Anti-mycobacterial activity of plumericin and isoplumericin against MDR Mycobacterium tuberculosis.

BACKGROUND AND OBJECTIVES: Because of the developing resistance of Mycobacterium species against currently available anti-mycobacterial drugs, there is an urgent need for new drug development. In this study, we have evaluated the in vitro anti-mycobacterial activity of Plumeria bicolor extract and its phytoconstituents - plumericin and isoplumericin against multi-drug resistance Mycobacterium tuberculosis. METHODS: The in vitro anti-mycobacterial activity of chloroform extract of P. bicolor, plumericin and isoplumericin were tested against M. tuberculosis (H37Rv) and four multi-drug resistant (MDR) clinical isolates by measuring the minimum inhibitory concentration (MIC) using MTT (Tetrazolium bromide [3-(4, 5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide]) assay. The extract and both compounds were further evaluated by standard assay procedures to determine their minimum bactericidal concentration (MBC). Cytotoxicity of these compounds was performed against J774G8 murine macrophage cell lines. The activity was represented in the mean (±SD) of duplicate samples from three independent assays. RESULTS: Plumericin showed better activity against pan sensitive as well as four MDR strains of M. tuberculosis with MIC values of 2.1 ± 0.12, 1.3 ± 0.15, 2.0 ± 0.07, 1.5 ± 0.13 & 2.0 ± 0.14 µg/mL and MBC values of 3.6 ± 0.22, 2.5 ± 0.18, 3.8 ± 0.27, 2.9 ± 0.20 & 3.7 ± 0.32 µg/mL than isoplumericin, respectively. Interestingly, both isolated active compounds showed an advantage over rifampicin (80 times) and isoniazid (8 times) by being highly active against the MDR strains. The extract and both compounds were found to be non-toxic against J774G8 macrophages up to the used concentrations. CONCLUSION: Plumericin showed more potent activity than isoplumericin. The excellent activity of these compounds against MDR strains opens a possibility of obtaining new anti-mycobacterial drug candidate in near future.

Antiparasitic activity of plumericin & isoplumericin isolated from Plumeria bicolor against Leishmania donovani.

BACKGROUND & OBJECTIVES: The severe toxicity, exorbitant cost and emerging resistance of Leishmania species against most of the currently used drugs underscores the urgent need for the alternative drugs. The present study evaluates in vitro anti-leishmanial activity of Plumeria bicolor and its isolated compounds. METHODS: The in vitro anti-parasitic activity of chloroform extract of Plumeria bicolor, plumericin and isoplumericin were tested alongwith appropriate controls against promastigote and amastigote forms of Leishmania donovani using 96 well microtiter plate. The concentration used for assessing the anti-leishmanial activity of extract of Plumeria bicolor and both isolated compounds were 100 µg/ml and 15 µM, respectively. The viability of the cells was assessed by MTT assay. The cytotoxicity of these compounds was performed against J774G8 murine macrophage cells lines at the concentration of 30 µM. RESULTS: The Plumeria bicolor extract showed activity with the IC 50 of 21±2.2 and 14±1.6 µg/ml against promastigote and amastigote forms of L. donovani, respectively. Plumericin consistently showed high activity with the IC 50 of 3.17±0.12 and 1.41±0.03 µM whereas isoplumericin showed the IC50 of 7.2±0.08 µM and 4.1±0.02 µM against promastigote and amastigote forms, respectively. Cytotoxic effect of the chloroform extract of P. bicolor, plumericin and isoplumericin was evaluated in murine macrophage (J774G8) model with CC50 value of 75±5.3 µg/ml, 20.6±0.5 and 24±0.7 µM, respectively. INTERPRETATION & CONCLUSIONS: Our results indicated that plumericin showed more potent activity than isoplumericin and might be a promising anti-leishmanial agent against L. donovani.

Effect of Saponins of Albizia lebbeck (L.) Benth bark on the reproductive system of male albino rats.

Oral administration of saponins isolated from Albizia lebbeck bark at the dose level of 50 mg/kg/b.w. per day for 60 days to male rats brought about a significant decrease in the weights of testes, epididymides, seminal vesicle and ventral prostate. The production of round spermatid was reduced by 73.04% in Albizia lebbeck treated rats. The population of preleptotene spermatocytes and spermatogonia were reduced by 65.07% and 47.48% and secondary spermatocytes by 73.41%, respectively. Cross sectional surface area of Sertoli cells as well as the cell counts were found to be depleted significantly. Leydig cell nuclear area and number of mature Leydig cells were decreased by 57.47% and 54.42%, respectively. Sperm motility as well as sperm density were reduced significantly. Albizia lebbeck reduced the fertility of male rats by 100%. There were no significant changes in RBC and WBC count, haemoglobin, haematocrit and glucose in the blood and cholesterol, protein, triglyceride and phospholipid in the serum. The protein, glycogen and cholesterol contents of the testes, fructose in the seminal vesicle and protein in epididymides were significantly decreased. Histoarchitecture of the testes showed vacuolization at primary spermatocytes stage. Highly reduced seminiferous tubular diameter and increased intertubular space were also observed when compared to controls.

