Splenic Elemental Composition of Breast Cancer-Suffering Rats Supplemented with Pomegranate Seed Oil and Bitter Melon Extract.

The aim of this study was to investigate how dietary modifications with pomegranate seed oil (PSO) and bitter melon aqueous extract (BME) affect mineral content in the spleen of rats both under normal physiological conditions and with coexisting mammary tumorigenesis. The diet of Sprague-Dawley female rats was supplemented either with PSO or with BME, or with a combination for 21 weeks. A chemical carcinogen (7,12-dimethylbenz[a]anthracene) was applied intragastrically to induce mammary tumors. In the spleen of rats, the selected elements were determined with a quadrupole mass spectrometer with inductively coupled plasma ionization (ICP-MS). ANOVA was used to evaluate differences in elemental composition among experimental groups. Multivariate statistical methods were used to discover whether some subtle dependencies exist between experimental factors and thus influence the element content. Experimental factors affected the splenic levels of macroelements, except for potassium. Both diet modification and the cancerogenic process resulted in significant changes in the content of Fe, Se, Co, Cr, Ni, Al, Sr, Pb, Cd, B, and Tl in rat spleen. Chemometric analysis revealed the greatest impact of the ongoing carcinogenic process on the mineral composition of the spleen. The obtained results may contribute to a better understanding of peripheral immune organ functioning, especially during the neoplastic process, and thus may help develop anticancer prevention and treatment strategies.

Pharmacotherapeutic Potential of Bitter Gourd (Momordica charantia) in Age-related Neurological Diseases.

Due to the growth of the elderly population, age-related neurological disorders are an increasing problem. Aging begins very gradually and later leads to several neurological issues such as lower neurotransmitter levels, oxidative stress, neuronal inflammation, and continual neuronal loss. These changes might contribute to brain disorders such as Alzheimer's disease (AD), dementia or mild cognitive impairment, and epilepsy and glioma, and can also aggravate these disorders if they were previously present. Momordica charantia (bitter gourd), a member of the Cucurbitaceae family, is a good source of carbohydrates, proteins, vitamins, and minerals. It is used for diabetes and known for its hypoglycemic and antioxidant effects. In this review, we discuss the pharmaceutical effects of M. charantia on age-related neurological disorders. We searched several databases, including PubMed and Google Scholar, using MeSH terms. We searched articles published up until 2022 regardless of publication language. M. charantia is rich in luteolin, which increases acetylcholine in neurons by binding to enzymes in acetylcholine metabolism pathways, including butyrylcholinesterase and acetylcholinesterase. This binding inhibits the hyperphosphorylation of tau protein by restraining its kinase enzyme. Furthermore, this substance can lower serum cholesterol and has multi-target activity in AD and memory loss. M. charantia can also improve memory by decreasing tau protein and it also has potent antioxidant activity and anti-inflammatory effects. This review highlights that M. charantia has effects on many age-related neurological disorders, and can be a cost-effective supplement with minimal side effects.

Polyphenolic profile and antioxidant properties of Momordica charantia L. 'Enaja' cultivar grown in Romania.

This is the first study describing phenolics of Momordica charantia L. 'Enaja' cultivar (bitter melon) produced in Romania. Total polyphenol content, total tannin content, total flavonoid content, and antioxidant activity of bitter melon stems and leaves, young fruits, and ripe fruits grown in Romania were analysed, along with fruits imported from India. The UPLC-DAD analysis led to the identification of (+)-catechin, (-)-epicatechin, luteolin-3',7-di-O-glucoside, luteolin-7-O-glucoside and vanillic acid. (-)-Epicatechin (859 µg/g) and (+)-catechin (1677 µg/g) were the most abundant compounds in stems and leaves, while in the ripe fruits, luteolin-7-O-glucoside (310 µg/g) was the main phenolic. Stems and leaves were the most active for capturing free DPPH radicals (IC50 = 216.9 ± 11.91 µg/ml); the scavenging activity strongly correlated with the flavonoid content (r = 0.8806, r2 = 0.7754). Momordica charantia fruits from Romania, both young and ripe, are a source of polyphenols as valuable as those imported from India.

