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Submitted: 04 June 2020 | Approved: 17 June 2020 | Published: 18 June 2020

How to cite this article: Arya V, Parmar RK. A Perspective on therapeutic potential of weeds. J Plant Sci Phytopathol. 2020; 4: 042-054.

DOI: 10.29328/journal.jpsp.1001050

ORCiD ID: orcid.org/0000-0002-6808-1754

Copyright License: © 2020 Arya V, et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Keywords: New Zealand; Phytoconstituents; Phytoremediation; Weeds

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A Perspective on therapeutic potential of weeds

Vikrant Arya1* and Ranjeet Kaur Parmar2

1Assistant Professor, Government College of Pharmacy, Rohru, Shimla, Himachal Pradesh, India
2Home Maker, Pranav Kuteer, Jayanti Vihar, Kangra, Himachal Pradesh, India

*Address for Correspondence: Vikrant Arya, Assistant Professor, Government College of Pharmacy, Rohru, Shimla, Himachal Pradesh-171207, India, Tel: 8628998699; Email: arya.vikrant30@gmail.com

Abstract
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Title Abstract Introduction Conclusion
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Nature gives us a diverse plethora of floral wealth. Weeds have been recognized as invasive plant by most of scholars in today’s world with extraordinary travel history. They are considered to be noxious for adjoining plant species and also as economic hazard. Weeds inhabited in almost entire biomes and have capability to survive in harsh conditions of environment thereby become source of inspiration for finding novel phytoconstituents. Weeds play a significant role in absorbing harmful micro pollutants that are affecting ecosystem adversely. There are so many examples like canna lily, bladder wort, coltsfoot, giant buttercup etc. playing crucial part in sustaining environment. Different isolation and characterization approaches like high pressure liquid chromatography, gas chromatography, ion exchange chromatography, nuclear magnetic resonance, mass spectroscopy etc. have also been fetched for obtaining novel constituents from weeds. The main aim of this review is to analyze the therapeutic potential of weeds established in New Zealand and effort to unfold the wide scope of its applications in biological sciences. Upon exploration of various authorized databases available it has been found that weeds not only are the reservoir of complex phytoconstituents exhibiting diverse array of pharmacological activities but also provide potential role in environment phytoremediation. Phytoconstituents reported in weeds have immense potential as a drug targets for different pathological conditions. This review focuses on the literature of therapeutic potential of weeds established in New Zealand and tried to unveil the hidden side of these unwanted plants called weeds.

Introduction
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Title Abstract Introduction Conclusion
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‘Horse Hoeing Husbandry’ named famous writing by Jethro Tull (1731) mentioned first time the word ‘weed’ [1]. Weeds may be considered as plants whose abundance must be over or above a specific level can cause major environmental concern [2]. Aldrich and Kremer, 1997 defined weed as a part of dynamic ecosystem [3]. Plant originated in natural environment and, in response to imposed or natural environments, evolved, and continues to do so, as an interfering associate with crops and activities. Weeds may interfere with the utilization of land and water resources thereby adversely affect human welfare [4]. According to Ancient Indian Literature earth is blessed with diverse flora and every existing plant has their own importance. Some plants are considered unwanted but they may have beneficial properties. Scholars are trying hard to explore the hidden potential of such unwanted plants [5]. Weeds have interactions with other organisms and some of these interactions can have direct effects on the functioning of agro-ecosystem [6]. They serve as an indirect resource for predatory species [7] and it could alternative food sources for organisms that play prominent role in insect control [8]. Weeds have a unique travel history. Clinton L. Evans in his book ‘The war on weeds in the prairie west- An Environmental History’ mentioned about travelling of weeds in ships, railways, automobiles from one country to another as food contaminants, animal feed, farm implements etc. during trade [9]. Weeds are firmly distributed and established all over New Zealand. Authors Ian Popay, Paul Champion and Trevor James in their book ‘An Illustrated Guide to Common Weeds of New Zealand’ (edition 3rd) published by New Zealand Plant Protection Society in 2010 mentioned the detailed description of around 380 weed species established in New Zealand [10]. Different scientific databases/ information resources (governmental, private, universities, initiatives, organizations etc.) of New Zealand extensively explored over a year as mentioned in table 1 to obtain data pertaining to weeds prevalent within geographical boundaries of New Zealand. After obtaining desired data of different weeds, a literature search was performed using the keyword ‘‘Name of weed (e.g. Aristea ecklonii) Pharmacology’’, ‘‘New Zealand plants’’, ‘‘weed pharmacology’’, ‘‘therapeutic weed’’ individually or all together in different scientific databases of Scopus, Web of Science and Pubmed to obtain therapeutic potential of weeds. Celastrus orbiculatus (Climbing spindle berry) [59], Robinia pseudoacacia (False acacia) [63], Daphne laureola (Green daphne laurel) [66], Glaucium flavum (Horned poppy) [70], Senecio latifolius (Pink ragwort) [80], Solanum nigrum (Black night shade) [86] have potent anticancer activities. Aristea ecklonii (Aristea) [50], Alocasia brisbanensis (Elephant ear) [62], Lycopus europaeus (Gypsywort) [68] exhibited antimicrobial activities. Pseudosasa japonica (Arrow bamboo) [51], Sambucus nigra (Elder) [61], Equisetum arvense (Field horsetail) [65] showed antioxidant effect. Hedera helix (Ivy) [72], Persicaria hydropiper (Mexican water lily) [75], Persicaria hydropiper (Water pepper) [106] showed anti-inflammatory properties. Weeds like Zantedeschia aethiopica (Arum lily) [112], Utricularia gibba (Bladderwort) [113], Canna indica (Canna lilly) [114], Tussilago farfara (Coltsfoot) [115], Egeria densa (Eregia) [116], Ranunculus acris (Giant buttercup) [117], Cytisus scoparius (Broom) [118], Poa annua (Annual poa) have prominent role in biomonitoring of heavy metals in multiple environments [119].

