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A new 2H-pyran-2-one derivative, 4-hydroxy-6-(4-methoxyphenethyl)-2H-pyran-2-one (1), together with four known compounds, 5,6-dehydrokawain (2), dihydro-5,6-dehydrokawain (3), (E)-labda-8(17),12-diene-15,16-dial (4), and quercetin (5) were isolated from the rhizomes of Alpinia zerumbet. (E)-Labda-8(17),12-diene-15,16-dial (4) and quercetin (5) exhibited potent inhibition, with IC50 values of 3.18 ± 1.13 and 1.17 ± 0.13 μg/mL, respectively, against formyl-L-methionyl-L-leucyl-L-phenylalanine (fMLP)-induced superoxide anion (O 2 − ) generation.

Background/Aims: Alpinia zerumbet (Pers.) Burtt. et Smith has been used as a flavor additive in food and a traditional medicine for centuries, especially in Guizhou Province, China, and it prolongs people’s lives with multiple beneficial effects. Thus, one of the aims of this review was to expound the chemical constituents of this plant, especially its fruits. Since cardiovascular diseases, including atherosclerosis, pose a health threat to humans, another aim was to expound the possible mechanisms of its potential use as an herbal medication for atherosclerosis. Methods: In this study, 10 reports are cited to expound the potential bioactive compounds. Moreover, 33 reports explain the antihypertensive and antiatherosclerotic effects of the plant by ameliorating inflammation and endothelial dysfunction, increasing vasodilation, improving hyperlipidemia, downgrading the glucose status, and working as an antioxidant. Results: A. zerumbetis rich in terpenes, essential oils, flavonoids, polyphenolics, and sterols. Pharmacological experiments showed that A. zerumbet has antioxidative and anti-inflammatory effects on the NF-κB signaling pathway and can ameliorate oxidative stress in the NOS-NO signaling pathway. Moreover, A. zerumbet demonstrates antihypertensive effects by accelerating vasorelaxant response and increasing 3T3-L1 intracellular cAMP, which has promising antiobesity properties, as well as hypolipidemic and anti-diabetic complication effects. Conclusions: A. zerumbet has potential functions and applications in the prevention of atherosclerosis, but further studies are required before clinical trials.

Alpinia zerumbet (Pers.) B.L.Burtt & R.M.Sm. (Zingiberaceae) is a perennial plant native to the East Indies and is widely distributed in South America, Oceania, and Asia. The mature fruits of the plant have been used in traditional medicine in China. In this study, we compared the chemical constituents in the methanol extracts of the leaves, the placenta, the pericarps, and the seeds obtained from the same plant using LC-MS, and we examined the NO inhibitory activities of the respective extracts and the isolated compounds. As a result of LC-MS analyses, kavalactone derivatives (1-6) were detected in the methanol extracts of the leaves, placenta, and pericarps. Of these, compound 6 was identified as a new asymmetrical cyclobutane dimer of 5,6-dehydrokawain. Quantitative analysis showed that the total amounts of kavalactone derivatives were highest in the methanol extract of the pericarps. Moreover, the results of measurements of the anti-inflammatory activity revealed that the pericarps extract showed the strongest activity. The compounds responsible for the anti-inflammatory activity of the extracts from A. zerumbet were identified. Of these, five were known kavalactone derivatives and one was a new kavalactone derivative (aniba dimer C). The results showed that the pericarps of A. zerumbet are a rich source of kavalactone derivatives, and that the pericarps of A. zerumbet can be utilized as an important medicinal resource.

In this work, the essential oils (EOs) of Alpinia zerumbet (Pers.) Burtt. et Smith were extracted from different organs (stems, leaves, flowers and fruits). The GC-MS analysis showed that two isomers m-cymene and o-cymene distributed totally diverse among different organs: m-cymene were relatively rich in the EOs from stems, flowers and fruits (7.1, 11.3 and 6.6%, respectively), but absent in the EO from leaves; o-cymene was predominant in the EO from leaves (14.9%), but missing in the EOs from other organs. A. zerumbet EOs from different organs, as well as seven characteristic compounds (m-cymene, o-cymene, camphene, eucalyptol, linalool, camphor, and borneol) showed varying degrees of insecticidal and repellent activities to Tribolium castaneum and Liposcelis bostrychophila. o-Cymene exhibited stronger fumigant and contact toxicity than m-cymene did to both insect species, suggesting that the relative position of methyl and isopropyl on benzene ring would influence the insecticidal activity. Positive correlation between relative content of camphor and LC50 value to T. castaneum was significant, while fumigant and contact toxicity of EOs appeared to be negatively correlated with the content of m-cymene.

Bone homeostasis is maintained by balancing bone formation and bone resorption, but an imbalance between them is associated with various bone-related diseases such as osteoporosis and rheumatoid arthritis. We found that 5,6-dehydrokawain (DK) and dihydro-5,6-dehydrokawain (DDK), which were isolated as promising compounds from Alpinia zerumbet rhizomes, promote differentiation of osteoblastic MC3T3-E1 cells. DK and DDK increased the alkaline phosphatase activity and matrix mineralization of MC3T3-E1 cells. DK exerts larger effects than DDK. The gene expression of runt-related transcription factor 2 and osterix, which are essential transcription factors in the early period of osteoblast differentiation, was significantly increased by DK treatment. The mRNA level of distal-less homeobox 5 was also enhanced by DK treatment, and DK activated the p38 mitogen-activated protein kinase pathway. Therefore, DK may have clinical potential for preventing osteoporosis, and could be considered as a potential anabolic therapeutic agent.

