Carica Papaya Leaf Extract to Improve Chemotherapy-Induced Thrombocytopenia: A Phase III Triple-Blinded, Randomized, Placebo-Controlled, Multicentric Trial.

12008 Background: There is a lack of approved therapeutic options to ameliorate CIT in patients with solid tumors receiving chemotherapy. Carica papaya leaf extract (CPLE) is known to increase platelet counts (PC) in certain infections. Methods: The PACT study is a triple blinded randomized phase III study conducted in two academic centres in patients with solid tumors receiving chemotherapy and developing at least grade 2 or grade 3 CIT (platelet counts < 75,000 x 10^9/ liter and > 25,000 x 10^9/liter). Patients were randomized 2:1 to CPLE arm (capsule CPLE per oral 1100mg three times daily) or placebo arm ( capsule per oral three times daily), which was continued till PC improved to greater than > 75,000 x 10^9/ liter, requirement for platelet transfusions or D+10 post intervention. Baseline PC were graded as per the Common Terminology Criteria for Adverse Events (CTCAE) grades. The primary endpoint of the study was to evaluate whether CPLE improves PC significantly faster (as assessed on D+4 of intervention) and above 75,000 x 10e9 /L as compared to placebo (spontaneous recovery of platelets). To achieve 80% power to detect a difference between the group proportions of 0.25 (50% to 75%) with an alpha of 0.05, 219 patients were required (146 in CPLE group and 73 in placebo group), assuming 10% loss to follow-up rates. Results: Between March 2020 and October 2024, 219 patients were randomized, of whom 198 patients (CPLE arm: 129; placebo arm: 69) were analysed for outcomes. All the baseline parameters were equally distributed in both the arms (2:1) except the proportion of patients in the placebo and the experimental arms had equal number of patients with grade 3 thrombocytopenia (17/129 vs 17/69; p = 0.049). The most common chemotherapeutic regimens were oxaliplatin based (37%) and carboplatin based (27%). The primary outcome of increasing PC > 75,000 x 10^9/ liter at D+4 was significantly improved by CPLE (83/129, 64% vs 33/69, 48%; p = 0.034) as compared to placebo. This improvement was significantly quicker in subgroups including three weekly regimen vs weekly/biweekly, palliative intent vs. curative, > 2 cycles of chemotherapy (< = 2 cycles vs. > 2 cycles) and body surface area (BSA) < 1.6 vs. more. There were no grade 3 or grade 4 treatment related adverse events associated with CPLE. Conclusions: CPLE is the first therapeutic intervention that appears to improve grade 2 and grade 3 chemotherapy induced thrombocytopenia faster and to a greater extent than placebo in this phase III randomized trial. It should be used as a secondary prophylaxis to maintain the chemotherapy intesnity. There were no major safety concerns with the use of CPLE. Clinical trial information: CTRI/2019/08/020987 .

Background: Chemotherapy-induced thrombocytopenia (CIT) is a detrimental side effect of cancer chemotherapy. Several pharmacologic agents have been evaluated, but their thrombopoietic activity is modest and often associated with unfavorable side effects. Carica papaya leaf extract (CPLE) is shown to overexpress ALOX-12 and platelet-activating factor receptor gene which stimulates the megakaryopoiesis. Aims and Objectives: To evaluate the efficacy and safety of CPLE in CIT. Materials and Methods: A total of 40 patients diagnosed to have CIT were randomized to two groups of 20 subjects each. Interventional group received CPLE 1100 mg TID for 7 days post chemotherapy day 7-14 and non-interventional group did not receive any active treatment. Complete hemogram was done at post chemotherapy day 7, 10, 13, and 16. Patients were followed up for 28 days for adverse effects. Results: The mean platelet count in interventional group was 49.700 ± 12.649/mm3, which increased to 55.350 ± 15.131/mm3 (P > 0.05), 147.540 ± 54.359/mm3 (P < 0.01), and 200.585 ± 51.893/mm3 (P < 0.01) on post chemotherapy day 7, 10, 13 and 16, respectively. The mean platelet count in non-interventional group was 47.361 ± 13.110/mm3, 42.580 ± 12.108/mm3, 46.367 ± 14.776/mm3, and 54.238 ± 16.053/mm3 on post chemotherapy day 7, 10, 13, and 16, respectively, with no statistically significant improvement (ANOVA, P). Increment in white blood cell from baseline to day 7 was statistically significant (P < 0.001) as compared to control. Conclusion: CPLE statistically increased platelet count by day 13 of post chemotherapy along with other hematological parameters. Hence, CPLE could be a viable option for treatment of CIT.