Table 1: Description of scientific databases/ information resources of New Zealand for weed identification.
PRIMARY INFORMATION SOURCES SECONDARY INFORMATION SOURCES*
Source name Source type Authors Web address Database/information resource
An encyclopedia of New Zealand, 1966 Encyclopedia McLintock AH http://www.agpest.co.nz AgPest: It is an open access tool available for New Zealand farmers and agricultural professionals containing information about weeds, pest identification, their biology, impact and management
Common weeds in New Zealand, 1976 Book Parham BEV,
Healy AJ 		http://www.agriculture.vic.gov.au Agriculture victoria : Platform is used to promote agriculture industry in New Zealand and encompass information related to weeds and plant protection
Weeds in New Zealand protected natural areas: A review for the Department of Conservation, 1990 Book Williams PA, Timmins SM http://www.cropscience.bayer.co.nz Bayer crop science: It is one of the major information providers of crop protection products
Problem weeds on New Zealand islands, 1997 Book
ISBN 0-478-01885-1 		Atkinson IAE http://www.gw.govt.nz Greater wellington university: It is a local government body in New Zealand represented by regional and territorial councils
New Zealand Journal of Agricultural Research, 50(2), 2007 Journal Bourdot GW, Fowler SV,
Edwards GR, Kriticos DJ,
Kean JM,
Rahman A,
Parsons AJ 		http://www.learnz.org.nzs Learnz: It is a initiative of free virtual field trips that help students to acquire inaccessible knowledge regarding various agricultural activities
 Consolidated list of environmental weeds in New Zealand, 2008 Journal
ISBN 978–0–478–14412–3 		Howell C http://www.massey.ac.nz Massey university: In Massey University, College of Sciences prepared a database dedicated to provide information regarding weeds in New Zealand
New Zealand Journal of Ecology, 33 (2), 2009 Journal Sullivan JJ,
Williams PA, Timmins SM,
Smale MC 		http://www.mpi.govt.nz Ministry for primary industries: The Ministry for Primary Industries is dedicated to improving agriculture productivity, food safety, increasing sustainability and reducing biological risk
An illustrated guide to common weeds of New Zealand, 2010 Book Popay I,
Champion P,
James T 		http://www.nzpcn.org.nz New Zealand plant conservation network: This network system is framed to conserve the floral wealth of New Zealand
New Zealand Journal of Ecology, 39(1), 2015 Journal McAlpine KG, Lamoureaux SL, Westbrooke I http://www.ourbigbackyard.nz Our big backyard: This aims to restore, create and maintain healthy habitats of New Zealand
Agronomy, 9, 2019 Journal Ghanizadeh H, Harrington KC http://www.waikoregion.govt.nz Waikato: This local government body works for maintaining agriculture resources and sustainability to ensure strong economy
Climate change risk assessment for terrestrial species and ecosystems in the Auckland region. Auckland Council, 2019 Technical report
ISBN 978-1-98-858966-4 		Bishop C,
Landers TJ 		http://www.weedbusters.org.nz Weedbusters: Programme facilitates to eradicate weeds in New Zealand
*Secondary information resources/databases have been explored from March 2019 to March 2020
Chemical profile of weeds established in New Zealand

