Solid Lipid Nanoparticles as an Innovative Lipidic Drug Delivery System.

In order to overcome some of the drawbacks of traditional formulations, increasing emphasis has recently been paid to lipid-based drug delivery systems. Solid lipid nanoparticles (SLNs) are among these delivery methods, and they hold promise because of their simplicity in production, capacity to scale up, biocompatibility, and biodegradability of formulation components. Other benefits could be connected to a particular route of administration or the makeup of the ingredients being placed into these delivery systems. This article aims to review the significance of solid lipid nanocarriers, their benefits and drawbacks, as well as their types, compositions, methods of preparation, mechanisms of drug release, characterization, routes of administration, and applications in a variety of delivery systems with a focus on their efficacy.

Magnetic nanosystem a tool for targeted delivery and diagnostic application: Current challenges and recent advancement.

Over the last two decades, researchers have paid more attention to magnetic nanosystems due to their wide application in diverse fields. The metal nanomaterials' antimicrobial and biocidal properties make them an essential nanosystem for biomedical applications. Moreover, the magnetic nanosystems could have also been used for diagnosis and treatment because of their magnetic, optical, and fluorescence properties. Superparamagnetic iron oxide nanoparticles (SPIONs) and quantum dots (QDs) are the most widely used magnetic nanosystems prepared by a simple process. By surface modification, researchers have recently been working on conjugating metals like silica, copper, and gold with magnetic nanosystems. This hybridization of the nanosystems modifies the structural characteristics of the nanomaterials and helps to improve their efficacy for targeted drug and gene delivery. The hybridization of metals with various nanomaterials like micelles, cubosomes, liposomes, and polymeric nanomaterials is gaining more interest due to their nanometer size range and nontoxic, biocompatible nature. Moreover, they have good injectability and higher targeting ability by accumulation at the target site by application of an external magnetic field. The present article discussed the magnetic nanosystem in more detail regarding their structure, properties, interaction with the biological system, and diagnostic applications.

A Review on Five and Six-Membered Heterocyclic Compounds Targeting the Penicillin-Binding Protein 2 (PBP2A) of Methicillin-Resistant Staphylococcus aureus (MRSA).

Staphylococcus aureus is a common human pathogen. Methicillin-resistant Staphylococcus aureus (MRSA) infections pose significant and challenging therapeutic difficulties. MRSA often acquires the non-native gene PBP2a, which results in reduced susceptibility to ß-lactam antibiotics, thus conferring resistance. PBP2a has a lower affinity for methicillin, allowing bacteria to maintain peptidoglycan biosynthesis, a core component of the bacterial cell wall. Consequently, even in the presence of methicillin or other antibiotics, bacteria can develop resistance. Due to genes responsible for resistance, S. aureus becomes MRSA. The fundamental premise of this resistance mechanism is well-understood. Given the therapeutic concerns posed by resistant microorganisms, there is a legitimate demand for novel antibiotics. This review primarily focuses on PBP2a scaffolds and the various screening approaches used to identify PBP2a inhibitors. The following classes of compounds and their biological activities are discussed: Penicillin, Cephalosporins, Pyrazole-Benzimidazole-based derivatives, Oxadiazole-containing derivatives, non-ß-lactam allosteric inhibitors, 4-(3H)-Quinazolinones, Pyrrolylated chalcone, Bis-2-Oxoazetidinyl macrocycles (ß-lactam antibiotics with 1,3-Bridges), Macrocycle-embedded ß-lactams as novel inhibitors, Pyridine-Coupled Pyrimidinones, novel Naphthalimide corbelled aminothiazoximes, non-covalent inhibitors, Investigational-ß-lactam antibiotics, Carbapenem, novel Benzoxazole derivatives, Pyrazolylpyridine analogues, and other miscellaneous classes of scaffolds for PBP2a. Additionally, we discuss the penicillin-binding protein, a crucial target in the MRSA cell wall. Various aspects of PBP2a, bacterial cell walls, peptidoglycans, different crystal structures of PBP2a, synthetic routes for PBP2a inhibitors, and future perspectives on MRSA inhibitors are also explored.

