Vaginal drug delivery system: A promising route of drug administration for local and systemic diseases.

Scientists around the globe have done cutting-edge research to facilitate the delivery of poorly absorbed drugs via various routes of administration and different delivery systems. The vaginal route of administration has emerged as a promising mode of drug delivery, attributed to its anatomy and physiology. Novel drug delivery systems overcome the demerits of conventional systems via nanobiotechnology. This review will focus on the disorders associated with women that are currently targeted by vaginal drug delivery systems. In addition, it will provide insights into innovations in drug formulations for the general benefit of women.

Design, fabrication, and evaluation of keratin and pectin incorporated supramolecular structured zero-oxidation state selenium nanogel blended 3D printed transdermal patch.

This study investigates the synthesis of selenium nanoparticles (SeNPs), owing to the low cost and abundance of selenium. However, the toxicity of SeNP prompts the development of a selenium nanocomposite (SeNC) containing pectin, keratin, and ferulic acid to improve the bioactivity of Se[0]. Further, incorporating the SeNC in a suitable formulation for drug delivery as a transdermal patch was worth studying. Accordingly, various analytical techniques were used to characterize the SeNPs and the SeNC, confirming successful synthesis and encapsulation. The SeNC exhibited notable particle size of 448.2 ± 50.2 nm, high encapsulation efficiency (98.90 % ± 2.4 %), 28.1 ± 0.45 drug loading, and sustained drug release at pH 5.5. Zeta potential and XPS confirmed the zero-oxidation state. The supramolecular structure was evident from spectral analysis endorsing the semi-crystalline nature of the SeNC and SEM images showcasing flower-shaped structures. Further, the SeNC demonstrated sustained drug release (approx. 22 % at 48 h) and wound-healing potential in L929 fibroblast cells. Subsequently, the SeNC loaded into a gelling agent exhibited shear thinning properties and improved drug release by nearly 58 %. A 3D printed reservoir-type transdermal patch was developed utilizing the SeNC-loaded gel, surpassing commercially available patches in characteristics such as % moisture uptake, tensile strength, and hydrophobicity. The patch, evaluated through permeation studies and CAM assay, exhibited controlled drug release and angiogenic properties for enhanced wound healing. The study concludes that this patch can serve as a smart dressing with tailored functionality for different wound stages, offering a promising novel drug delivery system for wound healing.

Molecular modelling and biological evaluation of phyto-molecules as potential activators of gluconolactone oxidase (GULO).

Diabetes, the cause of colossal economic and disease burden, is a key area of research in drug discovery programs. Elevated blood glucose levels in diabetes lead to several adverse consequences due to the formation of advanced glycation end products and free radicals. Vitamin C, a potent antioxidant, protects the body's cells and tissues from oxidative damage and dysfunctions. Glucose is the precursor of Vitamin C synthesis in plants and some mammals. L-gulono lactone oxidase (GULO) is the rate-limiting enzyme in producing Vitamin C. However, it is not synthesized in bats, primates, humans, and guinea pigs because of the pseudogene. Several phytomolecules having antioxidant properties are hypothesized to be promising and selective activators of GULO. Therefore, the present study focused on screening agonists of GULO from phytomolecules as an effective augmentor for Vitamin C synthesis, thereby suppressing the sequela of diabetic events. The 3D structure of GULO was generated by the ab-initio method. Subsequently, molecular docking explored the possible binding patterns of GULO protein with different plant phenolic compounds, followed by supplementation of the potent phytomolecules to diabetic guinea pigs. It is noteworthy that Resveratrol and Hydroxytyrosol showed better binding affinity. The molecular simulation also confirmed that Resveratrol is an activator of the GULO enzyme. Interestingly, it was also established that Vitamin C levels were improved in diabetic guinea pigs supplemented with the phytomolecules and comparatively Resveratrol modulates the concentration of glucose and Vitamin C levels substantially, thereby alleviating hyperglycemia. However, further studies are warranted to study the mechanisms.Communicated by Ramaswamy H. Sarma.

Synthesis, Characterization, and In V ivo Toxicological Evaluation of Copper (II) Oxide Containing Herbometallic Siddha Nanocomplex "Thamira Parpam".