Anticancer Activity of Bitter Melon-Derived Vesicles Extract against Breast Cancer.

Due to their low immunogenicity, high biocompatibility and ready availability in large quantities, plant-derived vesicles extracts have attracted considerable interest as a novel nanomaterial in tumor therapy. Bitter melon, a medicinal and edible plant, has been reported to exhibit excellent antitumor effects. It is well-documented that breast cancer gravely endangers women's health, and more effective therapeutic agents must be urgently explored. Therefore, we investigated whether bitter melon-derived vesicles extract (BMVE) has antitumor activity against breast cancer. Ultracentrifugation was used to isolate BMVE with a typical "cup-shaped" structure and an average size of approximately 147 nm from bitter melon juice. The experimental outcomes indicate that 4T1 breast cancer cells could efficiently internalize BMVE, which shows apparent anti-proliferative and migration-inhibiting effects. In addition, BMVE also possesses apoptosis-inducing effects on breast cancer cells, which were achieved by stimulating the production of reactive oxygen species (ROS) and disrupting mitochondrial function. Furthermore, BMVE could dramatically inhibit tumor growth in vivo with negligible adverse effects. In conclusion, BMVE exhibits a pronounced antitumor effect on 4T1 breast cancer cells, which has great potential for use in tumor therapy.

Accumulation of Antioxidative Phenolics and Carotenoids Using Thermal Processing in Different Stages of Momordica charantia Fruit.

The bitter taste of M. charantia fruit limits its consumption, although the health benefits are well known. The thermal drying process is considered as an alternative method to reduce the bitterness. However, processing studies have rarely investigated physiochemical changes in fruit stages. The antioxidant activities and physiochemical properties of various fruit stages were investigated using different thermal treatments. The color of the thermally treated fruit varied depending on the temperature. When heat-treated for 3 days, the samples from the 30 °C and 90 °C treatments turned brown, while the color of the 60 °C sample did not change significantly. The antioxidant activities were increased in the thermally processed samples in a temperature-dependent manner, with an increase in phenolic compounds. In the 90 °C samples, the 2,2-diphenyl-1-picrylhydrazyl radical scavenging activity presented a 6.8-fold higher level than that of nonthermal treatment in mature yellow fruit (S3), whereas the activity showed about a 3.1-fold higher level in immature green (S1) and mature green (S2) fruits. Regardless of the stages, the carotenoid content tended to decrease with increasing temperature. In terms of antioxidant activities, these results suggested that mature yellow fruit is better for consumption using thermal processing.

Interaction of sugar stabilised silver nanoparticles with Momordica charantia seed lectin, a type II ribosome inactivating protein.

Sugar-stabilised nanomaterials have received a lot of attention in cancer therapy in recent years due to their pronounced application as specific targeting agents and maximizing their therapeutic potential while bypassing off-target effects. Lectins, the carbohydrate-binding proteins, are capable of binding to receptors present on the target cell/tissue and interact with transformed glycans better than normal cells. Besides some of the lectins exhibit anticancer activity. Conjugating sugar-stabilised NPs with lectins there for is expected to multiply the potential for the early diagnosis of cancer cells and the specific release of drugs into the tumor site. Because of the prospective applications of lectin-sugar-stabilised nanoparticle conjugates, it is important to understand their molecular interaction and physicochemical properties. Momordica charantia Seed Lectin (MCL) is a type II RIP and has been known as an anti-tumor agent. Investigation of the interaction between sugar-stabilised silver nanoparticles and MCL has been performed by fluorescence spectroscopy to explore the possibility of creating an effective biocompatible drug delivery system against cancer cells. In this regard interaction between lectin and NPs should be well-preserved, while recognizing the specific cell surface sugar. Therefore experiments were carried out in the presence and absence of specific sugar galactose. Protein intrinsic fluorescence emission is quenched at ~ 20% at saturation during the interaction without any significant shift in fluorescence emission maximum. Binding experiments reveal a good affinity. Tetrameric MCL binds to a single nanoparticle. Stern-Volmer analysis of the quenching data suggests that the interaction is via static quenching leading to complex formation. Hemagglutination experiments together with interaction studies in the presence of specific sugar show that the sugar-binding site of the lectin is distinct from the nanoparticle-binding site and cell recognition is very much intact even after binding to AgNPs. Our results propose the possibility of developing MCL-silver nanoparticle conjugate with high stability and multiple properties in the diagnosis and treatment of cancer.