New Benzopyrrole Derivatives: Synthesis and Appraisal of Their Potential as Antimicrobial Agents.

A series of twenty compounds (23-42) were synthesized and characterized by spectral studies in order to explore newer antimicrobial compounds. The majority of the synthesized compounds reported significant antimicrobial properties against various pathogenic bacterial and fungal strains with the help of tube dilution method. Significant activities (MIC ranging from 3.9 to 15.62 µg/ml) have been shown against Gram-negative and Gram-positive bacteria with. In contrast, moderate to outstanding antibacterial activity was reported versus Gram-negative bacteria such as E. coli and P. aeruginosa along with Gram-positive bacteria such as S. aureus and B. subtilis. While antifungal activity was moderate to excellent against two fungus strains (Candida tropicalis, Candida glabrata). Compounds 25 and 34 had the utmost activity versus Gram-positive and Gram-negative bacteria too. The antifungal activity of compound 35 was comparable to that of standard. In-silico Molecular docking evaluations were performed for antibacterial and antifungal activities against the target DNA gyrase A (PDB: 1AB4) and 14 alpha-sterol demethylase enzyme (PDB: 1EA1), respectively. The dock score for typicals compounds for antibacterial and antifungal activity were -4.733 and -9.4, respectively. The three-dimensional QSAR examination was carried out by multiple linear regression (SA-MLR) with good predictive power (r2=0.9105, q2=0.8011). Establishment of several interactions between the ligand 25 and 34 and the active site of residue of both receptors, enable the ligand 25 and 34 to be fit well in the pocket of the active site, as seen in Molecular dynamics simulations analysis. Thus, data suggest that these ligands could be further explored as potential precursors to develop antimicrobial drugs.

Preparation of Terbinafin-Encapsulated Solid Lipid Nanoparticles Containing Antifungal Carbopol® Hydrogel with Improved Efficacy: In Vitro, Ex Vivo and In Vivo Study.

The present research was aimed to develop a terbinafin hydrochloride (TH)-encapsulated solid lipid nanoparticles (SLNs) hydrogel for improved antifungal efficacy. TH-loaded SLNs were obtained from glyceryl monostearate (lipid) and Pluronic® F68 (surfactant) employing high-pressure homogenization. The ratio of drug with respect to lipid was optimized, considering factors such as desired particle size and highest percent encapsulation efficiency. Lyophilized SLNs were then incorporated in the hydrogel prepared from 0.2-1.0% w/v carbopol 934P and further evaluated for rheological parameters. The z-average, zeta potential and polydispersity index were found to be 241.3 nm, -15.2 mV and 0.415, respectively. The SLNs show a higher entrapment efficiency of about 98.36%, with 2.12 to 6.3602% drug loading. SEM images, XRD and the results of the DSC, FTIR show successful preparation of SLNs after freeze drying. The TH-loaded SLNs hydrogel showed sustained drug release (95.47 ± 1.45%) over a period of 24 h. The results reported in this study show a significant effect on the zone of inhibition than the marketed formulation and pure drug in Candida albicans cultures, with better physical stability at cooler temperatures. It helped to enhance skin deposition inthe ex vivostudy and improved, in vitro and in vivo, the antifungal activity.

Mycobacterium enoyl acyl carrier protein reductase (InhA): A key target for antitubercular drug discovery.

