Ripe papaya pectins inhibit the proliferation of colon cancer spheroids and the formation of chemically induced aberrant crypts in rats colons.

Pectins are a class of soluble polysaccharides that can have anticancer properties through several mechanisms. This study aimed to characterize the molecular structure of water-soluble fractions (WSF) derived from ripe and unripe papayas and assess their biological effects in two models: the 3D colon cancer spheroids to measure cell viability and cytotoxicity, and the in vivo model to investigate the inhibition of preneoplastic lesions in rats. WSF yield was slightly higher in ripe papaya, and both samples mainly consisted of pectin. Both pectins inhibited the growth of colon cancer HT29 and HCT116 spheroids. Unripe pectin disturbed HT29/NIH3T3 spheroid formation, decreased HCT116 spheroid viability, and increased spheroid cytotoxicity. Ripe pectin had a more substantial effect on the reduction of spheroid viability for HT29 spheroids. Furthermore, in vivo experiments on a rat model revealed a decrease in aberrant crypt foci (ACF) formation for both pectins and increased apoptosis in colonocytes for ripe papaya pectins. The results suggest potential anticancer properties of papaya pectin, with ripe pectin showing a higher potency.

Phytochemical Extract from Carica papaya Leaves and Punica granatum Seeds as Therapy Against Cognitive Impairment in a Murine Model.

Mild cognitive impairment (MCI) is defined as inter-stage between normal cognitive aging and major neurocognitive disorder (MND). This state of decay is a crucial factor in treatment to prevent the progression to MND. In this study, our group developed a virtual screening process to evaluate 2568 phytochemical compounds against 5 key proteins associated with MCI and MND. As a result, two potential candidates were identified: carpaine, found in Carica papaya leaves, and punicalagin, present in Punica granatum. A model of cognitive impairment (CI) was developed in 10-month-old male Sprague Dawley rats by administering aluminum chloride (AlCl3) at a dose of 100 mg/kg/day for 30 days. After AlCl3 administration period, one of the groups received carpaine and punicalagin in a phytochemical extract (PE) by oral gavage for 30 days. Novel object recognition test (NOR) was assessed at three different time points (T1 - before CI, T2 - after CI, and T3 - after PE treatment). Glial fibrillary acidic protein (GFAP) and neurofilament light chain (NfL) were identified in the hippocampus of rats at the end of the study period. After administration of AlCl3, a reduction in discrimination index vs control rats (CI = 0.012 ± 0.08 vs Control = 0.076 ± 0.03), was observed. After phytochemical extract treatment, a significant increase in discrimination index values was observed in the PE group 0.4643 ± 0.13 vs CI group 0.012 ± 0.08. Additionally, the evaluation of immunohistochemistry showed an increase in GFAP positivity in the hippocampus of the CI groups, while a slight decrease was observed in the PE group. This work addressed a comprehensive methodology that utilized in silico tools to identify phytochemical compounds (carpaine and punicalagin) as potential candidates for affecting key proteins in CI. The phytochemical extract containing carpaine and punicalagin resulted in a trend in the decrease of GFAP expression in the hippocampus and improved recognition memory in rats with CI induced by age and AlCl3 administration.

Uses of Papaya Leaf and Seaweed Supplementations for Controlling Glucose Homeostasis in Diabetes.

