White residue from ginger juice

White residue from ginger juice

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I've been juicing some ginger by grating it and pressing it (by hand). A white residue collects at the bottom of the liquid. What is this?

I believe that this white residue is starch. According to Wikipedia, Ginger is 17.7% carbohydrates by weight, or 14% excluding sugar and dietary fiber.

I let the residue settle and decanted the liquid. The residue behaved remarkably similarly to wet corn starch. From this, I have concluded that it is starch of some form.

Although white ginger and red (or pink) ginger do exist, the different colors in sushi ginger are from a dye. The color in white sushi ginger comes from the pickling process and the red/pink color in ink sushi ginger comes from an artificial dye (usually E124 -cochineal red- or in other brands beet extract). The generic name for sushi ginger is gari and here's the Wikipedia page.

White gari/sushi ginger on the left and pink gari/sushi ginger on the right.

The bright pink ginger is pink because of food coloring.

Salt and acids (in the case of pickled ginger, vinegar and citric acid) turn ginger pink during the pickling process naturally. However, this hue will eventually fade to pale yellow and then brown in less than 3 months as the ginger gets exposed to UV light and heat. This is why food coloring is added to the pink variety. As for the yellow/white pickled ginger, sodium metabisuphite must be added to stop the product from turning brown. This sulphite is an allergen and must be accordingly labeled. If you want to preserve the natural pinkish hue of the pickled ginger, keep the product refrigerated at 2 degrees Celsius. Away from UV light and heat, the color will remain for up to 1 year.

How To Make Ginger Juice

Making your own ginger juice requires just 3 ingredients and give or take 20 minutes. It’s is easy to do with a blender, bullet blender, or food processor. Ginger juice can be served as as refreshing cold beverage on hot summer days or it can be served warm as ginger tea during chilly winter months.

It’s also great as a cocktail mixer, as a base for sauces, or the cook rice in.

Here’s how to do it:

  1. Measure and prepare the ginger. You can peel the skin off the ginger or if your ginger isn’t very dirty you can simply wash it. Remove any tough pieces, knobs, or deep crevices where dirt collects.
  2. Cut the ginger into 1-2″ pieces so it’s easier for your blender to break down.
  3. Add the ginger pieces and water to a blender with lemon juice and sweetener (if using) and blend for 30-60 seconds until no large pieces remain.
  4. Pour through a fine sieve or nut milk bag to strain the pulp and your shot is ready!

Here are some optional add-ins that taste fantastic with ginger juice:

  • Fresh herbs! Basil, mint, rosemary, and thyme all taste exceptional with ginger juice. Start by adding 2 tablespoons of fresh herbs and taste. Lemongrass would also be great.
  • Vanilla extract. Yes, vanilla and ginger are a great pair, as vanilla is mild and soothing compared to ginger’s fiery heat! Start with 1 teaspoon per 1 cup of ginger juice.
  • Citrus juice. Lemon juice, lime juice, and orange juice can all be added to this recipe.

How To Make Ginger Shots

Ginger shots intended as a health or wellness shot can be created a bit differently as you won’t slowly sip on ginger shots. Ginger shots are more concentrated so they have less water and less sugar but you can still make them easily in your blender or bullet blender.

These ginger juice shots consist of pure ginger juice and fresh lemon juice– adding sugar is optional.

To make ginger shots follow the steps to make ginger juice listed above with a few exceptions. If you’re making ginger health shots you don’t need to add the sugar as you won’t be sipping on it, you’ll be shootin’ it back!

Also, health shots are usually concentrated so we’ll use half the amount of water. These ginger shots will have a spicy, fiery kick so taste and adjust as needed by adding more water or sweetener.

Store ginger shots in the fridge in a sealed container for up to 5 days. You can also freeze them for longer storage if needed.

Ginger Juice Benefits

Why drink ginger juice or ginger shots? Ginger is in the health food spotlight for a variety of benefits especially those pertaining to stomach ailments. Ginger is known to help heal the gut with everything from nausea, to motion sickness, morning sickness, and menstrual cramps.

Additionally, ginger is believed to help ward off cold, flu, and infections- plus has been studied for anti-inflammatory and cholesterol-lowering properties! It’s also believed to help with digestion. (Source)

Quick Ginger Juice For Cooking

Now, some of you may be here because you need a quick ginger juice for cooking, maybe for an Asian inspired recipe or curry. There’s no need to make an entire batch or blender full of ginger juice when you only need a teaspoon or two.

You have 2 options for how to quickly make a few teaspoons of ginger juice:

How to Clean Your Juicer

Benjamin Schmerler, spokesperson for Breville, shares a tip to help you clean as you go: “To minimize cleaning, line the pulp container with a reusable bag and then use the pulp as compost or discard.” Pulp can also be repurposed to fortify veggie burgers, soups and muffins.

When it’s time to clean, start by unplugging your juicer, then disassemble the parts. The main base of the machine, which houses the motor (typically the largest part of the juicer), can be wiped down with a damp cloth, but it can never be submerged in water.

The chutes, feed tubes, centrifuge components and storage containers should be disassembled and washed with hot, soapy water. These parts may also be dishwasher-safe (check the details for your model) but should rinsed ahead to remove any stuck-on bits.

Arguably the hardest part to clean of most machines is the filter, or mesh basket, that is most often made of some sort of fine porous material. The juice is pressed through these tiny pores to produce a drink free of chunks. Scrubbing with a soft-bristled brush can help. Schmerler also recommends “soaking the stainless steel filter basket in hot, soapy water for approximately 10 minutes so that the fine pores don’t get clogged.”

Once all the parts have been cleaned, make sure they dry completely before putting the machine back together and storing.

Pregnant Women and Ginger Consumption

According to the U.S National Library of Medicine, using ginger during pregnancy is controversial. 1

There is some concern that ginger might affect fetal sex hormones. There is also a report of miscarriage during week 12 of pregnancy in a woman who used ginger for morning sickness. However, studies in pregnant women suggest that ginger can be used safely for morning sickness without harm to the baby.

The risk for major malformations in infants of women taking ginger does not appear to be higher than the usual rate of 1% to 3%. Also there doesn’t appear to be an increased risk of early labor or low birth weight.

There is some concern that ginger might increase the risk of bleeding, so some experts advise against using it close to your delivery date. As with any medication given during pregnancy, it’s important to weigh the benefit against the risk. Before using ginger during pregnancy, talk it over with your healthcare provider.

Pharmalogical activities of ginger and its constituents

Ginger showed its importance as a medicine in Asian countries since ancient times. Pharmalogical activities of ginger and its constituents in health managements through modulation of various biological activities described as following:

Antioxidant activity

Antioxidants are substances that play a role in the neutralization of free radicals and oxidative stress. The free radical production is balanced by the antioxidative defense system of our body [17]. Any alterations between reactive oxygen species (ROS) generation and its neutralization by antioxidant defense [18,19] cause oxidative stress. Several plants and their constituents are rich source of antioxidant and play a significant role in prevention of disease progression process. Ginger is a source of a large number of antioxidants and also plays an important role in the reduction of the lipid oxidation and inhibits the pathogenesis of diseases ( Figure 3 ). Previous study reported that ginger extract possesses antioxidative characteristics and shows a role in scavenge superoxide anion and hydroxyl radicals [20,21] and gingerol, inhibited ascorbate/ferrous complex induced lipid peroxidation in rat liver microsomes [22].

Ginger and its constituents shows role in diseases prevention.

The essential oil and oleoresin of Zingiber officinale exhibited significant antioxidant and antimicrobial activities [23]. 6 Dehydroshogaol, 6-shogaol and 1-dehydro-6-gingerdione has shown potent inhibitors of nitric oxide (NO) synthesis in activated macrophages [24]. Another report in the favor of ginger as antioxidant showed that 6-shogaol has potent antioxidant properties which can be attributed to the presence of unsaturated ketone moiety [25]. Another study has shown that phenolic substances possess strong anti-inflammatory and antioxidative properties and considerable anticarcinogenic and antimutagenic activities [26] and showed role as in scavenging of H2O2, which donate electrons to H2O2, thus neutralizing it to water [27]. Earlier report showed that antioxidative activity of ginger extract in animal model [28].

Anti-inflammatory activity

Inflammation is a complex immune process and various mediators such as interleukin-1 (IL-1), tumour necrosis factor (TNF) and anti-inflammatory cytokines involve in this process. Currently non steroidal anti-inflammatory drugs are commonly used to treat the inflammation but this drug shows an adverse side effect and gastric ulcer. Various medicinal plants and their constituents have shown a vital effect in the prevention of inflammatory process. Earlier study has shown that ginger oil (33 mg/kg), administered orally to rats for 26 days, showed significant repression of paw and joint swelling associated with severe chronic adjuvant arthritis [29]. Ginger also shows a vital role in the suppression/inhibition in synthesis of pro-inflammatory cytokines such as IL-1, TNF-α, and IL-8 [13,30,31]. Another finding revealed that, the elevated expression of TNF-α in liver cancer rats was blocked when treated with ginger extract (100 mg/kg body weight) [32]. In addition to that, Ginger play a role in the inhibition of COX and 5-lipoxygenase, essential for arachidonate metabolism [33], and down-regulating the induction of inflammatory genes [34,35].