Enoyl acyl carrier protein reductase (InhA) is a key enzyme involved in fatty acid synthesis mainly mycolic acid biosynthesis that is a part of NADH dependent acyl carrier protein reductase family. The aim of the present literature is to underline the different scaffolds or enzyme inhibitors that inhibit mycolic acid biosynthesis mainly cell wall synthesis by inhibiting enzyme InhA. Various scaffolds were identified based on the screening technologies like high throughput screening, encoded library technology, fragment-based screening. The compounds studied include indirect inhibitors (Isoniazid, Ethionamide, Prothionamide) and direct inhibitors (Triclosan/Diphenyl ethers, Pyrrolidine Carboxamides, Pyrroles, Acetamides, Thiadiazoles, Triazoles) with better efficacy against drug resistance. Out of the several scaffolds studied, pyrrolidine carboxamides were found to be the best molecules targeting InhA having good bioavailability properties and better MIC. This review provides with a detailed information, analysis, structure activity relationship and useful insight on various scaffolds as InhA inhibitors.

Mycobacterial Membrane Protein Large 3 (MmpL3) Inhibitors: A Promising Approach to Combat Tuberculosis.

Tuberculosis is a prominent aliment throughout the world and a leading cause of mortality among infectious diseases. Drug development for multi-drug resistance and reducing the current therapy time is the top priority. Mycobacterial membrane protein large 3 (MmpL3) is a promising target with high potential, however, it has not been explored to its greatest potential. It is a membrane transporter that translocates trehalose-monomycolate which is a precursor for the synthesis of mycolic acid that is essential for the synthesis of the bacterial cell wall and is pathogenic in nature. In this review, we have discussed the current development of MmpL3 inhibitors, different scaffolds, their derivatives, and their synthetic schemes and provide insight into the challenges in developing these inhibitors.

Development of novel indole-linked pyrazoles as anticonvulsant agents: A molecular hybridization approach.

A series of 3-{2-[1-acetyl-5-(substitutedphenyl)-4,5-dihydropyrazol-3-yl]hydrazinylidene}-1,3-dihydro-2H-indol-2-ones 24-43 was synthesized using an appropriate synthetic route and evaluated experimentally by the maximal electroshock test. These compounds were evaluated for antidepressant and antianxiety activities. The most active compound, 3-{2-[1-acetyl-5-(4-chlorophenyl)-4,5-dihydropyrazol-3-yl]hydrazinylidene}-1,3-dihydro-2H-indol-2-one 25, exhibited an ED50 of 13.19 mmol/kg, a TD50 of 43.49 mmol/kg, and a high protective index of 3.29, compared with the standard drug diazepam. To get insights into the intermolecular interactions, molecular docking studies were performed at the active site of the GABAA receptor and the MAO-A enzyme. Molecular docking studies are also in agreement with the pharmacological evaluation with potent compounds, exhibiting docking scores of -1.5180 and 0.7458 for the GABAA receptor and MAO-A, respectively. The 3D-QSAR analysis was carried out by Vlife MDS engine 4.3.1, and a statistically reliable model with good predictive power (r2 = 0.7523, q2 = 0.3773) was achieved. The 3D-QSAR plots gave insights into the structure-activity relationship of these compounds, which may aid in the design of potent benzopyrrole derivatives as anticonvulsant agents. So, our research can make a great impact on those medicinal chemists who work on the development of anticonvulsant agents.

Meloxicam encapsulated nanostructured colloidal self-assembly for evaluating antitumor and anti-inflammatory efficacy in 3D printed scaffolds.

