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Venkatesh Pooladanda, Soumya Bandi, Sandhya Rani Mondi, Krishna Mohan Gottumukkala, Chandraiah Godugu
Autophagy is a critical regulator of cellular homeostasis and its dysregulation often results in various disease manifestations, including cancer. Nimbolide, an active chemical constituent of neem (Azadirachta indica) exhibits potent anticancer effects. Although, nimbolide mediated apoptosis activation in breast cancer cells is well known. Nevertheless, its role in autophagy induction mechanism and epigenetic alteration is not explored previously. Our current study intended to bridge the gaps in the existing research by exploring the potential of nimbolide in inducing autophagy, which could counter regulate the transformations in breast cancer...
May 17, 2018: Toxicology in Vitro: An International Journal Published in Association with BIBRA
Mandakini J Patel, Shreya Tripathy, Keya D Mukhopadhyay, Tamna Wangjam, April B Cabang, Jay Morris, Michael J Wargovich
Colorectal cancer (CRC) is the third most commonly diagnosed cancer and the second leading cause of cancer death in men and women in the United States. Anti-inflammatory blockade has been proven to be a promising avenue of colorectal cancer prevention. However, NSAIDs while effective in curbing CRC risk are too toxic for long-term use in cancer prevention. The Neem tree (Azadirachta indica) is rich in liminoid terpenoids, collectively known as azadiractoids and has been shown to have anti-inflammatory effects...
April 26, 2018: Molecular Carcinogenesis
Md Fahim Ahmad, Mohd Owais Ansari, Sana Jameel, Ab Latif Wani, Nuzhat Parveen, Hifzur R Siddique, G G H A Shadab
Nimbolide is known to be an antioxidant found in neem plant. Hydroxyurea is a medication frequently used in sickle-cell disease, different cancers and HIV infection. The present study aimed to evaluate the adverse effect of HU and possible amelioration by nimbolide in Wistar rats. To test our hypothesis, we performed genotoxicity tests, biochemical assays, and histopathological studies. We observed that HU caused higher levels of genotoxicity in the treated animals. The observed genetic and oxidative damage might be due to the presence of reactive species as HU increased the level of the malondialdehyde-a biomarker of oxidative damage...
April 12, 2018: Environmental Toxicology and Pharmacology
Ghedeir M Alshammari, Aristatile Balakrishnan, Thirunavukkarasu Chinnasamy
Nimbolide is a bioactive compound found in Azadirachta indica. This work was devised to investigate the potential effects of nimbolide on intracellular lipid deposition and its associated redox modulation in primary hepatocytes (Heps). Lipid accumulation was induced in Heps by supplementing 1 mM oleic acid for 24 h which was marked by significant accumulation of lipids. The results demonstrated that nimbolide can decrease intracellular cholesterol, free fatty acids and triglycerides. Nimbolide may also improve hepatocytes function through its antioxidant effects by inhibiting oxidative DNA damage and lipid peroxidation by curtailing the reactive oxygen species levels...
December 2017: Molecular Biology Reports
Sandeep Kumar, Joseph R Inigo, Rahul Kumar, Ajay K Chaudhary, Jordan O'Malley, Srimmitha Balachandar, Jianmin Wang, Kristopher Attwood, Neelu Yadav, Steven Hochwald, Xinjiang Wang, Dhyan Chandra
Pancreatic ductal adenocarcinoma (PDAC) is highly aggressive disease and current treatment regimens fail to effectively cure PDAC. Development of resistance to current therapy is one of the key reasons for this outcome. Nimbolide (NL), a triterpenoid obtained from Azadirachta indica, exhibits anticancer properties in various cancer including PDAC cells. However, the underlying mechanism of this anticancer agent in PDAC cells remains undefined. We show that NL exerts a higher level of apoptotic cell death compared to the first-line agent gemcitabine for PDAC, as well as other anticancer agents including sorafenib and curcumin...
January 28, 2018: Cancer Letters
Subash Chandra Gupta, Sahdeo Prasad, Amit K Tyagi, Ajaikumar B Kunnumakkara, Bharat B Aggarwal
BACKGROUND: For centuries, agents derived from natural sources (mother nature), especially plants have been the primary source of medicine. Neem, also referred to as Azadirachta indica is one such plant that has been so named because it provides freedom from all diseases, and used for thousands of years in Indian and African continents. Different parts of the plant including flowers, leaves, seeds and bark have been used to treat both acute and chronic human diseases; and used as insecticide; antimicrobial, larvicidal, antimalarial, antibacterial, antiviral, and spermicidal...
October 15, 2017: Phytomedicine: International Journal of Phytotherapy and Phytopharmacology
Bandi Siva, Amujuri Devi, Arramsetti Venkanna, Borra Poornima, Genji Sukumar, Solipeta Divya Reddy, Movva Vijaya, Ramesh Ummanni, Katragadda Suresh Babu
A series of Nimbolide-triazole conjugates were synthesized through copper(I)- catalyzed azide-alkyne "click" chemistry approach and these derivatives (2-4, 2a-2l) were characterized using modern spectroscopic techniques. Antifeedant activities of these derivatives were studied on Tobacco Caterpillar, Spodoptera litura (F.) using no-choice leaf disk bioassay. Interestingly, the synthesized derivatives were more effective in reducing feedancy by insect species when compared to the parent nimbolide. Among the tested compounds, 2a, 2c, and 2d showed potent antifeedancy with ED50 values of 0...
