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Malaria is one of the most devastating infectious diseases that caused millions of clinical cases annually despite decades of prevention efforts. Recent cases of Plasmodium falciparum resistance against the only remaining class of effective antimalarial (artemisinin) in South East Asia may soon pose a significant threat. Hence, the identification of new antimalarial compounds with a novel mode of action is necessary to curb this problem. Protein kinase has been implicated as a valid target for drug development in diseases such as cancer and diabetes in humans. A similar approach is now recognized for the treatment of protozoan-related disease including malaria. Few Plasmodium protein kinases that are not only crucial for their survival but also have unique structural features have been identified as a potential target for drug development. In this review, studies on antimalarial drug development exploiting the size of Plasmodium protein kinase ATP gatekeeper over the past 15 years are mainly discussed. The ATP-binding site of Plasmodium protein kinases such as Pf CDPK1, Pf CDPK4, Pf PKG, Pf PK7, and Pf PI4K showed great potential for selective and multi-target inhibitions owing to their smaller or unique ATP-gatekeeper amino acid subunits compared to that of human protein kinase. Hence it is a feasible solution to identify a new class of active antimalarial agents with a novel mode of action and longer clinical life-span. [ABSTRACT FROM AUTHOR]

Peripheral nerve injury (PNI) is an incapacitating situation and has no effective therapy until now. We examined the possible role of crude leaves of Moringa oleifera Lam. at 200 mg/kg body weight in accelerating the functional regain in the sciatic nerve lesion induced mouse model (Adult male albino mice (BALB/c). Motor functions were evaluated by using the sciatic functional index, muscle mass, and muscle grip strength measurement, whereas the sensory functions were evaluated by using the hot plate test. Blood glucose levels and blood cell composition were also analyzed. We found that the Moringa oleifera crude leaves endorse the sensory and motor functions reclamation following the PNI with a statistically significant difference (p <.05). It also revitalizes the gastrocnemius muscle by mass restoration with glycemic management perspective. Conclusively, the crude powder of Moringa oleifera leaves exhibited a function restoration boosting property and further detailed studies for its application as a therapeutic agent are strongly recommended. [ABSTRACT FROM AUTHOR]

Theophylline‐7‐acetic acid (acefylline) (3) and its derivatives are pharmacologically active compounds and generally recognized as bronchodilators for the treatment of respiratory diseases like acute asthma for over 70 years. In this article, synthesis of 2‐((5‐((1,3‐dimethyl‐2,6‐dioxo‐2,3‐dihydro‐1H‐purin‐7(6H)‐yl)methyl)‐1,3,4‐oxadiazol‐2‐yl)thio)‐N‐arylacetamides (10a‐j) has been reported. All the synthesized derivatives (10a‐j) were structurally verified by FT‐IR, 1H NMR, 13C NMR and evaluated for their anti‐cancer (using MTT assay), hemolytic and thrombolytic potential. N‐(4‐Chlorophenyl)‐2‐(5‐((1,3‐dimethyl‐2,6‐dioxo‐2,3‐dihydro‐1H‐purin‐7(6H)‐yl)methyl)‐1,3,4‐oxadiazol‐2‐ylthio)acetamide (10g) was found to be the most active against human liver cancer cell lines (Huh7) having cell viability 53.58 ± 1.28 using 100 μg/mL concentration of compound which was further in‐silico modelled to describe the possible mechanistic insights for its anti‐proliferative activity. The results of hemolytic and thrombolytic activities indicated that these derivatives were less toxic and hold considerable potential as a drug candidate. 2‐(5‐((1,3‐Dimethyl‐2,6‐dioxo‐2,3‐dihydro‐1H‐purin‐7(6H)‐yl)methyl)‐1,3,4‐oxadiazol‐2‐ylthio)‐N‐(2‐fluorophenyl)acetamide (10c) of the series was found to be least toxic with 0.1% hemolysis relative to ABTS (95.5%) as positive control. 2‐(5‐((1,3‐Dimethyl‐2,6‐dioxo‐2,3‐dihydro‐1H‐purin‐7(6H)‐yl)methyl)‐1,3,4‐oxadiazol‐2‐ylthio)‐N‐(tetrahydro‐2H‐pyran‐4‐yl)acetamide (10j) exhibited potent clot lysis activity (90%) as compared to negative control DMSO (0.57%). [ABSTRACT FROM AUTHOR]

