Showing papers in "Planta Medica in 1984"
TL;DR: The mechanism of antihepatotoxic action of atractylon, a main sesquiterpenic constituent of ATRACTYLODES rhizomes, was studied and accumulated data support that although both CCl 4 and atractyl generate free radicals respectively by rat liver microsomes, free radical from CCl4 conducts lipid peroxidation and produces liver lesion.
Abstract: The mechanism of antihepatotoxic action of atractylon, a main sesquiterpenic constituent of ATRACTYLODES rhizomes, was studied. Atractylon inhibited carbon tetrachloride (CCl 4 )-induced cytotoxicity in primary cultured rat hepatocytes and CCl 4 -induced lipid peroxidation by rat liver microsomes. However, atractylon increased the free radical generation by CCl 4 with rat liver microsomes in the presence of a radical trapping agent, phenyl T-butyl nitrone (PBN). In addition, atractylon generated free radical PER SE. Experiments using 13 CCl 4 instead of CCl 4 indicated that the increased free radicals consisted of those from 13 CCl 4 and from atractylon. Accumulated data support that although both CCl 4 and atractylon generate free radicals respectively by rat liver microsomes, free radical from CCl 4 conducts lipid peroxidation and produces liver lesion, while atractylon forms free radical which scavenges CCl 3 radical in the absence of PBN, inhibits lipid peroxidation by CCl 4 and suppresses CCl 4 -induced liver lesion.
214 citations
TL;DR: Using serpentine fluorescence as an indicator of alkaloid production in cultured CATHARANTHUS ROSEUS cells, 6 cell lines producing alkaloids in excess of 300 mg/l were selected from more than 2 x 10 (5) individual colonies and their alkaloidal production was monitored over a period of 8 years.
Abstract: Using serpentine fluorescence as an indicator of alkaloid production in cultured CATHARANTHUS ROSEUS cells, 6 cell lines producing alkaloid in excess of 300 mg/l were selected from more than 2 × 10 5 individual colonies and their alkaloid production was monitored over a period of 8 years. Rapid loss of productivity invariably occurred during the first few months of cultivation, and spontaneous recovery of the initial production rates was never observed. Production of the indole alkaloid precursor, secologanin, followed the same pattern. Recovery of high alkaloid yielding strains was, however, possible at any time by repetition of the clonal selection procedure, but these strains were again instable. Clonal selection of high yielding plant cell strains apparently favours an inherent instability.
195 citations
TL;DR: Hypericin from HYPERICUM PERFORATUM was found to inhibit In VITRO type A and B monoamine oxidase (MAO's) prepared by treating rat brain mitochondria with selective inhibitors.
Abstract: Hypericin from HYPERICUM PERFORATUM was found to inhibit IN VITRO type A and B monoamine oxidase (MAO's) prepared by treating rat brain mitochondria with selective inhibitors. The inhibition of type A MAO by hypericin was higher than that of type B MAO. The inhibition was almost irreversible for both MAO types.
189 citations
TL;DR: The antihepatatoxic effects of flavonolignans and related constituents from SILYBUM MARIANUM were examined using carbon tetrachloride- and galactosamine-induced cytotoxicity in primary cultured rat hepatocytes as model systems and remarkable inhibitory actions were observed.
Abstract: The antihepatatoxic effects of flavonolignans and related constituents from SILYBUM MARIANUM were examined using carbon tetrachloride- and galactosamine-induced cytotoxicity in primary cultured rat hepatocytes as model systems. Remarkable inhibitory actions were observed with silandrin, 3-deoxysilychristin, silybin and silymonin in carbon tetrachloride-treated cultures, and silydianin and silymonin were effective in preventing galactosamine-produced cell lesions. Possible structure-activity relationships are discussed.
132 citations
TL;DR: Panax ginseng extract is capable of enhancing antibody plaque forming cell response and circulating antibody titre against sheep erythrocytes, cell mediated immunity against Semliki forest virus antigen, and natural killer cell activity in mice.
Abstract: Panax ginseng extract is capable of enhancing antibody plaque forming cell response and circulating antibody titre against sheep erythrocytes, cell mediated immunity against Semliki forest virus antigen, and natural killer cell activity in mice. It also enhanced production of interferon of both the pH stable and labile types induced by an interferon inducer of fungal origin.
