Characterization of ß-Cryptoxanthin and Other Carotenoid Derivatives from Rhodotorula taiwanensis, A Novel Yeast Isolated from Traditional Starter Culture of Assam.

The present investigation was intended to characterize pigments for the first time from Rhodotorula taiwanensis (LC011412) yeast isolated from the ethic fermentation starter culture source meant to evaluate its carotenoid contents for beneficial applications. The pigments were extracted by an optimized solvent system, purified by flash chromatography and were identified by TLC and UV/VIS spectroscopy. The absorbance spectra confirmed the presence of ß-carotene, ß-cryptoxanthin, torulene and torularhodin that showed maximum absorbance (λmax ) within the ranges. The fractions were further characterized by LC/MS and analyzed through FT-IR and NMR for structure elucidation. Spectral analyses also confirmed the presence of the compounds mentioned above. These compounds promise great commercial value and could be useful for large scale production anticipated for potential applications in food, nutraceutical, pharmaceutical and cosmetic sectors. It is pertinent that the characterized carotenoid pigments from the isolate have incredible prospects in industrial applications which require profound attention.

In Silico Molecular Docking, Synthesis of 4-(4-benzoylaminophenoxy) Phenol Derivatives as Androgen Receptor Antagonists.

AIM AND OBJECTIVE: To study the structural difference, optimization, molecular docking and development of new benzoyl amino phenoxy phenol derivatives as anti-prostate cancer agents. MATERIALS AND METHODS: Strategies towards the identification of novel benzoyl amino phenoxy phenol (BAPP), molecular docking was performed with the designed Androgen Receptor (AR) blockers. Pharmacophore-based studies revealed that the nitro- or cyano-substituted anilide groups have influenced the activity profiles of non-steroidal AR antagonists, followed by the molecular docking studies with five AR receptors. Molecular docking studies were carried out using Maestro from Schrödinger. Absorption, Distribution, Metabolism, and Excretion (ADME) properties of the BAPP derivatives were evaluated for the predictive bioavailability/drug-likeness. These studies supported vital information for designing new anti-prostate cancer agents. RESULTS AND DISCUSSION: There are 125 compounds were screened and best fit compounds (12 entries) were well-synthesized in good to excellent yields and anticancer activities were evaluated. The compounds, 6i showed the highest activities of this series (14.65 ± 1.35 µM). CONCLUSION: The present approach is simple and efficient for the synthesis of BAPP derivatives and the observed IC50 values of BAPPs were in good agreement with the glide scores obtained from the molecular docking. We, further, intend to carry out in vitro and in vivo AR binding studies for the active compounds.

In silico Molecular Modelling of Selected Natural Ligands and their Binding Features with Estrogen Receptor Alpha.

BACKGROUND: Breast cancer is one of the most common cancers diagnosed among women. It is now recognized that two receptors mediate estrogen action and the presence of estrogen receptor alpha (ERα) correlates with better prognosis and the likelihood of response to hormonal therapy. ERα is an attractive target for the treatment of breast cancer. Most of the drugs currently used for the breast cancer treatment have numerous side effects and they are often unsuccessful in removing the tumour completely. Hence, we focused on natural compounds like flavonoids, polyphenols, etc. which do not exhibit any high toxic effects against normal cells. OBJECTIVES: To identify the potential natural inhibitors for BCa through an optimised in silico approach. METHODS: Structural modification and molecular docking-based screening approaches were imposed to identify the novel natural compounds by using Schrödinger (Maestro 9.5). The Qikprop v3.5 was used for the evaluation of important ADME parameters and its permissible ranges. Cytotoxicity of the compounds was evaluated by MTT assay against MCF-7 Cell lines. RESULTS: From the docking studies, we found that the compounds, Myricetin, Quercetin, Apigenin, Luteolin and Baicalein showed the highest Glide Scores -10.78, -9.48, -8.92, -8.87 and -8.82 kcal mol-1 respectively. Of these, Luteolin and Baicalein showed the significant IC50 values (25 ± 4.0 and 58.3 ± 4.4 µM, respectively) against MCF-7 cell line. The ADME profiling of the test compounds was evaluated to find the drug-likeness and pharmacokinetic parameters. CONCLUSION: We mainly focused on in silico study to dock the compounds into the human estrogen receptor ligand binding domain (hERLBD) and compare their predicted binding affinity with known antiestrogens. Myricetin, Quercetin, Apigenin, Luteolin and Baicalein were identified as the most promising among all. Of these, Luteolin and Baicalein showed significant anticancer activities against MCF-7 cell line. These findings may provide basic information for the development of anti-breast cancer agents.