Weeds established in New Zealand encompass wide array of therapeutic phytoconstituents. Weeds serve as biosynthetic factory for synthesis of phytochemicals. They are sources of rich medicinal wealth which includes primary metabolites (polysaccharides) and secondary metabolites (alkaloids, flavonoids, glycosides, tannins, volatile oils etc.). They are the potential sources of complex phytoconstituents. Selaginella kraussiana (African club moss) [11], Lonicera japonica (Japnese honeysuckle) [32], Eriobotrya japonica (Loquat) [35] and Anredera cordifolia (Mignonette vine) [38] contains polysaccharides. Alternanthera philoxeroides (Alligator weed) [13] and Rhamnus alaternus (Evergreen buckthorn) [26] contains anthraquinone glycosides. Lamium galeobdolon (Artillery plant) [14] and Heracleum mantegazzianum (Giant hogweed) [27] contains appreciable amount of volatile oil. Modern spectroscopic methods have been explored for structural elucidation of bioactive constituents present in weeds. LC-MS has been used for quantitative detection of xyloglucan oligosaccharide in Selaginella kraussiana [11], betulonic acid in Alnus glutinosa (Black alder) [12], jasmonic acid in Drosera capensis (Cape sundew) [20], flavonoids in Gunnera tinctoria (Chilean rhubarb) [24], pyrrolizidine alkaloid esters in Gymnocoronis spilanthoides (Senegal tea) [42]. NMR employed for characterization of compounds present in Fraxinus excelsior (Ash) [15], Berberis glaucocarpa (Barberry) [17], Ligustrum sinense (Chinese privet) [25], Rhamnus alaternus [26], Cestrum parqui (Green cestrum) [30], Ranunculus sardous (Hairy buttercup) [49]. Detailed summary of chemical compounds isolated from weeds established in New Zealand indicated in table 2.

Table 2: A summary of compounds isolated from weeds established in New Zealand.
Common name Botanical name Native of Compound reported Analytical approach adopted References
African club moss Selaginella kraussiana
Selaginellaceae 		Africa Xyloglucan oligosaccharide Matrix assisted laser desorption ionization time of flight (MS), high performance anion exchange chromatography [11]
Black alder Alnus glutinosa
Betulaceae 		Eurasia, Africa Betulin, betulinic acid, betulonic acid, lupeol Desorption atmospheric pressure photoionization (MS) [12]
Alligator weed Alternanthera philoxeroides
Amaranthaceae 		South America Anthraquinone glycosides Spectral analysis [13]
Artillery plant Lamium galeobdolon
Lamiaceae 		Europe, Asia Volatile compounds GC-MS [14]
Ash Fraxinus excelsior
Oleaceae 		Europe, Asia, Africa Nodulisporiviridin M ID, 2D 1H & 13C NMR [15]
Asiatic knotweed Fallopia japonica
Polygonaceae 		Asia Carotenoid HPTLC, HPLC-MS [16]
Barberry Berberis glaucocarpa
Berberidaceae 		Himalayas Bisbenzylisoquinoline alkaloid, oxyacanthine 1D, 2D NMR [17]
Blackberry Rubus fruticosus
Rosaceae 		North temperate regions Polyunsaturated fatty acids Supercritical carbon dioxide method [18]
Boxthorn Lycium ferocissimum
Solanaceae 		South Africa Betaine Fast atom bombardment mass spectroscopy [19]
Cape sundew Drosera capensis
Droseraceae 		South Africa Jasmonic acid LC-MS/MS [20]
Castor oil Ricinus communis
Euphorbiaceae 		Africa, Eurasia Ricin Spectral analysis [21]
Century plant Agave americana
Agavaceae 		Mexico Fructans Thermogravimetric analysis [22]
Cherry laurel Prunus laurocerasus
Rosaceae 		South East Europe Cyanogenetic glycosides, benzoic acid derivative LC-ESIMS [23]
Chilean rhubarb Gunnera tinctoria
Gunneraceae 		South America Flavonoids HPLC-MS/MS [24]
Chinese privet Ligustrum sinense
Oleaceae 		China
10-hydroxyl-oleuropein, 3-O-alpha-L-rhamnopyranosyl-kaempherol-7-O-beta-D-glucopyranoside 1D, 2D NMR [25]
Evergreen buckthorn Rhamnus alaternus
Rhamnaceae 		Mediterranean region Anthraquinone glycosides 1D, 2D NMR,
FAB-MS 		[26]
Giant hogweed Heracleum mantegazzianum
Apiaceae 		Eurasia Essential oil GC-MS [27]
Giant knotweed Fallopia sachalinensis
Polygonaceae 		Asia Olymeric procyanidins, flavones, flavonoids GC-MS [28]
Giant reed Arundo donax
Gramineae 		Eurasia Bis-indole alkaloid, phenylpropanoid Spectral analysis [29]
Green cestrum Cestrum parqui
Solanaceae 		Chile, Peru Saponin 1H, 13C NMR [30]
Heather Calluna vulgaris
Ericaceae 		Europe Catechin, epicatechin HPLC-DAD-ESI/MS [31]
Japnese honeysuckle Lonicera japonica
Caprifoliaceae 		Japan Polysaccharides HPLC, FTIR [32]
Khasia berry Cotoneaster simonsii
Rosaceae 		China Tocopherols Spectral analysis [33]
Kudzu vine Pueraria lobata
Fabaceae 		Japan Lobatamunsolides A-C, norlignans LC-MS [34]
Loquat  Eriobotrya japonica
Rosaceae 		China, Japan Polysaccharides UMAE [35]
Manchurian rice grass Zizania latifolia
Poaceae 		China Proanthocyanidins UAE [36]
Mexican devil Ageratina adenophora
Asteraceae 		South America Thymol derivatives 1H NMR, HR-ESI-MS, IR [37]
Mignonette vine Anredera cordifolia
Basellaceae 		South America Water soluble polysaccharides UV, FTIR [38]
Moth plant Araujia hortorum
Asclepiadaceae 		Brazil, Argentina Protease (araujiain) Ultracentrifugation, ion exchange chromatography, MS [39]
Mysore thorn Caesalpinia decapetala
Fabaceae 		Asia Cassane type furanoditerpenoids HPLC, 1D NMR, 2D NMR, HRESIFTMS [40]
Plectranthus Plectranthus ciliates
Lamiaceae 		South Africa Anthocyanins UV [41]
Senegal tea Gymnocoronis spilanthoides
Asteraceae 		Mexico Pyrrolizidine alkaloid esters HPLC, MS-MS [42]
Tree of heaven Ailanthus altissimia
Simaroubaceae 		China Phenlypropanoids NMR, HRESIMS [43]
Tuber ladder fern Nephrolepis cordifolia
Davalliaceae 		Australia 2,4-hexadien-1-ol, nonanal, thymol GC-MS [44]
White bryony Bryonia cretica
Cucurbitaceae 		Eurasia Cucurbitane type triterpene Bioassay guided fractionation, NMR [45]
Bracken Pteridium esculentum
Dennstaedtiaceae 		Australia Ptesculentoside, caudatoside, ptaquiloside LC-MS [46]
Catsear Hypochaeris radicata
Asteraceae 		Eurasia Lignans, sesquiterpene lactones NMR, HRMS [47]
Creeping buttercup Ranunculus repens
Ranunculaceae 		Europe, Asia Methyl 3,4,5-trihydroxybenzoate 1D, 2D NMR [48]
Hairy buttercup Ranunculus sardous
Ranunculaceae 		Europe, Asia Ranunculin TLC, HPTLC [49]
Therapeutic potential of weeds established in New Zealand

