Skin diseases have recently become a major concern among people of all ages due to their highly visible symptoms and persistent and difficult treatment, which significantly impact their quality of life. Nigella sativa seeds, also known as "black seeds" or "kalonji," are one of the most commonly used herbal medicines due to their wide range of biological and pharmacological activities. It contains a wide range of bioactive constituents found in both fixed and essential oils. It has been used for hundreds of years as an alternative ethnomedicine to treat a wide range of skin conditions. N. sativa's dermatological applications in skin diseases are attributed to its potent antioxidant, anti-inflammatory, antimicrobial, and immunomodulatory properties, making it an intriguing skincare candidate. Several studies unravelled positive results associated with N. sativa on skin diseases. As N. sativa is the most studied medicinal plant, several preclinical and clinical studies have been conducted to establish its use in the treatment of various skin diseases. Thymoquinone has anti-inflammatory, antioxidant, and antibacterial properties, which mainly contributed to the treatment of skin diseases. In this context, the present review explores all the available studies on the association of N. sativa and its effect on treating skin diseases in light of recent studies and patents supporting its therapeutic applications.
{"title":"Dermaceutical Utilization of Nigella sativa Seeds: Applications and Opportunities.","authors":"Mariyam Khatoon, Poonam Kushwaha, Shazia Usmani, Kumud Madan","doi":"10.1055/a-2196-1815","DOIUrl":"10.1055/a-2196-1815","url":null,"abstract":"<p><p>Skin diseases have recently become a major concern among people of all ages due to their highly visible symptoms and persistent and difficult treatment, which significantly impact their quality of life. <i>Nigella sativa</i> seeds, also known as \"black seeds\" or \"kalonji,\" are one of the most commonly used herbal medicines due to their wide range of biological and pharmacological activities. It contains a wide range of bioactive constituents found in both fixed and essential oils. It has been used for hundreds of years as an alternative ethnomedicine to treat a wide range of skin conditions. <i>N. sativa's</i> dermatological applications in skin diseases are attributed to its potent antioxidant, anti-inflammatory, antimicrobial, and immunomodulatory properties, making it an intriguing skincare candidate. Several studies unravelled positive results associated with <i>N. sativa</i> on skin diseases. As <i>N. sativa</i> is the most studied medicinal plant, several preclinical and clinical studies have been conducted to establish its use in the treatment of various skin diseases. Thymoquinone has anti-inflammatory, antioxidant, and antibacterial properties, which mainly contributed to the treatment of skin diseases. In this context, the present review explores all the available studies on the association of <i>N. sativa</i> and its effect on treating skin diseases in light of recent studies and patents supporting its therapeutic applications.</p>","PeriodicalId":11451,"journal":{"name":"Drug Research","volume":" ","pages":"5-17"},"PeriodicalIF":2.2,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138451189","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 : 2024-01-01Epub Date: 2023-12-22DOI: 10.1055/a-2185-4916
Raja Shekhar Nunavath, Madhu Tanya Singh, Anubha Jain, Marjita Chakma, Rajaguru Arivuselvam, Mohamed Sheik Tharik Abdul Azeeze
The pharmaceutical industry has embraced the quality-by-design (QbD) approach as a promising development, formulation and manufacturing strategy. QbD provides a systematic and science-based framework for designing and producing high-quality products, with a particular focus on identifying, assessing and controlling risks throughout the development process. This review aims to assess the benefits of implementing QbD in pharmaceutical processes, evaluate its impact on regulatory compliance and explore its potential to enhance drug product quality. The primary objective of this review is to evaluate the influence of QbD on pharmaceutical development and manufacturing processes. It also seeks to examine the regulatory requirements associated with the implementation of QbD and highlight the advantages of this approach in terms of product quality and cost-effectiveness. Additionally, the review aims to explore the potential of QbD in improving the safety and efficacy of drug products. The QbD approach holds tremendous potential to revolutionize the pharmaceutical industry by optimizing drug development & manufacturing processes, reducing costs and enhancing product quality and consistency. However, implementing QbD requires a comprehensive understanding of the underlying science, as well as strict adherence to regulatory requirements in drug development and manufacturing. In conclusion, by embracing the QbD approach, the pharmaceutical industry can ensure the production of safe, effective and regulation-compliant products while simultaneously improving process efficiency. This strategic shift toward QbD represents a pivotal step in advancing pharmaceutical research and manufacturing capabilities, ultimately benefiting both the industry and more importantly, patients worldwide.
