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    A review on reported phytochemicals as druggable leads with antimalarial potential
    (Springer, 2023-07-04T00:00:00) Guchait, Avishek; Kumar, Asim; Singh, Roopam; Joshi, Gaurav; Dwivedi, Ashish Ranjan
    The science and practice of drug discovery and development is primarily benefitted from the natural sources. The chemistry of natural products has inspired medicinal chemists to develop and design various therapeutic molecules from the leads obtained from natural sources. This is evident from the growing number of publications on natural products derived from drug molecules. Some of the most successful bioactive natural product candidates so far are Taxol obtained from �Taxus Brevifolia,� Quinine obtained from the bark of the cinchona plant, morphine obtained from the dried latex of the poppy plant, Vincristine, and Vinblastine from �Vinca Rosea,� atropine from �Atropa Belladonna�, Digoxin and Digitoxin from �Digitalis Purpurea� and Artemisinin from �Artemisia Annua�. Parasitic pathogens are one of the significant menaces for the world as they lead to various diseases in hosts, and for many diseases, these parasite compromises the host�s immune system. Malaria is a parasitic disease especially endemic to tropical countries and is one of the leading causes of death worldwide. According to the latest data from WHO, millions of patients are suffering from malaria and its related complications on 30th March 2022. Natural products derived leads have brought a paradigm shift in the discovery of antimalarial drugs. The first antimalarial drug, quinine, was isolated from the Cinchona species (Family: Rubiaceae) in 1820 and is still used today. This was followed by another antimalarial drug a century later, chloroquine, discovered in the 1940s. After that, Artemisinin was founded in 1972 by Tu Youyou, co-recipient of the 2015 Nobel Prize in Medicine for her discovery. Unfortunately, the malarial parasite, mainly Plasmodium falciparum, develops resistance to these drugs, and thus there exists a need to explore other natural herbs for their role as antimalarials. The current review is therefore kept forth to congregate updated information on undergoing research in allied areas of natural product-based drug discovery, particularly for developing antimalarial agents. � 2023, The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.
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    Updated ethnobotanical notes, phytochemistry and phytopharmacology of plants belonging to the genus Morus (Family: Moraceae)
    (Elsevier B.V., 2021-09-17T00:00:00) Yadav, Sonam; Nair, Nisha; Biharee, Avadh; Prathap, Vivek Morris; Majeed, Jaseela
    Background: : Mulberry (Genus: Morus, Family: Moraceae) is a flowering plant utilized in Traditional Chinese Medicine (TCM) and Ayurveda for its ethnobotanical uses in fever, liver protection, diuretics, management of appropriate blood pressure, improving eyesight, and management of cardiovascular disease. Being a plant of multiple ethnobotanical prospects, it is used to prevent kidney diseases, hair problems, weakness, fatigue, constipation, blood disorders, anemia, and premature greying of hair, among few other ailments. This review aims to systematically organize information on the ethnobotanical uses, phytochemical constituents, phytopharmacological actions, and toxicity of the Morus genus as the information shall serve towards future research in drug discovery and help in unearthing molecular basis of pharmacological activity of Mulberry. Method: : Many relevant information sources, such as Elsevier, Science Direct, PubMed, ACS Publications, SciFinder, Wiley, and Google Scholar, Chinese Pharmacopoeia 2015, Chinese and Indian herbal classic texts, and Ph.D. dissertation, were used to gather relevant publications till February 2021 on the Morus genus. Results: : Many phytochemicals that are isolated from Morus genus such as Mulberrin, Morin, Deoxynojirimycin (DNJ), Epicatechin, Gallic acid, Vanillic acid, Oxyresveratrol, Quercetin, Flavone A, B and C, are proven to be pharmacologically important and have comprehensive biological actions such as anti-inflammatory, anticancer, antibacterial, anti-obesity, antidopaminergic, antioxidant activity, as well as skin whitening properties making the plants of Morus genus therapeutically important. Conclusions: : Plants of Morus genus are valuable and are popular in ancient herbal medicine with the extensive pharmacological potential to cure various ailments. While phytochemicals from plants of Morus genus have already been extensively analysed, there may still be unknown compounds that play a role in the plant's biological function which needs to be elucidated. There are significant gaps in our understanding of biological processes involved in activities of these phytochemicals that need more investigation. � 2021 The Author(s)