"Thamira parpam" (TP), a copper-based herbometallic oxide (copper (II) oxide) nanodrug has been used in Siddha medicine for centuries because of its anti-ulcerogenic property. However, the physicochemical properties and in vivo toxicity of TP still remain elusive. Rigorous clinical translation requires deciphering these vital properties. We have synthesized TP following a gold standard protocol in the traditional Siddha methodology. We assessed the size, phase, elemental constituents, and thermal stability of TP by SEM and TEM, XRD, EPR, and EDAX analyses, respectively. The results depicted the conversion of metallic copper into copper (II) oxide in the final stages of TP preparation and exhibited nanodimensions ranging between 10 and 50 nm. The XPS spectra revealed the presence of oxygen-deficient state and a carbonaceous coating was found on the surface of TP using TEM analysis. In vivo safety was studied in rat toxicity models by adopting OECD guidelines. Body weight changes, feed, and water intake were unaltered upon TP administration. Hematological, biochemical profiling, and histopathological findings also suggested its nontoxic nature with no abnormalities in major organs and its functions. Interestingly, we found that the metal toxicity could have been subdued because of the carbonaceous coating around the nanoparticle copper (II) oxide, confirming that the drug is safe at a low dose. Overall, our study has enlightened the safety of TP supporting the use of Siddha formulations.

Retraction Notice To: Potential Health Benefits of Broccoli- A Chemico-Biological Overview.

The article "Potential health benefits of broccoli- a chemico-biological overview, published in Mini-Rev Med Chem 2009 Jun;9(6):749-59. By Hannah R. Vasanthi, Subhendu Mukherjee and Dipak K. Das" has been retracted by the Editorial office of the journal Mini-reviews in Medicinal Chemistry, as the text in this review article are from sources which have been retracted or under investigation on the basis of data fabrication and falsification, authorship misconduct, duplicate publication, unethical research practices, text recycling/self-plagiarism, and unresolved concerns about data integrity and research conduct. The authors were informed of this complaint and were requested to give justification on the matter in their defense [1]. Some sources that have been retracted are as follows: 1) Agarwal et al. Dynamic Action of Carotenoids in Cardioprotection and Maintenance of Cardiac Health, Molecules 2012, 17, 4755-4769. http: https://pubmed.ncbi.nlm.nih.gov/24896014/ 2) Nagendran Balasundram, KalyanaSundram, SamirSamman. Phenolic compounds in plants and agri-industrial byproducts: Antioxidant activity, occurrence, and potential uses. Food Chemistry 2006, 99(1), 191-203. https://www.sciencedirect.com/science/article/abs/pii/S0308814605006242 Bentham Science apologizes to the readers of the journal for any inconvenience this may have caused. The Bentham Editorial Policy on Article Retraction can be found at https://benthamscience.com/editorial-policies-main.php. REFERENCES [1] Hannah R Vasanthi, Subhendu Mukherjee, Dipak K Das. Potential health benefits of broccoli- a chemico-biological overview. Mini Rev Med Chem., 2009, 9(6), 749-759. doi: 10.2174/138955709788452685. https://pubmed.ncbi.nlm.nih.gov/19519500/ Bentham Science Disclaimer: It is a condition of publication that manuscripts submitted to this journal have not been published and will not be simultaneously submitted or published elsewhere. Furthermore, any data, illustration, structure or table that has been published elsewhere must be reported, and copyright permission for reproduction must be obtained. Plagiarism is strictly forbidden, and by submitting the article for publication the authors agree that the publishers have the legal right to take appropriate action against the authors, if plagiarism or fabricated information is discovered. By submitting a manuscript, the authors agree that the copyright of their article is transferred to the publishers if and when the article is accepted for publication.

Retraction Notice: Tocotrienols and its Role in Cardiovascular Health- a Lead for Drug Design.

