Summary and Key Features
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Herbal tonics have been known for 5 millennia to be therapeutic for skin conditions.
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The increased efficacy of tonics compared to purified extracts is due to the entourage effect.
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The primary active chemicals from herbs are secondary metabolites.
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Secondary metabolites have synergistic effects with entourage chemicals.
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The large number of physiologic functions of secondary metabolites results in potentially very active products.
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Environment, processing, and permeation factors significantly impact the efficacy and safety of herbal products.
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Although not required for cosmeceuticals, efficacy clinical trials and safety studies should be performed on marketed herbal-based products by third parties to substantiate advertising claims and for one to sell in their practice.
See .
Introduction
Extracts derived from plants are referred to as botanical ingredients. But the plants providing extracts with medicinal therapeutics and health maintenance as well as spiritual and culinary value are known as herbs. There are about 1400 species used medicinally. Nearly 74% of cosmeceuticals contain natural ingredients to conquer abnormal skin, including aging. There are about 391,000 plant species known, but only 31,000 have documented human use.
Consumer interest is shifting to natural products as evidenced by 9.7% sales growth of herbal supplements in 2021. Elderberry is the highest-selling herb with 150% increase in sales over 2 years. Apple cider vinegar sales increased 129% in 1 year to become the third highest selling. Ashwagandha had the largest increase in sales, 226%, which moves it into the top 10 of herbs sold.
Domestic regulatory agencies did not have confidence in the efficacy and safety of herbal-based products at the turn of this century. There has been a burgeoning proliferation of not only products and brands but also new species of herbs being used in commercial products. A review of hair loss supplements published in November 2022 demonstrates the scientific credibility problem of herbal products including supplements. The review found that only 30 articles of the 6300 citations from the previous 2 years were considered worthy of scientific analysis. Only 12 of 20 different nutritional interventions had high-quality clinical trials. The herbs that were deemed likely to be effective and were found to be safe included saw palmetto ( Serenoa repens ), pumpkin seed ( Cucurbita maxima ), licorice ( Glycyrrhiza glabra ), and peony ( Paeonia lactiflora ). The number of pilot and open-label human clinical trials has also significantly expanded, but not at the same rate that sales increased. Multiple blind randomized controlled trials (RCTs) of statistically significantly sized subject panels using marketed products and conducted by third-party investigators have been performed at an increased rate, but still far slower than the increase in new product introductions. The US Food and Drug Administration (FDA) considers RCTs as unbiased and predictive of efficacy. But safety studies are nearly always lacking with new cosmetic/cosmeceutical products, since they are not required for a new herbal product to enter the market.
Plant research has yielded nearly 50,000 secondary metabolites (SMs), the key bioactive chemical substances from plants that modulate cells, tissues, and organs of animals, including humans. These chemicals are present in the plant to provide protection against various types of radiation, including ultraviolet light (UVL), and to neutralize toxins and their distribution within the plant. They further may provide protective coloration and storage functionalities. The majority of SMs have no metabolic pathway activity, but a small number of complex carbohydrates and fatty acids do. All SMs have multiple functionalities. They also come from multiple chemical categories that include anthocyanin, alkaloid, carotenoid, coumarin, flavonoid, glycoside, ligan, mineral including elements, phenolic acid, polyphenol, saponin, stilbene, tannin, terpene, and vitamin.
Many plant species contain multiple SMs, and many SMs exist in multiple plant species. For example, flavonoids are polyphenols that have a 15-carbon skeleton. Their general function is as an antioxidant, and they protect against toxin-induced inflammatory reactions. Specific examples include quercetin and resveratrol. The former is extracted from apples, ginkgo, grapes, onions, and soy. The latter is extracted from berries, grapes, peanuts, and wine. The multiple flavonoid functions include antiinflammatory, antimicrobial, antioxidant, and to chelate heavy metals. In addition, they are photoprotective against UVL and blue light, modulate hormones and immunity, arrest the cell cycle, and induce apoptosis. Flavonoids also stimulate synthesis of other chemicals, regenerate other antioxidants, and inhibit a variety of enzymatic and pathophysiologic pathways.