Nanostructured colloidal self-assembly (NCS) is one of the most promising drug delivery carriers in cancer treatment. The present research work aimed towards synthesizing meloxicam (MLX) loaded NCS for its improved circulation half-life and increased cellular internalization. NCS was formulated using glyceryl monoolein, Pluronic® F127, and MLX. Quality by Design experiments with a quadratic model was subjected to optimization of the formulation. The optimized NCS with an average particle size of 185.5 ± 3.02 nm showed higher MLX encapsulation (94.74 ± 3.41%) and sustained release behavior of MLX up to 24 hr. in vitro cytotoxicity of the developed NCS with MCF-7 and MDA-MB-231 cell lines confirmed lower cell viability and a higher rate of cell growth inhibition. This MLX loaded NCS showed dual activity as an antitumor and anti-inflammatory in highly invasive estrogen-dependent MDA-MB-231 cells due to the high expression of cyclooxygenase-2 (COX-2). Besides, an activity of the MLX-NCS was also observed in 3D printed MCF-7 cells. This investigation shows the possible use of MLX-NCS as an efficient cancer drug delivery system with excellent colloidal stability, sustained release of MLX, enhanced antitumor and anti-inflammatory efficacy in 3D printed scaffolds. In contrast to toxicity study in 2D culture, the 3D constructs revealed the activity of the MLX via COX-2 independent mechanism and demonstrated that the relationship between COX-2 expression and antitumor activity of inhibitors is limited. In conclusion, the overall observations and results of this study strengthen the hypothesized development of NCS as a next-generation therapeutics regimen for cancer therapy.

Design and Development of Novel 2-(Morpholinyl)-N-substituted Phenylquinazolin-4-amines as Selective COX-II Inhibitor.

BACKGROUND: A novel series of 2-(Morpholin-4-yl)-N-phenylquinazolin-4- amine derivatives were synthesized and confirmed with spectral and elemental techniques. METHODS: The compounds were tested for analgesic and anti-inflammatory activity by various pain models in rodents whereas the selectivity towards COX-2 receptor is determined by in vitro assay. RESULTS: Screening results of compounds exhibited comparable biological activity with that of standard compound Indomethacin used for study. Compound 5d was found to be significantly potent with respect to its anti-inflammatory and analgesic activity with substantial COX-II selectivity. CONCLUSION: In silico analysis by molecular docking and 3D-QSAR studies justifies activity profile of compound 5d, suggesting that it may have potential for further evaluation and development as lead molecule for therapy in pain management.

Development of self-assembled nanocarriers to enhance antitumor efficacy of docetaxel trihydrate in MDA-MB-231 cell line.

Self-assembled nanocarriers (SANs) as a novel colloidal controlled delivery for docetaxel trihydrate (DTX) were engineered by high-pressure homogenization method to overcome the several clinical problems. Drug-excipient compatibility was studied using DSC and FTIR spectroscopy. The fabricated SANs was characterized by particle size, zeta potential, and SEM. QbD based central composite design of experiment was employed for formula optimization. The cell viability of DTX-hydroalcoholic solution (DTX-HA) and DTX-loaded SANs has been determined in MDA-MB-231 cell line by MTT assay. The stability study of selected SANs formulations were carried out at various storage conditions as per ICH guidelines. The summary of results obtained shows high drug content with higher entrapment efficiency (91.23 ±â€¯3.41% w/w) of DTX-loaded SANs. It shows diffusion controlled release of DTX over the period of 12 h which is higher than DTX-HA solution, releases the DTX within 4 h. The MTT assay expressed lower cellular viability and improved cell inhibition leads to increase cytotoxicity of formulations towards cells. The stability study reveals stability of DTX-loaded SANs formulations at various storage conditions over a period of three months. The strong experimental evidence confirms the SANs as an effective approach to formulate the controlled delivery system of antineoplastics with improved stability.

Design, synthesis and anticancer studies of novel aminobenzazolyl pyrimidines as tyrosine kinase inhibitors.