Studies from laboratory animal models and complementary medical practices have implied that nutrients from special plants or herbs contain antidiabetic, antioxidant, anti-obese, anti-hypertensive, and anti-inflammatory properties. Seaweed and tropical papaya, which are widely available in Asian and Pacific countries, have been used as home remedies for centuries. The bioactive extracts from these plants contain vitamins A, C, B and E complexes, as well as polysaccharides, phenolic compounds, essential fatty acids, flavonoids, saponins, fucoidan, and phlorotannin. In this review, the authors examine the pathogenesis of diabetes characterized by hyperglycemia due to the dysregulation of glucose homeostasis, antidiabetic/antihyperglycemic seaweed or/and papaya derived bioactive phytochemicals and their proposed mechanisms of action in the management of Type 2 Diabetes Mellitus (T2DM). The authors also propose combining papaya and seaweed to enhance their antidiabetic effects, leveraging the advantages of herb-to-herb combination. Papaya and seaweed have demonstrated antidiabetic effects through in vitro assays, cellular models, and animal studies despite the limited clinical trials. Nutraceuticals with antidiabetic effects, such as secondary metabolites isolated from seaweed and papaya, could be combined for a synergistic effect on T2DM management. However, the application of these compounds in their purified or mixed forms require further scientific studies to evaluate their efficacy against diabetes-related complications, such as hyperlipidemia, elevated free radicals, pro-inflammatory molecules, insulin insensitivity, and the degeneration of pancreatic beta cells.

Antiviral and ROS scavenging potential of Carica papaya Linn and Psidium guajava leaves extract against HIV-1 infection.

Antiretroviral therapy is the only treatment option for HIV-infected patients; however, it has certain drawbacks in terms of developing multiple toxic side effects. Thus, there is a continuous need to explore safe and efficacious anti-retroviral agents. Carica papaya Linn and Psidium guajava are known for their various biological activities. In this study, we characterized the bioactive fractions of methanolic leaves extract from both plants using the High-resolution electrospray ionization mass spectrometry (HR-ESI-MS) technique, followed by the investigation of their potential as anti-HIV-1 and antioxidant agents through in vitro mechanistic assays. The anti-HIV-1 activity was examined in TZM-bl cells through luciferase gene assay against two different clades of HIV-1 strains, whereas the intracellular ROS generation was analyzed by Fluorescence-Activated Cell Sorting. Additionally, the mechanisms of action of these phyto-extracts were determined through the Time-of-addition assay. The characterization of Carica papaya Linn and Psidium guajava leaves extract through HR-ESI-MS fragmentation showed high enrichment of various alkaloids, glycosides, lipids, phenolic compounds, terpenes, and fatty acids like bioactive constituents. Both the phyto-extracts were found to be less toxic and exhibited potent antiviral activity against HIV-1 strains. Furthermore, the phyto-extracts also showed a decreased intracellular ROS in HIV-1 infected cells due to their high antioxidant potential. Overall, our study suggests the anti-HIV-1 potential of Carica papaya Linn and Psidium guajava leaves extract due to the synergistic action of multiple bioactive constituents.

Discovery of Potential Phytochemicals from Carica papaya Targeting BRCA-1 in Breast Cancer Treatment.

The BRCA1 and BRCA2 are genes that encode a protein that ensures the integrity of DNA and prevents the unregulated cells from proliferating. Mutations in the sequence of these genes are associated with the birth of inherited breast cancers. The research for possible human breast cancer treatment remains a vital step in the drug development process. In this study, in silico investigations involving a computational method for the discovery of active phytochemicals from Carica papaya against the BRCA-1 gene were carried out. The in silico studies for these phytochemicals datasets as BRCA-1 breast cancer therapeutic agents showed promising results through pharmacokinetics and pharmacodynamics studies. The Carica papaya compounds were found to follow the rule of five and have good bioavailability. The ADMET and drug-likeness screening score of the identified ligands also recognized their potential as a promising drug candidate against BRCA-1 while the DFT also confirm better biological and chemical reactivity of Carica papaya compounds with excellent intra-molecular charge transfer between electron donor and electron acceptor site. The results of the molecular docking provided useful information on possible target-lead interactions, demonstrating that the newly developed leads showed a high affinity for BRCA-1 targets and might be investigated for further research.

Molecular Docking of Bacterial Protein Modulators and Pharmacotherapeutics of Carica papaya Leaves as a Promising Therapy for Sepsis: Synchronising In Silico and In Vitro Studies.