Alpinia zerumbet (Pers.) B.L. Burtt. & R.M. Sm is an important perennial ginger plant in the tropics with various uses as foods, dietary supplement, cosmetics, essential oil production and traditional medicines. In this study, essential oils, phenolic acids, fatty acids, kavains, total phenols and antioxidant activity in A. zerumbet plants exposed to UV-C were investigated. Number and weights of essential oils increased rapidly from 1 to 3 days of exposure. Major extend of essential oils was recorded in methyl cinnamate and followed by benzyl acetone. The correspondence to the accumulation of palmitic acid was 15 folds, in contrast to the strong reduction of stearic quantity was 10 folds at 3 days of treatment. Changes in chemical components and antioxidant capacity in A. zerumbet are differed reversely between the exposure of UV-C and heavy toxic chemicals. The exposure of UV-C is beneficial for the increasing of essential oil production in A. zerumbet.

The aim of this study was to characterize components of the EOAz and its hexane (HFEOAz), chloroform (CFEOAz) and methanol (MFEOAz) fractions, and its antihypertensive effect. EOAz was extracted from leaves by hydrodistillation. Aliquot was subjected to selective desorption with silica gel column and eluted with hexane, chloroform and methanol. The components of the EOAz and fractions were analyzed by gas chromatography coupled with mass spectrometry and nuclear magnetic resonance spectroscopy of hydrogen. Experiments of vascular reactivity were performed with isolated aortic rings of male Wistar rats. Antihypertensive effect was evaluated in hypertensive rats submitted to the inhibition of synthesis of nitric oxide. Blood pressure was measured indirectly by tail plethysmography. MFEOAz showed the lowest EC50 (150.45 µg/mL), 1,8-cineole (27.81%) and terpinen-4-ol (57.35%) as main components. Single administration by nasogastric tube of EOAz, fractions and captopril significantly reduced the blood pressure of hypertensive rats, when compared to animals of the negative control group with distilled water. In conclusion, the potency of the MFEOAz was higher than that of EOAz and other fractions. The antihypertensive effect of EOAz and fractions was similar, higher than the negative control and lower than that of captopril.

Zingiberaceae has reportedly undergone frequent polyploidization and hybridization events. Here we describe the new chromosome counts and karyomorphological details for the three important members of the family. Root tip cells of plants of Alpinia zerumbet (earlier reported to be 2n = 48, 40) and Globba marantina (reportedly 2n = 44 to 2n = 96) showed 2n = 52 chromosomes, both being aneuploids, Hedychium spicatum plants (2n = 34 according to previous reports) were found to be tetraploid with somatic chromosome number of 2n = 68. Detailed karyomorphological analyses performed using various parameters revealed that all the three novel cytotypes had moderately symmetrical karyotypes with low levels of intra– and interchromosomal variation in terms of both chromosome lengths and centromeric indices.

Cepas multirresistentes de Corynebacterium ulcerans destacam a necessidade de pesquisas em novos medicamentos e o uso farmacologico de oleos essenciais (OE) pode ser uma alternativa terapeutica. Assim, este estudo teve como objetivo avaliar a atividade antibacteriana e o efeito da concentracao subinibidora de AZEO na morfologia bacteriana e na formacao de biofilme na superficie do poliestireno por C. ulcerans utilizados em caes. O AZEO foi usado por destilacao a vapor das folhas da planta. Os testes de inibicao de fosfomolibdenio e hemolise foram realizados para analisar, respectivamente, uma atividade antioxidante e toxicidade. Foram selecionados como inibidores e bactericidas minimos (MIC e MBC) do AZEO em C. ulcerans e a partir desses resultados foram testados subinibidos dos testes do AZEO. A inatividade do complexo fosfomolibdenio pelo AZEO foi menor que 1% e a capacidade hemolitica foi baixa. Os resultados do estudo antimicrobiano mostram que o AZEO inibiu o crescimento de fundos como cepas microbianas testadas. Os filamentos bacterianos foram observados na presenca do AZEO , bem como uma bacteria de controle automatico. Houve diferenca significativa na inibicao do biofilme. Sugerimos que A. zerumbet pode usar uma terapia alternativa para controlar infeccoes bacterianas induzidas por C. ulcerans .

Alpinia zerumbet (Zingiberaceae) is an important medicinal plant found in several countries and used in folk medicine. The hypotensive and anxiolytic effects of the preparations made from this plant are mainly attributed to flavonoids and kavalactones, respectively. The aim of this study was to compare infusions, hydroalcohol extracts and tinctures obtained with fresh and dried leaves of A. zerumbet collected in two Brazilian cities: Rio de Janeiro/RJ and Brasilia/DF. Colorimetric methods were used to evaluate the antioxidant activity, total phenolic and total flavonoid contents of the extracts. The flavonoids and dihydro-5,6-dehydrokavain (DDK) contents were analyzed by HPLC-DAD and the volatile compounds were evaluated by headspace solid phase extraction (SPE) followed by GC–MS analyses, which also evaluated the nonpolar fractions. The fresh and dried leaves from both Brazilian cities contain high amounts of flavonoids with antioxidant activity. The 80 % hydroalcohol extract prepared with fresh leaves collected in Brasilia exhibited the highest antioxidant activity by the phosphomolybdenum and DPPH methods. HPLC analyses of the infusions prepared with fresh leaves collected in Rio de Janeiro showed the highest DDK content, 6.63 mg/g of the extract. The GC–MS analyses of the nonpolar fractions from the aqueous extracts, from both cities, showed the presence of two major substances, the kavalactones DDK and 5,6-dehydrokavain. The evaluation of the loss of volatile substances by headspace SPE showed that even after a storage time of 30 days, there were still volatile substances in the dried plant material from both cities. In addition, the loss of terpinen-4-ol and γ-terpinene from the fresh leaves was very low, showing the slow release of these substances under the studied conditions. In conclusion, this work shows that the chemical standardization of A. zerumbet preparations contains terpenoids, kavalactones and phenolic compounds related to the biological activities which are important to corroborate the different uses of this species.