Abnormal signalling from the Protein tyrosine kinases (PTKs) like receptor tyrosine kinases and intracellular tyrosine kinases can lead to diseases such as cancer especially non-small cell lung cancer, chronic myeloid leukaemia and gastrointestinal stromal tumours. Various Protein tyrosine kinase inhibitors are available but face poor bioavailability, severe toxicities and recent cases of drug-resistant cancers prompts for development of better drug molecules. In this study we report the design and development of a novel Protein Tyrosine Kinase (PTK) inhibitor on the basis of pharmacophore modelling. Compound 2-(benzo[d]oxazol-2-ylamino)-N-(2-chloro-4-fluorophenyl)-4-methyl-6-(3-nitrophenyl) pyrimidine-5-carboxamide 31 was obtained containing essential pharmacophore structural features. This compound exhibited highest activity against leukaemia cell line (RPMI-8226) at 0.7244 µM, renal cancer cell line (A498) at 0.8511 µM and prostate cancer cell line (PC-3) at 0.7932 µM on the NCI five dose assay test. The PTK assay provides promising activity at IC50 of 0.07 µM in the human breast cancer cell line MDA-MB-468. Compound 31 had good intermolecular interaction with PTK in the molecular docking studies, this ligand-enzyme complex was found to stable in the MM-PBSA study over 100 ns. It had 54.22% oral bioavailability with Tmax of 0.60 h which is higher compared to the dasatinib with bioavailability and Tmax of 14-34% and 1-1.42 h respectively. Anticancer action of 31 was found to be impressive in pharmacokinetic studies making it a potential lead molecule.

Nanostructured Cubosomes in a Thermoresponsive Depot System: An Alternative Approach for the Controlled Delivery of Docetaxel.

The aim of the present study was to develop and evaluate a thermoresponsive depot system comprising of docetaxel-loaded cubosomes. The cubosomes were dispersed within a thermoreversible gelling system for controlled drug delivery. The cubosome dispersion was prepared by dilution method, followed by homogenization using glyceryl monooleate, ethanol and Pluronic® F127 in distilled water. The cubosome dispersion was then incorporated into a gelling system prepared with Pluronic® F127 and Pluronic® F68 in various ratios to formulate a thermoresponsive depot system. The thermoresponsive depot formulations undergo a thermoreversible gelation process i.e., they exists as free flowing liquids at room temperature, and transforms into gels at higher temperatures e.g., body temperature, to form a stable depot in aqueous environment. The mean particle size of the cubosomes in the dispersion prepared with Pluronic® F127, with and without the drug was found to be 170 and 280 nm, respectively. The prepared thermoresponsive depot system was evaluated by assessing various parameters like time for gelation, injectability, gel erosion, and in-vitro drug release. The drug-release studies of the cubosome dispersion before incorporation into the gelling system revealed that a majority (∼97%) of the drug was released within 12 h. This formulation also showed a short lag time (∼3 min). However, when incorporated into a thermoresponsive depot system, the formulation exhibited an initial burst release of ∼21%, and released only ∼39% drug over a period of 12 h, thus indicating its potential as a controlled drug delivery system.

Design, synthesis and pharmacological evaluation of pyrimidobenzothiazole-3-carboxylate derivatives as selective L-type calcium channel blockers.

L-type voltage gated calcium channels play essential role in contraction of various skeletal and vascular smooth muscles, thereby plays important role in regulating blood pressure. Dihydropyridine receptors have been targeted for development of newer antihypertensive agents, one of the structurally analogs nucleus dihydropyrimidines have been reported earlier by us as a potential agent toward development of calcium channel modulator. A pre-synthetic QSAR was run and on the basis of structure activity relationship a series of twenty three molecules was synthesized and studied by myosin light chain kinase assay (MLCK), Angiotensin Converting Enzyme (ACE) colorimetric assay, non-invasive blood pressure (NIBP) and invasive blood pressure (IBP) methods. Molecules with significant efficacy were studied for their single crystal X-ray diffraction, molecular docking, molecular dynamics and post-synthetic QSAR. The NIBP and IBP methods screened molecules with better percentage inhibition versus time compared to standard drug Nifedipine. The lead compound ethyl 2-methyl-4-(3-nitrophenyl)-4H-pyrimido [2,1-b] [1,3] benzothiazole-3-carboxylate (26) presented a triclinic structure with polymeric chain packing in lattice. 26 exhibited IC50 on MLCK assay of 2.1±1.7 µM with selectivity of L-type calcium channels and comparative to Nifedipine. It offered satisfactory physicochemical properties with partition coefficient of (ClogP) 4.64. Its pharmacokinetic profile is also good with Cmax at 0.40 µg/ml by oral route with Tmax reaching in 0.5 h which means in 30 min. 26 also exhibits superior t1/2 of 5.4 h and oral bioavailability of (F) 56.75% with an AUC0-∞ of 0.84 µg h/ml. Molecular docking studies indicates toward the interaction of lead compound via hydrogen bonds with Lys144, Glu181 and Asp183, it forms the Van der Walls interactions with Ser18, Asp20, Asn187, Pro185, Glu180, Glu181 and Arg10 with Glide score and Glide energy to be -3.602 and -47.098, respectively. Post-synthetic QSAR of newly synthesized molecules indicates toward improvement with respect to steric descriptor which contributed negatively in former series.

