Devesh Tewari

Ethnopharmacological Approaches for Dementia Therapy and Significance of Natural Products and Herbal Drugs

Dementia is a clinical syndrome wherein gradual decline of mental and cognitive capabilities of an afflicted person takes place. Dementia is associated with various risk factors and conditions such as insufficient cerebral blood supply, toxin exposure, mitochondrial dysfunction, oxidative damage, and often coexisting with some neurodegenerative disorders such as Alzheimers disease (AD), Huntingtons disease (HD), and Parkinsons disease (PD). Although there are well-established (semi-)synthetic drugs currently used for the management of AD and AD-associated dementia, most of them have several adverse effects. Thus, traditional medicine provides various plant-derived lead molecules that may be useful for further medical research. Herein we review the worldwide use of ethnomedicinal plants in dementia treatment. We have explored a number of recognized databases by using keywords and phrases such as “dementia”, “Alzheimers,” “traditional medicine,” “ethnopharmacology,” “ethnobotany,” “herbs,” “medicinal plants” or other relevant terms, and summarized 90 medicinal plants that are traditionally used to treat dementia. Moreover, we highlight five medicinal plants or plant genera of prime importance and discuss the physiological effects, as well as the mechanism of action of their major bioactive compounds. Furthermore, the link between mitochondrial dysfunction and dementia is also discussed. We conclude that several drugs of plant origin may serve as promising therapeutics for the treatment of dementia, however, pivotal evidence for their therapeutic efficacy in advanced clinical studies is still lacking.

Targeting activator protein 1 signaling pathway by bioactive natural agents: Possible therapeutic strategy for cancer prevention and intervention

&NA; Activator protein 1 (AP‐1) is a key transcription factor in the control of several cellular processes responsible for cell survival proliferation and differentiation. Dysfunctional AP‐1 expression and activity are involved in several severe diseases, especially inflammatory disorders and cancer. Therefore, targeting AP‐1 has recently emerged as an attractive therapeutic strategy for cancer prevention and therapy. This review summarizes our current understanding of AP‐1 biology and function as well as explores and discusses several natural bioactive compounds modulating AP‐1‐associated signaling pathways for cancer prevention and intervention. Current limitations, challenges, and future directions of research are also critically discussed. Graphical abstract Figure. No caption available. HighlightsActivator protein 1 (AP‐1) has a key role in several cellular processes.Targeting AP‐1 signaling pathways is therapeutic for cancer and inflammation.Natural bioactive compounds are of much interest in cancer prevention and therapy.Natural bioactive compounds modulate AP‐1‐associated signaling pathways in cancer.

Ethnopharmacological Approaches for Therapy of Jaundice: Part II. Highly Used Plant Species from Acanthaceae, Euphorbiaceae, Asteraceae, Combretaceae, and Fabaceae Families

In many developing countries, jaundice is the common symptom of hepatic diseases which are a major cause of mortality. The use of natural product-based therapies is very popular for such hepatic disorders. A great number of medicinal plants have been utilized for this purpose and some facilitated the discovery of active compounds which helped the development of new synthetic drugs against jaundice. However, more epidemiological studies and clinical trials are required for the practical implementation of the plant pharmacotherapy of jaundice. The focus of this second part of our review is on several of the most prominent plants used against jaundice identified in the analysis performed in the first part of the review viz. Andrographis paniculata (Burm.f.) Nees, Silybum marianum (L.) Gaertn., Terminalia chebula Retz., Glycyrrhiza glabra L. and some species of genus Phyllanthus. Furthermore, we discuss their physiological effects, biologically active ingredients, and the potential mechanisms of action. Some of the most important active ingredients were silybin (also recommended by German commission), phyllanthin and andrographolide, whose action leads to bilirubin reduction and normalization of the levels of relevant serum enzymes indicative for the pathophysiological status of the liver.

Vascular smooth muscle cell proliferation as a therapeutic target. Part 1: molecular targets and pathways

Cardiovascular diseases are a major cause of human death worldwide. Excessive proliferation of vascular smooth muscle cells contributes to the etiology of such diseases, including atherosclerosis, restenosis, and pulmonary hypertension. The control of vascular cell proliferation is complex and encompasses interactions of many regulatory molecules and signaling pathways. Herein, we recapitulated the importance of signaling cascades relevant for the regulation of vascular cell proliferation. Detailed understanding of the mechanism underlying this process is essential for the identification of new lead compounds (e.g., natural products) for vascular therapies.

