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Acorus Calamus Linn.) in Neurological and Metabolic Disorders: Evidence from Ethnopharmacology, Phytochemistry, Pharmacology and Clinical Study

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Acorus Calamus Linn.) in Neurological and Metabolic Disorders: Evidence from Ethnopharmacology, Phytochemistry, Pharmacology and Clinical Study Journal of Clinical Medicine Review Role of Vacha (Acorus calamus Linn.) in Neurological and Metabolic Disorders: Evidence from Ethnopharmacology, Phytochemistry, Pharmacology and Clinical Study Vineet Sharma 1 , Rohit Sharma 1,* , DevNath Singh Gautam 1 , Kamil Kuca 2,* , Eugenie Nepovimova 2 and Natália Martins 3,4,* 1 Department of Rasa Shastra and Bhaishajya Kalpana, Faculty of Ayurveda, Institute of Medical Sciences, BHU, Varanasi, Uttar Pradesh 221005, India; [email protected] (V.S.); [email protected] (D.S.G.) 2 Department of Chemistry, Faculty of Science, University of Hradec Králové, Rokitanskeho 62, 50003 Hradec Králové, Czech Republic; [email protected] 3 Faculty of Medicine, University of Porto, Alameda Prof. Hernani Monteiro, 4200-319 Porto, Portugal 4 Institute for research and Innovation in Heath (i3S), University of Porto, Rua Alfredo Allen, 4200-135 Porto, Portugal * Correspondence: [email protected] or [email protected] (R.S.); [email protected] (K.K.); [email protected] (N.M.) Received: 23 March 2020; Accepted: 14 April 2020; Published: 19 April 2020 Abstract: Vacha (Acorus calamus Linn. (Acoraceae)) is a traditional Indian medicinal herb, which is practiced to treat a wide range of health ailments, including neurological, gastrointestinal, respiratory, metabolic, kidney, and liver disorders. The purpose of this paper is to provide a comprehensive up-to-date report on its ethnomedicinal use, phytochemistry, and pharmacotherapeutic potential, while identifying potential areas for further research. To date, 145 constituents have been isolated from this herb and identified, including phenylpropanoids, sesquiterpenoids, and monoterpenes. Compelling evidence is suggestive of the biopotential of its various extracts and active constituents in several metabolic and neurological disorders, such as anticonvulsant, antidepressant, antihypertensive, anti-inflammatory, immunomodulatory, neuroprotective, cardioprotective, and anti-obesity effects. The present extensive literature survey is expected to provide insights into the involvement of several signaling pathways and oxidative mechanisms that can mitigate oxidative stress, and other indirect mechanisms modulated by active biomolecules of A. calamus to improve neurological and metabolic disorders. Keywords: Acorus calamus; ethnomedicinal; phytochemistry; toxicity; pharmacological action; clinical trial; neuroprotective; neurological; metabolic application 1. Introduction Globally, an estimated 450 million people are suffering from mental disorders and about 425 million are known diabetics [1,2]. In 2016, 650 million adults were obese and about 23.6 million people were estimated to die of cardiovascular diseases (CVDs) by the year 2030 [3]. Metabolic disorders are characterized by hypertension, hyperglycemia, abdominal obesity, and hyperlipidemia, which may worsen the neurological disease risk. Improper diet (high calorie intake), lifestyle (e.g., smoking, chronic alcohol consumption, sedentary habits), and/or low level of nitrosamines (through processed food, tobacco smoke, and nitrate-containing fertilizers) affect the liver and can further lead to fatty liver disease [4,5]. In this condition, fatty changes may be due to increased production or decreased use of fatty J. Clin. Med. 2020, 9, 1176; doi:10.3390/jcm9041176 www.mdpi.com/journal/jcm J. Clin. Med. 2020, 9, 1176 2 of 46 J. Clin. Med. 2020, 9, 1176 2 of 45 liver disease [4,5]. In this condition, fatty changes may be due to increased production or decreased use of fatty acids, which may lead to inflammatory injury of hepatocytes, where inflammatory acids,mediators, which such may as lead cytokines to inflammatory and interleukins, injury ofare hepatocytes, released, which, where along inflammatory with lower mediators, adipokines, such may as cytokineseventually and develop interleukins, hepatic areinsulin released, resistance which, [6]. along The same with lowerpathology adipokines, also medi mayates eventually diabetes, developobesity, hepaticand peripheral insulin resistance insulin resistance. [6]. The same Insulin pathology resistance also also mediates promotes diabetes, the release obesity, of and ceramides peripheral and insulin other resistance.toxic lipids Insulin which resistance enter the also circulation promotes and the releasecross the of ceramides blood–brain and barrier other toxic leading lipids to which brain enter insulin the circulationresistance, andinflammatory cross the blood–brain changes, and barrier further leading progression to brain insulinto neurodegeneration resistance, inflammatory