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Phyllanthus emblica fruit extract attenuates lipid metabolism in 3T3-L1 adipocytes via activating apoptosis mediated cell death

Balusamy SR, Veerappan K, Ranjan A, Kim YJ, Chellappan DK, Dua K, et al.

Phytomedicine, 2019 Oct 31;66:153129.
PMID: 31794911 DOI: 10.1016/j.phymed.2019.153129

BACKGROUND: Phyllanthus emblica L. (Indian gooseberry) is widely used in the Ayurveda for thousands of years to treat health complications including disorders of the immune system, diabetes, and obesity.
PURPOSE: For the first time, our study aims to demonstrate the molecular mechanisms of the fruit extract of Phyllanthus emblica (PEFE) involved in the promotion of fat cell apoptosis and alleviation of adipogenesis.
METHODS: The active constituents from PEFE were identified using high performance liquid chromatography-mass spectrometry (HPLC-MS). We carried out the 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl tetrazolium bromide (MTT) assay to evaluate the cytotoxic effects of PEFE using 3T3-L1 pre-adipocytes. The colonogenic assay was carried out to determine the inhibitory effect of 3T3-L1 adipocytes after PEFE treatment. In addition, inhibition of pancreatic lipase activity was performed and the lipolytic activity of PEFE and digallic acid was compared with the well-known standard drug orlistat. Besides, the molecular interaction and ligand optimization between digallic and adipogenesis/apoptosis markers were also carried out. Furthermore, to confirm fat cell apoptosis we have used several detection methods that includes Hoechst staining, PI staining, Oil staining and qPCR respectively.
RESULTS: Digallic acid was identified as a major component in the PEFE. The IC50 values of digallic acid and PEFE were found to be 3.82 µg/ml and 21.85 µg/ml respectively. PEFE and digallic acid showed significant anti-lipolytic activity compared to the standard drug orlistat. In the mature adipocytes, PEFE significantly decreased triglyceride accumulation by downregulating adiponectin, PPARγ, cEBPα, and FABP4 respectively. We further analyzed the expression of apoptosis related genes upon PEFE treatment. Apoptotic process initiated through upregulation of BAX and downregulation of BCL2 resulting in an increased caspase-3 activity. In addition, we have also confirmed the apoptosis and DNA fragmentation in 3T3-L1 cells using Hoechst, PI and TUNEL assays.
CONCLUSION: PEFE negatively regulates adipogenesis by initiating fat cell apoptosis and therefore it can be considered as a potential herbal medicinal product for treating obesity.
A comprehensive review on Moringa oleifera nanoparticles: importance of polyphenols in nanoparticle synthesis, nanoparticle efficacy and their applications

Perumalsamy H, Balusamy SR, Sukweenadhi J, Nag S, MubarakAli D, El-Agamy Farh M, et al.

J Nanobiotechnology, 2024 Feb 19;22(1):71.
PMID: 38373982 DOI: 10.1186/s12951-024-02332-8

Moringa oleifera is one of the popular functional foods that has been tremendously exploited for synthesis of a vast majority of metal nanoparticles (NPs). The diverse secondary metabolites present in this plant turn it into a green tool for synthesis of different NPs with various biological activities. In this review, we discussed different types of NPs including silver, gold, titanium oxide, iron oxide, and zinc oxide NPs produced from the extract of different parts of M. oleifera. Different parts of M. oleifera take a role as the reducing, stabilizing, capping agent, and depending on the source of extract, the color of solution changes within NP synthesis. We highlighted the role of polyphenols in the synthesis of NPs among major constituents of M. oleifera extract. The different synthesis methods that could lead to the formation of various sizes and shapes of NPs and play crucial role in biomedical application were critically discussed. We further debated the mechanism of interaction of NPs with various sizes and shapes with the cells, and further their clearance from the body. The application of NPs made from M. oleifera extract as anticancer, antimicrobial, wound healing, and water treatment agent were also discussed. Small NPs show better antimicrobial activity, while they can be easily cleared from the body through the kidney. In contrast, large NPs are taken by the mono nuclear phagocyte system (MPS) cells. In case of shape, the NPs with spherical shape penetrate into the bacteria, and show stronger antibacterial activity compared to the NPs with other shapes. Finally, this review aims to correlate the key characteristics of NPs made from M. oleifera extract, such as size and shape, to their interactions with the cells for designing and engineering them for bio-applications and especially for therapeutic purposes.
Fulltext Nanoemulsion and Encapsulation Strategy of Hydrophobic Oregano Essential Oil Increased Human Prostate Cancer Cell Death via Apoptosis by Attenuating Lipid Metabolism

Perumalsamy H, Shanmugam R, Kim JR, Anandapadmanaban G, Huq MA, Dua K, et al.

