Active chemical constituents in Acorus calamus L. Root 

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... this acid degradation. Higher cytokine level contributes to higher intensity of dysmenorrheal pain and associated symptoms (Chen et al., 2013). In western medicines, non-steroidal anti-inflammatory drugs (NSAIDs) are normally administered to treat primary dysmenorrheal symptoms. In spite of their quickness and effectiveness in relieving pain, NSAIDs have many serious side effects on the liver, kidney and gastrointestinal tract. Traditional Chinese Medicine (TCM) is an alternative way to treat primary dysmenorrhea. For example, YuanHu painkiller, which is composed of Corydalis yanhusuo and Angelica dahurica , has been recorded in the 2000, 2005, and 2010 edition of the Chinese Pharmacopoeia (volume one) as a drug for the treatment of primary dysmenorrhea, migrain, and stomachache (Chen et al., 2013). Prasaplai usage as a preparation to treat primary dysmenorrhea and anti-inflammatory effect was pharmacologically confirmed by Waltenberger et al. (2011). The chemical constituents in each plant component of the preparation concerning cyclooxygenase-1 (COX-1), cyclooxygenase-2 (COX-2) and other inflammatory mediators have been summarized (Waltenberger et al., 2011). 1. Zingiber cassumunar has been reported with IC 50 (inhibition concentration at 50%) values against COX-2, ranging from 2.71 to 20.98 μM (Han, 2005). The first two compounds are structurally related to phenyl propane, which are 4-(3,4-dimethoxy-phenyl)but-1,3-diene (DMPBD), 4- [2,4,5-trimethoxy-phenyl)but-1,3-diene (TMPBD), and showed high IC 50 of 14.97 and 20.68 μM, respectively (Fig. 1). The other two compounds containing tri-cyclics structure, which are trans -3-(3,4-dimethoxy-phenyl)-4-[(E)- 3 ́,4 ́ -dimethoxy-styryl] cyclohex-1-ene and (±)- trans -3-(4-hydroxy-3-methoxy-phenyl) -4-[(E)- 3 ́,4 ́ -dimethoxy-styryl]cyclohex-1-ene, exhibited low IC 50 of 2.71 and 3.64 μM, respectively. The tri-cyclics structure is selectively fitted into the COX-2 enzyme better than the phenyl propane derivatives (Tangyuenyongwatana et al., 2009). In the lipopolysaccharide-induced expression of cyclooxygenase-2, cis -3- (3 ́,4 ́ -dimethoxyphenyl)-4-[( E )- 3 ́ ́ ́, 4 ́ ́ ́ -dimethoxy-styryl] cyclohex-1-ene (compound B), cis -3- (2 ́,4 ́,5 ́ -trimethoxyphenyl)-4-[( E )- 2 ́ ́ ́,4 ́ ́ ́,5 ́ ́ ́ -trimethoxy-sty ryl]cyclohex-1-ene (compound C) and DMPBD reduced PGE 2 and COX-2 expression in dental pulp inflammation (Aupaphong et al., 2013; Koontongkaew et al., 2013). In addition, curcumin, which was found as a minor compound in Z. cassumunar , has an ability to suppress the expression of COX-2 (Surh and Kundu, 2007). Other mechanisms include the inhibitory effects on lipopolysaccharide (LPS)-induced nitric oxide (NO) production, experimented in mouse peritoneal macrophages in which DMPBD, TMPBD, and cassumunaquinone showed IC 50 of 69, 83, and 47 μM, respectively (Nakamura et al., 2009). In addition, Chaiwongsa and co-workers reported an anti-inflammatory activity of compound D against the IL-1 induced catabolic gene expression involved in cartilage degeneration (Chaiwongsa et al., 2013). Compound D behaved as an upstream inhibitor of the catabolic cascade in chronic joint erosion. In regards to immunostimulation, compound D, (E)-4- (2 ́,4 ́,5 ́ -trime thoxy phenyl)-3-en-1-ol and (E)-4- (3 ́,4 ́ -dimethoxyphenyl)-3-en-1- methoxy-1-ol, showed significant immunostimulant activity on phagocytosis potential and percentage activity of the phagocytosis (Chairul et al., 2009). 2. Zingiber officinale , a minor component in the Prasaplai preparation, contains five COX-2-inhibitory compounds, which are [6]-shogaol, [8]-gingerdiol, [6]-paradol, [8]-gingerol, and [8]-shogaol (Fig. 2) with IC 50 of 2.1, 12.5, 24.5, 10.0, and 7.2 μM, respectively (Tjendraputra et al., 2001). 3. Nigella sativa or black cumin is also a minor component in the preparation that shows both COX-1 and COX-2 inhibitory effects. Four compounds, thymoquinone, thymohydroquinone, dithymoquinone, and thymolm (Fig. 3) are responsible for the COX-2 inhibitory activity and exhibited excellent IC 50 of 0.3, 0.1, 0.9, and 1.0 μM, respectively (Marsik et al., 2005). Thymoquinone was explored as an anti- inflammatory agent on arthritis in rat models. Signs of inflammation on the claw and radiological signs were searched and tumor necrosis factor - alpha (TNF- α ) and IL-1beta were measured. The result showed that thymoquinone suppressed adjuvant-induced arthiritis in rats (Takeoglu et al., 2007). 4. Piper nigrum or black pepper is a general household ingredient and is a component in the preparation that showed COX-inhibition activities in the moderate manner. Spathulenol (Fig. 4) inhibited COX- 2 receptor 54% at 454 μM (Jayaprakasam et al., 2007) while piperine inhibited prostaglandin synthesis 33.4% at 37 μM (Wagner et al., 1986). Nonanal and trans-2-nonenal reduced arachidonic metabolites by 50% at about 0.25 μM (Sakuma et al., 1997). 