Current Drug Metabolism - Volume 19, Issue 5, 2018

Introduction: Traditional Persian Medicine (TPM) was the prevailing practice of medicine in the Eurasia region up through the 18th century, a practice of medicine stemming back to Hippocrates and to the 5000 year old civilization of the region. It is a school of medicine which touches on many a delicate points which may seem unimaginable within the realm of modern allopathic medicine. This practice of ancient medicine besides shedding light on various possible theoretical modern day disorders serves as a vast resource for therapeutics. In this paper, we present study of the manuscripts of this ancient medical practice in search of symptom presentations coinciding with presentation of multiple sclerosis (MS). Material & Method: This paper represents a comprehensive search through TPM texts and manuscripts with the intention to seek possible clues on MS from potentially valuable age-old resources. We predominantly focused our search on the works of five eminent physicians of Medieval Persia: Avicenna (980-1037 AD), Haly Abbas (949-982 AD), Rhazes (865-925 AD), Averroes (1126-1198 AD) and Jorjani (1042-1137 AD). Results: In this paper, the authors attempt a theory and conclude with high probability that a conjunction of a series of signs, symptoms found in TPM texts under the terms khadar, isterkha and falej form the symptoms and the disease pattern of modern day MS. This theory draws upon existent similarities in terms of disease pathology, disease patterns and predisposing factors seen between MS and the related morbidities within Persian Medicine. Conclusion: We recommend further examinations of such potentially valuable long-standing resources, examining the diagnoses and treatments as set forth by Persian Medicine through international collaboration within the global scientific community.

Background: Among various neurological disorders, multiple sclerosis (MS) is an expanding global immune- related inflammatory disease with complex etiologies. There is increasing demand for the use and administration of natural medicaments for this disorder. Traditional Persian Medicine (TPM) is a school of medicine and a medicinal plants-based resource for clinical studies put forward by Persian scholars. Objective: This paper aims to gather and study the effectiveness of all medicinal plants from the most popular Persian pharmacopeias. Five main Persian pharmacopeias from the 9th to the 18th century A.D. have been studied to identify the remedial plants for this disorder. Moreover, PubMed, and Scopus databases have been checked to derive relevant activities for these plants. Khaddar (numbness), Esterkha (Palsy) and Falej (quadriplegia) are traditional definitions; these are clinically close to what is known as MS in today's medicine. Conclusion: In all, 118 medicinal plants, related to 65 families, have been authenticated out of 157 chosen medicaments. Apiaceae is the most frequent family (13 reports). Fruits and roots of plants have been the most reported botanical parts (34 and 32 items). The employed routes of administration are topical, oral, or a combination of the two (27, 57, and 34 sequentially). Fifteen medicines have been reported for Khaddar, Esterkha, and Falej simultaneously. Antioxidant activities, immunomodulatory, and anti-inflammatory properties of medicines are known as some main mechanisms to manage MS. These functions are possessed by 81%, 36%, and 48% of the studied plants, respectively. Hence, conducting adducible clinical trials and highly approved experimental tests on animals may lead to novel drugs with lesser undesirable and much more therapeutic effects on controlling MS.

Background: Cerebrovascular disease caused by atherosclerosis affecting cerebral and pre-cerebral arteries is one of the leading causes of morbidity and mortality in high-income countries. Medications of botanical origin are often characterized by good tolerability and are suitable for long-term treatment. Therefore, phytotherapy provides an interesting possibility for developing new therapies for the prevention of atherosclerosis and its complications that could be used at preclinical stages of the disease. Objective: We reviewed the current literature studying the potential of various plant-based medications for prevention and treatment of early cerebral ischemia induced by atherosclerosis. Methods: Literature search was performed in PubMed, Scopus, and Cochrane library to find trials on phytotherapy in cerebrovascular prevention and treatment. Results: The present review covers the recent data on the prevention of cerebral ischemia with natural preparations and demonstrates the effect of anti-atherosclerotic therapy on the dynamics of minor neurological changes. Conclusion: Phytotherapy appears to have a great potential for cerebrovascular disease prevention, combining good safety profiles with pleiotropic effects on different mechanisms atherosclerosis-related cerebral ischemia development.