The drug resistance phenomenon in microbes is resulting in the ineffectiveness of available drugs to treat the infections. Thus, there is a continued need to discover new molecules to combat the drug resistance phenomenon. Norfloxacin is a fluoroquinolone antibiotic that is used for the treatment of urinary tract infections. In this research work, norfloxacin is structurally modified by hybridizing with a range of substituted acetohydrazidic moieties through a multistep reaction. The first step involves the coupling of norfloxacin 1 with methyl chloroacetate followed by the treatment with hydrazine hydrate to result in corresponding acetohydrazide 3. A range of substituted benzaldehydes were reacted with the acetohydrazide to form the targeted series of norfloxacin derivatives 4a-i. The final compounds were screened for antimicrobial activity. Among the tested compounds, 4c, 4d, 4e and 4f displayed better antifungal activity against F.avenaceum, while compound 4c and 4e were active against F. bubigeum. [ABSTRACT FROM AUTHOR]

Overuse of the fossil fuels to fulfill existing energy requirements has generated various environmental problems like global warming. Emergence of environmental issues due to burning of the fossil fuel resources has provoked researchers to explore alternative sources of fuel. In this scenario, microalgal biofuels could present a promising alternative fuel if produced cost‐effectively without competing for freshwater resources and arable land. Aim of the present study was to grow microalgae by employing lignocellulosic waste for production of lipids. Scenedesmus dimorphus NT8c was chosen based on its ability to tolerate heat, rapid growth, and ease of harvesting by overnight settling. Biochemical composition and growth parameters of microalgae were analyzed when cultivated mixotrophically on sugarcane bagasse hydrolysate, a low‐value agricultural by‐product, that is, currently underutilized. Despite a slight increase in turbidity in the medium, S. dimorphus NT8c cultures raised mixotrophically in 5 g/L sugarcane bagasse hydrolysate displayed significantly higher growth rates compared to photoautotrophic cultivation with an overall biomass productivity of 119.5 mg L d−1, protein contents of 34.82% and fatty acid contents of 15.41%. Thus, microalgae cultivated mixotrophically are capable of photosynthesizing while metabolizing and assimilating organic carbon, significant increases of biomass and lipid productivity can be achieved. However, high supplementation with organic carbon can result in unfavorable levels of turbidity and bacterial growth, reducing microalgal biomass productivity. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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-κB. EriB induced apoptosis in MDA-MB231 cells via inhibiting NF- κBp65, 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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Diabetes, a chronic metabolic disorder affecting millions worldwide, presents a significant health challenge characterized by impaired glucose regulation and potential complications. This study examines the antidiabetic effects of a polyherbal formulation (PENN-DIABEX) prepared from five different medicinal plant extracts. The objective is to ascertain its efficacy in managing streptozotocin (STZ) induced diabetes in rats. To accomplish this, six distinct groups of rats were involved five with induced diabetes and one serving as a normal control. Among the diabetic groups, one received no treatment, functioning as the diabetic control group. The remaining three groups were administered PHF in three different doses while the 6th group was given metformin. On the last day of the experiment, all rats were sacrificed, and blood samples were taken in collecting tubes to analyze blood biochemical parameters. Additionally, tissue samples from the liver, kidney, and pancreas were preserved in formalin solution for subsequent histopathological activity. The results of the study revealed that treatment with PHF in diabetic rats led to a significant (P < 0.01) improvement in fasting blood glucose levels (FBG), glycated hemoglobin (HbA1c), and various biochemical markers including LFTs, RFTs, and lipid profiling. Furthermore, the histology of the liver, kidney, and pancreas indicated that the formulation did not induce any metabolic toxicity. Comparative analysis of the antidiabetic effects of PHF with those of metformin, revealed that the PHF showed better results than the standard drug. This suggests its potential utilization as a safer and alternative approach in the treatment of diabetes. [ABSTRACT FROM AUTHOR]

Liver injury is a prevalent pathological process that can give rise to conditions such as fatty liver, cirrhosis, fibrosis, and even cancer. It has been observed that plants and natural products possess significant protective effects against liver injury. Current study was performed to investigate the efficacy of almonds shell against carbon tetrachloride (CCl 4) induced hepatotoxicity in rat model. As almonds shell contain a large variety of phenolic and flavonoid compounds, which are largely associated with antioxidant and hepatoprotective properties. For this purpose, screening of small-scale library of twenty plant extracts was performed for evaluation of antioxidant potential by DPPH assay. The data revealed that almonds shell extract (ASEE) exhibited potent antioxidant activity. This potent extract was further evaluated for hepatoprotective activity in in vivo rat model on 30 rats, divided into 6 groups of 5 rats each. On 29th day all rats were sacrificed and blood serum was collected for further analysis. Liver tissues were also preserved in formalin for histopathology. The results demonstrated that ASEE displayed a protective effect on liver function tests (LFT), renal function tests (RFT), and lipid biomarkers in comparison to the CCl4 group. The histological data also unveiled a substantial safeguarding impact on liver damage, characterized by a reduction in apoptosis, diminished liver hemorrhage, and decreased accumulation of cellular debris. The data indicates that ethanolic extract from almond shells possesses hepatoprotective potential, suggesting its viability as an alternative source for hepatoprotective drug development after pre-clinical research. [ABSTRACT FROM AUTHOR]

