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The bark ofwillowtrees containssalicylic acid,theactive metaboliteofaspirin,and has been used for millennia torelieve painand reducefever.[1]

Medicinal plants,also calledmedicinal herbs,have been discovered and used intraditional medicinepractices since prehistoric times.Plantssynthesize hundreds of chemical compounds for various functions, includingdefenseand protection againstinsects,fungi,diseases,andherbivorousmammals.[2]

The earliest historical records of herbs are found from theSumeriancivilization, where hundreds of medicinal plants includingopiumare listed on clay tablets,c. 3000 BC.TheEbers Papyrusfromancient Egypt,c. 1550 BC,describes over 850 plant medicines. The Greek physicianDioscorides,who worked in the Roman army, documented over 1000 recipes for medicines using over 600 medicinal plants inDe materia medica,c. 60 AD;this formed the basis ofpharmacopoeiasfor some 1500 years. Drug research sometimes makes use ofethnobotanyto search for pharmacologically active substances, and this approach has yielded hundreds of useful compounds. These include the common drugsaspirin,digoxin,quinine,andopium.The compounds found in plants are diverse, with most in four biochemical classes:alkaloids,glycosides,polyphenols,andterpenes.Few of these arescientifically confirmed as medicinesor used in conventional medicine.

Medicinal plants are widely used as folk medicine in non-industrialized societies, mainly because they are readily available and cheaper than modern medicines. The annual global export value of the thousands of types of plants with medicinal properties was estimated to be US$60 billion per year and growing at the rate of 6% per annum.[citation needed]In many countries, there is little regulation of traditional medicine, but theWorld Health Organizationcoordinates a network to encourage safe and rational use. The botanical herbal market has been criticized for being poorly regulated and containingplaceboandpseudoscienceproducts with no scientific research to support their medical claims.[3]Medicinal plants face both general threats, such asclimate changeandhabitat destruction,and the specific threat of over-collection to meet market demand.[3]

History

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Dioscorides's 1st centuryDe materia medica,seen here in ac. 1334copy in Arabic, describes some 1000 drug recipes based on over 600 plants.[4]
Further information:History of herbalismandHistory of pharmacy

Prehistoric times

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Plants, including many now used asculinary herbsandspices,have been used as medicines, not necessarily effectively, from prehistoric times. Spices have been used partly to counterfood spoilagebacteria, especially in hot climates,[5][6]and especially in meat dishes that spoil more readily.[7]Angiosperms (flowering plants) were the original source of most plant medicines.[8]Human settlements are often surrounded by weeds used asherbal medicines,such asnettle,dandelionandchickweed.[9][10]Humans were not alone in using herbs as medicines: some animals such as non-humanprimates,monarch butterfliesandsheepingest medicinal plants when they are ill.[11]Plant samples from prehistoric burial sites are among the lines of evidence that Paleolithic peoples had knowledge of herbal medicine. For instance, a 60,000-year-old Neanderthal burial site, "Shanidar IV",in northern Iraq has yielded large amounts of pollen from eight plant species, seven of which are used now as herbal remedies.[12]Also, amushroomwas found in the personal effects ofÖtzi the Iceman,whose body was frozen in theÖtztal Alpsfor more than 5,000 years. The mushroom was probably used againstwhipworm.[13]

Ancient times

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TheEbers Papyrus(c. 1550 BC) fromAncient Egyptdescribes the use of hundreds of plant medicines.[14]

In ancientSumeria,hundreds of medicinal plants includingmyrrhandopiumare listed on clay tablets from around 3000 BC. Theancient EgyptianEbers Papyruslists over 800 plant medicines such asaloe,cannabis,castor bean,garlic,juniper,andmandrake.[14][15]

In antiquity, various cultures across Europe, including the Romans, Celts, and Nordic peoples, also practiced herbal medicine as a significant component of their healing traditions.

