Angel Josabad Alonso-Castro

Mexican medicinal plants used for cancer treatment: Pharmacological, phytochemical and ethnobotanical studies

AIM OF THE STUDY This review provides a summary of Mexican medicinal flora in terms of ethnobotanical, pharmacology, and chemistry of natural products related to anticancer activity. MATERIALS AND METHODS Bibliographic investigation was carried out by analyzing recognized books and peer-reviewed papers, consulting worldwide accepted scientific databases from the last five decades. Mexican plants with attributed anti-cancer properties were classified into six groups: (a) plant extracts that have been evaluated for cytotoxic effects, (b) plant extracts that have documented anti-tumoral effects, (c) plants with active compounds tested on cancer cell lines, (d) plants with novel active compounds found only in Mexican species, (e) plants with active compounds that have been assayed on animal models and (f) plants with anti-cancer ethnopharmacological references but without scientific studies. RESULTS Three hundred plant species belonging to 90 botanical families used for cancer treatment have been recorded, of which only 181 have been experimentally analyzed. The remaining 119 plant species are in use in empirical treatment of diseases consistent with cancer symptomatology. Only 88 of the plant extracts experimentally studied in in vitro cellular models have demonstrated active cytotoxic effects in at least one cancer cell line, and 14 out of the 88 have also been tested in vivo with the results that one of them demonstrated anti-neoplasic effects. A total of 187 compounds, belonging to 19 types of plant secondary metabolites, have been isolated from 51 plant extracts with active cytotoxic effects, but only 77 of these compounds (41%) have demonstrated cytoxicity. Seventeen of these active principles have not been reported in other plant species. However, only 5 compounds have been evaluated in vivo, and 3 of them could be considered as active. CONCLUSION Clearly, this review indicates that it is time to increase the number of experimental studies and to begin to conduct clinical trials with those Mexican plants and its active compounds selected by in vitro and in vivo activities. Also, the mechanisms of action by which plant extracts and their active compounds exert anti-cancer effects remain to be studied.

Rutin exerts antitumor effects on nude mice bearing SW480 tumor

BACKGROUND AND AIMS We previously showed that extracts from Phoradendron serotinum and Croton lechleri exerted in vitro cytotoxic and in vivo antitumor effects and that their main component was rutin (RTN; 3-rhamnosyl-glucosylquercetin). However, it is unknown whether RTN exerts in vivo antitumoral effects on human colon cancer cells. The aim of this work was to evaluate the antitumor effects of RTN on a murine model. METHODS Cytotoxic effects of RTN on human cancer and non-tumorigenic cell lines were evaluated using the MTT assay. Different doses of RTN were injected intraperitoneally daily into nu/nu mice bearing tumors of SW480 colon cancer cells during 32 days. The growth and weight of tumors were measured. Serum levels of VEGF, survival time, increase in life span and toxicological effects on body weight and organ weight were also analyzed. RESULTS RTN showed the highest cytotoxic effects against SW480 cells (IC₅₀ = 125 μM) as compared to the other cancer cells lines and decreased, in a dose dependent manner, the tumor volume and weight of mice bearing SW480 tumor. RTN 20 mg/kg, the highest dose tested, lacked toxic effects on body weight and relative organ weight in mice, increased mean survival time by 50 days, and decreased by 55% the VEGF serum levels compared to untreated mice. CONCLUSIONS RTN exerts in vitro cytotoxic effects on SW480 cells, induces in vivo antitumor effects, lacks toxic effects on mice bearing SW480 tumor and exerts antiangiogenic properties.

Ethnobotany of medicinal plants used in Xalpatlahuac, Guerrero, México.

ETHNOPHARMACOLOGICAL IMPORTANCE Medicinal plants have been used for centuries for the empirical treatment of many diseases. This study documented the use of plant species in traditional medicine in the municipality of Xalpatlahuac, Guerrero, México. MATERIALS AND METHODS Direct interviews were performed with inhabitants from Xalpatlahuac. The interviews were analyzed with two quantitative tools: (a) the informant consensus factor (ICF) that estimates the level of agreement about which medicinal plants may be used for each category and (b) the relative importance (RI) that determines the extent of potential utilization of each species. RESULTS A total of 67 plant species with medicinal purposes, belonging to 36 families and used to treat 55 illnesses and 3 cultural filiations were reported by interviewees. Nineteen mixtures with medicinal plants were reported by the interviewers. Mentha piperita was the most used plant for combinations (4 mixtures). The results of the ICF showed that diseases of the respiratory and digestive systems had the greatest agreement. The most versatile species according to their RI are Marrubium vulgare, Mimosa albida and Psidium guajava.. CONCLUSION This study demonstrates that plant species play an important role in healing practices and magical-religious rituals among inhabitants from Xalpatlahuac, Guerrero, Mexico. Furthermore, pharmacological, phytochemical and toxicological studies with medicinal flora, including mixtures, are required for the experimental validation of their traditional uses.

