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1.
Biofactors ; 2020 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-32039535

RESUMO

Reprogrammed metabolism is key biochemical characteristic of malignant cells, which represents one of the emerging hallmarks of cancer. Currently, there is rising contemplation on oxidative pentose phosphate pathway (PPP) enzymes as potential therapeutic hits due to their affiliation with tumor metabolism. 6-Phosphogluconate dehydrogenase (6PGD), third oxidative decarboxylase of PPP, has received a great deal of attention during recent years due to its critical role in tumorigenesis and redox homeostasis. 6PGD has been reported to overexpress in number of cancer types and its hyperactivation is mediated through post-transcriptional and post-translational modifications by YTH domain family 2 (YTHDF2), Nrf2 (nuclear factor erythroid 2-related factor 2), EGFR (epidermal growth factor receptor) and via direct structural interactions with ME1 (malic enzyme 1). Upregulated expression of 6PGD provides metabolic as well as defensive advantage to cancer cells, thus, promoting their proliferative and metastatic potential. Moreover, enhanced 6PGD expression also performs key role in development of chemoresistance as well as radiation resistance in cancer. This review aims to discuss the historical timeline and cancer-specific role of 6PGD, pharmacological and genetic inhibitors of 6PGD and 6PGD as prognostic biomarker in order to explore its potential for therapeutic interventions. We anticipate that targeting this imperative supplier of NADPH might serve as tempting avenue to combat the deadly disease like cancer.

2.
Int J Biol Sci ; 16(1): 116-134, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31892850

RESUMO

Peripheral nerve injury is a complex condition with a variety of signs and symptoms such as numbness, tingling, jabbing, throbbing, burning or sharp pain. Peripheral nerves are fragile in nature and can easily get damaged due to acute compression or trauma which may lead to the sensory and motor functions deficits and even lifelong disability. After lesion, the neuronal cell body becomes disconnected from the axon's distal portion to the injury site leading to the axonal degeneration and dismantlement of neuromuscular junctions of targeted muscles. In spite of extensive research on this aspect, complete functional recovery still remains a challenge to be resolved. This review highlights detailed pathophysiological events after an injury to a peripheral nerve and the associated factors that can either hinder or promote the regenerative machinery. In addition, it throws light on the available therapeutic strategies including supporting therapies, surgical and non-surgical interventions to ameliorate the axonal regeneration, neuronal survival, and reinnervation of peripheral targets. Despite the availability of various treatment options, we are still lacking the optimal treatments for a perfect and complete functional regain. The need for the present age is to discover or design such potent compounds that would be able to execute the complete functional retrieval. In this regard, plant-derived compounds are getting more attention and several recent reports validate their remedial effects. A plethora of plants and plant-derived phytochemicals have been suggested with curative effects against a number of diseases in general and neuronal injury in particular. They can be a ray of hope for the suffering individuals.

3.
J Asian Nat Prod Res ; 22(1): 1-16, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29973097

RESUMO

Eupatilin (5,7-dihydroxy-3',4',6-trimethoxyflavone) is a pharmacologically active flavone which has been isolated from a variety of medicinal plants. Eupatilin is known to possess various pharmacological properties such as anti-cancer, anti-oxidant, and anti-inflammatory. It is speculated that eupatilin could be subjected to structural optimization for the synthesis of derivative analogs to reinforce its efficacy, to minimize toxicity, and to optimize absorption profiles, which will ultimately lead towards potent drug candidates. Although, reported data acclaim multiple pharmacological activities of eupatilin but further experimentations on its molecular mechanism of action are yet mandatory to elucidate full spectrum of its pharmacological activities.

4.
Crit Rev Food Sci Nutr ; 60(3): 351-374, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-30614244

RESUMO

Brain is a central and pivotal organ of human body containing the highest lipids content next to adipose tissue. It works as a monitor for the whole body and needs an adequate supply of energy to maintain its physiological activities. This high demand of energy in the brain is chiefly maintained by the lipids along with its reservoirs. Thus, the lipid metabolism is also an important for the proper development and function of the brain. Being a prominent part of the brain, lipids play a vast number of physiological activities within the brain starting from the structural development, impulse conduction, insulation, neurogenesis, synaptogenesis, myelin sheath formation and finally to act as the signaling molecules. Interestingly, lipids bilayer also maintains the structural integrity for the physiological functions of protein. Thus, in light to all of these activities, lipids and its metabolism can be attributed pivotal for brain health and its activities. Decisively, the impaired/altered metabolism of lipids and its intermediates puts forward a key step in the progression of different brain ailments including neurodegenerative, neurological and neuropsychiatry disorders. Depending on their associated underlying pathways, they serve as the potential biomarkers of these disorders and are considered as necessary diagnostic tools. The present review discusses the role and level of altered lipids metabolism in brain diseases including neurodegenerative diseases, neurological diseases, and neuropsychiatric diseases. Moreover, the possible mechanisms of altered level of lipids and their metabolites have also been discussed in detail.