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    Understanding the multifaceted role of miRNAs in Alzheimer�s disease pathology
    (Springer, 2023-07-28T00:00:00) Kaur, Sharanjot; Verma, Harkomal; Kaur, Sukhchain; Gangwar, Prabhakar; Yadav, Anuradha; Yadav, Bharti; Rao, Rashmi; Dhiman, Monisha; Mantha, Anil Kumar
    Small non-coding RNAs (miRNAs) regulate gene expression by binding to mRNA and mediating its degradation or inhibiting translation. Since miRNAs can regulate the expression of several genes, they have multiple roles to play in biological processes and human diseases. The majority of miRNAs are known to be expressed in the brain and are involved in synaptic functions, thus marking their presence and role in major neurodegenerative disorders, including Alzheimer�s disease (AD). In AD, amyloid beta (A?) plaques and neurofibrillary tangles (NFTs) are known to be the major hallmarks. The clearance of A? and tau is known to be associated with miRNA dysregulation. In addition, the ?-site APP cleaving enzyme (BACE 1), which cleaves APP to form A?, is also found to be regulated by miRNAs, thus directly affecting A? accumulation. Growing evidences suggest that neuroinflammation can be an initial event in AD pathology, and miRNAs have been linked with the regulation of neuroinflammation. Inflammatory disorders have also been associated with AD pathology, and exosomes associated with miRNAs are known to regulate brain inflammation, suggesting for the role of systemic miRNAs in AD pathology. Several miRNAs have been related in AD, years before the clinical symptoms appear, most of which are associated with regulating the cell cycle, immune system, stress responses, cellular senescence, nerve growth factor (NGF)�signaling, and synaptic regulation. Phytochemicals, especially polyphenols, alter the expression of various miRNAs by binding to miRNAs or binding to the transcriptional activators of miRNAs, thus control/alter various metabolic pathways. Awing to the sundry biological processes being regulated by miRNAs in the brain and regulation of expression of miRNAs via phytochemicals, miRNAs and the regulatory bioactive phytochemicals can serve as therapeutic agents in the treatment and management of AD. � 2023, The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.
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    Understanding the multifaceted role of miRNAs in Alzheimer�s disease pathology
    (Springer, 2023-07-28T00:00:00) Kaur, Sharanjot; Verma, Harkomal; Kaur, Sukhchain; Gangwar, Prabhakar; Yadav, Anuradha; Yadav, Bharti; Rao, Rashmi; Dhiman, Monisha; Mantha, Anil Kumar
    Small non-coding RNAs (miRNAs) regulate gene expression by binding to mRNA and mediating its degradation or inhibiting translation. Since miRNAs can regulate the expression of several genes, they have multiple roles to play in biological processes and human diseases. The majority of miRNAs are known to be expressed in the brain and are involved in synaptic functions, thus marking their presence and role in major neurodegenerative disorders, including Alzheimer�s disease (AD). In AD, amyloid beta (A?) plaques and neurofibrillary tangles (NFTs) are known to be the major hallmarks. The clearance of A? and tau is known to be associated with miRNA dysregulation. In addition, the ?-site APP cleaving enzyme (BACE 1), which cleaves APP to form A?, is also found to be regulated by miRNAs, thus directly affecting A? accumulation. Growing evidences suggest that neuroinflammation can be an initial event in AD pathology, and miRNAs have been linked with the regulation of neuroinflammation. Inflammatory disorders have also been associated with AD pathology, and exosomes associated with miRNAs are known to regulate brain inflammation, suggesting for the role of systemic miRNAs in AD pathology. Several miRNAs have been related in AD, years before the clinical symptoms appear, most of which are associated with regulating the cell cycle, immune system, stress responses, cellular senescence, nerve growth factor (NGF)�signaling, and synaptic regulation. Phytochemicals, especially polyphenols, alter the expression of various miRNAs by binding to miRNAs or binding to the transcriptional activators of miRNAs, thus control/alter various metabolic pathways. Awing to the sundry biological processes being regulated by miRNAs in the brain and regulation of expression of miRNAs via phytochemicals, miRNAs and the regulatory bioactive phytochemicals can serve as therapeutic agents in the treatment and management of AD. � 2023, The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.