Pleiotropic Effect of Mahanine and Girinimbine Analogs: Anticancer Mechanism and its Therapeutic Versatility.

Emerging evidence present credible support in favour of the potential role of mahanine and girinimbine. Non-toxic herbal carbazole alkaloids occur in the edible part of Murraya koenigii, Micromelum minutum, M. zeylanicum, and M. euchrestiolia. Mahanine and girinimbine are the major potent compounds from these species. In fact, they interfered with tumour expansion and metastasis development through down-regulation of apoptotic and antiapoptotic protein, also involved in the stimulation of cell cycle arrest. Consequently, these compounds were well proven for the in-vitro and in vivo evaluation that could be developed as novel agents either alone or as an adjuvant to conventional therapeutics. Therefore, mahanine and girinimbine analogs have the potential to be the promising chemopreventive agents for the tumour recurrence and the treatment of human malignancies. In this review, an updated wide-range of pleiotropic anticancer and biological effects induction by mahanine and girinimbine against cancer cells were deeply summarized.

Garcinia morella fruit, a promising source of antioxidant and anti-inflammatory agents induces breast cancer cell death via triggering apoptotic pathway.

A rapid rise in cancer cases worldwide, especially breast cancer in females, instigates the need for more effective and less side effect causing drugs from natural origin. Thereby, in the present study, Garcinia morella fruit was investigated for antioxidant, anti-inflammatory and anti-breast cancer activity. Preliminary antioxidant and anticancer evaluation of different fractions and crude methanol extract of G. morella fruit suggested chloroform fraction as the bioactive fraction. Time course analysis (by 24 h, 48 h and 72 h) of the bioactive fraction (1.56-25) µg/ml treatment on breast cancer cell lines (MCF7, MDAMB231 and SKBR3) showed dose and time dependent antiproliferative responses. Further, mechanistic studies involving morphological observation and western blotting analysis, revealed its apoptosis inducing effect on breast cancer. P53 dependent up-regulation of Bax and down-regulation of Bcl XL is suggested as the possible pathway of apoptosis followed by MCF7 cells on exposure to the bioactive fraction. The anti-inflammatory assays revealed that it significantly lowered the release of nitrite and TNF-α level of LPS induced RAW 264.7 cells (p < 0.05). Moreover, pre treatment of Carrageenan induced paw edema animals with 20 mg/kg of the bioactive fraction significantly (p < 0.05) inhibited paw inflammation and controlled the cytokine and nitrite levels of the edema induced rat. Its main bioactive component was identified to be Garcinol by UHPLC and ESI-MS/MS. Thereby, this study clearly reflects that G. morella fruit is a valuable antioxidant and anti-inflammatory gift of nature with the potential to be used against breast cancer. This is also the first report of isolation of bioactive compound Garcinol from G. morella fruit.

Functionalization of ß-lactam antibiotic on lysozyme capped gold nanoclusters retrogress MRSA and its persisters following awakening.

