Propriedades medicinais do óleo da Copaifera Langsdorfii: uma revisão integrativa da literatura / Medical properties of Copaifera Langsdorfii oil: an integrative literature review

O Brasil é o maior produtor de óleo extraído da Copaifera, uma das plantas medicinais mais estudadas do mundo, encontrada principalmente na região amazônica. Dentro desse contexto, o presente trabalho tem como objetivo identificar, com base na literatura, as principais utilizações medicinais do óleo de copaíba, avaliar sua composição fitoquímica e possível toxicidade. Trata-se de uma revisão integrativa da literatura, cujo seleção das literaturas foram nas bases de dados eletrônicas LILACS e MEDLINE, na biblioteca do SCIELO e em repositório de ensino superior. Os critérios de inclusão definidos para a seleção dos estudos foram: literaturas publicadas em português e inglês disponíveis na íntegra no período de 2011 a 04/2021; e exclusas literaturas pagas e duplicadas. Foram selecionados 34 estudos, distribuídos entre pesquisa em laboratórios 79,5% (27) e de revisão bibliográfica 20,5% (7), que comprovaram propriedades emolientes da copaíba quando utilizadas em curativos, cicatrizante de pele e mucosa, capacidade de penetração transcutânea (recurso viável para fisioterapia), anti-inflamatório, efeito bacteriostático, antimicrobiano em bactérias gram-positivas, o óleo-resina também mostrou-se eficaz como antifúngico e no combate a pragas. Portanto, foi possível notar consideráveis propriedades farmacologias presentes no óleo-resina da copaíba.

Brazil is the largest producer of oil extracted from Copaifera, one of the most studied medicinal plants in the world, found mainly in the Amazon region. Within this context, the present work aims to identify, based on literature, the main medicinal uses of copaiba oil, evaluate its phytochemical composition and possible toxicity. This is an integrative literature review, whose selection of literature was made in the electronic databases LILACS and MEDLINE, in the SCIELO library, and in a higher education repository. The inclusion criteria defined for the selection of studies were: literature published in Portuguese and English available in full from 2011 to 04/2021; and excluded paid and duplicated literature. Thirty-four studies were selected, distributed between laboratory research 79.5% (27) and literature review 20.5% (7), which proved emollient properties of copaiba when used in dressings, skin and mucosa healing, transcutaneous penetration capacity (viable resource for physiotherapy), anti-inflammatory, bacteriostatic effect, antimicrobial in gram-positive bacteria, the oil-resin also proved to be effective as antifungal and in fighting pests. Therefore, it was possible to note considerable pharmacological properties present in the oil-resin of copaiba.

Report: Cytotoxic activities of Rosa brunonii, Calligonum polygonoides, Pegnum harmala and Sueda fruticosa extract using brine shrimp.

The present study was carried out to record and evaluate the effect of Rosa brunonii, Calligonum polygonoides, Sueda fruticosa and Pegnum harmala L., extracts on brine shrimp collected during March-June 2013 from different regions of District Bannu. These four plants were medicinal xerophytes and widely distributed throughout Pakistan. Rosa brunonii is commonly used as a hedge plant for gardening. Calligonum polygonoides and Sueda fruticosa are locally used as a fuel, while Pegnum harmala (L.) is the most important multipurpose medicinal xeric plant, which is used for various purposes. All these selected medicinal xerophytes have inhibitory effect on bacterial growth. In this study the effect of different concentration (10-70 µ/ml) were tested on brine shrimp. The results showed that maximum cytotoxic activities were observed in Rosa brunonii (100.0±0.4), Calligonum polygonoides (100.0±0.2) and Pegnum harmala (L.) (90.0±5.2) while Sueda fruticosa (50.0±7.1) has less cytotoxic property. These activities are may be due to the presence of bioactive constituents.

Systematic investigation of ethanolic extract from Leea macrophylla: Implications in wound healing.