The article has been retracted by the Editorial office of the journal Current Pharmaceutical Design, due to some inconsistencies in the article [1]. The article appeared to be copied verbatim from published papers. Upon checking these facts, we have established that considerable portions of this review are made up of text copied verbatim from other published material. The Publisher has retracted this article in accordance with good ethical practices. REFERENCE [1] Vasanthi HR, Parameswari RP and Das DK. Tocotrienols and its Role in Cardiovascular Health- a Lead for Drug Design. Curr Pharm Des 2011; 17(21): 2170-5. Bentham Science apologizes to the readers of the journal for any inconvenience this may have caused. The Bentham Editorial Policy on Article Retraction can be found at https://benthamscience.com/editorial-policies-main.php. Bentham Science Disclaimer: It is a condition of publication that manuscripts submitted to this journal have not been published and will not be simultaneously submitted or published elsewhere. Furthermore, any data, illustration, structure or table that has been published elsewhere must be reported, and copyright permission for reproduction must be obtained. Plagiarism is strictly forbidden, and by submitting the article for publication the authors agree that the publishers have the legal right to take appropriate action against the authors, if plagiarism or fabricated information is discovered. By submitting a manuscript, the authors agree that the copyright of their article is transferred to the publishers if and when the article is accepted for publication.

Immunomodulatory activity of brown algae Turbinaria ornata derived sulfated polysaccharide on LPS induced systemic inflammation.

BACKGROUND: Inflammation and oxidative stress are common pathologies in a wide range of chronic diseases. Polysaccharides are known to exhibit antioxidant and anti-inflammatory potential and are suggested to possess immunomodulatory potential. PURPOSE: Herein, the immunomodulatory activity of a sulfated polysaccharide (PS) separated from a brown marine algae Turbinaria ornata is studied in LPS instigated systemic inflammation in experimental rats. STUDY DESIGN AND METHODS: Male SD rats are pretreated with different doses of PS (2.5, 5, 10 mg/kg bw) for a week followed by inducing systemic inflammation using LPS (10 mg/kg i.p.). Blood withdrawn after 8 h of LPS injection is subjected to hematological analysis (WBC, HCT, and PLT). After 24 h of LPS induction, cardiac tissue was isolated and subjected to biochemical, molecular, and histopathological analysis. Effect of PS pre-treatment (2.5, 5, 10 mg/kg bw) was checked by assessing serum parameters (AST, CK-MB, and γGT), antioxidant markers (LPO, GSH, SOD, Grx) and inflammatory markers (IL1ß, IL6, IL10, NFκB), followed by analyzing the iNOS, PI3k and Akt to identify the probable mode of action. RESULTS: Elevated levels of AST, CK-MB, and γGT in serum were significantly reduced on PS pretreatment. LPS significantly raised the LPO and Grx levels in heart tissue whereas, PS pre-treatment significantly reduced LPO and Grx levels. GSH and SOD levels were reduced upon LPS induction and were brought to near normal by HD of PS. PS also reduced the mRNA levels of IL6, Trx, and increased IL10 levels in the heart tissue substantiating its anti-inflammatory and antioxidant potency. Further, IL1ß, NFκB, iNOS, and pPI3k/pAkt expressions were significantly modulated by PS in the cardiac tissue substantiating the immunomodulatory effect. A trend of improvement in the inflammatory pathology was also observed in the heart tissue compared to LPS control, as confirmed by histopathology analysis. CONCLUSION: Altogether, this study concludes the immunomodulatory potential of PS from the marine macroalgae Turbinaria ornata significantly and prevents LPS induced systemic inflammation in the cardiac tissue presumably influenced by the glucopyranose and fucopyranose subunits in the polysaccharide.

Macrotyloma uniflorum a plant food alleviates the metabolic syndrome through modulation of adipokines and PPARs.

