Antioxidant approach to disease management and the role of ‘Rasayana’ herbs of Ayurveda

Piper species are aromatic plants used as spices in the kitchen, but their secondary metabolites have also shown biological effects on human health. These plants are rich in essential oils, which can be found in their fruits, seeds, leaves, branches, roots and stems. Some Piper species have simple chemical profiles, while others, such as Piper nigrum, Piper betle, and Piper auritum, contain very diverse suites of secondary metabolites. In traditional medicine, Piper species have been used worldwide to treat several diseases such as urological problems, skin, liver and stomach ailments, for wound healing, and as antipyretic and anti-inflammatory agents. In addition, Piper species could be used as natural antioxidants and antimicrobial agents in food preservation. The phytochemicals and essential oils of Piper species have shown strong antioxidant activity, in comparison with synthetic antioxidants, and demonstrated antibacterial and antifungal activities against human pathogens. Moreover, Piper species possess therapeutic and preventive potential against several chronic disorders. Among the functional properties of Piper plants/extracts/active components the antiproliferative, anti-inflammatory, and neuropharmacological activities of the extracts and extract-derived bioactive constituents are thought to be key effects for the protection against chronic conditions, based on preclinical in vitro and in vivo studies, besides clinical studies. Habitats and cultivation of Piper species are also covered in this review. In this current work, available literature of chemical constituents of the essential oils Piper plants, their use in traditional medicine, their applications as a food preservative, their antiparasitic activities and other important biological activities are reviewed.

Piper Species: A Comprehensive Review on Their Phytochemistry, Biological Activities and Applications.

This review aims to describe essential oils and their constituent compounds that exhibit bioactivity against Aedes aegypti L (Diptera: Culicidae) larvae, the immature stage of the primary vector of dengue This review is based on original articles obtained by searching on major databases Our literature review revealed that 361 essential oils from 269 plant species have been tested for their larvicidal activity More than 60 % of these essential oils were considered active (LC50<100 mg/L), and the majority of these active oils were derived from species belonging to Myrtaceae, Lamiaceae, and Rutaceae The most active essential oils exhibited effective concentrations comparable with the dosage recommended for the use of temephos in container breeding Approximately 27 % of the plants studied for their larvicidal activity against A aegypti were collected in Brazil Essential oils rich in phenylpropanoids, oxygenated sesquiterpenes, and monoterpene hydrocarbons were found to be the most active When the isolates were tested, phenylpropanoids and monoterpene hydrocarbons were the most active compound classes We describe the plant parts used and the major constituents of the essential oils In addition, we discuss factors affecting the activity (such as plant parts, age of the plant, chemotypes, larval source, and methods used), structure-activity relationships, and mechanisms of action of the essential oils and their compounds Essential oils have been widely investigated and show high larvicidal activity against A aegypti This review reveals that the essential oils are effective alternatives for the production of larvicides, which can be used in vector-borne disease control programmes

Essential oils and their compounds as Aedes aegypti L. (Diptera: Culicidae) larvicides: review

Antibacterial screening of some Peruvian medicinal plants used in Callería District

