In Vitro Cytotoxic Potential of Selected Jordanian Flora and Their Associated Phytochemical Analysis.

Traditional medicines are a significant source of phytochemicals with potential anticancer effects. Ten Jordanian plants were chosen to be tested for cytotoxicity on human colorectal (HT-29) and breast adenocarcinoma (MCF-7) cell lines. The ethanol extracts were screened for their potential cytotoxic effects using a Sulforhodamine B (SRB) colorimetric assay, using doxorubicin as positive control. Plants extracts exhibiting marked cytotoxic activity were further investigated by qualitative and quantitative phytochemical methods. Total phenolics were quantified using the Folin-Ciocalteu reagent, while flavonoids were quantified using aluminum chloride. The total saponins of the n-butanol fraction were estimated using diosgenin as a standard. The total alkaloids and total terpenoids were also evaluated using the gravimetric method. As results, Senecio leucanthemifolius (IC50: 13.84 µg/mL) and Clematis cirrhosa (IC50: 13.28 µg/mL) exhibited marked cytotoxic effects on human colorectal adenocarcinoma (HT-29) cell lines. Total phenolics, flavonoids, saponins, alkaloids, and terpenoids found in Senecio leucanthemifolius were (91.82, 14.90, 14.27, 101, and 135.4 mg/g of dry extract), respectively. They were revealed to be (68.18, 7.16, 31.25, 73.6, and 180 mg/g of dry extract) in Clematis cirrhosa, respectively. Senecio leucanthemifolius and Clematis cirrhosa have been found to possess cytotoxicity against colorectal (HT-29). In conclusion, the findings of this study offer a new perspective on Jordanian plant extracts anticancer activity research.

Natural Reno-Protective Agents against Cyclosporine A-Induced Nephrotoxicity: An Overview.

CA (cyclosporine A) is a powerful immunosuppressing agent that is commonly utilized for treating various autoimmune illnesses and in transplantation surgery. However, its usage has been significantly restricted because of its unwanted effects, including nephrotoxicity. The pathophysiology of CA-induced kidney injury involves inflammation, apoptosis, tubular injury, oxidative stress, and vascular injury. Despite the fact that exact mechanism accountable for CA's effects is inadequately understood, ROS (reactive oxygen species) involvement has been widely proposed. At present, there are no efficient methods or drugs for treating CA-caused kidney damage. It is noteworthy that diverse natural products have been investigated both in vivo and in-vitro for their possible preventive potential in CA-produced nephrotoxicity. Various extracts and natural metabolites have been found to possess a remarkable potential for restoring CA-produced renal damage and oxidative stress alterations via their anti-apoptosis, anti-inflammatory, and antioxidative potentials. The present article reviews the reported studies that assess the protective capacity of natural products, as well as dietary regimens, in relation to CA-induced nephrotoxicity. Thus, the present study presents novel ideas for designing and developing more efficient prophylactic or remedial strategies versus CA passive influences.

Anti-adhesive activity of Aframomum melegueta major phenolics on lower respiratory tract pathogens.

Recent studies have raised interest in the potential health effect of Aframomum melegueta, which is related to the phenolic content of its seeds. The methanolic extract of A. melegueta seeds showed a significant anti-adhesive effect against Staphylococcus aureus to lung carcinoma cell line in a concentration-dependent manner. The n-butanol and the chloroform fractions exhibited a significant antiadhesive activity against S. aureus. The chloroform fraction exhibited an antiadhesive effect of 49.53%, 40.15% and 70.34% at concentrations 25, 50 and 100 µg/mL, respectively. Through a biologically guided isolation, the chloroform fraction yielded a new diarylheptanoid identified using 1D, 2D NMR and HREIMS and named 3-(S)-acetyl-1-(4',5'-dihydroxy-3'- methoxyphenyl)-7-(3″,4″-dihydroxyphenyl)heptane(1), in addition to eight known compounds (2-9). Compounds (1), 6-paradol (5), [6]-shogaol (7), [8]-gingerol(8) and dihydro[6]paradol (9) exhibited a significant anti-adhesive activity against S. aureus with a % of inhibition of adhesion of 60.58, 50, 70.07, 85.4, 59.85% at 50 µg/mL, respectively. Additionally, the extract's capacity to reduce adhesion without reducing bacterial growth reduces the likeliness of resistance development.

P-glycoprotein inhibitors of natural origin as potential tumor chemo-sensitizers: A review.

