Toxicity assessment of watermelon seed supplemented diet in rats.

Health benefits have been attributed to the consumption of watermelon (Citrullus lanatus L.) seeds in sub-Saharan Africa and Asia but the potential toxicity especially on chronic use remains to be investigated. Here, diets containing watermelon seeds (WMSs) at 2.5% or 5% were eaten ad libitum daily for 21 d by male and female Wistar rats. Changes in body and organ (liver, kidney, brain, testis, and ovary) weights following diet supplementation were monitored. Biomarkers of organ injury, such as alanine aminotransferase (ALT), alkaline phosphatase (ALP), cholesterol (CHO), triglyceride (TRI), urea, and creatinine (CRE) were measured. WMS-formulated diet led to a decrease in body weight in male but not in female rats compared to the control group. Also, testes weight significantly increased, whereas a decrease in that of the ovaries was noted. Although the ingestion of WMS did not significantly alter the weights of the liver and brain, a trend toward reduction was noticed. No significant changes were observed for the serum levels of ALT, ALP, CHO, and TRI in all rats. However, the kidney may be targeted for toxicity as indicated by significant elevations in serum urea and CRE levels in male and female rats when compared to controls. Furthermore, the sperm morphology anomalies observed after WMS supplementation demonstrate the potentially detrimental effects of high consumption of the seeds on the male reproductive system. We conclude that WMSs at 2.5% or 5% dose in the diet may elicit negative effects in organs particularly on the kidney and testes in rats.

Unravelling the Anticancer Mechanisms of Traditional Herbal Medicines with Metabolomics.

Metabolite profiling of cancer cells presents many opportunities for anticancer drug discovery. The Chinese, Indian, and African flora, in particular, offers a diverse source of anticancer therapeutics as documented in traditional folklores. In-depth scientific information relating to mechanisms of action, quality control, and safety profile will promote their extensive usage in cancer therapy. Metabolomics may be a more holistic strategy to gain valuable insights into the anticancer mechanisms of action of plants but this has remained largely unexplored. This review, therefore, presents the available metabolomics studies on the anticancer effects of herbal medicines commonly used in Africa and Asia. In addition, we present some scientifically understudied 'candidate plants' for cancer metabolomics studies and highlight the relevance of metabolomics in addressing other challenges facing the drug development of anticancer herbs. Finally, we discussed the challenges of using metabolomics to uncover the underlying mechanisms of potential anticancer herbs and the progress made in this regard.

Chemoprevention of LA7-Induced Mammary Tumor Growth by SM6Met, a Well-Characterized Cyclopia Extract.

Breast cancer (BC) is the leading cause of cancer-related deaths in women. Chemoprevention of BC by using plant extracts is gaining attention. SM6Met, a well-characterized extract of Cyclopia subternata with reported selective estrogen receptor subtype activity, has shown tumor suppressive effects in a chemically induced BC model in rats, which is known to be estrogen responsive. However, there is no information on the estrogen sensitivity of the relatively new orthotopic model of LA7 cell-induced mammary tumors. In the present study, the potential chemopreventative and side-effect profile of SM6Met on LA7 cell-induced tumor growth was evaluated, as was the effects of 17ß-estradiol and standard-of-care (SOC) endocrine therapies, such as tamoxifen (TAM), letrozole (LET), and fulvestrant (FUL). Tumor growth was observed in the tumor-vehicle control group until day 10 post tumor induction, which declined afterward on days 12-14. SM6Met suppressed tumor growth to the same extent as TAM, while LET, but not FUL, also showed substantial anti-tumor effects. Short-term 17ß-estradiol treatment reduced tumor volume on days prior to day 10, whereas tumor promoting effects were observed during long-term treatment, which was especially evident at later time points. Marked elevation in serum markers of liver injury, which was further supported by histological evaluation, was observed in the vehicle-treated tumor control, TAM, LET, and long-term 17ß-estradiol treatment groups. Alterations in the lipid profiles were also observed in the 17ß-estradiol treatment groups. In contrast, SM6Met did not augment the increase in serum levels of liver injury biomarkers caused by tumor induction and no effect was observed on lipid profiles. In summary, the results from the current study demonstrate the chemopreventative effect of SM6Met on mammary tumor growth, which was comparable to that of TAM, without eliciting the negative side-effects observed with this SOC endocrine therapy. Furthermore, the results of this study also showed some responsiveness of LA7-induced tumors to estrogen and SOC endocrine therapies. Thus, this model may be useful in evaluating potential endocrine therapies for hormone responsive BC.

Effects of kolaviron on hepatic oxidative stress in streptozotocin induced diabetes.

BACKGROUND: Alteration in antioxidant defence and increase in oxidative stress that results in tissue injury is characteristic of diabetes. We evaluated the protective effects of kolaviron (a flavonoid complex extracted from the seeds of Garcinia kola) on hepatic antioxidants, lipid peroxidation and apoptosis in diabetic rats. METHODS: To induce diabetes, rats were injected with streptozotocin intraperitoneally at a single dose of 50 mg/kg. Kolaviron (100 mg/kg) was administered orally for 6 weeks (5 times weekly). Activities of liver antioxidant enzymes was analysed with Multiskan Spectrum plate reader. High performance liquid chromatography (HPLC) was used in the analysis of MDA (malondialdehyde), a product of lipid peroxidation. Apoptosis was assessed by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay. RESULT: Diabetic rats exhibited a significant increase in the peroxidation of hepatic lipids as observed from the elevated level of malondialdehyde (MDA). In addition, Oxygen Radical Absorbance Capacity (ORAC), level of reduced glutathione (GSH), ratio of reduced to oxidized glutathione (GSH: GSSG) and catalase (CAT) activity were decreased in the liver of diabetic rats. The activities of GPX (glutathione peroxidase) and SOD (superoxide dismutase) were unaltered in diabetic rats. TUNEL assay revealed increased apoptotic cell death in the liver. Kolaviron attenuated lipid peroxidation and apoptosis, increased CAT activity, GSH levels and GSH: GSSG ratio. The ORAC of kolaviron-treated diabetic liver was restored to near-normal values. CONCLUSION: Kolaviron protects the liver against oxidative and apoptotic damage induced by hyperglycemia.