ETHNOPHARMACOLOGICAL RELEVANCE: Leea macrophylla Roxb. ex Hornem. (Leeaceae) commonly known as Hastikarnapalasa is mainly distributed throughout the tropical parts of India. Traditionally, the plant is found to be effective against guinea worm, ringworm and is applied to sores and wounds. AIM OF THE STUDY: The present study aims to validate traditional wound healing claim of Leea macrophylla scientifically. MATERIAL AND METHODS: Box-Behnken design (BBD) was used to optimize the extraction process. The optimized root tuber extract of Leea macrophylla was standardized with chlorogenic acid by HPLC for the first time. Both oral and topical routes were selected as administrative means for the wound healing study using excision and incision wound model. For topical treatment bioadhesive gel was formulated and characterized for mechanical and physical characteristics by texture profile analysis (TPA) and scanning electron microscopy (SEM). The effect on wound healing was also assessed by evaluating antioxidant enzymes viz. glutathione (GSH), superoxide dismutase (SOD) and catalase (CAT), free radicals lipid peroxidation (LPO) and nitric oxide (NO), inflammatory marker myeloperoxidase (MPO), collagen markers hydroxyproline, hexosamine and hexuronic acid along with the histopathological examination. Furthermore, the effect on the level of the proinflammatory cytokines interleukin-1ß (IL-1ß), interleukin -6 (IL-6), tumor necrosis factor-α (TNF-α) and growth factor, vascular endothelial growth factor (VEGF) were determined. The expression of cell proliferation nuclear marker Ki-67 was also analyzed by Western blot analysis. RESULTS: With mesh openings Sieve no. 20, semi polar nature of solvent (92.5:7.5 ethanol-water blend) and extraction time of 18h, substantially greater extraction efficiency (29%) and phenolic yield (181.54mg/g) were obtained. The content of chlorogenic acid in ethanol extracts of Leea macrophylla was obtained as 9.01% w/w. In incision model, oral treatment with 500mg/kg ethanolic extract increased wound breaking strength by 23.41% while bioadhesive gel (5% w/v) showed a higher increase of 44.68%. Topical application produced complete wound contraction in 20 days against 22 days taken by oral treatment. Topical treatment also produced a significant (p<0.05) increase in antioxidants glutathione, superoxide dismutase and catalase whereas the level of enzymes lipid peroxidation and nitric oxide and inflammatory markers myeloperoxidase were reduced. Further advantageous effects were reflected by significantly (p<0.05) increased levels of hydroxyproline, hexosamine and hexuronic acid. Favorable effects on the level of proinflammatory cytokines interleukin-1ß, interleukin-6, tumor necrosis factor - α and growth factor, vascular endothelial growth factor were also observed. The wound healing potential of Leea macrophylla was further supported by its ability to promote cell proliferation during wound healing as demonstrated by Western blot analysis of proliferation marker Ki-67. CONCLUSION: The study justified traditional use of Leea macrophylla in wound healing and demonstrated that the bioadhesive gel of ethanolic extract produced faster and more significant healing as compared to oral treatment.

Photosensitisation of livestock grazing Narthecium ossifragum: Current knowledge and future directions.

Photosensitisation diseases can cause production and animal welfare losses world-wide. In North-West Europe a photosensitisation disease complex known as 'plochteach', 'yellowses', 'saut' and 'alveld' occurs in lambs on extensive pastures containing bog asphodel (Narthecium ossifragum). Affected lambs develop lesions on the ears, face and sometimes the back, with erythema, oedema, ulceration and necrosis that can be followed by secondary infection and death. Adult sheep appear unaffected, the incidence in lambs varies from year to year and there are variations in susceptibility between- and within-breeds. The definitive cause remains uncertain although ingestion of N. ossifragum, which contains hepatotoxic saponins, has been implicated in the aetiology. However, problems replicating the disease complex by feeding N. ossifragum in a controlled environment have led to alternative hypotheses, including possible intake of toxins from fungal spores and cyanobacteria. Further research is required to assess the putative role of N. ossifragum, the scale of economic and animal welfare losses associated with the disease, how best to identify affected animals before external clinical signs appear and the treatment and management of clinical cases. Given the challenges involved in isolating the causative agent(s) of plochteach, an animal breeding route may be effective if heritability of resistance/susceptibility can be demonstrated.

Toxicological screening of Daouri, a polyherbal formulation used in children in the Central Region of Togo.

