Article

Uterotrophic Effect of Curcuma comosa in Rats

Authors:
To read the full-text of this research, you can request a copy directly from the authors.

Abstract

Abstract Uterotrophic activities of various extracts of Curcuma comosa were investigated in rats. Among the four extracts tested (hexane, ethyl acetate, butanol and aqueous extract), hexane was the most effective in increasing uterine weight and glycogen content of bilaterally ovariectomized immature rats. The responses were dose-dependent. The hexane extract also induced cornification of vaginal epithelium, promote growth and induced keratinization of vaginal mucosa in ovariectomized mature rats. The duration of action and strength of the extract in increasing uterine weight, uterine levels of glycogen, DNA and protein, and inducing of morphological changes were less than those of estradiol. However, when the extract was given prior to, concurrent with, or after estradiol injection, it enhanced the uterine response to estradiol in all cases. These results suggest that the uterotrophic action C. comosa is mediated through weak estrogenic agonistic activity of the plant.

No full-text available

Request Full-text Paper PDF

To read the full-text of this research,
you can request a copy directly from the authors.

... C. comosa consists of two groups of chemical constituents: diarylheptanoids and acetophenones [2,3]. Several studies demonstrated that C. comosa extracts exhibited many pharmacological effects in animal models such as C. comosa hexane extract possessed uterotrophic effect and estrogenic activity [4,5]. Butanol and ethyl acetate extracts of C. comosa were most effective in choleretic activity [6]. ...
... Effects of estrogen on the expression of these cholinergic enzymes have been studied for the possible contribution of estrogen on brain beside its reproductive action [8,9,[11][12][13][14]. Several previous studies reported that C. comosa exhibited estrogenic-like effects [4,5]. Whether or not C. comosa demonstrates the positive effects on brain, similar to estrogen, is interested. ...
... The doses of the hexane extract of 250 and 500 mg/kg/day exhibited estrogenic effect in rats such as uterotropic effects, while of the alcoholic extract were shown to possess lipid-lowering effects [4,5,7]. In this study, effects of C. comosa extracts on ChAT and AChE activities were investigated in three brain regions such as basal forebrain, cerebral cortex and hippocampus, the brain regions which normally contain cholinergic neurons. ...
Article
Full-text available
Background: Curcuma comosa Roxb. (Zingiberazeae) is a well-known medicinal plant in Thailand. Rhizome of this plant has been traditionally used for the treatment of various abnormal symptoms of the uterus. Medicinal indications of C. comosa may be associated with its estrogenic-like effects reported by many studies. The objective of this study was to investigate effects of C. comosa hexane and fractionated ethanolic extracts on the activities of choline acetyltransferase (ChAT) and acetylcholinesterase (AChE) in the rat brain. Methods: Forty male rats were randomly divided into 5 treatment groups, 8 rats per group. In group 1, rats were administered orally with 1 ml/kg/day of corn oil (control group); group 2 and 3 with 250 and 500 mg/kg/day of C. comosa hexane extract; group 4 and 5 with 250 and 500 mg/kg/day of C. comosa fractionated ethanolic extract for 30 days, respectively. At the end of the treatment, rats were anesthesized and euthanized. Three regions of brain (cerebral cortex, basal forebrain and hippocampus) were dissected out and collected. Each brain region homogenate was prepared for enzyme activity assays. Results: The results showed that both dosages of C.comosa fractionated ethanolic extract caused an increase of ChAT activity in cerebral cortex and hippocampus but not in the basal forebrain. C. comosa hexane and fractionated ethanolic extracts did not affect AChE activities in any brain region. Conclusions: These findings suggest that C. comosa fractionated ethanolic extract potentially possesses a beneficial effect on the cholinergic nervous system, via enhancement effect on the activity of ChAT, an enzyme responsible for brain acetylcholine synthesis.
... (Zingiberaceae) has been widely used in Southeast Asia for the treatment of uterine inflammation, postpartum uterine bleeding, premenopausal bleeding, and as an aromatic stomachic. The pharmacological effects of its hexane extract have been reported including its estrogenic-like functions (1)(2)(3), anti-inflammatory effects (4), choleretic activities (5,6), hypolipidemic effects (7,8), and memory improvement (9,10). Among many traditional herbs in Thailand, the formulations of herbal medicines containing C. comosa are popular in the market for gynecological conditions. ...
... In the present study, the hexane extract of C. comosa and the two diarylheptanoids were lipophilic. In previous studies, the hexane extract of C. comosa extract was diluted in corn oil or olive oil to prepare formulations for administration of the animals (3,9). To reach a pharmacologically effective blood level, doses of 125-500 mg/kg body weight were administered (3,10). ...
... In previous studies, the hexane extract of C. comosa extract was diluted in corn oil or olive oil to prepare formulations for administration of the animals (3,9). To reach a pharmacologically effective blood level, doses of 125-500 mg/kg body weight were administered (3,10). Pharmacokinetic analysis showed that the bioavailability of the major compounds (DA1 and DA2) of C. comosa extract were reduced by 35% when dosed at 125 mg/kg in olive oil and that this value was further reduced when the dose was increased to 250 mg/kg (11). ...
Article
Full-text available
Curcuma comosa has long been used as a gynecological medicine. Several diarylheptanoids have been purified from this plant, and their pharmacological effects were proven. However, there is no information about the absorption of C. comosa components to support the formulation usage. In the present study, C. comosa hexane extract and the mixture of its two major compounds, (4E,6E)-1,7-diphenylhepta-4,6-dien-3-ol (DA1) and (6E)-1,7-diphenylhept-6-en-3-ol (DA2), were formulated into nanoemulsions. The physical properties of the nanoemulsions and the in situ intestinal absorptions of DA1 and DA2 were evaluated. The results demonstrated the mean particle sizes at 0.207 ± 0.001 and 0.408 ± 0.014 μm, and the zeta potential at -14.57 ± 0.85 and -10.47 ± 0.32 mV for C. comosa nanoemulsion (C.c-Nano) and mixture of diarlylheptanoid nanoemulsions (DA-Nano), respectively. The entrapments of DA1 and DA2 were 76.61% and 75.41%, and 71.91% and 71.63% for C.c-Nano and DA-Nano, respectively. The drug loading ratios of DA1 and DA2 were 351.47 and 614.53 μg/mg, and 59.48 and 126.72 μg/mg for C.c-Nano and DA-Nano. The intestinal absorption rates of DA1 and DA2 were 0.329 ± 0.015 and 0.519 ± 0.026 μg/min/cm(2) in C.c-Nano, and 0.380 ± 0.006 and 0.428 ± 0.036 μg/min/cm(2) in DA-Nano, which were five to ten times faster than those in oil. In conclusion, the formulation in nanoemulsion forms obviously increased the intestinal absorption rate of diarylheptanoids.
... Despite its long-term and wide use, there is scant scientific evidence on the anti-inflammatory activity of the plant. The result from previous study demonstrated the estrogenic-like activity of the plant and they suggested the presence of phytoestrogens in the hexane extract of this plant (Piyachaturawat et al., 1995). It has been reported that phytoestrogens possess anti-inflammatory and neuroprotective activities in the CNS (Dixon, 2004; Wang et al., 2001). ...
... Voucher herbarium specimen has been deposited in the Forestry Herbarium, Royal Forest Department, Bangkok (BKF No. 97298). Preparation of the plant extract has been previously reported (Piyachaturawat et al., 1995). Briefly, rhizomes were dried, cut into small pieces and ground to powder. ...
Article
Curcuma comosa is an indigenous plant of Thailand, which has been traditionally and widely used as an anti-inflammatory agent for the treatment of postpartum uterine bleeding and uterine inflammation. However, the scientific investigation on its anti-inflammatory activity has not been reported. In the present study, we investigated the anti-inflammatory effect of the extract from C. comosa on the responses in microglia stimulated with lipopolysaccharide (LPS). Pretreatment of highly aggressively proliferating immortalized (HAPI) cells, a rat microglial cell line, with the hexane extract of C. comosa rhizome at 10(-9) to 10(-5) g/ml significantly suppressed the levels of NO released from these cells. The attenuation in iNOS protein and mRNA expression was also observed suggesting an interference at transcriptional level. In addition, C. comosa extract inhibited interferon regulatory factor-1 expression which is an essential transcription factor governing the iNOS expression. Moreover, the levels of mRNA expressions of MCP-1 and IL-6 induced by LPS were also prominently decreased in the presence of C. comosa extract. These results suggest that C. comosa extract possesses a strong anti-inflammatory activity and has a potential to be developed as a therapeutic compound for diverse neurological disorders associated with inflammation.
... While, the CCE was determined for 1, 7 diphenyl-4,6-heptadiene-3-ol which was the active ingredient found in the extract using HPLC. The lowest dose (of 100 mg/kg/day) shown to decrease plasma triglyceride level and increased liver triglyceride content [6], whereas the dosage of 250 mg/kg/day was shown to possess uterotrophic effect [29]. The highest dose (of 500 mg/kg/day) shown to possess uterotrophic effect and estrogenic-like action [6,29,30] and also possess antihypercholesterolemic effect [6] as well as increase bile flow rate [5]. ...
... The lowest dose (of 100 mg/kg/day) shown to decrease plasma triglyceride level and increased liver triglyceride content [6], whereas the dosage of 250 mg/kg/day was shown to possess uterotrophic effect [29]. The highest dose (of 500 mg/kg/day) shown to possess uterotrophic effect and estrogenic-like action [6,29,30] and also possess antihypercholesterolemic effect [6] as well as increase bile flow rate [5]. Effects of C.comosa extracts on phase I (CYP enzymes) and phase II enzymes were also assessed in male rats at the dosages of 250 and 500 mg/kg/day [15,16]. ...