Earlier investigation has shown that, Ginger root and its constituents can inhibit NF-㮫 activation induced by a variety of agents [36-38] and downregulation of NF-㮫 gene products involved in cellular proliferation and angiogenesis [39]. DZO also shows a role in suppressing the expression of LPS-induced IFN-γ and IL-6, which are elevated in LPS-induced inflammation [40].

Anti-tumour activity

Tumour development and progressions are multi step process including genetic and metabolic changes [41,42]. Earlier study summarized the role of medicinal plant in the diseases management via modulation of various biological activities including cancer [43,44]. Ginger and its constituents show a vital effect in the control of tumour development through up regulation of tumour suppressor gene, induction of apoptosis and inactivation of VEGF pathways ( Figure 4 ). Angiogenic factor such as VEGF play a significant role in the development and progression of tumour. Therefore, Inhibition of VEGF is an important step in the prevention of tumour development/management. Earlier investigation has shown that, 6-gingerol has role in the suppression of the transformation, hyperproliferation, and inflammatory processes that involve in various steps of carcinogenesis, angiogenesis and metastasis [45-48]. Another numerous studies showed that 6-gingerol, constituents of ginger play a role in the induction of apoptosis in the prostate cancer cell line LnCaP by increasing the expression of p53 and Bax and also decreasing the expression of Bcl-2 [49-51]. Another important study has shown that 6-shogaol show anticancer activities against breast cancer via inhibition of cell invasion reduction of matrix metalloproteinase-9 expression [52]. Another important finding suggest that 6-gingerol stimulates apoptosis through upregulation of NAG-1 and G1 cell cycle arrest through downregulation of cyclin D1 [53].

Ginger and its constituent play pharmacological effect in cancer management via modulation of molecular mechanism.

An important study reported that ginger root extracts and gingerol play a significant role in inhibition of the growth of Helicobacter pylori CagA+ strains, which has a specific gene linked to the development of gastric premalignant and malignant lesions [54] Moreover, 6-shogaol has shown to induce apoptosis in human colorectal carcinoma cells via the production of reactive oxygen species and activation of caspase [31] and [6]-gingerol inhibited pulmonary metastasis in mice bearing B16F10 melanoma cells through the activation of CD8+ T cells [55]. Earlier finding has reported that 6-gingerol showed its anti-tumoral activity through induction of ROS which is also known to trigger activation of p53 and the cell cycle arrest and apoptosis [56]. Another important and first finding showed that in vitro and in vivo anticancer activity of whole GE for the management of prostate cancer [57].

Anti-microbial activity

Drug resistance is increasing worldwide and it is consider as a main culprit in the failure of treatment. The use of antibiotics against bacteria/microorganism is effective mode of treatment but also causes adverse complications. Earlier investigators have shown that, ginger and its constituents play a vital role in the prevention of microbial growth or acts as anti-microbial agents. An important study in the favors of ginger as anti-microbial activity showed that ginger has antimicrobial activity against E coli, Salmonella typhi and Bacillus subtilis and ethanolic extract of ginger showed widest zone of inhibition against Salmonella typhi [58]. Ginger rhizome contains several constituents which have antibacterial and anti fungal effects. The gingerol and shagelol are identified as more active agents [59]. Earlier studies have shown that, ginger has broad antibacterial activity and the ethanolic extract of ginger powder has pronounced inhibitory activities against Candida albicans [60-62] and other report also showed that antifungal properties of ginger extract, Gingerol [63]. Chief constituents such as [6]-gingerol and [12]-gingerol, isolated from ginger rhizome, showed antibacterial activity against periodontal bacteria [64] and [10]-gingerol has been reported as active inhibitor of M. avium and M. tuberculosis in vitro [65].

Anti-diabetic activity

Diabetes is a metabolic disorder and major global health problem worldwide. It is caused by abnormality of carbohydrate metabolism which is related to low blood insulin level or insensitivity of target organs to insulin [66]. As per estimation, one person is detected with diabetes every five second in the world whereas someone dies of it every 10 second [67]. Ginger and their constituents showed pivotal role in the control of diabetes and its complications via anti hyperglycemic effect. The exact mechanism of action of ginger in diabetes control is not fully understood but it might be due to the inhibition of oxidative stress and anti-inflammatory process.

An important finding based on in STZ treated-type 1 diabetic rat model reported that, oral administration of ethanolic extract of ginger significantly decrease fasting blood glucose level [68]. Earlier study reported that significant blood glucose lowering effect of ginger juice in diabetic and non-diabetic animals [69]. Another study has shown that a significant hypoglycemic activity in rats after administration of ginger extract [70].

Neuroprotective effect

Ginger and their constituents play a vital role as neuroprotector. The exact mechanism of action of ginger in this vista is not known fully. But it is thought ginger shows neuroprotector effect due to the phenolic and flavonoids compounds. An important study has shown that, 6-shogaol has neuroprotective effects in transient global ischemia via the inhibition of microglia [71]. Another finding in the support of ginger as neuroprotector suggests that, it exhibit neuroprotective effect by accelerating brain anti-oxidant defence mechanisms and down regulating the MDA levels to the normal levels in the diabetic rats [72]. A recent report on ginger juice showed that, ginger has protective effect by decreasing the LPO and increasing GSH, SOD, CAT, GPx, GST, GR and QR and protein level in treated rats [73].

Effect on osteoarthritis

Osteoarthritis is one of the leading causes of musculoskeletal pain and disability worldwide. Treatment of osteoarthritis based on anti-inflammatory drugs gives relief but also shows side effect and may cause gastric ulcer. Ginger shows a significant role in the treatment of osteoarthritis and also has important therapeutic importance in Ayurvedic and Unani medicine since ancient time. An important study on osteoarthritis (OA) patients of knee has revealed that, highly purified and standardized ginger extract had significant effect on reducing symptoms of OA of the knee [74]. Another report in the support of ginger showed that, ginger is effective as indomethacin in relieving symptoms of osteoarthritis with negligible side effects [75].

Gastroprotective effect

Peptic ulcer is a major problem worldwide in both sexes. Various factors including food ingredients, stress, Helicobacter pylori and drugs are responsible of gastric ulcer. Several medicinal plants and its constituents show anti-ulcer effect in various ways but the exact mechanism is not understood fully. Ginger and its constituents show a vital role in ulcer prevention via increasing mucin secretion. Earlier findings have shown anti-ulcerative effects of ginger in experimental gastric ulcer models [76,77]. Chief constituents of ginger such as [6]-gingerol and [6]-shogaol suppressed gastric contraction in situ and suppression by the [6]-shogaol was more intensive [78].

Anti-emetic effect

Ginger and its constituents show a significant effect on nausea and vomiting. Exact mechanism of action of ginger in nausea and vomiting is not clear but it is thought that such type of effect due to constituents present in ginger including gingerols, shogaols, and galanolactone and diterpenoid of ginger [79,80]. Studies based on animal model revealed that, ginger extract possesses antiserotoninergic and 5-HT3 receptor antagonism effects which play an important role in the etiology of postoperative nausea and vomiting [79-81]. A study in the favors of ginger role in nausea and vomiting indicating its effect and provide relief in severity in nausea and vomiting [82].

Hepato-protective effect

Earlier investigators based on experimental findings have shown that, ginger and its constituents play a significant role in hepato-protection. An important study on ginger showed its protective effect against the CCl4-induced hepatotoxicity [83]. Another report has shown that, administration of single dose of aqueous extract of ginger (200, 400 mg/kg prior to acetaminophen) was effective in preventing the acetaminophen-induced hepatotoxicity and also decreased ALT, AST and ALP levels and increased the activities of antioxidant enzymes levels in the liver [84]. Ginger is also useful in preventing the mancozeb-induced hepatotoxicity [85]. A recent report showed that, ginger is effective in reversing lead induced reduction in the liver weight, to increase plasma SOD and CAT activity, decrease LPx [86]. A recent report summarized the role of ginger in various types of diseases including diabetic liver, kidney, eye, and neural system complications [87].

Effect on migraine

An important study showed that administration of ginger powder at dose of 500-600 mg for 3-4 days with gap of 4 hours, showed relief from migraine attack [88].

Effect of ginger on eye

Ginger and its constituents show an important role in the management of diabetes and its related symptoms including retinopathy. Earlier report has shown that an extract of ginger with dose 0.1 and 1.0 mg/mL reduced CML-KLH and MGO-derived advanced glycation end products (AGE) products by 60%-80% and glucose-derived AGE products by 50%-60% [89].

