Swarna Bhasma Induces Antigen-Presenting Abilities of Macrophages and Helps Antigen Experienced CD4+ T Cells to Acquire Th1 Phenotypes Against Leishmania donovani Antigens.

In leishmaniasis, the protective immunity is largely mediated by proinflammatory cytokine producing abilities of T cells and an efficient parasite killing by phagocytic cells. Notwithstanding a substantial progress that has been made during last decades, the mechanisms or factors involved in establishing protective immunity against Leishmania are not identified. In ancient Indian literature, metallic "bhasma," particularly that of "swarna" or gold (fine gold particles), is indicated as one of the most prominent metal-based therapeutic medicine, which is known to impart protective and curative properties in various health issues. In this work, we elucidated the potential of swarna bhasma (SB) on the effector properties of phagocytes and antigen-activated CD4+ T cells in augmenting the immunogenicity of L. donovani antigens. The characterization of SB revealing its shape, size, composition, and measurement of cytotoxicity established the physiochemical potential for its utilization as an immunomodulator. The activation of macrophages with SB enhanced their capacity to produce nitric oxide and proinflammatory cytokines, which eventually resulted in reduced uptake of parasites and their proliferation in infected cells. Further, in Leishmania-infected animals, SB administration reduced the generation of IL-10, an anti-inflammatory cytokine, and enhanced pro-inflammatory cytokine generation by antigen activated CD4+ T cells with increased frequency of double (IFNγ+/TNFα+) and triple (IFNγ+TNFα+IL-2+) positive cells and abrogated disease pathogeneses at the early days of infection. Our results also suggested that cow-ghee (A2) emulsified preparation of SB, either alone or with yashtimadhu, a known natural immune modulator which enhances the SB's potential in enhancing the immunogenicity of parasitic antigens. These findings suggested a definite potential of SB in enhancing the effector functions of phagocytes and CD4+ T cells against L. donovani antigens. Therefore, more studies are needed to elucidate the mechanistic details of SB and its potential in enhancing vaccine-induced immunity.

Calotropis procera (Aiton) Dryand (Apocynaceae): State of the art of its uses and Applications.

Calotropis procera (Aiton) Dryand (Apocynaceae), popularly known as milkweed, has been traditionally used to treat diseases particularly associated with gastric disorders, skin disease and inflammatory processes. The present study aimed to review the current scientific evidence regarding the pharmacological effects of C. procera extracted phytochemicals and possible research opportunities as complementary and alternative medicine. Scientific publications were searched in various electronic databases (PubMed, Scopus, Web of Science, Google Scholar, Springer, Wiley, and Mendeley) using the following search terms: Calotropis procera, medicinal plants, toxicity, phytochemical characterization, and biological effects. Collected data showed that cardenolides, steroid glycoside and flavonoids are the main classes of phytochemicals identified in C. procera latex and leaves. In addition, lignans, terpenes, coumarins, and phenolic acids have been reported. These metabolites have been correlated with their biological activities, including mainly antioxidant, anti-inflammatory, antitumoral, hypoglycemic, gastric protective, anti-microbial, insecticide, anti-fungal, anti-parasitic, among others. However, some of the studies were carried out with only a single dose or with a high dose not achievable under physiological conditions. Therefore, the validity of C. procera biological activity may be questionable. Not less important to highlight are the risks associated with its use and the possibility of accumulation of heavy metals that can be toxic. Furthermore, there are no clinical trials with C. procera to date. In conclusion, the need of bioassayguided isolation of bioactive compounds, bioavailability and efficacy, as well as pharmacological and toxicity studies, are needed using in vivo models and clinical trials in order to support the traditionally claimed health benefits.

Tissue healing changes on wounds in rats after treatment with Hancornia speciosa latex in cream-gel formulation.

PURPOSE: Hancornia speciosa latex has shown pharmacological potential in wound healing processes due to its angiogenic, osteogenic, and anti-inflammatory activities. The aims of this study were to carry out a cream-gel formulation with 5, 10 and 25% of H. speciosa serum latex and to evaluate its potential to stimulate the skin regeneration in rats' wounds. METHODS: One hundred and twenty rats were divided into five groups: neutral control with saline (G1), cream-gel based on H. speciosa latex serum at 5% m/v (G2), cream-gel at 15% m/v (G3), cream-gel at 25% m/v (G4), and cream-gel (G5). The animals were euthanized at three, seven, 14 and 21 days after the injury induction, and some parameters were analyzed: wound contraction, necrosis, fibrin, polymorphonuclear and mononuclear infiltrates, fibroblast, angiogenesis, hemorrhage, and collagen. RESULTS: The therapeutic treatment with cream-gel at 15 and 25% is beneficial in the inflammatory phase of healing processes since it increased the angiogenesis and proliferation of mononuclear infiltrations in wounds. Regarding wound contraction, the treatment with cream-gel (5 and 15%) induced a higher rate of contraction in the proliferative phase. The 15% cream-gel formulation stimulated a greater production of collagen in the injured tissues. CONCLUSIONS: H. speciosa cream-gel is a low-cost herbal medicine which can aid in tissue repair.