... While, the CCE was determined for 1, 7 diphenyl-4,6-heptadiene-3-ol which was the active ingredient found in the extract using HPLC. The lowest dose (of 100 mg/kg/day) shown to decrease plasma triglyceride level and increased liver triglyceride content [6], whereas the dosage of 250 mg/kg/day was shown to possess uterotrophic effect [29]. The highest dose (of 500 mg/kg/day) shown to possess uterotrophic effect and estrogenic-like action [6,29,30] and also possess antihypercholesterolemic effect [6] as well as increase bile flow rate [5]. ...
... The lowest dose (of 100 mg/kg/day) shown to decrease plasma triglyceride level and increased liver triglyceride content [6], whereas the dosage of 250 mg/kg/day was shown to possess uterotrophic effect [29]. The highest dose (of 500 mg/kg/day) shown to possess uterotrophic effect and estrogenic-like action [6,29,30] and also possess antihypercholesterolemic effect [6] as well as increase bile flow rate [5]. Effects of C.comosa extracts on phase I (CYP enzymes) and phase II enzymes were also assessed in male rats at the dosages of 250 and 500 mg/kg/day [15,16]. ...
Article
Full-text available
Background: Rhizomes of Curcuma comosa Roxb. (Zingiberaceae) have been widely used traditionally to alleviate abnormal painful uterine symptoms. This study aims to investigate subacute toxicological effects of a C. comosa ethanolic extract (CCE) in female rats. Effects of the extract on the activities of hepatic cytochrome P450 (CYP) including CYP1A1, CYP1A2, CYP2B1/2B2, CYP2E1 and CYP3A were also investigated. Methods: Forty female Wistar rats were randomly divided into 4 groups of 10 rats each. The extract was given orally to female rats at doses of 0, 100, 250 and 500 mg/kg/day for 30 days. At the end of the treatment, blood samples were collected by heart puncture and were measured for hematology and blood chemistry parameters. Microsomes were prepared from livers for enzyme assays. Results: CCE at all dosages used in this study had no effects on the parameters of hematology and blood chemistry. Only serum alkaline phosphatase and potassium levels were significantly increased in the animals receiving the extract at 500 mg/kg/day. In addition, CCE did not change hepatic total CYP content and the activities of CYP1A2, CYP2E1 and CYP3A. However the activities of CYP1A1 and CYP2B1/2B2 were significantly increased following administration of CCE at dosages of 250 and 500 mg/kg/day. Conclusions: Results from this study indicated that CCE does not cause serious toxicities to many important rat organs/systems. In addition, this study provides information regarding the possibility of herb-drug interactions and the increased risks from any bioactivation reactions of the drugs or compounds that are metabolized or bioactivated via CYP1A1 and CYP2B1/2B2.
... While, the CCE was determined for 1, 7 diphenyl-4,6-heptadiene-3-ol which was the active ingredient found in the extract using HPLC. The lowest dose (of 100 mg/kg/day) shown to decrease plasma triglyceride level and increased liver triglyceride content [6], whereas the dosage of 250 mg/kg/day was shown to possess uterotrophic effect [29]. The highest dose (of 500 mg/kg/day) shown to possess uterotrophic effect and estrogenic-like action [6,29,30] and also possess antihypercholesterolemic effect [6] as well as increase bile flow rate [5]. ...
... The lowest dose (of 100 mg/kg/day) shown to decrease plasma triglyceride level and increased liver triglyceride content [6], whereas the dosage of 250 mg/kg/day was shown to possess uterotrophic effect [29]. The highest dose (of 500 mg/kg/day) shown to possess uterotrophic effect and estrogenic-like action [6,29,30] and also possess antihypercholesterolemic effect [6] as well as increase bile flow rate [5]. Effects of C.comosa extracts on phase I (CYP enzymes) and phase II enzymes were also assessed in male rats at the dosages of 250 and 500 mg/kg/day [15,16]. ...
Article
Full-text available
Background: Rhizomes of Curcuma comosa Roxb. (Zingiberaceae) have been widely used traditionally to alleviate abnormal painful uterine symptoms. This study aims to investigate subacute toxicological effects of a C. comosa ethanolic extract (CCE) in female rats. Effects of the extract on the activities of hepatic cytochrome P450 (CYP) including CYP1A1, CYP1A2, CYP2B1/2B2, CYP2E1 and CYP3A were also investigated. Methods: Forty female Wistar rats were randomly divided into 4 groups of 10 rats each. The extract was given orally to female rats at doses of 0, 100, 250 and 500 mg/kg/day for 30 days. At the end of the treatment, blood samples were collected by heart puncture and were measured for hematology and blood chemistry parameters. Microsomes were prepared from livers for enzyme assays. Results: CCE at all dosages used in this study had no effects on the parameters of hematology and blood chemistry. Only serum alkaline phosphatase and potassium levels were significantly increased in the animals receiving the extract at 500 mg/kg/day. In addition, CCE did not change hepatic total CYP content and the activities of CYP1A2, CYP2E1 and CYP3A. However the activities of CYP1A1 and CYP2B1/2B2 were significantly increased following administration of CCE at dosages of 250 and 500 mg/kg/day. Conclusions: Results from this study indicated that CCE does not cause serious toxicities to many important rat organs/systems. In addition, this study provides information regarding the possibility of herb-drug interactions and the increased risks from any bioactivation reactions of the drugs or compounds that are metabolized or bioactivated via CYP1A1 and CYP2B1/2B2.
... comosa) is a medicinal plant in the Zingiberaceae family. Its rhizome extract exhibits estrogenic-like activity by inducing vaginal cell cornification and increasing uterine weight [11]. Ethanol extract contains diarylheptanoids [12], among which non-phenolic (3R)-1,7-diphenyl-(4E,6E)-4,6-heptadien-3-ol (DPHD) is the most abundant constituent and possesses the most potent estrogenic-like activity [13,14]. ...
Article
Full-text available
Decline of ovarian function in menopausal women increases metabolic disease risk. Curcuma comosa extract and its major compound, (3 R )-1,7-diphenyl-(4 E ,6 E )-4,6-heptadien-3-ol (DPHD), improved estrogen-deficient ovariectomized (OVX) rat metabolic disturbances. However, information on their effects on metabolites is limited. Here, we investigated the impacts of C . comosa ethanol extract and DPHD on 12-week-old OVX rat metabolic disturbances, emphasizing the less hydrophobic metabolites. Metabolomics analysis of OVX rat serum showed a marked increase compared to sham-operated rat (SHAM) in levels of lysophosphatidylcholines (lysoPCs), particularly lysoPC (18:0) and lysoPC (16:0), and of arachidonic acid (AA), metabolites associated with inflammation. OVX rat elevated lysoPCs and AA levels reverted to SHAM levels following treatments with C . comosa ethanol extract and DPHD. Overall, our studies demonstrate the effect of C . comosa extract in ameliorating the metabolic disturbances caused by ovariectomy, and the elevated levels of bioactive lipid metabolites, lysoPCs and AA, may serve as potential biomarkers of menopausal metabolic disturbances.
... After extraction with n-hexane and ethanol, aqueous extract was evaporated to dryness to give a dark brownish viscous (like molasses) (34.06g) (Piyachaturawat et al., 1995). For animal treatment, the hexane extract was dissolved in DMSO and suspended in distilled water while the ethanolic and aqueous extracts were dissolved in distilled water. ...
Article
Diabetic nephropathy is one of the most common and most devastating complications of diabetes. During the course of diabetic retinopathy, the glomeruli are slowly destroyed, usually with no detectable signs until the later stages of the disease, when the kidneys filtration process can no longer function. Throughout this disease, blood flow through the kidneys increases "hyperfiltration", and the kidneys become enlarged. Damage to the glomeruli becomes evident, as well as a condition known "microalbuminuria", in which a blood protein, albumin, leaks into the urine. This loss of proteins and other nutrients in the blood progresses, as does the damage to the glomeruli. The kidneys progressively lose their ability to filter waste until the final stage, kidney failure, occurs. On the other hand, some species of the plants were reported having remarkable medical importance. Trifolium alexandrinum is a medicinal herb; it has been shown to improve the flow of blood through arteries and veins in diabetic patients. Therefore, the present study aims to determine the possible improvement effects of different extracts of Trifolium alexandrinum (CF) on some biochemical and histopathological changes in the kidneys of streptozotocin-induced diabetic rats. Sixty adult male albino rats (210 ± 5 g) were injected (IP) with streptozotocin (STZ) (50 mg/kg b.wt) for induction of diabetes. Animals were classified into five groups. Daily intake of water, hexane and ethanolic extracts of T. alexandrinum in drinking water for 4 weeks after diabetes induction were used. Urine glucose was detected every week. Serum total protein, albumen, urea, uric acid and creatinine levels were tested. Data were expressed statistical to elucidate the differences between treated and control groups. The kidney paraffin sections of control and treated groups were stained with haematoxylin and eosin for histological studies. A single dose of STZ induced diabetes produced remarkable effects on both structure and function of the rat kidneys. The kidney exhibited damage of some renal corpuscles revealed glomerular mesangial cells hypertrophy, dilatation of renal tubules together with necrosis of their lining cells. Serum total protein, albumen, urea, uric acid and creatinine were significantly increased. Daily urine volume and consequently renal excretion of albumen, urea, uric acid and creatinine were significantly increased. However, remarkable improvement of the renal structure and function of diabetic rats was observed after treating with Trifolium alexandrinum extracts especially the group treated with water extract. Conclusion: Extracts of Trifolium alexandrinum improved histological and biochemical alterations of the kidneys noticed in STZ-diabetic rats. These effects may be due to the presence of a high content of flavonoids which acts synergistically as antioxidants.