Weeds have been explored for diverse pharmacological actions like anti cancer, anti microbial, anti-inflammatory, antioxidant, antiviral etc. as mentioned in table 3 and figure 1.

Table 3: A summary of pharmacological activities exhibited by weeds.
Common name Botanical name Native of Reported pharmacological activity Outcome of study Reference
Aristea Aristea ecklonii
Iridaceae 		West and South Africa Antimicrobial Plumbagin isolated from plant exhibited antimicrobial activities with MIC 2 µg/ml and 16 µg/ml [50]
Arrow bamboo Pseudosasa japonica
Poaceae 		Japan, South Korea Antioxidant Leaves extract has potential to ameliorate oxidative stress by improving antioxidant activity [51]
Bear’s breeches Acanthus mollis
Acanthaceae 		South West Europe Antioxidant, anti-inflammatory Ethanol extract inhibited NO production [52]
Blue spur flower Plectranthus ecklonii
Lamiaceae 		South Africa Against pancreatic cancer Antiproliferative effect was found to be effective against BxPC3, PANC-1, Ins1-E, MICF-7, HaCat, Caco-2 cell lines [53]
Buddleia Buddleja davidii
Buddlejaceae 		China AChE inhibitory activity Linarin isolated from plant inhibit AChE activity [54]
Cape honeysuckle Tecomaria capensis
Bignoniaceae 		South Africa Analgesic, antipyretic, anti-inflammatory activities Methanolic extract of leaves significantly prevented increase in volume of paw edema [55]
Cat’s claw creeper Macfadyena unguis-cati
Bignoniaceae 		Central and South America Anti-inflammatory, cytotoxic Crude ethanol extract exhibited marked anti-inflammatory and cytotoxicity against lung cancer cell line [56]
Chocolate vine Akebia quinata
Lardizabalaceae 		China, Korea, Japan Anti-fatique agent Akebia extract showed marked improvement in lethargic behavioral test [57]
Clematis Clematis flammula
Ranunculaceae 		Southern Europe and Northern Africa Cytotoxic Weed extract cause kinases and transcription factor induction [58]
Climbing spindle berry Celastrus orbiculatus
Celastraceae 		Eastern Asia, Korea, Japan, China Against gastric cancer Compound 28-hydroxy-3-oxoolean-12-en-29-oic acid inhibited the migration and invasion of gastric cancer cells [59]
Darwin’s barberry Berberis darwinii
Berberidaceae 		Chile, Argentina Alzheimer’s disease Methanolic extract of stem bark exhibited acetylcholinestrase inhibitory activity [60]
Elder Sambucus nigra
Caprifoliaceae 		Europe, West Asia, North Africa Antioxidant Free radical scavenging potential [61]
Elephant ear Alocasia brisbanensis
Araceae 		Ceylon, Tahiti Antimicrobial Extract showed promising antimicrobial activities against Staphylococcus aureus [62]
False acacia Robinia pseudoacacia
Fabaceae 		South Eastern USA Antitumor Inhibition of IL-1β signaling [63]
False tamarisk Myricaria germanica
Tamaricaceae 		Eurasia Cytotoxic Compound tamgermanitin exhibited potent anti cancer effect [64]
Field horsetail Equisetum arvense
Equisetaceae 		Temperate Northern Hemisphere Antioxidant Potent antioxidant in DPPH assay [65]
Green daphne laurel Daphne laureola
Thymelaeaceae 		North Africa, South West Europe Anticancer Cytotoxic against lung cancer [66]
Green goddess Zantedeschia aethiopica
Araceae 		South Africa Antimicrobial Peptides in weed exhibited antimicrobial activities [67]
Gypsywort Lycopus europaeus
Lamiaceae 		Europe, Asia Antimicrobial Compound euroabienol showed broad spectrum activity [68]
Hop Humulus lupulus
Cannabaceae 		Europe, Western Asia, North America Osteogenic Activity evaluated via MC3T3-E1 cells lines [69]
Horned poppy Glaucium flavum
Papaveraceae 		Western Europe, South Western Asia Against breast cancer Bocconoline compound isolated from the plant inhibit viability of cancer cells [70]
Houttuynia Houttuynia cordata
Saururaceae 		Asia Antiviral Houttuynoid B isolated from the weed prevents cell entry of Zika virus [71]
Ivy Hedera helix
Araliaceae 		Europe, North Africa Anti-inflammatory Inhibition of Staphylococcus aureus strain [72]
Jerusalem cherry  Solanum pseudocapsicum
Solanaceae 		South America Acetylcholinestrase inhibitor Alkaloids reported in the plant exhibited AChE inhibition [73]
Lantana Lantana camara
Verbenaceae 		Tropical America Sedative Essential oil from weed possess CNS depressant effects [74]
Mexican water lily Nymphaea mexicana
Nymphaeaceae 		Mexico Anti-inflammatory  Cox-2 inhibition [75]
Nasturtium Tropaeolum majus
Tropaeolaceae 		Europe, America, Africa, Asia Antimicrobial Compound 3-[3-pyridinyl)-1,2,4-oxadiazol-5-yl] benzonitrile exhibited potent antimicrobial activities [76]
Needlebush Hakea sericea
Proteaceae 		Australia Cytotoxic Extract inhibited MCF-7 cell line [77]
Old man’s beard Clematis vitalba
Ranunculaceae 		Europe, South West Asia Antinociceptive and antipyretic Vitalboside isolated from weed exerted action [78]