New insights into the bioactive polysaccharides, proteins, and triterpenoids isolated from bitter melon (Momordica charantia) and their relevance for nutraceutical and food application: A review.

The recent trend in infectious diseases and chronic disorders has dramatically increased consumers' interest in functional foods. As a result, the research of bioactive ingredients with potential for nutraceutical and food application has rapidly become a topic of interest. In this optic, the plant Momordica charantia (M. charantia) has recently attracted the most attention owing to its numerous biological properties including anti-diabetic, anti-obesity, anti-inflammatory, anti-cancers among others. However, the current literature on M. charantia has mainly been concerned with the plant extract while little is known on the specific bioactive compounds responsible for the plant's health benefits. Hence, the present review aims to provide a comprehensive overview of the recent research progress on bioactives isolated from M. charantia, focusing on polysaccharides, proteins, and triterpenoids. Thus, this review provides an up-to-date account of the different extraction methods used to isolate M. charantia bioactives. In addition, the structural features and biological properties are presented. Moreover, this review discusses the current and promising applications of M. charantia bioactives with relevance to the nutraceutical and food industries. The information provided in this review will serve as a theoretical basis and practical support for the formulation of products enriched with M. charantia bioactives.

Effects of dietary wild bitter melon (Momordica charantia var. abbreviate Ser.) extract on glucose and lipid metabolism in HFD/STZ-induced type 2 diabetic rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Plant-based extracts to interfere with the onset of diabetes may be a promising approach towards type 2 diabetes mellitus (T2DM). Bitter gourd (Momordica charantia L.) is popularly consumed as an edible and medicinal resource with hypoglycemic effect in China. Wild bitter gourd (Momordica Charantia var. abbreviata Ser.) is a variant of bitter gourd, but there are relatively few studies on it. AIM OF THE STUDY: The purpose of the experiment is to first screen out the most effective extraction part of Momordica charantia L. and Momordica Charantia var. abbreviata Ser. through the hypoglycemic activity experiment in vitro, and by using a high-fat and high-sugar diet with STZ-induced diabetic rat model in vivo to explore the possible mechanism of action against diabetes. MATERIALS AND METHODS: This study first performed α-glucosidase, PTP1B and lipase activities inhibition experiments on the alcohol and water extracts of Momordica charantia L. and Momordica Charantia var. abbreviata Ser. Sprague Dawley rats were either given normal feed or a high sugar and fat diet for four weeks, followed STZ (25 mg/kg, via i. p.) was given. Rats with fasting blood glucose ≥11.1 mmol/l after one week were deemed to be diabetic, treatments were administered for four weeks, and then blood samples were used to evaluate hematological and biochemical indicators, and liver was removed for post-analysis. The expression levels of p-AMPK, AMPK, p-PI3K, PI3K, p-AKT, AKT, p-GSK3ß, GSK3ß, p-IRS-1, IRS-1, GLUT2 were determined by Western blot. At the same time, the chemical components was identified by liquid-mass spectrometry. RESULTS: Data showed that the ethanol extract of wild bitter gourd (WBGE) had the best ability to regulate glucose and lipid metabolism in vitro. Therefore, we further investigated the antidiabetic effects of oral consumption of WBGE on high-fat diet (HFD) and streptozotocin (STZ)-induced T2DM in SD rats. WBGE effectively reduced blood glucose and lipid levels, alleviated glucose intolerance and insulin resistant. Moreover, WBGE consumption could also inhibited oxidant responses and inflammatory damage. Mechanism studies have shown that WBGE may act by regulating AMPK/PI3K signaling pathway. On the other hand, the content of total phenol, total flavonoids, total saponins and total polysaccharide were measured by UV, 27 compounds were identified by LC-MS. CONCLUSIONS: These studies explored the role and mechanism of WBGE in regulating glucose and lipid metabolism, and may support the utilization and further investigation of wild bitter gourd as a dietary intervention strategy to prevent diabetes and related metabolic abnormalities.

