A comparative in vitro study on the effect of SGLT2 inhibitors on chemosensitivity to doxorubicin in MCF-7 breast cancer cells

Cancer frequently develops resistance to the majority of chemotherapy treatments.This study aimed to examine the synergistic cytotoxic and antitumor effects of SGLT2 inhibitors,specifically Canagliflozin(CAN),Dapagliflozin(DAP),Empagliflozin(EMP),and Doxorubicin(DOX),using in vitro experimentation.The precise combination of CAN+DOX has been found to greatly enhance the cytotoxic effects of doxorubicin(DOX)in MCF-7 cells.Interestingly,it was shown that cancer cells exhibit an increased demand for glucose and ATP in order to support their growth.Notably,when these medications were combined with DOX,there was a considerable inhibition of glucose consumption,as well as reductions in intracellular ATP and lactate levels.Moreover,this effect was found to be dependent on the dosages of the drugs.In addition to effectively inhibiting the cell cycle,the combination of CAN+DOX induces substantial modifications in both cell cycle and apoptotic gene expression.This work represents the initial report on the beneficial impact of SGLT2 inhibitor medications,namely CAN,DAP,and EMP,on the responsiveness to the anticancer properties of DOX.The underlying molecular mechanisms potentially involve the suppression of the function of SGLT2.

Essential oils used in aromatherapy: A systemic review

Nowadays, use of alternative and complementary therapies with mainstream medicine has gained the momentum. Aromatherapy is one of the complementary therapies which use essential oils as the major therapeutic agents to treat several diseases. The essential or volatile oils are extracted from the flowers, barks, stem, leaves, roots, fruits and other parts of the plant by various methods. It came into existence after the scientists deciphered the antiseptic and skin permeability properties of essential oils. Inhalation, local application and baths are the major methods used in aromatherapy that utilize these oils to penetrate the human skin surface with marked aura. Once the oils are in the system, they remodulate themselves and work in a friendly manner at the site of malfunction or at the affected area. This type of therapy utilizes various permutation and combinations to get relief from numerous ailments like depression, indigestion, headache, insomnia, muscular pain, respiratory problems, skin ailments, swollen joints, urine associated complications etc. The essential oils are found to be more beneficial when other aspects of life and diet are given due consideration. This review explores the information available in the literature regarding therapeutic, medical, cosmetic, psychological, olfactory, massage aromatherapy, safety issues and different plants used in aromatherapy. All the available information was compiled from electronic databases such as Academic Journals, Ethnobotany, Google Scholar, PubM ed, Science Direct, Web of Science, and library search.

A review on therapeutic potential of Nigella sativa:A miracle herb

Nigella sativa(N.sativa)(Family Ranunculaceae)is a widely used medicinal plant throughout the world.It is very popular in various traditional systems of medicine like Unani and Tibb,Ayurveda and Siddha.Seeds and oil have a long history of folklore usage in various systems of medicines and food.The seeds of N.saliva have been widely used in the treatment of different diseases and ailments.In Islamic literature,it is considered as one of the greatest forms of healing medicine.It has been recommended for using on regular basis in Tibb-e-Nabwi(Prophetic Medicine).It has been widely used as antihypertensive,liver tonics,diuretics,digestive,anti-diarrheal,appetite stimulant,analgesics,anti-bacterial and in skin disorders.Extensive studies on N.sativa have been carried out by various researchers and a wide spectrum of its pharmacological actions have been explored which may include antidiabetic,anticancer,immunomodulator,analgesic,antimicrobial,anti-inflammatory,spasmolytic,bronchodilator,hepato-protective,renal protective,gaslro-prolective,antioxidant properties,etc.Due to its miraculous power of healing,N.sativa has got the place among the top ranked evidence based herbal medicines.This is also revealed that most of the therapeutic,properties of this plant are due to the presence of thymoquinone which is major bioactive component of the essential oil.The present review is an effort to provide a detailed survey of the literature on scientific researches of pharmacognostical characteristics,chemical composition and pharmacological activities of the seeds of this plant.

Nigella sativa protects against isoproterenol-induced myocardial infarction by alleviating oxidative stress,biochemical alterations and histological damage

