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Various forms of cancer are rising all over the world, requiring newer therapy. The quest of anticancer drugs both from natural and synthetic sources is the demand of time. In this study, fourteen extracts of different parts of eleven Bangladeshi medicinal plants which have been traditionally used for the treatment of different types of carcinoma, tumor, leprosy, and diseases associated with cancer were evaluated for their cytotoxicity for the first time. Extraction was conceded using methanol. Phytochemical groups like reducing sugars, tannins, saponins, steroids, gums, flavonoids, and alkaloids were tested using standard chromogenic reagents. Plants were evaluated for cytotoxicity by brine shrimp lethality bioassay using Artemia salina comparing with standard anticancer drug vincristine sulphate. All the extracts showed potent to moderate cytotoxicity ranging from LC50 2 to 115 µg/mL. The highest toxicity was shown by Hygrophila spinosa seeds (LC50 = 2.93 µg/mL) and the lowest by Litsea glutinosa leaves (LC50 = 114.71 µg/mL) in comparison with standard vincristine sulphate (LC50 = 2.04 µg/mL). Among the plants, the plants traditionally used in different cancer and microbial treatments showed highest cytotoxicity. The results support their ethnomedicinal uses and require advanced investigation to elucidate responsible compounds as well as their mode of action.

The crude ethanolic extract of leaves, stem-bark and roots of J. flammea were tested for their cytotoxic effect against two mammalian cell lines (HeLa and RAW 264.7) and four bacterial species (Staphylococcus aureus, Bacillus subtilis, Escherichia coli and Pseudomonas aeruginosa). When tested at the concentration of 100 microg/mL, the root extract showed the highest cytotoxic activity against mammalian cells followed by the stem-bark extract while the leaves extract did not show significant activity. No antibacterial activity was detected for all extracts when tested up to 500 microg/disc in the disc diffusion assay. The cytotoxic root extract was subjected to fractionation using solvents of ascending polarity: petroleum ether, chloroform, ethylacetate, butanol and water. The water fraction which showed cytotoxic activity was further subjected to routine bioassay-guided fraction to lead to the isolation of sakurasosaponin as the active principle. The recorded IC50 value for sakurasosaponin was 11.3 +/- 1.52 and 3.8 +/- 0.25 microM (n=3) against HeLa and RAW 264.7 respectively. The identification of sakurasosaponin was based on analysis of spectroscopic data.

We studied the antihypertension action of Herniaria glabra saponins and compared the effect with that of furosemide. Spontaneously hypertensive rats were treated with H. glabra saponins at a dosage of 200mg/Kg of body weight. Treatment led to progressive decline in both systolic and diastolic blood pressures. After one month of therapy, pressures were: 141,60+/-7,51 / 90,40+/-5.46mmHg versus 187,60+/-5,94/119,10+/-7.79mmHg (p<0,001). We did not observe any change in heart rate. H. glabra saponins were able to lower blood pressure by a multifactorial mechanism.

We have reported that kalopanaxsaponin A (KPS-A) isolated from Kalopanax pictus have anti-rheumatoidal activity in the rat treated with Freunds complete adjuvant (FCA) reagent. In addition, it has been also reported that KPS-A is a potent antioxidant in the rheumatoidal rat. This research was undertaken to examine whether the saponins of KPS-A and -I could adjust the abnormal lipid metabolisms and hematological changes in immunological diseases. KPS-A significantly inhibited the increases in both triglycerides and total proteins in addition to the decrease in total cholesterol induced by FCA reagent treatment. KPS-A treatment decreased the number of leucocytes elevated by FCA reagent treatment. Excess dose of the methanol extract produced no severe toxicity on the body weight, wet organ weights and hepatic functions. Since LD50 value of K. pictus methanol extract was shown to be 4,033 mg/kg, it could be estimated to be a safe agent for anti-rheumatoidal herbal medicines.