109 citations
TL;DR: Some olefinic isobutylamides have been shown to possess considerable insecticidal activity and to be effective as molluscicides and cercaricides and thus are of potential use against bilharzia.
Abstract: The alkamides comprise a group of about 70 biogenetically closely related fatty acid amides with characteristic olefinic and acetylenic patterns. Purely olef inic derivatives have been found, so far, only in the Piperaceae, Aristolochiaceae and Rutaceae, whereas the Asteraceae tribes Heliantheae and Anthemideae additionally contain a great number of different acetylenic amides. With regard to the restricted distribution of alkamides, their occurrence deserves systematic attention and may contribute to a more natural grouping of genera at least within the two latter tribes. Some olefinic isobutylamides have been shown to possess considerable insecticidal activity and to be effective as molluscicides and cercaricides and thus are of potential use against bilharzia. Furthermore, alkamides have been used medicinally since ancient times as sialogogues, antitussives and analgesics. More recently, some acetylenic derivatives have been shown to inhibit the RNA-synthesis in mice-ascites-tumour tests. This review highlights the present state of knowledge on the structural relationships, distribution and biological activities of the alkamides.
106 citations
TL;DR: An aqueous methanol/water extract of the Oriental crude drug “ninjin” (ginseng), PANAX GINSENG roots from Korea, showed a remarkable hypoglycaemic activity on administration to mice.
Abstract: An aqueous methanol/water extract of the Oriental crude drug “ninjin” (ginseng), PANAX GINSENG roots from Korea, showed a remarkable hypoglycaemic activity on administration to mice. Fractionation of the extract, along with the pharmacological assays, led to isolation of five glycans, panaxans A, B, C, D and E. These constituents exhibited significant hypoglycaemic actions in normal and alloxan-induced hyperglycaemic mice.
98 citations
TL;DR: Structural-activity relationship suggests that the methylenedioxy group of the dibenzocyclooctane skeleton may play an important role in antihepatotoxic activity.
Abstract: The antihepatotoxic effects of twenty-three lignans, twenty-two from the fruits of SCHIZANDRA CHINENSIS and one from the fruits of KADSURA JAPONICA, were investigated utilizing carbon tetrachloride (CCl 4 )- and galactosamine (GalN)-induced cytotoxicity in primary cultured rat hepatocytes as model systems. Prominent protective actions were found with wuweizisu C and schisantherin D in CCl 4 -treated cultures, and deoxygomisin A, gomisin N, wuweizisu C, gomisin C and schisantherin D were effective in preventing GalN-induced cell damage. Structure-activity relationship suggests that the methylenedioxy group of the dibenzocyclooctane skeleton may play an important role in antihepatotoxic activity.
93 citations
TL;DR: The isolated ketosteroid showed a strong thyroid stimulatory action when administered to albino rats and brought about an increase in iodine-uptake by thyroid and enhanced activities of thyroid peroxidase and protease.
Abstract: A ketosteroid has been isolated from the oleo-resin of COMMIPHORA MUKUL and its structure (4,17(20)trans pregnandiene 3,16-dione; Z-guggulsterone) established from its physico-chemical properties, specially UV, IR, NMR and mass-spectra. The isolated ketosteroid showed a strong thyroid stimulatory action when administered to albino rats. Its administration (1 mg/100 g body weight) brought about an increase in iodine-uptake by thyroid and enhanced activities of thyroid peroxidase and protease as well as oxygen consumption by isolated slices of liver and biceps muscle.
85 citations
TL;DR: A new depside of D-(+)-beta-(3,4-dihydroxyphenyl)-lactic acid and 2-(3-4- dihydroxyyphenylethenol)-caffeic acid, named salvianolic acid A, was isolated from the dried roots of SALVIA MILTIORRHIZA Bunge.
Abstract: A new depside of D-(+)-beta-(3,4-dihydroxyphenyl)-lactic acid and 2-(3,4-dihydroxyphenylethenyl)-caffeic acid, named salvianolic acid A, was isolated from the dried roots of SALVIA MILTIORRHIZA Bunge. Its chemical structure was defined by spectral analysis and chemical degradation.
81 citations
TL;DR: Observations indicate that R A biosynthesis in ANCHUSA OFFICINALIS cultures is initiated after the decline of primary metabolism.
