The potential therapeutic effect of Carica papaya leaf juice has attracted wide interest from the public and scientists in relieving dengue related manifestations. Currently, there is a lack of evaluated evidence on its juice form. Therefore, this scoping review aims to critically appraise the available scientific evidence related to the efficacy of C. papaya leaf juice in dengue. A systematic search was performed using predetermined keywords on two electronic databases (PubMed and Google Scholar). Searched results were identified, screened and appraised to establish the association between C. papaya and alleviating dengue associated conditions. A total of 28 articles (ethnobotanical information: three, in vitro studies: three, ex vivo studies: one, in vivo study: 13, clinical studies: 10) were included for descriptive analysis, which covered study characteristics, juice preparation/formulations, study outcomes, and toxicity findings. Other than larvicidal activity, this review also reveals two medicinal potentials of C. papaya leaf juice on dengue infection, namely anti-thrombocytopenic and immunomodulatory effects. C. papaya leaf juice has the potential to be a new drug candidate against dengue disease safely and effectively.

Eurycoma longifolia is one of the commonly consumed herbal preparations and its major chemical compound, eurycomanone, has been described to have antimalarial, antipyretic, aphrodisiac, and cytotoxic activities. Today, the consumption of E. longifolia is popular through the incorporation of its extract in food items, most frequently in drinks such as tea and coffee. In the current study, the characterisation of the physicochemical and pharmacokinetic (PK) attributes of eurycomanone were conducted via a series of in vitro and in vivo studies in rats and mice. The solubility and chemical stability of eurycomanone under the conditions of the gastrointestinal tract environment were determined. The permeability of eurycomanone was investigated by determining its distribution coefficient in aqueous and organic environments and its permeability using the parallel artificial membrane permeability assay system and Caco-2 cultured cells. Eurycomanone’s stability in plasma and its protein-binding ability were measured by using an equilibrium dialysis method. Its stability in liver microsomes across species (mice, rat, dog, monkey, and human) and rat liver hepatocytes was also investigated. Along with the PK evaluations of eurycomanone in mice and rats, the PK parameters for the Malaysian Standard (MS: 2409:201) standardised water extract of E. longifolia were also evaluated in rats. Both rodent models showed that eurycomanone in both the compound form and extract form had a half-life of 0.30 h. The differences in the bioavailability of eurycomanone in the compound form between the rats (11.8%) and mice (54.9%) suggests that the PK parameters cannot be directly extrapolated to humans. The results also suggest that eurycomanone is not readily absorbed across biological membranes. However, once absorbed, the compound is not easily metabolised (is stable), hence retaining its bioactive properties, which may be responsible for the various reported biological activities.

Coffee infused with the additive Eurycoma longifolia, also known as Tongkat ali (TA), has become widely available in the Malaysian market. Safety evaluations for consumption of the products have been called for due to the herbal addition. This study investigates the acute, subacute and chronic effects of a commercial TA coffee in Sprague Dawley rats when given in a single, repeated and prolonged dosage. The dosages of 0.005, 0.05, 0.30 and 2 g/kg body weight (BW) were used in the acute study and 0.14, 0.29 and 1 g/kg BW were used in the repeated dose studies. The in-life parameters measured were food and water intake, body weight and clinical observations. Blood were collected for hematology and clinical biochemistry analyses. All animals were subjected to full necropsies. Non-toxicity-related changes were observed in the food and water consumption parameters. Body weight showed normal increments and none of the animals had any clinical signs of toxicity. Microscopically assessed organ tissues did not reveal any abnormalities. There was significant decrease of platelet count in all the chronic study male treated groups. Significant elevation of renal profile parameters in both gender groups given 0.29 g/kg BW, along with liver and lipid profile elevation in some female groups of the chronic study were noted. No dose-dependent relationship was apparent in the dosage range tested, though these changes may suggest an initial safety indication to the TA coffee. The study concludes that the no observed adverse effect level (NOAEL) for this commercial TA coffee was 1 g/kg BW.

