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In silico analysis of aqueous root extract of Rotula aquatica Lour for docking analysis of the compound 3-O-acetyl-11-keto-?-boswellic acid contents.

ABSTRACT: Molecular docking is a bioinformatics tool used to study and analyse ligand receptor interactions. This helps in identifying the receptors (molecular targets) for different ligands. Using these technologies, compound isolation and drug discovery from herbals is achieved. Herbs are widely used in treatment of various ailments from time immemorial. Phytochemists and drug developers are now interestingly working in developing new molecules that can act effectively than conventional drugs. As they are developing it mostly from herbs they are found to be effective and safer drugs and quantity to be used become minimum. Rotula aquatica Lour is a plant distributed widely in India and used for urinary disorders. The plant root was extracted and studied for its active compounds that possess antiurolithiatic activity. After performing various preliminary phytochemical studies and applying chromatographic methods, molecular docking was carried out with isolated bioactive compound and Tamm-Horsfall protein (THP). By docking analysis the bioactive compound 3-O-acetyl-11-keto-?-boswellic acid interacted with THP and it may inhibit calcium oxalate crystallization.

SUBMITTER: Vijayakumari B

PROVIDER: S-EPMC5011466 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

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In silico analysis of aqueous root extract of Rotula aquatica Lour for docking analysis of the compound 3-O-acetyl-11-keto-β-boswellic acid contents.

Vijayakumari Bhavaniamma B Sasikala Venkatachalam V Radha Singanallur Ramu SR Rameshwar Hiranmai Yadav HY

SpringerPlus 20160905 1

Molecular docking is a bioinformatics tool used to study and analyse ligand receptor interactions. This helps in identifying the receptors (molecular targets) for different ligands. Using these technologies, compound isolation and drug discovery from herbals is achieved. Herbs are widely used in treatment of various ailments from time immemorial. Phytochemists and drug developers are now interestingly working in developing new molecules that can act effectively than conventional drugs. As they a ...[more]

PMID: 27652060

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Project description:Glioblastoma multiforme (GBM) is the most common and most aggressive subtype of malignant gliomas. The current standard of care for newly diagnosed GBM patients involves maximal surgical debulking, followed by radiation therapy and temozolomide chemotherapy. Despite the advances in GBM therapy, its outcome remains poor with a median survival of less than two years. This poor outcome is partly due to the ability of GBM tumors to acquire adaptive resistance to therapy and in particular to radiation. One of the mechanisms contributing to GBM tumor progression and resistance is an aberrant activation of NF-ĸB, a family of inducible transcription factors that play a pivotal role in regulation of many immune, inflammatory and carcinogenic responses. Acetyl-11-keto-β-boswellic acid (AKBA) is a pentacyclic terpenoid extracted from the gum Ayurvedic therapeutic plant Boswellia serrata. AKBA is anti-inflammatory agent that exhibits potent cytotoxic activities against various types of tumors including GBM. One of the mechanisms underlying AKBA anti-tumor activity is its ability to modulate the NF-ĸB signaling pathway. The present study investigated in vitro and in vivo the effect of combining AKBA with ionizing radiation in the treatment of GBM and assessed AKBA anti-tumor activity and radio-enhancing potential. The effect of AKBA and/or radiation on the survival of cultured glioblastoma cancer cells was evaluated by XTT assay. The mode of interaction of treatments tested was calculated using CalcuSyn software. Inducing of apoptosis following AKBA treatment was evaluated using flow cytometry. The effect of combined treatment on the expression of PARP protein was analysed by Western blot assay. Ectopic (subcutaneous) GBM model in nude mice was used for the evaluation of the effect of combined treatment on tumor growth. Immunohistochemical analysis of formalin-fixed paraffin-embedded tumor sections was used to assess treatment-related changes in Ki-67, CD31, p53, Bcl-2 and NF-ĸB-inhibitor IĸB-α. AKBA treatment was found to inhibit the survival of all four tested cell lines in a dose dependent manner. The combined treatment resulted in a more significant inhibitory effect compared to the effect of treatment with radiation alone. A synergistic effect was detected in some of the tested cell lines. Flow cytometric analysis with Annexin V-FITC/PI double staining of AKBA treated cells indicated induction of apoptosis. AKBA apoptotic activity was also confirmed by PARP cleavage detected by Western blot analysis. The combined treatment suppressed tumor growth in vivo compared to no treatment and each treatment alone. Immunohistochemical analysis showed anti-angiogenic and anti-proliferative activity of AKBA in vivo. It also demonstrated a decrease in p53 nuclear staining and in Bcl-2 staining and an increase in IĸB-α staining following AKBA treatment both alone and in combination with radiotherapy. In this study, we demonstrated that AKBA exerts potent anti-proliferative and apoptotic activity, and significantly inhibits both the survival of glioblastoma cells in vitro and the growth of tumors generated by these cells. Combination of AKBA with radiotherapy was found to inhibit factors which involved in cell death regulation, tumor progression and radioresistence, therefore it may serve as a novel approach for GBM patients.