Objective: To evaluate the cardioprotective effect of Nigella sativa L.(N.sativa) in isoproterenol-induced myocardial infarction(MI).Methods: Groups were treated with different doses of ethanol extract of N.sativa(EENS)and N.sativa oil alone and along with enalapril for 28 days.MI was induced by subcutaneous administration of isoproterenol(85 mg/kg) in two consecutive doses.Levels of cardiac biomarkers and antioxidant enzymes such as creatine kinase–N-acetyl-L-cysteine, lactate dehydrogenase, aspartate aminotransferase, malondialdehyde, superoxide dismutase, reduced glutathione and catalase were evaluated along with gross histopathological examination.Results: Isoproterenol(85 mg/kg) induced MI by causing the significant(P < 0.01)reduction in the activity of cardiac biomarkers(creatine kinase–N-acetyl-L-cysteine,lactate dehydrogenase, aspartate aminotransferase) and antioxidant markers(superoxide dismutase, catalase, glutathione) along with significant(P < 0.01) increase in the level of malondialdehyde.Furthermore, histopathological evaluation also confirmed the isoproterenol-induced MI.Pretreatment with EENS(800 mg/kg) and combination of EENS(800 mg/kg) with enalapril(1 mg/kg) significantly(P < 0.01) prevented the development of these alteration and restored activity of cardiac biomarkers as well as antioxidant markers almost near to normal levels.Histopathological evaluation of cardiac tissue further confirmed the restoration of biochemical activity.Conclusions: Experimental findings thus indicate that EENS(800 mg/kg) demonstrated cardioprotective effect against isoproterenol-induced MI by restoring cardiac biomarkers and antioxidant status.

Quantification of total phenol,flavonoid content and pharmacognostical evaluation including HPTLC fingerprinting for the standardization of Piper nigrum Linn fruits

Objective:To carry out the physicochemical and phytochemical standardization with high performance thin layer chromatography fingerprinting of Piper nigrum L.(P.nigrum)fruits in order to ascertain the standard pharmacognostical parameters of this king of spices.Methods:Many standardization parameters like extractive values,total ash value,water soluble ash value and acid insoluble ash,moisture content,loss on drying and pH values of P.nigrum L.fruits were analyzed.The method of Harborne was adopted for the preliminary phytochemicals screening.Analysis of total phenolic and flavonoid contents,pesticides residues,aflatoxin and heavy metals were also performed.CAMAG-high performance thin layer chromatography system was used for fingerprinting of methanolic extract of P.nigrum L.fruits.Results:The results of phytochemicals testing indicated the presence of carbohydrates,phenolic compounds,flavonoids,alkaloids,proteins,saponins,lipids,sterols and tannins in various solvent extracts.Total phenolic and flavonoid contents in methanolic extract were found to be 1.728 1 mg/g and 1.087 ug/g,respectively.Heavy metals concentrations were found to be within standard limits.Aflatoxins and pesticides residues were absent.Conclusions:The outcome of this study might prove beneficial in herbal industries for identification,purification and standardization of P.nigrum L.fruits.

Anxiolytic potential of ursolic acid derivative-a stearoyl glucoside isolated from Lantana camara L.(verbanaceae)

Objective:To investigate the anxiolytic activity of newly isolated compound by our lab called ursolic acid stearoyl glucoside(UASG) from the leaves of Lantana camam(L camam).Methods: Column chromatography was used to isolate UASG.Anxiolytic potential was experimentally proved and demonstrated through Elevated plus-maze,Open field and light and dark test. Results:The UASG showed marked increased in time spent(%) and number of frequent movements made by animals in open arm of elevated plus-maze apparatus.In light and dark model,UASG produced marked increase in time spent by animal,number of crossing and reduced duration of immobility in light box.Conclusions:UASG showed significant increase in number of rearing,assisted rearing and number of square crossed in open field established test model.UASG showed its anxiolytic effect in dose dependent manner.

A novel polyherbal formulation containing thymoquinone attenuates carbon tetrachloride-induced hepatorenal injury in a rat model

Objective:To evaluate a novel polyherbal formulation(BSVT)containing the standardized extracts from the leaves of Boerhavia diffusa,Solidago virgaurea,Vitex negundo,and thymoquinone in CCl4 induced hepatorenal toxicity in rats.Methods:A total of 36 rats were divided into six groups including normal control,CCl4(2 mL/kg,i.p.),CCl4(2 mL/kg,i.p.)+Cystone?(750 mg/kg p.o.),CCl4(2 mL/kg,i.p.)+BSVT(25 mg/kg,p.o.),CCl4(2 mL/kg,i.p.)+BSVT(50 mg/kg,p.o.),and CCl4(2 mL/kg,i.p.)+BSVT(100 mg/kg,p.o.).All treatments were given for four weeks.Serum levels of aspartate transaminase,alanine transaminase,alkaline phosphatase,cholesterol,total protein,serum urea,blood urea nitrogen and creatinine were assessed.Superoxide dismutase,malondialdehyde,and glutathione peroxidase were evaluated in tissue homogenate.The histopathological study of liver and kidney tissues was also done.Results:Aspartate transaminase,alanine transaminase,alkaline phosphatase,cholesterol,serum urea,blood urea nitrogen and creatinine were significantly elevated(P<0.001)while total protein was considerably reduced in the CCl4 group as compared to the normal control(P<0.001),which indicated hepatorenal toxicity.In addition,superoxide dismutase and glutathione peroxidase activities were significantly decreased(P<0.001)while malondialdehyde levels were increased markedly(P<0.001).Treatment with BSVT formulation recovered these parameters towards a normal level in a dose-dependent manner.Conclusions:BSVT formulation ameliorates the hepatorenal toxicity in a dose-dependent manner.Furthermore,clinical studies are required to confirm its efficacy.