In the present work a systematic study was initiated with crocine, ginsenoside and cannabinoid derivatives on multidrug resistant mouse lymphoma cells, viral tumor antigen expression and some human leukocyte functions. Among saffron derivatives, crocin and picrocrocin, triglucosyl and diglucosyl crocetin were ineffective on the reversal of multidrug resistance of lymphoma cells. Ginsenoside increased drug accumulation and tumor antigen expression at 2.0-20.0 micrograms/mL. Some cannabinoid derivatives such as cannabinol, cannabispirol and cannabidiol increased drug accumulation, while cannabidiolic acid, delta-9-THC and tetrahydro-cannabidiolic acid reduced drug accumulation of the human mdr1-gene transfected mouse lymphoma cells. The reversal of multidrug resistance is the result of the inhibition of the efflux pump function in the tumor cells. Crocetin esters were less potent than crocin itself in the inhibition of EBV early antigen expression. However crocin and diglucosylcrocetin inhibited early tumor antigen expression of adenovirus infected cells, but triglucosylcrocetin was less effective at 0.01-1.0 microgram/mL. The crocin had no antiviral effect [on HSV-2 infected vero cells] up to 25 micrograms/mL concentration. Ginsenosides had a moderate inhibitory effect except ginsenoside Rb1 (was the less effective) on the drug efflux pump. Among the cannabinoid derivatives the cannabinol and cannabispirol increased drug accumulation, while cannabidiolic acid and delta-8-THC, delta-9-THC and tetrahydro-cannabinol reduced drug accumulation in multidrug resistant mouse lymphoma cells. It is interesting that ginsenosides had a chemical structure-dependent immunomodulating effect by enhancing the activity of NK-cells and ADCC activities.

We have identified saponins in the root of Polygala senega L., a plant indigenous to the Canadian prairies, which display immunopotentiation activity to protein and viral antigens. By two-step extraction and hemolytic activity-guided fractionation by silica flush chromatography six saponin fractions were generated and their HPLC profiles determined. Two dominant fractions, designated as PS-1 and PS-2, were tested for adjuvant activity in mice immunized with ovalbumin, and hens immunized with rotavirus. The resulting adjuvant activity was compared with that of Quil A saponin. The P. senega saponins increased specific antibody levels to the antigens, in both mice and hens. In mice, there was a preferential increase of the IgG2a subclass, and upon in vitro secondary antigen stimulation, high IL-2 and IFN-gamma levels were observed in spleen cell cultures from P. senega saponins-immunized animals. The saponins were tested for their toxicity by lethality in mice and were found to be less toxic at the same dose than their counterpart Quil A. The results of this study indicated the potential of P. senega saponins as vaccine adjuvants to increase specific immune responses.

Chemical examination of the aerial parts of Dracaena draco has led to the isolation of a total of nine steroidal saponins, including five new ones. The structures of the new saponins were determined by spectral data and a few chemical transformations to be (23S,24S)-spirosta-5,25(27)-diene-1 beta,3 beta,23,24-tetrol 1-O-{O-(2,3,4-tri-O-acetyl-alpha-L-rhamnopyranosyl)-(1-->2)-alpha-L -arabinopyranosyl} 24-O-beta-D-fucopyranoside, (23S,24S)-spirosta-5,25(27)-diene-1 beta,3 beta, 23,24-tetrol 1-O-{O-alpha-L-rhamnopyranosyl-(1-->2)-alpha-L -arabinopyranoside}, (23S,24S)-spirosta-5,25(27)-diene-1 beta,3 beta,23,24-tetrol 1-O-{O-(4-O- acetyl-alpha-L-rhamnopyranosyl)-(1-->2)-alpha-L-arabinopyransoide} , (23S)-spirosta-5,25(27)-diene-1 beta,3 beta,23-triol 1-O-{O-alpha-L- rhamnopyranosyl)-(1-->2)-alpha-L-arabinopyranoside} and (23S,24S)-spirosta-5,25(27)-diene-1 beta,3 beta,23-triol 1-O-{O-(4-O-acetyl-alpha-L-rhamnopyranosyl)-(1-->2)-alpha-L- arabinopyranoside}. The isolated saponins were evaluated for their cytostatic activity on leukemia HL-60 cells.