... Diarylheptanoids have been reported to have a variety of therapeutic actions in vitro such as inhibition of platelet aggregation (Doug et al. 1998), anti oxidation (Yao et al. 2007), anti inflammation (Sodsai et al. 2007), and antitumor-promoting effects (Chun et al. 1999;Lee et al. 1998). Because Curcuma comosa Roxb., an indigenous medicine, has estrogen-like activity (Piyachaturawat et al. 1995a(Piyachaturawat et al. , 1995b and has been extensively used among menopausal women, it is essential to characterize its biological action to avoid any risk that may occur from chronic consumption or environmental exposures. Recently, diarylheptanoids isolated from C. comosa have also been reported to exhibit estrogenic activity both in vitro (Suksamrarn et al. 2008) and in vivo (Winuthayanon et al. 2009) and are useful for nutraceutical health promotion and hormone replacement therapy. ...
Article
Full-text available
Diarylheptanoids isolated from Curcuma comosa Roxb. have been recently identified as phyto estrogens. However, the mechanism underlying their actions has not yet been identified. We characterized the estrogenic activity of three active naturally occurring diarylheptanoids both in vitro and in vivo. We characterized mechanisms of estrogenic action of the diarylheptanoids (3S)-1,7-diphenyl-(6E)-6-hepten-3-ol (D1), 1,7-diphenyl-(6E)-6-hepten-3-one (D2), and (3R)-1,7-diphenyl-(4E,6E)-4,6-heptadien-3-ol (D3) by using a real-time polymerase chain reaction assay, a mammalian transfection model, and a uterotrophic assay in mice. All diarylheptanoids up-regulated estrogen-responsive genes in estrogen-responsive breast cancer cells (MCF-7). In HepG2 cells transfected with estrogen receptor (ER) beta or different ERalpha functional receptor mutants and the Vit-ERE-TATA-Luc reporter gene, all diarylheptanoids induced transcription through a ligand-dependent human ERalpha-ERE-driven pathway, which was abolished with ICI 182,780 (ER antagonist), whereas only D2 was active with ERbeta. An ERalpha mutant lacking the functional AF2 (activation function 2) region was not responsive to 17beta-estradiol (E(2)) or to any of the diarylheptanoids, whereas ERalpha lacking the AF1 domain exhibited wild-type-like activity. D3 markedly increased uterine weight and proliferation of the uterine epithelium in ovariectomized mice, whereas D1 and D2 were inactive. D3, like E(2), up-regulated lactoferrin (Ltf) gene expression. The responses to D3 in the uterus were inhibited by ICI 182,780. In addition, D3 stimulated both classical (Aqp5) and nonclassical (Cdkn1a) ER-mediated gene regulation. The results suggest that the D3 diarylheptanoid is an agonist for ER both in vitro and in vivo, and its biological action is ERalpha selective, specifically requiring AF2 function, and involves direct binding via ER as well as ERE-independent gene regulation.
... These effects were similar to the effects of estradiol in this model. Moreover, the Curcuma comosa extract treatment effectively induces and increases specific estradiol binding in uterine nuclei (Piyachaturawat et al., 1995b). These results suggest that Curcuma comosa may have estrogenic-like effects by acting at specific estradiol binding sites. ...
Article
Curcuma comosa extract and some purified compounds from this plant have been reported to have estrogenic-like effects, and estrogen improves learning in some animals and potentially in postmenopausal women; therefore, this study tested the hypothesis that Curcuma comosa and estrogen have similar beneficial effects on spatial learning and memory. Curcuma comosa hexane extract, containing 0.165 mg of (4E,6E)-1,7-diphenylhepta-4,6-dien-3-one per mg of the crude extract, was orally administered to ovariectomized Wistar rats at the doses of 250 or 500 mg/kg body weight. 17beta-estradiol (10 microg/kg body weight, subcutaneously) was used as a positive control. Thirty days after the initiation of treatment, animals were tested in a Morris water maze for spatial learning and memory. They were re-tested every 30 days and a final probe trial was run on day 119. Compared to control rats, OVX rats displayed significant memory impairment for locating the platform in the water maze from day 67 after the surgery, onward. In contrast, OVX rats treated with either Curcuma comosa or estrogen were significantly protected from this decline in cognitive function. Further, the protection of cognitive effects by Curcuma comosa was larger at higher dose. These results suggest that long-term treatment with Curcuma comosa has beneficial effects on learning and memory function in rats.
... Recently, a novel phytoestrogen, diaryltheptanoid-D3 or (3R)-1,7-diphenyl-(4E,6E)-4,6-heptadien-3-ol (hereafter referred to as D3), was isolated and identified from Curcuma comosa, a member of the Zingiberaceae family. 13,14 C. comosa is extensively used by menopausal women in many forms, including dried rhizome powder and crude extracts, 16,17 and it is possible that D3 or other phytoestrogens may be the active compound in these preparations. D3 has the capacity to increase the endotheliumdependent relaxation of rat aortic rings, and its nongenomic mechanism is associated with enhanced phosphorylation of eNOS and Akt proteins. ...
Article
Phytoestrogens have been implicated as promising therapeutic agents to treat the vascular impairment seen in menopausal women. The present study investigated the long-term effects of phytoestrogens from Curcuma comosa Roxb. on vascular relaxation of isolated thoracic aorta from ovariectomized (OVX) rats. Treatment of OVX rats for 12 weeks with C. comosa powder, hexane extract, and a novel phytoestrogen, diarylheptanoid-D3, [(3R)-1,7-diphenyl-(4E,6E)-4,6-heptadien-3-ol] prevented impairment of the endothelium-dependent relaxation response to acetylcholine in OVX, but not the endothelium-denude aortic ring relaxation in response to sodium nitroprusside. These data suggest that the vascular relaxation effect of C. comosa is mediated via endothelial cells. Treatment with D3 also increased endothelial nitric oxide synthase (eNOS) and estrogen receptor-α (ERα) protein expression in the aorta of OVX rats and suppressed elevated tumor necrosis factor-α (TNF-α) expression in OVX aortic rings. These results indicate that C. comosa treatment prevents impairment of vascular relaxation in estrogen-deficient animals via the ER-eNOS pathway as well as through its ability to promote an anti-inflammatory response.
... Extract of Curcuma comosa was prepared as described previously (Piyachaturawat et al., 1995a). Rhizomes ...
Article
Full-text available
We investigated the effect of a hexane extract of Curcuma comosa Roxb., previously reported to mediate estrogenic activity, on fertility in adult male rats. Intragastric administration of the C. comosa extract at a dose of 500 mg/kg BW for 7 consecutive days significantly decreased weights of testes, ventral prostate and seminal vesicles. The decreased testicular weight corresponded with a marked regression of spermatogonia and spermatids in the seminiferous tubules. Biochemical analysis revealed significantly decreased activity of acid phosphatase in the ventral prostate. The activity of a-glucosidase in the cauda epididymides, and the fructose content in coagulating glands, were not significantly affected. Sperm concentration and motility in the cauda epididymides were also significantly suppressed. However, this 7-day treatment did not significantly affect fertility of the animals. Alterations by C. comosa extract were similar to effects mediated by estradiol. This suggests that the suppressing effect of C. comosa on male reproductive organs is mediated through the estrogenic-like action of the plant extract.
... 15 It has also been shown that the vasoactive effect of genistein on coronary blood flow involves oestrogen ERa and ERb receptors and the release of nitric oxide (NO) through vasodilatory b 2 -adrenoreceptors in pigs. 16 Rhizome extracts of Curcuma comosa Roxb., which have been used as indigenous medicines in Thailand, have various biological activities, including uterotrophic and oestrogenic actions, 17,18 the ability to lower concentrations of circulating cholesterol, stimulation of bile secretion 19 and anti-inflammatory effects. 20,21 The active components responsible for the uterotrophic and oestrogenic activity of C. comosa have been identified in the fraction containing diaryheptanoids, representing a new group of phytooestrogens. ...
Article
The mechanisms by which the hexane extract of C. comosa increases femoral blood flow (FBF) in ovariectomised rats are not known. This study, therefore, investigated the acute effects and modes of action of a diarylhaptanoid (D3: (3R)-1,7-diphenyl-(4E,6E)-4,6-heptadien-3-ol), a phyto-oestrogen isolated from C. comosa, on FBF in ovariectomised rats. On day 7 after ovariectomy, three groups of rats were intra-arterially injected with D3 (100, 200, 400, and 800 μg/kg body weight (BW)), 17-β-oestradiol (E2) (1, 2, 4, and 8 μg/kg BW) or vehicle. Mean arterial blood pressure (mABP) and FBF were recorded using a pressure transducer and a Laser Doppler Flow meter, respectively. D3 and E2 dose dependently increased FBF without any alterations in mABP and heart rate. The EC(50) at 120 min for D3 and E2 were 195.8 μg/kg BW and 1.8 μg/kg BW, respectively. Both D3 and E2 also dose-dependently decreased femoral vascular resistance (FVR). The EC(50) of D3 was about 100-fold greater than that of E2. The effects of D3 and E2 on FBF and FVR were diminished after intravenous injection of N(G) -nitro-L-arginine methyl ester (L-NAME) (10 mg/kg BW). Pretreatment with L-NAME (10 mg/kg BW), 1 H-[1,2,4] oxadiazolo-[4,3-a] quinoxalin-1-one (ODQ) (900 μg/kg BW) or ICI 128,780 (900 μg/kg BW) for 30 minutes prevented the effects of D3 and E2 on FBF and FVR. The results suggest that a phyto-oestrogen, D3, increases FBF in ovariectomised rats via oestrogen receptor and NO-guanylyl cyclase signaling, which, in turn, relaxes the femoral vascular resistance. © 2013 The Authors Clinical and Experimental Pharmacology and Physiology © 2013 Wiley Publishing Asia Pty Ltd.
