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.

Formulation, Characterization, and In Vitro Mineral Absorption of Ficus Palmata Fruit Extract Nanoemulsion.

OBJECTIVE: Loss of vital bioactive components of Ficus palmata fruit extract during food processing is a major issue. Therefore, to retain the antioxidant potential and to increase the mineral bioavailability, gum arabic stabilized nanoemulsion of Fig fruit extract was prepared. METHOD: . Nanoemulsion was formulated using three different levels (1, 3, and 5%) of fig extract, however, to optimize the fig extract concentration, the amount of gum arabic and linoleic acid was kept constant. RESULTS: The average droplet size of nanoemulsion was observed in the range of 22.88-37.87 nm, whereas the Fourier Transform Infrared (FTIR) Spectroscopy confirmed the presence of functional groups in the emulsion system. Also, increased ionic concentration significantly (p < 0.05) increased the average droplet size and zeta potential of nanoemulsion during storage. Increased shear rate and temperature unveiled a slight decrease in apparent viscosity of the nanoemulsion. Non-significant (p < 0.05) difference in TBA value confirmed the oxidative stability of the emulsion. Significantly (p < 0.05) higher mineral bioavailability for calcium was observed as compared to iron and zinc. CONCLUSION: Our results manifested improved anti-oxidant activity, mineral bioavailability, and oxidative stability of Fig extract nanoemulsion, suggesting its potential use as a therapeutic alternative.

Phytochemistry, Pharmacology, and Nutraceutical Profile of Carissa Species: An Updated Review.

Carissa, a genus of the Apocynaceae family, consists of evergreen species, such as shrubs as well as small trees that are native to Asia, Africa, and Oceania's subtropical and tropical regions. Most of the Carissa species are traditionally used to treat various diseases, such as chest pain, headaches, gonorrhoea, rheumatism, syphilis, oedema, rabies, stomach pain, hepatitis, cardiac diseases, and asthma. The pharmacological studies on Carissa species revealed its antioxidant, antimicrobial, anticancer, cardioprotective, antipyretic, analgesic, wound healing, anticonvulsant, antiarthritic, adaptogenic, anti-inflammatory, and antidiabetic activities, thus validating its use in indigenous medicine systems. The review article summarised the comprehensive literature available, including morphology, indigenous uses, bioactive composition, nutraceutical, and pharmacological activities of Carissa species. A total of 155 research papers were cited in this review article. The Carissa fruits are rich in dietary fibre, lipids, proteins, carbohydrates, vitamin C, and macro- and micro-elements. A total of 121 compounds (35 polyphenols (flavonoids and phenolic acids), 30 lignans, 41 terpenoids, 7 steroids, 2 coumarins, and 6 cardiac glycosides) have been extracted from C. spinarum, C. carandas, and C. macrocarpa. Among all chemical constituents, lupeol, carissol, naringin, carisssone, scopoletin, carissaeduloside A, D, J, carandinol, sarhamnoloside, carissanol, olivil, carinol, 3ß-hydroxyolean-11-en-28,13ß-oilde, ursolic acid, and carissone are the key bioactive constituents responsible for pharmacological activities of genus Carissa. The gathered ethnopharmacological information in the review will help to understand the therapeutic relevance of Carissa as well as paving a way for further exploration in the discovery of novel plant-based drugs.

The Wonderful Activities of the Genus Mentha: Not Only Antioxidant Properties.

Medicinal plants and their derived compounds have drawn the attention of researchers due to their considerable impact on human health. Among medicinal plants, mint (Mentha species) exhibits multiple health beneficial properties, such as prevention from cancer development and anti-obesity, antimicrobial, anti-inflammatory, anti-diabetic, and cardioprotective effects, as a result of its antioxidant potential, combined with low toxicity and high efficacy. Mentha species are widely used in savory dishes, food, beverages, and confectionary products. Phytochemicals derived from mint also showed anticancer activity against different types of human cancers such as cervix, lung, breast and many others. Mint essential oils show a great cytotoxicity potential, by modulating MAPK and PI3k/Akt pathways; they also induce apoptosis, suppress invasion and migration potential of cancer cells lines along with cell cycle arrest, upregulation of Bax and p53 genes, modulation of TNF, IL-6, IFN-γ, IL-8, and induction of senescence phenotype. Essential oils from mint have also been found to exert antibacterial activities against Bacillus subtilis, Streptococcus aureus, Pseudomonas aeruginosa, and many others. The current review highlights the antimicrobial role of mint-derived compounds and essential oils with a special emphasis on anticancer activities, clinical data and adverse effects displayed by such versatile plants.