{"title":"Quality by Design in Pharmaceuticals: A Review of its Impact on Regulatory Compliance and Product Quality.","authors":"Raja Shekhar Nunavath, Madhu Tanya Singh, Anubha Jain, Marjita Chakma, Rajaguru Arivuselvam, Mohamed Sheik Tharik Abdul Azeeze","doi":"10.1055/a-2185-4916","DOIUrl":"10.1055/a-2185-4916","url":null,"abstract":"<p><p>The pharmaceutical industry has embraced the quality-by-design (QbD) approach as a promising development, formulation and manufacturing strategy. QbD provides a systematic and science-based framework for designing and producing high-quality products, with a particular focus on identifying, assessing and controlling risks throughout the development process. This review aims to assess the benefits of implementing QbD in pharmaceutical processes, evaluate its impact on regulatory compliance and explore its potential to enhance drug product quality. The primary objective of this review is to evaluate the influence of QbD on pharmaceutical development and manufacturing processes. It also seeks to examine the regulatory requirements associated with the implementation of QbD and highlight the advantages of this approach in terms of product quality and cost-effectiveness. Additionally, the review aims to explore the potential of QbD in improving the safety and efficacy of drug products. The QbD approach holds tremendous potential to revolutionize the pharmaceutical industry by optimizing drug development & manufacturing processes, reducing costs and enhancing product quality and consistency. However, implementing QbD requires a comprehensive understanding of the underlying science, as well as strict adherence to regulatory requirements in drug development and manufacturing. In conclusion, by embracing the QbD approach, the pharmaceutical industry can ensure the production of safe, effective and regulation-compliant products while simultaneously improving process efficiency. This strategic shift toward QbD represents a pivotal step in advancing pharmaceutical research and manufacturing capabilities, ultimately benefiting both the industry and more importantly, patients worldwide.</p>","PeriodicalId":11451,"journal":{"name":"Drug Research","volume":" ","pages":"18-23"},"PeriodicalIF":2.2,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138884698","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 : 2023-11-01Epub Date: 2023-11-07DOI: 10.1055/a-2176-4098
Wanfeng Qian, Ruheng Ji, Qiujie Ye, Wenjun Hu, Linying Zhou, Hongwu Pan, Xiaoming Li
Osteoarthritis is a common chronic degenerative disease, of which the essence is the degenerative changes of bone and joint cartilage, involving damage in multiple structures such as bone, synovium and joints. In the mechanism of arthritis inflammation is closely related, and therefore the exploration to inhibit inflammatory mediators is crucial for the clinical prevention and treatment of osteoarthritis. Inotodiol is a lanostane triterpenoid isolated from Inonotus obliquus, which had been extensively reported to be an anti-inflammatory agent, but its effect on arthritis remains unknown. In this study, we firstly demonstrated that inotodiol significantly reduced IL-1β-induced chondrocyte injury and inhibited the release of inflammatory factors. At the same time, experiments in vivo showed that inotodiol could effectively improve the symptoms of joint injury in mice and reduce the area of cartilage destruction, indicating that inotodiol may be a potential therapeutic drug for osteoarthritis.