Modulatory potential of α-amyrin against hepatic oxidative stress through antioxidant status in Wistar albino rats.

ETHNOPHARMACOLOGICAL RELEVANCE: α-Amyrin (a pentacyclic triterpene widely distributed in nature and isolated from a variety of plant sources and pharmacologically shown a wide spectrum of activity including anti-inflammatory, anti-ulcer, anti-hyperlipidemic, anti-tumor, and hepatoprotective actions) explored as hepatomodulator from the ethanol extract of the stem bark of Alstonia scholaris Linn. against CCl4-induced hepatic oxidative stress through antioxidant status in wistar albino rats. MATERIALS AND METHODS: Experimental rats, hepato-oxidatively stressed by CCl4 (0.2 ml/kg b wt/twice a week, intra-peritoneally), were concurrently received α-amyrin (20mg/kg body weight/day, orally) for 30 consecutive days. Hepatomodulatory potential was assessed by using the serum- markers like γ-glutamyl transpeptidase (GGT), aspartate and alanine transaminases (AST, ALT), lactate dehydrogenase (LDH), alkaline phosphatase (ALP), acid phosphatase (ACP), sorbitol dehydrogenase (SDH), glutamate dehydrogenase (GDH), and total bilirubin, total protein, glutathione reduced (GSH), ceruloplasmin, ß-carotene, vitamin C and vitamin E in serum concomitantly with the hepatic-antioxidants like superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione reductase (GR), glutathione-s-transferase (GST), and 5´-nucleotidase, acid ribonuclease, glucose-6-phosphatase, succinic dehydrogenase and cytochrome-P-450 in liver tissue whereas lipid peroxidation (LPO) was estimated in both serum and liver contents. RESULTS: The assessment of all biochemical parameters registered a significant (P<0.001) hepatic oxidative stress in CCl4 treated rats, which was considerably recovered near to almost normal level in rats co-administered with α-amyrin at the dose level of 20mg/kg body weight/day for 30 consecutive days. The histoarchitectural examination of liver sections from treated groups further corroborated the hepatomodulatory potential of α-amyrin and compared with standard drug-silymarin. CONCLUSIONS: These findings indicate that the modulatory potential of α-amyrin against hepatic oxidative stress possibly involve mechanism related to its ability to block the P-450 mediated CCl4 bioactivation through selective inhibitors of ROS (reactive oxygen species) as antioxidants brought about significant inhibition of the formation of LPO suggesting possible involvement of O2(●-), HO2, HO2(●-), H2O2 and •OH. Therefore this study suggests that the use of α-amyrin as a hepatomodulatory potent to feasibility for a promising liver curative drug.

Effect of Alstonia scholaris bark extract on testicular function of Wistar rats.

AIM: To evaluate the antifertility effect of Alstonia scholaris bark extract in male rats. METHODS: In male Wistar rats Alstonia scholaris bark extract was given by oral route at a dose of 200 mg/day for 60 days. The fertility and testicular function were assessed by mating tests, sperm motility, sperm concentration, biochemical indices and testicular cell population dynamics. RESULTS: Oral feeding with the extract at a dose of 200 mg/day for the period of 60 days did not cause body weight loss, while the weights of testes, epididymides, seminal vesicle and ventral prostate were significantly reduced. The production of step-19 spermatids was reduced by 79.6% in treated rats. The population of preleptotene and pachytene spermatocytes were decreased by 61.9% and 60.1%, respectively. Spermatogonia and Sertoli cell population were also affected. The seminiferous tubule and Leydig cell nuclear area were reduced significantly (P<0.01) when compared to the controls. Reduced sperm count and motility resulted in a total suppression of fertility. A significant fall in the protein and sialic acid content of the testes, epididymides, seminal vesicle and ventral prostate as well as glycogen content of testes were also noticed. The fructose content in the seminal vesicle was lowered whereas the testicular cholesterol was elevated as compared with the controls. The following compounds were obtained from the extract with chromatographic separation over Si-gel column: agr-amyrin, bgr-amyrin, lupiol acetate, venenative, rhazine and yohimbine. CONCLUSION: At the dose level employed, Alstonia scholaris bark extract has a significant antifertility effect in male rats; the primary site of action may be post meiotic germ cells (Step 19 spermatids).