Antiproliferative efficacy of the antioxidant bioactive compounds of defatted seeds of Azadirachta indica and Momordica charantia against the regulatory function of tumor suppressor gene inducing oral carcinoma.

The present study focuses on the antiproliferative activity of polyphenolic flavonoids found in defatted seeds of Azadirachta indica and Momordica charantia with the regulatory function of tumor suppressor genes inducing Oral Squamous Cell Carcinoma. Polyphenolic flavonoid in extracts was characterized using chromatographic analysis and has confirmed the presence of quercetin, rutin and tannic acid in the extracts of A. indica and M. charantia. According to DPPH assay and reducing power assays, free radical scavenging was found to be high in ethanolic extract of defatted seeds. Antiproliferative efficacies of defatted seed extracts against KB cell line (mouth) were studied by MTT assay and revealed that aqueous extract of defatted seeds of M. charantia has exhibited maximum antiproliferative activity against KB cells. Antioxidant activity of defatted seed extracts were observed on treated KB cells by determining enzymatic activity (SOD, Cat, and GST) and nonenzyme content (GSH and MDA Content). Using the AutoDock tool, quercetin, rutin and tannin acid revealed that mutant p53, TWIST related protein, TGF-ß and Snail I have the best binging energy results. MD simulation was observed on best docking results between the molecule and identified flavonoid by Desmond V 5.9 package . This leads to the conclusion that bioactive extracts with antiproliferative activity, antioxidant capacity and polyphenols with binding efficacy against tumor suppressor gene regulatory function could be used as a herbal remedy.Communicated by Ramaswamy H. Sarma.

Recent advances in the development of bitter gourd seed oil: from chemical composition to potential applications.

Non-conventional seed oils are being considered novelty foods due to the unique properties of their chemical constituents. Numerous such seed oils serve as nutritional and functional supplements, making them a point of interest for scholars. Bitter gourd (Momordica charantia L.) seed oil (BGSO) has been widely used in folk medicine worldwide for the treatment of different pathologies, such as diabetes, cancer, and several inflammatory diseases. Therefore, its nutritional and medicinal value has been extensively studied. Considering the potential use of BGSO, it is imperative to have a comprehensive understanding of this product to develop and use its biologically active ingredients in innovative food and pharmaceutical products. An extensive understanding of BGSO would also help improve the economic feasibility of the bitter gourd seed processing industry and help prevent environmental pollution associated with the raw waste produced during the processing of bitter gourd seeds. This review addresses the potential uses of BGSO in terms of food and pharmaceuticals industry perspectives and comprehensively summarizes the oil extraction process, chemical composition, biological activity, and the application prospects of BGSO in clinical medicine.

Cytotoxicity and maternal toxicity attributed to exposure to Momordica charantia L. (Cucurbitaceae) dry leaf extract.

Momordica charantia L. (Cucurbitaceae), popularly known as "bitter melon" or "bitter gourd," is a climbing plant well-adapted to tropical countries. This plant is used traditionally to treat several conditions including diabetes mellitus, inflammation, liver dysfunctions, and cancer. Given the widespread ethnopharmacological use, this study aimed to examine the cytogenetic, maternal, and developmental toxicity attributed to exposure to dry extract of M. charantia leaves using Allium cepa and Wistar rats as test models. First, phytochemical characterization of the dry extract by high performance liquid chromatography (HPLC) analyses was performed. Then, Allium cepa roots were exposed to three different concentrations of the dry extract (0.25, 0.5, or 1 mg/ml) to determine the mitotic index, frequency of chromosomal aberrations, and nuclear abnormalities. In addition, pregnant Wistar rats were administered either 500; 1,000 or 2,000 mg/kg dry extract during the gestational period (GD) days 6-15, and subsequently possible toxic effect on the dams and fetuses were recorded. HPLC analyses confirmed rutin as the main secondary metabolite present in the dry extract. In the Allium cepa test, the dry extract was cytotoxic. In Wistar rats, dry extract administration reduced water and feed intake and mean body mass gain, indicating maternal toxicity during the organogenesis period. However, the dry extract did not markedly affect reproductive outcome parameters evaluated. Regarding developmental toxicity assessment, the dry extract treatment did not significantly alter number of skeletal malformations in the offspring. Data demonstrated that the dry extract of M. charantia leaves presents cytotoxicity and low maternal toxicity, indicating indiscriminate use needs to be avoided.

