Constituents of Pterocarpus marsupium: an ayurvedic crude drug.

Five new flavonoid C-glucosides, 6-hydroxy-2-(4-hydroxybenzyl)-benzofuran-7-C-beta-d-glucopyranoside (1), 3-(alpha-methoxy-4-hydroxybenzylidene)-6-hydroxybenzo-2(3H)-furanone-7-C-beta-d-glucopyranoside (2), 2-hydroxy-2-p-hydroxybenzyl-3(2H)-6-hydroxybenzofuranone-7-C-beta-d-glucopyranoside (4), 8-(C-beta-d-glucopyranosyl)-7,3',4'-trihydroxyflavone (5) and 1,2-bis(2,4-dihydroxy,3-C-glucopyranosyl)-ethanedione (6) and two known compounds C-beta-d-glucopyranosyl-2,6-dihydroxyl benzene (7) and sesquiterpene (8), were isolated from an aqueous extract of the heartwood of Pterocarpus marsupium. The structure has been established using spectroscopic data.

Protective effect of acorus calamus against acrylamide induced neurotoxicity.

Exposure of rats to acrylamide (ACR) caused hind limb paralysis in 58% of the animals on day 10 and decreased behavioural parameters, namely distance travelled, ambulatory time, stereotypic time and basal stereotypic movements compared with the control group. These rats also had a decrease in the reduced glutathione (GSH) content and glutathione-S-transferase (GST) activity in the corpus striatum and an increase in striatal dopamine receptors, as evident by an increase in the binding of 3H-spiperone to striatal membranes. Treatment with the ethanol:water (1:1) extract of the rhizomes of Acorus calamus (AC-002) increased the GSH content and GST activity in the corpus striatum while insignificant changes were observed in other parameters. Rats treated with ACR and AC-002 in combination had a lower incidence of paralysis (18%) compared with those treated with ACR alone on day 10 of the experiment. The rats also showed a partial recovery in other behavioural parameters. The levels of GSH content and GST activity increased in the corpus striatum, while the dopamine receptors decreased compared with the ACR treated rats. The results suggest that the neurobehavioural changes produced by ACR may be prevented following treatment with Acorus calamus rhizomes.

Hepatoprotective activity of indigtone--a bioactive fraction from Indigofera tinctoria Linn.

A bioactive fraction, indigtone (FA), obtained by fractionation of a petroleum ether extract of the aerial parts of Indigofera tinctoria, showed significant dose related hepatoprotective activity against CCl(4) induced liver injury in rats and mice. Hexobarbitone induced 'sleeptime', zoxazolamine induced 'paralysis time', levels of transaminases, bilirubin and total protein in serum were employed as indices of liver injury. Pre and post treatment with FA significantly reversed the majority of the parameters altered by the hepatotoxin. This indicated the preventive and restorative effect of FA in the process of CCl(4) induced liver damage. The fraction possessed a high therapeutic ratio, as no mortality was observed up to a dose of 2 g/kg p.o. in mice.

Antiinflammatory activity and chemical composition of extracts of Verbena officinalis.

In an attempt to locate the biologically active fraction(s) of the plant Verbena officinalis Linn. (Verbenaceae), a preliminary screening of successive petroleum ether, chloroform and methanol extracts of aerial parts for antiinflammatory activity using carrageenan paw oedema model was carried out. All three extracts were found to exhibit antiinflammatory activity with the chloroform extract being the most active. Chemical investigations of petroleum ether and chloroform extracts led to the isolation of beta-sitosterol, ursolic acid, oleanolic acid, 3-epiursolic acid, 3-epioleanolic acid, and minor triterpenoids of derivatives of ursolic acid and oleanolic acids. Chromatographic purification of the methanol extract yielded two iridoid glucosides, verbenalin and hastatoside, a phenylpropanoid glycoside, verbascoside and beta-sitosterol-D-glucoside.

Anti-inflammatory and anti-arthritic activities of silymarin acting through inhibition of 5-lipoxygenase.

Silymarin, a mixture of flavonolignans, comprised mainly of three isomers, silybin, silydianin and silychristin isolated from the fruits of Silybum marianum, is currently in therapeutic use as a hepatoprotective agent. Silymarin on evaluation exhibited significant antiinflammatory and antiarthritic activities in the papaya latex induced model of inflammation and mycobacterial adjuvant induced arthritis in rats. Results of the study indicate its action through inhibition of 5-lipoxygenase for antiinflammatory and antiarthritic activities.