5.
Pak J Pharm Sci ; 32(4(Supplementary)): 1761-1766, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31680070

RESUMO

Peripheral nerve injury is a complex condition which results in restricted physical activity. Despite the tremendous efforts to figure out effective remedies, the complete functional retrieval is still a goal to be achieved. So, the need of hour is the exploration of potential natural compounds to recover this functional loss. Here, we have investigated the role of a local plant "Neurada procumbens" in ameliorating the functional recovery after an induced nerve compression injury in a mouse model. A dose of N. procumbens (50mg/kg of body weight) was administered orally from the day of injury to onwards. The motor functional recovery was assessed by evaluating muscle grip strength and sciatic functional index; while the sensory functions were gauged by the hotplate test. The serological parameters were carried out to analyze the effect of N. procumbens on oxidative stress level. The recovery of sensory and motor functions was significantly improved and perceived earlier in the treatment group. Moreover, the elevated antioxidant level was statistically significant in the treatment group. These results indicate that the supplementation of N. procumbens accelerates functional recovery after sciatic nerve crush injury.

6.
Pak J Pharm Sci ; 32(4(Supplementary)): 1797-1803, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31680075

RESUMO

Leukemia is a type of blood cancer where abnormal and immature leucocytes are produced in the bone marrow. Methadone hydrochloride is a man-made drug that is commonly used in the maintenance treatment for drug addiction. The objective of this research was to determine the cytotoxic activity and apoptotic effects of methadone hydrochloride treatment towards two leukemia cell lines which are CCRF-CEM and HL-60. CCRF-CEM and HL-60 cells were treated with methadone hydrochloride for 24 and 48 hours to determine the cytotoxic activity. IC50 at 24 hours obtained for CCRF-CEM was 121.6µmol/L while IC50 for HL-60 cells was 97.18µmol/L. Result obtained from DNA fragmentation assay showed no characteristic DNA ladder pattern in CCRF-CEM leukemia cells treated with methadone hydrochloride. Characteristics DNA ladder pattern was observed in methadone hydrochloride treated HL-60 cells. Formation of comets was seen in methadone hydrochloride treated CCRF-CEM and HL-60 cells with varying degree of DNA damage. The comets formed by methadone hydrochloride treated HL-60 cells were more prominent as compared to methadone-treated CCRF-CEM cells. The expression of apoptotic-related proteins in methadone-treated CCRF-CEM and HL-60 cells were checked by incubating the cell lysate with Raybio® Human Apoptosis Antibody Array. Significant alterations in expression level of apoptosis-related proteins in methadone hydrochloride treated CCRF-CEM cells were found involving upregulation of caspase-8 expression and downregulation of survivin expression. Methadone hydrochloride induced apoptosis in HL-60 cells involved upregulation of Bid and caspase-8 expression and downregulation of Bcl-2, p21 and survivin expression.

7.
Int J Biol Sci ; 15(10): 2256-2264, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31592132

RESUMO

Nature has generously offered life-saving therapies to mankind by providing evolutionarily optimized drug-like entities in the form of natural products. These splendid gifts of nature have served as most suitable candidates for anti-cancer drug discovery due to their pleiotropic activity on target molecules. This review aims to provide an update on the natural sources and bioactivities of such gifts from nature, salvianolic acid A & B, which are major bioactive constituents of a traditional Chinses medicinal herb, Salvia miltiorrhiza. Salvianolic acid A & B have been reported to owe anti-cancer, anti-inflammatory and cardioprotective activities. Currently salvianolic acids have been emerged as potent anti-cancer molecules. Salvianolic acid A & B fight cancer progression by prompting apoptosis, halting cell cycle and adjourning metastasis by targeting multiple deregulated signaling networks of cancer. Moreover, salvianolic acid A & B display potency towards sensitizing cancer cells to chemo-drugs. The review purposes that salvianolic acid A & B supply a novel opportunity for drug discovery but further experimentation is mandatory to embellish the knowledge of their pharmacological usage and to access their toxicological limits in order to establish these compounds as potential multitarget future drugs.