Ethnopharmacological Approaches for Therapy of Jaundice: Part I

Jaundice is a very common symptom especially in the developing countries. It is associated with several hepatic diseases which are still major causes of death. There are many different approaches to jaundice treatment and the growing number of ethnomedicinal studies shows the plant pharmacology as very promising direction. Many medicinal plants are used for the treatment of jaundice, however a comprehensive review on this subject has not been published. The use of medicinal plants in drug discovery is highly emphasized (based on their traditional and safe uses in different folk medicine systems from ancient times). Many sophisticated analytical techniques are emerging in the pharmaceutical field to validate and discover new biologically active chemical entities derived from plants. Here, we aim to classify and categorize medicinal plants relevant for the treatment of jaundice according to their origin, geographical location, and usage. Our search included various databases like Pubmed, ScienceDirect, Google Scholar. Keywords and phrases used for these searches included: “jaundice,” “hyperbilirubinemia,” “serum glutamate,” “bilirubin,” “Ayurveda.” The first part of the review focuses on the variety of medicinal plant used for the treatment of jaundice (a total of 207 medicinal plants). In the second part, possible mechanisms of action of biologically active secondary metabolites of plants from five families for jaundice treatment are discussed.

Phytochemical, Antioxidant and Antidepressant Evaluation of Ocimum basilicum, O. tenuiflorum, O. kilimandscharicum Grown in India

Abstract Ocimum is used in traditional medicine, as a culinary herb and a well known source of flavouring principle. The antioxidant activity in three Ocimum taxa viz. O. basilicum, O. tenuiflorum, O. kilimandscharicum was determined by DPPH free radical scavenging ability and reducing power assay. Total phenolic, flavonoids and tannins were determined using spectrophotometric technique and comparative antidepressant activity was evaluated using forced swim test. It was observed that all the three species of Ocimum found in western Himalayan region show significant antioxidant and antidepressant activities, however the O. kilimandscharicum was found to have highest antioxidant and antidepressant activity.

Phytochemical Screening and Antioxidant Profile of Syngonium podophyllum Schott Stems: A Fecund Phytopharmakon

Background : Oxidative stress has been shown to play an imperative role in copious disease pathology. Plants are acquaintances of mankind and mainstay for the treatment of oxidative stress linked disorders. Therefore, the objective of the existing study was to assess the phytochemical contents and antioxidant activity of crude methanol extract (CME), n-hexane (NHF), chloroform (CLF), ethyl acetate (EAF) and aqueous (AQF) fractions of Syngonium podophyllum ( S. podophyllum ) Schott stems. Methods : The S. podophyllum Schott stems extract and its fractions were subjected to phytochemical analysis to detect the presence of alkaloids, carbohydrates, saponins, tannins, resins, flavonoids and steroids. The antioxidant profile was determined by total antioxidant activity (TAA), reducing power activity (RPA) and DPPH (2,2-diphenyl-1-picrylhydrazyl) radical scavenging activity tests and correlated with the estimation of total flavonoid content (TFC). Results : In CME and its fractions of S. podophyllum Schott stems all of the tested phytoconstituents (alkaloids, tannins, resins, flavonoids and steroids) were detected at various concentration except carbohydrates and saponins. In TAA test, highest absorbance (2.18 nm) which is a measure of high antioxidant activity was reported in CME compared to remaining fractions. Likely in RPA test with respect to all fractions similar denouements were found for CME (3.29 nm). In case of DPPH scavenging test, the CME showed highest scavenging activity (77.89 %) having IC 50 of 41.02 ?g/ml (P < 0.05) compared to remaining fractions. The antioxidant activity is possibly due to the highest TFC (7.45 mg of GAE/g of dried extract) reported in CME compared to existing fractions. Conclusion : The aforementioned outcomes recommend that CME of S. podophyllum Schott stems can be a possible cradle of plant-derived natural antioxidant and can be used to avert diseases linked with free radicals.

