":479738,"journal":{"name":"Current Indian Science","volume":"32 5","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135322660","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}
Abstract: Biofilm formation often has detrimental effects from clinical and industrial perspectives. They are found to be resistant to antibiotics, detergents, etc., causing their treatment and cure to be onerous. Therefore, it becomes a necessity to develop novel methods to inhibit it. Iron is an essential regulator of bacterial biofilm formation. Studies suggest that by modulating iron concentration using either iron-chelating substances or iron salts, biofilm inhibition can be achieved depending on the mechanism of biofilm formation. This approach inhibits the expression of several genes responsible for adherence and colonization of bacteria. The use of nanoparticles is gaining rapid interest for biofilm inhibition. The ability of nanoparticles to act as antibacterial agents depends on their surface-to-mass ratio. Owing to their small size, certain metal nanoparticles can penetrate the EPS and inhibit bacterial adhesion and biofilm formation. Nanoparticles (NP) bring about cell lysis by interacting with cell membranes or producing Reactive Oxygen Species (ROS). Owing to the mechanical, thermal, or physiochemical properties of nanocomposite material, it is also studied for biofilm inhibition in various organisms. A widely appreciated method of NP synthesis is green synthesis, which makes use of plant extracts and microorganisms. Interestingly, plant extracts inherently are known to possess antimicrobial and anti-biofilm effects owing to their bioactive compounds. Plants synthesize secondary metabolites such as steroids, terpenoids, alkaloids, quinones, tannins, flavonoids, etc., for their defense, pollination, flavor, etc. Plant extracts made using appropriate solvents can be used to inhibit biofilm formed on various surfaces. They have been known to reduce biofilm by hindering exopolysaccharide formation and quorum sensing. In this review, we aim to describe these potential methods of biofilm inhibition.
{"title":"Combating Biofilm Formation by Modulating Iron Concentration, using Nanoparticles and Plant Extracts","authors":"Seema Rodge, Gayatri Kulkarni, Poorva Mahale, Shraddha Joshi, Sneha Dhanawade","doi":"10.2174/012210299x265522231006041656","DOIUrl":"https://doi.org/10.2174/012210299x265522231006041656","url":null,"abstract":"Abstract: Biofilm formation often has detrimental effects from clinical and industrial perspectives. They are found to be resistant to antibiotics, detergents, etc., causing their treatment and cure to be onerous. Therefore, it becomes a necessity to develop novel methods to inhibit it. Iron is an essential regulator of bacterial biofilm formation. Studies suggest that by modulating iron concentration using either iron-chelating substances or iron salts, biofilm inhibition can be achieved depending on the mechanism of biofilm formation. This approach inhibits the expression of several genes responsible for adherence and colonization of bacteria. The use of nanoparticles is gaining rapid interest for biofilm inhibition. The ability of nanoparticles to act as antibacterial agents depends on their surface-to-mass ratio. Owing to their small size, certain metal nanoparticles can penetrate the EPS and inhibit bacterial adhesion and biofilm formation. Nanoparticles (NP) bring about cell lysis by interacting with cell membranes or producing Reactive Oxygen Species (ROS). Owing to the mechanical, thermal, or physiochemical properties of nanocomposite material, it is also studied for biofilm inhibition in various organisms. A widely appreciated method of NP synthesis is green synthesis, which makes use of plant extracts and microorganisms. Interestingly, plant extracts inherently are known to possess antimicrobial and anti-biofilm effects owing to their bioactive compounds. Plants synthesize secondary metabolites such as steroids, terpenoids, alkaloids, quinones, tannins, flavonoids, etc., for their defense, pollination, flavor, etc. Plant extracts made using appropriate solvents can be used to inhibit biofilm formed on various surfaces. They have been known to reduce biofilm by hindering exopolysaccharide formation and quorum sensing. In this review, we aim to describe these potential methods of biofilm inhibition.","PeriodicalId":479738,"journal":{"name":"Current Indian Science","volume":"69 2","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135460400","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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