A sedentary lifestyle combined with the intake of high-calorie diet has been the paramount cause of metabolic syndrome (MS) which is now a serious concern of public health worldwide as it involves the coexistence of hypertension, hyperlipidemia, glucose intolerance, and obesity. Hence, identifying a suitable strategy to overcome the worldwide menace of MS is imperative. Macrotyloma uniflorum a lesser known legume is highly nutritious and notable for its ethano-medicinal potential. Herein, the influence of M. uniflorum in high-fat dietinduced metabolic changes in a rodent model of metabolic syndrome was evaluated. Serum levels of glucose, total cholesterol, triglycerides, VLDL-c, and bodyweight were decreased, whereas HDL-c was increased in M. uniflorum-treated MS rats. The protein expression (AMPK-α, PPAR-α, and PPAR-γ) and gene expression (leptin, adiponectin, resistin, UCP2, NF-κB, and IL-6) results are impressive to highlight that M. uniflorum modulates the pathological conditions of MS and proves to be cardioprotective. Furthermore, the histopathological analysis confirmed the pathological changes and substantiates the influence of M. uniflorum to overcome MS. The HPLC and GC (MS) profiling reveals the presence of an array of polyphenols such as rutin (694.61 µg/g), catechin (500.12 µg/g), epicatechin (158.10 µg/g), gallic acid (17.98 µg/g), ferulic acid (10.911 µg/g), daidzein (6.51 µg/g), and PUFA, respectively, which probably exhibits the therapeutic effect on MS and associated complications by modulating lipid metabolism and adipogenesis. PRACTICAL APPLICATIONS: Metabolic disorders like CVD and diabetes are leading cause of mortality and morbidity worldwide. With emerging issues on adverse effects of modern drugs, the emphasis on "Food is Medicine and Medicine as Food" has taken dramatic dimensions in the healthcare sector. Therefore, nutraceuticals are in great demand in the developed world off late. Legumes, are potent elements in a balanced diet next to cereals. Exploring the medicinal properties of legumes could bring a revolution in public health and nutraceutical industries. This study scientifically validated the phytochemicals in M. uniflorum for its functional potential in the management of Metabolic Syndrome (MS). This study would help the nutraceutical industries to develop functional foods using M. uniflorum seeds to make porridges and soups or nutraceutical supplements with the bioflavonoids isolated from M. uniflorum for the management of metabolic disorders by mitigating hyperlipidemia, oxidative stress, and inflammation.

Retraction Notice: Phytochemicals from Plants to Combat Cardiovascular Disease.

The article entitled "Phytochemicals from Plants to Combat Cardiovascular Disease", by Hannah R. Vasan-thi, Nitin ShriShri Mal, Dilip Kumar Das, published in Curr. Med. Chem. 2012; 19(14): 224251. https://www.eurekaselect.com/97287/article has been retracted on a complaint of plagiarism with a previously pub-lished article entitled "Resveratrol in cardiovascular health and disease" in the journal Annals of the New York Academy of Sciences as Ann N Y Acad Sci . 2011 Jan;1215:22-33. doi: 10.1111/j.1749-6632.2010.05843.x The authors were informed of this complaint and were requested to give justification on the matter, in their de-fence. However, no reply was received from them in this regard. Bentham Science apologizes to the readers of the journal for any inconvenience this may have caused. The Bentham Editorial Policy on Article Withdrawal can be found at https://benthamscience.com/editorial-policies-main.php.

Sulfated polysaccharide from Turbinaria ornata suppress lipopolysaccharide-induced inflammatory response in RAW 264.7 macrophages.

BACKGROUND: Marine macroalgae known for its polysaccharides exhibit potent biomedical properties and its potential as an anti-inflammatory agent has increased in the recent past as inflammation is a major pathology noted in many chronic diseases. PURPOSE: The present study investigates the anti-inflammatory potential of a sulfated polysaccharide (PS) isolated from the marine algae Turbinaria ornata collected from the Indian waters on LPS induced inflammation in RAW 264.7 macrophages. STUDY DESIGN AND METHODS: PS isolated from the macroalgae was characterized using ESI(MS) and was screened for its antioxidant and anti-inflammatory potential in RAW 264.7 cells by assessing markers of oxidative stress, and inflammation. RESULTS: LPS significantly increased the levels of LPO and LDH in RAW 264.7 cells which were significantly reduced in PS pre-treatment groups. Pretreatment significantly increased the antioxidants GSH and SOD and significantly reduced mRNA levels of IL6 and TNFα in vitro confirming its anti-inflammatory potential. NFκB and iNOS were significantly modulated by PS confirming the probable mode of action. CONCLUSION: Altogether, it can be concluded that PS isolated from Turbinaria ornata collected from the Southeast Coast of India exhibits antioxidant and anti-inflammatory potential probably mediated by the sulfated polysaccharide containing glucopyranose and fucopyranose moieties.

Positive interaction of mangiferin with selected oral hypoglycemic drugs: a therapeutic strategy to alleviate diabetic nephropathy in experimental rats.

