Summary of Phytochemical’s – Plant Hormetic Compounds
Phytochemicals are chemicals of plant origin. Phytochemicals (from Greek phyto, meaning “plant”) are chemicals produced by plants through primary or secondary metabolism. They generally have biological activity in the plant host and play a role in plant growth or defense against competitors, pathogens, or predators. These are Essential for us to combat oxidative stress & free radicals produced during oxidative phosphorylation, chronic stress and exposures to radiation & pollution. Generally, phytochemicals have been classified into six major categories based on their chemical structures and characteristics. These categories include carbohydrate, lipids, phenolics as in Polyphenols, terpenoids and alkaloids, and other nitrogen-containing compounds .
Plant Hormetic Compounds which are also a specific class of phytonutrients and Nutraceuticals.
Compelling evidence from epidemiological studies suggest beneficial roles of dietary phytochemicals in protecting against chronic disorders such as cancer, and inflammatory and cardiovascular diseases. Emerging findings suggest that several dietary phytochemicals also benefit the nervous system and, when consumed regularly, may reduce the risk of disorders such as Alzheimer’s and Parkinson’s diseases. The evidence supporting health benefits of vegetables and fruits provide a rationale for identification of the specific phytochemicals responsible, and for investigation of their molecular and cellular mechanisms of action. One general mechanism of action of phytochemicals that is emerging from recent studies is that they activate adaptive cellular stress response pathways. From an evolutionary perspective, the noxious properties of such phytochemicals play an important role in dissuading insects and other pests from eating the plants. However at the relatively small doses ingested by humans that consume the plants, the phytochemicals are not toxic and instead induce mild cellular stress responses. This phenomenon has been widely observed in biology and medicine, and has been described as ‘preconditioning’ or ‘hormesis’.
Hormetic pathways activated by phytochemicals may involve kinases and transcription factors that induce the expression of genes that encode antioxidant enzymes, protein chaperones, phase-2 enzymes, neurotrophic factors and other cytoprotective proteins. Specific examples of such pathways include the sirtuin – FOXO pathway, the NF-κB pathway and the Nrf-2 –ARE pathway. In this article we describe the hormesis hypothesis of phytochemical actions with a focus on the Nrf2/ARE signaling pathway as a prototypical example of a neuroprotective mechanism of action of specific dietary phytochemicals. Phytochemicals serve numerous functions in plants and contribute to their color, flavor, smell and texture. Increasing data suggest associations between the type of food people eat, their health and their life expectancy; the consumption of vegetables and fruits may protect against cancers, cardiovascular disease and neurodegenerative disorders (Heber, 2004). Phytochemicals include compounds with various biological properties (i.e. antioxidant, antiproliferative, DNA repair) which have presumably evolved, in part, to allow plants to cope with environmental challenges including exposure to radiation and toxins, and defense against pests and infectious agents (Tuteja et al., 2001; Huffman, 2003). Chemicals that are concentrated in the skin of fruits and the growing buds of vegetables include those that function as natural pesticides and, indeed, identification and large-scale production of such “biopesticides” has received much attention from both basic science and commercialization perspectives (Isman, 2006). These chemicals may be produced by the plants themselves or by endophytes (symbiotic bacteria or fungi) that live in the plants (Sudakin, 2003).
Everything is a poison, nothing is a poison. It is the dose that makes the poison” ― Paracelsus
Diets rich in vegetables, herbs, plants and fruits are associated with reduced risk of several major diseases, including neurodegenerative disorders. Although some beneficial phytochemicals might function solely as antioxidants, it is becoming clear that many of the beneficial chemicals in vegetables, herbs, plants and fruits evolved as toxins (to dissuade insects and other predators) that, at subtoxic doses, activate adaptive cellular stress-response pathways in a variety of cells including neurons. Examples of such ‘preconditioning’ or ‘neurohormesis’ pathways include those involving cell-survival signaling kinases, the transcription factors NRF2 and CREB, and histone deacetylases of the sirtuin family. In these ways, neurohormetic phytochemicals such as resveratrol, sulforaphanes and curcumin might protect neurons against injury and disease by stimulating the production of antioxidant enzymes, neurotrophic factors, protein chaperones and other proteins that help cells to withstand stress. Thus, as we discuss in this review, highly conserved longevity and survival pathways in neurons are the targets of many phytochemicals.
The term hormesis has long been used to describe the phenomenon where a specific chemical is able to induce biologically opposite effects at different doses; most commonly there is a stimulatory or beneficial effect at low doses and an inhibitory or toxic effect at high doses. In the case of natural compounds an example of hormesis is vitamin A which in relatively low amounts is essential for normal development and eye function, but in high amounts can cause anorexia, headaches, drowsiness, altered mental states and other symptoms. In the present article, we describe evidence supporting a major role for hormesis as a mechanism of action of phytochemicals on cells and organisms, with a focus on the health-promoting and neuroprotective actions of phytochemicals. The term hormesis is commonly used by toxicologists to describe biphasic dose response curve such that a chemical has a stimulatory effect at low doses, but is toxic at high doses. Recently the concept of hormesis has been adopted in the fields of biology and medicine to portray the adaptive response of cells and organisms to moderate stress. In other words, a mild stress induces the activation of signaling pathways, leading to intrinsic changes conferring resistance to a more severe stress. Typically, the stress-inducing agent elicits molecular responses that not only protect the cell against higher doses of the same agent, but also against other agents or even less specific stressors including oxidative, metabolic and thermal stress. Major components of the hormetic response include various stress resistance proteins such as heat-shock proteins, antioxidants, and growth factors. Classical examples of hormetic stress are exercise and calorie restriction (CR). Epidemiological studies have consistently demonstrated that moderate levels exercise and CR promote good health, whereas excessive levels are harmful. As mentioned above, the need to protect themselves against bacteria, fungi, viruses, and hazardous environmental changes, has lead plants to concentrate defensive chemicals in their most vulnerable parts (i.e. leaves, flowers and roots). Like moderate exercise or CR, many of these ‘poisons’ also exhibit hormetic properties, being harmful at high doses yet beneficial at relevantly low doses.
The Following are just some examples of Hormetic Compounds: Neurohormetic phytochemicals: low-dose toxins that induce adaptive neuronal stress responses.
