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Antiprotozoal Effects of Wild Plants
Published in Mahendra Rai, Shandesh Bhattarai, Chistiane M. Feitosa, Ethnopharmacology of Wild Plants, 2021
Muhammad Subbayyal Akram, Rao Zahid Abbas, José L. Martinez
Derris trifoliata belongs to family Fabaceae and is commonly found in the coastal swamps of Konkan, India, and Kenya. Many rotenoloids, spirohomo-carotenoid and unique isoflavonoid derivatives have been isolated from the roots (Yenesew et al. 2005) and seeds (Yenesew et al. 2006) of Derris trifoliata which show anti-parasitic and larvicidal activities (Figure 7.1).
Novel Anti-Cancer Drugs Based On Hsp90 Inhibitory Mechanisms: A Recent Report
Published in Debarshi Kar Mahapatra, Sanjay Kumar Bharti, Medicinal Chemistry with Pharmaceutical Product Development, 2019
Derrubone (isolfavone isolated from Derris robusta) is another nature-based novel Hsp90 inhibitor that executes its action by blocking Cdc37-Hsp90 interaction [189]. Cdc37 is a co-chaperone involved in the recruitment of numerous Hsp90 client peptides (mainly kinases) [190, 191]. Hence, disruption of Cdc37-Hsp90 bonding leads to the degradation of numerous client proteins of Hsp90. However, the exact mode of inhibiting Hsp90-Cdc37 bondage is still not clearly elucidated. It is proposed that it carries out its function with the help of heme-regulated eIF2a kinase (HRI) kinase enzyme, a Hsp90 client [183, 189].
Rapid Ageing in Thailand and Implications for Thai Traditional Medicine
Published in Goh Cheng Soon, Gerard Bodeker, Kishan Kariippanon, Healthy Ageing in Asia, 2022
Anchalee Chuthaputti, Khwanchai Wisithanon
Symptoms and some traditional and herbal medicines commonly prescribed for the elderly are as follows: Symptoms associated with wind dhatu commonly found in the elderly (e.g. dizziness, fainting and nausea): the group of traditional medicine preparations called ‘yahom’, e.g. Yahom Dhebhachit, Yahom Nawakot (Tanaskilankoon and Sitthitanyakij, 2019)Gastrointestinal disorders Indigestion, flatulence: turmeric capsule, ginger capsule, cinnamon stomachic (Tanasilangkoon, 2018)Diarrhea: Ya Lueng Pidsamut, Andrographis paniculata capsule (Government of Thailand, 2019)Constipation: Senna alata infusion, Senna alexandrina tablet (Tanasilangkoon and Sitthitanyakij, 2016)Haemorrhoid: Cissus quadrangularis traditional medicine preparations (Tanasilangkoon, 2018)Fever: Chantaleela capsule (Government of Thailand, 2019)Respiratory symptoms and diseases Cough: Emblic myrobalan (Phyllanthus emblica)-containing traditional medicine antitussives, Triphala (equal proportion of fruits of Terminalia chebula, Terminalia bellirica, Phyllanthus emblica) capsule, pill or infusion (Tanasilangkoon, 2018)Common cold: Andrographis paniculata capsule, Ya Prab Chompu Taweep (Tanasilangkoon, 2018)Musculoskeletal symptomsMuscle ache: Plai (Zingiber montanum) cream, Plai oil, Sahassatara capsule, Ya Toranee Santakat, Derris scandens capsule and Derris scandens-containing traditional medicine preparations (Tanasilangkoon, 2018)KOA: hot herbal compress, Plai cream or oil, herbal knee poultice preparations, Derris scandens capsule (Subcharoen, 2001; Tanasilangkoon and Sitthitanyakij, 2016)
Hedgehog signaling pathway inhibitors: an updated patent review (2015–present)
Published in Expert Opinion on Therapeutic Patents, 2020
Deborah Quaglio, Paola Infante, Lucia Di Marcotullio, Bruno Botta, Mattia Mori
Previous studies developed by researchers at Sapienza University of Rome, University of Siena, and the Italian Institute of Technology in Italy identified compound 85 (GlaB, Figure 15), an isoflavone naturally found in the seeds of Derris glabrescens (Leguminosae), as a potent Hh inhibitor acting at a downstream level by directly blocking GLI1 transcription factor [38]. Several studies revealed the capability of 85 to inhibit the growth of Hh-dependent brain tumor cells (e.g. DAOY and GL261) in vitro and in vivo as well as the self-renewal ability and clonogenicity of tumor-derived stem cells [44,83–85]. In a recent study, the same researchers exploited the high versatility of the isoflavone scaffold toward Hh inhibition by demonstrating that the insertion of a bulky substituent in meta or in para position of the isoflavone’s ring B enhanced the specific affinity of these compounds for GLI or SMO, respectively, and that their simultaneous administration provided synergistic Hh inhibition [42,86]. Based on these findings, a third generation of isoflavones (i.e. compounds 86 and 87, Figure 15) was designed and synthesized revealing potent Hh multitarget inhibition targeting both SMO and GLI1 [87]. In particular, compound 87 was demonstrated to strongly inhibit Hh-dependent tumor growth in human and murine MB cells at sub-micromolar concentration, inducing reduction in GLI1 protein levels. Intratumoral administration of 87 (5 mg/Kg) reduced Hh-driven tumor growth in an in vivo allograft model of MB by suppressing cell proliferation and promoting apoptosis.