Project description:BACKGROUND:Glioblastoma (GBM) is the most common, malignant, and lethal primary brain tumor in adults accounting for about 50% of all gliomas. Up to now, the chemotherapy approaches for GBM were limited. 3-O-acetyl-11-keto-?-boswellic acid (AKBA), the major active ingredient of the gum resin from Boswellia serrata and Boswellia carteri Birdw., was reported to inhibit the growth of many types of cancer cells; however, the underlying mechanism of its anticancer effects are still unclear. METHODS:The effects of AKBA on cell viability and its cytotoxicity were determined using CCK8 and LDH kits respectively. The EdU-DNA synthesis assay was used to evaluate inhibition of cell proliferation by AKBA. The role of AKBA in glioblastoma cell functions such as migration/invasion, and colony formation was evaluated using transwell chambers and soft agar, respectively. Flow cytometry and western blotting were used to detect AKBA-induced apoptosis. Potential mechanisms of AKBA action were explored by RNA sequencing and the identified hub genes were validated by real-time quantitative PCR and western blotting. Finally, the in vivo anti-tumor activity of AKBA was evaluated against a human glioblastoma cell line, U87-MG, in a xenograft mouse model. RESULTS:AKBA inhibited cell proliferation, caused the release of LDH, decreased DNA synthesis, and inhibited the migration, invasion, and colony formation of U251 and U87-MG human glioblastoma cell lines. AKBA increased apoptosis as well as the activity of caspase 3/7 and the protein expression of cleaved-caspase 3 and cleaved PARP, while decreasing mitochondrial membrane potential. RNA-sequencing analyses showed that AKBA suppressed the expression of pRB, FOXM1, Aurora A, PLK1, CDC25C, p-CDK1, cyclinB1, Aurora B, and TOP2A while increasing the expression of p21 and GADD45A. These findings were validated by qRT-PCR and western blotting. The data are consistent with a mechanism in which AKBA arrested the cell cycle in glioblastoma cells at the G2/M phase by regulating the p21/FOXM1/cyclin B1 pathway, inhibited mitosis by downregulating the Aurora B/TOP2A pathway, and induced mitochondrial-dependent apoptosis. Oral administration of AKBA (100 mg/kg) significantly suppressed the tumorigenicity of U87-MG cells in a xenograft mouse model. CONCLUSIONS:Taken together, these results suggest that AKBA (molecular weight, 512.7 Da) might be a promising chemotherapy drug in the treatment of GBM.

Dataset Information

In silico analysis of aqueous root extract of Rotula aquatica Lour for docking analysis of the compound 3-O-acetyl-11-keto-?-boswellic acid contents.

Publications

In silico analysis of aqueous root extract of Rotula aquatica Lour for docking analysis of the compound 3-O-acetyl-11-keto-β-boswellic acid contents.

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