Although some phytochemicals possess direct free radical-scavenging properties at high concentrations, in lower amounts typical of those obtained in the diet, phytochemicals may activate one or more adaptive cellular stress responses pathways. Activation of such hormetic pathways in neurons results in the production of several types of cytoprotective proteins including neurotrophic factors, protein chaperones, antioxidant and phase II enzymes and anti-apoptotic proteins. One specific pathway that is receiving considerable attention in regards to hormesis in the nervous system involves the transcription factor Nrf2 which binds the ARE, thereby inducing the expression of genes encoding phase II detoxifying enzymes. Preclinical and clinical studies of the therapeutic potential of phytochemicals that activate the Nrf2/ARE pathway (curcumin, for example) in several different neurodegenerative disorders are in progress. Other hormetic pathways involved in neuronal stress resistance and plasticity include those that activate FOXO and NF-κB transcription factors. Using neurohormetic phytochemicals as base compounds for medicinal chemistry will likely result in the development of a range of plant based nootropics that enhance neuroplasticity and protect against synaptic dysfunction and neurodegeneration. Try our range of nootropics at Plant Based Academy made using some of the powerful ingredients listed below.
Compelling evidence from epidemiological studies suggest beneficial roles of dietary phytochemicals in protecting against chronic disorders such as cancer, and inflammatory and cardiovascular diseases. Emerging findings suggest that several dietary phytochemicals also benefit the nervous system and, when consumed regularly, may reduce the risk of disorders such as Alzheimer’s and Parkinson’s diseases. The evidence supporting health benefits of vegetables and fruits provide a rationale for identification of the specific phytochemicals responsible, and for investigation of their molecular and cellular mechanisms of action. One general mechanism of action of phytochemicals that is emerging from recent studies is that they activate adaptive cellular stress response pathways. From an evolutionary perspective, the noxious properties of such phytochemicals play an important role in dissuading insects and other pests from eating the plants. However at the relatively small doses ingested by humans that consume the plants, the phytochemicals are not toxic and instead induce mild cellular stress responses. This phenomenon has been widely observed in biology and medicine, and has been described as ‘preconditioning’ or ‘hormesis’. Hormetic pathways activated by phytochemicals may involve kinases and transcription factors that induce the expression of genes that encode antioxidant enzymes, protein chaperones, phase-2 enzymes, neurotrophic factors and other cytoprotective proteins. Specific examples of such pathways include the sirtuin – FOXO pathway, the NF-κB pathway and the Nrf-2 –ARE pathway. In this article we describe the hormesis hypothesis of phytochemical actions with a focus on the Nrf2/ARE signaling pathway as a prototypical example of a neuroprotective mechanism of action of specific dietary phytochemicals.
In summary All these compounds do at least two things:
Phase 1 biotransformation enzymes convert pro carcinogens into their active carcinogenic state. Phase 2 enzymes are major detoxification enzymes and an important part of cellular defense against carcinogens, oxidants, and other toxic chemicals
There are thousands of phytochemicals divided into many classes and subclasses, many of them are considered powerful Plant Hormetic compounds activating our endogenous antioxidant system, some more understood than others. In this section we will attempt to present many of these compounds, their classification and subclassifications.
There are four major classes of polyphenols;
Furthermore, each of these polyphenol classes has further subclasses which contain different polyphenolic compounds. To illustrate, you can see some of these subclasses below along with some of the foods that contain them;
Flavonoids: We can divide flavonoids into various subclasses and over 400 compounds.
Lignans: We can commonly find lignans in fibrous plant foods, with seeds being a particularly high source. Specifically, flax seeds are the world’s best source of lignans. There is only one sub-class of lignans and it contains 53 polyphenols.
Phenolic Acids: There are various subclasses of phenolic acids and 168 different compounds.
Stilbenes: There is one subclass of stilbenes and it contains 27 compounds. In fact, you probably know the most prevalent of these. The name is Resveratrol and it’s a major constituent of red wine but also found in many red and purple fruits and vegetables.
Phytochemical Explained Further: Phytochemical benefits include
Anticancer activities: Block tumour formation, Reduce cell proliferation, Reduce oxidative damage to DNA, Repair DNA damage & Induce enzyme systems that help rid the body of carcinogens (cancer-causing substances).
Antioxidant activities: Neutralise free radicals, which damage vital components of cells, including DNA
Anti-estrogenic and weak estrogenic activities : Anti-estrogenic effects may reduce the risk of hormone-related cancers. Weak estrogenic effects could help maintain bone density and improve blood cholesterol levels.
Cardiovascular protective activities: Decrease damage to blood vessel walls, Decrease oxidation of LDL cholesterol, Decrease platelet stickiness, Increase blood flow, Lower blood pressure, Reduce blood cholesterol levels, Reduce blood clot formation and Slow cholesterol synthesis.
Immune-enhancing activities: Increase activity of cells that protect the body from microoragisms that cause disease and Modulation of cell-signaling pathways, which regulate the growth, division and death of cells.
