Low-laser action analysis associated with Himatanthus drasticus extract in wound healing.

The aim of this study was to analyze the healing action of low-intensity laser therapy associated with Himatanthus drasticus in wound healing in mice. The study was experimental, analytical, controlled, randomized, and prospective. Twenty Wistar rats were divided into four groups: control with injury, injury + laser, wound + Himatanthus drasticus, and wound + laser + Himatanthus drasticus. The animals underwent surgical skin wounds on their backs, and different treatments were applied based on the group. The healing process was evaluated histologically through the analysis of collagen fibers, neovascularization, and inflammatory reaction. The results showed that low-intensity laser therapy and Himatanthus drasticus treatment improved the healing process in terms of collagen synthesis, decreased inflammatory cell migration, fibroblast proliferation, neovascularization, wound size reduction, and edema reduction. However, the combination of laser and Himatanthus drasticus did not show significant improvement compared to individual treatments. There were no statistical differences in polymorphonuclear cells between the treatment groups. Low-intensity laser therapy and Himatanthus drasticus have demonstrated positive properties in improving the healing process. Further research is needed to better understand their individual and combined effects. The study contributes to the exploration of alternative wound healing methods and encourages further investigation in this field.

Wound tissue remodeling by latex exudate of Himatanthus drasticus: A plant species used in Brazilian folk medicine.

This work investigated the healing properties of proteins extracted of latex (HdLP) on excisional wounds. Cell toxicity of HdLP was investigated carried out in murine fibroblasts after incubation with HdLP (12.5-100 µg/ml). The dermal irritability test was performed to evaluate dermal reactions. The wounds were performed and treated with vehicle or HdLP (0.5 %, 1.0 %, and 2.0 %). The macroscopic parameters, histological analysis and measurement of inflammatory markers and mediators were evaluated. HdLP did not exhibit cytotoxicity and did not induce skin irritation. HdLP stimulated the release of IL-1ß at the beginning of the inflammatory phase. This effect probably favored the earlier release of IL-10 by macrophages, during the proliferative phase. The shortening and completeness of healing were characterized by fibroblast proliferation and the presence of newly synthesized collagen fibers. This was accompanied by well-organized re-epithelialization. The involvement of latex proteins in this activity is reported for the first time.

Chemical profiling of secondary metabolites from Himatanthus drasticus (Mart.) Plumel latex with inhibitory action against the enzymes α-amylase and α-glucosidase: In vitro and in silico assays.

ETHNOPHARMACOLOGICAL RELEVANCE: Himatanthus drasticus is an important medicinal plant whose latex is traditionally used in Northeast Brazil to treat various diseases, including diabetes. The use of α-amylase and α-glucosidase inhibitors can be an effective strategy to modulate levels of postprandial hyperglycemia via control of starch metabolism. AIMS OF THE STUDY: This study aimed to verify if H. drasticus latex has inhibitory activity against enzymes linked to type 2 diabetes, besides chemically characterizing the metabolites responsible for such activities. In addition, in silico analysis was performed to support the traditional claim of possible antidiabetic activity of this latex. MATERIALS AND METHODS: Latex from H. drasticus stems was sequentially partitioned with n-hexane (FHDH), CHCl3 (FHDC) and EtOH (FHDHA). Wash extraction of the FHDHA fraction was performed to obtain the other extract fractions. The FHDHA was submitted to chromatography in a SPE C18 cartridge using gradient elution with MeOH/H2O to produce five fractions: FHDHA1, FHDHA2, FHDHA3, FHDHA4 and FHDHA5. The FHDHA1 was subjected to semi-preparative reverse phase HPLC. Lineweaver-Burk plots were used to investigate the kinetic parameters of α-amylase and α-glucosidase inhibitory activity. The interactions between plumieride and porcine pancreatic α-amylase and α-glucosidase were analyzed through an in silico molecular docking study. RESULTS: Phytochemical identification of compounds present in the FHDHA fraction of H. drasticus latex was possible by 1H, 13C NMR analysis and mass spectrometry, and the results were compared with the literature. The identified compounds were α-ethyl glucoside, protocatechuic acid, 3-O-caffeoylquinic acid, 15-demethylplumieride acid, 5-O-caffeoylquinic acid, caffeic acid, vanillic acid, plumieride, and catechin. The inhibition results of the fractions tested against α-amylase and α-glucosidase showed inhibitory activities dependent on the increase of fractions and compound concentrations. The IC50 results obtained from FHDHA, FHDHA1 and plumieride fractions against α-amylase were 36.46, 72.61, 33.87 µg/mL respectively. The IC50 of plumieride was the closest to that of acarbose (22.52 µg/mL), a result similar to that obtained for α-glucosidase. The type of inhibition was competitive for both enzymes. CONCLUSIONS: There was strong inhibition of α-amylase and α-glucosidase by FHDHA, FHDHA1 and plumieride, suggesting that these enzymes slow glucose absorption.