8.
J Food Biochem ; 43(9): e12983, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31489666

RESUMO

Peripheral nerve injury is one of the major health concerns of the present era which can lead to the long-lasting disability and even demise. Currently, no effective and side effect free remedy exists and exploration of effective therapeutic strategies to regain functional outcome is a need of hour. In the present study, we used BALB/c mice (N = 14 age, 10-12 weeks & weight 32-34 g) that were divided into two groups: Normal chow (n = 7) and Fennel chow (n = 7) group. Here, we have explored the role of crude Foeniculum vulgare mill seeds in promoting functional recovery following a mechanical insult to the sciatic nerve by an oral administration of a crude dose of 500 mg/kg BW. The recovery of both sensory and motor functions was significantly (p > .05) accelerated in the treatment group, assessed by behavioral analyses alongside total antioxidant capacity increase. Conclusively, F. vulgare can be a potential therapeutic candidate for accelerating functional recovery after peripheral nerve injury. PRACTICAL APPLICATIONS: The outcomes of study have vital practical application both for scientists and consumers. The therapeutic role of phytochemicals on functional recovery has not been explored yet. This study will help figure out plant based regimen as booster for brain health and intervention against traumatic nerve injuries. Moreover, it may also attract the food and pharmaceutical industries to formulate cost effective therapeutic products. Likewise, it can prove instrumental for scientists for advance research on this aspect with more mechanistic targets.

9.
Biomed Res Int ; 2019: 5854315, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31467899

RESUMO

Nature, a vast reservoir of pharmacologically active molecules, has been most promising source of drug leads for the cure of various pathological conditions. Formononetin is one of the bioactive isoflavones isolated from different plants mainly from Trifolium pratense, Glycine max, Sophora flavescens, Pycnanthus angolensis, and Astragalus membranaceus. Formononetin has been well-documented for its anti-inflammatory, anticancer, and antioxidant properties. Recently anticancer activity of formononetin is widely studied. This review aims to highlight the pharmacological potential of formononetin, thus providing an insight of its status in cancer therapeutics. Formononetin fights progression of cancer via inducing apoptosis, arresting cell cycle, and halting metastasis via targeting various pathways which are generally modulated in several cancers. Although reported data acclaims various biological properties of formononetin, further experimentation on mechanism of its action, medicinal chemistry studies, and preclinical investigations are surely needed to figure out full array of its pharmacological and biological potential.


Assuntos
Proliferação de Células/efeitos dos fármacos , Isoflavonas/farmacologia , Neoplasias/tratamento farmacológico , Apoptose/efeitos dos fármacos , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Humanos , Isoflavonas/química , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Soja/química , Trifolium/química
10.
IUBMB Life ; 71(11): 1701-1710, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31301214

RESUMO

Secreted frizzled-related protein 4 (SFRP4) is a member of secreted protein family with sequence similarity to frizzled receptors of wingless-related integration site (Wnt) signaling pathways. These proteins control diverse functions from embryonic development to adults in many organisms including humans. Initially, SFRPs were recognized as antagonists of Wnt signaling and supposed to interact with Wnts. Further research demonstrated their interactions to frizzled receptors and a functional diversity was related to these proteins, Wnt signaling potentiation in addition to modulation. SFRP4 is the largest member of SFRP family and is implicated in many diseases including obesity, type 2 diabetes (T2D), and cancer. SFRP4 acts as a biomarker for T2D and was expressed several years before clinical diagnosis of disease. This review mainly focusses on the role of SFRP4 in obesity and how it can lead to ß-cell failure and ultimately to T2D. The role of SFRP4 in adipose tissues causing increased production of adipokines lead to the oxidative stress in pancreas that particularly have low amount of antioxidant enzymes in pancreatic ß-cells leading to failure in exocytosis of insulin containing granules causing T2D. Obesity-induced inflammation is a principal factor in pathogenesis of insulin resistance as well as metabolic syndrome. Pro-inflammatory cytokines have potential to cause insulin resistance in skeletal muscles, adipose tissue, and liver via inhibition of insulin signal transduction. Secretion of SFRP4 is mediated by interleukin 1-ß (IL1-ß). This review highlights the molecular mechanisms by which SFRP4 leads to T2D. Understanding of molecular mechanism and targeting SFRP4 could help to eradicate or reduce chances of developing T2D.

