Cytotoxic activity of medicinal plants of the Kakamega County (Kenya) against drug-sensitive and multidrug-resistant cancer cells.

ETHNOPHARMACOLOGICAL RELEVANCE: The geographical location of Kakamega County proximal to the Kakamega Rain Forest in Kenya and its rich flora represents an interesting resource of traditional medicinal plants. The medicinal plants in the present study are traditionally used to treat cancer in Kakamega County as recorded in published literature. AIM OF THE STUDY: Due to multidrug resistance (MDR) and severe side effects of currently used drugs in clinical oncology, new candidate compounds are urgently required to improve treatment outcome. The present study explored the in vitro cytotoxic potential of 34 organic and 19 aqueous extracts of Kakamega medicinal plants towards sensitive and multidrug-resistant cancer cell lines. METHODS AND RESULTS: The cytotoxicity was determined using the resazurin assay. Eight organic and two aqueous plant extracts inhibited the growth of CCRF-CEM leukemia cells by more than 50%. The organic extracts were Harungana madagascariensis Lam. ex poir (6.6% of untreated control), Prunus africana (Hook.f.) Kalkman (19.4%), Entada abyssinica Steud. ex A. Rich (38.6%), Phyllanthus fischeri Pax (40.7%), Shirakiopsis elliptica (Hochst.) Esser Synonym: Sapium ellipticum (Hochst. kraus) Pax (41.8%), Bridelia micrantha (Hochst.) Baill (45.4%) and Futumia africana Benth. (45.8%) and Microglossa pyrifolia (Lam.) Kuntze (48%). The aqueous extracts were Bridelia micrantha (Hochst.) Baill (31.3%) and Shirakiopsis elliptica (Hochst.) Esser Synonym: Sapium ellipticum (Hochst. Kraus) Pax (48.2%). In addition to P-glycoprotein-expressing tumor cells, we also investigated other mechanisms of drug resistance, i.e. BCRP- or EGFR-transfected and TP53-knockout tumor cells. Some extracts also showed considerable cytotoxic activity against these drug-resistant cell lines. As demonstrated for selected examples, some extracts exhibited enhanced cytotoxicity towards cancer cells, if applied in combination with other extracts. DISCUSSION: The panel of medicinal plants used in the Kakamega County for cancer treatment revealed indeed cytotoxicity to various extent towards cancer cells in vitro. Hence, our results may at least in part substantiate the traditional use of these compounds to treat cancer. Even more interesting, several extracts inhibited otherwise drug-resistant tumor cell lines with similar or even better efficacy than their drug-sensitive counterparts. This provides an attractive perspective for further exploration of their anticancer potential to combat drug resistance of refractory tumors.

Dose-response inhibitory effects of purified cathinone from khat (Catha edulis) on cortisol and prolactin release in vervet monkeys (Chlorocebus aethiops).

This study reports acute and sub-chronic effects of cathinone on hormonal alterations in single-caged vervet monkeys. Fourteen adult vervet monkeys were used, 12 of which were treated and 2 controls. Pre-treatment phase of 1 month aimed at establishing baseline levels of hormones while treatment phase of 4 months considered the dose- and time-response effects of cathinone on serum cortisol and prolactin levels. Test animals were allocated four groups of three animals each and administered 0.8, 1.6, 3.2 and 6.4 mg/kg body weight of cathinone orally while controls were administered normal saline. Treatment was done at alternate days of each week. Serum prolactin and cortisol immunoassays were done. Hormonal data was analysed by repeated measures ANCOVA. Results indicate a dose [F (4, 8) = 218, P < 0.001] and time [F (18, 142) = 21.7, P < 0.001] dependent effect of cathinone on cortisol levels with a significant dose by week interaction [F (71, 142) = 4.86, P < 0.001]. Similarly, there was a decrease in serum prolactin [F (4, 8) = 267, P < 0.001] with escalating doses of cathinone with a significant dose x week interaction [F (59, 118) = 13.03, P < 0.001]. The findings demonstrate that at high doses and long-term exposure, cathinone causes hormonal alterations probably via changes in hypothalamo-hypophyseo-adrenocortical and gonadal axes integrity.