Safety, efficacy and toxicity of ginger

Numerous plants and its constituents show an important therapeutic effect in the health management. Measurement of toxicity and lethal dose level is important before using in health management. Several studies were performed to check the safe dose in animal model study.The dose and toxicity of ginger has been checked and recommended by various earlier investigators. A study in this vista, showed that dose of 0.5-1.0 g of ginger powder ingested 2-3 times for periods of 3 months to 2.5 years did not cause any adverse effects [114]. Another study on animals showed that the doses of 2.5 gram/kg body weight were tolerated without any mortality. But, when the dose was increased to 3-3.5 gram/kg body weight then there was 10-30% mortality [115]. An important study showed that ginger extract with different dosages such as 100, 333 and 1000 mg/kg administered to pregnant rats for 10 days during the period of organogenesis caused neither maternal nor developmental toxicity [116]. Other study conducted in both male and female rats at the dosages of 500, 1000 and 2000 mg/kg body weight for 35 days and results proved that chronic administration of ginger was not associated with any mortalities and abnormalities in general conditions, behavior, growth, and food and water consumption [117].


Because ginger and its metabolites appear to accumulate in the gastrointestinal tract, the consistent observations of ginger exerting many of its effects in this area are not surprising. Ginger has been purported to exert a variety of powerful therapeutic and preventive effects and has been used for thousands of years for the treatment of hundreds of ailments from colds to cancer. Like many medicinal herbs, much of the information has been handed down by word of mouth with little controlled scientific evidence to support the numerous claims. However, in the last few years, more organized scientific investigations have focused on the mechanisms and targets of ginger and its various components. In Sections 7.6.1 through 7.6.5, the evidence for the effectiveness of ginger as an antioxidant, anti-inflammatory agent, antinausea compound, and anticancer agent as well as the protective effect of ginger against other disease conditions are reviewed (Figure 7.2).


The variety of protective effects wielded by ginger.

7.6.1. G eneral A ntioxidant P roperties of G inger

The presence of oxidative stress is associated with numerous diseases and a common mechanism often put forth to explain the actions and health benefits of ginger is associated with its antioxidant properties (Aeschbach et al. 1994 Ahmad, Katiyar, and Mukhtar 2001). Ginger was reported to decrease age-related oxidative stress markers (Topic et al. 2002) and was suggested to guard against ethanol-induced hepatotoxicity by suppressing oxidative consequences in rats treated with ethanol (Mallikarjuna et al. 2008). Ginger root contains a very high level (3.85 mmol/100 g) of total antioxidants, surpassed only by pomegranate and some types of berries (Halvorsen et al. 2002). The phorbol ester, 12-O-tetradecanoylphorbol-13-acetate (TPA), promotes oxidative stress by activating the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase system or the xanthine oxidase system or both. Ginger was reported to suppress TPA-induced oxidative stress in human promyelocytic leukemia (HL)-60 cells and Chinese hamster ovary AS52 cells (Kim et al. 2002). Others have shown that ginger compounds effectively inhibit superoxide production (Krishnakantha and Lokesh 1993). Several reports indicate that ginger suppresses lipid peroxidation and protects the levels of reduced glutathione (GSH Reddy and Lokesh 1992 Ahmed, Seth, and Banerjee 2000 Ahmed, Seth, Pasha, and Banerjee 2000 Shobana and Naidu 2000 Ahmed et al. 2008 El-Sharaky et al. 2009).

Reactive nitrogen species, such as nitric oxide (NO), influence signal transduction and cause DNA damage, which contributes to disease processes. Nitric oxide is produced by inducible nitric oxide synthase (iNOS), which is stimulated in response to various stresses. [6]-gingerol was reported to dose-dependently inhibit NO production and reduce iNOS in lipopolysaccharide (LPS)-stimulated mouse macrophages (Ippoushi et al. 2003). [6]-gingerol also effectively suppressed peroxynitritemediated oxidative damage (Ippoushi et al. 2003). Ippoushi et al. (2003) later proposed that [6]-gingerol and peroxynitrite form a symmetric dimer with [6]-gingerol covalently linked at the aromatic ring of peroxynitrite, attenuating peroxynitrite-induced oxidation and nitration reactions (Ippoushi et al. 2005). [6]-shogaol, 1-dehydro-[10]-gingerdione, and [10]-gingerdione also decreased LPS-induced NO production, and [6]-shogaol and 1-dehydro-[10]-gingerdione were reported to effectively reduce iNOS expression (Koh et al. 2009). In the bromobenzene (BB)-induced hepatotoxicity model, orally given ginger extract (100 mg/kg body weight [BW]) normalized NO levels and total and reduced glutathione levels, and also decreased the level of lipid peroxidation (El-Sharaky et al. 2009). Ginger consumption has also been reported to decrease lipid peroxidation and normalize the activities of superoxide dismutase and catalase, as well as GSH and glutathione peroxidase, glutathione reductase, and glutathione-S-transferase, in rats (Ahmed et al. 2008). Ginger supplementation before ischemia/reperfusion resulted in a higher total antioxidant capacity (i.e., normalized glutathione peroxidase and superoxide dismutase activities) and lower total oxidant (lower tissue malondialdehyde, NO, and protein carbonyl contents) status levels compared to an untreated group of Wistar albino rats (Uz et al. 2009). Overall, the rats fed ginger (5%) experienced less kidney damage due to oxidative stress induced by ischemia/reperfusion (Uz et al. 2009).

Ginger extract has been reported to exert radioprotective effects in mice exposed to gamma radiation (Jagetia et al. 2003), and the effect was associated with decreased lipid peroxidation and protection of GSH levels (Jagetia, Baliga, and Venkatesh 2004). [6]-gingerol pretreatment also decreased oxidative stress induced by ultraviolet B (UVB) and activated caspase-3, -8, -9, and Fas expression (Kim et al. 2007). Evidence does seem to suggest that ginger and some of its components are effective antioxidants in vitro. However, whether the physiological activity occurs in humans in vivo is not clear, and the specific mechanism and cellular targets are still to be determined.

7.6.2. A nti -I nflammatory E ffECTS Of G lnger

One of the many health claims attributed to ginger is its purported ability to decrease inflammation, swelling, and pain. [6]-gingerol (Young et al. 2005), a dried ginger extract, and a dried gingerol-enriched extract (Minghetti et al. 2007) were each reported to exhibit analgesic and potent anti-inflammatory effects. Earlier animal studies suggest that rat hind limbs perfused with [6]-gingerol showed increased heat production that was associated with increased oxygen consumption and lactate efflux (Eldershaw et al. 1992). The thermogenesis was at least partly associated with vasoconstriction independent of adrenergic receptors or secondary catecholamine release. In contrast, larger doses of ginger components inhibited oxygen consumption, which was attributed to disruption of mitochondrial function (Eldershaw et al. 1992). These results were supported in a later study in which rats that were given a single intraperitoneal injection of [6]-gingerol (2.5 or 25 mg/kg) exhibited a rapid, marked drop in body temperature and a significant decrease in metabolic rate (Ueki et al. 2008).

Data suggest that ginger may exhibit anti-inflammatory effects through the modulation of calcium levels mediated through transient receptor potential vanilloid subtype 1 (TRPV1), which is a heat-and pain-sensitive receptor that can interact with [6]-gingerol (Dedov et al. 2002). [6]-gingerol has been reported to induce a substantial rise in intracellular calcium levels in Madin-Darby canine kidney renal tubular cells by stimulating both extracellular calcium influx and thapsigargin (an endoplasmic reticulum Ca 2+ pump inhibitor)-sensitive intracellular calcium release (Chen et al. 2008). The gingerols are known to be TRPV1 agonists (Dedov et al. 2002), and the [6,8,10]-gingerols and [6,8,10]-shogaols can increase the intracellular calcium concentration in TRPV1-expressing HEK293 cells through TRPV1 (Iwasaki et al. 2006). Shogaols appear to be more potent than the gingerols, and most of the compounds cause aversive or nociceptive responses mediated by TRPV1 when applied to the eye or following subcutaneous injection to the hind paw, respectively (Iwasaki et al. 2006). In this case, most of the ginger compounds also promoted adrenal catecholamine secretion, which influences energy consumption (Iwasaki et al. 2006).