5. Acorus calamus is a minor component that contains α– asarone and asaraldehyde (Fig. 5) with COX-1 and COX-2 inhibitory activities. They demonstrated moderate inhibitory activity against COX-2 at 64.39% (480 μM) and 52.69% (510 μM ), repectivly. 6. Allium sativum or garlic, of which the ethyl acetate fraction inhibited the LPS-induce dimerization of toll-like receptor 4 (TLR4), resulting in the inhibition of NF- κB activation and the expression of COX-2 and NO synthase (iNOS). The garlic extract could directly inhibit the TLRs- mediated signaling pathway at the receptor level (Youn et al., 2008). 7. Citrus hystrix contains three coumarins, i.e. bergamottin, oxypeucedanin, and psoralen (Fig. 6) which could inhibit both lipopolysacharide and interferon-induced NO generation in RAW 264.7 cells (Murakami et al., 1999). 8. Curcuma zedoaria , the anti-inflammatory activity of sesquiterpene furanodiene and furanodienone (Fig. 7) could suppress the 12-O-tetradecanoylphobol-13-acetate (TPA) induced inflammation of mouse ears by 75% and 53%, respectively, at dose of 1.0 μmol (Makabe et al., 2006). Oh et al. (2007) used bioassay-guided fractionation which led to an isolation of curdione from the rhizome of C. zedoaria with the inhibitory effect on the production of PGE2 in LPS-stimulated mouse macrophage RAW 264.7 cells in a concentration- dependent manner (IC 50 = 1.1 μM). Jang et al. (2004) reported active compounds, 1,7-bis(4-hydroxyphenyl)-1,4,6-heptatriene- 3-one, procurcumenol, and epiprocurcumenol, isolated from C. zedoaria which inhibited the NO production in LPS-activated macrophages. It was found that 1,7-bis(4-hydroxyphenyl)- 1,4,6-heptatriene-3-one was the most potent (IC 50 = 8  M) compound and inhibited NO production through suppression of iNOS expression. 9. Piper retrofractum , the 80% aqueous acetone extract from the fruits of P. retrofractum was found to show protective effects on ethanol- and indomethacin-induced gastric lesions in rats (Morikawa et al., 2004). The extract composes of piperine, piperanine, pipernonaline, dehydropipernonaline, piper loguminine, N-isobutyl-(2E,4E)-octadecadienamide, N-isobutyl -(2E,4E)-eicosatrienamide, methyl piperate and retrofractamide which significantly inhibited ethanol-induced gastric lesions at a dose of 25 mg/kg. All of these compounds may potentially possess the synergistic effect with other herbs. 10. Eleutherine americana , its biological activity of the rhizome was tested on isolated guinea pig heart, and showed effective activity on angina pectoris in a preliminary clinical trial. The naphthalene derivatives, eleuterol, eleutherin, hongconin, and isoeleutherin, were effective in increasing coronary flow of isolated guinea pig heart. When the mixture of naphthalene derivatives was prepared as tablets for clinical use against angina pectoris, it was as effective as dipyidamol in clinical trial (Tang and Eisenbrand, 1992). Paramapojn et al. (2008) reported the anti-acetylchlorinesterase of eleutherin and isoeleutherin with the IC 50 of 5.71 and 5.69 μM, respectively. This herb may synergistically enhance other herbs’ activities in the preparation. Oriental medicines, whether it is TCM or Ayurvedic medicines, often display a similar trend or philosophy in their formulation. Also in Thai traditional medicine, many medicinal plants are selectively and carefully combined for the treatment of diseases. Like TCM, a traditional prescription normally includes different parts, constituting four components - the principal (monarch), adjuvant (minister), auxiliary (assistant), and conductor (guide). The principal herb provides the main curative action; the adjuvant strengthens the principal activity; the auxiliary relieves side effects of the principal herb; while the conductor directs the actions of the principal and adjuvant herbs to the affected area. This preparation philosophy, combining with comprehensive knowledge and wisdom of medicinal herbs, also applies to the Prasaplai preparation. Z. cassumunar , being a major component (50%) in the preparation and possessing potent anti-inflammatory activity, is the principal ingredient. The other herbs, which are Z. officinale , N. sativa , A. calamus , A. sativum , and C. zedoaria , may act as adjuvants on anti-inflammatory activity. P. nigrum and P. retrofractum , having moderate anti-inflammatory activity, may behave as assistant and guide the herbs in the preparation. Piperine from P. nigrum and P. retrofractum , being able to enhance bioavailability of drugs and phytochemical compounds, may enhance the activity of the principal and adjuvant herbs in Prasaplai preparation (Johnson et al., 2011; Lambert et al., 2004). Nualkaew et al. (2004) reported 3 artifacts originated during the storage of Prasaplai. Two artifacts, (E)-4-(3,4- dimethoxyphe-nyl)but-3-en-1-yl linoleate ( 1 ) and (E)- 4-(3,4- dimethoxy-phenyl)but-3-en-1-yl oleate ( 2 ) were new fatty acid esters. Another one was the known (E)-4-(3,4-dimethoxy- phenyl)but-3-en-1-yl palmitate ( 3 ) (Fig. 8). The artifacts were found after ...