Jemimah A. Oduma

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.

Practices of traditional birth attendants in Machakos District, kenya.

ETHNOPHARMACOLOGICAL RELEVANCE The aim of the study was to document TBAs practices as well as the indigenous herbal remedies they use to manage pre, intra and post partum complications in a rural Kenyan community. MATERIALS AND METHODS A cross sectional study was conducted on practicing TBAs and their clients living in the study area. Data was collected using structured questionnaires and interviews. Focused group discussions were held with the TBAs to supplement the interviews and questionnaire survey. RESULTS Two hundred TBAs and 20 clients were interviewed. The majority of the TBAs were females 75% of them having attended to over 200 pregnant women over a period of 5 years and above compared to only 6% of the males. A total of 10 pregnancy related complications and symptoms including threatened abortion, labor complications, post partum hemorrhage and retained after birth were recorded. Fifty five plant species most of them belonging to Euphorbiaceae family were identified for the management of the complications. CONCLUSION Traditional Birth Attendants still have a role to play in assisting pregnant women in rural communities. Their knowledge on herbal medicines is equally important and should be preserved for posterity.

IN VIVO AND IN VITRO EFFECTS OF GRADED DOSES OF THE PESTICIDE HEPTACHLOR ON FEMALE SEX STEROID HORMONE PRODUCTION IN RATS

Adult female Sprague-Dawley rats were injected with corn oil or 5 mg, 20 mg, 25 mg or 30 mg per kg body weight of heptachlor solution every other day for up to 18 days. The rats were killed at the end of the experimental period, and blood samples were assayed for progesterone and oestrogen by radioimmunoassay. Ovarian cells from the rats were isolated and incubated either on their own, or in the presence of LH or FSH, and production of progesterone and oestrogen determined. Control incubations consisted of cells from corn oil-treated rats. The latter were also incubated on their own or in the presence of LH or FSH. Heptachlor significantly suppressed blood progesterone and oestradiol levels (P < 0.05 to P < 0.001), the degree of suppression depending on the dose and the stage of the oestrous cycle in which samples were obtained. Production of oestradiol by ovarian cells from heptachlor-treated rats was lower than for corn oil-treated controls. Cells from rats treated with low doses of heptachlor (5 mg per kg body weight) showed an increased production of progesterone, while high doses (> 20 mg per kg body weight) suppressed production.

Effects of graded doses of the pesticide heptachlor on body weight, mating success, oestrous cycle, gestation length and litter size in laboratory rats

Adult female Sprague-Dawley rats were injected with 5 or 20 mg/kg body weight heptachlor solution every other day for up to 18 days. They were weighed every day and the stage of oestrus determined by vaginal smears. One experimental group was mated and pregnancy characteristics studied. Heptachlor affected body weights, cycle patterns, length of gestation period and litter sizes in a dose-related manner. At a dose of 20 mg/kg body weight, heptachlor caused a significant decrease in average body weight (P < 0.01), disrupted and/or prolonged oestrous cycles, decreased mating success (P < 0.001), slightly increased gestation length (P < 0.05) and decreased litter size (P < 0.01).

Preliminary investigation of contractile activity of Ricinus communis and Euclea divinorum extracts on isolated rabbit uterine strips.

UNLABELLED Ricinus communis and Euclea divinorum of the family Euphorbiaceae and Ebenaceae, respectively, are traditionally used by Traditional Birth Attendants (TBAs) in Machakos district of Kenya to induce or augment labor, manage protracted labor, post-partum hemorrhage and retained after birth. Ethno-pharmacological relevance of the study will be the provision of scientific evidence and justification for the ethnic use of both plants as oxytocic agents in the initiation of labor, treatment of prolonged labor, post-partum hemorrhage and retained placenta. MATERIALS AND METHODS The plants were harvested in the wild, identified and voucher specimens preserved. The root bark was processed to powder form, from which aqueous and ethanol extracts were obtained. Each of the extracts was separately tested on isolated uterine muscle tissue from non-pregnant and pregnant rabbits. The effect on contraction frequency (number of contractions per second) in the absence or presence of oxytocin was evaluated statistically using ANOVA. P values <0.05 were considered significant. RESULTS AND CONCLUSIONS All uteri exhibited a strong initial contraction following exposure to the aqueous and ethanol root bark extracts of both plants. After recovery, the resumed contraction frequencies varied with the plant extract and exogenous hormone. The results show that the extracts of both plants were able to stimulate uterine tissue contractility directly and to augment the tissues response to oxytocin. The increase in uterine contractions as a percentage relative to negative controls was particularly significant in pregnant rabbit tissues in the presence of oxytocin, where increments of up to 245% were observed. Further pharmacological studies are however required to determine the active principles, possible mechanisms of action, efficacy and safety margins of the plant extracts.