Ficus dubia latex extract prevent DMH-induced rat early colorectal carcinogenesis through the regulation of xenobiotic metabolism, inflammation, cell proliferation and apoptosis.

Ficus dubia latex is recognized as a remedy in Asian traditional medicine with various therapeutic effects. The present study aimed to determine the preventive action of Ficus dubia latex extract (FDLE) on 1,2-dimethylhydrazine (DMH)-induced rat colorectal carcinogenesis and its mechanisms. The experiment included an initiation model in which rats were orally administered with FDLE daily for 1 week before DMH injection until the end of the experiment, while only after DMH injection until the end in the post-initiation model. The results firstly indicated that FDLE treatment could reduce the level of methylazoxymethanol (MAM) in rat colonic lumen by inhibition of the activities of both phase I xenobiotic metabolizing enzymes in the liver and ß-glucuronidase in the colon, leading to reduced DNA methylation in colonic mucosal cells, related to the number of ACF in the initiation stage. Besides, FDLE modulated the inflammation which could suppress the growth and induce apoptosis of aberrant colonic mucosal cells, leading to retardation of ACF multiplicity. Therefore, FDLE showed the ability to suppress the DMH-induced rat ACF formation and inflammation promoted growth of ACF. In conclusion, FDLE had the potential to prevent carcinogens-induced rat colorectal carcinogenesis in the initiation stage.

The Activity of Chelidonium majus L. Latex and Its Components on HPV Reveal Insights into the Antiviral Molecular Mechanism.

Yellow-orange latex of Chelidonium majus L. has been used in folk medicine as a therapeutic agent against warts and other visible symptoms of human papillomavirus (HPV) infections for centuries. The observed antiviral and antitumor properties of C. majus latex are often attributed to alkaloids contained therein, but recent studies indicate that latex proteins may also play an important role in its pharmacological activities. Therefore, the aim of the study was to investigate the effect of the crude C. majus latex and its protein and alkaloid-rich fractions on different stages of the HPV replication cycle. The results showed that the latex components, such as alkaloids and proteins, decrease HPV infectivity and inhibit the expression of viral oncogenes (E6, E7) on mRNA and protein levels. However, the crude latex and its fractions do not affect the stability of structural proteins in HPV pseudovirions and they do not inhibit the virus from attaching to the cell surface. In addition, the protein fraction causes increased TNFα secretion, which may indicate the induction of an inflammatory response. These findings indicate that the antiviral properties of C. majus latex arise both from alkaloids and proteins contained therein, acting on different stages of the viral replication cycle.

Successful Pre-Clinical Management of Irinotecan-Debilitated Animals: A Protein- Based Accessory Phytomedicine.

BACKGROUND: Calotropis procera is a laticiferous plant (Apocynaceae) found in tropical regions all over the world. The ultrastructural characteristics of laticifers, their restricted distribution among different taxonomic groups, and in some species in each clade, as peptidases from latex, make them very attractive for biological analysis. OBJECTIVE: The study aims to investigate the effects of LP-PII-IAA (laticifer protein (LP) sub-fraction II (PII) of C. procera presenting an iodoacetamide-inhibited cysteine proteinase activity) on irinotecan-induced intestinal mucositis, a serious adverse effect of this medicine for the treatment of cancer. METHODS: LP-PII-IAA is composed of closely related isoforms (90%) of peptidases derived from catalysis and an osmotin protein (5%). Animals receiving co-administration of LP-PII-IAA presented a significant decrease in mortality, absence of diarrhea, histological preservation, and normalization of intestinal functions. RESULTS: Clinical homeostasis was accompanied by a reduction in MPO activity and declined levels of IL-1ß, IL-6 and KC, while the IL-10 level increased in LP-PII-IAA-treated animals. COX-2 and NF-kB immunostaining was reduced and the levels of oxidative markers (GSH, MDA) were normalized in animals that received LP-PII-IAA. CONCLUSION: We suggest that peptidases from the latex of Calotropis procera were instrumental in the suppression of the adverse clinical and physiological effects of irinotecan.