Sepsis is a serious health concern globally, which necessitates understanding the root cause of infection for the prevention of proliferation inside the host's body. Phytochemicals present in plants exhibit antibacterial and anti-proliferative properties stipulated for sepsis treatment. The aim of the study was to determine the potential role of Carica papaya leaf extract for sepsis treatment in silico and in vitro. We selected two phytochemical compounds, carpaine and quercetin, and docked them with bacterial proteins, heat shock protein (PDB ID: 4PO2), surfactant protein D (PDB ID: 1PW9), and lactobacillus bacterial protein (PDB ID: 4MKS) against imipenem and cyclophosphamide. Quercetin showed the strongest interaction with 1PW9 and 4MKS proteins. The leaves were extracted using ethanol, methanol, and water through Soxhlet extraction. Total flavonoid content, DPPH assay, HPTLC, and FTIR were performed. In vitro cytotoxicity of ethanol extract was screened via MTT assay on the J774 cell line. Ethanol extract (EE) possessed the maximum number of phytocomponents, the highest amount of flavonoid content, and the maximum antioxidant activity compared to other extracts. FTIR analysis confirmed the presence of N-H, O-H, C-H, C=O, C=C, and C-Cl functional groups in ethanol extract. Cell viability was highest (100%) at 25 µg/mL of EE. The present study demonstrated that the papaya leaves possessed antibacterial and cytotoxic activity against sepsis infection.

Papaya (Carica papaya L.) for cancer prevention: Progress and promise.

Cancer is a leading cause of morbidity and mortality across the globe. Emerging evidence suggests that consumption of a well-balanced diet containing a wide variety of vegetables, fruits, and whole grains can prevent the development of, halt, or reverse cancer progression. Carica papaya L. (papaya) has a wide distribution throughout many countries. Although the fruits of C. papaya are primarily consumed as food, various parts of this tree, including the bark, fruits, latex, seeds, and roots, have been used in traditional medicine for health promotion and disease mitigation. While numerous individual studies have investigated anticancer efficacies of various products and constituents of C. papaya, an up-to-date, comprehensive, and critical evaluation of available research data covering its role in the prevention and intervention of various human malignancies has not been conducted according to our knowledge. The purpose of this review is to present a systematic, comprehensive, and critical analysis of the cancer-preventive potential of C. papaya extracts, fractions, and isolated phytochemicals with a special emphasis on the cellular and molecular mechanisms of action. Moreover, the bioavailability, pharmacokinetics, and safety profiles of individual phytochemicals of C. papaya, as well as current limitations, challenges, and future directions of research, have also been discussed.

Effects of the Seed Oil of Carica papaya Linn on Food Consumption, Adiposity, Metabolic and Inflammatory Profile of Mice Using Hyperlipidic Diet.

BACKGROUND: Studies indicate that different parts of Carica papaya Linn have nutritional properties that mean it can be used as an adjuvant for the treatment of various pathologies. METHODS: The fatty acid composition of the oil extracted from the seeds of Carica papaya Linn was evaluated by gas chromatography, and an acute toxicity test was performed. For the experiment, Swiss mice were fed a balanced or high-fat diet and supplemented with saline, soybean oil, olive oil, or papaya seed oil. Oral glucose tolerance and insulin sensitivity tests were performed. After euthanasia, adiposity, glycemia, total cholesterol and fractions, insulin, resistin, leptin, MCP-1, TNF-α, and IL-6 and the histology of the liver, pancreas, and adipose tissue were evaluated. RESULTS: Papaya seed oil showed predominance of monounsaturated fatty acids in its composition. No changes were observed in the acute toxicity test. Had lower food intake in grams, and caloric intake and in the area of adipocytes without minimizing weight gain or adiposity and impacting the liver or pancreas. Reductions in total and non-HDL-c, LDL-c, and VLDL-c were also observed. The treatment had a hypoglycemic and protective effect on insulin resistance. Supplementation also resulted in higher leptin and lower insulin and cytokine resistance. CONCLUSIONS: Under these experimental conditions, papaya seed oil led to higher amounts of monounsaturated fatty acids and had hypocholesterolemic, hypotriglyceridemic, and hypoglycemic effects.