Herbal “tonics” are known to often perform better than a highly purified (fewer than 10 chemicals) liquid or dust extract that is particularly rich in a specific SM. The reason is due to the herbal entourage effect . This occurs from SM interacting with other endogenous bioactive compounds, ions, and elements. The interaction results in improved stability, wider distribution among different plant parts, and enhanced functional potency. This interaction sometimes provides additional beneficial functions and reduce the frequency and severity of adverse reactions to any herbal extract.
Regulatory
The US Department of Agriculture determines and enforces regulations. “Organic certified” means the plant was grown in soil with no synthetic fertilizers or pesticides for more than 3 years. Animal products must not use antibiotics or hormones to achieve this certification. When packaged products are “made with organic ingredients,” it means they contain 70% organically produced ingredients. There is no federal regulatory definition of natural . Natural does not mean safe.
The United States does not regulate herbal products not used as prescriptions to treat disease, which would be defined as drugs. Other countries have established herbal regulatory bodies. The German Commission E was established in 1978 to determine which herbs have documented clinical effectiveness and safety with topical and oral administration; there are currently 187 herbs listed. Japan established an over-the-counter (OTC) and traditional herbal medicine agency in 1970 called Kampo; currently there are 294 herbs listed. The US National Library of Medicine lists 112 herbs accepted as therapeutic.
Product Development Challenges
Biomass Quality
Herbal-based products are much more susceptible to variations than synthetic products, because the plant’s bioactive substances are affected by environmental, processing, formulating, and packaging factors. This is primarily due to the much greater number and diversity of chemicals in the extracts. The quality of the biomass comprising the harvested herb impacts the SM and entourage chemical concentrations, stability, bioavailability, potency, and delivery to targeted tissues. The safety and efficacy of the marketed product are then very likely affected. Plant biomass quality factors include:
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Growing conditions of the plant, which are affected by climate and season as well as humidity, temperature, sunlight frequency and intensity, rainfall, and soil nutrients
- 2
Health of each of the plant parts, which may be affected by wind, hail, fertilization, pesticide use, and presence of infectious organisms
- 3
Time and method of harvest
- 4
Time and type of transportation of biomass
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Storage method and time until processing.
Biomass Processing
This is another step that significantly impacts herbal extract’s efficacy and safety. It includes the following factors:
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Selection of the proper plant part that has the greatest density of targeted SMs.
- 2
Processing prior to extraction consists of air, sun, or oven drying; crushing, grinding, or comminuting (fracturing); or pressing with cold or heat.
- 3
The goal of extraction is to improve the consistency of bioactive concentration, potency, purity, and yield. There are more than 20 extraction methods currently in use. This author has been involved in developing two of them. The most common methods for commercialized herbal-based products include water or solvent baths and steam distillation. Solvents include alcohol, glycols, glycerin, esters, and oils. The most effective but more complex methods include microwave, ultrasound, column chromatography, freeze drying, and supercritical and subcritical fluids.
Sequential use of multiple methods may be employed to maximize yield of bioactive chemicals but at increased cost and time of processing.
- 4
The sensitivity of bioactive chemicals to processing and extraction determines the chemical integrity, stability, function, and potential toxicity.
- a
Antioxidant enzymes are the most effective protectors against reactive oxygen species and damaging oxidative reactions. Being proteins, enzymes are susceptible to heat denaturation and alkaline and chemical degradation. A significant number of these antioxidant molecules are completely destroyed or significantly damaged during processing.
- b
Low-molecular-weight bioactives such as albumin, carotenoids, glutathione, urea, uric acid, metallothioneins, ubiquinone, and vitamins A and C are all damaged by temperature extremes and UVL exposure in a manufacturing and packaging facility. This is a major reason many marketed products claiming to have retinol or ascorbic acid do not have measurable amounts in products when tested by third parties.
