A Review of Bioactive Compounds and Antioxidant Activity Properties of Piper Species.

Antioxidants are compounds that are able to inhibit the negative effects that come from free radicals. The phenomenon of imbalanced antioxidant production and the accumulation of free radicals in cells and tissues can cause oxidative stress. Excessive free radicals that enter the body cannot be warded off by endogenous antioxidant compounds so that the required antioxidant compounds can come from the outside, which helps in the performance of endogenous antioxidants. Antioxidants that come from outside consist of synthetic and natural antioxidants; however, synthetic antioxidants are not an option because they have toxic and carcinogenic effects. Therefore, the use of natural ingredients is an alternative method that is needed to create a new natural antioxidant compound. Piper species are being considered as possible medicinal plants for the development of new sources of antioxidants. Several studies have been carried out starting from the extract levels, fractions, and compounds of the Piper species, which showed good antioxidant activity. Currently, some of these plants are being used as ingredients in traditional medicines to treat allergies, toothaches, and coughs. This review examines the distribution, botanical data, pharmacology, especially antioxidant activity, and the compounds contained in five Piper species, namely Piper amalago L., Piper betle L., Piper hispidum Sw., Piper longum L., and Piper umbellatum L.

Evaluation of the safety of ethanolic extract from Piper amalago L. (Piperaceae) leaves in vivo: Subacute toxicity and genotoxicity studies.

Piper amalago L. (Piperaceae) is traditionally used due to its anti-inflammatory, analgesic, diuretic, and antiparasitic properties. However, few studies have focused on its adverse effects, compromising its safe use. This study evaluated the toxicological safety of ethanolic extract from Piper amalago leaves (EEPA), through subacute toxicity and genotoxicity assays in rodents. In subacute toxicity, 100, 200 or 300 mg/kg of EEPA were tested in female Wistar rats, by gavage, for 28 days. For genotoxicity test, female Swiss mice were orally treated with 17.5, 175 or 1750 mg/kg of EEPA and the comet, micronucleus, and splenic phagocytic assays were evaluated. In subacute toxicity, the extract induced an increase in the food and water intakes, as well as in the liver absolute weight, and in the heart and kidney relative weights. EEPA also provoked alterations in histopathological analysis of liver and in hemato-biochemical parameters, evidenced by a decrease in hematocrit levels and albumin levels, and an increase in the number of platelets and in alkaline phosphatase and cholesterol levels. However, EEPA did not presented genotoxic nor mutagenic properties. EEPA showed hemato-biochemical toxicity profile in rats and should be used with caution, especially when for prolonged period.

The wound healing effect of aqueous extract from Piper amalago L. in diabetic patient.

Diabetes patients present a complex healing process due to several factors directly linked to their pathology. The use of medicinal plants that aid in tissue repair can bring great benefits to such individuals. This case report describes how the topical application of the aqueous extract produced from the leaves of Piper amalago L. was used to aid the healing of a lacerated wound in the left thumb of a patient with type 2 diabetes mellitus. The aqueous extract of the leaves of Piper amalago L. was prepared in boiling water. During the boiling process the dried leaves were submerged in the boiling water and left for five min. The injured thumb was submerged in the solution and the leaves were placed on the injury. The action of the aqueous extract obtained from the leaves of P. amalago was shown to be promising in the healing of a wound in a patient with type 2 diabetes mellitus. The topical application of the aqueous extract produced from the leaves of P. amalago assisted in the healing of a lacerated wound in the left thumb of a patient with type 2 diabetes mellitus over a period of 15 days.

Chemical characterisation of Piper amalago (Piperaceae) essential oil by comprehensive two-dimensional gas chromatography coupled with rapid-scanning quadrupole mass spectrometry (GC×GC/qMS) and their antilithiasic activity and acute toxicity.

INTRODUCTION: Piper amalago has a distribution from Mexico to Brazil; their aerial parts have been used in folk medicine to treat diuretic and kidney diseases. OBJECTIVE: The purpose of this study was to obtain a deeper understanding of the chemical composition of essential oils (EOs) extracted from both the leaves and stems of P. amalago, compare them, and evaluate their antilithiasic activity and acute toxicity. METHODOLOGY: Extraction was performed by hydrodistillation, whereas chemical characterisation by two-dimensional gas chromatography coupled with rapid-scanning quadrupole mass spectrometry (GC×GC/qMS). The antilithiasic activity was evaluated by the effect of the EOs on calcium oxalate crystallisation in vitro. The turbidity index and the number of crystals formed were determined and used as an estimative of the activity. In the acute toxicity assay, the effects of a single oral dose of the EOs in Wistar rats were determined. General behaviour, adverse effects, and mortality were determined. RESULTS: A total of 322 compounds were identified in the EOs. The sesquiterpenes displayed the highest contribution in leaves EOs among which included bicyclogermacrene and δ-cadinene. Sesquiterpenes and oxygenated sesquiterpenes displayed the highest contribution in EOs from stems, among which included bicyclogermacrene and α-cadinol. The EOs demonstrated an excellent action on the crystals growth inhibition, and the oral dose tested did not induce significant changes in the parameters for acute toxicity. CONCLUSION: The oils have a high chemical complexity, and there are differences between their compositions, which could explain the observed differences in antilithiasic activity. The findings support the use of this plant in folk medicine to treat kidney diseases.

Anti-nociceptive, anti-hyperalgesic and anti-arthritic activity of amides and extract obtained from Piper amalago in rodents.