Antihepatotoxic activity of Swertia chirata on paracetamol and galactosamine induced hepatotoxicity in rats.

The extracts of Swertia chirata were evaluated for antihepatotoxic activity using paracetamol and galactosamine models. The methanol extract of the whole plant was found active at a dose of 100 mg/kg i.p. On fractionating this extract into chloroform soluble and butanol soluble fractions, the activity was retained in the chloroform soluble fraction which was most active at a dose level of 25 mg/kg i.p. with overall protection of 81% and 78% against paracetamol and galactosamine, respectively. The butanol soluble fraction, rich in bitter secoiridoids, was devoid of significant activity. The protective effect observed against these two hepatotoxins which are different in their mechanisms of inducing hepatotoxicity, suggests broader and non-specific protection of the liver against these two toxins by non-bitter components of Swertia chirata.

Antihepatotoxic activity of Swertia chirata on carbon tetrachloride induced hepatotoxicity in rats.

The methanol extract of Swertia chirata was evaluated for antihepatotoxic activity against carbon tetrachloride induced liver toxicity in experimental rats. The extract was found to be active and on fractionation into butanol soluble and chloroform soluble fractions, the activity was traced and found more profound in the chloroform soluble fraction. The butanol soluble bitter rich fraction showed marginal activity. The results based on biochemical estimations have been expressed statistically and are additionally supported by histopathological examination of the liver of experimental rats and pentobarbitone induced sleep time studies in mice.

Hepatoprotective activity of Apium graveolens and Hygrophila auriculata against paracetamol and thioacetamide intoxication in rats.

Seeds of Apium graveolens L. (Apiaceae) and Hygrophila auriculata (K. Schum.) Heine (Syn. Astercantha auriculata Nees, Acanthaceae) are used in Indian systems of medicine for the treatment of liver ailments. The antihepatotoxic effect of methanolic extracts of the seeds of these two plants was studied on rat liver damage induced by a single dose of paracetamol (3 g/kg p.o.) or thioacetamide (100 mg/kg, s.c.) by monitoring several liver function tests, viz. serum transaminases (SGOT and SGPT), alkaline phosphatase, sorbitol dehydrogenase, glutamate dehydrogenase and bilirubin in serum. Furthermore, hepatic tissues were processed for assay of triglycerides and histopathological alterations simultaneously. A significant hepatoprotective activity of the methanolic extract of the seeds of both the plants was reported.

Chemical investigation and anti-inflammatory activity of Vitex negundo seeds.

The CHCl3 extract of the defatted seeds of Vitex negundo exhibited anti-inflammatory activity and yielded four triterpenoids: 3 beta-acetoxyolean-12-en-27-oic acid [1], 2 alpha, 3 alpha-dihydroxyoleana-5,12-dien-28-oic acid [2], 2 beta,3 alpha-diacetoxyoleana-5,12-dien-28-oic acid [3], and 2 alpha,3 beta-diacetoxy-18-hydroxyoleana-5,12-dien-28-oic acid [5]. This is the first report of the isolation of compounds 2, 3, and 5 from a natural source.

Hepatoprotective activity of andrographolide against galactosamine & paracetamol intoxication in rats.

Hepatoprotective effect of andrographolide (the major active diterpenoid lactone of the plant Andrographis paniculata) was studied on acute hepatitis induced in rats by single dose of galactosamine (800 mg/kg, ip)/paracetamol (3g/kg, po). Hepatoprotective activity was monitored by estimating the serum transaminases (GOT and GPT), alkaline phosphatase and bilirubin in serum, hepatic triglycerides, and by histopathological changes in the livers of experimental rats. Pre-treatment and/or post-treatment of rats at different time intervals with different doses of andrographolide in the two experimental models of hepatotoxicity showed that treatment of rats with 400 mg/kg, ip or 800 mg/kg, po, 48, 24 and 2 h before galactosamine administration or with 200 mg/kg, ip, 1, 4 and 7 h after paracetamol challenge leads to complete normalisation of toxin-induced increase in the levels of all the five biochemical parameters, and significantly ameliorates toxin-induced histopathological changes in the livers of experimental rats. The results confirmed the in vivo hepatoprotective effect of andrographolide against galactosamine or paracetamol-induced hepatotoxicity in rats. Since the protective effect of andrographolide was observed in two types of intoxication, which are very different in their primary mechanism of inducing hepatotoxicity, it is suggested that protective mechanisms of andrographolide which are not specific to galactosamine or paracetamol toxicity may be responsible for the hepatoprotective activity of the compound.