In this study we have reported an efficient antibacterial hybrid fabricated through surface functionalization of lysozyme capped gold nanoclusters (AUNC-L) with ß-lactam antibiotic ampicillin (AUNC-L-Amp). The prepared hybrid not only reverted the MRSA resistance towards ampicillin but also demonstrated enhanced antibacterial activity against non-resistant bacterial strains. Most importantly, upon awakening through cis-2-decenoic acid (cis-DA) exposure, the MRSA persister got inhibited by the AUNC-L-Amp treatment. Intraperitoneal administration of this hybrid eliminates the systemic MRSA infection in a murine animal model. Topical application of this nano conjugate eradicated MRSA infection from difficult to treat diabetic wound of rat and accelerated the healing process. Due to inherent bio-safe nature of gold, AUNC-L alone or in the construct (AUNC-L-Amp) demonstrated excellent biocompatibility and did not indicate any deleterious effects in in vivo settings. We postulate that AUNC-L-Amp overcomes the elevated levels of ß-lactamase at the site of MRSA antibiotic interaction with subsequent multivalent binding to the bacterial surface and enhanced permeation. Coordinated action of AUNC-L-Amp components precludes MRSA to attain resistance against the hybrid. We proposed that the inhibitory effect of AUNC-L-Amp against MRSA and its persister form is due to increased Amp concentration at the site of action, multivalent presentation and enhanced permeation of Amp through lysozyme-mediated cell wall lysis.

Glycogen-gold nanohybrid escalates the potency of silymarin.

In this study, a glycogen-gold nanohybrid was fabricated to enhance the potency of a promising hepatoprotective agent silymarin (Sly) by improving its solubility and gut permeation. By utilizing a facile green chemistry approach, biogenic gold nanoparticles were synthesized from Annona reticulata leaf phytoconstituents in combination with Sly (SGNPs). Further, the SGNPs were aggregated in glycogen biopolymer to yield the therapeutic nanohybrids (GSGNPs). Transmission electron microscopy, UV-Vis spectroscopy, X-ray diffraction, and Fourier transform infrared spectroscopy analysis confirmed the successful formation and conjugation of both SGNPs and GSGNPs. The fabricated nanohybrids showed significant protection against CCl4-induced hepatic injury in Wistar rats and maintained natural antioxidant (superoxide dismutase and catalase) levels. Animals treated with GSGNPs (10 mg/kg) and SGNPs (20 mg/kg) retained usual hepatic functions with routine levels of hepatobiliary enzymes (aspartate transferase, alanine transaminase, alkaline phosphatase, and lactate dehydrogenase) and inflammatory markers (interleukin-1ß and tumor necrosis factor-α) with minimal lipid peroxidation, whereas those treated with 100 mg/kg of Sly showed the similar effect. These results were also supported by histopathology of the livers where pronounced hepatoprotection with normal hepatic physiology and negligible inflammatory infiltrate were observed. Significant higher plasma Cmax supported the enhanced bioavailability of Sly upon GSGNPs treatment compared to SGNPs and free Sly. Graphite furnace atomic absorption spectrophotometry analysis also substantiated the efficient delivery of GSGNPs over SGNPs. The fabricated therapeutic nanohybrids were also found to be biocompatible toward human erythrocytes and L929 mouse fibroblast cells. Overall, due to increased solubility, bioavailability and profuse gut absorption; GSGNPs demonstrated tenfold enhanced potency compared to free Sly.

Design, Synthesis and Biological Evaluation of Novel 1, 3- thiazolidine-2, 4-diones as Anti-prostate Cancer Agents.

BACKGROUND: Androgen receptor is an attractive target for the treatment of prostate cancer. The 1,3- thiazolidine-2,4-diones possess a wide diversity of important biochemical effects and interesting pharmacological properties. OBJECTIVE: The aim of the study is to find the experimental and computational methods to investigate the interference of 1,3-thiazolidine-2,4-diones with androgen receptor against prostate cancer. METHOD: Structural modification and molecular docking-based virtual screening approaches were imposed to identify the novel 1,3-thiazolidine-2,4-diones by using Schrödinger (Maestro 9.5). The best fit molecules (3-12 & 23-31) were synthesized and characterized using spectroscopic techniques, then in vitro antioxidant and antiprostate cancer activities were evaluated. Further, the structure of the intermediate (18) was confirmed by single crystal XRD analysis. The mechanism studies were performed through the gene expression for the compounds, 29, 30, and 31, the standards, dihydrotestosterone and R-bicalutamide. RESULTS: The compounds, 29, 30 and 31 showed comparatively significant antioxidant activity and better antiproliferative activity against PC-3 and LNCaP cell lines. Also, very low cytotoxicity was observed in the noncancerous cell (3T3). The compounds, 29, 30 and 31 significantly decreased the mRNA expression of ARstimulated genes, PSA and TMPRSS2, which demonstrated their anti-prostate cancer activities. ADME/T properties prediction of the compounds (3-12 and23-31) showed the promising drug-likeness and pharmacokinetic parameters without toxicity. Moreover, DFT calculations apparently confirmed the stable conformer of the compound, 31. CONCLUSION: These findings may provide the essential information for the development of anti-prostate cancer agents.