The Romans had a rich tradition of herbal medicine, drawing upon knowledge inherited from the Greeks and expanding upon it. Notable works include those of Pedanius Dioscorides, whose "De Materia Medica" served as a comprehensive guide to medicinal plants and remained influential for centuries.[16]Additionally, Pliny the Elder's "Naturalis Historia" contains valuable insights into Roman medical plant practices[17]

Among the Celtic peoples of ancient Europe, herbalism played a vital role in both medicine and spirituality. Druids, the religious leaders of the Celts, were reputed to possess deep knowledge of plants and their medicinal properties. Although written records are scarce, archaeological evidence, such as the discovery of medicinal plants at Celtic sites, provides insight into their herbal practices[18]

In the Nordic regions, including Scandinavia and parts of Germany, herbal medicine was also prevalent in ancient times. The Norse sagas and Eddic poetry often mention the use of herbs for healing purposes. Additionally, archaeological findings, such as the remains of medicinal plants in Viking-age graves, attest to the importance of herbal remedies in Nordic culture[19]

From ancient times to the present,Ayurvedic medicineas documented in theAtharva Veda,theRig Vedaand theSushruta Samhitahas used hundreds of herbs and spices, such asturmeric,which containscurcumin.[20]TheChinese pharmacopoeia,theShennong Ben Cao Jingrecords plant medicines such aschaulmoografor leprosy,ephedra,andhemp.[21]This was expanded in theTang dynastyYaoxing Lun.[22]In the fourth century BC,Aristotle's pupilTheophrastuswrote the first systematic botany text,Historia plantarum.[23]In around 60 AD, the Greek physicianPedanius Dioscorides,working for the Roman army, documented over 1000 recipes for medicines using over 600 medicinal plants inDe materia medica.The book remained the authoritative reference on herbalism for over 1500 years, into the seventeenth century.[4]

Middle Ages

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Illustration of a 1632 copy ofAvicenna's 1025The Canon of Medicine,showing a physician talking to a female patient in a garden, while servants prepare medicines.

During the Middle Ages, herbalism continued to flourish across Europe, with distinct traditions emerging in various regions, often influenced by cultural, religious, indigenous, and geographical factors.

In theEarly Middle Ages,Benedictine monasteriespreserved medical knowledge inEurope,translating and copying classical texts and maintainingherb gardens.[24][25]Hildegard of BingenwroteCausae et Curae( "Causes and Cures" ) on medicine.[26]

In France, herbalism thrived alongside the practice of medieval medicine, which combined elements of Ancient Greek and Roman traditions. Catholic monastic orders played a significant role in preserving and expanding herbal knowledge. Manuscripts like the "Tractatus de Herbis" from the 15th century depict French herbal remedies and their uses.[27]Monasteries and convents served as centers of learning, where monks and nuns cultivated medicinal gardens. Likewise, in Italy, herbalism flourished with contribution Italian physicians like Matthaeus Platearius who compiled herbal manuscripts, such as the "Circa Instans," which served as practical guides for herbal remedies.[28]

In the Iberian Peninsula, the regions of the North remained independent during the period of Islamic occupation, and retained their traditional and indigenous medical practices. Galicia and Asturias, possessed a rich herbal heritage shaped by its Celtic and Roman influences. The Galician people were known for their strong connection to the land and nature and preserved botanical knowledge, with healers, known as "curandeiros" or "meigas," who relied on local plants for healing purposes[29]The Asturian landscape, characterized by lush forests and mountainous terrain, provided a rich source of medicinal herbs used in traditional healing practices, with "yerbatos," who possessed extensive knowledge of local plants and their medicinal properties[30]Barcelona, located in the Catalonia region of northeastern Spain, was a hub of cultural exchange during the Middle Ages, fostering the preservation and dissemination of medical knowledge. Catalan herbalists, known as "herbolarios," compiled manuscripts detailing the properties and uses of medicinal plants found in the region. The University of Barcelona, founded in 1450, played a pivotal role in advancing herbal medicine through its botanical gardens and academic pursuits.[31]

In Scotland and England, herbalism was deeply rooted in folk traditions and influenced by Celtic, Anglo-Saxon, and Norse practices. Herbal knowledge was passed down through generations, often by wise women known as "cunning folk." The "Physicians of Myddfai," a Welsh herbal manuscript from the 13th century, reflects the blending of Celtic and Christian beliefs in herbal medicine.[32]

In theIslamic Golden Age,scholars translated many classical Greek texts including Dioscorides intoArabic,adding their own commentaries.[33] Herbalism flourished in the Islamic world, particularly inBaghdadand inAl-Andalus.Among many works on medicinal plants,Abulcasis(936–1013) ofCordobawroteThe Book of Simples,and Ibn al-Baitar (1197–1248) recorded hundreds of medicinal herbs such asAconitum,nux vomica,andtamarindin hisCorpus of Simples.[34]Avicennaincluded many plants in his 1025The Canon of Medicine.[35]Abu-Rayhan Biruni,[36]Ibn Zuhr,[37]Peter of Spain,andJohn of St Amandwrote furtherpharmacopoeias.[38]