Pig’s ear Cotyledon orbiculata
Crassulaceae 		Africa Anticonvulsant Aqueous and methanolic extracts showed prominent effects on gabaergic and glutaminergic mechanisms [79]
Pink ragwort Senecio latifolius
Asteraceae 		South Africa Cytotoxic Cytotoxicity in HepG2 cells caused depletion of cellular GSH [80]
Rough horsetail Equisetum hyemale
Equisetaceae 		Temperate Northern Hemisphere
Antitrypanosomal n-butanol fraction exert antiprotozoal effect [81]
Royal fern Osmunda regalis
Osmundaceae 		Europe, India, Africa Inhibition of head and neck cancer cell proliferation Extract revealed growth inhibiting effect on HLaC78 and FaDu [82]
Tree privet Ligustrum lucidum
Oleaceae 		China Hepatocellular carcinoma Inactivation of PL3K/Akt pathway [83]
Tutsan Hypericum androsaemum
Clusiaceae 		South and Western Europe Anti-lipid peroxidation n-hexane fraction exerted desired activity [84]
Chingma lantern Abutilon theophrasti
Malvaceae 		Temperate region Antibacterial Extract showed activity against Staphylococcus aureus [85]
Black night shade Solanum nigrum
Solanaceae 		North Western Africa Antitumor Active against breast cancer cell line MCF7 [86]
Broad leaved dock Rumex obtusifolius
Polygonaceae 		Eurasia Hypoglycemic Ethanolic extract improved glucose tolerance in rabbits [87]
Broad leaved fleabane Conyza sumatrensis
Asteraceae 		South America Antiplasmodial Study confirmed the traditional use of weed [88]
Broad leaved plantain Plantago major
Plantaginaceae 		Eurasia Potential wound healer Showed activity against hyaluronidase and collangenase enzymes [89]
Chick weed Stellaria media
Caryophyllaceae 		India Antifungal Peptides in weed were responsible for its potent activity [90]
Cleavers Galium aparine
Rubiaceae 		Temperate zone Immunomodulator Ethanolic extract stimulated immunocompetent blood cells [91]
Dandelion Taraxacum officinale
Asteraceae 		Africa Antioxidant Extract from leaf provide protection against free radical mediated oxidative stress [92]
Father Chenopodium album
Amaranthaceae 		Temperate zone Antioxidant Weed showed protection against mercury induced oxidative stress [93]
Galinsoga Galinsoga parviflora
Asteraceae 		Tropical America Photocarcinogenesis Caffeic acid derivative protect dermal UVA-induced oxidative stress [94]
Hedge mustard Sisymbrium officinale
Brassicaceae 		Southern Europe Inhibition of oxidative mutagenicity Polyphenols in weed exhibited desired action [95]
Hemlock Conium maculatum Apiaceae Temperate region Antimicrobial Essential oils reported in weed showed activity against Pseudomonas aeruginosa [96]
Manuka Leptospermum scoparium
Myrtaceae                      		New Zealand, South East Australia Antibacterial Oils exhibited activity against gram negative pathogens [97]
Nettle Urtica urens
Urticaceae 		Europe Anxiolytic Extract increased the time spent in bright-lit chamber of light/dark box pharmacological model [98]
Pennyroyal Mentha pulegium
Lamiaceae 		Northern Africa Antidiabetic Aqueous extract revealed improvement of glucose tolerance in in-vivo rat model [99]
Red dead nettle Lamium purpureum
Lamiaceae 		Eurasia Haemostatic activity Extracts showed promising results in haemostatic test [100]
Scarlet pimpernel Anagallis arvensis
Primulaceae 		Northern Africa Molluscicidal Aqueous leaf extract showed activity against Schistosoma mansoni [101]
Scotch thistle Cirsium vulgare
Asteraceae 		Europe Hepatoprotective Hexane extract showed anti-necrotic and anti-cholestatic effects [102]
Scrambling speedwell Veronica persica
Plantaginaceae 		Eurasia, America Antiviral Extract showed synergistic activity in combination with acyclovir anti-HSV therapy [103]
Selfheal Prunella vulgaris
Lamiaceae 		Eurasia, America Inhibition of IHNV infection Ursolic acid decrease cytopathic effect and viral titer [104]
Sow thistle Sonchus oleraceus
Asteraceae 		Asia Nephroprotective Extract showed desired effect by inhibiting ischemia reperfusion in rats [105]
Water pepper Persicaria hydropiper
Polygonaceae 		Eurasia Anti-inflammatory Extract showed desired therapeutic effect [106]
Yarrow Achillea millefolium
Asteraceae 		Eurasia, North America Antibabesial activity Different extract were active against Brucella canis [107]
Woolly mullein Verbascum thapsus
Scrophulariaceae 		Eurasia Antimicrobial Ethanolic extract were potent against gram positive bacteria [108]
Wild teasel Dipsacus fullonum
Caprifoliaceae 		Australia Antibacterial Compounds isolated from root exhibited activity against Staphylococcus aureus [109]
Cocklebur Xanthium strumarium
Asteraceae 		Temperate zone Hepatocellular carcinoma Weed induce apoptosis in HCC cell lines in a dose dependent manner [110]