Fruit and Vegetable Peels: Utilization of High Value Horticultural Waste in Novel Industrial Applications.

Fruits and vegetables are the highly used food products amongst the horticultural crops. These items are consumed uncooked, nominally cooked or fully cooked, according to their nature and cooking process. With the change in diet habits and rising population, the production, as well as the processing of horticultural crops, has exponentially improved to meet its increasing demand. A large amount of peel waste is generated from fruit and vegetable-based industries and household kitchen and has led to a big nutritional and economic loss and environmental problems. Processing of fruits and vegetables alone generates a significant waste, which amounts to 25-30% of the total product. Most common wastes include pomace, peels, rind and seeds, which are highly rich in valuable bioactive compounds such as carotenoids, enzymes, polyphenols, oils, vitamins and many other compounds. These bioactive compounds show their application in various industries such as food to develop edible films, food industries for probiotics and other industries for valuable products. The utilization of these low-cost waste horticultural wastes for producing the value-added product is a novel step in its sustainable utilization. The present review intends to summarize the different types of waste originating from fruits as well as vegetables peels and highlight their potential in developing edible films, probiotics, nanoparticles, carbon dots, microbial media, biochar and biosorbents.

Review on essential oils, chemical composition, extraction, and utilization of some conifers in Northwestern Himalayas.

Essential oils (EOs) are regarded as alternative therapeutic agents for many diseases. In phytotherapy research areas, it is now well reported that conifers are the rich source of EOs. This review aims to update information on the biological sources and the best extraction processes of the significant constituents along with the traditional and therapeutic properties of the EOs from selected conifers of Himachal Pradesh, Northwestern Himalaya. In the present review, ten conifer species of high values have been selected. Results from several studies suggest that the conifers contain monoterpenes, sesquiterpenes, diterpenes, ketones, alcohols, and esters, which are used in medicines, food products, and cosmetics as well as other commercial and industrial products. Traditionally, the EOs from the conifers have been reported to be used against fever, cough, bronchitis, skin diseases, gastrointestinal disorders, and asthma. The pharmacological studies suggest that these EOs can be used as antirheumatic, antiseptic, antispasmodic, anticancer, anti-inflammatory, antitoxic, aphrodisiac, and astringent agents. It is, therefore, concluded that the EOs from the conifers might be one of the promising tools for the treatment of various diseases. Extensive research is required to ascertain the efficacy of the EOs from unstudied conifers.

NPB001-05 inhibits Bcr-Abl kinase leading to apoptosis of imatinib-resistant cells.

The deregulated activity of the Bcr-Abl tyrosine kinase provides a rational basis for the development therapeutics in all phases of Chronic Myelogenous Leukemia (CML). Although a well studied imatinib therapy has clinical success against CML, resistance to imatinib due to mutations in the kinase domain, especially T315I poses a major problem for the ultimate success of CML therapy by this agent. Herein we describe an NPB001-05, derived from extract of Piper betle leafs, which is highly active in specifically inhibiting Bcr-Abl expressing cells. NPB001-05 inhibited the proliferation of BaF3 cells ectopically expressing wild type Bcr-Abl phenotype and 12 different imatinib-resistant mutations of clinical relevance (average IC50 5.7 microg/ml). Moreover, NPB001-05 was highly inhibitory to wild type P210(Bcr-Abl) and P210(Bcr-Abl-T315I) kinase activity and abrogated the autophosphorylating enzyme in time- and dose- dependent manner. NPB001-05 was non-toxic on normal cells, but was inhibitory to CML patient derived peripheral blood mononuclear cells. Treatment with NPB001-05 caused apoptosis induction and G0G1 cell cycle arrest in both Bcr-Abl wild type and T315I mutant cell lines.

Antitumor activity of NPB001-05, an orally active inhibitor of Bcr-Abl tyrosine kinase.