Early Modern

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An early illustrated book of medicinal plants,[39]The Grete Herball,1526

TheEarly Modernperiod saw the flourishing of illustratedherbalsacross Europe, starting with the 1526Grete Herball.John Gerardwrote his famousThe Herball or General History of Plantsin 1597, based onRembert Dodoens,andNicholas Culpeperpublished hisThe English Physician Enlarged.[39] Many new plant medicines arrived in Europe as products ofEarly Modern explorationand the resultingColumbian Exchange,in which livestock, crops and technologies were transferred between the Old World and the Americas in the 15th and 16th centuries. Medicinal herbs arriving in the Americas included garlic, ginger, and turmeric; coffee, tobacco and coca travelled in the other direction.[40][41] In Mexico, the sixteenth centuryBadianus Manuscriptdescribed medicinal plants available in Central America.[42]

19th and 20th centuries

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Further information:Pharmacognosy

The place of plants in medicine was radically altered in the 19th century by the application ofchemical analysis.Alkaloidswere isolated from a succession of medicinal plants, starting withmorphinefrom thepoppyin 1806, and soon followed byipecacuanhaandstrychnosin 1817,quininefrom thecinchonatree, and then many others. As chemistry progressed, additional classes of potentially active substances were discovered in plants. Commercial extraction of purified alkaloids including morphine began atMerckin 1826.Synthesisof a substance first discovered in a medicinal plant began withsalicylic acidin 1853. Around the end of the 19th century, the mood of pharmacy turned against medicinal plants, asenzymesoften modified the active ingredients when whole plants were dried, and alkaloids and glycosides purified from plant material started to be preferred. Drug discovery from plants continued to be important through the 20th century and into the 21st, with important anti-cancer drugs fromyewandMadagascar periwinkle.[43][44][45]

Context

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Medicinal plants are used with the intention of maintaining health, to be administered for a specific condition, or both, whether inmodern medicineor intraditional medicine.[3][46]TheFood and Agriculture Organizationestimated in 2002 that over 50,000 medicinal plants are used across the world.[47]TheRoyal Botanic Gardens, Kewmore conservatively estimated in 2016 that 17,810 plant species have a medicinal use, out of some 30,000 plants for which a use of any kind is documented.[48]

In modern medicine, around a quarter[a]of the drugs prescribed to patients are derived from medicinal plants, and they are rigorously tested.[46][49]In other systems of medicine, medicinal plants may constitute the majority of what are often informal attempted treatments, not tested scientifically.[50]TheWorld Health Organizationestimates, without reliable data, that some 80 percent of the world's population depends mainly on traditional medicine (including but not limited to plants); perhaps some two billion people are largely reliant on medicinal plants.[46][49]The use of plant-based materials including herbal or natural health products with supposed health benefits, is increasing in developed countries.[51]This brings attendant risks of toxicity and other effects on human health, despite the safe image of herbal remedies.[51]Herbal medicines have been in use since long before modern medicine existed; there was and often still is little or no knowledge of the pharmacological basis of their actions, if any, or of their safety. The World Health Organization formulated a policy on traditional medicine in 1991, and since then has published guidelines for them, with a series of monographs on widely used herbal medicines.[52][53]

Medicinal plants may provide three main kinds of benefit: health benefits to the people who consume them as medicines; financial benefits to people who harvest, process, and distribute them for sale; and society-wide benefits, such as job opportunities, taxation income, and a healthier labour force.[46]However, development of plants or extracts having potential medicinal uses is blunted by weak scientific evidence, poor practices in the process ofdrug development,and insufficient financing.[3][54]

Phytochemical basis

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Further information:Phytochemistry

