Four Togolese plant species exhibiting cytotoxicity and antitumor activities lightning polytherapy approach in cancer treatment.

Background: Cancer is leading to premature deaths across the globe. Therapeutic approaches are still being developed to enhance the survival of cancer patients. In our previous study, extracts from four Togolese plants, namely, Cochlospermum planchonii (CP), Piliostigma thonningii (PT), Paullinia pinnata (PP), and Securidaca longipedunculata (SL), actually used in traditional medicine for cancer treatment, showed beneficial health effects against oxidative stress, inflammation, and angiogenesis. Purpose: In the present study, we aimed to investigate the cytotoxicity and antitumor activities of these four plant extracts. Material and methods: Breast, lung, cervical, and liver cancer cell lines were exposed to the extracts, and viability was assessed using the Sulforhodamine B method. P. pinnata and S. longipedunculata with significant cytotoxicity were selected for in vivo tests. The acute oral toxicity of these extracts was assessed using BALB/c mice. The antitumor activity was evaluated using the EAC tumor bearing mice model, wherein mice were orally treated with extracts at different concentrations for 14 days. The standard drug was cisplatin (3.5 mg/kg, i.p), single dose. Results: Cytotoxicity tests revealed that SL, PP, and CP extracts have more than 50% cytotoxicity at 150 µg/mL. The acute oral toxicity of PP and SL at 2000 mg/kg did not show any toxic signs. At therapeutic doses of 100 mg/kg, 200 mg/kg and 400 mg/kg of PP and 40 mg/kg, 80 mg/kg, and 160 mg/kg of SL, extracts showed beneficial health effects by modulating several biological parameters. SL extract significantly reduced tumor volume (P < 0.001), cell viability, and normalized hematological parameters. SL also demonstrated a strong anti-inflammatory activity similar to the standard drug. The SL extract also revealed a significant increase of the life span of treated mice. PP extract reduced the tumor volume and significantly improved the values of endogenous antioxidants. Both PP and SL extracts also exerted significant anti-angiogenic potency. Conclusion: The study indicated that polytherapy would be a panacea for the efficient use of medicinal plant extracts against cancer. This approach will make it possible to act simultaneously on several biological parameters. Molecular studies of both extracts targeting key cancer genes in several cancer cells are currently underway.

Ethnopharmacological evaluation of antioxidant, anti-angiogenic, and anti-inflammatory activity of some traditional medicinal plants used for treatment of cancer in Togo/Africa.

ETHNOPHARMACOLOGICAL RELEVANCE: Cancer is a multistep disease and its management is exceedingly expensive. Nowadays medicinal plants are gaining more attention in drug discovery and approximately 70% of anticancer drugs were developed from natural products or plants. A strong candidate from medicinal plant with anticancer potential should have four major properties: antioxidant, anti-inflammatory, anti-angiogenic, and cytotoxic activities. AIM OF THE STUDY: In order to assess Togolese traditional healer's claims about the anticancer potential of medicinal plants and obtain candidate plants for anticancer drug discovery, some species were selected from surveys and evaluated for their antioxidant, anti-inflammatory, anti-angiogenic and cytotoxic activities. METHODS: Four species, Cochlospermum planchonii (CP), Piliostigma thonningii (PT), Paullinia pinnata (PP), and Securidaca longipedunculata (SL) were selected and analyzed to detect the phytochemical components. The mentioned bioactivities were evaluated using in vitro, ex vivo and in vivo assays. RESULTS: Relative to SL extract, CP and PT have shown significantly high polyphenols and flavonoids content. The DPPH, FRAP, and TAC of the extracts revealed that CP, PT, and PP have a potent antioxidant effect compared to SL. MDA analysis revealed the same antioxidant activity as CP, PT and PP showed a minor MDA level. The egg albumin denaturation assay showed that IC50 of CP and PP was significantly higher than control (P < 0.05). In contrast, the Bovine Serum Albumin (BSA) results showed a nonsignificant effect (P > 0.05). Notably, SL extract was nonsignificant to control in both Egg Albumin and BSA. Furthermore, angiogenesis assay showed that SL at 50 µg/ml and PP at 100 µg/ml effectively reduced the number of blood vessels than control and showed a potent anti-angiogenic effect (2.7-fold and 2.5-fold, respectively, P < 0.05). No cytotoxicity on PBMC was reported for CP, PP, and PT up to 1000 µg/ml, whereas SL at 1000 µg/ml exhibit benign cytotoxicity (P < 0.0001). CONCLUSION: This study provided in vitro evidence supporting further evaluation on cancer cell lines and tumors in vivo.