ETHNOPHARMACOLOGICAL RELEVANCE: Piper amalago (Piperaceae) has been used in folk medicine as an analgesic. This study aimed to evaluate the pharmacological effects of extract and pure amides obtained from P. amalago on pain to provide a pharmacological basis for their use in traditional medicine. AIM OF THE STUDY: This study evaluated the anti-nociceptive, anti-hyperalgesic, anti-arthritic and anti-depressive activities of the ethanolic extract of P. amalago (EEPA) and the amides N-[7-(3',4'-methylenedioxyphenyl)-2(Z),4(Z)-heptadienoyl] pyrrolidine (1) and N-[7-(3',4'-methylenedioxyphenyl)-2(E),4(E)-heptadienoyl] pyrrolidine (2) obtained from P. amalago in animal models. MATERIALS AND METHODS: Mice treated daily with EEPA (100mg/kg, p.o.) were assayed for 20 days for knee edema (micrometer measurement), mechanical hyperalgesia (analgesiometer analysis), heat sensitivity and immobility (forced swim test) in the Complete Freund's Adjuvant (CFA) model. Cold (acetone test) and mechanical hyperalgesia (electronic von Frey analysis) responses were evaluated for 15 days in rats treated with oral EEPA (100mg/kg) in the spared nerve injury (SNI) model. Meanwhile, mice were evaluated for carrageenan-induced edema and mechanical hyperalgesia and for nociception using the formalin model after a single administration of EEPA (100mg/kg) or amides 1 and 2 (1mg/kg). RESULTS: Amides (1) and (2) were detected and isolated from the EEPA. The EEPA inhibited mechanical hyperalgesia, knee edema, and heat hyperalgesia, but not depressive-like behavior, induced by the intraplantar injection of CFA. When evaluated in the SNI model, the EEPA inhibited mechanical and cold hyperalgesia. The EEPA, 1 and 2 prevented the mechanical hyperalgesia induced by carrageenan and the anti-nociceptive effects in both phases of formalin nociception. The EEPA did not induce alterations in the open field test. CONCLUSION: The EEPA was effective for inhibition of pain and arthritic parameters but was not effective against depressive-like behavior; additionally, it did not alter locomotor activity. The amides obtained seemed to be the active component(s) present in the EEPA because they proved to be anti-nociceptive and anti-hyperalgesic in models of acute pain. Considering that few drugs are currently available for the treatment of chronic pain, especially neuropathic pain, the present results may have clinical relevance and open new possibilities for the development of new anti-hyperalgesic and anti-arthritic agents from P. amalago.

Anatomical investigations of Piper amalago (jaborandi-manso) for the quality control

Abstract Piper amalago L., Piperaceae, popularly known as jaborandi-manso, is a shrub that spans a height of 2–7 m. It can be found in the regions of Southern America downward up to the south of Brazil. Traditionally it is used to treat digestive problems, heart problems, and burns. This study aims to conduct an anatomical investigation and analysis of the leaves and stems of P. amalago through electron scanning and optical micro techniques. The analysis showed that P. amalago has a hypostomatic leaf, with a subepidermal layer on its surface. There are grandular trichomes that resemble sacs, conic non-glandular trichomes, dorsiventral mesophyll, and a plano-convex midrib having a single vascular bundle in the center. The petiole is short with irregularly shaped and adaxially grooved. The stem is circular in shape and contains two circles of vascular bundles and a sclerenchymatic sheath in the perimedular region. These anatomical features of the Piper amalago's leaves and stems make it easy to pick it out among other species of the Piper genus. This is helpful when conducting quality control process.

Diuretic and antilithiasic activities of ethanolic extract from Piper amalago (Piperaceae).

OBJECTIVE: Piper amalago is used in Brazilian folk medicine as diuretic and for the treatment of urinary calculus disease, although no scientific data have been described to support these effects. Thus, this study aims to evaluate the diuretic effects and antilithiatic activity of the ethanolic extract of P. amalago (EEPam). MATERIALS AND METHODS: Ethanolic extracts of P. amalago (125, 250 and 500mg/kg) were orally administered in male Wistar rats (n=5) and urinary excretion was measured at intervals of up to 24h after administration. The antilithiasic effect of EEPam on calcium oxalate urolithiasis crystallization was examined in a turbidimetric model. RESULTS: The oral administration of all doses of EEPam significantly increased urine output after 24h when compared to control group. Moreover, the application of EEPam, induced an inhibitory effect on calcium oxalate crystallization. CONCLUSIONS: According to results, P. amalago extracts showed diuretic and natriuretic activity and antilithiasic effects.

Antileishmanial activity of amides from Piper amalago and synthetic analogs

Two natural amides isolated from the chloroform extract of Piper amalago L., Piperaceae, leaves, a hydrogenated derivative and seven synthetic analogs were tested against the promastigote and intracellular amastigote forms of Leishmania amazonensis. The antileishmanial activity was evaluated in terms of growth inhibitory concentration for 50% of protozoa (IC50). The cytotoxicity toward the J774A1 macrophages was evaluated in terms of the cytotoxic concentrations for 50% of macrophages (CC50). The ability to induce nitric oxide production was also investigated for all compounds. The saturated amide 7-(1,3-benzodioxol-5-yl)-1-(1-pyrrolidinyl)-1-heptanone was obtained by hydrogenation of the natural compound N-[7-(3',4'-methylenedioxyphenyl)-2(Z),4(Z)-heptadienoyl]pyrrolidine. Synthetic amides were prepared by addition of the appropriate amine to the corresponding acyl chloride. The natural compound, N-[7-(3',4'-methylenedioxyphenyl)-2(E),4(E)-heptadienoyl]pyrrolidine, was the most active of all tested compounds against the promastigote and intracellular amastigote forms with IC50 values of 15 µM and 14.5 µM, respectively. None of the compounds modulated the production of nitric oxide.