Agaricus blazei extract abrogates rotenone-induced dopamine depletion and motor deficits by its anti-oxidative and anti-inflammatory properties in Parkinsonic mice
Published in Nutritional Neuroscience, 2018
Veerappan Venkatesh Gobi, Srinivasagam Rajasankar, Muthu Ramkumar, Chinnasamy Dhanalakshmi, Thamilarasan Manivasagam, Arokiasamy Justin Thenmozhi, Musthafa Mohamed Essa, Ranganathan Chidambaram, Ameer Kalandar
Parkinson’s disease (PD) is the second most chronic and progressive neurodegenerative disease, affecting 1% of the elderly (∼60 years) globally.1 Major pathological changes in PD include loss of dopaminergic neurons in the substantia nigra (SN) and presence of Lewy bodies. The PD patients exhibit motor dysfunction including tremors at rest, bradykinesia, rigidity, and postural instability. Several animal models have been developed to understand the pathology and therapeutic implications, which can be broadly categorized into: (i) toxin models employed 1-methyl-4-phenyl-1,2,4,5-tetrahydropyridine (MPTP), 6-hydroxydopamine and rotenone, (ii) inflammatory models induced by lipopolysaccharide, (iii) pharmacological models stimulated by reserpine and haloperidol, and (iv) genetic models employed by genetic modifications of α-synuclein, LRRK2, parkin, PINK1, and DJ-1.2 Rotenone is a naturally occurring toxin that structurally belongs to the flavonoid family of compounds. It is a potent herbicide and derived from roots/stems of several tropical and subtropical plants including the family of Leguminosae, especially Loncho carpusor Derris.3,4 Due to its high lipophilic nature, it can readily cross the blood–brain barrier, accumulates in sub-cellular organelles such as mitochondria of brain, interferes with the electron transport chain, and blocks the electron transfer from Fe–S centers in complex I to ubiquinone, thus inhibiting the oxidation of NADH-linked substrates.5,6 This will result in the formation of reactive species, which is an indication of the oxidative stress and will lead to a consumption and depletion of endogenous antioxidants.7
A significant mechanism of molecular recognition between bioflavonoids and P-glycoprotein leading to herb-drug interactions
Published in Toxicology Mechanisms and Methods, 2018
Pathomwat Wongrattanakamon, Piyarat Nimmanpipug, Busaban Sirithunyalug, Sunee Chansakaow, Supat Jiranusornkul
Plant-derived compounds including several subclasses of flavonoids like flavans, flavanones, prenylated flavonoids, flavones, and isoflavones are discovered in many Thai medicinal plants, for example, Albizia myriophylla and Derris scandens, which are utilized for remedy of oral diseases and cancers in Thai traditional medicine, respectively (Joycharat et al. 2016; Sangmalee et al. 2016). Molecular modeling studies have been utilizing to estimate pharmacokinetics along with potential risks of herb-drug interactions of phytochemicals including the plant-derived flavonoids. These studies are more rapid, proficient and high-throughput in analyzing the interactions with deducted labor and animal handling when compared with conventional cell-based and in vivo assays (Qiu et al. 2015). This study was combined the molecular docking, pharmacophore modeling, and MD simulation of the P-gp inhibitors that bound to the NBD2. It was suggested in previous studies that NBD2 could be the binding site for the flavonoid compounds. Some flavonoids, such as aurones, chalcones, flavones, flavonols, and isoflavones were shown to have binding affinity toward the NBD2 of P-gp (Di Pietro et al. 2002; Wang et al. 2005; Václavíková et al. 2006). The combined computational study of Gadhe et al. (2013) toward the binding of desmosdumotin to the NBD2 supports our results. Their study combines the docking and MD simulation. The information of detailed atomic interactions of desmosdumotin-NBD2 was obtained utilizing MD simulation. The study showed that the van der Waals and electrostatic interactions between desmosdumotin and the NBD2 could be of significant importance for the P-gp inhibition mechanism. The backbone RMSD values of the NBD2 and desmosdumotin pointed out that both were stable after the equilibration stage. Another study using homology P-gp modeling was performed by Badhan and Penny (2006). Interactions between the NBD2 and flavonoids were investigated utilizing molecular docking approach. The study showed that the hydrogen bonding interactions and hydrophobic stacking interactions between flavonoids and the NBD2 could be major determinants for the inhibition mechanism. These flavonoids were also reported their in vitro NBD2 binding affinities. These flavonoids occupied with the same binding site of ATP in the NBD2 suggesting that these compounds acted as an ATP competitive inhibitor and the developed structure-based modeling is useful to screen a potential inhibitory activity of flavonoids that can be applied in anti-cancer drug development and herb–drug interaction analysis via the mechanism of P-gp inhibition.