Miscellaneous supportive therapies for stress, ageing, cancer and debility

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Chapter 25 Miscellaneous supportive therapies for stress, ageing, cancer and debility

Although their effects are very difficult to evaluate, preventative medicines are extremely popular with patients and are an essential element of most types of Oriental medicine. They have been collected together here as they are generally used for a multitude of disorders, and to prevent degenerative conditions, including ageing and some forms of cancer. Most of the herbs mentioned here originated in Asia and China. In traditional Chinese medicine they are used to treat ‘empty’ diseases, to restore ‘qi’ energy and tonify the organs, having a balancing effect on yin and yang rather than affecting only one. They are thought to strengthen the immune system, improve memory and alertness, enhance sexual performance, promote healing and stimulate the appetite. In the West, the most important Chinese herbs are ginseng, ginkgo, astragalus, shizandra, reishi mushroom, baical scullcap and tea. In Ayurveda, some rejuvenating and tonic herbs are called ‘rasayanas’ and are considered to have a beneficial effect, balancing the tridosha. In Asian medicine, ashwagandha and Centella asiatica are very widely used. Many of these herbs contain saponins or steroidal compounds of some kind and it has been suggested that they act in a similar way to corticosteroids or enhance the effect of naturally occurring steroid hormones in the body. This type of drug is known as an adaptogen, and is considered to be a substance helping the body to deal with, or adapt to, stress or other adverse conditions.

While very contentious, this group is a fast growing area of phytotheray, but use is often based on very limited scientific evidence.

Cancer chemoprevention

During the 1960s and 1970s, work done at the University of Minnesota by LW Wattenberg showed that various compounds, especially from fruits and vegetables (indoles and isothiocyanates), could inhibit chemically induced tumours in laboratory animals. Termed ‘chemoprophylaxis of carcinogenesis’, this was of obvious benefit to maintenance of human health and had enormous dietary significance. After intensive studies using retinoids (vitamin A related natural products), the term ‘cancer chemoprevention’ was first used.

Cancer chemoprevention can be defined as ‘the prevention of cancer in human populations by ingestion of chemical agents that prevent carcinogenesis’. It is also important to differentiate between cancer prevention (e.g. cessation of cigarette smoking) and cancer chemotherapy (the use of cytotoxic drugs after cancer diagnosis). Cancer chemoprevention has now developed into a well-defined discipline. Several recent epidemiological studies have demonstrated that dietary factors may reduce the incidence of cancers. In one study, involving 250,000 people, an inverse correlation was found between the incidence of lung cancer among people who smoke and consume carotene-rich foods. As well as carotenoids, there was a similar finding for vitamin C and oesophageal and stomach cancers; selenium and various cancers; and vitamin E and lung cancer. Epidemiological studies may help to find leads for chemopreventive agents, which can then be tested in laboratory experiments. Almost 600 ‘chemopreventive’ agents are known and they are usually classified as: inhibitors of carcinogen formation (ascorbic acid, tocopherols, phenols), inhibitors of initiation (phenols, flavones) and inhibitors of postinitiation events (β-carotene, retinoids, terpenes). Many are items of food or beverages (e.g. tea) and are sometimes called ‘functional foods’ or ‘nutraceuticals’. Those that are used purely as foods are not covered here, but some others can be found in the chapters for which they are most useful (e.g. ginger, Chapter 14; garlic, Chapter 15). Further examples are given in Table 25.1.

Table 25.1 Known types of chemopreventive agents

Group	Examples
Micronutrients	Vitamins A, C and E, selenium, calcium, zinc
Food additives	Antioxidants
Non-nutritive molecules	Carotenoids, coumarins, indoles, alkaloids
Industrial reagents	Photographic developers, herbicides, UV-light protectors
Pharmaceuticals	Retinoids, antiprostaglandins, antithrombogenic agents, non-steroidal antiinflammatory drugs
Hormones and antihormones	Dehydroepiandrosterone, tamoxifen

Chemopreventive agents may even work in synergy, with several components contributing to the overall effect, which may be the case with plant drugs. This approach has great promise, with both natural products and synthetics being potentially useful. Dietary campaigns by government bodies, the American Cancer Society and others recommend that 5–7 servings of vegetables be consumed daily to function as a source of cancer chemopreventive agents. However, it is not reasonable to assume that chemopreventive agents will safeguard humans from known carcinogenic risks such as smoking. As knowledge of these agents increases they will play an increasing role in cancer prevention. Chemoprevention will not be covered further, apart from tea, as it is a vast subject in its own right. However, there are some useful recent reviews which discuss compounds, mechanisms and future directions available, such as Shu et al (2010), Gullett et al (2010) and Cerella et al (2010). Some data on the chemopreventive effects of garlic, anthocyanins (bilberry) and others can be found in the monographs of these plants.

Tonics, stimulants, adaptogens and supportive therapies

Açai berry, euterpe oleracea mart. (euterpe fructus)

The fruits of the palm Euterpe oleracea Martius (açai, Arecaceae) have been acclaimed as having a wide range of health-promoting and therapeutic benefits due to their reportedly high levels of antioxidants. Açai has a history of use as a medicinal plant and as a staple food in many parts of Brazil. Traditionally, it has been used to treat fevers, skin complications, digestive disorders and parasitic infections. In recent years, açai berry has been advertised widely, for example, via the internet.

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).

Ashwagandha, withania somniferum (L.) dunal

Ashwagandha, also known as winter cherry (Solanaceae), is a woody shrub native to the Middle East, Africa and parts of Asia, growing in stony and semi-arid regions; it is cultivated widely. The leaves are elliptical with an acute apex and the flowers campanulate and greenish yellow, developing into red berries enclosed in a papery membrane. The dried root is used medicinally. Ashwagandha has been used in Ayurvedic medicine for over 4000 years, as an adaptogen, sedative and tonic for debility. It is used to enhance fertility in both men and women, and as an aphrodisiac. The name ‘ashwagandha’ comes from the Sanskrit ashva (meaning ‘horse’) and gandha (meaning ‘smell’), and refers to the odour of the root. It is also widely used for inflammation, colds, asthma and many other disorders.

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.

Centella, centella asiatica (L.) urban (centellae herba)

The herb has already been described in Chapter 22 (Skin). In addition to the wound healing effects, the plant is considered a ‘rasayana’ in Ayurvedic medicine; it enhances the immune system and is considered to have a rejuvenating, neurological ‘tonic’ and mild sedative effect. The immunomodulating effects of the herb have been shown in vitro and in vivo in mice. Studies in rats have shown that asiatic acid has some benefits on memory and learning (Nasir et al 2011), and that the extract can protect against certain types of neurodegeneration (Haleagrahara and Ponnusamy 2010), but in general, evidence for this use is lacking. A small double-blind, placebo-controlled, randomized trial in healthy elderly volunteers in Thailand found that their health-related quality of life was improved and lower extremity strength increased after taking centella extract for 3 months (Mato et al 2009). It may be taken orally, often as an infusion, and applied topically. Other reported effects for the herb include anti-ulcer activity and spasmolytic effects. The powdered leaf is taken at an internal dose of 0.5–1 g daily, or the equivalent in the form of an extract.