Hepatoprotective activity of andrographolide from Andrographis paniculata against carbontetrachloride.

Andrographolide, a diterpenoid lactone, was isolated (yield 0.78% w/w) from A. paniculata (whole plant). Its LD50 in male mice was 11.46 g/kg, ip. Antihepatotoxic activity of andrographolide (100 mg/kg, ip) was compared with 861.33 mg/kg, ip, of the methanolic extract (equivalent to 100 mg/kg of andrographolide) and 761.33 mg/kg ip, of the andrographolide-free methanolic extract (equivalent to 861.33 mg/kg of the methanolic extract) of the plant, using CCl4-intoxicated rats. Biochemical parameters like serum transaminases--GOT and GPT, serum alkaline phosphatase, serum bilirubin and hepatic triglycerides were estimated to assess the liver function. Overall inhibition of CCl4-induced increase in the five biochemical parameters was found to be 48.6 per cent (andrographolide), 32.0 per cent (methanolic extract) and 15.0 per cent (andrographolide-free methanolic extract). These biochemical observations were supplemented by histopathological examination of the liver slices. Further, andrographolide (100 mg/kg, ip) was found to normalize completely the CCl4-induced increase in the pentobarbitone induced sleep time of mice. The results suggest that andrographolide is the major active antihepatotoxic principle present in A. paniculata.

Growth inhibitory, insecticidal and antifeedant effects of some antileukemic and cytotoxic quassinoids on two species of agricultural pests.

Several quassinoids, obtained by isolation and derivatization from Simaba multiflora and Soulamea soulameoides, were evaluated for growth inhibitory and insecticidal effects against the tobacco budworm (Heliothis virescens) and for antifeedant effects against H. virescens and the fall armyworm (Spodoptera frugiperda). The relative activity of the quassinoids as insect growth inhibitors generally paralleled their known relative potency as antileukemic and cytotoxic agents.

Plant Anticancer Agents XXXIII. Constituents of Passerina vulgaris1.

Two lignans of known structure, (+)-syringaresinol, a cytotoxic agent, and (+)-nortrachelogenin, a compound with demonstrated antileukemic activity, were isolated from a biologically active extract of the stems of PASSERINA VULGARIS.

Plant anticancer agents XXIX. Cleomiscosin A from Simaba multiflora, Soulamea soulameoides, and Matayba arborescens.

Cleomiscosin A (1) has been isolated from Simaba multiflora and Soulamea soulameoides in the Simaroubaceae through bioactivity-directed fractionation and from Matayba arborescens in the Sapindaceae . The structure of cleomiscosin A (1) was established through spectroscopic studies and chemical reactions.

Plant anticancer agents XXVII: Antileukemic and cytotoxic constituents of Dirca occidentalis (Thymelaeaceae).

Two antileukemic daphnane esters, Pimelea factor P2 (I) and the new compound dircin (II), were isolated from the twigs and flowers of Dirca occidentalis A. Gray (Thymelaeaceae). Three lignans, (-)-medioresinol (III), (+)-syringaresinol (IV), and (-)-lariciresinol (V), as well as the coumarin daphnoretin (VI), were found to be additional cytotoxic constitents of this taxon.

Plant anticancer agents XXV. Constituents of Soulamea soulameoides.

Three simaroubolides, glaucarubolone (1), holacanthone (2), and isobrucein A (3) were found to be responsible for the cytotoxic and antileukemic activities observed for extracts of the wood stem, stem bark, and twigs of Soulamea soulameoides. Other cytotoxic constituents isolated include a coumarinolignan cleomiscosin A (4) and the hydroxy canthin-6-one derivative 5. Picrasin B (6) was also obtained, but was not active.

Plant anticancer agents. XXVI. Constituents of Peddiea fischeri.

The in vitro P-388 lymphocytic leukemia activity of the chloroform-soluble fraction of the roots of Peddiea fischeri (Thymelaceaceae) was found to be due principally to the quinone 2,6-dimethoxybenzoquinone (2,6-DMBQ), and to a lesser extent the two coumarins daphnoretin and umbelliferone. This is the first report of the occurrence of 2,6-DMBQ in the family Thymelaeaceae. The occurrence of 2,6-DMBQ in higher plants is reviewed.