Immunomodulatory effects and associated mechanisms of Momordica charantia and its phytochemicals.

Momordica charantia L. (M. charantia), which is a member of the Cucurbitaceae family and widely distributed in tropical and subtropical regions, has been consumed as a vegetable and also used as herbal medicine for thousands of years worldwide. M. charantia has received great attention in biological and biomedical research due to its remarkable antidiabetic/hypoglycaemic, anti-inflammatory, antioxidant, antiviral and antitumour activities both in vivo and in vitro. Numerous studies have revealed that the typical health-promoting activities of M. charantia are mainly attributed to its phytochemicals including saponins, proteins/peptides, phenolic compounds, alkaloids, triterpenoids and polysaccharides. In particular, it has been attested that there is a strong relationship between the antidiabetic activity and the saponins and proteins of M. charantia. In recent years, studies on the immunoenhancing and immunostimulating effects of M. charantia have attracted much attention and made significant progress. Therefore, this review focuses on the immunomodulatory effects and associated mechanisms of M. charantia and its bioactive phytochemicals. The clinical applications of M. charantia in immune-related diseases are also discussed, aiming to broaden the exploration of M. charantia as a functional food.

Alternativas de controle do diabetes / Alternatives for diabetes control / Alternativas para el control de la diabetes

O Diabetes desde a antiguidade tem sido uma das maiores causas de morte entre as populações do globo, e segundo a Organização Mundial da Saúde continua assolando nos nossos dias. Apesar das descobertas de tratamentos mais eficazes, a doença vem avançando em progressões assustadoras atualmente, com projeções preocupantes para a saúde pública. Como estratégia de acompanhamento terapêutico, estatístico direcionado a portadores de diabetes, o Governo Federal lançou o programa HIPERDIA (Hipertensos e Diabéticos), que faz o acompanhamento da evolução da doença e das complicações dos pacientes. E neste sentido, também são utilizadas terapêuticas mais acessíveis como as plantas medicinais. O objetivo desta pesquisa consiste em realizar uma revisão bibliográfica abordando as opções de terapias de controle do diabetes oferecidas no Sistema Único de Saúde e pesquisar fitoterápicos com potencial hipoglicêmico aprovados pela Anvisa. Através de levantamento bibliográfico, foram identificadas oito espécies vegetais utilizadas pela medicina popular no controle do diabetes, sendo estas: Bauhinia Forficata, Syzygium Cumini, Annona Muricata, Cynara Scolymus, Momordica Charantia, Eugenia Uniflora e Baccharis Trimera. Essas plantas do programa, embora tenham comprovação de seu efeito hipoglicêmico e redutores dos sintomas diabéticos, pelas suas propriedades antioxidantes e antiinflamatórias, colabora para uma melhor qualidade de vida aos pacientes.

Since antiquity, Diabetes has been one of the biggest causes of death amon-g populations around the globe, and according to the World Health Organization, it continues to plague our days. Despite discoveries of more effective treatments, the disease is currently advancing in frightening progressions, with worrying projections for public health. As a therapeutic, statistical follow-up strategy aimed at people with diabetes, the Federal Government launched the HIPERDIA (Hypertensive and Diabetic) program, which monitors the evolution of the disease and the complications of patients. And in this sense, more accessible therapies such as medicinal plants are also used. The objective of this research is to carry out a literature review addressing the options for diabetes control therapies offered in the Unified Health System and to search for herbal medicines with hypoglycemic potential approved by Anvisa. Through a bibliographical survey, eight plant species used by folk medicine to control diabetes were identified, namely: Bauhinia Forficata, Syzygium Cumini, Annona Muricata, Cynara Scolymus, Momordica Charantia, Eugenia Uniflora and Bacharis Trimera. These plants in the program, although they have evidence of their hypoglycemic effect and reduce diabetic symptoms, due to their antioxidant and anti-inflammatory properties, contribute to a better quality of life for patients.