Natural occurrence of mycotoxins in maize and sorghum in Togo.

Mycotoxins are fungal secondary metabolites frequently affecting agronomical crops and consequently imposing a major challenge for food safety and public health. In this study, a total of 67 raw cereals (55 maize and 12 sorghum) were collected from the market of Togo. The samples were investigated on the occurrence of 21 mycotoxins using state-of-the-art high-performance liquid chromatography coupled to tandem mass spectrometry (HPLC-MS/MS). The most frequent occurring mycotoxins were fumonisins (88 and 67% for maize and sorghum respectively) with concentrations ranging from 101 to 1838 µg/kg for maize and 81.5 to 361 µg/kg for sorghum, respectively. Aflatoxin B1 was detected in 38% of the maize samples with maximum contamination levels of 256 µg/kg, and 25% of the sorghum samples (range 6-16 µg/kg). The concentrations of aflatoxins were high in maize, with some cases exceeding the maximum legislative limits (EU) for unprocessed maize placed on the market. In addition to these high contamination levels, the co-occurrence of three classes of mycotoxins (i.e., aflatoxins, fumonisins, and trichothecenes) was observed in this study. For the first time, the multi-mycotoxins occurrence in agronomical crops in Togo was reported.

Preliminary evaluation of the wound healing effect of Vitex doniana sweet (Verbenaceae) in mice.

Vitex doniana is traditionally used in Togo to treat various diseases including wounds. The aim of this work was to evaluate the efficiency of Vitex doniana on cutaneous wound healing. Wounds were induced in ICR mice divided into four groups as following: Group I received carbopol 974P NF empty gel, Groups II and III were treated topically with carbopol gel containing 2.5% and 5% of Vitex doniana extract. Group IV received Betadine® 10% as standard drug. The efficacy of treatment was evaluated by planimetry and histological analysis. We secondary used the gel containing Vitex doniana at 2.5% and the pure extract at 10 mg/ml on the model of ear edema induced by xylene. Skin toxicity test was performed with the gel containing Vitex doniana at 5% and the pure extract at 30 mg/ml. Vitex doniana at 5% and 2.5% provided better wound contraction (91.14% and 86.38%) at day 12 post-excision when compared to control (51.15%). The results of histological evaluation supported the outcome of excision wound model. Moreover Vitex doniana inhibited significantly edema induced by xylene when compared to control (p< 0.05). In skin toxicity test, no abnormal symptoms were developed over 14 day-time period. Vitex doniana inhibits the topical inflammation and accelerate cutaneous wound repair.

[Effect of Morinda lucida Benth. (Rubiaceae) and Newbouldia leavis P. Beauv. (Bignoniaceae) on sickling of red blood cells]. / Effet de Morinda lucida Benth. (Rubiaceae) et de Newbouldia leavis P. Beauv. (Bignoniaceae) sur la falciformation.

