Publications by authors named "Y L Ramachandra"

27 Publications

Anti-neoplastic pharmacophore benzophenone-1 coumarin (BP-1C) targets JAK2 to induce apoptosis in lung cancer.

Apoptosis 2021 Nov 27. Epub 2021 Nov 27.

Molecular Biomedicine Laboratory, Postgraduate Department of Studies and Research in Biotechnology, Sahyadri Science College, Kuvempu University, Shivamogga, Karnataka, 577203, India.

Reigning of the abnormal gene activation associated with survival signalling in lung cancer leads to the anomalous growth and therapeutic failure. Targeting specific cell survival signalling like JAK2/STAT3 nexus has become a major focus of investigation to establish a target specific treatment. The 2-bromobenzoyl-4-methylphenoxy-acetyl hydra acetyl Coumarin (BP-1C), is new anti-neoplastic agent with apoptosis inducing capacity. The current study was aimed to develop antitumor phramacophore, BP-1C as JAK2 specific inhibitor against lung neoplastic progression. The study validates and identifies the molecular targets of BP-1C induced cell death. Cell based screening against multiple cancer cell lines identified, lung adenocarcinoma as its specific target through promotion of apoptosis. The BP-1C is able to induce, specific hall marks of apoptosis and there by conferring anti-neoplastic activity. Validation of its molecular mechanism, identified, BP-1C specifically targets JAK2 phosphorylation, and inhibits its downstream STAT3 signalling pathway to induce cell death. As a consequence, modulation in Akt/Src survival signal and altered expression of interwoven apoptotic genes were evident. The results were reproducible in an in-vivo LLC tumor model and in-ovo xenograft studies. The computational approaches viz, drug finger printing confers, BP-1C as novel class JAK2 inhibitor and molecular simulations studies assures its efficiency in binding with JAK2. Overall, BP-1C is a novel JAK2 inhibitor with experimental evidence and could be effectively developed into a promising drug for lung cancer treatment.
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http://dx.doi.org/10.1007/s10495-021-01699-5DOI Listing
November 2021

Mitigation of organophosphorus insecticides from environment: Residual detoxification by bioweapon catalytic scavengers.

Environ Res 2021 09 31;200:111368. Epub 2021 May 31.

Laboratory of Plant Healthcare and Diagnostics, P.G. Department of Biotechnology and Microbiology, Karnatak University, Dharwad, Karnataka, 580003, India. Electronic address:

Organophosphorus insecticides (OPIs) have low persistence and are easily biodegradable in nature. The United States and India are the major countries producing OPIs of about 25% and 17% of the world, respectively. OPIs commonly used for agricultural practices occupy a major share in the global market, which leads to the increasing contamination of OPIs residues in various food chains. To overcome this issue, an enzymatic degradation method has been approved by several environmental toxic, and controlling agencies, including United States Environmental Protection Agency (USEPA). Different catalytic enzymes have been isolated and identified from various microbial sources to neutralize the toxic pesticides and/or insecticides. In this review, we have gathered information on OPIs biotransformation and their residual toxicity in the environment. Particularly, it focuses on OPIs degrading enzymes such as chlorpyrifos hydrolase, diisopropylfluorophosphatase, organophosphate acid anhydrolase, organophosphate hydrolases, and phosphotriesterases like lactonasesspecific activity either P-O link group type or P-S link group of pesticides. To summarize, the catalytic degradation of organophosphorus insecticides is not only profitable but also environmentally friendly. Hence, the enzymatic catalyst is an ultimate and super bio-weapon to mitigate or decontaminate various OPIs residues in both terrestrial and aqueous environments.
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http://dx.doi.org/10.1016/j.envres.2021.111368DOI Listing
September 2021

Evaluating the Anticancer Potential of Ethanolic Gall Extract of Terminalia chebula (Gaertn.) Retz. (Combretaceae).

Pharmacognosy Res 2016 Jul-Sep;8(3):209-12

Toxinology/Toxicology and Drug Discovery Unit, Centre for Emerging Technologies, Jain University, Ramanagara, Karnataka, India.

Unlabelled: Plants have been an important source for discovery of anticancer compounds. With the current decline in the number of new molecular entities from the pharmaceutical industry, novel anticancer agents are being sought from traditional medicines; therefore the anticancer efficacy of many plants that are used in traditional medicine is yet to be verified. The objective of the study was to evaluate the cytotoxic potential of ethanolic leaf gall extract of Terminalia chebula are evaluated against buffalo rat liver 3A, MCF-7 (Human mammary gland adenocarcinoma) and A-549 (Human lung cancer) cell lines. The cytotoxic effect of the ethanolic extract was evaluated by MTT assay. The extract was potent and effective in inducing cytotoxic effects in all the cell lines with an IC50 value of 305.18 ± 1.7 μg/mL, 643.13 ± 4.2 μg/mL, and 208.16 ± 3.7 μ/mL, respectively. The extract was more effective against A549 cell lines when compared to others. The presences of phenolics, triterpenoids, and flavonoids were identified in the extract. The extract showed total phenolic and flavonoid content of 478 ± 2.2 mg of gallic acid equivalent/g d.w and 538 ± 1.4 mg of quercetinequivalent/g d.w, respectively. This higher content of total phenolics and flavonoids found in the ethanolic extract was directly associated to higher cytotoxicity activity.