Phytochemical’s, Class & subclass type, their sources and activities:
Phenols and polyphenols
Monopenols: ( Carnosol & Carvacrol)
Carnosol: Food sources: Rosemary
Activities: Antioxidant, anti-inflammatory, anticancer
Carvacrol : Food sources: Oregano, thyme
Flavonoids (Polyphenols): ( Anthocyanin & Flavones)
Anthocyanin: Food sources: Purple/Blue foods such as blackberries, black currants, blueberries, cherries, plums
Flavones (such as Apigenin, Luteolin and Tangeritin): Food sources: Celery, parsley, thyme
Activities: Beneficial effects against atherosclerosis, certain cancers, diabetes, osteoporosis
(Flavonols, Flavanols, Flavanones & Isolflavones)
Flavonols (such as kaempferol, myricetin and quercetin): Food sources: Apples, berries, broccoli, cherries, green tea, onions, red wine
Activities: Anticancer, antihypertensive, anti-inflammatory, antimutagenic
Flavanols (such as Cathechins, Epicatechins and proanthocyanidins): Food sources: Dark chocolate, grapes, green tea, red wine, white tea
Activities: Antitumor, anticardiovascular disease activity
Flavanones (such as Eriodictyol, Hesperetin and Naringenin): Food sources: Citrus fruits
Activities: Antiallergenic, anticancer, anti-inflammatory, antimicrobial
Isoflavones (such as Coumestrol, Daidzein, Genestein and Glycitein): Food sources: Soybeans, Soybean products
Activities: Exert weak pro- and antiestrogenic effects
(Capasaicin, Curcumin, Ellagic Acid, Salicylic Acid, Tannic Acid, Vanillin, Hydroxycinnamic Acid, Zingerone, Caffeic Acid, Coumaric Acid & Ferulic Acid)
Capsaicin: Food sources: Chiles
Activities: Analgesic, anti-inflammatory, possible antitumor
Capsaicin: Food sources: Chiles
Activities: Analgesic, anti-inflammatory, possible antitumor
Curcumin: Food sources: Turmeric
Activities: Anticancer, anti-inflammatory, antioxidant, wound healing
Ellagic acid: Food sources: Berries, grapes, nuts, pomegranates
Salicylic acid: Food sources: Almonds, certain spices, fruits, peanuts, some vegetables
Activities: Anticancer, anticardiovascular disease
Tannic Acid or Tannins (such as gallic acid): Food sources: Tea and red wine
Activities: Antioxidant (note: tannins reduce the absorption of trace minerals, particularly non-heme iron)
Vanillin: Food sources: Vanilla beans, cloves
Zingerone (Metabolized from Gingerol): Food sources: Ginger
Activities: Anti-inflammatory, antioxidant, antinausea
Hydroxycinnamic acids: ( Caffeic Acids, Coumaric Acid & Ferulic Acid)
Caffeic acid: Food sources: Coffee, some vegetables and fruits
Coumaric acids: Food sources: Basil, carrots, grapes, green peppers, peanuts, pineapple, strawberries, tomatoes, turmeric, wine
Activities: Anticancer, antioxidant
Ferulic acid: Food sources: Cereal brans, cumin
Resveratrol: Food sources: Grapes, peanuts, red wine
Activities: Antioxidant, antihrombotic, inhibits carcinogenesis
Lariciresinol, Matairesinol, Pinoresinol and Secoisolariciresinol: Food sources: Beans, grains, seeds (flax, pumkpin and sesame), some vegetables and fruits
Activities: Antioxidant, phytoestrogenic
Terpenes and Terpenoids: ( Carotenoids, Monoterpenes, Saponins, Thiols)
Carotenoids: (Pro Vitamin A Converts to Vitamin A)
Alpha-Carotene ( Pro Vitamin A): Food sources: Orange and yellow vegetables
Activities: Antioxidant, immune system enhancer
Beta-carotene ( Pro Vitamin A): Food sources: Green leafy vegetables, orange and yellow vegetables
Activities: Antioxidant, immune systen enhancer
Beta-Cryptoxanthin ( Pro Vitamin A): Food sources: Orange and red fruits and vegetables
Activities: Antioxidant, immune system enhancer
Lutein: Food sources: Dark green leafy vegetables
Activities: Filters out harmful light, protects against macular degeneration
Lycopene: Food sources: Red grapefruit, tomatoes, watermelon
Activities: Reduces risk of prostate cancer, may inhibit all cancer cell growth
Zeaxanthin: Food sources: Corn, dark green leafy vegetables
Activities: Filters out harmful light, protects against macular degeneration
Monoterpenes: ( Limonoids & Phytosterols)
Limonoids: Food sources: Citrus fruits
Activities: Cardioprotective, induces enzyme systems required for detoxification of carcinogens
Phytosterols: (Beta-Sitosterol, Campesterol, Stigmasterol)
Beta-Sitosterol, Campesterol, Stigmasterol: Food sources: Corn, dark chocolate, legumes, nuts, seeds, soybeans, vegetable oils, whole grains
Activities: Reduces cholesterol absorption and total and LDL cholesterol
Saponins: Food sources: Legumes, especially adaptogenic herbs, soybeans, vegetables
Activities: Anticancer, antioxidant, cholesterol lowering, immune-enhancing
Thiols (Organosulfur Compounds) & Glucosinolates: (Indoles, Isothiocyanates, Ajoenes, Allicin, Allylic Sulfides, Vinyl Dithiins)
Indoles (such as indolyl-3-carbinol): Food sources: Cruciferous vegetables
Activities: Anticancer, favorably influences estrogen metabolism
Isothiocyanates (such as Sulforaphane): Food sources: Cruciferous vegetables
Activities: Anticancer, potent inducers of Phase 2 enzymes Thiosulfinates:
Ajoenes, Allicin, Allylic Sulfides, Vinyl Dithiins: Food sources: Allium vegetables
Activities: Antibacterial, anticancer, antifungal, antiviral, cardioprotective
Although colourful fruits and vegetables are the phytochemical champions, legumes, nuts, seeds, grains, spices and teas all deserve an honourable mention. The benefits of phytochemical seem to be much more pronounced when we consume whole plant based foods rather than supplements, as the natural combination of beneficial compounds in a whole food appears to have a synergistic effect. A summary of those compounds of which have been scientifically studied extensively and validated as powerful anti cancer pharmaceuticals in addition to complex sugars and fibre such as the polysaccharides Beta Glucan found in medicinal mushrooms are Below. Polyphenols are secondary metabolites of plants and are generally involved in defense against ultraviolet radiation or aggression by pathogens. In the last decade, there has been much interest in the potential health benefits of dietary plant polyphenols as antioxidant. Epidemiological studies and associated meta-analyses strongly suggest that long term consumption of diets rich in plant polyphenols offer protection against development of cancers, cardiovascular diseases, diabetes, osteoporosis and neurodegenerative diseases. Here we present knowledge about the biological effects of plant polyphenols in the context of relevance to human health.
