Momordica balsamina improves glucose handling in a diet-induced prediabetic rat model.

Prolonged exposure to high energy diets has been implicated in the development of pre-diabetes, a long-lasting condition that precedes type 2 diabetes mellitus (T2DM). A combination of pharmacological treatment and dietary interventions are recommended to prevent the progression of pre-diabetes to T2DM. However, poor patient compliance leads to negligence of the dietary intervention and thus reduced drug efficiency. Momordica balsamina (MB) has been reported to possess anti-diabetic effects in type 1 diabetic rats. However, the effects of this medicinal plant in conjunction with dietary intervention on pre-diabetes have not yet been established. Consequently, this study sought to evaluate the effects of MB on glucose homeostasis in a diet-induced pre-diabetes rat model in the presence and absence of dietary intervention. Pre-diabetes was induced on male Sprague Dawley rats by a high fat high carbohydrate (HFHC) diet for a period of 20 weeks. Pre-diabetic male Sprague Dawley rats were treated with MB (250 mg/kg p.o.) in both the presence and absence of dietary intervention once a day every third day for a period of 12 weeks. The administration of MB with and without dietary intervention resulted in significantly improved glucose homeostasis through reduced caloric intake, body weights, with reduced plasma ghrelin concentration and glycated hemoglobin by comparison to the pre-diabetic control. MB administration also improved insulin sensitivity as evidenced by the expression of glucose transporter 4 (GLUT 4) and glycogen synthase on the prediabetic treated animals. These results suggest that MB has the potential to be used to manage pre-diabetes and prevent the progression to overt type 2 diabetes as it demonstrated the ability to restore glucose homeostasis even in the absence of dietary and lifestyle intervention.

Anti-human immunodeficiency virus-1 activity of MoMo30 protein isolated from the traditional African medicinal plant Momordica balsamina.

BACKGROUND: Plants are used in traditional healing practices of many cultures worldwide. Momordica balsamina is a plant commonly used by traditional African healers as a part of a treatment for HIV/AIDS. It is typically given as a tea to patients with HIV/AIDS. Water-soluble extracts of this plant were found to contain anti-HIV activity. METHODS: We employed cell-based infectivity assays, surface plasmon resonance, and a molecular-cell model of the gp120-CD4 interaction to study the mechanism of action of the MoMo30-plant protein. Using Edman degradation results of the 15 N-terminal amino acids, we determined the gene sequence of the MoMo30-plant protein from an RNAseq library from total RNA extracted from Momordica balsamina. RESULTS: Here, we identify the active ingredient of water extracts of the leaves of Momordica balsamina as a 30 kDa protein we call MoMo30-plant. We have identified the gene for MoMo30 and found it is homologous to a group of plant lectins known as Hevamine A-like proteins. MoMo30-plant is distinct from other proteins previously reported agents from the Momordica species, such as ribosome-inactivating proteins such as MAP30 and Balsamin. MoMo30-plant binds to gp120 through its glycan groups and functions as a lectin or carbohydrate-binding agent (CBA). It inhibits HIV-1 at nanomolar levels and has minimal cellular toxicity at inhibitory levels. CONCLUSIONS: CBAs like MoMo30 can bind to glycans on the surface of the enveloped glycoprotein of HIV (gp120) and block entry. Exposure to CBAs has two effects on the virus. First, it blocks infection of susceptible cells. Secondly, MoMo30 drives the selection of viruses with altered glycosylation patterns, potentially altering their immunogenicity. Such an agent could represent a change in the treatment strategy for HIV/AIDS that allows a rapid reduction in viral loads while selecting for an underglycosylated virus, potentially facilitating the host immune response.

MAP30 and luffin-α: Novel ribosome-inactivating proteins induce plant systemic resistance against plant viruses.