Abstract: The kinetics of growth, rosmarinic acid (RA) accumulation, major nutrient uptake and respiration rate of ANCHUSA OFFICINALIS cell suspension cultures have been investigated. The biosynthesis of RA is restricted to the linear phase of the growth cycle, resulting in a marked increase in RA accumulation from 1% to 6% of dry weight. The onset of RA synthesis coincided with the almost complete depletion of phosphate and nitrate from the medium and also with a striking drop in respiration rate of the cultured cells. Linear phase cells also showed the highest rate of incorporation of exogeneously supplied tyrosine (>30%) and phenylalanine (>20%) into the caffeoyl ester. These observations indicate that R A biosynthesis in ANCHUSA OFFICINALIS cultures is initiated after the decline of primary metabolism.
TL;DR: In ulcer healing tests, nimbidin significantly enhanced the healing process in acetic acid induced chronic gastric lesions in albino rats and dogs.
Abstract: Nimbidin, an ester of terpenic origin, which forms the major bitter principle isolated from the oil of seed scernels of AZADIRACHTA INDICA (Meliaceae) was found to possess significant anti-ulcer potential in various experimental models Anti-ulcer studies (preventive tests) revealed very significant protective effect of the test drug in doses of 20 to 40 mg/kg (po) in acetylsalicylic acid, stress, serotonin and indomethacin induced gastric lesions in rats The test drug also afforded remarkable protection in both types of chemically induced duodenal lesions in rodents In ulcer healing tests, nimbidin significantly enhanced the healing process in acetic acid induced chronic gastric lesions in albino rats and dogs
TL;DR: Results indicate that both activities are caused by different polysaccharide molecules and that the mitogenic activity is due to a minor polysacchide or other component rather than to the majorpolysaccharides.
Abstract: Water-soluble crude polysaccharide (AR-1) prepared from the root of ANGELICA ACUTILOBA Kitagawa (Japanese name = Yamato Tohki) was fractionated into three polysaccharide fractions, AR-2, AR-3 and AR-4 by the addition of cetyltrimethylammonium bromide. The major polysaccharide fraction, AR-2, consisted of a pectic acid-like molecule, and all fractions contained arabinose, galactose and glucose as the major neutral sugars. AR-4 showed the highest anti-complementary activity and interferon inducing activity, but mitogenic activity was shown only in the AR-1. When AR-4 was further fractionated by anion-exchange chromatography, the anti-complementary and interferon inducing activities were observed in the different polysaccharide subfractions. These results indicate that both activities are caused by different polysaccharide molecules and that the mitogenic activity is due to a minor polysaccharide or other component rather than to the major polysaccharides.
TL;DR: Preliminary structure activity relationship studies have shown the 3-methoxyfunction of the flavones to be essential for the observed antiviral effects.
Abstract: An investigation of the constituents responsible for the pronounced antiviral activity observed for extracts of EUPHORBIA GRANTII Oliv. stems has afforded four related 3-methoxyflavones exhibiting remarkable activities against picornaviruses and vesicular stomatitis virus. All compounds were found to be derivatives of 3-methylquercetin. The concentration of 3-methylquercetin (3-MQ) and 3,3'-dimethyl-quercetin (3,3'-DMQ) inhibiting 90 % of polio type 1 and coxsackie B4 viruses in tissue culture was about 0.01 microg/ml, whereas the 50 % cytotoxic concentration was 40 microg/ml. When administered intraperitoneally, 3-MQ protected mice from viremia and lethal infections from coxsac kie B4 virus at a daily dose of 20 mg/kg for a period of nine days. Biochemical studies on the mechanism of action of 3-MQ or 3,3'-DMQ on poliovirus replication suggested that these 3-methoxyflavones are able to protect the host cells from a viral induced shutdown of the cellular protein synthesis. Preliminary structure activity relationship studies have shown the 3-methoxyfunction of the flavones to be essential for the observed antiviral effects.
TL;DR: The intracellular localization and secretion process of naphthoquinone pigments (shikonin derivatives) in cell cultures of LITHOSPERMUM ERYTHRORHIZON were investigated chiefly by electron microscopy and suggested that the pigments accumulate in "secretion vesicles" which originate from electron dense, spherical swellings formed in highly elongated, rough endoplasmic reticula.