Papaya Leaf Extracts as Potential Dengue Treatment: An In-Silico Study.

Dengue fever (DF), dengue hemorrhagic fever (DHF), and dengue shock syndrome (DSS) cause serious public health problems, with nearly 390 million people affected and 20,000 deaths per year in tropical and subtropical countries. Despite numerous attempts, no antiviral drug or vaccine is currently available to combat the manifestation. The challenge of discovering an efficient vaccine is enhanced by the surplus presence of efficient vectors and drug resistance from the virus. For centuries, papaya (Carica papaya) extracts have been traditionally used to treat DF, DHF, and DSS. In the present study, we systematically investigated seven compounds isolated from papaya leaf extract with regard to their potential as inhibitors for non-structural (NS) proteins, NS3 and NS5, which play a crucial role in viral RNA replication. The computational tools applied stretched across classical molecular docking, molecular dynamics (MD) simulations and SwissADME used to calculate binding affinities; binding free energies; Absorption, Distribution, Metabolism, and Excretion (ADME); and drug-likeness properties, thus, identifying Kaempferol, Chlorogenic acid, and Quercetin as potential candidates, with Kaempferol and Quercetin scoring best. Therefore, for the Kaempferol and Quercetin complexes, hybrid quantum mechanical/molecular mechanical (QM/MM) geometry and frequency calculations were performed, followed by the local mode analysis developed in our group to quantify Kaempferol-NS and Quercetin-NS hydrogen bonding. Given the non-toxic nature and the wide availability of the Kaempferol and Quercetin papaya extract in almost all of the susceptible regions, and our results showing high NS3 and NS5 binding affinities and energies, strong hydrogen bonding with both NS3 and NS5, and excellent ADME properties, we suggest Kaempferol and Quercetin as a strong NS3 and NS5 inhibitor to be further investigated in vitro.

The modulatory effects of alkaloid extracts of Cannabis sativa, Datura stramonium, Nicotiana tabacum and male Carica papaya on neurotransmitter, neurotrophic and neuroinflammatory systems linked to anxiety and depression.

This study investigated the modulatory effects of alkaloid extracts of Cannabis sativa (CSAE), Datura stramonium (DSAE), Nicotiana tabacum (NTAE) and male Carica papaya (CMAE) on neurotransmitter, neurotrophic and neuro-inflammatory systems linked to anxiety and depression. Male Wistar rats were orally administered the alkaloid extracts in doses of 5, 50, 500, and 2000 mg/kg for 90 days. On day 91, neurobehavioural studies were evaluated, rats were sacrificed, brain hippocampus removed and tissue homogenate prepared. Biochemical, cytokine and neurotransmitter metabolisms were estimated in the hippocampus. Expressions of genes linked to anxiety and depression were evaluated by RT-qPCR. Results showed CSAE, NTAE and CMAE act as anxiolytic and antidepressant agents by depleting TNF-α, IL-1ß and reactive oxygen species concentrations, and monoamine oxidase, angiotensin 1-converting enzyme and acetylcholinesterase activities while elevating IL-10 and dopamine concentrations and glutamate dehydrogenase activity at doses of 5, 50 and 500. Same doses of CSAE, NTAE and CMAE also depleted the gene expressions of GSK3ß, JNK, NF-ĸB, and Nesfatin-1 while increasing expressions of CREB, BDNF, serotonin and Nrf2. However, administration of DSAE and 2000 mg/kg CSAE, NTAE and CMAE had adverse modulatory effects on the neurochemical concentrations and activities as well as the gene expressions of the evaluated neurotransmitter, neurotrophic and inflammatory systems. In conclusion, the study established the sub-chronic instrumentalization potential of CSAE, CMAE, and NTAE for anxiolytic and anti-depressive moods, though their use may be associated with dependence and addiction, which may result in more detrimental effects than any therapeutic potential they may proffer.