Acute and sub-chronic effects of purified cathinone from khat (Catha edulis) on behavioural profiles in vervet monkeys (Chlorocebus aethiops).

We investigated the cumulative effects of cathinone on behavioural alterations in single-caged vervet monkeys. Fourteen adult vervets were divided into tests (12 animals) and controls (2 animals), and exposed to escalating doses of cathinone at alternate days of each week for 4 months in presence and absence of cage enrichment. One month of pre-treatment phase served to establish baseline values. Composite behavioural scores of aggression, anxiety, abnormal responses, withdrawal and appetite loss were done. A series of repeated measures analysis of variances were conducted to examine the extent to which cathinone administration was associated with patterns of changes in behavioural data. Results indicate a dose-dependent effect of cathinone on increases of aggression, anxiety, abnormal responses, withdrawal, and appetite loss. The findings demonstrate that at high doses and long-term exposure, cathinone causes behavioural alterations probably via changes in presynaptic striatal dopamine system.

Medicinal plants used in treatment and management of cancer in Kakamega County, Kenya.

ETHNOPHARMACOLOGICAL RELEVANCE: Traditional medicine plays a critical role in treatment of chronic debilitating and life threatening conditions and diseases. Cancer is one such condition whose therapeutic intervention is commonly through inexpensive traditional herbal remedies. Increasingly industrialised societies are developing drugs and chemotherapeutics from these traditional herbal plants. Plant biogeography determines the abundance and availability of medicinal plants which in turn determine their use by local communities. The present study was carried out in Kakamega County of Kenya to identify and document medicinal plants used for treatment and management of cancer states by communities living adjacent to Kakamega Tropical rainforest of Kakamega County, Kenya. MATERIALS AND METHODS: An ethnobotanical survey was done using semi-structured questionnaires administered to 32 randomly selected herbalists from Kakamega County. RESULTS AND DISCUSSION: Sixty five (65) plants of 59 genera and 32 families were identified as candidates in therapeutic intervention against cancer states. Most commonly cited plant species were Spathodea campanulata P. Beauv. ssp. nilotica (Seem), Microglossa pyrifolia (Lam.) Kuntze, Harungana madagascariensis Lam. ex poir, Prunus africana (Hook. f.) kalkman, Cyphostemma serpens (A. Rich), Catharanthus roseus (L.) G. Don and Aloe volkensii Engl. The following were documented for the first time; Aeschynomene abyssinica (A. Rich.) Vatke, Synsepalum cerasiferum (welw.) T. D penn., Albizia coriaria Welw. ex Oliv., Aloe volkensii Engl. Bridelia micrantha (Hochst.) Baill, Croton macrostachyus Delile, Cyphostemma serpens (A. Rich), Dicliptera laxata C.B. Clarke, Ekebergia capensis Sparrm., Gardenia volkensii K. schum. ssp. volkensii, Glycine wightii (wight & Arn.), Ocimum gratissimum Suave, Olea hotcsh spp. hochstetteri, Pavetta abyssinica Fresen., Phyllanthus fischeri Pax, Psydrax schimperiana (A. Rich), Rhus vulgaris Meikle, Senna didymobotyra (Fresen.) Irwin and Barneby, Solanecio nandensis (S. Moore) C. Jeffrey, Solanum mauritianum Scop, Spathodea campanulata P. Beauv. ssp. nilotica (Seem), Spermacoce princea (K. Schum.) Verdc., Tabernaemontana stapfiana Britten, Tragia brevipes Pax and Zanthoxylum gilletii (De Wild.) P.G.Waterman. The most frequently used plant parts were fresh or dried leaves and stem barks. Administration to patients was almost exclusively oral, with the exceptions being topical application especially for breast cancer and skin sarcomas. CONCLUSIONS: This study identified diverse medicinal plants used in therapeutic and management intervention against cancer by communities living adjacent to Kakamega Tropical Rainforest. The primary mode of administration was oral.