and neurological changes, anddisorders further (Figure progression 1) [7]. to neurodegeneration and neurological disorders (Figure1) [7]. Figure 1. Pathophysiology of insulin resistance, metabolic malfunction, and progression to a neurological disorder.Figure 1. TNF, Pathophysiology tumor necrosis of factor; insulin IL, interleukin. resistance, metabolic malfunction, and progression to a neurological disorder. TNF, tumor necrosis factor; IL, interleukin. Acorus calamus Linn. (Acoraceae), also known as Vacha in Sanskrit, is a mid-term, perennial, fragrantAcorus herb calamus which Linn. is practiced (Acoraceae), in the also Ayurvedic known (Indianas Vacha traditional) in Sanskrit, and is thea mid-term, Chinese systemperennial, of medicine.fragrant herb The which plant’s is rhizomes practiced are in brown the Ayurvedi in color,ctwisted, (Indian cylindrical,traditional) curved,and the and Chinese shortly system nodded. of Themedicine. leaves The are radiantplant’s green,rhizomes with are a sword-likebrown in color, structure, twisted, which cylindrical, is thicker curved, in the middle and shortly and has nodded. curvy marginsThe leaves (Figure are radiant2)[ 8]. green, Several with reports a sword-like ascertained structure, a wide which range ofis thicker biological in the activities middle involving and has itscurvy myriad margins of active (Figure phytoconstituents. 2) [8]. Several reports In this sense,ascertained the intent a wide of this range review of biological is to assemble activities and summarizeinvolving its the myriad geographical of active distribution, phytoconstituents. ethnopharmacology, In this sense, the phytochemistry, intent of this review mechanism is to assemble of action ofandA. summarize calamus along the withgeographical preclinical distribution, and clinical et claimshnopharmacology, that are relevant phytochemistry, to manage neurological mechanism and of metabolicaction of A. disorders. calamus along To the with best preclinical of our knowledge, and clinical so far,claims none that of theare publishedrelevant to reviews manage has neurological described alland the metabolic characteristics disorders. of this To medicinal the best plantof our [ 9knowle–11]. Thedge, present so far, report none isof expected the published to produce reviews a better has understandingdescribed all the of thecharacteristics characteristics, of bioactivities,this medicinal and plant mechanistic [9–11]. The aspects present of this report plant andis expected to provide to newproduce leads a forbetter future understanding research. of the characteristics, bioactivities, and mechanistic aspects of this plant and to provide new leads for future research. J. Clin. Med. 2020, 9, 1176 3 of 46 J. Clin. Med. 2020, 9, 1176 3 of 45 J. Clin. Med. 2020, 9, 1176 3 of 46 (A) (B) (C) Figure 2. Photographs(A) of Acorus calamus: (A) Natural(B) habitat; (B) Fresh rhizome;(C) (C) Dried rhizome. Figure 2. PhotographsFigure 2. Photographs of Acorus of Acorus calamus calamus:(:A (A)) Natural Natural habitat; habitat; (B) (FreshB) Fresh rhizome; rhizome; (C) Dried (C rhizome) Dried. rhizome. 2. Methodology 2. Methodology2. Methodology The literatureThe literature available available in thein the Ayurvedic Ayurvedic classicalclassical texts, texts, technical technical reports, reports, online scientific online scientific recordsThe such literaturerecords as SciFinder,such available as SciFinder, Google in theGoogle AyurvedicScholar, Scholar, MEDL MEDL classicalINE,INE, EMBASE, texts, EMBASE, technical Scopus Scopus directory reports, directory were online explored werescientific forexplored records for suchethnomedicinal as SciFinder,ethnomedicinal uses, Google geographical uses, Scholar, geographical MEDLINE, distribution, distribution, EMBASE, phytochemistry, Scopus directory pharmacology, pharmacology, were explored and biomedicine and for biomedicine ethnomedicinal by by applying the following keywords: “Acorus calamus”, “Vacha”, “Medhya”, “neuroprotective”, uses,applying geographical the following distribution, keywords: phytochemistry, “Acorus calamus pharmacology,”, “Vacha”, and “Medhya”, biomedicine “neuroprotective”, by applying the “phytochemistry”, “obesity”, “oxidative stress”, “anticonvulsant”, “antidepressant”, following keywords: “Acorus calamus”, “Vacha”, “Medhya”, “neuroprotective”, “phytochemistry”, “phytochemistry”,“antihypertensive”, “obesity”, “anti-inflammatory”, “oxidative “immunomodulator”,stress”, “anticonvulsant”, “antioxidant”, “diabetes”,“antidepressant”, “obesity”,“antihypertensive”, “oxidative“mechanism stress”, of “anti-inflammatory”,action” “anticonvulsant”, with their correspondin “antidepressant”,“immunomodulator”,g medical subject “antihypertensive”, headings “antioxidant”, (MeSH) “anti-inflammatory”,terms using “diabetes”, “immunomodulator”,“mechanismconjunctions of action” OR/AND. “antioxidant”, with The their search “diabetes”, correspondin was focused
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