Natural rubber (NR) has been used as a binding matrix for Calendula officinalis, where it is used as a vulcanizate. Various doses of the plant covering the range from 100 up to 200 parts per 100 of rubber (phr) were found suitable for processing conditions using conventional rubber mixing equipment. The release rate of saponin was extended to over 4 months. Incorporation of fillers, such as HAF and Hisil, in the compounded rubber decreased the release of saponin; especially in the first period of immersion. The amount of saponin released was affected by the environmental temperature and the type of fillers present in the formulations. The scanning electron micrographs illustrate the presence of a tortuous pass and pore structure that formed after soaking in water and leaching process occurred.

Tribulus terrestris L. is an annual plant which has been commonly used in folk medicine as diuretic and against colic pains, hypertension and hypercholesterolemia in Turkey. This study investigated the effects of liophilized saponin mixture of this plant on several smooth muscle preparations in vitro. The liophilized material was obtained from dried and powdered T. terrestris L. by specific extraction method for saponins. Median lethal dose (LD50) of saponin mixture on Swiss albino mice was calculated according to Litchfield-Wilcoxon method via i.p. route. LD50 and its 95% confidence limits were 813 and 739-894 mg.kg-1 respectively. Saponin mixture has caused a significant decrease on peristaltic movements of isolated sheep ureter and rabbit jejunum preparations in a dose-dependent manner (p < 0.05). However it has been observed no effect on isolated rabbit aorta and its contractile response to KCl or noradrenaline (p > 0.05). According to these results it has been suggested that T. terrestris L. or its saponin mixture may be useful on some smooth muscle spasms or colic pains.

The methanolic extract and 1-butanol-soluble fraction of American ginseng, the roots of Panax quinquefolium L., were found to exhibit a protective effect on liver injury induced by D-galactosamine and lipopolysaccharide. Five new dammarane-type triterpene oligoglycosides called quinquenosides I, II, III, IV, and V were isolated together with fourteen known dammarane-type triterpene oligoglycosides such as chikusetsusaponin IVa, pseudo-ginsenoside-RC1, malonyl-ginsenoside-Rb1, and notoginsenosides-A,-C, and -K from the 1-butanol-soluble fraction. From the ethyl acetate-soluble fraction, four known acetylenic compounds and 6'-O-acetyl ginsenoside-Rg1 were isolated. The structures of quinquenosides I, II, III, IV, and V were determined on the basis of chemical and physicochemical evidence as 3-O-[6-O-(E)-2-butenoyl-beta-D-glucopyranosyl(1-->2)-beta-D- glucopyranosyl]-20-O-(beta-D-glucopyranosyl) 20(S)-protopanaxadiol (quinquenoside I), 3-O-[6-O-(E)-2-octenoyl-beta-D- glucopyranosyl(1-->2)-beta-D-glucopyranosyl]-20-O-[beta-D-glucopyranosyl (1-->6)-beta-D-glucopyranosyl] 20(S)-protopanaxadiol (quinquenoside II), 3-O-[beta-D-glucopyranosyl (1-->2)-6-O-acetyl-beta-D-glucopyranosyl]-20-O-(beta-D-glucopyranosyl) 20(S)-protopanaxadiol (quinquenoside III), 3-O-[beta-D-glucopyranosyl(1-->2)-beta-D-glucopyranosyl]-20-O-beta-D- glucopyranosyl(1-->6)-beta-D-glucopyranosyl]-3 beta, 7 beta, 20(S)-trihydroxydammar-5,24-diene (quinquenoside IV), and 3-O-[beta-D-glucopyranosyl(1-->2)-beta-D-glucopyranosyl]-20-O-[alpha-D- glucopyranosyl(1-->4)-beta-D-glucopyranosyl(1-->6)-beta-D-glucopyranosyl ] 20(S)-protopanaxadiol (quinquenoside V).