ETHNOPHARMACOLOGICAL RELEVANCE: Daouri, a combination of several plants, is an old African Traditional Medicine based on ancestral knowledge transmitted from generation to generation and is used by the Kotokoli Community in Togo. The combination of several plants may potentiate or attenuate the toxicity of individual plants. The present investigation aims to study the composition and potential toxicity of Daouri used in children in the Kotokoli community. MATERIALS AND METHODS: Surveys were performed using a semi-structured questionnaire to determine the composition of Daouri. On the basis of these data collected, Standard Daouri was formulated, and its aqueous extract was orally administered at 300, 600 and 1200mg/kg to rats for 28 days. On the 29th day, the rats were sacrificed and their serum were analysed to evaluate hepatic and renal toxicities. RESULTS: Four categories of Daouri were collected. The plant combinations used in each Daouri formulation varied according to the pathological conditions, including the age of the children and the availability of each plant. The most plants cited in the four Daouri were Khaya senegalensis (Desv.) A. Juss, Odina acida (A. Rich.) Oliv.,Lophira lanceolata Tiegh, Paullinia pinnata L. and Pteleopsis suberosa Engl. & Diels. Although there was an increase in the alkaline phosphatase concentration, different doses of the aqueous extract of Standard Daouri were not toxic after 28 days of administration. In addition, the concentrations of alanine transaminase, creatinine and urea were not different between the Daouri-treated and control groups. CONCLUSION: Daouri is plant combination used in children in the Kotokoli community as a part of African Traditional Medicine. Standard Daouri is not toxic in rats.

Unusual amino acids and monofluoroacetate from Dichapetalum michelsonii (Umutambasha), a toxic plant from Rwanda.

In the course of our investigations on Umutambasha in order to identify its convulsant principles, small quantities of monofluoroacetate were observed in stem bark, leaves, and fruits of this plant newly identified as Dichapetalum michelsonii Hauman. Conclusive evidence for a monofluoroacetate presence came from its isolation from the freeze-dried extract of stem bark. Three free unusual amino acids, named N-methyl-α-alanine, N-methyl-ß-alanine, and 2,7-diaminooctan-1,8-dioic acid, described for the first time in a plant, and known trigonelline were also isolated from the stem bark of D. michelsonii. Structure elucidations were mainly achieved by spectroscopic methods (1H-NMR, 2D-NMR, MS) and by comparison with authentic references. These unusual amino acids were detected by a fast, reliable TLC analysis in all our batches of Umutambasha, suggesting that they could be used for identification purposes in case of human or livestock intoxications. Finally, EEG recordings and behavioural observations performed in mice suggested that the convulsive patterns produced by Umutambasha are the consequence of monofluoroacetate presence in D. michelsonii.

Antioxidant, antiglycation and cytotoxicity evaluation of selected medicinal plants of the Mascarene Islands.

BACKGROUND: Many indigenous plants of Mascarene Islands have been used in folkloric medicine to manage diabetes but few species have received scientific attention. Selected traditional medicinal plants (Antidesma madagascariense Lam. -Euphorbiaceae (AM), Erythroxylum macrocarpum O.E.Schulz -Erythroxylaceae (EM), Pittosporum senacia Putterl -Pittosporaceae (PS), Faujasiopsis flexuosa Lam. C.Jeffrey -Asteraceae (FF), Momordica charantia Linn -Cucurbitaceae (MC) and Ocimum tenuiflorum L -Lamiaceae (OT) were evaluated for their antioxidant, antiglycation and cytotoxic potential in vitro. METHODS: Graded concentrations (1.25-100 µg/mL) of the crude methanolic and water extracts and fractions (dichloromethane, ethyl-acetate, n-butanol and water) were evaluated for abilities to scavenge 2,2-diphenyl-2-picrylhydrazyl hydrate (DPPH), nitric oxide (NO), superoxide (SO) radicals and to inhibit lipoxygenase and formation of advanced glycation endproduct (AGE) in vitro. The MTT (3-(4, 5-dimethylthazol-2-yl)-2,5-diphenyl tetrazonium bromide) cytotoxicity test was performed on 3T3 cell line. RESULTS: Only IC50 for DPPH, SO, NO and lipoxygenase for AM, FF and OT crude extracts and fractions were comparable to ascorbic acid and quercetin activity. Crude aqueous extracts of AM and FF showed IC50 of 4.08 and 3.89 µg/mL respectively for lipoxygenase which was significantly lower (p < 0.05) than quercetin (10.86 ± 0.68 µg/mL). The three crude aqueous extracts of these plants and their n-butanol fractions also showed antiglycation activities (p < 0.05) comparable to aminoguanidine. Increasing concentrations (250-2000 µg/mL) of the six crude extracts (Methanol and water) and their fractions did not inhibit mitochondrial respiration as measured by MTT cytotoxicity assay. CONCLUSION: AM, FF and OT crude extracts and fractions have potent antioxidant and antiglycation properties with no apparent cytotoxicity and might have prophylactic and therapeutic potentials in the management of diabetes and related complications. Our study tends to validate the traditional use of these medicinal herbs and food plants as complementary and alternative medicines.