Bioactive Fraction of Annona reticulata Bark (or) Ziziphus jujuba Root Bark along with Insulin Attenuates Painful Diabetic Neuropathy through Inhibiting NF-κB Inflammatory Cascade.

The present study explains the neuroprotective ability of bioactive fractions of Annona reticulata bark (ARB) and Ziziphus jujuba root bark (ZJ) along with insulin against diabetic neuropathy. By using different solvents of increasing polarity ARB and ZJ were undergone for bioactive guided fractionation. The neuroprotective ability of the all the plant fractions were tested against H2O2 induced toxicity in SHSY5Y neuroblastoma cell lines and DRG neuronal cells. Among all the fractions tested, the methanol extract of ARB and ZJ (ARBME and ZJME) and its water fractions (ARBWF and ZJWF) exhibited significant neuroprotection against H2O2 induced toxicity in SHSY5Y cells and DRG neuronal cells. Further both the active fractions were tested against streptozotocin (55 mg/kg i.p.) induced diabetic neuropathy in male Wistar rats. Body weight changes, blood glucose levels and pain threshold through hot plate, tail immersion, cold plate and Randall-Sillitto methods were measured throughout the study at weekly interval. After completion of the drug treatment period, all the animals were sacrificed to measure the sciatic nerve lipid peroxidation, antioxidative enzyme levels (SOD, catalase, and GSH) and cytokine levels (IL-1ß, IL-6, IL-10, TNF-α, iNOS, and NFκB) through ELISA and western blotting analysis. Results of this study explain that ARBME, ZJME, ARBWF, and ZJWF along with insulin potentially attenuate the thermal, mechanical hyperalgesia and cold allodynia in diabetic neuropathic rats, where insulin treatment alone failed to diminish the same. Reduction of sciatic nerve oxidative stress, NF-κB and iNOS mediated inflammatory cascade and normalization of abnormal cytokine release confirms the possible mechanism of action. The present study confirms the neuroprotective ability of ARB and ZJ against painful diabetic neuropathy through inhibiting oxidative stress and NF-κB inflammatory cascade.

Design, synthesis and biological evaluation of 2-(4-phenylthiazol-2-yl) isoindoline-1,3-dione derivatives as anti-prostate cancer agents.

The structural modification and molecular docking-based screening approaches on thiazole-based isoindolinediones were imposed to find the novel 2-(4-phenylthiazol-2-yl) isoindoline-1,3-dione derivatives. The best fit compounds (6a-n) were synthesized and evaluated their antiproliferative activities on the prostate cancer cell lines (PC-3 & LNCaP). Among them, the compound, 6m exhibited good activity, particularly on LNCaP (IC50=5.96±1.6µM), moderately active against PC-3 cell lines as compared to bicalutamide. The compound, 6m decreased the androgen-mediated transcription of ARE-mRNA in PSA, TMPRSS2, c-myc and cyclin D1 than R-bicalutamide. The compounds, 6e and 6f were reconfirmed through single crystal XRD analysis. The ADME profiling of the test compounds was evaluated to find the drug-likeness and pharmacokinetic parameters. These findings may provide vital information for the development of anti-prostate cancer agents.

Nuclear Factor Kappa B: A Potential Target to Persecute Head and Neck Cancer.