... Diarylheptanoids are phytoestrogens isolated from Curcuma comosa, a plant in the Zingiberaceae family. C. comosa has been marketed as a plant-derived dietary supplement product traditionally used in indigenous medi cine as an alternative remedy for hormone replacement therapy in menopausal women (Piyachaturawat et al. 1995). Other diaryl heptanoids are found in Curcuma and other plants in the ginger family (Keserü and Nógrádi 1995). ...
Article
Full-text available
Background: Diarylheptanoid (D3) isolated from the medicinal plant, Curcuma comosa, has estrogenic activity. Objective: We aimed to elucidate the mechanism(s) of D3 action and compare it with that of 17β-estradiol (E2) using both in vitro and in vivo uterine models. Methods: We used human uterine (Ishikawa) cells to determine the estrogenic action of D3 on the activation and nuclear translocation of estrogen receptor α (ERα). In addition, we further characterized the uterine response to D3 treatment in vivo. Results: D3 activated an estrogen responsive element (ERE) luciferase reporter through ERα, and molecular modeling suggested that D3 could be accommodated in the ERα binding pocket. Using modified ERα to assay ligand-dependent nuclear translocation, we observed D3-dependent ERα interaction and translocation. In mouse uteri, early- and late-phase estrogen-regulated gene responses were increased in D3-treated ovariectomized wild-type animals, in a manner similar to that of E2; no response was seen in ERα knockout animals. We observed a divergence in estrogen responses after D3 treatment: D3 induced robust DNA synthesis in uterine epithelial cells, linked to an increase in cell-cycle–related genes; however, no increase in uterine weight was observed 24 hr after treatment. D3 also affected uterine progesterone receptor expression patterns similar to E2. When D3 and E2 were administered together, we observed no additive or antagonistic effects of D3 on E2. Our findings suggest that D3 is a weak estrogenic agonist compound. Conclusion: D3 is a weakly acting phytoestrogen that mimics the mitogenic responses produced by E2 in an ERα-dependent manner, but it is unable to increase uterine weight or enhance or antagonize the effects of estrogen.
... The use of C elata, which contains other compounds, as C comosa may lead to adverse effects and toxic reactions. In considering the amount of zederone to be taken by human, if C elata extract is used at the same dose as that of the C comosa extract (500-1000 mg/kg BW), 43 zederone at approximately 50 to 92 mg would be taken. The hepatotoxicity of zederone at this dose level was also evident in the present study by causing an increase in plasma activity of ALT (Table 3). ...
Article
Full-text available
The present study aimed to investigate the hepatotoxicity of zederone isolated from Curcuma elata in mice. Adult male mice were intraperitoneally injected with a single dose of zederone (50-300 mg/kg body weight [BW]). Twenty-four hours after the injection, zederone induced liver enlargement with scattered white foci over the organ. The medium lethal dose (LD50) value at 24 hours of zederone was approximately 223 mg/kg BW. Hepatic centrilobular necrosis with marked increases in plasma alanine transaminase activity and total bilirubin levels was observed. Zederone at a dose of 200 mg/kg BW markedly decreased the activity of superoxide dismutase and the hepatic glutathione content, whereas the activity of catalase was not altered. The compound at this dose also increased the messenger RNA (mRNA) expression of Cyp2b10 and Cyp3a11, which are the main drug-metabolizing enzymes in the liver. The mRNA expression of proinflammatory cytokine tumor necrosis factor α was increased. The nuclear factor-E2-related factor 2 protein, which is the transcription factor regulating the antioxidant gene expression, was decreased. The histopathology of massive hepatic centrilobular necrosis with an increase in the expression of cytochrome P450 (Cyp) suggests that the possible potentiation of zederone-induced hepatotoxicity implicated the induction of Cyps, which leads to the formation of biological reactive metabolites and that cause the oxidative stress and liver cell injuries.
... Rhizomes of C. comosa comprise various chemical compounds include diarrylheptanoids such as trans-1,7diphenyl-5-hydroxy-1-heptene; trans-1,7-diphenyl -6-hepten-3-one-5-ol; trans-1,7-diphenyl-3-acetoxy-6-heptene; trans-1,7-diphenyl-6-heptene-3-one; trans,trans-1,7-diphenyl-1,3-heptadien-5-ol; trans, trans-1,7-diphenyl-4,6-heptadien-3-one 1) , 1,7diphenyl-5-hydroxy-(1E)-1-heptene; 5-hydroxy-7-(4hydroxyphenyl)-1-phenyl-(1E)-1-heptene; 7-(3,4hydroxyphenyl-5-hydroxy-1-phenyl(1E)-1-heptene 2) and phloracetophenone glucoside such as 4,6dihydroxy-2-O-(β-D-glucopyranosyl) acetophe-none 2) . Many studies have revealed pharmacological effects of C. comosa, such as uterotrophic effect 3) , estrogenic-like effect 4,5) , anti-inflammatory effect 6) . Other pharmacological effects of C. comosa have also been documented such as choleretic effect 7) which is the effect of phloracetophenone glucoside 2) , cholesterol lowering effect [7][8][9] and nematocidal effect 1) . ...
Article
Full-text available
Curcuma comosa Roxb. (Zingiberaceae) is an indigenous plant of Thailand. The rhizome of this plant has been widely used in Thai traditional medicine for treatment of abnormal uterine symptoms. The purpose of this study was to investigate effects of C. comosa hexane extract and ethanolic extract on hepatic cytochrome P450 (CYP) in rats. Fifty male Wistar rats were randomly divided into 5 groups (10 rats/group). Rats were given orally with C. comosa hexane extract or ethanolic extract (250 and 500 mg/kg/day) or corn oil in a control group for 30 consecutive days. At the end of the treatment, rats were sacrificed and liver microsomes were prepared. Hepatic microsomal total CYP content and CYP activity were determined. The results showed that both C. comosa hexane and ethanolic extracts at 250 mg/kg/day caused a significant increase of total CYP contents and the activity of CYP1A1. Lower dose of both extracts (250 mg/kg/day) caused a more increase of CYP1A1 activity than the higher dose (500 mg/kg/day). Also, both C. comosa hexane and ethanolic extracts caused a dose-dependent increase of CYP2B1/2B2 activities and the increase was higher in the hexane extract group than the ethanolic extract group. Hexane and ethanolic extracts of C. comosa did not affect CYP1A2, CYP2E1 and CYP3A activities. These results indicated the possibilities of C. comosa hexane and ethanolic extracts regarding herb-drug interactions and the increase risk of toxicity, mutagenesis and/or carcinogenesis from drugs or compounds that are metabolized or bioactivated via CYP1A1 and CYP2B1/2B2.
... (C. comosa), a plant in Zingiberaceae family, has been widely used as a dietary supplement for relieving postmenopausal symptoms in Thailand [14]. Consistent with the presence of a phytoestrogen, hexane extract of C. comosa rhizomes prevent bone loss in estrogen deficient mice [15]. ...
Article
Full-text available
Phytoestrogens have been implicated in the prevention of bone loss in postmenopausal osteoporosis. Recently, an active phytoestrogen from Curcuma comosa Roxb, diarylheptanoid (DPHD), (3R)-1,7-diphenyl-(4E,6E)-4,6-heptadien-3-ol, was found to strongly promote human osteoblast function in vitro. In the present study, we demonstrated the protective effect of DPHD on ovariectomy-induced bone loss (OVX) in adult female Sprague-Dawley rats with 17β-estradiol (E2, 10 µg/kg Bw) as a positive control. Treatment of OVX animals with DPHD at 25, 50, and 100 mg/kg Bw for 12 weeks markedly increased bone mineral density (BMD) of tibial metaphysis as measured by peripheral Quantitative Computed Tomography (pQCT). Histomorphometric analysis of bone structure indicated that DPHD treatment retarded the ovariectomy-induced deterioration of bone microstructure. Ovariectomy resulted in a marked decrease in trabecular bone volume, number and thickness and these changes were inhibited by DPHD treatment, similar to that seen with E2. Moreover, DPHD decreased markers of bone turnover, including osteocalcin and tartrate resistant acid phosphatase (TRAP) activity. These results suggest that DPHD has a bone sparing effect in ovariectomy-induced trabecular bone loss and prevents deterioration of bone microarchitecture by suppressing the rate of bone turnover. Therefore, DPHD appears to be a promising candidate for preserving bone mass and structure in the estrogen deficient women with a potential role in reducing postmenopausal osteoporosis.
... In 1994 Jurgen et al. 3 reported the nematicidal activity of diarylheptanoids, and the active principal agents in hexane-soluble fraction of the methanol extract of C. comosa. Piyachaturawat et al. [4][5][6][7][8] investigated the biological activities of C. comosa crude extracts. It was found that the hexane extract was effective in the uterotropic activity by increasing uterine weight and glycogen content in rats, whereas the ethylacetate extract exhibited the hypolipidemic activity in mice. ...
Article
Full-text available
The powerful antioxidative and HeLa cytotoxic activity of crude ethanol extract of Curcuma comosa Roxb. prompted us to carry out biologically-guided separation of the active constituent. Chromatographic separation of the ethanol extract yielded fractions Zcc(R)-E-1 and Zcc(R)-E-2. The potent fraction Zcc(R)-E-1 was subsequently bioassay-guided separated and the active fraction Zcc(R)-E-15 was obtained. Recrystal-lization of fraction Zcc(R)-E-15 yielded compound A, exhibited antioxidant power 1064.73 ± 60.96 μM vita-min C equivalence and HeLa cell cytotoxicity with IC50 4.44 ± 0.85 μg/ml. With structure elucidation via spectroscopic techniques, compound A was identified as 4,6-dihydroxy-2-O-(β-D-glucopyranosyl)acetophenone.
... 4 D3 is believed to have estrogenic properties 5 and is used by Thai women to relieve symptoms of menopause. 6 In the current study, both the uterine effects and the gene transcription activity of D3 at 2 and 24 hours were consistent with a short-acting estrogen. 3 The high-throughput in vitro methods used in ToxCast are powerful and necessary, says Cheryl Walker, a toxicologist at the Texas A&M Health Science Center, but they do not tell us everything. ...
