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.

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.

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.

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.

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.

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.

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.

Momordica cochinchinensis seed extracts suppress migration and invasion of human breast cancer ZR-75-30 cells via down-regulating MMP-2 and MMP-9.

OBJECTIVE: Metastases and invasion are the main reasons for oncotherapy failure. Momordica cochinchinensis (Mu Bie Zi in Chinese) had been used for a variety of purposes, and shown anti-cancer action. In this article, we focused on effects on regulation of breast cancer cell ZR-75-30 metastases and invasion by extracts of Momordica cochinchinensis seeds (ESMCs). METHODS: Effect of ESMCs on ZR-75-30 human breast cancer cells proliferation were evaluated by MTT assay and on invasion and migration by wound-healing and matrigel invasion chamber assays. Expression and protease activity of two matrix metalloproteinases (MMPs), MMP-2 and MMP-9, were analyzed by Western blotting and gelatin zymography, respectively. RESULTS: ESMC revealed strong growth inhibitory effects on ZR-75-30 cells, and effectively inhibited ZR-75-30 cell invasion in a dose-dependent manner. Western blot and gelatin zymography analysis showed that ESMC significantly inhibited the expression and secretion of MMP-2 and MMP-9 in ZR-75-30 cells. CONCLUSIONS: ESMC has the potential to suppress the migration and invasion of ZR-75-30 cancer cells, and it might prove to of interest in the development of novel inhibitors for breast cancer.