All plants produce chemical compounds which give them anevolutionaryadvantage, such asdefending against herbivoresor, in the example ofsalicylic acid,as ahormonein plant defenses.[55][56]These phytochemicals have potential for use as drugs, and the content and known pharmacological activity of these substances in medicinal plants is the scientific basis for their use in modern medicine, if scientifically confirmed.[3]For instance, daffodils (Narcissus) contain nine groups of alkaloids includinggalantamine,licensed for use againstAlzheimer's disease.The alkaloids are bitter-tasting and toxic, and concentrated in the parts of the plant such as the stem most likely to be eaten by herbivores; they may also protect againstparasites.[57][58][59]

Modern knowledge of medicinal plants is being systematised in the Medicinal Plant Transcriptomics Database, which by 2011 provided a sequence reference for thetranscriptomeof some thirty species.[60]Major classes of plantphytochemicalsare described below, with examples of plants that contain them.[8][53][61][62][63]

Alkaloids

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Further information:Alkaloids

Alkaloidsare bitter-tasting chemicals, very widespread in nature, and often toxic, found in many medicinal plants.[64]There are several classes with different modes of action as drugs, both recreational and pharmaceutical. Medicines of different classes includeatropine,scopolamine,andhyoscyamine(all fromnightshade),[65]the traditional medicineberberine(from plants such asBerberisandMahonia),[b]caffeine(Coffea),cocaine(Coca),ephedrine(Ephedra),morphine(opium poppy),nicotine(tobacco),[c]reserpine(Rauvolfia serpentina),quinidineandquinine(Cinchona),vincamine(Vinca minor), andvincristine(Catharanthus roseus).[63][68]

Glycosides

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Further information:Glycosides

Anthraquinoneglycosidesare found in medicinal plants such asrhubarb,cascara,andAlexandrian senna.[70][71]Plant-basedlaxativesmade from such plants includesenna,[72]rhubarb[73]andAloe.[63]

Thecardiac glycosidesare powerful drugs from medicinal plants includingfoxgloveandlily of the valley.They includedigoxinanddigitoxinwhich support the beating of the heart, and act asdiuretics.[55]

Polyphenols

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Further information:PolyphenolandHealth effects of polyphenols

Polyphenolsof several classes are widespread in plants, having diverse roles in defenses against plant diseases and predators.[55]They include hormone-mimickingphytoestrogensand astringenttannins.[63][75]Plants containing phytoestrogens have been administered for centuries forgynecologicaldisorders, such as fertility, menstrual, and menopausal problems.[76]Among these plants arePuerariamirifica,[77]kudzu,[78]angelica,[79]fennel,andanise.[80]

Many polyphenolic extracts, such as fromgrape seeds,olivesormaritime pine bark,are sold asdietary supplementsandcosmeticswithout proof or legalhealth claimsfor medicinal effects.[81]InAyurveda,the astringent rind of thepomegranate,containing polyphenols calledpunicalagins,is used as a medicine, with no scientific proof of efficacy.[81][82]

Terpenes

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Further information:Terpenes

Terpenesandterpenoidsof many kinds are found in a variety of medicinal plants,[84]and inresinousplants such as theconifers.They are strongly aromatic and serve to repel herbivores. Their scent makes them useful inessential oils,whether forperfumessuch asroseandlavender,or foraromatherapy.[63][85][86]Some have medicinal uses: for example,thymolis an antiseptic and was once used as avermifuge(anti-worm medicine).[87]

In practice

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Licensed commercial cultivation ofopium poppies,Tasmania, 2010
Main articles:HerbalismandList of plants used in herbalism

Cultivation

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Medicinal plants demand intensive management. Different species each require their own distinct conditions of cultivation. TheWorld Health Organizationrecommends the use ofrotationto minimise problems with pests and plant diseases. Cultivation may be traditional or may make use ofconservation agriculturepractices to maintain organic matter in the soil and to conserve water, for example withno-till farmingsystems.[88]In many medicinal and aromatic plants, plant characteristics vary widely with soil type and cropping strategy, so care is required to obtain satisfactory yields.[89]

Preparation

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A Medieval physician preparing an extract from a medicinal plant, from an Arabic Dioscorides, 1224

Medicinal plants are often tough and fibrous, requiring some form of preparation to make them convenient to administer. According to the Institute for Traditional Medicine, common methods for the preparation of herbal medicines includedecoction,powdering, and extraction with alcohol, in each case yielding a mixture of substances. Decoction involves crushing and then boiling the plant material in water to produce a liquid extract that can be taken orally or applied topically.[90]Powdering involves drying the plant material and then crushing it to yield a powder that can be compressed intotablets.Alcohol extraction involves soaking the plant material in cold wine or distilled spirit to form atincture.[91]

