DRAFT 12.1Symptoms of General Nausea 2.1.1 The Cause of Nausea2.1.1.1 Motion SicknessSome people feel very sick while travelling in an airplane, boat, train, or car. This sickness is called motion sickness. The symptom of motion sickness will start to improve as human body adapts to the conditions causing the problem. The problems are like queasy, nausea, vomit and headache. From all of ages, children are more susceptible to motion sickness than adults. There are lots of types of motion sickness divided by the transportation they drive, for example car sickness, sea sickness and others. When we are in transportation which moves continuously with relatively slow and prolonged motion, the organ of balance in human ear may be affected, causing motion sickness. In motion sickness, a discrepancy exists between the motion that is expected to occur and the actual motion sensed by the organ of balance in the inner ear. These unexpected signals translate into confused message by the brain, leading to the development of symptoms. The important roles of motion sickness are acetylcholine and dopamine. 2.1.1.2 Pregnancy Commonly, nausea and vomit cant be separated from pregnancy. We often call it as morning sickness. Although this is misnomer because the symptom will often persist throughout the day. From the Journal of Nausea and Vomiting in Pregnancy, up to 85% of women experience nausea in early pregnancy with approximately half of women vomiting as well. On the other hand, gestational vomiting results from various metabolic and endocrine factors, many of placental origin. The most implicated factor is human chorionic gonadotropin (hCG). In addition, nausea and vomiting are often worse in pregnant women with conditions associated with elevated hCG levels such as molar pregnancies, multiple gestations, and Down syndrome. Moreover, a study by Goodwin et al. found that concentrations of hCG correlated positively with the severity of nausea and vomiting in women with HG. 2.1.1.3 Post-ChemoterapyBased on Nausea and Vomiting Journal, not all cancer patients will experience nausea, vomiting (emesis), or both. The most common causes are emetogenic chemotherapy drugs and radiation therapy to the gastrointestinal (GI) tract, liver, or brain. Several patient characteristics have also been identified, such as:2.1.1.3.1 Incidence and severity of nausea and vomiting (N&v) during past courses of chemotherapy. Patients with poor control of N&V during prior chemotherapy cycles are likely to experience N&V in subsequent cycles. 2.1.1.3.2 History of chronic alcohol use. N&V is less likely in patients with history of chronic high intake of alcohol2.1.1.3.3 Age. N&V is more likely in patients younger than 50 years old. 2.1.1.3.4 Gender. N&V and more likely in women2.1.1.4 Post-operativeApfel and colleagues identified four risk factors, which can trigger Post-Operative Induced Nausea, like female gender, motion sickness, non-smoking status and use of post-operative opioids. Based on the British Journal of Anaesthesia, the four factors which have been mention above can increase the likelihood of PONV by 18-22%. The causes of Post-Operative Induced Nausea are multifactorial. It can be categorized into three factors such as patient risk factors, anaesthetic technique, and surgical procedure. Based on the Apfel criteria, patient risk factors include female gender from puberty, non-smoking status, previous history of Post-Operative Nausea and Vomiting (PONV) or motion sickness, and genetic predisposition. Anaesthetic technique includes the use of inhalation agents, nitrous oxide, large-dose neostigmine, and intraoperative and postoperative opioid use. The duration of surgery and different types of surgeries, as the part of surgical procedure, can affect the cause of PONV. From the research, the duration of surgeries is unacceptable. However, higher doses of opioids and longer exposure to inhalation anaesthetic are likely to occur and are known risk factors of PONV.

Picture .Algorithm for Management of Postoperative Nausea and Vomiting(Source: Gan, Tong J., etc. 2014. Consensus Guidelines for the Management of Postoperative Nausea and Vomiting. Anest Analg:118:85-113)

2.1.2 Mechanism of Nausea In central nervous system, there are three structures which are considered as a coordination reflex centre of vomiting, which is called Chemoreceptor Trigger Zone (CTZ), vomiting centre, and Nucleus Tractus Solitarus (NTS). All of those structure is located in the areas of brain stem. In case of mechanism of nausea and vomiting, there are two anatomical regions in the medulla which takes role in reflex of vomiting, such as CTZ and Central Vomiting Centre (CVC). CTZ is located in the area of postrema in the caudal part of the fourth ventricle which is labeled at bottom center, outside the blood-brain barrier. Receptors in this region are activated by pro-emetic substances in blood circulation or in the Cerebrospinal Fluid (CSF). Efferent signals from CTZ are sent to CVC. Then, through the vagus nerve as a pathway efferent, there was a series of sympathetic and parasympathetic reaction which ended with vomiting reflex. CVC is located near the Nucleus Tractus Solutarus (NTS) and around the formation reticularis of the medulla below the CTZ. Chemoreceptor trigger zone contains receptors for various neuroactive compounds which can lead to vomit reflex. Gag reflex stimuli is derived from gastrointestinal, vestibule-ocular, higher afferent cortical toward CVC. Then it causes the symptom of nausea, retching and expulsion of gastric content. In addition, the vomiting center in medulla oblongata is in the close proximity to other visceral center like the respiratory and vasomotor center. Four types of receptors are involved cholinergic, dopaminergic, histaminic and serotonergic.