{"title":"Inotodiol ameliorates the progression of osteoarthritis: An in vitro and in vivo study.","authors":"Wanfeng Qian, Ruheng Ji, Qiujie Ye, Wenjun Hu, Linying Zhou, Hongwu Pan, Xiaoming Li","doi":"10.1055/a-2176-4098","DOIUrl":"10.1055/a-2176-4098","url":null,"abstract":"<p><p>Osteoarthritis is a common chronic degenerative disease, of which the essence is the degenerative changes of bone and joint cartilage, involving damage in multiple structures such as bone, synovium and joints. In the mechanism of arthritis inflammation is closely related, and therefore the exploration to inhibit inflammatory mediators is crucial for the clinical prevention and treatment of osteoarthritis. Inotodiol is a lanostane triterpenoid isolated from Inonotus obliquus, which had been extensively reported to be an anti-inflammatory agent, but its effect on arthritis remains unknown. In this study, we firstly demonstrated that inotodiol significantly reduced IL-1β-induced chondrocyte injury and inhibited the release of inflammatory factors. At the same time, experiments <i>in vivo</i> showed that inotodiol could effectively improve the symptoms of joint injury in mice and reduce the area of cartilage destruction, indicating that inotodiol may be a potential therapeutic drug for osteoarthritis.</p>","PeriodicalId":11451,"journal":{"name":"Drug Research","volume":"73 9","pages":"506-512"},"PeriodicalIF":2.2,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71479416","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 : 2023-11-01Epub Date: 2023-07-21DOI: 10.1055/a-2095-0826
Sahil Kumar, Vandana Roy
Drug discovery and development is a time-consuming and costly procedure that necessitates a substantial effort. Drug repurposing has been suggested as a method for developing medicines that takes less time than developing brand new medications and will be less expensive. Also known as drug repositioning or re-profiling, this strategy has been in use from the time of serendipitous drug discoveries to the modern computer aided drug designing and use of computational chemistry. In the light of the COVID-19 pandemic too, drug repurposing emerged as a ray of hope in the dearth of available medicines. Data availability by electronic recording, libraries, and improvements in computational techniques offer a vital substrate for systemic evaluation of repurposing candidates. In the not-too-distant future, it could be possible to create a global research archive for us to access, thus accelerating the process of drug development and repurposing. This review aims to present the evolution, benefits and drawbacks including current approaches, key players and the legal and regulatory hurdles in the field of drug repurposing. The vast quantities of available data secured in multiple drug databases, assisting in drug repurposing is also discussed.
{"title":"Repurposing Drugs: An Empowering Approach to Drug Discovery and Development.","authors":"Sahil Kumar, Vandana Roy","doi":"10.1055/a-2095-0826","DOIUrl":"10.1055/a-2095-0826","url":null,"abstract":"<p><p>Drug discovery and development is a time-consuming and costly procedure that necessitates a substantial effort. Drug repurposing has been suggested as a method for developing medicines that takes less time than developing brand new medications and will be less expensive. Also known as drug repositioning or re-profiling, this strategy has been in use from the time of serendipitous drug discoveries to the modern computer aided drug designing and use of computational chemistry. In the light of the COVID-19 pandemic too, drug repurposing emerged as a ray of hope in the dearth of available medicines. Data availability by electronic recording, libraries, and improvements in computational techniques offer a vital substrate for systemic evaluation of repurposing candidates. In the not-too-distant future, it could be possible to create a global research archive for us to access, thus accelerating the process of drug development and repurposing. This review aims to present the evolution, benefits and drawbacks including current approaches, key players and the legal and regulatory hurdles in the field of drug repurposing. The vast quantities of available data secured in multiple drug databases, assisting in drug repurposing is also discussed.</p>","PeriodicalId":11451,"journal":{"name":"Drug Research","volume":" ","pages":"481-490"},"PeriodicalIF":2.2,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9848842","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}
Eukaryotic organisms contain an enzyme family called poly (ADP-ribose) polymerases (PARPs), which is responsible for the poly (ADP-ribosylation) of DNA-binding proteins. PARPs are members of the cell signaling enzyme class. PARP-1, the most common isoform of the PARP family, is responsible for more than 90% of the tasks carried out by the PARP family as a whole. A superfamily consisting of 18 PARPs has been found. In order to synthesize polymers of ADP-ribose (PAR) and nicotinamide, the DNA damage nick monitor PARP-1 requires NAD+ as a substrate. The capability of PARP-1 activation to boost the transcription of proinflammatory genes, its ability to deplete cellular energy pools, which leads to cell malfunction and necrosis, and its involvement as a component in the process of DNA repair are the three consequences of PARP-1 activation that are of particular significance in the process of developing new drugs. As a result, the pharmacological reduction of PARP-1 may result in an increase in the cytotoxicity toward cancer cells.
