Elsevier

Phytochemistry

Volume 117, September 2015, Pages 554-568
Phytochemistry

Gingerols and shogaols: Important nutraceutical principles from ginger

https://doi.org/10.1016/j.phytochem.2015.07.012Get rights and content

Highlights

  • Ginger is a reputed folk remedy used to treat a range of disorders.

  • Gingerols display various nutraceutical benefits including counteracting obesity and diabetes.

  • Malignant tumours were successfully treated by gingerols in animal models.

  • Ginger metabolites have a favourable toxicity profile.

Abstract

Gingerols are the major pungent compounds present in the rhizomes of ginger (Zingiber officinale Roscoe) and are renowned for their contribution to human health and nutrition. Medicinal properties of ginger, including the alleviation of nausea, arthritis and pain, have been associated with the gingerols. Gingerol analogues are thermally labile and easily undergo dehydration reactions to form the corresponding shogaols, which impart the characteristic pungent taste to dried ginger. Both gingerols and shogaols exhibit a host of biological activities, ranging from anticancer, anti-oxidant, antimicrobial, anti-inflammatory and anti-allergic to various central nervous system activities. Shogaols are important biomarkers used for the quality control of many ginger-containing products, due to their diverse biological activities. In this review, a large body of available knowledge on the biosynthesis, chemical synthesis and pharmacological activities, as well as on the structure–activity relationships of various gingerols and shogaols, have been collated, coherently summarised and discussed. The manuscript highlights convincing evidence indicating that these phenolic compounds could serve as important lead molecules for the development of therapeutic agents to treat various life-threatening human diseases, particularly cancer. Inclusion of ginger or ginger extracts in nutraceutical formulations could provide valuable protection against diabetes, cardiac and hepatic disorders.

Graphical abstract

Gingerols and the corresponding shogaols are the major pungent compounds present in the rhizomes of fresh and dried ginger (Zingiber officinale), respectively. The compounds have a favourable toxicity profile, but are cytotoxic towards a range of cancer cell lines. Tumours induced in several animal models were successfully treated by gingerols.

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Introduction

Zingiber officinale Roscoe (Zingiberaceae), commonly known as ginger, is indigenous to tropical Asia, probably to southern China or India. The rhizomes of the plant have a powerful aroma and are extensively used as a spice and as medicine. Precise information concerning the plant’s origin has been lost, due to its long history of cultivation in these regions. The history of ginger is beautifully related by Elzebroek and Wind (2008). According to these authors, ginger is mentioned in the earliest recordings of Chinese herbals and is firmly entrenched in the culinary and medicinal practises of natives of Asian countries. The plant was well known by the Greeks and was mentioned by the Ancient Greek physician, botanist and apothecary Dioscorides (40–90 AD), in his works (Elzebroek and Wind, 2008). After an orgy, the Greeks are said to have eaten ginger wrapped in bread to combat nausea. The Roman writer, naturalist and philosopher Plinius Secundus (23–79 AD 79), known as Pliny the Elder, also described the medicinal use of ginger in his works, Naturalis Historia (Elzebroek and Wind, 2008). The spice was known in Germany and France by the 9th century. Marco Polo, introduced to ginger while visiting China and Sumatra in the 13th century, transported some to Europe. During the same period, ginger spread to East Africa from India by the Arabs. Later, in the 16th century, the Portuguese introduced ginger to West Africa. Elzebroek and Wind (2008) also discuss how the cultivation of ginger in Mexico was initiated by the Spaniard, Francesco de Mendoza. Throughout the Middle Ages, ginger was used to flavour beer. The English botanist William Roscoe named the plant Zingiber officinale in 1807. The genus name is from the Greek word ‘zingiberis’, which is derived from the Sanskrit word ‘shringavera’, aptly meaning ‘shaped like a deer’s antlers’, while officinale pertains to the medicinal properties of the rhizomes (Elzebroek and Wind, 2008). Ginger is commercially cultivated throughout the world and is a common crop in Africa, Latin America and south-east Asia.