Severe thrombocytopenia in dengue often prompts platelet transfusion primarily to reduce bleeding risk. In India, about 11–43% of dengue patients report receiving platelet transfusions which is considered scarce and expensive especially in resource limited settings. Herein, we evaluated the efficacy and safety of Carica papaya leaf extract (CPLE) in the management of severe thrombocytopenia (≤30,000/μL) in dengue infection. 51 laboratory confirmed adult dengue patients with platelet counts ≤30,000/μL were randomly assigned to either treatment (n = 26) or placebo (n = 24) group. By day 3, CPLE treated patients reported significantly (p = 0.007) increased platelet counts (482%± 284) compared to placebo (331%±370) group. In the treatment group, fewer patients received platelet transfusions (1/26 v/s 2/24) and their median time for platelets to recover to ≥ 50,000/μL was 2 days (IQR 2–3) compared to 3 days (IQR 2–4) in placebo. Overall, CPLE was safe and well tolerated with no significant decrease in mean hospitalization days. Plasma cytokine profiling revealed that by day 3, mean percent increase in TNFα and IFNγ levels in treatment group was less compared to that observed in placebos; (TNFα: 58.6% v/s 127.5%; p = 0.25 and IFNγ: 1.93% v/s 62.6% for; p = 0.12). While a mean percent increase in IL-6 levels occurred in placebos (15.92%±29.93%) by day 3, a decrease was noted in CPLE group (12.95%±21.75%; p = 0.0232). Inversely, CPLE treated patients reported a mean percent increase compared to placebo by day 3 (143% ±115.7% v/s 12.03%± 48.4%; p = 0.006). Further, by day 3, a faster clearance kinetics of viral NS1 antigenemia occurred–mean NS1 titers in treatment group decreased to 97.3% compared to 88% in placebos (p = 0.023). This study demonstrates safety and efficacy of CPLE in increasing platelet counts in severe thrombocytopenia in dengue infections. A possible immunomodulatory and antiviral activity may be attributed to CPLE treatment. These findings merit validation in larger prospective studies.Trial registrationName of the registry: Clinical Trials Registry—India (CTRI)Registration No.: CTRI-REF/2017/02/013314

The human pathogen, Salmonella, constitutes a significant source of human infections through poultry products. Salmonella is a bacteria that exists in both domestic and wild animals, and there are need to subdue its strength since its remains a significant source of food borne infection worldwide. The aims of these work are to investigate the antimicrobial susceptibility of Salmonella when exposed to natural organic substances, specifically carica papaya (pawpaw) leaf extract, and to bring to the understanding of the medicinal and vital importance of pawpaw leaf. Household cockroaches, known as carrier of salmonella, were used as the as source of bacterial isolation. To do this, isolation of Salmonella were obtained from the bodies of thirty household cockroaches samples by immersion in peptone water, followed by a serial dilution was performed in order to reduce the microbial load, which is aseptically cultured in a sterile disposable petri dish containing Xylose lysine deoxycholate agar to selectively grow Salmonella colonies. The distilled water and ethanol were used as solvent in producing the carica papaya leaf extract in varying concentration to perform an antimicrobial susceptibility tests. In conjunction, Antimicrobial susceptibility tests were conducted using the agar well diffusion method to evaluate the inhibitory effects of the extracts on the Salmonella isolates. The results indicated that pawpaw leaf extracts possess bioactive compound capable of inhibiting Salmonella growth, with ethanol extracts showing higher antimicrobial activity compared to aqueous extracts. However, limitations of this research were explored, and we considered ways to improve its accuracy. This research has implications for food safety, human well-being, and the development of natural antimicrobial agents and future studies should focus on optimizing extraction method and identifying specific active compounds to enhance its efficacy.