{"title":"A Review of PARP-1 Inhibitors: Assessing Emerging Prospects and Tailoring Therapeutic Strategies.","authors":"Soundarya Ramesh, Shannon D Almeida, Sameerana Hammigi, Govardan Katta Radhakrishna, Golla Sireesha, Theivendren Panneerselvam, Shangavi Vellingiri, Selvaraj Kunjiappan, Damodar Nayak Ammunje, Parasuraman Pavadai","doi":"10.1055/a-2181-0813","DOIUrl":"10.1055/a-2181-0813","url":null,"abstract":"<p><p>Eukaryotic organisms contain an enzyme family called poly (ADP-ribose) polymerases (PARPs), which is responsible for the poly (ADP-ribosylation) of DNA-binding proteins. PARPs are members of the cell signaling enzyme class. PARP-1, the most common isoform of the PARP family, is responsible for more than 90% of the tasks carried out by the PARP family as a whole. A superfamily consisting of 18 PARPs has been found. In order to synthesize polymers of ADP-ribose (PAR) and nicotinamide, the DNA damage nick monitor PARP-1 requires NAD+ as a substrate. The capability of PARP-1 activation to boost the transcription of proinflammatory genes, its ability to deplete cellular energy pools, which leads to cell malfunction and necrosis, and its involvement as a component in the process of DNA repair are the three consequences of PARP-1 activation that are of particular significance in the process of developing new drugs. As a result, the pharmacological reduction of PARP-1 may result in an increase in the cytotoxicity toward cancer cells.</p>","PeriodicalId":11451,"journal":{"name":"Drug Research","volume":" ","pages":"491-505"},"PeriodicalIF":2.2,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"61561578","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 : 2023-11-01Epub Date: 2023-11-07DOI: 10.1055/a-2182-3665
Viviane Miranda Bispo Steimbach, Ritade Cássia Vilhena da Silva, Luísa Nathália Bolda Mariano, Mariana Zanovello, Anelise Felício Macarini, Luisa Mota da Silva, Priscila de Souza
Background: Previous studies indicate the renal vasodilating effects of boldine, an alkaloid found in Peumus boldus. However, its potential to induce diuresis still needs to be studied.
Methods: Wistar rats were used and the urine volume was noted for 8 h and further studied.
Results: The acute treatment at 0.1 and 0.3 mg/kg of boldine showed a diuretic, natriuretic, and Ca2+-sparing effect in rats without changing the urinary elimination of K+and Cl-. When boldine was given in combination with hydrochlorothiazide, there was an increase in urinary volume compared to the vehicle group. However, this was not different from the treatments in its isolated form. Urine Ca2+values remained low but were not enhanced by this association. The excretion of Na+and Cl- was significantly increased compared to the group that received only vehicle or boldine. On the other hand, although the association of amiloride plus boldine did not result in a diuretic effect, the increase in Na+and the reduction in K+excretion were significantly potentiated. Furthermore, in the presence of the non-selective muscarinic receptor antagonist atropine, boldine showed reduced capacity to increase urinary volume, maintaining the natriuretic and Ca2+-sparing effect, besides a very evident K+-sparing action. Similar results were obtained in the presence of the non-selective cyclooxygenase inhibitor indomethacin. Furthermore, boldine showed an ex vivo antiurolithiasis activity, reducing calcium oxalate's precipitation and crystallization.
Conclusions: This study reveals the diuretic, natriuretic, Ca2+-sparing, and antiurolithiatic effects of boldine, an action possibly related to muscarinic receptor activation and prostanoid generation.