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Figure 1: Therapeutic potential of weeds.

Anticancer weeds: Some important cytotoxic weeds include Clematis flammula [58], Hakea sericea (Needlebush) [77], Robinia pseudoacacia (False acacia) [63], Daphne laureola [66]. Myricaria germanica (False tamarisk) [64], Senecio latifolius (Pink ragwort) [80]. Osmunda regalis (Royal fern) [82]. Parvifloron D isolated from Plectranthus ecklonii via flash dry column chromatography exhibited antiproliferative effects against pancreatic cancer when evaluated against HaCat, BxPC3, Caco-2, MCF-7, Ins1-E and PANC-1 cell lines [53]. Aqueous extract of weed Solanum nigrum at concentration of 10 g/l caused 43% cytotoxicity in MCF7 cell line by inhibiting migration, suppression of hexokinase and pyruvate kinase [86]. Triterpene (28-Hydroxy-3-oxoolean-12-en-29-oic acid) present in Celastrus orbiculatus showed inhibitory activity on SGC-7901 and BGC-823 cells lines [59]. Bocconoline alkaloid isolated from dried roots of Glaucium flavum (Horned poppy) exhibited cytotoxicity with IC50 value of 7.8µM [70].

Antimicrobial weeds: Invasive weed Aristea ecklonii containing Plumbagin exhibited antimicrobial activity with minimum inhibitory concentration between 2 μg/ml and 16 μg/ml [50]. Antimicrobial peptides isolated from arum lily (Zantedeschia aethiopica) exhibited potent antimicrobial activity [67]. Euroabienol (abietane-type diterpenoid) isolated from fruits of Lycopus europaeus exhibited broad spectrum antimicrobial activity [68]. Compounds 3-[3-(3-pyridinyl)-1,2,4-oxadiazol-5-yl] benzonitrile and [3,5-Bis (1,1-dimethylethyl)-4-hydroxyphenyl] isolated from weed Tropaeolum tuberosum when tested against Candida tropicalis exhibited antifungal activities with MICs of 100 μM and 50 μM [76]. Extracts obtained from leaves of weed Abutilon theophrasti elicit antimicrobial potential against Staphylococcus aureus, Salmonella, Streptococcus and E. coli species [85]. Essential oils isolated from weeds Conium maculatum, Leptospermum scoparium showed antimicrobial activity against several strains of Pseudomonas aeruginosa [96,97]. Ethanolic extracts of woolly mullein reported positive against gram positive bacteria (Bacillus cereus) [108]. Phenolic compounds from Dipsacus fullonum exerted inhibitory effects on Staphylococcus aureus DSM 799 and E. coli ATCC 10536 strains [109].