Bioinorg Chem Appl, 2022;2022:9569226.
PMID: 35662912 DOI: 10.1155/2022/9569226

Origanum vulgare essential oil (EO) is traditionally well-known for its aromatic properties and biomedical applications, including anticancer. This was the first report where oregano essential oil-based nano emulsion (OENE) was synthesized for studying its effects on prostate cancer cell lines (PC3). At first, we have synthesized OENE and characterized using various spectroscopic analyses. The toxicity and inhibitory concentration (IC50) of OENE toward prostate cancer by MTT analysis were performed. The lipid biogenesis mediated, molecular target pathway analyses were performed using fluorescence cellular staining techniques, real-time RT-PCR, or western blotting analysis. OENE showed IC50 at 13.82 µg/mL and significantly induced distinct morphological changes, including cell shrinkage, cell density, and cell shape reduction. In addition, OENE could also significantly decreased lipid droplet accumulation which was confirmed by studying mRNA transcripts of 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR) (0.31-fold), fatty acid synthase (FASN) (0.18-fold), and sterol regulatory element-binding protein (SREPB1) (0.11-fold), respectively. Furthermore, there is a significant upregulation BAX (BCL2 associated X) and caspase 3 expressions. Nevertheless, OENE decreased the transcript level of BCL2 (B-cell lymphoma 2), thus resulting in apoptosis. Overall, our present work demonstrated that OENE could be a therapeutic target for the treatment of prostate cancer and warrants in vivo studies.
Evaluation of the sub-acute toxicity of Acacia catechu Willd seed extract in a Wistar albino rat model

Thangavelu L, Balusamy SR, Shanmugam R, Sivanesan S, Devaraj E, Rajagopalan V, et al.

Regul Toxicol Pharmacol, 2020 Jun;113:104640.
PMID: 32169672 DOI: 10.1016/j.yrtph.2020.104640

Acacia catechu (A. catechu) or Khair (Hindi) is used in several herbal preparations in the Ayurvedic system of medicine in India. Traditionally, this drug is beneficial against several gastrointestinal and stomach related ailments, and leprosy. The present investigation was carried out to evaluate the sub-acute oral toxicity of the ethanolic extract of A. catechu seeds in Wistar albino rats. Results obtained from the quantitative chemical analysis of A. catechu seed extract were compared with commercially available standards. A. catechu seed extract was administered orally at the doses of 250, 500 and 1000 mg/kg b.w. daily for 28 days. General behavior, bodyweight and mortality were examined during the entire study period. At the end of 28 days, hematological and biochemical parameters along with the relative organ weights were determined. It was observed that the extract did not induce death or any significant changes in the body weight, relative weight of vital organs and in hematological parameters for up to a dose of 1000 mg/kg. The oral administration of the plant extract did not produce any significant changes in the levels of glucose. In addition, there were no significant changes in the activity of both hepatotoxic and nephrotoxic marker enzymes in the serum. Oral administration of A. catechu also did not produce any significant changes in the levels of oxidative markers. Furthermore, the findings from the biochemical studies were, well corroborated with the histological findings.
MicroRNAs as Biomarker for Breast Cancer

Aggarwal T, Wadhwa R, Gupta R, Paudel KR, Collet T, Chellappan DK, et al.

Endocr Metab Immune Disord Drug Targets, 2020;20(10):1597-1610.
PMID: 32342824 DOI: 10.2174/1871530320666200428113051

Regardless of advances in detection and treatment, breast cancer affects about 1.5 million women all over the world. Since the last decade, genome-wide association studies (GWAS) have been extensively conducted for breast cancer to define the role of miRNA as a tool for diagnosis, prognosis and therapeutics. MicroRNAs are small, non-coding RNAs that are associated with the regulation of key cellular processes such as cell multiplication, differentiation, and death. They cause a disturbance in the cell physiology by interfering directly with the translation and stability of a targeted gene transcript. MicroRNAs (miRNAs) constitute a large family of non-coding RNAs, which regulate target gene expression and protein levels that affect several human diseases and are suggested as the novel markers or therapeutic targets, including breast cancer. MicroRNA (miRNA) alterations are not only associated with metastasis, tumor genesis but also used as biomarkers for breast cancer diagnosis or prognosis. These are explained in detail in the following review. This review will also provide an impetus to study the role of microRNAs in breast cancer.
Rapid biosynthesis of silver nanoparticles using Crotalaria verrucosa leaves against the dengue vector Aedes aegypti: what happens around? An analysis of dragonfly predatory behaviour after exposure at ultra-low doses

Murugan K, Sanoopa CP, Madhiyazhagan P, Dinesh D, Subramaniam J, Panneerselvam C, et al.