Carica papaya L. Leaves: Deciphering Its Antioxidant Bioactives, Biological Activities, Innovative Products, and Safety Aspects.

The prevalence of viral infections, cancer, and diabetes is increasing at an alarming rate around the world, and these diseases are now considered to be the most serious risks to human well-being in the modern period. There is a widespread practice in Asian countries of using papaya leaves (C. papaya L.) as herbal medicine, either alone or in combination with prescribed medications, to treat a variety of ailments. The importance of conducting the necessary descriptive studies in order to determine the safety of papaya leaf consumption is also emphasized in the context of their application in the healthcare sector. Electronic databases such as Google Scholar, Scopus, and PubMed were used to gather information on papaya leaves, their therapeutic potential, and clinical evidence-based studies. The literature was gathered from publications on papaya leaves, their therapeutic potential, and clinical evidence-based studies. The antidengue, anticancer, antidiabetic, neuroprotective, and anti-inflammatory effects of papaya leaves discussed in this article are supported by evidence from preclinical, in vivo, in vitro, and clinical trial studies, as well as from other sources. Leaves have been investigated for their mechanism of action as well as their potential to be used in the development of novel herbal products for the health business. According to the reports gathered, only a small number of research demonstrated that leaf extract at high concentrations was hazardous to certain organs. The collective literature reviewed in this review provides insights into the use of papaya leaves as a cure for epidemic diseases, highlighting the phytochemical composition and pharmacological attributes of papaya leaves, as well as the results of various preclinical and clinical studies that have been conducted so far on the subject. The review clearly demonstrates the successful medical evidence for the use of papaya leaf extracts in the healthcare system as a supplemental herbal medication in a variety of clinical settings.

Effects of acidified blanching water and pectinase enzyme pretreatments on physicochemical properties and antioxidant capacity of Carica papaya juice.

The high pectin content in papaya (Carica papaya) causes the juice extraction to be difficult and results in a low yield. This study aims to determine the effect of acidified blanching water and pectinase enzyme pretreatments on the yield, physicochemical properties, and antioxidant activities of the papaya juice. For acidified blanching treatment, papaya cubes (3 cm3 ) were blanched in water containing 0%, 0.5%, 1.5%, and 2.5% w/v citric acid at 95℃ for 2 min. For enzyme treatment, a pectinase enzyme (10, 20, and 30 ppm) was added to the homogenous papaya puree and incubated at 45℃ (200 rpm) for 60 min. The enzyme reaction was stopped by pasteurization at 74℃ for 2 min. The puree was filtered, and the juice was pasteurized at 74℃ for 7 min. All pretreated papaya juice were analyzed for physicochemical properties (color, clarity, viscosity, pH, total soluble solids [TSSs], total carotenoid content, total phenolic content [TPC], and total flavonoid content [TFC]), and antioxidant activities (2,2-diphenyl-1-picrylhydrazyl [DPPH] and ferric reducing antioxidant power [FRAP] assay). Both pretreatments improved the clarity of papaya juice, and was significantly greater after pretreatment with pectinase enzyme. The TPC and antioxidant activities of papaya juice were conserved and maintained by acidified blanching at 1.5% (w/v) citric acid. Increased concentrations of pectinase enzyme significantly reduced the TPC and total carotenoid content. Pretreatment with pectinase enzyme up to 20 ppm does not significantly reduce the TFC and antioxidant activities. Acidified blanching and pectinase enzyme pretreatments have an impact on extraction of papaya fruit juice while retaining the nutritional composition of the juice. PRACTICAL APPLICATION: Papaya (Carica papaya) is a fruit with great nutritional values but is highly perishable and prone to postharvest loss. Juice has become a more cost-effective and convenient option for preserving the fruit. However, since papaya is a pectin-rich fruit, the extraction of juice using mechanical pressing is difficult due to the bonding of juice to the pulp in the form of a jellied mass, which results in juice with low yield. Using acidified blanching and pectinase enzyme to clarify the juice not only increases the yield but also retains the nutrient composition of the juice.