Ribosome-inactivating proteins (RIPs) are toxic N-glycosylase that act on eukaryotic and prokaryotic rRNAs, resulting in arrest protein synthesis. RIPs are widely found in higher plant species and display strong antiviral activity. Previous studies have shown that PAP and α-MMC have antiviral activity against TMV. However, the localization of RIPs in plant cells and the mechanism by which RIPs activate plant defense against several plant viruses remain unclear. In this study, we obtained four RIPs (the C-terminal deletion mutant of pokeweed antiviral proteins (PAP-c), alpha-momorcharin (α-MMC), momordica anti-HIV protein of 30 kDa (MAP30) and luffin-α). The subcellular localization results indicated that these four RIPs were located on the plant cell membrane. Heterologous expression of RIPs (PAP-c, α-MMC, MAP30, luffin-α) enhanced tobacco mosaic virus (TMV) resistance in N. benthamiana. Compared with the control treatment, these RIPs significantly reduced the TMV content (149-357 fold) and altered the movement of TMV in the leaves of N. benthamiana. At the same time, heterologous expression of RIPs (MAP30 and luffin-α) could relieve TMV-induced oxidative damage, significantly inducing the expression of plant defense genes including PR1 and PR2. Furthermore, application of these RIPs could inhibit the infection of turnip mosaic virus (TuMV) and potato virus x (PVX). Therefore, this study demonstrated that MAP30 and luffin-α could be considered as new, effective RIPs for controlling plant viruses by activating plant systemic defense.

Cucumis melo var. momordica as a Potent Antidiabetic, Antioxidant and Possible Anticovid Alternative: Investigation through Experimental and Computational Methods.

Diabetes mellitus is a typical life threatening of disease, which generate due to the dysfunction of ß cells of pancreas. In 2014, WHO stated that 422 million people were infected with DM. The current pattern of management of diabetes included synthetic or plant based oral hypoglycemic drugs and insulin but drug resentence is become a very big issues in antidiabetic therapy. Thus, it's very earnest to discover now medication for this disease. Now the days, it is well acknowledged that diabetic patients are more prone towards covid and related complications. Thus, medical practitioners reformed the methodology of prescribing medication for covid infected antidiabetic therapy and encouraging the medication contains dual pharmacological properties. It is also well know that polyphenols specifically hold a significant role in oxidative stress and reduced the severity of many inflammatory diseases. Cucumis melo has rich history as ethano-pharmacological use in Indian subcontinent. The fruit and seed are well-known for the treatment of various diseases due to the presence of phenolics. Therefore, in this study, the combined mixture of flower and seeds were used for the extraction of polyphenolic rich extract and tested for antidiabetic activity through the antioxidant and in vivo experiments. The antioxidant potential measurement exhibited that the selected plant extract has the significant competence to down-regulate oxidative stress (DPPH scavenging IC50 at 60.7±1.05 µg/mL, ABTS IC50 at 62.15±0.50 µg/mL). Furthermore, the major polyphenolic phyto-compounds derived from the Cucumis melo were used for in silico anticovid activity, docking, and complementarity studies. The anticovid activity prognosis reflected that selected phyto-compounds amentoflavone and vanillic acid have optimal possibility to interact with 3C-like protease and through this moderate anticovid activity can be exhibit. The docking experiments established that the selected compounds have propensity to interact with protein tyrosine phosphatase 1B, 11ß-Hydroxysteroid dehydrogenase, superoxide dismutase, glutathione peroxidase, and catalase ß-glucuronidase receptor. In vivo experiments showed that 500 mg/kg, Cucumis melo extract ominously amplified body weight, plasma insulin, high-density lipoprotein levels, and biochemical markers. Furthermore, extract significantly downregulate the blood glucose, total cholesterol, triglycerides, low-density lipoprotein, and very low-density lipoprotein.

Predictive medicinal metabolites from Momordica dioica against comorbidity related proteins of SARS-CoV-2 infections.