Antioxidant weeds: Strong antioxidant activity was reported by ferulic acid derived from leaves of weed Pseudosasa japonica when evaluated using DPPH (54 %) and ABTS (65 %) [51]. Antioxidant potential of Taraxacum officinale was determined using in vitro methods (DPPH, ABTS, FRAP). The ABTS method reveled that antioxidant activity was 156±5.28 µg/ml [92]. Other potential antioxidant weed includes Acanthus mollis [52], Sambucus nigra [61], Equisetum arvense [65].

Anti-inflammatory weeds: A study by Akhtar, et al. 2019 investigated the anti-inflammatory properties of Hedera helix and its major compounds on Staphylococcus aureus induced inflammation in mice. Hederacoside-C isolated from weed exerted profound anti-inflammatory effects [72]. Mexican water lily (Nymphaea mexicana) was found to be potent COX-2 inhibitor [75]. Active compounds isolated from aerial parts of weed Clematis vitalba when evaluated in vivo against carrageenan, serotonin, PGE-2 induced hind paw edema showed antinociceptive and antipyretic effects [78]. Methanolic extract of leaves of Tecomaria capensis significantly prevented increase in volume of paw edema [55]. Extract of Persicaria hydropiper exerted marked anti-inflammatory effects [106]. Aqueous extract alongwith compounds (calceorioside B, homoplantaginin, plantamajoside) isolated from the aerial parts of Plantago major showed inhibition against hyaluronidase enzyme [89].

Antiviral weeds: Methanolic extract of scrambling speedwell weed (Veronica persica) reported potent activity against herpes simplex viruses and synergistic activity in combination with acyclovir anti-HSV therapy [103]. Ursolic acid isolated form weed Prunella vulgaris inhibited IHNV infection in aquaculture with an inhibitory concentration of 99.3 % at 100 mg/l [104].

Weeds acting on CNS: Methanolic extract of stem bark of darwin’s barberry (Berberis darwinii) inhibited acetylcholinestrase in vitro with IC50 value of 1.23 ± 0.05 microg/mL thereby provide relief in alzheimer’s disease [60]. Alkaloid solanocapsine isolated from weed Solanum pseudocapsicum reported to inhibit activity of enzyme acetylcholinestrase [73]. Nettle (Urtica urens) exhibited anxiolytic activity in mice when evaluated using hole board test, light-dark box test and rota rod test. Extract showed increased head-dip duration and head-dip counts in hole board test [98]. Aqueous (50-400 mg/kg i.p.) and methanolic extracts (100-400 mg/kg i.p.) of Pig’s ear (Cotyledon orbiculata) exhibited anticonvulsant activity which predominantly delayed onset of seizures induced by N-methyl-dl-aspartic, bicuculline, picrotoxin in mice models [79].

Other pharmacological activities of weeds: Aqueous extract of Akebia quinata showed positive effect against fatigue in mice exposed to chronic restraint stress when evaluated using forced swimming behavioral test, sucrose preference and open field tests [57]. n-butanol fraction of weed Equisetum hyemale exerted antiprotozoal effects against Trypanosoma evansi trypomastigotes after nine hours exposure [81]. Chen, et al. 2019 reported osteogenic activities of Humulus lupulus in MC3T3-E1 cell lines [69]. Ethanolic extract of weed Galium aparine stimulated the transformational activity of immunocompetent blood cells in vitro [91]. Aqueous extract of aerial parts of Mentha pulegium (20 mg/kg) showed antihyperglycemic effect by marked improvement in oral glucose tolerance test in streptozotocin induced diabetic rats [99]. Butanolic extracts of aerial parts of Lamium album and Lamium pupureum showed haemostatic activity in wistar rats when evaluated by tail bleeding time determination and acenocoumarol carrageenan test compared to vitamin K [100]. Anagallis arvensis (Scarlet pimpernel) leaf extract showed molluscicidal activity against Biomphalaria alexandrina at LC50 37.9 mg/l and LC90 48.3 mg/l [101]. Hexane extract rich in lupeol acetate of weed scotch thistle (Cirsium vulgare) prevented carbon tetrachloride induced liver damage in rats by diminishing lipid peroxidation and nitric oxide levels [102]. Extracts of Sonchus oleraceus (Sow thistle) were reported to be nephroprotective against kidney ischemia reperfusion injury in wistar rats [105]. Water extract, ethanol extract, hexane/acetone extract obtained from Achillea millefolium (Yarrow) were effective against Babesia canis parasite at 2 mg/ml concentration [107].