O presente estudo teve por objetivo avaliar a toxicidade e a atividade larvicida do óleo essencial (OE) das folhas de Alpinia zerumbet. O (OE) foi extraído por hidrodestilação a 100°C por 3h e determinaram-se os parâmetros físico-químicos mediante a Farmacopeia Brasileira. A toxicidade foi realizada através do bioensaio de Artemia salina Leach, em seguida, avaliou-se a atividade larvicida frente ao Aedes aegypti.Calculou-se a CL50 para a toxicidade e a atividade larvicida frente as larvas do mosquito com base no método de Reed-Muench. Classificou-se o OE quanto à toxicidade e utilizou-se o critério de Dolabela. No bioensaio de toxicidade, o CL50321,15 mg L-1, sendo classificado como atóxico. A atividade larvicida frente ao Aedes aegyptiapresentou 50,70 mg L-1 segundo o OE. Os fenólicos totais apresentaram resultado de 513,574 mg EAT g-1. O OE apresentou resultados satisfatórios contra os microrganismos testados, revelando sua eficiência no combate e controle de microrganismos patogênicos e larvicidas.

Este estudo teve por objetivo a determinação dos fenólicos totais, avaliação da toxicidade e a atividade antimicrobiana do óleo essencial (OE) das folhas de Alpinia zerumbet. O OE foi extraído por hidrodestilação e os parâmetros físico-químicos foram determinados de acordo com a Farmacopeia Brasileira. O ensaio da toxicidade seguiu o bioensaio de letalidade frente ao organismo não-alvo Artemia salina Leach. A atividade antimicrobiana seguiu a metodologia descrita pelo Clinical and Laboratory Standards Institute utilizando o Método de Difusão de Disco e Diluição em Caldo para determinação da Concentração Inibitória Mínima (CIM) para ação do OE frente à Escherichia coli, Staphylococcus aureus, Aspergillus sp. e Penicilium sp. O rendimento do OE foi de 0,71%. A Concentração Letal 50% (CL50) para a ação do OE frente a Artemia salina L. foi de 280,40 mg/L, sendo considerado atóxico. Através dos ensaios antimicrobianos, o OE apresentou atividade bactericida frente às bactérias E. coli e S. aureus, e atividade fungicida frente aos fungos Aspergillus sp. e Penicillium sp. Conclui-se que o OE apresenta um bom potencial antimicrobiano, sendo sua aplicação apreciada pela sua classificação como OE atóxico.

Ethnopharmacology relevance The leaves of Alpinia zerumbet is used in folk medicine in Brazil to treat hypertension. However, the cardioprotective effect of this plant has not been studied yet. Aim of this study To evaluate the cardioprotective effects of the hydroalcoholic extract of the leaves of Alpinia zerumbet (AZE) against isoproterenol (ISO)-induced myocardial infarction in rats. Material and methods Rats were pretreated orally with AZE (300 mg/kg) for 30 days prior to ISO-induced myocardial infarction. The rats were sacrificed and hearts were collected and homogenized for biochemical analysis. At the end of the experiment, cardiac marker enzyme levels, histological and morphometric parameters, and hemodynamic measurements were assessed. Phytochemical compounds were verified by gas chromatography-mass spectrometry (GC-MS). Results Rats administered with ISO showed a significant increase in cardiac marker enzymes, i.e., in creatine kinase-NAC (CK-NAC) and CK-MB. Triphenyltetrazolium chloride (TTC) staining exhibited an increase in infarct areas. In the animals treated with ISO induced a significant increase in heart rate. Pretreatment with AZE significantly inhibited these effects of ISO. Moreover, biochemical findings were supported by histopathological observations. The GC-MS analyses of AZE identified volatile oils, kavalactones, and phytosterols. Conclusions Haemodynamic, biochemical alteration and histopathological results suggest a cardioprotective protective effect of oral administration of AZE in isoproterenol induced cardiotoxicity.

In this report, a rapid and selective analytical method for the determination of monoterpenes in Alpinia zerumbet essential oil (AZEO) by gas chromatography (GC) flame ionization detection (FID) was developed, optimized and validated. The suitability of six different capillary columns was investigated by polarity phase constants calculated based on the methodology proposed by Rohrschneider and McReynolds. The most suitable column was then used in a central composite design applying the following GC factors to investigate responses based on peak resolutions and analysis time: initial oven temperature, heating rate and carrier gas flow rate. The optimized method has initial oven temperature of 60 ºC, heating rate of 5.1 ºC min-1 and flow rate of 1.0 mL min-1 using the DB-35 capillary column. The validation acceptance criteria were met in all cases. The method was successfully applied for the quantification of major monoterpenes found in AZEO in different samples of Alpinia zerumbet.

Zingiberaceae family is widely distributed in the tropical realm of Asia. Considering its diverse applications as spices and therapeutics, the present study was undertaken to evaluate the cytotoxic and antioxidant effect of the ethanolic rhizome extracts of five plants, namely Alpinia galanga (L.) Willd., Alpinia zerumbet (Pers.) B.L. Burtt and R. M. Smith, Curcuma caesia Roxb., Zingiber officinale Rosc., and Zingiber zerumbet (L.) Smith on Allium cepa Linn. system. Materials and Methods: Cytotoxicity was evaluated by 2,3,5-triphenyltetrazolium chloride (TTC) and 2’,7’-dichlorofluorescein diacetate (DCFDAH2) assays. Further, in vitro DNA protection assay was performed to confirm the antioxidant potentials of the extracts. Characterization of phytochemicals was done by performing qualitative tests. Results and Discussion: TTC reduction assay revealed that the extracts (2.5, 5, and 10 μg/ml) had no cytotoxic effect on A. cepa root cells. Roots treated with extracts (2.5 μg/ml) were stained with reactive oxygen species-sensitive dye DCFDAH2 and visualized under the fluorescence microscope. The result confirmed that the extracts did not exert any prooxidant effect. Further, the extracts established their substantial antioxidant potential by inhibiting oxidative DNA damage in an in vitro system. In addition, qualitative analysis showed that the rhizomes are rich in phytochemicals. Conclusion: From the current observations, it can be concluded that the selected herbs can be utilized safely for human consumption.