Mushrooms, a treasure of diverse bioactive scaffolds, have been widely admired due to their nutritional and medicinal significance all over the world. The current study intended to evaluate the therapeutic potentiality of an edible mushroom, Leucoagaricus leucothites (Vittad.) Wasser. Thus, anti-oxidant potential of L. leucothites was determined using DPPH assay and for the determination of anti-microbial potential agar dilution procedure was followed. TOS (total oxidant status), TAS (total anti-oxidant status), and OSI (oxidative stress index) values were evaluated utilizing Rel Assay Kits. For the assessment of heavy metal contents, wet decomposition approach with atomic absorption spectrophotometry was adopted. Screening of phytochemicals present in ethanolic extract of L. leucothites were determined by HPLC. TAS, TOS and OSI values were found to be 8.291mmol/L, 10.797μmol/L and 0.130 respectively. Our results declared that heavy metal contents are generally in the safe range. Phytochemical analysis of L. leucothites has affirmed the presence of important phenolics such as gallic acid, catechin, and hesperidin. Investigations on anti-oxidant and anti-microbial potential of L. leucothites has uncovered the fact that this naturally occurring, biologically active, and therapeutically effective mushroom specie has natural borne anti-oxidant and anti-microbial potential and it would be worthwhile to use it for nutritional as well as medicinal purpose. [ABSTRACT FROM AUTHOR]

This review article aims to provide an update on the sources, pharmacological and biological profile of a β-carboline alkaloid, harmine which is a major bioactive component of various plants mainly Peganum harmala. Harmine's wide range of pharmacological properties has been welldocumented as anti-cancer, anti-inflammatory, anti-oxidant, neuroprotective, anti-depressant, and antimicrobial. Although reported data suggests a multifunctional pharmacological role of harmine but farther experimentation on its molecular mechanism of action, synthetic chemistry approaches, and preclinical studies are yet obligatory to fully uncover its pharmacological efficacy. [ABSTRACT FROM AUTHOR]

Roots, bark, stem/twigs, and leaves of Fraxinus xanthoxyloides are being used regionally for the cure of malaria, jaundice, internal injuries, pneumonia, pain, rheumatism and also in fracture of bones. Our objective was to assess the methanolic leaves extract of F. xanthoxyloides for its antioxidant capability against oxidative stress induced by carbon tetrachloride (CCl4) in the kidney of Sprague-Dawley rats. Duration of this experiment was 30 days and doses were given on alternative days. Urine of rats was assessed for kidney function and renal tissues for antioxidant enzymes activity, biochemical markers, comet assay and histopathology. Enhanced urinary creatinine, urobilinogen levels and decreased creatinine clearance, protein contents, and albumin levels were observed by CCl4 administration when matched to controls. CCl4 injection also decreased the level of reduced glutathione, catalase, super oxide dismutase, peroxidase, glutathione s-transferase, glutathione reductase, and tissue protein while elevated the levels of thiobarbituric acid reactive substances, DNA damages and H2O2 in renal tissues of experimental animals. Co-treatment of FXM and silymarin, lead to the restoration of all the above tested parameters of kidney. Through this study we affirmed the ameliorating role of F. xanthoxyloides in oxidative stress affiliated disorders of kidney. [ABSTRACT FROM AUTHOR]

[Display omitted] Guar Gum has been evaluated for its importance in food and pharmaceutical industry. A blended biopolymeric hydrogel was prepared by solution casting technique using guar gum (GG), chitosan (CS), polyvinyl alcohol (PVA), chemically crosslinked with tetra orthosilicate (TEOS) and impregnated with methotrexate (MTX) to assess its drug carrying capacity against colon cancer (HCT-116). The surface morphology, chemical bonding, hydrophilicity and water absorbing capacity were analyzed by atomic force microscopy (AFM), Fourier transform infrared spectroscopy (FTIR), contact angle measurements and swelling properties in variable conditions. Furthermore, degradation, drug release kinetics, hemocompatibility, and cytotoxicity of MTX-loaded hydrogel was tested. The release of MTX from GG/CS/PVA biopolymeric blend occurred in sustained manner. Results displayed that in 7 h 25 min duration 96% of the drug was released in phosphate buffer saline (PBS) at pH 7.4. These blends were non-hemolytic, and antiproliferative against HCT-116. Furthermore, the MTT assay has revealed that MTX-loaded hydrogel had prominently decreased the cell viability (with IC50 11.7 µg/ml) as compared to free MTX (with IC50 21.57 µg/ml). Hence, these results suggest that guar gum based hydrogels are potential biomaterials for colon cancer treatment. [ABSTRACT FROM AUTHOR]