Infusions prepared from ginger are reputed folk remedies in many countries for a wide range of conditions, but primarily to treat coughs, colds and flu (Khaki and Fathiazad, 2012). Beer containing ginger is used to settle stomach upsets. In Burma, a mixture of ginger and palm tree juice is taken to alleviate flu, whereas in Colombia, ginger mixed with hot panela is used to treat colds and flu. An infusion of ginger rhizomes with brown sugar is administered to relieve common colds, while scrambled eggs with powdered ginger is taken as a home remedy to reduce coughing in China. A mixture of ginger and mango juice is considered to be a panacea (medicine to cure all) in the Congo. Khaki and Fathiazad (2012) also mention the use of ginger rhizomes, prepared as a paste, for external application to cure headaches and taken orally to offer relief of colds in India and Nepal, while its mixture with lemon and black salt is extensively used to combat nausea. In Indonesia, ginger is believed to reduce fatigue, prevent rheumatism and improve digestion, whereas in the Philippines, it is taken to sooth a sore throat. Ginger is used in the United States as a remedy to alleviate motion sickness and morning sickness during pregnancy and to reduce heat cramps. Peruvians take ginger infusions to reduce stomach cramps, while the Japanese use ginger to improve blood circulation. Ginger plays an important role in Ayurvedic, Chinese, Arabic and African traditional medicines used to treat headaches, nausea, colds, arthritis, rheumatism, muscular discomfort and inflammation (Baliga et al., 2011, Dehghani et al., 2011).

Ginger is well known for its nutraceutical value, which can be ascribed to a variety of bioactive compounds, including the gingerols, zingiberene and the shogaols (Butt and Sultan, 2011). The pungent taste of fresh ginger rhizome is attributed to the presence of the gingerols (GNs), a group of volatile phenolic compounds. Gingerol (6-GN) is the major compound of the rhizome responsible for the pungency, while other GNs, such as 4-, 8-, 10- and 12-GN, are present in lesser concentrations. These compounds are thermally labile and are transformed at high temperatures to shogaols (SGs), which impart a pungent and spicy-sweet fragrance (Wohlmuth et al., 2005). During the preparation of dried ginger, GNs are also rapidly converted to the corresponding SGs, of which 6-SG is the most common dehydration product (Ok and Jeong, 2012). In many cases, 6-SG has been reported to have better biological activities than 6-GN. In the plant, GNs co-occur with various analogues, including the gingerdiones (Wang et al., 2011a). The concentrations of 6-, 8- and 10-GN were found to diminish when fresh ginger was roasted, dried and charred, whereas the concentrations of 6-SG increased with the corresponding treatments (Zhang et al., 2012). Although some reports have claimed that 6-SG occurs in fresh ginger rhizome (Wang et al., 2011b), this has not been conclusively proven. Park and Jung (2012) developed a sensitive high performance liquid chromatography-time-of-flight mass spectrometry method for the quantification of ginger-related compounds in fresh and dry ginger and in a hot water extract. They concluded that fresh ginger is devoid of the shogaols, but suggested that these compounds are artefacts formed from the corresponding gingerols through heat-catalysed dehydration reactions. In contrast, Bhattarai et al. (2007) are of the opinion that 6-GN and 6-SG undergo reversible first-order dehydration and hydration reactions to form 6-SG and 6-GN, respectively.

Thresh first isolated 6-GN, a volatile yellow oil at room temperature, in 1879 from the rhizomes of ginger (Thresh, 1879, Wohlmuth, 2008). After the discovery of 6-GN, various studies focussed on determining its structure (Lapworth et al., 1917, Nelson, 1917). Although the rhizomes of ginger are the primary source of GNs, many species of the Zingiberaceae, in addition to others, produce GNs as major compounds. These compounds have been reported to be present in other species in the genus Zingiber and also in related genera, including Zingiber zerumbet (L.) Smith (Zingiberaceae) (Chang et al., 2012) and Aframomum melegueta K. Schum. (Zingiberaceae) (Groblacher et al., 2012). However, the presence of gingerol and zingerone was reported in seeds of Trigonella foenum-graecum L. (Leguminosae) (Al-Daghri et al., 2012). Gas chromatography–mass spectrometry was used to identify the two analytes, but retention indices and the use of reference standards were not mentioned. Since no other accompanying gingerol metabolites were identified, this report should perhaps be viewed with some degree of caution until further research supports the findings. A range of gingerols and shagaols were isolated from the roots of Lycianthes marlipoensis C.Y. Wu & S.C. Huang (Solanaceae) and their structures elucidated using NMR spectroscopy (Guo and Li, 2011). Although the Solanaceae is taxonomically distant from Zingiber, this report seems more credible. The biotransformation of 6-GN and 6-SG by Aspergillus niger in the rhizomes of ginger to form their tasteless metabolites, a primary alcohol from 6-GN and both a ketoalcohol and a diol from 6-SG, was described by Takahashi et al. (1993). A recent study (Chari et al., 2013) revealed the roles of specific enzymes, including α-amylase, viscozyme, cellulase, protease and pectinase, in increasing the yield of GN in the rhizomes of ginger.