Despite the consistent and significant advancements made in the treatment of head and neck cancer (HNSCC), it remains one of the most devastating cancers globally killing approximately 350,000 people every year. Both clinical and basic research revealed that the transcription factor NF-κB, is constitutively expressed in HNSCC and this persistent expression of NF-κB is the root cause of this disease resulting in cancer cell proliferation, survival, invasion, metastases and poor survival of patients. Activation of NF-κB is pragmatic in most of the premalignant dysplastic lesions indicating it as an early episode in malignant transformation of this disease. Therefore, therapies designed to inhibit or block the activity of NF-κB, would result in downregulation of key cellular processes involved in tumor growth and its dissemination to metastatic sites. In addition, substantial evidences have revealed that NF-κB plays an indispensable role in the development of both chemo and radiation resistance in HNSCC which is identified to be a primary cause for the failure of therapies. This shows the potential of targeting NF- κB in developing therapies against this disease. This review summarises the role of NF-κB in the development of HNSCC and the potential of using NF-κB as a target to develop novel highly effective therapies for this disease.

Specific Targeting of Akt Kinase Isoforms: Taking the Precise Path for Prevention and Treatment of Cancer.

Akt kinase is a serine threonine kinase that exists in three isoforms, located in different chromosomes and has distinct sites of expression which orchestrates diverse cellular processes required for normal functioning of the cell. Though, these Akt isoforms have some overlapping actions, but they also have specific roles and interestingly, sometimes they even perform contrasting functions. There are various alterations such as amplification, overexpression, mutation, etc. associated with these isoforms which have great implications in the development of cancer. Moreover, these alterations also induce chemo and radio resistance in cancer cells that impede the existing treatment modules. Furthermore, many reports have shown their potential as efficient prognostic biomarkers. Although, many studies have discussed the implications of Akt kinase proteins in different cancers but in-depth analysis of isoform- specific involvement is least examined and hence demands more attention. This review discusses the divergent roles of Akt isoforms comprehensively in different cancers and finding their immense prospects as potential targets for cancer prevention and treatment.

Recent development of targeted approaches for the treatment of breast cancer.

Breast cancer is the most prominent cause of cancer death in women worldwide. The highlights of this review are to provide an overview of the targeted therapeutic agents, challenges with metastatic breast cancer (MBCa), mechanisms of action through Hedgehog/Gli 1 signaling pathway and future prospective. Over a decade of success, several drugs have been approved and are in the advanced stages of clinical trials that target the receptors such as estrogen receptor, growth factor receptor, receptor activator of nuclear factor kappa-B, etc. Currently, several monoclonal antibodies are also used for the treatment of breast cancer. Advances in understanding tumor biology, particularly signaling pathways such as Notch signaling pathway, Hedgehog/Gli 1 signaling pathway, and inhibitors are considered to be important for bone metastasis. These studies may provide vital information for the design and development of new strategies with respect to efficacy, reduction of the side effects, and treatment strategies.

In vitro and In vivo Antioxidant, Anti-hyperlipidemic Properties and Chemical Characterization of Centella asiatica (L.) Extract.

The study aimed to identify the phenolic compounds present in Centella asiatica (L.) (C. asiatica) extract and evaluate the respective antioxidant potential as well as its cholesterol-lowering effects in the experimental animal model. Herein, the antioxidant potential of extracts was assessed by its free radical scavenging activity such as 2, 2-diphenyl -1- picrylhydrazyl as well as reducing capability. The anti-hyperlipidemic effects of C. asiatica extract (CAE) were evaluated in high cholesterol-fed (HCF) rats for 4 weeks, where different concentrations of extracts (0.25, 0.5, and 1 g/kg/day) were orally administrated daily. Lipid and antioxidant profiles, including total cholesterol (TC), triglyceride (TG), low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C) and superoxide dismutase (SOD), together with the indices of hepatic functions were also examined. C. asiatica revealed excellent free radical scavenging activity as revealed by 2-2- diphenyl-1-picryl-hydrazyl (DPPH) assay, with the IC50 values (9.62 ± 0.88 µg/mL). Furthermore, C. asiatica extracts and fenofibrate remarkably lowered the level of TC, TG, LDL-C, and showed elevated levels of HDL-C, SOD. The histopathological observations further demonstrated clear differentiation and structural changes in liver of HCF and CAE treated group. Furthermore, gulonic acid, ferulic acid, kaempferol, chlorogenic acid, and asiatic acid were identified to be the major components which might be responsible for the antioxidant activity of the C. asiatica extract as evidenced from an ultra-high performance liquid chromatography-mass spectrometer. Taken together, these results signifies the excellent antioxidant and anti-hyperlipidemic properties of C. asiatica leaf extracts, which might be useful for the treatment of oxidative-stress related diseases such as hyperlipidemia.