Folk medicinal use of fauna in Mapimi, Durango, México

AIM OF THE STUDY To document the use of animal species in traditional medicine from the municipality of Mapimi, Durango, México. MATERIALS AND METHODS Direct interviews were performed in several short visits with inhabitants from the municipality of Mapimi, Durango. The interviews were analyzed with two quantitative tools. The informant consensus factor that estimates the level of agreement between interviewees over which animals to use for each category and the fidelity level which indicates the percentage of informants claiming the use of a certain animal species for the same medicinal purpose. RESULTS A total of 18 animal species, belonging to 17 families and four taxonomic categories, were reported by interviewees as used for medicinal purposes. Thirteen medicinal species were identified not previously reported. The results of the informant consensus factor showed that the dermatological, diabetes and reproductive categories had the greatest agreement. The most important species according to their fidelity level are: Mephitis macroura and Crotalus atrox. CONCLUSION This study demonstrates that many animal species play an important role in healing practices among inhabitants from Mapimi, Durango. Further experiments with medicinal fauna from Mapimi are needed to be carried out to obtain experimental information about their traditional uses, especially with C. atrox.

Medicinal plants used in the Huasteca Potosina, México.

ETHNOPHARMACOLOGICAL IMPORTANCE Medicinal plants have been a source of medicinal compounds since ancient times. This study documented the use of plant species in traditional medicine in the municipality of Aquismón, San Luis Potosí, México. MATERIALS AND METHODS Direct interviews were performed with inhabitants from Aquismón. The interviews were analyzed with two quantitative tools: (a) the informant consensus factor (ICF) that estimates the level of agreement about which medicinal plants may be used for each category and (b) the relative importance (RI) that determines the extent of potential utilization of each species. RESULTS A total of 73 plant species with medicinal purposes, belonging to 37 families and used to treat 52 illnesses and 2 cultural filiations were reported by interviewees. Nineteen mixtures with medicinal plants were reported by the interviewers. Matricaria recutita was the most used plant for combinations (five mixtures). The results of the ICF showed that diseases of the digestive and respiratory systems had the greatest agreement. The most versatile species according to their RI are Ruta graveolens, Tagetes erecta, Ocimum basilicum and Erigeron karwinskianus. CONCLUSION This study demonstrates that plant species play an important role in healing practices and magical-religious rituals among inhabitants from Huasteca Potosina. Further studies with medicinal flora, including mixtures, from Aquismón are required for the experimental validation of their traditional uses.

Kaempferitrin induces apoptosis via intrinsic pathway in HeLa cells and exerts antitumor effects

ETHNOPHARMACOLOGICAL RELEVANCE Justicia spicigera is used for the empirical treatment of cervical cancer in Mexico. Recently, we showed that Justicia spicigera extracts exerted cytotoxic and antitumoral effects and the major component of this extract was kaempferitrin (KM). MATERIALS AND METHODS The cytotoxic and apoptotic effect of KM on human cancer cells and human nontumorigenic cells were evaluated using MTT and TUNEL assays, and Annexin V/Propidium iodide detection by flow cytometry. The effect of KM on cell cycle was analyzed by flow cytometry with propidium iodide. The apoptotic and cell cycle effects were also evaluated by western blot analysis. Also, different doses of KM were injected intraperitoneally daily into athymic mice bearing tumors of HeLa cells during 32 days. The growth and weight of tumors were measured. RESULTS KM induces high cytotoxic effects in vitro and in vivo against HeLa cells. The general mechanisms by which KM induces cytotoxic effects include: cell cycle arrest in G1 phase and apoptosis via intrinsic pathway in a caspase dependent pathway. Also, KM exerts chemopreventive and antitumor effects. CONCLUSION KM exerts cytotoxic and antitumor effects against HeLa cells.

Antitumor effect of Croton lechleri Mull. Arg. (Euphorbiaceae)

UNLABELLED ETHNOPHARMAGOLOGICAL RELEVANCE: Medicinal plants are an important source of antitumor compounds. This study evaluated the acute toxicity in mice, as well as the cytotoxic and antitumoral effects of methanolic extracts of Croton lechleri leaves (CLE). MATERIALS AND METHODS The cytotoxicity of CLE on human cancer cell lines and human non-cancerous cells was evaluated using the MTT and apoptosis assays. Apoptosis induced by CLE on human cancer cell lines was determined using flow cytometry with annexin-Alexa 488/propidium iodide. The acute toxicity in mice was performed according to the Lorke procedure. Different doses of CLE were injected intraperitoneally daily into athymic mice bearing tumor during 18 days. The growth and weight of tumors was measured. RESULTS CLE showed low IC(50) values on HeLa (17μg/ml) cells but lack toxic effects against human normal cells. Induction of cell death in HeLa cells by CLE was confirmed by an increase of apoptosis (Annexin/PI) by 30% compared to untreated cells. The LD(50) was 356mg/kg by intraperitoneal route (i.p.) and 500mg/kg by oral route. CLE administrated at 1, 10 and 50mg/kg i.p. inhibited the tumor growth by 38%, 48% and 59%, respectively, in mice bearing HeLa tumor. CONCLUSION Croton lechleri shows moderate toxic effects in vivo, exerts cytotoxic effects on HeLa cells and has antitumor effects in mice bearing HeLa tumor.