Phytochemical Screening of Medicinal Plants of the Kakamega Country,Kenya Commonly Used against Cancer

Phytochemical constituents of 35 selected anticancer medicinal plant extracts were analyzed by thin layer chromatography (TLC) for alkaloids, anthraquinones, xanthines, valepotriates, cardiac glycosides, flavonoids, essential oils, coumarins, lignans, saponins and arbutin compounds. These plants sourced from Kakamega tropical rain forest have been previously reported to be used for cancer treatment in the Kakamega County, Kenya. The medicinal plants investigated were Harungana madagascariensis Lam. ex poir, Fuerstia africana T.C.E. Fr., Sida rhombifolia L., Zanthoxylum rubescens Hook. f, Bridelia micrantha (Hochst.) Baill, Juniperus procera Endl., Tragia brevipes Pax, Phyllanthus sapialis, Conyza sumatrensis, Momordica foetida Schumach., Synsepalum cerasiferum Synonym: Afrosersalisia cerasifera (Welw.) Aubrev, Aloe volkensii Engl, Aeschynomene abyssinica (A. Rich.) Vatke, Futumia africana Benth. Cyphostemma serpens (A. Rich), Ipomoea cairica (L.), Spathodea campanulata P. Beauv. ssp. nilotica (Seem), Abrus precatorius L. ssp africanus Verdc., Triumfetta rhomboidea Jacq., Psydrax schimperiana (A.Rich), Ficus thonningii, Rotheca myricoides (Hochst. Steane and Mabb), Croton macrostachyus Delile, Vernonia lasiopus O Hoffin, Albizia gummifera (J.F. Gmel.), Zanthoxylum gilletii (De Wild.) P.G. Waterman, Microglossa pyrifolia (Lam.)Kuntze, Senna didymobotyra (Fresen.) Irwinand Barneby, Trichilia emetica Vahl, Entada abyssinica Steud.ex A.Rich., Shirakiopsis elliptica (Hochst.)Esser Synonym: Sapium ellipticum (Hochst.kraus) Pax, Ocimum gratissimum L.Suave wiild O.tomentosum oliv., Prunus africana (Hook.f.) Kalkman, Phyllanthus fischeri Pax and Olea hotch spp. Hochstetteri. The phytochemical distribution in the 35 plants included:71.4% alkaloids, 57.1% anthraquinones, 94.2% xanthines, 82.8% valepotriates, 94.2% cardioactive glycosides, 82.8% flavonoids, 77.1% essential oils, 85.7% coumarin drugs, 68.5% lignans, 80% saponins and 62.85% arbutin drugs. Our findings provided evidence that crude organic and inorganic solvent extracts of these tested plants contain medicinally important bioactive compounds and provide a rational basis for their use in traditional medicine.

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.

Immunohistochemical localization of anterior pituitary cell types of vervet monkey (Chlorocebus aethiops) following sub-chronic cathinone exposure

ETHNOPHARMACOLOGICAL RELEVANCE Khat (Catha edulis) contains cathinone, an active principal that is customarily used as a psychostimulant that wards off fatigue and to some extent used as an aphrodisiac. AIM OF STUDY To investigate effects of escalating doses of cathinone on hormone expression by different anterior pituitary cell types using specific antibodies. MATERIAL AND METHODS Eleven vervet monkeys (6 males and 5 females) divided into tests (n=9) and controls (n=2) were used. Animals were allocated as group I (saline controls), group II (0.8 mg/kg), group III (3.2 mg/kg) and group IV (6.4 mg/kg) of cathinone. All treatments were via oral route at alternate days of each week. At the end of 4-month treatment phase, GnRH agonist (ZOLADEX) was administered to group II (low dose) and group IV (high dose) alongside cathinone for 2 additional weeks. RESULTS High cathinone dose at long-term exposure caused proliferation of gonadotrophs but decrease in lactotrophs and corticotrophs in anterior pituitary sections of animals while effect of low dose on these cells was insignificant. Subsequent GnRH agonist co-treatment with low and high cathinone doses enhanced gonadotroph proliferation but no change on decline of lactotrophs and corticotrophs. CONCLUSION We believe that there was a possible potentiation of cathinone on pituitary hormone synthesis thereby influencing reproductive function. Suppression of corticotrophic and lactotrophic functions suggest lowering of stress levels and modulation of reproductive function based on dose level and chronicity of exposure. The findings are consistent with the hypothesis that cathinone interferes with pituitary cell integrity and consequently target organs, but further studies are required to address the precise mechanism underlying this phenomenon.

Partial purification of a putative membrane bound androgen binding protein in the dog cauda epididymis.

1. An androgen binding protein(s) has been partially purified from cell plasma membranes of dog epididymides. 2. The protein(s) has a pI of 5.3 and an association constant of (1.13 x 10(9) M-1). 3. Conclusive demonstration of androgen receptors in epididymal plasma membranes would be of significance in understanding epididymal physiology.