title: Antioxidant, hepatoprotective and cytotoxic effects of icetexanes isolated from stem-bark of Premna tomentosa.
abstract: The study investigates the antioxidant, hepatoprotective and antiproliferative effects of novel icetexane diterpenoids (ice 1-4) isolated from hexane extract of stem bark of Premna tomentosa. A549, HT-29, MCF-7, MDA-MB-231, A431 cells were used to assess the antiproliferative activity by MTT assay. Cell death induced by apoptosis was determined by morphological assessment studies using acridine orange/ethidium bromide staining (dual staining), mitochondrial potential measurement by JC-1 staining, and cell cycle analysis by propidium iodide staining method by Muse cell analyser. Anti oxidant activity was investigated by in vitro assays such as DPPH, nitric oxide and superoxide scavenging activities. Hepatoprotective activity was determined in vitro with HepG2 cells and in vivo by tBHP induced hepatic damage mice model. Based on the in vitro cytotoxic assays and morphological assessment studies using fluorescence microscopic study (acridine orange and ethidium bromide double staining) and mitochondrial potential measurements, it was found that ice 2 and 3 possess good antiproliferative effect via mitochondrial mediated apoptosis in human lung and breast cancer cells. Results of in vitro antioxidant studies demonstrated that ice-4 has showed good antioxidant activity. The restoration of serum levels of SGOT, SGPT and ALKP, liver GSH status and reduction or inhibition of lipid peroxidation in liver of tBHP intoxicated mice after administration of ice-4 at dose of 250mg/kg indicated its potential use for hepatoprotective activity.
authors.affiliation: Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research, Hyderabad 500037, India.
authors.forename: Naidu
authors.initials: N
authors.lastname: V G M
authors.affiliation: Division of Natural Product Chemistry, CSIR-Indian Institute of Chemical Technology, Hyderabad 500007, India.
authors.forename: Hymavathi
authors.initials: H
authors.lastname: Atmakur
authors.affiliation: Division of Natural Product Chemistry, CSIR-Indian Institute of Chemical Technology, Hyderabad 500007, India.
authors.forename: Suresh Babu
authors.initials: SB
authors.lastname: Katragadda
authors.affiliation: Division of Medicinal Chemistry and Pharmacology, CSIR-Indian Institute of Chemical Technology, Hyderabad 500007, India.
authors.forename: Bhavana
authors.initials: B
authors.lastname: Devabakthuni
authors.affiliation: Division of Medicinal Chemistry and Pharmacology, CSIR-Indian Institute of Chemical Technology, Hyderabad 500007, India.
authors.forename: Anudeep
authors.initials: A
authors.lastname: Kota
authors.affiliation: Division of Medicinal Chemistry and Pharmacology, CSIR-Indian Institute of Chemical Technology, Hyderabad 500007, India.
authors.forename: Chenna Keshava Reddy
authors.initials: CK
authors.lastname: S
authors.affiliation: Division of Medicinal Chemistry and Pharmacology, CSIR-Indian Institute of Chemical Technology, Hyderabad 500007, India.
authors.forename: Madhusudana
authors.initials: M
authors.lastname: Kuncha
authors.affiliation: Division of Medicinal Chemistry and Pharmacology, CSIR-Indian Institute of Chemical Technology, Hyderabad 500007, India.
authors.forename: Vishnu Vardhan
authors.initials: VV
authors.lastname: M V P S
authors.affiliation: Division of Medicinal Chemistry and Pharmacology, CSIR-Indian Institute of Chemical Technology, Hyderabad 500007, India.
authors.forename: Prasad
authors.initials: P
authors.lastname: Kulkarni
authors.affiliation: Division of Natural Product Chemistry, CSIR-Indian Institute of Chemical Technology, Hyderabad 500007, India.
authors.forename: Madhusudana Rao
authors.initials: MR
authors.lastname: Janaswamy
authors.affiliation: Division of Medicinal Chemistry and Pharmacology, CSIR-Indian Institute of Chemical Technology, Hyderabad 500007, India. Electronic address: sistla@iict.res.in.
authors.forename: Ramakrishna
authors.initials: R
authors.lastname: Sistla
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000032:analysis* / Q000494:pharmacology; D000975:Antioxidants / Q000032:analysis*; D017209:Apoptosis / Q000187:drug effects*; D002453:Cell Cycle / Q000187:drug effects; D004224:Diterpenes / Q000302:isolation & purification*; D004354:Drug Screening Assays, Antitumor; D019073:HT29 Cells; D056945:Hep G2 Cells; D006801:Humans; D008099:Liver / Q000187:drug effects; D061986:MCF-7 Cells; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D010946:Plants, Medicinal / Q000737:chemistry; D029648:Verbenaceae / Q000737:chemistry*
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D000975:Antioxidants; D004224:Diterpenes
keywords: Anticancer; Antioxidant; Hepatoprotective; Icetexanes; Premna tomentosa