Diabetic nephropathy (DN) is one of the notorious diabetes associated complications. Despite many therapeutic strategies available, metabolic control of DN continues to poses a challenge. In this study, the interactions of mangiferin with selected oral hypoglycemic drugs, metformin and gliclazide to effectively alleviate the symptoms of renal injury in DN are evaluated. Male Sprague Dawley rats were used as experimental model and type II diabetes was induced by administration of high fat diet and low dose streptozotocin. Oral intervention of mangiferin with metformin and gliclazide for a period of 28 days was given to diabetic rats. At the end of the treatment period, biochemical parameters, kidney function markers, anti-oxidant enzymes levels, oxidative stress mediated gene expression and histology were analysed. Significant reduction in the serum biochemical markers (glucose, urea and creatinine) were observed in the groups treated with combination drugs. Marked improvement in the combination treated groups in terms of inflammation and oxidative damage in the gene (TNFα, NFκB, TGFß, VEGF, PKC) and protein expression (NFκB, VEGF) were noted in the kidney tissue alleviating the symptoms of DN. These results were further corroborated with histopathological results. Scientific data in the present study reveals that the combinations of mangiferin with the oral hypoglycemic drugs have been favorable in alleviating renal injury. Hence, a combination therapy to alleviate the vascular complication, diabetic nephropathy may be considered as a possible therapeutic strategy by including natural phytocompounds as an add on therapy to conventional oral hypoglycemic drugs.

Type 5 17-hydroxysteroid dehydrogenase/prostaglandin F synthase (AKR1C3) inhibition and potential anti-proliferative activity of cholest-4-ene-3,6-dione in MCF-7 breast cancer cells.

Cholest-4-ene-3,6-dione (KS) is a cholesterol oxidation product which exhibits anti-proliferative activity. However, its precise mechanism of action remains unknown. In this study, the effects of KS on AKR1C3 inhibition and anti-proliferative activities were investigated in the hormone-dependent MCF-7 breast cancer cells. We identified that KS arrested the enzymatic conversion of estrone to 17-ß estradiol, by inhibiting AKR1C3 in intact MCF-7 cells. The anti-proliferative effects of KS were evaluated by MTT assay, acridine orange and ethidium bromide dual staining, cell cycle analysis and Western blotting. KS arrested the cell cycle progression in the G1 phase with a concomitant increase of the Sub-G0 population to increase in concentration and time. It also enhanced the p53 and NFkB expression and induced caspase-12, 9 and 3 processing and down-regulated the Bcl-2 expression. Molecular docking studies performed to understand the inhibition mechanism of KS on AKR1C3 revealed that KS occupied the binding region of AKR1C3 with almost similar orientation as indomethacin (IM), thereby acting as an antagonistic agent for AKR1C3. Based on the results it is identified that KS induces inhibition of AKR1C3 and cell death in MCF-7 cells. These results indicate that KS can be used as a molecular scaffold for further development of novel small-molecules with better specificity towards AKR1C3.

Correction to: Neophytadiene from Turbinaria ornata Suppresses LPS-Induced Inflammatory Response in RAW 264.7 Macrophages and Sprague Dawley Rats.

The publisher made a mistake in the published version of this article.

Neophytadiene from Turbinaria ornata Suppresses LPS-Induced Inflammatory Response in RAW 264.7 Macrophages and Sprague Dawley Rats.

This study investigates the mode of action of Neophytadiene (MT), a molecule isolated from a marine algae Turbinaria ornata in LPS-induced inflammation in both in vitro and in vivo conditions. Neophytadiene (25, 50, 100 µM/mL) was treated to LPS-stimulated RAW 264.7 macrophages cells to identify its anti-inflammatory potential by measuring the level of tumour necrosis factor (TNF-α) by enzyme-linked immunosorbent assay (ELISA) and nitric oxide (NO) using Griess reagent. The mRNA levels of inflammatory cytokines, interleukin (IL-6 and IL-10), and the protein expression of nuclear factor-κB (NF-κB) and inducible nitric oxide synthase (iNOS) were quantified by Western blot analysis. Subsequently, Neophytadiene (12, 25, 50 mg/kg b.wt/p.o) was pre-treated for 7 days to the experimental animals followed by LPS (10 mg/kg) injection interaperitonially. After LPS induction, blood was collected and the haematological parameters were analysed followed by isolation of heart tissue for biochemical molecular and histopathological analysis Neophytadiene significantly inhibited the NO production and inflammatory cytokines TNF-α, IL-6 and IL-10 both in in vitro and in vivo conditions. Further, the expression of TNF-α, IL1ß, NF-κB, iNOS, PI3k/Akt and MAPK in the heart tissue was modulated by Neophytadiene significantly confirming the anti-inflammatory potential. Thus, the effect of Neophytadiene on LPS-induced cardiac injury can be attributed to its anti-inflammatory antioxidant and cardioprotective properties.