Scientists are constantly searching for phytochemical compounds with anti-cancer activity. In this study, activity of plant extract NPB001-05 from Piper betle was tested on human chronic myelogenous leukemia (CML) xenograft models. NPB001-05 was active when dosed orally (500 mg/kg) once or twice a day in xenograft tumor models. NPB001-05 showed activity to T315I tumor xenograft, where imatinib failed to show antitumor activity. NPB001-05 showed no relevant toxicity in animal models during 2 weeks exposure to drug. Responsive tumor showed inhibition of tyrosine kinase activity with lowered Bcr-Abl protein levels and increased apoptosis. Microarray based transcription profiling studies demonstrated that both imatinib and NPB001-05 dysregulated imatinib- responsive genes. NPB001-05 showed additional genes selectively dysregulated from ER stress, PI3K/AKT, MAPK pathways. Additionally, we tested gene expression of PI3K, AKT1, JUN, CASP3 and DDIT3 in K562, BaF3P210(BCR-ABL) and BaF3 P210(BCR-ABLT315I) cell line treated for 6- and 12- hours with NPB001-05 and imatinib. The data indicates that NPB001-05 mediated cell death in K562 affects the function of ER stress. NPB001-05 shows antitumor activity with favorable toxicity profile.

Oral bioavailability, efficacy and gastric tolerability of P2026, a novel nitric oxide-releasing diclofenac in rat.

The present study was designed to evaluate, P2026 [(2-((2-(nitrooxy)ethyl)disulfanyl)ethyl 2-(2-(2,6-dichlorophenylamino)phenyl)acetate)], a novel NO (nitric oxide) donor prodrug of diclofenac for its ability to release NO and diclofenac, and whether P2026 provides advantage of improved activity/gastric tolerability over diclofenac. Oral bioavailability of P2026 was estimated from plasma concentration of diclofenac and nitrate/nitrite (NOx). Anti-inflammatory activity was evaluated in three different models of inflammation: acute (carrageenan-induced paw oedema), chronic (adjuvant-induced arthritis), and systemic (lipopolysaccharide-induced endotoxic shock). Gastric tolerability was evaluated from compound's propensity to cause gastric ulcers. P2026 exhibited dose-dependent diclofenac and NOx release. Similar to diclofenac, P2026 showed potent anti-inflammatory activity in acute and chronic model, whereas it improved activity in systemic model. Both diclofenac and P2026 inhibited gastric prostaglandin, but only diclofenac produced dose-dependent haemorrhagic ulcers. Thus, the results suggest that coupling of NO and diclofenac contribute to improved gastric tolerability while retaining the anti-inflammatory properties of diclofenac.

Novel leads from Heliotropium ovalifolium, 4,7,8-trimethoxy-naphthalene-2-carboxylic acid and 6-hydroxy-5,7-dimethoxy-naphthalene-2-carbaldehyde show specific IL-6 inhibitory activity in THP-1 cells and primary human monocytes.

From our screening program, we identified the anti-inflammatory effects of the extracts of Heliotropium ovalifolium in its ability to inhibit specific cytokines. The H. ovalifolium extract was found to be moderately active with an IC(50) equaling 10 microg/ml for inhibition of interleukin-6 (IL-6) in a human monocytic cell line. Interleukin-6 is a pleiotropic cytokine with implications in the regulation of the immune response, inflammation and hematopoiesis. This prompted us to examine and identify the active molecules that are responsible for the bioactivity in THP-1 cells. Bioassay guided fractionation identified two compounds 4,7,8-trimethoxy-naphthalene-2-carboxylic acid and 6-hydroxy-5,7-dimethoxy-naphthalene-2-carbaldehyde with an IC(50) of 2.4 and 2.0 microM for IL-6 inhibition and an IC(50) of 15.6 and 7.0 microM for tumor necrosis factor-alpha (TNF-alpha) inhibition in THP-1 cells. The protein expression data were supported by the inhibitory effect on mRNA gene expression. The compounds isolated from H. ovalifolium were also non-toxic in human peripheral blood monocytes from normal donors and the activity profile was similar to that obtained on THP-1 cells. Thus, we believe that these scaffolds may be of interest to develop leads for treating rheumatoid arthritis, psoriasis, ulcerative colitis, Crohn's disease and other inflammatory disorders. However, more detailed investigations need to be carried out to explain the efficacy of these compounds as drugs.