Picture. Pharmacologist view of emetic stimuli(Source: Islam, Saeda., Jain. 2004. Post-Operative Nausea and Vomiting (PONV). Indian Journal Anaesth : 48(4): 253-258)2.2.2Anti-Nausea Herbs 2.2.2.1 Ginger (Zingiber officinale)

Picture. Ginger(Source: http://www.lifehack.org/articles)2.2.2.1.1 Gingers Habitat (Zingiber officinale)Zingiber officinaleis best known as the source of the pungent, aromatic spice called ginger. This spice is produced from the rhizome (underground stem) of the plant. Other spices in the ginger family (Zingiberaceae) include cardamom (Elettaria cardamomum) and turmeric (Curcuma longa). Ginger has been grown in the lowlands to the mountain above the sea level. Ginger thrives near the flow of water or wells. Indonesia is one of the best habitat for ginger to grow.2.2.2.1.2 Active Compounds in Ginger and Their PropertiesSeveral compounds in ginger (e.g., [6]-gingerol, [6]-shogaol, and galanolactone) have been shown to have anti- serotonin (5-hydroxytryptamine) effects (Yamahara et al., 1989; Huang et al., 1991). This may possibly suggest that the anti-emetic action of either ginger or some of its constituents may be mediated centrally via 5-HT3 receptors, as these constituents have small molecular weights and could easily cross the blood brain barrier. In Suncus murinus (a house musk shrew), it has been shown that orally administered [6]-gingerol completely prevented vomiting in response to cyclophosphamide, presumably via a central effect (Yamahara et al., 1989)Several authors have shown that ginger is endowed with strong in vitro and in vivo anti-oxidant properties. The antioxidant action of ginger has been proposed as one of the major possible mechanisms for the protective actions of the plant against toxicity and lethality of radiation and a number of toxic agents such as carbon tetrachloride and cisplatin and as an anti-ulcer drug (Siddaraju and Dharmesh, 2007).2.2.2.13 Method of Extracting the Active Compounds in GingerBased on the thesis of Extraction of Essential Oils from Ginger Rhizome Using Steam Distillation Method, Aizam (2006:2) said that in Zingiber officinale Roscoe, there are many constituents such as acids, shoagaols, gingerol, essential oils, fiber, amino acids and minerals. There are two ways of extraction, that is using steam distillation and solvent extraction. In order to get oleoresin, solvent extraction technique is used but to obtain essential oil, steam distillation technique is used. Steam distillation method is used for temperature sensitive material like natural aromatic compounds. For this method, there is no solvent is used to extract the material but pure water is the main component to do it.

2.2.2.2 Peppermint

Picture. Peppermint Leaves(sources: http://thebathtubdiva.com/peppermint-power)2.2.2.2.1 Peppermints Habitat Peppermint also known as Mentha L. Mentha genus are widely distributed and can be found in many environments. Most of them grow best in wet environments and moist soils. Mints will grow 10-120 cm tall and can spread over an indeterminate area.2.2.2.2.2 Active Compounds in Peppermint and Their PropertiesMedicinally, peppermint is used to aid the various processes of digestion: to combat gas, increase bile flow, heal the stomach and liver, etc. Its active constituents are found in its essential oil, mainly menthol, menthone and menthyl acetate. Menthyl acetate is responsible for peppermints minty aroma and flavor. Menthol, peppermints main active ingredient, is found in the leaves and flowering tops of the plants. The menthol content of peppermint oil determines the quality of its essential oil. This varies depending upon climate, habitat and where the peppermint is grown. The oil's spasmolytic, anti-ulcer, anti-inflammatory, and antibacterial properties have been experimentally verified (Herman, 1977:2).Various constituents of peppermint oil as per monographs of Internation Pharmacopoeia are limonene (1.0-5.0%), cineole (3.5-14.0%), menthone (14.0-32.0%),menthofuran (1.0 -9.0%), isomenthone (1.5-10.0%),menthyl acetate (2.8-10.0%), isopulegol (max. 0.2%),menthol (30.0-55.0%), pulegone (max. 4.0%) and carvone (max. 1.0%). The ratio of cineole content to limonene content should be minimum two.More recently, its use has been advocated for transport-related nausea1 as well as for PONV in children and adults. Winston (1989:4) found that isopropyl alcohol inhalation relieved PONV more rapidly than ondansetron 4 mg IV, but a placebo group was not studied. A randomized, doubleblind, placebo-controlled study on surgery patients indicate that initial treatment of postoperative nausea with aromatherapy reduces patients subjective perception of nausea and IV antiemetic use in the PACU by nearly 50%.