Plant Hormetic compounds:
PolyPhenols & AntiCancer Properties :
Polyphenols can form potentially toxic quinones producing a defense agent toxic xenobiotics. Albumin plays an important role in the bioavailability of polyphenols. All phenolic compounds arise from phenylalanine or shikimic acid in plants. Dietary polyphenols are a diverse and complex group of compounds that are linked to human health. Many of their effects have been attributed to the ability to poison (i.e., enhance DNA cleavage by) topoisomerase II. Polyphenols act against the enzyme by at least two different mechanisms. Some compounds are traditional, redox-independent topoisomerase II poisons, interacting with the enzyme in a noncovalent manner. Conversely, others enhance DNA cleavage in a redox-dependent manner that requires covalent adduction to topoisomerase II. Unfortunately, the structural elements that dictate the mechanism by which polyphenols poison topoisomerase II have not been identified. To resolve this issue, the activities of two classes of polyphenols against human topoisomerase IIα were examined. The first class was a catechin series, including (−)-epigallocatechin gallate (EGCG), (−)-epigallocatechin (EGC), (−)-epicatechin gallate (ECG), and (−)-epicatechin (EC). The second was a flavonol series, including myricetin, quercetin, and kaempferol. Compounds were categorized into four distinct groups: EGCG and EGC were redox-dependent topoisomerase II poisons, kaempferol and quercetin were traditional poisons, myricetin utilized both mechanisms, and ECG and EC displayed no significant activity. Based on these findings, a set of rules is proposed that predicts the mechanism of bioflavonoid action against topoisomerase II. The first rule centers on the B ring. While the C4’-OH is critical for the compound to act as a traditional poison, the addition of –OH groups at C3’ and C5’ increases the redox activity of the B ring and allows the compound to act as a redox-dependent poison. The second rule centers on the C ring. The structure of the C ring in the flavonols is aromatic, planar, and includes a C4-keto group that allows the formation of a proposed pseudo ring with the C5-OH. Disruption of these elements abrogates enzyme binding and precludes the ability to function as a traditional topoisomerase II poison.
Beta-glucans are naturally occurring polysaccharides. These glucose polymers are constituents of the cell wall of certain pathogenic bacteria and fungi. The healing and immunostimulating properties of mushrooms have been known for thousands of years in the Eastern countries. These mushrooms contain biologically active polysaccharides that mostly belong to group of beta-glucans. These substances increase host immune defense by activating complement system, enhancing macrophages and natural killer cell function. The induction of cellular responses by mushroom and other beta-glucans is likely to involve their specific interaction with several cell surface receptors, as complement receptor 3 (CR3; CD11b/CD18), lactosylceramide, selected scavenger receptors, and dectin-1 (betaGR). beta-Glucans also show anticarcinogenic activity. They can prevent oncogenesis due to the protective effect against potent genotoxic carcinogens. As immunostimulating agent, which acts through the activation of macrophages and NK cell cytotoxicity, beta-glucan can inhibit tumor growth in promotion stage too. Anti-angiogenesis can be one of the pathways through which beta-glucans can reduce tumor proliferation, prevent tumor metastasis. beta-Glucan as adjuvant to cancer chemotherapy and radiotherapy demonstrated the positive role in the restoration of hematopiesis following by bone marrow injury. Immunotherapy using monoclonal antibodies is a novel strategy of cancer treatment. These antibodies activate complement system and opsonize tumor cells with iC3b fragment. In contrast to microorganisms, tumor cells, as well as other host cells, lack beta-glucan as a surface component and cannot trigger complement receptor 3-dependent cellular cytotoxicity and initiate tumor-killing activity. This mechanism could be induced in the presence of beta-glucans.
Catechins (Flavonoid) (matcha) – Topoisomerase Poisoning Effect. Works more effectively than popular anticancer drugs – Chemo also targets Topoisomerase ll
C – Catechin
EC – EPIcatechin
EGC – Epigallocatechin
ECG – Epicatechingallat
EGCG – Epgiallocatechingallet
Kaempferol – Also anti cancer & works like chemo. Promotes apoptosis in malignant cells – chemo drugs. Found in broccoli, strawberries, kale, wheatgrass & blueberries
Kaempferol is a polyphenol antioxidant found in fruits and vegetables. Many studies have described the beneficial effects of dietary kaempferol in reducing the risk of chronic diseases, especially cancer. Epidemiological studies have shown an inverse relationship between kaempferol intake and cancer. Kaempferol may help by augmenting the body’s antioxidant defense against free radicals, which promote the development of cancer. At the molecular level, kaempferol has been reported to modulate a number of key elements in cellular signal transduction pathways linked to apoptosis, angiogenesis, inflammation, and metastasis. Significantly, kaempferol inhibits cancer cell growth and angiognesis and induces cancer cell apoptosis, but on the other hand, kaempferol appears to preserve normal cell viability, in some cases exerting a protective effect.
Quercetin – Red onions, ginkgo, raw capers and blueberries
Quercetin is a natural flavonoid found abundantly in vegetables and fruits. There is growing evidence suggesting that quercetin has therapeutic potential for the prevention and treatment of different diseases, including cardiovascular disease, cancer, and neurodegenerative disease. Mechanistically, quercetin has been shown to exert antioxidant, anti-inflammatory, and anticancer activities in a number of cellular and animal models, as well as in humans through modulating the signaling pathways and gene expression involved in these processes. This chapter focuses on experimental studies supporting the anticancer, cardioprotective, and neuroprotective effects of quercetin.
Flavoinoids & Terpenes:
Flavonoids are one of the largest nutrient families known to scientists, and include over 6,000 already-identified family members. About 20 of these compounds, including apigenin, quercetin, cannflavin A and cannflavin B (so far unique to cannabis), β-sitosterol, vitexin, isovitexin, kaempferol, luteolin and orientin have been identified in the cannabis plant and should generally be available via CBD oil. Flavonoids and terpenes are known for their antioxidant and anti-inflammatory health benefits, as well as their contribution of vibrant color and powerful scent to the many of the foods we eat (the blue in blueberries, the red in raspberries, the scent and oils from clove and ginger). Lions Mane is a great example of a food source loaded with terpenes. Hericium erinaceus, most commonly known as lion’s mane, is an edible fungus, with a long history of use in Traditional Chinese Medicine. The mushroom is abundant in bioactive compounds including β-glucan polysaccharides; hericenones and erinacine terpenoids; isoindolinones; sterols; and myconutrients, which potentially have neuroprotective and neuroregenerative properties. Because of its anti-inflammatory properties and promotion of nerve growth factor gene expression and neurite (axon or dendrite) outgrowth, H. erinaceus mycelium shows great promise for the treatment of Alzheimer’s and Parkinson’s diseases. Lions Mane has become a very popular Nootropic for very good reasons.