Antitumor and immunomodulatory effects of Justicia spicigera Schltdl (Acanthaceae).

ETHNOPHARMACOLOGICAL RELEVANCE Medicinal plants are an important source of antitumor compounds. This study evaluated the acute toxicity in vitro and in vivo, as well as the cytotoxic, antitumor and immunomodulatory effects of ethanolic extracts of Justicia spicigera leaves (JSE). MATERIALS AND METHODS The in vitro and in vivo toxicity of JSE was evaluated with comet assay in peripheral blood mononuclear cells (PBMC) and acute toxicity in mice, according to the Lorke procedure, respectively. The apoptotic effect of JSE on human cancer cells and human noncancerous cells was evaluated using flow cytometry with annexin-Alexa 488/propidium iodide. Also, different doses of JSE were injected intraperitoneally daily into athymic mice bearing tumors of HeLa cells during 18 days. The growth and weight of tumors were measured. The in vitro immunomodulatory effects of JSE were evaluated estimating the effects of JSE on the phagocytosis of the yeast Saccharomyces cerevisiae, NO production and H(2)O(2) release in macrophages, as well as the proliferation of splenocytes and NK activity. RESULTS The comet assay showed that only JSE tested at 200 and 1000 μg/ml induced a significantly DNA damage in PBMC, compared to untreated cells, whereas the LD(50) was >5000 mg/kg by intraperitoneal route (i.p.) and by oral route. JSE showed pro-apoptotic (Annexin/PI) effects by 35% against HeLa cells, but lack toxic effects against human normal cells. JSE administrated at 10, 50 and 100 mg/kg i.p. inhibited the tumor growth by 28%, 41% and 53%, respectively, in mice bearing HeLa tumor. JSE stimulated, in a concentration dependent manner, the phagocytosis of Saccharomyces cerevisiae yeasts, the NO production and H(2)O(2) release by human differentiated macrophages. In addition, JSE stimulated the proliferation of murine splenocytes and induced the NK cell activity. CONCLUSION Justicia spicigera shows low toxic effects in vitro and in vivo, exerts apoptotic effects on HeLa cells, has antitumor effects in mice bearing HeLa tumor and induces immunomodulatory activities in vitro.

Zootherapeutic practices in Aquismón, San Luis Potosí, México

ETHNOPHARMACOLOGICAL IMPORTANCE Animal derived products have been a source of medicinal compounds since ancient times. This work documents the use of animal species in traditional medicine in the municipality of Aquismón, San Luis Potosí, México. MATERIALS AND METHODS Direct interviews were performed with inhabitants from Aquismón. The interviews were analyzed with two quantitative tools: (a) the informant consensus (ICF) that estimates the level of agreement about which animals may be used for each category and (b) the relative importance (RI) that determines the extent of potential utilization of each species. RESULTS A total of 24 animal species used for medicinal purposes, belonging to 22 families and 4 taxonomic categories, were reported by interviewees. Nine medicinal species had not been reported in scientific literature. The results of the IFC showed that diseases of the respiratory systems had the greatest agreement. The most versatile species according to their RI are Crotalus atrox and Mephitis macroura. CONCLUSION Further studies with medicinal fauna from Aquismón are required for the experimental validation of their traditional uses, especially with Mephitis macroura and Crotalus atrox.

Kaempferitrin induces immunostimulatory effects in vitro

ETHNOPHARMACOLOGICAL RELEVANCE Justicia spicigera is a plant used as immunostimulatory in Mexican traditional medicine. Recently, we showed that Justicia spicigera extracts exerted immunostimulatory effects and the major component of this extract was kaempferitrin (KM). This work shows a correlation between the medical traditional use of Justicia spicigera and kaempferitrin, its active compound. MATERIALS AND METHODS The in vitro immunostimulatory effects of KM were evaluated on the proliferation of murine splenocytes and macrophages, and human peripheral blood mononuclear cells (PBMC). The effects of KM on NO production, lysosomal enzyme activity and neutral red uptake were assayed in murine macrophages RAW 264.7. The effects of KM on the NK cell activity were also assayed. RESULTS KM at 25μM, the highest concentration tested, increased the proliferation of murine macrophages (23%) and splenocytes (17%), and human PBMC (24%) in the absence of lipopolysaccharides (LPS), compared to untreated cells. KM also stimulated the pinocytosis (25%) and lysosomal enzyme activity (57%) in murine macrophages with a similar potency than LPS 1μg/ml. In addition, KM induced the NK cell activity (11%). CONCLUSION KM exerts immunostimulatory effects on immune responses mediated by splenocytes, macrophages, PBMC and NK cells.