Inhibition of Cyclooxygenase Enzyme by Bioflavonoids in Horsegram Seeds Alleviates Pain and Inflammation.

BACKGROUND: Inflammation and pain, mainly induced by the prostaglandins synthesized by the cyclooxygenase enzymes, may cause distress. To overcome this unpleasant stress in a safer manner, numerous natural molecules are proven for modulating the COX enzymes. Epicatechin and daidzein are two bioactive natural compounds present in horsegram, a legume known for its medicinal properties. OBJECTIVE: The present study aims at evaluating the potential of horsegram, and some of its bioactive molecules, to be used as an anti-inflammatory and analgesic agent mediated by the inhibition of COX enzymes, which can be recommended as a substitute for chemically synthesized NSAIDs. METHODS: The present work involved the quantification of epicatechin and daidzein present in horsegram seeds. The COX enzyme inhibitory nature of epicatechin and daidzein was tested using in silico docking analysis with Autodock software and was further confirmed by in vitro COX inhibitory biochemical assays. Furthermore, the anti-inflammatory and analgesic activities of the horsegram seeds were evaluated in animal experiments. RESULTS: Horsegram seeds contain 158.1 microgram/g and 6.51 microgram/g of epicatechin and daidzein respectively. The docking studies reveal that both the bioactive molecules exhibit better binding efficiency with COX-2 protein as compared to COX-1. Hence, in vitro COX-2 inhibitory assay was performed for epicatechin, daidzein and compared with known analgesic agent diclofenac which revealed a pronounced dose dependent inhibitory activity. Furthermore, the analgesic and anti-inflammatory activity of horsegram in experimental animals exhibited a dose dependent effect which might be due to the presence of the bioactive compounds such as epicatechin and daidzein. CONCLUSION: The results suggest that epicatechin and daidzein present in horsegram are potent cyclooxygenase inhibitors and thus would be helpful in the management of inflammation and pain.

Palliative Role of Aqueous Ginger Extract on N-Nitroso-N-Methylurea-Induced Gastric Cancer.

Ginger (Zingiber officinale) is a spice and also an herbal medicine used worldwide for managing GI tract disturbances. However, its role in gastric cancer is sparingly known. This study ensures the standardization of gastric cancer by the induction of N-nitroso N-methyl Urea (MNU) and to determine the role of the aqueous extract of ginger (AGE) in MNU-induced gastric cancer in albino Wistar rats. Accordingly, the anticancer potential of AGE and its possible mode of action were assessed on rats exposed to MNU, by various biochemical and molecular assays. As evidenced by the extent of lipid peroxidation, gastrin levels and histopathological sections in MNU-induced cancerous lesions at 8 wk which was stabilized at 16 wk confirming the induction of gastric carcinoma by the chemical carcinogen. Further, results revealed that AGE alleviated the oxidative stress as evidenced by the stomach antioxidant enzymes (SOD, catalase, GPx, and GR), markers of oxidative stress (TRx, GRx) and Gastrin, a specific marker for gastric cancer and a decreased level of pro-inflammatory markers (NF-kB, TNF-α, IL-6, PGE2) which was further confirmed by histopathological analysis. AGE is responsible to mitigate oxidative stress and inflammation related to gastric cancer and could be used as a potential dietary intervention in gastric cancer therapy.

Dalspinin isolated from Spermacoce hispida (Linn.) protects H9c2 cardiomyocytes from hypoxic injury by modulating oxidative stress and apoptosis.