A combined polyherbal formulation containing tongkat ali (Eurycoma longifolia) and kacip fatimah (Labisia pumila) aqueous extracts was evaluated for its safety aspect. A repeated dose 28-day toxicity study using Wistar rats was conducted where the polyherbal formulation was administered at doses 125, 500 and 2000 mg/kg body weight to male and female treatment groups daily via oral gavage, with rats receiving only water as the control group. In-life parameters measured include monitoring of food and water consumption and clinical and functional observations. On day 29, blood was collected for haematological and biochemical analysis. The rats were necropsied and the organs were collected for histopathological examination. This study showed that the combined formulation did not induce any significant toxicity effect at any dose level in terms of morbidity, mortality, behaviour, functional observation, body weight, food and water consumption, whole blood haematology and serum biochemistry. However, there were some microscopic changes in the histopathological examinations of some organs given 2000 mg/kg body weight, which may suggest an early response to the polyherbal formulation. From this study, the no observed adverse effect level is estimated to be more than 500 mg/kg body weight but not exceeding 2000 mg/kg body weight. The observed effects at the highest dose indicate the need for further study of longer dosing duration.

Background Immunomodulatory properties of Carica papaya leaf have been previously highlighted in vitro and in vivo. However, repeated dose pre-treatment effect of C. papaya leaf juice and its compounds in inflammatory model is scarce in the literature. Therefore, this study aims to evaluate the anti-inflammatory effects of freeze-dried C. papaya leaf juice (FD-CPLJ) and citropten pre-administrations in a rat model of carrageenan-induced inflammation. Methods Rats in four treatment groups were pre-administered with distilled water (negative control), FD-CPLJ (2,000 mg/kg body weight (BW)), citropten (20 mg/kg BW) and indomethacin as a positive control (10 mg/kg BW) respectively as a single dose for five consecutive days. On Day 5, inflammation was induced by carrageenan injection to the sub-plantar region of the rat’s left hind paw in the treatment groups. Non-carrageenan stimulated groups were pre-administered with distilled water, FD-CPLJ and citropten. Paw volumes were measured using digital water plethysmometer at certain time intervals (one, three, six and 24 hours) post-induction. The paw tissues were harvested and the expression levels of NOS3, CCL2 and TNF genes were quantitated by quantitative reverse transcription PCR. The expression levels of MCP-1 and TNF-α proteins were determined by Western blot analysis. Results Paw volume evaluation shows some reduction in the first and third hour post-induction in groups treated with FD-CPLJ and citropten. The TNF-α expression was slightly downregulated in the citropten pre-treated rats but not in the FD-CPLJ pre-treated rats. The expression of NOS3 gene and the expression of MCP-1 protein was downregulated in FD-CPLJ and citropten pre-treated rats. In contrast to MCP-1 result, the expression of CCL-2 was upregulated in the FD-CPLJ pre-treated rats. Conclusion Citropten administration shows anti-inflammatory potential which warrants further investigation at different dosages to further elicit its potential. The contrary results in the gene and protein level for FD-CPLJ-treated group requires further investigation into its mechanism of action.

In vivo real-time detection of pharmacokinetics of systemically administrated drugs in microenvironments advance pharmacology and clinical medicine. Here, we describe an analytical platform targeting dermal interstitial fluid with a needle-type microsensor of a boron-doped diamond (BDD) electrode. A test analyte was doxorubicin, an anticancer drug that induces acute cardiotoxicity. Upon intravenous bolus injection of doxorubicin to anesthetized rats, a BDD microsensor inserted into the dermis unexpectedly detected two sequential phases of the concentration change: a first component elicited in several minutes with fast kinetics and a sharp peak, and a subsequent second response maximized from 15 min to 1 h with slow kinetics. Furthermore, the BDD microsensing system was combined with electrocardiography, visualizing a relationship between doxorubicin's behavior in the skin and induction of QT-interval prolongation. Our approach may clarify detailed local pharmacokinetics and its correlation with pharmacodynamics and provide a prototype wearable device for next-generation drug monitoring.