The Determination of Efficacy of CircuCare on Blood Circulation and Metabolism: An Animal Model Study.

OBJECTIVES: To determine whether feeding CircuCare to rats improves blood circulation, metabolism, immune regulation, endocrine activity, and oxidative stress. METHODS: 28 eight-week-old male Sprague-Dawley rats were evenly randomized into control and experimental groups. The control group was fed with ordinary drinking water, while the experimental group was fed with CircuCare at a daily dose of 93.75 mg per 300 g of body weight over eight weeks. Both groups were subjected to a swimming test, and blood samples were taken to observe any variations in various biochemical parameters before and after the test. Key Findings. The experimental group's mean swimming exhaustion duration was 53.2% longer and had a significantly higher lactic acid removal ratio. Their mean prostaglandin E2 level and mean glucose, cortisol, and glutathione level (30 minutes after swimming test) were also significantly higher. No undesirable impacts from CircuCare relating to general blood biochemistry values and bone mineral density were reported. CONCLUSIONS: The present results show that CircuCare can be safely used to increase stamina and exercise capability, expedite the metabolism of lactic acid, accelerate muscle repair, and promote the antioxidant activity of cells in rats.

The Future of Carica papaya Leaf Extract as an Herbal Medicine Product.

Carica papaya (papaya) leaf extract has been used for a long time in a traditional medicine to treat fever in some infectious diseases such as dengue, malaria, and chikungunya. The development of science and technology has subsequently made it possible to provide evidence that this plant is not only beneficial as an informal medication, but also that it has scientifically proven pharmacological and toxicological activities, which have led to its formal usage in professional health care systems. The development of formulations for use in nutraceuticals and cosmeceuticals has caused this product to be more valuable nowadays. The use of good manufacturing practice (GMP) standards, along with the ease of registering this product facilitated by policies of the national government, will absolutely increase the value of papaya leaf extract as a vital nutraceutical and cosmeceutical products in the near future. In this article, we review the potential of papaya leaf extract to be a high-value commodity in terms of its health effects as well as its industrial benefits.

Chemical Composition, Antioxidant and Cytoprotective Potentials of Carica papaya Leaf Extracts: A Comparison of Supercritical Fluid and Conventional Extraction Methods.

The leaves of Carica papaya (CP) are rich in natural antioxidants. Carica papaya has traditionally been used to treat various ailments, including skin diseases. This study aims to decipher the antioxidant effects and phytochemical content of different CP leaf extracts (CPEs) obtained using supercritical carbon dioxide (scCO2) and conventional extraction methods. The antioxidant activities of CPEs were evaluated by cell-free (1,1-diphenyl-2-picryl-hydrazyl (DPPH) and ferric-reduced antioxidative power (FRAP)) and cell-based (H2O2) assay. Both C. papaya leaf scCO2 extract with 5% ethanol (CPSCE) and C. papaya leaf scCO2 extract (CPSC) exhibited stronger DPPH radical scavenging activity than conventional extracts. In the FRAP assay, two hydrophilic extracts (C. papaya leaf ethanol extract (CPEE) and C. papaya freeze-dried leaf juice (CPFD)) showed relatively stronger reducing power compared to lipophilic extracts. Cell-based assays showed that CPFD significantly protected skin fibroblasts from H2O2-induced oxidative stress in both pre-and post-treatment. CPEE protected skin fibroblasts from oxidative stress in a dose-dependent manner while CPSCE significantly triggered the fibroblast recovery after treatment with H2O2. GC-MS analysis indicated that CPSCE had the highest α-tocopherol and squalene contents. By contrast, both CP hydrophilic extracts (CPEE and CPFD) had a higher total phenolic content (TPC) and rutin content than the lipophilic extracts. Overall, CPEs extracted using green and conventional extraction methods showed antioxidative potential in both cell-based and cell-free assays due to their lipophilic and hydrophilic antioxidants, respectively.

