Ten new glycosides, carissaedulosides A-J from the root barks of Carissa edulis and their cytotoxicities.

Ten previously undescribed glycosides, carissaedulosides A-J (1-10) referring to six apiosylated phenylpropanoids (1-6), one coumarin-secoiridoid hybrid (7), and three furofuran lignans (8-10) were isolated from the root barks of Carissa edulis, together with 13 known analogues (11-23). Their structures were elucidated by spectroscopic analysis, ECD computational methods, and chemical derivations for configurations of sugar moieties. The new lignan bisdesmoside, 10, exhibited significant cytotoxicity against A549 (IC50 = 3.87 ± 0.03 µM) and MCF-7 (IC50 = 9.231 ± 0.290 µM) cell lines, while the known lignan monodesmoside, 12, showed impressive cytotoxic efficacy (IC50 = 5.68 ± 0.180 µM) against only MCF-7 cell line. It is noted that a known cardenolide, 11, displayed strong cytotoxic potency against HL-60, A549, MCF-7 and SW480 cell lines with IC50 values ranging from 0.023 to 0.137 µM. Moreover, compound 11 induced dose-dependent apoptosis on SW480 cell, but not explicit dose-dependent apoptosis on HL-60 cells.

Immunomodulatory and anticancer potential of Gan cao (Glycyrrhiza uralensis Fisch.) polysaccharides by CT-26 colon carcinoma cell growth inhibition and cytokine IL-7 upregulation in vitro.

BACKGROUND: Chinese licorice, (Glycyrrhiza uralensis Fisch.) is one of the commonly prescribed herbs in Traditional Chinese Medicine (TCM). Gancao, as commonly known in China, is associated with immune-modulating and anti-tumor potential though the mechanism of action is not well known. In this study, we investigated the in vitro immunomodulatory and antitumor potential of Glycyrrhiza uralensis polysaccharides fractions of high molecular weight (fraction A), low molecular weight (fraction B) and crude extract (fraction C). METHODS: Cell proliferation and cytotoxicity was investigated using Cell Counting kit 8 (CCK-8) on Intestinal epithelial cell line (IEC-6) and Colon carcinoma cell line (CT-26). IL-7 gene expression relative to GAPDH was analysed using Real time PCR. The stimulation and viability of T lymphocytes was determined by Trypan blue exclusion assay. RESULTS: G.uralensis polysaccharides did not inhibit proliferation of IEC-6 cells even at high concentration. The ED50 was found to be 100 µg/ml. On the other hand, the polysaccharides inhibited the proliferation of cancer cells (CT-26) at a concentration of ≤50 µg/ml. Within 72 h of treatment with the polysaccharides, expression of IL-7 gene was up-regulated over 2 times. It was also noted that, IEC-6 cells secrete IL-7 cytokine into media when treated with G.uralensis polysaccharides. The secreted IL-7 stimulated proliferation of freshly isolated T lymphocytes within 6 h. The effect of the polysaccharides were found to be molecular weight depended, with low molecular weight having a profound effect compared to high molecular weight and total crude extract. CONCLUSION: Our findings indicate that G.uralensis polysaccharides especially those of low molecular weight have a potential as anticancer agents. Of great importance, is the ability of the polysaccharides to up-regulate anticancer cytokine IL-7, which is important in proliferation and maturation of immune cells and it is associated with better prognosis in cancer. Therefore, immunomodulation is a possible mode of action of the polysaccharides in cancer therapy.

In vitro antioxidant activities of Carissa edulis ((Forssk) Vahl) and Pappea capensis (Eckyl. & Zeyh) extracts.

Herbal medications are gaining popularity due to their long history of use in traditional medicine. They serve as a reservoir for a diverse array of phytocompounds linked to amelioration of oxidative stress. Oxidative stress is a disturbance in the balance between generation and elimination of reactive species in human body. Moreover, reactive species are implicated in the onset and progression of chronic disorders. The current therapeutic approaches despite showing efficacy are characterized by several limitations such as adverse effects and prohibitive costs. This drives the need to explore alternatives that can inhibit, ameliorate or reverse conditions caused by oxidative stress. Several studies have evaluated antioxidant effects of diverse plant extracts. C. edulis and P. capensis are used as traditional therapy among the African communities to manage oxidative stress-related ailments. However, there is limited research on the antioxidant effects of these medicinal plants. The current study, therefore, sought to evaluate the antioxidant and phytochemical profile, of C. edulis and P. capensis extracts. Samples were collected from Embu County, Kenya. In vitro antioxidant properties of the extracts were evaluated through ferric reduction, Iron chelating, hydroxyl radical, and DPPH radical scavenging activities. Activities of catalase, superoxide dismutase and glutathione reductases of the extracts were further determined. Phytochemical profiles were determined using Liquid Chromatography Mass Spectrophotometer (LC-MS) and Gas Chromatography Mass Spectrophotometer (GC-MS) analyses. The extracts displayed concentration dependent antioxidant activities. Phytochemical analyses revealed presence compounds which are associated with antioxidant activities including flavonoids, phenolics, tocopherols and terpenoids. The findings provide a scientific validation for the folklore use of C. edulis and P. capensis in management of oxidative stress. Nevertheless, there is a need for further purification and characterization of phytochemicals associated with antioxidant activities.

In Vitro Antiproliferative Effects and Phytochemical Characterization of Carissa edulis ((Forssk) Vahl) and Pappea capensis (Eckyl and Zeyh) Extracts.

Cancer mortality is a global concern. The current therapeutic approaches despite showing efficacy are characterized by several limitations. Search for alternatives has led to the use of herbal plants including C. edulis and P. capensis. However, there is limited research on antiproliferative effects of these medicinal plants. The study sought to evaluate antiproliferative effects of the plants against human breast and prostate cancers using cell viability, and gene expression assays to determine modulation of apoptotic genes. Further, Liquid Chromatography Mass Spectrophotometer (LC-MS) and Gas Chromatography Mass Spectrophotometer (GC-MS) analyses were performed to confirm phytocompounds in the extracts. The results indicated that ethylacetate extracts of C. edulis and P. capensis had the highest activity against cancer cells with IC50 values of 2.12 ± 0.02, and 6.57 ± 0.03 µg/ml on HCC 1395 and 2.92 ± 0.17 and 5.00 ± 0.17 µg/ml on DU145, respectively. Moreover, the plants extracts exhibited relatively less cytotoxic activities against Vero cell lines (IC50 > 20 µg/ml). The extracts also exhibit selectivity against the cancer cells (SI > 3). Further, mRNA expression of p53 in the treated HCC 1395 was increased by 7 and 3-fold, whereas by 3 and 2-fold in DU145 cells, upon treatment with ethylacetate extracts of C. edulis and P. capensis, respectively. Similarly, several-fold increases were observed in the number of transcripts of Bax in HCC 1395 and HOXB13 in DU145 cells. Phytochemical analyses detected presence of phytocompounds including flavonoids, phenolics, tocopherols and terpenoids which are associated with anticancer activity. Findings from this study provide a scientific validation for the folklore use of these plants in management of cancer.