Genotoxicity of polar and apolar extracts obtained from Qualea multiflora and Qualea grandiflora.

ETHNOPHARMACOLOGICAL RELEVANCE: The species Qualea grandiflora and Qualea multiflora, which belong to the Vochysiaceae family, are common in the Brazilian savannah (Cerrado biome), and the local inhabitants use these species to treat external ulcers and gastric diseases and as an anti-inflammatory agent. Studies have demonstrated that these plants contain compounds that exhibit pharmacological activities; however, the risks associated with their consumption are not known. MATERIAL AND METHODS: In the present study, the mutagenicity of polar and apolar extracts from Qualea grandiflora and Qualea multiflora were assessed by employing the Ames assay with and without metabolic activation. Additionally, phytochemical analyses (HPLC-ESI-IT-MS, HPLC-UV-PDA and GC-IT-MS) were performed to identify the chemical constituents present in these species, including the evaluation of physico-chemical properties, such as polarity or apolarity of the organic compounds, which are related to each fraction obtained. These studies provide important information regarding the biochemical behaviour of these compounds. RESULTS: All extracts exhibited mutagenicity, inducing frameshift mutations and base substitutions in DNA. Phytochemical analysis identified terpenes, ellagic acid derivatives and phytosteroids. CONCLUSIONS: The mutagenicity observed might be due to the presence of pentacyclic triterpenes and polyphenols, which are able to generate reactive oxygen species (ROS) and result in the potential to cause DNA damage. The genetic risk identified in this present work shows that special attention should be considered for the use of compounds obtained from these plant species in medicinal treatments. Further studies must be conducted to identify safe therapeutic doses.

Microbiological and mucociliary properties of the ethanol extract of Hymenocardia acida on selected respiratory clinical isolates.

The antimicrobial property of the ethanol leaf extract of Hymenocardia acida (H. acida) on some opportunistic respiratory pathogens was evaluated in this study. We also assessed the activity of the extract on tracheal mucociliary activity using murine tracheal mucus exudation and mucociliary motility in pigeons as experimental models. Phytochemical screening of the extract was done; and acute toxicity of the extract in mice was carried out using Lorke's method for estimation of its median lethal dose. Results show the presence of carbohydrates, saponins, tannins, flavonoids, alkaloids, resins, and balsams in the extract and the absence of anthraquinones, terpenes, and sterols. Results of the acute toxicity test showed that the extract was slightly toxic, with an estimated median lethal dose of 1,767.77 mg/kg body weight. At 50, 100, and 200 mg/kg body weight of H. acida, tracheal mucus exudation was increased by 14.29, 19.24, and 33.82%, respectively. The effect on mucociliary velocity was dose-dependent as 50, 100, and 200 mg/kg body weight of the extract led to increased ciliary activity by 7.69, 61.5, and 81.6%, respectively. The effects of the extract (200 mg/kg body weight) on mucus exudation and clearance were significant (p < .05) and higher than the effect of ammonium chloride. Although the extract did not inhibit the growth of C. albicans and K. pneumoniae, it exhibited moderate antimicrobial activity against Escherichia coli, Proteus mirabilis, Pseudomonas aeruginosa, and Staphylococcus aureus. These findings show the mucociliary activity and antimicrobial properties of H. acida ethanol extract, and justify its use in the treatment of airway disorders.

Evaluation of safety of the herbal formula Ojeok-san: acute and sub-chronic toxicity studies in rats.