Other potential applications of weeds established in New Zealand

A large number of weed communities has been reported to clean environment through phytoremediation process and act as bioindicators (Figure 2). Phytoremediation is described as a process of eradicating toxic contaminants from soil, water and air. This process involves phytoextraction (harvesting of biomass), phytostabilization (contaminants stabilized into less toxic compounds), phytotransformation (chemical modification of contaminants), phytostimulation (rhizosphere degradation), phytovolatilization (conversion of toxic compounds into volatile form) and rhizofiltration (filtration through roots) [111]. Arum lily (Zantedeschia aethiopica) acts as micropollutant removal by removing accumulation of copper, zinc, carbamazepine and linear alkylbenxene sulphonates [112]. Bladderwort (Utricularia gibba) [113], canna lilly (Canna indica) [114], coltsfoot (Tussilago farfara) [115], egeria (Egeria densa) [116], giant buttercup (Ranunculus acris) [117], broom (Cytisus scoparius) [118], annual poa (Poa annua) have been involved in removing toxic metals (chromium, cadmium, zinc, lead) from the environment [119]. Parrot feather (Myriophyllum aquaticum) aids in removing antibiotic (tetracycline) from water [120]. Oxeye daisy (Leucanthemum vulgare) potentiated crude oil phytoremediation and used in eliminating pollution from environment [121]. Apart from these properties weeds have also been found to be employed in other industries e.g. buffalo grass weed (Stenotaphrum secundatum) used in turf grass industry [122]. Mucoadhesive properties of water soluble gum obtained from Hakea gibbosa added in sustained release dosage forms [123]. Silver nanoparticles having average particle size 20 nm synthesized from Cestrum nocturnum showed more antioxidant potential as compared to vitamin C alongwith strong antibacterial activity against Vibrio cholerae with MIC of 16 µg/ml [124]. Organic fertilizer manufactured via aquatic weed Salvinia molesta when evaluated using FT-IR, plant bioassay test for determination of its fertilizer value and chemical composition showed promising results as vermicompost [125]. Eragrostis species (E. capensis, E. curvula) and grass Stenotaphrum secundatum exhibited drought resistant ability [126,127].


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Figure 2: An overview of Phytoremediation process.

Besides the therapeutic potential exhibited by weeds, toxicity profile should be taken into consideration while exploring them. Equisetum arvense (Field horsetail) exerted hepatotoxicity in rats [128], weeds like Zantedeschia aethiopica (Arum lily), Conium maculatum (Hemlock), Solanum nigrum (Black night shade) are considered poisonous in New Zealand [129]. Hedera helix (Ivy) caused contact dermatitis [130], Lantana camara exerted in vivo cell toxicity [131], Xanthium strumarium (Cocklebur) responsible for causing poisoning in cattle [132].

Conclusion
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Title Abstract Introduction Conclusion
References

Humans define weeds as per their appropriateness and understanding of the plant. A plant investigated as weed in some region may be a plant of medicinal importance for another region. The usefulness of weeds has been ignored by humans for long time because of their invasive growth, competitors of genuine crop and no economic value. This human behaviour might be developed over time due to lack of proper knowledge of phytochemical screening as well as therapeutic potential of weeds. Weeds are the sources of human food, fodder in agriculture, shelter for some animals, helpful against soil erosion, indicators of soil nutrients, as well as sources of commercially important essential oils. In this era weeds have been extensively explored for their immense phytopharmacological prospects. It is evidenced that weeds have been sources of potential targets for different pathological conditions. However there is need of more scientific and clinical investigations required in assessment of toxicity profile to get the maximum potential of weeds. Weeds have protective role in environment as a component of phytoremediation and for sustainable ecosystem. Because of immense therapeutic potential implicit by weeds a new chain of thoughts emerge in our mind to consider the value of these important plants so called ‘weeds’. Are they need to be redefined or we need to rethink the concept of weeds? It is clear from the studies documented in this review that the approach of whether a plant is wanted or not should depends on its pharmacological potential and role in ecosystem other than merely the competitive effect of plant with the particular crop. Further advancements are required in order to spin the concept of weeds into therapeutic weeds.

Important abbreviations used
ABTS = 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid)
COX = Cyclooxygenase
DPPH = 2,2-diphenyl-1-picrylhydrazyl
ESI = Electrospray ionization
FAB = Fast atom bombardment
FRAP = Fluorescence recovery after photobleaching
FTIR = Fourier-transform infrared spectroscopy
GC = Gas chromatography
GSH = Glutathione
HepG2 = Hepatoblastoma cells
HPLC = High-performance liquid chromatography
HPTLC = High-performance thin-layer chromatography
HRESIFTMS = High resolution electrospray ionization fourier transform mass spectrometry
HR-ESI-MS = High-resolution electrospray ionization mass spectrometry
HSV = Herpes simplex virus
IC50 = Inhibitory concentration
IHNV = Infectious hematopoietic necrosis virus
LC-ESIMS = Liquid chromatography electrospray ionisation mass spectroscopy
MCF7, SGC-7901, BGC-823 cells, BxPC3, PANC-1, Ins1-E, MICF-7, HaCat, Caco-2, HCC, HLaC78, FaDu = Cancer cell lines
MS = Mass spectroscopy
NMR = Nuclear magnetic resonance
NO = Nitric oxide
PGE-2 = Prostaglandin E2
TLC = Thin layer chromatography
UAE = Ultrasound-assisted extraction
UV = Ultraviolet spectroscopy
UVA = Ultra violet radiation
References
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