- a
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It is unlikely that the more sophisticated and effective methods are used by private-label manufacturers due to their increased cost. Techniques such as nitrogen blanketing remove oxygen, moisture, and contaminants during manufacturing to prevent bioactive damage.
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Elements including minerals, ions, and trace elements may be bound to unstable chemical substances created during processing, which reduces effectiveness.
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Delivery Challenges
Significant problems for clinical efficacy of herbal bioactives include lack of adequate epidermal permeation through the stratum corneum (SC) to achieve therapeutic concentrations in the epidermis. SC is a robust proteohydrolipid barrier with tortuous channels. Many of the herbal bioactive chemicals lack the molecular parameters to cross the SC and penetrate the multiple epidermal strata to diffuse into the basement membrane zone. Very few of the bioactives can be expected to reach the dermis due to molecular weight and architecture, lipophilicity, and chemical instability. Vehicles or excipients enhance distribution into and throughout the skin of SMs and entourage substances.
The different solubilities, polarities, sizes, and architectures of the several to hundreds of multiple SMs in herbal extracts create permeation difficulties. Moreover, the degree of biodegradability, biocompatibility, toxicity, release profile, and antigenicity also varies among the multiple SMs in one extract. Contributing to the challenge is the different SMs binding to cells, receptors, and organelles in different epidermal strata modulate the many biologic pathways, including signalling, inflammation, and skin repair.
For example, polyphenols have poor stability in water and are polar. About 90% of hydrophilic polyphenols, including catechins, curcumin, and chlorogenic acid, accumulate in the SC. On the contrary, 90% of retinols are distributed throughout the epidermis below the SC. A small percentage of small-molecular-weight resveratrol permeates into the dermis. Excipients such as urea and isopropanol hinder release of the polyphenol rutin from topical formulations, reducing its benefit. Propylene glycol at 5% enhances rutin’s release. Thermodynamically stable microemulsions enhance delivery of polyphenols, quercetin, and chlorogenic acid. Promising delivery technologies for herbal bioactives include nanoemulsions, nanocarriers, liposomes, niosomes, cubosomes, phytosomes, nanocrystals, polymeric nanoparticles, carbon nanotubes, fullerenes, dendrimers, nanostructured lipid carriers, transferosomes, and cosmetotextiles.
Two decades ago, six delivery systems were developed by this author that modulate epidermal structure, metabolism, and catabolism to increase penetration of bioactive chemicals without triggering inflammatory cascades. Multiple SMs from 21 herbal species have been successfully delivered, which was proven by blinded controlled human clinical trials. Chemicals from multiple SM classes have had enhanced penetration up to 20-fold with these systems, resulting in increased therapeutic efficacy.
Safety
These above challenges mean the presence of an herbal extract in a product you are asked to sell to reverse aging or diseased skin most likely does not have therapeutic benefit. It is more likely to have an increased incidence of contact irritation or sensitization. The most common chemical insults in herbal-based skin care products include volatile and essential oils, proteins, saps, plant parts (leaf, flower, stem), and pollens.
Sensitive skin is the most common reaction to cosmetics, experienced by 30–50% of females. The reaction rate among adults to all cosmetics and cosmeceuticals is 18.4%. Fragrances can induce both contact irritant and allergic reactions. They are the most common culprit and account for 37.5% of contact reactions. Nearly 90% of contact reactions are nonimmunologic irritation reactions. Only 8 of the 80 international contact patch test allergens are herbal. This would indicate that a sensitization reaction is much more likely to be allergic to a component of the formulation other than the herb. The eight herbs include compositae, jasminum, tea tree, ylang-ylang, peppermint, lavender, lemon, and cinnamon. None of the top 10 allergens are herbal, but the second most common allergen is fragrance, which contains a few potential sensitizing herbal extracts such as linalool. The seventh most common allergen is Balsam of Peru, which cross-reacts with multiple herbs including citrus, tomato, cinnamon, and curry.