... (Zingiberaceae), an indigenous plant in Thailand commonly known as Wanchak motluk, has traditionally been used for the treatment of inflammation such as those in postpartum uterine bleeding and liver inflammation. C. comosa has been reported to possess several pharmacological activities including uterotrophic, choleretic, lowering plasma cholesterol, inhibit plague formation, immunomodulation, and protective effect against CCl 4 -induced hepatotoxicity in mice (Piyachaturawat et al. 1995(Piyachaturawat et al. ,1996(Piyachaturawat et al. ,1999Sodsai et al. 2007;Weerachayaphorn et al. 2010;Ratanachamnong et al. 2012). Its hepatoprotection was demonstrated to be related to the induction of the endogenous detoxifying system by increasing the activity of glutathione-S-transferase (GST) and preserving the intracellular glutathione (GSH) level which led to the reduction of the bioactivated metabolite of CCl 4 . ...
Article
Full-text available
Context: Curcuma comosa Roxb. (Zingiberaceae) has traditionally been used as an anti-inflammatory agent in liver, and recent study has shown its hepatoprotective effect against CCl4-induced liver injury in vivo. Objective: This study further assesses the protective effect of C. comosa extracts and its isolated compounds against tert-butyl hydroperoxide (t-BHP)-induced hepatotoxicity in isolated primary rat hepatocytes. Materials and methods: Isolated primary hepatocytes were pretreated with either ethanol (5-50 μg/ml) or hexane extract (1-50 μg/ml), or two diarylheptanoids (4-35 μM): compound D-91 [1-(4-hydroxyphenyl)-7-phenyl-(6E)-6-hepten-3-ol] and compound D-92 [(3S)-1-(3,4-dihydroxyphenyl)-7-phenyl-(6E)-6-hepten-3-ol], from C. comosa for 2 h prior to exposure to 1.5 mM t-BHP for 15 and 30 min. Their hepatoprotective activities were then determined. Results: t-BHP markedly caused the formation of MDA and ALT leakage from the hepatocytes. Pretreatment with the C. comosa ethanol extract showed greater protective effect than the hexane extract, and the effect was concentration related. Treating the hepatocytes with compound D-92 provided greater protective effect than compound D-91. IC50 values of compounds D-91, D-92, and silymarin for the protection of ALT leakage at 30 min were 32.7 ± 1.1, 9.8 ± 0.7, and 160 ± 8 μM, respectively. Further investigation showed that compound D-92 was more effective in maintaining the intracellular glutathione content in the t-BHP treated group, whereas the reduction in antioxidant enzymes, glutathione peroxidase and glutathione-S-transferase activities, were not improved. Discussion and conclusion: Results suggest that diarylheptanoids are the active principles that provide protection against t-BHP-induced injury. Their ability to maintain intracellular glutathione content is the main mechanisms underlying the protective action.
... The hexane extract of C. comosa rhizomes was shown to have an estrogenic-like action in rats. It exhibited a uterotrophic activity, induced cornification of vaginal epithelium, and keratinization of the mucosal surface of the vagina in ovariectomized mature rats, which is typical characteristics of estrogenic action (3). Recently, diarylheptanoids, which can be extracted from C. comosa rhizome, have also been reported to exhibit estrogenic-like function activity both in vitro and in vivo (2,4). ...
Article
Curcuma comosa (C. comosa) is widely used in traditional medicine as a dietary supplement for health promotion in postmenopausal women in Thailand. It contains several diarylheptanoids, which are considered to be a novel class of phytoestrogens. However, the diarylheptanoids isolated from the plant rhizome are shown to have low oral bioavailability and faster elimination characteristics. The aim of this study was to investigate the permeation behavior of the active compounds of diarylheptanoids. The effects of binary vehicle systems and permeation enhancers on diarylheptanoids permeation and accumulation within the skin were studied using side-by-side diffusion cells through the porcine ear skin. Among the tested binary vehicle systems, the ethanol/water vehicle appeared to be the most effective system for diarylheptanoids permeation with the highest flux and shortest lag time. The presence of transcutol in the vehicle system significantly increased diarylheptanoid's permeation and accumulation within the skin in a concentration-dependent manner. Although the presence of terpenes in formulation decreased the flux of diarylheptanoids, it raised the amount of diarylheptanoids retained within the skin substantially. Based on the feasibility of diarylheptanoid permeation, C. comosa extract should be further developed into an effective transdermal product for health benefits and hormone replacement therapy.
... Thai traditional practitioners use its rhizome as an anti-inflammatory agent for the treatment of postpartum uterine bleeding. It enhanced involution and reduced inflammation of uterus after vaginal delivery (Piyachaturawat et al., 1995). Interestingly, C. comosa and its diarylheptanoid component were reported to have anti-oxidant and anti-inflammatory properties (Jantaranotai et al., 2006;Suksamrarn et al., 2008). ...
... Various pharmacological activities have also been reported, e.g. anti-lipidemic (Piyachaturawat et al., 1995c(Piyachaturawat et al., , 1999a, choleretic (Suksamrarn et al., 1997), estrogenic (Winuthayanon et al., 2009a,b;Bhukkhai et al., 2012), uterotroic (Piyachaturawat et al., 1995a), growth suppressing on male reproductive organs (Piyachaturawat et al., 1998), male fertility (Piyachaturawat et al., 1999b), plasma cholesterol reduction (Piyachaturawat et al., 1999a), anti-inflammatory (Jantaratnotai et al., 2006;Sodsai et al., 2007), and anti-oxidant effect (Niumsakul et al., 2007). Moreover, in ovariectomized rats with estrogen deficiency, this plant could protect bone loss and accelerate human osteoblast proliferation and differentiation (Tantikanlayaporn et al., 2013a,b;Weerachayaphorn et al., 2011), enhance vascular relaxation (Intapad et al., 2009(Intapad et al., , 2012, prevent neuron loss and improve learning and memory function (Su et al., 2010(Su et al., , 2011(Su et al., , 2012a. ...
Article
Full-text available
Curcuma comosa Roxb., Zingiberaceae, a phytoestrogen-producing herb with vernacularly named “Wan Chak Mod Loog” in Thailand, has been traditionally used for treatment of gynecologic diseases and sold as food supplement in the market. However, similar rhizomes of its related species may lead to the confusion in the uses of this plant. This study was aimed to investigate the phytochemical constituents of different Curcuma spp. that used as “Wan Chak Mod Loog”. Characteristic major compounds were isolated and identified. Phytochemical analysis of 45 Curcuma samples representing Curcuma sp., C. latifolia, and C. comosa were analyzed and compared with their phylogenetic relationship inferred by Amplified Fragment Length Polymorphism analysis. Phytoestrogen diarylheptanoids were found in all samples of C. comosa while sesquiterpenoids including hepatoxic zederone were found in C. latifolia and Curcuma sp. samples.
Article
Curcuma comosa (C. comosa) is a Thai medicinal herb that provides numerous pharmacologic activities due to its estrogen-like action. This study aimed to investigate the use of liquisolid technique to prepare tablets containing oleoresin-like crude extract of C. comosa, and to improve the dissolution profiles of its major compounds, diarylheptanoids (DAs). Free flowing powders of C. comosa extract were obtained by adsorption onto solid carriers, microcrystalline cellulose, with colloidal silica as coating material. FTIR results ruled out possible interactions between C. comosa extract and excipients. The results indicated that all of liquisolid tablets met the USP requirements. The release of DAs were significantly increased through liquisolid formulations, compared to crude extract. By decreasing the ratio of carrier to coating from 20 to 10, an improvement in dissolution rate was observed. Addition of additives - namely polymer (polyvinyl pyrrolidone) and/or nonvolatile liquid (propylene glycol) affected tablet properties which involved longer disintegration time and lower DA dissolution. Optimized C. comosa liquisolid formulation was prepared in a carrier to coating ratio of 10 without additives. Stability studies showed that physical properties of liquisolid tablet were not affected by aging, but percent remaining and dissolution profiles of DAs were influenced by storage temperature. In vivo pharmacokinetic behavior of the optimized C. comosa liquisolid tablets was investigated following a single oral administration to rabbits. The results proved that the method used for preparation of liquisolid led to C. comosa tablets with low variation in content uniformity and tablet properties, as well as enhanced dissolution behavior.
Article
In the present study, the effect of oral administration of Melia azedarach Linn. (dharek) seed extract on fertility index, uterine weight and various histological and biochemical parameters of uterus were studied in the adult cyclic Wistar rats. Average number of embryos and implantation losses in the pregnant animals treated with dharek seed extract was also studied. The extract was prepared using a flash evaporator at 35 degrees C and dissolved in olive oil to prepare doses on per kg body weight basis. The results indicated a reduction in fertility index and average number of embryos in mated rats treated with the dharek extract. Pre-implantation, post-implantation and total prenatal mortalities were increased in rats treated with dharek seed extract during early (D1-D7) and late (D7-D18) stages of gestation period at doses of 5, 10 and 20 mg kg(-1) body wt day(-1). Histological studies showed a significant reduction in myometrial thickness, uterine gland diameter, luminal diameter of uterine glands and luminal epithelial cell height in rats treated with dharek seed extract at 1mg kg(-1) body wt day(-1) for 18 days. Pits and folds in luminal epithelial, mitotic activity in luminal and glandular epithelial cells of uterus were observed to be absent. Biochemically, a significant increase in protein and glycogen contents was observed. Thus, in conclusion, the application of this plant extract in rodent control programme may help to elevate the socioeconomic status of the society.