Protective Effect of Bioactivity Guided Fractions of Ziziphus jujuba Mill. Root Bark against Hepatic Injury and Chronic Inflammation via Inhibiting Inflammatory Markers and Oxidative Stress.

The tribal communities of North Eastern India rely on herbal medicine to cure various disease conditions. Ziziphus jujuba Mill. (Rhamnaceae) is one of such medicinal plants used for curing liver ailments, insomnia, anemia, diarrhea, diabetic complications, cancer, and loss of appetite. The present study was aimed to describe the protective ability of Z. jujuba root bark (ZJRB) against hepatic injury and chronic inflammation. Bioactivity guided fractionation of Z. jujuba methanol extract (ZJME) was performed using different solvents of increasing polarity viz. hexane (ZJHF), chloroform (ZJCF), ethyl acetate (ZJEAF), water (ZJWF), and residue (ZJMR). In vitro antioxidant results revealed that both ZJME and ZJWF possess strong antioxidant activity among all the fractions and mother extract tested. Further, ZJME and ZJWF showed significant protection against CCl4 intoxicated HepG2 cell lines by means of increased cell viability and decreased LDH levels compared to control group. ZJME at 200, 400 mg/kg and ZJWF at 50, 100 mg/kg inhibited the lipid peroxidation and significantly restored the liver function markers (AST, ALT, ALP, LDH, SOD, and CAT) and cytokine levels (TNF-α, Il-1ß, and Il-10) in CCl4 induced acute liver damage in rats. All the results were comparable with standard drug silymarin which was further confirmed by histopathology analysis of liver. Similarly, inflammation and increase inflammatory cytokines levels of carrageenan induced paw edema in rats have been refurbished to normal levels on par with the standard drug indomethacin. ZJWF demonstrated potent response than ZJME in all the biological tests conducted. The results of the study signify the ability of ZJRB as good therapeutic agent for liver toxicity and chronic inflammation.

Chitosan-Iron Oxide Coated Graphene Oxide Nanocomposite Hydrogel: A Robust and Soft Antimicrobial Biofilm.

We report a robust biofilm with antimicrobial properties fabricated from chitosan-iron oxide coated graphene oxide nanocomposite hydrogel. For the first time, the coprecipitation method was used for the successful synthesis of iron oxide coated graphene oxide (GIO) nanomaterial. After this, films were fabricated by the gel-casting technique aided by the self-healing ability of the chitosan hydrogel network system. Both the nanomaterial and the nanocomposite films were characterized by techniques such as scanning electron microscopy, FT-IR spectroscopy, X-ray diffraction, and vibrating sample magnetometry. Measurements of the thermodynamic stability and mechanical properties of the films indictaed a significant improvement in their thermal and mechanical properties. Moreover, the stress-strain profile indicated the tough nature of the nanocomposite hydrogel films. These improvements, therefore, indicated an effective interaction and good compatibility of the GIO nanomaterial with the chitosan hydrogel matrix. In addition, it was also possible to fabricate films with tunable surface properties such as hydrophobicity simply by varying the loading percentage of GIO nanomaterial in the hydrogel matrix. Fascinatingly, the chitosan-iron oxide coated graphene oxide nanocomposite hydrogel films displayed significant antimicrobial activities against both Gram-positive and Gram-negative bacterial strains, such as methicillin-resistant Staphylococcus aureus, Staphylococcus aureus, and Escherichia coli, and also against the opportunistic dermatophyte Candida albicans. The antimicrobial activities of the films were tested by agar diffusion assay and antimicrobial testing based on direct contact. A comparison of the antimicrobial activity of the chitosan-GIO nanocomposite hydrogel films with those of individual chitosan-graphene oxide and chitosan-iron oxide nanocomposite films demonstrated a higher antimicrobial activity for the former in both types of tests. In vitro hemolysis potentiality tests and MTT assays of the nanocomposite films indicated a noncytotoxic nature of the films, which conveyed the possibility of potential applications of these soft and tough films in biomedical as well as in the food industry.