A basic panel of topical safety studies should be performed with the marketed product for aged skin before launch, because aged skin is already damaged. No safety panel is required for cosmeceuticals/cosmetics. Nearly 80% of females surveyed did not know that cosmetics/cosmeceuticals are not required to be tested to substantiate claims and document safety. Medical and skin care professionals should question the safety on any marketed product they are asked to sell. This basic safety panel should consist of three tests: (1) repeat insult patch test (RIPT) of 50 or more subjects to assess risk of irritant and allergic contact dermatitis; (2) microbial assessment for the presence of pathogens; and (3) microbial assessment for the presence of formaldehyde and releasing agents, all on the finished product. For products containing known photosensitizers such as tea tree oil, a 10-subject phototoxicity test should also be added. These safety tests are required by institutional review boards prior to performing RCTs with a test product.
Other safety issues with herbal-based products applied topically have potentially serious complications, just as any chemical product does. German chamomile ( Matricaria recutita ), cayenne ( Capsicum annuum ), echinacea ( Echinacea angustifolia ), and poison ivy ( Rhus toxicodendron ) have been reported to produce anaphylactic reactions resulting in death. Jaborandi ( Pilocarpus microphyllus ) induces death via cardiac arrest. Very rare fatalities have been reported with aloe, aristocholia, arnica, black mustard, cascara, Chinese rhubarb, comfrey, croton, kava kava, mistletoe, senna, Scotch pine, spruce, and yohimbe. Oleander and mahuang have a much higher fatality rate than other herbs, including with topical application.
As noted in the third edition of this volume, Chinese practitioners are concerned about the well-known side effects of hepatotoxicity, contact dermatitis, and teratogenicity that occur in up to one-third of people using topical traditional Chinese medicines, which are mixes of herbs. A significant number of congenital anomalies occur when these herbs are used topically during pregnancy.
Another risk of herbal products is the relatively high incidence of cross-reactivity with other herbs. In 106 dermatitis-afflicted people, 12 were allergic to tea tree oil and had one or more positive patch test reactions to 10 other herbs, most commonly lavender.
Efficacy
The gold standard for determining efficacy is a blind, randomized controlled clinical trial of a statistically significant number of subjects approved by an institutional review board using the product and packaging to be marketed. The trial should be performed by a third-party contract research organization with trained investigators and appropriate assessment devices. The FDA has determined these are unbiased even when funded by the corporation that produced the product. Strong confidence in effectiveness of a cosmeceutical technology is indicated when the marketed product is compared to a prescription product. These have been performed very rarely. The first such trials were sponsored by this author.
Other methods to increase product efficacy include fermentation and bioliquifaction. Aspergillus yeast fermentation increased the amount, bioavailability, and efficacy of polysaccharides and polyphenols of four herbal species. Antimicrobial effectiveness was also increased against seven bacterial pathogens. Fermenting the herb with Lactobacillus enhanced antiinflammatory and pigment-reducing effectiveness.
Clinical proof from RCTs of antiaging benefits from botanical-based cosmeceuticals is still surprisingly limited. Tables 8.1– 8.6 are divided into groups of pathophysiologic processes causing visible skin aging. They have a different arrangement and data than those in the third edition of this volume.
