Ikuko Kimura Leonara R Pancho and Hiroshi Tsuneki

Ginger rhizomes have been widely used as a cooking spice and herbal remedy to treat a variety of conditions. Fresh and dried gingers are used for different clinical purposes in traditional Chinese medicine (Kampo). Fresh ginger (Zingiberis Recens Rhizoma; Sheng Jiang in Chinese; Shoga in Japanese) is used as antiemetic, antitussive, or expectorant, and is used to induce perspiration and dispel cold, whereas dried ginger (Zingiberis Rhizoma; Gan Jiang in Chinese) is used for stomachache, vomiting, and diarrhea accompanied by cold extremities and faint pulse (Bensky and Gamble, 1986). Dried ginger, either simply dried in the shade (Gan Sheng Jiang, or simply Gan Jiang in Chinese; Shokyo in Japanese) or processed ones that are heated in pans or with hot sand (Rhizoma Zingiberis Preparata: Pao Jiang in Chinese) are often used in China. The simply dried ginger and the processed ginger are not clearly differentiated in clinical use. On the other hand, different types of dried gingers have been used in traditional Japanese medicine, such as dried ginger (Shokyo in Japanese, as shown above) and steamed and dried ginger (Zingiberis Siccatum Rhizoma; Kankyo in Japanese). Steamed and dried ginger is rarely used in traditional Chinese medicine. Here we describe the "simply dried ginger" as "dried ginger" (Shokyo), and the "steamed and dried ginger" as "steamed ginger" (Kankyo). Gingerols and shogaols are identified as the main components of dried ginger (Shokyo) and steamed ginger (Kankyo), respectively (Aburada, 1987). However, before we conducted this study, little was known about the scientific reasons why Shokyo and Kankyo are used for different clinical purposes.

The juice from freshly squeezed ginger (contains gingerols) has been reported to be hypoglycemic in diabetic rats (Sharma and Shukla, 1977). The diabetic state alters the microvascular function (Vandana and Brecher, 1987) and affects the synthesis of prostacyclin, thromboxane, and leukotrienes (Jeremey et al., 1983; Rosenblum and Hirsh, 1984). Similarly, the gingerols have been reported to inhibit both cyclooxygenase and lipoxygenase and to diminish the production of prostaglandins and leukotrienes (Kiuchi et al., 1992). The chemical structures of gingerols are similar in part to those of prostaglandins.

The therapeutic application of gingerol in the diabetic state (i.e., gingerol lowers the blood glucose level) is an area of interest. In this chapter the major focus is on the effects of gingerols on the eicosanoid-induced contraction in isolated mice mesenteric veins because the mesenteric veins control the blood flow from the liver to the digestive area. The study includes the investigations on the relation of the chemical structures of gingerol and related analogues in the modulation of prostaglandin (PG)F2a-induced contractions, the modulation of other eicosanoid-induced contractions by gingerols, and the possible mechanisms involved in the potentiation of PGF2a-induced contractions by gingerol in isolated blood vessels.

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The new insight into the role of gingerols as a modulator of eicosanoid responses in vascular smooth muscles will be useful in clinically evaluating the effects of ginger (or its active components) on vascular smooth muscles. The results of such studies will provide an area of investigation for the development of novel therapeutics.

Differences Between Dried Ginger (Shokyo) and Steamed Ginger (Kankyo) Properties

Fresh ginger occurs in compressed tuberous pieces, 4 to 10 cm long and 1 to 2 cm thick, externally yellowish brown, with distinct nodes and internodes. The texture is fibrous with a juice extravasate when broken. The rhizomes have an aromatic odor and characteristic pungent taste (Lou et al., 1982).

Dried ginger (Shokyo) occurs in compressed tuberous pieces, 3 to 6 cm long, externally it is grayish yellow. The texture is rigid. The rhizomes have an aromatic odor and characteristic pungent taste (Lou et al., 1982). To prepare dried ginger, the skin from rhizomes of raw ginger are peeled off, sprinkled with lime water and the rhizomes are dried in the shade. Dried ginger is formulated in various traditional medicines in Japan, China, and India (Figure 13.1).

Steamed ginger (Kankyo) occurs in flattened pieces with finger-like branches, 3 to 6 cm long (see Figure 13.1). Externally it is grayish brown or pale grayish brown and rough with longitudinal wrinkles. The texture is compact. The rhizomes have an aromatic odor

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Figure 13-1 Components of dried ginger (Shokyo) and steamed ginger (Kankyo).

and characteristic pungent taste. To prepare steamed ginger, the rhizomes of raw ginger are peeled off the skin, steamed, and then dried under heat.