Bioactive Guided Fractions of Annona reticulata L. bark: Protection against Liver Toxicity and Inflammation through Inhibiting Oxidative Stress and Proinflammatory Cytokines.

Herbal medicine is popularized worldwide due to its ability to cure the diseases with lesser or no side effects. North Eastern part of India comes under one of the world biodiversity hotspots which is very rich in traditional herbal medicine. Annona reticulata L. (Annonaceae) is one such plant used for the treatment of inflammatory diseases, liver ailments and diabetes by traditional healers. The present study was aimed to scientifically validate this folk knowledge and to develop an herbal remedy through evaluating bioactive guided fractions of A. reticulata (AR) bark against hepatotoxicity and inflammation using in vitro and in vivo models. Results of this study demonstrates that among all fractions of AR bark, methanol extract and its water fraction possess strong anti-oxidant ability and showed protection against CCl4 induced toxicity in HepG2 cell lines and rats. Both the fractions also exhibit dose dependent anti-inflammatory activity against carrageenan induced inflammation in rats. Water fraction showed potent response in the entire tests conducted than methanol extract, which states that polar components of the AR bark methanol extract were responsible for these activities. Further, from the experiments conducted to elucidate the mechanism of action, the results revealed that AR bark showed liver protection and anti-inflammatory response through inhibiting the oxidative stress and inflammatory cytokines.

Chemical Composition and Anti-Candidiasis Mediated Wound Healing Property of Cymbopogon nardus Essential Oil on Chronic Diabetic Wounds.

Poor wound healing is one of the major complication of diabetic patients which arises due to different factors like hyperglycemia, oxidative stress, vascular insufficiency and microbial infections. Candidiasis of diabetic wounds is a difficult to treat condition and potentially can lead to organ amputation. There are a few number of medications available in market to treat this chronic condition; which demands for alternative treatment options. In traditional system of medicine like Ayurveda, essential oil extracted from leaves of Cymbopogon nardus L. (Poaceae) has been using for the treatment of microbial infections, inflammation and pain. In this regard, we have evaluated anti-Candida and anti-inflammatory activity mediated wound healing property of C. nardus essential oil (EO-CN) on candidiasis of diabetic wounds. EO-CN was obtained through hydro-distillation and subjected to Gas chromatography-mass spectroscopy (GC-MS) analysis for chemical profiling. Anti-Candida activity of EO-CN was tested against Candida albicans, C. glabrata and C. tropicalis by in vitro zone of inhibition and minimum inhibitory concentration (MIC) assays. Anti-candidiasis ability of EO-CN was evaluated on C. albicans infected diabetic wounds of mice through measuring candida load on the 7th, 14th, and 21st day of treatment. Further progression in wound healing was confirmed by measuring the inflammatory marker levels and histopathology of wounded tissues on last day of EO-CN treatment. A total of 95 compounds were identified through GC-MS analysis, with major compounds like citral, 2,6-octadienal-, 3,7-dimethyl-, geranyl acetate, citronellal, geraniol, and citronellol. In vitro test results demonstrated strong anti-Candida activity of EO-CN with a MIC value of 25 µg/ml against C. albicans, 50 µg/ml against C. glabrata and C. tropicalis. EO-CN treatment resulted in significant reduction of candida load on diabetic wounds. Acceleration in wound healing was indicated by declined levels of inflammatory cytokines at wounded area in EO-CN treated animals compared to non-treated group, which was further confirmed by histopathological examination. This study suggests that through significant anti-Candida and anti-inflammatory activity, EO-CN attenuates the growth of the fungus on diabetic wounds and simultaneously reduces the inflammation which leads to acceleration of the wound healing process.

