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.

Green Fabrication, Characterization of Zinc Oxide Nanoparticles Using Plant Extract of Momordica charantia and Curcuma zedoaria and Their Antibacterial and Antioxidant Activities.

In recent years, the rapid increase in the resistance of microorganisms to antibiotics has produced major health issues. Novel applications for these compounds have been developed by integrating modern technologies such as nanotechnology and material science with the innate antibacterial activity of metals. The current study demonstrated the synthesis of zinc oxide nanoparticles (ZnO NPs) from Momordica charantia and Curcuma zedoaria plant extracts, as well as their antibacterial properties. The synthesis of ZnO NPs was confirmed via UV-visible spectroscopy, showing clear peaks at 375 and 350 nm for M. charantia and C. zedoaria, respectively. Scanning electron microscopy (SEM) analysis revealed crystals of irregular shapes for the majority of the nanoparticles synthesized from both plants. The existence of ZnO NPs was confirmed using X-ray diffraction while the particle size was calculated using Scherrer's equation, which was 19.65 for C. zedoaria and 17.02 for M. charantia. Different functional groups were detected through Fourier transform infrared spectroscopy analysis. The antibacterial activity of the ZnO NPs at three different concentrations (250, 500, and 1000 µg/ml) was assessed against three different bacterial strains, i.e., Escherichia coli (E. coli), Staphylococcus aureus (S. aureus), and Pseudomonas aeruginosa (P. aeruginosa), using disc diffusion methods. The ZnO nanoparticles showed promising antibacterial activity against bacterial strains. For C. zedoaria, the highest growth inhibition was observed at a concentration of 1000 µg/ml, which was 18, 19, and 18 mm as compared to antibiotics (15, 11, and 15.6 mm) against E. coli, P. aeruginosa, and S. aureus, respectively. Similarly, at 1000 µg/ml of NPs, M. charantia showed the highest growth inhibition (18, 15, and 17 mm) as compared to antibiotics (15, 11, and 14.6 mm) against E. coli, P. aeruginosa, and S. aureus, respectively. In conclusion, compared to pure plant extract and antibiotics, ZnO NPs at a higher concentration (1000 µg/ml) exhibited a significant difference in zone of inhibition against all the bacterial strains. Different concentrations of ZnO using M. charantia and C. zedoaria caused increments in the scavenging of 2,2-diphenyl-1-picrylhydrazyl (DPPH) radicals and 2,2-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS). The nanoparticles extracted using C. zedoaria exhibited higher antioxidant activity than M. charantia. Greenly synthesized ZnO nanoparticles have remarkable antibacterial properties and antioxidant activity, making them a promising contender for future pharmaceutical application.

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.

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.

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.

Two new triterpenoids preventing the hydrocortisone-induced injury in HMEC-1 cells from Momordica charantia L.

Momordica charantia L. (M. charantia) is an annual climbing herb in Cucurbitaceae. As a medicinal and edible homologous plant, it has a long history of application. This study aims to isolate and identify the chemical constituents from M. charantia and evaluate their prevention effect on hydrocortisone-induced injury in HMEC-1 cells. 10 kg of M. charantia was extracted with 95% ethanol for three times and partitioned with petroleum ether, dichloromethane and n-butanol. The dichloromethane part was performed by silica, ODS silica, Sephadex LH-20 column chromatography and semi-preparative HPLC to obtain two new compounds. The prevention effect on hydrocortisone-induced injury in HMEC-1 cells of these two compounds was determined by the method of CCK-8. The cell viability of HMEC-1 cells treated with 2 (25 µM) was 85.85% ± 4.39%. The results indicated that 2 exhibited significantly prevention effect on hydrocortisone-induced injury in HMEC-1 cells but 1 exhibited no this activity in vitro.

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.

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.

Anti-adipogenic activities of pheophorbide a and pyropheophorbide a isolated from wild bitter gourd (Momordica charantia L. var. abbreviata Seringe) in vitro.

BACKGROUND: The wild bitter gourd (WBG) is a commonly consumed vegetable in Asia that has antioxidant and hypoglycemic properties. The present study aimed to investigate the anti-adipogenic activities of isolated compounds from WBG on 8-day differentiated cultures of 3 T3-L1 adipocytes that were then stained with Oil Red O (ORO) or diamidino-2-phenylindole (DAPI). RESULTS: ORO stains of the methanol extracts of de-seeded HM86 cultivar of WBG (WBG-M) and the ethyl acetate fractions (WBG-M-EA) showed anti-adipogenic activities against differentiated adipocytes. Two chlorophyll-degraded compounds, pheophorbide a (1) and pyropheophorbide a (2), were isolated from WBG-M-EA. Treatments with 1 (5, 10, and 20 µmol L-1 ) and 2 (2.5, 5, and 10 µmol L-1 ) showed dose-dependent reductions in lipid accumulations and reduced nuclear DAPI stains in differentiated 3 T3-L1 adipocytes. The concentrations for 50% inhibition against lipid accumulations of 1 and 2, respectively, were 16.05 and 7.04 µmol L-1 . Treatments with 1 and 2 showed enhanced lactate dehydrogenase release in the first 4-day cell mitotic clonal expansions during the differentiating cultural processes, although the effect was less on the non-differentiating cultural processes. Thus, 1 and 2 were more toxic to differentiating adipocytes than to non-differentiated pre-adipocytes, which partly resulted in anti-adipogenic activities with lowered lipid accumulations. CONCLUSION: Both 1 and 2 showed anti-adipogenic activities in cell models. These chlorophyll-degraded compounds commonly exist in several vegetables during storage or edible seaweeds, which will provide resources for further investigations aiming to test anti-obesity in animal studies. © 2022 Society of Chemical Industry.