Antinociceptive and anti-inflammatory activities of a triterpene-rich fraction from Himatanthus drasticus

Himatanthus drasticus (Mart.) Plumel belongs to the Apocynaceae family and the latex from its trunk bark (Hd) is known as "janaguba milk". This latex is widely used in Northeast Brazil, mainly in the Cariri region, for its gastroprotective, anti-inflammatory, and antitumor properties. The objective of this study was to investigate a triterpene-rich fraction (FJNB) from H. drasticus latex on acute models of nociception and inflammation and to clarify its mechanisms of action. Wistar rats or Swiss mice were subjected to the carrageenan-induced paw edema test or the formalin test, respectively, after the acute oral treatment with FJNB. The inflamed paws from the carrageenan-induced paw edema and formalin tests were processed for histological and immunohistochemical assays, respectively. The results were analyzed by ANOVA and considered significant at P<0.05. FJNB (10 mg/kg) decreased the paw edema by 25% at the 3rd h after the carrageenan injection. Indomethacin, used as reference, inhibited the paw edema by 59% at the same time-point. In the formalin test, FJNB inhibited the 1st phase by 27, 49, and 52% and the 2nd phase by 37, 50, and 67%, at the doses of 1, 5, and 10 mg/kg, respectively. In addition, FJNB significantly inhibited the expressions of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), and the inflammatory cytokine tumor necrosis factor (TNF)-alpha. The histone deacetylase (HDAC) expression and the transcription factor nuclear factor kappa (NF-kB) were also inhibited at the same doses. In conclusion, the FJNB inhibitory actions on iNOS, COX-2, TNF-α, HDAC, and NF-kB could be involved with the drug anti-inflammatory activity.

Insights into milk-clotting activity of latex peptidases from Calotropis procera and Cryptostegia grandiflora.

Latex fractions from Calotropis procera, Cryptostegia grandiflora, Plumeria rubra, and Himatanthus drasticus were assayed in order to prospect for new plant peptidases with milk-clotting activities, for use as rennet alternatives. Only C. procera and C. grandiflora latex fractions exhibited proteolytic and milk-clotting activities, which were not affected by high concentrations of NaCl and CaCl2. However, pre-incubation of both samples at 75°C for 10min eliminated completely their activities. Both proteolytic fractions were able to hydrolyze k-casein and to produce peptides of 16kDa, a similar SDS-PAGE profile to commercial chymosin. RP-HPLC and mass spectrometry analyses of the k-casein peptides showed that the peptidases from C. procera or C. grandiflora hydrolyzed k-casein similar to commercial chymosin. The cheeses made with both latex peptidases exhibited yields, dry masses, and soluble proteins similar to cheeses prepared with commercial chymosin. In conclusion, C. procera and C. grandiflora latex peptidases with the ability to coagulate milk can be used as alternatives to commercial animal chymosin in the cheese manufacturing process.

Avaliação da qualidade de amostras comerciais de leite de janaguba (Himatanthus drasticus (Mart. ) Plumel) em Fortaleza – Ceará / Quality assessment of commercial samples of janaguba’s milk (Himatanthus drasticus (Mart. ) Plumel) in Fortaleza – Ceará.

RESUMO Os fitoterápicos à base de leite de janaguba (Himatanthus drasticus (Mart.) Plumel), usados para o tratamento de câncer, úlcera gástrica e outras doenças, são muito vendidos em mercados públicos de Fortaleza (CE). No entanto, registros mencionam que é comum a troca deste leite por látex de mangabeira (Hancornia speciosa Gomes). O trabalho objetivou avaliar a qualidade físico-química, química e microbiológica de amostras comerciais do leite de janaguba. Dez amostras comerciais foram adquiridas de um mercado de Fortaleza; quatro amostras autênticas de látex de janaguba foram obtidas da chapada do Araripe e uma amostra de látex de mangabeira foi obtida em Paracuru (CE). Foram determinados o aspecto geral, densidade, pH, resíduo seco, volume de sedimentação, perfil cromatográfico e qualidade microbiológica das amostras. Os resultados mostraram elevada contaminação microbiológica nas preparações comerciais e adulteração em seis destas amostras, o que aponta a urgente implantação de uma efetiva farmacovigilância dos fitoterápicos a fim de tornar seu consumo mais seguro e racional.

ABSTRACT The herbal medicines made from janaguba milk (Himatanthus drasticus (Mart.) Plumel), used to treat gastric ulcer, cancer and other diseases, and arewidely sold in the public markets of Fortaleza (CE). However, records mention that it is common to make fake copies of the milk by using mango tree latex (Hanconia speciosa Gomes). This study aimed to evaluate the chemical, physical-chemical and microbiological quality of commercial samples of janaguba milk. Ten commercial samples were purchased from a Fortaleza market; four authentic samples of janaguba latex were obtained from the Araripe plateau, and one mango tree latex sample was obtained in Paracuru (CE). We determined the general appearance, density, pH, dry residue, sedimentation volume, chromatographic profile and microbiological qualities. Results showed high microbiological contamination in the commercial preparations and evidence of tampering in six of these samples, which indicates the need for an urgent implementation of an effective pharmacovigilance strategy for herbal medicines in order to make its consumption more secure and rational.