Ethnopharmacological relevance Fructus Alpinia zerumbet (FAZ), a dry and ripe fruit of Alpinia zerumbet (Pers.) Burtt. et Smith, is widely used as a spice to treat cardiovascular diseases in clinic as a miao folk medicine in Guizhou Province of China. Essential oil extracted from FAZ (EOFAZ) is the key bioactive ingredients. Aim of the study This study aimed to examine the effects and mechanisms of EOFAZ on lipopolysaccharide (LPS)-induced endothelial cell injury, inflammation and apoptosis in vitro and in vivo. Materials and methods For the in vitro study, LPS-treated human aortic endothelial cells were used to perform PCR, western blot analysis and immunofluorescence. For the in vivo study, male mouse were divided into four groups, vehicle control group and LPS group received 0.5% Tween-80 in saline; and two EOFAZ groups receive different dose of EOFAZ (90 mg kg −1·day−1, 180 mg kg −1·day−1) respectively. Each group was fed for 7 days by intragastrical administration at daily base. Then, except vehicle control group received saline, mice in other three groups were administered with LPS (1 mg kg −1, dissolved in saline) by intraperitoneal injection. 24 h later, Aorta tissue was collected and frozen immediately in liquid N2, stored at −80 °C for western blot analysis. Results We found that EOFAZ completely prevented LPS-induced HAEC activation and inflammation in vitro and in vivo, as assessed by expression of endothelial adhesion molecules, ICAM-1 and VCAM-1. Similarly, EOFAZ significantly blunted LPS-induced endothelial injury, as tested by MTT assay, LDH release and caspase-3 activation. We further demonstrated that TLR4-dependent NF-κB signaling may be involved in the process. Conclusion EOFAZ protected against LPS-induced endothelial cell injury and inflammation likely via inhibition of TLR4-dependent NF-κB signaling.

The longevity of the population in the Okinawa Islands of Japan has been ascribed to genetic factors and the traditional Okinawa cuisine, which is low in calories and high in plant content. This diet includes shell ginger (Alpinia zerumbet (Pers.) B.L. Burtt & R.M. Sm) of the ginger family (Zingiberaceae). Due to its local popularity, Alpinia zerumbet has become the subject of a good deal of study at the University of the Ryukyus in Okinawa. Personal local experience and review of the literature now suggest that culinary shell ginger may contribute to longevity among the population in Okinawa. This is supported by its abundant phytochemical content, with antioxidant and anti-obesity properties. The major bioactive phytochemicals are dihydro-5,6-dehydrokawain (DDK; 80–410 mg g−1 fresh weight), 5,6-dehydrokawain (DK; ≤100 mg g−1), and essential oils, phenols, phenolic acids, and fatty acids (≤150 mg g−1 each). Further, Alpinia zerumbet extends the lifespan in animals by 22.6%. In conclusion, culinary shell ginger may significantly contribute to human longevity in Okinawa.

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In this report, a rapid and selective analytical method for the determination of monoterpenes in Alpinia zerumbet essential oil (AZEO) by gas chromatography (GC) flame ionization detection (FID) was developed, optimized and validated. The suitability of six different capillary columns was investigated by polarity phase constants calculated based on the methodology proposed by Rohrschneider and McReynolds. The most suitable column was then used in a central composite design applying the following GC factors to investigate responses based on peak resolutions and analysis time: initial oven temperature, heating rate and carrier gas flow rate. The optimized method has initial oven temperature of 60 oC, heating rate of 5.1 oC min-1 and flow rate of 1.0 mL min-1 using the DB-35 capillary column. The validation acceptance criteria were met in all cases. The method was successfully applied for the quantification of major monoterpenes found in AZEO in different samples of Alpinia zerumbet.

PAK1 (RAC/CDC42-activated kinase 1) is the major oncogenic kinase, and a number of herbal PAK1-blockers such as propolis and curcumin have been shown to be anti-oncogenic and anti-melanogenic as well as anti-alopecia (promoting hair growth). Previously, we found several distinct PAK1-inhibitors in Okinawa plants including Alpinia zerumbet (alpinia). Thus, here, we tested the effects of these herbal compounds and their derivatives on the growth of cancer or normal hair cells, and melanogenesis in cell culture of A549 lung cancer, hair follicle dermal papilla cell, and B16F10 melanoma. Among these herbal PAK1-inhibitors, cucurbitacin I from bitter melon (Goya) turned out to be the most potent to inhibit the growth of human lung cancer cells with the IC50 around 140 nM and to promote the growth of hair cells with the effective dose around 10 nM. Hispidin, a metabolite of 5,6-dehydrokawain from alpinia, inhibited the growth of cancer cells with the IC50 of 25 μM as does artepillin C, the major anti-cancer ingredient in Brazilian green propolis. Mimosine tetrapeptides (MFWY, MFYY, and MFFY) and hispidin derivatives (H1-3) also exhibited a strong anti-cancer activity with the IC50 ranging from 16 to 30 μM. Mimosine tetrapeptides and hispidin derivatives strongly suppressed the melanogenesis in melanoma cells.

