Constituents

Açai has a relatively high content of polyphenols. Most notable are anthocyanins and flavonoids, as well as fatty acids. Recently, small amounts of lignans have been reported.

Therapeutic uses and available evidence

This botanical drug has become very popular despite a lack of scientific evidence. Clinical data are lacking. The high content of polyphenols has been linked to a range of reported (mostly in vitro) antioxidant, antiinflammatory, antiproliferative and cardioprotective properties. Açai demonstrates promising potential with regard to antiproliferative activity and cardioprotection, but further studies are required (Heinrich et al In press).

Constituents

The root contains steroidal lactones (the withanolides A–Y), withaferin A (Fig. 25.1), withasomniferols A–C and others, phytosterols (such as the sitoindosides) and the alkaloids anahygrine, cuscohygrine, ashwagandhine, ashwagandhinine, withasomnine, withaninine, somniferine and others.

Fig. 25.1

Therapeutic uses and available evidence

Extracts are antioxidant, immunomodulatory and sedative but, despite their wide usage, much of the clinical knowledge is still anecdotal. The few clinical trials which have been carried out are of doubtful quality and cannot be used to confirm efficacy, but they do show that the herb is generally safe. Many of the pharmacological effects have been substantiated in animal studies: for example, the adaptogenic and antistress activity was found to be comparable to that of ginseng, in mice and rats, and immunomodulatory activity has been confirmed. The extract has sedative activity and is reported to be anxiolytic, acting via the GABA-ergic system (Bhattarai et al 2010) and numerous other actions have been documented (for review, see Kulkarni and Dhir 2008). The usual dose of powdered root is 3–6 g daily. Side effects are rare but high doses can cause gastrointestinal irritation.

Constituents

All types contain saponin glycosides (the ginsenosides Ra, Rb, Rg₁, Rg₂, Rs, etc.; Fig. 25.2). The ginsenosides are sometimes referred to as the panaxosides, but this nomenclature uses the suffixes A–F, which do not correspond to those of the ginsenosides. In Siberian ginseng (Eleutherococcus), the saponins (eleutherosides A–F) are chemically different, but have similar properties. Glycans (panaxans) also occur in P. ginseng. The actual composition of ginseng extracts depends upon the species and method of preparation.

Fig. 25.2

Therapeutic uses and available evidence

Ginseng is taken as a tonic for debility, insomnia, natural and premature ageing, to increase alertness and improve sexual inadequacy, and for diabetes, as well as an adaptogen to relieve stress and improve stamina and concentration. It has been suggested that these effects are due to changes in cholinergic activity and also neuro-protection, as well as antioxidant activity (Wang et al 2007). The adaptogenic effect may be due to the elevation of serum levels of corticosteroids and the reduction of catecholamines, which results in homoeostasis. Ginsenoside Rb₁ acts as a central nervous system sedative and Rg₁ has antifatigue and stimulant properties. In animals, an extract increases the capacity of skeletal muscle to oxidize free fatty acids in preference to glucose to produce cellular energy, which would support the antifatigue activity seen in conventional exhaustion tests. Ginseng also has a traditional use in diabetes, and the glycans (panaxans A–E) are hypoglycaemic in mice. Other documented effects include immunomodulatory activity, potentiation of analgesia and anticancer effects (by ginsenosides R_s3 and R_s4).

Trials of ginseng for improving ‘quality of life’, including mental health parameters, show beneficial effects for up to 8 weeks of treatment, but as far as cognition is concerned, a recent Cochrane review concludes that further, better quality studies are needed (Geng et al 2010). Since that review, the results of a placebo-controlled, double-blind, randomized, crossover study assessing the effects of Panax ginseng on subjective mood and aspects of ’working’ memory processes in healthy young adults, following both single dose and sub-chronic (7 days) ingestion, has been published. Dose-related treatment effects were found: 200 mg slowed a fall in mood, but also slowed responding on a mental arithmetic task across day 1, whereas the 400 mg dose also improved calmness (restricted to day 1) and improved mental arithmetic across days 1 and 8. No evidence of additional benefits, nor attenuation of acute effects, was found with repeated ingestion (Reay et al 2010). The dose is very variable but, in general, for a short course in the young and healthy, 0.5–1 g daily is recommended for up to 20 days; for long-term treatment in the sick or elderly, 0.4–0.8 g daily is more usual. Ginseng is taken widely, and side effects are well documented. They include oestrogenic effects, hypertension and irritability. A ‘ginseng abuse’ syndrome has been described.

Constituents

The mature fruiting body of the fungus contains a series of triterpenes, mainly lanostanes such as the ganoderic acids A–Z, ganoderals A and B, ganoderiols A and B, epoxyganoderiols A–C, ganolucidic acids A–E, lucidones A–C, lucidenic acids A–M. Polysaccharides, mainly glucans and arabinoxyoglucans, and peptidoglycans (known as ganoderans A–C) are also present.