Ginger has been suggested to be effective against inflammation, osteoarthritis, and rheumatism (Reginster et al. 2000). However, inconsistencies in clinical studies have led to debate regarding the effectiveness and safety of ginger for treatment of arthritis (Marcus and Suarez-Almazor 2001). An earlier study showed that ginger oil (33 mg/kg), administered orally to rats for 26 days, caused a significant repression of paw and joint swelling associated with severe chronic adjuvant arthritis (Sharma, Srivastava, and Gan 1994). More recently, the effectiveness of a crude ginger extract was compared with a fraction containing only gingerols and derivatives to inhibit joint swelling in the streptococcal cell wall-induced arthritis animal model of rheumatoid arthritis (Funk et al. 2009). Results indicated that although both extracts could prevent joint inflammation, the crude dichloromethane extract, which also contained essential oils and more polar compounds, was more effective (when normalized to gingerol content) in preventing both joint inflammation and destruction (Funk et al. 2009). In humans, one study showed no difference between placebo and ginger in patients with osteoarthritis of the hip or knee (Bliddal et al. 2000). In contrast, patients suffering from osteoarthritis of the knee showed a consistently greater response to treatment with ginger extract compared with the control group (Altman and Marcussen 2001). In addition, relief from pain and swelling was reported in patients suffering from rheumatoid arthritis, osteoarthritis, or general muscular discomfort when using powdered ginger as a dietary supplement for 3 months to 2 years (Srivastava and Mustafa 1992). Besides pain relief from arthritis, results of a double-blind comparative clinical trial indicated that ginger (250-mg capsules) was as effective as the nonsteroidal anti-inflammatory drugs mefenamic acid (250 mg) and ibuprofen (400 mg) in relieving pain in women with primary dysmenorrhea (Ozgoli, Goli, and Moattar 2009). In contrast, consumption of 2 g of ginger before 30 minutes of cycling exercise (60% VO2) had no effect on quadriceps muscle pain, rating of perceived exertion, work rate, heart rate, or oxygen uptake (Black and Oconnor 2008).

Researchers have hypothesized that the anti-inflammatory effects of ginger might be related to its ability to inhibit prostaglandin and leukotriene biosynthesis (Srivastava and Mustafa 1992). Some others have showed that gingerols actively inhibit arachidonate 5-lipoxygenase, an enzyme of leukotriene biosynthesis (Kiuchi et al. 1992). [8]-gingerol, but not [6]-gingerol, was shown to inhibit cyclooxygenase-2 (COX-2) expression, which is induced during inflammation to increase formation of prostaglandins (Tjendraputra et al. 2001). Others have also reported that ginger extract suppresses the activation of tumor necrosis factor α (TNF-α) and expression of COX-2 in human synoviocytes (Frondoza et al. 2004). Proinflammatory cytokines such as TNF-α, interleukin (IL)-1β, and IL-12, which are produced primarily by macrophages, play an important role in sepsis, ischemia/reperfusion injury, and transplant rejection. [6]-gingerol was reported to inhibit the production of proinflammatory cytokines from LPS-stimulated peritoneal macrophages, but to have no effect on the function of antigen presenting cells (APC) or the LPS-induced expression of proinflammatory chemokines (Tripathi et al. 2007). However, this same group later reported that a ginger extract attenuated the production of IL-12, TNF-α, and IL-1β proinflammatory cytokines and RANTES (regulated upon activation, normal T cell expressed and secreted) and monocyte chemoattractant protein 1 (MCP-1) proinflammatory chemokines in LPS-stimulated murine peritoneal macrophages (Tripathi, Bruch, and Kittur 2008). In general, ginger extract inhibited macrophage activation and APC function, and indirectly suppressed T-cell activation (Tripathi, Bruch, and Kittur 2008). Other stable [6]-gingerol metabolites or analogs were reported to suppress LPS-induced NO production in murine macrophages mainly by reducing inos gene and iNOS protein production (Aktan et al. 2006). Some of ginger’s anti-inflammatory effects appear to be associated with decreased I㮫α degradation and impaired nuclear factor 㮫 (NF-㮫) nuclear translocation of p65 (Aktan et al. 2006 Lee et al. 2009). The majority of scientific evidence does seem to suggest that ginger and its various components have anti-inflammatory effects both in vitro and ex vivo. However, the data supporting ginger as an effective anti-inflammatory agent in humans in vivo are still contradictory and incomplete.

7.6.3. G inger as an A ntinausea A gent

The most common and well-established use of ginger throughout history is probably its utilization in alleviating symptoms of nausea and vomiting. The benefits and dangers of herbal treatment of liver and gastrointestinal distress have been reviewed (Langmead and Rampton 2001), and several controlled studies have reported that ginger is generally effective as an antiemetic (Aikins Murphy 1998 Ernst and Pittler 2000 Jewell and Young 2000, 2002, 2003 Langmead and Rampton 2001 Dupuis and Nathan 2003 Boone and Shields 2005 Borrelli et al. 2005 Bryer 2005 Mahesh, Perumal, and Pandi 2005 Chaiyakunapruk et al. 2006 Thompson and Potter 2006 Quimby 2007). The effectiveness of ginger as an antiemetic has been attributed to its carminative effect, which helps to break up and expel intestinal gas. This idea was supported by the results of a randomized, double-blind trial in which healthy volunteers reported that ginger effectively accelerated gastric emptying and stimulated antral contractions (Wu et al. 2008). Previously, [6]-gingesulfonic acid, isolated from ginger root, was showed to be effective against HCl/ethanol-induced gastric lesions in rats (Yoshikawa et al. 1992). This compound showed weaker pungency but more potent antiulcer activity than [6]-gingerol or [6]-shogaol (Yoshikawa et al. 1994).

Ginger root is commonly recommended for preventing seasickness (Schmid et al. 1994) and is found to be superior to dimenhydrinate (Dramamine) or placebo against symptoms of motion sickness (Mowrey and Clayson 1982). A follow-up study also indicated that 1 g of ginger might be effective in reducing the subjective severity of seasickness in naval cadets on the high seas (Grontved et al. 1988). On the other hand, additional research studies showed no benefits of using ginger for treating motion sickness (Wood et al. 1988 Stewart et al. 1991), and at least one group reported that patients receiving ginger extract for treating osteoarthritis experienced more, although mild, gastrointestinal adverse events compared to a placebo-treated group (Altman and Marcussen 2001). The exact antiemetic mechanism of ginger is not clear, although some evidence suggests that it inhibits serotonin receptors and exerts its antiemetic effects directly on the gastrointestinal system and in the central nervous system (DerMarderosian and Beutler 2006). Although the antiemetic effects of ginger are the most well-studied effects of this condiment and have been reviewed extensively, the effectiveness and safety of ginger for treating nausea and vomiting have been questioned in the past because the findings reported were often contradictory (Wilkinson 2000b). At the same time, ginger continues to be recommended for alleviating nausea and vomiting associated with pregnancy, chemotherapy, and certain surgical procedures.

Nausea and vomiting during pregnancy affects most pregnant women, and over the years ginger has been used to try to alleviate the condition (Aikins Murphy 1998 Jewell and Young 2000, 2002, 2003 Fugh-Berman and Kronenberg 2003 Boone and Shields 2005 Borrelli et al. 2005 Bryer 2005 Chrubasik, Pittler, and Roufogalis 2005 White 2007). At least one survey indicated that the overall use of dietary supplements in pregnant women appears to be low, but ginger is commonly recommended and used to prevent nausea (Tsui, Dennehy, and Tsourounis 2001). Several double-blind, randomized, placebo-controlled clinical trials have indicated that ginger consumption is effective and safe in helping to prevent nausea and vomiting during pregnancy (Portnoi et al. 2003 Willetts, Ekangaki, and Eden 2003). Randomized trials suggest that although ginger might not be as potent as some treatments (Jewell and Young 2000), its consumption for treating nausea or vomiting or both in early pregnancy has very few or no adverse side effects and seems to be effective (Niebyl 1992 Jackson 2001 Vutyavanich, Kraisarin, and Ruangsri 2001 Jewell and Young 2002 Niebyl and Goodwin 2002). In fact, ginger has been reported to be as effective as dimenhydrinate (i.e., Dramamine) in treating nausea and vomiting in pregnancy with fewer side effects (Pongrojpaw, Somprasit, and Chanthasenanont 2007). Women who received ginger (250-mg capsules) appeared to experience less vomiting and nausea compared to those receiving placebo (Ozgoli, Goli, and Simbar 2009), and ginger also relieved pain from primary dysmenorrhea (Ozgoli, Goli, and Simbar 2009). The effectiveness of ginger has been compared with that of vitamin B6 (another recommended therapy) in randomized, double-blind, controlled trials. Results indicated that ginger and vitamin B6 therapy were equally effective in reducing nausea and the number of vomiting episodes during pregnancy (Sripramote and Lekhyananda 2003 Smith et al. 2004). In a later randomized, double-blind, controlled trial, pregnant women were randomly divided to receive either 650 mg of ginger or 25 mg of vitamin B6 (3xd/4 days). In this case, ginger actually appeared to be more effective than vitamin B6, with only minor side effects (Chittumma, Kaewkiattikun, and Wiriyasiriwach 2007). These results were supported in an additional trial in which pregnant women with nausea were randomized into groups to receive either 1 g of ginger/day or 40 mg of vitamin B6/day for 4 days. Results of this trial indicated that compared with a baseline, nausea and vomiting in the ginger group were significantly less than those reported by the vitamin B6 group (Ensiyeh and Sakineh 2009). A systematic review of the results of other double-blind, randomized, controlled trials, uncontrolled trials, case reports, and observational studies indicated that ginger is superior to placebo and as effective as vitamin B6 in relieving the severity of nausea and vomiting, with no reported side effects or adverse effects on pregnancy (Borrelli et al. 2005). A similar review of the literature regarding the safety and efficacy of ginger in the management of nausea and vomiting during pregnancy revealed that ginger appears to be a relatively low-risk and effective treatment for these symptoms (Boone and Shields 2005). Importantly, no differences in birth weight, gestational age, or frequencies of congenital abnormalities have been observed between ginger-treated and untreated mothers (Willetts, Ekangaki, and Eden 2003). A survey of a group of obstetricians and gynecologists revealed that most of them would recommend taking an antiemetic (71.3%), and specifically ginger (51.8%), to patients suffering from moderate to severe nausea (Power, Holzman, and Schulkin 2001).