Momordica dioica have proven medicinal potential of antidiabetic, antiviral and immune stimulating properties. Flavonoids and triterpenoids from M. dioica were more extensively investigated for antiviral, antidiabetic and immunomodulatory activities. In this present study, we have predicted the reported bioactive flavonoids and triterpenoids of the plant against the SARS-CoV-2 main protease, RNA-dependent RNA polymerase (RdRp), spike protein, angiotensin converting enzyme (ACE-2) receptor and dipeptidyl peptidase (DPP4) receptor through molecular docking and in silico ADME predictions methods. According to the binding affinities, the two triterpenoids, hederagenin and oleanolic acid exhibited the best docking scores with these proteins than the catechin and quercetin with compared to standard remdesivir, favipiravir and hydroxychloroquine. The in vitro protein-drug studies have also showed significant interaction of catechin and quercetin compounds than standard drugs. The in silico binding studies correlated with the in silico binding studies. Further, M. dioica being used as antidiabetic and its metabolite had significant interaction with DDP4, a comorbidity protein involved in aiding the viral entry. Out of all the natural ligands, quercetin was reported relatively good and safe for humans with high gastrointestinal tract permeability and poor blood brain barrier crossing abilities. Hence, M. dioica phytocompounds reflects promising therapeutic properties against SARS-CoV-2 infections under comorbid conditions such as diabetes, cardiovascular disease and kidney disorders.Communicated by Ramaswamy H. Sarma.

Anticancer Activity and Molecular Mechanism of Momordica cochinchinensis Seed Extract in Chronic Myeloid Leukemia Cells.

Targeting Bcr-Abl is the key to the treatment of chronic myeloid leukemia. Despite great progress in the treatment of patients with chronic CML, advanced CML patients are still unable to obtain effective and safe drugs. Momordica cochinchinensis seed is the dried ripe seed of Momordica cochinchinensis, which is a kind of fruit and consumed for dietary as well as medicinal uses. This study aimed to investigate the anticancer activity of Momordica cochinchinensis seed extract (MCSE) in CML cells. CML cells (KBM5 and KBM5-T315I) were treated with MCSE and analyzed for growth, apoptosis, and signal transduction. Nude mouse xenograft model was used to evaluate the antitumor activity of MCSE In Vivo. MCSE significantly reduced the cell viability of CML cells, triggered G0/G1 phase arrest in KBM5 cells and S phase arrest in KBM5-T315I cells. Concurrently, MCSE caused the activation of caspase-3, -8, -9, PARP and the degradation of Mcl-1, ultimately triggering endogenous and exogenous cell apoptosis. Meanwhile, MCSE downregulated Bcr-Abl levels and its downstream signaling pathways. Additionally, MCSE inhibited the growth of CML cells in nude mouse xenografts. Taken together, this study demonstrated the anticancer mechanism of MCSE, namely blocking Bcr-Abl and downregulating Mcl-1, and finally induced apoptosis of CML cells.

The legumain McPAL1 from Momordica cochinchinensis is a highly stable Asx-specific splicing enzyme.

Legumains, also known as asparaginyl endopeptidases (AEPs), cleave peptide bonds after Asn/Asp (Asx) residues. In plants, certain legumains also have ligase activity that catalyzes biosynthesis of Asx-containing cyclic peptides. An example is the biosynthesis of MCoTI-I/II, a squash family-derived cyclic trypsin inhibitor, which involves splicing to remove the N-terminal prodomain and then N-to-C-terminal cyclization of the mature domain. To identify plant legumains responsible for the maturation of these cyclic peptides, we have isolated and characterized a legumain involved in splicing, McPAL1, from Momordica cochinchinensis (Cucurbitaceae) seeds. Functional studies show that recombinantly expressed McPAL1 displays a pH-dependent, trimodal enzymatic profile. At pH 4 to 6, McPAL1 selectively catalyzed Asp-ligation and Asn-cleavage, but at pH 6.5 to 8, Asn-ligation predominated. With peptide substrates containing N-terminal Asn and C-terminal Asp, such as is found in precursors of MCoTI-I/II, McPAL1 mediates proteolysis at the Asn site and then ligation at the Asp site at pH 5 to 6. Also, McPAL1 is an unusually stable legumain that is tolerant of heat and high pH. Together, our results support that McPAL1 is a splicing legumain at acidic pH that can mediate biosynthesis of MCoTI-I/II. We purport that the high thermal and pH stability of McPAL1 could have applications for protein engineering.

Quality attributes of convective hot air dried spine gourd (Momordica dioica Roxb. Ex Willd) slices.