{"title":"Diuretic, Natriuretic, And Ca2+-Sparing Effect Of The Alkaloid Boldine In Rats.","authors":"Viviane Miranda Bispo Steimbach, Ritade Cássia Vilhena da Silva, Luísa Nathália Bolda Mariano, Mariana Zanovello, Anelise Felício Macarini, Luisa Mota da Silva, Priscila de Souza","doi":"10.1055/a-2182-3665","DOIUrl":"10.1055/a-2182-3665","url":null,"abstract":"<p><strong>Background: </strong>Previous studies indicate the renal vasodilating effects of boldine, an alkaloid found in <i>Peumus boldus</i>. However, its potential to induce diuresis still needs to be studied.</p><p><strong>Methods: </strong>Wistar rats were used and the urine volume was noted for 8 h and further studied.</p><p><strong>Results: </strong>The acute treatment at 0.1 and 0.3 mg/kg of boldine showed a diuretic, natriuretic, and Ca<sup>2+</sup>-sparing effect in rats without changing the urinary elimination of K<sup>+</sup>and Cl<sup>-</sup>. When boldine was given in combination with hydrochlorothiazide, there was an increase in urinary volume compared to the vehicle group. However, this was not different from the treatments in its isolated form. Urine Ca<sup>2+</sup>values remained low but were not enhanced by this association. The excretion of Na<sup>+</sup>and Cl<sup>-</sup> was significantly increased compared to the group that received only vehicle or boldine. On the other hand, although the association of amiloride plus boldine did not result in a diuretic effect, the increase in Na<sup>+</sup>and the reduction in K<sup>+</sup>excretion were significantly potentiated. Furthermore, in the presence of the non-selective muscarinic receptor antagonist atropine, boldine showed reduced capacity to increase urinary volume, maintaining the natriuretic and Ca<sup>2+</sup>-sparing effect, besides a very evident K<sup>+</sup>-sparing action. Similar results were obtained in the presence of the non-selective cyclooxygenase inhibitor indomethacin. Furthermore, boldine showed an ex vivo antiurolithiasis activity, reducing calcium oxalate's precipitation and crystallization.</p><p><strong>Conclusions: </strong>This study reveals the diuretic, natriuretic, Ca<sup>2+</sup>-sparing, and antiurolithiatic effects of boldine, an action possibly related to muscarinic receptor activation and prostanoid generation.</p>","PeriodicalId":11451,"journal":{"name":"Drug Research","volume":"73 9","pages":"513-519"},"PeriodicalIF":2.2,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71479414","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 : 2023-11-01Epub Date: 2023-11-07DOI: 10.1055/a-2160-2186
Nagwa I Helal, Noha M El-Khodary, Gamal A Omran, Soha M El-Masry
The objective of the current study was to investigate the effects of resveratrol (RSV), a natural herbal remedy used as an adjacent anti-inflammatory supplement on, the pharmacokinetics of celecoxib in healthy male volunteers. Twelve healthy human participants were involved in two-period open-labeled trial. Celecoxib (200 mg) was given as a single oral dose under fasting conditions as a control phase. Afterward, RSV (500 mg) commenced as a single oral dose for ten days as a treatment phase. Blood samples were collected during the control and treatment phases and analyzed using the validated High-performance liquid chromatography (HPLC) method. RSV pre-exposure significantly increased the area under the curve (AUC0-24), peak plasma concentration (Cmax), absorption rate constant (ka), and prolongated half-life (t1/2), along with a decrease in elimination rate constant (ke). Meanwhile, the volume of distribution (Vd/F) and apparent total body clearance (CL/F) were significantly decreased for celecoxib. There was no significant change in the time it takes for celecoxib to reach the maximum concentration (tmax) was observed. The obtained results suggested the presence of a beneficial pharmacokinetic interaction between RSV and celecoxib. Consequently, combining resveratrol as an herbal remedy and celecoxib as an anti-inflammatory drug may synergistically reduce inflammation and osteoarthritis with minimal side effects.