CD147 is a multifunctional trans-membrane glycoprotein, which is highly expressed in many cancers. However, the mechanism by which CD147 modulates cell proliferation is not fully understood. The aim of this study is to investigate the role of CD147 in cell proliferation associated with the TGF-β/Smad4 signaling pathway. Here, we used cell viability and clone formation assays in LNCaP prostate cancer cells to demonstrate that CD147 promotes cell proliferation. The luciferase assay and western blotting show that silencing CD147 using shRNA enhances transcription and expression of p21 WAF1 . Using immunofluorescence and nuclear-cytoplasmic separation, we show that this is primarily attributed to transport of Smad4 from the cytoplasm to nucleus. Other assays (GST pull-down, co-immunoprecipitation and immunofluorescence) demonstrate that Smad4 is a new interaction partner of CD147, with the Smad4 MH2 domain and CD147 intracellular domain (CD147-ICD) being involved in the interaction. Furthermore, we report that a phosphoserine (pSer) in CD147 (pSer252) is responsible for this interaction and inhibition of the Smad4/p21 WAF1 signal that promotes cell proliferation. Our results provide a novel molecular mechanism for CD147-induced cell proliferation associated with Smad4 signal inhibition. [ABSTRACT FROM AUTHOR]

Altholactone, a natural compound isolated from Goniothalamus spp., has demonstrated anti-inflammatory and anticancer activities, but its molecular mechanisms are still not fully defined. Nuclear factor kappa B (NF-κB) and signal transducer and activator of transcription 3 (STAT3) play pivotal roles in the cell survival of many human tumors. The objective of this study was to elucidate the mechanism of action of altholactone against prostate cancer DU145 cells and to evaluate whether its effects are mediated by inhibition of NF-κB and STAT3 activity. Altholactone inhibited proliferation of DU145 cells and induced cell cycle arrest in S phase and triggered apoptosis. Reporter assays revealed that altholactone repressed p65- and TNF-α-enhanced NF-κB transcriptional activity and also inhibited both constitutive and IL-6-induced transcriptional activity of STAT3. Consistent with this, altholactone down-regulated phosphorylation of STAT3 and moreover, decreased constitutively active mutant of STAT3 (STAT3C)-induced transcriptional activity. Altholactone treatment also results in down-regulation of STAT3 target genes such as survivin, and Bcl-2 followed by up regulation of pro-apoptotic Bax protein. However, pre-treatment with the antioxidant N-acetylcysteine (NAC) significantly inhibited the activation of Bax and prevented down-regulation of STAT3 target genes. Collectively, our findings suggest that altholactone induces DU145 cells death through inhibition of NF-κB and STAT3 activity. [ABSTRACT FROM AUTHOR]

[Display omitted] Biocompatible polymer-functionalized magnetic nanoparticles could offer promising applications in biomedical sciences. We fabricated polymer functionalized tri-manganese tetra oxide (Mn 3 O 4) nanoparticles with the co-precipitation method and an octahedral crystal structure having a crystallite size of 10–17 nm was identified via XRD analyses. The SEM graph depicted the non-uniform and smooth surface of PEG-functionalized Mn 3 O 4 NPs as compared to Mn 3 O 4 and chitosan-coated Mn 3 O 4 NPs. Elemental composition in the prepared sample was examined by EDX analysis. Various modes such as MnO, Mn O H, OH, symmetric, and anti-symmetric of CH 2 attached to the spectrum of Mn 3 O 4 NPs were observed with FTIR analysis. The magnetization factor decreased and increase the coreacivity and retentivity of surface functionalized Mn 3 O 4 -NPs was calculated via VSM analysis. In-vitro bioassay, antibacterial activity was tested against Escherichiacoli , Bacillus cereus, and anti-fungal activities against two Fusarium strains indicated clear antimicrobial activities. The MTT assay to examine the anticancer activity against the MCF-7 cancer cell line was performed and the T 1 MRI contrast agent demonstrated that PEG-coated Mn 3 O 4 NPs exhibited anti-cancer activities. We propose that surface-functionalized magnetic NPs used for the treatment of cancer by using a remote controlled process of hyperthermia therapy. [ABSTRACT FROM AUTHOR]