Conclusion: The ethanolic leaf gall extract of T. chebula showed effective cytotoxic activities; which might be attributed to the phenolics/flavonoids present in higher concentration. Future work will be interesting to know the chemical composition of the extract and also better understand the mechanism of action of the constituents present in the extract to develop it as drug for therapeutic application.

Summary: The present investigation establishes the anticancer activities of T. chebula leaf gall extracts on BRL3A, MCF-7, and A-549 cells. Presumably, these activities could be attributed in part to the phenolics/flavanoids features of the extract that has been demonstrated to act as cytotoxic agents. The experimental evidence obtained in the laboratory model could provide a rationale for the traditional use of plant as a source of easily available effective anticancer agents to the people, particularly in developing countries.
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http://dx.doi.org/10.4103/0974-8490.182919DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4908852PMC
July 2016

In vivo Toxicity Studies on Gall Extracts of Terminalia chebula (Gaertn.) Retz. (Combretaceae).

Pharmacognosy Res 2016 Jul-Sep;8(3):199-201

Toxinology/Toxicology and Drug Discovery Unit, Centre for Emerging Technologies, Jain University, Ramanagara, Karnataka, India.

Unlabelled: The galls of Terminala chebula (Gaertn.) Retz. (Combretaceae) are used for the treatment of various diseases in folk medicine and has been found to posses anti-inflammatory, anti-bacterial, anti-helmintic, anti-tyrosinase, and anti-aging activities. Considering the ethano-botanical and diverse pharmacological applications of galls of T. chebula, in this study, we investigate the possible toxic effects of different gall extracts of T. chebula by Brine shrimp (Artemia salina) toxicity assay. The cytotoxicity test of leaf gall extracts (petroleum ether, chloroform, ethanol, and aqueous) of T. chebula was evaluated by Brine shrimp (A. salina) toxicity assay, which is based on the ability to kill laboratory cultured Artemia nauplii (animals eggs) and also total content of polyphenols, flavonoids with other qualitative phytochemical analysis of the extract were determined. It was observed that the petroleum ether extract was virtually nontoxic on the shrimps, and exhibited very low toxicity with LC50 value of 4356.76 μg/ml. Furthermore, the chloroform extract exhibited very low toxicity, giving LC50 value of 1462.2 μg/ml. On the other hand, the ethanol extract was very toxic to brine shrimps with LC50 value of 68.64 μg/ml. The ethanol extract had the highest total phenolic and flavonoid content of 136 ± 1.5 mg of gallic acid equivalent/g d.w and 113 ± 1.6 mg of quercetin equivalent/g d.w, respectively. The higher toxicity effect was positively correlated to the high content of total polyphenols/flavonoids in the extract. This significant lethality of different extracts to brine shrimp is an indicative of the presence of potent cytotoxic components which warrants further investigation.

Summary: The present study investigates the toxicity effect of different extracts of galls of T. chebulla, which would serve as an index for formulation of drugs for treatment of various diseases. Presumably, these activities could be attributed in part to the polyphenolic features of the extract, as there was a strong correlation of higher toxic effect with that of high total phenolic and flavonoids content in the ethanolic leaf gall extracts of T. chebula.
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http://dx.doi.org/10.4103/0974-8490.182914DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4908849PMC
July 2016

Anti-Lipoxygenase Activity of Leaf Gall Extracts of Terminalia chebula (Gaertn.) Retz. (Combretaceae).

Pharmacognosy Res 2016 Jan-Mar;8(1):78-82

Department of Toxinology/Toxicology and Drug Discovery, Center for Emerging Technologies, Jain University, Kanakpura Taluk, Ramanagara, Karnataka, India.

Unlabelled: Lipoxygenase (LOX) inhibitors are the promising therapeutic target for treating a wide spectrum of inflammatory-related diseases such as cancer, asthma, lymphoma, leukemia, and autoimmune disorders. In the present study, the photochemical constituents and the anti-LOX potential of leaf galls of Terminalia chebula are evaluated to exemplify its further potential development as medicine. Extracts of T. chebula galls were tested for anti-LOX activity using linoleic acid as substrate and lipoxidase as an enzyme and also the total content of polyphenols with phytochemical analysis of the extract were determined. The presence of highest total phenolic and flavonoid content of 141 ± 2.2 mg of gallic acid equivalent/g d.w and 125 ± 1.4 mg of quercetin equivalent/g d.w and maximal LOX inhibitory activity (52.67%) at 800 μg/mL concentrations were identified in the ethanolic extracts of leaf galls of T.chebula. The higher LOX inhibitory activity was positively correlated to the high content of total polyphenols/flavonoids. The results of this study confirm the folklore use of T. chebula leaves gall extracts as a natural anti-inflammatory agent and justify its ethnobotanical use. Therefore, the results encourage the use of T. chebula leave gall extracts for medicinal health, functional food, and nutraceuticals applications.

Summary: The present investigation demonstrated promising anti-LOX proper-ties of T. chebula leaves gall extracts. Presumably, these activities could be attributed in part to the polyphenolic features of the extract, as there was a strong correlation of higher LOX inhibiting activities with that of high total phenolic and flavonoid content in the methanolic leaf gall extracts of T. chebula. The results of this study confirm the folklore use of T. chebula leaves gall extracts as a natural anti-inflammatory agent and justify the ethnobotanical approach in the search for novel bioactive com-pounds.
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http://dx.doi.org/10.4103/0974-8490.171103DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4753765PMC
March 2016
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