Article
Full-text available
Effect of drug praziquantel (PZQ) and C. longa extract on S. mansoni infected mice is reported. The level of glycogen, alkaline and acid phosphatases (ALP and ACP respectively), and body weight, liver weight and liver weight/body weight ratio were studied in mice infected with S. mansoni. ALP level was increased after infection. C. longa treated mice showed marked reduction in ALP level more than after PZQ-treatment. C. longa enhanced the concentration of glycogen after being reduced by infection, while PZQ-treatment revealed more reduction. C. longa caused enhancement in body weight while PZQ treatment had no effect. The formation of granuloma around schistosome eggs in the liver produced inflammation. C. longa extract and PZQ were effective in reducing granuloma size in infected mice.
Preprint
Full-text available
Members of the Curcuma genus are among the most commonly used rhizomatous herbs worldwide. There are two species of Curcuma referred to as “Wan Chak Motluk” in Thai, C. comosa Roxb. and C. latifolia Roscoe, and their herbal materials are often confused. C. comosa is widely used as a traditional herbal remedy for its phytoestrogenic activity, but its morphology is highly similar to that of C. latifolia , which contains a compound that causes hepatotoxicity. In this study, the complete chloroplast (cp) genomes of these species were determined for the first time using Illumina sequencing. Our results showed that their cp genomes were 162,272 bp ( C. comosa ) and 162,289 bp ( C. latifolia ) in length. A total of 133 unique genes were identified, including 87 protein-coding genes, 38 tRNA genes and 8 rRNA genes . Comparative analyses with other species of Curcuma indicated high similarity in gene content and structural organization. The analyses also reveal variable hotspots in the genomes at ndh A, trn T -trn L, and ndh C -trn V that can serve as species-specific nucleotide barcodes. Indeed, mislabeling of these two species among samples sold at market was detected using these species-specific markers, indicating that cp genomes can provide more information for better elucidating and improving discriminatory power for species authentication.
Article
The aim of this study was to establish ultrasound-assisted extraction (UAE) conditions needed to maximize diarylheptanoid recovery from Curcuma comosa Roxb. The performances of a response surface methodology (RSM) and an artificial neural network (ANN) were compared in terms of the predicted yield of the target diarylheptanoids. Key parameters, including the amplitude of the ultrasonic wave (X1), the extraction temperature (X2) and the irradiation time (X3), were studied by using ethanol as extraction solvent. The experimental data were also used to train a multilayer perceptron for creating an ANN model with a 3-7-3 architecture. The optimal UAE conditions predicted by RSM to provide the highest yield of the three diarylheptanoids were 57.32% X1, 64.60 °C X2, and 17.02 min X3. By contrast, the ANN model offered the optimal values for X1, X2 and X3 of 60.27%, 63.92 °C and 16.60 min, respectively. Both statistical tools offered satisfactory results, and superior predictability was observed with the ANN. A vaginal epithelium cornification assay verified the estrogen-like properties of the plant extract. The integrated approach was not only effective at achieving a high recovery of the desired phytoestrogens but could also serve as a useful guide for the large-scale production of diarylheptanoid-rich C. comosa extract.
Article
The present study aims to examine the effects and mechanisms of Curcuma comosa Roxb., an indigenous medicinal plant containing phytoestrogens, on vascular relaxation. Using an organ bath system, acute exposure of intact or endothelium-denuded aortic rings to the hexane extract of C. comosa or an isolated diarylheptanoid compound, D3, did not induce relaxation. However, pre-incubation of aortic rings for 20 min with hexane extract of C. comosa (10 microg/ml) or the isolated diarylheptanoid compound, D3, (0.1, 1 and 10 microg/ml) markedly enhanced endothelial-dependent relaxation in response to ACh. The hexane extract did not modulate the relaxation of denuded aortic rings in response to SNP, which suggested a predominant effect on endothelial cells rather than on vascular smooth muscle cells. Co-incubation with ICI 182,780 (estrogen receptor antagonist), L-NAME (nitric oxide synthase inhibitor) or ODQ (guanylase cyclase inhibitor) inhibited the enhancing effects of C. comosa on ACh-induced relaxation. These findings suggest that the actions of C. comosa are mediated through estrogen receptor (ER) and NO-cGMP-dependent mechanisms. In addition, C. comosa also increased the phosphorylation of serine 1177 eNOS and serine 473 Akt proteins, and these effects were abolished by ICI 182,780. The results suggest that C. comosa acutely increases endothelium-dependent relaxation of aortic rings through the ER-Akt-eNOS pathway. This is the first evidence indicating non-genomic action of a novel phytoestrogen from C. comosa, on vascular relaxation.
Article
Wan-chak-motluk is a Thai local name for native species of Curcuma (Zingiberaceae) that produce phytoestrogen in their rhizomes. Wan-chak-motluk has long been used in Thai traditional medicine for treatment of illness in the uterus and ovarian hormone deficit, and therefore it is cultivated for economic purposes throughout Thailand. The rhizome morphology of wan-chak-motluk is highly variable and this may be related to its medicinal properties. Thus, this study aimed to identify and classify wan-chak-motluk collected from cultivation sites in 16 provinces of Thailand. Chromosome numbers, together with inflorescent, floral, and leaf morphology, were used to separate wan-chak-motluk into five cultivars belonging to three species: C. comosa, C. elata, and C. latifolia. Curcuma comosa has short (2-5 cm) peduncle, glabrous lower leaf, and consists of two cultivars. One cultivar has a cylindrical spike 13-17 cm long and 5-8 cm wide, whereas the cylindrical spike of the other cultivar is shorter (10-15 cm) but larger (8-12 cm). The former cultivar has 2n = 42 and the latter has 2n = 63, seldom 2n = 62 or 64. Both C. elata and C. latifolia have long (10-25 cm) peduncle and pubescent lower leaf. They differ in that C. latifolia has 2n = 63 and 84 with a red path along the midrib, whereas C. elata has 2n = 63 without a red path along the midrib. This study shows that chromosome numbers can be used to accurately verify the taxonomic identification of wan-chak-motluk.
Article
Full-text available
On the process of drug research and development, drug interaction study is required either preclinically or clinically. Modulation of drug metabolism is one of the etiology of drug interaction resulting in reduction of drug efficacy or in the other hand, increase of drug toxicity. This interaction is mostly associated with induction or inhibition at phase I or phase II metabolism. The objective of this study was to investigate effects of Curcuma comosa hexane and ethanolic extracts on phase II drug metabolizing enzymes involving in drug metabolism such as UDP-glucuronosy-ltransferase (UDPGT), sulfotransferase (SULT), glutathione S-transferase (GST), and NAD(P)H quinoneoxidoreductase (NQOR) in rat livers. Fifty male Wistar rats were randomly divided into 5 groups of 10 rats each. Rats in the control group were given corn oil at 1 ml/kg/day whereas rats in group 2 and 3 received C. comosa hexane extract (which was dissolved in corn oil) orally at dosages of 250 and 500 mg/kg/day. Rats in group 4 and 5 received C. comosa ethanolic extract orally at dosages of 250 and 500 mg/kg/day. At the end of the extract administration (30 days), rats were anesthesized. Microsomes and cytosols were prepared from the livers for enzyme activity assays. The results showed that C. comosa hexane extracts at the dosages of 250 and 500 mg/kg/day significantly increased UDPGT activity whereas NQOR activity was significantly increased when C. comosa hexane extract at 500 mg/kg/day was given. Both extracts did not affect SULT and GST activities. These results indicated that co-administration of C. comosa hexane extract with some drugs that are metabolized by UDPGT and/or NQOR may affect drug level resulting in reduction of efficacy or increase of adverse drug reaction. In addition, an increase of UDPGT and NQOR activities by C. comosa indicated a potential benefit of this plant for a decrease of risks from chemical-induced carcinogenesis and/or mutagenesis. Effects of C. comosa extracts on other phase II drug metabolizing enzymes should be further explored. INTRODUCTION: Rhizomes of Curcuma comosa Roxb., a plant in family ZINGIBERACEAE, have been used extensively in Thai traditional medicine as an anti-inflammatory agent particularly for the treatment of female postpartum uterine inflammation. Rhizomes of C. comosa comprise various chemical compounds including diaryl-heptanoids and phloracetophenone glucoside 1,2) . Many studies have revealed pharmacological effects of C. comosa, such as uterotrophic effect 3) , estrogenic-like effect 4,5) , anti-inflammatory effect 6) . Other pharmacological effects of C. comosa have also been documented such as choleretic effect 7) , cholesterol lowering effect 7,8,9) , antiatherosclerotic effect 10) and nematocidal effect 1) . These beneficial effects of C. comosa are promising to be developed as an alternative medicine. On the process of drug research and development, drug interaction study is required either preclinically or clinically 11) . Modulation of drug metabolism is one of the etiology of drug interaction resulting in reduction of drug efficacy or in the other hand, increase of drug toxicity. This interaction is mostly associated with induction or inhibition at phase I or phase II metabolism 12) . Effect of C. comosa on cytochrome P450, the phase I drug metabolizing enzyme, had been reported earlier 13) . Therefore, the aim of this study was to investigate effects of C. comosa hexane and ethanolic extracts on phase II enzymes involving in drug metabolism such as UDPGT, SULT, GST, and NQOR in rat livers.
Article
Curcuma comosa was reported to have uterotrophic effects in ovariectomized (OVX) rats. The present study aims to investigate the plant estrogenic-like effects of C. comosa hexane extract on spatial memory and estrogen receptors (ER) in the hippocampus. Female rats received 5 days' Morris water maze training before the ovariectomy, followed by the daily intraperitoneal administration of C. comosa hexane extract at a dose of 250 and 500 mg/kg body weight for 4 weeks. Estradiol (10 μg/kg body weight) was used as the positive control. OVX significantly increased the latency of the animal to the platform, while estradiol and both doses of C. comosa hexane extract reversed the memory impairments. By using the reverse transcription polymerase chain reaction technique, C. comosa hexane extract was shown to produce a selective increase of the ER alpha subtype but not beta subtype in hippocampus, while estradiol increased both of them. C. comosa did not affect spatial memory, learning ability, and ER mRNA levels in the sham OVX rats. In conclusion, C. comosa hexane extract improved the spatial memory of the OVX rats, which was similar to estrogen. The influence on the memory changes might be selectively related to ER alpha in the hippocampus.