The purpose of this study was to evaluate the In vitro anti-sickling activity of two plants widely used for treatment of sickle cell disease in Togo, i.e., Morinda lucida et Newbouldia leavis. A concentration-dependent decrease in the rate of sickling was observed after incubation of red blood cells with plant extracts and 2% sodium metabisulfite as compared to incubation with 0.9% NaCl. On samples with a SS blood genotype the inhibition rate of Morinda lucida was 17.30% at a concentration of 1 mg/ml and 92.31% at a concentration of 30 mg/ml. On samples with an AS blood genotype, the inhibition rate of Morinda lucida 48.10% at a concentration of 1 mg/ml and 99.34% at a concentration of 30 mg/ml. Using Newbouldia leavis the inhibition rates at concentrations of 1 mg/ml and 30 mg/ml were 15.66% and 90.42% respectively on samples with a SS blood genotype and 64.03% and 99.02% respectively on samples with an AS blood genotype. The study protocol appeared to be adequate for both SS and AS blood genotypes since the Pearson correlation coefficient between rates measured on the two types of samples was 0.92 for Newuboulida and 0.89 for Morinda. These findings show that these two plants have clear-cut in vitro anti-sickling activity and support their use in traditional medicine.

Anti-ulcer and Anti-inflammatory Effects of Hydro-Alcohol Extract of Aloe buettneri A. Berger (lilliaceae)

Purpose: Aloe buettneri A. Berger is commonly used in Togolese folk medicine to treat inflammation and gastric ulcer. In this study we investigated the anti-oedema; analgesic; antipyretic and ulcer healing properties of the hydro-alcohol extract of their leaves. Methods: Rat oedema paw were induced by the injection of 0.1 ml of formaldehyde 1; tail flick method is used to study analgesic property; hyperthermia was induced by subcutaneous injection of 15of a brewers' yeast suspension at dose of 10 ml/kg and ulcers were induced by ethanol or HCl/ethanol mixture. Results: The extract showed anti-inflammatory properties at doses between 250-500 mg/kg. It inhibited; in a dose- dependent manner; the oedema induced by 0.1 ml of formaldehyde 1. Scores of 73.70and 83.63were obtned when the doses of extract administered were 100 and 500 mg/kg; respectively. The tail flick analgesic index showed an increase of 36.56when the dose was 500 mg/kg. The extract decreased significantly the hyperthermia induced by the injection of yeast. 1000 mg/kg of the extract inhibited 63.77of the gastric lesion induced by acid-water-ethanol mixture while daily administration of the same dose accele- rated the cicatrisation of gastric ulcer induced by 95ethanol. Conclusion: The results obtained show that the hydro-alcohol extract of Aloe buettneri A. Berger (Lillia- ceae) has anti-inflammatory; anti-ulcer and wound healing properties

Effet de Morinda lucida Benth. (Rubiaceae) et de Newbouldia leavis P. Beauv. (bignoniaceae) sur la falciformation

Ce travail a ete realise dans le but d'evaluer l'activite inhibitrice de falciformation in vitro des extraits de deux plantes couramment utilisees dans le traitement de la drepano- cytose au Togo :Morinda lucida et Newbouldia leavis. Lorsque les hematies sont incubees en presence des extraits vegetaux et du metabisulfite de sodium a 2; on note une diminution concentration- dependante du taux de falciformation par rapport au sang temoin qui a ete incube en presence de NaCl a 0;9a la place des extraits. Morinda a montre un taux d'inhibition de 17;30a la concentration de 1 mg/ml et de 92;31a la concentration de 30 mg/ml sur le sang SS. Sur le sang AS; a la concentration de 1 mg/ml de cet extrait; l'inhibition est de 48;10et 99;34pour 30 mg/ml. Avec N. leavis on a obtenu une inhibition de 15;66a 1 mg/ml et 90;42a 30 mg/ml sur le sang SS. Sur le sangAS cette inhibition est de 64;03pour 1 mg/ml et 99;02pour 30 mg/ml. Ce protocole semble approprie pour travailler aussi bien avec le sang AS qu'avec le sang SS car les effets compares de chacun des extraits sur la falciformation du sang AS et SS ont donne un coefficient de correlation de Pearson qui est de 0;92 pour Newbouldia et de 0;89 pour Morinda. Nos resultats montrent que ces deux plantes ont un effet anti-falciformant evident in vitro et soutiennent l'interet de leur usage en medecine traditionnelle