Natural product-based nanomedicines for wound healing purposes: therapeutic targets and drug delivery systems

Wound healing process is an intricate sequence of well-orchestrated biochemical and cellular phenomena to restore the integrity of the skin and subcutaneous tissue. Several plant extracts and their phytoconstituents are known as a promising alternative for wound healing agents due to the presence of diverse active components, ease of access, and their limited side effects. The development of nanotechnological methods can help to improve the efficacy of different therapeutics as well as herbal-based products. Here, we present a review of the efficacy of the plant based-nanomaterials in the management of wounds and discuss the involved therapeutic targets. For this purpose, a profound search has been conducted on in vitro, in vivo, and/or clinical evidences evaluating the efficacy and pharmacological mechanisms of natural product-based nanostructures on different types of wounds. Different pharmacological targets are involved in the wound healing effects of herbal-based nanostructures, including suppressing the production of inflammatory cytokines and inflammatory transduction cascades, reducing oxidative factors and enhancing antioxidative enzymes, and promoting neovascularization and angiogenic pathways through increasing the expression of vascular endothelial growth factor, fibroblast growth factor, and platelet-derived growth factor. Moreover, nanostructure of plant extracts and their phytochemicals can enhance their bioavailability, control their release in the form of sustained delivery systems to the wound site, and enhance the permeability of these therapeutics to the underlying skin layers, which are all necessary for the healing process. Overall, various plant extracts and their natural compounds, used in nanoformulations, have demonstrated high activity in the management of wounds and thus can be assumed as future pharmaceutical drugs.

Targeting ERK signaling pathway by polyphenols as novel therapeutic strategy for neurodegeneration

Numerous chemicals, such as phenolic compounds are strong radical scavengers, capable of alleviating oxidative stress induced neurodegeneration. Dietary antioxidants, especially flavonoids, are being considered as a promising approach to prevent or slow the pathological development of neurological illness and aging. One of the major advantage of natural products is that of their anti-amyloid effects over synthetic counterpart, however a healthy diet provides these beneficial natural substances as nutraceuticals. The extracellular-signal-regulated kinase (ERK) is one of the main pharmacological target of natural phenolic compounds, participating in several therapeutic effects. Mounting evidence revealed that numerous bioflavonoids, obtained from a variety of dietary fruits or plants as well as medicinal herbal sources, exhibit protective or therapeutic functions versus development of neurodegenerative diseases mainly through modulation of different compartments of ERK signaling pathway. Currently, there is remarkable interest in the beneficial effects of natural flavonoids to improve neural performance and prevent the onset and development of major neurodegenerative diseases. Natural products originated from medicinal plants, in particular antioxidants, have gained a great deal of attention due to their safe and non-toxic natures. Here, we summarized the effect of natural bioflavonoids on ERK signaling pathway and their molecular mechanism.

An update on dietary consideration in inflammatory bowel disease: anthocyanins and more

ABSTRACT Introduction: Inflammatory bowel disease (IBD) is a chronic idiopathic inflammatory disorder. A wealth of data pointed out that various aspects of chronic inflammation may be affected by several specific dietary factors. This paper calls attention to anthocyanins enriched plant food and anthocyanin dietary supplements, whose role in the management of IBD and its associated oncogenesis deems crucial. Area covered: We updated the most relevant dietary anthocyanins with potential anti-colitis and preventive effect on inflammatory associated colorectal cancer based on the recent animal and human researches along with revealing the major cellular and molecular mechanisms of action. Mounting evidence reported that anthocyanins enriched plant foods perform their protective role on IBD and inflammatory-induced colorectal cancer via different cellular transduction signaling pathways, including inflammatory transcription factors, SAPK/JNK and p38 MAPK cascade, JAK/STAT signaling, NF-kB/pERK/MAPK, Wnt signaling pathway, Nrf2 cytoprotective pathway as well as AMPK pathway and autophagy. Expert commentary: Combination of anthocyanins enriched dietary supplements with existing medications can provide new therapeutic options for IBD patients. Further, well-designed randomized control trials (RCTs) are essential to evaluate the role of anthocyanins enriched medicinal foods as well as isolated anthocyanin components as promising preventive and therapeutic dietary agents for IBD and its associated oncogenesis.