Active Components

Besides starch, protein, and lipids, ginger contains active chemical constituents—volatile oil (zingeberene, curcumene, borneol, neral, geranial, geraniol, citronyl acetate, a-terpi-neol, and linalool), pungent compounds (gingerols and shogaols), and minor components related to gingerols (gingediols, gingediacetates, paradol, and hexahydrocurcumin) (Mustafa et al., 1993).

(6)-Gingerol and shogaol are the main pungent constituents of dried and steamed ginger, respectively (see Figure 13.1). Dried ginger contains 0.6 to 1.1 percent w/w S-( + )-(6)-gingerol and 0.05 to 0.1 percent w/w shogaol, whereas steamed ginger contains 0.2 to 0.7 percent w/w S-( + )-(6)-gingerol and 0.3 to 0.7 percent w/w shogaol. Gingerols are chemically unstable and heat sensitive. The amount of S-( + )-(6)-gingerol equalizes to that of shogaol when ginger has been processed (steamed and dried) for 12 hours (Kano, 1987). During the processing, the amount of shogaol increases, whereas that of (6)-gingerol decreases as a result of dehydration of gingerols (Aburada, 1987).

Use in Traditional Medicine

Fresh ginger is used to induce perspiration and dispel cold, to warm the stomach and stop vomiting, and to resolve phlegm and relieve cough with expectoration of whitish thin sputum (Tu, 1992). Dried ginger is used for epigastric pain with a cold feeling, for vomiting and diarrhea accompanied by cold extremities and faint pulse, to warm the lung and resolve phlegm retention, for cough and dyspnea with copious frothy expectoration, for abnormal uterine bleeding, for spitting blood, and to keep the blood circulating within the vessels (Tu, 1992).

Pharmacological Studies on Ginger Extract and Active Components Fresh and Dried Ginger Extracts

In vitro studies have demonstrated that an aqueous extract of fresh ginger inhibits the activities of cyclooxygenase; as a result, it inhibits arachidonic acid metabolism and platelet aggregation (Srivastava, 1984). In vivo animal studies have demonstrated that an acetone extract of fresh ginger prevents vomiting in Suncus murmunus. Oral administration of the acetone extract of dried ginger also promotes gastrointestinal motility in rats (Mustafa et al., 1993). In addition, the juice of fresh ginger showed a hypoglycemic effect in diabetic rats (Sharma and Shukla, 1977). The pharmacological effect of ginger also has been reported in clinical studies: The powdered rhizome of dried ginger reduced the tendency of vomiting and cold sweating significantly better than placebo did in motion sickness (Gr0ntved et al., 1988). In a Danish study, blood thromboxane B2 levels were lowered after consumption of fresh ginger, an effect which must be due to inhibition of cyclooxygenase by the active components of fresh ginger (Mustafa et al., 1993). Moreover, dried ginger is described to be useful in rheumatoid arthritis because more than 75 percent of the arthritis patients who consumed powder of ginger rhizome experienced relief of pain and reduction in joint swelling (Mustafa et al., 1993). One of the mechanisms by which the dried ginger elicits an ameliorative action against the inflammatory disease may be related to the inhibition of prostaglandin biosynthesis.

Active Components

Gingerols have been found to be potent inhibitors of prostaglandin biosynthesis (Kiuchi et al., 1992) and show potent positive inotropic effects on isolated atria of guinea pigs (Shoji et al., 1982). Shogaol inhibits carrageenin-induced paw edema in rats by inhibiting the cyclooxygenase activity (Suekawa et al., 1986). Gingerols and shogaols inhibit gastric contractions in situ (Suekawa et al., 1984), show significant antihepatotoxic actions in primary cultured rat hepatocytes (Hikino et al., 1985), and exert an antiemetic action through the central nervous system (Kawai et al., 1994).

Effects of Ginger Extracts and Active Components on PGF2a-lnduced Contractions in Mice Mesenteric Veins

The methanol extract of dried ginger (10 fxg/ml), ^-( + )-(6)-gingerol (9 to 90 (xg/ml and (±)-(6)-gingerol (30 to 90 fxg/ml) significantly potentiated the contractile response to PGF2a and decreased the EC50 (50 percent effective concentration) values. The ginger extract was more potent than the gingerol compounds on the percent maximal contraction induced by PGF2a. ^-( + )-(6)-gingerol was more potent than (±)-(6)-gingerol. On the other hand, dried ginger extract (10 fxg/ml) and shogaol (8 fxg/ml) similarly inhibited the PGF2a-induced contraction (Table 13.1).

Table 13.1 Effects of ginger extracts and active components on the contractions induced by PGF2a in mice mesenteric veins
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