Anti-inflammatory and antioxidant effect of methanol extract of latex of Calotropis procera in rat model of colorectal cancer.

ETHNOPHARMACOLOGICAL RELEVANCE: Preparations derived from the plant Calotropis procera, have been used for medicinal purpose though the plant is known for its toxic effects. The aerial parts of the plant contain latex in plenty and have been found effective in treating disorders of gastrointestinal system and cancer. AIM OF THE STUDY: This study evaluated the efficacy of C. procera dried latex extract prepared in methanol (MeDL) against inflammation and oxidative stress in experimental model of colorectal carcinoma (CRC). MATERIALS AND METHODS: Two subcutaneous injections of chemical carcinogen, 1,2-dimethylhydrazine (DMH; 150 mg/kg) were given at an interval of one week to induce CRC in rats. The MeDL (50 and 150 mg/kg) and aspirin (60 mg/kg) were given daily and their effect was evaluated on markers of oxidative stress and inflammation after completion of 8 weeks following second injection of carcinogen. A comparison was made with normal and experimental control groups. The colon tissue levels of glutathione (GSH), thiobarbituric acid reactive substances (TBARS), superoxide dismutase (SOD), nitrite and myeloperoxidase (MPO) were determined. Enzyme-linked immunosorbent assay was performed to determine the levels of prostaglandin E2 (PGE2) and tumor necrosis factor-alpha (TNF-α) and immunohistochemical analysis was performed for IL-1ß. RESULTS: Induction of cancerous changes in the colon resulted in altered oxidative homeostasis as evident from a reduction in GSH level and SOD activity and rise in TBARS level when compared with normal rats. Elevated levels of nitrite, MPO, TNF-α, PGE2 and immunoreactivity of IL-1ß were also observed in these rats. The levels of these markers were normalized when the rats were treated with MeDL or anti-inflammatory drug, aspirin. CONCLUSION: This study demonstrates that suppression of oxidative stress and inflammation contributes to the beneficial effect of MeDL in rat model of colon carcinogenesis.

In-vivo anti-plasmodial activity of phosphate buffer extract of Calotropis procera latex in mice infected with Plasmodium berghei.

ETHNOPHARMACOLOGICAL RELEVANCE: Malaria is a global health problem with the greatest burden in sub-Saharan Africa (sSA). The resistance to available antimalarial agents necessitate for the development of new and safe drugs for which medicinal plants provides credible alternative sources for discovering new and cheap therapeutic agents. Calotropis procera is used in several folk or traditional medicines for the treatment of various diseases across different regions of the world. In Nigeria traditional medicine, C. procera latex is used either alone or in combination with other herbs to cure common diseases including malaria. In Malaka district (Indonesia), Calotropis gigantea (a member of Apocyanceae), is one of the most used herbs to treat malaria patient via the massage method. AIM OF THE STUDY: This study aimed to evaluate the anti-plasmodial activity of phosphate buffer extract of Calotropis procera latex in mice infected with Plasmodium berghei. MATERIALS AND METHODS: The plant's anti-plasmodial agent was extracted using 0.2 M-phosphate buffer (pH 7.0), followed by precipitation using acetone. 90 (ninety) mice were divided into three main groups of 30 (thirty) mice each, used for the curative, suppressive and prophylactic tests, respectively. The 30 (thirty) mice in each of the main groups were sub-divided into five groups of 6 (six) mice. The mice in the group 1, 2 and 3 (test groups) were made to receive graded doses of 25 mg/kg, 50 mg/kg and 75 mg/kg of the extract of C. procera latex intraperitoneally; group 4 (negative control group) received 0.2 ml of normal saline; while group 5 (positive control group) were administered with 5 mg/kg chloroquine. The phytochemical constituents of the plant and its intraperitoneal median lethal dose (LD50) were also undertaken. RESULTS: The freeze-dried acetone extract exhibited acute toxicity with median lethal dose (LD50) of 745 mg/kg body weight in mice. The highest percentage parasite suppression (61.85%), percentage parasite cure (50.26%), and percentage parasite prophylaxis (65.47%), were obtained for the groups treated with 75 mg/kg bodyweight/day of the extract. The least percentage parasite suppression (44.74%), percentage parasite cure (35.21%), and percentage parasite prophylaxis (45.21%), were obtained for the groups treated with 25 mg/kg body weight of the extract. Also, a dose-dependent percentage parasite suppression (53.03%), percentage parasite cure (39.70%), and percentage parasite prophylaxis (49.82%) were obtained for the groups treated with 50 mg/kg body weight. This is comparable to the groups treated with standard chloroquine. The extract also produced a significant elevation in body weight of the animals for suppressive and curative tests. However, there were observable significant decreases in body weight of the animals in the case of prophylactic test. CONCLUSION: This study showed that the phosphate buffer extract of C. procera latex possess anti-plasmodial activity. The results of this study can be used as a basis for further phytochemical investigations in the search for new and locally affordable antimalarial agents.

