No abstract

Faisal et al.: G. Extensum Combined with P. Nigrum Induces Apoptosis This study aims to investigate the cytotoxicity of Andrographis paniculata, Ziziphus spina-christi and Gymnanthemum extensum crude extracts and their combination with low piperine fractional Piper nigrum extract. All plants were extracted with water and five organic solvents (methanol, ethanol, dichloromethane, ethyl acetate and hexane). Cytotoxicity was assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay on three cancer types (breast, colorectal and ovarian cancers) and two non-cancerous cells. The combination among extracts with low piperine fractional Piper nigrum extract was separately conducted in several tests including cytotoxicity, apoptosis and multi caspase activity. We found that, the dichloromethane crude extract of Andrographis paniculata, Ziziphus spinachristi and Gymnanthemum extensum exhibited the strongest cytotoxicity on colorectal cancer cells SW-620 (7.49±0.04 µg. ml -1 ), breast cancer cells Michigan Cancer Foundation-7 (13.35±0.30 µg. ml -1 ) and ovarian cancer cells A2780 (15.58±1.81 µg. ml -1 ), respectively. Gas chromatography mass spectrometry study of dichloromethane crude extract of Andrographis paniculata, Ziziphus spina-christi and Gymnanthemum extensum identified major compounds including 1-heptatriacotanol (60.29 %) and palmitic acid (26.92 % for dichloromethane crude extract of Ziziphus spina-christi and 21.40 % for dichloromethane crude extract of Gymnanthemum extensum), respectively. The combination of dichloromethane crude extract of Ziziphus spina-christi and low piperine fractional Piper nigrum extract at ratio IC 50 :0.5IC 50 showed a moderate synergistic effect on Michigan Cancer Foundation-7 cells. Interestingly, the mixture of dichloromethane crude extract of Gymnanthemum extensum with low piperine fractional Piper nigrum extract at ratio IC 50 :IC 50 , 0.5 IC 50 :IC 50 and IC 50 :0.5 IC 50 exhibited a synergistic effect on Michigan Cancer Foundation-7 cells. Moreover, combination of dichloromethane crude extract of Gymnanthemum extensum with low piperine fractional Piper nigrum extract induced the apoptosis and multi caspase activity in a time dependent manner. In conclusion, dichloromethane crude extract of Andrographis paniculata, Ziziphus spina-christi and Gymnanthemum extensum displayed potent anticancer activities and the combination of dichloromethane crude extract of Gymnanthemum extensum with low piperine fractional Piper nigrum extract can be a promising regimen for an alternative cancer treatment.

ScopePrunus avium fruit is the richer source of phenolics known to exert anticancer and anti-invasive activities. The study aimed at elucidating antiproliferative and chemo-preventive potential of sweet cherries (P. avium) against the in vivo hepatocarcinoma model.Methods and resultsThe quantification of ultrasound-assisted extract (UAE) of P. avium depicted anthocyanins, ferulic acid, gallic acid, quercetin, syringic acid and p- and m-coumaric acids as major phytochemicals. The hepatocarcinoma (HCC) was induced in rats through intraperitoneal administration of DMBA (20 mg/kg B.W) once a week for the period of eight weeks. The intragastric administration of P. avium UAE, as cotreatment (500 mg/Kg B.W) to treatment group, significantly (p < 0.01) attenuated the raised serum alpha-fetoprotein (AFP), carcinoembryonic antigen (CEA), alanine aminotransferase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase (LDH) as well as total oxidative stress (TOS) and enhanced total antioxidant capacity TAOC in contrast to diseased rats. Moreover, microscopic examination of hepatic tissues confirmed the pleomorphism, nests of neoplastic hepatocytes and necrosis in HCC-bearing rats as compared to extract-fed rats, where these necrotic changes were suppressed. Besides, qRT-PCR analysis of hepatic tissues demonstrated the higher mRNA expression of CHEK1, CHEK2 and P21/CDKN1α genes, while downexpression of ATM gene in extract fed rats, further denoting the anti-mutagenic potential.ConclusionConsequently, the polyphenol-rich sweet cherries UAE exhibited antiproliferative and chemo-preventive potential by reducing tumor biomarkers, serum transaminases and oxidative stress, as well as enhancing antioxidant status. It further upregulated the downstream targets of ATM signaling cascade.

Stellaria media Vill. is widely distributed throughout the world and traditionally used to treat inflammatory, respiratory, heart and gastrointestinal diseases. This study was designed to phytochemically characterize and investigate the anti-ulcer activity of methanol extract of S. media (SME) on piroxicam (PRX)-induced gastric ulcer in rats. The plant extract was subjected to qualitative as well as quantitative analysis (HPLC and FT-IR) to elucidate the phytochemical composition of the extract. DPPH radical scavenging assay was done to determine in vitro antioxidant capacity. In 14 days of animal study, PRX (30 mg/kg, i.g.) was co-administered with omeprazole (OMP; 20 mg/kg, i.g.) as standard gastroprotective drug and SME at 150, 300 and 450 mg/kg, i.g., respectively. The gastric pH, acid volume, acidity, ulcer score, hematological parameters and serum levels of oxidants/antioxidants were determined along with histopathological studies of gastric tissue. Phytochemical analysis showed the presence of considerable phenolic and flavonoid contents which corroborated with a significant DPPH radical scavenging (IC50: 27.94 µg/mL) activity of extract. Administration of SME at 150, 300 and 450 mg/kg exhibited a dose-dependent gastroprotective effect evidenced by increased gastric pH and acidity but decreased gastric acid volume, decreased gastric ulcer score and ulcer index, reversed altered hematological parameters and oxidative stress markers (TOS, MDA, TAC and CAT). In addition, histopathological findings supported the aforementioned results. Conclusively this study suggests that Stellaria media possess promising gastroprotective activity against piroxicam-induced gastric ulcer.