Terpenes and terpenoids are known as secondary metabolites since they are formed due to the enzymatic resections of primary metabolites (amino acids, sugars, vitamins, etc.). Terpenes belong to the biggest class of secondary metabolites and basically consist of five carbon isoprene units which are assembled to each other (many isoprene units) by thousands of ways. Terpenes are simple hydrocarbons, while terpenoids are modified class of terpenes with different functional groups and oxidized methyl group moved or removed at various positions. Terpenoids are divided into monoterpenes, sesquiterpenes, diterpenes, sesterpenes, and triterpenes depending on its carbon units. Most of the terpenoids with the variation in their structures are biologically active and are used worldwide for the treatment of many diseases. Many terpenoids inhibited different human cancer cells and are used as anticancer drugs such as Taxol and its derivatives. Many flavorings and nice fragrances are consisting on terpenes because of its nice aroma. Terpenes and its derivatives are used as antimalarial drugs such as artemisinin and related compounds. Meanwhile, terpenoids play a diverse role in the field of foods, drugs, cosmetics, hormones, vitamins, and so on. Terpenes have been found to be essential building blocks of complex plant hormones and molecules, pigments, sterols and even cannabinoids. Most notably, terpenes are responsible for the pleasant, or not so pleasant, aromas of cannabis and the physiological effects associated with them. Terpenes also play an incredibly important role by providing the plant with natural protection from bacteria and fungus, insects and other environmental stresses. Terpenes act on receptors and neurotransmitters; they are prone to combine with or dissolve in lipids or fats; they act as serotonin uptake inhibitors (similar to antidepressants like Prozac); they enhance norepinephrine activity (similar to tricyclic antidepressants like Elavil); they increase dopamine activity; and they augment GABA (the “downer” neurotransmitter that counters glutamate, the “upper”). However, more specific research is needed for improved accuracy in describing and predicting how terpenes in cannabis can be used medicinally to help treat specific ailments / health conditions.
Monoterpenes: Monoterpenes consist of 10 carbon atoms with two isoprene units and molecular formula C10H16. These are naturally present in the essential and fixed oils of plants and relatedsources. Monoterpenes are structurally divided into the acyclic, monocyclic, and bicyclic type of compound. The compounds belong to this class usually have strong aroma and odor and are used in many pharmaceutical companies. Mixture of different monoterpene-based oils is used as fragrances for making perfumes and in other cosmetics. Most of the monoterpenes are active biologically with strong antibacterial activities. Several studies have shown in vitro and in vivo antitumor activity of many essential oils obtained from plants. The antitumor activity of essential oils of many species has been related to the presence of monoterpenes in their composition
Sesquiterpenes : Sesquiterpenes are the class of secondary metabolites consisting of three isoprene units (C15H24) and found in linear, cyclic, bicyclic, and tricyclic forms. Sesquiterpenes are also found in the form of lactone ring. Many of the latex in latex-producing plants contain sesquiterpene, and these are potent antimicrobial and anti-insecticidal agent. Artemisinin, a sesquiterpene lactone, one of the most active compounds in Artemisia annuashoots and roots.
Diterpenoids : Diterpenoids belong to a versatile class of chemical constituents found in different natural sources having C20H32 molecular formula and four isoprene units. This class of compounds showed significant biological activities including anti-inflammatory, antimicrobial, anticancer, and antifungal activities. Some of the diterpenes also have cardiovascular activity, such as grayanotoxin, forskolin, eleganolone, marrubenol, and 14-deoxyandrographolide. Kaurane and pimarane-type diterpenes are also biologically active metabolites isolated from the roots and leaves of different plants.
Sesterpenes: Sesterpenes consist of 25 carbon atoms with 5 isoprene units and molecular formula C25H40. These are naturally present in the fungus, marine organism, insects, sponges, lichens, and protective waxes of insects. These types of compounds are biologically active having anti- inflammatory, anticancer, antimicrobial, and antifungal activities
Triterpenes: A major class of secondary metabolites are known as triterpenes and it usually contains 30 carbon atoms consisting of 6 isoprene units. It is derived from the squalene biosynthetic pathway. Triterpenes have many methyl groups and it can be oxidized into alcohols, aldehydes, and carboxylic acids, which make it complex and differentiate it biologically. Triterpenes have many active sites for the glycosylation which converts it into another big class of compounds, namely, saponins (triterpene glycoside). Herein, we are discussing some recently published bioactive triterpenes
Meroterpenes: Meroterpenes are the secondary metabolites with partial terpenoid skeleton. Meroterpenoids were partially derived from mevalonic acid pathways and widely derived from animals, plants, bacteria, and fungi. Meroterpene biosynthesis expands the diversity available to isoprenoid pathways alone and allows for the assembly of natural products with highly unique structural attributes. Organisms belonging to the fungal kingdom have become proficient at exploiting this broad chemical synthesis platform for complex metabolite production. Herein, we are discussing some of the recently published bioactive meroterpenes
Myrcene, specifically β-myrcene, is a monoterpene and the most common terpene produced by cannabis (some varieties contain up to 60% of the essential oil). Its aroma has been described as musky, earthy, herbal – akin to cloves. A high myrcene level in cannabis (usually above 0.5%) results in the well-known “couch-lock” effect of classic Indica strains. Myrcene is found in oil of hops, citrus fruits, bay leaves, eucalyptus, wild thyme, lemon grass and many other plants. Myrcene has some very special medicinal properties, including lowering the resistance across the blood to brain barrier, allowing itself and many other chemicals to cross the barrier easier and more quickly. In the case of cannabinoids (like THC), myrcene allows the effects of the cannabinoid to take effect more quickly. More uniquely still, myrcene has been shown to increase the maximum saturation level of the CB1 receptor, allowing for a greater maximum psychoactive effect. Myrcene is a potent analgesic, anti-inflammatory, antibiotic and antimutagenic. It blocks the action of cytochrome, aflatoxin B and other pro-mutagenic carcinogens. The Bonamin et al study focused on the role of β-myrcene in preventing peptic ulcer disease. The study revealed that β-myrcene acts as an inhibitor of gastric and duodenal ulcers, suggesting it may be helpful in preventing peptic ulcer disease. Its sedative and relaxing effects also make it ideal for the treatment of insomnia and pain. Since myrcene is normally found in essential oil from citrus fruit, many claim eating a fresh mango about 45 minutes before consuming cannabis will result in a faster onset of psycho activity and greater intensity. Be sure to choose a mango that is ripe otherwise the myrcene level will be too low to make a difference.