Dihydro-5,6-dehydrokavain (DDK) is the major and most promising component of the tropical plant Alpinia zerumbet (shell ginger), a species of the ginger family Zingiberaceae. Alpinia zerumbet is known for its human use as a traditional herbal medicine, food, and dietary supplement. With its α-lactone ring, DDK belongs to the large chemical group of kavalactones, which are also found in kava (Piper methysticum), another herbal medicine; DDK is characterized by a double-bond linkage at positions 5,6 and the absence of a double-bond linkage at positions 7,8. This dissociates DDK from other kavalactones with their linkages at positions 7,8 and 5,6 that are both either completely saturated or unsaturated, or may have an unsaturated bond at the position 7,8 as well as a saturated bond at the position 5,6. DDK is easily identified and quantified by HPLC and GC. DDK contents in fresh leaves, stems and rhizomes range from 80 to 410 mg/g, requiring solvent extraction procedures to ensure high DDK yield. This is best achieved by hexane extraction from fresh rhizomes that were previously boiled in water, allowing DDK yields of up to 424 mg/g. Successful synthesis of DDK can be achieved by asymmetric pathways, whereas its simple chemical structure facilitates the synthesis of DDK derivatives by HCl hydrolysis. Thus, all synthesized products may be used for various commercial purposes, including the potential development of promising antiobesity pharmaceutical drugs, preparation of specific and safe dietary supplements, and use as effective natural herbicides or fungicides.

Essential oils are new natural medicines, which have been studied extensively in recent years. In this paper, the chemical composition of the essential oil from Alpinia zerumbet leaves and its ability to modulate the activity of aminoglycoside antibiotics is reported. The essential oil was extracted by hydrodistillation and analyzed by gas chromatography (GC) and GC–mass spectrometry (GC/MS). The antibacterial activity of the essential oil alone or in association with aminoglycosides was determined by a microdilution test against twelve strains (standards and multi-resistant clinical isolates obtained from sputum and wounds), seven Gram negative and five Gram positive. The major components identified by GC/MS were 4-terpineol (32.9 ± 4.0%), 1,8-cineole (21.4 ± 1.2%), γ-terpinolene (10.0 ± 1.8%) and sabinene (7.1 ± 4.6%), with a strong predominance of monoterpenes. The results indicated that the multi-resistant clinical isolates Staphylococcus aureus 358 and Escherichia coli 27 were more sensitive to the e...

Recently several compounds from Okinawa plants including Alpinia zerumbet (alpinia) were shown to inhibit directly the oncogenic/ageing kinase PAK1 (p21-activated kinase 1). Furthermore, it was recently revealed that both PAK1 and PAK4 (p21-activated kinase 4) are equally essential for the melanogenesis in melanoma cells. Thus, in this study, we tested if several alpinia compounds inhibit the melanogenesis in melanoma (B16F10) cells, as well as the PAK1-dependent up-regulation of both reactive oxygen species (ROS) and nitric oxide (NO) in cultured adipocytes (3T3-L1) without any cytotoxicity. The effect of alpinia compounds on the melanogenesis was measured by both the melanin content and intracellular tyrosinase activity in melanoma cells treated with 3-isobutyl-1-methylxanthine (IBMX), a melanogenesis stimulating hormone. We found that (1E,3E,5E)-6-methoxyhexa-1,3,5-trien-1-yl)-2,5-dihydrofuran (MTD), 5,6-dehydrokawain (DK), labdadiene, hispidin and dihydro-5,6-dehydrokawain (DDK) at 50 μg/mL reduced the melanin content by 63-79%. The MTD, DK and hispidin, at 50 μg/mL, inhibited tyrosinase activity by 70-83% in melanoma cells. Among these compounds, labdadiene, MTD, (E)-2,2,3,3-Tetramethyl8-methylene-7-(oct-6-en-1-yl)octahydro-1H-quinolizine (TMOQ) and hispidin strongly inhibited the ROS production. Hispidin, labdadiene and MTD at 20 μg/mL inhibited NO production by over 70%. These findings altogether suggest that some of these alpinia compounds could be potentially useful for the prevention or treatment of hyperpigmentation and obesity.

Natural products are a major source of drugs for the treatment of cancer. The species Alpinia zerumbet (Pers.) B.L. Burtt & R.M. Sm, Zingiberaceae, is widely distributed in Brazil where it is known as “colônia”. The leaves are commonly used in the treatment of hypertension and dyspepsia, however, the effects of A. zerumbet extracts and isolated substances on human cancer cells remain to be elucidated. This study was designed to identify the chemical constituents of hydroalcoholic and dichloromethane extracts from A. zerumbet leaves and to investigate their in vitro antiproliferative activity. The isolated phytochemicals included kaempferol, dihydro-5,6-dehydrokavain, 5,6-dehydrokavain, and pinostrobin. The hydroalcoholic extract inhibited cellular proliferation only at high concentrations, while the dichloromethane extract showed a moderate antiproliferative effect against leukemia and lung tumor cell lines. 5,6-Dehydrokavain showed potent cytostatic activity against glioblastoma cells and a moderate effect on all other tumor cell lines. Pinostrobin showed potent activity against leukemia and breast tumor cell lines and moderate cytostatic effect against ovarian cell. Furthermore, this is the first report on the isolation of kaempferol and pinostrobin from A. zerumbet leaves. Moreover, the purification process described in this study was effective. These results suggest that A. zerumbet leaves are a promising source of anticancer compounds. Keywords: Medicinal plants, Antiproliferative effects, 5,6-Dehydrokavain, Pinostrobin, Antitumor agents

Purpose: To investigate the cellular response to injury, analyzing histopathologic changes associated with increased cellularity, degeneration and disorganization of collagen fibers. Methods: Thirty wistar rats were divided in two groups after partial Achilles tenotomy: the right hind paw were treated with the essential oil of Alpinia zerumbet (EOAz), diluted to 33% (0.3 mL kg-1), and the left hind paw received sunflower oil for 3, 14, 30 and 90 days. Statistical significance was determined using a Chi-square and Pearson Correlation qualitative variables test. Moreover, Mann-Whitney U-test test for comparison between different groups of the same cell, one-way ANOVA, and Tukey’s test of quantitative measurement. Results: A decrease hyperemia (p < 0.001) was observed in the acute phase of inflammatory cell number (p < 0.001), whereas sub-acute phase was marked by significant correlation with macrophages in fibroblasts (r = 0.17, p = 0.03), with probable induction a dense and modeled tissue. At chronic phase, it was found an increase in the number of fibroblasts and a higher percentage of type I collagen fibers (78%) compared with control collagen fibers (55%). Conclusion: Oil of Alpinia zerumbet stimulated the process of maturation, organization and tissue repair which gave it greater resistance.