In the present study, spine gourd slices were dried in a convective dryer at 40, 50, 60 and 70 °C temperature. The change in quality of spine guard was determined by analyzing the change in proximate, minerals, functional group, chlorophyll, ascorbic acid, and antioxidant characteristics. Increase in drying temperature changed the protein (4.62-12.88 g/100 g), fiber (3.14-3.53 g/100 g), total phenolic (14.85-14.99 mg gallic acid equivalent/g) and total flavonoid (30.1-64.8 mg quercetin equivalent/100 g) content while reduction occurred in fat (4.02-3.07 g/100 g), carbohydrate (76.13-55.22 g/100 g), chlorophyll (0.34-0.100 mg/g), ascorbic acid (29.94-4.50 mg/100 g) and antioxidant activity (96.58-85.06%). Mineral content of fresh SG differed significantly with dried samples (p < 0.05), while variable effects were associated with the change in drying temperatures. Changes in functional groups were analyzed by Fourier transform infrared spectrophotometer. The observed parameters were optimized using principal component analysis. The sample dried at 40 °C was superior in quality whereas higher protein and antioxidants were found at 70 °C.

Antistress and anti-aging activities of Caenorhabditis elegans were enhanced by Momordica saponin extract.

BACKGROUND: Momordica saponin extract (MSE) was found to not only improve longevity and neuroprotection but also alleviate fat accumulation in Caenorhabditis elegans in our previous study. However, the lipid-lowering activity of MSE alone could not fully explain its ability to improve health, so the antistress effects of MSE were further studied. METHODS: Using C. elegans as an in vivo animal, the lifespan of MSE-treated C. elegans under various stressors (H2O2, paraquat and heat) and normal conditions was studied. Furthermore, the antioxidant activities of MSE were discussed. To study the underlying mechanisms, the expression of stress resistance genes and the resistance of related mutants to H2O2 stress were tested. RESULTS: MSE significantly improved the lifespan of C. elegans under stress and normal conditions. Meanwhile, the mobility of C. elegans was also improved. Moreover, the activities of SOD and CAT and the ratio of GSH/GSSG were elevated. Consistently, the levels of ROS and lipid oxidation (the NEFA and MDA content) were reduced. Furthermore, MSE treatment upregulated the expression of the sod-3, sod-5, clt-1, clt-2, hsp-16.1 and hsp-16.2 genes. All biomarkers indicated that the antistress and anti-aging activities of MSE were due to its strong antioxidant activities. Finally, MSE induced nuclear DAF-16::GFP localization. Studies with mutants revealed that skn-1 and hsf-1 were involved in the activity of MSE, which might upregulate the expression of downstream stress-responsive genes. CONCLUSIONS: Therefore, in addition to its lipid-lowering property, the ability of MSE to improve healthspan was also attributed to the stress resistance effect. Together, MSE might serve as a lead nutraceutical in geriatric research.

Induction of extrinsic and intrinsic apoptosis in cervical cancer cells by Momordica dioica mediated gold nanoparticles.

Bio-fabrication of gold nanoparticles (AuNPs) has several advantages like biocompatibility, less toxicity, and eco-friendly in nature over their chemical and physical methods. Currently, the authors fabricated AuNPs using aqueous root extract of Momordica dioica (M. dioica) and explored their anticancer application with mechanistic approaches. Different biophysical techniques such as UV-visible spectroscopy, Fourier transform infrared, X-ray diffraction, transmission electron microscopy, selected area electron diffraction, and dynamic light scattering were employed for AuNPs characterisation. The synthesised AuNPs were mono-dispersed, crystalline in nature, anionic surface (-23.9 mV), and spherical particle of an average diameter of 9.4 nm. In addition, the AuNPs were stable in buffers solutions and also biocompatible towards normal human cells (human vascular endothelial cells and human lung cells). The AuNPs were exhibited anticancer activity against different cancer cell lines such as human breast cancer cells, human cervical cancer cells (HeLa) and human lung cancer cells. Further, the pro-apoptotic genes such as Bcl2 were down-regulated and BAX, Caspase-3, -8, and -9 were up-regulated in HeLa cells as compared to untreated cells. Annexin-V-FITC assay results showed that the AuNPs were induced apoptosis by accumulation of intracellular reactive oxygen species. To their knowledge, this is the first report on the synthesis of bioactive metal nanoparticles from M. dioica and it may open up new avenues in therapeutic applications.