Thrombin- and plasmin-like and platelet-aggregation-inducing activities of Plumeria alba L. latex: Action of cysteine protease.

ETHNOPHARMACOLOGICAL RELEVANCE: In folk medicine, parts of Plumeria alba L. are used for the treatment of many diseases, with its latex being used for curing skin diseases and promoting wound healing. AIM OF THE STUDY: This study aimed to study the role of P. alba L. latex in hemostasis and platelet aggregation. MATERIALS AND METHODS: The latex of P. alba L. was processed to remove waxes and enrich protein content, and the final extract was named Plumeria alba L. natant latex (PaNL). PaNL was analyzed for protease activity against casein. The type of protease in PaNL was identified by using protease inhibitors such as E-64, phenylmethylsulfonyl fluoride, ethylenediaminetetraacetic acid, and pepstatin A. Human fibrinogen, fibrin, and collagen types I and IV were subjected to hydrolysis with different concentrations of PaNL. The thrombin-like activity of PaNL was determined by analyzing its fibrinogen-clotting and procoagulant activities. The role of PaNL in platelet aggregation was also investigated. Its hemorrhagic and edema-inducing activities were evaluated in a mouse model. Phytochemical compounds were identified by gas chromatography-mass spectroscopy. RESULTS: The findings of casein/gelatin zymography confirmed that PaNL possesses protease activity. The results of the protease inhibition study indicated the presence of a cysteine-type protease(s) in PaNL. PaNL hydrolyzed the subunits of fibrinogen, fibrin, and collagen types I and IV. Its fibrin-degradation activity indicated that PaNL possesses plasmin-like activity. PaNL induced clotting of citrated human plasma within 3 min of incubation in the absence of CaCl2, indicating the presence of thrombin-like activity, which was further confirmed by the results of the fibrinogen-clotting assay. PaNL induced platelet aggregation in the absence of agonists. There was no hemolytic activity. Mice injected with PaNL did not show edema/ hemorrhagic activity. CONCLUSION: PaNL possesses procoagulant, fibrino(geno)lytic, thrombin- and plasmin-like activities and induces platelet aggregation, which could explain its usage for wound treatment in folk medicine.

Physico-chemical characterization and tissue healing changes by Hancornia speciosa Gomes latex biomembrane.

Skin wounds have been a public health concern of high frequency, in addition to requiring intensive and expensive care. The natural rubber latex (NRL) from Hancornia speciosa Gomes has been used to treat many problems in traditional medicine and also present healing properties, antifungal and anti-inflammatory activity and antinociceptive effects. The purpose of this study was to characterize the new biomembrane from the NRL of H. speciosa (HS) by Fourier transform infrared (FTIR) and mechanical strength test and to investigate its biological properties by the cytotoxicity assay and in vivo healing activity. The results showed that the HS biomembrane exhibited characteristic bands of the main component cis-1,4-polyisoprene. Besides, its Young modulus was close to human skin with adhesive-compatible mechanical characteristics. The cytotoxicity assays revealed that the HS biomembrane was not toxic to fibroblast cells neither using agar diffusion test nor MTT assay. Furthermore, the HS biomembrane stimulated the inflammatory cells and the angiogenesis, increased significantly the collagenesis and improved the quality of heal until the remodeling phase induced by implants in mice. Thus, this biomembrane has proven to be a safe and biocompatible biomaterial with healing potential, becoming an effective and low-cost alternative for the treatment of skin wounds.