| Aloe ( Aloe barbadensis ) |
| Agrimony ( Agrimonia eupatoria ) |
| Alpenrose ( Rhododendron ferrugineum ) |
| Apple-orchard ( Malus domestica ) |
| Apricot ( Prunus armeniaca ) |
| Argan ( Argania spinosa ) |
| Asparagus ( Asparagus officinalis ) |
| Avocado ( Persea americana ) |
| Bengal coffee ( Coffea benghalensis ) |
| Bilberry/Huckleberry ( Vaccinium myrtillus ) |
| Bitter orange ( Citrus aurantium ) |
| Blackwattle ( Acacia mearnsii and A. decurrens ) |
| Cacay ( Caryodendron orinocense ) |
| CNP ( Cleistocalyx nervosum var. paniala ) |
| Cocoa ( Theobroma cacao ) |
| Coconut ( Cocos nucifera ) |
| Coffee ( Coffea arabica ) |
| Coneflower ( Echinacea angustifolia ) |
| Corn ( Zea mays ) |
| Cornflower ( Centaurea cyanus ) |
| Creosote bush ( Larrea tridentata ) |
| Dandelion ( Taraxacum officinale ) |
| Dark crimson cinquefoil ( Potentilla atrosanguinea ) |
| Edelweiss ( Leontopodium alpinum ) |
| Evening primrose ( Oenothera biennis and O. paradox ) |
| Feverfew ( Tanacetum parthenium ) |
| Gentian ( Gentiana lutea ) |
| Ginkgo ( Ginkgo biloba ) |
| Ginseng ( Panax ginseng ) |
| Grape ( Vitis vinifera ) |
| Green tea ( Camellia sinensis ) |
| Honeybush ( Cyclopia intermedia ) |
| Horsetail ( Equisetum arvense ) |
| Jojoba ( Simmondsia chinensis ) |
| Jonquil ( Narcissus jonquilla ) |
| Kiwi ( Actinidia chinensis ) |
| Lady’s bedstraw ( Galium verum ) |
| Lady’s mantle ( Alchemilla vulgaris ) |
| Licorice ( Glycyrrhiza glabra ) |
| Loddon lily ( Leucojum aestivum ) |
| Lupin ( Lupinus albus ) |
| Mango ( Mangifera indica ) |
| Marigold ( Calendula officinalis ) |
| Meadowfoam ( Limnanthes alba ) |
| Moth bean ( Vigna aconitifolia and V. radiata ) |
| Mountain hydrangea ( Hydrangea serrata ) |
| Muskmelon ( Cucumis melo ) |
| Pea ( Pisum sativum ) |
| Peach/Peach kernal ( Prunus persica ) |
| Pine ( Pinus brutia , P. sylvestris , P. pinaster ) |
| Pollen (multiple genuses) |
| Pomegranate ( Punica granatum ) |
| Purslane ( Portulaca oleracea ) |
| Red poppy ( Papaver rhoeas ) |
| Rooibos ( Aspalathus linearis ) |
| Rose (French) ( Rosa gallica ) |
| Rosehip/Wild rose ( Rosa canina ) |
| Rosemary ( Rosmarinus officinale ) |
| Shea ( Butyrospermum parkii ) |
| Soybean/Soy ( Glycine max and G. soja ) |
| Sunflower ( Helianthus annuus ) |
| Swiss apple ( Uttwiler spätlauber ) |
| Tobacco ( Nicotiana quadrivalvis ) |
| Tomato ( Solanum lycopersicum ) |
| Turmeric ( Curcuma longa ) |
| Wheat ( Triticum aestivum ) |
| White lily ( Lilium candidum ) |
| White nettle ( Lamium album ) |
| Yarrow/Milfoil ( Achillea millefolium ) |
| Yerba mate ( Ilex paraguariensis ) |
| Agrimony ( Agrimonia eupatoria ) |
| Aloe ( Aloe barbadensis ) |
| Anise ( Pimpinella anisum ) |
| Apple-orchard ( Malus domestica ) |
| Ashwagandha ( Withania somnifera ) |
| Asparagus ( Asparagus officinale ) |
| Avocado ( Persea americana ) |