Platelet enhancement by Carica papaya L. leaf fractions in cyclophosphamide induced thrombocytopenic rats is due to elevated expression of CD110 receptor on megakaryocytes.

ETHNOPHARMACOLOGICAL RELEVANCE: Carica papaya leaf juice/decoction has been in use in folk medicine in Srilanka, Malaysia and in few parts of India for enhancing the platelet counts in dengue. In Siddha medicine, a traditional form of medicine in India, papaya leaf juice has been used for increasing the platelet counts. Papaya leaf has been reported to enhance blood volume in ancient Ayurveda books in India. Carica papaya leaf is well known for its platelet enhancement activity. Although many preclinical and clinical studies have demonstrated the ability of papaya leaf juice for platelet enhancement, but the underlying mechanisms are still unclear. AIM OF THE STUDY: The study is aimed at identifying the key ingredients of papaya leaf extract and elucidate the mechanism (s) of action of the identified potent component in mitigating thrombocytopenia (Thp). MATERIALS AND METHODS: C. papaya leaf juice was subjected for sequential fractionation to identify the anti-thrombocytopenic phytochemicals. In vivo, stable thrombocytopenia was induced by subcutaneous injection of 70 mg/kg cyclophosphamide (Cyp). After induction, rats were treated with 200 and 400 mg/kg body weight papaya leaf juice and with identified fractions for 14 days. Serum thrombopoietin level was estimated using ELISA. CD110/cMpl, a receptor for thrombopoietin on platelets was measured by western blotting. RESULTS: Administration of cyclophosphamide for 6 days induced thrombocytopenia (210.4 ± 14.2 × 103 cells/µL) in rats. Treating thrombocytopenic rats with papaya leaf juice and butanol fraction for 14 days significantly increased the platelet count to 1073.50 ± 29.6 and 1189.80 ± 36.5 × 103 cells/µL, respectively. C.papaya extracts normalized the elevated bleeding and clotting time and decreased oxidative markers by increasing endogenous antioxidants. A marginal increase in the serum thrombopoietin (TPO) level was observed in Cyp treated group compared to normal and treatment groups. Low expression of CD110/cMpl receptor found in Cyp treated group was enhanced by C. papaya extracts (CPJ) and CPJ-BT. Furthermore, examination of the morphology of bone marrow megakaryocytes, histopathology of liver and kidneys revealed the ability of CPJ and fractions in mitigating Cyp-induced thrombocytopenia in rats. CONCLUSION: C. papaya leaf juice enhances the platelet count in chemotherapy-induced thrombocytopenia by increasing the expression of CD110 receptor on the megakaryocytes. Hence, activating CD110 receptor might be a viable strategy to increase the platelet production in individuals suffering from thrombocytopenia.

Metabolic analysis of unripe papaya (Carica papaya L.) to promote its utilization as a functional food.

Papaya (Carica papaya L.) is widely cultivated in tropical and subtropical countries. While ripe fruit is a popular food item globally, the unripe fruit is only consumed in some Asian countries. To promote the utilization of unripe papaya based on the compositional changes of biological active metabolites, we performed liquid chromatography-Orbitrap-mass spectrometry-based analysis to reveal the comprehensive metabolite profile of the peel and pulp of unripe and ripe papaya fruits. The number of peaks annotated as phenolics and aminocarboxylic acids increased in the pulp and peel of ripe fruit, respectively. Putative carpaine derivatives, known alkaloids with cardiovascular effects, decreased, while carpamic acid derivatives increased in the peel of ripe fruit. Furthermore, the functionality of unripe fruit, the benzyl glucosinolate content, total polyphenol content, and proteolytic activity were detectable after heating and powder processing treatments, suggesting a potential utilization in powdered form as functional material.

Carica papaya leaf extract inhibits prostatitis-associated prostatic hyperplasia via the TRAF6/TAK1/MEK/NF-κB pathway.