La diabetes ha sido desde la antigüedad una de las principales causas de muerte entre las poblaciones del planeta, y según la Organización Mundial de la Salud sigue haciendo estragos en nuestros días. A pesar de los descubrimientos de tratamientos más eficaces, la enfermedad avanza actualmente con una progresión aterradora, con proyecciones preocupantes para la salud pública. Como estrategia de seguimiento terapéutico, estadísticamente dirigida a las personas con diabetes, el Gobierno Federal puso en marcha el programa HIPERDIA (Hipertensión y Diabetes), que controla la evolución de la enfermedad y las complicaciones de los pacientes. En este sentido, también se utilizan terapias más accesibles, como las plantas medicinales. El objetivo de esta investigación es realizar una revisión bibliográfica que aborde las opciones de terapias para el control de la diabetes ofrecidas en el Sistema Único de Salud y buscar fitoterapias con potencial hipoglucemiante aprobadas por Anvisa. Mediante un estudio bibliográfico, se identificaron ocho especies vegetales utilizadas por la medicina popular en el control de la diabetes, a saber: Bauhinia Forficata, Syzygium Cumini, Annona Muricata, Cynara Scolymus, Momordica Charantia, Eugenia Uniflora y Baccharis Trimera. Estas plantas del programa, aunque han demostrado su efecto hipoglucemiante y reductor de los síntomas diabéticos, por sus propiedades antioxidantes y antiinflamatorias, colaboran a una mejor calidad de vida para los pacientes.

Cytotoxic and Anti-Inflammatory Triterpenoids in the Vines and Leaves of Momordica charantia.

The vines and leaves of Momordica charantia L. are used as herbal medicines to treat inflammation-related disorders. However, their safety profile remains uncharacterized, and the constituents in their extracts that exert anti-inflammatory and adverse effects remain unclear. This study isolated the characteristic cucurbitane-type triterpenoid species in the vines and leaves of M. charantia L. and analyzed their cytotoxicity, anti-inflammatory effects, and underlying mechanisms. Four structurally related triterpenoids-momordicines I, II, IV, and (23E) 3ß,7ß,25-trihydroxycucurbita-5,23-dien-19-al (TCD)-were isolated from the triterpenoid-rich fractions of extracts from the vines and leaves of M. charantia. Momordicine I was cytotoxic on normal cells, momordicine II exerted milder cytotoxicity, and momordicine IV and TCD had no obvious adverse effects on cell growth. TCD had anti-inflammatory activity both in vivo and in vitro. In lipopolysaccharide-stimulated RAW 264.7 cells, TCD inhibited the inhibitor kappa B kinase/nuclear factor-κB pathway and enhanced the expression of nuclear factor erythroid 2-related factor 2, heme oxygenase-1, and glutamate-cysteine ligase modifier subunit through the extracellular signal-regulated kinase1/2 and p38. Thus, the vines and leaves of M. charantia should be used with caution. An extraction protocol that can enrich TCD but remove momordicine I would likely enhance the safety of the extract.

Bitter melon fruit extract enhances intracellular ATP production and insulin secretion from rat pancreatic ß-cells.

Bitter melon (Momordica charantia L.) has been shown to have various health-promoting activities, including antidiabetic and hypoglycaemic effects. Improvement in insulin sensitivity and increase in glucose utilisation in peripheral tissues have been reported, but the effect on insulin secretion from pancreatic ß-cells remains unclear. In this study, we investigated the effect of bitter melon fruit on insulin secretion from ß-cells and the underlying mechanism. The green fruit of bitter melon was freeze-dried and extracted with methanol. The bitter melon fruit extract (BMFE) was fractionated using ethyl acetate (fraction A), n-butanol (fraction B) and water (fraction C). Insulin secretory capacity from INS-1 rat insulinoma cell line and rat pancreatic islets, as well as glucose tolerance in rats by oral glucose tolerance test (OGTT), was measured using BMFE and fractions. ATP production in ß-cells was also examined. BMFE augmented insulin secretion from INS-1 cells in a dose-dependent manner. The significant augmentation of insulin secretion was independent of the glucose dose. Fraction A (i.e. hydrophobic fraction), but not fractions B and C, augmented insulin secretion significantly at the same level as that by BMFE. This finding was also observed in pancreatic islets. In OGTT, BMFE and fraction A decreased blood glucose levels and increased serum insulin levels after glucose loading. The decrease in blood glucose levels was also observed in streptozotocin-induced diabetic rats. In addition, BMFE and fraction A increased the ATP content in ß-cells. We concluded that hydrophobic components of BMFE increase ATP production and augment insulin secretion from ß-cells, consequently decreasing blood glucose levels.