Healing effects of natural latex serum 1% from Hevea brasiliensis in an experimental skin abrasion wound model

Abstract Background Dermabrasion is related with mechanical and surgical traumas on the skin; usually topical antiseptics and/or saline have been used for healing. Natural products for wound healing can also be used for abrasions, such as latex from Hevea brasiliensis. Objective This study aimed to evaluate the in vitro viability and migratory/proliferative effects of latex serum from H. brasiliensis and to compare with a commercially available standard antiseptic solution and saline in experimental dermabrasion on rats. Methods For in vitro evaluation, MTT and scratch assays were used. In vivo testing was performed in 72 rats submitted to dermabrasion, treated with saline, antiseptic, or latex serum. This study evaluated re-epithelialization, neutrophilic infiltration, and the quantification of crust and epidermis. Results Latex showed viability at 1% and 0.1% concentrations and migratory/proliferative activity at 0.01% concentrations. The re-epithelialization was highest in latex group on 7th day. The latex group displayed lower thickness of crusts and greater extent of epidermal layers. The latex and antiseptic groups showed increases of myeloperoxidase levels on the 2nd day and showed important reductions from the 7th day. Study limitations Acute superficial wound model in rats and non-use of gel-cream (medium) without latex. Conclusion In conclusion, non-toxic latex stimulated migration/proliferation of keratinocytes in vitro and significantly accelerated wound healing in animal excoriation models compared to chlorhexidine or saline.

Healing effects of natural latex serum 1% from Hevea brasiliensis in an experimental skin abrasion wound model.

BACKGROUND: Dermabrasion is related with mechanical and surgical traumas on the skin; usually topical antiseptics and/or saline have been used for healing. Natural products for wound healing can also be used for abrasions, such as latex from Hevea brasiliensis. OBJECTIVE: This study aimed to evaluate the in vitro viability and migratory/proliferative effects of latex serum from H. brasiliensis and to compare with a commercially available standard antiseptic solution and saline in experimental dermabrasion on rats. METHODS: For in vitro evaluation, MTT and scratch assays were used. In vivo testing was performed in 72 rats submitted to dermabrasion, treated with saline, antiseptic, or latex serum. This study evaluated re-epithelialization, neutrophilic infiltration, and the quantification of crust and epidermis. RESULTS: Latex showed viability at 1% and 0.1% concentrations and migratory/proliferative activity at 0.01% concentrations. The re-epithelialization was highest in latex group on 7th day. The latex group displayed lower thickness of crusts and greater extent of epidermal layers. The latex and antiseptic groups showed increases of myeloperoxidase levels on the 2nd day and showed important reductions from the 7th day. STUDY LIMITATIONS: Acute superficial wound model in rats and non-use of gel-cream (medium) without latex. CONCLUSION: In conclusion, non-toxic latex stimulated migration/proliferation of keratinocytes in vitro and significantly accelerated wound healing in animal excoriation models compared to chlorhexidine or saline.

Hancornia speciosa serum fraction latex stimulates the angiogenesis and extracellular matrix remodeling processes.

The Hancornia speciosa latex reveals angiogenic, osteogenic, and anti-inflammatory properties, which present its potential for developing of wound healing drugs; however, the latex compounds responsible for angiogenesis remain unknown. One strategy to screen these active compounds is evaluation of latex fractions. This study aimed to obtain different fractions of latex and evaluate its angiogenic activity separately using the chick chorioallantoic membrane (CAM) assay. The serum (SE) fraction was responsible for angiogenesis, which was subject to biochemical characterization and computational simulations in order to understand the contribution of H. speciosa latex in wound healing process. Our results revealed weak antioxidant potential and absence of antimicrobial activity in the SE fraction. Phytochemical analysis identified chlorogenic acids (CGA) as the main compound of SE fraction. CGA bioactivity predictions identify different molecules associated with extracellular matrix (ECM) remodeling, such as metalloproteinases, which also are overexpressed in our CAM assay experiment. Docking simulations revealed the interactions between CGA and matrix metalloproteinase 2. In conclusion, SE latex fraction stimulates angiogenesis and may influence ECM remodeling. These properties may contribute to the wound healing process, and also confirm the widespread use of this plant.

Characterization and Evaluation of Antioxidant Activity of Aloe schelpei Reynolds.