{"title":"Effects of Resveratrol Co-Administration on Celecoxib Disposition and Pharmacokinetics in Healthy Volunteers.","authors":"Nagwa I Helal, Noha M El-Khodary, Gamal A Omran, Soha M El-Masry","doi":"10.1055/a-2160-2186","DOIUrl":"10.1055/a-2160-2186","url":null,"abstract":"<p><p>The objective of the current study was to investigate the effects of resveratrol (RSV), a natural herbal remedy used as an adjacent anti-inflammatory supplement on, the pharmacokinetics of celecoxib in healthy male volunteers. Twelve healthy human participants were involved in two-period open-labeled trial. Celecoxib (200 mg) was given as a single oral dose under fasting conditions as a control phase. Afterward, RSV (500 mg) commenced as a single oral dose for ten days as a treatment phase. Blood samples were collected during the control and treatment phases and analyzed using the validated High-performance liquid chromatography (HPLC) method. RSV pre-exposure significantly increased the area under the curve (AUC<sub>0-24</sub>), peak plasma concentration (C<sub>max</sub>), absorption rate constant (ka), and prolongated half-life (t<sub>1/2</sub>), along with a decrease in elimination rate constant (ke). Meanwhile, the volume of distribution (Vd/F) and apparent total body clearance (CL/F) were significantly decreased for celecoxib. There was no significant change in the time it takes for celecoxib to reach the maximum concentration (t<sub>max</sub>) was observed. The obtained results suggested the presence of a beneficial pharmacokinetic interaction between RSV and celecoxib. Consequently, combining resveratrol as an herbal remedy and celecoxib as an anti-inflammatory drug may synergistically reduce inflammation and osteoarthritis with minimal side effects.</p>","PeriodicalId":11451,"journal":{"name":"Drug Research","volume":"73 9","pages":"520-527"},"PeriodicalIF":2.2,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71479415","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 : 2023-10-01Epub Date: 2023-08-17DOI: 10.1055/a-2142-5774
V Soumya, S Deepa, Knolin K Thachil, J Saravanan, R Hariprasad
Poly cystic ovary syndrome (PCOS) is considered as one of the common hormonal disorders affecting 6-20% of women in their reproductive age with characteristic features include anovulatory infertility, hyperandrogenism, cystic follicles and insulin resistance. The gene CYP play an important role in pathophysiology of hyperandrogenism associated with PCOS. An elevated androgens are reported in PCOS condition due to overexpression of the enzyme CYP450 17 α: . As well as diminished levels of aromatase (CYP450 19) were observed in several hyperandrogenic PCOS patients. The powdered leafy material of Cinnamomum malabatrum was subjected to Soxhlet extraction. The plant extract was subjected to Gas chromatography-MS analysis (GC-MS), and the chromatogram obtained revealed the presence of active chemical constituents like 1(10),9(11)-B-Homolanistadiene for the first time and other potential compounds. Hypothesis has raised to interpret the efficiency of phytoconstituents of Cinnamomum malabatrum on these enzyme targets and which may be a novel drug candidate for the treatment and maintenance of hyperandrogenism associated with PCOS. Thus, the results obtained from the in-silico study of Cinnamomum malabatrum leaf extract using computational approaches indicate that the phytoconstituents have good affinities for the selected two key targets. ADME and PASS studies has been performed for active phytoconstituents homolanistadiene, β-sitosterol, cycloartenol and a pyrazole derivative, and results revealed the Lipinski drug-likeness and pharmacological potential. In conclusion, this work throws a new insight into the possibility of the active phytoconstituents on binding the two active CYP45017 α and CYP45019 aromatase enzymes which facilitates development of novel compounds for hyperandrogenism associated with PCOS.