11.
Int J Biol Sci ; 15(8): 1600-1609, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31360103

RESUMO

Natural products, an infinite treasure of bioactive scaffolds, have provided an excellent reservoir for the discovery of drugs since millennium. These naturally occurring, biologically active and therapeutically effective chemical entities have emerged as novel paradigm for the prevention of various diseases. This review aims to give an update on the sources as well as pharmacological profile of curcumol, a pharmacologically active sesquiterpenoid, which is an imperative bioactive constituent of several plants mainly from genus Curcuma. Curcumol has potential to fight against cancer, oxidative stress, neurodegeneration, microbial infections, and inflammation. Curcumol has been documented as potent inducer of apoptosis in numerous cancer cells via targeting key signaling pathways as MAPK/ERK, PI3K/Akt and NF-κB which are generally deregulated in several cancers. The reported data reveals multitarget activity of curcumol in cancer treatment suggesting its importance as anticancer drug in future. It is speculated that curcumol may provide an excellent opportunity for the cure of cancer but further investigations on mechanism of its action and preclinical trials are still mandatory to further validate the potential of this natural cancer killer in anticancer therapies.

13.
IUBMB Life ; 71(10): 1418-1427, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31169978

RESUMO

Altered enzymatic machineries are a substantial biochemical characteristic of tumor cell metabolism that switch metabolic profile from oxidative phosphorylation to amplified glycolysis as well as increased lactate production under hypoxia conditions. Reprogrammed metabolic profile is an emerging hallmark of cancer. Overexpression of several glycolytic enzymes and glucose transporters has been reported in 24 different types of cancers that represent approximately 70% of all the cancer cases around the globe. Thus, targeting glycolytic enzymes could serve as tempting avenue for drug design against cancer. Phosphoglycerate mutase 1 (PGAM1) is an important glycolytic enzyme that catalyzes the conversion of 3-phosphoglycerate to 2-phosphoglycerate. Recent investigations have revealed the overexpression of PGAM1 in several human cancers that is linked with tumor growth, survival, and invasion. The aim of this review is to update scientific research network with cancer-specific role of PGAM1 to elucidate its capability as bonafide therapeutic target for cancer therapy. Moreover, we have also summarized the reported genetic and pharmacological inhibitors of PGAM1. This study suggests that further investigations on PGAM1 should focus on the exploration of molecular mechanisms of PGAM1 overexpression in development of cancer, assessment of biosafety profiles of known inhibitors of PGAM1, and utilization of PGAM1 inhibitors in combinatorial therapies. These future studies will surely support the unbiased strategies for the development of novel PGAM1 inhibitors for cancer therapies.

14.
Molecules ; 24(12)2019 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-31200495

RESUMO

Neurodegenerative and neuropsychiatric diseases are characterized by the structural and functional abnormalities of neurons in certain regions of the brain. These abnormalities, which can result in progressive neuronal degeneration and functional disability, are incurable to date. Although comprehensive efforts have been made to figure out effective therapies against these diseases, partial success has been achieved and complete functional recovery is still not a reality. At present, plants and plant-derived compounds are getting more attention because of a plethora of pharmacological properties, and they are proving to be a better and safer target as therapeutic interventions. This review aims to highlight the roles of tannins, 'the polyphenol phytochemicals', in tackling neurodegenerative diseases including Alzheimer's and Parkinson's diseases as well as neuropsychiatric disorders like depression. Among the multifarious pharmacological properties of tannins, anti-oxidative, anti-inflammatory, and anti-cholinesterase activities are emphasized more in terms of neuroprotection. The current review also throws light on mechanistic pathways by which various classes of tannins execute neuroprotective effects. Despite their beneficial properties, some harmful effects of tannins have also been elaborated.