BACKGROUND: The role of free radical reactions in disease pathology is well known to be involved in many acute and chronic disorders in human beings, such as diabetes, atherosclerosis, aging, immunosuppression and neurodegeneration. The search for new drugs of plant origin becomes increasingly urgent due to drug resistance. Aloe schelpei is an endemic Aloe species traditionally used for the treatment of infectious and chronic diseases. AIM: This study was conducted to evaluate free radical scavenging activities of leaf latex of Aloe schelpei and its isolated compounds. METHODS: The leaf latex of A. schelpei was subjected to preparative thin-layer chromatography to afford three compounds. Free radical scavenging activities of the leaf latex and its constituents was carried out using a 2, 2-diphenyl-1-picrylhydrazyl method. RESULTS: Phytochemical investigation of the leaf latex Aloe schelpei by prepartive thin layer chromatography led to the isolation of three compounds, identified as microdontin A/B (1), aloin A/B (2) and aloinoside A/B (3). The results showed that the leaf latex had a strong free radical scavenging activity reaching a maximum of 84.3% at a concentration of 100 µg/mL, and with an IC50 value of 25.3 ± 2.45 µg/mL (p < 0.05). Among the isolated compounds, microdontin A/B (1) was found to have the strongest free radical scavenging activity with an IC50 value of 0.07 ± 0.005 mµ, followed by aloinoside A/B (IC50 = 0.13 ± 0.01 mM) and aloin A/B (IC50 = 0.15 ± 0.02 mM). CONCLUSION: The traditional medicinal practice of the leaf latex may be due to the antioxidant activities of the leaf latex of A. schelpei and the isolated compounds.

Consumption of latex from Euphorbia tirucalli L. promotes a reduction of tumor growth and cachexia, and immunomodulation in Walker 256 tumor-bearing rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Euphorbia tirucalli L. is an African plant that grows well in Brazil. Individuals diagnosed with cancer frequently consume latex from E. tirucalli, dissolved in drinking water. In vitro studies confirm the antitumor potential of E. tirucalli latex, but in vivo evaluations are scarce. AIM OF THE STUDY: To evaluate the effect of intake of an aqueous solution of E. tirucalli latex on tumor growth, cachexia, and immune response in Walker 256 tumor-bearing rats. MATERIALS AND METHODS: Latex from E. tirucalli was collected and analyzed by LC-MS. Sixty male Wistar rats (age, 90 days) were randomly divided into four groups: C, control group (without tumor); W, Walker 256 tumor-bearing group; SW1, W animals but treated with 25 µL latex/mL water; and SW2, W animals but treated with 50 µL latex/mL water. Animals received 1 mL of latex solution once a day by gavage. After 15 d, animals were euthanized, tumor mass was determined, and glucose and triacylglycerol serum levels were measured by using commercial kits. Change in the body weight during tumor development was calculated, and proliferation capacity of tumor cells was assessed by the Alamar Blue assay. Phagocytosis and superoxide anion production by peritoneal macrophages and circulating neutrophils were analyzed by enzymatic and colorimetric assays. Data are analyzed by one-way ANOVA followed by Tukey's post-hoc test, with the significance level set at 5%. RESULTS: The analysis of the latex revealed the presence of triterpenes. The ingestion of the latex aqueous solution promoted 40% and 60% reduction of the tumor mass in SW1 and SW2 groups, respectively (p < 0.05). The proliferative capacity of tumor cells from SW2 group was 76% lower than that of cells from W group (p < 0.0001). Animals treated with latex gained, on average, 20 g (SW1) and 8 g (SW2) weight. Glucose and triacylglycerol serum levels in SW1 and SW2 animals were similar to those in C group rats. Peritoneal macrophages and blood neutrophils from SW1 and SW2 animals produced 30-40% less superoxide anions than those from W group animals (p < 0.05), but neutrophils from SW2 group showed an increased phagocytic capacity (20%, vs. W group). CONCLUSIONS: E. tirucalli latex, administered orally for 15 d, efficiently reduced tumor growth and cachexia in Walker 256 tumor-bearing rats. Decreased tumor cell proliferative capacity was one of the mechanisms involved in this effect. Further, the data suggest immunomodulatory properties of E. tirucalli latex. The results agree with folk data on the antitumor effect of latex ingestion, indicating that it may be useful as an adjunct in the treatment of cancer patients. For this, further in vivo studies in animal and human models need to be conducted.

Antimalarial activity of the aqueous extract of the latex of Aloe pirottae Berger. (Aloaceae) against Plasmodium berghei in mice.