Corrosion poses significant economic, environmental, and safety challenges in the oil and gas industry, particularly affecting pipeline integrity and longevity. Traditional synthetic corrosion inhibitors, while effective, often incur high costs and environmental drawbacks. Traditional synthetic inhibitors, such as sodium silicate have been used traditionally to manage corrosion but are risky to the environment and health. This study is aimed at evaluating the effectiveness and potential of Carica papaya leaves extract as a natural/green corrosion inhibitor for mild steel in Hydrochloric acid (HCl) medium and compares it to a synthetic inhibitor Sodium silicate (Na2SiO3) in simulated corrosive environments. The Carica papaya leaf extract (CPLE) was obtained using a Soxhlet apparatus with ethanol as the solvent for efficient extraction of bioactive compounds. Corrosion inhibition efficiency was determined through the weight loss method for a period of 15 days by exposing mild steel specimens to the corrosive medium that mimicked the environment and conditions of oil pipelines. Inhibition efficiency of the pawpaw leaf extract was compared to that of sodium silicate, which is a synthetic inhibitor. Some important parameters that were determined included corrosion rate, inhibition efficiency, and the effect of varying inhibitor concentrations (i.e., 0.3 g/L, 0.6 g/L, and 0.9 g/L). It was found that Carica papaya leaf extract (CPLE) demonstrates an improvement in inhibition efficiency with increasing concentrations but diminishes with prolonged immersion time. A maximal inhibition efficiency of 63.64%, 50.00%, 45.45%, 77.27% and 63.64% was observed for Carica papaya leaf extract (CPLE) at the concentrations of 0.3g/L, 0.6g/L, 0.9g/L, 1.2g/L, and 1.5g/L respectively, contrasting with sodium silicate's (Na2SiO3) peak efficiency of 45.45%, 40.00%, 27.27%, 63.64%, and 54.55% at 0.3g/L, 0.6g/L, 0.9g/L, 1.2g/L, and 1.5g/L concentrations respectively. Over time, for Carica papaya leaf extract (CPLE) demonstrated impressive durability; even after two weeks, it inhibited with a notable 55.00%, 50.00%, 46.97%, 74.48%, and 56.82% efficiency at the concentrations of 0.3g/L, 0.6g/L, 0.9g/L, 1.2g/L, and 1.5g/L respectively. In sharp contrast, sodium silicate (Na2SiO3) dwindled to 42.86%, 42.42%, 36.36%, 53.23%, and 57.14% efficiency at the concentrations of 0.3g/L, 0.6g/L, 0.9g/L, 1.2g/L, and 1.5g/L respectively by the end of the experiment. Results showed that the Carica papaya leaf extract (CPLE) successfully reduced the corrosion rate with maximum inhibition efficiency at high concentrations. Conversely, sodium silicate was found to be somewhat less efficient under the same testing conditions. The research also noted that inhibition efficiency reduced with longer immersion time, indicating the necessity for regular reapplication or more advanced inhibitor chemicals. Findings indicate that Carica papaya leaves extract exhibit significant inhibition efficiencies, offering environmentally friendly and cost-effective alternatives to synthetic inhibitors. This research emphasizes the potential for the application of Carica papaya leaf extract (CPLE) as a green and sustainable alternative for corrosion control in oil pipelines. By harnessing bio-based inhibitors, industries can reduce the application of toxic chemicals without affecting the anti-corrosive activity. This study underscores the potential of utilizing plant-based extracts in sustainable corrosion management strategies within the oil and gas sector. Future studies should involve the isolation of active constituents of the extract, optimizing the dosage, and assessing its performance and activity in different corrosive media.

Papaya leaf water extract (Carica papaya L) contains flavonoids, tannins, saponins, and beta-carotene, which are herbal feed additives for ducks. This study aims to examine the benefits of papaya leaf water extract through drinking water in improving the blood lipid profile of male Bali ducks. This study was conducted in Kerambitan, Tabanan, bali, for 10 weeks. This study used a completely randomized design (CRD) with four treatments and five replicates, each experimental unit using five male Bali ducks weighing 46.04±2.21 grams. The four treatments were drinking water without papaya leaf extract (A); drinking water with 2% papaya leaf extract (B); drinking water with 4% papaya leaf extract (C); and drinking water with 6% papaya leaf extract (D). The variables measured were total cholesterol, triglycerides, HDL, and LDL. The results obtained from this study were that total cholesterol, triglycerides, HDL, and LDL in the four treatments were not statistically significant (P&gt;0.05). The conclusion from the results of this study is that the administration of papaya leaf extract at levels of 2%, 4%, and 6% had no effect on the blood lipid profile of Bali ducks.