Article
Curcuma comosa is widely used as a traditional herbal medicine for gynecological diseases in South East Asia. Previous studies reported that it has phytoestrogenic activity, and several diarylheptanoids were found to be the active constituents. In this study, the pharmacokinetics profile and organ distribution of three active compounds of C. comosa hexane extract were investigated. Rats were separately administered C. comosa hexane extract intravenously at the dose of 125 mg/kg and orally at the doses of 125 and 250 mg/kg body weight, after which blood and target organs were collected at specified time intervals from 0 to 24 h. HPLC was used to measure the concentration of three major compounds, (6E)-1,7-diphenylhept-6-en-3-one (DPH1), (4E,6E)-1,7-diphenylhepta-4,6-dien-3-ol (DPH2), and (6E)-1,7-diphenylhept-6-en-3-ol (DPH3), which were found to be present in the blood and tissues and were subsequently used as markers. In the intravenous study, the volumes of distribution (V d) were 1.06, 8.57, and 6.56 L/kg and clearance values (CLs) were 0.28, 5.56, and 3.39 L/kg/h for DPH1, DPH2, and DPH3, respectively. After oral administration, the three major compounds of both doses reached a maximum systemic concentration at 2 h with maximum concentration (C max) of 0.85, 0.17, and 0.53 mg/L for the lower dose and 1.46, 0.17, and 0.61 mg/L for the higher dose. The bioavailabilities were 31.2, 24.01, and 31.56% for lower dose and 22.61, 17.66, and 17.73% for higher dose with a terminal half-life (t 1/2) of 10.86, 6.3, and 4.62 h for lower dose and 3.85, 2.77, and 2.10 h for higher dose for DPH1, DPH2, and DPH3, respectively. These three major compounds are all found distributed in the brain, liver, kidneys, ovaries, and uterus after oral and intravenous administration and their related pharmacokinetic parameters are described. This study provides the essential pharmacokinetic data for diarylheptanoid phytoestrogenic compounds of C. comosa extract which are required for clinical dose and dosage design.
Article
Full-text available
A method for quantification of diarylheptanoids in Curcuma comosa rhizomes and selected pharmaceutical preparations was established by using HPLC-DAD. The chromatographic separation of three diarylheptanoids [(3S)-1-(3,4-dihydroxy-phenyl)-7-phenyl-(6E)-6-hepten-3-ol (1), (3R)-1,7-diphenyl-(4E,6E)-4,6-heptadien-3-ol (2), and (3S)-1,7-diphenyl-(6E)-6-hepten-3-ol (3)] was performed on a Luna C18 analytical column using gradient elution with 0.5% acetic acid in water and acetonitrile with a flow rate of 1 mL/min and a column temperature of 35 °C. The calibration curves for the analytes showed good linearity (R² > 0.999), high precision (RSD < 2%) and acceptable recovery (98.35–103.90%, RSD < 2%). The limit of detection (LOD) and limit of quantification (LOQ) were 0.06–0.22 and 0.18–0.69 µg/mL, respectively. The results of all validated parameters were within the limits according to the International Conference on Harmonization (ICH) Guidelines. The established method was successfully applied for qualitative and quantitative determination of the three constituents in different samples of C. comosa and some commercial products in capsules. The simplicity, rapidity, and reliability of the method could be useful for the fingerprint analysis and standardization of diarylheptanoids, which are responsible for the estrogenic activity in raw materials and herbal medicinal products of C. comosa.
Article
Full-text available
Curcuma comosa Roxb. is a medicinal plant that belongs to the Zingiberaceae family. The plant has been used in traditional Thai medicine for the treatment of postpartum uterine bleeding. The major compounds found in this plant are diarylheptanoids, which are reported to have estrogenic activity. The aim of the study was to understand the three-dimensional (3-D) aspects of diarylheptanoids from C. comosa on ER- estrogenic receptor at the molecular level. The binding conformations of diarylheptanoid analogues with ER- receptor were obtained by the AutoDock 4.2 program using the Lamarckian genetic algorithm (LGA) in conjunction with an empirical force field to calculate the complex binding free energy. From the analysis of docking results, diarylheptanoid analogues with higher activity have a hydroxyl group in ring C which can be modified by using the isosteres groups while the other phenyl ring have less polarity to fit into the hydrophobic pocket of the ER- receptor. In addition, the heptyl chain needs some flexibility to allow the phenyl ring to adjust suitably into the receptor-binding pocket. Molecular modeling using AutoDock 4.2 was effectively applied to understand the binding conformation of diarylheptanoid analogues with ER- receptor. Information of three-dimensional conformation can be applied in rational drug design for further searching the new highly activity ER- receptor agonists.
Article
Full-text available
Triploidy is relatively common in Curcuma, especially among vegetatively propagated species in cultivation. The aim of this study was to investigate the extent of triploidy and the level of genome size variation among commercially cultivated phyto-oestrogen producing Curcuma and related species in Thailand. Meiosis was also examined in order to validate the triploid status and to infer genomic relationship in the triploids. A total of 47 accessions belonging to C. comosa, C. latifolia, C. sp.‘elata-latifolia’, C. caesia, C. cf. zedoaroides, C. cf. zedoaria and Curcuma sp. 1 were differentiated by ploidy based on chromosome numbers and by genome size based on flow cytometry data. The results revealed three distinct groups: (1) diploid C. comosa cultivars with small rhizomes, having 2n = 42 and mean 2C DNA content of 1.690 pg; (2) triploid cultivars from all but one Curcuma species investigated, with 2n = 63 and mean 2C DNA content of 2.549 pg; and (3) tetraploid cultivars of C. latifolia and C. cf. zedoaria, with 2n = 84 and mean 2C DNA content of 3.439 pg. The mean triploid genome size is right between the diploid and tetraploid values. Only Curcuma caesia showed statistically significant difference in genome size from all other triploid taxa. The study of male meiosis revealed different meiotic figures. The triploid C. comosa is clearly an autotriploid as it showed 21 trivalents, whereas the diploid C. comosa showed 21 bivalents. This confirms the base number x = 21. Triploid cultivars of C. latifolia and C. sp. ‘elata-latifolia’ showed irregularities in their meiotic figures, thus indicating allotriploidy.
Article
Choleretic properties of various extracts of Curcuma comosa Roxb. (Zingiberaceae) were investigated in rats. Butanol and ethyl acetate extracts of the rhizome were the most effective in producing a choleretic effect. Intraduodenal administration of the ethyl acetate extract caused a dose-dependent stimulation of bile secretion. A high dose of the extract increased bile flow rate with decreased bile salt concentration whereas low doses increased the bile flow rate without altering bile salt concentration. With regard to the total output of biliary constituents, the high dose of extract did not alter secretory bile salt output, but markedly increased biliary cholesterol output. Concurrent with increased biliary cholesterol secretion, C. comosa caused a decrease in plasma cholesterol level. This result suggests potential development of this plant as a source of choleretic and hypocholesterolemic drugs.
Article
Curcuma comosa Roxb. is widely used as a gynaecological traditional medicine in South-East Asia and recent behavioral studies have shown that C. comosa extract significantly improved the spatial memory in rats. The present study investigated the protective effects of Curcuma comosa hexane extract on the ethanol (EtOH)-induced oxidation in rat brains. Young female Wistar rats were given 20% of EtOH intraperitoneally to induce the oxidative stress. Subsequently, C. comosa hexane extract was intraperitoneally co-administered at the doses of 100 and 250 mg kg(-1) b.wt. to the EtOH-induced rats for 14 days. The neuron densities of CA1, CA3 and CA4 areas of the hippocampus were counted and the activities of hippocampal Catalase (CAT), Glutathione Peroxidase (GPx) and Superoxide Dismutase (SOD) were determined. EtOH significantly decreased the neuron densities in Cornu Ammonis (CA), including CA1 and CA3 areas; however, the decrease was prevented by C. comosa co-administration. EtOH administration also increased the CAT and GPx activities in the hippocampus which were reversed by C. comosa co-administration. Moreover, C. comosa administration increased the SOD activity in a dose-dependent manner in the EtOH treated groups. C. comosa prevented the neuron loss in the hippocampus caused by EtOH. The possible neural protective mechanism may involve with the changes in activities of the antioxidant enzymes in the hippocampus.
Article
Full-text available
Ultraviolet-B (UVB) exposure is one of the primary extrinsic factors causing skin photoaging. It stimulates inflammatory responses and arrests the cell cycle. Matrix metalloproteinase-1 (MMP-1) secreted by keratinocytes is one of the important extracellular matrixes to attenuate UVB-induced skin aging via collagen degradation. Curcuma aromatica (CA) and Curcuma comosa (CC), the herbaceous plants in the Zingiberaceae family, are commonly used in Thai traditional women’s medicines. The present work was aimed to investigate the potential of the CA and CC extracts and their isolated compounds to attenuate UVB-induced MMP-1 and cell cycle arrest in HaCaT keratinocytes. Total phenolic contents and antioxidant capacities of the extracts were determined. CC extract contains more phenolic components and provides more potent antioxidant activities than CA extract. HaCaTs were pretreated with the extracts or their isolated constituents 1–4 for 24 h and then repeatedly exposed to UVB at 100 mJ/cm2 10 times. Both extracts and compounds 1–4 effectively reduce UVB-induced MMP-1 levels in HaCaT cells and restore cell cycle arrest. This is the first report on the potential of CA and CC extracts in reducing UVB-induced MMP-1 expression and regulating cell proliferation in HaCaT cells. Thus, CA and CC extracts might be used as alternative natural agents to prevent UVB-induced skin photoaging.