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    Obesity and Cancer
    (Springer Singapore, 2021-07-18T00:00:00) Kumar, Shashank; Gupta, Sanjay
    This book highlights the concordance between signaling pathways that are involved in obesity and cancer cross-talks. It describes the role of cytokines, chemokines, growth factors, insulin, and adipokines in the development of obesity-associated cancers. The book reviews the role of inflammatory signaling pathways such as estrogen-mediated signaling, mTOR and AMP-activated protein kinase pathway and the involvement of adaptive and innate immunity, oxidative stress, gene polymorphism, dietary phytochemicals, and miRNAs in obesity and cancer. In addition, it covers the latest research on the drugs and natural therapeutic agents that target obesity-induced cancers and discusses various in vivo models for studying obesity and obesity-associated cancer. Lastly, it analyses the role of genetic polymorphisms in the obesity-related genes that influence cancer development. The book is a useful resource for researchers in the field of cancer, pharmacology, food chemistry, and clinical biochemistry. � The Editor(s) (if applicable) and The Author(s), under exclusive license to Taylor and Francis Pte Ltd. 2021.
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    Phytochemicals present in Indian ginseng possess potential to inhibit SARS-CoV-2 virulence: A molecular docking and MD simulation study
    (Academic Press, 2021-05-24T00:00:00) Kushwaha, Prem Prakash; Singh, Atul Kumar; Prajapati, Kumari Sunita; Shuaib, Mohd; Gupta, Sanjay; Kumar, Shashank
    Coronaviruses are deadly and contagious pathogens that affects people in different ways. Researchers have increased their efforts in the development of antiviral agents against coronavirus targeting Mpro protein (main protease) as an effective drug target. The present study explores the inhibitory potential of characteristic and non-characteristic Withania somnifera (Indian ginseng) phytochemicals (n ? 100) against SARS-Cov-2 Mpro protein. Molecular docking studies revealed that certain W. somnifera compounds exhibit superior binding potential (?6.16 to ?12.27 kcal/mol) compared to the standard inhibitors (?2.55 to ?6.16 kcal/mol) including nelfinavir and lopinavir. The non-characteristic compounds (quercetin-3-rutinoside-7-glucoside, rutin and isochlorogenic acid B) exhibited higher inhibitory potential in comparison to characteristic W. somnifera compounds withanolide and withanone. Molecular dynamics (MD) simulation studies of the complex for 100 ns confirm favorable and stable binding of the lead molecule. The MMPBSA calculation of the last 10 ns of the protein-ligand complex trajectory exhibited stable binding of quercetin-3-rutinoside-7-glucoside at the active site of SARS-Cov-2 Mpro. Taken together, the study demonstrates that the non-characteristic compounds present in W. somnifera possess enhanced potential to bind SARS-Cov-2 Mpro active site. We further recommend in vitro and in vivo experimentation to validate the anti-SARS-CoV-2 potential of these lead molecules. � 2021 Elsevier Ltd
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    Characterization of phytochemicals and validation of antioxidant and anticancer activity in some Indian polyherbal ayurvedic products
    (Springer, 2021-03-13T00:00:00) Kushwaha, Prem Prakash; Kumar, Ramesh; Neog, Panchi Rani; Behara, Malay Ranjan; Singh, Pratibha; Kumar, Ajay; Prajapati, Kumari Sunita; Singh, Atul Kumar; Shuaib, Mohd; Sharma, Amit Kumar; Pandey, Abhay Kumar; Kumar, Shashank
    In the present comparative study, the authors studied the antioxidant and anticancer activity of commercially available polyherbal Indian Ayurvedic products namely Divya Sarvakalp Kwath (DSKK), Divya Sanjivani Vati (DSV), Kanchanar Guggulu (KG) and Shakti Drop (SD). Authors also quantified phenolic and flavonoid contents in the samples. Solid powdered samples (DSKK, DSV, and KG) were extracted in methanol and water (1:1) using cold extraction method. Spectrophotometry technique was used to quantify the phytochemicals present in test samples. DSKK showed comparatively higher content of total phenolics (247.65 � 0.05 ?gPGE/g) and flavonoid (34.66 � 0.19 �gQE/mg). Radical scavenging, metal ion chelation and reducing potential of test products were studied using nitric oxide scavenging, DPPH, metal ion chelation, reducing power ability, and phosphomolybdate in vitro antioxidant assays at different concentration. Dose-dependent antioxidant activity was observed in all the test samples at 100�500��g or �l/ml concentration. Anticancer efficacy of the test samples were studied in lung (A549), colon (Colo205), and breast cancer (MCF7) cell lines at different concentrations (10�100��g or �l/ml) using MTT assay. Confocal microscopy was used to reveal the apoptotic induction, mitochondrial membrane integrity disruption and reactive oxygen species production ability of test products in cancer cells. The present study revealed that DSKK possesses comparatively better antioxidant potential and SD has potent anticancer activity against breast cancer cells. � 2021, Society for Plant Research.