| Baobab ( Adansonia digitata ) |
| Bitter orange ( Citrus aurantium ) |
| Black seed ( Nigella sativa ) |
| Blackberry ( Rubus fruticosus ) |
| Buckbean ( Menyanthes trifoliata ) |
| Cacay ( Caryodendron orinocense ) |
| Calendula ( Calendula officinalis ) |
| Carrot ( Daucus carota ) |
| Cedar wood ( Cedrus deodarn ) |
| Chamomile, German ( Matricaria recutita ) and Roman ( Chamaemelum nobilis ) |
| Chicory ( Cichorium intybus ) |
| Chinese rhubarb ( Rheum palmatum ) |
| Coconut ( Cocos nucifera ) |
| Coltsfoot ( Tussilago farfara ) |
| Comfrey ( Symphytum officinale ) |
| Coneflower ( Echinacea angustifolia ) |
| Coriander ( Coriandrum sativum ) |
| Cowslip ( Primula veris ) |
| Cranesbills ( Geranium maculatum ) |
| Dandelion ( Taraxacum officinale ) |
| Dwarf everlast ( Helichrysum arenarium ) |
| Eye bright ( Euphrasia officinalis ) |
| Gotu kola ( Centella asiatica ) |
| Grape ( Vitus vinifera ) |
| Heather ( Calluna vulgaris ) |
| Horsetail ( Equisetum arvense ) |
| Indian cress/Nasturtium ( Tropaeolum majus ) |
| Java/Cat’s whiskers ( Orthosiphon stamineus ) |
| Jojoba ( Simmondsia chinensis ) |
| Laurel ( Laurus nobilis ) |
| Lavender ( Lavandula officinale ) |
| Lemon ( Citrus limon ) |
| Lemon balm ( Melissa officinalis ) |
| Licorice ( Glycyrrhiza glabra ) |
| Magnolia ( Magnolia officinalis ) |
| Mango ( Mangifera indica ) |
| Marshmallow ( Althaea officinale ) |
| Mimosa tenuiflora ( Mimosa hostilis ) |
| Mountain daisy ( Arnica montana ) |
| Mustard ( Brassica juncea ) |
| Olive ( Olea europaea ) |
| Onion ( Allium cepa ) |
| Panama bark ( Quillaja saponaria ) |
| Papaw ( Asimina triloba ) |
| Papaya ( Carica papaya ) |
| Peach/Peach kernal ( Prunus persica ) |
| Peanut ( Arachis hypogaea ) |
| Pellitory ( Anacyclus pyrethrum ) |
| Peruvian bark ( Cinchona officinalis ) |
| Pine ( Pinus pinaster, P. brutia, P. sylvestris ) |
| Plantain ( Plantago major ) |
| Prickly ash ( Zanthoxylum americanum ) |
| Prickly pear ( Opuntia ficus-indica ) |
| Purple coneflower ( Echinacea purpurea ) |
| Rambutan ( Nephelium lappaceum ) |
| Red clover ( Trifolium pratense ) |
| Red poppy ( Papaver rhoeas ) |
| Rose (Damask) ( Rosa damascena ) |
| Rose (French) ( Rosa gallica ) |
| Rosehip/Wild rose ( Rosa canina ) |
| Rosemary ( Rosmarinus officinale ) |
| Sage ( Salvia officinalis ) |
| Sea buckthorn ( Hippophae rhamnoides ) |
| Slippery elm ( Ulmus rubra ) |
| St. John’s wort ( Hypericum perforatum ) |
| Sweet almond ( Aloysia virgata ) |
| Sweet orange ( Citrus sinensis ) |
| Tara tree ( Ceratonia siliqua and Caesalpinia spinosa ) |
| Thyme ( Thymus vulgaris ) |
| Tormentilla ( Potentilla officinalis ) |
| Valerian ( Valeriana officinalis ) |
| White cedar ( Thuja occidentalis ) |
| Wild pansy/Heartsease ( Viola tricolor ) |
| Wood avens ( Geum urbanum ) |
| Aloe ( Aloe barbadensis ) |