Ginger has been recommended to combat nausea associated with chemotherapy (Sharma and Gupta 1998 Grant and Lutz 2000). Gingerol was reported to reduce cisplatin (a platinum-based chemotherapy drug)-induced emesis in a vomiting model of mink possibly by inhibiting the central or peripheral increase of 5-hydroxytryptamine, dopamine, and substance P (Qian et al. 2009). In contrast, addition of ginger root powder (1 g/day) to a standard antiemetic regimen with metoclopramide had no advantage in reducing nausea or vomiting in acute or delayed phases of cisplatin-induced emesis in gynecologic cancer patients (Manusirivithaya et al. 2004). Cisplatin can cause renal oxidative and nitrosative stress and dysfunction. However, rats that were administered cisplatin and [6]-gingerol exhibited lower lipid peroxidation and conservation of GSH coupled with enhanced superoxide dismutase and catalase, which resulted in a restoration of normal renal function (Kuhad et al. 2006). Complementary intervention with ginger has also been suggested to have possible benefits in preventing acute chemotherapy-induced nausea and vomiting (CINV) in children (Dupuis and Nathan 2003). However, the results of a randomized, double-blind, placebo-controlled trial indicated that ginger did not provide any additional benefit in reducing CINV when given with a 5-hydroxytryptamine 3 (HT3) receptor antagonist and/or aprepitant (a substance P antagonist Zick et al. 2009). Notably, compared with a normal diet, high-protein meals with ginger consumed twice daily were reported to reduce the delayed nausea of chemotherapy and decrease the use of antiemetic medications (Levine et al. 2008).

Ginger was suggested to be an effective postoperative prophylactic antiemetic (Phillips, Ruggier, and Hutchinson 1993) that is not associated with effects on gastric emptying (Phillips, Ruggier, and Hutchinson 1993). However, the effectiveness of ginger in preventing postoperative nausea and vomiting has been disputed (Visalyaputra et al. 1998). One study indicated that pretreatment with ginger extracts reversed experimentally induced delay in gastric emptying in rats (Gupta and Sharma 2001), and ginger was also reported to reduce food transit time in experimental rats, an effect that might have implications in the prevention of colon cancer or constipation (Platel and Srinivasan 2001). The digestive stimulatory effects of ginger and other spices might be associated with positive effects on trypsin and pancreatic lipase (Platel and Srinivasan 2000) and ginger’s ability to increase gastric motility (Micklefield et al. 1999).

Several groups have studied the effectiveness of ginger in preventing nausea associated with gynecological laparoscopy. Patients who took ginger (1 g) appeared to experience less nausea incidence, especially within 2-4 hours of the procedure, and some reported less vomiting also (Pongrojpaw and Chiamchanya 2003). These results were supported by a later study involving 60 patients who received either 3 g of ginger or placebo 1 hour before the procedure. Although nausea was less in the ginger group at 2 hours postprocedure, vomiting did not vary between the two groups (Apariman, Ratchanon, and Wiriyasirivej 2006). However, at 6 hours, patients who had received ginger reported significantly less nausea and vomiting than the placebo group (Apariman, Ratchanon, and Wiriyasirivej 2006). Results of another similar trial indicated that ginger (1 g) taken 1 hour before major gynecologic surgery decreased nausea and vomiting at 2 and 6 hours postsurgery compared to placebo, and had no adverse side effects (Nanthakomon and Pongrojpaw 2006). In contrast, at least one trial indicated that ginger was not effective in reducing the incidence of postoperative nausea and vomiting in patients undergoing gynecologic laparoscopy (Eberhart et al. 2003). Finally, a systematic review and meta-analysis of randomized, controlled trials comparing ginger with placebo in preventing postoperative nausea and vomiting revealed that a fixed dose of at least 1 g of ginger appears to be more effective than placebo (Chaiyakunapruk et al. 2006). Overall, these results suggest that ginger is probably fairly effective in alleviating nausea and vomiting associated with a variety of conditions. Although the mechanism is not clear, ginger appears to have no adverse side effects and never seems to worsen nausea and vomiting.

7.6.4. A nticarcinogenic A ctivities of G inger

A great deal of interest by numerous research groups, including our own, is now being focused on the cancer-preventive and potential cancer therapeutic applications of ginger and its various components. Several aspects of the chemopreventive effects of numerous phytochemical dietary and medicinal substances, including ginger, have been reviewed previously (Surh, Lee, and Lee 1998 Surh 1999, 2002 Bode and Dong 2004 Shukla and Singh 2007 Aggarwal et al. 2008). Studies focused on the anticancer activities of various forms of ginger from a crude or partially purified extract to gingerols, especially [6]-gingerol shogaols, especially [6]-shogaol and zerumbone, a sesquiterpene compound derived from ginger and a number of minor components and metabolites. The effectiveness of ginger in preventing or suppressing cancer growth has been examined in a variety of cancer types, including lymphoma, hepatoma, colorectal cancer, breast cancer, skin cancer, liver cancer, and bladder cancer. The mechanisms proposed to explain the anticancer activities of ginger and its components include antioxidant activity and the ability to induce apoptosis, decrease proliferation, cause cell-cycle arrest, and suppress activator protein 1 (AP-1) and NF-㮫/COX-2 signaling pathways (Figure 7.3).


The anticancer activities exerted by ginger.

The anticancer activities of [6]-gingerol and zerumbone have been associated with their antioxidant activities. Several ginger components were reported to have effective anticancer promoter activity based on their ability to inhibit TPA-induced Epstein-Barr virus early antigen (EBV-EA) in Raji cells (Vimala, Norhanom, and Yadav 1999 Kapadia et al. 2002). [6]-gingerol was reported to suppress the reactive oxygen species-potentiated invasive capacity of ascites hepatoma AH109A cells by reducing peroxide levels (Yagihashi, Miura, and Yagasaki 2008). In normal RL34 rat liver epithelial cells, zerumbone was found to induce glutathione S-transferase and the nuclear localization of the transcription factor Nrf2, which binds to the antioxidant response element (ARE) of phase II enzyme genes (Nakamura et al. 2004). Zerumbone potentiated the expression of several Nrf2/ARE-dependent phase II enzyme genes, including Y-glutamyl-cysteine synthetase, glutathione peroxidase, and hemeoxygenase-1 (Nakamura et al. 2004). Others have reported that zerumbone decreases TPA-induced hydrogen peroxide formation and edema corresponding to enhanced levels of various antioxidant enzymes (Murakami et al. 2004). These types of changes have been linked with lower 7,12-dimethylbenz[a]anthracene (DMBA)-initiated/TPA-promoted tumor incidence, number of tumors per mouse, and tumor volume (Murakami et al. 2004).

Zerumbone has also been reported to downregulate CXC chemokine receptor 4 (CXCR4), which is highly expressed in various tumors, including breast, ovary, prostate, gastrointestinal, head and neck, bladder, brain, and melanoma tumors (Sung et al. 2008). Because the CXCR4 mediates homing of tumor cells to specific organs that express its ligand, CXCL12, zerumbone was suggested as a potential suppressor of cancer metastasis and was effective in suppressing CXCR4 in a variety of cancers, including those of the pancreas, lung, kidney, and skin (Sung et al. 2008). Furthermore, zerumbone effectively attenuated osteoclast formation induced by human breast tumor cells and by multiple myeloma and decreased osteolysis dose-dependently in MDA-MB-231 breast cancer tumor-bearing athymic nude mice, suggesting that it might be effective in preventing cancer-associated bone loss or osteoporosis (Sung et al. 2009). [6]-gingerol has also been reported to suppress adhesion, invasion, motility, matrix metalloproteinase (MMP)-2, and MMP-9 messenger ribonu-cleic acid (mRNA) expression and protein activities in MDA-MB-231 human breast cancer cell lines (Lee, Seo, Kang, and Kim 2008).