ETHNOPHARMACOLOGICAL RELEVANCE: Spermacoce hispida (S.hispida), a potential medicinal plant has been traditionally used as an antibacterial, antieczemic, antihypertensive, antidiabetic and antihyperlipidemic agent. Although, this plant has been claimed to protect against oxidative injury and inflammatory conditions in recent studies, its cardioprotective effect and the active constituents responsible for its bioactivity is sparsely studied. Hence this work is undertaken to study the active biomolecule responsible for modulating the cardiomyocytes on hypoxic injury relevant to its ethanopharmacology. AIM OF THE STUDY: The current study is to isolate and characterize a bioactive molecule from S.hispida, which exhibits protection against hypoxic injury in an in vitro hypoxic model of cultured H9c2 cardiomyocytes. MATERIALS AND METHODS: The methanolic extract of S.hispida plant was fractionated with various solvents sequentially. The ethyl acetate fraction that was concentrated and chromatographed over silica gel column eluted 18 fractions, which yielded 5 compounds, which were characterized using spectral data. The isolated new compound was further tested for its protective effect against hypoxic injury, wherein cobalt chloride (CoCl2) was used to induce hypoxia in H9c2 cardiomyoblasts. To evaluate the protective effect of the isolated compound, the markers of oxidative stress, apoptosis, and cell death were checked by endogenous levels of antioxidants, [malondialdehyde (MDA), superoxide dismutase (SOD), reduced glutathione (GSH)], lactate dehydrogenase (LDH) activity and immunoblot (HIF-α, Bcl2, Bax, procaspase and cleaved caspase-3). RESULTS: Among the five compounds isolated and characterized from S. hispida methanolic extract, ß-sitosterol, ursolic acid, quercetin and rutin were known phytochemicals, while the new isoflavone was identified as dalspinin-7-0-ß-D-galactopyranoside (DBG). Among the isolated compounds, the antioxidant potential of DBG confirmed by DPPH free radical scavenging and ORAC assays was superior. CoCl2-induced hypoxic condition significantly decreased cell viability, SOD activity, GSH concentration and increased the level of MDA and LDH activity. Western blot studies revealed an upregulation of HIF-1α, Bax and caspase and down regulation of Bcl-2 expression. The oxidative abnormalities were ameliorated by DBG pretreatment, as deduced by the reduced CoCl2-induced cytotoxicity, MDA concentration, LDH activity and the expression of HIF-1α, Bax and caspase and the enhanced levels of SOD, GSH and Bcl2 expression in a dose-dependent manner. CONCLUSION: DBG protects H9c2 cells from CoCl2-induced hypoxic damage by mitigating oxidative stress and preserving cell viability. The overall findings highlight the protective action of DBG, a potential source of antioxidant of natural origin against hypoxic injury and may help in mitigating the progress of oxidative stress in cardiac cell death.

Antidiabetic effect of mangiferin in combination with oral hypoglycemic agents metformin and gliclazide.

BACKGROUND: Diabetes mellitus poses serious threat to the global population due to the alarming diabetic complications it leads to. The current therapeutic options available can be improved for better efficiency and maximum benefits. Combination therapy has been commonly used to improve the efficacy and to minimize the side effects of drugs in current clinical use. PURPOSE: The present study aims to assess the interaction between a natural molecule mangiferin with the commercially available oral hypoglycemic drugs metformin and gliclazide in diabetic rats. METHODS: In this study, the in vitro cytotoxicity and glucose uptake studies were performed in HepG2 cells. Based on experimental data, the combination index of the hypoglycemic drugs like metformin and gliclazide in combination with different doses of mangiferin was determined using COMPUSYN software. Further, in vivo studies were performed in HFD + STZ induced diabetic male Sprague Dawley rats. Serum parameters, enzyme markers, hepatic oxidative stress markers, gene and protein expression studies and histopathological analyses were performed in rat liver to identify the mode of action of the combination drug administration. RESULTS: The in vitro studies on HepG2 cells suggest a positive interaction of mangiferin with both metformin and gliclazide at specific concentrations as evidenced by glucose uptake. The hepatic enzymes, oxidative stress markers, carbohydrate metabolizing enzymes, gene (AMPK, Akt, ACC ß and Glut-2) and protein (PPARα, PPARγ) expression confirmed the results of the in vitro studies. Both the combinations of mangiferin with metformin and mangiferin with gliclazide exhibited potent antidiabetic effect. The combination of mangiferin with metformin was insulin dependent (Akt pathway) whereas the combination of mangiferin and gliclazide was insulin independent (AMPK pathway). CONCLUSION: The overall results suggest that combination of mangiferin with both metformin and gliclazide alleviates diabetic conditions potentially at specific doses and modulates the adverse effect of high dose of commonly used OHD's. This combination therapy can be translated for its clinical use as a diabetes management strategy.