2.2.2.2.3 Method of Extracting the Active Compounds in Peppermint Peppermint oil is extracted from the whole plant above ground just before flowering. The oil is extracted by steam distillation from the fresh or partly dried plant and the yield is 0.1 - 1.0 %. Recently on new method was developed by Farid Chemet et al. for the extraction of essential oils that is much more faster as compared with the conventional hydro distillation process.2.2.2.3 Chamomile

Picture. Chamomile Flower(Source: http://globe-views.com/chamomile.html)2.2.2.3.1 Chamomiles HabitatChamomile is one of the most ancient medicinal herbs known to mankind. It is a member ofAsteraceae/Compositaefamily. The main natural habitats of this species are grazed grasslands on cliff-tops, heaths, commons and village greens with moderately acid clay soils. At present it thrives in a number of cricket pitches, where mowing and rolling create ideal short turf conditions2.2.2.3.2 Active Compounds in Chamomile and Their PropertiesBased on a NCBI jurnal, Chamomile, A Herbal Medicine of The Past with Bright Future, Srivastava (2011:1) said that different classes of bioactive constituents are present in chamomile, which have been isolated and used as medicinal preparations and cosmetics. The plant contains 0.24%1.9% volatile oil, composed of a variety of separate oils. When exposed to steam distillation, the oil ranges in color from brilliant blue to deep green when fresh but turns to dark yellow after storage. Despite fading, the oil does not lose its potency. Approximately 120 secondary metabolites have been identified in chamomile, including 28 terpenoids and 36 flavonoids. The principal components of the essential oil extracted from the German chamomile flowers are the terpenoids -bisabolol and its oxide azulenes including chamazulene and acetylene derivatives. Chamomiles essential oil comprises 0.5% to 1.5% of the flower head. One hundred twenty chemical constituents have been identified in chamomile, including terpenoids, flavonoids, and coumar. Chamazulene and bisabolol are very unstable and are best preserved in an alcoholic tincture. It also contains farnesene and -pinene. Among flavonoids, apigenin is the most promising compound. It is present in very small quantities as free apigenin, but predominantly exists in the form of various glycosides.2.2.2.3.3 Method of Extracting the Active Compounds in ChamomileFrom A Herbal Medicine of The Past with Bright Future Journal, Srivastava et al. (2011: 3) explain that chamomile is known to be used in various forms of its preparations. Dry powder of chamomile flower is recommended and used by many people for traditionally established health problems. Medicinal ingredients are normally extracted from the dry flowers of chamomile by using water, ethanol or methanol as solvents and corresponding extracts are known as aqueous, ethanolic (alcoholic) and/or methanolic extracts. Optimum chamomile extracts contain about 50 percent alcohol. Normally standardized extracts contain 1.2% of apigenin which is one of the most effective bioactive agents. Aqueous extracts, such as in the form of tea, contain quite low concentrations of free apigenin but include high levels of apigenin-7-O-glucoside.2.2.2.4 Basil

Picture. Basil Leaves(source: http://planetforward.ca/ organic-garden-journal-basil-experiment/)2.2.2.4.1 Basils Habitat Basil has its unique place to grow. The soil should be light and slightly acidic. It will achieve the best growth if the soil is well-drained and nutrient rich having lots of humus and minerals. The basil can tolerate pH between 4.3 until 8.4. Commonly, plant needs sunlight, so basil will grow if it get an enough sunlight and water. Excess of water will not make the Basil grow because it cant grow in such condition. In conclusion, basil will grow in the garden.2.2.2.4.2 Active Compounds in Chamomile and Their PropertiesBasil has long been made into an herbal tea to treat digestive problems, and has also traditionally been used for its antiseptic and antibacterial properties. Herbalists also recommend basil to treat a variety of ailments including insect bites, anxiety, headaches, cramps, nausea and digestion. Basil has a high economic value due to the presence of specific substances such as estragol, lineol, linalool, eugenol, methyl cinamato, limonene and geraniol. From the journal of Basil Medicine plant, Husein (2011: 2) explain that the various basils have such different scents because the herb has a number of different essential oils that come together in different proportions for various breeds. The strong clove scent of sweet basil is derived from eugenol, the same chemical as actual cloves (Fandohan et al., 2008).