A review of medicinal plants showing anticonvulsant activity.

The term epilepsy is collectively designated for a group of chronic central nervous system disorders characterized by spontaneous occurrence of seizures generally associated with the loss of consciousness and body movements (convulsions). The disease has its origin from an early age. Anticonvulsant drugs are used to control the convulsions by inhibiting the discharge and then producing hypnosis. Various synthetic drugs, viz. sodium diphenyl hydantoin (Dialtin) barbiturates, pyrimidon, succinamides, diazepines etc. are used for the treatment. In this paper various medicinal plants and plant components, which are being used as anticonvulsant and antiepileptic, are discussed.

Antifertility studies of the root extract of the Barleria prionitis Linn in male albino rats with special reference to testicular cell population dynamics.

Oral administration of root extract of Barleria prionitis L. to male rats (100 mg/rat per day) for the period of 60 days did not cause body weight loss. The root extract brought about an interference with spermatogenesis. The round spermatids were decreased by 73.6% (P< or =0.001). No significant change was found in the population of secondary spermatocytes. However, the population of preleptotene spermatocytes were decreased by 41.9%. The extract reduced the fertility of male rats by 100%. Cross sectional surface area of Sertoli cells and mature Leydig cell numbers were significantly reduced (36.9%). The total protein, sialic acid contents of the testes, epididymides, seminal vesicle and prostate were reduced. Testicular glycogen contents were low. Antifertility effects of Barleria seemed to be mediated by disturbances in testicular somatic cells functions (Leydig and Sertoli cells) resulting in the physio-morphological events of spermatogenesis.

Antifertility studies of Colebrookia oppositifolia leaf extract in male rats with special reference to testicular cell population dynamics.

Oral feeding of male rats with the ethanolic leaf extract of Colebrookia oppositifolia at dose levels of 100 and 200 mg/kg for 8-10 weeks did not cause body weight loss, while the weights of testes and epididymides were significantly decreased. Seminal vesicles and ventral prostate showed a significant reduction at the higher dose only. Treated animals showed a notable depression of spermatogenesis. Following 100 and 200 mg/kg extract feeding, the preleptotene spermatocytes were decreased by 46.5 and 39.8%, the secondary spermatocytes by 13.4 and 12.7%, the step-19 spermatids by 36.6 and 35.2%, and the mature Leydig cells by 31.2 and 39.5%, respectively. At both dose levels, the seminiferous tubule diameter, Leydig cells nuclear area and cytoplasmic area, as well as the cross-sectional surface area of Sertoli cells, were significantly reduced (P<0.001) when compared to controls. Reduced sperm count and motility resulted in 100% negative fertility at 200 mg/kg dose level. A significant fall in the total protein and sialic acid content and acid phosphatase enzyme activity of the testes, epididymides, seminal vesicle and ventral prostate, as well as in the glycogen content of testes, was also observed at both dose levels in comparison with controls.

Evaluation of antidiabetic and antioxidant potential of lupeol in experimental hyperglycaemia.

Oxidative stress, produced under diabetic conditions, is a possible cause of various forms of tissue damage. The concentrations of antioxidant enzymes in cases of diabetes are significantly decreased, with a concomitant increase in lipid peroxidation. In this study, lupeol, a phytoconstituent from Solanum xanthocarpum, is shown to suppress the progression of diabetes after 21 days. Lupeol treatment caused decreases in glycated haemoglobin, serum glucose and nitric oxide, with a concomitant increase in serum insulin level. Furthermore, treatment with lupeol also increased antioxidant levels, with a decrease in the level of thiobarbituric acid-reactive oxygen species.

Antidiabetic and antioxidant potential of ß-sitosterol in streptozotocin-induced experimental hyperglycemia.

BACKGROUND: Oxidative stress, produced under diabetic conditions, may cause tissue damage. Although several drugs are currently available for the treatment of diabetes, their continued use may cause unwanted side effects. The aim of the present study was to evaluate the antioxidant potential of ß-sitosterol (BS), a phytosterol from Solanum surattense, using an experimental model for diabetes-induced oxidative damage. METHODS: The effects of 21 days treatment with BS (10, 15 and 20 mg/kg, p.o.) on blood, serum, and tissue biochemical parameters were evaluated in control and streptozotocin-induced diabetic rats. Nine experimental groups, including a control group, a diabetic group, and BS- and glibenclamide-treated diabetic groups, were evaluated. RESULTS: All three dose levels dose dependently resulted in decreases in glycated hemoglobin, serum glucose, and nitric oxide, with concomitant increases in serum insulin levels. Furthermore, treatment with BS doses also increased pancreatic antioxidant levels, with a concomitant decrease in thiobarbituric acid-reactive substances. CONCLUSIONS: ß-Sitosterol has promising antidiabetic as well as antioxidant effects and may be considered in clinical studies for drug development.