Abstract: The intracellular localization and secretion process of naphthoquinone pigments (shikonin derivatives) in cell cultures of LITHOSPERMUM ERYTHRORHIZON were investigated chiefly by electron microscopy. The results have suggested that the pigments accumulate in "secretion vesicles" which originate from electron dense, spherical swellings formed in highly elongated, rough endoplasmic reticula. Most of these vesicles appeared to fuse with the plasma membrane to secrete the contents consisting mainly of shikonin pigments, lipids, and proteins to the outside of the cell wall.
TL;DR: Intracellular ajmalicine and serpentine levels increased with sucrose concentration, whereas intracellular tryptamine (nitrogen precursor) levels were unaffected and the role of sucrose in the alkaloid pathway is discussed.
Abstract: The fates of major nutritional elements and the synthesis of tryptophan, tryptamine and 2 alkaloid markers in C. ROSEUS cells, cultivated in media containing 20 and 60 g/l of sucrose, were studied. Sucrose effects were greatest, with these parameters, during the stationary growth phase. Intracellular ajmalicine and serpentine levels increased with sucrose concentration, whereas intracellular tryptamine (nitrogen precursor) levels were unaffected. The role of sucrose in the alkaloid pathway is discussed.
TL;DR: The elicitors of acridone epoxide accumulation did not effect an increase of rutacridone in RUTA cultures and chitosan and alginate scarcely had an effect, arachidonic acid and elaidic acid were ineffective.
Abstract: Light and dark grown suspension cultures of RUTA GRAVEOLENS produced small amounts (1-50 microg/g dry weight) of the antimicrobial alkaloids rutacridone epoxide and hydroxyrutacridone epoxide. Acrid-one epoxide accumulation could be increased up to a 100 fold within 72 h by elicitation through addition of a suspension of either living free or immobilized yeasts, of dead RHODOTORULA RUBRA cells or crude cell wall fraction. Chitosan and alginate, exhibiting elicitor properties in other systems, scarcely had an effect, arachidonic acid and elaidic acid were ineffective. The elicitors of acridone epoxide accumulation did not effect an increase of rutacridone in RUTA cultures.
TL;DR: It has been established that the highest yield of ginsenosides is found in PANAX GINSENG C. A. Meyer and therefore the best time for harvesting the roots is at the end of the summer of the 5th year.
Abstract: The roots of PANAX GINSENG C. A. Meyer contain a relatively high percentage of ginsenosides from their first year of life onwards. Since the major development of weight of roots occurs between the 4th and 5th year of life, it has been established that the highest yield of ginsenosides and therefore the best time for harvesting the roots is at the end of the summer of the 5th year.
TL;DR: Diospyrin, a bis-naphthoquinone derivative, has been identified as a biologically active principle present in the bark extract of DIOSPYROS MONTANA Roxb.
Abstract: Diospyrin, a bis-naphthoquinone derivative, has been identified as a biologically active principle present in the bark extract of DIOSPYROS MONTANA Roxb. which inhibited the IN VIVO growth of EHRLICH ASCITES CARCINOMA (E.A.C.), in Swiss A mice. A series of IN VITRO and IN VIVO investigations have been carried out to confirm this observation.
TL;DR: Spectroscopic and degradative studies demonstrated that panaxan A is mainly composed of α - 1 →; 6 linked D-glucopyranose residues having branching at the C-3 position, the ratio of terminals, branching positions and intermediate units being 1:1:2.
Abstract: A hypoglycaemic constituent, panaxan A, isolated from the roots of PANAX GINSENG, was revealed to be a glycan with molecular weight of ca. 14000. Spectroscopic and degradative studies demonstrated that panaxan A is mainly composed of α - 1 →; 6 linked D-glucopyranose residues having branching at the C-3 position, the ratio of terminals, branching positions and intermediate units being ca. 1:1:2.
TL;DR: In this article, it was shown that chamomile allergy is due to anthecotulid a linear sesquiterpene lactone which is detectable in this chemical strain at variable but low levels.