Background: Dementia is a chronic neurodegenerative disease causing progressive and gradual impairment of different brain's cognitive functions. The prevalence of dementia is about 3 to 7% in different parts of the world. Objective: The aim of this study was to determine the etiologies of dementia according to the Traditional Persian Medicine scientists' viewpoint and introduce their recommended herbal remedies for this disease. Method: The authors explored six main Traditional Persian Medicine textbooks for the disease of dementia, its etiologies and related recommended herbal treatments. Two main keywords of “Lisarghes” and “Nesyan” were searched for this purpose. Medical databases, including PubMed, Scopus, Google Scholar, and Science Direct were searched for related articles published between 1966 and 2016 to review the pharmacological components and active ingredients of suggested herbal medicines. Results: According to the Traditional Persian Medicine, dementia is resulted from brain dystemperament, a condition caused by cold and moist or cold and dry tempers. To treat this disease, Traditional Persian scientists recommended various herbal remedies. Current studies have demonstrated that some of these medicinal plants have beneficial effects for the aforementioned disease, including acetyl cholinesterase inhibitory function, neuroprotective effects, and memory enhancing role. Conclusion: The Traditional Persian Medicine literature suggested different herbal remedies for treating dementia. Modern studies support the usefulness of some of these medicines. However, the effect of a large number of these remedies has remained unexamined, a matter which needs to be investigated in future researches.

Background: In recent decades, complementary and alternative medicine (CAM) has become very popular in the treatment of several chronic diseases. Natural products as one of the CAM modalities offer potential opportunities to discover lead compounds for novel drug development. The use of CAM or natural products in the prevention of neurodegenerative diseases is comparatively a newer area. Method: A structured online literature search for peer-reviewed research articles was conducted on the PubMed, Europe PMC, Medline and Google Scholar portals, using phrases: natural products for neurologic disorders, phytomedicine for neurodegenerative diseases, natural therapeutics for neurological symptopms etc. Results: The retrieved data showed the natural therapeutics with anti-oxidative and anti-inflammatory salutations evidently plays a crucial role in protecting neurons. Of these, the most promising are caffeine, trigonelline, shogaol, curcumin, resveratrol, baicalein, wogonin, ginsenosides, tanshinones, withanolides, picrosides, parthenolide, cannabinoids, Devil's claw and white willow bark, including Chinese formulations Renshen Shouwu and Shengmai San. Though several herbs and their active ingredients have been studied in laboratory and clinical settings, only a few have been investigated for their molecular mechanisms of action. Notably, despite the promising and safe therapeutic benefits of CAM/herbal medicines, there exists a possible risk when combining them with prescription drugs. As a result, many drugs have shown changes in blood pressure, hepatotoxicity, seizures etc. when combined with certain herbs. Conclusion: Certainly, extensive work is needed to make sure that patients should take a regimen of protective and restorative therapy under an experienced healthcare professional. This article updates on the current knowledge of promising natural products used in neurological disorders.

Background: Neurodegenerative diseases are a progressive loss of structure and/or function of neurons. Weak therapeutic response and progressive nature of the diseases, as well as a wide range of side effects caused by conventional therapeutic approaches make patients seek for complementary and alternative medicine. Objective: The aim of the present paper is to discuss the neuropharmacological basis of medicinal plants and their principle phytochemicals which have been used in traditional Persian medicine for different types of neurodegenerative diseases. Results: Medicinal plants introduced in traditional Persian medicine perform beneficial effects in neurodegenerative diseases via various cellular and molecular mechanisms including suppression of apoptosis mediated by an increase in the expression of anti-apoptotic agents (e.g. Bcl-2) as well as a decrease in the expression and activity of proapoptotic proteins (e.g. Bax, caspase 3 and 9). Alleviating inflammatory responses and suppressing the expression and function of pro-inflammatory cytokines like Tumor necrosis factor α and interleukins, as well as improvement in antioxidative performance mediated by superoxide dismutase and catalase, are among other neuroprotective mechanisms of traditional medicinal plants. Modulation of transcription, transduction, intracellular signaling pathways including ERK, p38, and MAPK, with upstream regulatory activity on inflammatory cascades, apoptosis and oxidative stress associated pathways, play an essential role in the preventive and therapeutic potential of the plants in neurodegenerative diseases. Conclusion: Medicinal plants used in traditional Persian medicine along with their related phytochemicals by affecting various neuropharmacological pathways can be considered as future drugs or adjuvant therapies with conventional pharmacotherapeutics; though, further clinical studies are necessary for the confirmation of their safety and efficacy.

Background: Herbal drugs are being used worldwide in a variety of debilitating neurological and psychiatric disorders such as cerebrovascular accident, Alzheimer's disease, Parkinson's disease and schizophrenia. However, unlike drugs of modern medicine, herbal drugs are complex products containing multiple pharmacologically active constituents. The nature and relative amounts of these constituents vary due to diverse factors such as but not limited to source of the plant(s), local environmental conditions, parts of the plant used, storage, method of extract preparation, accidental contamination or intentional adulteration. Further, they are handled by the human body like modern drugs and subjected to the processes of absorption, distribution, metabolism and excretion. In each of these processes, they can potentially interact with modern drugs due to sharing of similar transport proteins, metabolizing cytochrome P450 (CYP450) enzymes and uptake / efflux pumps. Moreover, herbal drugs can also inhibit or induce CYP450 enzymes or inactivate transporters leading to Herb-Drug interactions (HDIs). Method: In this narrative review, we have analyzed the clinically reported as well as potential HDIs between 10 common herbal drugs viz. Ginkgo, Ginseng, St. John's Wort, Grapefruit, Black and Long Pepper, Curcumin, Brahmi, Kava, Garlic and Valerian and modern medicines used in neurological and psychiatric disorders with their proven or postulated underlying mechanism(s). Results: Though a number of potential pharmacokinetic and/or pharmacodynamic HDIs have been examined, clinically significant alteration of response to modern medicines and/or serious adverse effects are apparently scarce except for Grapefruit and St. John's Wort. Conclusion: Physicians and patients should exercise caution when using herbal drugs and modern medicines concomitantly so that the recognized serious HDIs can be avoided.