An imbalance between bone resorption by osteoclasts and bone formation by osteoblasts can cause bone loss and bone-related disease. In a previous search for natural products that increase osteogenic activity, we found that 5,6-dehydrokawain (1) from Alpinia zerumbet promotes osteoblastogenesis. In this study, we synthesized and evaluated series of 5,6-dehydrokawain analogs. Our structure-activity relationships revealed that alkylation of para or meta position of aromatic ring of 1 promote osteogenic activity. Among the potential analogs we synthesized, (E)-6-(4-Ethylstyryl)-4-methoxy-2H-pyran-2-one (14) and (E)-6-(4-Butylstyryl)-4-methoxy-2H-pyran-2-one (21) both significantly up-regulated Runx2 and Osterix mRNA expression at 10µM. These osteogenic activities could be mediated by bone morphogenetic protein (BMP) and activation of p38 MAPK signaling pathways. Compounds 14 and 21 also inhibited RANKL-induced osteoclast differentiation of RAW264 cells. These results indicated that novel 5,6-dehydrokawain analogs not only increase osteogenic activity but also inhibit osteoclast differentiation, and could be potential lead compounds for the development of anti-osteoporosis agents.

PAK1 (p21-activated kinase 1) is an emerging target for the treatment of hair loss (alopecia) and cancer; therefore, the search for PAK1 blockers to treat these PAK1-dependent disorders has received much attention. In this study, we evaluated the anti-alopecia and anticancer effects of PAK1 inhibitors isolated from Alpinia zerumbet (alpinia) in cell culture. The bioactive compounds isolated from alpinia were found to markedly promote hair cell growth. Kaempferol-3-O-β-d-glucuronide (KOG) and labdadiene, two of the isolated compounds, increased the proliferation of human follicle dermal papilla cells by approximately 117%–180% and 132%–226%, respectively, at 10–100 μM. MTD (2,5-bis(1E,3E,5E)-6-methoxyhexa-1,3,5-trien-1-yl)-2,5-dihydrofuran) and TMOQ ((E)-2,2,3,3-tetramethyl-8-methylene-7-(oct-6-en-1-yl)octahydro-1H-quinolizine) showed growth-promoting activity around 164% and 139% at 10 μM, respectively. The hair cell proliferation induced by these compounds was significantly higher than that of minoxidil, a commercially available treatment for hair loss. Furthermore, the isolated compounds from alpinia exhibited anticancer activity against A549 lung cancer cells with IC50 in the range of 67–99 μM. Regarding the mechanism underlying their action, we hypothesized that the anti-alopecia and anticancer activities of these compounds could be attributed to the inhibition of the oncogenic/aging kinase PAK1.

Alpinia species, used as ornamental plants and flavoring agents, are renowned for their therapeutic properties and their subsequent use in traditional medicines throughout the world. Alpinia zerumbet (Pers.) B.L.Burtt and R.M.Sm. is the most common Alpinia species encountered in Martinique. Several essential oils (EOs) obtained by hydrodistillation of A.zerumbet flowers collected in various locations on the island at different seasons were analysed to evaluate the influence of the collection period and area on the EOs' chemical compositions and to assess their bioactivity. A combination of GC-FID and GC/MS techniques was used to examine the volatile constituents, leading to the identification of a total of 71 components accounting for 97.8-99.3% of the respective total GC-FID areas : among them, nineteen compounds were characterized for the first time in A.zerumbet EOs. The antimicrobial activity of these EOs was assessed against eight bacterial, yeast and fungal strains and two multi-resistant strains: some significant bacteriostatic and fungistatic activities of A.zerumbet flower oils were evidenced. Finally, an interesting insecticidal activity of the flower EO was highlighted for the first time against Aedes aegypti.

Obesity and its related disorders have become leading metabolic diseases. In the present study, we used 3T3-L1 adipocytes to investigate the anti-obesity activity of hispidin and two related compounds that were isolated from Alpinia zerumbet (alpinia) rhizomes. The results showed that hispidin, dihydro-5,6-dehydrokawain (DDK), and 5,6-dehydrokawain (DK) have promising anti-obesity properties. In particular, all three compounds significantly increased intracellular cyclic adenosine monophosphate (cAMP) concentrations by 81.2% ± 0.06%, 67.0% ± 1.62%, and 56.9% ± 0.19%, respectively. Hispidin also stimulated glycerol release by 276.4% ± 0.8% and inhibited lipid accumulation by 47.8% ± 0.16%. Hispidin and DDK decreased intracellular triglyceride content by 79.5% ± 1.37% and 70.2% ± 1.4%, respectively, and all three compounds inhibited glycerol-3-phosphate dehydrogenase (GPDH) and pancreatic lipase, with hispidin and DDK being the most potent inhibitors. Finally, none of the three compounds reduced 3T3-L1 adipocyte viability. These results highlight the potential for developing hispidin and its derivatives as anti-obesity compounds.