Abstract: A bibliographic review reveals that about 50 reports refer to allergic reactions following “chamomile”. However, only in five papers, the botanical identification of the material allowed to establish a correlation between the observed allergic lesions and the suspicious plant species ( CHAMOMILLA RECUTITA). In the majority of the other instances effects were caused by species of the genus ANTHEMIS, frequently called “chamomile” as well. Experimental studies in guinea pigs using a rigorous sensitizing technique proved CH. RECUTITA (German chamomile) as well as KAMILLOSAN®, a total extract from its bisabololtype, to possess a low sensitizing capacity. Under identical test conditions the bisabolol oxide B-chemotype of CH. RECUTITA has an evident moderate allergenic activity. Evidence was given that chamomile allergy is due to anthecotulid a linear sesquiterpene lactone which is detectable in this chemical strain at variable but low levels. Negative test reactions were ascertained with further isolated compounds from CH. RECUTITA and various sesquiterpene lactones from Compositae using sensitized guinea pigs treated with KAMILLOSAN®. Therefore, chamomile for pharmaceutical and cosmetic purposes should be free of the sensitizing sesquiterpene lactone. Anthecotulid previously isolated from ANTHEMIS COTULA (Dog fennel, Stinking mayweed) at concentrations up to 7.3%, proved to be the reason of commonly observed primary irritant contact dermatitis specific of this species. Its low yield in German chamomile flowers of bisabolol oxide B-chemotype does not induce primary irritations. Specific hypersensitivity might rarely be induced by chamomile of bisabolol oxide B-type and the other known chemotypes in particular.
TL;DR: From rhizomes of Hemsleya macrosperma, three new saponins of oleanolic acid named hemslosides-Ma1, -Ma2 and -Ma3 were isolated along with dihydrocucurbitacin F, its 25-O-acetate and β-glucosyl oleanolate and their structures were elucidated.
Abstract: From rhizomes of Hemsleya macrosperma, three new saponins of oleanolic acid named hemslosides-Ma1, -Ma2 and -Ma3 were isolated along with dihydrocucurbitacin F, its 25-O-acetate and β-glucosyl oleanolate and their structures were elucidated From rhizomes of H chinensis, dihydrocucurbitacin F, its 25-O-acetate, β-glucosyl oleanolate, hemslosides-Ma1 and -Ma3 and chikusetsusaponin-IVa (a saponin from Panax japonicus and other Panax spp) were also isolated The close structural relationship of saponins of these planiste those of Panax japonicus (Araliaceae) is noted
TL;DR: Lupanine is more efficient than sparteine for antagonizing secondary reflex hypertension in carotid occlusion and hypotension resulting from the stimulation of the pneumogastric nerve in both the cat and the dog.
Abstract: The pharmacological properties of lupanine (ketonic derivative of sparteine) isolated from seeds of LUPINUS ALBUS, in comparison with sparteine were investigated. Ganglioplegic activities and affinity for cholinergic receptors were studied. Lupanine is more efficient than sparteine for antagonizing secondary reflex hypertension in carotid occlusion and hypotension resulting from the stimulation of the pneumogastric nerve in both the cat and the dog. Furthermore, lupanine is much less toxic in one single injection in both the mouse and the guinea-pig. The two substances have an identical inhibitory action on nicotinic type hypertension produced by injection of acetylcholine (500 μg/ kg i.v.) in the atropine-treated dog. The IN VITRO binding study confirms the selectivity on nicotinic sites with similar affinities for the two drugs. Differences in the bio-availability and the pharmacokinetics of the two alkaloids are presumed. Lupanine may diffuse and disappear more rapidly in ganglia than sparteine.
TL;DR: A comparison of the anti-inflammatory properties showed that 3β-hydroxy-2,3-dihydro-withanolide F is approximately 5 times more active than phenylbutazone and equally active to that of hydrocortisone on weight basis.
Abstract: Anti-inflammatory activity of 3β-hydroxy-2,3-dihydro-withanolide F has been assessed and it was found to possess marked effects in sub-acute inflammation. A comparison of the anti-inflammatory properties showed that it is approximately 5 times more active than phenylbutazone and equally active to that of hydrocortisone on weight basis. The withanolide did not exhibit any effect on CNS.
TL;DR: It is concluded that the powders of E. PROSTRATA and F. PARVIFLORA plants produce significant hypoglycaemic effects in the normal rabbits only and act probably by initiating the release of insulin from the pancreatic beta cells of normal rabbits.