AIM OF THE STUDY: Ojeok-san (OJS; wuji powder in China and goshaku-san in Japan), a widely used herbal formula in traditional Korean medicine and Japanese herbal medicine (Kampo medicine), has been used to treat common cold and illnesses including fatigue and gastrointestinal disorders, but there is very little information on its safety. To provide information on the safety of OJS, we evaluated its acute and sub-chronic toxicity in rats. MATERIALS AND METHODS: The single and sub-chronic toxicity of OJS was examined using male and female Sprague-Dawley rats. The rats were treated with the OJS extract orally at the highest dose level of 2000 mg/kg/day body weight. After single administration, signs of toxicity were observed every hour for the first 6h and every day for two weeks. In the sub-chronic toxicity study, OJS was administered for 13 weeks. Mortality, clinical signs, body weight changes, food and water consumption, ophthalmologic findings, urinalysis, hematological and biochemical parameters, gross findings, organ weights and histological markers were monitored during the study period. RESULTS: We found no mortality and no abnormality in clinical signs, body weight, and necropsy findings for any of the animals in the acute and sub-chronic toxicity study following oral administration of OJS. CONCLUSION: OJS may not have any single dose toxicity. The lethal dose with a 50% mortality rate (LD(50)) was over 2000 mg/kg. The no-observed adverse effects level (NOAEL) was considered to be 2000 and 1000 mg/kg/day for male and female rats, respectively.

Toxicity of botanical insecticides on golden apple snail (Pomacea canaliculata).

The molluscicidal activity of crude extracts from five highly potential plants, Annona squamosa seed, Nerium indicum Leaves, Stemona tuberose root, Cyperus rotundus corm and Derris elliptica root was assessed to Pomacea canaliculata. D. elliptica root and C. rotundus corm extracts showed the highest toxicity against 3-month old snails which have LC50 as 23.68 +/- 2.96 mg/l and 133.20 +/- 7.94 mg/l, respectively. The C. rotundus corm extracts were chosen for detoxification enzyme in vivo assay which shows esterase and glutathione S-transferase activity in stomach, intestinal tracts and digestive glands of survival treated P. canaliculata were inhibited.

Enzymatic detoxification of jojoba meal and effect of the resulting meal on food intake in rats.

When defatted jojoba meal is used as animal food, it causes food-intake reduction and growth retardation. Detoxification procedures by chemical, microbiological, and solvent extraction methods are reported by several authors. Here we report a successful detoxification of jojoba meal using enzymes. We establish reaction conditions that yield new meal which has the same nutritional qualities in proteins as the original meal. The enzymatic reaction gives rise to one major compound to which the structure of an amide is assigned on the basis of IR, 1H and 13C NMR spectra. The effect of the resulting jojoba meal on the food intake in rats is checked. In contrast, the detoxified meal containing the amide derivatives shows no toxicological activity since rats receiving oral administration of the obtained meal show normal growth. Thus, it is expected that this meal could be used as an animal feed ingredient.

Screening of hepatoprotective effect of a herbal mixture against CCl4 induced hepatotoxicity in Swiss albino mice.

The hepatoprotective potential of a herbal mixture was evaluated against CCl4 induced liver injury in Swiss albino mice. Liv 52, a commercially available polyherbal hepatoprotective drug was evaluated for comparison. The potential toxicity of the above herbal hepatoprotective agents was also compared. It was observed that there was a reduction in the enzyme biomarkers (Aspartate and Alanine Transaminase) of liver injury in the herbal mixture treated groups, which was similar to the reduction initiated by Liv 52. An increase in glutathione was observed in the herbal mixture treated groups and it was assumed that the herbal mixture protects the liver by virtue of its antioxidant nature along with high regeneration initiation potential. From the study it is also concluded that the herbal mixture is safer than Liv 52.

Sapogenin levels in Narthecium ossifragum plants and Ovis aries lamb faeces during two alveld outbreaks in Møre og Romsdal, Norway, 2001.