2.2.2.43 Method of Extracting the Active Compounds in BasilMostly, basil extracts into an oil for aromatic and medicinal thing. These species are known specifically for possessing biological activity, such as antibacterial, antifungal and antioxidant properties. The molecules inside basil are extremely sensitive to heat. If there is a contact with heat, the chemical will changes and occurs some losses of volatile compounds in higher or lower concentration. Several methods can be used to this extraction such as conventional methods. Conventional methods are hydro distillation, steam distillation, solvent extraction, Soxhlet extraction. It also use the unconventional method such as supercritical carbon dioxide extraction.2.4 Comparisons of Active Compounds in Anti-Nausea Herbs with Others Herbs

Types of CharacteristicHerbs Plant

GingerPeppermintChamomileBasil

Scientific nameZingiber officinaleMentha piperitaChamaemelum nobileOcimum basilicum L.

Chemical componentZingiberene, -bisabolene, -farnesne, n-hexane, monoterpene hydrocarbons, gingerols, paradols, shogaols, and gingerones and etc. limonene, cineole, menthone, menthofuran, isomenthone, menthyl acetate, isopulegol, menthol, pulegone and carvone.Terpenoids -bisabolol, chamazulene, acetylene, farnesene, spiro-ether quiterpene lactones, glycosides, hydroxycoumarins, flavonoids, coumarins, apigenin, and mucilageButylated hydroxytoluene (BHT), Linoleic acid, -carotene, 2,2-diphenyl-1-picrylhydrazyl (DPPH), anhydrous carbonate, ferrous chloride, ammonium thiocyanate, chloroform and methanol

Medicinal propertiesanti-inflammatory, antioxidant and antiproliferative activities, indicating its promising role as a chemopreventive agentAntimicrobial and anti-plasmid activities, postoperative nausea, against herpes simplex virus, larvicidal and mosquito repellent action, indisgestion and etc.Anti-inflammatory and antiphlogistic properties, anticancer activity, common cold, cardiovascular conditions, and etc.Antiseptic, antioxidant, anti-cancer, anti-viral and anti-bacteria properties.

Potential health effectstreatment of such disorders as arthritis, stomach upset, asthma, diabetes, and menstrual irregularities, to name a few. Ginger may alleviate the symptoms of nausea and vomiting following pregnancy, surgery, cancer therapy and etc.used in food, pharmaceutical and perfumery and flavouring industry. Its main constituent, menthol, is used in the manufacture of lozenges, toothpastes, pain balms, cold balms, Dabur Pudin Hara, etc.used to treat wounds, ulcers, eczema, gout, skin irritations, bruises, burns, canker sores, neuralgia, sciatica, rheumatic pain, hemorrhoids, mastitis and other ailments. used for supplementary treatment of stress, asthma and diabetes

Tabel 1. Perbandingan karakteristik tanaman herbal anti-nausea(Source: reproduced)

References Aizam, Khairu. 2006. Extraction of Essential Oils from Ginger Rhizome Using Steam Distillation Method. Thesis of Chemical and Natural Resources Engineering, University College of Engineering & Technology Malaysia.Keith. 2010. Ginger: An Overview of Health Benefits. Journal of Food and Science: Volume 45: pp 171-183.Alankar, Shrivastava. 2009. A Review on Peppermint Oil. Asian Journal of Pharmaceutical and Clinical Research : Volume 2: Issue 2. Srivasta, Janmejai K., Shankar. E, Gupta, S. 2010. Chamomile: A Herbal Medicine of The Past With Bright Future. NCBI Journal : 3(6): 895-901Tilebeni, Hossein Gholami. 2011. Review to Basil Medicinal Plant. International Journal of Agronomy and Plant Production : Volume 2 (1): 5-9Ali, Badrekin., Blunden, Gerald., Tanira, Musbah. 2007. Some Phytochemical, Pharmacological and Toxicological Properties of Ginger (Zingiber officinale Roscoe): AReview of Recent Research. Journal of Food and Chemical Toxicology: 46 : 409-420.Ernst, E., Pitler, M. H. 2000. Efficacy of Ginger for Nausea and Vomiting: A Systematic Review of Randomized Clinical Trials. British Journal of Anaesthesia: 84(3):367-71.Khresheh, Reham. 2011. How Women Manage Nausea and Vomiting During Pregnancy : a Jordanian Study. Journal of Maternal and Child Health : 27:42-45Andrykowski MA, Gregg ME.1992. The role of psychological variables in post-chemotherapy nausea: anxiety and expectation. Psychosom Med 54 (1): 48-58