AMPK activators for the prevention and treatment of neurodegenerative diseases.

INTRODUCTION: As the global population ages at an unprecedented rate, the burden of neurodegenerative diseases is expected to grow. Given the profound impact illness like dementia exert on individuals and society writ large, researchers, physicians, and scientific organizations have called for increased investigation into their treatment and prevention. Both metformin and aspirin have been associated with improved cognitive outcomes. These agents are related in their ability to stimulate AMP kinase (AMPK). Momordica charantia, another AMPK activator, is a component of traditional medicines and a novel agent for the treatment of cancer. It is also being evaluated as a nootropic agent. AREAS COVERED: This article is a comprehensive review which examines the role of AMPK activation in neuroprotection and the role that AMPK activators may have in the management of dementia and cognitive impairment. It evaluates the interaction of metformin, aspirin, and Momordica charantia, with AMPK, and reviews the literature characterizing these agents' impact on neurodegeneration. EXPERT OPINION: We suggest that AMPK activators should be considered for the treatment and prevention of neurodegenerative diseases. We identify multiple areas of future investigation which may have a profound impact on patients worldwide.

Molecular Docking and Simulation Studies of Antidiabetic Agents Devised from Hypoglycemic Polypeptide-P of Momordica charantia.

Diabetes mellitus termed as metabolic disorder is a collection of interlinked diseases and mainly body's inability to manage glucose level which leads to cardiovascular diseases, renal failure, neurological disorders, and many others. The drugs contemporarily used for diabetes have many inevitable side effects, and many of them have become less responsive to this multifactorial disorder. Momordica charantia commonly known as bitter gourd has many bioactive compounds with antidiabetic properties. The current study was designed to use computational methods to discover the best antidiabetic peptides devised from hypoglycemic polypeptide-P of M. charantia. The binding affinity and interaction patterns of peptides were evaluated against four receptor proteins (i.e., as agonists of insulin receptor and inhibitors of sodium-glucose cotransporter 1, dipeptidyl peptidase-IV, and glucose transporter 2) using molecular docking approach. A total of thirty-seven peptides were docked against these receptors. Out of which, top five peptides against each receptor were shortlisted based on their S-scores and binding affinities. Finally, the eight best ligands (i.e., LIVA, TSEP, EKAI, LKHA, EALF, VAEK, DFGAS, and EPGGGG) were selected as these ligands strictly followed Lipinski's rule of five and exhibited good ADMET profiling. One peptide EPGGGG showed activity towards insulin and SGLT1 receptor proteins. The top complex for both these targets was subjected to 50 ns of molecular dynamics simulations and MM-GBSA binding energy test that concluded both complexes as highly stable, and the intermolecular interactions were dominated by van der Waals and electrostatic energies. Overall, the selected ligands strongly fulfilled the drug-like evaluation criterion and proved to have good antidiabetic properties.

Saponins of Momordica charantia increase insulin secretion in INS-1 pancreatic ß-cells via the PI3K/Akt/FoxO1 signaling pathway.