Resistance of solid tumors to treatment is significantly attributed to pharmacokinetic reasons at both cellular and multi-cellular levels. Anticancer agent must be bio-available at the site of action in a cytotoxic concentration to exert its proposed activity. P-glycoprotein (P-gp) is a member of the ATP-dependent membrane transport proteins; it is known to pump substrates out of cells in ATP-dependent mechanism. The over-expression of P-gp in tumor cells reduces the intracellular drug concentrations, which decreases the cytotoxicity of a broad spectrum of antitumor drugs. Accordingly, P-gp inhibitors/blockers are potential enhancer for the cellular bioavailability of several clinically important anticancer drugs such as, anthracyclines, taxanes, vinca alkaloids, and podophyllotoxins. Besides several chemically synthesized P-gp inhibitors/blockers, some naturally occurring compounds and plant extracts were reported for their modulation of multidrug resistance; however, this review will focus only on major classes of naturally occurring inhibitors viz., flavonoids, coumarins, terpenoids, alkaloids and saponins.

Protective effect of Aframomum melegueta phenolics against CCl4-induced rat hepatocytes damage; role of apoptosis and pro-inflammatory cytokines inhibition.

Aframomum melegueta is a commonly used African spice. Through a hepatoprotective bioassay-guided isolation, the chloroform fraction of A.melegueta seeds yielded one new diarylheptanoid named 3-(S)-acetyl-1-(4'-hydroxy-3', 5'-di methoxyphenyl)-7-(3″,4″, 5″-trihydroxyphenyl)heptane (1), and two new hydroxyphenylalkanones, [8]-dehydrogingerdione (2) and [6]-dehydroparadol (3), in addition to six known compounds (4-9). The hepatoprotective effect of A. melegueta methanol extract, sub-fractions and isolated compounds was investigated using carbon tetrachloride (CCl4)-induced liver injury in a rat hepatocytes model. The methanol, chloroform extracts and compounds 1, 5, 8 and 9 of A. melegueta significantly inhibited the elevated serum alanine aminotransferase (ALT), thiobarbituric acid reactive substances (TBARS), tumor necrosis factor (TNFα), interleukin-1beta (Il-1ß), caspase3 and 9 and enhanced the reduced liver glutathione (GSH) level caused by CCl4 intoxication. These results indicate that A.melegueta extracts, and isolated compounds play a protective role in CCl4 induced acute liver injury which might be due to elevated antioxidative defense potentials, suppressed inflammatory responses and apoptosis of liver tissue.

New bioactive metabolites from a crown gall induced on an Eucalyptus tereticornis Sm. tree.

Applying a bioactivity-guided isolation strategy for the ethanolic extract of crown gall tumours induced on an Eucalyptus tereticornis tree, two new compounds in addition to a known one were isolated. The new compounds were identified as an amino acid derivative named 1-ethyl-6-(1'-methyl-1'-phenylethyl) piperidin-2-one (1) and a lanostane tetracyclic triterpene named 3beta-hydroxy-24-methyllanosta-8,17(20),24(28)-trien-22-oic acid (2), together with stigmasterol-3-O-glucoside (3). The three compounds exhibited significant cytotoxic activity against two human cell lines, breast (MCF7) and colon (HCT116), with IC50 values of 1.01, 1.54, and 2.15 microg/ml, respectively, against MCF7 and 3.49, 3.83, and 3.39 microg/ ml, respectively, against HCT116. Furthermore, in rats elevated levels of blood cholesterol, triglycerides, and low-density lipoprotein (LDLc) were significantly reduced, while the level of high-density lipoprotein (HDLc) was significantly increased by administration of the ethanolic extract as well as of 3. These results support a correlation between the reduction of blood cholesterol levels and improvement of colorectal cancer.

Screening for estrogenic and antiestrogenic activities of plants growing in Egypt and Thailand.

BACKGROUND: There is a growing demand for the discovery of new phytoestrogens to be used as a safe and effective hormonal replacement therapy. MATERIALS AND METHODS: The methanol extracts of 40 plants from the Egyptian and Thailand folk medicines were screened for their estrogen agonist and antagonist activities. The estrogenic and antiestrogenic effects of the tested extracts were carried out using the yeast two-hybrid assay system expressing ERα and ERß. In addition, all the extracts were subjected to a naringinase treatment and retested for their estrogenic activity. RESULTS: The methanol extracts of Derris reticulata and Dracaena lourieri showed the most potent estrogenic activity on both estrogen-receptor subtypes, while, the methanol extracts of Butea monosperma, Erythrina fusca, and Dalbergia candenatensis revealed significant estrogenic activity on ERß only. Nigella sativa, Sophora japonica, Artabotrys harmandii, and Clitorea hanceana showed estrogenic effect only after naringinase treatment. The most potent antiestrogenic effect was revealed by Aframomum melegueta, Dalbergia candenatensis, Dracena loureiri, and Mansonia gagei.