An investigation of Serjania salzmanniana for biologically active substances has led to the isolation of two novel saponins, salzmannianoside A (3-O-[[beta-D- glucopyranosyl-(1-->4)]-[alpha-L-rhamnopyranosyl-(1-->2)]-alpha-L- arabinopyranosyl] gypsogenin) [3] and salzmannianoside B (3-O-[[beta-D-glucopyranosyl-(1-->4)]-[alpha-L- arabinopyranosyl-(1-->3)-alpha-L-rhamnopyranosyl-(1-->2)] -alpha-L-arabinopyranosyl] hederagenin) (4). Two known saponins, pulsatilla saponin D (3-O-[[beta-D- glucopyranosyl-(1-->4)]-[alpha-L-rhamnopyranosyl-(1-->2)]-alpha-L- arabinopyranosyl] hederagenin) (1) and 3-O-[[beta-D-glucopyranosyl-(1-->4)]-[alpha-L-rhamnopyranosyl-(1-->2)]-a lpha-L- arabinopyranosyl] oleanolic acid (2) were also isolated from this plant. The structures of 3 and 4 were elucidated by FABMS and 2D NMR techniques. All these four saponins were mollusicidal, causing 70-100% mortality at 10 ppm against Biomphalaria alexandrina, a vector of Schistosoma mansoni in the Nile Valley. The saponins also showed antifungal activity against Cryptococcus neoformans and Candida albicans at minimal inhibitory concentrations of 8 and 16 micrograms/mL, respectively.

Analgesic activities of Randia siamensis CRAIB (R. siamensis) extract and pseudoginsenoside-RP1, a constituent of the extract, were examined in the writhing test, hot plate test and Randall-Selitto test. Oral administration of R. siamensis extract dose-dependently decreased the number of writhings and stretchings induced by 0.6% acetic acid in the writhing test in mice. Moreover, in the Randall-Selitto test in rats, the extract raised the nociceptive threshold of the carrageenan-inflamed but not of non-inflamed paw. It did not affect the nociceptive response in the hot plate test in mice. The R. siamensis extract did not affect hexobarbital-induced sleep or spontaneous motor activity in mice, suggesting that it has no sedative effect. Pseudoginsenoside-RP1 produced similar effects to the R. siamensis extract, but its effective doses in the analgesic tests were lower than those with the extract. These results suggest that R. siamensis extract produces anti-nociceptive actions similar to those of a peripherally acting analgesic drug aspirin, and that pseudoginsenoside-RP1 may partly contribute, but is not the main contributor, to the antinociceptive action of the extract.

From the leaves of Acanthopanax hypoleucus Makino (Araliaceae), five triterpenoidal saponins, having oleanolic acid and hederagenin as sapogenins, were isolated. On the basis of chemical and spectral data, the structures of two new saponins, named hypoleucosides A (1), and B (5) were elucidated as follows: 1; 3-O-beta-D-glucopyranosyl 11 alpha-methoxy-oleanolic acid 28-O-beta-D-glucopyranosyl ester, 5; 3-O-beta-D-glucopyranosyl-(1----2)-alpha-L-arabinopyranosyl-(1---- 4)-beta-D-glucopyranosyl oleanolic acid 28-O-beta-D-glucopyranosyl-(1----6)-beta-D-glucopyranosyl ester.

The teratogen action of Boicil tablets was studied in two animal species, rats and mice, the prefertilization and implantation stages being the main interest. Three generations of animals were followed up. The active powder suspended in distilled water (0.1 ml/10 g for mice and 1 ml/100 g for rats) was administered per os in a single dose, prepared on spot and in two doses, 2 mg/kg body weight and 20 mg kg body weight, respectively. The administered doses were equivalent to the daily maximum therapeutic dose prescribed in humans (110 mg active principle). The first gestational day was determined differently in the two species. For estimating the effect on prefertilization, Boicil tablets was administered for 5 days before making and for its effects on the number of implantations during the first 3 gestational days. The two parameters under investigation were within normal limits and all newborn animals followed up for three generations did not present pathological microscopic and gross alterations or somatic malformations. It was concluded that Boicil tablets is not teratogenic.