Background: This review focuses on the efficacy and safety of herbal medicines in the management of autism spectrum disorder (ASD) in humans and animals. Method: PubMed, Scopus, Google Scholar, Web of Science, and Science Direct databases were searched up to October 30, 2016. The key terms used were “ASD”, “Asperger”, “autism”, “healing plants”, “herbal medicine”, and “medicinal plants”. In each database, the searches consisted of each of three key terms describing the disorder and subtypes plus each of the terms describing the therapy. All human and animal studies on the effects of herbs with the key outcome of change in autism symptoms were included. In vitro studies were excluded. Results: From the publications perused in the initial database, 3157 results were identified, reviewed and a total of 23 studies were included. Preclinical studies using critically validated models were conducted, with some promising preliminary results. Data availability on controlled clinical studies is currently very limited. The use of different methodologies and the very small number of patients raise doubts about the effects of these preparations. Conclusion: Available data do not yet allow us to suggest the effectiveness of herbal medicines as an add-on in the treatment of ASD symptoms.

Background: The etiopathogenetic mechanisms of peripheral neuropathies include genetic, traumatic, toxic, metabolic, infectious, nutritional, inflammatory and paraneoplastic causes. Their treatment should primarily address their contributing causes. However, symptomatic therapy is also key in these conditions, particularly in pain relief. Method: Relevant studies were identified using the PubMed electronic database in January 2017. After a preliminary search, we focused on the single compounds for which randomized controlled trials versus placebo or comparing high and low doses were performed. Studies in which a combination of different compounds was tested were not considered, with the exception of complex B multivitamins. Results: Several nutraceuticals have been used in the treatment of peripheral neuropathies and seem promising, due to assumed neurotrophic action, low toxicity and favorable metabolic profile. We performed a review of the literature to evaluate safety and effectiveness of nutraceutical compounds in peripheral neuropathies, focusing on the single agents for which randomized controlled trials versus placebo were performed. Vitamin B complex, alpha lipoic acid, L-acetylcarnitine, vitamin E and Coenzyme Q proved effective to different extents in neuropathic pain in polyneuropathies. They all proved less consistently effective on other neuropathic symptoms, neuropathic signs and neurophysiological parameters. All the considered compounds were tolerable even for long periods, however alpha lipoic acid at doses equal or larger than 1200 mg/die was associated with nausea and vomiting in a large number of patients. Conclusion: The findings of this review confirm a possible role for some adequately dosed nutraceuticals in the management of peripheral neuropathy.

Background: The plant Nardostachys jatamansi from Valerianaceae family is a well known antidepressant plant and has historically been used in traditional medicine. As N. jatamansi contains many different compounds, to identify its mechanisms of action, we need a network-based study. Network-based studies are becoming an increasingly important tool in understanding the mechanisms of actions of drugs. Systems pharmacology (SP) and bioinformatics are two emerging tools that use computation to develop an understanding of drug actions in molecular and cellular levels. SP can provide mechanistic understanding of protein-protein (drug-target) interaction involved in a common biological pathway. The present study was undertaken to identify unknown targets and mechanisms of antidepressant activity of N. jatamansi according to a systems pharmacology approach. Method: First of all a list of all the targets (receptors and metabolites) involved in depression process were provided based on KEGG database. The 3D structures of protein targets were collected as PDB files and their active sites coordinates were found. In the next step the structures of known compounds of N. jatamansi were collected. For identifying the protein-lagand interactions, a docking process was run in AutoDock and an output was received. To complete our study, the similarity between antidepressant conventional drugs and N. jatamansi compounds was analyzed. A SP map figured by Cytoscape Software, shows the relations between herbal compounds, molecular targets and depression. Results: According to the docking results, we can suggest several important targets that we have no drugs for, or several natural compounds that play an important role in depression process. According to the similarity results we can suggest several molecules for extraction or synthesis that need more researches for their therapeutic effects. This study shows that how N. jatamansi can effect on depression by multiple molecular targeting with multiple compounds.