Development of selective DprE1 inhibitors: Design, synthesis, crystal structure and antitubercular activity of benzothiazolylpyrimidine-5-carboxamides.

Decaprenylphosphoryl-b-D-ribose 20-epimerase (DprE1) is a potential drug target for development of antitubercular agents. Structure based drug discovery approach yielded twenty novel derivatives of benzothiazolylpyrimidine-5-carboxamides (7a-t) which were synthesised by three component one pot reaction involving benzothiazolyl oxobutanamide, thiourea and substituted aromatic benzaldehydes. These derivatives were evaluated for antitubercular activity to determine MIC and compound 7a, 7e, 7f and 7o were found to be potentially active against Mycobacterium tuberculosis (H37Rv). Log P of these compounds was found to be between 2.0 and 3.0 making them suitable for oral dosing. DprE1 selectivity and pharmacokinetic studies were carried out for these compounds of which 7a and 7o were found to be highly selective and bioavailability was found to be above 52% by oral dose. Crystal structure of 7a was studied and molecular packing was determined, it exhibited a triclinic crystal lattice arrangement having hydrogen bonded dimeric arrangement. Drug receptor interactions were studied which exhibited docking in the active site of receptor with hydrogen bonding, hydrophobic interactions, vdW interactions with amino acid residues such as Cys387, Asn385, Lys418, Tyr314, Gln334 and Lys367 respectively. 3D QSAR analysis was carried out by kNN-MFA method to determine and develop theoretical model, best suitable model was found to be based on Simulated Annealing k-Neariest Neighbour Molecular Field Analysis (SA kNN-MFA). The model provided with hydrophobic descriptors in positive side indicating the need of bulky groups, steric and electronegative descriptors in negative coordinates hints with contribution by the electronegative substitutions as favourable and desirable moieties for enhancing the activity. The q(2), q(2)_se and Pred_r(2)se were found to be 0.5000, 0.6404 and 1.0094 respectively. A pharmacophore model was generated which suggested for necessity of aromatic, aliphatic carbon centre and hydrogen bond donor for development of newer DprE1 selective inhibitors.

Chandipura Virus: an emerging tropical pathogen.

Chandipura Virus (CHPV), a member of Rhabdoviridae, is responsible for an explosive outbreak in rural areas of India. It affects mostly children and is characterized by influenza-like illness and neurologic dysfunctions. It is transmitted by vectors such as mosquitoes, ticks and sand flies. An effective real-time one step reverse-transcriptase PCR assay method is adopted for diagnosis of this virus. CHPV has a negative sense RNA genome encoding five different proteins (N, P, M, G, and L). P protein plays a vital role in the virus's life cycle, while M protein is lethal in nature. There is no specific treatment available to date, symptomatic treatment involves use of mannitol to reduce brain edema. A Vero cell based vaccine candidate against CHPV was evaluated efficiently as a preventive agent against it. Prevention is the best method to suppress CHPV infection. Containment of disease transmitting vectors, maintaining good nutrition, health, hygiene and awareness in rural areas will help in curbing the menace of CHPV. Thus, to control virus transmission some immense preventive measures need to be attempted until a good anti-CHPV agent is developed.