The study of the chemical composition of Calendula arvensis var. eu arvensis Maire reveals the presence of saponins. These saponins confer a haemolytic property on the plant. In our work we have, first determined the saponin responsible for the haemolytic property; and then we have studied the impact of the saponins on the acute toxicity and the anti-inflammatory activity induced by carrhageenin oedema.

Calendulozide B--trioside of oleanolic acid, isolated from rhizomes of Calendula officinalis, Fam. Compositae, used perorally in doses of 5, 10, 20 and 50 mg/kg exerted an antiulcerous action in 3 experimental ulcer models of different genesis (caffein-arsenic, butadion and induced by ligation of pylorus) and also displayed a certain antiphlogistic and sedative action. It did not have any effect on the cardiovascular system, the tone of intestinal smooth muscles, diuretic renal function and electrolytes excretion with urine or on the biligenic function of the liver. The drug is devoid of locally irritation properties, manifests a relatively low hemolytic activity (15000 after Kofler) and an insignificant toxicity both with its one-time and chronic administration.

The pharmacological properties of seven pure saponins isolated from Panax ginseng C. A. Meyer were studied. 1. The ginseng saponins showed weak toxicities in mice. Especially, Rg1, Rf and Rb 1, which contained glucose as a sugar component, were weaker in their toxicities than the rest, which contained arabinose and/or rhamnose. It was also noted that the saponins containing protopanaxadiol as sapogenin were more toxic than those containing protopanaxatriol. 2. All the saponins diminished ACh-induced contraction of the isolated ileum of the guinea pig. On the other hand high concentrations of Rb 2 caused contraction of the ileum by itself. 3. All of the saponins induced a decrease in heart rate and showed biphasic actions on the blood pressure in rats, while they little affected respiration. They caused blood pressure fall preceded by slight rise. Among them, Rg 1 showed the most prominent action and it produced a blood pressure rise with doses of 30 to 100 mg/kg. The pressor as well as depressor action was not influenced by the pretreatment with any of atropine, diphenhydramine, phentolamine and propranolol. 4. Rg 1 and Re showed vasodilator action in dogs, the potencies of which were 1/20 and 1/50 of that of papaverine, respectively. Rc and Rb 2 showed very weak vasodilator actions but Rb 1 did not. 5. Among the 7 saponins, Rd, Re and Rb 2 showed more potent hemolytic actions than those of the rest and the potencies were proportional to their toxicities. 6. Whereas single administration of Rf, Re and Rd significantly suppressed the conditioned avoidance response, repeated administration of them caused facilitation of the response. On the other hand, Rb 2 always showed very weak suppressant action. 7. Rg 1, Rf, Re and Rd significantly suppressed the fighting of mice induced by foot shock, while Rb 1, Rb 2 and Re little affected the fighting. 8. All the saponins showed antifatigue action. They markedly increased the movement after compulsory gait and the action was consistent and independent of their action on the movement before compulsory gait. 9. The saponins showed moderate depressant actions on the EEG and the behavior in cats. They were qualitatively similar in their actions, although Rg 1, Re and Rb 2 were more potent than the rest. They also suppressed EEG arousal response induced by electrical stimulation of the mid brain in cats.

The pharmacokinetics of ginsenosides A1, A2, B2, and C were studied in rabbits and were best described with a one-component open model. Ginsenoside C (protopanaxadiol group ginseng saponin) showed a significantly longer half-life, higher plasma protein binding, and lower metabolic and renal clearance than ginsenosides A1, A2, and B2 (protopanaxatriol group ginseng saponins). All ginsenosides except ginsenoside A1 were slowly absorbed after intraperitoneal administration. Ginsenosides were not found in rabbit plasma or urine samples after oral administration. The observed differences in the pharmacokinetics of the ginsenosides may be ascribed to differences in protein binding. Ginsenoside C was more toxic than ginsenoside A2 after intraperitoneal administration to mice. Toxicity was not observed after oral administration of any of the ginsenosides. The genins, panaxadiol and panaxatriol, were more toxic and had larger volumes of distribution than the ginsenosides.