Estudo etnofarmacológico e etnobotânico de Himatanthus drasticus (Mart. ) Plumel (janaguba) / Ethnopharmacological and ethnobotanical study of Himatanthus drasticus (Mart. ) Plumel (janaguba).

RESUMO Himatanthus drasticus (Mart.) Plumel, janaguba, produz um látex em seu caule que é usado para o tratamento de alguns tipos de câncer, vermes intestinais, febre, menstruações irregulares, infertilidade feminina e úlceras gástricas. Estudos fitoquímicos revelaram a presença de acetato de lupeol e proteínas; e estudos farmacológicos, os efeitos antiúlcera, antitumoral, imunomodulador, analgésico e anti-inflamatório. O presente trabalho objetivou realizar levantamento etnobotânico e etnofarmacológico sobre H. drasticus como contribuição ao conhecimento científico da referida espécie. Foi elaborado um questionário, que foi aplicado em entrevista a 21 raizeiros nos mercados das cidades de Crato, Fortaleza e Pacajus do estado do Ceará (CE). Observou-se que 38,1% dos raizeiros têm mais de 10 anos de serviço e 47,6%, estão na faixa etária de 40 a 59 anos, o que representa um fator positivo quanto à experiência com plantas medicinais. Aproximadamente 85,7% dos raizeiros relataram o uso do látex da H. drasticus para tratamento de úlcera; 66,7% para inflamação; 66,7% para câncer. Verificou-se que as principais indicações terapêuticas relatadas pelos raizeiros sobre esta espécie estão de acordo com as informações científicas. Os levantamentos etnobotânicos e etnofarmacológicos exercem um papel primordial no resgate do conhecimento tradicional, nos meios rurais e urbanos, tanto por seu valor histórico-cultural, como também pela necessidade de confirmação das indicações de uso.

ABSTRACT The Himatanthus drasticus (Mart.) Plumel, janaguba, produces a latex whose stem is used to treat some types of cancer, intestinal worms, fever, irregular menses, female infertility and gastric ulcers. Phytochemical studies revealed the presence of lupeol acetate and proteins in the latex; and pharmacological studies indicated antiulcer, anti-tumor, immunomodulating, analgesic and anti-inflammatory effects. This study aimed to conduct surveys on ethnopharmacological and ethnobotanical species H. drasticus as a contribution to the scientific knowledge about the species. A questionnaire and interviews were made with 21 healers in the markets of the cities of Crato, Fortaleza and Pacajús, in state of Ceara (CE). It was observed that 38.1% of the healers have more than 10 years of service, and 47.6% are between 40-59 years old, which is a positive factor about the experience with medicinal plants. Approximately 85.7% of the healers reported to apply latex H. drasticus for the treatment of ulcers, 66.7% for inflammation, and 66.7% for cancer. It was found that the main therapeutic indications mentioned by the healers about this species are consistent with the scientific information available. The ethnobotanical and ethnopharmacological surveys play an essential role on keeping the traditional knowledge in rural and urban areas, both for its historical and cultural value, but also for the need of confirmation of the intended use.

Antitumor activity of leaves of himatanthus drasticus (mart. ) plumel-apocynaceae (janaguba) in the treatment of Sarcoma 180 tumor

Himatanthus drasticus, also known as janaguba, is used popularly in Brazil's Northeastern region in the treatment of cancer. However, no scientific reports are available. The present study is the first investigation on the antitumor activity of crude methanolic extract from Himatanthus drasticus leaves against Sarcoma 180 tumor and on its side effects including acute oral toxicity. The OECD 423 methodology was used to study acute oral toxicity, and the STOCK methodology to assess antitumor activity. The crude extract showed low toxicity at the tested doses (50, 300 and 2000 mg/kg) administered orally. The histopathological analyses demonstrated alterations in liver lung, spleen and kidney. It also showed activity against Sarcoma 180 tumor in male Swiss albino mice, evidencing tumor growth inhibition of 67.7 percent and 68 percent at 300 mg/kg and 400 mg/kg doses, respectively.

Himatanthus drasticus, conhecida popularmente como janaguba, tem uma longa história de emprego na cura do câncer no nordeste brasileiro, porém quase sem registro na literatura. O objetivo desse trabalho foi investigar a atividade antitumoral do extrato bruto metanólico das folhas de Himatanthus drasticus frente ao modelo experimental Sarcoma 180 e avaliar sua toxicidade aguda. A determinação da toxicidade aguda foi realizada segundo a metodologia da OECD 423 e o transplante do tumor sólido de sarcoma 180 foi realizado seguindo a metodologia de Stock. O extrato apresentou baixa toxicidade nas doses testadas (50, 300 e 2000 mg/kg) por via oral. A análise histopatológica apresentou alterações em nível hepático, pulmonar, baço e renal. A atividade antineoplásica apresentou inibição tumoral significativa em relação ao grupo controle nas doses de 300 mg/kg e 400 mg/kg de peso do animal com um percentual de inibição de 67.7 por cento e 68 por cento respectivamente. Na menor dose analisada, 200 mg/kg, o percentual de inibição tumoral foi apenas de 32.8 por cento.