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.

Indigenous knowledge and quantitative ethnobotany of the Tanawal area, Lesser Western Himalayas, Pakistan.

Ethnobotanical field surveys were carried out in the Tanawal area of the Lesser Himalayan Region, Khyber Pakhtunkhawa, Province from April 2016 to October 2017. The area is located between 34.36 (34° 21' 30 N) latitude and 73.07 (73° 4' 0 E) longitude with an average elevation of 1374 meters above sea level. Ethnomedicinal data were collected through Participatory Rural Appraisal (PRA), and participants were selected through the snow-boll technique. Semi-structured, in-depth and open-ended interviews were conducted. The data were quantitatively evaluated using ethnomedicinal indices i.e. Relative frequency of citation (RFCs), Fidelity level (FL), and Use Value (UV). The ethnobotanical data were also comparatively analyzed through the Jaccard Index (JI). The study yielded 66 medicinal plants in 62 genera and 43 families. Asteraceae and Solanaceae were the most important families with five medicinal taxa each. Regarding medicinal plant part utilization, leaves (43.28%) were used predominantly, followed by whole plant (14.92%) and fruits (14.92%). Decoction was the main drug formulation applied to 21 species (31.15%) and the oral route was most common (56.1%) while 31.2% of medicinal plants were used for both oral and topical applications. Fifty health disorders were recorded and grouped in 15 categories. Maximum species were used to treat gastrointestinal disorders i.e. 13 species, dermal problems (12 species), and respiratory tract ailments (9). The calculated RFCs ranged between 81 to 31. The most important medicinal plants were Acacia modesta, Citrullus vulgaris, Tamarindus indica, and Momordica charantia with an RGFC of 81 each. The UV ranged between 0.58 and 3.6. Medicinal taxa with the highest UV were Dioscorea deltoidea (3.6), Withania coagulans (3.3), Momordica charantia (3.5), Silybum marianum and Pyrus pashia (3.2). FL values showed that 28 (41.79%) species had a FL value below 50 (74.62%) while 39 (58.20%) had higher FL values. Momordica charantia, Tamarindus indica, Acacia modesta and Citrullus vulgaris were 95.2 each. The Jaccard Index (JI) values ranged from16.77 to 0.98. The current study also reported 16 medicinal plants, commonly used around the globe, have been rarely documented for their medicinal values in the local ethnomedicinal literature i.e. Althaea officinalis, Plantanus orientalis, Jasminum sombac, Maytenus royleana, Cucurbita maxima, Phyllanthus emblica, Citrullus vulgaris. Polygonatum verticilliatum, Caseria tomentosa, Cistanche tubulosa, Bambusa arundinacea, Schinus molle, Tamarindus indica, Pongamia pinnata, Citrus limon and Catharanthus roseus. However, 48 medicinal plants had been reported in the literature but the current study reported their novel medicinal uses. Important taxa should be established in botanical gardens for in-situ conservation, chemical investigation and sustainable utilization. It would also be effective to improve the livelihoods of the local population.

Synergistic antidiabetic activity of Taraxacum officinale (L.) Weber ex F.H.Wigg and Momordica charantia L. polyherbal combination.

Type 2 Diabetes Mellitus accounts for 90% of most diabetes cases. Many commercial drugs used to treat this disease come with adverse side effects and eventually fail to restore glucose homeostasis. Therefore, an effective, economical and safe antidiabetic remedy from dietary source is considered. Taraxacum officinale (L.) Weber ex F.H.Wigg and Momordica charantia L. were chosen since both are used for centuries as traditional medicine to treat various ailments and diseases. In this study, the antidiabetic properties of a polyherbal combination of T. officinale and M. charantia ethanol extracts are evaluated. The bioactive solvent extracts of the samples selected from in vitro antidiabetic assays; α-amylase, α-glucosidase, and dipeptidyl peptidase-4 (DPP-4) inhibition, and glucose-uptake in L6 muscle cells were combined (1:1) to form the polyherbal combination. The antidiabetic efficacy of polyherbal combination was evaluated employing the above stated in vitro antidiabetic assays and in vivo oral glucose tolerance test and streptozotocin-nicotinamide (STZ-NA) induced diabetic rat model. A quadrupole time-of-flight liquid chromatography-mass spectrometry (Q-TOF LCMS) analysis was done to identify active compounds. The polyherbal combination exerted improved antidiabetic properties; increased DPP-4, α-amylase, and α-glucosidase inhibition. The polyherbal combination tested in vivo on diabetic rats showed optimum blood glucose-lowering activity comparable to that of Glibenclamide and Metformin. This study confirms the polyherbal combination of T. officinale and M. charantia to be rich in various bioactive compounds, which exhibited antidiabetic properties. Therefore, this polyherbal combination has the potential to be further developed as complex phytotherapeutic remedy for the treatment of Type 2 Diabetes Mellitus.