Article
Three new diarylheptanoids, a 1:2 mixture of (3S)- and (3R)-1-(4-methoxyphenyl)-7-phenyl-(6E)-6-hepten-3-ol (13a and 13b) and 1-(4-hydroxyphenyl)-7-phenyl-(6E)-6-hepten-3-one (15), together with two synthetically known diarylheptanoids 1,7-diphenyl-(1E,3E,5E)-1,3,5-triene (9) and 1-(4-hydroxyphenyl)-7-phenyl-(4E,6E)-4,6-heptadien-3-one (16), and nine known diarylheptanoids, 2, 8, 10-12, 14, a 3:1 mixture of 17a and 17b, and 18, were isolated from the rhizomes of Curcuma comosa Roxb. The absolute stereochemistry of the isolated compounds has also been determined using the modified Mosher's method. The isolated compounds and the chemically modified analogues were evaluated for their estrogenic-like transcriptional activity using RT-PCR in HeLa cell line. Some of the isolated diarylheptanoids and their modified analogues exhibited estrogenic activity comparable to or higher than that of the phytoestrogen genistein. Based on the transcriptional activation of both estrogenic targets, Bcl-xL and ERbeta gene expression, the structural features for a diarylheptanoid to exhibit high estrogenic activity are the presence of an olefinic function conjugated with the aromatic ring at the 7-position, a keto group at the 3-position, and a phenolic hydroxyl group at the p-position of the aromatic ring attached to the 1-position of the heptyl chain.
Article
In the hypophysectomized albino rat which is protected from contact with steroids in the ration and environment the uterus and vagina are highly atrophic but are sensitive indicators of activity of substances which promote their growth. Both the pituitary growth hormone and certain steroids have the common property of inducing growth of these tissues. The vaginal epithelium consists of 2 layers of cells which differ profoundly in their growth in response to steroids, depending on the molecular structure of these compounds. The differential response to modifications of chemical structures of steroids permits evaluation of the importance of the intramolecular components for the process of growth. The number and site of functional groups, the geometry of the molecule and the state of oxidation are of high importance in determining physiologic activity of steroids in the androstane series; these features are less specific in the estrane series. Side groups at positions C3 and C17 are of importance in the promotion of growth by steroids in the androstane series, but these active centers are not equivalent in their physiological influence. As a generalization, hydrogenation of the oxygen function at C17 (but not at C3) and dehydrogenation at critical areas of the ring structure increase the quantitative efficacy of steroids in promoting growth. The position of double bonds and the state of oxidation at both C3 and C17 determine the qualitative type of growth—cellular pattern, which a compound in the androstane series induces in the vaginal epithelium.
Article
In order to understand differences in the mechanism of action of estrogens and antiestrogens, it is essential to make comparisons between compounds with similar duration of action. Hence, in these studies, we compare the action of a long-acting estrogen (17alpha-ethinyl estriol-3-cyclopentyl ether, EE3CPE) and a long-acting antiestrogen (U-11,100AUA) on the immature rat uterus and analyze different dosage regimens (single and multiple injections) in studying the effects of these compounds on the uterine estrogen receptor and on uterine growth and sensitivity to estradiol. During the first 24 h, UA (50 microng) and EE3CPE (5 microng) evoke remarkably similar receptor distribution patterns and uterine wet weight increase; however, pronounced differences are seen with long-term, multiple injection regimens (every 12 or 24 h for 72 h). Such treatment with UA results in maintenance of high nuclear receptor levels and very low cytoplasmic receptor levels (ca. 10% of total), but no further increase in uterine weight, DNA or protein content, or total receptor content beyond 24-48 h. In contrast, multiple injections of EE3CPE produce not only a prolonged nuclear retention of receptor, but a progressive increase in total receptor content in the tissue and 35-50% of total receptor is cytoplasmic; uterine weight and DNA and protein content also continue to increase markedly above the 24 h level, and responsiveness to estradiol is maintained. However, regardless of whether the uterus continues to grow (as the EE3CPE) or stops growing after 24-48 h (as with UA), the receptor content on a cell basis is similar. Hence, uterine responsiveness to estradiol and continued uterine growth appear not to be related to the total content of receptor per cell, but rather are correlated with the cytoplasmic receptor level within the cell. As there is a continuous translocation of cytoplasmic receptor to the necleus in the growing uterus, the antagonistic action of antiestrogens appears to derive from their ability to effect a marked perturbation in the subcellular distribution of receptor, whereby very little of receptor (ca. 10%) is cytoplasmic, and further estrogen receptor accumulation (most likely synthesis) is blocked.
Article
We have shown previously that estradiol, estriol, and Nafoxidine (Upjohn 11, 100A) have differential effects on uterine growth and that these effects are associated with the retention of the estrogen receptor by the nucleus. In order to examine these relationships further, we have studied the effect of these hormones on endogenous nuclear RNA polymerase I and II in the immature rat uterus. All three compounds caused a rapid elevation in polymerase II activity that reached a peak by the first hour and declined to almost control levels by 2 h after the injection. This transient peak in polymerase II activity was followed by a second elevation by the fourth hour in estradiol- and Nafoxidine-treated animals which was not observed in estriol-treated rats. The activity of polymerase I increased monotonically to very high levels by 4 h and was maintained 12 h or longer in estradiol- and Nafoxidine-treated animals. A similar elevation was observed in estriol-treated rats but the activity declined very rapidly to control levels by 12 h. The second elevation in polymerase II activity and the sustained stimulation of polymerase I activity were correlated with the stimulation of true uterine growth. These data confirm our previous suggestion that long-term nuclear retention of the receptor is a requirement for true uterine growth and suggest that an obligatory response in the production of true growth is the stimulation of a second rise in polymerase II activity and an elevated and sustained activity of polymerase I.
Article
The rhizomes of Curcuma xanthorrhiza Roxb, are used in Indonesian folk medicine as cholagogues, aromatic stomachics, analgesics, a rheumatic remedy, etc. The present study was carried out to elucidate the antiinflammatory effect of the methanol extract obtained from these rhizomes and its active principles. The methanol extract was partitioned between ether and water, and then the ether-soluble fraction was extracted with n-hexane. The n-hexane-soluble fraction was chromatographed (fr. I-IV), fr. II was rechromatographed (fr. V-VII), and then fr. V was rechromatographed (fr. VIII-X) by silica gel column chromatography. The antiinflammatory activity of these fractions was investigated on carrageenin-induced edema in rats and acetic acid-induced vascular permeability as well as the writhing symptom in mice. The methanol extract (p.o.) showed both an antiinflammatory activity and an analgesic activity and these activities shifted successively to the ether-soluble fraction, the n-hexane-soluble fraction, fr. II, V and IX. The chemical structure of fr. IX was identified as germacrone. These results suggest that the antiinflammatory action of Curcuma xanthorrhiza is the result of the germacrone that it contains.
Article
Anticancer activity of the rhizomes of turmeric was evaluated in vitro using tissue culture methods and in vivo in mice using Dalton's lymphoma cells grown as ascites form. Turmeric extract inhibited the cell growth in Chinese Hamster Ovary (CHO) cells at a concentration of 0.4 mg/ml and was cytotoxic to lymphocytes and Dalton's lymphoma cells at the same concentration. Cytotoxic effect was found within 30 min at room temperature (30 degrees C). The active constituent was found to be 'curcumin' which showed cytotoxicity to lymphocytes and Dalton's lymphoma cells at a concentration of 4 micrograms/ml. Initial experiments indicated that turmeric extract and curcumin reduced the development of animal tumours.
Article
Four bisabolane sesquiterpenoids, α-curcumene, ar-turmerone, β-atlantone and xanthorrhizol, were isolated as major antitumor constituents (against Sarcoma 180 ascites in mice) from the rhizomes of Curcuma xanthorrhiza. Their structures were deduced from spectroscopic evidence. The antitumor effectiveness was rated (+++) for α-curcumene, (++) for ar-turmerone and (++) for xanthorrhizol at 50 mg/kg in the total packed cell volume method.
Article
Curcuma comosa is a member of the economically important plant family, Zingiberaceae. A methanolic extract of C. comosa was shown to be nematocidal when tested against the free-living nematode Caenorhabditis elegans. Five diphenylheptanoids [1-5], one new and four known, have been isolated and shown to be responsible for the activity. This is the first report of three of these compounds [1, 2, 4] being isolated from a natural source.
Article
Bioassay-guided fractionation of a hexane extract of the rhizomes of Curcuma xanthorrhiza Roxb. (Zingiberaceae) led to the isolation of three non-phenolic diarylheptanoids, identified mainly by high-field 1H-NMR as trans-trans-1,7-diphenyl-1,3-heptadien-4-one (alnustone), trans-1,7-diphenyl-1-hepten-5-ol, and trans,trans-1,7-diphenyl-1,3-heptadien-5-ol. The latter is reported for the first time as a plant constituent. Germacrone, curzerenone, and cinnamaldehyde were also isolated and identified. The three diarylheptanoids all exerted significant anti-inflammatory activity in the assay of carrageenin-induced hind paw edema in rats.
Article
The presence of a 17ß-hydroxyl group endows the simple androstane molecule with the ability to produce growth of the uterus, vagina, and prostate of the female hypophysectomized albino rat. It appears that hydrogen atoms at position 17 are of critical importance since related compounds with a ketone group at this site are inactive. Monofunctional steroids with a hydroxyl or a ketone group at position 3 likewise are devoid of activity. If a phenolic A-ring is present in monofunctional steroids the 17ß-hydroxyl group is not obligatory for growth. Proliferation of the uterus and vagina were found to follow the administration of 17-desoxyestradiol.
  • O H Lowry
  • N J Rosenbough
  • A L Farr
  • R J Randall