Abstract: Blood glucose levels of the normal and alloxan-diabetic male albino rabbits were determined after oral administration of various doses of the powdered plants of EUPHORBIA PROSTRATA, Lit. (Euphorbiaceae) and FUMARIA PARVIFLORA Lam. (Fumariaceae). From the data obtained, it is concluded that the powders of E. PROSTRATA and F. PARVIFLORA plants produce significant hypoglycaemic effects in the normal rabbits only. The methanol extract of E. PROSTRATA also decreased the blood glucose of normal rabbits while that of F. PARVIFLORA did not produce this effect. In the alloxan-treated rabbits, these plants do not lower the blood glucose levels. Moreover, acute toxicity studies and records of behavioural patterns carried out in rabbits and rats, respectively showed no adverse effects in the dosages tested. It is conceivable that both plants contain some hypoglycaemic principles which act probably by initiating the release of insulin from the pancreatic beta cells of normal rabbits.
TL;DR: The extract showed anticonvulsant action on pentylenetetrazole induced seizures, increasing both its onset time and survival period, and reduced the spontaneous motor activity and the sleeping time induced by pentobarbital sodium in mice.
Abstract: Dry extract obtained from leaves of PASSIFLORA ALATA yielded 0.217 mg% of harman-like alkaloids and 44.8 mg% of flavonoids. Intraperitoneal administration (i. p.) of 75 and 150 mg/kg of this extract reduced the spontaneous motor activity and prolonged the sleeping time induced by pentobarbital sodium in mice. The extract showed anticonvulsant action on pentylenetetrazole induced seizures, increasing both its onset time and survival period. All animals treated previously with 75 mg/kg of extract died after clonic and tonic convulsions, while 16.7% of the group treated with 150 mg/kg survived. The DL50 value of the extract was estimated as 456 (424-491) mg/kg i. p. in mice.
TL;DR: Both the antihepatotoxic activity and the dimethylesculetin content in this plant were found to vary markedly with the date of harvesting, which was assumed to be a reason for remarkable variations of the anti hepatotoxicity activity in commercially available preparations of this crude drug.
Abstract: Since an extract of the crude drug "inchinko", the buds of ARTEMISIA CAPILLARIS, showed significant antihepatotoxic activity by means of carbon tetrachloride-induced liver lesion IN VIVO and IN VITRO, the extract was fractionated by monitoring the activity to yield a number of flavonoids and a coumarin (6,7-dimethylesculetin). Antihepatotoxic effects of these constituents were determined by IN VITRO assay methods using carbon tetrachloride- and galactosamine-induced cytotoxicity in primary cultured rat hepatocytes. Some analogues of dimethylesculetin were also assayed for liver-protective activity. Both the antihepatotoxic activity and the dimethylesculetin content in this plant were found to vary markedly with the date of harvesting, which was assumed to be a reason for remarkable variations of the antihepatotoxic activity in commercially available preparations of this crude drug.
TL;DR: Two new sesquiterpenoid aromatic esters, armillarin and armillaridin, have been isolated from the artificially cultured mycelium of ARMILLARIA MELLEA (Vahl. ex Fr.) Quel.
Abstract: Two new sesquiterpenoid aromatic esters, armillarin and armillaridin, have been isolated from the artificially cultured mycelium of ARMILLARIA MELLEA (Vahl. ex Fr.) Quel. (Tricholometaceae). On the basis of spectral (UV, IR, 1 H-NMR, 13 C-NMR and MS) analysis and chemical degradation as well as X-ray crystallography, their structures were identified as ( 1) and ( 2), respectively.
TL;DR: A method for the isolation and preparation of 12-deoxyphorbol from Euphorbium resin was established to provide substantial amounts of 1-esters for bioassays and both ester types were tested for their irritant activities.
Abstract: A method for the isolation and preparation of 12-deoxyphorbol ( 1) from Euphorbium resin ( EUPHORBIA RESINIFERA Berg) was established to provide substantial amounts of 1-esters for bioassays. Acylation of 1 yielded 12-deoxyphorbol-13,20-diesters ( 2, esters with acids CH (3)(CH (2)) (n)COOH, n = 0, 4, 8, 12, 16, 20; and with benzoic, oleic, elaidic and linoleic acid). Upon mild transesterification the 13,20-diesters 2 yielded the 13-monoesters 3. Both ester types were tested for their irritant activities, the 13-monoesters were also assayed for their tumor-promoting activity. A dependance of both of these activities on the chain length of the acyl residues is noticeable. For both probably a broad maximum exists around the tetradecanoate.