| Apple ( Malus domestica ) |
| Apricot ( Prunus armeniaca ) |
| Ashwagandha ( Withania somnifera ) |
| Asparagus ( Asparagus officinale ) |
| Avocado ( Persea americana ) |
| Baobab ( Adansonia digitata ) |
| Bengal coffee ( Coffea benghalensis ) |
| Bitter orange ( Citrus aurantium ) |
| Blackberry ( Rubus fruticosus ) |
| Bladder wrack ( Fucus vesiculosus ) |
| Borage ( Borago officinalis ) |
| Calendula ( Calendula officinalis ) |
| Chamomile, German ( Matricaria recutita ) and Roman Chamaemelum nobilis ) |
| Chickweed ( Stellaria media ) |
| Coconut ( Cocos nucifera ) |
| Coltsfoot ( Tussilago farfara ) |
| Comfrey ( Symphytum officinale ) |
| Coriander ( Coriandrum sativum ) |
| Corn ( Zea mays ) |
| Cornflower ( Centaurea cyanus ) |
| Cotton ( Gossypium herbaceum ) |
| Cucumber ( Cucumis sativus ) |
| Elderberry ( Sambucus nigra ) |
| Fennel ( Foeniculum vulgare ) |
| Fenugreek ( Trigonella foenum-graecum ) |
| Fig ( Ficus carica ) |
| Flax ( Linum usitatissimum ) |
| Grape ( Vitis vinifera ) |
| Hawthorn ( Crataegus oxyacantha ) |
| Hazelnut ( Corylus colurna ) |
| Hibiscus ( Hibiscus abelmoschus ) |
| Horsetail ( Equisetum arvense ) |
| Iris ( Iris versicolor ) |
| Jojoba ( Simmondsia chinensis ) |
| Jonquil ( Narcissus jonquilla ) |
| Kiwi ( Actinidia chinensis ) |
| Lavender ( Lavandula angustifolia ) |
| Lemon ( Citrus medica limonum ) |
| Lettuce ( Lactuca sativa ) |
| Licorice ( Glycyrrhiza glabra ) |
| Lime-blossum ( Tilia sylvestris ) |
| Linden tree ( Tilia platyphyllos ) |
| Lupin ( Lupinus angustifolius ) |
| Macadamia ( Macadamia integrifolia , M. tetraphylla , M. ternifolia ) |
| Mallow ( Malva neglecta and M. sylvestris ) |
| Mango ( Mangifera indica ) |
| Marshmallow ( Althaea officinalis ) |
| Moth bean ( Vigna aconitifolia and V. radiata ) |
| Millet ( Panicum miliaceum ) |
| Muskmelon ( Cucumis melo ) |
| Myrrh ( Commiphora myrrha ) |
| Oat ( Avena sativa ) |
| Olive ( Oleo europaea ) |
| Papaw ( Asimina triloba ) |
| Papaya ( Carica papaya ) |
| Peach/Peach kernal ( Prunus persica ) |
| Pear ( Pyrus communis ) |
| Pellitory ( Parietaria officinalis ) |
| Pine ( Pinus pinaster, P. brutia, P. sylvestris ) |
| Pollen (multiple genuses) |
| Pomegranate ( Punica granatum ) |
| Prickly pear ( Opuntia ficus-indica ) |
| Provence rose ( Rosa x centifolia ) |
| Raspberry ( Rubus idaeus ) |
| Red poppy ( Papaver rhoeas ) |
| Sandalwood ( Santalum album ) |
| Sea buckthorn ( Hippophae rhamnoides ) |
| Sesame ( Sesamum indicum ) |
| Strawberry ( Fragaria vesca ) |
| Sweet almond ( Prunus amygdalus ) |
| Vanilla ( Vanilla planifolia ) |
| Walnut ( Juglans regia ) |
| Watercress ( Nasturtium officinale ) |
| Watermelon ( Citrullus lanatus ) |
| Wheat ( Triticum aestivum ) |
| White lily ( Lilium candidum ) |
| Wild almond ( Sterculia foetida ) |
| Yarrow/Milfoil ( Achillea millefolium ) |