In this paper, the biosynthesis, chemical synthesis and biological properties of 6-gingerol ((5S)-5-hydroxy-1-(4-hydroxy-3-methoxyphenyl)decan-3-one), 8-gingerol ((5S)-5-hydroxy-1-(4-hydroxy-3-methoxyphenyl)dodecan-3-one), 10-gingerol ((5S)-5-hydroxy-1-(4-hydroxy-3-methoxyphenyl)tetradecan-3-one), 6-shogaol ((E)-1-(4-hydroxy-3-methoxyphenyl)dec-4-en-3-one), 8-shogaol ((E)-1-(4-hydroxy-3-methoxyphenyl)dodec-4-en-3-one) and 10-shogaol ((E)-1-(4-hydroxy-3-methoxyphenyl)tetradec-4-en-3-one) (Fig. 1) are comprehensively reviewed.

Section snippets

Biosynthesis

Macleod and Whiting (1979) stressed the importance of dihydroferulic acid and hexanoic acid in the biosynthesis of (S)-6-GN in ginger. The roles of these compounds were further elucidated when the complete route of biosynthesis of (S)-(+)-6-GN in ginger was proposed by Denniff and Whiting (1976a) and Denniff et al. (1980). According to these researchers, phenylalanine is converted to dihydroferulic acid, which subsequently participates in a biological Claisen reaction with malonate and

Chemical synthesis

The commercial value of the GNs prompted the development of a large number of efficient and cost-effective procedures for their synthesis. The first procedure was reported by Hirao et al. (1973) for the synthesis of dl- and d-GN via dl-benzylgingerol, which was produced by the condensation of benzylzingerone with caproic aldehyde. Denniff and Whiting (1976b) and Denniff et al. (1981) synthesised (±)-2-, 4-, 6-, 10- and 12-GN by deprotonation of trimethylsilyl zingerone and trimethylsilyl

Pharmacological significance

Apart from culinary uses, ginger and its major components, GNs and SGs, are known to have beneficial medicinal properties. Numerous pre-clinical studies have supported their value in the treatment of diabetes, obesity, diarrhoea, allergies, pain, fever, rheumatoid arthritis, inflammation and various forms of cancer. Tumours induced in the bowel, breast, ovaries and pancreas were successfully treated by GNs in various animal models. Liver-, CNS- and cardiovascular disorders have been effectively

Pharmacokinetic studies

Many pharmacokinetic studies have been carried out to determine the efficacy and bioavailability of GNs and SGs, using a variety of analytical tools, including high performance liquid chromatography (HPLC), liquid chromatography–mass spectrometry (LC–MS), gas chromatography–mass spectrometry (GC–MS) and high performance thin layer chromatography (HPTLC).

Ding et al. (1991) developed and validated a HPLC method to determine 6-GN in the plasma of rats that had been intravenously dosed with 3 mg/kg

Toxicity

The ginger metabolites, 6-, 8- and 10-GN and 6-SG, were found to be safe for healthy human subjects up to doses of 2000 mg (Zick et al., 2008). This value is below the recommended guidelines set by the U.S. National Cancer Institute Common Toxicity Criteria. A few individuals experienced minor gastrointestinal symptoms, including eructation, heartburn and indigestion at the highest doses.

Bioactive markers for quality control of various products

Many commercial products derived from ginger are available. These products originate mainly from China, Korea, India and Japan. Since GNs and SGs are the principle active components of the rhizomes of Z. officinale, they are used as marker compounds for the quality control of ginger raw materials and commercial products. The isolation or synthesis of pure reference standards is necessary for any quantitative work. Modern instrumentation can assist in the rapid and cost-effective isolation of

Conclusions and future perspectives

Although many people are aware of the health benefits of ginger, few people realise that pre-clinical studies have indicated that this natural product may have value as a complementary treatment for various forms of cancer. In recent years, nutraceutical compounds have gained wide acceptance as preferred alternatives to various synthetic drugs available on the market, particularly against cancer and diabetes. The long-term use of synthetic drugs is often associated with serious side effects

Acknowledgments

The work was financially supported by the National Research Foundation, South Africa and the Tshwane University of Technology, Pretoria, South Africa.

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