Traditionalpoulticeswere made by boiling medicinal plants, wrapping them in a cloth, and applying the resulting parcel externally to the affected part of the body.[92]

When modern medicine has identified a drug in a medicinal plant, commercial quantities of the drug may either besynthesisedor extracted from plant material, yielding a pure chemical.[43]Extraction can be practical when the compound in question is complex.[93]

Usage

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Aherbalist's shop in thesoukofMarrakesh, Morocco
Further information:Herbalism,Psychoactive drug,andDrug discovery

Plant medicines are in wide use around the world.[94]In most of the developing world, especially in rural areas, localtraditional medicine,including herbalism, is the only source of health care for people, while in thedeveloped world,alternative medicineincluding use ofdietary supplementsis marketed aggressively using the claims of traditional medicine. As of 2015, most products made from medicinal plants had not been tested for their safety and efficacy, and products that were marketed in developed economies and provided in the undeveloped world by traditional healers were of uneven quality, sometimes containing dangerous contaminants.[95]Traditional Chinese medicinemakes use of a wide variety of plants, among other materials and techniques.[96]Researchers fromKew Gardensfound 104 species used fordiabetesin Central America, of which seven had been identified in at least three separate studies.[97][98]TheYanomamiof the Brazilian Amazon, assisted by researchers, have described 101 plant species used for traditional medicines.[99][100]

Drugs derived from plants including opiates, cocaine and cannabis have both medical andrecreational uses.Different countries have at various times madeuse of illegal drugs,partly on the basis of the risks involved in takingpsychoactive drugs.[101]

Effectiveness

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The bark of thecinchonatree contains thealkaloidquinine,traditionally given formalaria.

Plant medicines have often not been tested systematically, but have come into use informally over the centuries. By 2007, clinical trials had demonstrated potentially useful activity in nearly 16% of herbal extracts; there was limited in vitro or in vivo evidence for roughly half the extracts; there was only phytochemical evidence for around 20%; 0.5% were allergenic or toxic; and some 12% had basically never been studied scientifically.[53]Cancer Research UK caution that there is no reliable evidence for the effectiveness of herbal remedies for cancer.[102]

A 2012phylogeneticstudy built a family tree down togenuslevel using 20,000 species to compare the medicinal plants of three regions, Nepal, New Zealand and the Cape of South Africa. It discovered that the species used traditionally to treat the same types of condition belonged to the same groups of plants in all three regions, giving a "strong phylogenetic signal".[103]Since many plants that yield pharmaceutical drugs belong to just these groups, and the groups were independently used in three different world regions, the results were taken to mean 1) that these plant groups do have potential for medicinal efficacy, 2) that undefined pharmacological activity is associated with use in traditional medicine, and 3) that the use of a phylogenetic groups for possible plant medicines in one region may predict their use in the other regions.[103]

Regulation

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The practice ofAyurvedain India, such as the running of this Ayurvedic pharmacy inRishikesh,is regulated by a government department,AYUSH.

The World Health Organization (WHO) has been coordinating a network called the International Regulatory Cooperation for Herbal Medicines to try to improve the quality of medical products made from medicinal plants and the claims made for them.[104]In 2015, only around 20% of countries had well-functioning regulatory agencies, while 30% had none, and around half had limited regulatory capacity.[95]In India, whereAyurvedahas been practised for centuries, herbal remedies are the responsibility of a government department,AYUSH,under the Ministry of Health & Family Welfare.[105]

WHO has set out a strategy for traditional medicines[106]with four objectives: to integrate them as policy into national healthcare systems; to provide knowledge and guidance on their safety, efficacy, and quality; to increase their availability and affordability; and to promote their rational, therapeutically sound usage.[106]WHO notes in the strategy that countries are experiencing seven challenges to such implementation, namely in developing and enforcing policy; in integration; in safety and quality, especially in assessment of products and qualification of practitioners; in controlling advertising; in research and development; in education and training; and in the sharing of information.[106]

Drug discovery

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The anticancer drugtaxolwas developed after screening of the Pacific yew,Taxus brevifolia(foliage and fruit shown) in 1971.
Further information:Drug discovery