Ginger and its constituents have been reported to inhibit tumor promotion in mouse skin (Katiyar, Agarwal, and Mukhtar 1996). In particular, [6]-gingerol has been reported to be highly effective as an anticancer agent in skin in vivo in the two-stage initiation-promotion mouse skin model. In this model, tumors are initiated by a one time application of DMBA followed by repeated topical applications of TPA beginning a few days later. Topical application of [6]-gingerol on the shaved backs of female ICR mice decreased the incidence of DMBA-initiated/TPA-promoted skin papilloma formation and also suppressed TPA-induced epidermal ornithine decarboxylase activity and inflammation (Park et al. 1998). Results of a similar study indicated that in the DMBA/TPA skin tumor model, topical application of [6]-paradol or [6]-dehydroparadol prior to the application of TPA significantly decreased both the number of tumors per mouse and the number of mice exhibiting tumors (Chung et al. 2001).

Earlier studies suggest that gingerol is an effective inhibitor of azoxymethane-induced intestinal carcinogenesis in rats (Yoshimi et al. 1992). Ginger supplementation (50 mg/kg BW) was reported to suppress the number of tumors as well as the incidence of 1, 2-dimethylhydrazine (DMH)-induced colon cancer (Manju and Nalini 2005). The effect was attributed to decreased oxidative damage associated with enhanced catalase, superoxide dismutase, glutathione peroxidase, and glutathione transferase activities as well as increased GSH (Manju and Nalini 2005). This group later reported that administration of ginger to DMH-treated rats significantly decreased the incidence and number of tumors as well as the activity of microbial enzymes, β-glucuronidase, and mucinase (Manju and Nalini 2006). Finally, Wistar rats that were fed a ginger extract (1% mixed in diet) exhibited significantly lower multiplicity of urothelial lesions (hyperplasia and neoplasia) than untreated groups (Ihlaseh et al. 2006).

Studies suggest that ginger compounds suppress proliferation of human cancer cells through the induction of apoptosis (Lee et al. 1998 Lee and Surh 1998 Thatte, Bagadey, and Dahanukar 2000). A saline extract prepared from ginger extract suppressed the proliferation of HEp-2 cells by inducing cytotoxic effects and DNA fragmentation (Vijaya Padma, Arul Diana Christie, and Ramkuma 2007). Ginger extract and especially [6]-gingerol were reported to effectively decrease proliferation of YYT colon cancer cells and the angiogenic potential of endothelial cell tubule formation in immortalized MS1 endothelial cells (Brown et al. 2009). [10]-gingerol was reported to cause a significant and prolonged increase in intracellular calcium and cytotoxicity in human colorectal cancer SW480 cells (Chen, Li, and Kuo 2009). [6]-gingerol was reported to inhibit both proliferation and invasion of ascites hepatoma AH109A cells and appeared to act by causing an S-phase arrest, elongated doubling time of hepatoma cells, and an increased rate of apoptosis (Yagihashi, Miura, and Yagasaki 2008). This compound also induced cell-cycle arrest and suppressed the growth of human pancreatic cancer cell lines, human pancreatic adenocarcinoma (HPAC) cells, which express wild-type p53 and BxPC-3 cells that express a mutant p53 protein (Park et al. 2006). Interestingly, [6]-gingerol appeared to be most effective in inducing apoptosis in p53-mutant cells and induced arrest, but not apoptosis, in p53-expressing cells (Park et al. 2006). [6]-gingerol was further reported to suppress proliferation and induce apoptosis or G1 cell-cycle arrest in several colorectal cell lines, including HCT116, SW480, HT29, LoVo, and Caco2 cells (Lee, Cekanova, and Baek 2008). These effects were associated with a decreased abundance of cyclin D1 (a proto-oncoprotein that is overexpressed in cancer) and increased expression of a nonsteroidal anti-inflammatory drug (NSAID)-activated gene (NAG-1), a proapoptotic and antitumorigenic protein (Lee, Cekanova, and Baek 2008).

Through the comparison of promotion-sensitive (P + ) and promotion-resistant (P - ) derivatives of the mouse epidermal JB6 cell lines, AP-1 was reported to have a critical role in tumor promotion (Huang, Ma, Bowden, and Dong 1996 Huang, Ma, and Dong 1996). In addition, blocking the tumor promoter–induced activation of AP-1 inhibited neoplastic transformation (Dong et al. 1994). Epidermal growth factor (EGF) is known to induce a relatively high level of AP-1 activity and cell transformation (Huang, Ma, and Dong 1996). We previously investigated the effect of two structurally related compounds of the ginger family, [6]-gingerol and [6]-paradol, on EGF-induced cell transformation and AP-1 activation (Bode et al. 2001). Our results provided the first evidence that both compounds block EGF-induced cell transformation, but by different mechanisms. [6]-gingerol appeared to act by directly inhibiting AP-1 DNA binding activity and transactivation, whereas [6]-paradol appeared to act by inducing apoptosis (Bode et al. 2001). Others report that [6]-gingerol causes DNA fragmentation and suppresses Bcl-2 expression in promyelocytic leukemia HL-60 cells (Wang et al. 2003), and also induces growth inhibition and caspase-mediated apoptosis in human epidermoid carcinoma A431 cells (Nigam et al. 2009). [6]-paradol and other structurally related derivatives, such as [10]-paradol, [3]-dehydroparadol, [6]-dehydroparadol, and [10]-dehydroparadol, inhibited proliferation of KB oral squamous carcinoma cells in a time-and dose-dependent manner (Keum et al. 2002). [6]-dehydroparadol (75 μM) was more potent than the other compounds tested, and it induced apoptosis through a caspase-3-dependent mechanism (Keum et al. 2002).

[6]-shogaol [1-(4-hydroxy-3-methoxyphenyl)-4-decen-3-one], an alkanone from ginger, exhibited the most potent cytotoxicity against human A549, SK-OV-3, SK-MEL-2, and HCT15 tumor cells, compared to [4]-, [6]-, [8]-, and [10]-gingerols (Kim et al. 2008). This compound also inhibited proliferation of several transgenic mouse ovarian cancer cell lines, including C1 and C2 (Kim et al. 2008). Further, [6]-shogaol was reported to inhibit the growth of and induce apoptosis in COLO 205 cells (Pan et al. 2008). Treatment with [6]-shogaol, but not [6]-gingerol, induced DNA fragmentation in COLO 205 colon cancer cells. Apoptosis was mediated by activation of caspase-9, -3, and -8, resulting in the release of mitochondrial cytochrome c, upregulation of proapoptotic Bax, and downregulation of antiapoptotic Bcl2, and the induction of growth arrest and DNA damage (GADD)-inducible transcription factor 153 (GADD153) mRNA and protein (Pan et al. 2008). [6]-shogaol induced apoptosis of hepatoma cells mediated by activation of caspase-3 and -7 (Chen et al. 2007). The compound was also reported to reduce the viability of gastric cancer cells by directly damaging microtubules and inducing mitotic arrest (Ishiguro et al. 2007).

NF-㮫 is a rapidly induced stress-responsive transcription factor that functions to intensify the transcription of a variety of genes, including cytokines, growth factors, and acute response proteins (Baldwin 1996). Its activation is also linked to mitogen-activated protein (MAP) kinase signaling pathways (Schulze-Osthoff et al. 1997). The mechanism for NF-㮫 activation is well known. In its inactive form, NF-㮫 is found in the cytosol bound to an inhibitory protein called inhibitory kappa B (I㮫). When stimulated, I㮫 is phosphorylated by an I㮫 kinase, which releases it from NF-㮫 and is subsequently degraded. Following its separation from I㮫, NF-㮫 is translocated into the nucleus, where it activates gene transcription by binding to its specific DNA sequence found in certain genes. Importantly, NF-㮫 activation is associated with initiation or acceleration of tumorigenesis (Gilmore 1997), and in JB6 cells, inhibition of NF-㮫 also blocks tumor promoter-induced cell transformation (Li et al. 1997). [6]-gingerol might exert its effects by suppressing the NF-㮫/COX-2 pathway. This idea is supported by data indicating that the reduction of UVB-induced expression and transactivation of COX-2 by [6]-gingerol was associated with the suppression of I㮫α phosphorylation (Ser32) resulting in a decreased translocation of NF-㮫 from cytosol to nucleus in HaCaT cells (Kim et al. 2007). A ginger extract fed to rats with experimentally induced liver cancer resulted in decreased NF-㮫 and TNF-α expression (Habib et al. 2008). [6]-gingerol was reported to suppress TNF related apoptosis induced ligand (TRAIL)-induced NF-㮫 activation, resulting in apoptosis mediated by caspase-3 or -7 activation, which was associated with the down-regulation of clAP1, a negative regulator of these caspases (Ishiguro et al. 2007).