Pinene is a bicyclic monoterpenoid. Akin to its name, pinene has distinctive aromas of pine and fir. There are two structural isomers of pinene found in nature: α-pinene and β-pinene. Both forms are important components of pine resin. α-pinene is the most widely encountered terpenoid in nature. Pinene is found in many other conifers, as well as in non-coniferous plants. It is found mostly in balsamic resin, pine woods and some citrus fruits. The two isomers of pinene constitute the main component of wood turpentine. Pinene is one of the principal monoterpenes that is important physiologically in both plants and animals. It tends to react with other chemicals, forming a variety of other terpenes (like limonene) and other compounds. Pinene is used in medicine as an anti-inflammatory, expectorant, bronchodilator and local antiseptic. α-pinene is a natural compound isolated from pine needle oil which has shown anti-cancer activityand has been used as an anti-cancer agent in Traditional Chinese Medicine for many years. It is also believed that the effects of THC may be lessened if mixed with pinene.
Limonene is a monocyclic monoterpenoid and one of two major compounds formed from pinene. As the name suggests, varieties high in limonene have strong citrusy smells like oranges, lemons and limes. Strains high in limonene promote a general uplift in mood and attitude. This citrusy terpene is the major constituent in citrus fruit rinds, rosemary, juniper and peppermint, as well as in several pine needle oils. Limonene is highly absorbed by inhalation and quickly appears in the bloodstream. It assists in the absorption of other terpenes through the skin and other body tissue. It is well documented that limonene suppresses the growth of many species of fungi and bacteria, making it an ideal antifungal agent for ailments such as toenail fungus. Limonene may be beneficial in protecting against various cancers, and orally administered limonene is currently undergoing clinical trials in the treatment of breast cancer. Limonene has been found to even help promote weight-loss. Plants use limonene as a natural insecticide to ward off predators. Limonene was primarily used in food and perfumes until a couple of decades ago, when it became better known as the main active ingredient in citrus cleaner. It has very low toxicity and adverse effects are rarely associated with it.
Beta-caryophyllene is a sesquiterpene found in many plants such as Thai basils, cloves, cinnamon leaves and black pepper, and in minor quantities in lavender. It’s aroma has been described as peppery, woody and/or spicy. Caryophyllene is the only terpene known to interact with the endocannabinoid system (CB2). Studies show β–caryophyllene holds promise in cancer treatment plans. Research shows shows that β–caryophyllene selectively binds to the CB2 receptor and that it is a functional CB2 agonist. Further, β–caryophyllene was identified as a functional non-psychoactive CB2 receptor ligand in foodstuff and as a macrocyclic anti-inflammatory cannabinoid in cannabis. The Fine/Rosenfeld pain study demonstrates that other phytocannabinoids in combination, especially cannabidiol (CBD) and β-caryophyllene, delivered by the oral route appear to be promising candidates for the treatment of chronic pain due to their high safety and low adverse effects profiles. The Horváth et al study suggests β-caryophyllene, through a CB2 receptor dependent pathway, may be an excellent therapeutic agent to prevent nephrotoxicity (poisonous effect on the kidneys) caused by anti-cancer chemotherapy drugs such as cisplatin. The Jeena, Liju et al study investigated the chemical composition of essential oil isolated from black pepper, of which caryophyllene is a main constituent, and studied its pharmacological properties. Black pepper oil was found to possess antioxidant, anti-inflammatory and antinociceptive properties. This suggests that high-caryophyllene strains may be useful in treating a number of medical issues such as arthritis and neuropathy pain. Beta-caryophyllene is used especially in chewing gum when combined with other spicy mixtures or citrus flavorings.
Linalool is a non-cyclic monoterpenoid and has been described as having floral and lavender undertones. Varieties high in linalool promote calming, relaxing effects. Linalool has been used for centuries as a sleep aid. Linalool lessens the anxious emotions provoked by pure THC, thus making it helpful in the treatment of both psychosis and anxiety. Studies also suggest that linalool boosts the immune system; can significantly reduce lung inflammation; and can restore cognitive and emotional function (making it useful in the treatment of Alzheimer’s disease). As shown by the Ma, J., Xu et al study, linalool may significantly reduce lung inflammation caused by cigarette smoke by blocking the carcinogenesis induced by benz[α]anthracene, a component of the tar generated by the combustion of tobacco. This finding indicates limonene may be helpful in reducing the harm caused by inhaling cannabis smoke. Linalool boosts the immune system as it directly activates immune cells through specific receptors and/or pathways. The Sabogal-Guáqueta et al study suggests linalool may reverse the histopathological (the microscopic examination of biological tissues to observe the appearance of diseased cells and tissues in very fine detail) hallmarks of Alzheimer’s Disease and could restore cognitive and emotional functions via an anti-inflammatory effect. The Environmental Protection Agency has approved its use as a pesticide, flavor agent and scent. It is used in a wide variety of bath and body products and is commonly listed under ingredients for these products as beta linalool, linalyl alcohol, linaloyl oxide, p-linalool and alloocimenol. Its vapors have been shown to be an effective insecticide against fruit flies, fleas and cockroaches. Linalool has been isolated in several hundred different plants. The Lamiaceae plant and herb family, which includes mints and other scented herbs, are common sources. The Lauraceae plant family, which includes laurels, cinnamon, and rosewood, is also a readily available source. The Rutaceae family, which contains citrus plants, is another viable source. Birch trees and several different plant species that are found in tropical and boreal climate zones also produce linalool. Although technically not plants, some fungi produce linalool, as well. Linalool is a critical precursor in the formation of Vitamin E.
Terpinolene is a common component of sage and rosemary and is found in the oil derived from Monterey cypress. Its largest use in the United States is in soaps and perfumes. It is also a great insect repellent. Terpinolene is known to have a piney aroma with slight herbal and floral nuances. It tends to have a sweet flavor reminiscent of citrus fruits like oranges and lemons. Terpinolene has been found to be a central nervous system depressant used to induce drowsiness or sleep or to reduce psychological excitement or anxiety. Further, terpinolene was found to markedly reduce the protein expression of AKT1 in K562 cells and inhibited cell proliferation involved in a variety of human cancers.