NMR-based metabolomic profiling of the differential concentration of phytomedicinal compounds in pericarp, skin and seeds of Momordica charantia (bitter melon).

Momordica charantia is a medicinal plant which is widely used in different traditional medicinal systems to treat several diseases. We have identified the differential distribution of phytomedicinally important metabolites in the pericarp, skin and seeds of M. charantia fruit via NMR spectroscopy. Multivariate statistical analysis showed a clustering of the metabolic profiles of seeds and pericarp, and their clear separation from the metabolic profile of the skin. The total phenolic and flavonoid content of the fruit extracts were estimated via bioassays, the radical scavenging activity was estimated via in vitro DPPH and ABTS assays and an inhibitory activity test of α-glucosidase was also performed. The pericarp and seeds contained significant amounts of phenolic compounds and flavonoids, indicating that they are a good source for antioxidants. The skin contained a significantly higher amount of phytosterols such as Charantin and momordicine, which are known to correlate with antidiabetic activity.

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.

Targeting novel coronavirus SARS-CoV-2 spike protein with phytoconstituents of Momordica charantia.

BACKGROUND: Infections by the SARS-CoV-2 virus causing COVID-19 are presently a global emergency. The current vaccination effort may reduce the infection rate, but strain variants are emerging under selection pressure. Thus, there is an urgent need to find drugs that treat COVID-19 and save human lives. Hence, in this study, we identified phytoconstituents of an edible vegetable, Bitter melon (Momordica charantia), that affect the SARS-CoV-2 spike protein. METHODS: Components of Momordica charantia were tested to identify the compounds that bind to the SARS-CoV-2 spike protein. An MTiOpenScreen web-server was used to perform docking studies. The Lipinski rule was utilized to evaluate potential interactions between the drug and other target molecules. PyMol and Schrodinger software were used to identify the hydrophilic and hydrophobic interactions. Surface plasmon resonance (SPR) was employed to assess the interaction between an extract component (erythrodiol) and the spike protein. RESULTS: Our in-silico evaluations showed that phytoconstituents of Momordica charantia have a low binding energy range, -5.82 to -5.97 kcal/mol. A docking study revealed two sets of phytoconstituents that bind at the S1 and S2 domains of SARS-CoV-2. SPR showed that erythrodiol has a strong binding affinity (KD = 1.15 µM) with the S2 spike protein of SARS-CoV-2. Overall, docking, ADME properties, and SPR displayed strong interactions between phytoconstituents and the active site of the SARS-CoV-2 spike protein. CONCLUSION: This study reveals that phytoconstituents from bitter melon are potential agents to treat SARS-CoV-2 viral infections due to their binding to spike proteins S1 and S2.

Momordica charantia L. Extract Protects Hippocampal Neuronal Cells against PAHs-Induced Neurotoxicity: Possible Active Constituents Include Stigmasterol and Vitamin E.

Polycyclic aromatic hydrocarbons (PAHs) have been recognized to cause neurobehavioral dysfunctions and disorder of cognition and behavioral patterns in childhood. Momordica charantia L. (MC) has been widely known for its nutraceutical and health-promoting properties. To date, the effect of MC for the prevention and handling of PAHs-induced neurotoxicity has not been reported. In the current study, the neuroprotective effects of MC and its underlying mechanisms were investigated in mouse hippocampal neuronal cell line (HT22); moreover, in silico analysis was performed with the phytochemicals MC to decipher their potential function as neuroprotectants. MC was demonstrated to possess neuroprotective effect by reducing reactive oxygen species' (ROS') production and down-regulating cyclin D1, p53, and p38 mitogen-activated protein kinase (MAPK) protein expressions, resulting in the inhibition of cell apoptosis and the normalization of cell cycle progression. Additionally, 28 phytochemicals of MC and their competence on inhibiting cytochrome P450 (CYP: CYP1A1, CYP1A2, and CYP1B1) functions were resolved. In silico analysis of vitamin E and stigmasterol revealed that their binding to either CYP1A1 or CYP1A2 was more efficient than the binding of each positive control (alizarin or purpurin). Together, MC is potentially an interesting neuroprotectant including vitamin E and stigmasterol as probable active components for the prevention for PAHs-induced neurotoxicity.

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.