{"title":"GC-MS analysis and in silico docking of constituents of Cinnamomum malabatrum against CYP450 17α and CYP450 19 (Aromatase)- Key targets for hyperandrogenism.","authors":"V Soumya, S Deepa, Knolin K Thachil, J Saravanan, R Hariprasad","doi":"10.1055/a-2142-5774","DOIUrl":"10.1055/a-2142-5774","url":null,"abstract":"<p><p>Poly cystic ovary syndrome (PCOS) is considered as one of the common hormonal disorders affecting 6-20% of women in their reproductive age with characteristic features include anovulatory infertility, hyperandrogenism, cystic follicles and insulin resistance. The gene CYP play an important role in pathophysiology of hyperandrogenism associated with PCOS. An elevated androgens are reported in PCOS condition due to overexpression of the enzyme CYP<sub>450</sub> 17 α: . As well as diminished levels of aromatase (CYP<sub>450</sub> 19) were observed in several hyperandrogenic PCOS patients. The powdered leafy material of <i>Cinnamomum malabatrum</i> was subjected to Soxhlet extraction. The plant extract was subjected to Gas chromatography-MS analysis (GC-MS), and the chromatogram obtained revealed the presence of active chemical constituents like 1(10),9(11)-B-Homolanistadiene for the first time and other potential compounds. Hypothesis has raised to interpret the efficiency of phytoconstituents of C<i>innamomum malabatrum</i> on these enzyme targets and which may be a novel drug candidate for the treatment and maintenance of hyperandrogenism associated with PCOS. Thus, the results obtained from the <i>in-silico</i> study of <i>Cinnamomum malabatrum</i> leaf extract using computational approaches indicate that the phytoconstituents have good affinities for the selected two key targets. ADME and PASS studies has been performed for active phytoconstituents homolanistadiene, β-sitosterol, cycloartenol and a pyrazole derivative, and results revealed the Lipinski drug-likeness and pharmacological potential. In conclusion, this work throws a new insight into the possibility of the active phytoconstituents on binding the two active CYP<sub>450</sub>17 α and CYP<sub>450</sub>19 aromatase enzymes which facilitates development of novel compounds for hyperandrogenism associated with PCOS.</p>","PeriodicalId":11451,"journal":{"name":"Drug Research","volume":" ","pages":"441-447"},"PeriodicalIF":2.2,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10077514","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 : 2023-10-01Epub Date: 2023-07-24DOI: 10.1055/a-2088-3889
Patnam Nageswari, K Swathi
Globally, Urolithiasis is the most prevalent urological problem which affects the populations across the ages and races. In recent years, several phytochemicals are being investigated to improve the efficacy and safety of anti-urolithiasis formulations. To develop drugs based on traditional medicines, it is essential to understand the molecular mechanism of action of these drugs. We present the results of in silico docking and molecular dynamic (MD) simulation studies on selected phytochemical including catechin, epicatechin, gallic acid, gallocatechin, epigallocatechin, epigallocatechin 3-o-gallate, 4-methoxy-nor-securine, nor-securinine, and fisetin with human glycolate oxidase (hGOX) and oxalate oxidase (OxO). Gallic acid, gallocatechin and fisetin showed better docking scores than the rest. In MD simulation analysis, stable interactions of the gallic acid with hGOX and OxO; gallocatechin and fisetin with hGOX were observed. It was found that, gallic acid stably interacts withTYR26, LYS 236, ARG 315, and ASP 291 residues of hGOX. On other hand, gallic acid stably interacs with GLU 58 residue of OxO. Gallocatechin, forms stable interactions with TYR 26, ASP 170, ARG 167 and THR 161 of HGOX. In MD simulations, fisetin stably interacted with TYR 26, TRP110 and ARG 263 as we predicted in molecular docking. None of the interactions was formed during the MD simulation of OxO with gallocatechin and fisetin. Together, these results suggest that gallic acid, gallocatechin and fisetin are the potential candidates for the development of phytochemicals for the management of urolithiasis in humans.