Behind the Myth of the Fruit of Heaven, a Critical Review on Gac (Momordica cochinchinensis Spreng.) Contribution to Nutrition.

Gac, Momordica cochinchinensis (Lour.) Spreng. belongs to the Cucurbitaceae family. It is more considered as a super fruit. The demand for this plant is growing in countries where its reputation is high, including traditional countries of gac culture and countries fond of super fruits and food supplements. In these latter countries, the industrial strategy aims at producing high added value in food supplements or nutritional rich preparations. However, when marketing is not the driving force and claims have to be related to scientific data, the situation of gac is less "heavenly", mainly because its most remarkable properties are in the field of micronutrients. These latter components are indeed very important for health but their supplementation on healthy populations brings no significant advantage. This paper proposes to review aspects important for the nutritional reputation of this plant: where it comes from, how it is cultured to have an optimal nutritional composition, what is its composition and how it can impact health of consumers, in which products it is used and what are the regulations to use it in different markets. One important goal of this review is to give a critical and scientific approach to confirm data on this fruit, which has been promoted by marketing departments injecting so many wrong and unverified information. Missing data will be highlighted and potential positive applications are proposed all along the text.

Binding and structural studies of the complexes of type 1 ribosome inactivating protein from Momordica balsamina with uracil and uridine.

Ribosome inactivating protein (RIP) catalyzes the cleavage of glycosidic bond formed between adenine and ribose sugar of ribosomal RNA to inactivate ribosomes. Previous structural studies have shown that RNA bases, adenine, guanine, and cytosine tend to bind to RIP in the substrate binding site. However, the mode of binding of uracil with RIP was not yet known. Here, we report crystal structures of two complexes of type 1 RIP from Momordica balsamina (MbRIP1) with base, uracil and nucleoside, uridine. The binding studies of MbRIP1 with uracil and uridine as estimated using fluorescence spectroscopy showed that the equilibrium dissociation constants (KD ) were 1.2 × 10-6 M and 1.4 × 10-7 M respectively. The corresponding values obtained using surface plasmon resonance (SPR) were found to be 1.4 × 10-6 M and 1.1 × 10-7 M, respectively. Structures of the complexes of MbRIP1 with uracil (Structure-1) and uridine (Structure-2) were determined at 1.70 and 1.98 Å resolutions respectively. Structure-1 showed that uracil bound to MbRIP1 at the substrate binding site but its mode of binding was significantly different from those of adenine, guanine and cytosine. However, the mode of binding of uridine was found to be similar to those of cytidine. As a result of binding of uracil to MbRIP1 at the substrate binding site, three water molecules were expelled while eight water molecules were expelled when uridine bound to MbRIP1.

Application of Raman spectroscopy in type 2 diabetes screening in blood using leucine and isoleucine amino-acids as biomarkers and in comparative anti-diabetic drugs efficacy studies.