Therapeutic uses and available evidence

Lingzhi is used as an adaptogen and general tonic, in the hope of prolonging life, retarding ageing and generally improving wellbeing and mental faculties. The most common indication is to enhance the immune system, and various animal and clinical studies support such a use. More recently, reishi has been applied as an adjunctive treatment to chemotherapy and radiation in cancer patients, to support immune resistance. The active principles are considered to be the triterpenes and polysac-charides. Extracts inhibit angiotensin-converting enzyme and produce hypotensive effects; cholesterol-lowering effects have been seen in animals. It is also a sedative, liver protectant and cholesterol-lowering agent (for review, see Sanodiya et al 2009). Clinical studies to support the uses are few and some are of doubtful quality.

The dose of the dried fruiting body of the fungus is 6–12 g daily, or the equivalent in extract. Lingzhi is well tolerated, although transient side effects of gastrointestinal disturbance and rashes in sensitive individuals have been reported. Animal studies have shown no toxic effects after long-term high doses, but as with other immune modulators it should probably be avoided in auto-immune disease.

Constituents

The main active constituents of the root and rhizome are monoterpene alcohols and their glycosides, such as salidroside (previously known as rhodioloside or rhodosin), rhodioniside, rhodiolin, rosin, rosavin, rosarin and rosiridin. These compounds are thought to be responsible for the adaptogenic properties of rhodiola. Other phenolic constituents such as p-tyrosol, gallic acid, caffeic acid, chlorogenic acid and flavonoids (catechins and proanthocyanidins) are present. Geraniol and other essential oil constituents, such as geranyl formate, geranyl acetate, benzyl alcohol and phenylethyl alcohol, give the root its rose-like odour.

Therapeutic uses and available evidence

Rhodiola rhizome preparations exhibit adaptogenic effects, and these include neuroprotective, cardioprotective, anti-fatigue, antidepressive, anxiolytic and CNS stimulating activity. A number of small clinical trials demonstrate that repeated administration of a Rhodiola rosea extract (SHR-5) may exert an anti-fatigue effect and increase mental performance in healthy subjects (measured as an ability to concentrate), and reduce burnout in patients with mild fatigue syndrome. Rhodiola may help in mild to moderate depression and generalized anxiety. Mechanisms of action which may contribute to the clinical effect include interactions with the HPA-system (reducing cortisol levels) and defense mechanism proteins (some heat shock proteins). It does not seem to interact with other drugs and appears to be safe, with only minor adverse effects. For review, see Panossian et al 2010, Panossian and Wikman 2009.

Constituents

The active constituents are lignans, including schizandrin A (= deoxyschisandrin or wuweizu A), schizandrin B (= wuweizu B or γ-schizandrin B; Fig. 25.3), schizandrol A (= schizandrin), schizandrol B (= gomisin A), schisandrin C, schisantherin A (= gomisin C), schisantherin B (= gomisin B), gomisins H, K, L, M, N, schizanhenol, wuweizu C, schisantherin C and others.

Fig. 25.3

Therapeutic uses and available evidence

Schisandra has been used in China since ancient times to prolong life and increase energy (‘qi’) and act as a general and sexual tonic, especially for men. It is also used to reduce sweating, detoxify the liver, enhance kidney function and suppress cough in lung disease. The adaptogenic and antifatigue properties have been tested in several animal studies; for example, the effect on the physical recovery of racehorses was found to be beneficial, as well as producing a general improvement in performance. Schizanhenol and schizandrin B protect against peroxidative damage associated with ageing and ischaemia in the rat brain, and a human study has suggested that intellectual activity can be enhanced. Many pharmacological studies support the use of schisandra, although few good clinical trials have been performed. Hepatoprotective effects have been documented in animal and cell culture studies. Schizandrin B, schisandrin C and gomisin A reduced liver enzyme levels and prevented histological damage in experimental models of liver injury, inhibited lipid peroxidation and stimulated glycogen synthesis in the liver. Antioxidant and free radical scavenging effects have also been described in vivo and in vitro. Deoxyschisandrin, gomisin A, B and C increase liver cytochrome P450 enzymes, which supports the detoxifying and anticancer properties attributed to the plant. Antitumour-promoting and antiinflammatory properties have also been shown in skin and the lignans are known to be platelet activating factor antagonists. For review, see Panossian and Wikman (2008, 2009). Daily doses of powdered berry are usually 1.5–6 g or higher if used to treat kidney disease.

Few toxicity studies have been carried out but, although relatively safe, schisandra is reputed to increase gastric acidity and may cause allergy in susceptible individuals. It should be avoided during pregnancy (possible uterine stimulation) and epilepsy.