{"title":"In silico docking and Molecular Dynamic (MD) simulations studies of selected phytochemicals against Human Glycolate Oxidase (hGOX) and Oxalate oxidase (OxO).","authors":"Patnam Nageswari, K Swathi","doi":"10.1055/a-2088-3889","DOIUrl":"10.1055/a-2088-3889","url":null,"abstract":"<p><p>Globally, Urolithiasis is the most prevalent urological problem which affects the populations across the ages and races. In recent years, several phytochemicals are being investigated to improve the efficacy and safety of anti-urolithiasis formulations. To develop drugs based on traditional medicines, it is essential to understand the molecular mechanism of action of these drugs. We present the results of <i>in silico</i> docking and molecular dynamic (MD) simulation studies on selected phytochemical including catechin, epicatechin, gallic acid, gallocatechin, epigallocatechin, epigallocatechin 3-o-gallate, 4-methoxy-nor-securine, nor-securinine, and fisetin with human glycolate oxidase (hGOX) and oxalate oxidase (OxO). Gallic acid, gallocatechin and fisetin showed better docking scores than the rest. In MD simulation analysis, stable interactions of the gallic acid with hGOX and OxO; gallocatechin and fisetin with hGOX were observed. It was found that, gallic acid stably interacts withTYR26, LYS 236, ARG 315, and ASP 291 residues of hGOX. On other hand, gallic acid stably interacs with GLU 58 residue of OxO. Gallocatechin, forms stable interactions with TYR 26, ASP 170, ARG 167 and THR 161 of HGOX. In MD simulations, fisetin stably interacted with TYR 26, TRP110 and ARG 263 as we predicted in molecular docking. None of the interactions was formed during the MD simulation of OxO with gallocatechin and fisetin. Together, these results suggest that gallic acid, gallocatechin and fisetin are the potential candidates for the development of phytochemicals for the management of urolithiasis in humans.</p>","PeriodicalId":11451,"journal":{"name":"Drug Research","volume":" ","pages":"459-464"},"PeriodicalIF":2.2,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9866180","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 : 2023-10-01Epub Date: 2023-07-24DOI: 10.1055/a-2081-4232
Nunavath Raja Shekhar, Krishnaveni Nagappan, Madhu Tanya Singh, S P Dhanabal
Nitrosamines are a class of chemical compounds that have been found to be impurities in a variety of pharmaceutical products. These impurities have raised concerns due to their potential carcinogenic effects. Recent studies have identified nitrosamines as impurities in a number of pharmaceutical products including angiotensin II receptor blockers (ARBs) and proton pump inhibitors (PPIs). The presence of nitrosamines in these products has led to recalls and market withdrawals. In addition to pharmaceuticals, nitrosamines have also been found in some herbal medicines particularly those containing traditional Chinese medicinal ingredients. The presence of nitrosamines in herbal formulations poses a significant risk to public health and highlights the need for quality control and regulations in the herbal drug industry. The present review article aims to discuss nitrosamine impurities (NMI) prominent causes, risks and scientific strategies for preventing NMI in herbal formulations. The primary objective of this study is to examine the origins of nitrosamine contamination in herbal formulations, the risks associated with these contaminants, and the methods for reducing them. The significance of thorough testing and examination before releasing herbal products to the public is also emphasized. In conclusion, the presence of nitrosamines is not limited to pharmaceutical products and poses a significant threat to the safety of herbal drugs as well. Adequate testing and extensive research are crucial for producing and distributing herbal medicines to the general population.
{"title":"Nitrosamine Impurities in Herbal Formulations: A Review of Risks and Mitigation Strategies.","authors":"Nunavath Raja Shekhar, Krishnaveni Nagappan, Madhu Tanya Singh, S P Dhanabal","doi":"10.1055/a-2081-4232","DOIUrl":"10.1055/a-2081-4232","url":null,"abstract":"<p><p>Nitrosamines are a class of chemical compounds that have been found to be impurities in a variety of pharmaceutical products. These impurities have raised concerns due to their potential carcinogenic effects. Recent studies have identified nitrosamines as impurities in a number of pharmaceutical products including angiotensin II receptor blockers (ARBs) and proton pump inhibitors (PPIs). The presence of nitrosamines in these products has led to recalls and market withdrawals. In addition to pharmaceuticals, nitrosamines have also been found in some herbal medicines particularly those containing traditional Chinese medicinal ingredients. The presence of nitrosamines in herbal formulations poses a significant risk to public health and highlights the need for quality control and regulations in the herbal drug industry. The present review article aims to discuss nitrosamine impurities (NMI) prominent causes, risks and scientific strategies for preventing NMI in herbal formulations. The primary objective of this study is to examine the origins of nitrosamine contamination in herbal formulations, the risks associated with these contaminants, and the methods for reducing them. The significance of thorough testing and examination before releasing herbal products to the public is also emphasized. In conclusion, the presence of nitrosamines is not limited to pharmaceutical products and poses a significant threat to the safety of herbal drugs as well. Adequate testing and extensive research are crucial for producing and distributing herbal medicines to the general population.</p>","PeriodicalId":11451,"journal":{"name":"Drug Research","volume":" ","pages":"431-440"},"PeriodicalIF":2.2,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9866182","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}