The present study describes the chemical composition and neuraminidase (NA) enzyme inhibition and anti-atherogenic properties of the essential oils (EO) of two varieties of Alpinia zerumbet (alpinia) leaves. A total of forty eight compounds were identified using GC-MS studies, which showed that tairin variety contained more compounds than shima variety. The EO inhibited NA in a dose-dependent manner with IC50 values of 41.5 ± 2.7 and 62.3 ± 3.1 μg/ml for tairin and shima varieties, respectively. Furthermore, the kinetic studies of NA inhibitions revealed that tairin EO exhibited slow, time-dependent and mixed type of inhibitions. It seems that the minor components of tairin EO have better inhibitory properties. In order to assess the anti-atherogenic activities of EO, inhibitions of 15-lipoxygenase (15-LOX) and low density lipoprotein (LDL) oxidation were investigated. The results also showed that tairin EO had better activities against 15-LOX and LDL oxidation (IC50 = 235 ± 7, and 133 ± 3 g/ml), than shima EO (IC50 = 465 ± 12, and 195 ± 5 μg/ml). Finally, the acute toxicity analysis using Caenorhabditis elegans showed that LC50 values were more than 2500 μg/ml. These findings suggest that tairin EO could be a possible candidate for further investigations in search for bioactive compounds against neuraminidase. DOI: http://dx.doi.org/10.3126/jfstn.v7i0.10563 J. Food Sci. Technol. Nepal, Vol. 7 (22-30), 2012

Alpinia zerumbetis amiaofolk medicinal plant widely used in the Guizhou Province of southwest China that contains several bioactive constituents and possesses protective effects against cardiovascular diseases. In the present study, we evaluated the protective effect of essential oils derived from FructusAlpiniae zerumbet(EOFAZ) on oxidized lowdensity-lipoprotein- (ox-LDL-) induced apoptosis in human aortic endothelial cells (HAECs). Following exposure to ox-LDL, HAECs presented with classical characteristics of apoptosis. However, EOFAZ ameliorated these morphological alterations and also inhibited the decrease in cell viability. In addition, EOFAZ abrogated the number of TUNEL or Hoechst 33258 stained positive cells observed after ox-LDL challenge. Investigation into the mechanisms of this inhibition revealed that EOFAZ treatment resulted in a downregulation of Bax and Caspase-3 at both the protein and mRNA expression levels. Moreover, EOFAZ was found to upregulate Bcl-2 protein and mRNA levels and to attenuate ox-LDL-induced HAECs injury caused by apoptosis, revealing both its therapeutic potential for endothelial cell injury protection and its clinical application for atherosclerosis.

Objective: To evaluate antibacterial activity and the bioactive compounds of 50% hydroethanolic extract of Alpinia zerumbet (A. zerumbet) rhizomes. Methods: Eight reference microbial strains including two Gram-positive bacteria [Staphylococcus aureus (ATCC 29213) and Enterococcus faecalis (ATCC 29212)] and six Gram-negative bacteria [Escherichia coli (ATCC 25922), Klebsiella pneumoniae (ATTC 700603), Proteus mirabilis (DMST 8212), Salmonella enterica subsp. enterica serovar Vellore. (ATCC 15611), Shigella flexneri (ATCC 12022) and Pseudomonas aeruginosa (ATCC 27853)], were used to test antimicrobial susceptibility by the broth microdilution method. Bioactive compounds were analyzed by using HPLC. Results: The minimum inhibitory concentration values of A. zerumbet extract were 8 mg/mL for Staphylococcus aureus, Escherichia coli and Shigella flexneri and 16 mg/mL for Enterococcus faecalis and the other four Gram-negative bacilli. HPLC chromatograms revealed that the A. zerumbet extract contained hydroxybenzoic acids, hydroxycinnamic acids and flavonoids. Conclusions: The constituents of A. zerumbet rhizomes could be a potential source of antibacterial compounds, warranting further study of A. zerumbet extract.

Alpinia zerumbet is a medicinal plant from Asian origin used in folk medicine for the treatment of hypertension, which effect is attributed to terpinen-4-ol, the major component of the essential oil. The objective of this work was to identify the essential oil secretory structures in the leaf, flower, root and rhizome of this plant, and analyze the content and the chemical composition of the oil in the different organs of the plant. Sections were subjected to histochemical test with Nadi reagent for in situ localization of secretion. The essential oil extraction was performed by hydrodistillation in a Clevenger apparatus and the compounds were identified in CG-EM/FID. The histochemical test was positive for terpenoids, confirming the presence of essential oil stored in secretory structures named oils cells present in all analyzed organs. The higher essential oil content was found on the leaf (0.30%), while the petal and the rhizome presented content of 0.10% and 0.06%, respectively. It was not possible to determine essential oil content of the root due to the low amount of biomass produced. There were qualitative and quantitative differences in the chemical composition of the essential oil in the different plant organs, but the major constituent in all of them was the terpinen-4-ol, followed by 1,8 cineol in the leaf and by the α-terpineol in the flower and rhizome.

Alpinia zerumbet is used in folk medicine in Brazil to treat hypertension. However, several pathways involved in the mechanism of vasorelaxation are still unclear. This study was designed to verify the antihypertensive effect of the methanolic fraction of the essential oil of A. zerumbet (MFEOAz) and to characterize its mechanism of action. The thoracic aortic rings from the Wistar rats were perfused in the organ chambers filled with Kreb's solution, where the tension of each ring was measured. The antihypertensive effect of MFEOAz was assessed in rats submitted to chronic hypertension by inhibition of nitric oxide synthesis by indirect measurement of blood pressure with indirect tail cuff method. MFEOAz relaxed phenylephrine and KCl-induced contraction of either endothelium-intact or endothelium-denuded rat aortic rings in a concentration-dependent manner. Pre-incubation with MFEOAz (100 and 300 μg/mL) in Ca(2+)-free Krebs solution attenuated phenylephrine- or caffeine-induced contraction. Pre-incubation with L-NAME, ODQ, wortmannin, atropine, indomethacin, catalase, SOD, TEA, 4-aminopyridine, glibenclamide, apamin, charybdotoxin, or iberiotoxin did not affect MFEOAz-induced relaxation. The intragastric administration of MFEOAz induced an antihypertensive effect. MFEOAz it seems inhibited the calcium influx via voltage-operated calcium channels and receptor-operated calcium channels, as well as inhibition of calcium mobilization from intracellular stores.