Saponins are the main bioactive substances with anti-hyperglycemic activities of Momordica charantia. This study aimed to verify the effects of M. charantia saponins on insulin secretion and explore the potential underlying mechanisms in INS-1 pancreatic ß-cells. We injured INS-1 cells with 33.3mM glucose and then treated them with saponins. Saponins improved cell morphology and viability as demonstrated by inverted microscopy and CCK8 detection and significantly increased insulin secretion in a concentration-dependent manner as shown by ELISA. Thus, we obtained the optimal concentration for the subsequent experiments. Potential mechanisms were explored by immunofluorescence, western blotting, and RT-qPCR techniques. First, saponins increased the mRNA and protein levels of IRS-2 but decreased the serine 731 phosphorylation level of IRS-2. Moreover, saponins increased the phosphorylation of Akt protein and decreased the protein level of FoxO1, which were both reversed by the PI3K inhibitor ly294002. Furthermore, saponins increased the protein level of the downstream molecule and insulin initiating factor PDX-1, which was also reversed by ly294002. Saponins also increased Akt and PDX-1 mRNA and decreased FoxO1 mRNA, which were both reversed by ly294002. Saponins increased glucose-stimulated insulin secretion (GSIS) and intracellular insulin content, which were reversed by ly294002, as determined by ELISA. The immunofluorescence results also confirmed this tendency. In conclusion, our findings improve our understanding of the function of saponins in INS-1 pancreatic ß-cells and suggest that saponins may increase insulin secretion via the PI3K/Akt/FoxO1 signaling pathway.

Inhibitory Effects of Cucurbitane-Type Triterpenoids from Momordica charantia Fruit on Lipopolysaccharide-Stimulated Pro-Inflammatory Cytokine Production in Bone Marrow-Derived Dendritic Cells.

The bitter melon, Momordica charantia L., was once an important food and medicinal herb. Various studies have focused on the potential treatment of stomach disease with M. charantia and on its anti-diabetic properties. However, very little is known about the specific compounds responsible for its anti-inflammatory activities. In addition, the in vitro inhibitory effect of M. charantia on pro-inflammatory cytokine production by lipopolysaccharide (LPS)-stimulated bone marrow-derived dendritic cells (BMDCs) has not been reported. Phytochemical investigation of M. charantia fruit led to the isolation of 15 compounds (1-15). Their chemical structures were elucidated spectroscopically (one- and two-dimensional nuclear magnetic resonance) and with electrospray ionization mass spectrometry. The anti-inflammatory effects of the isolated compounds were evaluated by measuring the production of the pro-inflammatory cytokines interleukin IL-6, IL-12 p40, and tumor necrosis factor α (TNF-α) in LPS-stimulated BMDCs. The cucurbitanes were potent inhibitors of the cytokines TNF-α, IL-6, and IL-12 p40, indicating promising anti-inflammatory effects. Based on these studies and in silico simulations, we determined that the ligand likely docked in the receptors. These results suggest that cucurbitanes from M. charantia are potential candidates for treating inflammatory diseases.

A triterpenoid-enriched extract of bitter melon leaves alleviates hepatic fibrosis by inhibiting inflammatory responses in carbon tetrachloride-treated mice.

Liver fibrosis is a progression of chronic liver disease characterized by excess deposition of fibrillary collagen. The aim of this study was to investigate the protective effect of a triterpenoid-enriched extract (TEE) from bitter melon leaves against carbon tetrachloride (CCl4)-induced hepatic fibrosis in mice. Male ICR mice received TEE (100 or 150 mg kg-1) by daily oral gavage for one week before starting CCl4 administration and throughout the entire experimental period. After intraperitoneal injection of CCl4 for nine weeks, serum and liver tissues of the mice were collected for biochemical, histopathological and molecular analyses. Our results showed that TEE supplementation reduced CCl4-induced serum aspartate aminotransferase and alanine aminotransferase activities. Histopathological examinations revealed that CCl4 administration results in hepatic fibrosis, while TEE supplementation significantly suppressed hepatic necroinflammation and collagen deposition. In addition, TEE supplementation decreased α-smooth muscle actin (α-SMA)-positive staining and protein levels of α-SMA and transforming growth factor-ß1. TEE-supplemented mice had lower mRNA expression levels of interleukin-6, tumor necrosis factor-α, and toll-like receptor 4. Moreover, TEE (150 mg kg-1) supplementation significantly reduced intrahepatic inflammatory Ly6C+ monocyte infiltration. We demonstrated that TEE could ameliorate hepatic fibrosis by regulating inflammatory cytokine secretion and α-SMA expression in the liver to reduce collagen accumulation.