Comparison of UV spectrophotometry and high performance liquid chromatography methods for the determination of repaglinide in tablets.

BACKGROUND: Repaglinide is a miglitinide class of antidiabetic drug used for the treatment of type 2 diabetes mellitus. A fast and reliable method for the determination of repaglinide was highly desirable to support formulation screening and quality control. OBJECTIVE: UV spectrophotometric and reversed-phase high performance liquid chromatography (RP-HPLC) methods were developed for determination of repaglinide in the tablet dosage form. MATERIALS AND METHODS: The UV spectrum recorded between 200 400 nm using methanol as solvent and the wavelength 241 nm was selected for the determination of repaglinide. RP-HPLC analysis was carried out using Agilent TC-C18 (2) column and mobile phase composed of methanol and water (80:20 v/v, pH adjusted to 3.5 with orthophosphoric acid) at a flow rate of 1.0 ml/min. Parameters such as linearity, precision, accuracy, recovery, specificity and ruggedness are studied as reported in the International Conference on Harmonization (ICH) guidelines. RESULTS: The developed methods illustrated excellent linearity (r(2) > 0.999) in the concentration range of 5-30 µg/ml and 5-50 µg/ml for UV spectrophotometric and HPLC methods, respectively. Precision (%R.S.D < 1.50) and mean recoveries were found in the range of 99.63-100.45% for UV spectrophotometric method and 99.71-100.25% for HPLC method which shows accuracy of the methods. CONCLUSION: The developed methods were found to be reliable, simple, fast, accurate and successfully used for the quality control of repaglinide as a bulk drug and in pharmaceutical formulations.

Smallest organism; highest threat.

Ever since the discovery of virus in beginning of 20th century, infections caused by these organisms have captured attention of researchers. The evolution of viruses is still a controversy, even same for their categorization in either living or non-living. It is clear that besides many controversies virus remains challenging to treat as well as to control in some extent. Though vaccines are available as prophylactic tool and antiviral drugs for treatment, still virus exist in host cells if they successfully invade biological machinery. Now it remains as challenge to treat these smallest organisms with high degree of efficacy and safety. To answer the demand of the present world there is urgent need of more potent and novel drugs for treatment and vaccines to prevent infection. Answer to this problem will definitely reduce casualties occurring worldwide. This review presents few of the pandemics, their causative agents, current status of treatment and future prospective.

Isolation of phytosterols and antihyperlipidemic activity of Lagenaria siceraria.

Lagenaria siceraria (Molina) Standl in the Cucurbitaceae family is a large, pubescent, climbing, or trailing herb cultivated throughout India and the tropical regions of the world. Phytochemical investigation of the methanol extract obtained from the fruits of the plant L. siceraria showed a positive Liebermann-Burchard test for sterols. The white sterol crystals or phytosterols from the methanol extract were isolated for the first time and identified as a mixture of four sterols, including fucosterol (1), racemosol (2), stigmasterol (3), and stigmasta-7,22-dien-3ß,4ß-diol (4). These compounds were identified by spectroscopic evidence including FTIR, (1)H-NMR, MS, and GC. The white sterol crystals, which are the mixture of four sterols, were evaluated for antihyperlipidemic activity in Wistar rats. The blood samples were collected from the retro-orbital plexus and serum was separated and analyzed for lipid profiles. These sterol crystals (30 mg/kg) showed significant reductions in lipid profiles which included cholesterol, triglycerides, LDL and VLDL. In addition, a significant increase in HDL cholesterol observed, which is a good cholesterol that protects hearts from coronary artery diseases. These sterol crystals or phytosterols can be used as an antihyperlipidemic agent to treat the hyperlipidemic.