Prostatitis, defined as a pathological inflammatory change in the prostate tissue, is one of the most prevalent urological conditions in men. However, optimal management of prostatitis remains unclear, and treatment outcomes are unsatisfactory owing to adverse effects. Carica papaya leaf extract (PAL) is known for its antioxidant, immunomodulatory, and anticancer properties; however, evidence of its anti-inflammatory effect in prostatic tissues remains elusive. In this study, the therapeutic effects and underlying molecular mechanisms of PAL in mice with experimental autoimmune prostatitis (EAP) and a prostatic cell line (RWPE-1 cells) exposed to inflammatory conditioned medium were investigated. PAL suppressed pathological alterations in EAP and markedly reduced prostate weight in EAP mice. Histological analysis revealed that PAL alleviates prostatic hyperplasia. Furthermore, PAL significantly reduced cyclooxygenase-2 mRNA and protein expression; production of inflammatory cytokines, including interleukin-6, tumor necrosis factor-α, and transforming growth factor-ß; and TRAF6/TAK1/MEK/ERK and NF-κB pathway-related protein expression. TRAF6/TAK1/MEK/ERK and NF-κB pathway-related proteins were upregulated in inflammatory conditioned medium-stimulated RWPE-1 cells, but PAL reduced the expression of these markers. Particularly, PAL treatment suppressed the nuclear translocation of NF-κB p65 and phosphorylation of p65 in RWPE-1 cells exposed to the inflammatory conditioned medium. Collectively, the results demonstrate the anti-proliferative and anti-inflammatory effects of PAL in the experimental prostatitis model, which highlights the potential of PAL as a new therapeutic agent in the treatment of prostatic disease.

Carica papaya in Cancer Prevention: An Overview.

Carica papaya is an essential medicinal plant having anticancer activities through diverse mechanisms and is not so far thoroughly investigated. In this review, we have summarized the systematic research outputs of different parts of the papaya plant extracts and elaborated the role of its phytochemicals, anticancer activities, therapeutic targets and mechanisms. Several phenolic compounds have been identified from this plant. Of these, Caffeic acid, Quinic acid and Chlorogenic acid show significant properties and act as principal bioactive phytoconstituents among others. We have explored the nutraceutical and functional aspects of Caffeic acid, Quinic acid and Chlorogenic acid along with the new understanding of the mechanism and its action in diverse cancer models. Also, we have highlighted its bioavailability, natural food additive properties and cost-effectiveness.

Antibacterial activity and main action pathway of benzyl isothiocyanate extracted from papaya seeds.

The development of natural antimicrobial agents has attracted long-term attention due to the increasing demand for food preservation. Papaya, a widely cultivated nutritious tropical fruit, has benzyl isothiocyanate (BITC) as one of the most important secondary metabolites in its seeds. And the antibacterial activity of BITC toward different strains and the main antibacterial pathway remain unclear. The current study focused on characterizing the antibacterial effect and exploring the major bacteriostatic pathway of BITC. BITC was shown to have a broad-spectrum antibacterial effect, with a minimum inhibitory concentration of 1 µL/mL for Escherichia coli, Bacillus subtilis, and Aspergillus niger, and 0.5 µL/mL for Salmonella enterica, Staphylococcus aureus, and Penicillium citrinum. Additionally, BITC was identified to affect the integrity of the biological oxidation system rather than the permeability or morphology of cell membranes. Furthermore, BITC was found not only to affect ATP production but also to hinder a series of important chemical reactions of the coenzymes involved in the transfer of hydrogen ions in the respiratory chain. The bacteriostatic pathway of BITC was shown to be implicated in an incomplete respiratory chain and the deregulation of the metabolism system. These results indicate the potential of BITC as a natural preservative in the food industry. PRACTICAL APPLICATION: BITC is present in papaya seeds and can be extracted and purified. Exploring its antibacterial activity and main action pathway may facilitate its application as a new bacteriostatic agent in food industry.