Diabetes is an irreversible condition characterized by elevated blood glucose levels. Currently, there are no predictive biomarkers for this disease and the existing ones such as hemoglobin A1c and fasting blood glucose are used only when diabetes symptoms are noticed. The objective of this work was first to explore the potential of leucine and isoleucine amino acids as diabetes type 2 biomarkers using their Raman spectroscopic signatures. Secondly, we wanted to explore whether Raman spectroscopy can be applied in comparative efficacy studies between commercially available anti-diabetic drug pioglitazone and the locally used anti-diabetic herbal extract Momordica spinosa (Gilg.)Chiov. Sprague Dawley (SD) rat's blood was used and were pipetted onto Raman substrates prepared from conductive silver paste smeared glass slides. Prominent Raman bands associated with glucose (926, 1302, 1125 cm-1), leucine (1106, 1248, 1302, 1395 cm-1) and isolecucine (1108, 1248, 1437 and 1585 cm-1) were observed. The Raman bands centered at 1125 cm-1, 1395 cm-1 and 1437 cm-1 associated respectively to glucose, leucine and isoleucine were chosen as biomarker Raman peaks for diabetes type 2. These Raman bands displayed decreased intensities in blood from diabetic SD rats administered antidiabetic drugs pioglitazone and herbal extract Momordica spinosa (Gilg.)Chiov. The intensity decrease indicated reduced concentration levels of the respective biomarker molecules: glucose (1125 cm-1), leucine (1395 cm-1) and isoleucine (1437 cm-1) in blood. The results displayed the power and potential of Raman spectroscopy in rapid (10 seconds) diabetes and pre-diabetes screening in blood (human or rat's) with not only glucose acting as a biomarker but also leucine and isoleucine amino-acids where intensities of respectively assigned bands act as references. It also showed that using Raman spectroscopic signatures of the chosen biomarkers, the method can be an alternative for performing comparative efficacy studies between known and new anti-diabetic drugs. Reports on use of Raman spectroscopy in type 2 diabetes mellitus screening with Raman bands associated with leucine and isoleucine molecules acting as reference is rare in literature. The use of Raman spectroscopy in pre-diabetes screening of blood for changes in levels of leucine and isoleucine amino acids is particularly interesting as once elevated levels are noticed, necessary interventions to prevent diabetes development can be initiated.

Carotenoids from gac fruit aril (Momordica cochinchinensis [Lour.] Spreng.) are more bioaccessible than those from carrot root and tomato fruit.

Using a simulated digestion procedure in vitro, liberation and bioaccessibility of ß-carotene (29.5±1.7% and 22.6±0.9%, respectively) and lycopene (51.3±2.6% and 33.2±3.1%, respectively) from gac fruit aril were found to be significantly higher than from carrot root (ß-carotene, 5.2±0.5% and 0.5±0.2%, respectively) and tomato fruit (lycopene, 15.9±2.8% and 1.8±0.5%, respectively). Gac fruit aril naturally contained significantly more lipids (11% on fresh weight base) than carrot root and tomato fruit (<1%). However, when test meals were supplemented with an O/W emulsion to match the content of gac fruit aril, carotenoid bioaccessibility was still considerably lower than that from genuine gac fruit aril. Carotenoids in gac fruit aril were found to be stored in small, round-shaped chromoplasts. Despite the high lipid content, these carotenoids are unlikely to occur in a lipid-dissolved state according to simple solubility estimations, instead being possibly deposited as submicroscopic crystallites. In contrast, carotenoids of carrot root and tomato fruit were stored in large, needle-like crystallous chromoplasts. Consequently, we hypothesized the natural deposition form to be majorly responsible for the observed differences in bioaccessibility. A favorable surface-to-volume ratio of the deposition form in gac fruit aril might have allowed a more rapid micellization during digestion, and thus, an enhanced bioaccessibility. Irrespective of the ultimate reason, gac fruit aril provided a highly bioaccessible form of both lycopene and provitamin A (ß-carotene), thus offering a most valuable dietary source of both carotenoids. Currently, gac is majorly grown in Southeast Asia, where its consumption might help to diminish the 'hidden hunger' namely the insufficient supply with vitamin A. Ultimately, gac fruit might thus contribute to alleviating most severe health implications of vitamin A deficiency, such as anaemia and xerophthalmia, the prevailing cause of preventable childhood blindness, as well as mortality from infectious diseases.

Isolation and partial characterization of 3 nontoxic d-galactose-specific isolectins from seeds of Momordica balsamina.