Zerumbone has been reported to suppress NF-㮫 activation induced by a variety of stimuli, including tumor necrosis factor (TNF), cigarette smoke condensate, and hydrogen peroxide (Takada, Murakami, and Aggarwal 2005). It also suppressed I㮫α kinase phosphorylation and degradation, resulting in a downregulation of constitutively active NF-㮫 and many of its regulated gene targets, such as COX-2, cyclin D1, Bcl2, and other antiapoptotic genes, thereby enhancing apoptosis induced by chemotherapeutic agents (Takada, Murakami, and Aggarwal 2005). Zerumbone was also reported to suppress receptor activator of NF-㮫 ligand (RANKL) activity in mouse monocytes (osteoclast precursor cells) by inhibiting I㮫α kinase activity, phosphorylation, and degradation (Sung et al. 2009). Oral administration of zerumbone (100, 250, or 500 ppm) to ICR mice decreased inflammation and the multiplicity of colon adenocarcinomas induced by intraperitoneal injection of azoxymethane (AOM, 10 mg/kg BW Kim et al. 2009). Additionally, zerumbone (250 or 500 ppm) effectively suppressed 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone-induced lung adenoma formation in female A/J mice (Kim et al. 2009). This ginger derivative appeared to exert its effects by inhibition of proliferation, induction of apoptosis, and suppression of NF-㮫 and heme oxygenase expression in both colon and lung cancer tissues (Kim et al. 2009). In an earlier study, [6]-gingerol was reported to inhibit both the vascular endothelial growth factor (VEGF)-and basic fibroblast growth factor (bFGF)-induced proliferation of human endothelial cells and cause cell-cycle arrest in the G1 phase (Kim, Min et al. 2005). [6]-gingerol also blocked capillary-like tube formation by endothelial cells in response to vascular endothelial growth factor (VEGF), and strongly inhibited sprouting of endothelial cells in the rat aorta and formation of new blood vessels in the mouse cornea in response to VEGF (Kim, Min et al. 2005).

Investigators suggested that the effectiveness of ginger might be related to its ability to inhibit prostaglandin and leukotriene biosynthesis (Srivastava and Mustafa 1992). Some researchers showed that gingerol actively inhibits arachidonate 5-lipoxygenase, an enzyme of leukotriene biosynthesis (Kiuchi et al. 1992). The leukotriene A4 hydrolase (LTA4H) protein is regarded as a relevant target for cancer therapy, and our in silico prediction using a reverse-docking approach revealed that LTA4H might be a potential target for [6]-gingerol (Jeong et al. 2009). Our prediction was supported by work showing that [6]-gingerol suppresses anchorage-independent cancer cell growth by binding to LTA4H and inhibiting LTA4H activity in HCT116 colorectal cancer cells. We further found that [6]-gingerol effectively suppressed tumor growth in vivo in nude mice, an effect that was mediated by the inhibition of LTA4H activity. Collectively, these findings indicate a crucial role of LTA4H in cancer and also support the anticancer efficacy of [6]-gingerol targeting of LTA4H for the prevention of colorectal cancer (Jeong et al. 2009). Importantly, these are the first results that identify a direct target of [6]-gingerol to explain its anticancer activity.

Cyclooxygenase-2 is an important enzyme in prostaglandin biosynthesis, and is regarded as a promising molecular target for many anti-inflammatory as well as chemopreventive agents. Topical application of [6]-gingerol was reported to suppress TPA-induced COX-2 expression, p38 phosphorylation, and NF-㮫 DNA binding activity in mouse skin (Kim et al. 2004). These results were further expanded to show that pretreatment of mouse skin with [6]-gingerol resulted in decreased TPA-induced NF-㮫 DNA binding and transcriptional activity by suppressing both I㮫α phosphorylation and degradation and p65 phosphorylation and nuclear translocation (Kim, Kundu et al. 2005). The interaction of phosphorylated p65 (Ser536) with CREB (cAMP response element binding) protein, a transcriptional coactivator of NF-㮫, was prevented by [6]-gingerol, and the inhibitory effect of [6]-gingerol on p38 phosphorylation, an upstream mediator of COX-2 activation, was observed (Kim, Kundu et al. 2005).

Treatment of cultured ovarian cancer cells with [6]-shogaol caused a marked growth inhibition that was associated with suppression of NF-㮫 activation as well as the diminished secretion of angiogenic factors, VEGF and IL-8 (Rhode et al. 2007), suggesting a role for this compound in preventing angiogenesis in cancer. In contrast to most reports, dietary consumption of ginger (0.5% or 1.0%) did not suppress aberrant crypt foci (ACF) formation or reduce the number of crypts per ACF in DMH-treated rats compared to untreated control rats (Dias et al. 2006). Dietary ginger did not significantly change the proliferative or apoptotic indexes of the colonic crypt cells induced by DMH (Dias, 2006). In marked contrast to many studies, ginger extract was not able to inhibit the development of N-butyl-N-(4-hydroxybutyl)-nitrosamine (BBN)/N-methyl-N-nitrosourea (MNU)-induced bladder cancer in male Swiss mice. In fact, in BBN/MNU/2% ginger-treated mice, the incidence of grade 2 transitional cell carcinoma was increased (Dias et al. 2006 Bidinotto et al. 2006).

7.6.5. C ardiovascular and O ther D isease -P reventive E ffECTs of G inger

In addition to its effects in relation to cancer, some evidence supports a protective role for ginger in cardiovascular function and a number of other disease conditions. Ginger has gained interest for its potential to treat various aspects of cardiovascular disease, and the in vitro and animal data supporting the anti-inflammatory, antioxidant, antiplatelet, hypotensive, and hypolipidemic effects of this condiment have been reviewed (Nicoll and Henein 2009). However, human trials are less convincing and more investigations are needed (Nicoll and Henein 2009). Caution when taking ginger and other herbal extracts has been suggested because of an apparent association of ginger with reported incidences of increased risk of bleeding following surgery (Chang and Whitaker 2001 Pribitkin and Boger 2001) or if taken with anticoagulant drugs such as warfarin (Heck, DeWitt, and Lukes 2000). However, the data are not conclusive (Vaes and Chyka 2000). At least one study indicates that ginger has no effect on blood pressure, heart rate, or coagulation parameters and does not interact with anticoagulant drugs such as warfarin (Weidner and Sigwart 2000). These findings were supported in a later study in which ginger was reported to have no effect on clotting status or the pharmacokinetics or pharmacodynamics of warfarin in healthy subjects (Jiang, Williams et al. 2005). An aqueous ginger extract was reported to induce a dose-dependent decrease in arterial blood pressure in a variety of animal models (Ghayur and Gilani 2005a,b).

At least one group found that administration or consumption of standardized ginger extract decreased aortic atherosclerotic lesion areas, plasma triglycerides and cholesterol, low-density lipoprotein (LDL)-associated lipid peroxides, and LDL aggregation in mice (Fuhrman et al. 2000). In rabbits that were fed a high-cholesterol diet, administration of ginger extract resulted in a significant antihyperlipidemic effect and a lower degree of atherosclerosis compared to the group that was fed cholesterol alone (Bhandari, Sharma, and Zafar 1998). Importantly, ginger powder (3 g/day in 1-g capsule 3xd) significantly lowered lipid levels in volunteer patients in a double-blind, controlled clinical trial study (Alizadeh-Navaei et al. 2008). Triglyceride and cholesterol were substantially decreased as was LDL levels compared to placebo group. Notably, the high-density lipoprotein (HDL) level of the ginger group was higher than that of the placebo group, whereas the very-low-density lipoprotein (VLDL) level of the placebo group was higher than that of the ginger group (Alizadeh-Navaei et al. 2008). Dried ginger powder (0.1 g/kg BW, per oral administration [p.o.] for 75 days) significantly lowered (50%) the development of atheroma in the aorta and coronary arteries of rabbits that were fed cholesterol (Verma et al. 2004). This effect was associated with decreased lipid peroxidation and increased fibrinolytic activity with ginger, but blood lipid levels were not different from control animals (Verma et al. 2004). Another compound isolated from ginger, (E)-8 β,17-epoxylabd-12-ene-15,16-dial, was reported to inhibit cholesterol biosynthesis (Tanabe et al. 1993), and ginger meal (1%) decreased serum cholesterol levels significantly (Dias et al. 2006). Ginger was also reported to slightly reduce retinoid-binding protein mRNA expression levels in liver and visceral fat in male rats that were fed cholesterol to induce hyperlipidemia (Matsuda et al. 2009). These results hint that ginger consumption might improve lipid metabolism (Matsuda et al. 2009).