Prospective of extracellular matrix and drug correlations in disease management

The extracellular matrix(ECM)comprises of many structural molecules that constitute the extracellular environment.ECM molecules are characterized by specific features like diversity,complexity and signaling,which are also results of improvement or development of disease mediated by some physiological changes.Several drugs have also been used to manage diseases and they have been reported to modulate ECM assembly,including physiological changes,beyond their primary targets and ECM metabolism.This review highlights the alteration of ECM environment for diseases and effect of different classes of drugs like nonsteroidal anti-inflammatory drugs,immune suppressant drug,steroids on ECM or its components.Thus,it is summarized from previously conducted researches that diseases can be managed by targeting specific components of ECM which are involved in the pathophysiology of diseases.Moreover,the drug delivery focused on targeting the ECM components also has the potential for the discovery of targeted and site specific release of drugs.Therefore,ECM or its components could be future targets for the development of new drugs for controlling various disease conditions including neurodegenerative diseases and cancers.

Eslicarbazepine acetate:A therapeutic agent of paramount importance in acute anticonvulsant therapy

Eslicarbazepine acetate (ESL) is a new, once daily, orally administered, third generation antiepileptic drug which is indicated in the treatment of partial-onset seizures. ESL is known to exert it's anticonvulsant effect by blocking the voltage-gated sodium channels. Several clinical trials and pharmacological studies have revealed that seizure control was better with ESL monotherapy (1 200 or 1 600 mg once daily) following a switch from other antiepileptic drugs in comparison with pseudo-placebo patients. The studies have indicated the ESL to be well tolerated and produced only mild to moderate emergent adverse events with the therapy. Being a dibenzazepine family member, structure and chemistry of ESL resembles more or less to carbamazepine and oxcarbazepine. ESL differs structurally from carbamazepine and oxcarbazepine at the 10, 11 position of dibenazepine nucleus. This molecular variation results in differences in metabolism and thus helps to prevent the formation of toxic epoxide metabolites. ESL following oral administration is rapidly metabolised to active metabolite namely S-licarbazepine which is responsible for its pharmacological activity. ESL exhibits acceptable pharmacokinetic profile and shows insignificant drug-drug interactions. In phase III clinical program, ESL was found to be efficacious and well tolerated in adult patients with partial onset seizures previously not controlled with treatment with one or two other antiepileptic drugs.

Ethnobotany,phytochemistry and pharmacological potential of Vitex negundo L.(five-leaved chaste tree):An updated review

In the past two decades,a shift in paradigm has been observed in the development of new drugs from the plants for the treatment of diseases.Many scientists are focusing on the evidence based use of medicinal plants to develop pharmacotherapy for various human ailments.An important medicinal plant that has caught the attention of researchers all over the globe is Vitex negundo Linn.This plant is commonly used in various traditional systems of medicine like Ayurveda,Chinese,Siddha and Unani to treat various diseases and has been the subject of extensive research studies lately.Its roots and leaves are widely used in various disorders and illnesses such as skin eczema,ringworm,liver disorders,spleen enlargement,rheumatic pain,gout,abscess,backache etc.Seeds are also used as folklore medicine in bronchitis,eye disorders,female reproductive disorders,cold,dropsy,malarial fever and as demulcent.The current article is an effort to compile an updated review to disseminate knowledge and information among the scientific fraternity covering the progress made in the pharmacology and phytochemistry of this useful medicinal plant.This review on a very important traditional medicine,Vitex negundo L.can serve as a reference to the scientific community for their future research on this plant.

Chemical modification of acetaminophen：PASS assisted in vivo antiinflammatory activity of chalcones,flavanones and Schiff bases

In the present study,synthetic chalcones,flavanones and Schiff bases were prepared starting from paraceamol,and evaluated their anticipated anti-inflammatory activity.Chalcones were synthesized by reacting 3-acetyl-4-hydroxy acetanilide and aromatic aldehydes in alcoholic potassium hydroxide(KOH) solution under Claisen-Schmidt condensation conditions.The chalcones were cyclized in the presence of piperidine in isoamyl alcohol to obtain flavonone derivatives.Schiff bases were synthesized by condensing 3-acetyl-4-hydroxy anilines with aromatic aldehydes in the presence of HCl.These Schiff bases were further reacted with other aromatic aldehydes in alcoholic KOH solution.PASS cheminformatics software was used to predict the anti-inflammatory activity of synthesized compounds.PASS software predicted that chalcone-based Schiff bases 6a–d contained structural features that can exhibit anti-inflammatory activity.All the prepared derivatives of acetaminophen exhibited moderate to excellent in vivo anti-inflammatory activity in carrageenan-induced edema in rat paw.All the Schiff bases coupled chalcones showed good anti-inflammatory activity compared with the reference drug,diclofenac.Further evaluation of their therapeutic potential and safety profile is required in the future study.