Bacterial resistance to antibiotic has made the reduction in the use of antibiotic a concern in animal production. The restriction of antibiotic application in animal production can be achieved if the antimicrobial strategy is available. Papaya leaf extract has some antibacterial properties that make it is potential to be used as a substitute for commercial antibiotic. This study was aimed at assessing the efficacy and potential of papaya leaf extract inclusion in drinking water in controlling pathogenic bacteria and improving the production efficiency and feed conversion ratio (FCR) of layer quails. The study was conducted from 24 August to 20 September 2016 at the poultry farm of Department of Animal Husbandry, Djuanda University, Bogor. One-hundred layer quails were allocated into 4 treatments and 3 replicates in a completely randomized design. The treatments consisted of five levels of papaya leaf extract inclusions in drinking water , namely drinking water + commercial antibiotic of 0.5 g/liter water (R1), drinking water + papaya leaf extract of 10 ml/liter water (R2), drinking water + papaya leaf extract of 20 ml/liter water (R3), and drinking water + papaya leaf extract of 30 ml/liter water (R4). Data were subjected to an analysis of variance and a Duncan test. Results showed that the inclusion of papaya leaf extract in drinking water gave significant effects on egg mass, egg production efficiency, FCR, egg quality index, and egg shell thickness but not on feed intake, egg weight, and mortality rate. It was concluded that papaya leaf extract produced by a boiling method could be used as a substitute for synthetic antibiotic. Key words: Papaya leaf extract, production efficiency, feed conversion, layer quail.

Influenza outbreaks in aquaculture, coupled with the growing resistance to chemical antiparasitics,underscore the urgent need for safer botanical alternatives. Infestations for Argulus spp. lead to substantial stress and mortality in ornamental fish, yet effective and low-risk treatments remain scrace. Therrefore, this study evaluated the effectiveness of papaya (Carica papaya) leaf extract at different immersion durations in controlling Argulus infestation in comet fish (Carassius auratus). Sixty fish (4.94 ± 0.28 cm; 1.32 ± 0.22 g) were randomly distributed into 12 aquaria and infected with 120 Argulus spp. parasites. The experiment followed a completely randomized design with four immersion durations, 0, 45, 60, and 75 minutes, each replicated three times, using papaya leaf extract prepared by infusion at 14 mL/L. Immersion in the extract did not significantly affect fish survival, which remained high across treatments (93.33 ± 11.55% in the control and 100.00 ± 0.00% in all treated groups). However, Argulus detachment increased with immersion time, reaching 60.00 ± 10.00% at 75 minutes. Exposed parasites initially showed vigorous movement that weakened over time, eventually leading to detachment and immobility. These results indicate that a 75-minute immersion in 14 mL/L papaya leaf extract effectively induces parasite detachment and alleviates clinical symptoms without compromising fish survival, supporting its potential as a safe botanical antiparasitic for ornamental fish culture.

The purpose of this research was to analyze the effect of papaya (Carica papaya L) leaf extract and flour on a mixed feed made from elephant grass (Pennisetum purpureum) and pollard(Triticum aestivum) on gas production, in vitro digestibility dry matter (DDM), digestibility organic matter (DOM), and the value of energy. The materials used in this research was mixed feed consisting of grass, pollard and papaya leafs as feed supplement. The method used is a Randomized Block Design with 5 treatments and 3 replications. P0 was control feed, P1 was P0 + 2% of papaya leaf flour, P2 was P0 + 4% of papaya leaf flour, P3 was P0 + 2% papaya leaf extract, and P4 was P0 + 4% papaya leaf extract. Duncan's Multiple Range Test was carried out if there found any difference in treatments. The result of the research shows that papaya leaf extract and flour did not give significant influence (P&gt; 0,05) for gas production, in vitro digestibility dry matter and digestibility organic matter , and energy value , but gave significant influence (P &lt;0,01) for net energy. The addition of 4% papaya leaf extract gave the best results for gas production value (value b = 133,16 ml/500 mgDM and value c=0,064 ml/h), digestibility dry matter and digestibility organic value (DDM = 63,57 % and DOM = 65,49 %), metabolizable energy 8,47 MJ/KgDM value and net energy 6,29 MJ/KgDM value. Those can be concluded that addition of 2% and 4% papaya leaf extract and papaya flour can’t increase gas production, in vitro digestibility of dry matter and organic matter but increases net energy value. Suggestions from this research was that feeding a mixture of grass and pollard added with 4% of papaya leaf flour should be conducted to determine the level of productivity. Keywords : Papaya leaf, gas production, in vitro digestibility, energy

Efficacy and Safety of Extended Use of Romiplostim Treatment for Chemotherapy-Induced Thrombocytopenia