ETHNOPHARMACOLOGICAL RELEVANCE: In spite of worldwide efforts, malaria remains one of the most devastating illnesses in the world. The huge number of lives it takes and the resistance of malaria parasites to current drugs necessitate the search for new effective antimalarial drugs. Medicinal plants have been the major source of such drugs and A. pirottae is one of these plants used traditionally for the treatment of malaria in Ethiopia. AIM: This study was aimed at evaluating the antimalarial activity of the aqueous extract of A. pirottae against chloroquine sensitive P. berghei in mice. MATERIALS AND METHODS: The extract was obtained by macerating the latex of A. pirottae with distilled water. To determine its antiplasmodial activity, a 4-day suppressive model was used by dividing 40 mice into five groups of 8 mice each and given 200, 400 & 600mg/kg of the extract, the standard drug (chloroquine 25mg/kg) and the vehicle (distilled water). Then parasite suppression by the extract, survival time and prevention of loss of body weight, rectal temperature and packed cell volume were assessed. All data were presented as the Mean ±â€¯SEM (Standard Error of the Mean) and analyzed using IBM SPSS version 20. RESULTS: The extract showed moderate antimalarial activity by significantly (p < 0.001) suppressing parasitemia at all dose levels with maximum parasitemia suppression of 47.0% and significantly (p < 0.01) increasing survival time. Furthermore, 400 mg/kg and 600 mg/kg doses showed significant (p < 0.01) prevention of loss in body weight, rectal temperature and packed cell volume. CONCLUSION: Based to the results of this study, A. pirottae is endowed with a moderate antimalarial activity that is in agreement with the traditional claim of A. pirottae, hence may be used as a basis for further studies to be conducted on antimalarial activity of the plant.

Anthelminthic potential of the Ficus insipida latex on monogeneans of Colossoma macropomum (Serrasalmidae), a medicinal plant from the Amazon.

INTRODUCTION: Herbal therapy is a potentially beneficial alternative for fish aquaculture, since it may be cheaper and more effective than chemotherapy. The aim of this study was to investigate the in vitro efficacy of Ficus insipida latex on monogeneans of Colossoma macropomum gills. MATERIALS AND METHODS: To evaluate the anthelmintic activity, four concentrations of F. insipida latex (250, 500, 750 and 1000 µL/L) and exposure time to cause immobilization on monogeneans were used. In addition, two control groups, being one with water from the breeding tank and the other with breeding water from the tank + 70% ethyl alcohol were used. RESULTS: At the concentration of 250 µL/L of F. insipida latex, the immobilization of the monogeneans occurred after 4 h of exposure, while at the concentration of 500 µL/L, it occurred after 2 h. At the concentrations of 750 and 1000 µL/L of F. insipida latex, the immobilization of the monogeneans occurred after 1 h and 30 min, respectively. After exposure to 250 µL/L of F. insipida latex, 100% of immobilization of monogeneans was observed within 4 h, to 500 and 750 µL/L, 100% immobilization occurred within 4 h and to 1000 µL/L, 100% mortality occurred after 2 h. CONCLUSIONS: Thus, we recommended the use of 1000 µL/L of F. insipida latex for therapeutic baths in of C. macropomum against monogeneans, after previous test of toxicity.

Plant Latex, from Ecological Interests to Bioactive Chemical Resources.

Historically, latex-bearing plants have been regarded as important medicinal resources in many countries due to their characteristic latex ingredients. They have also often been endowed with a social or cultural significance in religious or cult rituals or for hunting. Initial chemical studies focused on the protein or peptide content but recently the interest extended to smaller molecules. Latex has been found to contain a broad range of specialized metabolites such as terpenoids, cardenolides, alkaloids, and phenolics, which are partly responsible for their antibacterial, antifungal, anthelmintic, cytotoxic, and insect-repellent activities. The diversity in biology and chemistry of latexes is supposedly associated to their ecological roles in interactions with exogenous factors. Latexes contain unique compounds that are different to those found in their bearing plants. Exploring the feasibility of plant latex as a new type of bioactive chemical resource, this review paper covers the chemical characterization of plant latexes, extending this to various other plant exudates. Also, the factors influencing this chemical differentiation and the production, transportation, and chemistry of the latex exudates are described, based on ecological and biochemical mechanisms. We also proposed a latex coagulation model involving 4 general conserved steps. Therefore, the inherent defensive origin of latexes is recognized as their most valuable character and encourages one to pay attention to these materials as alternative sources to discover metabolites with insecticidal or antimicrobial activity.

Analytical methods to access the chemical composition of an Euphorbia tirucalli anticancer latex from traditional Brazilian medicine.