Assuntos
Fármacos Neuroprotetores/química , Fármacos Neuroprotetores/uso terapêutico , Taninos/química , Taninos/uso terapêutico , Doença de Alzheimer/tratamento farmacológico , Humanos , Neuropsiquiatria , Doença de Parkinson/tratamento farmacológico , Compostos Fitoquímicos/química , Compostos Fitoquímicos/uso terapêutico
15.
Pak J Pharm Sci ; 32(2 (Supplementary)): 751-757, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31103967

RESUMO

Gut microbiome, a new organ; represent targets to alter pharmacokinetics of orally administered drugs. Recently, in vitro trials endorsed the idea that orally administered drugs interact and some of their quantity may be taken up by normal microbiome during transit through gut. Such transport mechanisms in microbiome may compete for drug with the host itself. Currently, no data confirms specific transport system for paracetamol uptake by gut microbiome. In vivo trial was conducted in normal healthy male rats (n=36). Paracetamol was administered orally in a single dose of 75mg/kg to isolate microbial mass after transit of 2, 3, 4, 5 and 6 hours post drug administration. Paracetamol absorbance by microbiome was pursued by injecting extracted microbial lysate in RP-HPLC-UV with C18 column under isocratic conditions at 207nm using acetonitrile and water (25:75 v/v) pH 2.50 as mobile phase. Paracetamol absorbance (14.10±0.75µg/mg of microbial mass) and percent dose recovery (13.16±0.55%) seen at transit of 4 hours was significantly higher (P<0.05) compared to other groups. Study confirms the hypothesis of homology between membrane transporters of the gut microbiome and intestinal epithelium. Orally administered drugs can be absorbed by gut microbes competitively during transit in small intestine and it varies at various transit times.


Assuntos
Acetaminofen/farmacocinética , Microbioma Gastrointestinal/fisiologia , Acetaminofen/administração & dosagem , Acetaminofen/análise , Administração Oral , Animais , Cromatografia Líquida de Alta Pressão , Microbioma Gastrointestinal/efeitos dos fármacos , Absorção Intestinal , Intestino Delgado/efeitos dos fármacos , Intestino Delgado/fisiologia , Masculino , Ratos
16.
Pak J Pharm Sci ; 32(2 (Supplementary)): 785-792, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31103973

RESUMO

Peripheral nerve injury is a common condition with a multitude of signs and symptoms. The major consequence of injury is limited physical activity. Presently, we are lacking effective therapies for PNI and it is need of the hour is to explore potential remedies for the recovery of functional loss. Here, we have investigated the role of crude Cannabis sativa L. leaf powder in promoting functions recovery, in mouse model subjected to a traumatic sciatic nerve injury. A dose of 200mg/kg of the body weight per day was administered orally from the day of nerve crush till the end of the experiment. The motor functions were evaluated by measuring sciatic functional index, muscle grip strength and muscle mass; whereas the sensory functions were assessed by hotplate test. The haematology and serum analyses were carried out to estimate the effect of treatment on the systemic index and oxidative stress. The gain of motor functions was significantly improved and was early noticed in the treated mice. Restoration of muscle mass and elevated haemoglobin level were statistically significant in the treatment group. This study indicates that Cannabis sativa L. supplementation accelerates the motor functions recovery after nerve compression injury.


Assuntos
Cannabis , Traumatismos dos Nervos Periféricos/tratamento farmacológico , Nervo Isquiático/lesões , Animais , Glicemia/metabolismo , Peso Corporal/efeitos dos fármacos , Suplementos Nutricionais , Modelos Animais de Doenças , Ingestão de Alimentos/efeitos dos fármacos , Hemoglobinas/metabolismo , Masculino , Camundongos , Atividade Motora/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Traumatismos dos Nervos Periféricos/sangue , Traumatismos dos Nervos Periféricos/fisiopatologia , Folhas de Planta/química , Pós/farmacologia , Recuperação de Função Fisiológica
17.
Eur J Pharm Sci ; 131: 9-22, 2019 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-30735822

RESUMO

We report the synthesis and biological evaluation of two new series of 2-amino-6-benzyl-4-phenyl-4,6-dihydrobenzo[c]pyrano[2,3-e][1,2]thiazine-3­carbonitrile 5,5-dioxides and 2-amino-6-methyl-4-phenyl-4,6-dihydrobenzo[c]pyrano[2,3-e][1,2]thiazine-3­carbonitrile 5,5-dioxides. The synthetic methodology involves a multistep reaction starting with methyl anthranilate which was coupled with methane sulfonyl chloride. The product of the reaction was subjected to N-benzylation and N-methylation reactions followed by ring closure with sodium hydride resulting in the formation of respective 2,1-benzothiazine 2,2-dioxides. These 2,1-benzothiazine precursors were subjected to multicomponent reaction with malononitrile and substituted benzaldehydes for the synthesis of two new series of pyranobenzothiazines (6a-r and 7a-r). The synthesized compounds were screened as selective inhibitors of monoamine oxidase A and monoamine oxidase B. The in vitro results suggested that compound 6d and 7q are the selective inhibitors of monoamine oxidase A, however, the selective and potent inhibitors of monoamine oxidase B included compounds 6h and 7r. Moreover, some dual inhibitors were noticed like 7l having more inhibitory activity towards both the isozymes. Moreover, the binding modes of the selective and potent inhibitors of monoamine oxidase A and B were investigated by molecular docking analysis. The results suggested that the synthetic derivatives may be potential towards the monoamine oxidase isozymes.