Skullcap, Scutellaria baicalensis Georgi (Scutellaria baicalensis radix)

Scutellaria baicalensis (Huan qin, Lamiaceae) is sometimes known as baical skullcap to differentiate it from American skullcap (S. laterifolia L.). It grows in northern China, Siberia and Manchuria. The leaves are opposite, lanceolate and sessile with an acute apex. The flowers are blue, with a helmet-shaped upper lip (hence the name). The root is used medicinally.

Constituents

The root contains flavonoids including baicalin, baicalein, wogonin, chrysin, oroxylin A, skullcapflavones I and II, and others (Fig. 25.4).

Fig. 25.4

Therapeutic uses and available evidence

Skullcap is used for a wide variety of ailments, particularly fevers, infections, jaundice, thirst and nosebleeds, and as an antidote and sedative. Baicalin is antiinflammatory and anti-allergic; it inhibits the formation of lipoxygenase products and, to a lesser extent, cyclo-oxygenase products in leukocytes. It also inhibits the generation of inflammatory cytokines and is synergistic with β-lactam antibiotics against methicillin-resistant Staphylococcus aureus in vitro. Extracts of S. baicalensis inhibit lipid peroxidation in rat liver and the herb has been clinically tested in China in patients with chronic hepatitis, where it improved symptoms in over 70% of patients, increasing appetite, relieving abdominal distension and improving the results of liver function tests. Wogonin also suppresses production of hepatitis B virus surface antigen. The flavones interact with the benzodiazepine-binding site of the GABA_A receptor, with wogonin and baicalein being the most potent; this supports the sedative use of the herb. Baicalein is antigenotoxic in vitro and inhibits adhesion molecule expression induced by thrombin and cell proliferation of several types of cells. Wogonin inhibits nitric oxide production in activated C6 rat glial cells, acting via NF-κB inhibition and thus suppressing cell death. It also reduces skin inflammation in mice (induced by phorbol ester expression of COX-2) and inhibits monocyte chemotactic protein-1 gene expression in human endothelial cells. Antioxidant and antibiotic activities have also been reported for extracts. These activities all support the antiinflammatory and other uses of skullcap, although clinical trial evidence is sparse (for review, see Li-Weber 2009, Wang et al 2007). The daily dose of skullcap root is usually 5–8 g. Generally, baical skullcap is well tolerated, but little information as to side effects and contraindications is available.

Constituents

Tea contains caffeine, and much smaller amounts of other xanthines such as theophylline and theobromine. The polyphenols are the antioxidant constituents [in green tea these are mainly (−)-epigallocatechin; Fig. 25.5], together with theogallin, trigalloyl glucose. In black tea, they have been oxidized to form the ‘tea pigments’, the theaflavins, thearubigens and theaflavic acids.

Fig. 25.5

Therapeutic uses and available evidence

Tea is a stimulant, diuretic, astringent and antioxidant. Green tea is used medicinally more frequently than black tea. The stimulant and diuretic properties are due to the caffeine content, and the astringency and antioxidant effects to the polyphenols (Wang et al 2007).

Tea is useful in diarrhoea, and in China is used for many types of dysentery. The polyphenols in green tea have cancer chemopreventive properties due to their antioxidant capacity. Habitual consumption of green tea is generally associated with a lower incidence of cancer (for review, see Lambert and Elias 2010) and black tea is now known to have similar health benefits, which are ascribed to the tea pigments (for review, see Kumar et al 2010). Anti-inflammatory and antitumour effects have been described, and attributed to inhibition of the transcription factor NF-κB, and the risk of breast and stomach cancers appears to be lower for green tea drinkers. Black tea consumption is associated with a lower risk of death from ischaemic heart disease and has been shown to reverse endothelial dysfunction in coronary heart disease. Tea is also antimicrobial and anticariogenic, and is even reputed to help weight loss. Tea is drunk in nearly every country in the world for its refreshing, mildly stimulating and analgesic effects. There is no recommended dose for tea, and consumption varies widely.

Tea as a beverage is non-toxic in the usual amounts ingested, although it can cause gastrointestinal upsets and nervous irritability, due to the caffeine content. However there is now some concern about the safety of concentrated preparations or excessive consumption of green tea. Cases of hepatotoxicity have been associated with consumption of high doses of green tea-containing dietary supplements (10–29 mg/kg/d p.o.). In most cases, patients presented with elevated serum alanine aminotransferase (ALT) and bilirubin levels and in some cases liver biopsies were performed, and periportal and portal inflammation were observed. All cases resolved following cessation of supplement consumption, and re-injury was observed in some studies when the subject began reusing the same preparations, suggesting a causative effect of the green tea. There is also a case report of a 45-year-old man who developed jaundice and elevated serum ALT following consumption of 6 cups/d green tea infusion for 4 months (reviewed by Mazzanti et al 2009).