Camphene, a plant-derived monoterpene, emits pungent odors of damp woodlands and fir needles. Camphene may play a critical role in cardiovascular disease. The Vallianou et al study found camphene reduces plasma cholesterol and triglycerides in hyperlipidemic rats. Given the importance that the control of hyperlipidemia plays in heart disease, the results of this study provide insight into to how camphene might be used as an alternative to pharmaceutical lipid lowering agents which are proven to cause intestinal problems, liver damage and muscle inflammation. This finding alone warrants further investigation. Camphene is a minor component of many essential oils such as turpentine, camphor oil, citronella oil and ginger oil. It is used as a food additive for flavoring, and also used in the preparation of fragrances. It is produced industrially by catalytic isomerization of the more common α-pinene.
α-Terpineol, terpinen-4-ol, and 4-terpineol are three closely related monoterpenoids. The aroma of terpineol has been compared to lilacs and flower blossoms. Terpineol is often found in cannabis varieties that have high pinene levels, which unfortunately mask the fragrant aromas of terpineol. Terpineol, specifically α-terpineol, is known to have calming, relaxing effects. It also exhibits antibiotic, AChe inhibitor and antioxidant antimalarial properties. Other sources are essential oils of cajuput, pine and petit grain.
Phellandrene is described as pepperminty, with a slight scent of citrus. Phellandrene is believed to have special medicinal values. It has been used in Traditional Chinese Medicine to treat digestive disorders. It is one of the main compounds in turmeric leaf oil, which is used to prevent and treat systemic fungal infections. Phellandrene is perhaps the easiest terpene to identify in the lab. When a solution of phellandrene in a solvent (or an oil containing phellandrene) is treated with a concentrated solution of sodium nitrate and then with a few drops of glacial acetic acid, very large crystals of phellandrene nitrate speedily form. Phellandrene was first discovered in eucalyptus oil. It wasn’t until the early 1900s that it was actually constituted and shown that phellandrene from eucalyptus oil contained two isomeric phellandrene (usually referred to as α-phellandrene and β-phellandrene), and on oxidation with potassium permanganate gave distinct acids, concluding that the acids had been derived from two different isomeric phellandrene. Before that, phellandrene was mistaken for pinene or limonene. Today, we are aware of many essential oils where phellandrene is present. It is, however, a somewhat uncertain terpene as it can only be detected in the oils of some species, especially in Eucalypts, at particular times of the year. Phellandrene can be found in a number of herbs and spices, including cinnamon, garlic, dill, ginger and parsley. A number of plants produce β-phellandrene as a constituent of their essential oils, including lavender and grand fir. The recognizable odors of some essential oils depend almost entirely upon the presence of phellandrene. Oil of pepper and dill oil are composed almost entirely of phellandrene. The principal constituent in oil of ginger is phellandrene. Phellandrene, particularly α-phellandrene, is absorbed through the skin, making it attractive for use in perfumes. It is also used as a flavoring for food products.
Delta-3-carene is a bicyclic monoterpene with a sweet, pungent odor. It is found naturally in many healthy, beneficial essential oils, including cypress oil, juniper berry oil and fir needle essential oils. In higher concentrations, delta-3-carene can be a central nervous system depressant. It is often used to dry out excess body fluids, such as tears, mucus, and sweat. It is nontoxic, but may cause irritation when inhaled. Perhaps high concentrations of delta-3-carene in some strains may be partially responsible for symptoms of coughing, itchy throat and eye afflictions when smoking cannabis. Delta-3-carene is also naturally present in pine extract, bell pepper, basil oil, grapefruit and orange juices, citrus peel oils from fruits like lemons, limes, mandarins, tangerines, oranges and kumquats. Carene is a major component of turpentine and is used as a flavoring in many products.
Humulene is a sesquiterpene also known as α-humulene and α–caryophyllene; an isomer of β–caryophyllene. Humulene is found in hops, cannabis sativa strains, and Vietnamese coriander, among other naturally occurring substances. Humulene is what gives beer its distinct ‘hoppy’ aroma. Humulene is considered to be anti-tumor, anti-bacterial, anti-inflammatory, and anorectic (suppresses appetite). It has commonly been blended with β–caryophyllene and used as a major remedy for inflammation. Humulene has been used for generations in Chinese medicine. It aids in weight loss by acting as an appetite suppressant.
Pulegone, a monocyclic monoterpenoid, is a minor component of cannabis. Higher concentrations of pulegone are found in rosemary. Rosemary breaks down acetylcholine in the brain, allowing nerve cells to communicate more effectively with one another. An ethnopharmacology study indicates pulegone may have significant sedative and fever-reducing properties. It may also alleviate the side effects of short-term memory loss sometimes associated with higher levels of THC. Pulegone has a pleasant peppermint aroma and is considered to be a strong insecticide.
Sabinene is a bicyclic monoterpene whose aromas are reminiscent of the holidays (pines, oranges, spices). Results of an ongoing study by Valente et al suggest that sabinene should be explored further as a natural source of new antioxidant and anti-inflammatory drugs for the development of food supplements, nutraceuticals or plant-based medicines. Sabinene occurs in many plants, including Norway spruce, black pepper, basil and Myristica fragrans (an evergreen indigenous to the Moluccas)—the Spice Islands of Indonesia. The seeds of the Myristica fragrans are the world’s main source of nutmeg. Sabinene exists as (+)- and (–)-enantiomers.
Geraniol produces a sweet, delightful smell similar to roses. This makes geraniol a popular choice for many bath and body products. It is also known to be an effective mosquito repellant. Medically, geraniol shows promise in the treatment of neuropathy.