ed from in the transition state. This answers the question of both the retention and the inversion of stereochemistry for the simple exchange reaction giving back I (which it should be noted is highly disfavored because k2 ≫ k−1). Retention of configuration would occur by first noting that the potassium ion would also be coordinated to the same face as the abstracted hydrogen atom because it was originally coordinated to the oxygen of the base. A molecule of deuterated alcohol can then approach this same face through coordination to the potassium. Rotation of these ligands around potassium would result in the deuterated alcohol now hydrogen bonded to the allylic anion (IV-top), which following collapse would return the chiral alkene I-d with the same configuration. On the other hand, inversion of stereochemistry would occur via the deuterated solvent approaching from the face of the allylic anion opposite to that hydrogen bonded, and exchange with the alcohol giving (IV-bottom). This could collapse and give chiral alkene I-d with inversion of configuration. The E/Z ratio of 60 for product III-h is also important because this value is extremely high as compared to the equilibrium value of 4.2 for the diastereoisomers, and compares to other systems as well. For example, the isomerization of allylbenzene into 1-propenylbenzene has an E/Z ratio of 44 when using potassium t-butoxide in DMSO. The reason for this higher-than-equilibrium ratio is explained in Scheme 3. Two “conformations” of the chiral alkene I are suitable for deprotonation and will lead to either the E or the Z allylic anions as shown. The rate of “conformational rotation” must be many orders of magnitude greater than the rates for Scheme 2. Proposed Base-Mediated Reaction Mechanism Scheme 3. Interactions Leading to Observed E/Z Ratios Chemical Reviews Review DOI: 10.1021/acs.chemrev.5b00052 Chem. Rev. XXXX, XXX, XXX−XXX E deprotonation (kE and kZ), and thus the E/Z ratio in the product must be related to the kE/kZ ratio. The transition state leading to the Z-allylic anion must thus be higher in energy than the one leading to the E-allylic anion, presumably due to the disfavored 1,3-allylic interactions, which would make charge stabilization through conjugation more difficult. Cram has reported this in more detail, including an analysis of collapse ratios (i.e., ratio of protonation of either carbon on the allylic anion), the stereochemical stability of allylic and vinyl anions, and the kinetic and thermodynamic stabilities of olefinic products formed by protonation of allylic anions. 2.2. Transition Metal-Mediated Mechanisms The mechanisms for the transition metal-mediated isomerizations have in some cases been very carefully determined, while in many they are assumed from one of two generally accepted pathways (Schemes 4 and 5). The first involves a discrete transition metal−hydride active catalyst and the formation of a transition metal−alkyl intermediate, while the second involves the formation and collapse of a η-allyl hydride complex. Each of the mechanisms described below bases its premise on the fact that each step is reversible, and thus the reactions are under thermodynamic control at equilibrium. 2.2.1. Alkyl Mechanism. For this mechanism to occur, the transition metal catalyst must have both an empty 2e− coordination site (e.g., via dissociation of a ligand) and a metal hydride bond that is typically generated in situ under the reaction conditions (see Scheme 4). The catalyst first coordinates to the π-electrons of the alkene followed by an insertion reaction to give either a primary or a secondary metal−alkyl intermediate. The primary metal−alkyl is generally formed faster for many catalysts, but is a mechanistic dead-end returning the starting material through β-hydride elimination and is thus a nonproductive pathway. The secondary metal− alkyl intermediate can however produce either the Eor the Z1-propenylbenzene on β-hydride elimination, which is clearly thermodynamically favored because of the conjugation to the benzene ring. 2.2.2. Allyl Mechanism. The allyl mechanism, however, requires a transition metal capable of having two vacant coordination sites, and, more specifically, no metal−hydride should be present or the alkyl mechanism will take place (see Scheme 5). The first step involves coordination of the πelectrons of the allylbenzene to one of the transition metal’s vacant sites. This is followed by an oxidative addition reaction giving an η-allyl metal−hydride complex, which can collapse to either the starting material or the rearranged and thus more stable alkene. The η-complex may also rearrange to the ηcomplex as part of the reaction pathway. The difference between these two mechanisms can be determined through deuterium labeling with 32 and crossover experiments (Scheme 6). The allyl mechanism is entirely intramolecular and involves an effective 1,3-hydride shift as the only mechanistic pathway. Thus, in a crossover