Antiplatelet therapy is an effective approach for preventing coronary heart disease. Ginger components are suggested as a potential new class of platelet-activation inhibitors without the potential side effects of aspirin, which is most commonly used in this approach. In a comparison of gingerols and analogs with aspirin, ginger compounds were found to be less potent compared to aspirin in inhibiting arachidonic acid-induced platelet release and aggregation and COX activity (Koo et al. 2001). However, several analogs had a significant inhibitory effect, suggesting that further development of more potent gingerol analogs might have value as an alternative to aspirin therapy in preventing ischemic heart disease (Koo et al. 2001). Consumption of ginger (5 g) inhibited platelet aggregation induced in men who consumed 100 g of butter daily for 7 days (Verma et al. 1993), and a later study showed that ginger enhanced fibrinolytic activity (Verma and Bordia 2001). An evaluation of the antiplatelet activity of 20 pungent constituents of ginger revealed that [8]-paradol was the most potent COX-1 inhibitor and antiplatelet aggregation agent (Nurtjahja-Tjendraputra et al. 2003). [8]-gingerol and [8]-shogaol were also found to be effective antiplatelet aggregation agents (Nurtjahja-Tjendraputra et al. 2003). Ginger and nifedipine (a calcium-channel blocker) were reported to have a synergistic effect on antiplatelet aggregation in normal human volunteers and hypertensive patients (Young et al. 2006). Ginger oil (24% citral) effectively lowered spontaneous or prostoglandin F2-alpha (PGF2-alpha)-2α-induced rat myometrial (uterus) contractility, and increases in external calcium concentration reversed the relaxant effects of ginger oil (Buddhakala et al. 2008). Ginger compounds have been reported to directly stimulate myocardial sarcoplasmic reticulum (SR) calcium uptake (Antipenko, Spielman, and Kirchberger 1999 Maier et al. 2000), but its therapeutic use in treating heart failure has not been advocated (Maier et al. 2000). Ginger is also used to treat asthma, diabetes, and other conditions.

Asthma is a chronic disease characterized by inflammation and hypersensitivity of airway smooth muscle cells to different substances that induce spasms, and ginger has been used for centuries in treating respiratory illnesses. Components of ginger rhizomes are reported to contain potent compounds capable of suppressing allergic reactions and might be useful for the treatment and prevention of allergic diseases (Chen et al. 2009). Ghayur, Gilani, and Janssen (2008) reported that a ginger extract inhibits airway contraction and associated calcium signaling, possibly by blocking plasma membrane calcium channels. In a mouse model of Th2-mediated pulmonary inflammation, an intraperitoneal injection of a ginger extract mainly comprised of gingerols markedly decreased the recruitment of eosinophils to the lungs in ovalbumin-sensitized mice and also suppressed the Th2 cell-driven response to allergen (Ahui et al. 2008).

Ginger has been suggested to have antidiabetic effects. In the streptozotocin-induced diabetic rat model, rats that were fed ginger exhibited better glucose tolerance and higher serum insulin levels than untreated rats, suggesting that it can help control blood sugar levels (Islam and Choi 2008). Treatment with a ginger extract produced a significant reduction in fructose-induced elevation in lipid levels, body weight, hyperglycemia, and hyperinsulinemia associated with insulin resistance (Kadnur and Goyal 2005). An aqueous extract of raw ginger (administered daily, 500 mg/kg intraperitoneally) to streptozotocin-induced diabetic rats lowered serum glucose, cholesterol, and triacylglycerol levels decreased urine protein levels, water intake, and urine output and prevented the weight loss associated with diabetes in this model (Al-Amin et al. 2006). [6]-gingerol has also been found to enhance differentiation of 3T3-L1 preadipocytes and to enhance insulin-sensitive glucose uptake (Sekiya, Ohtani, and Kusano 2004). A later study showed that [6]-shogaol or [6]-gingerol significantly inhibited TNF-α-mediated downregulation of adiponectin expression in 3T3-L1 adipocytes (Isa et al. 2008). [6]-shogaol appeared to function as a peroxisome proliferator-activated receptor (PPAR)γ agonist, whereas [6]-gingerol acted by suppressing TNF-α-induced JNKs signaling (Isa et al. 2008). These results give some suggestion that ginger might be valuable in managing the effects of diabetes in humans.

Dried ginger may have beneficial effects in treating dementia, including Alzheimer’s disease (Ghayur, Gilani, Ahmed, Khalid, Nawaz, Agbedahunsi, Choudhary, and Houghton 2008). Ulcerative colitis is a chronically recurrent inflammatory bowel disease of unknown origin, and in rats, ginger extract alleviated the symptoms of acetic acid-induced ulcerative colitis (El-Abhar, Hammad, and Gawad 2008).


Schistosomiasis, a parasite that damages the liver and intestines, may respond well to treatment with ginger extract, according to researchers in the biology department of King Khaled University, Saudi Arabia. Ginger produced the most inhibition of the parasite among several tested plants in the study. Worms treated with ginger had altered surface structures with loss of certain areas and erosion in others. Microscope evaluation of liver tissue showed fewer and smaller affected areas in ginger-treated animals. The study was published in the February 2011 issue of the journal "Parasitology Research."

This Simple Drink Will Clear Mucus From Your Lungs And Give An Instant Boost To Your Immune System

Our body’s final defense wall is our immune system, which protects us from viruses and diseases, and prevents the attacks of numerous microorganisms that enter the body via food.

The immune system consists of tissues and organs work together to fight foreign bodies.

Lungs are also important since their primary function is to inhale and store oxygen, and to exhale carbon dioxide through the nose. Yet, if the nose is blocked with mucus, it influences the lungs.

The following drink will strengthen your immune system and remove mucus from the lungs. It can be used by both, children and adults, and provides quick and significant effects.

Children often play in the water, dirt, and filth, so they are more prone to sickness. Yet, their immune systems are developing and they become resistant to various diseases.

Yet, children most commonly suffer from a cough and colds. If these issues persist, it indicates that mucus is accumulated in the lungs.

Our body creates lots of mucus on a daily basis, almost 1-2 liters. The majority of it is spat out, but in the case of colds, it clogs the breathing tubes and leads to health issues, including allergies.

If it persists and turns greenish in color, or even mixed with blood, the health problem may be serious, so you should visit a doctor.

The immune system prevents diseases and foreign bodies and reduces various health risks, germs, parasites, viruses, and bacteria. It contains lymph nodes, which produce and store the cells which protect us from bacteria and viruses.

Additionally, the bone marrow is another component which creates white blood cells and stores the stem cells, which have the ability to morph into any human cell.

The immune system also includes the spleen, which involves the white blood cells, and controls the amount of blood. The immune system this creates antibodies which destroy viruses which may cause diseases.

Therefore, the following recipe will be of great help, as it boosts the immune system and eliminates excess mucus from the lungs:

  • 100 grams honey
  • 100ml water
  • 4 tbsp freshly squeezed lemon juice
  • 1 inch of ginger (grinded)
  • 50 grams oats

Initially, rinse the oats and mix them with the water and the grinded ginger . Then, boil the mixture for several minutes. After it cools add the honey and the lemon juice and leave it thus overnight. Store the drink in the fridge, and you can use it up to a week.

Every morning, on an empty stomach, drink 30-40ml of this drink. Repeat this for 40 days to boost the immune system. Then, make a 15-day break, and repeat the treatment for 40 more days. It can also be used in children, and it will strengthen their immunity to prevent all kinds of viruses and bacteria.

Also if you want to speed up the process of eliminating excess mucus from the lungs we highly recommend you to use steam:

Leftover Juice Pulp Gets a Second Life with These DIYs

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One of the questions I get asked most about juicing is “What can I do with the juice pulp?” Tons of things! Read on for 20 of my favorite uses for leftover juice pulp — and get inspired to reduce your food waste and make fantastic use of healthful fiber.

1. Blend pulp into a smoothie to add fiber.
2. Add to a soup to thicken and boost fiber and nutrient density.
3. Use fruit pulp to make frozen “pulpsicles” or fruit pulp ice.
4. Make a veggie broth by boiling pulp with water, herbs, and spices, then straining.
5. Make a “fruit tea” by boiling fruit pulp with water, adding spices such as cinnamon or ginger, cooling, and then straining.
6. Use veggie pulp to add nutrient density to mac n’ cheese or pasta sauce, or layer into a lasagne.
7. Make fabulous fruit leathers.
9. Use in homemade veggie burgers or fritters. Pulp adds moisture, flavor, and nutrition.
10. Mix pulp into baked goods like muffins, cakes, bread, dehydrated or baked cookies, and granola bars. Celery, onion, carrot, sweet potato, spinach, apple, and berry all work beautifully.
11. Use fruit or veggie pulp to add flavor, texture, and moisture to pancakes.
12. Make dehydrated pulp crackers.
13. Use pulp for raw pizza crust.
14. Make pulp marmalade.
15. Make a pulp crumble by mixing pulp with fruit and juice, reducing, and then topping with oats, spices, nuts, or seeds.
16. Dehydrate and make trail mix with raw nuts, seeds, and dried fruits.
17. Dehydrate and use like bread crumbs.
18. Use in DIY skincare recipes like scrubs, masks, and soap.
19. Mix pulp into your dog’s food or make dog treats.
If all else fails:
20. Feed it to your chickens, freeze it in ice cube trays to use later, or compost it.

*Please note, the moisture content of your juice pulp can vary depending on your juicer, so you may need to squeeze out excess juice for the best results in some of these recipes.

Tess Masters is an Australian actor, presenter, voice-over artist, cook, and writer living in Los Angeles. Her alter-ego,“The Blender Girl”writes the quirky vegetarian recipe blog Healthy Blender Recipes, where she shares super quick and easy gluten-free, vegetarian, vegan, and raw recipes. Join Tess on Facebook, Twitter,Pinterest, You Tube, and Google +.

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