Antioxidant and Hepatoprotective Potentiality of Randia dumetorum Lam. Leaf and Bark via Inhibition of Oxidative Stress and Inflammatory Cytokines.

Randia dumetorum Lam. (RD) (Rubiaceae) is traditionally used by some tribes of Assam and Manipur of North East India for the treatment of liver ailments. In this context, to scientifically validate this indigenous traditional knowledge, we have evaluated the antioxidant and hepatoprotective activity of RD leaf and bark. The methanol extracts of RD leaf and bark were evaluated for in vitro antioxidant activity which exhibited good antioxidant activity in terms of reducing power assay, total antioxidant assay and DPPH (1,1-diphenyl-2-picrylhydrazyl) radical scavenging assay. Total phenolic and flavonoid content were found to be 112 ± 3.24 mg and 138 ± 2.46 mg gallic acid equivalents/g extract and 2.6 ± 0.26 mg and 3.34 ± 0.31 mg rutin equivalents/g extract respectively for RD leaf and bark methanol extracts. The in vivo hepato protective activity of the RD leaf and bark extract was evaluated against carbon tetrachloride (CCl4) induced hepatic damage in male wistar rats. CCl4 administration induced hepatic damage in rats resulted in increased levels of aspartate transaminase, alanine transaminase, alkaline phosphatase, lactate dehydrogenase, thiobarbituric acid reacting substances, albumin, bilirubin, TNF-α, IL-1ß and decreased levels of total protein and antioxidant enzymes like superoxide dismutase, catalase, and glutathione reductase. RD leaf and bark methanol extracts pre-treatment exhibited protection against CCl4 induced hepatotoxicity by reversing all the abnormal parameters to significant levels. Histopathological results revealed that RD leaf and bark extracts at 400 mg/kg protects the liver from damage induced by CCl4. The results of this study scientifically validate the traditional use of RD leaf and bark for the treatment of liver ailments.

Antidiabetic and Antilipidemic Effect of Musa balbisiana Root Extract: A Potent Agent for Glucose Homeostasis in Streptozotocin-Induced Diabetic Rat.

Folklore studies have revealed that Musa balbisiana Colla (MB; Family: Musaceae) has high medicinal properties. The purpose of the present study is to evaluate antihyperglycemic, and antioxidant activity of MB extracts in streptozotocin (STZ) induced diabetic rats. In vitro antioxidant and antidiabetic activity of MB extracts, i.e., root extract (RE), shoot extract and inflorescence extract were determined by using various methods viz 1,-1-diphenyl-2-picrylhydrazyl (DPPH) and a method to assess their possible effect on glucose diffusion across gastrointestinal tract and identify bioactive compound of potent extract. In vivo antilipidemic and antidiabetic activity was evaluated by administrating oral dose of RE for 15 days on STZ- induced diabetic rat. RE showed highest antioxidant activity by scavenging DPPH radical (IC50 32.96 µg/ml) and inhibit 30% glucose movement in vitro. The methanol extract of root showed the presence of calyx [4] arene category of the compound. Furthermore, RE treated rat revealed a reduction in fasting blood glucose (62.5%), serum total cholesterol (36.2%), triglyceride (54.5%), and low-density lipoprotein (50.94%) after 15 days as compared to STZ treated animal. There was an initiation of regenerative structures of the affected organs after 15 days of RE treatment. Histopathological observations clearly differentiate the structural changes in pancreas, liver, and kidney of STZ and RE treated group. The presence of calyx [4] arene class of compound may be responsible for its antioxidant and antidiabetic properties by absorbing glucose in vivo.