experiment, such as that in Scheme 6, the deuterium should (a) only be found at the 1and 3-positions of the allylic system, that is, 34, and (b) not be incorporated into the second nondeuterated substrate. In the case of the alkyl mechanism, products similar to those of the allyl mechanism may be detected in addition to (a) the nondeuterated substrate showing some deuterium incorporation and (b) the loss of deuterium and incorporation of hydrogen on the deuterated substrate. Furthermore, deuterium incorporation at the 2-position of the allylic system, 35, is also expected because the initial metal−hydride insertion reaction may have poor regioselectivity as already explained in Scheme 2. Of course it should be noted that these two general mechanisms are just that, and the specific reaction pathway for different transition metal catalysts will depend heavily on the transition metal, ligand, solvent, and substrate combinations. More detailed mechanistic data can be obtained from kinetic studies supplemented by state-of-the-art measurements, for example, nanosecond time-resolved IR, NMR, and DFT calculations. These studies have invariably revealed Scheme 4. Alkyl Mechanism M = transition metal; [L]n = bound ligand(s); [L]0 = dissociating ligand or vacant 2e− site. Scheme 5. Allyl Mechanism M = transition metal; [L]n = bound ligand(s); [L]0 = dissociating ligand or vacant 2e− site. Chemical Reviews Review DOI: 10.1021/acs.chemrev.5b00052 Chem. Rev. XXXX, XXX, XXX−XXX F mechanisms more complicated than those presented above, but at the same time generally holding true to them. One major mechanistic departure has been that proposed by Harvey and Lloyd-Jones in which they suggest a binuclear palladium complex being involved in the E/Z isomerization of alkenes. However, it should be noted that this is only applicable in some cases. More important is that the specific mechanisms themselves answer questions related to E/Z selectivity in these transition metal-mediated isomerizations. Simplistically, the reactions can be considered to be under thermodynamic control, and therefore the E/Z ratios will favor the E-isomer. The π-allyl mechanism has been linked, in a general sense, with higher E/Z ratios, but can by no means be used as proof for a particular mechanism. This is because the E/Z selectivity in the reaction is strongly governed not only by the thermodynamic stability of the E isomer (and intermediates leading to the E-isomer), but can be shifted through ligand and or kinetic control to high ratios of either the E or the Z isomers. The sections below detailing the specific examples in the literature will highlight these selectivities. 3. ISOMERIZATION METHODS − GENERAL Perusal of the literature quickly confirms that 2-propenylaryl isomerization reactions have been promoted by mainly two classes of methods, viz., the application of bases (section 4) or transition metal complexes (section 5). In this Review, these sections will thus be discussed separately, in addition to a final section describing miscellaneous allylaryl isomerizations (section 6). In each section, substrates of particular interest will be highlighted, with particular care being taken to convey important experimental data such as yields, the cis/trans ratios obtained, and any other relevant information. 4. BASE-MEDIATED ISOMERIZATIONS In general, base-initiated reactions require at least a stoichiometric amount of base to accomplish the isomerization of an allylbenzene. This method has seen much application in the past literature, and some general information has been collated in book chapters. 4.1. Hydroxide/Alkoxide Ion-Mediated Isomerizations This particular method involves the use of fairly harsh reaction conditions in that it generally comprises heating the substrate in a protic solution (ethanol, methanol, or n-butanol) of sodium or potassium hydroxide (giving rise to a mixture of the hydroxide and corresponding alkoxide under equilibrium conditions). Other examples include the use of hydroxide in DMSO. Of interest is that the KOH/ethylene glycolmediated isomerization of eugenol 5 has actually been incorporated into the curriculum of a teaching laboratory to demonstrate how the kinetics of a reaction can be studied using NMR spectroscopic, GC, and HPLC laboratory techniques. It should also be mentioned here that the importance of the potassium t-butoxide system means that a separate subsection will be dedicated to this method (see section 4.2). In the first section, examples of where hydroxide-mediated isomerization has been applied will be highlighted. This will be followed by methods in which the isomerization approach has been modified, albeit with additives (phase transfer), microwave heating, or different solvent systems. 4.1.1. Hydroxide/Alkoxide Ions in Alcohol (Methanol, Ethanol, n-Butanol) or without Solvent. It should be noted that the use of sodium ethoxide has been rigorously studied, showing that the isomerization of para-substi