Thepharmaceutical industryhas roots in theapothecaryshops of Europe in the 1800s, where pharmacists provided local traditional medicines to customers, which included extracts like morphine, quinine, and strychnine.[107]Therapeutically important drugs likecamptothecin(fromCamptotheca acuminata,used in traditional Chinese medicine) andtaxol(from the Pacific yew,Taxus brevifolia) were derived from medicinal plants.[108][43]TheVinca alkaloidsvincristineandvinblastine,used as anti-cancer drugs, were discovered in the 1950s from the Madagascar periwinkle,Catharanthus roseus.[109]

Hundreds of compounds have been identified usingethnobotany,investigating plants used by indigenous peoples for possible medical applications.[110]Some important phytochemicals, includingcurcumin,epigallocatechin gallate,genisteinandresveratrolarepan-assay interference compounds,meaning thatin vitrostudies of their activity often provide unreliable data. As a result, phytochemicals have frequently proven unsuitable as the lead substances indrug discovery.[111][112]In the United States over the period 1999 to 2012, despite several hundred applications fornew drug status,only twobotanical drugcandidates had sufficient evidence of medicinal value to be approved by theFood and Drug Administration.[3]

The pharmaceutical industry has remained interested in mining traditional uses of medicinal plants in its drug discovery efforts.[43]Of the 1073 small-molecule drugs approved in the period 1981 to 2010, over half were either directly derived from or inspired by natural substances.[43][113]Among cancer treatments, of 185 small-molecule drugs approved in the period from 1981 to 2019, 65% were derived from or inspired by natural substances.[114]

Safety

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The ThornappleDatura stramoniumhas been used for asthma, because it contains the alkaloidatropine,but it is also a powerful and potentially fatalhallucinogen.[115]
Further information:List of herbs with known adverse effects

Plant medicines can cause adverse effects and even death, whether by side-effects of their active substances, by adulteration or contamination, by overdose, or by inappropriate prescription. Many such effects are known, while others remain to be explored scientifically. There is no reason to presume that because a product comes from nature it must be safe: the existence of powerful natural poisons like atropine and nicotine shows this to be untrue. Further, the high standards applied to conventional medicines do not always apply to plant medicines, and dose can vary widely depending on the growth conditions of plants: older plants may be much more toxic than young ones, for instance.[116][117][118][119][120][121]

Plant extracts may interact with conventional drugs, both because they may provide an increased dose of similar compounds, and because some phytochemicals interfere with the body's systems that metabolise drugs in the liver including thecytochrome P450system, making the drugs last longer in the body and have a cumulative effect.[122]Plant medicines can be dangerous during pregnancy.[123]Since plants may contain many different substances, plant extracts may have complex effects on the human body.[5]

Quality, advertising, and labelling

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Herbal medicine anddietary supplementproducts have been criticized as not having sufficient standards or scientific evidence to confirm their contents, safety, and presumed efficacy.[124][125][126][127]Companies often make false claims about their herbal products promising health benefits that aren't backed by evidence to generate more sales. The market for dietary supplements and nutraceuticals grew by 5% during the COVID-19 pandemic, which led to the United States taking action to stop the deceptive marketing of herbal products to combat the virus.[128][129]

Threats

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Where medicinal plants are harvested from the wild rather than cultivated, they are subject to both general and specific threats. General threats includeclimate changeandhabitat lossto development and agriculture. A specific threat is over-collection to meet rising demand for medicines.[130]A case in point was the pressure on wild populations of the Pacific yew soon after news of taxol's effectiveness became public.[43]The threat from over-collection could be addressed by cultivation of some medicinal plants, or by a system of certification to make wild harvesting sustainable.[130]A report in 2020 by the Royal Botanic Gardens, Kew identifies 723 medicinal plants as being at risk of extinction, caused partly by over-collection.[131][114]

See also

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Notes

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  1. ^Farnsworth states that this figure was based on prescriptions from American community pharmacies between 1959 and 1980.[49]
  2. ^Berberine is the main active component of an ancient Chinese herbCoptis chinensisFrench, which has been administered for what Yin and colleagues state is "diabetes"for thousands of years, although with no sound evidence of efficacy.[66]
  3. ^Tobacco has "probably been responsible for more deaths than any other herb", but it was used as a medicine in the societies encountered by Columbus and was considered apanaceain Europe. It is no longer accepted as medicinal.[67]

References

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