Diabetes is a chronic metabolic disorder identified by raised blood glucose levels due to suppressed insulin production. Heparin, a familiar anticoagulant, has been shown to hinder the insulin channeling and increase blood glucose levels. Carica papaya Leaf Extract (CPLE) is attracting attention as a potential natural therapeutic agent for managing high blood glucose levels in patients with diabetes. This study investigates the effects of CPLE and Heparin on body weight, diet consumption, and blood glucose levels in experimental Wistar rats. This preliminary pilot study was conducted for 1 month, from November 2023 to December 2023, at the Animal House Facility of the Department of Physiology at the University of Karachi. A total of 20 male Wistar rats were taken and randomly divided into four groups (n=5). Control, Heparin-induced, CPLE-induced, and a combination Heparin and CPLE-induced group. Heparin was administered intravenously at 0.1 ml/100 g body weight, whereas CPLE was administered orally at 2000 mg/kg body weight. Diet intake and body weight were observed during the trial. Blood glucose levels were estimated at the end of the study. The Kruskal-Wallis test was used to compare the medians across groups. P-value &lt;0.05 was considered significant. The study found a notable decline in dietary intake (p&lt;0.001) and body weight (p&lt;0.001) in all treatment groups. Blood glucose levels were elevated in all treatment groups except the CPLE-treated group, where they decreased from baseline (p&lt;0.001). In conclusion, CPLE and Heparin may affect blood glucose levels in Wistar rats. CPLE may lower blood glucose levels, while Heparin raises them.

Thromboelastographic (TEG) Characterization of Patients with Hematologic Malignancy and Chemotherapy Induced Thrombocytopenia (CIT).

This research aims to determine the effect of giving papaya leaf extract on the growth of gourami fish (Osphronemus goramy). This research was carried out in May - June 2021 in Bengkulu City for 60 days. The test fish used were gourami fish measuring 6-8 cm. The method used was a Completely Randomized Design (CRD) with 4 treatments, namely P1: Without papaya leaf extract (control), P2: Dose of papaya leaf extract (10%), P3: Dose of papaya leaf extract (20%), P4: Dose of extract papaya leaves (30%). Each treatment was repeated six times. The research data was analyzed using analysis of variance then continued with further tests for BNT 5% and 1%. The research results of adding papaya leaf extract to the growth of gourami fish for 60 days had a very significant effect on the parameters of absolute weight, absolute length, feed conversion and feed efficiency and had no effect on the survival of the gourami fish. The best treatment for the growth of gourami fish is an additional dose of 20% - 30% papaya leaf extract.

Corrosion is a complicated problem in everyday life. Corrosion causes many losses because it reduces the life span of metal-based goods or buildings. One solution is to use organic corrosion inhibitors. Organic corrosion inhibitors are an alternative choice because they are more environmentally friendly. Heteroatomic organic compounds containing nitrogen, oxygen, or sulfur in molecules such as those found in MSG, papaya leaves and aloe vera can be used as organic corrosion inhibitors, because they can be well adsorbed on metal surfaces. Amino acids such as glutamic acid which have two carboxylic groups and one amine group are expected to be able to inhibit corrosion by adsorbing metal (iron) surfaces. This study aims to determine the use of MSG, aloe vera and papaya leaves as alternative materials for organic corrosion inhibitors. The results showed that the rust level using MSG solution was 8.33%, aloe vera extract was 9.09%, papaya leaf extract was 8%, and the container with a mixture of aloe vera extract, papaya leaf extract and MSG was added 4.35 %. This shows that aloe vera extract, papaya leaf extract and MSG can be used as an alternative to organic corrosion inhibitors.

Infectious diseases are one of the diseases that have suffered by many Indonesian people for a long time. S. aureus bacteria is the cause of pyogenic infections. Basil plants (Ocymum x africanum L.) and papaya plants (Carica papaya L.) can be used as antibacterial. This study aims to determine the antibacterial activity of the combination of basil and papaya leaf extracts against S. aureus bacteria. Using the Experimental Method with a combination of extract concentrations, namely K1 (0+100%), K2 (20%+80%), K3 (40%+60%), K4 (50%+50%), K5 (60%+40% ), K6 (80%+20%), K7 (100%+0%), K(-) aquadest, K(+) Oxfloxacin, followed by a test for S. aureus bacteria using the well method. The test results were analyzed using One Way Annova. with sig value (0.000) &lt; p-value (0.05) followed by Tukey's further test which showed the combination of concentrations showed significant differences between the test groups. From this explanation, it can be concluded that the combination of basil leaf extract and papaya leaf extract can increase the inhibition zone, the largest inhibition zone is in K4 (50% basil leaf extract + 50% papaya leaf extract) the inhibitory response that appears 19.69 mm belongs to the strong category. inhibit the growth of S. aureus bacteria. Keywords: Antibacterial, basil leaf, papaya leaf, Staphylococcus aureus.