November 2017: Fitoterapia
Muhammad Kashif, Yawon Hwang, Gyeongmi Hong, Gonhyung Kim
The present study was conducted to find the cytotoxicity in vitro of nimbolide, limonoids derivative of flowers and leaves from Azadirachta indica (neem tree) on the selected cell lines of cancer (Du-145, PC-3, A-549) and normal fibroblast cell lines (NIH3T3, CCD-18Co) using MTT assay. The cells were seeded in 96 multi-well tissue plate using different concentrations of nimbolide for 24hrs and 48hrs. The percentage of viability of cell lines was calculated by optical density obtained by micro plate reader and cytotoxic effect in term of IC50 value was determined by using linear regression analysis...
May 2017: Pakistan Journal of Pharmaceutical Sciences
Hua Lin, Shiyang Qiu, Lihua Xie, Chun Liu, Shenghua Sun
Nimbolide plays an important role in treating human diseases. In these years, the anticancer property of nimbolide has been paid more and more attention. However, the role of nimbolide in non-small cell lung cancer (NSCLC) remains unclear. In this study, we found that nimbolide treatment suppressed the invasion and migration of NSCLC cells, in a dose-dependent manner. Moreover, nimbolide treatment dose-dependently inhibited ERK1/2 activation, decreased Snail and MMP-3 expression, and increased E-cadherin expression...
August 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Jaganathan Kowshik, Rajakishore Mishra, Josephraj Sophia, Satabdi Rautray, Kumaraswamy Anbarasu, G Deepak Reddy, Madhulika Dixit, Sundarasamy Mahalingam, Siddavaram Nagini
Reversion-inducing cysteine-rich protein with Kazal motifs (RECK), a potent inhibitor of matrix metalloproteinases (MMPs) is a common negative target of oncogenic signals and a potential therapeutic target for novel drug development. Here, we show that sequential RECKlessness stimulates angiogenesis and Notch signalling in the 7,12-dimethylbenz[a]anthracene (DMBA)-induced hamster buccal pouch (HBP) carcinogenesis model, a paradigm for oral oncogenesis and chemointervention. We also report the chemotherapeutic effect of nimbolide, a limonoid from the neem tree (Azadirachta indica) based on the upregulation of RECK as well as modulation of the expression of key molecules involved in invasion and angiogenesis...
May 17, 2017: Scientific Reports
Zunjia Wen, Binbin Mei, Haiying Li, Yang Dou, Xiaodi Tian, Meifen Shen, Gang Chen
This study aimed to study the role of P2X7 in intracerebral hemorrhage (ICH)-induced secondary brain injury (SBI) and the underlying mechanisms. An autologous blood injection was used to induce ICH model in Sprague-Dawley rats, and cultured primary rat cortical neurons were exposed to oxyhemoglobin to mimic ICH in vitro. siRNA interference and over-expression of P2X7, agonists and antagonists of P2X7, p38 MAPK and ERK were exploited. The protein levels were assessed using Western blotting and immunofluorescence staining...
August 2017: Neurochemical Research
Su-Yu Chien, Ching-Hui Hsu, Chia-Chieh Lin, Yi-Ching Chuang, Yu-Sheng Lo, Yi-Ting Hsi, Ming-Ju Hsieh, Mu-Kuan Chen
Nasopharyngeal carcinoma (NPC), a tumor arising from epithelial cells that cover the surface and line the nasopharynx, is a rare malignancy worldwide but is prevalent in certain geographical areas, such as Southern Asia (Taiwan, Hong Kong, Singapore, Malaysia, and Southern China) and North Africa. Despite advances in diagnostic techniques and improvements in treatment modalities, the prognosis of NPC remains poor. Therefore, an effective chemotherapy regimen that enhances tumor sensitivity to chemotherapeutics is urgently required...
August 2017: Environmental Toxicology
Paulraj Raja Singh, Elayapillai Sugantha Priya, Solaimuthu Balakrishnan, Ramachandran Arunkumar, Govindaraj Sharmila, Manikkam Rajalakshmi, Jagadeesan Arunakaran
Prostate cancer is most common malignancy among men in the world. PI3K-Akt signaling appears to be critical to prostate cancer cell proliferation and survival. Our earlier study reveals that nimbolide (2 µM) prevents cell survival via IGF signaling pathway through PI3K/Akt and induces apoptosis in PC-3 cell line. Akt mediates the phosphorylation and activation of mTOR that plays a critical role in the regulation of protein translation and synthesis, angiogenesis, and cell cycle progression. The present study was aimed to investigate the effect of nimbolide on tPI3K, tAkt, pAkt, tmTOR, GSK3β, pGSK3β, PCNA, c-Myc, Cyclin D1, and Survivin protein levels by western blot analysis...