| African mangosteen ( Garcinia livingstonei ) |
| Aloe ( Aloe barbadensis ) |
| Ammoniacum ( Dorema ammoniacum ) |
| Asian beautyberry ( Callicarpa longissima ) |
| Azarolus ( Crataegus azarolus ) |
| Bearberry ( Uva-ursi ) |
| Butcher’s-broom ( Ruscus aculeatus ) |
| Chickpea ( Cicer arietinum ) |
| China camellia ( Camellia chinensis ) |
| Chinese chaste tree ( Vitex negundo ) |
| Chinese juniper ( Juniperus chinensis ) |
| Cowslip ( Primula veris ) |
| Cutch tree ( Acacia catechu ) |
| Daisy/Belides ( Bellis perennis ) |
| Dandelion ( Taraxacum officinale ) |
| Elderberry ( Sambucus nigra ) |
| Giant salvia ( Brillantaisia cicatricosa lindau ) |
| Ginkgo ( Ginkgo biloba ) |
| Ginseng ( Panax ginseng ) |
| Grape seed ( Vitis vinifera ) |
| Ground ivy ( Glechoma hederacea ) |
| Himalayan cherry ( Prinsepia utilis ) |
| Horseradish ( Armoracia rusticana ) |
| Indian gooseberry ( Emblica officinalis ) |
| Indian sarsaparilla ( Hemidesmus indicus ) |
| Jamaica cherry ( Muntingia calabura ) |
| Japanese stewartia ( Stewartia pseudocamellia ) |
| Kudzu ( Pueraria thunbergiana ) |
| Lady’s mantle ( Alchemilla vulgaris ) |
| Lamb’s quarters ( Chenopodium album and C. uganda ) |
| Lemon balm ( Melissa officinalis ) |
| Licorice ( Glycyrrhiza glabra ) |
| Loddon lily ( Leucojum aestivum ) |
| Magnolia ( Magnolia officinalis ) |
| Mallow ( Malva sylvestris and M. neglecta ) |
| Mandarin melon berry ( Cudrania tricuspidata ) |
| Mountain daisy ( Arnica montana ) |
| Muskmelon ( Cucumis melo ) |
| Nut grass ( Cyperus rotundus ) |
| Parsley ( Petroselinum crispum ) |
| Passion fruit ( Passiflora edulis ) |
| Peach/Peach kernal ( Prunas persica ) |
| Peppermint ( Mentha piperita ) |
| Prostrate spurge ( Euphorbia supina ) |
| Purple nutsedge ( Cyperus rotundus ) |
| Purslane ( Portulaca oleracea ) |
| Rosy periwinkle ( Catharanthus roseus ) |
| Sacred lotus ( Nelumbo nucifera ) |
| Safflower ( Carthamus tinctorius ) |
| Saffron crocus ( Crocus sativus ) |
| Sambong/Ngai camphor ( Blumea balsamifera ) |
| Sanchi ( Panax notoginseng ) |
| Sandalwood ( Santalum album ) |
| Sappan wood ( Caesalpinia sappan ) |
| Saw-wort ( Serratula tinctoria seoanei ) |
| Seagrape ( Coccoloba uvifera ) |
| Sesame ( Sesamum angolense ) |
| Shaggy sparrow-wort ( Thymelaea hirsuta ) |
| Silver birch/European white birch ( Betula pendula ) |
| Soybean ( Glycine max and G. soja ) |
| Strawberry ( Fragaria ananassa ) |
| Sweet violet ( Viola odorata ) |
| Tall woodland sugarbush ( Protea madiensis ) |
| Taro ( Colocasia antiquorum ) |
| Tarragon ( Artemisia dracunculus ) |
| Tomato ( Solanum lycopersicum ) |
| Turmeric ( Curcuma longa ) |
| Western dock ( Rumex occidentalis ) |
| Wheat bran ( Triticum sativum ) |
| White mulberry ( Morus alba ) |
| Yarrow/Milfoil ( Achillea millefolium ) |
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