Three isolectins denoted hereforth MBaL-30, MBaL-60, and MBaL-80 were isolated from seeds extract of Momordica balsamina by 30%, 60%, and 80% ammonium sulfate saturations, respectively. The native molecular weights of these lectins, as judged by gel filtration, were 108, 56, and 160 kDa, respectively. On SDS-PAGE, under reduced condition, 27 kDa band was obtained for all isolectins. The lectins hemagglutinating activities were variably inhibited by d-galactose (minimum inhibitory concentrations = 12.5mM, 50mM, and 0.391mM, respectively). MBaL-30 and -60 could agglutinate all human blood types with slight preference for the A and O blood groups, whereas MBaL-80 did not agglutinate B and AB blood types. The 3 isolectins were purified from crude seeds extract, collectively, in a single step on the affinity matrix Lactamyl-Seralose 4B; this purified lectin fraction, which contains all isolectins, is termed MBaL. The N-terminal of MBaL till the 25th amino acid was NLSLSELDFSADTYKSFIKNLRKQL, which shares 88% sequence identity with Momordica charantia lectin type-2 ribosomal inactivating protein from Momordica charantia and 50% with momordin II from Momordica balsamina. MBaL retained 100% activity at up to 50°C for 30 minutes. MBaL-30 and MBaL-60 exhibited maximum activities in the pH range between 4 and 8, while MBaL-80 was showing maximum activity in the pH range between 3 and 5. Treatment of MBaL-30 and MBaL-60 with EDTA completely abolished their hemagglutinating activities. Addition of Zn and Fe ions to the ethylenediaminetetraacetic acid-treated MBaL-30 and MBaL-60 lectins did not only regained the loss of activity but also resulted in 200% to 300% increase in activity, respectively. MBaL-30 and -60 agglutinated gram positive Listeria monocytogenes and Staphylococcus aureus, whereas MBaL-30 could merely agglutinate Escherichia coli. None of these lectins could arrest bacterial growth. Addition of MBaL to cancer cell lines (Gastric cancer cell line (AGS) and Gastric cencer cell line (MKN45), Glioblastoma (ECV-304), and Human urinary bladder cancer cell line (U87-MG)) at varying concentrations did not cause statistically significant changes on cell growth and viability.

Neurotrophic Effects of Mu Bie Zi (Momordica cochinchinensis) Seed Elucidated by High-Throughput Screening of Natural Products for NGF Mimetic Effects in PC-12 Cells.

Post-mitotic central nervous system (CNS) neurons have limited capacity for regeneration, creating a challenge in the development of effective therapeutics for spinal cord injury or neurodegenerative diseases. Furthermore, therapeutic use of human neurotrophic agents such as nerve growth factor (NGF) are limited due to hampered transport across the blood brain barrier (BBB) and a large number of peripheral side effects (e.g. neuro-inflammatory pain/tissue degeneration etc.). Therefore, there is a continued need for discovery of small molecule NGF mimetics that can penetrate the BBB and initiate CNS neuronal outgrowth/regeneration. In the current study, we conduct an exploratory high-through-put (HTP) screening of 1144 predominantly natural/herb products (947 natural herbs/plants/spices, 29 polyphenolics and 168 synthetic drugs) for ability to induce neurite outgrowth in PC12 dopaminergic cells grown on rat tail collagen, over 7 days. The data indicate a remarkably rare event-low hit ratio with only 1/1144 tested substances (<111.25 µg/mL) being capable of inducing neurite outgrowth in a dose dependent manner, identified as; Mu Bie Zi, Momordica cochinchinensis seed extract (MCS). To quantify the neurotrophic effects of MCS, 36 images (n = 6) (average of 340 cells per image), were numerically assessed for neurite length, neurite count/cell and min/max neurite length in microns (µm) using Image J software. The data show neurite elongation from 0.07 ± 0.02 µm (controls) to 5.5 ± 0.62 µm (NGF 0.5 µg/mL) and 3.39 ± 0.45 µm (138 µg/mL) in MCS, where the average maximum length per group extended from 3.58 ± 0.42 µm (controls) to 41.93 ± 3.14 µm (NGF) and 40.20 ± 2.72 µm (MCS). Imaging analysis using immunocytochemistry (ICC) confirmed that NGF and MCS had similar influence on 3-D orientation/expression of 160/200 kD neurofilament, tubulin and F-actin. These latent changes were associated with early rise in phosphorylated extracellular signal-regulated kinase (ERK) p-Erk1 (T202/Y204)/p-Erk2 (T185/Y187) at 60 min with mild changes in pAKT peaking at 5 min, and no indication of pMEK involvement. These findings demonstrate a remarkable infrequency of natural products or polyphenolic constituents to exert neurotrophic effects at low concentrations, and elucidate a unique property of MCS extract to do so. Future research will be required to delineate in depth mechanism of action of MCS, constituents responsible and potential for therapeutic application in CNS degenerative disease or injury.