Background Alpinia zerumbet (Pers.) B.L. Burtt & R.M. Sm., Zingiberaceae, is traditionally used in Brazil to treat hypertension, inflammation, anxiety, and hysteria. However, investigations of antioxidant and central effects of A . zerumbet extract are lacking. Objective The aim of this study was to verify the effects of a hydroethanolic extract of A . zerumbet (HEA) on tail suspension and light/dark tests to screen for possible antidepressant- and anxiolytic-like activities, respectively. We also evaluated the in vitro antioxidant effects of HEA. Materials and methods Swiss male mice were orally treated with saline or HEA (200, 400 or 800 mg/kg) 60 min before testing. The in vitro antioxidant activity of HEA was determined using the ferric-reducing antioxidant property method and assays involving free radical and reactive oxygen species scavenging. Protections against glutathione oxidation and lipid peroxidation were also evaluated. Results HEA (200, 400 and 800 mg/kg) significantly reduced the period of immobility in the tail suspension test, similarly to imipramine. In the tail suspension test, HEA (400 and 800 mg/kg but not 200 mg/kg) and diazepam significantly increased time spent in the light side. The antioxidant activity of HEA was remarkable, as it showed significant ferric-reduction power, 1,1-diphenyl-2-picrylhydrazyl radical and hydrogen peroxide scavenging activity, and protection against lipid peroxidation. Conclusion This study showed the antioxidant, antidepressant- and anxiolytic-like effects of HEA in mice. More studies and the identification of active components of the extract are necessary to further assess the therapeutic potential of this species in the treatment of psychiatric diseases.

The beneficial effects of the phytochemical compounds in fruits and vegetables have been extrapolated mainly from in vitro studies or short-term dietary supplementation studies. Recent approaches using animal models of Caenorhabditis elegans are becoming quite popular, and in this regard the effects of Alpinia zerumbet leaf extract (ALP) on C. elegans lifespan were investigated under both normal and stress conditions. ALP significantly increased, mean lifespan by 22.6%, better than the positive control, resveratrol. Furthermore, both under thermal and oxidative stressed conditions, ALP increased the survival rate significantly better than quercetin. Further studies indicated that the significant longevity-extending effects of ALP on C. elegans can be attributed to its in vitro free-radical scavenging effects and its upregulation of stress-resistance proteins, including superoxide dismutase 3 (SOD-3) and heat-shock protein (HSP-16.2). These results suggest that phytochemical compounds in A. zerumbet have beneficial effects on the lifespan of C. elegans, and that they can be used as a source of dietary supplements for aging and age-related diseases.

RESUMO: O presente trabalho descreve a atividade antibacteriana do óleo essencial e do extrato etanólico das folhas de Alpinia zerumbet (colônia) sobre cepas de Staphylococcus aureus isoladas de vacas com mastite subclínica e cepas padrão ATCC 29213 e ATCC 25923, por meio do método de difusão em ágar. Foram utilizados 10 tratamentos contendo diferentes concentrações do óleo essencial e do extrato etanólico (100,0; 50,0; 25,0; 12,5 e 6,3 mg.mL-1) e o grupo controle (álcool etílico a 50% e Tween a 1%). Os constituintes majoritários do óleo essencial foram p -cimeno (32,72%), 1,8-cineol (24,05%) e 4-terpineol (20,23%), sendo esses determinados por cromatografia a gás acoplada a espectrometria de massas e cromatografia a gás com detector de ionização de chama (CG-EM/DIC). No extrato etanólico foi detectado o ácido elágico e três flavonoides: rutina, quercetina e campferol, por meio de cromatografia a líquido de alta eficiência acoplada a detector de arranjo de diodo (CLAE-DAD). Todas as cepas apresentaram sensibilidade aos tratamentos com óleo essencial e extrato etanólico. A melhor resposta foi obtida com o óleo essencial de A. zerumbet que, na concentração de 100 mg.mL-1 proporcionou inibição total do crescimento bacteriano. Esses resultados sugerem o potencial antibacteriano do óleo essencial e do extrato etanólico de A. zerumbet no controle da mastite bovina. ABSTRACT: The present work describes the antibacterial activity of the essential oil and the ethanol extract from leaves of Alpinia zerumbet (colônia) on Staphylococcus aureus strains isolated from cows with subclinical mastitis and standard strains ATCC 29213 and ATCC 25923, using the agar diffusion method. Ten treatments containing different concentrations of essential oil and ethanol extract (100.0; 50.0; 25.0; 12.5 and 6.3 mg.mL-1) and the control group (50% ethyl alcohol and 1% Tween solutions) were used for antimicrobial testing. The major constituents of the essential oil were p -cimeno (32.72%), 1.8-cineol (24.05%) and 4-terpineol (20.23%), which were determined by gas chromatographymass spectrometry and gas chromatography - flame ionization detector (CG-MS/FID). Ellagic acid and three flavonoids (rutin, quercetin and campferol) were detected in the ethanol extract by means of high performance liquid chromatography-photodiode array detector (HPLC-PDA). All strains showed sensitivity to the treatments with essential oil and the ethanol extract. The best response was obtained with A. zerumbet essential oil at a 100 mg.mL-1, showing complete inhibition of bacterial growth. These results demonstrate the antibacterial potential of essential oil and ethanol extract of A. zerumbet in the control of bovine mastitis.