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.

Acute and Sub-Acute Toxicity Studies of Plumeria alba Linn. (Apocynaceae) Hydroalcoholic Extract in Rat.

Plumeria alba Linn (Apocynaceae) is used in Togolese traditional medicine to treat diabetes mellitus and wounds. The present investigation was carried out to evaluate the toxicity of hydroalcoholic extract of Plumeria alba roots in Sprague Dawley rats. The acute toxicity test was conducted by administering orally dose of 5 g/Kg. General behavior and mortality were examined for up to 14 days. The sub-acute toxicity test was performed by daily gavage at 250, 500 and 1000 mg/Kg for 28 days. Body weight and blood glucose were measured weekly. Hematological and biochemical parameters, relative organ weight were determined at the end of the 28 days administration. In acute study, no adverse effect of the extract was observed at 5.0 g/Kg. Sub-acute oral administration of the extract at the dose up to 1000 mg/Kg did not induce death or significant changes in body weight, relative weight of vital organs, hematological parameters and was not associated with liver and kidney toxicity.

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.

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