Assuntos
Inibidores da Monoaminoxidase/química , Tiazinas/química , Cristalografia por Raios X , Simulação de Acoplamento Molecular , Monoaminoxidase/química
18.
Lipids Health Dis ; 18(1): 26, 2019 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-30683111

RESUMO

Brain is a vital organ of the human body which performs very important functions such as analysis, processing, coordination, and execution of electrical signals. For this purpose, it depends on a complex network of nerves which are ensheathed in lipids tailored myelin; an abundant source of lipids in the body. The nervous system is enriched with important classes of lipids; sphingolipids and cholesterol which compose the major portion of the brain particularly in the form of myelin. Both cholesterol and sphingolipids are embedded in the microdomains of membrane rafts and are functional units of the neuronal cell membrane. These molecules serve as the signaling molecules; hold important roles in the neuronal differentiation, synaptogenesis, and many others. Thus, their adequate provision and active metabolism are of crucial importance in the maintenance of physiological functions of brain and body of an individual. In the present review, we have highlighted the physiological roles of cholesterol and sphingolipids in the development of the nervous system as well as the association of their altered metabolism to neurological and neurodegenerative diseases.


Assuntos
Encéfalo/crescimento & desenvolvimento , Colesterol/metabolismo , Doenças do Sistema Nervoso/genética , Esfingolipídeos/metabolismo , Animais , Encéfalo/metabolismo , Membrana Celular/genética , Colesterol/genética , Humanos , Lipídeos/genética , Microdomínios da Membrana/genética , Bainha de Mielina/genética , Bainha de Mielina/metabolismo , Doenças do Sistema Nervoso/metabolismo , Doenças do Sistema Nervoso/fisiopatologia , Neurônios/metabolismo , Neurônios/patologia , Esfingolipídeos/genética
19.
Pak J Pharm Sci ; 32(6(Supplementary)): 2795-2800, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32024616

RESUMO

Four series of pyrazolobenzothiazine derivatives were evaluated for their anticancer activity against six different cancer cell lines i.e., KB (human oral carcinoma cells), MCF-7(human breast carcinoma cells), A549 (human alveolar adenocarcinoma cells), Hep-G2 (liver carcinoma cells), SGC-7901(human gastric carcinoma cells) and S1 (human colon carcinoma cells) using MTT assay. Among eighteen compounds tested, six compounds i.e., 1a, 1b, 1d, 4a, 4d and 4e were more active than 5-florouracil against human oral carcinoma cells (KB). Moreover, compounds 2b and 2c showed activity comparable to 5-FU against KB cell line. In addition, eight compounds were non-toxic to human PBM cells and thus exhibit selective anticancer activity.

20.
Pak J Pharm Sci ; 32(6(Supplementary)): 2843-2848, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32024623

RESUMO

Eriocalyxin B (EriB), a potent ent-kaurene extracted from Isodon eriocalyx, has turned up as novel anti-cancer agent during recent years against a range of cancer types. TNBC (Triple negative breast cancer) is highly aggressive breast cancer, which is resistant towards current therapeutics due to absence of drug targets. Here, we have probed the molecular mechanism of EriB-induced apoptosis in TNBC (MDA-MB231) cells to check whether its anticancer activity is mediated by modulation of STAT3 and NF-Ï°B. EriB induced apoptosis in MDA-MB231 cells via inhibiting NF-Ï°Bp65, STAT3 phosphorylation, increasing Bax/Bcl-2 ratio, MMP dissipation, and activation of caspase-3. These results provide a rationale for further in vivo investigations on EriB, which might also prove to be a potential drug candidate for developing novel therapeutics against TNBC.

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