March 2017: Molecular and Cellular Biochemistry
P Raja Singh, E Sugantha Priya, S Balakrishnan, R Arunkumar, G Sharmila, M Rajalakshmi, J Arunakaran
BACKGROUND: Prostate cancer is the most prominent cancer in men, experiencing a relapse in disease often express high serum TNF-α levels. It has been correlated with increased cell survival and proliferation of prostate cancer cells. Previous studies reported that nimbolide, a terpenoid derived from the leaves and flowers of neem tree inhibits cancer growth through selective modulation of cell signaling pathways linked to inflammation, survival, proliferation, angiogenesis and metastasis...
December 2016: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Prodipta Sarkar, Saurabh Acharyya, Anirban Banerjee, Amarendra Patra, Karthika Thankamani, Hemanta Koley, Prasanta K Bag
Staphylococcus aureus is a leading aetiologic agent of nosocomial- and community-acquired infectious diseases worldwide. The public health concern regarding staphylococcal infections is inflated by the increasing occurrence of multidrug-resistant strains, e.g. multidrug- and meticillin-resistant S.aureus (MDR MRSA). This study was designed to evaluate the intracellular killing, membrane-damaging and biofilm-inhibitory activities of nimbolide isolated from Azadirachta indica against MDR MRSA. In vitro antibacterial activity of nimbolide was determined by performing MIC, minimal bactericidal concentration (MBC) and time-kill kinetic studies...
October 2016: Journal of Medical Microbiology
Subash C Gupta, Simone Reuter, Kanokkarn Phromnoi, Byoungduck Park, Padmanabhan S Hema, Mangalam Nair, Bharat B Aggarwal
No abstract text is available yet for this article.
August 5, 2016: Journal of Biological Chemistry
Ji Yeon Seo, Changhyun Lee, Sung Wook Hwang, Jaeyoung Chun, Jong Pil Im, Joo Sung Kim
Nimbolide is a limonoid extracted from neem tree (Azadirachta indica) that has antiinflammatory properties. The effect of nimbolide on the nuclear factor-kappa B (NF-κB) pathway in intestinal epithelial cells (IECs), macrophages and in murine colitis models was investigated. The IEC COLO 205, the murine macrophage cell line RAW 264.7, and peritoneal macrophages from interleukin-10-deficient (IL-10(-/-) ) mice were preconditioned with nimbolide and then stimulated with tumor necrosis factor-α (TNF-α) or lipopolysaccharide...
October 2016: Phytotherapy Research: PTR
Chantana Chantana, Chavi Yenjai, Prasert Reubroycharoen, Pornthip Waiwut
Tumor necrosis factor (TNF-α), an inflammatory cytokine that plays an important role in the control of cell proliferation, differentiation, and apoptosis, has previously been used in anti-cancer therapy. However, the therapeutic applications of TNF-α are largely limited due to its general toxicity and anti-apoptotic influence. To overcome this problem, the present study focused on the effect of active constituents isolated from a medicinal plant on TNF-α-induced apoptosis in human colon adenocarcinoma (HT-29) cells...
2016: Asian Pacific Journal of Cancer Prevention: APJCP
Jay Morris, Yuan Fang, Keya De Mukhopdhyay, Michael J Wargovich
Aerodigestive cancers are on an increasing level in both occurrence and mortality. A major cause in many of these cancers is disruption of the inflammatory pathway, leading to increased cell proliferation, and epigenetic silencing of normal regulatory genes. Here we review the research on several natural products: silibinin, silymarin, quercetin, neem & nimbolide, gingerol, epigallatecatechin-3- gallate, curcumin, genistein and resveratrol conducted on aerodigestive cancers. These types of cancers are primarily those from oral cavity, esophagus/windpipe, stomach, small and large intestine, colon/rectum and bile/pancreas tissues...
February 2016: Current Pharmacology Reports
Lingzhi Wang, Do Dang Khoa Phan, Jingwen Zhang, Pei-Shi Ong, Win Lwin Thuya, Ross Soo, Andrea Li-Ann Wong, Wei Peng Yong, Soo Chin Lee, Paul Chi-Lui Ho, Gautam Sethi, Boon Cher Goh
Nimbolide is one of the main components in the leaf extract of Azadirachta indica (A. indica). Accumulating evidence from various in vitro and in vivo studies indicates that nimbolide possesses potent anticancer activity against several types of cancer and also shows potential chemopreventive activity in animal models. The main mechanisms of action of nimbolide include anti-proliferation, induction of apoptosis, inhibition of metastasis and angiogenesis, and modulation of carcinogen-metabolizing enzymes. Although multiple pharmacodynamic (PD) studies have been carried out, nimbolide is still at the infant stage in the drug development pipeline due to the lack of systematic pharmacokinetic (PK) studies and long-term toxicological studies...
July 12, 2016: Oncotarget
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