ETHNOPHARMACOLOGICAL RELEVANCE: Euphorbia tirucalli L. is widely used by Brazilian folk medicine, mainly for its anticancer activity. However, its commercialization was banned by The Brazilian National Sanitary Surveillance Agency (ANVISA) due to the presence of some compounds considered toxic, such as the diterpene esters. AIM OF THE STUDY: Chemical and biological analyses were performed with the Brazilian Euphorbia tirucalli latex to support its wide traditional use in Brazil. MATERIAL AND METHODS: Latex was collected by using two procedures, in a solution of dichloromethane: methanol (3:1, 100 mL) and in 100 mL of distilled water. The first procedure was concentrated as a crude extract and the second one was partitioned with hexane and dichloromethane. The partitions and crude extract were subjected to phytochemical analyses using three different methods: Fourier transform-ion cyclotron resonance mass spectrometry (FT-ICR MS) with electrospray ionization sources in negative mode (ESI(-)) as well as in tandem mass spectrometry ESI(-) MS/MS and Atmospheric Pressure Chemical Ionization in positive mode (APCI(+)), Gas Chromatography coupled Mass Spectrometry (GC-MS) and Nuclear Magnetic Resonance (NMR) (1H-NMR and 13C-NMR). The cytotoxic potential was evaluated using the crude extract in macrophages RAW 264.7 and Gastric Adenocarcinoma (AGS) cancer cells. The evaluation of immunomodulatory activity was made through the detection of Nitric Oxide (NO) and cytokines as Tumor necrosis factor α (TNF-α) and Interleukin-6 (IL-6). RESULTS: GC-MS showed the presence of some esters of fatty acids, for instance myristic, palmitic, stearic, oleic and linoleic acid and, mainly, triterpenes such as euphol and tirucallol. With NMR, most of the signals were related to triterpenoids euphol and tirucallol. However, when the latex was analyzed with ESI(-) FT-ICR MS, a wide variety of molecules from different classes of natural products (fatty acids, diterpenes, triterpenes, steroids) were found. On the other hand, when APCI(+)FT-ICR MS was used, the ion M+. At ratio mass-charge (m/z) 426.38567, related to triterpenes euphol and tirucallol masses, presented the most intense peak, with a mass error of -0.11, indicating high accuracy. Diterpene esters from 4-deoxyphorbol and ingenol were identified only by ESI(-)FT-ICR MS and ESI(-)FT-ICR MS/MS. When evaluated biologically, the crude latex showed immunomodulatory activity, as it reduced the production of the pro-inflammatory cytokines TNF-α, IL-6 and NO, and the effect on NO reduction was more significant, obtaining in a similar result to the N(ω)-Nitro-L-Arginine Methyl Ester (L-NAME) standards, as well as significant cytotoxic activity with half inhibitory concentration (IC50) values of 69.43 ±â€¯1.29 µg/mL against AGS without damaging healthy ones. CONCLUSION: It was verified that the Brazilian Euphorbia tirucalli latex consists mainly of the triterpenes euphol and tirucallol, which may be the main cause of the anticancer activity attributed to the plant, but many other minor compounds could have been determined by the FT-ICR MS method, such as the diterpene esters. It has antitumor potential because it acts selectively against cancer cells and it also prevents the progression of tumors, because it carries an important immunomodulatory effect.

Protection afforded by methanol extract of Calotropis procera latex in experimental model of colitis is mediated through inhibition of oxidative stress and pro-inflammatory signaling.

Calotropis procera, a latex producing plant is known to possess medicinal properties including its beneficial effect in gastrointestinal disorders. The anti-inflammatory effect of its latex in various experimental models is noteworthy and in light of this the present study was carried out with an objective to evaluate its efficacy in ulcerative colitis, an inflammatory condition of the colon. Colitis was induced in rats by acetic acid and the rats were divided into four groups where one group served as experimental control and the other groups were treated with two doses of methanol extract of dried latex of C. procera (MeDL; 50 and 150 mg/kg) and mesalazine (MSZ; 300 mg/kg). The study also included normal control (NC) group for comparison of various parameters related to colon like macroscopic changes, ulcer score, adherent mucus content, weight/length ratio, small intestinal transit, oxidative stress and inflammatory markers, tissue histology and immunoreactivity of cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS) and nuclear factor kappa beta (NFκB) subunit p65. Treatment of colitic rats with MeDL produced a significant reduction in colonic mucosal damage as revealed by macroscopic and microscopic evaluation and normalization of tissue levels of oxidative stress markers and pro-inflammatory mediators. The protection afforded by MeDL was also evident from its restorative effect on tissue histology and expression of COX-2, iNOS and NFκB(p65). This study shows that by targeting oxidative stress and NFκB(p65) mediated pro-inflammatory signaling, the latex of C. procera affords protection in colitis and its effect was comparable to that of mesalazine. This study suggests that latex of C. procera could serve as a promising therapeutic option for treating inflammatory conditions of the colon.