Nat Prod Res, 2016 Apr;30(7):826-33.
PMID: 26284510 DOI: 10.1080/14786419.2015.1074230

Aedes aegypti is a primary vector of dengue, a mosquito-borne viral disease infecting 50-100 million people every year. Here, we biosynthesised mosquitocidal silver nanoparticles (AgNP) using the aqueous leaf extract of Crotalaria verrucosa. The green synthesis of AgNP was studied by UV-vis spectroscopy, SEM, EDX and FTIR. C. verrucosa-synthesised AgNPs were toxic against A. aegypti larvae and pupae. LC50 of AgNP ranged from 3.496 ppm (I instar larvae) to 17.700 ppm (pupae). Furthermore, we evaluated the predatory efficiency of dragonfly nymphs, Brachydiplax sobrina, against II and III instar larvae of A. aegypti in an aquatic environment contaminated with ultra-low doses of AgNP. Under standard laboratory conditions, predation after 24 h was 87.5% (II) and 54.7% (III). In an AgNP-contaminated environment, predation was 91 and 75.5%, respectively. Overall, C. verrucosa-synthesised AgNP could be employed at ultra-low doses to reduce larval population of dengue vectors enhancing predation rates of dragonfly nymphs.
Immunological axis of berberine in managing inflammation underlying chronic respiratory inflammatory diseases

Tew XN, Xin Lau NJ, Chellappan DK, Madheswaran T, Zeeshan F, Tambuwala MM, et al.

Chem Biol Interact, 2020 Feb 01;317:108947.
PMID: 31968208 DOI: 10.1016/j.cbi.2020.108947

Inflammatory responses play a remarkable role in the mechanisms of acute and chronic respiratory diseases such as chronic obstructive pulmonary disease (COPD), asthma, pulmonary fibrosis and lung cancer. Currently, there is a resurgence in the use of drugs from natural sources for various ailments as potent therapeutics. Berberine, an alkaloid prominent in the Chinese traditional system of medicine has been reported to exert therapeutic properties in various diseases. Nevertheless, the number of studies focusing on the curative potential of berberine in inflammatory diseases involving the respiratory system is limited. In this review, we have attempted to discuss the reported anti-inflammatory properties of berberine that function through several pathways such as, the NF-κB, ERK1/2 and p38 MAPK pathways which affect several pro-inflammatory cytokines in the pathophysiological processes involved in chronic respiratory diseases. This review would serve to provide valuable information to researchers who work in this field and a new direction in the field of drug discovery with respect to respiratory diseases.
Emerging Complexity and the Need for Advanced Drug Delivery in Targeting Candida Species

Wadhwa R, Pandey P, Gupta G, Aggarwal T, Kumar N, Mehta M, et al.

Curr Top Med Chem, 2019;19(28):2593-2609.
PMID: 31746290 DOI: 10.2174/1568026619666191026105308

BACKGROUND: Candida species are the important etiologic agents for candidiasis, the most prevalent cause of opportunistic fungal infections. Candida invasion results in mucosal to systemic infections through immune dysfunction and helps in further invasion and proliferation at several sites in the host. The host defence system utilizes a wide array of the cells, proteins and chemical signals that are distributed in blood and tissues which further constitute the innate and adaptive immune system. The lack of antifungal agents and their limited therapeutic effects have led to high mortality and morbidity related to such infections.
METHODS: The necessary information collated on this review has been gathered from various literature published from 1995 to 2019.
RESULTS: This article sheds light on novel drug delivery approaches to target the immunological axis for several Candida species (C. albicans, C. glabrata, C. parapsilosis, C. tropicalis, C. krusei, C. rugose, C. hemulonii, etc.).
CONCLUSION: It is clear that the novel drug delivery approaches include vaccines, adoptive transfer of primed immune cells, recombinant cytokines, therapeutic antibodies, and nanoparticles, which have immunomodulatory effects. Such advancements in targeting various underpinning mechanisms using the concept of novel drug delivery will provide a new dimension to the fungal infection clinic particularly due to Candida species with improved patient compliance and lesser side effects. This advancement in knowledge can also be extended to target various other similar microbial species and infections.