Plant Hormetic Compounds in Adaptogenic Herbs:
Adaptogens are harmless herbs which have pharmaceutical benefits due to their balancing regulative and tonic functions: All resemble corticosteroids that act as stress hormones involved in protective inactivation of the stress system. Adaptogens were initially defined as substances that enhance the “state of non-specific resistance” in stress, a physiological condition that is linked with various disorders of the neuroendocrine-immune system. Studies on animals and isolated neuronal cells have revealed that adaptogens exhibit neuroprotective, anti-fatigue, antidepressive, anxiolytic, nootropic and CNS stimulating activity. In addition, a number of clinical trials demonstrate that adaptogens exert an anti-fatigue effect that increases mental work capacity against a background of stress and fatigue, particularly in tolerance to mental exhaustion and enhanced attention. Indeed, recent pharmacological studies of a number of adaptogens have provided a rationale for these effects also at the molecular level. It was discovered that the stress—protective activity of adaptogens was associated with regulation of homeostasis via several mechanisms of action, which was linked with the hypothalamic-pituitary-adrenal axis and the regulation of key mediators of stress response, such as molecular chaperons (e.g., HSP70), stress-activated c-Jun N-terminal protein kinase 1 (JNK1), Forkhead box O (FOXO) transcription factor DAF-16, cortisol and nitric oxide.
– Anti fatigue
– Anti depressive
– CNS stimulating activity
– Anti toxic activity
Complex phenolics and tetracyclic triterpenoids (steroids)
– Cucurbitancin R
– Phytosterol glycosides
– Eleutheroside A
Monoterpene – Glucoside rosindrin (Rhodiola)
Phenolic compounds – phenylpropanoids
– Schisandrin B
Found in various medicinal plants, notably in foxgloves and in lily of the valley, cardiac glycosides such as digitoxin, digoxin and convallotoxin have a strong, direct action on the heart, supporting its strength and rate of contraction when it is failing. Cardiac glycosides are also significantly diuretic. They help to stimulate urine production, thus increasing the removal of fluid from the tissues and circulatory system.
Though these glycosides are based on cyanide, a very potent poison, in small doses they have a helpful sedative and relaxant effect on the heart and muscles. The bark of wild cherry and the leaves of elder both contain cyanogenic glycosides, which contribute to the plant’s ability to suppress and soothe irritant dry coughs. Many fruit kernels contain high levels of cyanogenic glycosides, for example those of apricot.
Found in all plants, polysaccharides are multiple units of sugar molecules linked together. From a herbal point of view, the most important polysaccharides are the “sticky” mucilages and gums, which are commonly found in roots, bark, leaves and seeds. Both mucilage and gum soak up large quantities of water, producing a sticky, jelly-like mass that can be used to soothe and protect irritated tissue, for example, dry irritated skin and sore or inflamed mucous membranes in the gut. Mucilaginous herbs, such as slippery elm and linseed or flaxsee are best prepared by soaking in plenty of cold water. Some polysaccharides stimulate the immune system, for example acemannan, which is found in the leaves of aloe vera.
Found exclusively in species of the mustard and cabbage family, glucosilinates have an irritant effect on the skin, causing inflammation and blistering. Applied as poultices to painful or aching joints, they increase blood flow to remove the build-up of waste products. On eating, glucosilinates are broken down and produce a strong pungent taste. Radish and watercress are typical glucosilinate-containing plants.
Bitters are a varied roup of constituents linked only by their pronounced bitter taste. The bitterness itself stimulatess secretions by the salivary glands and digestive organs. Such secretions can dramatically improve the appetite and strengthen the overall function of the digestive system. With the improved digestion and absorption of nutrients that follow, the body is nourished and strengthened. Many herbs have bitter constituents, notably wormwood, chiretta and hops.
A very mixed group, alkaloids mostly contain a nitrogen-bearing molecule (-NH2), that makes them particularly pharmalogically active. Some are well-known drugs and have a recognized medical use. Vincristine, for example, derived from Madagascar periwinkle, is used to treat some types of cancer. Other alkaloids, such as atropine, found in deadly nightshade, have a direct effect on the body, reducing spasms, relieving pain and drying up bodily secretions.
Though often overlooked, many medicinal plants contain useful levels of vitamins. Some are well known for their vitamin content, for example dog rose, has high levels of vitamin C, and carrot is rich in beta-carotene (pro-vitamin A), but many are less well recognized. Watercress, for example contains appreciable levels of vitamins B1, B2, C and E as well as beta-carotene, while seabuckthorn can be regarded as a vitamin and mineral supplement in its own right.
Like vegetable foods, many medicinal plants provide high levels of minerals. Plants, especiallt˝ organically grown ones, draw minerals from the soil and convert them into a form that is more easily absorbed and used by the body. Whether plants are eaten as a vegetable, like cabbage or taken as a medicine, like bladderwrack, in many cases the mineral content is a key factor in the plant’s therapeutic activity within the body. Dandelion leaf is a potent diuretic, balanced by its high potassium content, while the high silica content of horsetail supports the repair of connective tissue, making it useful in arthritis.
6 Major Carotenoids:
Vitamin A – Retinol ( for vegans vitamin A must be converted via carotenoids and lots of them via full ranges of colours specifically orange, yellow, red) α-Carotene, β-carotene and β-cryptoxanthin are provitamin A carotenoids, meaning they can be converted by the body to retinol. Lutein, zeaxanthin, and lycopene are non provitamin A carotenoids because they cannot be converted to retinol. All carotenoids are also antioxidants and not completely destroyed with heat in fact in some cases enhanced. However Conversion is not straight forward and it takes a lot of carotenoids to be converted to 1 Vitamin A retinol . Ensure Diet very rich in these colours as Vitamin A is essential . Vitamin A has multiple functions: it is important for growth and development, for the maintenance of the immune system and good vision.
Carotenoids are important antioxidants, which protect your cells from damage. Most notably, they support the clearance of free radicals in your body. Although these are responsible for the bright colors of many fruits and vegetables, they’re actually found in greater amounts in leafy green vegetables. The chlorophyll in dark-green vegetables masks carotenoids pigments, so the vegetables appear green in color.
Major Medicinal Compounds in The colours :
Red– Lycopene & Resveratol
Orange– Beta-Carotene, zeaxanthin
Yellow– B-Cryptothanxin, Lutein, Zeaxanthin
Green– Clorophyll, magnesium, Calcium, Folate
Purple/Blue– Phenolics, Anthocyanins
White– Beta-Glucans (polysacharide ) ( Complex sugar & Fibre)
Major Medicinal Compounds in Strong Smelling Herbs & Spices
Terpenes from Resins & Oils Can be identified by their smell, all of which have very powerful phytochemical nutraceutical benefits