The proposal that saponins produced by the lily bog asphodel (Narthecium ossifragum) may be the direct cause of the hepatogenous photosensitization disease alveld seen in Norwegian lambs was investigated by comparing sapogenin levels in two control and two toxic pastures, and in faeces from lambs grazing the four pastures in the Halsa and Surnadal municipalities, Møre og Romsdal county, Norway. Generally similar levels of sapogenins, determined after hydrolysis of parent plant saponins, were found in Narthecium leaves collected in June/July 2001 from the two alveld outbreak areas and two nearby control areas. Differences in the median sapogenin levels determined for leaf samples in outbreak and control areas were not statistically significant. The total level of free and conjugated sapogenins in faeces recovered from the rectums of lambs grazing the outbreak and control pastures areas varied greatly. The results obtained do not support the hypothesis that a dose-response relationship exists between Narthecium saponin levels and the occurrence of alveld outbreaks.

[Comparison among families of Mutong].

OBJECTIVE: To distinguish families of Mutong correctly and direct effective and safe clinical administration. METHOD: Comparison among families of Mutong on Herbs, Taxology, Clinic, Pharmacology and Toxicology. RESULT: 1. There are mainly three families of Mutong: Lardizabalaceae, Ranunculaceae, Aristolochiaceae, which were all included in China Pharmacopeia in 1963. However only Mutong of Ranunculaceae and Aristolochiaceae family have been included in China Pharmacopeia since 1977, but Mutong of Lardizabalaceae family has not been included in China Pharmacopeia ever since. 2. It was Mutong of Lardizabalaceae family that was used mainly through the ages without toxic records, and Mutong of Aristolochiaceae e.g. Caulis Aristolochia manshuriensis (CAM) was not put down in writing of past ages but is mainly used today with toxicity repeatedly. 3. CAM contain aristolochic acid and aristololactam with high toxicity, which plays an uncertain role in diuresis with poor bactericidal power. Mutong of Lardizabalaceae family e.g. Akebia trifoliata (Thunb.) Koidz. var. australis (Diels) Rehd (ATKV) don't contain aristolochic acid and aristololactam, which has low toxicity and plays a certain role in diuresis with high bactericidal power. CONCLUSION: It may be quite safe to use ATKV instead of CAM in clinics. So we suggest that ATKV should be reused as first Mutong in China Pharmacopeia revised edition in order to ensure a correct understanding of the facts and reveal Mutong in its true colors, and CAM should be used as second Mutong strictly according to the rules in China Pharmacopeia revised edition.

Allelopathic effects of Lantana camara Linn. on spore germination of Asterella angusta Steph.--a liverwort.

Extract from root, stem and leaf of L. camara proved inhibitory for germination of the spores of A. angusta. Leaf extract was found to exhibit maximum allelopathic potentiality followed by stem and root extract and may be interpreted to be the result of phytotoxic substances which are possibly synthesized in the leaf and translocated to other organs.

The toxic effects of Coleus barbatus B. on the different periods of pregnancy in rats.

Extracts of Coleus barbatus B. have been used in folk medicine to interrupt pregnancy. In order to evaluate if this plant interferes with embryo implantation or with the normal development of the concepts, pregnant Wistar rats were treated with increasing doses (220, 440 and 880 mg/kg per day) of a hydroalcoholic extract of C. barbatus. The rats received the extract by gavage from days 0 to 5 of pregnancy (preimplantation period) or 6 to 15 (organogenic period). Control groups received distilled water during the same periods. The animals were killed at term for the evaluation of maternal and fetal parameters. The results showed that the treatment with 880 mg/kg per day of the extract of C. barbatus before embryo implantation caused delayed fetal development and an anti-implantation effect, which justifies the popular use of this extract with abortive purposes. After embryo implantation delayed development associated with maternal toxicity was observed in the fetuses of the group which received 880 mg/kg per day.

[Effects of processing on toxicity and pharmacological action of flos Genkwa].

Daphne genkwa can not be taken unless the toxicity is removed. The study on the effect of processing on the toxicity and pharmacological action of Flos Genkwa has shown that the toxicity of vinegar-processed Flos Genkwa is lower than that of the rude drug, but the pharmacological action is better. Both genkwanin and its vinegar-processed imitation have antitussive and expectorant actions without marked difference in efficacy. Both yuanhuacine and its vinegar-processed imitation could cause contraction of the extracorporeal womb and the intestinal canal, and the efficacy is almost similar in the concentration of 1:10(-5)-10(-6). The gestational womb was observed more sensitive than the normal one.