Antihyperlipidemic and biochemical activities of Mcy protein in streptozotocin induced diabetic rats.

BACKGROUND: This study was aimed to evaluate the protective effects of a novel anti-hyperglycemic "Mcy protein" isolated from the fruits of Momordica cymbalaria in streptozotocin induced- diabetes rat model. MATERIALS AND METHODS: Wild type and Streptozotocin induced diabetic male wistar albino rats were either treated with single intraperitoneal injection of 2.5 mg Mcy protein/kg body weight or acetate buffer daily for 30 days. Fasting blood glucose and, serum and tissue lipid levels were measured along with biochemical analysis for hepatic and renal function tests. RESULTS: Mcy protein significantly reduced the fasting blood glucose and, serum as well as tissue lipid levels (p<0.05), besides normalizing the levels of liver and kidney function markers in the treated diabetic rats when compared to the diabetic controls. Our studies also showed the pancreatic islet regeneration in Mcy treated rats. CONCLUSION: Mcy protein can alleviate hyperlipidemia and help manage diabetes by stimulating insulin secretion without evident toxic effects on liver and kidney.

Oxidative metabolites of lycopene and γ-carotene in gac (Momordica cochinchinensis).

Three new oxidative metabolites of lycopenes, (erythro)-lycopene-5,6-diol, (threo)-lycopene-5,6-diol, and 1,16-dehydro-2,6-cyclolycopene-5-ol B, and four new oxidative metabolites of γ-carotenes, 2',6'-cyclo-γ-carotene-1',5'-diol A, 2',6'-cyclo-γ-carotene-1',5'-diol B, (erythro)-γ-carotene-5,6-diol, and (threo)-γ-carotene-5,6-diol, were isolated as minor components from the aril of gac, Momordica cochinchinensis. These structures were determined on the basis of spectroscopic data, and some of them were compared to the structures of synthetic samples. Furthermore, the oxidative metabolic conversion pathways of lycopene and γ-carotene were discussed.

The evolution of Momordica cyclic peptides.

Cyclic proteins have evolved for millions of years across all kingdoms of life to confer structural stability over their acyclic counterparts while maintaining intrinsic functional properties. Here, we show that cyclic miniproteins (or peptides) from Momordica (Cucurbitaceae) seeds evolved in species that diverged from an African ancestor around 19 Ma. The ability to achieve head-to-tail cyclization of Momordica cyclic peptides appears to have been acquired through a series of mutations in their acyclic precursor coding sequences following recent and independent gene expansion event(s). Evolutionary analysis of Momordica cyclic peptides reveals sites that are under selection, highlighting residues that are presumably constrained for maintaining their function as potent trypsin inhibitors. Molecular dynamics of Momordica cyclic peptides in complex with trypsin reveals site-specific residues involved in target binding. In a broader context, this study provides a basis for selecting Momordica species to further investigate the biosynthesis of the cyclic peptides and for constructing libraries that may be screened against evolutionarily related serine proteases implicated in human diseases.

Dual-stage triterpenoids from an African medicinal plant targeting the malaria parasite.

Sixteen triterpenoids (1-16), previously isolated from the aerial parts of the African medicinal plant Momordica balsamina or obtained by derivatization, were evaluated for their activity against liver stages of Plasmodium berghei, measuring the luminescence intensity in Huh-7 cells infected with a firefly luciferase-expressing P. berghei line, PbGFP-Luccon. Toxicity of compounds (1-16) was assessed on the same cell line through the fluorescence measurement of cell confluency. The highest activity was displayed by a derivative bearing two acetyl residues, karavoate B (7), which led to a dose-dependent decrease in the P. berghei infection rate, exhibiting a very significant activity at the lowest concentration employed (1 µM) and no toxicity towards the Huh-7 cells. It is noteworthy that, in previous studies, this compound was found to be a strong inhibitor of blood-stages of Plasmodium falciparum, thus displaying a dual-stage antimalarial activity.