Isomerization of allylbenzenes.

The essential oils of eight samples of Piper aduncum L., collected at different localities of the Amazon region, were analysed by GC–MS. The major component identified in all samples was dillapiole (31.5–97.3%). Sample A, collected at Serra do Navio (AP), showed a yield of oil and dillapiole content of 3.3% and 31.5%, respectively; sample B, collected at Melgaco (PA), 1.8% and 50.8%; sample C, collected at Benfica (PA), 1.6% and 56.3%; samples D and E, collected at Belem (PA), 1.2% and 82.2%; 1.5% and 86.9%, respectively; sample F, collected at Manaus (AM), 3.4% and 91.1%; sample G, collected at Road Manaus-Caracarai, km 30 (AM), 3.0% and 97.3%; sample H, collected at Cruzeiro do Sul (AC), 3.2% and 88.1%. The yield of oil and dillapiole content of samples of P. aduncum occurring in Malaysia and Fiji showed 1.3% and 64.5%; and 0.5% and 58.0%, respectively. By comparison, the plants growing wild in Amazonas State had the highest oil yield and dillapiole content. © 1998 John Wiley & Sons, Ltd.

Constituents of the essential oil of Piper aduncum L. growing wild in the Amazon region

The essential oils of the specimens of Piper aduncum that occur in deforested areas of Brazilian Amazon, North Brazil, are rich in dillapiole (35-90%), a derivative of phenylpropene, to which are attributed biological properties. On the other hand, the oils of the specimens with occurrence in the Atlantic Forest, and Northeastern and Southeastern Brazil, do not contain dillapiole, but only terpene compounds such as (E)-nerolidol and linalool. One specimen existing in the Amazon was hydrodistilled. The obtained oil was fractioned on a silica chromatographic column, resulting in fractions rich in dillapiole (95.0-98.9%) utilized for analyses by GC and GC/MS, structural characterization by NMR, confirmation of their biological properties, and to obtain the isomer isodillapiole. Dillapiole showed a fungicide action against the fungus Clinipellis perniciosa (witches' broom) by inhibition of its basidiospores, in concentrations ranging from 0.6 to 1.0 ppm. The larvicide and insecticide actions of dillapiole were tested against the larvae and the adult insects of Anopheles marajoara and Aedes aegypti (malaria and dengue mosquitoes), resulting in mortality of the larvae (48 h, 100%) at a concentration of 100 ppm, and mortality of the insects (30 min, 100%) at a concentration of 600 ppm. The isomeric isodillapiole showed no significant activity in the same biological tests.

Chemical variation in Piper aduncum and biological properties of its dillapiole-rich essential oil.

This paper contains data on the chemical composition of the essential oils of 22 leaf samples of Piper marginatum Jacq. collected in different areas and ecosystems of the brazilian Amazon, as well as an overview of the available literature. The species presents a large synonymy based on their different leaf characteristics and distinct scents where some of them smell like anise or very close compounds. By GC, GC/MS, and cluster analysis, we identified seven chemotypes for the leaf oils. The main components found in chemotype I were safrole (1) and 3,4-(methylenedioxy)propiophenone (2). The chemotype II was dominated by 3,4-(methylenedioxy)propiophenone (2) and p-mentha-1(7),8-diene (10). The major compounds identified in chemotype III were 3,4-(methylenedioxy)propiophenone (2), myristicin (3), (E)-beta-ocimene (11), and gamma-terpinene (12). In the chemotype IV, the principal constituents were beta-caryophyllene (13), alpha-copaene (14), and 3,4-(methylenedioxy)propiophenone (2). The chemotype V was dominated by (E)-isoosmorhizole (6), (E)-anethole (8), and isoosmorhizole (7). The main compounds found in the chemotype VI were 2-methoxy-4,5-(methylenedioxy)propiophenone (4), methoxy-4,5-(methylenedioxy)propiophenone isomer 5, and (E)-isoosmorhizole (6). The major constituents in chemotype VII were beta-caryophyllene (13), bicyclogermacrene (15), and (E)-asarone (9).

Variability in Essential‐Oil Composition of Piper marginatum sensu lato

Six samples of aerial parts of Piper cyrtopodon were collected in the brazilian Amazon. The samples were hydro distilled and the resulting oils analyzed by GC and GC-MS. Eighty-four compounds were identified in the oils. The main compounds found in the oil of sample 1 were β-caryophyllene (19.2%), bicyclogermacrene (13.0%), germacrene D (10.0%), spathulenol (8.4%) and ot-cubebene (5.1%); in the oil of sample 2 were a mixture of bicyclogermacrene plus curzerene (23.3%) with the predominance of the former, beyond germacrene D (17.9%), spathulenol (6.9%) and p-cymene (6.3%); in the oil of sample 3 were β-caryophyllene (34.6%), bicyclogermacrene (21.4%), germacrene D (13.6%), and ot-pinene (7.5%); in the oil of sample 4 were elemicin (26.8%), germacrene D (14.8%), bicyclogermacrene (14.0%) and ot-pinene (4.7%); in the oil of sample 5 were β-caryophyllene (18.1%), bicyclogermacrene (14.9%), germacrene D (13.6%), elemicin (10.1%) and ot-cubebene (6.7%); in the oil of sample 6 were epi-ot-bisabolol (26....

Cleber N. Bastos

Papers

Constituents of the essential oil of Piper aduncum L. growing wild in the Amazon region

Chemical variation in Piper aduncum and biological properties of its dillapiole-rich essential oil.

Variability in Essential‐Oil Composition of Piper marginatum sensu lato

Essential Oil Composition of Piper cyrtopodon (Miq.) C. DC