Antifungal activity of plumericin and isoplumericin.

This study evaluated the in vitro antifungal activity of the chloroform extract of Plumeria bicolor and its phytoconstituents plumericin and isoplumericin against Candida species and Cryptococcus neoformans by measuring the Minimum Inhibitory Concentration (MIC) and Minimum Fungicidal Concentration (MFC). Plumericin's consistently high activity against Candida albicans, C. krusei, C. glabrata, C. tropicalis and Cryptococcus neoformans was more potent than isoplumericin and the standard antifungal drug nystatin suggesting its potential as a drug candidate for candidiasis and cryptococcosis.

Phytochemical evaluation and antispermatogenic activity of Thevetia peruviana methanol extract in male albino rats.

This study was conducted to evaluate the antifertility potential of Thevetia peruviana (Apocynaceae) in male albino rats with their phytochemical evaluations. Phytochemical examination showed that plant is rich in active constituents, i.e. α-amyrin acetate, lupeol acetate, α-amyrin, ß-amyrin, lupeol and thevetigenin. T. peruviana stem bark methanol extract (TPMtE) administered orally to male rats at the dose level of 100 mg/rat/day did not cause any significant reduction in body weight, while the weight of reproductive organs reduced significantly. A significant fall in the total protein and sialic acid content of the testes, epididymides, seminal vesicle and ventral prostate, as well as in the glycogen content of testes was also observed; however, cholesterol was increased significantly. TPMtE also caused a decline in spermatogenic elements, i.e. preleptotene and pachytene spermatocytes, secondary spermatocytes, round spermatids and mature Leydig cells. At this dose level Leydig cell nuclear diameter, seminiferous tubular diameter and Sertoli area were significantly reduced (p < 0.001). The reduction in sperm density and motility resulted in 18% residual fertility. In conclusion, T. peruviana inhibited spermatogenesis in rats, indicating the possibility of developing a herbal male contraceptive.

Hypocholesterolaemic effect of the oleoresin of Capsicum annum L. in gerbils (Meriones hurrianae Jerdon).

The effect of capsicum oleoresin (CO) on dietary hypercholeterolaemia were observed in male gerbils at a dose of 75 mg/kg body wt/day. The oleoresin reduced serum cholesterol and triglycerides by 70% and 66%, whereas, liver cholesterol and triglycerides were lowered by 70.9% and 68.7% respectively, in comparison with atherogenic fed controls. CO feeding prevented the accumulation of cholesterol and triglycerides in the liver and aorta. The faecal excretion of cholesterol and triglycerides were significantly increased in oleoresin fed gerbils.

A review on potentiality of medicinal plants as the source of new contraceptive principles.

Recently, a review has already been made on the synthetic contraceptive agents whereas this review embraces the natural contraceptives upto year 2001 with 355 references. It also includes the isolation of their active principles, methods of analysis of active ingredients through TLC, HPLC, their side effects and pharmacological action.

Effects of Organoantimony(III) Compounds of Sterically Hindered Bifunctional Tetradentate Ligands on the Reproductive System of Male Rats.

The antifertility activity of organoantimony(III) complexes PhSb[RC(NC(6)H(4)S)CH(2)(NC(6)H(4)S)CR'] {R' = CH(3) (R(1)) and R = R' = CF(3) (R(2))} derived from corresponding sterically hinlered bifuinctional tetradentate ligands in the male rats was determined. The administration of compounds R(1) and R(2) at the dose level of 20 mg/kg. b. wt. siignificantly reduced the weights of testes and epididymides. Auxiliary glands showed a significant reduction after the treatment of compound R(1) only. Treated animals showed a notable depression of spermatogenesis. The preleptotene spermatocytes were decreased by 76.19 and 47.06; the secondary spermatocytes by 87.4% and 54.87337; and the step-19 spermatids by 72.9 and 46.77% respectively, following the compound R(1) and R(2) treatment. Reduced sperm count and motility resulted in 100% negative fertility in both the treated groups. A significant fall in the content of various biochemical parameters of eproductive tissues was observed after R(1) and R(2) treatment in comparison to controls.